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Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa.

ABSTRACT: Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes. In this study, we collected 76 intestinal carbapenem-resistant P. aeruginosa (CRPA) strains from clinical inpatients admitted to our hospital from 2014 to 2019, together with their medical data. We aim to analyze the clinical risk factors associated with CRPA infection and its molecular features. We found that the prevalence of CRPA in P. aeruginosa strains was 41.3% (95% confidence interval [CI], 34.1 to 48.8%). We also identified four variables associated with intestinal CRPA positivity, prior antibiotic exposure to aminoglycosides or carbapenems, underlying diabetes mellitus, and extraintestinal P. aeruginosa isolation. bla_KPC-2 is the only detected carbapenemase gene, accounting for 21.1% of CRPA strains. The genetic environment showed that the bla_KPC-2 gene was flanked immediately by ISKpn8 and ISKpn6 and several other mobile elements further upstream or downstream. Four sequence types (STs) were identified, with ST463 as the dominant sequence type. In conclusion, screening for P. aeruginosa colonization upon hospital admission could reduce the risk of P. aeruginosa infection and spread of CRPA in the hospital. IMPORTANCE Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes. Risk factor analysis and molecular epidemiology are critical for preventing their potential dissemination. Here, we identified four risk factors associated with intestinal CRPA-prior antibiotic exposure to aminoglycosides or carbapenems, underlying diabetes mellitus, and extraintestinal P. aeruginosa isolation. Further, we found similar genetic environments with several mobile elements surrounding the bla_KPC gene, a carbapenemase gene only detected in intestinal CRPA strains in this study. These findings are of significant public health importance, as the information will facilitate the control of the emergence and spread of CRPA.

SUBMITTER: Hu Y

PROVIDER: S-EPMC8612150 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Increasing prevalence of ertapenem-resistant, carbapenem-susceptible Enterobacteriaceae (ERE) in Singapore presents a major therapeutic problem. Our objective was to determine risk factors associated with the acquisition of ERE in hospitalized patients; to assess associated patient outcomes; and to describe the molecular characteristics of ERE. METHODS: A retrospective case-case-control study was conducted in 2009 at a tertiary care hospital. Hospitalized patients with ERE and those with ertapenem-sensitive Enterobacteriaceae (ESE) were compared with a common control group consisting of patients with no prior gram-negative infections. Risk factors analyzed included demographics; co-morbidities; instrumentation and antibiotic exposures. Two parallel multivariate logistic regression models were performed to identify independent variables associated with ERE and ESE acquisition respectively. Clinical outcomes were compared between ERE and ESE patients. RESULTS: Twenty-nine ERE cases, 29 ESE cases and 87 controls were analyzed. Multivariate logistic regression showed that previous hospitalization (Odds ratio [OR], 10.40; 95% confidence interval [CI], 2.19-49.20) and duration of fluoroquinolones exposure (OR, 1.18 per day increase; 95% CI, 1.05-1.34) were unique independent predictors for acquiring ERE. Duration of 4(th)-generation cephalosporin exposure was found to predict for ESE acquisition (OR, 1.63 per day increase; 95% CI, 1.05-2.54). In-hospital mortality rates and clinical response rates were significantly different between ERE and ESE groups, however ERE infection was not a predictor of mortality. ERE isolates were clonally distinct. Ertapenem resistance was likely to be mediated by the presence of extended-spectrum β-lactamases or plasmid-borne AmpC in combination with impermeability due to porin loss and/or efflux pumps. CONCLUSION: Prior hospitalization and duration of fluoroquinolone treatment were predictors of ERE acquisition. ERE infections were associated with higher mortality rates and poorer clinical response rates when compared to ESE infections.

Project description:All (236) Pseudomonas aeruginosa isolates resistant to imipenem and/or meropenem collected during a multicenter (127-hospital) study in Spain were analyzed. Carbapenem-resistant isolates were found to be more frequently resistant to all beta-lactams and non-beta-lactam antibiotics than carbapenem-susceptible isolates (P < 0.001), and up to 46% of the carbapenem-resistant isolates met the criteria used to define multidrug resistance (MDR). Pulsed-field gel electrophoresis revealed remarkable clonal diversity (165 different clones were identified), and with few exceptions, the levels of intra- and interhospital dissemination of clones were found to be low. Carbapenem resistance was driven mainly by the mutational inactivation of OprD, accompanied or not by the hyperexpression of AmpC or MexAB-OprM. Class B carbapenemases (metallo-beta-lactamases [MBLs]) were detected in a single isolate, although interestingly, this isolate belonged to one of the few epidemic clones documented. The MBL-encoding gene (bla(VIM-2)), along with the aminoglycoside resistance determinants, was transferred to strain PAO1 by electroporation, demonstrating its plasmid location. The class 1 integron harboring bla(VIM-2) was characterized as well, and two interesting features were revealed: intI1 was found to be disrupted by a 1.1-kb insertion sequence, and a previously undescribed aminoglycoside acetyltransferase-encoding gene [designated aac(6')-32] preceded bla(VIM-2). AAC(6')-32 showed 80% identity to AAC(6')-Ib' and the recently described AAC(6')-31, and when aac(6')-32 was cloned into Escherichia coli, it conferred resistance to tobramycin and reduced susceptibility to gentamicin and amikacin. Despite the currently low prevalence of epidemic clones with MDR, active surveillance is needed to detect and prevent the dissemination of these clones, particularly those producing integron- and plasmid-encoded MBLs, given their additional capacity for the intra- and interspecies spread of MDR.

