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Liu M, Wu J, Zhao J, Xi Y, Jin Y, Yang H, Chen S, Long J, Duan G. Global epidemiology and genetic diversity of mcr-positive Klebsiella pneumoniae: A systematic review and genomic analysis. ENVIRONMENTAL RESEARCH 2024; 259:119516. [PMID: 38950813 DOI: 10.1016/j.envres.2024.119516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 06/25/2024] [Accepted: 06/29/2024] [Indexed: 07/03/2024]
Abstract
The rapid increase of mcr-positive Klebsiella pneumoniae (K. pneumoniae) has received considerable attention and poses a major public health concern. Here, we systematically analyzed the global distribution of mcr-positive K. pneumoniae isolates based on published articles as well as publicly available genomes. Combining strain information from 78 articles and 673 K. pneumoniae genomes, a total of 1000 mcr-positive K. pneumoniae isolates were identified. We found that mcr-positive K. pneumoniae has disseminated widely worldwide, especially in Asia, with a higher diversity of sequence types (STs). These isolates were disseminated in 57 countries and were associated with 12 different hosts. Most of the isolates were found in China and were isolated from human sources. Moreover, MLST analysis showed that ST15 and ST11 accounted for the majority of mcr-positive K. pneumoniae, which deserve sustained attention in further surveillance programs. mcr-1 and mcr-9 were the dominant mcr variants in mcr-positive K. pneumoniae. Furthermore, a Genome-wide association study (GWAS) demonstrated that mcr-1- and mcr-9-producing genomes exhibited different antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), thereby indicating a distinct evolutionary path. Notably, the phylogenetic analysis suggested that certain mcr-positive K. pneumoniae genomes from various geographical areas and hosts harbored a high degree of genetic similarities (<20 SNPs), suggesting frequent cross-region and cross-host clonal transmission. Overall, our results emphasize the significance of monitoring and exploring the transmission and evolution of mcr-positive K. pneumoniae in the context of "One health".
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Affiliation(s)
- Mengyue Liu
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Jie Wu
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Jiaxue Zhao
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Yanyan Xi
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Yuefei Jin
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Haiyan Yang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Shuaiyin Chen
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Jinzhao Long
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
| | - Guangcai Duan
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
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Kim UJ, Choi SM, Kim MJ, Kim S, Shin SU, Oh SR, Park JW, Shin HY, Kim YJ, Lee UH, Choi OJ, Park HY, Shin JH, Kim SE, Kang SJ, Jung SI, Park KH. Hospital water environment and antibiotic use: key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens. J Hosp Infect 2024; 151:69-78. [PMID: 38740300 DOI: 10.1016/j.jhin.2024.04.021] [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: 01/29/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). AIM To report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analysed. FINDINGS The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics was associated with acquisition of KPC-SM (P < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant micro-organisms, underscoring the necessity of enhancing infection control practices in these areas.
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Affiliation(s)
- U J Kim
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - S-M Choi
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - M J Kim
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - S Kim
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - S U Shin
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - S-R Oh
- Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - J-W Park
- Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - H Y Shin
- Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Y J Kim
- Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - U H Lee
- Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - O-J Choi
- Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - H-Y Park
- Department of Pharmacy, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - J-H Shin
- Department of Laboratory Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - S E Kim
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - S-J Kang
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - S I Jung
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - K-H Park
- Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infection Control Unit, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea.
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Vicente Arranz JL, Sánchez-Ramírez C, Saavedra P, Rivero Perdomo Y, Lorenzo-Martín MV, Blanco-López J, Domínguez Cabrera C, Hernández-Socorro CR, Ruiz-Santana S. The Relationship between Selective Digestive Decontamination and Nosocomial Infections in Patients Receiving Continuous Renal Replacement Therapy in ICUs: A Multicenter Study. J Clin Med 2024; 13:4211. [PMID: 39064251 PMCID: PMC11278040 DOI: 10.3390/jcm13144211] [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: 06/22/2024] [Revised: 07/17/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Background: Nosocomial infections are a worldwide healthcare issue, especially in intensive care units (ICUs), and they had a prevalence of 21.1% in 2023 in Spain. Numerous predisposing risk factors have been identified, with the most relevant being invasive techniques, including renal replacement therapies (RRTs). Several outstanding strategies have been published that prevent or reduce their incidence, including the nationwide ZERO in Spain, which consists of structured guidelines to be implemented to tackle this problem. One of these strategies, which is defined as 'highly recommended' in these projects, is selective digestive decontamination (SDD). The main aim of this study is to compare the incidences of ICU-acquired infections, including those due to multidrug-resistant bacteria (MDRB), in two cohorts of RRT with or without SDD. Methods: We conducted a multicenter, prospective, observational study at two tertiary hospitals in Spain. In total, 140 patients treated with RRT were recruited based on their exposure to SDD. Surveillance microbiological samples and nosocomial infection risk factors were obtained. Infection rates per 1000 days of exposure and the MDRB incidence density ratio were determined. Results: SDD statistically significantly reduced RRT-associated nosocomial infections (OR: 0.10, 95% CI: (0.04-0.26)) and the MDRB incidence density ratio (IDR: 0.156, 95% CI = 0.048-0.506). However, mechanical ventilation (OR: 7.91, 95% CI: (2.54-24.66)) and peripheral vascular disease (OR: 3.17, 95% CI: (1.33-7.56)) were significantly associated with increases in infections. Conclusions: Our results favor the use of SDD in ICU patients with renal failure undergoing CRRT as a tool for infection control.
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Affiliation(s)
- Juan Luis Vicente Arranz
- Intensive Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n, E-35010 Las Palmas de Gran Canaria, Spain; (J.L.V.A.); (C.S.-R.); (Y.R.P.)
| | - Catalina Sánchez-Ramírez
- Intensive Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n, E-35010 Las Palmas de Gran Canaria, Spain; (J.L.V.A.); (C.S.-R.); (Y.R.P.)
| | - Pedro Saavedra
- Department of Mathematics, University of Las Palmas de Gran Canaria, E-35010 Las Palmas de Gran Canaria, Spain;
| | - Yasmina Rivero Perdomo
- Intensive Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n, E-35010 Las Palmas de Gran Canaria, Spain; (J.L.V.A.); (C.S.-R.); (Y.R.P.)
| | - María Victoria Lorenzo-Martín
- Intensive Care Unit, Complejo Hospitalario Universitario Insular-Materno Infantil, Avenida Marítima del Sur s/n, E-35016 Las Palmas de Gran Canaria, Spain; (M.V.L.-M.); (J.B.-L.)
| | - José Blanco-López
- Intensive Care Unit, Complejo Hospitalario Universitario Insular-Materno Infantil, Avenida Marítima del Sur s/n, E-35016 Las Palmas de Gran Canaria, Spain; (M.V.L.-M.); (J.B.-L.)
| | - Casimira Domínguez Cabrera
- Central Laboratory, Department of Clinical Analysis, Hospital Universitario de Gran Canaria Dr. Negrín, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n, E-35010 Las Palmas de Gran Canaria, Spain;
| | - Carmen-Rosa Hernández-Socorro
- Department of Radiology, Hospital Universitario de Gran Canaria Dr. Negrín, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n, E-35010 Las Palmas de Gran Canaria, Spain;
| | - Sergio Ruiz-Santana
- Intensive Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n, E-35010 Las Palmas de Gran Canaria, Spain; (J.L.V.A.); (C.S.-R.); (Y.R.P.)
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Freire MP, Pouch S, Manesh A, Giannella M. Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review. Transpl Int 2024; 37:12469. [PMID: 38952482 PMCID: PMC11215024 DOI: 10.3389/ti.2024.12469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 05/07/2024] [Indexed: 07/03/2024]
Abstract
Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.
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Affiliation(s)
- Maristela Pinheiro Freire
- Department of Infectious Diseases, Hospital das Clínicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Stephanie Pouch
- Transplant Infectious Diseases, Emory University School of Medicine, Atlanta, GA, United States
| | - Abi Manesh
- Department of Infectious Diseases, Christian Medical College, Vellore, India
| | - Maddalena Giannella
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Rodríguez-Gascón A, Lloréns-Villar Y, Solinís MÁ, Barrasa H, Canut-Blasco A. Does selective digestive decontamination (SDD) increase antibiotic resistance? Long-term comparison of two intensive care units (with and without SDD) of the same tertiary hospital. Eur J Clin Microbiol Infect Dis 2024; 43:885-893. [PMID: 38460030 PMCID: PMC11108900 DOI: 10.1007/s10096-024-04792-0] [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: 09/27/2023] [Accepted: 02/26/2024] [Indexed: 03/11/2024]
Abstract
PURPOSE The aim of this study was to to compare the antimicrobial resistance rate and its relationship with the antibiotic consumption in two separate Intensive Care Units (ICUs) of the same hospital, one with and other without selective decontamination of the digestive tract (SDD). METHODS We performed a retrospective study in the two ICUs of the Araba University Hospital. Trauma and neurosurgical patients are admitted to the SDD-ICU, and general digestive surgery patients go to the no SDD-ICU. From 2014 to 2018 we analyzed the number of isolates, and the bacterial resistance trends of 47 antimicrobial-microorganism combinations. Additionally, antimicrobial consumption was estimated in both ICUs. Resistance rates were also compared with those reported in ENVIN-HELICS Spanish national registry. RESULTS In the ICU with SDD protocol, there was a significant decrease in the resistance of E. coli to amoxicillin/clavulanic acid and in the resistance of E. faecalis to high concentration of gentamycin and high concentration of streptomycin. A significant increase of resistance of Staphylococcus coagulasa negative (CoNS) to linezolid in the no SDD-ICU was also detected. Overall, the level of resistance in the SDD-ICU was lower or of the same order than in the ICU without SDD and that reported in the Spanish national registry. CONCLUSIONS SDD had neither a clinically relevant impact on emergence and spread of resistance, nor in the overall systemic antimicrobial use. The patient type rather than the SDD protocol showed to condition the ecology and therefore, the resistance rate in the ICUs.
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Affiliation(s)
- Alicia Rodríguez-Gascón
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain.
- Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, Vitoria-Gasteiz, 01009, Spain.
| | - Yanire Lloréns-Villar
- Hospital Pharmacy Service, Araba University Hospital, Osakidetza Basque Health Service, Vitoria-Gasteiz, 01009, Spain
| | - María Ángeles Solinís
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain
- Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, Vitoria-Gasteiz, 01009, Spain
| | - Helena Barrasa
- Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, Vitoria-Gasteiz, 01009, Spain
- Intensive Care Unit, Osakidetza Basque Health Service, Araba University Hospital, Vitoria-Gasteiz, 01009, Spain
| | - Andrés Canut-Blasco
- Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, Vitoria-Gasteiz, 01009, Spain
- Microbiology Service, Osakidetza Basque Health Service, Araba University Hospital, Vitoria-Gasteiz, 01009, Spain
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Ko S, Kim J, Lim J, Lee SM, Park JY, Woo J, Scott-Nevros ZK, Kim JR, Yoon H, Kim D. Blanket antimicrobial resistance gene database with structural information, BOARDS, provides insights on historical landscape of resistance prevalence and effects of mutations in enzyme structure. mSystems 2024; 9:e0094323. [PMID: 38085058 PMCID: PMC10871167 DOI: 10.1128/msystems.00943-23] [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: 09/05/2023] [Accepted: 11/02/2023] [Indexed: 01/24/2024] Open
Abstract
Antimicrobial resistance (AMR) in pathogenic bacteria poses a significant threat to public health, yet there is still a need for development in the tools to deeply understand AMR genes based on genetic or structural information. In this study, we present an interactive web database named Blanket Overarching Antimicrobial-Resistance gene Database with Structural information (BOARDS, sbml.unist.ac.kr), a database that comprehensively includes 3,943 reported AMR gene information for 1,997 extended spectrum beta-lactamase (ESBL) and 1,946 other genes as well as a total of 27,395 predicted protein structures. These structures, which include both wild-type AMR genes and their mutants, were derived from 80,094 publicly available whole-genome sequences. In addition, we developed the rapid analysis and detection tool of antimicrobial-resistance (RADAR), a one-stop analysis pipeline to detect AMR genes across whole-genome sequencing (WGSs). By integrating BOARDS and RADAR, the AMR prevalence landscape for eight multi-drug resistant pathogens was reconstructed, leading to unexpected findings such as the pre-existence of the MCR genes before their official reports. Enzymatic structure prediction-based analysis revealed that the occurrence of mutations found in some ESBL genes was found to be closely related to the binding affinities with their antibiotic substrates. Overall, BOARDS can play a significant role in performing in-depth analysis on AMR.IMPORTANCEWhile the increasing antibiotic resistance (AMR) in pathogen has been a burden on public health, effective tools for deep understanding of AMR based on genetic or structural information remain limited. In this study, a blanket overarching antimicrobial-resistance gene database with structure information (BOARDS)-a web-based database that comprehensively collected AMR gene data with predictive protein structural information was constructed. Additionally, we report the development of a RADAR pipeline that can analyze whole-genome sequences as well. BOARDS, which includes sequence and structural information, has shown the historical landscape and prevalence of the AMR genes and can provide insight into single-nucleotide polymorphism effects on antibiotic degrading enzymes within protein structures.
