Zhanwei Wang

In Vitro Activities of Ceftazidime-Avibactam and Aztreonam-Avibactam against 372 Gram-Negative Bacilli Collected in 2011 and 2012 from 11 Teaching Hospitals in China

ABSTRACT Ceftazidime-avibactam, aztreonam-avibactam, and comparators were tested by reference broth microdilution against 372 nonrepetitive Gram-negative bacilli (346 unselected plus 26 selected meropenem-nonsusceptible Enterobacteriaceae isolates) collected from 11 teaching hospitals in China in 2011 and 2012. Meropenem-nonsusceptible isolates produced extended-spectrum β-lactamases (ESBLs; e.g., CTX-M-14/3), AmpCs (e.g., CMY-2), and/or carbapenemases (e.g., KPC-2 and NDM-1). Avibactam potentiated the activity of ceftazidime against organisms with combinations of ESBLs, AmpCs, and KPC-2. Aztreonam-avibactam was active against all β-lactamase producers (including producers of NDM-1 and IMP-4/8) except blaOXA-containing Acinetobacter baumannii and some Pseudomonas aeruginosa isolates.

Antimicrobial resistance trends among 5608 clinical Gram-positive isolates in China: results from the Gram-Positive Cocci Resistance Surveillance program (2005-2010)

A total of 5608 clinical isolates of Gram-positive bacteria were collected from 12 teaching hospitals across China from 2005 to 2010. The minimum inhibitory concentrations (MICs) of 19 antimicrobial agents were determined by the agar dilution method at the central laboratory. Overall, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRSCoN) were 46.8% and 81.5%, respectively. Isolates from inpatients exhibited a higher rate of MRSA than that from outpatients (52.3% versus 26.2%, P < 0.001). The prevalence of MRSA in respiratory infections (67.5%) was higher than in other sources of infections (P < 0.001). A shift in vancomycin MICs from <0.5 to 1.0 μg/mL was observed during the 6-year period. In 2005, 70.5% of S. aureus isolates were inhibited at the vancomycin MIC of 0.5 μg/mL, while in 2010, 89% of the isolates were inhibited at the vancomycin MIC of 1 μg/mL. With the use of penicillin oral breakpoints, penicillin-resistant Streptococcus pneumoniae (PRSP) increased from 28.6% in 2005 to 59.5% in 2010 and varied among different age groups, with an average rate of 70.6% for children under 5 years old. Importantly, an obvious penicillin MIC right shift was observed from 0.032 to 4 μg/mL during the study period. Serotyping for the isolates from 2005 and 2010 indicated that the high rate of PRSP could be due to the increased prevalence of serogroup 19. The prevalence of vancomycin-resistant enterococci (VRE) increased from 0 in 2005 to 4.9% in 2010. Of the 27 VRE isolates, vanA gene was the most prevalent gene. During the study period, 97.9-100% of different species tested were susceptible to teicoplanin. Linezolid and tigecycline showed potent activities, and no resistant isolate was identified. In conclusion, although the prevalence of MRSA and MRSCoN remained stable over the 6 years, a sharp increase in the prevalence of PRSP was identified. In addition, MIC shifts, including the MICs of penicillin against S. pneumoniae and vancomycin against S. aureus, were observed. Continuous surveillance is warranted to evaluate the resistance trend of clinically important Gram-positive organisms in the future.

Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: Predominance of KPC-2 enzyme

Among 228 carbapenem-nonsusceptible Enterobacteriaceae isolated in China, 65 were carbapenemase-producing Enterobacteriaceae (CPE). Among them, 41, 22, 1, and 1 produced KPC-2, IMP-4, IMP-8, and IMP-1, respectively. KPC-2-producing CPE showed higher resistance than IMP-4-producing ones. Furthermore, the first outbreak of ST11 KPC-2-producing Klebsiella pneumoniae in a Beijing second-degree hospital was identified.

Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms

Genetic characterisation of linezolid-resistant Gram-positive cocci in a multicentre study in China has not been reported previously. To study the mechanism underlying the resistance of linezolid-resistant isolates, nine Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii isolates with various levels of resistance were collected from five hospitals across China in 2009-2012. The nine E. faecalis isolates were classified into seven sequence types, indicating that these linezolid-resistant E. faecalis isolates were polyclonal. Enterococci isolates had reduced susceptibility to linezolid (MICs of 4-8 mg/L) and had mutation of ribosomal protein L3, with three also having mutation of L4, but without the multidrug resistance gene cfr or the 23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like insertion sequence, indicating that the transferable form of linezolid resistance is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant Gram-positive cocci in different regions of China is of concern. The cfr gene and the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii, and the L3 and L4 mutations are associated with low-level linezolid resistance in enterococci.

