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Haedge F, Bruns T. Antibiotics in decompensated liver disease - who, when and for how long? Expert Rev Gastroenterol Hepatol 2025; 19:111-130. [PMID: 39921440 DOI: 10.1080/17474124.2025.2464044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/26/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
INTRODUCTION Bacterial infections are a leading cause of hospitalization and mortality in patients with decompensated cirrhosis. Antibiotic prophylaxis in cirrhotic patients has demonstrated significant short-term reductions in bacterial infections in randomized controlled trials, but at the cost of drug resistance and with uncertain survival benefits. AREAS COVERED This review examines antibiotic use in cirrhosis, focusing on patients most likely to benefit from antibiotic prophylaxis, management strategies for infections through risk-based antibiotic selection and timely treatment initiation, challenges posed by the emergence of multidrug-resistant organisms, and principles of antimicrobial stewardship. EXPERT OPINION The efficacy of prophylaxis has decreased over time, and current registry data have questioned its use, emphasizing the need for better risk-based individualized strategies. When bacterial infections occur, the efficacy of antimicrobial therapies depends heavily on local epidemiological patterns and individual patient risk factors, necessitating tailored antibiotic selection based on regional resistance data and specific clinical scenarios. Nosocomial infections, colonization with multidrug-resistant organisms, and prior exposure to systemic antibiotics are key risk factors that should guide empirical therapy selection. Until evidence-based algorithms are available, clinicians should continue to adopt individualized approaches, guided by available evidence, local specificities, and antimicrobial stewardship principles to optimize patient outcomes.
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Affiliation(s)
- Frederic Haedge
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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2
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Ferrarese A, Senzolo M, Sasset L, Bassi D, Cillo U, Burra P. Multidrug-resistant bacterial infections in the liver transplant setting. Updates Surg 2024; 76:2521-2529. [PMID: 38918314 PMCID: PMC11602820 DOI: 10.1007/s13304-024-01903-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 05/21/2024] [Indexed: 06/27/2024]
Abstract
Bacterial infections pose a life-threatening complication in patients with decompensated liver cirrhosis and acute-on-chronic liver failure. An increasing prevalence of infections caused by multidrug-resistant organisms (MDROs) has been observed in these patients, significantly impacting prognosis. A growing body of evidence has identified the most common risk factors for such infections, enabling the development of preventive strategies and therapeutic interventions. MDRO infections may also occur after liver transplantation (most commonly in the early post-operative phase), affecting both graft and patient survival. This review provides an overview of MDRO infections before and after liver transplantation, discussing epidemiological aspects, risk factors, prevention strategies, and novel therapeutic approaches. Furthermore, it examines the implications of MDRO infections in the context of prioritizing liver transplantation for the most severe patients, such as those with acute-on-chronic liver failure.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Marco Senzolo
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Lolita Sasset
- Infectious Disease Unit, Padua University Hospital, Padua, Italy
| | - Domenico Bassi
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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3
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Hassall J, Coxon C, Patel VC, Goldenberg SD, Sergaki C. Limitations of current techniques in clinical antimicrobial resistance diagnosis: examples and future prospects. NPJ ANTIMICROBIALS AND RESISTANCE 2024; 2:16. [PMID: 39843577 PMCID: PMC11721362 DOI: 10.1038/s44259-024-00033-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 05/07/2024] [Indexed: 01/24/2025]
Abstract
Antimicrobial resistance is a global threat to public health. Without proactive intervention, common infections may become untreatable, restricting the types of clinical intervention that can be undertaken and reversing improvements in mortality rates. Effective antimicrobial stewardship represents one approach to restrict the spread of antimicrobial resistance but relies on rapid and accurate diagnostics that minimise the unnecessary use of antibiotics. This is increasingly a key unmet clinical need. In this paper, we describe existing techniques for the detection of antimicrobial resistance, while examining their drawbacks and limitations. We also discuss emerging diagnostic technologies in the field, and the need for standardisation to allow for swifter and more widespread clinical adoption.
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Affiliation(s)
- Jack Hassall
- Science Research and Innovation, Medicines and Healthcare products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK
| | - Carmen Coxon
- Science Research and Innovation, Medicines and Healthcare products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK
| | - Vishal C Patel
- The Roger Williams Institute of Hepatology London, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK
| | - Simon D Goldenberg
- Centre for Clinical Infection and Diagnostics Research, Guy's and St Thomas' NHS Foundation Trust and King's College, London, UK
| | - Chrysi Sergaki
- Science Research and Innovation, Medicines and Healthcare products Regulatory Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK.
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Chen T, Chen G, Wang G, Treeprasertsuk S, Lesmana CRA, Lin HC, Al-Mahtab M, Chawla YK, Tan SS, Kao JH, Yuen MF, Lee GH, Alcantara-Payawal D, Nakayama N, Abbas Z, Jafri W, Kim DJ, Choudhury A, Mahiwall R, Hou J, Hamid S, Jia J, Bajaj JS, Wang F, Sarin SK, Ning Q. Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections. Hepatol Int 2024; 18:817-832. [PMID: 38460060 DOI: 10.1007/s12072-023-10637-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 12/22/2023] [Indexed: 03/11/2024]
Abstract
End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.
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Affiliation(s)
- Tao Chen
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Guang Chen
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Sombat Treeprasertsuk
- Department of Medicine, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, and Thai Red Cross, Bangkok, Thailand
| | - Cosmas Rinaldi Adithya Lesmana
- Internal Medicine, Hepatobiliary Division, Dr. Captor Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, DKI, Indonesia
| | - Han-Chieh Lin
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Yogesh K Chawla
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Soek-Siam Tan
- Department of Hepatology, Hospital Selayang, Selangor Darul Ehsan, Malaysia
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Guan-Huei Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | | | - Nobuaki Nakayama
- Department of Gastroenterology & Hepatology, Saitama Medical University, Saitama, Japan
| | - Zaigham Abbas
- Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan
| | - Wasim Jafri
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Dong-Joon Kim
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital of Hallym University Medical Center, Chuncheon, Korea
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Mahiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Jinlin Hou
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Saeed Hamid
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - J S Bajaj
- Department of Medicine, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, VA, USA
| | - Fusheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Qin Ning
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, P.R. China.
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Trad N, Mohamed G, Bizid S, Abdallah HB, Bouali R, Abdelli MN. Clinical impact of multidrug-resistant bacterial infections in patients with cirrhosis. Future Sci OA 2024; 10:FSO945. [PMID: 38813115 PMCID: PMC11131343 DOI: 10.2144/fsoa-2023-0160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 11/17/2023] [Indexed: 05/31/2024] Open
Abstract
Aim: Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their clinical impact on patients with decompensated cirrhosis. Methods: A retrospective study included consecutive cirrhotic patients hospitalized for acute decompensation (AD) between January 2010 and December 2019. Results: A total of 518 AD admissions in 219 patients were included, with 260 BI episodes (50.2%). MDRO prevalence was 38.2% of the total isolates. Recent antibiotic use (OR = 4.91), nosocomial infection (OR = 2.95), and healthcare-associated infection (OR = 3.45) were their main risk factors. MDROs were associated with empiric treatment failure (OR = 23.42), a higher prevalence of sepsis (OR = 4.93), ACLF (OR = 3.42) and mortality. Conclusion: The clinical impact of MDROs was pejorative, with an increased risk of empiric treatment failure, organ failure and death.
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Affiliation(s)
- Nouha Trad
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Ghanem Mohamed
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Sondes Bizid
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Hatem Ben Abdallah
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Riadh Bouali
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Mohamed Nabil Abdelli
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
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Xiang Z, Song Y, Liu J, Xu C, Zhou Z, Li J, Su R, Shu W, Lu Z, Wei X, Yang J, Yang Y, Zheng S, Xu X. Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China. Int J Surg 2024; 110:2196-2206. [PMID: 38285095 PMCID: PMC11019992 DOI: 10.1097/js9.0000000000001114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 01/09/2024] [Indexed: 01/30/2024]
Abstract
BACKGROUND Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05). CONCLUSION Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.
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Affiliation(s)
- Ze Xiang
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Yisu Song
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Jianrong Liu
- Surgical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou
| | - Chenhao Xu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Zhisheng Zhou
- National Center for Healthcare Quality Management in Liver Transplant
| | - Jiarui Li
- Zhejiang University School of Medicine
| | - Renyi Su
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Wenzhi Shu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Zhengyang Lu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | | | - Jiayin Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center
| | - Shusen Zheng
- NHC Key Laboratory of Combined Multi-organ Transplantation
- National Center for Healthcare Quality Management in Liver Transplant
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou
| | - Xiao Xu
- Zhejiang University School of Medicine
- NHC Key Laboratory of Combined Multi-organ Transplantation
- National Center for Healthcare Quality Management in Liver Transplant
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7
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Lemos GT, Terrabuio DRB, Nunes NN, Song ATW, Oshiro ICV, D'Albuquerque LAC, Levin AS, Abdala E, Freire MP. Pre-transplant multidrug-resistant infections in liver transplant recipients-epidemiology and impact on transplantation outcome. Clin Transplant 2024; 38:e15173. [PMID: 37877950 DOI: 10.1111/ctr.15173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/22/2023] [Accepted: 10/17/2023] [Indexed: 10/26/2023]
Abstract
BACKGROUND Cirrhotic patients are highly exposed to healthcare services and antibiotics. Although pre-liver transplantation (LT) infections are directly related to the worsening of liver function, the impact of these infections on LT outcomes is still unclear. This study aimed to identify the effect of multidrug-resistant microorganism (MDRO) infections before LT on survival after LT. METHODS Retrospective study that included patients who underwent LT between 2010 and 2019. Variables analyzed were related to patients' comorbidities, underlying diseases, time on the waiting list, antibiotic use, LT surgery, and occurrences post-LT. Multivariate analyses were performed using logistic regression, and Cox regression for survival analysis. RESULTS A total of 865 patients were included; 351 infections were identified in 259 (30%) patients, of whom 75 (29%) had ≥1 pre-LT MDRO infection. The most common infection was spontaneous bacterial peritonitis (34%). The agent was identified in 249(71%), 53(15%) were polymicrobial. The most common microorganism was Klebsiella pneumoniae (18%); the most common MDRO was ESBL-producing Enterobacterales (16%), and carbapenem-resistant (CR) Enterobacterales (10%). Factors associated with MDRO infections before LT were previous use of therapeutic cephalosporin (p = .001) and fluoroquinolone (p = .001), SBP prophylaxis (p = .03), ACLF before LT (p = .03), and days of hospital stay pre-LT (p < .001); HCC diagnosis was protective (p = .01). Factors associated with 90-day mortality after LT were higher MELD on inclusion to the waiting list (p = .02), pre-LT MDRO infection (p = .04), dialysis after LT (p < .001), prolonged duration of LT surgery (p < .001), post-LT CR-Gram-negative bacteria infection (p < .001), and early retransplantation (p = .004). CONCLUSION MDRO infections before LT have an important impact on survival after LT.