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Affiliation(s)
- Seyoung Ko
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
- School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Jaehyung Kim
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Jaewon Lim
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Sang-Mok Lee
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Joon Young Park
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Jihoon Woo
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Zoe K. Scott-Nevros
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
| | - Jong R. Kim
- School of Engineering and Digital Sciences, Nazarbayev University, Astan, Kazakhstan
| | - Hyunjin Yoon
- Department of Molecular Science and Technology, Ajou University, Suwon, South Korea
| | - Donghyuk Kim
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
- School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
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Woodworth MH, Conrad RE, Haldopoulos M, Pouch SM, Babiker A, Mehta AK, Sitchenko KL, Wang CH, Strudwick A, Ingersoll JM, Philippe C, Lohsen S, Kocaman K, Lindner BG, Hatt JK, Jones RM, Miller C, Neish AS, Friedman-Moraco R, Karadkhele G, Liu KH, Jones DP, Mehta CC, Ziegler TR, Weiss DS, Larsen CP, Konstantinidis KT, Kraft CS. Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement. Sci Transl Med 2023; 15:eabo2750. [PMID: 37910603 PMCID: PMC10821315 DOI: 10.1126/scitranslmed.abo2750] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 06/05/2023] [Indexed: 11/03/2023]
Abstract
Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.
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Affiliation(s)
- Michael H. Woodworth
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Emory Antibiotic Resistance Center; Atlanta, Georgia, 30322, USA
| | - Roth E Conrad
- Ocean Science & Engineering, School of Biological Sciences, Georgia Institute of Technology; Atlanta, Georgia, 30332, USA
| | | | - Stephanie M. Pouch
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Emory Antibiotic Resistance Center; Atlanta, Georgia, 30322, USA
| | - Ahmed Babiker
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Emory Antibiotic Resistance Center; Atlanta, Georgia, 30322, USA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Aneesh K. Mehta
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Emory Transplant Center; Atlanta, Georgia, 30322, USA
| | - Kaitlin L. Sitchenko
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Charlotte H. Wang
- Emory College of Arts and Sciences, Emory University; Atlanta, Georgia, 30322, USA
| | - Amanda Strudwick
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Jessica M. Ingersoll
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Cécile Philippe
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Sarah Lohsen
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Kumru Kocaman
- School of Civil and Environmental Engineering, Georgia Institute of Technology; Atlanta, Georgia, 30332, USA
| | - Blake G. Lindner
- School of Civil and Environmental Engineering, Georgia Institute of Technology; Atlanta, Georgia, 30332, USA
| | - Janet K. Hatt
- School of Civil and Environmental Engineering, Georgia Institute of Technology; Atlanta, Georgia, 30332, USA
| | - Rheinallt M. Jones
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Candace Miller
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Andrew S. Neish
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - Rachel Friedman-Moraco
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | | | - Ken H. Liu
- Clinical Biomarkers Laboratory, Department of Medicine, Emory University; Atlanta, Georgia, 30322, USA
| | - Dean P. Jones
- Clinical Biomarkers Laboratory, Department of Medicine, Emory University; Atlanta, Georgia, 30322, USA
| | - C. Christina Mehta
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University; Atlanta, GA, 30322, USA
| | - Thomas R. Ziegler
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
| | - David S. Weiss
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Emory Antibiotic Resistance Center; Atlanta, Georgia, 30322, USA
| | | | | | - Colleen S. Kraft
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
- Emory Antibiotic Resistance Center; Atlanta, Georgia, 30322, USA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine; Atlanta, Georgia, 30322, USA
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Weng Y, Wang T, Huang B, Yu H, Jia W, Shan B, Qu F, Tang Y, Chen L, Du H. Multicenter Study of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Strains in China. Microbiol Spectr 2023; 11:e0221822. [PMID: 37428093 PMCID: PMC10434274 DOI: 10.1128/spectrum.02218-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 06/23/2023] [Indexed: 07/11/2023] Open
Abstract
Colistin has been considered a last-line option for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Heterogeneous resistance to colistin leads to unexplained clinical colistin treatment failure for CRKP. Our study aimed to investigate the extent of colistin heteroresistance among CRKP strains in China. A total of 455 colistin-susceptible strains, collected from six tertiary care hospitals in China, were characterized. The overall rate of colistin heteroresistance was 6.2%, as determined by the population analysis profiles (PAPs). Genomic analysis revealed that 60.7% of the colistin-heteroresistant isolates belonged to the epidemic sequence type 11 (ST11) clone. Single-nucleotide polymorphisms (SNPs) suggested that 6 ST5216 strains shared the same origin. Each of the subpopulations had a ≥8-fold decrease in colistin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), which indicated that heteroresistance could be suppressed by an efflux pump inhibitor. In addition, our results suggested that the PhoPQ pathway plays an important role in the mechanisms of heteroresistance. IMPORTANCE The problem of CRKP has raised alarms concerning global health. Our study enriches the epidemiological study of colistin heteroresistance among CRKP strains in China, where the prevalence of this phenomenon was previously unknown. Importantly, colistin-heteroresistant strains may cause the failure of clinical treatment with colistin, even if the clinical laboratory reports that the strains are sensitive. The commonly used broth microdilution method is unable to detect this special phenomenon. Additionally, our results indicate that efflux pumps play a major role in colistin heteroresistance, and inhibitors can effectively reverse it. Our study is the first to provide a detailed analysis of the prevalence of colistin heteroresistance in China, as well as an analysis of the genetic mechanisms of this phenomenon.
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Affiliation(s)
- Yuesong Weng
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Department of Clinical Laboratory, The Affiliated Peoples' Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Laboratory Medicine, Ningbo First Hospital, Ningbo, Zhejiang, China
| | - Tao Wang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Bin Huang
- Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hua Yu
- Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China
| | - Wei Jia
- Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Bin Shan
- Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Fen Qu
- Laboratory Medicine Center, Aviation General Hospital, Beijing, China
| | - Yiwei Tang
- Department of Medical Affairs, Danaher Diagnostic Platform/Cepheid (China), New York, New York, USA
| | - Liang Chen
- Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA
- Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
| | - Hong Du
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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9
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Dolci G, Burastero GJ, Paglia F, Cervo A, Meschiari M, Guaraldi G, Chester J, Mussini C, Franceschini E. Epidemiology and Prevention of Early Infections by Multi-Drug-Resistant Organisms in Adults Undergoing Liver Transplant: A Narrative Review. Microorganisms 2023; 11:1606. [PMID: 37375108 DOI: 10.3390/microorganisms11061606] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/03/2023] [Accepted: 06/14/2023] [Indexed: 06/29/2023] Open
Abstract
Invasive bacterial infections are a leading cause of morbidity and mortality after liver transplant (LT), especially during the first months after LT, and infections due to multi-drug-resistant organisms (MDRO) are increasing in this setting. Most of the infections in patients in intensive care unit arise from the endogenous microflora and, for this reason, pre-LT MDRO rectal colonization is a risk factor for developing MDRO infections in the post-LT. Moreover, the transplanted liver may carry an increased risk of MDRO infections due to organ transportation and preservation, to donor intensive care unit stay and previous antibiotic exposure. To date, little evidence is available about how MDRO pre-LT colonization in donors and recipients should address LT preventive and antibiotic prophylactic strategies, in order to reduce MDRO infections in the post-LT period. The present review provided an extensive overview of the recent literature on these topics, with the aim to offer a comprehensive insight about the epidemiology of MDRO colonization and infections in adult LT recipients, donor-derived MDRO infections, possible surveillance, and prophylactic strategies to reduce post-LT MDRO infections.
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Affiliation(s)
- Giovanni Dolci
- Infectious Diseases Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy
| | - Giulia Jole Burastero
- Infectious Diseases Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy
| | - Francesca Paglia
- Infectious Diseases Unit, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Adriana Cervo
- Infectious Diseases Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy
| | - Marianna Meschiari
- Infectious Diseases Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy
| | - Giovanni Guaraldi
- Infectious Diseases Unit, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Johanna Chester
- Department of Dermatology, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Cristina Mussini
- Infectious Diseases Unit, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Erica Franceschini
- Infectious Diseases Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy
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10
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Alsolami A, ALGhasab NS, Alharbi MSM, Bashir AI, Saleem M, Syed Khaja AS, Aldakheel DF, Rakha E, Alshammari JA, Taha TE, Melibari Z, Alharbi YH, Almutlag AA, Said KB. Community-Acquired Methicillin-Resistant Staphylococcus aureus in Hospitals: Age-Specificity and Potential Zoonotic-Zooanthroponotic Transmission Dynamics. Diagnostics (Basel) 2023; 13:2089. [PMID: 37370983 PMCID: PMC10297644 DOI: 10.3390/diagnostics13122089] [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: 05/08/2023] [Revised: 05/29/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023] Open
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) lineages are a devastating clinical and public health issue. Data on local lineage profiles are limited. We report on the frequency of community-acquired and hospital-acquired cases (CA-MRSA, HA-MRSA). We studied 147 isolates from King Khalid tertiary care hospitals (KKH), each from a case in a patient and including 33 patients at the Maternity and Children's Hospital (MCH). Of the 147 isolates, 87 males (59%) and 60 females (41%) were in KKH. The overwhelming majority (80%; n = 119/147) were CA-MRSA in KKH. Intriguingly, despite significant differences between males (70%) and females (53%), lineage-acquisition remained age-specific around 58-60 years in both genders. However, while CA-MRSA dominated early in life (0-20, 70% MCH), it increased with age in KKH adults; 21-50 (28%), >50 (59%) until the overall 80% (n = 144/180). Major specimens included skin-wounds, surgeries (70.3%), blood (13.5%), sputum (8.8%), very rarely urine (4.1%), and nasal (3.4%), albeit most patients showed severe enteritis and necrotizing pneumonia. Antibiograms showed high beta lactam resistances, including amoxicillin-clavulanate (83%), oxacillin (84%), cefoxitin FOX (100%), penicillin and ampicillin (~100%), as well as high resistance (82%) to carbapenem. Fortunately, high susceptibility was seen to non-beta lactams and, to a lesser extent, gentamicin, erythromycin, and fusidic acid; 33%, 34%, and 38%, respectively, in KKH. A similar pattern was seen in MCH except for a low resistance pattern to gentamicin CN, clindamycin CD, erythromycin E, and tobramycin TOB; 34%, 31%, 39%, and 41%, respectively, except for fusidic acid. These findings have significant clinical implications for MRSA patient management strategies. Clinical- and lineage-profiles imply host-selection and zoonotic-zooanthroponotic transmission dynamics. Future molecular typing, sequencing, and characterization of dominant clone(s) is imperative.
