Prevention and Control of Multidrug-Resistant Gram-Negative Bacteria in Adult Intensive Care Units: A Systematic Review and Network Meta-analysis

Abstract Infections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies – covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73–0.93, p = 0.002, I2 = 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.

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Transmission of multidrug-resistant Gram-negative bacteria from colonized mothers to their infants: a systematic review and meta-analysis

Journal of Hospital Infection ◽

10.1016/j.jhin.2019.10.001 ◽

2020 ◽

Vol 104 (1) ◽

pp. 57-67

Author(s):

A.N.H. Bulabula ◽

A. Dramowski ◽

S. Mehtar

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Negative

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Phenotypic characterization of carbapenem non-susceptible gram-negative bacilli isolated from clinical specimens

PLoS ONE ◽

10.1371/journal.pone.0256556 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0256556

Author(s):

Abera Abdeta ◽

Adane Bitew ◽

Surafel Fentaw ◽

Estifanos Tsige ◽

Dawit Assefa ◽

...

Keyword(s):

Public Health ◽

Prevention And Control ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Extensively Drug Resistant ◽

Gram Negative Organisms ◽

And Control ◽

Public Health Institute

Background Multidrug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health. Objective The study was aimed to detect and phenotypically characterize carbapenem no- susceptible gram-negative bacilli at the Ethiopian Public Health Institute. Materials and methods A prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated for each sample in accordance with standard protocol. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disk diffusion method. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant isolates were classified using a standardized definition established by the European Centre for Disease Prevention and Control and the United States Centers for Disease Prevention and Control. Gram-negative organisms with reduced susceptibility to carbapenem antibiotics were considered candidate carbapenemase producers and subjected to modified carbapenem inactivation and simplified carbapenem inactivation methods. Meropenem with EDTA was used to differentiate metallo-β-lactamase (MBL) from serine carbapenemase. Meropenem (MRP)/meropenem + phenylboronic acid (MBO) were used to differentiate Klebsiella pneumoniae carbapenemase (KPC) from other serine carbapenemase producing gram-negative organisms. Results A total of 1,337 clinical specimens were analyzed, of which 429 gram-negative bacterial isolates were recovered. Out of 429 isolates, 319, 74, and 36 were Enterobacterales, Acinetobacter species, and Pseudomonas aeruginosa respectively. In our study, the prevalence of multidrug-resistant, extensively drug-resistant, carbapenemase-producing, and carbapenem nonsusceptible gram-negative bacilli were 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 429 isolates, 66 demonstrated reduced susceptibility to the antibiotics meropenem and imipenem. These isolates were tested for carbapenemase production of which 34.8% (23/66) were carbapenemase producers. Out of 23 carbapenemase positive gram-negative bacteria, ten (10) and thirteen (13) were metallo-beta-lactamase and serine carbapenemase respectively. Three of 13 serine carbapenemase positive organisms were Klebsiella pneumoniae carbapenemase. Conclusion This study revealed an alarming level of antimicrobial resistance (AMR), with a high prevalence of multidrug-resistant (MDR) and extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at the health facility level. These findings point to a scenario in which clinical management of infected patients becomes increasingly difficult and necessitates the use of “last-resort” antimicrobials likely exacerbating the magnitude of the global AMR crisis. This mandates robust AMR monitoring and an infection prevention and control program.

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Questions linked to Wilson APR, Livermore DM, Otter JA, et al. Prevention and control of multidrug-resistant (MDR) Gram-negative bacteria – recommendations from a Joint Working Party. J Hosp Infect 2016;92S1:S1–S44.

