Fupin Hu

Intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE carriage) poses a health risk to the elderly. It was aimed to study the prevalence and the risk factors of intestinal ESBL-PE carriage in the elderly. An observational study of a 921-elderly cohort was examined at health checkup for intestinal ESBL-PE carriage at a tertiary medical center in Shanghai. The prevalence and risk factors of intestinal ESBL-PE carriage, especially antimicrobial use in the preceding 9 months, were studied. The prevalence of intestinal ESBL-PE carriage was 53.3% (491/921) in community-dwelling elderly people. A total of 542 ESBL-producing isolates, including E. coli (n = 484) and K. pneumoniae (n = 58), were obtained. On genotyping, the CTX-M-9 ESBL was the most prevalent for 66.0% (358/542) of all isolates. Multivariate analysis showed that antibiotic exposure, age (61–70 years), and nursing home residence were independent risk factors of the ESBL-PE carriage. The analysis on the monthly use of antimicrobials showed that antibiotic exposure during the 6 months prior to sample collection contributed to the high prevalence of ESBL-PE carriage. A single exposure to an antimicrobial increased the risk of the carriage significantly, and the risk increased with the frequency of antimicrobial exposure (RR, 1.825 to 5.255). Prior use of second or third generation cephalosporins, fluoroquinolones, and macrolides increased the risk of the carriage. The results of this study indicate the importance of using antimicrobials judiciously in clinical settings to reduce antimicrobial resistance. Further studies with multiple center surveillance and with comparison of ESBL-PE carriage in the elderly and in the general population simultaneously are needed.

The in vitro activities of ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C-T), and comparators were determined for 1,774 isolates of Enterobacteriaceae and 524 isolates of Pseudomonas aeruginosa collected by 30 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2017. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution method, and bla _KPC and bla _NDM were detected by PCR for all carbapenem-resistant Enterobacteriaceae (CRE).

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Beiwei Yu1, 2, *, Dong Dong2, 3, *, Mingxia Wang1, 2, Yan Guo2, 3, Dandan Yin4 and Fupin Hu2, 3 1Department of Laboratory Medicine, Jinhua People’s Hospital, Zhejiang Province, China 2Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China 3NHC Key Laboratory of Clinical Pharmacology of Antibiotics, Fudan University, Shangai, China 4The Clinical Microbiology Laboratory, Department of Nosocomial Infection Control, Children’s Hospital of Fudan University, Shanghai, China *These authors contributed equally to this work Correspondence to: Fupin Hu, email: hufupin@163.com Keywords: modified carbapenem inactivation method; carbapenemases; enterobacteriaceae; bla_KPC-2; bla_NDM-1 Received: August 09, 2017 Accepted: February 27, 2018 Published: June 26, 2018 ABSTRACT Modified carbapenem inactivation method (mCIM) testing was currently recommended by Clinical and Laboratory Standards Institute (CLSI) for detection of carbapenemase among Enterobacteriaceae clinical isolates. In this study, a panel of 145 clinical strains were collected for evaluating the mCIM for detection of carbapenemase. Antimicrobial susceptibility testing were performed by microbroth dilution and the results were interpreted according to CLSI guidelines. All strains were resistant to ertapenem with high MIC₅₀ and MIC₉₀ (64 mg/L –>128 mg/L). For bla_NDM-1-positive or bla_OXA-232-positive strains, the zone of inhibition of meropenem were all 6 mm despite the incubation time of 6 h, 18 h or 24 h. For 6 h, the zone of meropenem inhibition for most of carbapenemase-positive isolates were meet the positive criteria 6–15 mm. However, for carbapenemase-negative isolates, the zone of meropenem inhibition were 16–18 mm after 6 h incubation which should be considered indeterminate for standard incubating time such as 18 h or 24 h. After incubating for 18 h or 24 h, the zone of meropenem inhibition were 22–25 mm for carbapenemase-negative isolates and meet the negative criteria. Our study indicate mCIM is a simple and effective method to identify the carbapenemases producers among Enterobacteriaceae clinical isolates.