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Affiliation(s)
- Ahmed Alsolami
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (A.A.); (M.S.M.A.)
| | - Naif Saad ALGhasab
- Department of Cardiology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia;
| | - Mohammed S. M. Alharbi
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (A.A.); (M.S.M.A.)
| | - Abdelhafiz I. Bashir
- Department of Physiology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia
| | - Mohd Saleem
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
| | - Azharuddin Sajid Syed Khaja
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
| | | | - Ehab Rakha
- Departments of Microbiology, King Khalid Hospital, Ha’il 55421, Saudi Arabia;
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Jabar Aziz Alshammari
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
| | - Taha E. Taha
- Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | - Ziyad Melibari
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
| | - Yaseer H. Alharbi
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
| | - Ali A. Almutlag
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
| | - Kamaleldin B. Said
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55476, Saudi Arabia; (M.S.); (A.S.S.K.); (J.A.A.); (Z.M.); (Y.H.A.); (A.A.A.)
- Genomics, Bioinformatics and Systems Biology, Carleton University, 1125 Colonel-By Drive, Ottawa, ON K1S 5B6, Canada
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11
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Leone M, Duclos G, Lakbar I, Martin-Loeches I, Einav S. Antimicrobial resistance and outcome in the critically ill patient: An opinion paper. J Crit Care 2023; 77:154352. [PMID: 37302284 DOI: 10.1016/j.jcrc.2023.154352] [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: 03/17/2023] [Revised: 05/31/2023] [Accepted: 05/31/2023] [Indexed: 06/13/2023]
Abstract
Antimicrobial resistance (AMR) is associated with increased mortality and resources consumption in critically ill patients. However, the causality of AMR in this mortality remains unclear. This opinion paper aims to overview the effects of multidrug resistant (MDR) pathogens on the outcomes of critically ill patients, considering different variables as appropriateness of empirical antimicrobial therapy, severity of sepsis, comorbid conditions and frailty. Large studies based on national database associated MDR and increased mortality in critically ill patients. However, the patients carrying MDR pathogens, as compared with those carrying non-MDR pathogens, are those with co-morbid conditions, high risk of frailty and invasive procedures. In addition, inappropriate empirical antibiotics are more often used in these patients as well as withholding and withdrawing of life-sustained therapy. Future studies on AMR should report the rate of appropriateness of empirical antimicrobial therapy, withholding and withdrawing of life-sustained therapy.
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Affiliation(s)
- Marc Leone
- Department of Anaesthesiology and Intensive Care Unit, North Hospital, Assistance Publique Hôpitaux Universitaires de Marseille, Aix Marseille University, Marseille, France; Centre for Nutrition and Cardiovascular Disease (C2VN), INSERM, INRAE, Aix Marseille University, 13005 Marseille, France.
| | - Gary Duclos
- Department of Anaesthesiology and Intensive Care Unit, North Hospital, Assistance Publique Hôpitaux Universitaires de Marseille, Aix Marseille University, Marseille, France
| | - Ines Lakbar
- Department of Anaesthesiology and Intensive Care Unit, North Hospital, Assistance Publique Hôpitaux Universitaires de Marseille, Aix Marseille University, Marseille, France; CEReSS, Health Service Research and Quality of Life Centre, School of Medicine, La Timone, Aix-Marseille University, Marseille, France
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James' Hospital, Dublin, Ireland
| | - Sharon Einav
- Hebrew University Faculty of Medicine, Jerusalem 23456, Israel; Intensive Care Unit of the Shaare Zedek Medical Center, Jerusalem Y56L5, Israel
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12
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Lee EH, Lee SK, Cheon JH, Koh H, Lee JA, Kim CH, Kim JN, Lee KH, Lee SJ, Kim JH, Ahn JY, Jeong SJ, Ku NS, Yong DE, Yoon SS, Yeom JS, Choi JY. Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube. J Hosp Infect 2023; 131:234-243. [PMID: 36414164 DOI: 10.1016/j.jhin.2022.11.007] [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: 07/28/2022] [Revised: 11/08/2022] [Accepted: 11/12/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.
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Affiliation(s)
- E H Lee
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - S K Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - J H Cheon
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - H Koh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Severance Children's Hospital, Severance Pediatric Liver Disease Research Group, Yonsei University College of Medicine, Seoul, South Korea
| | - J A Lee
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - C H Kim
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - J N Kim
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - K H Lee
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - S J Lee
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - J H Kim
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - J Y Ahn
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - S J Jeong
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - N S Ku
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - D E Yong
- Division of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea
| | - S S Yoon
- Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, South Korea
| | - J S Yeom
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - J Y Choi
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
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13
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COVID-19 Secondary Infections in ICU Patients and Prevention Control Measures: A Preliminary Prospective Multicenter Study. Antibiotics (Basel) 2022; 11:antibiotics11081016. [PMID: 36009884 PMCID: PMC9405068 DOI: 10.3390/antibiotics11081016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/22/2022] [Accepted: 07/26/2022] [Indexed: 12/15/2022] Open
Abstract
The incidence of secondary infections in critically ill coronavirus disease 2019 (COVID-19) patients is worrisome. We investigated whether selective digestive decontamination (SDD) added to infection control measures during an intensive care unit (ICU) stay modified these infection rates. Methods: A retrospective observational cohort study was carried out in four ICUs in Spain. All consecutive ventilated patients with a SARS-CoV-2 infection engaged in national infection control programs between 1 March and 10 December 2020 were investigated. Patients were grouped into two cohorts according to the site of ICU admission. Secondary relevant infections were included. Infection densities corresponding to ventilator-associated pneumonia (VAP), catheter bacteremia, secondary bacteremia, and multi-resistant germs were obtained as the number of events per 1000 days of exposure and were compared between SDD and non-SDD groups using Poisson regression. Factors that had an independent association with mortality were identified using multidimensional logistic analysis. Results: There were 108 patients in the SDD cohort and 157 in the non-SDD cohort. Patients in the SDD cohort showed significantly lower rates (p < 0.001) of VAP (1.9 vs. 9.3 events per 1000 ventilation days) and MDR infections (0.57 vs. 2.28 events per 1000 ICU days) and a non-significant reduction in secondary bacteremia (0.6 vs. 1.41 events per 1000 ICU days) compared with those in the non-SDD cohort. Infections caused by MDR pathogens occurred in 5 patients in the SDD cohort and 21 patients in the non-SDD cohort (p = 0.006). Differences in mortality according to SDD were not found. Conclusion: The implementation of SDD in infection control programs significantly reduced the incidence of VAP and MDR infections in critically ill SARS-CoV-2 infected patients.
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A prospective matched case-control study on the genomic epidemiology of colistin-resistant Enterobacterales from Dutch patients. COMMUNICATIONS MEDICINE 2022; 2:55. [PMID: 35607432 PMCID: PMC9122983 DOI: 10.1038/s43856-022-00115-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 04/20/2022] [Indexed: 11/08/2022] Open
Abstract
Abstract
Background
Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing.
Methods
A six-month prospective matched case-control study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maximum of five colistin-resistant Escherichia coli or Klebsiella pneumoniae (COLR-EK) isolates and five colistin-susceptible isolates (COLS-EK) to the reference laboratory, matched for patient location, material of origin and bacterial species. Epidemiological/clinical data were collected and included in the analysis. Characteristics of COLR-EK/COLS-EK isolates were compared using logistic regression with correction for variables used for matching. Forty-six ColR-EK/ColS-EK pairs were analysed by next-generation sequencing (NGS) for whole-genome multi-locus sequence typing and identification of resistance genes, including mcr genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of pmrAB, phoPQ, mgrB and crrB.
Results
In total, 72 COLR-EK/COLS-EK pairs (75% E. coli and 25% K. pneumoniae) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR > 2.9). Of COLR-EK isolates, five contained mcr-1 and two mcr-9. One isolate lost mcr-9 after repeated sub-culturing, but retained colistin resistance. Among 46 sequenced COLR-EK isolates, genetic diversity was large and 19 (41.3%) isolates had chromosomal mutations potentially associated with colistin resistance.
Conclusions
Colistin resistance is present but uncommon in the Netherlands and caused by the mcr gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.
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15
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Association between Timing of Colonization and Risk of Developing Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infection in Hospitalized Patients. Microbiol Spectr 2022; 10:e0197021. [PMID: 35323035 PMCID: PMC9045231 DOI: 10.1128/spectrum.01970-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Colonization by KPC-producing Klebsiella pneumoniae (KPC-Kp) is associated with the risk of developing KPC-Kp infection. The impact of the time elapsed since a patient becomes colonized on this risk is not well known. An observational, prospective, longitudinal cohort study of colonized patients undergoing active rectal culture screening to rule out KPC-Kp colonization (July 2012 to November 2017). Patients with a positive culture at inclusion (colonized at start of follow-up) and those with a negative culture at inclusion who became colonized within 90 days (colonized during follow-up) were included in the analysis. CART analysis was used to dichotomize variables according to their association with infection. Kaplan–Meier infection-free survival curves and the log-rank test were used for group comparisons. Logistic regression was used to identify variables associated with KPC-Kp infection. Among 1310 patients included, 166 were colonized at the end of follow-up. Forty-seven out of 118 patients colonized at start of follow-up developed infection (39.8%) versus 31 out of 48 patients colonized during follow-up (64.6%; P = 0.006). Variables associated with KPC-Kp infection in the logistic regression analysis were: colonization detection during follow-up (OR, 2.74; 95% CI, 1.07 to 7.04; P = 0.03), Giannella risk score (OR, 1.51; 95% CI, 1.32 to 1.73; P < 0.001), high-risk ward (OR, 4.77; 95% CI, 1.61 to 14.10; P = 0.005) and urological manipulation after admission (OR, 3.69; 95% CI, 1.08 to 12.60; P = 0.04). In 25 out of 31 patients (80.6%) colonized during follow-up who developed KPC-Kp infection, infection appeared within 15 days after colonization. The risk of KPC-Kp infection was higher when colonization is recently acquired during hospitalization. In this prospective study, we concluded that the timing of colonization was a factor to assess when considering empirical treatment for suspected KPC-Kp infection and prophylaxis or infection control. IMPORTANCE In this study, it was confirmed that patients who became colonized during hospitalization had a higher risk of developing KPC-Kp infection than hospitalized patients who were already colonized at the start of follow-up. Besides, the risk of infection in the group of patients who became colonized during follow-up was greater in the first weeks immediately after colonization was confirmed. Our findings support the need for designing preventive strategies for patients at the highest risk of infection development, including those admitted in high-risk hospital wards and those undergoing urological procedures.
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Főldes A, Székely E, Voidăzan ST, Dobreanu M. Comparison of Six Phenotypic Assays with Reference Methods for Assessing Colistin Resistance in Clinical Isolates of Carbapenemase-Producing Enterobacterales: Challenges and Opportunities. Antibiotics (Basel) 2022; 11:antibiotics11030377. [PMID: 35326840 PMCID: PMC8944616 DOI: 10.3390/antibiotics11030377] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 02/27/2022] [Accepted: 03/09/2022] [Indexed: 02/01/2023] Open
Abstract
The global escalation of severe infections due to carbapenemase-producing Enterobacterales (CPE) isolates has prompted increased usage of parenteral colistin. Considering the reported difficulties in assessing their susceptibility to colistin, the purpose of the study was to perform a comparative evaluation of six phenotypic assays—the colistin broth disc elution (CBDE), Vitek 2 Compact (bioMérieux SA, Marcy l’Etoile, France), the Micronaut MIC-Strip Colistin (Merlin Diagnostika GMBH, Bornheim-Hensel, Germany), the gradient diffusion strip Etest (bioMérieux SA, Marcy l’Etoile, France), ChromID Colistin R Agar (COLR) (bioMérieux SA, Marcy l’Etoile, France), and the Rapid Polymyxin NP Test (ELITechGroup, Signes, France)—versus the reference method of broth microdilution (BMD). All false resistance results were further assessed using population analysis profiling (PAP). Ninety-two nonrepetitive clinical CPE strains collected from two hospitals were evaluated. The BMD confirmed 36 (39.13%) isolates susceptible to colistin. According to the BMD, the Micronaut MIC-Strip Colistin, the CBDE, and the COLR medium exhibited category agreement (CA) of 100%. In comparison with the BMD, the highest very major discrepancy (VMD) was noted for Etest (n = 15), and the only false resistance results were recorded for the Rapid Polymyxin NP Test (n = 3). Only the PAP method and the Rapid Polymyxin NP Test were able to detect heteroresistant isolates (n = 2). Thus, there is an urgent need to further optimize the diagnosis strategies for colistin resistance.
