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Iapascurta V, Fiodorov I, Belii A, Bostan V. Multi-Agent Approach for Sepsis Management. Healthc Inform Res 2025; 31:209-214. [PMID: 40384072 DOI: 10.4258/hir.2025.31.2.209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Accepted: 04/02/2025] [Indexed: 05/20/2025] Open
Abstract
OBJECTIVES The high incidence of sepsis necessitates the development of practical decision-making tools for intensivists, especially during the early, critical phases of management. This study evaluates a multi-agent system intended to assist clinicians with antibiotic therapy and adherence to current sepsis management guidelines before diagnostic results become available. METHODS A multi-agent system incorporating three specialized agents was developed: a sepsis management agent, an antibiotic recommendation agent, and a sepsis guidelines compliance agent. A sepsis case from the MIMIC IV database, organized as a clinical vignette, was used to integrate and test these agents for generating management recommendations. The system leverages retrieval-augmented generation to improve decision-making through the integration of current literature and guidelines. RESULTS The application produced management recommendations for a sepsis case associated with pneumonia, including early initiation of broad-spectrum antibiotics and close monitoring for clinical deterioration. Two expert intensivists evaluated these recommendations as "acceptable" and reported moderate interrater agreement (Cohen's kappa = 0.622, p = 0.003) across various aspects of recommendation usefulness. CONCLUSIONS The multi-agent system shows promise in enhancing decision-making for sepsis management by optimizing antibiotic therapy and ensuring guideline compliance. However, reliance on a single case study limits the generalizability of the findings, highlighting the need for broader validation in diverse clinical settings to improve patient outcomes.
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Affiliation(s)
- Victor Iapascurta
- Department of Software Engineering and Automatics, Technical University of Moldova, Chisinnu, Republic of Moldova
- Department of Anesthesia and Intensive Care, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinnu, Republic of Moldova
| | - Ion Fiodorov
- Department of Software Engineering and Automatics, Technical University of Moldova, Chisinnu, Republic of Moldova
| | - Adrian Belii
- Department of Anesthesia and Intensive Care, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinnu, Republic of Moldova
| | - Viorel Bostan
- Department of Software Engineering and Automatics, Technical University of Moldova, Chisinnu, Republic of Moldova
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Nohra E, Appelbaum RD, Farrell MS, Carver T, Jung HS, Kirsch JM, Kodadek LM, Mandell S, Nassar AK, Pathak A, Paul J, Robinson B, Cuschieri J, Stein DM. Fever and infections in surgical intensive care: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document. Trauma Surg Acute Care Open 2024; 9:e001303. [PMID: 38835635 PMCID: PMC11149120 DOI: 10.1136/tsaco-2023-001303] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 04/11/2024] [Indexed: 06/06/2024] Open
Abstract
The evaluation and workup of fever and the use of antibiotics to treat infections is part of daily practice in the surgical intensive care unit (ICU). Fever can be infectious or non-infectious; it is important to distinguish between the two entities wherever possible. The evidence is growing for shortening the duration of antibiotic treatment of common infections. The purpose of this clinical consensus document, created by the American Association for the Surgery of Trauma Critical Care Committee, is to synthesize the available evidence, and to provide practical recommendations. We discuss the evaluation of fever, the indications to obtain cultures including urine, blood, and respiratory specimens for diagnosis of infections, the use of procalcitonin, and the decision to initiate empiric antibiotics. We then describe the treatment of common infections, specifically ventilator-associated pneumonia, catheter-associated urinary infection, catheter-related bloodstream infection, bacteremia, surgical site infection, intra-abdominal infection, ventriculitis, and necrotizing soft tissue infection.
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Affiliation(s)
- Eden Nohra
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Rachel D Appelbaum
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | - Thomas Carver
- Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Hee Soo Jung
- Department of Surgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Jordan Michael Kirsch
- Department of Surgery, Westchester Medical Center/ New York Medical College, Valhalla, NY, USA
| | - Lisa M Kodadek
- Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Samuel Mandell
- Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Aussama Khalaf Nassar
- Department of Surgery, Section of Acute Care Surgery, Stanford University, Stanford, California, USA
| | - Abhijit Pathak
- Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
| | - Jasmeet Paul
- Department of Surgery, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Bryce Robinson
- Department of Surgery, Harborview Medical Center, Seattle, Washington, USA
| | - Joseph Cuschieri
- Department of Surgery, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California, USA
| | - Deborah M Stein
- Department of Surgery, University of Maryland Baltimore, Baltimore, Maryland, USA
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Viertel K, Feles E, Schulte M, Annecke T, Mattner F. Serum concentration of continuously administered vancomycin influences efficacy and safety in critically ill adults: a systematic review. Int J Antimicrob Agents 2023; 62:107005. [PMID: 37839714 DOI: 10.1016/j.ijantimicag.2023.107005] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/12/2023] [Accepted: 09/29/2023] [Indexed: 10/17/2023]
Abstract
OBJECTIVES Vancomycin is used to treat Gram-positive infections in critically ill adults. For vancomycin administered by continuous infusion (CI), various target ranges have been used, ranging from 15-20 mg/L to 30-40 mg/L. This systematic literature review was conducted to investigate the impact of steady-state serum concentration (Css) of CI on safety and efficacy of therapy in critically ill adults. METHODS Relevant literature was identified by searching two electronic databases (PubMed, Cochrane Library) and Google Scholar from inception until July 2023, focusing on studies reporting measured Css and treatment outcomes (e.g. mortality, nephrotoxicity) with CI. Due to study heterogeneity, a narrative synthesis of the evidence was performed. RESULTS Twenty-one publications were included with a total of 2949 patients. Mortality was higher (two studies, n = 388 patients) and clinical cure was lower (one study, n = 40 patients) with Css < 15 mg/L measured 24 h after initiation of CI (C24). An adequate loading dose appeared most important for maintaining higher C24. Generally, higher Css was associated with higher rates of acute kidney injury (AKI) (15 studies, n = 2331 patients). It was calculated that Css < 25 mg/L (versus ≥25 mg/L) was preferable for reducing nephrotoxicity (three studies, n = 515 patients). CONCLUSIONS Despite sparse data availability, the target range of 15-25 mg/L in CI may increase clinical cure and reduce mortality and AKI. In future research, vancomycin Css cohorts should be formed to allow evaluation of the impact of Css of CI on treatment outcomes.