Widespread multidrug resistance caused by the abuse of antibiotics calls for novel strategies and materials. Gold nanoclusters (AuNCs) are scarcely explored for combating multidrug‐resistant (MDR) bacteria in vivo. We herein synthesized a novel class of AuNCs, namely quaternary ammonium (QA) capped AuNCs (QA‐AuNCs) as potent antibiotics selectively targeting MDR Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococci (VRE), in vivo. QA‐AuNCs kill bacteria through a combined physicochemical mechanism, and show excellent therapeutic effects in both a skin infection model and a bacteremia model induced by MRSA. In addition, owing to their intense fluorescence, QA‐AuNCs can be used for the discrimination of live/dead bacteria and bacteria counting, suggesting their potential for clinical theranostics.

Widespread multidrug resistance caused by the abuse of antibiotics calls for novel strategies and materials. Gold nanoclusters (AuNCs) are scarcely explored for combating multidrug‐resistant (MDR) bacteria in vivo. We herein synthesized a novel class of AuNCs, namely quaternary ammonium (QA) capped AuNCs (QA‐AuNCs) as potent antibiotics selectively targeting MDR Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococci (VRE), in vivo. QA‐AuNCs kill bacteria through a combined physicochemical mechanism, and show excellent therapeutic effects in both a skin infection model and a bacteremia model induced by MRSA. In addition, owing to their intense fluorescence, QA‐AuNCs can be used for the discrimination of live/dead bacteria and bacteria counting, suggesting their potential for clinical theranostics.

Carbapenem-resistant Acinetobacter baumannii (CRAB) which is noted as a major pathogen associated with healthcare-associated infections has steadily developed beyond antibiotic control. Lytic bacteriophages with the characteristics of infecting and lysing specific bacteria have been used as a potential alternative to traditional antibiotics to solve multidrug-resistant bacterial infections. Here, we isolated A. baumannii-specific lytic phages and evaluated their potential therapeutic effect against lung infection caused by CRAB clinical strains. The combined lysis spectrum of four lytic phages’ ranges was 87.5% (42 of 48) against CRAB clinical isolates. Genome sequence and analysis indicated that phage SH-Ab15519 is a novel phage which does not contain the virulence or antibiotic resistance genes. In vivo study indicated that phage SH-Ab15519 administered intranasally can effectively rescue mice from lethal A. baumannii lung infection without deleterious side effects. Our work explores the potential use of phages as an alternative therapeutic agent against the lung infection caused by CRAB strains.

Five OXA-232 carbapenemase-producing Klebsiella pneumoniae isolates, belonging to the pandemic clone sequence type 15 (ST15), were isolated from neonates and coproduced bla _CTX-M-15 and bla _SHV-1 genes. All isolates were resistant to ertapenem (MICs of >32 μg/ml) and meropenem (MICs of 4 to 8 μg/ml) and susceptible or intermediate to imipenem (MICs of 1 to 2 μg/ml). The bla _OXA-232 gene was located on a ColE-type transformable plasmid of 6,141 bp. To the best of our knowledge, this is the first report of OXA-232 carbapenemase among clinical isolates in China.

The purpose of this study was to investigate the epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Shanghai Children’s Hospital in China. Twenty-two non-duplicate CRKP strains were collected from pediatric patients between March and June in 2014. Antimicrobial susceptibility testing was conducted by the agar dilution method. Beta-lactamases were characterized by polymerase chain reaction (PCR) and DNA sequencing. The transferability of bla _NDM-1 was investigated by conjugation experiment. The plasmids bearing antibiotic resistance genes were characterized by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization. Clonal relatedness was evaluated by PFGE and multilocus sequence typing (MLST). The clinical data of patients were retrospectively reviewed. The 22 CRKP strains were resistant to most of the antimicrobial agents tested, except tigecycline and colistin. Overall, 59, 77, and 100 % of these strains were resistant to imipenem, meropenem, and ertapenem, respectively. The bla _NDM-1 was positive in 77.3 % (17/22) of the CRKP strains, of which the 16 isolates from inpatients were designated as ST37 (n = 9) and ST76 (n =7) and one isolate from an outpatient belonged to ST846. The 17 bla _NDM-1-positive isolates belonged to PFGE type A (n = 9), type C (n = 7), or type B (n = 1). The plasmids bearing bla _NDM-1 could be transferred into recipient Escherichia coli J53 through conjugation in 88.2 % (15/17) of the strains. The hybridization results showed that the plasmids carrying the bla _NDM-1 gene were approximately 50–240 kb in size. This is the first report of an outbreak caused by NDM-1-producing K. pneumoniae ST76 and ST37 among neonates.