Dataset Information

Environmental colonization and onward clonal transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) in a medical intensive care unit: the case for environmental hygiene.

ABSTRACT: Background:In May 2015, we noticed an increase in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in the Medical Intensive Care Unit (MICU). To investigate this, we studied the extent of environmental contamination and subsequent onward clonal transmission of CRAB. Methods:We conducted a one-day point prevalence screening (PPS) of the patients and environment in the MICU. We screened patients using endotracheal tube aspirates and swabs from nares, axillae, groin, rectum, wounds, and exit sites of drains. We collected environmental samples from patients' rooms and environment outside the patients' rooms. CRAB isolates from the PPS and clinical samples over the subsequent one month were studied for genetic relatedness by whole genome sequencing (WGS). Results:We collected 34 samples from seven patients and 244 samples from the environment. On the day of PPS, we identified 8 CRAB carriers: 3 who screened positive and 5 previously known clinical infections. We detected environmental contamination in nearly two-thirds of the rooms housing patients with CRAB. WGS demonstrated genetic clustering of isolates within rooms but not across rooms. We analysed 4 CRAB isolates from clinical samples following the PPS. One genetically-related CRAB was identified in the respiratory sample of a patient with nosocomial pneumonia, who was admitted to the MICU five days after the PPS. Conclusion:The extensive environmental colonization of CRAB by patients highlights the importance of environmental hygiene. The transmission dynamics of CRAB needs further investigation.

SUBMITTER: Ng DHL

PROVIDER: S-EPMC5891964 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Environmental colonization and onward clonal transmission of carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) in a medical intensive care unit: the case for environmental hygiene.

Ng Deborah H L DHL Marimuthu Kalisvar K Lee Jia Jun JJ Khong Wei Xin WX Ng Oon Tek OT Zhang Wei W Poh Bee Fong BF Rao Pooja P Raj Maya Devi Rajinder MDR Ang Brenda B De Partha Pratim PP

Antimicrobial resistance and infection control 20180410

<h4>Background</h4>In May 2015, we noticed an increase in carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections in the Medical Intensive Care Unit (MICU). To investigate this, we studied the extent of environmental contamination and subsequent onward clonal transmission of CRAB.<h4>Methods</h4>We conducted a one-day point prevalence screening (PPS) of the patients and environment in the MICU. We screened patients using endotracheal tube aspirates and swabs from nares, axillae, gr ...[more]

PMID: 29644052

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Project description:Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) are one of the most difficult pathogen to treat. The only drug recently approved by the FDA that is active against CRAB is cefiderocol. However, recent studies have shown higher all-cause mortality rate in the group of patients treated with cefiderocol, that may be due to heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Previous studies showed that adding human fluids to CRAB cultures can lead to CFDC heteroresistance. To better understand the nature of this phenomenon, we carried out molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations. Methods: The CRAB strain AMA40 was cultured in the presence of cefiderocol and human pleural fluid (HPF) to isolate heteroresistant variants. Two of them, AMA40 IHC_1 and IHC_2, were subjected to whole genome sequencing and transcriptomic analysis to identify the mutations and transcriptomic changes responsible for the development of cefiderocol resistance. The impact of mutations on the pharmacodynamic activity of cefiderocol was assessed by susceptibility testing, EDTA and Boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Variants AMA40 IHC_1 and IHC_2 had 53 mutations, forty of which were common to both heteroresistant strains. None of the mutations are located inside genes associated with iron-uptake systems or β-lactam resistance. However, pipA, a gene associated with iron homeostasis in other species, was mutated in heteroresistant strains. Transcriptomic analyses revealed modifications in levels of expression of genes associated with antibiotic resistance. The blaNDM-1, blaADC-2, pbp3, and pbp1 were expressed at higher levels. At the same time, the carO and ompA genes’ expression was reduced. Collateral resistance to amikacin was observed in the heteroresistant variants. Static time-kill assays showed that when CA-MHB was supplemented with human serum albumin, the main protein component of HPF, cefiderocol killing activity was considerably reduced in all three strains. Conclusions: We conclude that heteroresistance to cefiderocol in CRAB, when exposed to fluids containing high HSA, is caused by mutations and modifications in the expression of genes associated with resistance to β-lactams.

Project description:The epidemiology of patients with gastrointestinal colonization of carbapenem-resistant Acinetobacter baumannii (CRAB) has not been systematically analyzed. We aimed to analyze the incidence, risk factors, and clinical outcomes of patients with newly identified gastrointestinal colonization of CRAB in a healthcare region in Hong Kong, where a multi-pronged screening strategy for gastrointestinal colonization of CRAB, together with other multidrug-resistant organisms (MDROs), was conducted by collecting fecal specimens (rectal swab or stool) upon admission and during hospitalization. From 1 October 2015 to 31 December 2019, a total of 161,339 fecal specimens from 63,588 patients, 61,856 (97.3%) of whom were hospitalized patients, and 54,525 (88.1%) were screened upon admission, with 1309 positive for CRAB (2.4% prevalence). Among patients positive for CRAB in fecal specimens, 698 (53.3%) had newly detected gastrointestinal colonization of CRAB, giving an incidence of 10.03 per 10,000 patient admissions and constituting 2646 CRAB colonization days in the general wards. Excluding the 164 patients with co-colonization of other MDROs, 534 patients had gastrointestinal colonization with only CRAB, and 12.5% (67/534) developed symptomatic CRAB infections at a median of 61 days (range: 2 to 671 days), during prospective follow-up for 2 years. Compared with age- and sex-matched controls, patients being referred from residential care homes for the elderly, the presence of indwelling devices, use of beta-lactam/beta-lactamase inhibitors, carbapenems, and proton pump inhibitors in the preceding 6 months, and history of hospitalization in the past 6 months were significantly associated with gastrointestinal colonization with CRAB, as shown by multivariable analysis. Log-rank test showed that cases had significantly shorter survival duration than controls (p < 0.001). The adjusted hazard ratio of gastrointestinal colonization of CRAB was 1.8 (95% CI: 1.5-2.2; p < 0.001), as shown by Cox regression analysis. Whole-genome sequencing of eight patients with CRAB isolates in their blood cultures and rectal swabs during the same episode of hospitalization revealed ST-195 as the predominant type, as shown by multilocus sequencing type. Gastrointestinal colonization of CRAB poses a considerable challenge for infection prevention and control.

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

Environmental colonization and onward clonal transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) in a medical intensive care unit: the case for environmental hygiene.

Publications

Environmental colonization and onward clonal transmission of carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) in a medical intensive care unit: the case for environmental hygiene.

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