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Affiliation(s)
- Annamária Főldes
- Department of Microbiology, Laboratory of Medical Analysis, “Dr. Constantin Opriş” County Emergency Hospital, 430031 Baia Mare, Romania
- Doctoral School of Medicine and Pharmacy, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania
- Correspondence:
| | - Edit Székely
- Department of Microbiology, Central Clinical Laboratory, County Emergency Clinical Hospital, 540136 Targu Mures, Romania;
- Department of Microbiology, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania
| | - Septimiu Toader Voidăzan
- Department of Epidemiology, “George Emil Palade’’ University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania;
| | - Minodora Dobreanu
- Department of Clinical Biochemistry, Central Clinical Laboratory, County Emergency Clinical Hospital, 540136 Targu Mures, Romania;
- Department of Laboratory Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania
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17
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Deshayes C, Arafath MN, Apaire-Marchais V, Roger E. Drug Delivery Systems for the Oral Administration of Antimicrobial Peptides: Promising Tools to Treat Infectious Diseases. FRONTIERS IN MEDICAL TECHNOLOGY 2022; 3:778645. [PMID: 35146486 PMCID: PMC8821882 DOI: 10.3389/fmedt.2021.778645] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022] Open
Abstract
Antimicrobial peptides (AMPs) have a great potential to face the global expansion of antimicrobial resistance (AMR) associated to the development of multidrug-resistant (MDR) pathogens. AMPs are usually composed of 10–50 amino acids with a broad structural diversity and present a range of antimicrobial activities. Unfortunately, even if the oral route is the most convenient one, currently approved therapeutic AMPs are mostly administrated by the intravenous route. Thus, the development of novel drug delivery systems (DDSs) represents a promising opportunity to protect AMPs from chemical and enzymatic degradation through the gastrointestinal tract and to increase intestinal permeability leading to high bioavailability. In this review, the classification and properties as well as mechanisms of the AMPs used in infectiology are first described. Then, the different pharmaceutical forms existing in the market for oral administration are presented. Finally, the formulation technologies, including microparticle- and nanoparticle-based DDSs, used to improve the oral bioavailability of AMPs are reviewed.
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Affiliation(s)
| | | | | | - Emilie Roger
- University of Angers, INSERM, CNRS, MINT, SFR ICAT, Angers, France
- *Correspondence: Emilie Roger
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18
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Szychowiak P, Villageois-Tran K, Patrier J, Timsit JF, Ruppé É. The role of the microbiota in the management of intensive care patients. Ann Intensive Care 2022; 12:3. [PMID: 34985651 PMCID: PMC8728486 DOI: 10.1186/s13613-021-00976-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 12/15/2021] [Indexed: 12/13/2022] Open
Abstract
The composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter's consequences. Last, we assess the means to prevent or correct microbiota alteration.
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Affiliation(s)
- Piotr Szychowiak
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Service de Médecine Intensive-Réanimation, Centre Hospitalier Régional Universitaire de Tours, 37000, Tours, France
| | - Khanh Villageois-Tran
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Laboratoire de Bactériologie, AP-HP, Hôpital Beaujon, 92110, Paris, France
| | - Juliette Patrier
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Service de Réanimation Médicale Et Infectieuse, AP-HP, Hôpital Bichat, 75018, Paris, France
| | - Jean-François Timsit
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Service de Réanimation Médicale Et Infectieuse, AP-HP, Hôpital Bichat, 75018, Paris, France
| | - Étienne Ruppé
- Université de Paris, IAME, INSERM, 75018, Paris, France.
- Laboratoire de Bactériologie, AP-HP, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018, Paris, France.
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19
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Park NH, Lee SJ, Lee EB, Birhanu BT, Park SC. Colistin Induces Resistance through Biofilm Formation, via Increased phoQ Expression, in Avian Pathogenic Escherichia coli. Pathogens 2021; 10:pathogens10111525. [PMID: 34832681 PMCID: PMC8620993 DOI: 10.3390/pathogens10111525] [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: 10/13/2021] [Revised: 11/12/2021] [Accepted: 11/17/2021] [Indexed: 11/16/2022] Open
Abstract
This study aimed to optimize the colistin-based antibacterial therapy to prevent antimicrobial resistance related to biofilm formation in avian pathogenic Escherichia coli (APEC) in chicken. Of all the bacterial isolates (n = 136), 69 were identified as APEC by polymerase chain reaction (PCR). Through a series of antibiotic susceptibility tests, susceptibility to colistin (<2 μg/mL) was confirmed in all isolates. Hence, a mutant selection window (MSW) was determined to obtain colistin-induced resistant bacteria. The minimum inhibitory concentration (MIC) of colistin against the colistin-induced resistant APEC strains ranged from 8 to 16 μg/mL. To identify the inhibitory activity of colistin against the resistant strains, the mutant prevention concentration (MPC) was investigated for 72 h, and the single and multi-dose colistin activities were determined through the time-kill curve against APEC strains. Bacterial regrowth occurred after 12 h at a double MIC50 concentration (1.00 μg/mL), and regrowth was not inhibited even during multiple exposures. However, upon exposure to 8 μg/mL—a concentration that was close to the MPC—the growth of APEC was inhibited, including in the resistant strains. Additionally, colistin-induced resistant strains showed a slower growth compared with the susceptible ones. Colistin-induced resistant APEC strains did not show colistin resistance gene (mcr-1). However, the expression of higher mgrB and phoQ levels was observed in the resistant strains. Furthermore, these strains showed increased formation of biofilm. Hence, the present study indicated that colistin could induce resistance through the increased formation of biofilm in APEC strains by enhancing the expression of phoQ.
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Affiliation(s)
- Na-Hye Park
- Laboratory Animal Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea;
| | - Seung-Jin Lee
- Reproductive and Developmental Toxicology Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea;
| | - Eon-Bee Lee
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea;
| | - Biruk Tesfaye Birhanu
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea;
- Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Korea
- Correspondence: (B.T.B.); (S.-C.P.); Tel.: +82-53-950-5964 (B.T.B. & S.-C.P.)
| | - Seung-Chun Park
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea;
- Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Korea
- Correspondence: (B.T.B.); (S.-C.P.); Tel.: +82-53-950-5964 (B.T.B. & S.-C.P.)
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20
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Mills JP, Marchaim D. Multidrug-Resistant Gram-Negative Bacteria: Infection Prevention and Control Update. Infect Dis Clin North Am 2021; 35:969-994. [PMID: 34752228 DOI: 10.1016/j.idc.2021.08.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Multidrug-resistant gram-negative bacteria (MDR-GNB) pose one of the greatest challenges to health care today because of their propensity for human-to-human transmission and lack of therapeutic options. Containing the spread of MDR-GNB is challenging, and the application of multifaceted infection control bundles during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article will review the utility of various infection control measures in containing the spread of various MDR-GNB and will provide the supporting evidence for these interventions.
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Affiliation(s)
- John P Mills
- Division of Infectious Diseases, University of Michigan Medical School, F4177 University Hospital South, 1500 E. Medical Center Dr, Ann Arbor, MI 48109-5226, USA.
| | - Dror Marchaim
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Infectious Diseases, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
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21
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Ishnaiwer M, Bezabih Y, Javaudin F, Sassi M, Bemer P, Batard E, Dion M. In vitro and in vivo activity of new strains of Bacillus subtilis against ESBL-producing Escherichia coli: an experimental study. J Appl Microbiol 2021; 132:2270-2279. [PMID: 34679216 DOI: 10.1111/jam.15329] [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: 06/07/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 11/29/2022]
Abstract
AIMS The gastro-intestinal tract is a major reservoir of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. Bacillus spores may be used as probiotics to decrease digestive colonization by ESBL-E. coli. Our aim was to assess the in vitro and in vivo activity of new Bacillus strains against ESBL-E. coli. METHODS AND RESULTS We screened the in vitro activity of 50 Bacillus strains against clinical isolates of ESBL-E. coli and selected B. subtilis strains CH311 and S3B. Both strains decreased ESBL-E. coli titers by 4 log10 CFU L-1 in an in vitro model of gut content, whereas the B. subtilis CU1 strain did not. In a murine model of intestinal colonization by ESBL-E. coli, CH311 and S3B did not decrease fecal titers of ESBL-E. coli. Ten sequences of putative antimicrobial peptides were identified in the genomes of CH311 and S3B, but not in CU1. CONCLUSIONS Two new B. subtilis strains showed strong in vitro activity against ESBL-E. coli. SIGNIFICANCE AND IMPACT OF STUDY Despite strong in vitro activities of new B. subtilis strains against ESBL-E. coli, intestinal colonisation was not altered by curative Bacillus treatment even if their spores proved to germinate in the gut. Thus, this work underlines the importance of in vivo experiments to identify efficient probiotics. The use of potential antimicrobial compounds identified by genome sequencing remains an attractive alternative to explore.
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Affiliation(s)
| | | | - François Javaudin
- MiHAR Lab, EE1701, University of Nantes, Nantes, France.,Emergency Department, CHU Nantes, Nantes, France
| | - Mohamed Sassi
- Inserm, BRM [Bacterial Regulatory RNAs and Medicine] - UMR_S 1230, Université de Rennes 1, Rennes, France
| | - Pascale Bemer
- MiHAR Lab, EE1701, University of Nantes, Nantes, France.,Department of Bacteriology, University Hospital, CHU Nantes, Nantes, France
| | - Eric Batard
- MiHAR Lab, EE1701, University of Nantes, Nantes, France.,Emergency Department, CHU Nantes, Nantes, France
| | - Michel Dion
- MiHAR Lab, EE1701, University of Nantes, Nantes, France
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22
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Modelling and Simulation of the Effect of Targeted Decolonisation on Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections in Haematological Patients. Infect Dis Ther 2021; 11:129-143. [PMID: 34665434 PMCID: PMC8847524 DOI: 10.1007/s40121-021-00550-3] [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: 04/22/2021] [Accepted: 10/11/2021] [Indexed: 11/21/2022] Open
Abstract
Introduction Haematological patients are at higher risk of bloodstream infections (BSI) after chemotherapy. The aim of this study was to develop a simulation model assessing the impact of selective digestive decontamination (SDD) of haematological patients colonised with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) on the incidence of ESBL-E BSI after chemotherapy. Methods A patient population was created by a stochastic simulation model mimicking the patients’ states of colonisation with ESBL-E during hospitalisation. A systematic literature search was performed to inform the model. All ESBL-E carriers were randomised (1:1) to either the intervention (targeted SDD) or the control group (placebo). ESBL-E BSI incidence was the outcome of the model. Sensitivity analyses were performed by prevalence of ESBL-E carriage at hospital admission (low: < 10%, medium: 10–25%, high: > 25%), duration of neutropenia after receiving chemotherapy, administration of antibiotic prophylaxis with quinolones, and time interval between SDD and chemotherapy. Results The model estimated that the administration of targeted SDD before chemotherapy reduces the incidence of ESBL-E BSI in the hospitalised haematological population up to 27%. The greatest benefit was estimated in high-prevalence settings, regardless of the duration of neutropenia, the time interval before chemotherapy, and the administration of antibiotic prophylaxis with quinolones (p < 0.05). In medium-prevalence settings, SDD was effective in patients receiving quinolone prophylaxis, with either 1-day time interval before chemotherapy and a neutropenia duration > 6 days (p < 0.05) or 7-day time interval before chemotherapy and a neutropenia duration > 9 days (p < 0.05). No benefit was observed in low-prevalence settings. Conclusions Our model suggests that targeted SDD could decrease the rate of ESBL-E BSI in haematological carriers before chemotherapy in the setting of high ESBL-E prevalence at hospital admission. These estimates require confirmation by well-designed multicentre RCTs, including the assessment of the impact on resistance/disruption patterns of gut microbiome. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00550-3.