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Affiliation(s)
- Katrin Viertel
- Central Pharmacy, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany; Institute of Hygiene, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany; Division of Hygiene and Environmental Medicine, Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Alfred-Herrhausen-Straße 50, 58455 Witten, Germany.
| | - Elisabeth Feles
- Central Pharmacy, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany; Institute of Hygiene, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany; Division of Hygiene and Environmental Medicine, Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Alfred-Herrhausen-Straße 50, 58455 Witten, Germany
| | - Melanie Schulte
- Central Pharmacy, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany
| | - Thorsten Annecke
- Department of Anaesthesiology and Intensive Care Medicine, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany
| | - Frauke Mattner
- Institute of Hygiene, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, Ostmerheimer Str. 200, 51109 Cologne, Germany; Division of Hygiene and Environmental Medicine, Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Alfred-Herrhausen-Straße 50, 58455 Witten, Germany
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Luo Y, Guo Z, Li Y, Ouyang H, Huang S, Chen Y, Li K, Ji Y, Zhu H, Luo W, Liu X, Li X, Xia J, Liu X. Appropriateness of Empirical Antibiotic Therapy in Hospitalized Patients with Bacterial Infection: A Retrospective Cohort Study. Infect Drug Resist 2023; 16:4555-4568. [PMID: 37465180 PMCID: PMC10350404 DOI: 10.2147/idr.s402172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 06/22/2023] [Indexed: 07/20/2023] Open
Abstract
Objective The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection. Methods A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model. Results A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135-70,155] vs 31,489 [14,894-101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135-70,155] vs 30,960 [16,475-90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT. Conclusion Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.
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Affiliation(s)
- Yuting Luo
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Zhaowang Guo
- Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Ying Li
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Hui Ouyang
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Shanfeng Huang
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Yuanli Chen
- Department of Hospital Infection Control, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Kenan Li
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Yuxin Ji
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Hongqiong Zhu
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Wentao Luo
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Xu Liu
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Xinghua Li
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Jinyu Xia
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
| | - Xi Liu
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China
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Zhang Y, Cheng Z, Hu Y, Tang LV. Management of Complex Infections in Hemophagocytic Lymphohistiocytosis in Adults. Microorganisms 2023; 11:1694. [PMID: 37512867 PMCID: PMC10383929 DOI: 10.3390/microorganisms11071694] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/20/2023] [Accepted: 06/27/2023] [Indexed: 07/30/2023] Open
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune system activation and inflammatory response due to a variety of primary and secondary factors that can cause a range of clinical symptoms and, in severe cases, life-threatening conditions. Patients with HLH are at increased risk of infection due to their abnormal immune function as well as chemotherapy and immunosuppressive therapy at the time of treatment. At the same time, the lack of specific clinical features makes complex infections in HLH challenging to diagnose and treat. The management of complex infections in HLH requires a multidisciplinary and integrated approach including the early identification of pathogens, the development of anti-infection protocols and regimens, and the elimination of potential infection factors. Especially in HLH patients with septic shock, empirical combination therapy against the most likely pathogens should be initiated, and appropriate anti-infective regimens should be determined based on immune status, site of infection, pathogens, and their drug resistance, with timely antibiotic adjustment by monitoring procalcitonin. In addition, anti-infection prophylaxis for HLH patients is needed to reduce the risk of infection such as prophylactic antibiotics and vaccinations. In conclusion, complex infection in HLH is a serious and challenging disease that requires vigilance, early identification, and timely anti-infective therapy.
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Affiliation(s)
- Yi Zhang
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
| | - Zhipeng Cheng
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
| | - Yu Hu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
| | - Liang V Tang
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
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Kulikov AV, Shifman EM, Protsenko DN, Ovezov AM, Роненсон АМ, Raspopin YS, Artymuk NV, Belokrynitskaya TE, Zolotukhin KN, Shchegolev AV, Kovalev VV, Matkovsky AA, Osipchuk DO, Pylaeva NY, Ryazanova OV, Zabolotskikh IB. Septic shock in obstetrics: guidelines of the All-Russian public organization “Federation of Anesthesiologists and Reanimatologists”. ANNALS OF CRITICAL CARE 2023:7-44. [DOI: 10.21320/1818-474x-2023-2-7-44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
The article reflects the main provisions of the clinical guidelines on septic shock in obstetrics, approved by the All-Russian public organization “Federation of Anesthesiologists-Resuscitators” in 2022. The relevance of the problem is associated with high mortality and morbidity rates from sepsis and septic shock in obstetrics. The main issues of etiology, pathogenesis, clinical picture, methods of laboratory and instrumental diagnostics, features of using the qSOFA, SOFA, MOEWS, SOS, MEWC, IMEWS scales for sepsis verification are consistently presented. The article presents the starting intensive therapy (the first 6–12 hours) of the treatment of septic shock in obstetrics, taking into account the characteristics of the pregnant woman's body. The strategy of prescribing vasopressors (norepinephrine, phenylephrine, epinephrine), inotropic drugs (dobutamine) is described, antibiotics and optimal antibiotic therapy regimens, features of infusion and adjuvant therapy are presented. The issues of surgical treatment of the focus of infection and indications for hysterectomy, as well as the organization of medical care and rehabilitation of patients with sepsis and septic shock were discussed. The basic principles of prevention of sepsis and septic shock in obstetrics are described. The criteria for the quality of medical care for patients with septic shock and the algorithms of doctor's actions in the diagnosis and intensive care of patients with septic shock in obstetrics are presented.
