Dissemination and characteristics of carbapenem-resistant Klebsiella pneumoniae in nine district hospitals in southwestern China.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is epidemically transmitted globally, but few studies focused on the prevalence in district-level hospitals. In this study, we investigated CRKP strains collected from nine district hospitals from September 2019 to September 2020, aiming to determine the resistance mechanisms, virulence profiles, and molecular epidemiological characteristics of CRKP in district hospitals in Southwest China. Methods: A total of 51 CRKP strains were collected from 9 district-level hospitals. Matrix-assisted laser desorption/ionization-time of flight mass spectrometer was used for strain identification review, and the micro-broth dilution method was used for antibiotic sensitivity detection. Molecular epidemiological investigation of strains was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) methods. PCR and efflux pump inhibition tests were used to detect CRKP resistance mechanisms. PCR and serum killing tests were used to detect capsular serotype, virulence-related genes, and virulence validation. Results: The CRKP strains in district hospitals presented high levels of MIC50 and MIC90 in carbapenem antibiotics especially ertapenem and meropenem. A total of 90.2% (46/51) CRKP strains were detected as carbapenemase producers, and the proportion of strains co-expressing carbapenemases was 11.8% (6/51). All CRKP strains were grouped into eight MLST types, and ST11 was the most prevalent genotype. A total of 11.8% (6/51) CRKP isolates were positive for the string test, and three strains of hypervirulent and carbapenem-resistant K. pneumoniae (HV-CRKP) were positive in serum killing test. The molecular typing of all the CRKP isolates was grouped into 29 different PFGE patterns, and 40 ST11 isolates belonged to 20 different PFGE clusters. Conclusion: CRKP strains showed high-level antibiotic resistance and virulence phenotype in district hospitals in Southwest China, which suggested that we should immediately pay attention to the rapid dissemination of the CRKP in regional hospitals. Our study will provide new insights into the epidemiology of CRKP in regional hospitals, which will help regional hospitals develop nosocomial infection prevention and control policies tailored to local conditions.

Heteroresistance to cefepime in Pseudomonas aeruginosa bacteraemia.

INTRODUCTION: Heteroresistance to antibiotic agents can lead to diagnostic and therapeutic failures; however, to date, cefepime heteroresistance (FEP-HR) in Pseudomonas aeruginosa (P. aeruginosa) bacteraemia has not been characterised. The primary goal of this study was to investigate the molecular epidemiology, mechanisms and risk factors for cefepime-heteroresistant P. aeruginosa bacteraemia over approximately 6 years in Southwest China. RESULTS: A high prevalence (57.3%) of heteroresistance to cefepime was observed during the study period, and these FEP-HR isolates were not clonally related. Mechanistic studies revealed that AmpC hyperproduction contributed to the development of this phenomenon. In addition, patients with advanced age, haematological malignancies, central venous catheters, and previous cephalosporin therapy were identified as independent risk factors for acquiring FEP-HR P. aeruginosa bacteraemia. Furthermore, patients infected with FEP-HR were generally at a greater risk for an adverse prognosis compared with those with non-FEP-HR. More importantly, characterisation of three successive P. aeruginosa isolates recovered from the same patient revealed that heteroresistance can act as an intermediate stage during the evolution from susceptibility to full resistance in patients undergoing antibiotic therapy for prolonged periods. CONCLUSION: These findings emphasised the necessity of antimicrobial stewardship programs in clinical settings, as well as the need for some rapid screening methods for detecting this phenomenon.

Carbapenem-Resistant Enterobacter cloacae Causing Nosocomial Infections in Southwestern China: Molecular Epidemiology, Risk Factors, and Predictors of Mortality.

BACKGROUND: The emergence and spread of carbapenem-resistant Enterobacter cloacae (CR-ECL) have posed a serious threat to clinical management. This retrospective study assessed the epidemiological characteristics of CR-ECL to explore the risk factors and predictors of mortality in patients with CR-ECL infection. METHODS: We performed a retrospective 1:2 case-control study of hospitalized patients from January 2014 to December 2017. A total of 85 consecutive unique CR-ECL strains comprised the case group, and 170 matched patients with carbapenem-susceptible Enterobacter cloacae (CS-ECL) infection at the same period as the control group. Isolates were screened for potential resistance genes by polymerase chain reaction (PCR) and molecular typing was performed by multilocus sequence typing (MLST). RESULTS: The results of drug resistance gene detection showed that blaNDM-1 was the most common carbapenem resistance gene. The MLST results showed that ST51 was the predominant epidemic type, followed by ST88. ICU admission (P<0.001), drainage tube (P=0.002), central venous catheter (P=0.005), and carbapenem exposure (P=0.003) were independent risk factors for CR-ECL infection. Significant predictors for 28-day mortality included solid tumours (P=0.005), septic shock (P=0.019), and mechanical ventilation (P=0.027). CONCLUSION: Our study indicated that ST51 and ST88, which are closely related, were the predominant epidemic types of CR-ECL producing blaNDM-1 in southwestern China. Strengthening the surveillance of patients with solid tumours, septic shock and mechanical ventilation is an urgent need.

