Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical intracranial infection due to multidrug-resistant and extensively drug-resistant Gram-negative bacteria: A systematic review and 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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Multidrug resistant, extensively drug resistant and pan drug resistant gram negative bacteria at a tertiary care centre in Bhubaneswar

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20190170 ◽

2019 ◽

Vol 6 (2) ◽

pp. 567 ◽

Cited By ~ 4

Author(s):

Dipti Pattnaik ◽

Subhra Snigdha Panda ◽

Nipa Singh ◽

Smrutilata Sahoo ◽

Ipsa Mohapatra ◽

...

Keyword(s):

Tertiary Care ◽

Multidrug Resistant ◽

Diffusion Method ◽

Gram Negative Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Extensively Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Esbl Producers

Background: Multidrug resistance has emerged as a challenge in health care settings. Again increasing prevalence of multidrug resistant (MDR), extensively drug resistant (XDR) and pan drug resistant (PDR) gram negative bacteria is making the condition more critical because of limited options of antibiotics, increasing morbidity, mortality and hospital stay of the patients. The present study is carried out with an aim to estimate the prevalence of MDR, XDR, PDR gram negative bacteria in a tertiary care hospital.Methods: Total of 912 gram negative bacterial isolates obtained from various samples of indoor patients in a tertiary care hospital, were studied over a period of six months. The bacteria were identified by conventional methods. Antibiotic sensitivity testing was done by Kirby Bauer disc diffusion method. Minimum inhibitory concentration (MIC) of antibiotics for the resistant isolates were detected by Vitek-2 automated method. MDR, XDR and PDR were determined according to the definitions suggested by European Centre for Disease Prevention and Control (ECDC), and Centers for Disease Control and Prevention (CDC). Prevalence of extended spectrum beta lactamase (ESBL) producers was estimated.Results: Out of 912 isolates, prevalence of MDR, XDR and PDR were 66.12%, 34.32% and 0.98% respectively. Prevalence of MDR and XDR were higher in ICUs than clinical wards (p<0.0001). Prevalence of ESBL producers was 48.4%.Conclusions: The study highlights increased prevalence of multidrug resistant and extensively drug resistant strains in our hospital. Stringent surveillance, proper implementation of hospital infection control practices and antimicrobial stewardship will help in limiting the emergence and spread of drug resistant strains.

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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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475. High Rate of Extended-Spectrum β-Lactamase Producing Gram-Negative Infections and Associated Mortality in Ethiopia: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.548 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S232-S232 ◽

Cited By ~ 1

Author(s):

Tafese B Tufa ◽

Takele Beyene Tufa ◽

Fuchs André ◽

Feldt Torsten

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Multidrug Resistant ◽

High Rate ◽

Clinical Samples ◽

Published Data ◽

Gram Negative Bacteria ◽

Salmonella Spp ◽

Gram Negative ◽

Extended Spectrum

Abstract Background Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria have become a serious threat to global health. The rapid increase of ESBL-producing bacteria is associated with high mortality due to ineffective antibiotic treatment. To date, regular surveillance of multidrug-resistant (MDR) pathogens is lacking in Ethiopia. For this report, published data regarding ESBL-producing bacteria in different regions of Ethiopia were reviewed systematically. To our knowledge, this is the first systematic review from Ethiopia on ESBL-producing infections and associated mortality in the country. Methods A literature search was conducted in PubMed, PubMed Central, and Google Scholar from January 1, 1990 to April 28, 2019, using the following search terms: “ESBL producing Enterobacteriaceae,” “Gram-negative bacteria infection associated mortality,” and “Ethiopia.” Patient mortality associated with infections by ESBL-producing Gram-negative bacteria was recorded. Results Fourteen publications qualified for review. Totally, 1,782 Gram-negative bacteria isolated from 5,191 clinical samples were included. The phenotypic pooled rate of ESBL-producing Gram-negatives was estimated to be 52.9(95% CI: 50.5%–55.4%). Among different species, ESBL rates were 65. 7% (262/399) Klebsiella spp., 60.6% (20/33) for Enterobacter spp., 47.8% (22/46) for Citrobacter spp., 47.0% (383/815) for E. coli, 45.7% (85/186) for Salmonella spp., 27.8%(15/54) for Proteus spp., 16.7%(4/24) for P. aeruginosa, 14.3% (3/21) for Acinetobacter spps., and 40.5% (15/37) for others, respectively. ESBL genes were confirmed in three studies. blaCTX-M-1 and blaTEM were the predominately detected genes. Two studies reported mortality associated with Gram-negative infections and 86% (12/14) of the patients infected with ESBL-producing bacteria died. Conclusion In this meta-analysis, the pooled phenotypic prevalence of ESBL-producing pathogens is considerably high. Also, the mortality due to ESBL-producers is high but data are scarce. This highlights the need for establishing and upgrading of clinical microbiology laboratories in the country for routine antibiotic susceptibility testing. The capacity to detect ESBL genes is desirable for continuous surveillance of MDR. Disclosures All authors: No reported disclosures.

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