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Affiliation(s)
| | - E. M. Shifman
- Moscow Regional Research and Clinical Institute, Moscow, Russia
| | - D. N. Protsenko
- Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia; Moscow’s Multidisciplinary Clinical Center “Kommunarka”, Moscow, Russia
| | - A. M. Ovezov
- Moscow Regional Research and Clinical Institute, Moscow, Russia
| | - А. М. Роненсон
- Tver State Medical University, Tver, Russia; E.M. Bakunina Tver Regional Clinical Perinatal Centre, Tver, Russia
| | - Yu. S. Raspopin
- Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia; Krasnoyarsk Regional Clinical Center for Maternal and Child Health, Krasnoyarsk, Russia
| | | | | | | | | | - V. V. Kovalev
- Ural State Medical University, Yekaterinburg, Russia
| | - A. A. Matkovsky
- Ural State Medical University, Yekaterinburg, Russia; Ural State Medical University, Yekaterinburg, Russia
| | - D. O. Osipchuk
- Regional Children's Clinical Hospital. Yekaterinburg, Russia
| | - N. Yu. Pylaeva
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - O. V. Ryazanova
- D.O. Ott Research Institute of Obstetrics and Gynecology RAMS, St. Petersburg, Russia
| | - I. B. Zabolotskikh
- Kuban State Medical University, Krasnodar, Russia; Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia; Regional Clinical Hospital No 2, Krasnodar, Russia
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Lim S, Yoo YM, Kim KH. No more tears from surgical site infections in interventional pain management. Korean J Pain 2023; 36:11-50. [PMID: 36581597 PMCID: PMC9812697 DOI: 10.3344/kjp.22397] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 12/31/2022] Open
Abstract
As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.
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Affiliation(s)
- Seungjin Lim
- Division of Infectious Diseases, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Yeong-Min Yoo
- Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea
| | - Kyung-Hoon Kim
- Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea,Correspondence: Kyung-Hoon Kim Pain Clinic, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea, Tel: +82-55-360-1422, Fax: +82-55-360-2149, E-mail:
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8
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Pas ML, Bokma J, Lowie T, Boyen F, Pardon B. Sepsis and survival in critically ill calves: Risk factors and antimicrobial use. J Vet Intern Med 2022; 37:374-389. [PMID: 36562487 PMCID: PMC9889718 DOI: 10.1111/jvim.16607] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 11/23/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Sepsis is a life-threatening disease for which critically important antimicrobials (CIA) frequently are used. Diagnostic and therapeutic guidelines for sepsis and critically ill calves are largely lacking. OBJECTIVES Identify factors associated with mortality in critically ill calves and describe bacteria obtained from blood cultures of critically ill calves with sepsis and their antimicrobial resistance. ANIMALS Two-hundred thirty critically ill calves, mainly Belgian Blue beef cattle. METHODS Retrospective cohort study. Logistic regression, survival analysis, and decision tree analysis were used to determine factors associated with mortality. RESULTS Of the critically ill calves, 34.3% had sepsis and 61.3% died. The final survival model indicated that calves with sepsis (hazard risk [HR]: 1.6; 95% confidence interval [CI]: 1.0-2.5; P = .05), abnormal behavior (HR: 2.3; 95% CI: 1.3-4.0; P = .005), and hypothermia (HR: 0.82; 95% CI: 0.72-0.95; P = .01) had a significantly higher mortality risk. In a second survival model, hypothermia (HR: 0.87; 95% CI: 0.78-0.96; P = .004) and hypoglycemia (HR: 2.2; 95% CI: 1.5-3.3; P < .001) were risk factors for mortality. Decision tree analysis emphasized the importance of behavior, hypochloremia, hypoglycemia, hyperkalemia, and lung ultrasonography for mortality risk. Escherichia coli (30.6%) was most frequently isolated from blood cultures, of which 90.9% were multidrug resistant. Inappropriate use of antimicrobials was frequent for penicillin, amoxicillin, and sulfamethoxazole/trimethoprim, but less for CIA. CONCLUSIONS AND CLINICAL IMPORTANCE Many critically ill calves have sepsis, which increases mortality risk. Bacteria involved are often resistant to first-intention antimicrobials but less resistant to CIA. The other identified risk factors for mortality can support therapeutic decision-making.
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Affiliation(s)
- Mathilde L. Pas
- Department of Internal Medicine, Reproduction and Population MedicineGhent UniversityMerelbekeBelgium
| | - Jade Bokma
- Department of Internal Medicine, Reproduction and Population MedicineGhent UniversityMerelbekeBelgium
| | - Thomas Lowie
- Department of Internal Medicine, Reproduction and Population MedicineGhent UniversityMerelbekeBelgium
| | - Filip Boyen
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - Bart Pardon
- Department of Internal Medicine, Reproduction and Population MedicineGhent UniversityMerelbekeBelgium
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Gao P, Wei Y, Wan RE, Wong KW, Iu HTV, Tai SSC, Li Y, Yam HCB, Halebeedu Prakash P, Chen JHK, Ho PL, Yuen KY, Davies J, Kao RYT. Subinhibitory Concentrations of Antibiotics Exacerbate Staphylococcal Infection by Inducing Bacterial Virulence. Microbiol Spectr 2022; 10:e0064022. [PMID: 35758685 PMCID: PMC9431598 DOI: 10.1128/spectrum.00640-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 05/17/2022] [Indexed: 01/24/2023] Open
Abstract
Antibiotics are widely used for the treatment of bacterial infections. However, injudicious use of antibiotics based on an empirical method may lead to the emergence of resistant strains. Despite appropriate administration of antibiotics, their concentrations may remain subinhibitory in the body, due to individual variations in tissue distribution and metabolism rates. This may promote bacterial virulence and complicate the treatment strategies. To investigate whether the administration of certain classes of antibiotics will induce bacterial virulence and worsen the infection under in vivo conditions. Different classes of antibiotics were tested in vitro for their ability to induce virulence in a methicillin-resistant S. aureus strain Mu3 and clinical isolates. Antibiotic-induced pathogenicity was assessed in vivo using mouse peritonitis and bacteremia models. In vitro, β-lactam antibiotics and tetracyclines induced the expression of multiple surface-associated virulence factors as well as the secretion of toxins. In peritonitis and bacteremia models, mice infected with MRSA and treated with ampicillin, ceftazidime, or tetracycline showed enhanced bacterial pathogenicity. The release of induced virulence factors in vivo was confirmed in a histological examination. Subinhibitory concentrations of antibiotics belonging to β-lactam and tetracycline aggravated infection by inducing staphylococcal virulence in vivo. Thus, when antibiotics are required, it is preferable to employ combination therapy and to initiate the appropriate treatment plan, following diagnosis. Our findings emphasize the risks associated with antibiotic-based therapy and underline the need for alternative therapeutic options. IMPORTANCE Antibiotics are widely applied to treat infectious diseases. Empirically treatment with incorrect antibiotics, or even correct antibiotics always falls into subinhibitory concentrations, due to dosing, distribution, or secretion. In this study, we have systematically evaluated in vitro virulence induction effect of antibiotics and in vivo exacerbated infection. The major highlight of this work is to prove the β-lactam and tetracyclines antibiotics exacerbated disease is due to their induction effect on staphylococcal virulence. This phenomenon is common and suggests that if β-lactam antibiotics remain the first line of defense during empirical therapy, we either need to increase patient reliability or the treatment approach may improve in the future when paired with anti-virulence drugs.