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Affiliation(s)
- Gabriela T Lemos
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Debora R B Terrabuio
- Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Nathalia N Nunes
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Alice T W Song
- Division of Liver and Gastrointestinal Transplant, Hospital das Clínicas, Department of Surgery, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Isabel C V Oshiro
- Working Committee for Hospital Epidemiology and Infection Control, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Luiz Augusto C D'Albuquerque
- Division of Liver and Gastrointestinal Transplant, Hospital das Clínicas, Department of Surgery, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Anna S Levin
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Edson Abdala
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Maristela P Freire
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
- Working Committee for Hospital Epidemiology and Infection Control, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
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Schmid S, Koch C, Zimmermann K, Buttenschoen J, Mehrl A, Pavel V, Schlosser-Hupf S, Fleischmann D, Krohn A, Schilling T, Müller M, Kratzer A. Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure. Antibiotics (Basel) 2023; 12:1730. [PMID: 38136763 PMCID: PMC10740747 DOI: 10.3390/antibiotics12121730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/10/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
(1) Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing disease in patients with liver cirrhosis. Meropenem is crucial for treating severe infections. Therapeutic drug monitoring (TDM) offers an effective means to control drug dosages, especially vital for bactericidal antibiotics like meropenem. We aimed to assess the outcomes of implementing TDM for meropenem using an innovative interprofessional approach in ACLF patients on a medical intensive care unit (ICU). (2) Methods: The retrospective study was conducted on a medical ICU. The outcomes of an interprofessional approach comprising physicians, hospital pharmacists, and staff nurses to TDM for meropenem in critically ill patients with ACLF were examined in 25 patients. Meropenem was administered continuously via an infusion pump after the application of an initial loading dose. TDM was performed weekly using high-performance liquid chromatography (HPLC). Meropenem serum levels, implementation of the recommendations of the interprofessional team, and meropenem consumption were analyzed. (3) Results: Initial TDM for meropenem showed a mean meropenem serum concentration of 20.9 ± 9.6 mg/L in the 25 analyzed patients. Of note, in the initial TDM, only 16.0% of the patients had meropenem serum concentrations within the respective target range, while 84.0% exceeded this range. Follow-up TDM showed serum concentrations of 15.2 ± 5.7 mg/L (9.0-24.6) in Week 2 and 11.9 ± 2.3 mg/L (10.2-13.5) in Week 3. In Week 2, 41.7% of the patients had meropenem serum concentrations that were within the respective target range, while 58.3% of the patients were above this range. In Week 3, 50% of the analyzed serum concentrations of meropenem were within the targeted range, and 50% were above the range. In total, 100% of the advice given by the interprofessional team regarding meropenem dosing or a change in antibiotic therapy was implemented. During the intervention period, the meropenem application density was 37.9 recommended daily doses (RDD)/100 patient days (PD), compared to 42.1 RDD/100 PD in the control period, representing a 10.0% decrease. (4) Conclusions: Our interprofessional approach to TDM significantly reduced meropenem dosing, with all the team's recommendations being implemented. This method not only improved patient safety but also considerably decreased the application density of meropenem.
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Affiliation(s)
- Stephan Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Chiara Koch
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Katharina Zimmermann
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Jonas Buttenschoen
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Alexander Mehrl
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Vlad Pavel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Sophie Schlosser-Hupf
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Daniel Fleischmann
- Hospital Pharmacy, University Hospital Regensburg, 93053 Regensburg, Germany; (D.F.); (A.K.)
| | - Alexander Krohn
- Department of Interdisciplinary Acute, Emergency and Intensive Care Medicine (DIANI), Klinikum Stuttgart, 70174 Stuttgart, Germany; (A.K.); (T.S.)
| | - Tobias Schilling
- Department of Interdisciplinary Acute, Emergency and Intensive Care Medicine (DIANI), Klinikum Stuttgart, 70174 Stuttgart, Germany; (A.K.); (T.S.)
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (C.K.); (K.Z.); (J.B.); (A.M.); (V.P.); (S.S.-H.); (M.M.)
| | - Alexander Kratzer
- Hospital Pharmacy, University Hospital Regensburg, 93053 Regensburg, Germany; (D.F.); (A.K.)
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9
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Mohammed Abdul MK, Osman KT, Cappuccio JM, Spencer C, Satapathy SK. Nosocomial spontaneous bacterial peritonitis is associated with high mortality - a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:1333-1339. [PMID: 37982715 DOI: 10.1080/17474124.2023.2284825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 11/14/2023] [Indexed: 11/21/2023]
Abstract
INTRODUCTION It is unclear if Nosocomial Spontaneous Bacteria Peritonitis (NSBP) is associated with higher mortality compared with community acquired spontaneous bacterial peritonitis. METHODS Database search from inception to May 2022 was conducted. The databases included MEDLINE, EMBASE, Cochrane registry of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Inclusion criteria were as follows: adult patients, age >18 years, with a diagnosis of NSBP. Pooled estimates of mortality were calculated following the restricted maximum likelihood method. The mortality rate between NSBP and CA-SBP was reported as odds ratio (OR) and 95% confidence interval (CI). Data synthesis was obtained using random effects meta-analysis. Heterogeneity was reported as I2. RESULTS A total of 482 unique titles were screened. Twenty-two articles were included. A total of 2,145 patients with NSBP were included. Patients were followed for a median of 90 days. The pooled mortality rate of NSBP was 52.51% (95% CI 42.77-62.06%; I2 83.72%). Seven studies compared the mortality outcome of patients with NSBP and CA-SBP. NSBP was significantly associated with a higher rate of mortality (OR 2.78, 95% CI 1.87-4.11; I2 36.00%). CONCLUSION NSBP was associated with higher mortality rate compared to CA-SBP, which could be due to a higher rate of resistance organisms.
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Affiliation(s)
| | - Karim T Osman
- Department of Internal Medicine, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Joseph M Cappuccio
- Department of Internal Medicine, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Carol Spencer
- Department of Library Services, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Sanjaya K Satapathy
- Sandra Atlas Bass Center for Liver Diseases and Transplantation, Manhasset, NY, USA
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10
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Iqbal A, Gangwani MK, Beran A, Dahiya DS, Sohail AH, Lee-Smith W, Aziz M, Hassan M. Nosocomial vs healthcare associated vs community acquired spontaneous bacterial peritonitis: Network meta-analysis. Am J Med Sci 2023; 366:305-313. [PMID: 37394136 DOI: 10.1016/j.amjms.2023.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 03/24/2023] [Accepted: 06/26/2023] [Indexed: 07/04/2023]
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is a common complication in decompensated liver cirrhosis with ascitic fluid polymorphonuclear cell count > 250/mm3. Community acquired SBP (CA-SBP) occurs within the first 48 hours after hospital admission. Nosocomial SBP (N-SBP) occurs 48-72 hours after hospitalization. Healthcare associated SBP (HA-SBP) occurs in patients hospitalized in the preceding 90 days to months. We aim to evaluate mortality and resistance patterns to third generation cephalosporin among the three types. METHODS Multiple databases were systematically searched from inception through August 1st, 2022. Both pairwise (direct) and network (direct + indirect) meta-analysis was performed using a random effects model and DerSimonian Laird approach. Relative Risk (RR) with 95% confidence intervals (CI) were calculated. Network meta-analysis was conducted using frequentist approach. RESULTS A total of 14 studies with a total of 2302 SBP episodes were evaluated. On direct meta-analysis, mortality rate was higher in N-SBP compared to HA-SBP (RR 1.84, CI 1.43- 2.37) and CA-SBP (RR 1.69, CI 1.4-1.98), but not significantly different between HA-SBP and CA-SBP (RR=1.40, CI=0.71-2.76). Resistance to third generation cephalosporins was significantly higher in N-SBP compared to HA-SBP (RR=2.02, CI 1.26-3.22) and CA-SBP (RR=3.96, CI=2.50-3.60) as well as in HA-SBP compared to CA-SBP (RR=2.25, CI=1.33-3.81). CONCLUSIONS Our network meta-analysis shows increased mortality and antibiotic resistance with nosocomial SBP. We recommend clearly identifying such patients to manage accordingly as well as developing guidelines geared towards nosocomial infections to be able to optimally steer resistance patterns and reduce mortality.
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Affiliation(s)
- Amna Iqbal
- Department of Medicine, University of Toledo Medical Center, Toledo, Ohio, USA
| | | | - Azizullah Beran
- Department of Gastroenterology and Hepatology, Indiana University School of Medicine, Indiana, USA
| | | | - Amir Humza Sohail
- Department of General Surgery, New York University Langone Health, Long Island, NY,USA
| | - Wade Lee-Smith
- University of Toledo Libraries, University of Toledo, Toledo, Ohio, USA
| | - Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo Medical Center, Toledo, Ohio, USA
| | - Mona Hassan
- Division of Gastroenterology and Hepatology, University of Toledo Medical Center, Toledo, Ohio, USA
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11
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Jimenez JV, Garcia-Tsao G, Saffo S. Emerging concepts in the care of patients with cirrhosis and septic shock. World J Hepatol 2023; 15:497-514. [PMID: 37206653 PMCID: PMC10190696 DOI: 10.4254/wjh.v15.i4.497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/19/2023] [Accepted: 03/23/2023] [Indexed: 04/20/2023] Open
Abstract
Septic shock impacts approximately 6% of hospitalized patients with cirrhosis and is associated with high rates of morbidity and mortality. Although a number of landmark clinical trials have paved the way for incremental improvements in the diagnosis and management of septic shock in the general population, patients with cirrhosis have largely been excluded from these studies and critical knowledge gaps continue to impact the care of these individuals. In this review, we discuss nuances in the care of patients with cirrhosis and septic shock using a pathophysiology-based approach. We illustrate that septic shock may be challenging to diagnose in this population in the context of factors such as chronic hypotension, impaired lactate metabolism, and concomitant hepatic encephalopathy. Furthermore, we demonstrate that the application of routine interventions such as intravenous fluids, vasopressors, antibiotics, and steroids should be carefully considered among those with decompensated cirrhosis in light of hemodynamic, metabolic, hormonal, and immunologic disturbances. We propose that future research should include and characterize patients with cirrhosis in a systematic manner, and clinical practice guidelines may need to be refined accordingly.
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Affiliation(s)
- Jose Victor Jimenez
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520, United States
| | - Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520, United States
| | - Saad Saffo
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520, United States.
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12
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Terra C, de Mattos ÂZ, Chagas MS, Torres A, Wiltgen D, Souza BM, Perez RM. Impact of multidrug resistance on the management of bacterial infections in cirrhosis. World J Clin Cases 2023; 11:534-544. [PMID: 36793638 PMCID: PMC9923851 DOI: 10.12998/wjcc.v11.i3.534] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/22/2022] [Accepted: 01/05/2023] [Indexed: 01/23/2023] Open
Abstract
Patients with cirrhosis have an increased risk of infection and differently from other complications, that over the years are improving in their outcomes, infections in cirrhotic patients are still a major cause of hospitalization and death (up to 50% in-hospital mortality). Infections by multidrug-resistant organisms (MDRO) have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact. About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years. MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution. An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects, such as the type of infection (spontaneous bacterial peritonitis, pneumonia, urinary tract infection and spontaneous bacteremia), bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition (community acquired, healthcare associated or nosocomial). Furthermore, regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology. Antibiotic treatment is the most effective measure to treat infections caused by MDRO. Therefore, optimizing antibiotic prescribing is critical to effectively treat these infections. Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality. On the other hand, the supply of new agents to treat these infections is very limited. Thus, specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.
