Qiwen Yang

Molecular Epidemiology of Clinical Isolates of Carbapenem-Resistant Acinetobacter spp. from Chinese Hospitals

ABSTRACT Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all β-lactams and were only susceptible to colistin. blaOXA-23-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the blaOXA-23 carbapenemase gene. Analysis of the genetic context of blaOXA-23 showed the presence of ISAba1 upstream of blaOXA-23. All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a blaOXA-51-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of blaOXA-66 for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated blaOXA-58 carbapenemase gene, while one isolate of another clone (clone L) carried the blaOXA-72 carbapenemase gene. Only 1 isolate of clone Q carried the blaIMP-8 metallo-β-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried blaPER-1-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA-23 carbapenemase in China.

High Prevalence of Plasmid-Mediated Quinolone Resistance Genes qnr and aac(6′)-Ib-cr in Clinical Isolates of Enterobacteriaceae from Nine Teaching Hospitals in China

ABSTRACT Quinolone resistance is an emerging problem in China. To investigate the prevalence of the plasmid-mediated quinolone resistance genes qnr and aac(6′)-Ib-cr, a total of 265 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Enterobacter cloacae with ciprofloxacin MICs of ≥0.25 μg/ml were screened at nine teaching hospitals in China. The qnrA, qnrB, qnrS, and aac(6′)-Ib genes were detected by PCR. The aac(6′)-Ib-cr gene was further identified by digestion with BtsCI and/or direct sequencing. The qnr gene was present in significantly smaller numbers of isolates with cefotaxime MICs of <2 μg/ml than isolates with higher MICs (≥2.0 μg/ml) (20.6% and 42.1%, respectively; P < 0.05). aac(6′)-Ib-cr was present in 17.0% of the isolates tested, and 7.9% of the isolates carried both the qnr and the aac(6′)-Ib-cr genes. Among the isolates with cefotaxime MICs of ≥2.0 μg/ml, qnr and aac(6′)-Ib-cr were present in 65.7% and 8.6% of E. cloacae isolates, respectively; 65.5% and 21.8% of K. pneumoniae isolates, respectively; 63.3% and 26.7% of C. freundii isolates, respectively; and 6.5% and 16.9% of E. coli isolates, respectively. The 20 transconjugants showed 16- to 128-fold increases in ciprofloxacin MICs, 14 showed 16- to 2,000-fold increases in cefotaxime MICs, and 5 showed 8- to 32-fold increases in cefoxitin MICs relative to those of the recipient due to the cotransmission of blaCTX-M-14, blaCTX-M-3, blaDHA-1, blaSHV-2, and blaSHV-12 with the qnr and aac(6′)-Ib-cr genes. Southern hybridization analysis showed that these genes were located on large plasmids of different sizes (53 to 193 kb). These findings indicate the high prevalence of qnr and aac(6′)-Ib-cr in members of the family Enterobacteriaceae and the widespread dissemination of multidrug resistance in China.

Phenotypic and genotypic characterization of Enterobacteriaceae with decreased susceptibility to carbapenems: results from large hospital-based surveillance studies in China.

ABSTRACT The resistance mechanism of 49 Enterobacteriaceae isolates with decreased susceptibility to carbapenems collected from 2004 to 2008 at 16 teaching hospitals in China was investigated. Moderate- to high-level carbapenem resistance in most isolates was more closely associated with loss or decreased expression of both major porins combined with production of AmpC or extended-spectrum β-lactamase enzymes, while KPC-2, IMP-4, and IMP-8 carbapenemase production may lead to a low to moderate level of carbapenem resistance in Enterobacteriaceae in China.

Carbapenem-Resistant Isolates of Klebsiella pneumoniae in China and Detection of a Conjugative Plasmid (blaKPC-2 plus qnrB4) and a blaIMP-4 Gene

Wei et al. ([13][1]) recently described the emergence of plasmid-mediated KPC-2 carbapenemase in a Klebsiella pneumoniae isolate from China. Interestingly, KPC-producing isolates, which were initially restricted to hospitals located in the New York City area ([2][2]), have recently been detected in

Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009-2010

A multicentre resistance surveillance study [Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of 2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12 antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints for oral penicillin V recommended by the Clinical and Laboratory Standards Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP) ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable resistance rates of 0-88% against S. pneumoniae, 0-57% against MSSA and 0-76.5% against Streptococcus spp. isolates. The prevalence of extended-spectrum β-lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. β-Lactamase production rates amongst H. influenzae isolates ranged from 15% to 46.6% and amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%, respectively, were found, mainly in Mainland China. Levofloxacin resistance rates of 0-3.9% with a MIC(90) (minimum inhibitory concentration causing inhibition of 90% of isolates) of 1-2mg/L and moxifloxacin resistance rates of 0-1.7% with a MIC(90) of 0.125-0.5mg/L were found amongst PNSSP isolates. Moxifloxacin was very active against Streptococcus spp., H. influenzae and M. catarrhalis isolates, with MIC(90) values of 0.125-0.25, 0.032-0.5 and 0.064-0.125mg/L, respectively. These results from the CARTIPS study have confirmed some significant regional differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K. pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of antimicrobial surveillance programmes for guiding empirical therapy and for focusing interventional control of antimicrobial resistance in distinct geographic areas.

Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: the 2002–2009 Study for Monitoring Antimicrobial Resistance Trends (SMART)

The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum β-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China.

A 10 year surveillance for antimicrobial susceptibility of Escherichia coli and Klebsiella pneumoniae in community- and hospital-associated intra-abdominal infections in China.

The objective of this study was to investigate the susceptibility of hospital-associated (HA) and community-associated (CA) Escherichia coli and Klebsiella pneumoniae isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2011, the minimum inhibitory concentrations (MICs) of 12 antibiotics against 3074 E. coli and 1025 K. pneumoniae from 23 centres located in 16 cities were determined by the broth microdilution method. During the 10 year study period, ertapenem, imipenem, amikacin and piperacillin-tazobactam retained high and stable activity against E. coli and K. pneumoniae isolates regardless of whether their source was HA or CA and regardless of their extended-spectrum beta-lactamase (ESBL) production. However, the susceptibility of E. coli to cephalosporins and ampicillin-sulbactam decreased dramatically during the 10 years, especially for the CA isolates. Fluoroquinolones showed low activity against E. coli. During the whole study period, the ESBL rates for E. coli isolates from IAIs increased from 36.1 % in 2002-2003 to 68.1 % in 2010-2011 (P<0.001). Correspondingly, the ESBL rates in HA isolates increased from 52.2 % in 2002-2003 to 70.0 % in 2010-2011 (P = 0.001), and in CA isolates from 19.1 % in 2002-2003 to 61.6 % in 2010-2011 (P<0.001). The ESBL-positive rate in K. pneumoniae remained between 30.1 and 39.3 % of the total isolates with no significant change during the 10 years. In conclusion, carbapenems retained the highest susceptibility rates against HA and CA E. coli and K. pneumoniae. High prevalence of ESBL in HA E. coli and fast-growing resistance in CA E. coli severely limit the empirical use of the third- and fourth-generation cephalosporins in the therapy of IAIs.

Involvement of MarR and YedS in Carbapenem Resistance in a Clinical Isolate of Escherichia coli from China

ABSTRACT A carbapenem-resistant clinical isolate of Escherichia coli, which lacked OmpF and OmpC porins, carried a marR mutation and expressed a functional yedS, a normally nontranslated gene. MarR and YedS are described here as having effects on the ability of this strain to resist carbapenems. Additionally, expression of YedS was regulated by the small RNA MicF in a MarA-dependent way. These findings illustrate how broadly bacteria can mutate within a selective clinical setting, in this case, resistance to carbapenems, by altering three porin genes and one regulatory gene.

Antimicrobial susceptibility of Pseudomonas aeruginosa in China: a review of two multicentre surveillance programmes, and application of revised CLSI susceptibility breakpoints.

The aim of this study was to review the antimicrobial susceptibility of Pseudomonas aeruginosa in China from two nationwide surveillance programmes, namely Surveillance by Etest and Agar Dilution of Nationwide Isolate Resistance (SEANIR) and the Study for Monitoring Antimicrobial Resistance Trends (SMART). A total of 1479 and 187 P. aeruginosa isolates were collected in SEANIR 2005-2008 and SMART 2008-2010, respectively. Minimum inhibitory concentrations of β-lactam/β-lactamase inhibitor combinations, cephalosporins, carbapenems, aminoglycosides and fluoroquinolones were determined and were interpreted following recently revised Clinical and Laboratory Standards Institute (CLSI) guidelines. From SMART, isolation rates of P. aeruginosa were observed to increase by year; moreover, decreasing trends in activity of all antimicrobials were seen. Multidrug-resistant P. aeruginosa strains accounted for 25.2% of SEANIR and 23.0% of SMART isolates. By applying new CLSI interpretive criteria, susceptibilities to piperacillin/tazobactam and carbapenems decreased by 5.4-12.8%. Antimicrobial resistance of the pseudomonads, including P. aeruginosa, remains a challenge for clinical treatment in China. This review emphasises the need for antibiotic stewardship and longitudinal surveillance.

High ceftaroline non-susceptibility in Staphylococcus aureus isolated from acute skin infections in 15 tertiary hospitals in China.

Ceftaroline is a novel, semisynthetic, Nphosphono prodrug cephalosporin with broad-spectrum activity. As ceftaroline possesses high binding affinity for the mecA-encoded penicillin-binding protein 2a (PBP2a) due to structural differences, this drug has excellent activity against both meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-sensitive S. aureus (MSSA). Furthermore, ceftaroline possesses good activity against penicillin-resistant pneumococci and exhibits similar activity against Gram-negative pathogens to thirdgeneration cephalosporins (Jones et al., 2010; Richter et al., 2011; Saravolatz et al., 2011). This new antibiotic was approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia by the US Food and Drug Administration (FDA) in October 2010. However, there has yet to be a report on testing the activity of ceftaroline against S. aureus isolates collected in China to date.