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Affiliation(s)
- Peng Gao
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yuanxin Wei
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Rachel Evelyn Wan
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Ka Wing Wong
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Ho Ting Venice Iu
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Sherlock Shing Chiu Tai
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yongli Li
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Hin Cheung Bill Yam
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Pradeep Halebeedu Prakash
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Jonathan Hon Kwan Chen
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
- Department of Microbiology, Queen Mary Hospital, Pok Fu Lam, Hong Kong
| | - Pak Leung Ho
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
- Department of Microbiology, Queen Mary Hospital, Pok Fu Lam, Hong Kong
- State Key Laboratory of Emerging Infectious Diseases and the Research Centre of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
- Carol Yu Centre for Infection, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Kwok Yung Yuen
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
- Department of Microbiology, Queen Mary Hospital, Pok Fu Lam, Hong Kong
- State Key Laboratory of Emerging Infectious Diseases and the Research Centre of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Julian Davies
- Department of Microbiology and Immunology, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Richard Yi Tsun Kao
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
- State Key Laboratory of Emerging Infectious Diseases and the Research Centre of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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10
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Zhao J, Wei Q, Guo S, Wang H, Zhao C, Hu C, Liu C, Dai Q, Wang R. Efficacy of Oxymatrine Plus Antiviral in the Treatment of Sepsis and Its Effect on the Levels of Endotoxin and Inflammatory Factors. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:1938325. [PMID: 35656463 PMCID: PMC9155921 DOI: 10.1155/2022/1938325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/16/2022] [Accepted: 04/22/2022] [Indexed: 11/17/2022]
Abstract
Objective To assess the clinical efficacy of oxymatrine plus antiviral therapy in the treatment of sepsis and its effects on the levels of endotoxin and inflammatory factors. Methodology. 90 patients with sepsis were selected for retrospective analysis and were assigned to receive either conventional treatment (control group) or oxymatrine plus antiviral treatment (study group). The clinical endpoint was treatment efficacy. Results There were no significant differences in baseline patient profile between the two groups (P > 0.05). The study group showed a higher efficiency versus the control group (P < 0.05). Patients in the study group had a significantly shorter mechanical ventilation duration and ICU stay versus those in the control group (P < 0.05). Both groups had reduced Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Marshall score, levels of endotoxin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, C-reactive protein (CRP), and procalcitonin (PCT) after treatment, with lower results in the study group versus the control group (P < 0.05). Conclusion Oxymatrine plus antiviral therapy effectively improves clinical efficacy, reduces the levels of endotoxin and inflammatory factors, protects organ function, and boosts recovery. Further clinical trials are, however, required prior to general application in clinical practice.
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Affiliation(s)
- Jinglin Zhao
- Department of Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Qi Wei
- Department of Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Shengchao Guo
- Department II of Hepatobiliary and Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Hao Wang
- Department of Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Chao Zhao
- Department of Pharmacology, Cangzhou Medical College, Cangzhou, Hebei, China
| | - Caihong Hu
- Department of Pharmacology, Cangzhou Medical College, Cangzhou, Hebei, China
| | - Cuicui Liu
- Department of Pharmacology, Cangzhou Medical College, Cangzhou, Hebei, China
| | - Qingchun Dai
- Department of Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Rui Wang
- Department of Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China
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Kong PH, Chiang CH, Lin TC, Kuo SC, Li CF, Hsiung CA, Shiue YL, Chiou HY, Wu LC, Tsou HH. Discrimination of Methicillin-resistant Staphylococcus aureus by MALDI-TOF Mass Spectrometry with Machine Learning Techniques in Patients with Staphylococcus aureus Bacteremia. Pathogens 2022; 11:586. [PMID: 35631107 PMCID: PMC9143686 DOI: 10.3390/pathogens11050586] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/11/2022] [Accepted: 05/13/2022] [Indexed: 11/29/2022] Open
Abstract
Early administration of proper antibiotics is considered to improve the clinical outcomes of Staphylococcus aureus bacteremia (SAB), but routine clinical antimicrobial susceptibility testing takes an additional 24 h after species identification. Recent studies elucidated matrix-assisted laser desorption/ionization time-of-flight mass spectra to discriminate methicillin-resistant strains (MRSA) or even incorporated with machine learning (ML) techniques. However, no universally applicable mass peaks were revealed, which means that the discrimination model might need to be established or calibrated by local strains' data. Here, a clinically feasible workflow was provided. We collected mass spectra from SAB patients over an 8-month duration and preprocessed by binning with reference peaks. Machine learning models were trained and tested by samples independently of the first six months and the following two months, respectively. The ML models were optimized by genetic algorithm (GA). The accuracy, sensitivity, specificity, and AUC of the independent testing of the best model, i.e., SVM, under the optimal parameters were 87%, 75%, 95%, and 87%, respectively. In summary, almost all resistant results were truly resistant, implying that physicians might escalate antibiotics for MRSA 24 h earlier. This report presents an attainable method for clinical laboratories to build an MRSA model and boost the performance using their local data.
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Affiliation(s)
- Po-Hsin Kong
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; (P.-H.K.); (Y.-L.S.)