Project description:Background: The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses an immediate threat to treatment worldwide. This retrospective study assessed the molecular epidemiology and determined the risk factors for and outcomes of CRKP infections in a general teaching hospital in Shanghai, China. Methods: From January 2013 to July 2015, 100 consecutive unique CRKP isolates isolated from hospitalized patients were collected. Isolates were screened for antibiotic resistance genes by polymerase chain reaction and molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Patients infected with CRKP comprised the case group and were compared to the control group of patients infected with carbapenem-susceptible Klebsiella pneumoniae. Therapeutic effects were compared in the CRKP infection group. Results: Among the 100 CRKP isolates, the percentages of multidrug-resistant, extensively drug-resistant (XDR), and pandrug-resistant were 50.0, 50.0, and 0%, respectively. All the CRKP isolates produced KPC-2 and could be divided into 18 PFGE clusters (A-O) and 70 subtypes. No dominant intra-hospital PFGE type was detected using a cutoff of 80% similarity. The ratio of CRKP infection to colonization was 51 to 49. Risk factors correlated with CRKP infection included pulmonary disease (p = 0.038), ICU stay (p = 0.002), invasive ventilation (p = 0.009), blood transfusion (p = 0.028), parenteral nutrition (p = 0.004), sputum suction (p = 0.006), medical history of previous hospitalization (p = 0.022), exposure to antibiotics 90 days before infection (p = 0.030), and antibiotic exposure during hospital stay including carbapenems (p = 0.013), enzyme inhibitors (p = 0.021), nitroimidazoles (p = 0.029), and glycopeptides (p = 0.000). Multivariable analysis showed that sputum suction (odds ratio 3.090, 95% confidence intervals 1.004-9.518, p = 0.049) was an independent risk factor for CRKP infections. Patients infected with CRKP with longer carbapenems treatment course (p = 0.002) showed better outcome. Conclusion: This study showed the severity of CRKP infection in eastern China. Sputum suction was an independent risk factor for CRKP infection. Prolonged duration of treatment with carbapenems benefited the patients infected with CRKP.

Project description:BackgroundCarbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.MethodsStool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.ResultsThe total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P = 0.018), the history of pulmonary infection within past 3 months (P = 0.001) and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months (P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.ConclusionsThe present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.

Project description:Objective:This retrospective study was conducted to determine the prevalence and molecular epidemiology characteristics of carbapenem-resistant Escherichia coli (CRE). Methods:A total of 593 Escherichia coli (E. coli) isolates were recovered from pigs and urban river from 2009 to 2014 in Heilongjiang Province of China. Forty CRE including 22 strains isolated from fecal samples of pigs and 18 strains isolated from water samples were selected. PCR detection of resistance determinants, multi-locus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and phylogenetic groups were performed to characterize CRE isolates. Conjugation experiments, plasmid stability testing, PCR-based replicon typing (PBRT), and PCR mapping were conducted to analyze bla NDM-carrying plasmids. In vitro time-growth studies and competition experiments were carried out to assess the fitness impact of NDM carriage. Results:Five NDM-1-positive E. coli isolates were identified from water samples. Genetic environment analysis revealed that a cluster of genes (ISAba125-bla NDM-1-ble MBL-?trpF) was detected in all of the NDM-1-positive isolates. Conjugation assays showed that bla NDM-1 could be successfully transferred to E. coli J53 from 5 donor strains at frequencies of 4.6×10-5 to 2.6×10-2. The plasmids from all transconjugants belonged to different plasmid replicon types including IncA/C (n=2), IncFII (n=1) and IncX3 (n=2). In vitro time-growth studies revealed that bla NDM-1 did not have a significant impact on cell proliferation. Meanwhile, competition experiments showed that the acquisition of bla NDM-1 can place an energy burden on the bacterial host and incur fitness cost. However, plasmid stability testing showed that bla NDM-1-carrying plasmid remained stable in the hosts after seven passages without antimicrobial selection. Conclusion:The study revealed the early molecular epidemiology and dissemination characteristics of CRE. In addition, the overall antimicrobial resistance in E. coli recovered from water samples is higher than the strains isolated from fecal samples of pigs. Furthermore, we isolated and identified five NDM-1-producing E. coli strains from water samples.

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Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa.

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