Evolution of tigecycline- and colistin-resistant CRKP (carbapenem-resistant Klebsiella pneumoniae) in vivo and its persistence in the GI tract.

Emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that also exhibit resistance to tigecycline and colistin have become a major clinical concern, as these two agents are the last-resort antibiotics used for treatment of CRKP infections. A leukemia patient infected with CRKP was subjected to follow-up analysis of variation in phenotypic and genotypic characteristics of CRKP strains isolated from various specimens at different stages of treatment over a period of 3 years. Our data showed that (1) carbapenem treatment led to the emergence of CRKP in the gastrointestinal (GI) tract of the patient, which subsequently caused infections at other body sites as well as septicemia; (2) treatment with tigecycline led to the emergence of tigecycline-resistant CRKP, possibly through induction of the expression of a variant tet(A) gene located in a conjugative plasmid; (3) colistin treatment was effective in clearing CRKP from the bloodstream but led to the emergence of mcr-1-positive Enterobacteriaceae strains as well as colistin-resistant CRKP in the GI tract due to inactivation of the mgrB gene; and (4) tigecycline- and colistin-resistant CRKP could persist in the human GI tract for a prolonged period even without antibiotic selection pressure. In conclusion, clinical CRKP strains carrying a conjugative plasmid that harbors the blaKPC-2 and tet(A) variant genes readily evolve into tigecycline- and colistin-resistant CRKP upon treatment with these two antibiotics and persist in the human GI tract.

Characteristics of clinical and environmental vanM-carrying vancomycin-resistant enterococci isolates from an infected patient.

vanM, an uncommon glycopeptide resistance gene, was first identified in an Enterococcus faecium isolate (Efm-HS0661) from Shanghai, China, in 2006 and has been predominant in this city since 2011. A vanM-carrying E. faecium was isolated from the bloodstream of a patient in an intensive care unit (ICU) in Hangzhou, China, in 2014. Further surveillance screening of a rectal swab and environmental surfaces of the patient yielded a large number of vanM-positive E. faecium. These isolates (including 1 from the bloodstream, 1 from the rectal swab and 43 representative isolates from environmental samples) were classified into four pulsed-field gel electrophoresis (PFGE) patterns and two sequence types (ST78 and ST564). PCR amplification and sequence analysis indicated that the genetic structure surrounding the vanM gene of these isolates was similar to that of the original vanM-carrying isolate Efm-HS0661. This study highlights the emergence of infections and environmental contamination caused by vanM-carrying E. faecium in an ICU of another Chinese city outside of Shanghai.

Emergence of Proteus mirabilis harboring blaKPC-2 and qnrD in a Chinese Hospital.

Nineteen carbapenem-nonsusceptible Proteus mirabilis isolates were recovered from intensive care units in the Second Affiliated Hospital of Zhejiang University during a 3-month period. The isolates showed a high level of resistance against ciprofloxacin, in addition to their resistance against the carbapenems. Pulsed-field gel electrophoresis (PFGE) analysis showed that these isolates belonged to three clonal strains. PCRs and DNA sequence analysis of the carbapenemase and other ß-lactamase genes indicated that all the isolates harbored the bla(KPC-2) gene. Twelve of 19 isolates harbored the plasmid-mediated quinolone resistance (PMQR) genes, both the qnrD and aac(6')-Ib-cr genes. Eight representative isolates with high levels of quinolone resistance carried the similar mutation profiles of S83I in gyrA, E466D in gyrB, and S80I in parC. Reduced carbapenem susceptibility was transferred to Escherichia coli (EC600) in a conjugation experiment, while the quinolone resistance was not. DNA hybridization showed that qnrD was located on a plasmid of approximately 4.5 kb. In summary, large clonally related isolates of KPC-2-producing P. mirabilis emerged in a Chinese hospital, and qnrD was detected in KPC-producing P. mirabilis for the first time.

Risk factors for the acquisition of nosocomial infection with carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported all over the world. In this study, we aimed to investigate the risk factors for the acquisition of nosocomial CRKP infections. METHODS: We conducted a case-control study with data collected from thirty-nine patients with nosocomially acquired CRKP infection between July 2006 and July 2008. Controls were selected at a ratio of 1:2 from patients with nosocomial carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection and were matched with CRKP cases for site of infection and the date of hospital admission (± within 5 days). T test, chi-square test, and logistic regression were used for statistical analysis. RESULTS: Bivariable analysis showed that the age of the patients (P=0.038), days of hospital stay prior to isolation of Klebsiella pneumoniae (K. pneumoniae) (P=0.043), altered consciousness (P=0.007), intensive care unit (ICU) admission within two weeks (P=0.003), tracheal intubation (P=0.027), mechanical ventilation (P=0.009), number of changes in antibiotics≥4 (P=0.001), exposure to carbapenems (P = 0.002), exposure to fourth-generation cephalosporins (P=0.027), and exposure to piperacillin-tazobactams/cefoperazone-sulbactams (P=0.043) and glycopeptides (P=0.042) were related to CRKP infection. The multivariable analysis showed that ICU admission (within two weeks) [odds ratio (OR):4.68, 95% confidence intervals (CI):1.15-19.09, P=0.031], exposure to carbapenems (OR: 12.69, 95% CI: 2.09-77.10, P=0.006) and exposure to glycopeptides (OR: 3.57, 95% CI: 1.11-11.42, P=0.032) were independent risk factors for nosocomial CRKP infections. CONCLUSION: Several factors are related to CRKP infections. ICU admission (within two weeks) or prior exposure to carbapenems or glycopeptides are independent risk factors for the acquisition of nosocomial CRKP infections.