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23
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Catho G, Martischang R, Boroli F, Chraïti MN, Martin Y, Koyluk Tomsuk Z, Renzi G, Schrenzel J, Pugin J, Nordmann P, Blanc DS, Harbarth S. Outbreak of Pseudomonas aeruginosa producing VIM carbapenemase in an intensive care unit and its termination by implementation of waterless patient care. Crit Care 2021; 25:301. [PMID: 34412676 PMCID: PMC8376114 DOI: 10.1186/s13054-021-03726-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 08/09/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Long-term outbreaks of multidrug-resistant Gram-negative bacilli related to hospital-building water systems have been described. However, successful mitigation strategies have rarely been reported. In particular, environmental disinfection or replacement of contaminated equipment usually failed to eradicate environmental sources of Pseudomonas aeruginosa. METHODS We report the investigation and termination of an outbreak of P. aeruginosa producing VIM carbapenemase (PA-VIM) in the adult intensive care unit (ICU) of a Swiss tertiary care hospital with active case finding, environmental sampling and whole genome sequencing (WGS) of patient and environmental strains. We also describe the implemented control strategies and their effectiveness on eradication of the environmental reservoir. RESULTS Between April 2018 and September 2020, 21 patients became either infected or colonized with a PA-VIM strain. For 16 of them, an acquisition in the ICU was suspected. Among 131 environmental samples collected in the ICU, 13 grew PA-VIM in sink traps and drains. WGS confirmed the epidemiological link between clinical and environmental strains and the monoclonal pattern of the outbreak. After removing sinks from patient rooms and implementation of waterless patient care, no new acquisition was detected in the ICU within 8 months after the intervention. DISCUSSION Implementation of waterless patient care with removal of the sinks in patient rooms was successful for termination of a PA-VIM ICU outbreak linked to multiple environmental water sources. WGS provides highly discriminatory accuracy to investigate environment-related outbreaks.
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Affiliation(s)
- Gaud Catho
- Infection Control Program, WHO Collaborating Center for Patient Safety, Faculty of Medicine, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 4, CH-1205, Geneva, Switzerland.
| | - R Martischang
- Infection Control Program, WHO Collaborating Center for Patient Safety, Faculty of Medicine, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 4, CH-1205, Geneva, Switzerland
| | - F Boroli
- Division of Critical Care, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - M N Chraïti
- Infection Control Program, WHO Collaborating Center for Patient Safety, Faculty of Medicine, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 4, CH-1205, Geneva, Switzerland
| | - Y Martin
- Infection Control Program, WHO Collaborating Center for Patient Safety, Faculty of Medicine, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 4, CH-1205, Geneva, Switzerland
| | - Z Koyluk Tomsuk
- Division of Critical Care, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - G Renzi
- Bacteriology Laboratory, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - J Schrenzel
- Bacteriology Laboratory, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - J Pugin
- Division of Critical Care, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - P Nordmann
- Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
- Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland
| | - D S Blanc
- Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland
- Service of Hospital Preventive Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - S Harbarth
- Infection Control Program, WHO Collaborating Center for Patient Safety, Faculty of Medicine, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 4, CH-1205, Geneva, Switzerland
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24
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Wang Q, Miao J, Feng K, Liu J, Li W, Li J, Yang Z, Cao Y. Antibacterial action of peptide F1 against colistin resistance E. coli SHP45 ( mcr-1). Food Funct 2021; 11:10231-10241. [PMID: 33169751 DOI: 10.1039/d0fo01923b] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The emergence of the plasmid-mediated colistin resistance mechanism (mcr-1) makes bacterial resistance to colistin increasingly serious. This mcr-1 mediated bacterial resistance to colicin is conferred primarily through modification of lipid A in lipopolysaccharides (LPS). In our previous research, antimicrobial peptide F1 was derived from Tibetan kefir and has been shown to effectively inhibit the growth of Gram-negative bacteria (E. coli), Gram-positive bacteria (Staphylococcus aureus), and other pathogenic bacteria. Based on this characteristic of antibacterial peptide F1, we speculated that it could inhibit the growth of the colicin-resistant E. coli SHP45 (mcr-1) and not easily produce drug resistance. Studies have shown that antimicrobial peptide F1 can destroy the liposome structure of the phospholipid bilayer by destroying the inner and outer membranes of bacteria, thereby significantly inhibiting the growth of E. coli SHP45 (mcr-1), but without depending on LPS. The results of this study confirmed our hypothesis, and we anticipate that antimicrobial peptide F1 will become a safe antibacterial agent that can assist in solving the problem of drug resistance caused by colistin.
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Affiliation(s)
- Qun Wang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
| | - Jianyin Miao
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
| | - Konglong Feng
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
| | - Jianhua Liu
- National Risk Assessment Laboratory for Antimicrobial Resistance of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - Wei Li
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
| | - Jun Li
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
| | - Zhijie Yang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
| | - Yong Cao
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
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Pruss A, Kwiatkowski P, Łopusiewicz Ł, Masiuk H, Sobolewski P, Fijałkowski K, Sienkiewicz M, Smolak A, Giedrys-Kalemba S, Dołęgowska B. Evaluation of Chemical Changes in Laboratory-Induced Colistin-Resistant Klebsiella pneumoniae. Int J Mol Sci 2021; 22:ijms22137104. [PMID: 34281159 PMCID: PMC8268070 DOI: 10.3390/ijms22137104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 06/25/2021] [Accepted: 06/29/2021] [Indexed: 12/03/2022] Open
Abstract
This study evaluates the electrical potential and chemical alterations in laboratory-induced colistin-resistant Klebsiella pneumoniae, as compared to the susceptible strain using spectroscopic analyses. The minimal inhibitory concentration (MIC) of colistin, ζ-potential and chemical composition analysis of K. pneumoniae strains are determined. The results obtained for the K. pneumoniaeCol-R with induced high-level colistin resistance (MIC = 16.0 ± 0.0 mg/L) are compared with the K. pneumoniaeCol-S strain susceptible to colistin (MIC = 0.25 ± 0.0 mg/L). Fourier transform infrared (FTIR) and Raman spectroscopic studies revealed differences in bacterial cell wall structures and lipopolysaccharide (LPS) of K. pneumoniaeCol-R and K. pneumoniaeCol-S strains. In the beginning, we assumed that the obtained results could relate to a negative charge of the bacterial surface and different electrostatic interactions with cationic antibiotic molecules, reducing the affinity of colistin and leading to its lower penetration into K. pneumoniaeCol-R cell. However, no significant differences in the ζ-potential between the K. pneumoniaeCol-R and K. pneumoniaeCol-S strains are noticed. In conclusion, this mechanism is most probably associated with recognisable changes in the chemical composition of the K. pneumoniaeCol-R cell wall (especially in LPS) when compared to the susceptible strain.
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Affiliation(s)
- Agata Pruss
- Department of Laboratory Medicine, Chair of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (A.P.); (B.D.)
| | - Paweł Kwiatkowski
- Department of Diagnostic Immunology, Chair of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
- Correspondence: ; Tel.: +48-91-466-1659
| | - Łukasz Łopusiewicz
- Center of Bioimmobilisation and Innovative Packaging Materials, Faculty of Food Sciences and Fisheries, West Pomeranian University of Technology Szczecin, Janickiego 35, 71-270 Szczecin, Poland;
| | - Helena Masiuk
- Department of Medical Microbiology, Chair of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (H.M.); (S.G.-K.)
| | - Peter Sobolewski
- Department of Polymer and Biomaterials Science, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology Szczecin, Piastów 45, 70-311 Szczecin, Poland;
| | - Karol Fijałkowski
- Department of Microbiology and Biotechnology, West Pomeranian University of Technology Szczecin, Piastów 45, 70-311 Szczecin, Poland;
| | - Monika Sienkiewicz
- Department of Allergology and Respiratory Rehabilitation, Medical University of Łódź, Żeligowskiego 7/9, 90-752 Łódź, Poland;
| | - Adam Smolak
- Microbiological Laboratory, Independent Public Clinical Hospital No. 1 in Szczecin, Unii Lubelskiej 1, 71-252 Szczecin, Poland;
| | - Stefania Giedrys-Kalemba
- Department of Medical Microbiology, Chair of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (H.M.); (S.G.-K.)
| | - Barbara Dołęgowska
- Department of Laboratory Medicine, Chair of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (A.P.); (B.D.)
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Lv Z, Shen Y, Liu W, Ye H, Liu D, Liu J, Fu Y, Peng C, Chen K, Deng X, Liu B, He J, Yang L, Xu C, Cai C, Wang Y, Ke Y, Shen J. Prevalence and risk factors of mcr-1-positive volunteers after colistin banning as animal growth promoter in China: a community-based case-control study. Clin Microbiol Infect 2021; 28:267-272. [PMID: 34197932 DOI: 10.1016/j.cmi.2021.06.033] [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] [Received: 12/10/2020] [Revised: 05/19/2021] [Accepted: 06/19/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVES China banned the use of colistin as animal growth promoter in April 2017. Herein, we report the prevalence of mcr-1 in the intestine of healthy humans and risk factors associated with mcr-1 carriage after the implementation of the ban. METHODS We recruited 719 healthy volunteers from Shenzhen City from 1 March 2018 to 31 December 2019 to investigate the prevalence of mcr-1 in human intestine, and undertook a case-control study to ascertain the risk factors associated with the mcr-1-positive population. A further comparative study was conducted to identify differences between genetic characteristics of mcr-1-positive and mcr-1-negative Escherichia coli. RESULTS Overall, 56 (7.8%, 95% CI 5.9%-10.0%, n = 719) individual faecal samples were positive for mcr-1, and prevalence of mcr-1 among individuals in 2019 (2.4%, 95% CI 8.7%-15.0%, 7/294) was significantly lower than that in 2018 (11.5%, 95% CI 1.0%-4.8%, 49/425) (p < 0.0001). After the colistin ban, animal-derived food (pork and chicken meat) was no longer a risk factor for mcr-1 carriage in human intestine, whereas a higher intake of fish and seafood (>75 g/day) and whole grains (>150 g/day) was associated with higher and lower risk of mcr-1 carriage, respectively (OR 2.175, 95% CI 1.047-4.517; OR 0.045, 95% CI 0.004-0.567). Compared with mcr-1-negative E. coli, the mcr-1-positive E. coli had different patterns of resistance genes and genetic heterogeneity. CONCLUSIONS Our study implicates aquatic food as beeing associated with mcr-1 carriage in the healthy population, even after the ban on colistin. Dietary modification (e.g. whole grains) may help to combat mcr-1-positive bacterial colonization of the gut.