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Affiliation(s)
- Carlos Terra
- Gastroenterology-Liver Unit, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Liver Unit, Casa de Saúde São José-Rede Santa Catarina, Rio de Janeiro 22271-080, Rio de Janeiro, Brazil
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Liver Unit, Federal Hospital of Lagoa, Rio de Janeiro 22470-050, Rio de Janeiro, Brazil
| | - Ângelo Zambam de Mattos
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90020-090, Rio Grande do Sul, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Rio Grande do Sul, Brazil
| | - Marcelo Souza Chagas
- Gastroenterology-Liver Unit, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Internal Medicine, Federal Hospital of Lagoa, Rio de Janeiro 22470-050, Rio de Janeiro, Brazil
| | - Andre Torres
- Gastroenterology-Liver Unit, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
| | - Denusa Wiltgen
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Department of Internal Medicine, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Barbara Muniz Souza
- Gastroenterology-Liver Unit, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
| | - Renata Mello Perez
- Alliance of Brazilian Centers for Cirrhosis Car, The ABC Group, Rio de Janeiro 20551-030, Rio de Janeiro, Brazil
- Hepatology Division, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Rio de Janeiro, Brazil
- IDOR, D’Or Institute for Research and Education, Rio de Janeiro 22281-100, Rio de Janeiro, Brazil
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13
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Feldman S, Russo A, Ceccarelli G, Borrazzo C, Madge C, Venditti M, Merli M. Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections in Patients With Liver Cirrhosis. J Clin Exp Hepatol 2022; 12:1293-1300. [PMID: 36157152 PMCID: PMC9499843 DOI: 10.1016/j.jceh.2022.04.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 04/17/2022] [Indexed: 12/12/2022] Open
Abstract
Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients with cirrhosis represent a significant therapeutic challenge as they are associated with poor outcomes due to high rates of treatment failure, and frequently induce liver decompensation. Aims To evaluate treatment failure and in-hospital mortality in two cohorts of patients with cirrhosis and with CRKP infections treated with antibiotic regimens including or excluding Ceftazidime-avibactam. Methods Data from hospitalized patients with liver cirrhosis and CRKP infections were extracted and retrospectively analyzed. Results During the study period, 39 cirrhotic patients with confirmed invasive CRKP infections were enrolled. Overall, the median age was 60 years with a median MELD score of 16 points. Urinary tract infections were diagnosed in 46%, followed by pneumonia in 23%, and primary bacteremia in 18% of patients. Treatment failure was reported in 10 patients (26%), while in-hospital mortality in 15 patients (38%). A monotherapy was used in 8 patients (20.5%), while a combination therapy was required in 31 patients (79.5%). Ceftazidime-avibactam therapy was associated with lower rates of treatment failure (7% vs. 38%, P = 0.032) independent of severity of liver disease (Child Class) and mono or combination antibiotic therapy. Acute kidney injury, hepatorenal syndrome, and acute-on-chronic liver failure were the consequences more frequently observed in patients with treatment failure. In-hospital mortality was associated with treatment failure, and Ceftazidime-avibactam therapy improved in-hospital survival (log rank test: P = 0.035) adjusted for Child class and mono or combination therapy. Conclusion Treatment including ceftazidime-avibactam was associated with a lower rate of treatment failure in cirrhotic patients with CRKP infections. Considering the favorable efficacy and outcomes of ceftazidime-avibactam, this drug should be considered for the treatment of these severe infections in patients with liver cirrhosis, though further investigation is required.
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Key Words
- ACLF, Acute-on-Chronic Liver Failure
- AKI, Acute Kidney Injury
- CAZ-AVI, Ceftazidime-Avibactam
- COPD, Chronic Obstructive Pulmonary Disease
- CRKP, Carbapenem-Resistant Klebsiella Pneumoniae
- DCT, Double-Carbapenem Therapy
- EASL-CLIF, European Association for the Study of the Liver- Chronic Liver Failure
- EUCAST, EUropean Committee for Antimicrobial Susceptibility Testing
- Ecdc, European Centre for Disease Prevention and Control
- HCC, Hepatocellular Carcinoma
- HRS, Hepatorenal Syndrome
- MDR, Multi-Drug Resistant
- MELD, Model for End-stage Liver Disease
- MIC, Minimum Inhibitory Concentration
- NASH, Non-Alcoholic Steatohepatitis
- TIPS, Transjugular Intrahepatic Portosystemic Shunt
- antibiotic therapy
- bacterial infections
- carbapenem-resistant strains
- liver cirrhosis
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Affiliation(s)
- Shani Feldman
- Division of Gastroenterology, Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale Dell’Università 37, 00185 Rome, Italy
| | - Alessandro Russo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Viale Dell’Università 37, 00185, Rome, Italy
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Viale Dell’Università 37, 00185, Rome, Italy
| | - Cristian Borrazzo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Viale Dell’Università 37, 00185, Rome, Italy
| | - Chiara Madge
- Division of Gastroenterology, Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale Dell’Università 37, 00185 Rome, Italy
| | - Mario Venditti
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Viale Dell’Università 37, 00185, Rome, Italy
| | - Manuela Merli
- Division of Gastroenterology, Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale Dell’Università 37, 00185 Rome, Italy
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14
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Kulkarni AV, Premkumar M, Arab JP, Kumar K, Sharma M, Reddy ND, Padaki NR, Reddy RK. Early Diagnosis and Prevention of Infections in Cirrhosis. Semin Liver Dis 2022; 42:293-312. [PMID: 35672014 DOI: 10.1055/a-1869-7607] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective β-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of β-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Juan P Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Karan Kumar
- Department of Hepatology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nageshwar D Reddy
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nagaraja R Padaki
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Rajender K Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
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15
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Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives. Biomedicines 2022; 10:biomedicines10071561. [PMID: 35884867 PMCID: PMC9313066 DOI: 10.3390/biomedicines10071561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/11/2022] [Accepted: 06/27/2022] [Indexed: 01/03/2023] Open
Abstract
End-stage liver disease patients undergoing liver transplantation are prone to develop numerous infectious complications because of immunosuppression, surgical interventions, and malnutrition. Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80%. The challenges faced in the early post-transplant period tend to be linked to transplant procedures and nosocomial infections commonly in bloodstream, surgical, and intra-abdominal sites. Viral infections represent an additional complication of immunosuppression; they can be donor-derived, reactivated from a latent virus, nosocomial or community-acquired. Bacterial and viral infections in solid organ transplantation are managed by prophylaxis, multi-drug resistant screening, risk assessment, vaccination, infection control and antimicrobial stewardship. The aim of this review was to discuss the epidemiology of bacterial and viral infections in liver transplants, infection control issues, as well as surgical frontiers of ex situ liver perfusion.
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16
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Ning Q, Chen T, Wang G, Xu D, Yu Y, Mao Q, Li T, Li L, Li J, Lu X, Li J, Li Z, Zhang W, Xiao Y, Meng Q, Mi Y, Shang J, Yu Y, Zhao Y, Zhao C, Zhao H, Huang J, Peng J, Tang H, Tang X, Hu J, Hu B, Guo W, Zheng B, Chen B, Zhang Y, Wei J, Sheng J, Chen Z, Wang M, Xie Q, Wang Y, Wang FS, Hou J, Duan Z, Wei L, Jia J. Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infections. INFECTIOUS DISEASES & IMMUNITY 2022; 2:168-178. [DOI: 10.1097/id9.0000000000000055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Indexed: 10/13/2023]
Abstract
Abstract
End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
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Affiliation(s)
- Qin Ning
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Tao Chen
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Dong Xu
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yanyan Yu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Qing Mao
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Taisheng Li
- Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jun Li
- Department of Infectious Disease, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Xiaoju Lu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Jiabin Li
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei 230031, China
| | - Zhiwei Li
- Department of Infectious Diseases, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110801, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Institute of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yonghong Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Qinghua Meng
- Department of Severe Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Yuqiang Mi
- Nankai University Second People's Hospital, Tianjin 300071, China
| | - Jia Shang
- Department of Infectious Disease, People's Hospital of Henan Province, Zhengzhou 450003, China
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Caiyan Zhao
- Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Jianrong Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xiaoping Tang
- Research Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Jinhua Hu
- Liver Failure Treatment and Research Center, The Fifth Medical Center, China PLA General Hospital, Beijing 100039, China
| | - Bijie Hu
- Department of Infectious Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Wei Guo
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Bo Zheng
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China
| | - Baiyi Chen
- Department of Infectious Diseases, The First Hospital of China Medical University, Shenyang 110002, China
| | - Yuexin Zhang
- Center of Infectious Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Jia Wei
- Department of Infectious Disease, The Second People's Hospital, Kunming 650201, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Minggui Wang
- Department of Infectious Diseases, Institute of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Fu-Sheng Wang
- Liver Failure Treatment and Research Center, The Fifth Medical Center, China PLA General Hospital, Beijing 100039, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Lai Wei
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center for Digestive Diseases, Beijing 100050, China
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17
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Abstract
Antimicrobial Resistance (AMR) has become a global threat to public health systems around the world in recent decades. In 2017, Italy was placed among the worst-performing nations in Europe by the European Centre for Disease Prevention and Control, due to worryingly high levels of AMR in Italian hospitals and regions. The aim of this systematic review was to investigate the state of the art of research on AMR in Italy over the last five years. The PubMed database was searched to identify studies presenting original data. Forty-three of the 9721 records identified were included. Overall, AMR rates ranged from 3% (in a group of sheep farmers) to 78% (in a hospital setting). The methods used to identify the microorganisms, to test their susceptibility and the criteria adopted for the breakpoint were deficient in 7, 7 and 11 studies, respectively. The main findings of our review were that most studies (79.1%) considered hospitalised patients only, 4 studies (9.3%) analysed non-hospitalised populations only. In addition, only 7 studies were multicentric and no scientific literature on the subject was produced in 7 Italian regions. In order to have a solid basis on the topic for the interventions of public health professionals and other stakeholders, studies analysing the phenomenon should be conducted in a methodologically standardised manner, should include all areas of the country and should also focus on out-of-hospital and community-based care and work settings.
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Caccamo G, Franzè MS, Saffioti F, Pitrone C, Porcari S, Alibrandi A, Filomia R, Mondello P, Cacciola I, Saitta C, Squadrito G, Raimondo G, Maimone S. Cirrhotic Patients with Bacterial Infection and Negative Cultures Have a More Advanced Disease and an Increased Short-Term Mortality Rate. Dig Dis Sci 2022; 67:2655-2665. [PMID: 34041650 DOI: 10.1007/s10620-021-07047-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 05/09/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The negative clinical impact of bacterial infections (BI) in patients with cirrhosis is well documented. In cirrhotic patients, failure to isolate the pathogen is a frequent event, occurring in 30-40% of cases. AIM The aim of this study was to compare the clinical characteristics, early (30-day) and short-term (90-day) mortality rates, in a cohort of cirrhotic patients with BI, between those with positive (C-pos) and those with negative (C-neg) microbiological cultures. METHODS We retrospectively enrolled 279 consecutive hospitalized cirrhotic patients with BI. Survival and predictors of 30-day and 90-day mortality were assessed by Kaplan-Meier curves and logistic regression analysis, respectively. RESULTS Cultures tested negative in 108/279 (38.7%) patients. C-neg patients were more frequently males (p = 0.035), had higher Child-Pugh-Turcotte (CPT; p = 0.007) and model for end-stage liver disease-sodium (MELD-Na; p = 0.043) scores, and had more frequently decompensated liver disease (p = 0.04). Mortality rate was higher in C-neg than in C-pos patients, both at 30 days (22.2% versus 11.7%, p = 0.024) and 90 days (46.3% versus 33.3%, p = 0.030). MELD-Na score and non-selective beta-blockers (NSBBs) were independent risk factors for 30-day and 90-day mortality. In particular, the use of NSBBs was independently associated with a lower 30-day and 90-day mortality risk (OR 0.41, CI95% 0.17-0.94, p = 0.040; and OR 0.43, CI95% 0.25-0.75, p = 0.003, respectively). CONCLUSIONS Cirrhotic patients with BI and negative microbiological cultures have significantly higher mortality compared to those with positive cultures. Early mortality and short-term mortality are mainly influenced by the underlying severity of liver disease. In this contest, therapy with NSBBs has a positive impact on short-term survival.