Molecular Epidemiology of and Risk Factors for Extensively Drug-Resistant Klebsiella pneumoniae Infections in Southwestern China: A Retrospective Study.

Background: The increasing prevalence of extensively drug-resistant Klebsiella pneumoniae (XDR-KP) poses a serious threat to clinical anti-infective treatment. This retrospective study assessed the molecular epidemiology of and risk factors for infections with XDR-KP to investigate the mechanism of drug resistance and the epidemiological characteristics. Methods: A retrospective 1:2 case-control study was conducted at Chongqing Renji Affiliated Hospital of the Chinese Academy of Sciences University from January 2015 to December 2017. A total of 69 non-repetitive XDR-KP strains were collected. Patients infected with XDR-KP comprised the case group, and 138 matched patients with non-XDR-KP infection at the same site comprised the control group. The chi-square test and logistic regression were performed to evaluate the related risk factors. Molecular typing was performed by multilocus sequence typing (MLST). Potential resistance genes were detected by polymerase chain reaction (PCR) and sequencing. Predictors of 28-day mortality in patients with XDR-KP infection were also identified in our study. Results: Only tigecycline and polymyxin B showed favorable in vitro drug sensitivity tests. These XDR-KP strains had a high prevalence rate (n = 66, 95.7%) of carbapenemase-related drug resistance genes. Among them, KPC-2 was the most frequently detected gene (n = 52, 75.4%). Particularly, all of the isolates harbored multiple drug resistance genes. Epidemiological analysis showed that fifty-eight XDR-KP isolates were resistant strains with the ST-11 genotype. Multivariate logistic regression analysis showed that ICU admission (OR: 3.28, 95% CI: 1.66-6.49, P < 0.001), tracheal cannula (OR: 3.16, 95% CI: 1.48-6.76, P = 0.003), and carbapenem exposure (OR: 3.16, 95% CI: 1.25-7.98, P = 0.015) were independent risk factors for XDR-KP infection. Solid tumors (OR: 7.22, 95% CI: 1.84-28.34, P = 0.005) and septic shock (OR: 9.46, 95% CI: 2.00-44.72, P = 0.005) were independent risk factors for 28-day mortality from XDR-KP infection. Conclusion: This study showed that XDR-KP isolates were highly resistant and exhibited clonal transmission. ST11 was the predominant epidemic type of XDR-KP producing KPC-2 in Southwestern China. Physicians should be aware of these high-risk patients with notable predictive factors for XDR-KP infection. These findings may provide some recommendation for the diagnosis and treatment of patients infected with XDR-KP strains in Southwestern China.

Epidemiology of and risk factors for infection with extended-spectrum ß-lactamase-producing carbapenem-resistant Enterobacteriaceae: results of a double case-control study.

PURPOSE: Carbapenem-resistant Enterobacteriaceae (CRE) have been increasingly reported worldwide and pose a serious public threat, but the clinical significance of extended-spectrum ß-lactamase (ESBL) production in CRE is not well established. PATIENTS AND METHODS: A retrospective case-case-control study was conducted to identify the clinical characteristics of patients with ESBL-CRE. The susceptibility of isolates obtained from these patients was assessed. The detection of ESBL and carbapenemase-related genes was performed by PCR methods. Predictors of 30-day mortality in patients with ESBL-CRE infection were also identified in our study. RESULTS: A total of 149 patients with CRE infection caused by Enterobacter cloacae (n=74), Escherichia coli (n=38), and Klebsiella pneumoniae (n=37) were identified in Chongqing, Southwestern China, between January 2011 and December 2014. Of the 35 isolates detected with carbapenemase-related genes, 16 isolates had New Delhi metallo-ß-lactamase (NDM), nine isolates had K. pneumoniae carbapenemase (KPC), seven isolates had imipenemase (IMP), and four isolates had oxacillinase (OXA)-1. One strain of enterobacter cloacae carried both NDM-1 and IMP-8 genes. ESBL isolates included the genes CTX-M (72/149), SHV (64/149), and TEM (54/149). All ESBL-CRE isolates exhibited ertapenem resistance, and the rate of cephalosporin resistance was relatively high in general. Independent risk factors for infection with ESBL-CRE included previous exposure to ß-lactam antibiotics, transfer from another hospital, and some underlying diseases. In addition, solid tumors, hypoalbuminemia, and central venous catheters were independent predictors of mortality in patients with ESBL-CRE infection. CONCLUSION: Physicians should understand the peculiar predictors for the identification of these organisms among high-risk patients.