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Affiliation(s)
- Ziquan Lv
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Yingbo Shen
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Weiwen Liu
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Hailing Ye
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Dejun Liu
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Juan Liu
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Yulin Fu
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Changfeng Peng
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Kun Chen
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Xiangxiao Deng
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Bang Liu
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Jie He
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
| | - Lu Yang
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Chunyan Xu
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Chang Cai
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A and F University, Hangzhou, China
| | - Yang Wang
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yuebin Ke
- Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Centre for Disease Control and Prevention, Shenzhen, China.
| | - Jianzhong Shen
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
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Rossi DA, Dumont CF, Santos ACDS, Vaz MEDL, Prado RR, Monteiro GP, Melo CBDS, Stamoulis VJ, dos Santos JP, de Melo RT. Antibiotic Resistance in the Alternative Lifestyles of Campylobacter jejuni. Front Cell Infect Microbiol 2021; 11:535757. [PMID: 34055658 PMCID: PMC8155616 DOI: 10.3389/fcimb.2021.535757] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 04/21/2021] [Indexed: 01/18/2023] Open
Abstract
Campylobacter jejuni is the main pathogen identified in cases of foodborne gastroenteritis worldwide. Its importance in poultry production and public health is highlighted due to the growing antimicrobial resistance. Our study comparatively investigated the effect of five different classes of antimicrobials on the planktonic and biofilm forms of 35 strains of C. jejuni with high phylogenetic distinction in 30 of them. In the planktonic form, the existence of susceptible strains to colistin (7/35 - 20%) and resistance to meropenem (3/35 - 8.6%) represent a novelty in strains evaluated in Brazil. In biofilms formed with the addition of chicken juice, the number of resistant strains was significantly higher for colistin, erythromycin and meropenem (100%), but the susceptibility to tetracycline was shown as a control strategy for specific cases. High concentrations (1,060 ± 172.1mg/L) of antibiotics were necessary to control the biofilm structure in susceptible strains in the planktonic form, which is consistent with the high biomass produced in these strains. Stainless steel and polyurethane were the most (BFI=2.1) and least (BFI=1.6) favorable surfaces for the production of biomass treated with antimicrobials. It is concluded that the antimicrobial action was detected for all tested drugs in planktonic form. In sessile forms, the biomass production was intensified, except for tetracycline, which showed an antibiofilm effect.
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Affiliation(s)
- Daise Aparecida Rossi
- Laboratory of Molecular Epidemiology, Faculty of Veterinary Medicine, Federal University of Uberlândia, Uberlândia, Brazil
| | - Carolyne Ferreira Dumont
- Laboratory of Molecular Epidemiology, Faculty of Veterinary Medicine, Federal University of Uberlândia, Uberlândia, Brazil
| | - Ana Carolina de Souza Santos
- Laboratory of Cellular and Molecular Biology, Faculty of Veterinary Medicine, University of Uberaba, Uberaba, Brazil
| | - Maria Eduarda de Lourdes Vaz
- Laboratory of Cellular and Molecular Biology, Faculty of Veterinary Medicine, University of Uberaba, Uberaba, Brazil
| | - Renata Resende Prado
- Laboratory of Molecular Epidemiology, Faculty of Veterinary Medicine, Federal University of Uberlândia, Uberlândia, Brazil
| | - Guilherme Paz Monteiro
- Laboratory of Molecular Epidemiology, Faculty of Veterinary Medicine, Federal University of Uberlândia, Uberlândia, Brazil
| | - Camilla Beatriz da Silva Melo
- Laboratory of Cellular and Molecular Biology, Faculty of Veterinary Medicine, University of Uberaba, Uberaba, Brazil
| | - Vassiliki Jaconi Stamoulis
- Laboratory of Cellular and Molecular Biology, Faculty of Veterinary Medicine, University of Uberaba, Uberaba, Brazil
| | - Jandra Pacheco dos Santos
- Multidisciplinary Laboratory, Department of Veterinary Medicine, Goiás University Center, Goiânia, Brazil
| | - Roberta Torres de Melo
- Laboratory of Molecular Epidemiology, Faculty of Veterinary Medicine, Federal University of Uberlândia, Uberlândia, Brazil
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Su F, Luo Y, Yu J, Shi J, Zhao Y, Yan M, Huang H, Tan Y. Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review. Eur J Med Res 2021; 26:37. [PMID: 33910622 PMCID: PMC8080403 DOI: 10.1186/s40001-021-00508-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 04/13/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes. CASE PRESENTATION We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488 days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE. CONCLUSIONS CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.
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Affiliation(s)
- Fengqin Su
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yi Luo
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jian Yu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jimin Shi
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yanmin Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Mengni Yan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yamin Tan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. .,Hematology Department, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China.
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Abstract
Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of "safer" antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative "superbugs," every effort must be made to improve the clinical utility of the last-line polymyxins. SIGNIFICANCE STATEMENT: Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.
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Affiliation(s)
- Sue C Nang
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Mohammad A K Azad
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Tony Velkov
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Qi Tony Zhou
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Jian Li
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
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Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States. mBio 2021; 12:mBio.02881-20. [PMID: 33500343 PMCID: PMC7858057 DOI: 10.1128/mbio.02881-20] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States.
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Minozzi S, Pifferi S, Brazzi L, Pecoraro V, Montrucchio G, D'Amico R. Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation. Cochrane Database Syst Rev 2021; 1:CD000022. [PMID: 33481250 PMCID: PMC8094382 DOI: 10.1002/14651858.cd000022.pub4] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients treated with mechanical ventilation in intensive care units (ICUs) have a high risk of developing respiratory tract infections (RTIs). Ventilator-associated pneumonia (VAP) has been estimated to affect 5% to 40% of patients treated with mechanical ventilation for at least 48 hours. The attributable mortality rate of VAP has been estimated at about 9%. Selective digestive decontamination (SDD), which consists of the topical application of non-absorbable antimicrobial agents to the oropharynx and gastroenteric tract during the whole period of mechanical ventilation, is often used to reduce the risk of VAP. A related treatment is selective oropharyngeal decontamination (SOD), in which topical antibiotics are applied to the oropharynx only. This is an update of a review first published in 1997 and updated in 2002, 2004, and 2009. OBJECTIVES To assess the effect of topical antibiotic regimens (SDD and SOD), given alone or in combination with systemic antibiotics, to prevent mortality and respiratory infections in patients receiving mechanical ventilation for at least 48 hours in ICUs. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, PubMed, and Embase on 5 February 2020. We also searched the WHO ICTRP and ClinicalTrials.gov for ongoing and unpublished studies on 5 February 2020. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. SELECTION CRITERIA Randomised controlled trials (RCTs) and cluster-RCTs assessing the efficacy and safety of topical prophylactic antibiotic regimens in adults receiving intensive care and mechanical ventilation. The included studies compared topical plus systemic antibiotics versus placebo or no treatment; topical antibiotics versus no treatment; and topical plus systemic antibiotics versus systemic antibiotics. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included a total of 41 trials involving 11,004 participants (five new studies were added in this update). The minimum duration of mechanical ventilation ranged from 2 (19 studies) to 6 days (one study). Thirteen studies reported the mean length of ICU stay, ranging from 11 to 33 days. The percentage of immunocompromised patients ranged from 0% (10 studies) to 22% (1 study). The reporting quality of the majority of included studies was very poor, so we judged more than 40% of the studies as at unclear risk of selection bias. We judged all studies to be at low risk of performance bias, though 47.6% were open-label, because hospitals usually have standardised infection control programmes, and possible subjective decisions on who should be tested for the presence or absence of RTIs are unlikely in an ICU setting. Regarding detection bias, we judged all included studies as at low risk for the outcome mortality. For the outcome RTIs, we judged all double-blind studies as at low risk of detection bias. We judged five open-label studies as at high risk of detection bias, as the diagnosis of RTI was not based on microbiological exams; we judged the remaining open-label studies as at low risk of detection bias, as a standardised set of diagnostic criteria, including results of microbiological exams, were used. Topical plus systemic antibiotic prophylaxis reduces overall mortality compared with placebo or no treatment (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.73 to 0.96; 18 studies; 5290 participants; high-certainty evidence). Based on an illustrative risk of 303 deaths in 1000 people this equates to 48 (95% CI 15 to 79) fewer deaths with topical plus systemic antibiotic prophylaxis. Topical plus systemic antibiotic prophylaxis probably reduces RTIs (RR 0.43, 95% CI 0.35 to 0.53; 17 studies; 2951 participants; moderate-certainty evidence). Based on an illustrative risk of 417 RTIs in 1000 people this equates to 238 (95% CI 196 to 271) fewer RTIs with topical plus systemic antibiotic prophylaxis. Topical antibiotic prophylaxis probably reduces overall mortality compared with no topical antibiotic prophylaxis (RR 0.96, 95% CI 0.87 to 1.05; 22 studies, 4213 participants; moderate-certainty evidence). Based on an illustrative risk of 290 deaths in 1000 people this equates to 19 (95% CI 37 fewer to 15 more) fewer deaths with topical antibiotic prophylaxis. Topical antibiotic prophylaxis may reduce RTIs (RR 0.57, 95% CI 0.44 to 0.74; 19 studies, 2698 participants; low-certainty evidence). Based on an illustrative risk of 318 RTIs in 1000 people this equates to 137 (95% CI 83 to 178) fewer RTIs with topical antibiotic prophylaxis. Sixteen studies reported adverse events and dropouts due to adverse events, which were poorly reported with sparse data. The certainty of the evidence ranged from low to very low. AUTHORS' CONCLUSIONS Treatments based on topical prophylaxis probably reduce respiratory infections, but not mortality, in adult patients receiving mechanical ventilation for at least 48 hours, whereas a combination of topical and systemic prophylactic antibiotics reduces both overall mortality and RTIs. However, we cannot rule out that the systemic component of the combined treatment provides a relevant contribution in the observed reduction of mortality. No conclusion can be drawn about adverse events as they were poorly reported with sparse data.
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Affiliation(s)
- Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Silvia Pifferi
- Department of Anesthesiology and Intensive Care, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Luca Brazzi
- Department of Surgical Sciences, University of Turin, Turin, Italy
- Department of Anaesthesia, Intensive Care and Emergency, 'Città della salute e della Scienza' Hospital, Turin, Italy
| | - Valentina Pecoraro
- Department of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense, Modena, Italy
| | - Giorgia Montrucchio
- Department of Anaesthesia, Intensive Care and Emergency, 'Città della salute e della Scienza' Hospital, Turin, Italy
| | - Roberto D'Amico
- Italian Cochrane Centre, University of Modena and Reggio Emilia, Modena, Italy
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia School of Medicine, Modena, Italy
- Unit of Methodological/Statistical Support to Clinical Research, Azienda-Ospedaliero Universitaria, Modena, Italy
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Fariñas MC, González-Rico C, Fernández-Martínez M, Fortún J, Escudero-Sanchez R, Moreno A, Bodro M, Muñoz P, Valerio M, Montejo M, Nieto J, Ruiz-San Millan JC, Casafont-Morencos F, Martinez-Martínez L, Fariñas-Álvarez C. Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial. Clin Microbiol Infect 2020; 27:856-863. [PMID: 33359562 DOI: 10.1016/j.cmi.2020.12.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 12/12/2020] [Accepted: 12/13/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. METHODS Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. RESULTS MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. CONCLUSIONS DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.