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Affiliation(s)
- Gaia Caccamo
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy.
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy.
| | - Maria Stella Franzè
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Francesca Saffioti
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Windmill Road, Heading, Oxford, OX1 HP, UK
| | - Concetta Pitrone
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Serena Porcari
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Division of Gastroenterology and Inflammatory Bowel Diseases, University Hospital of Messina, Via Consolare Valeria 1, 98124, Messina, Italy
| | - Angela Alibrandi
- Department of Economics Unit of Statistical and Mathematical Science, University of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Roberto Filomia
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Placido Mondello
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Division of Infectious Diseases, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Irene Cacciola
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Giovanni Squadrito
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Division of Internal Medicine, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
| | - Sergio Maimone
- Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
- Department of Medical Sciences, University Hospital of Messina, "Policlinico G. Martino", Via Consolare Valeria 1, 98124, Messina, Italy
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Primary Norfloxacin Prophylaxis for APASL-Defined Acute-on-Chronic Liver Failure: A Placebo-Controlled Double-Blind Randomized Trial. Am J Gastroenterol 2022; 117:607-616. [PMID: 35041634 DOI: 10.14309/ajg.0000000000001611] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/14/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria. METHODS Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome. RESULTS A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10-28.9) and 33.8% (95% CI, 23-46) (P = 0.03); and the incidence of bacterial infections at day 90 was 46% (95% CI, 34-58) and 62% (95% CI, 49.67-73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43-86.73) and 64.8% (95% CI, 52.54-75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11-69.84) and 43.7% (95% CI, 31.91-55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%). DISCUSSION Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.
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Interprofessional Collaboration between ICU Physicians, Staff Nurses, and Hospital Pharmacists Optimizes Antimicrobial Treatment and Improves Quality of Care and Economic Outcome. Antibiotics (Basel) 2022; 11:antibiotics11030381. [PMID: 35326844 PMCID: PMC8944851 DOI: 10.3390/antibiotics11030381] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 12/29/2022] Open
Abstract
(1) Background: Antibiotic resistance is a worldwide health threat. The WHO published a global strategic plan in 2001 to contain antimicrobial resistance. In the following year, a workshop identified crucial barriers to the implementation of the strategy, e.g., underdeveloped health infrastructures and the scarcity of valid data as well as a lack of implementation of antibiotic stewardship (ABS) programs in medical curricula. Here, we show that interprofessional learning and education can contribute to the optimization of antibiotic use and preserving antibiotic effectiveness. We have initiated interprofessional rounds on a medical intensive care unit (MICU) with a focus on gastroenterology, hepatology, infectious diseases, endocrinology, and liver transplantation. We integrated ICU physicians, hospital pharmacists, nursing staff, and medical students as well as students of pharmacy to broaden the rather technical concept of ABS with an interprofessional approach to conceptualize awareness and behavioral change in antibiotic prescription and use. Methods: Clinical performance data and consumption figures for antibiotics were analyzed over a 10-year period from 2012 to 2021. The control period covered the years 2012–2014. The intervention period comprised the years 2015–2021, following the implementation of an interprofessional approach to ABS at a MICU of a German university hospital. Data from the hospital pharmacy, hospital administration, and hospital information system were included in the analyses. A specific electronic platform was developed for the optimization of documentation, interprofessional learning, education, and sustainability. The years 2020 and 2021 were analyzed independently due to the SARS-CoV-2 pandemic and the care of numerous COVID-19 patients at the MICU. Results: Implementation of an interprofessional ABS program resulted in the optimization of antibiotic management at the MICU. The suggestions of the hospital pharmacist for optimization can be divided into the following categories (i) indication for and selection of therapy (43.6%), (ii) optimization of dosing (27.6%), (iii) drug interactions (9.4%), (iv) side effects (4.1%), and (v) other pharmacokinetic, pharmacodynamic, and pharmacoeconomic topics (15.3%). These suggestions were discussed among the interprofessional team at the MICU; 86.1% were consequently implemented and the prescription of antibiotics was changed. In addition, further analysis of the intensive care German Diagnosis Related Groups (G-DRGs) showed that the case mix points increased significantly by 31.6% during the period under review. Accordingly, the severity of illness of the patients treated at the ICU as measured by the Simplified Acute Physiology Score (SAPS) II increased by 21.4% and the proportion of mechanically ventilated patients exceeded 50%. Antibiotic spending per case mix point was calculated. While spending was EUR 60.22 per case mix point in 2015, this was reduced by 42.9% to EUR 34.37 per case mix point by 2019, following the implementation of the interprofessional ABS program on the MICU. Through close interprofessional collaboration between physicians, hospital pharmacists, and staff nurses, the consumption of broad-spectrum antibiotics, e.g., carbapenems, was significantly reduced, thus improving patient care. In parallel, the case mix and case mix index increased. Thus, the responsible use of resources and high-performance medicine are not contradictory. In our view, close interprofessional and interdisciplinary collaboration between physicians, pharmacists, and nursing staff will be of outstanding importance in the future to prepare health care professionals for global health care to ensure that the effectiveness of our antibiotics is preserved.
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Spontaneous Bacterial Peritonitis among Cirrhotic Patients: Prevalence, Clinical Characteristics, and Outcomes. J Clin Med 2021; 11:jcm11010227. [PMID: 35011969 PMCID: PMC8746105 DOI: 10.3390/jcm11010227] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 12/25/2021] [Accepted: 12/30/2021] [Indexed: 12/16/2022] Open
Abstract
(1) Background: Spontaneous bacterial peritonitis (SBP) is a feared complication of liver cirrhosis. We investigated the prevalence of SBP, positive ascitic fluid cultures, and risk factors for mortality. (2) Methods: A retrospective analysis of all patients with cirrhosis hospitalized or in follow-up in a single center between 1996 and 2020. The clinical data, long-term complications, and mortality of SBP patients were compared with those of non-SBP patients. Ascitic fluid positive culture was compared with those without growth. (3) Results: We included 1035 cirrhotic patients, of which 173 (16.7%) developed SBP. Ascitic fluid culture growth was found in 47.4% of the SBP cases, with Escherichia coli bacteria detected in 38%, 24.4% grew ESBL-producing bacteria, and 14.5% displayed multidrug resistance. In a Cox regression model, SBP, male sex, prolonged INR at diagnosis, and hepatocellular carcinoma were found to be risk factors for mortality in cirrhotic patients. The long-term all-cause mortality was 60% in non-SBP and 90% in SBP patients. (4) Conclusions: Only a minority of cirrhotic patients developed SBP, 47.4% of which had positive ascitic fluid cultures with high antibiotic resistance. Growth of ESBL and multidrug resistant organisms is becoming more frequent in the clinical setting, reaching SBP mortality of 90%.
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22
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Schultze TG, Ferstl PG, Villinger D, Hogardt M, Bechstein WO, Göttig S, Wichelhaus TA, Zeuzem S, Trebicka J, Waidmann O, Welker MW, Kempf VAJ. Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates. Front Microbiol 2021; 12:791574. [PMID: 34880850 PMCID: PMC8645865 DOI: 10.3389/fmicb.2021.791574] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 10/27/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes. Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts. Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN. Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
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Affiliation(s)
- Tilman G Schultze
- Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt, Germany.,University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,University Center of Competence for Infection Control of the State of Hesse, Frankfurt, Germany
| | - Philip G Ferstl
- University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,Division of Gastroenterology and Hepatology, Department for Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - David Villinger
- Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt, Germany.,University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,University Center of Competence for Infection Control of the State of Hesse, Frankfurt, Germany
| | - Michael Hogardt
- Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt, Germany.,University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,University Center of Competence for Infection Control of the State of Hesse, Frankfurt, Germany
| | - Wolf O Bechstein
- Department of General and Visceral Surgery, Goethe University Frankfurt, Frankfurt, Germany
| | - Stephan Göttig
- Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt, Germany.,University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,University Center of Competence for Infection Control of the State of Hesse, Frankfurt, Germany
| | - Thomas A Wichelhaus
- Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt, Germany.,University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,University Center of Competence for Infection Control of the State of Hesse, Frankfurt, Germany
| | - Stefan Zeuzem
- University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,Division of Gastroenterology and Hepatology, Department for Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Jonel Trebicka
- University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,Division of Gastroenterology and Hepatology, Department for Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Oliver Waidmann
- University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,Division of Gastroenterology and Hepatology, Department for Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Martin-Walter Welker
- University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,Division of Gastroenterology and Hepatology, Department for Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Volkhard A J Kempf
- Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt, Germany.,University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.,University Center of Competence for Infection Control of the State of Hesse, Frankfurt, Germany
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23
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Elzouki AN, Hamad A, Almasri H, Ata M, Ashour A, Othman M, Badi A, Errayes M, Zahid M, Danjuma M. Predictors of Short-Term Mortality Following First Episode of Spontaneous Bacterial Peritonitis in Hospitalized Cirrhotic Patients. Cureus 2021; 13:e18999. [PMID: 34853741 PMCID: PMC8609112 DOI: 10.7759/cureus.18999] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2021] [Indexed: 11/25/2022] Open
Abstract
Background and aims Spontaneous bacterial peritonitis (SBP) is an important cause of morbidity and mortality in patients with cirrhosis. This study aimed to identify the factors impacting morbidity and short-term mortality in a cohort of patients with cirrhosis following an index episode of SBP. Methods In a retrospective study of hospitalized cirrhotic cohort, 333 patient records were reviewed. Demographic, clinical, and laboratory, as well as radiological characteristics of the patient population were analyzed on day 1 of admission. The diagnosis of cirrhosis was based on the combination of laboratory, clinical, and radiological features. The diagnosis of SBP was established by abdominal paracentesis in the presence of cellular, biochemical, and microbiological features consistent with SBP. All independent variables were analyzed to generate a predictive model of mortality by using the Cox proportional hazards regression analysis (adjusted for age and gender). Results A total of 61 cirrhotic patients with ascites and a first episode of SBP were identified. The overall mortality among hospitalized patients was 19.7% and was associated with longer length of stay (12.6 vs. 7.6 days; p=0.01). Patient cohorts with multiple antibiotic resistant bacteria as a cause of SBP had a significantly higher mortality compared to those with other bacterial phenotypes (p=0.03). Multivariate analyses showed that a model for end-stage liver disease (MELD) score (hazard ratio [HR]=1.29; 95% CI: 1.10 to 1.92; p=0.023), Child-Turcotte-Pugh score (HR=1.23; 95% CI: 1.05 to 1.82; p=0.027), and acute kidney injury (HR=2.09; 95% CI: 1.41 to 3.47; p=0.01) were the predictors of mortality from SBP. Conclusion SBP predicts in-hospital mortality in cirrhotic patients. In addition to multiple antibiotic resistant bacteria, thresholds of both hepatic and renal injury independently predict adverse outcomes.
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Affiliation(s)
- Abdel-Naser Elzouki
- Internal Medicine, Hamad Medical Corporation, Doha, QAT.,Internal Medicine, College of Medicine, Qatar University, Doha, QAT.,Internal Medicine, Weill Cornel Medical College, Doha, QAT
| | | | | | - Mohamed Ata
- Internal Medicine, Hamad Medical Corporation, Doha, QAT
| | - Anas Ashour
- Internal Medicine, Hamad Medical Corporation, Doha, QAT
| | - Muftah Othman
- Internal Medicine, Hamad Medical Corporation, Doha, QAT
| | - Ahmad Badi
- Internal Medicine, Hamad Medical Corporation, Doha, QAT
| | - Mehdi Errayes
- Internal Medicine, Hamad Medical Corporation, Doha, QAT
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Haque LY, Garcia‐Tsao G. A Historical Overview of Spontaneous Bacterial Peritonitis: From Rare to Resistant. Clin Liver Dis (Hoboken) 2021; 18:63-75. [PMID: 34745584 PMCID: PMC8555457 DOI: 10.1002/cld.1122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 03/26/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Audio Recording.