- Center for Precision Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan;
| | - Cheng-Hsiung Chiang
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan; (C.-H.C.); (C.A.H.); (H.-Y.C.)
| | - Ting-Chia Lin
- Center for Precision Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan;
- Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
| | - Shu-Chen Kuo
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan;
| | - Chien-Feng Li
- Department of Medical Research, Chi Mei Medical Center, Tainan 71004, Taiwan;
| | - Chao A. Hsiung
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan; (C.-H.C.); (C.A.H.); (H.-Y.C.)
| | - Yow-Ling Shiue
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; (P.-H.K.); (Y.-L.S.)
- Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
| | - Hung-Yi Chiou
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan; (C.-H.C.); (C.A.H.); (H.-Y.C.)
- School of Public Health, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan
- Master’s Program in Applied Epidemiology, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan
| | - Li-Ching Wu
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; (P.-H.K.); (Y.-L.S.)
- Center for Precision Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan;
| | - Hsiao-Hui Tsou
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan; (C.-H.C.); (C.A.H.); (H.-Y.C.)
- Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung 40402, Taiwan
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Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia. Microbiol Spectr 2022; 10:e0153021. [PMID: 35438533 PMCID: PMC9241907 DOI: 10.1128/spectrum.01530-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.
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Arya V, Shukla AK, Prakash B, Bhargava JK, Gupta A, Patel BB, Tiwari P. Tuberculosis-Associated Septic Shock: A Case Series. Cureus 2022; 14:e23259. [PMID: 35449613 PMCID: PMC9012569 DOI: 10.7759/cureus.23259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2022] [Indexed: 11/05/2022] Open
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Lazzaro A, De Girolamo G, Filippi V, Innocenti GP, Santinelli L, Ceccarelli G, Trecarichi EM, Torti C, Mastroianni CM, d’Ettorre G, Russo A. The Interplay between Host Defense, Infection, and Clinical Status in Septic Patients: A Narrative Review. Int J Mol Sci 2022; 23:ijms23020803. [PMID: 35054993 PMCID: PMC8776148 DOI: 10.3390/ijms23020803] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/05/2022] [Accepted: 01/09/2022] [Indexed: 01/08/2023] Open
Abstract
Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients.
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Affiliation(s)
- Alessandro Lazzaro
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Gabriella De Girolamo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Valeria Filippi
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Giuseppe Pietro Innocenti
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Letizia Santinelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Enrico Maria Trecarichi
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
| | - Carlo Torti
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
| | - Claudio Maria Mastroianni
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Gabriella d’Ettorre
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Alessandro Russo
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
- Correspondence:
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Xiao H, Wang G, Wang Y, Tan Z, Sun X, Zhou J, Duan M, Zhi D, Tang Z, Hang C, Zhang G, Li Y, Wu C, Li F, Zhang H, Wang J, Zhang Y, Zhang X, Guo W, Qi W, Xie M, Li C. Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial. Shock 2022; 57:63-71. [PMID: 34618727 DOI: 10.1097/shk.0000000000001870] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
INTRODUCTION Long-term use of antibiotics for septic patients leads to bacterial resistance, increased mortality, and hospital stay. In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. METHODS In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 days. Secondary endpoints were the percentage of patients with a recurrent infection, length of stay in ICU and hospital, hospitalization costs, days of first episode of antibiotic treatment, percentage of antibiotic administration and multidrug-resistant bacteria, and SOFA score. RESULTS Overall, 656 out of an initial 708 patients were eligible and assigned to the presepsin group (n = 327) or the control group (n = 329). Patients in the presepsin group had significantly more days without antibiotics than those in the control group (14.54 days [SD 9.01] vs. 11.01 days [SD 7.73]; P < 0.001). Mortality in the presepsin group showed no difference to that in the control group at days 28 (17.7% vs. 18.2%; P = 0.868) and 90 (19.9% vs. 19.5%; P = 0.891). Patients in the presepsin group had a significantly shorter mean length of stay in the hospital and lower hospitalization costs than control subjects. There were no differences in the rate of recurrent infection and multidrug-resistant bacteria and the SOFA score tendency between the two groups. CONCLUSIONS Presepsin guidance has potential to shorten the duration of antibiotic treatment in patients with sepsis without risking worse outcomes of death, recurrent infection, and aggravation of organ failure. TRIAL REGISTRATION ChiCTR, ChiCTR1900024391. Registered 9 July 2019-Retrospectively registered, http://www.chictr.org.cn.
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Affiliation(s)
- Hongli Xiao
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guoxing Wang
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yan Wang
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhimin Tan
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xuelian Sun
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jie Zhou
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Meili Duan
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Deyuan Zhi
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ziren Tang
- EICU of Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Chenchen Hang
- EICU of Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Guoqiang Zhang
- EICU of Department of Emergency Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Yan Li
- EICU of Department of Emergency Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Caijun Wu
- EICU of Department of Emergency Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Fengjie Li
- EICU of Department of Emergency Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Haiyan Zhang
- EICU of Department of Emergency Medicine, The Hospital of Shunyi District Beijing, China Medical University, Beijing, China
| | - Jing Wang
- EICU of Department of Emergency Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yun Zhang
- EICU of Department of Emergency Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xinchao Zhang
- EICU of Department of Emergency Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Guo
- EICU of Department of Emergency Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wenjie Qi
- Department of Infectious Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Miaorong Xie
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chunsheng Li
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Mora-Guzmán I, Rubio-Perez I, Domingo-Garcia D, Martin-Perez E. Risk Factors for Intra-Abdominal Infections Caused by Carbapenemase-Producing Enterobacteriaceae in a Surgical Setting. Surg Infect (Larchmt) 2021; 22:864-870. [PMID: 33857380 DOI: 10.1089/sur.2020.472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: The aim of this study was to identify risk factors for acquisition of intra-abdominal infections (IAI) caused by carbapenemase-producing Enterobacteriaceae (CPE) in surgical patients. Methods: A matched case-control study was performed. We included all cases with CPE-related IAI acquired during admission to a general surgery department from January 2013 to December 2018, and they were matched with control subjects with IAI caused by non-resistant bacteria (ratio 1:3). Independent risk factors were obtained by logistic regression. Results: Forty patients with IAI-CPE were matched with 120 control subjects. Independent risk factors for acquisition of IAI-CPE were previous hospitalization (odds ratio [OR] 2.56; 95% confidence interval [CI] l 1.01-6.49; p = 0.047), digestive endoscopy (OR 4.11; 95% CI 1.40-12.07; p = 0.010), carbapenem therapy (OR 9.54; 95% CI 3.33-27.30; p < 0.001), and aminoglycoside use (OR 45.41; 95% CI 7.90-261.06; p < 0.001). Conclusions: Four clinical factors can identify patients at high-risk of IAI-CPE.