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Affiliation(s)
- Maria Carmen Fariñas
- Infectious Diseases Service, Hospital Universitario Marques de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
| | - Claudia González-Rico
- Infectious Diseases Service, Hospital Universitario Marques de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
| | | | - Jesús Fortún
- Infectious Diseases Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
| | | | - Asunción Moreno
- Infectious Diseases Service, Hospital Clinic-IDIBAPS, Universidad de Barcelona, Barcelona, Spain
| | - Marta Bodro
- Infectious Diseases Service, Hospital Clinic-IDIBAPS, Universidad de Barcelona, Barcelona, Spain
| | - Patricia Muñoz
- Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañon, IiSGM, Universidad Complutense de madrid, Madrid, Spain
| | - Maricela Valerio
- Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañon, IiSGM, Universidad Complutense de madrid, Madrid, Spain
| | - Miguel Montejo
- Infectious Diseases Unit, Hospital Universitario de Cruces, Baracaldo, Vizcaya, Spain
| | - Javier Nieto
- Infectious Diseases Unit, Hospital Universitario de Cruces, Baracaldo, Vizcaya, Spain
| | | | | | - Luis Martinez-Martínez
- Unit of Microbiology, Hospital Universitario Reina Sofía, IMIBIC, Universidad de Cordoba, Cordoba, Spain
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Colistin Update on Its Mechanism of Action and Resistance, Present and Future Challenges. Microorganisms 2020; 8:microorganisms8111716. [PMID: 33147701 PMCID: PMC7692639 DOI: 10.3390/microorganisms8111716] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/26/2020] [Accepted: 10/30/2020] [Indexed: 02/07/2023] Open
Abstract
Colistin has been extensively used since the middle of the last century in animals, particularly in swine, for the control of enteric infections. Colistin is presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumanni, and Pseudomonas aeruginosa. Transferable bacterial resistance like mcr-genes was reported in isolates from both humans and animals. Researchers actively seek strategies to reduce colistin resistance. The definition of guidelines for colistin therapy in veterinary and human medicine is thus crucial. The ban of colistin use in swine as a growth promoter and for prophylactic purposes, and the implementation of sustainable measures in farm animals for the prevention of infections, would help to avoid resistance and should be encouraged. Colistin resistance in the human-animal-environment interface stresses the relevance of the One Health approach to achieve its effective control. Such measures should be addressed in a cooperative way, with efforts from multiple disciplines and with consensus among doctors, veterinary surgeons, and environment professionals. A revision of the mechanism of colistin action, resistance, animal and human use, as well as colistin susceptibility evaluation is debated here.
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Yang Q, Pogue JM, Li Z, Nation RL, Kaye KS, Li J. Agents of Last Resort: An Update on Polymyxin Resistance. Infect Dis Clin North Am 2020; 34:723-750. [PMID: 33011049 DOI: 10.1016/j.idc.2020.08.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Polymyxin resistance is a major public health threat, because the polymyxins represent last-line therapeutics for gram-negative pathogens resistant to essentially all other antibiotics. Minimizing any potential emergence and dissemination of polymyxin resistance relies on an improved understanding of mechanisms of and risk factors for polymyxin resistance, infection prevention and stewardship strategies, together with optimization of dosing of polymyxins (eg, combination regimens).
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Affiliation(s)
- Qiwen Yang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.9 Dongdan Santiao, Dongcheng District, Beijing, China.
| | - Jason M Pogue
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA
| | - Zekun Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.9 Dongdan Santiao, Dongcheng District, Beijing, China
| | - Roger L Nation
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Victoria 3052, Australia
| | - Keith S Kaye
- Department of Internal Medicine, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109, USA
| | - Jian Li
- Laboratory of Antimicrobial Systems Pharmacology, Department of Microbiology, Monash University, Victoria 3800, Australia
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Genome sequences of two clinical Escherichia coli isolates harboring the novel colistin-resistance gene variants mcr- 1.26 and mcr- 1.27. Gut Pathog 2020; 12:40. [PMID: 32908612 PMCID: PMC7472697 DOI: 10.1186/s13099-020-00375-4] [Citation(s) in RCA: 17] [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: 04/16/2020] [Accepted: 07/22/2020] [Indexed: 12/18/2022] Open
Abstract
Background Colistin is still a widely used antibiotic in veterinary medicine although it is a last-line treatment option for hospitalized patients with infections caused by multidrug-resistant Gram-negative bacteria. Colistin resistance has gained additional importance since the recent emergence of mobile colistin resistance (mcr) genes. In the scope of a study on colistin resistance in clinical Escherichia coli isolates from human patients in Germany we characterized the mcr-1 gene variants. Results Our PCR-based screening for mcr-carrying E. coli from German patients revealed the presence of mcr-1-like genes in 60 isolates. Subsequent whole-genome sequence-based analyses detected one non-synonymous mutation in the mcr-1 gene for two isolates. The mutations were verified by Sanger sequencing and resulted in amino acid changes Met1Thr (isolate 803-18) and Tyr9Cys (isolate 844-18). Genotyping revealed no relationship between the isolates. The two clinical isolates were assigned to sequence types ST155 (isolate 803-18) and ST69 (isolate 844-18). Both mcr-1 variants were found to be located on IncX4 plasmids of 33 kb size; these plasmids were successfully conjugated into sodium azide resistant E. coli J53 Azir in a broth mating experiment. Conclusions Here we present the draft sequences of E. coli isolate 803-18 carrying the novel variant mcr-1.26 and isolate 844-14 carrying the novel variant mcr-1.27. The results highlight the increasing issue of transferable colistin resistance.
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Dimitriou V, Biehl LM, Hamprecht A, Vogel W, Dörfel D, Peter S, Schafhausen P, Rohde H, von Lilienfeld-Toal M, Klassert TE, Slickers P, Ehricht R, Slevogt H, Christ H, Hellmich M, Farowski F, Tsakmaklis A, Higgins PG, Seifert H, Vehreschild MJGT. Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR). J Antimicrob Chemother 2020; 74:2065-2074. [PMID: 31220256 DOI: 10.1093/jac/dkz124] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 03/01/2019] [Accepted: 03/02/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients. METHODS We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology-oncology departments. Patients colonized with ESBL-EC/KP received a 7 day antimicrobial regimen of oral colistin (2 × 106 IU 4×/day), gentamicin (80 mg 4×/day) and fosfomycin (three administrations of 3 g every 72 h), or placebo. Faecal, throat and urine specimens were collected on day 0, 6 ± 2, 11 ± 2, 28 ± 4 and 42 ± 4 after treatment initiation, and the quantitative burden of ESBL-EC/KP, resistance genes and changes in intestinal microbiota were analysed. Clinicaltrials.gov: NCT01931592. RESULTS As the manufacture of colistin powder was suspended worldwide, the study was terminated prematurely. Overall, 29 (18 verum/11 placebo) out of 47 patients were enrolled. The short-term intestinal eradication was marginal at day 6 (verum group 15/18, 83.3% versus placebo 2/11, 18.2%; relative risk 4.58, 95% CI 1.29-16.33; Fisher's exact test P = 0.001) and not evident at later timepoints. Quantitative analysis showed a significant decrease of intestinal ESBL-EC/KP burden on day 6. Sustained intestinal eradication (day 28 + 42) was not achieved (verum, 38.9% versus placebo, 27.3%; P = 0.299). In the verum group, mcr-1 genes were detected in two faecal samples collected after treatment. Microbiome analysis showed a significant decrease in alpha diversity and a shift in beta diversity. CONCLUSIONS In this prematurely terminated study of a 7 day oral antimicrobial eradication regimen, short-term ESBL-EC/KP suppression was marginal, while an altered intestinal microbiota composition was clearly apparent.
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Affiliation(s)
- Vassiliki Dimitriou
- Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.,German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
| | - Lena M Biehl
- Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.,German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
| | - Axel Hamprecht
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.,Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany
| | - Wichard Vogel
- Department of Oncology, Haematology, Immunology, Rheumatology and Pulmonology, Internal Medicine II, University Hospital Tübingen, Tübingen, Germany
| | - Daniela Dörfel
- Department of Oncology, Haematology, Immunology, Rheumatology and Pulmonology, Internal Medicine II, University Hospital Tübingen, Tübingen, Germany
| | - Silke Peter
- Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.,German Center for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany
| | - Philippe Schafhausen
- Department of Oncology and Haematology, Hubertus Wald Tumorzentrum/University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Holger Rohde
- Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Tilman E Klassert
- Host Septomics Research Group, Jena University Hospital, Jena, Germany
| | | | - Ralf Ehricht
- Center for Applied Research, InfectoGnostics Research Campus, Jena, Germany.,Department for Optical Molecular Diagnostics and Systems Technology, Leibniz-Institute of Photonic Technology (IPHT), Jena, Germany
| | - Hortense Slevogt
- Host Septomics Research Group, Jena University Hospital, Jena, Germany
| | - Hildegard Christ
- Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany
| | - Martin Hellmich
- Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany
| | - Fedja Farowski
- Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.,German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
| | - Anastasia Tsakmaklis
- Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.,German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
| | - Paul G Higgins
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.,Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany
| | - Harald Seifert
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.,Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany
| | - Maria J G T Vehreschild
- Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.,German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.,Department of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, Frankfurt am Main, Germany
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A critical review of antibiotic resistance in probiotic bacteria. Food Res Int 2020; 136:109571. [PMID: 32846610 DOI: 10.1016/j.foodres.2020.109571] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 12/12/2022]
Abstract
Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host. At present, probiotics are gaining popularity worldwide and are widely used in food and medicine. Consumption of probiotics is increasing with further in-depth research on the relationship between intestinal flora and host health. Most people pay more attention to the function of probiotics but ignore their potential risks, such as infection and antibiotic resistance transfer to pathogenic microbes. Physiological functions, effects and mechanisms of action of probiotics were covered in this review, as well as the antibiotic resistance phenotypes, mechanisms and genes found in probiotics. Typical cases of antibiotic resistance of probiotics were also highlighted, as well as the potential risks (including pathogenicity, infectivity and excessive immune response) and corresponding strategies (dosage, formulation, and administration route). This timely study provides an avenue for further research, development and application of probiotics.
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Choy A, Freedberg DE. Impact of microbiome-based interventions on gastrointestinal pathogen colonization in the intensive care unit. Therap Adv Gastroenterol 2020; 13:1756284820939447. [PMID: 32733601 PMCID: PMC7370550 DOI: 10.1177/1756284820939447] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 06/15/2020] [Indexed: 02/04/2023] Open
Abstract
In the intensive care unit (ICU), colonization of the gastrointestinal tract by potentially pathogenic bacteria is common and often precedes clinical infection. Though effective in the short term, traditional antibiotic-based decolonization methods may contribute to rising resistance in the long term. Novel therapies instead focus on restoring gut microbiome equilibrium to achieve pathogen colonization resistance. This review summarizes the existing data regarding microbiome-based approaches to gastrointestinal pathogen colonization in ICU patients with a focus on prebiotics, probiotics, and synbiotics.
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Affiliation(s)
| | - Daniel E. Freedberg
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA
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Hurley JC. Structural equation modeling the "control of gut overgrowth" in the prevention of ICU-acquired Gram-negative infection. Crit Care 2020; 24:189. [PMID: 32366267 PMCID: PMC7199305 DOI: 10.1186/s13054-020-02906-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 04/17/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Conceptually, the "control of gut overgrowth" (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. METHODS Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups. RESULTS In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. CONCLUSIONS Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis.
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Affiliation(s)
- James C Hurley
- Melbourne Medical School, University of Melbourne, Melbourne, Australia.
- Internal Medicine Service, Ballarat Health Services, PO Box 577, Ballarat, Victoria, 3353, Australia.
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Yoon YK, Suh JW, Kang EJ, Kim JY. Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: beyond Clostridioides difficile infection. Ann Med 2019; 51:379-389. [PMID: 31468999 PMCID: PMC7877873 DOI: 10.1080/07853890.2019.1662477] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment.Key messagesThe development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed.Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens.A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.