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Affiliation(s)
- Lamia Y. Haque
- Section of Digestive DiseasesYale School of MedicineNew HavenCT
- Department of MedicineYale School of MedicineNew HavenCT
| | - Guadalupe Garcia‐Tsao
- Section of Digestive DiseasesYale School of MedicineNew HavenCT
- Department of MedicineYale School of MedicineNew HavenCT
- Digestive DiseasesVeterans Administration Connecticut Healthcare SystemWest HavenCT
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25
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Tay PWL, Xiao J, Tan DJH, Ng C, Lye YN, Lim WH, Teo VXY, Heng RRY, Yeow MWX, Lum LHW, Tan EXX, Kew GS, Lee GH, Muthiah MD. An Epidemiological Meta-Analysis on the Worldwide Prevalence, Resistance, and Outcomes of Spontaneous Bacterial Peritonitis in Cirrhosis. Front Med (Lausanne) 2021; 8:693652. [PMID: 34422858 PMCID: PMC8375592 DOI: 10.3389/fmed.2021.693652] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 07/12/2021] [Indexed: 01/30/2023] Open
Abstract
Background and Aims: Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP. Methods: A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals. Results: Ninety-Nine articles, comprising a total of 5,861,142 individuals with cirrhosis were included. Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63-21.30%), highest in Africa (68.20%; CI: 12.17-97.08%), and lowest in North America (10.81%; CI: 5.32-20.73%). Prevalence of community-acquired SBP was 6.05% (CI: 4.32-8.40%), and 11.11% (CI: 5.84-20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.77% (CI: 7.63-17.73%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83-9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32-11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41-8.46%). Subgroup analysis comparing prevalence, antibiotic resistance, and outcomes between income groups was conducted to explore a link between socioeconomic status and SBP, which revealed decreased risk of SBP and negative outcomes in high-income countries. Conclusion: SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.
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Affiliation(s)
- Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Cheng Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Yan Nerng Lye
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Vanessa Xin Yi Teo
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Ryan Rui Yang Heng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Marcus Wei Xuan Yeow
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Lionel Hon Wai Lum
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Guan Sen Kew
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Guan Huei Lee
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
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26
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Fernández J, Piano S, Bartoletti M, Wey EQ. Management of bacterial and fungal infections in cirrhosis: The MDRO challenge. J Hepatol 2021; 75 Suppl 1:S101-S117. [PMID: 34039482 DOI: 10.1016/j.jhep.2020.11.010] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/12/2022]
Abstract
Bacterial infections are frequent in cirrhotic patients with acute decompensation or acute-on-chronic liver failure and can complicate the clinical course. Delayed diagnosis and inappropriate empirical treatments are associated with poor prognosis and increased mortality. Fungal infections are much less frequent, usually nosocomial and associated with extremely high short-term mortality. Early diagnosis and adequate empirical treatment of infections is therefore key in the management of these patients. In recent decades, antibiotic resistance has become a major worldwide problem in patients with cirrhosis, warranting a more complex approach to antibiotic treatment that includes the use of broad-spectrum antibiotics, new administration strategies, novel drugs and de-escalation policies. Herein, we review epidemiological changes, the main types of multidrug-resistant organisms, mechanisms of resistance, new rapid diagnostic tools and currently available therapeutic options for bacterial and fungal infections in cirrhosis.
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Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain.
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Michele Bartoletti
- Infectious Disease Unit- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Emmanuel Q Wey
- ILDH, Division of Medicine, University College London Medical School, London, United Kingdom; Centre for Clinical Microbiology, Division of Infection & Immunity, UCL, London, United Kingdom; Department of Infection, Royal Free London NHS Trust London, United Kingdom
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Yang YY, Hsu YC. Effectiveness of sepsis bundle application and outcomes predictors to cirrhotic patients with septic shock. BMC Infect Dis 2021; 21:483. [PMID: 34039297 PMCID: PMC8157624 DOI: 10.1186/s12879-021-06194-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 05/17/2021] [Indexed: 12/29/2022] Open
Abstract
Introduction Cirrhotic patients with septic shock have a poorer prognosis compared with the general population. Our study aimed to investigate the survival benefit of the implementation of hour-1 bundle proposed by Surviving Sepsis Campaign, and to analyze the predictors associated with short-term mortality of these patients. Methods A single-center, retrospective case-control study was conducted among adult patients who visited the emergency department between January 1, 2018 and December 31, 2019. All patients with a diagnosis of liver cirrhosis and septic shock were enrolled. Their baseline characteristics, laboratory results, source of sepsis, and sepsis bundle management were recorded. We further divided the patients into survivor and non-survivor groups to identify independent prognostic factors. Results A total of 88 patients were eligible for this study. The overall 30-day mortality rate was 53.4% (47/88). The proportion of hour-1 bundle achievement was 30.7% (27/88). There were no significant mortality differences between the hour-1 bundle achievement and non-achievement groups (44.4% vs. 57.4%, p = 0.35). Compared with the patients in the survivor group, patients in the non-survivor group had significantly more advanced stage of cirrhosis and a lower proportion of receiving source control (4.3% vs. 22.0%, p = 0.02). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score (adjusted hazard ratio [AHR] =1.52, p < 0.01), serum lactate (AHR =1.03, p < 0.01), and source control (AHR =0.54, p = 0.02) were identified as independent prognostic factors in the multivariate regression model. Furthermore, the CLIF-SOFA score (area under curve [AUC]: 0.81) and lactate levels (AUC: 0.77) revealed good mortality discrimination ability in cirrhotic patients with septic shock. Conclusions The application of the hour-1 bundle did not reveal a significant survival benefit to cirrhotic patients with septic shock. Clinicians could utilize CLIF-SOFA scores and lactate levels for mortality risk stratification and put more emphasis on the feasibility of source control to improve their prognosis.
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Affiliation(s)
- Yong-Ye Yang
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, No.1, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung City, 82445, Taiwan
| | - Yin-Chou Hsu
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, No.1, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung City, 82445, Taiwan. .,School of Medicine for International Student, I-Shou University, Kaohsiung, Taiwan.
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Ferstl PG, Filmann N, Heilgenthal EM, Schnitzbauer AA, Bechstein WO, Kempf VAJ, Villinger D, Schultze TG, Hogardt M, Stephan C, Mutlak H, Weiler N, Mücke MM, Trebicka J, Zeuzem S, Waidmann O, Welker MW. Colonization with multidrug-resistant organisms is associated with in increased mortality in liver transplant candidates. PLoS One 2021; 16:e0245091. [PMID: 33481811 PMCID: PMC7822319 DOI: 10.1371/journal.pone.0245091] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 12/21/2020] [Indexed: 02/07/2023] Open
Abstract
Objectives Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail. Methods Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list. Results In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0–1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died. Conclusions Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
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Affiliation(s)
- Philip G. Ferstl
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
- * E-mail:
| | - Natalie Filmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, Frankfurt, Germany
| | - Eva-Maria Heilgenthal
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Andreas A. Schnitzbauer
- Department of General and Visceral Surgery, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Wolf O. Bechstein
- Department of General and Visceral Surgery, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Volkhard A. J. Kempf
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - David Villinger
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - Tilman G. Schultze
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - Michael Hogardt
- Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- University Center of Competence for Infection Control of the State of Hesse, Frankfurt Main, Germany
| | - Christoph Stephan
- Department for Internal Medicine II / Infectious Diseases, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Haitham Mutlak
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Nina Weiler
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Marcus M. Mücke
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Jonel Trebicka
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Oliver Waidmann
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
| | - Martin-Walter Welker
- Department for Internal Medicine I / Gastroenterology and Hepatology, University Hospital, Goethe University, Frankfurt am Main, Germany
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Fiore M, Di Franco S, Alfieri A, Passavanti MB, Pace MC, Petrou S, Martora F, Leone S. Spontaneous bacterial peritonitis due to carbapenemase-producing Enterobacteriaceae: Etiology and antibiotic treatment. World J Hepatol 2020; 12:1136-1147. [PMID: 33442443 PMCID: PMC7772732 DOI: 10.4254/wjh.v12.i12.1136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/08/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023] Open
Abstract
Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gram-negative bacteria. Over the last decade, carbapenem-resistant Enterobacteriaceae (CRE) have emerged as organisms causing spontaneous bacterial peritonitis. Infections caused by CRE have shown a higher mortality rate than those caused by bacteria sensitive to carbapenem antibiotics. Current antibiotic guidelines for the treatment of spontaneous bacterial peritonitis are insufficient, and rapid de-escalation of empiric antibiotic treatment is not widely recognized. This review summarizes the molecular characteristics, epidemiology and possible treatment of spontaneous bacterial peritonitis caused by CRE.
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Affiliation(s)
- Marco Fiore
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy.
| | - Sveva Di Franco
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Aniello Alfieri
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Beatrice Passavanti
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Caterina Pace
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Stephen Petrou
- Department of Emergency Medicine, Good Samaritan Hospital Medical Center, NY 11795, United States
| | - Francesca Martora
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Sebastiano Leone
- Division of Infectious Diseases, "San Giuseppe Moscati" Hospital, Avellino 83100, Italy
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Allaire M, Cadranel JF, Nguyen TTN, Garioud A, Zougmore H, Heng R, Perignon C, Ollivier-Hourmand I, Dao T. Management of infections in patients with cirrhosis in the context of increasing therapeutic resistance: A systematic review. Clin Res Hepatol Gastroenterol 2020; 44:264-274. [PMID: 31706985 DOI: 10.1016/j.clinre.2019.10.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 09/23/2019] [Accepted: 10/04/2019] [Indexed: 02/04/2023]
Abstract
Patients with cirrhosis are prone to develop bacterial infections, which consist in one of the major precursors of Acute-on-Chronic Liver Failure (ACLF) and are responsible for a high mortality rate. In recent years, the management of bacterial infections in patients with cirrhosis has become increasingly complicated due to a change in bacterial ecology associated with a higher rate of cocci gram positive bacteria in Europe and America along with the emergence of a multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria leading to a decrease in the efficacy of empirical strategies based on the administration of third-generation cephalosporins. MDR and XDR now account for about 40% of the infections worldwide, and up to 70% in India. Among them, the most common ones are extended-spectrum beta-lactamase producing (ESBL-P) bacteria, carbapenem-resistant enterobacteriaceae (CRE), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). An early diagnosis associated to an empirical antibiotic adapted to the site of infection and potential bacterial resistance is now crucial in order to improve the chances of survival and contain the resistance phenomenon. Moreover, a fungal infection must always be discussed in these high-risks patients, especially in the absence of clinical improvement under appropriate antibiotic treatment. In this review, we will focus on the emerging threat of MDR and XDR organisms, as well as fungal infections, in order to better adapt the therapeutic management of cirrhotic patients with infections.