Journal of Hospital Infection ◽

10.1016/j.jhin.2015.08.010 ◽

2016 ◽

Vol 92 (1) ◽

pp. 106

Keyword(s):

Prevention And Control ◽

Working Party ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Hosp Infect ◽

And Control

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Controlling the Diffusion of Multidrug-Resistant Organisms in Intensive Care Units

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0039-1696980 ◽

2019 ◽

Vol 40 (04) ◽

pp. 558-568 ◽

Cited By ~ 3

Author(s):

Solen Kernéis ◽

Jean-Christophe Lucet

Keyword(s):

Intensive Care ◽

Hand Hygiene ◽

Intensive Care Units ◽

Multidrug Resistant ◽

Control Measures ◽

Behavioral Approach ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Contact Precautions ◽

Multidrug Resistant Organisms

AbstractThe prevalence of multidrug-resistant organisms (MDROs) in intensive care units (ICUs) is increasing worldwide, with very large variations across countries, microorganisms, and settings. Emerging MDR gram-negative bacteria and fungi raise particular concerns that require improved prevention and control strategies. Vertical approaches are mainly based on screening and contact precautions and/or decolonization of MDRO carriers. On the other hand, horizontal strategies are not pathogen-specific and include standard precautions (i.e., hand hygiene), universal decolonization, antimicrobial stewardship, and environmental cleaning. The impacts of the different strategies vary between MDROs and compliance with control measures, and are intermixed in most infection control programs. Based on historical data, hand hygiene remains the cornerstone to prevent transmission of MDROs in ICUs. In the context of high hand hygiene compliance, screening and contact precautions for carriers seem to have a limited additional effect, particularly for MDR gram-negative bacteria. Studies on skin decolonization with chlorhexidine bathing show conflicting results, impairing its widespread adoption. Selective oral and digestive decontaminations have shown positive impact on clinical outcomes in ICUs with low levels of antibiotic resistance, but raised ecological concerns in high-prevalence settings. Antibiotic stewardship programs have been associated with reductions in antimicrobial use, duration of stay, and costs with no negative impact on mortality and should be widely promoted in ICUs. Whatever the strategy, compliance with the recommended measures is of crucial importance and implementation should rely on behavioral approach and change in the institutional and safety culture.

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Detection and phenotypic characterization of carbapenem non susceptible gram-negative bacilli isolated from clinical specimens

10.1101/2021.08.17.456671 ◽

2021 ◽

Author(s):

Abera Abdeta ◽

Adane Bitew ◽

Surafel Fentaw ◽

Estifanos Tsige ◽

Dawit Assefa ◽

...

Keyword(s):

Public Health ◽

Prevention And Control ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Clinical Specimens ◽

Extensively Drug Resistant ◽

And Control ◽

Public Health Institute

Background Multi-drug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health. Objective The study was aimed to determine the magnitude of multi-drug resistant, extremely drug-resistant, carbapenem non-susceptible, and carbapenemase-producing gram-negative bacilli at Ethiopian Public Health Institute. Materials and methods Prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated in accordance to standard protocol for each sample. Antimicrobial susceptibility testing was done using Kirby Bauer disk diffusion. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant were classified using a standardized definition established by European Centers for Disease prevention and control and the United States Centers for Disease prevention and control experts. Carbapenemase production was confirmed by modified carbapenem inactivation and a simplified carbapenem inactivation method. Meropenem with EDTA was used to differentiate serine carbapenemase and Metallo β-lactamase. Results A total of 1337 clinical specimens were analyzed, of which 429-gram negative bacilli isolates were recovered. Out of 429 isolates 319, 74, and 36 were Enterobacterales, Acinetobacter species, and P. aeruginosa respectively. In our study, the prevalence of Multidrug-resistant, extensively drug-resistant, Carbapenemase-producing, and carbapenem non-susceptible Gram-negative bacilli were, 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 66 isolates screened for Carbapenemase, 34.8% (23/66) were Carbapenemase enzyme producers. Ten out of twenty-three Carbapenemase-positive organisms were Metallo-beta-lactamase producers. Thirteen out of twenty-three isolates were serine carbapenemase producers. Three out of 13 serine Carbapenemase positive organisms were Klebsiella pneumoniae Carbapenemase. Conclusion The finding from this study revealed a high prevalence of Multidrug-resistant, extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among Intensive care unit patients at the health facility level, this necessitates a robust laboratory-based antimicrobial resistance monitoring and infection prevention and control program.

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