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Affiliation(s)
- Young Kyung Yoon
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jin Woong Suh
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Eun-Ji Kang
- Korea University Medical Library, Seoul, Korea
| | - Jeong Yeon Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Martin Mateos R, Albillos A. Sepsis in Patients With Cirrhosis Awaiting Liver Transplantation: New Trends and Management. Liver Transpl 2019; 25:1700-1709. [PMID: 31408581 DOI: 10.1002/lt.25621] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Accepted: 08/06/2019] [Indexed: 02/07/2023]
Abstract
Bacterial infections are more frequent and severe in patients with advanced liver disease and, therefore, in liver transplant candidates. The increased risk of infection in these patients parallels the severity of the immune dysfunction associated with cirrhosis, which is related to systemic inflammation and progressive immunodeficiency. Other factors contribute to this risk, such as genetic polymorphisms, proton pump inhibitor overuse, the numerous invasive procedures and hospitalizations these patients go through, or the immunosuppressive effects of malnutrition or alcohol abuse. Bacterial infections have a great impact on disease progression and significantly increase mortality rates before and after liver transplantation. Mechanisms leading to organ failure in sepsis are associated not only with the hemodynamic derangement but also with an excessive inflammatory response triggered by infection. Furthermore, prophylactic and empirical antibiotic treatment strategies in patients with cirrhosis are being modified according to the growing prevalence of multidrug-resistant bacteria in the past decade. Also, new criteria have been introduced for the diagnosis of sepsis and septic shock. These new definitions have been validated in patients with cirrhosis and show a better accuracy to predict in-hospital mortality than previous criteria based on systemic inflammatory response syndrome. Accurate prophylaxis and early identification and treatment of bacterial infections are key to reducing the burden of sepsis in patients with cirrhosis awaiting liver transplantation.
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Affiliation(s)
- Rosa Martin Mateos
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Agustín Albillos
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
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Abstract
The prevalence of antimicrobial resistance among many common bacterial pathogens is increasing. The emergence and global dissemination of these antibiotic-resistant bacteria (ARB) is fuelled by antibiotic selection pressure, inter-organism transmission of resistance determinants, suboptimal infection prevention practices and increasing ease and frequency of international travel, among other factors. Patients with chronic kidney disease, particularly those with end-stage renal disease who require dialysis and/or kidney transplantation, have some of the highest rates of colonization and infection with ARB worldwide. These ARB include methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp. and several multidrug-resistant Gram-negative organisms. Antimicrobial resistance limits treatment options and increases the risk of infection-related morbidity and mortality. Several new antibiotic agents with activity against some of the most common ARB have been developed, but resistance to these agents is already emerging and highlights the dire need for new treatment options as well as consistent implementation and improvement of basic infection prevention practices. Clinicians involved in the care of patients with renal disease must be familiar with the local epidemiology of ARB, remain vigilant for the emergence of novel resistance patterns and adhere strictly to practices proven to prevent transmission of ARB and other pathogens.
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Affiliation(s)
- Tina Z Wang
- NewYork Presbyterian-Weill Cornell Medical Center, New York, NY, USA
| | | | - David P Calfee
- NewYork Presbyterian-Weill Cornell Medical Center, New York, NY, USA.
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.
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Gargiullo L, Del Chierico F, D’Argenio P, Putignani L. Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives. Front Microbiol 2019; 10:1704. [PMID: 31402904 PMCID: PMC6671974 DOI: 10.3389/fmicb.2019.01704] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/10/2019] [Indexed: 01/10/2023] Open
Abstract
The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.
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Affiliation(s)
- Livia Gargiullo
- Division of Immunology and Infectious Diseases, University-Hospital Pediatric Department, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy
| | | | - Patrizia D’Argenio
- Division of Immunology and Infectious Diseases, University-Hospital Pediatric Department, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy
| | - Lorenza Putignani
- Human Microbiome Unit and Parasitology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, 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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Zhong YM, Liu WE, Zheng ZF. Epidemiology and molecular characterization of mcr-1 in Escherichia coli recovered from patients with bloodstream infections in Changsha, central China. Infect Drug Resist 2019; 12:2069-2076. [PMID: 31372014 PMCID: PMC6634265 DOI: 10.2147/idr.s209877] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 06/27/2019] [Indexed: 12/11/2022] Open
Abstract
Objectives The main aim of this study was to investigate the prevalence and molecular characteristics of the mcr-1 gene in Escherichia coli isolates obtained from all patients with bloodstream infections over a year in a Chinese teaching hospital. We also assessed the susceptibility profiles of the mcr-1-positive strains and prognostic impact of this gene on the patients. Methods A total of 144 consecutive, non-repetitive E. coli isolates causing bloodstream infections were collected at a teaching hospital in Changsha, China from January to December 2016. The presence of the mcr-1 gene was assessed by PCR. All mcr-1-positive E coli isolates were characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST), a conjugation experiment, and plasmid replicon typing. Clinical data were obtained from medical records. Results The mcr-1 gene was detected in three (2.1%) of the 144 E. coli isolates. The three mcr-1-positive E. coli isolates were resistant to colistin. All three isolates showed a lower resistance to other classes of antibacterials, with all three being susceptible to carbapenems. The MLST results indicated that the three E. coli isolates were assigned to three different sequence types: ST457, ST101, and ST1413, respectively. The conjugation experiment showed that the mcr-1 gene was successfully transferred to the recipient (E. coli EC600) from two isolates, one of which possessed IncI1 replicons and the other of which carried IncHI2 and IncN replicons. The patients with bloodstream infections caused by mcr-1-positive isolates had severe underlying diseases and were cured after antibacterial treatment. Conclusion The prevalence of the mcr-1 gene in patients with E. coli bloodstream infection was 2.1% in Changsha, China. The mcr-1-positive E. coli isolates had varied susceptibility profiles, although all three were susceptible to carbapenems. This therapeutic window is crucial given the risk of rapid deterioration in high-incidence areas worldwide.
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Affiliation(s)
- Yi-Ming Zhong
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Wen-En Liu
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Zhao-Feng Zheng
- Faculty of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
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Woodworth MH, Hayden MK, Young VB, Kwon JH. The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions. Open Forum Infect Dis 2019; 6:ofz288. [PMID: 31363779 PMCID: PMC6667716 DOI: 10.1093/ofid/ofz288] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 06/14/2019] [Indexed: 12/17/2022] Open
Abstract
The intestinal tract is a recognized reservoir of antibiotic-resistant organisms (ARO), and a potential target for strategies to reduce ARO colonization. Microbiome therapies such as fecal microbiota transplantation (FMT) have been established as an effective treatment for recurrent Clostridioides difficile infection and may be an effective approach for reducing intestinal ARO colonization. In this article, we review the current published literature on the role of FMT for eradication of intestinal ARO colonization, review the potential benefit and limitations of the use of FMT in this setting, and outline a research agenda for the future study of FMT for intestinal ARO colonization.
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Affiliation(s)
- Michael H Woodworth
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Mary K Hayden
- Division of Infectious Diseases, Department of Internal Medicine, Rush Medical College, Chicago, Illinois
| | - Vincent B Young
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor
| | - Jennie H Kwon
- Division of Infectious Diseases, John T. Milliken Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
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Buitinck S, Jansen R, Rijkenberg S, Wester JPJ, Bosman RJ, van der Meer NJM, van der Voort PHJ. The ecological effects of selective decontamination of the digestive tract (SDD) on antimicrobial resistance: a 21-year longitudinal single-centre study. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2019; 23:208. [PMID: 31174575 PMCID: PMC6555978 DOI: 10.1186/s13054-019-2480-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/19/2019] [Indexed: 02/03/2023]
Abstract
Background The long-term ecological effects on the emergence of antimicrobial resistance at the ICU level during selective decontamination of the digestive tract (SDD) are unknown. We determined the incidence of newly acquired antimicrobial resistance of aerobic gram-negative potentially pathogenic bacteria (AGNB) during SDD. Methods In a single-centre observational cohort study over a 21-year period, all consecutive patients, treated with or without SDD, admitted to the ICU were included. The antibiotic regime was unchanged over the study period. Incidence rates for ICU-acquired AGNB’s resistance for third-generation cephalosporins, colistin/polymyxin B, tobramycin/gentamicin or ciprofloxacin were calculated per year. Changes over time were tested by negative binomial regression in a generalized linear model. Results Eighty-six percent of 14,015 patients were treated with SDD. Most cultures were taken from the digestive tract (41.9%) and sputum (21.1%). A total of 20,593 isolates of AGNB were identified. The two most often found bacteria were Escherichia coli (N = 6409) and Pseudomonas (N = 5269). The incidence rate per 1000 patient-day for ICU-acquired resistance to cephalosporins was 2.03, for polymyxin B/colistin 0.51, for tobramycin 2.59 and for ciprofloxacin 2.2. The incidence rates for ICU-acquired resistant microbes per year ranged from 0 to 4.94 per 1000 patient-days, and no significant time-trend in incidence rates were found for any of the antimicrobials. The background prevalence rates of resistant strains measured on admission for cephalosporins, polymyxin B/colistin and ciprofloxacin rose over time with 7.9%, 3.5% and 8.0% respectively. Conclusions During more than 21-year SDD, the incidence rates of resistant microbes at the ICU level did not significantly increase over time but the background resistance rates increased. An overall ecological effect of prolonged application of SDD by counting resistant microorganisms in the ICU was not shown in a country with relatively low rates of resistant microorganisms. Electronic supplementary material The online version of this article (10.1186/s13054-019-2480-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sophie Buitinck
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands.,TIAS School for Business and Society, Warandelaan 2, 5037 AB, Tilburg, The Netherlands
| | - Rogier Jansen
- Department of Medical Microbiology, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands
| | - Saskia Rijkenberg
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands
| | - Jos P J Wester
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands
| | - Rob J Bosman
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands
| | - Nardo J M van der Meer
- TIAS School for Business and Society, Warandelaan 2, 5037 AB, Tilburg, The Netherlands.,Department of Intensive Care, Amphia Hospital, Molengracht 21, 4814 CK, Breda, The Netherlands
| | - Peter H J van der Voort
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands. .,TIAS School for Business and Society, Warandelaan 2, 5037 AB, Tilburg, The Netherlands.
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48
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Prevel R, Boyer A, M'Zali F, Lasheras A, Zahar JR, Rogues AM, Gruson D. Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2019; 23:170. [PMID: 31088542 PMCID: PMC6518813 DOI: 10.1186/s13054-019-2460-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 04/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU. METHODS Every article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy. RESULTS Among 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting. CONCLUSION Current knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.
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Affiliation(s)
- Renaud Prevel
- CHU Bordeaux, Medical Intensive Care Unit, Pellegrin Hospital, F-33000, Bordeaux, France. .,UMR 5234 CNRS, Bordeaux University, F-33000, Bordeaux, France. .,, Bordeaux, France.
| | - Alexandre Boyer
- CHU Bordeaux, Medical Intensive Care Unit, Pellegrin Hospital, F-33000, Bordeaux, France
| | - Fatima M'Zali
- UMR 5234 CNRS, Bordeaux University, F-33000, Bordeaux, France
| | - Agnès Lasheras
- Univ. Bordeaux, CHU Bordeaux, Hygiène hospitalière, F-33000, Bordeaux, France
| | - Jean-Ralph Zahar
- Unité INSERM - IAME UMR 1137, Université Paris-13, Bobigny, France
| | - Anne-Marie Rogues
- Univ. Bordeaux, CHU Bordeaux, Hygiène hospitalière, F-33000, Bordeaux, France.,Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, team pharmacoepidemiology, UMR 1219, F-33000, Bordeaux, France
| | - Didier Gruson
- CHU Bordeaux, Medical Intensive Care Unit, Pellegrin Hospital, F-33000, Bordeaux, France
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49
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Emergence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Colonization: What Termites Can Teach Us About the Gut Microbiota. Crit Care Med 2019; 45:752-754. [PMID: 28291103 DOI: 10.1097/ccm.0000000000002279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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50
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Hawkey PM, Warren RE, Livermore DM, McNulty CAM, Enoch DA, Otter JA, Wilson APR. Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother 2019. [PMID: 29514274 DOI: 10.1093/jac/dky027] [Citation(s) in RCA: 208] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.
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Affiliation(s)
- Peter M Hawkey
- Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | | | | | - Cliodna A M McNulty
- Microbiology Department, Gloucestershire Royal Hospital, Great Western Road, Gloucester GL1 3NN, UK
| | - David A Enoch
- Public Health England, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - A Peter R Wilson
- Department of Microbiology and Virology, University College London Hospitals, London, UK
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