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Affiliation(s)
- Manon Allaire
- Service d'hépato-gastro-entérologie et nutrition, CHU Côte de Nacre, 14000 Caen, France; Unité Inserm-U1149, Centre de recherche sur l'inflammation, 75018 Paris, France.
| | - Jean-François Cadranel
- Service d'hépato-gastro-entérologie de nutrition et d'alcoologie, GHPSO, 60100 Creil, France
| | - Thi Thu Nga Nguyen
- Service d'hépato-gastro-entérologie et nutrition, CHU Côte de Nacre, 14000 Caen, France
| | - Armand Garioud
- Service d'hépato-gastro-entérologie de nutrition et d'alcoologie, GHPSO, 60100 Creil, France
| | - Honore Zougmore
- Service d'hépato-gastro-entérologie de nutrition et d'alcoologie, GHPSO, 60100 Creil, France
| | - Ratmony Heng
- Service d'hépato-gastro-entérologie de nutrition et d'alcoologie, GHPSO, 60100 Creil, France
| | - Claire Perignon
- Service d'hépato-gastro-entérologie et nutrition, CHU Côte de Nacre, 14000 Caen, France
| | | | - Thông Dao
- Service d'hépato-gastro-entérologie et nutrition, CHU Côte de Nacre, 14000 Caen, France
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Liu J, Gao Y, Wang X, Qian Z, Chen J, Huang Y, Meng Z, Lu X, Deng G, Liu F, Zhang Z, Li H, Zheng X. Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies. Yonsei Med J 2020; 61:145-153. [PMID: 31997623 PMCID: PMC6992456 DOI: 10.3349/ymj.2020.61.2.145] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/13/2019] [Accepted: 12/16/2019] [Indexed: 12/15/2022] Open
Abstract
PURPOSE This study investigated multidrug-resistant (MDR) pathogens and antibiotic strategies of culture-positive spontaneous ascitic infection (SAI) in patients with acute decompensated cirrhosis. MATERIALS AND METHODS We retrospectively analyzed 432 acute decompensated cirrhotic patients with culture-positive SAI from 11 teaching hospitals in China (January 2012 to May 2018). A Cox proportional hazards model analysis was conducted to identify independent predictors of 28-day mortality. RESULTS A total of 455 strains were isolated from 432 ascitic culture samples. Gram-negative bacteria (GNB), gram-positive bacteria (GPB), and fungi caused 52.3, 45.5, and 2.2% of all SAI episodes, respectively. Episodes were classified as nosocomial (41.2%), healthcare-related (34.7%), and community-acquired (24.1%). Escherichia coli (13.4%) and Klebsiella pneumoniae (2.4%) were extended-spectrum β-lactamase producing isolates. The prevalence of methicillin-resistant Staphylococcus aureus was 1.1%. Ceftazidime, cefepime, aztreonam, and amikacin were recommended as first-line antibiotics agents for non-MDR GNB infections; piperacillin/tazobactam and carbapenems for MDR GNB in community-acquired and healthcare-related or nosocomial infections, respectively; and vancomycin or linezolid for GPB infections, regardless of drug-resistance status. Multivariate analysis revealed days of hospital stay before SAI, upper gastrointestinal bleeding, white blood cell count, alanine aminotransferase, serum creatinine concentration, total bilirubin, and international normalized ratio as key independent predictors of 28-day mortality. CONCLUSION MDR pathogens and antibiotic strategies were identified in patients with acute decompensated cirrhosis with culture-positive SAI, which may help optimize therapy and improve clinical outcomes.
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Affiliation(s)
- Jing Liu
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
| | - Yanhang Gao
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Xianbo Wang
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhiping Qian
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Jinjun Chen
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yan Huang
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Infectious Disease, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Zhongji Meng
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Infectious Disease, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiaobo Lu
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Liver Disease Center, First Affiliated Hospital of Xinjiang Medical University, Urumuqi, China
| | - Guohong Deng
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Liu
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Zhiguo Zhang
- School of Medicine and Health Management, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Hai Li
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Chinese Acute-on-Chronic Liver Failure Consortium, CATCH-LIFE, Shanghai, China.
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Garcia‐Tsao G. Prophylactic Antibiotics in Cirrhosis: Are They Promoting or Preventing Infections? Clin Liver Dis (Hoboken) 2019; 14:98-102. [PMID: 31632658 PMCID: PMC6784797 DOI: 10.1002/cld.819] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 02/26/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Guadalupe Garcia‐Tsao
- Section of Digestive DiseasesYale University School of MedicineNew HavenCT
- Section of Digestive DiseasesVA‐CT Healthcare SystemWest HavenCT
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Ferrarese A, Vitale A, Sgarabotto D, Russo FP, Germani G, Gambato M, Cattelan AM, Angeli P, Cillo U, Burra P, Senzolo M. Outcome of a First Episode of Bacterial Infection in Candidates for Liver Transplantation. Liver Transpl 2019; 25:1187-1197. [PMID: 31021050 DOI: 10.1002/lt.25479] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 04/22/2019] [Indexed: 12/13/2022]
Abstract
Bacterial infection (BI) is a major cause of worsening of liver function and death in patients with cirrhosis who are awaiting liver transplantation (LT). This study aimed to evaluate the outcome of LT candidates after a first episode of BI between January 2006 and December 2014 at Padua University Hospital. Among 876 LT candidates with cirrhosis, 114 (13%) experienced an episode of BI. Of the 114 patients, 79 were male and 35 were female, and the median (interquartile range) age and Model for End-Stage Liver Disease scores were 58 (12) years and 19 (8), respectively. When compared with matched LT candidates who experienced no BI, they had a higher probability of death (P = 0.004) and a lower probability of undergoing LT (P = 0.01). Considering only patients who recovered from BI within 30 days, their probabilities of death and of undergoing LT were similar to those of matched controls (P = 0.34 and P = 0.43, respectively). The 90-day post-LT mortality was equal between groups (P = 0.90). BI was a strong predictor of early death on the waiting list for LT. Conversely, patients who fully recovered from a BI episode within 30 days did not have a higher mortality risk than matched controls without infection.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplant Center, Padua University Hospital, Padua, Italy
| | - Dino Sgarabotto
- Tropical and Infectious Diseases Unit, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Anna Maria Cattelan
- Tropical and Infectious Diseases Unit, Padua University Hospital, Padua, Italy
| | - Paolo Angeli
- Internal Medicine, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Center, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Pouch SM, Patel G. Multidrug-resistant Gram-negative bacterial infections in solid organ transplant recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13594. [PMID: 31102483 DOI: 10.1111/ctr.13594] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 05/11/2019] [Indexed: 12/11/2022]
Abstract
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug-resistant (MDR) Gram-negative bacilli in the pre- and post-transplant period. MDR Gram-negative bacilli, including carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram-negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram-negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram-negative pathogens, especially in the setting of organ transplantation.
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Affiliation(s)
| | - Gopi Patel
- Icahn School of Medicine at Mount Sinai, New York, New York
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High Prevalence of Multidrug Resistant Bacteria in Cirrhotic Patients with Spontaneous Bacterial Peritonitis: Is It Time to Change the Standard Antimicrobial Approach? Can J Gastroenterol Hepatol 2019; 2019:6963910. [PMID: 31214551 PMCID: PMC6535816 DOI: 10.1155/2019/6963910] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 03/20/2019] [Accepted: 04/03/2019] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) has a deleterious clinical impact in end-stage liver disease, and multidrug resistance has increased, raising concern about effectiveness of traditional antibiotic regimens. PATIENTS AND METHODS Single-center retrospective study of ascitic fluid infections in cirrhotic patients. RESULTS We analyzed medical records related to 2129 culture-positive ascitic fluid and found 183 samples from cirrhotic patients. There were 113 monobacterial SBP cases from 97 cirrhotic patients; 57% of patients were male; hepatitis C and alcohol were the main etiologies for cirrhosis. Multidrug resistant bacteria were isolated in 46.9% of SBP samples, and third-generation cephalosporin and quinolone resistant reached 38.9% and 25.7% of SBP cases. CONCLUSION SBP due to multidrug resistant bacteria is a growing problem, and one should consider reported resistance profiles for the decision-making process of empirical first-line treatment prescription.
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Vargas-Alzate CA, Higuita-Gutiérrez LF, Jiménez-Quiceno JN. Direct medical costs of urinary tract infections by Gram-negative bacilli resistant to beta-lactams in a tertiary care hospital in Medellín, Colombia. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2019; 39:35-49. [PMID: 31529847 DOI: 10.7705/biomedica.v39i1.3981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Indexed: 06/10/2023]
Abstract
Introduction: Urinary tract infections are very frequent in the hospital environment and given the emergence of antimicrobial resistance, they have made care processes more complex and have placed additional pressure on available healthcare resources. Objective: To describe and compare excess direct medical costs of urinary tract infections due to Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa resistant to beta-lactams. Materials and methods: A cohort study was conducted in a third level hospital in Medellín, Colombia, from October, 2014, to September, 2015. It included patients with urinary tract infections caused by beta-lactam-susceptible bacteria, third and fourth generation cephalosporin-resistant, as well as carbapenem-resistant. Costs were analyzed from the perspective of the health system. Clinical-epidemiological information was obtained from medical records and the costs were calculated using standard tariff manuals. Excess costs were estimated with multivariate analyses. Results: We included 141 patients: 55 (39%) were sensitive to beta-lactams, 54 (38.3%) were resistant to cephalosporins and 32 (22.7%) to carbapenems. The excess total adjusted costs of patients with urinary tract infections due to cephalosporin- and carbapenem-resistant bacteria were US$ 193 (95% confidence interval (CI): US$ -347-734) and US$ 633 (95% CI: US$ -50-1316), respectively, compared to the group of patients with beta-lactam sensitive urinary tract infections. The differences were mainly found in the use of broad-spectrum antibiotics such as meropenem, colistin, and fosfomycin. Conclusion: Our results show a substantial increase in the direct medical costs of patients with urinary tract infections caused by beta-lactam-resistant Gram-negative bacilli (cephalosporins and carbapenems). This situation is of particular concern in endemic countries such as Colombia, where the high frequencies of urinary tract infections and the resistance to beta-lactam antibiotics can generate a greater economic impact on the health sector.
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Affiliation(s)
- Carlos Andrés Vargas-Alzate
- Línea de Epidemiología Molecular Bacteriana, Grupo de Microbiología Básica y Aplicada, Escuela de Microbiología, Universidad de Antioquia, Medellín, Colombia.
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Abstract
Spontaneous bacterial peritonitis (SBP) is associated with risk of acute on chronic liver failure (ACLF). Current guidelines recommend primary and secondary antibiotic prophylaxis for patients with cirrhosis and ascites who are at risk of a first episode and to prevent recurrence, respectively. Factors associated with prophylaxis failure leading to SBP, ACLF, and increased mortality are not well established. Gram-positive and multidrug-resistant organisms have become more frequently associated with SBP, particularly in the setting of ACLF. Efforts to understand how long-term antibiotic therapy may affect individual risk of SBP in this population will be critical to developing optimal preventive strategies.