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Affiliation(s)
- Ismael Mora-Guzmán
- Department of General Surgery. Hospital General La Mancha Centro, Alcázar de San Juan, Spain
| | - Inés Rubio-Perez
- Department of General Surgery, Hospital Universitario La Paz, Madrid, Spain
| | - Diego Domingo-Garcia
- Department of Clinical Microbiology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Elena Martin-Perez
- Department of General Surgery, Hospital Universitario de La Princesa, Madrid, Spain
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Khosrojerdi A, Soudi S, Zavaran Hosseini A, Ghaffari Khaligh S, Hashemi SM. Imipenem alters systemic and liver inflammatory responses in CLP- induced sepsis mice in a dose-dependent manner. Int Immunopharmacol 2021; 93:107421. [PMID: 33548581 DOI: 10.1016/j.intimp.2021.107421] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 01/14/2021] [Accepted: 01/18/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Considering the role of inflammation in the outcome of sepsis and the widespread use of imipenem in the disease, this study was designed to assess the effect of imipenem on the dynamics of inflammatory responses in the sepsis mouse model. METHODS Cecal Ligation and Puncture (CLP) model was used to induce sepsis in mice. C57BL/6 mice were divided into sham, CLP-induced sepsis mice, CLP-induced sepsis mice receiving 25 mg/kg, and 125 mg/kg imipenem. Blood and liver samples were obtained and bacterial load, endotoxin level, and liver enzymes were evaluated. The concentration and mRNA expression of cytokines were also determined. RESULTS Sepsis mice treated with a high dose (125 mg/kg) of imipenem showed a significant reduction in bacterial load, while increased liver enzymes, endotoxin level, and inflammatory cytokine production in plasma and liver. In contrast, significant reduction in the liver enzymes, bacterial load, endotoxin levels, and inflammatory cytokine levels was observed in the mice treated with a low dose (25 mg/kg) of imipenem compared with other mice groups. Liver tissue pathology of mice indicated little tissue destruction in the sepsis mice treated with 25 mg/kg of imipenem compared to other groups. Mice receiving 25 mg/kg of imipenem had better survival rate. CONCLUSIONS Our results demonstrated the dose-dependent effect of subcutaneous administration of imipenem on the inflammatory responses in sepsis mice. A dose of 25 mg/kg imipenem resulted in better pathology, lower inflammatory mediators, and increased survival rate in sepsis mice.
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Affiliation(s)
- Arezou Khosrojerdi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Ahmad Zavaran Hosseini
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sahar Ghaffari Khaligh
- Department of Pathology, Faculty of Veterinary Medicine, Semnan University, Semnan, Iran
| | - Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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What Do We Know about Early Management of Sepsis and Septic Shock in Polish Hospitals? A Questionnaire Study. Healthcare (Basel) 2021; 9:healthcare9020140. [PMID: 33535608 PMCID: PMC7912914 DOI: 10.3390/healthcare9020140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 01/23/2021] [Accepted: 01/25/2021] [Indexed: 11/26/2022] Open
Abstract
Background: Sepsis and septic shock are medical emergencies with a high risk of poor prognosis. We investigate the correspondence between Surviving Sepsis Campaign (SSC) guidelines and clinical practice in Poland, with special attention given to differences between ICU and non-ICU environments as well as regional variations within the country. Methods: A web-based questionnaire study was performed on a random sample of 60 hospitals from the three most populated regions in Poland—Masovia, Silesia, and Greater Poland. A 19-item questionnaire was built based on the most recent edition of SSC guidelines. Results: Sepsis diagnosis was primarily based on clinical evaluation (ICUs: 94%, non-ICUs: 62%; p = 0.02). There were significant differences between ICUs and non-ICUs regarding taking blood cultures for pathogen identification (2-times more frequent in ICUs) and having hospital-based operating procedures to adjust antimicrobial treatment to a clinical scenario (a difference of 17%). Modification of empiric antimicrobial treatment was required post-ICU admission in 70% of cases. ICUs differed from non-ICUs with regard to the methods of fluid responsiveness assessment and the types of catecholamines and fluids used to treat septic shock. The mean fluid load applied before the implementation of catecholamines was 25.8 ± 10.6 mL/kg. Norepinephrine was the first-line agent used to treat shock, and balanced crystalloids were preferred in both ICUs and non-ICUs. Conclusion: Compliance with SCC guidelines in Polish hospitals is insufficient, especially outside ICUs. There is a need for education among healthcare professionals to reach at least an acceptable level of knowledge and attitude in this field.
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Effect of delayed entry on performance of the BACT/ALERT FAN PLUS bottles in the BACT/ALERT VIRTUO blood culture system. Eur J Clin Microbiol Infect Dis 2020; 40:699-705. [PMID: 33034779 PMCID: PMC7979663 DOI: 10.1007/s10096-020-04042-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/15/2020] [Indexed: 02/08/2023]
Abstract
Delayed entry of patient blood culture samples into a microbial detection system is unavoidable at times, due to off-shift staffing or transporting samples to centralized laboratories. Pre-incubation time and temperature of blood culture bottles are the most critical factors impacting recovery and detection of microorganisms. A total of 1377 BACT/ALERT® (BTA) Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles (FA PLUS, FN PLUS, and PF PLUS) were tested after delayed entry times of 24 and 36 h at 20–25 °C (room temperature, RT) prior to loading into the BACT/ALERT® VIRTUO® microbial detection system (VIRTUO). Clinically relevant organisms were inoculated into bottles with 5–84 colony forming units (CFU) per bottle, and human blood (0 to 10 mL), and then loaded into the VIRTUO. When bottles were loaded without delay, a mean time to detection (TTD) of 9.6 h was observed. For delayed bottles, the TTD reported by the VIRTUO was added to the 24-h and 36-h delay times and resulted in average time to results of 32.5 h and 42.5 h, respectively. The FAN PLUS bottles in conjunction with the VIRTUO produced acceptable results when delays up to 24 h at 20–25 °C occur in loading.
