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Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in Healthcare Facilities: A Systematic Review and Reanalysis of Quasi-experimental Studies.

ABSTRACT: Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) are a serious cause of healthcare-associated infections, although the evidence for their control remains uncertain. We conducted a systematic review and reanalysis to assess infection prevention and control (IPC) interventions on CRE-CRAB-CRPsA in inpatient healthcare facilities to inform World Health Organization guidelines. Six major databases and conference abstracts were searched. Before-and-after studies were reanalyzed as interrupted time series if possible. Effective practice and organization of care (EPOC) quality criteria were used. Seventy-six studies were identified, of which 17 (22%) were EPOC-compatible and interrupted time series analyses, assessing CRE (n = 11; 65%), CRAB (n = 5; 29%) and CRPsA (n = 3; 18%). IPC measures were often implemented using a multimodal approach (CRE: 10/11; CRAB: 4/5; CRPsA: 3/3). Among all CRE-CRAB-CRPsA EPOC studies, the most frequent intervention components included contact precautions (90%), active surveillance cultures (80%), monitoring, audit and feedback of measures (80%), patient isolation or cohorting (70%), hand hygiene (50%), and environmental cleaning (40%); nearly all studies with these interventions reported a significant reduction in slope and/or level. The quality of EPOC studies was very low to low.

SUBMITTER: Tomczyk S

PROVIDER: S-EPMC6389314 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesWidespread antimicrobial resistance often limits the availability of therapeutic options to only a few last-resort drugs that are themselves challenged by emerging resistance and adverse side effects. Apramycin, an aminoglycoside antibiotic, has a unique chemical structure that evades almost all resistance mechanisms including the RNA methyltransferases frequently encountered in carbapenemase-producing clinical isolates. This study evaluates the in vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii, and provides a rationale for its superior antibacterial activity in the presence of aminoglycoside resistance determinants.MethodsA thorough antibacterial assessment of apramycin with 1232 clinical isolates from Europe, Asia, Africa and South America was performed by standard CLSI broth microdilution testing. WGS and susceptibility testing with an engineered panel of aminoglycoside resistance-conferring determinants were used to provide a mechanistic rationale for the breadth of apramycin activity.ResultsMIC distributions and MIC90 values demonstrated broad antibacterial activity of apramycin against Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Morganella morganii, Citrobacter freundii, Providencia spp., Proteus mirabilis, Serratia marcescens and A. baumannii. Genotypic analysis revealed the variety of aminoglycoside-modifying enzymes and rRNA methyltransferases that rendered a remarkable proportion of clinical isolates resistant to standard-of-care aminoglycosides, but not to apramycin. Screening a panel of engineered strains each with a single well-defined resistance mechanism further demonstrated a lack of cross-resistance to gentamicin, amikacin, tobramycin and plazomicin.ConclusionsIts superior breadth of activity renders apramycin a promising drug candidate for the treatment of systemic Gram-negative infections that are resistant to treatment with other aminoglycoside antibiotics.

Project description:Carbapenems are effective drugs against bacterial pathogens and resistance to them is considered a great public health threat, especially in notorious nosocomial pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa. In this study, we aimed to determine the prevalence of carbapenem resistance in A. baumannii and P. aeruginosa infections in Sub-Saharan Africa. Databases (PubMed, Scopus, Web of Science, and African Journal Online) were systematically searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2020 statements for articles reporting carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) prevalence between 2012 and 2022. Pooled prevalence was determined with the random effect model and funnel plots were used to determine heterogeneity in R. A total of 47 articles were scanned for eligibility, among which 25 (14 for carbapenem-resistant A. baumannii and 11 for carbapenem-resistant P. aeruginosa) were included in the study after fulfilling the eligibility criteria. The pooled prevalence of CRPA in the present study was estimated at 8% (95% CI; 0.02-0.17; I2 = 98%; P <0.01). There was high heterogeneity (Q = 591.71, I2 = 98.9%; P<0.0001). In addition, this study's pooled prevalence of CRAB was estimated at 20% (95% CI; 0.04-0.43; I2 = 99%; P <0.01). There was high heterogeneity (Q = 1452.57, I2 = 99%; P<0.0001). Also, a funnel plot analysis of the studies showed high degree of heterogeneity. The carbapenemase genes commonly isolated from A. baumannii in this study include blaOXA23, blaOXA48, blaGES., blaNDM, blaVIM, blaOXA24, blaOXA58, blaOXA51, blaSIM-1, blaOXA40, blaOXA66, blaOXA69, blaOXA91, with blaOXA23 and blaVIM being the most common. On the other hand, blaNDM, blaVIM, blaIMP, blaOXA48, blaOXA51, blaSIM-1, blaOXA181, blaKPC, blaOXA23, blaOXA50 were the commonly isolated carbapenemase genes in P. aeruginosa, among which blaVIM and blaNDM genes were the most frequently isolated. Surveillance of drug-resistant pathogens in Sub-Saharan Africa is essential in reducing the region's disease burden. This study has shown that the region has significantly high multidrug-resistant pathogen prevalence. This is a wake-up call for policymakers to put in place measures to reduce the spread of these critical priority pathogens.

Project description:BackgroundWith an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.MethodsPatients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.ResultsTwenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.ConclusionsColistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Dataset Information

Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in Healthcare Facilities: A Systematic Review and Reanalysis of Quasi-experimental Studies.

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