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Fernández J, Prado V, Trebicka J, Amoros A, Gustot T, Wiest R, Deulofeu C, Garcia E, Acevedo J, Fuhrmann V, Durand F, Sánchez C, Papp M, Caraceni P, Vargas V, Bañares R, Piano S, Janicko M, Albillos A, Alessandria C, Soriano G, Welzel TM, Laleman W, Gerbes A, De Gottardi A, Merli M, Coenraad M, Saliba F, Pavesi M, Jalan R, Ginès P, Angeli P, Arroyo V. Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe. J Hepatol 2019; 70:398-411. [PMID: 30391380 DOI: 10.1016/j.jhep.2018.10.027] [Citation(s) in RCA: 239] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 10/23/2018] [Accepted: 10/28/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Antibiotic resistance has been increasingly reported in patients with decompensated cirrhosis in single-center studies. Prospective investigations reporting broad epidemiological data are scarce. We aimed to analyze epidemiological changes in bacterial infections in patients with decompensated cirrhosis. METHODS This was a prospective evaluation of 2 series of patients hospitalized with decompensated cirrhosis. The Canonic series included 1,146 patients from Northern, Southern and Western Europe in 2011. Data on epidemiology, clinical characteristics of bacterial infections, microbiology and empirical antibiotic schedules were assessed. A second series of 883 patients from Eastern, Southern and Western Europe was investigated between 2017-2018. RESULTS A total of 455 patients developed 520 infections (39.7%) in the first series, with spontaneous bacterial peritonitis, urinary tract infections and pneumonia the most frequent infections. Nosocomial episodes predominated in this series. Nearly half of the infections were culture-positive, of which 29.2% were caused by multidrug-resistant organisms (MDROs). MDR strains were more frequently isolated in Northern and Western Europe. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were the most frequent MDROs isolated in this series, although prevalence and type differed markedly among countries and centers. Antibiotic resistance was associated with poor prognosis and failure of antibiotic strategies, based on third-generation cephalosporins or quinolones. Nosocomial infection (odds ratio [OR] 2.74; p < 0.001), intensive care unit admission (OR 2.09; p = 0.02), and recent hospitalization (OR 1.93; p = 0.04) were identified as independent predictors of MDR infection. The prevalence of MDROs in the second series (392 infections/284 patients) was 23%; 38% in culture-positive infections. A mild increase in the rate of carbapenem-resistant Enterobacteriaceae was observed in this series. CONCLUSIONS MDR bacterial infections constitute a prevalent, growing and complex healthcare problem in patients with decompensated cirrhosis and acute-on-chronic liver failure across Europe, negatively impacting on prognosis. Strategies aimed at preventing the spread of antibiotic resistance in cirrhosis should be urgently evaluated. LAY SUMMARY Infections caused by bacteria resistant to the main antibiotic families are prevalent in patients with cirrhosis. This study demonstrates that this healthcare problem is increasing and extends through all European regions. Infections caused by these difficult to treat bacteria resolve less frequently and often cause the death of the patient. The type of resistant bacteria varies markedly among different hospitals.
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Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain.
| | - Verónica Prado
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Jonel Trebicka
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain; University of Bonn, Germany
| | - Alex Amoros
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Thierry Gustot
- Liver Transplant Unit, Erasme Hospital, Brussels, Belgium
| | - Reiner Wiest
- Department of Medicine and Surgery, Inselspital, University of Bern, Bern, Switzerland
| | - Carme Deulofeu
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Elisabet Garcia
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | | | | | | | - Cristina Sánchez
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Maria Papp
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Hungary
| | | | - Victor Vargas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain; Hospital Vall d'Hebron, Barcelona, Spain
| | - Rafael Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain; Hospital Gregorio Marañon, Madrid, Spain
| | | | | | | | | | - German Soriano
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain; Hospital of Santa Creu i Sant Pau, Barcelona, Spain
| | | | | | - Alexander Gerbes
- Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Germany
| | - Andrea De Gottardi
- Department of Medicine and Surgery, Inselspital, University of Bern, Bern, Switzerland
| | | | | | - Faouzi Saliba
- Centre Hepato-Biliare, Hòpital Paul Brousse, Paris, France
| | - Marco Pavesi
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Rajiv Jalan
- ILDH, Division of Medicine, University College London Medical School, London, United Kingdom
| | - Pere Ginès
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain
| | | | - Vicente Arroyo
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
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40
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Sagnelli E, Starace M, Minichini C, Pisaturo M, Macera M, Sagnelli C, Coppola N. Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure. Infection 2018; 46:761-783. [PMID: 30084057 DOI: 10.1007/s15010-018-1188-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients. METHODS The Medline was searched for "HCV infection", "HCV treatment", "Directly acting antivirals","HCV resistance". RESULTS Most patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. CONCLUSIONS Patients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing.
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Affiliation(s)
- Evangelista Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy.
| | - Mario Starace
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Carmine Minichini
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Mariantonietta Pisaturo
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Margherita Macera
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Caterina Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
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41
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Oey RC, van Buuren HR, de Jong DM, Erler NS, de Man RA. Bacterascites: A study of clinical features, microbiological findings, and clinical significance. Liver Int 2018; 38:2199-2209. [PMID: 29992711 PMCID: PMC6282964 DOI: 10.1111/liv.13929] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 06/14/2018] [Accepted: 07/06/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Knowledge about bacterascites is limited and management guidelines are based on small patient series. The purpose of this study was to add further insight into the clinical characteristics, microbiological findings, and prognosis of patients diagnosed with bacterascites. METHODS Retrospective analysis of patients with advanced chronic liver disease diagnosed with bacterascites and SBP between January 2003 and August 2016. RESULTS In this study, 123 patients were included with 142 episodes of bacterascites. The median MELD score was 20 and clinical symptoms of infection were present in 78%. Empiric antibiotic treatment was initiated in 68%. In 26 untreated patients undergoing repeated paracentesis, 42% were diagnosed with either ongoing bacterascites or SBP. The presence of signs or symptoms of infection was not an independent predictor for mortality or spontaneous resolution of infection. The 1-month and 1-year mortality rates of the 123 patients studied, were 32% and 60%, respectively; these results were in line with data pertaining to the prognosis of SBP. CONCLUSIONS Patients with bacterascites and SBP are highly comparable with respect to severity of liver disease and overall prognosis. If left untreated, bacterascites is likely to persist or to evolve to SBP in a significant proportion of patients. The results of this study support current guidelines regarding the treatment of ascitic fluid infection, but could not confirm the prognostic relevance of symptomatic disease at the time of diagnosis. We suggest that the threshold to initiate antibiotic treatment, in particular in cases with severely advanced liver disease, should be low.
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Affiliation(s)
- Rosalie C. Oey
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands
| | - Henk R. van Buuren
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands
| | - David M. de Jong
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands
| | - Nicole S. Erler
- Department of BiostatisticsErasmus MCUniversity Medical CenterRotterdamThe Netherlands
| | - Robert A. de Man
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands
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Ferstl PG, Müller M, Filmann N, Hogardt M, Kempf VA, Wichelhaus TA, Lange CM, Vermehren J, Zeuzem S, Reinheimer C, Waidmann O. Noninvasive screening identifies patients at risk for spontaneous bacterial peritonitis caused by multidrug-resistant organisms. Infect Drug Resist 2018; 11:2047-2061. [PMID: 30464547 PMCID: PMC6223386 DOI: 10.2147/idr.s172587] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background and aims Spontaneous bacterial peritonitis (SBP) is a severe complication of decompensated cirrhosis. The prevalence of multidrug-resistant organisms (MDROs) in patients with cirrhosis is increasing. Identification of patients at risk for SBP due to MDROs (ie, SBP with the evidence of MDROs or Stenotrophomonas maltophilia in ascitic culture, MDRO-SBP) is crucial to the early adaptation of antibiotic treatment in such patients. We therefore investigated whether MDROs found in ascitic cultures can also be found in specimens determined by noninvasive screening procedures. Patients and methods This retrospective study was conducted at the liver center of the University Hospital Frankfurt, Germany. Between 2011 and 2016, patients with cirrhosis were included upon diagnosis of SBP and sample collection of aerobic/anaerobic ascitic cultures. Furthermore, the performance of at least one complete MDRO screening was mandatory for study inclusion. Results Of 133 patients diagnosed with SBP, 75 (56.4%) had culture-positive SBP and 22 (16.5%) had MDRO-SBP. Multidrug-resistant Escherichia coli (10/22; 45.5%) and vancomycin-resistant enterococci (7/22; 36.4%) resembled the major causatives of MDRO-SBP. Rectal swabs identified MDROs in 17 of 22 patients (77.3%) who developed MDRO-SBP with a time-dependent sensitivity of 77% and 87% after 30 and 90 days upon testing, while negative predictive value was 83% and 76%, respectively. The majority of patients were included from intensive care unit or intermediate care unit. Conclusion MDRO screening may serve as a noninvasive diagnostic tool to identify patients at risk for MDRO-SBP. Patients with decompensated cirrhosis should be screened for MDROs from the first day of inpatient treatment onward.
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Affiliation(s)
- Philip G Ferstl
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Mona Müller
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Natalie Filmann
- Institute of Biostatistics and Mathematical Modeling, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Michael Hogardt
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Volkhard Aj Kempf
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Thomas A Wichelhaus
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Christian M Lange
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Johannes Vermehren
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Stefan Zeuzem
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Claudia Reinheimer
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Oliver Waidmann
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
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Righi E. Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions. World J Gastroenterol 2018; 24:4311-4329. [PMID: 30344417 PMCID: PMC6189843 DOI: 10.3748/wjg.v24.i38.4311] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 09/11/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early post-transplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa (P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.
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Affiliation(s)
- Elda Righi
- Department of Infectious Diseases, Santa Maria della Misericordia University Hospital, Udine 33100, Italy
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Maraolo AE, Gentile I, Pinchera B, Nappa S, Borgia G. Current and emerging pharmacotherapy for the treatment of bacterial peritonitis. Expert Opin Pharmacother 2018; 19:1317-1325. [PMID: 30071176 DOI: 10.1080/14656566.2018.1505867] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is the quintessential model of bacterial infection in cirrhotic patients. In these particularly frail subjects, infections clearly worsen prognosis increasing substantially mortality. Furthermore, treatment of SBP has become more challenging because of the growing impact of multidrug-resistant (MDR) bacteria. AREAS COVERED This review addresses the reasons behind the change in therapeutic recommendations for SBP that have occurred in the past few years, by focusing on the following aspects: the importance of an early appropriate empirical treatment, the difference between nosocomial and non-nosocomial forms and the overall microbiological shift (rise of Gram-positive bacteria and MDR strains) that have affected SBP. EXPERT OPINION Until recently, third-generation cephalosporins have represented the cornerstone of SBP treatment, a safe choice covering the most important causative agents, namely Enterobacteriaceae. Unfortunately, massive exposure to health systems makes cirrhotic patients prone to MDR infections, which poses significant challenges, all the while not forgetting to strike a balance between effective antimicrobial activity and the risk of toxicity in these fragile subjects. Moreover, there is sparse information about new antibiotics in cirrhotic patients and about drugs levels in ascitic fluid. Therefore, further research is needed to optimize the treatment of SBP.
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Affiliation(s)
- Alberto Enrico Maraolo
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Ivan Gentile
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Biagio Pinchera
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Salvatore Nappa
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Guglielmo Borgia
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
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Alferink LJM, Oey RC, Hansen BE, Polak WG, van Buuren HR, de Man RA, Schurink CAM, Metselaar HJ. The impact of infections on delisting patients from the liver transplantation waiting list. Transpl Int 2018; 30:807-816. [PMID: 28403563 DOI: 10.1111/tri.12965] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 03/15/2017] [Accepted: 04/06/2017] [Indexed: 12/14/2022]
Abstract
Approximately 20% of the patients listed for liver transplantation die before transplantation can be accomplished. Understanding risk factors for waiting list mortality may help to improve survival and organ allocation. Infections are very common in patients with cirrhosis and are associated with significant morbidity and mortality. This study analysed the frequency and characteristics of infections in patients awaiting liver transplantation, identified risk factors for withdrawal from the waiting list and evaluated the impact of infections on the clinical outcome. A retrospective analysis of consecutive patients listed for liver transplantation in Rotterdam, the Netherlands from 2007 to 2014 was conducted. Infections occurred in 144 of 327 studied patients (44%). In this cohort, 23.4% of the patients on the liver transplantation waiting list were delisted or died before transplantation. Patients with an infection were 5.2 times more likely to become delisted than noninfected patients. In the 30 days after the first infection, patients were 33.8 times more likely to become delisted compared to noninfected patients. High age, high MELD score, refractory ascites and inappropriate antibiotic therapy were independent predictors for delisting due to infection. Infections occur frequently in patients on the liver transplantation waiting list. Emphasis on appropriate and timely antimicrobial therapy is required.