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Administrative Database and Empiric Therapy Are Always Useful for Appropriate Treatment of Pediatric Patients? Crit Care Med 2020; 48:438-440. [PMID: 32058384 DOI: 10.1097/ccm.0000000000004175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Yoshida J, Tamura T, Otani K, Inoue M, Miyatake E, Ishimitsu T, Nakahara C, Tanaka M. Mortality related to drug-resistant organisms in surgical sepsis-3: an 8-year time trend study using sequential organ failure assessment scores. Eur J Clin Microbiol Infect Dis 2020; 40:535-540. [PMID: 32954476 PMCID: PMC7892503 DOI: 10.1007/s10096-020-04037-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 09/10/2020] [Indexed: 11/04/2022]
Abstract
The difference in sequential organ failure assessment (SOFA) scores from the baseline to sepsis is a known predictor of sepsis-3 outcome, but the prognostic value of drug-resistant organisms for mortality is unexplained. We employed sepsis stewardship and herein report an observational study. Study subjects were patients admitted to the Departments of Surgery/Chest Surgery from 2011 through 2018 with a diagnosis of sepsis and a SOFA score of 2 or more. Our sepsis stewardship methods included antimicrobial and diagnostic stewardship and infection control. We determined the primary endpoint as in-hospital death and the secondary endpoint as the annual trend of the risk-adjusted mortality ratio (RAMR). For mortality, we performed logistic regression analysis based on SOFA score, age, sex, comorbid disease, and the presence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase inhibitor–producing bacteria. In a total of 457 patients, two factors were significant predictors for fatality, i.e., SOFA score of 9 or more with an odds ratio (OR) 4.921 and 95% confidence interval [95% CI] 1.968–12.302 (P = 0.001) and presence of MRSA with an OR 1.83 and 95% CI 1.003–3.338 (P = 0.049). RAMR showed a decrease during the study years (P < 0.05). Early detection of MRSA may help patients survive surgical sepsis-3. Thus, MRSA-oriented diagnosis may play a role in expediting treatment with anti-MRSA antimicrobials.
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Affiliation(s)
- Junichi Yoshida
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan.
| | - Tetsuro Tamura
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
| | - Kazuhiro Otani
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
| | - Masaaki Inoue
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
| | - Eiji Miyatake
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
| | - Toshiyuki Ishimitsu
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
| | - Chihiro Nakahara
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
| | - Masao Tanaka
- Department of Surgery/Chest Surgery, Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki, 750-8520, Japan
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Anderson CM, Pitt WG. Effect of dilution on sedimentational separation of bacteria from blood. Biotechnol Prog 2020; 36:e3056. [PMID: 32715664 DOI: 10.1002/btpr.3056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/18/2020] [Accepted: 07/04/2020] [Indexed: 11/07/2022]
Abstract
Bacteria must be separated from septic whole blood in preparation for rapid antibiotic susceptibility tests. This work improves upon past work isolating bacteria from whole blood by exploring an important experimental factor: Whole blood dilution. Herein, we use the continuity equation to model red blood cell sedimentation and show that overall spinning time decreases as the blood is diluted. We found that the bacteria can also be captured more efficiently from diluted blood, up to approximately 68 ± 8% recovery (95% confidence interval). However, diluting blood both requires and creates extra fluid that end users must handle; an optimal dilution, which maximizes bacteria recovery and minimizes waste, was found to scale with the square root of the whole blood hematocrit. This work also explores a hypothesis that plasma backflow, which occurs as red cells move radially outward, causes bacterial enrichment in the supernatant plasma with an impact proportional to the plasma backflow velocity. Bacteria experiments carried out with diluted blood demonstrate such bacterial enrichment, but not in the hypothesized manner as enrichment occurred only in undiluted blood samples at physiological hematocrit.
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Affiliation(s)
- Clifton M Anderson
- Department of Chemical Engineering, Brigham Young University, Provo, Utah, USA
| | - William G Pitt
- Department of Chemical Engineering, Brigham Young University, Provo, Utah, USA
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Bray C, Kennedy C. Improving timely sepsis care using the surviving sepsis campaign one-hour bundle in a rural emergency department. J Am Assoc Nurse Pract 2020; 33:246-253. [PMID: 32618733 DOI: 10.1097/jxx.0000000000000436] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/20/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Sepsis is deadly when not recognized and treated in a timely manner and leads to 270,000 deaths each year in America. Mortality increases eight percent for each hour treatment is delayed. Sepsis-related admission is the most expensive condition in the United States with a median cost per patient of $32,421. LOCAL PROBLEM Baseline data for patients with sepsis revealed that only 30% were recognized in triage, only 20% received correct amounts of fluids, and only 45% received antibiotics within one hour. The aim of this project was to improve timely sepsis care to 75% for patients in a rural emergency department within 90 days. METHODS A rapid cycle quality improvement project was completed, consisting of four plan-do-study-act cycles over 90 days. Each cycle included tests of change related to team and patient engagement, screening, and the use of timely sepsis orders. Data were collected three times weekly and analyzed using run charts. INTERVENTIONS Interventions included screening in triage with positively screened patients receiving participatory education, team handoff communication, a sepsis checklist for nurse-driven orders, and Power Hour for timely care. RESULTS Team communication improved to 83%. Patient education exceeded goal, with 100% of patients taking an active role in care. Sepsis screening improved to 100%. The recommended One-Hour Bundle for timely sepsis treatment improved to 83%. CONCLUSION The project was successful in improving patient and team engagement, screening, and sepsis care within 1 hour for emergency department patients.