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Affiliation(s)
- Louise J M Alferink
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Rosalie C Oey
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Liver Centre, Toronto Western & General Hospital, University Health Network, Toronto, Canada
| | - Wojciech G Polak
- Division Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Henk R van Buuren
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Carolina A M Schurink
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Lucidi C, Lattanzi B, Di Gregorio V, Incicco S, D'Ambrosio D, Venditti M, Riggio O, Merli M. A low muscle mass increases mortality in compensated cirrhotic patients with sepsis. Liver Int 2018; 38:851-857. [PMID: 29323441 DOI: 10.1111/liv.13691] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 12/28/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Severe infections and muscle wasting are both associated to poor outcome in cirrhosis. A possible synergic effect of these two entities in cirrhotic patients has not been previously investigated. We aimed at analysing if a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis. METHODS Consecutive cirrhotic patients hospitalized for sepsis were enrolled in the study. Patients were classified for the severity of liver impairment (Child-Pugh class) and for the presence of "low muscle mass" (mid-arm muscle circumference<5th percentile). The development of complication during hospitalization and survival was analysed. RESULTS There were 74 consecutive cirrhotics with sepsis. Forty-three of these patients showed low muscle mass. In patients with and without low muscle mass, severity of liver disease and characteristics of infections were similar. Mortality tended to be higher in patients with low muscle mass (47% vs 26%, P = .06). A multivariate analysis selected low muscle mass (P < .01, HR: 3.2, IC: 1.4-4.8) and Child-Pugh C (P < .01, HR: 3.3, 95% IC: 1.5-4.9) as independent predictors of in-hospital mortality. In Child-Pugh A-B patients, mortality was higher in patients with low muscle mass compared with those without (50% vs 16%; P = .01). The mortality rate and the incidence of complications in malnourished patients classified in Child-Pugh A-B were similar to those Child-Pugh C. CONCLUSIONS Low muscle mass worsen prognosis in cirrhotic patients with severe infections. This is particularly evident in patients with Child A-B cirrhosis in whom the coexistence of low muscle mass and sepsis caused a negative impact on mortality similar to that observable in all Child C patients with sepsis.
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Affiliation(s)
- Cristina Lucidi
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Barbara Lattanzi
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Vincenza Di Gregorio
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Simone Incicco
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Daria D'Ambrosio
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Mario Venditti
- Department of Infectious Disease, La Sapienza University of Rome, Rome, Italy
| | - Oliviero Riggio
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
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Bartoletti M, Giannella M, Tedeschi S, Viale P. Opportunistic infections in end stage liver disease. Infect Dis Rep 2018; 10:7621. [PMID: 29721243 PMCID: PMC5907735 DOI: 10.4081/idr.2018.7621] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 02/02/2018] [Indexed: 02/07/2023] Open
Abstract
Liver cirrhosis is the 10th most common cause of death in Western world and infection is associated with a high morbidity and mortality, and represents the leading cause of acute liver decompensation. Patients with end-stage liver disease exhibit an important impairment of immune system. This condition, called cirrhosis-associated immune dysfunction, summarizes both local and systemic immune system alterations in liver cirrhosis that play a pivotal role in determining both the high incidence of infections and the ominous infections related mortality in this population. Another concerning feature of infections in cirrhotic patients is the growing prevalence of multidrug- resistant or extensively drug-resistant pathogens, which are associated with higher mortality, increased length of in-hospital stay and higher healthcare related costs if compared with infection caused by susceptible strains. Finally, patient with liver cirrhosis have several unique pathophysiological characteristics including hypoalbuminemia and reduction binding to proteins; altered distribution; altered clearance of the antimicrobials that can affect the pharmacokinetic/ pharmacodynamic of antimicrobials.
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Affiliation(s)
- Michele Bartoletti
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy
| | - Maddalena Giannella
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy
| | - Sara Tedeschi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy
| | - Pierluigi Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy
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Prevalence and Impact of Bacterial Infections in Children With Liver Disease-A Prospective Study. J Clin Exp Hepatol 2018; 8:35-41. [PMID: 29743795 PMCID: PMC5938332 DOI: 10.1016/j.jceh.2017.08.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Accepted: 08/24/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Risk of infections is increased in patients with Acute Liver Failure (ALF) and Decompensated Chronic Liver Disease (DCLD). We evaluated the frequency, site, type and risk-factors for bacterial infections in children with ALF and DCLD and its effect on outcome. METHODS ALF or DCLD children were enrolled prospectively. Clinical and laboratory details were recorded. Cultures (blood, urine and ascites) and chest X-ray were done at admission followed by weekly surveillance cultures. RESULTS 173 patients, 68 ALF and 105 DCLD were enrolled. Infections were more common in DCLD than ALF (60/105 [57.1%] vs. 27/68 [39.7%]; P = 0.02). Ascitic fluid infection, pneumonia, urinary tract infection and bacteremia were seen in 19%, 17.9%, 13.2% and 12.1% patients respectively. Healthcare-Associated (HCA) infections were most frequent (39/87, 44.8%), followed by Nosocomial (NC, 32%) and Community-Acquired (CA, 23%). Nearly 3/4th of bacterial isolates were resistant to cephalosporins and quinolones, 23% being Multiresistant Bacteria (MRB). DCLD patients with infection had higher Child-Pugh Score (10 [6-14] vs. 7 [6-14]; OR 3.2 [1.77-5.10]: P = 0.007), need for ICU care (26/60 vs. 3/45; OR 10.70 [2.98-38.42]: P = 0.01), in-hospital mortality (24/60 vs. 8/45;OR 3.08 [1.22-7.75]: P = 0.04) and mortality at 3 month follow-up (32/60 vs. 9/45; OR 4.57 [1.87-11.12]: P = 0.00). Infection did not affect the outcome in ALF. CONCLUSION Infections develop in 40% ALF and 57% DCLD children. HCA and NC infections account for 77% of infections. Most culture isolates are resistant to cephalosporins and fluoroquinolones and 23% have MRB. Risk of infections is higher in DCLD patients with advanced liver disease.
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Key Words
- ALF, Acute Liver Failure
- CA, Community Acquired
- DCLD, Decompensated Chronic Liver Diseases
- GIB, Gastrointestinal Bleeding
- GNB, Gram Negative Bacilli
- GPC, Gram Positive Cocci
- HCA, Healthcare Associated
- HE, Hepatic Encephalopathy
- ICU, Intensive Care Unit
- INR, International Normalized Ratio
- MRB, Multiresistant Bacteria
- NC, Nosocomial
- SBP, Spontaneous Bacterial Peritonitis
- UTI, Urinary Tract Infection
- chronic liver disease
- infections
- liver failure
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Fiore M, Gentile I, Maraolo AE, Leone S, Simeon V, Chiodini P, Pace MC, Gustot T, Taccone FS. Are third-generation cephalosporins still the empirical antibiotic treatment of community-acquired spontaneous bacterial peritonitis? A systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2018; 30:329-336. [PMID: 29303883 DOI: 10.1097/meg.0000000000001057] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common complication among cirrhotic patients. Guidelines recommend third-generation cephalosporins (3GCs) as empiric antibiotic therapy (EAT) of SBP. Recently, a broad-spectrum EAT was shown to be more effective than cephalosporins in the treatment of nosocomial spontaneous bacterial peritonitis (N-SBP); however, the prevalence of 3GCs-resistant bacteria is high in the nosocomial setting and broad-spectrum EAT cannot be used in all cases of SBP. AIM The aim of this study was to evaluate the 3GCs resistance distribution between N-SBP and community-acquired spontaneous bacterial peritonitis (CA-SBP) to clarify whether 3GCs are still an effective therapeutic intervention for CA-SBP. METHODS We searched for studies that reported the aetiology of SBP and the resistance profile of both gram-positive and gram-negative bacteria in MEDLINE and Google Scholar databases (since 1 January 2000 to 30 April 2017). A meta-analysis was carried out to estimate the risk difference [relative risk (RR) and 95% confidence intervals (CIs)] for 3GCs resistance in N-SBP and CA-SBP. Heterogeneity was assessed using the I-test. RESULTS A total of eight studies were included, including 1074 positive cultures of ascitic fluid in cirrhotic patients; 462 positive cultures were from N-SBP and, among these, 251 (54.3%) were 3GCs resistant. Six hundred and twelve positive cultures were from CA-SBP and, among these, 207 (33.8%) were 3GCs-resistant SBP. A pooled RR of 3GCs resistance in N-SBP compared with CA-SBP showed a significant difference (RR=1.67, 95% CI: 1.14-2.44; P=0.008). We carried out two subgroup analyses: the first according to the median year of study observation (before vs. since 2008) and the second according to the country of the study (China vs. others). The studies carried out before 2008 (327 SBP-positive culture) showed a significantly higher risk for 3GCs-resistant strains in N-SBP compared with CA-SBP (RR=2.36, 95% CI: 1.39-3.99; P=0.001), whereas this was not found in SBP acquired after 2008 (RR=1.24, 95% CI: 0.83-1.84; P=0.29). N-SBP occurring in China had no significantly higher risk for 3GCs-resistant strains compared with CA-SBP (RR=1.44, 95% CI: 0.87-2.37; P=0.16). CONCLUSION Our findings suggest that although the pooled RR of 3GCs resistance in N-SBP compared with CA-SBP show that 3GCs are still an effective option for the treatment of CA-SBP, the subanalysis of studies that enroled patients in the last decade did not show a significant higher RR of 3GCs resistance in N-SBP compared with CA-SBP. Therefore, in centres where local patterns of antimicrobial susceptibility (with low rates of 3GCs resistance) are not available, 3GCs should not be used initially for CA-SBP treatment. Future studies are needed to confirm this trend of 3GCs resistance.
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Affiliation(s)
- Marco Fiore
- Department of Anaesthesiological, Surgical & Emergency Sciences
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', Naples
| | - Alberto E Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', Naples
| | - Sebastiano Leone
- Department of General and Specialized Medicine, Division of Infectious Diseases, 'San Giuseppe Moscati' Hospital, Avellino, Italy
| | - Vittorio Simeon
- Department of Public, Clinical and Preventive Medicine, Medical Statistics Unit, University of Campania 'Luigi Vanvitelli'
| | - Paolo Chiodini
- Department of Public, Clinical and Preventive Medicine, Medical Statistics Unit, University of Campania 'Luigi Vanvitelli'
| | - Maria C Pace
- Department of Anaesthesiological, Surgical & Emergency Sciences
| | | | - Fabio S Taccone
- Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
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Ferrarese A, Zanetto A, Becchetti C, Sciarrone SS, Shalaby S, Germani G, Gambato M, Russo FP, Burra P, Senzolo M. Management of bacterial infection in the liver transplant candidate. World J Hepatol 2018; 10:222-230. [PMID: 29527258 PMCID: PMC5838441 DOI: 10.4254/wjh.v10.i2.222] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 12/29/2017] [Accepted: 01/23/2018] [Indexed: 02/06/2023] Open
Abstract
Bacterial infection (BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcare-associated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Chiara Becchetti
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Salvatore Stefano Sciarrone
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
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