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Affiliation(s)
- Carla Bray
- Tippah County Hospital, Ripley, Mississippi
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Algethamy HM, Morish A, Numan MS, Alotaibi AF. "Appropriate" Versus "Inappropriate" Antibiotic Administration, "Prior To" Versus "After" the Diagnosis of Septic Shock. Impact on Patients with Sepsis Admitted to a Saudi Intensive Care Unit. Mater Sociomed 2020; 32:20-28. [PMID: 32410887 PMCID: PMC7219728 DOI: 10.5455/msm.2020.32.20-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Introduction: Delaying broad-spectrum antibiotics beyond 1-2 hours once the septic shock is diagnosed increases patients’ risk of death. However, what is the impact of already being on antibiotics when a septic shock is diagnosed? Aim: We compared demographics, clinical characteristics and outcomes in septic shock patients on antibiotics initiated prior to versus after septic shock was diagnosed; whose initial antibiotics were considered appropriate for the offending organism(s); and who died in versus were discharged from the ICU. Methods: Data were prospectively collected on 161 patients ≥ 14-years-old (female: male=1:1; mean age 61.1yrs) admitted to the ICU for septic shock, and followed for ≥30 days, or until hospital discharge or death. Results: Few inter-group differences were identified. Those treated early were more likely to have a nosocomial infection (p=0.03), skin or soft tissue source of their infection (p=0.01), or a diabetes-related limb amputation (p=0.02); but received fewer antibiotics (p=0.01). Those on appropriate antibiotics were more likely to be female (p=0.048), but less likely to have a skin or soft tissue source of infection (p=0.03). Neither starting antibiotics early, nor being on appropriate antibiotics impacted any outcome measure, including survival. Predictors of mortality were ≥1 co-morbid condition (p=0.03), more versus fewer co-morbid conditions (p=0.009), cardiovascular disease at baseline (p=03), requiring dialysis at baseline (p=0.008), and a higher day#1 SOFA score (p<0.001). Conclusions: Our data fail to demonstrate any benefit to being on antibiotics prior to the diagnosis, irrespective of whether the ultimately-identified offending organism is sensitive or resistant.
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Affiliation(s)
- Haifa M Algethamy
- Department of Anesthesia and Critical Care Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ayman Morish
- Department of Anesthesia and Critical Care Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammad S Numan
- Department of Internal Medicine, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
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Mishra R, Patel HK, Singasani R, Vakde T. Tuberculosis septic shock, an elusive pathophysiology and hurdles in management: A case report and review of literature. World J Crit Care Med 2019. [DOI: 10.5492/wjcc.v8.i5.64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Mishra R, Patel HK, Singasani R, Vakde T. Tuberculosis septic shock, an elusive pathophysiology and hurdles in management: A case report and review of literature. World J Crit Care Med 2019; 8:72-81. [PMID: 31559146 PMCID: PMC6753395 DOI: 10.5492/wjccm.v8.i5.72] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 08/13/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Tuberculosis (TB) is a rare etiology of the septic shock. Timely administration of the anti-microbial agents has shown mortality benefit. Prompt diagnosis and a high index of suspicion are crucial to the management. We present three cases of TBSS with poor outcome in the majority despite timely and susceptible antibiotic administration. CASE SUMMARY Sixty-seven-year-old woman with latent TB presented with fever, cough, and shortness of breath. She was promptly diagnosed with active TB and started on the appropriate anti-microbial regimen; she had a worsening clinical course with septic shock and multi-organ failure after initiation of antibiotics. Thirty-three-year-old man immunocompromised with acquired immune deficiency syndrome presented with fever, anorexia and weight loss. He had no respiratory symptoms, and first chest X-ray was normal. He had enlarged liver, spleen and lymph nodes suspicious for lymphoma. Despite broad-spectrum antibiotics, he succumbed to refractory septic shock and multi-organ failure. It was shortly before his death that anti-TB antimicrobials were initiated based on pathology reports of bone marrow and lymph node biopsies. Forty-nine-year-old woman with asthma and latent TB admitted with cough and shortness of breath. Although Initial sputum analysis was negative, a subsequent broncho-alveolar lavage turned out to be positive for acid fast bacilli followed by initiation of susceptible ant-TB regimen. She had a downward spiral clinical course with shock, multi-organ failure and finally death. CONCLUSION Worse outcome despite timely initiation of appropriate antibiotics raises suspicion of TB immune reconstitution as a possible pathogenesis for TB septic shock.
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Affiliation(s)
- Rashmi Mishra
- Pulmonary and Critical Care, Penn Highlands Healthcare, Dubois, PA 15801, United States
| | - Harish K Patel
- Division of Gastroenterology, Department of Medicine, Bronx Care Health system, Bronx, NY 10457, United States
| | - Rakesh Singasani
- Department of Medicine, SBH Health System, Bronx, NY 10457, United States
| | - Trupti Vakde
- Division of Pulmonary and Critical Care, Department of Medicine, Bronx Care Health System, Bronx, NY 10457, United States
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Mishra R, Patel HK, Singasani R, Vakde T. Tuberculosis septic shock, an elusive pathophysiology and hurdles in management: A case report and review of literature. World J Crit Care Med 2019. [DOI: 10.5492/wjccm.v8.i5.64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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28
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McConnell MJ. Where are we with monoclonal antibodies for multidrug-resistant infections? Drug Discov Today 2019; 24:1132-1138. [PMID: 30853568 DOI: 10.1016/j.drudis.2019.03.002] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/21/2019] [Accepted: 03/01/2019] [Indexed: 01/17/2023]
Abstract
Widespread antibiotic resistance threatens the continued efficacy of antimicrobial therapy based on small-molecule antibiotics. Infections caused by multidrug-resistant Gram-negative bacteria are particularly worrisome owing to the lack of antimicrobials retaining sufficient activity against these microorganisms. Despite the explosion in monoclonal antibody therapies that have been developed for oncologic and rheumatic indications, only three antibacterial monoclonal antibodies have been approved for clinical use. In the present review, the therapeutic potential of this drug class for treating multidrug-resistant infections is discussed, and considerations for the development of antibacterial monoclonal antibodies are presented. Finally, the state of development of monoclonal antibody therapies for some of the most problematic multidrug-resistant Gram-negative infections is summarized.
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Affiliation(s)
- Michael J McConnell
- Antimicrobial Resistance and Hospital Acquired Infections Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain.
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