Predominant characteristics of CTX-M-producing Klebsiella pneumoniae isolates from patients with lower respiratory tract infection in multiple medical centers in China

From February 2010 to July 2011, 183 of 416 presumptive Klebsiella pneumoniae isolates with reduced susceptibility to third-generation cephalosporins from patients with lower respiratory tract infection were collected from seven tertiary hospitals in China. Phenotypic and genotypic methods were employed to characterize 158 extended-spectrum β-lactamase (ESBL)-producers. Among the 158 isolates analyzed, 134 (84.8%) harbored bla(CTX-M) , within which the most predominant ESBL gene was CTX-M-14 (49.4%), followed by CTX-M-15 (12.0%) and CTX-M-27 (10.8%). Also, 120 (75.9%) harbored bla(SHV) . One novel SHV variant, bla(SHV -142) with T18A and L35Q substitutions, was identified. Ninety-one isolates carried bla(TEM-1). An isolate containing bla(TEM-135) was first identified in Klebsiella spp. bla(KPC)-2) was detected in 5 isolates. More than one ESBL combination was detected in 18 isolates (11.4%). Fifty-four (34.2%) isolates demonstrated the multidrug resistant (MDR) phenotype. Seventy-four sequence types (STs) were identified, which showed large genetic background diversity in ESBL-producing K. pneumoniae isolates from the six areas. This is the first report on the high prevalence of CTX-M-27 in China with the possible transmission of a single clone (ST48). The correlated surveillance of organisms with MDR phenotype should be investigated in future.

Genetic characterisation of clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline: Role of the global regulator RamA and its local repressor RamR.

Laboratory-derived Klebsiella pneumoniae mutants demonstrated that the ramA locus mediated low-level tigecycline resistance. The aim of this study was to elucidate the underlying mechanisms of tigecycline resistance in clinical K. pneumoniae isolates. In total, 106 isolates with tigecycline MICs ranging from 0.125 mg/L to 16 mg/L were collected to determine the correlations between expression of the global regulon ramA, marA, soxS, the acrB pump gene and tigecycline MICs. PCR was used to determine whether mutations in ramR, acrR or the rpsJ gene encoding 30S ribosomal protein S10 were responsible for tigecycline resistance. ramA or ramR inactivation and corresponding trans-complemented strains were used to characterise the contribution of RamA and RamR to tigecycline resistance. Tigecycline MICs were correlated with transcriptional levels of ramA and acrB, but were negatively correlated with marA and soxS. Disrupting ramA strikingly reduced the tigecycline MIC by 16-fold, accompanied by a 0.5-fold downregulation of acrB expression and 3.14- and 3.80-fold upregulation of marA and soxS, respectively. Complementation with plasmid-borne ramA restored the original parental phenotype of decreased tigecycline susceptibility. Of 34 tigecycline-non-susceptible isolates, 21 harbouring diverse mutations in RamR led to ramA overexpression. Disrupting the mutated ramR gene and complementing the mutated ramR gene with a wild-type gene downregulated expression of ramA but maintained the same tigecycline-resistant phenotype as the parental strain; the complemented strain exhibited 4.21- and 27.51-fold increased expression of acrB and marA, respectively. In conclusion, for the majority of tigecycline-resistant K. pneumoniae, ramA, depressed by ramR, was the major factor accounting for tigecycline resistance.

In vitro antimicrobial activity of the novel oxazolidinone tedizolid and comparator agents against Staphylococcus aureus and linezolid-resistant Gram-positive pathogens: a multicentre study in China

∗∗ Corresponding author. were recovered from lower respiratory tract infections. Of the 43 linezolid-resistant CoNS isolates, 42 (97.7%) were recovered ∗ Corresponding author. Present address: Room F816, IMCAS, 1st Beichen West Road, Chaoyang District, Beijing 100101, PR China. Tel.: +86 10 6480 7665; fax: +86 10 6480 7665. E-mail addresses: huanqindai@gmail.com (H. Dai), lzhang03@gmail.com (L. Zhang).

Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated from community-acquired respiratory tract infections in China: Results from the CARTIPS Antimicrobial Surveillance Program

This study investigated the antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates causing adult community-acquired respiratory tract infections (CARTIs) in China. A multicentre resistance surveillance study (CARTIPS) investigating 1046 clinical isolates from 19 hospitals in China was conducted from 2013 to 2014. Based on the minimum inhibitory concentration (MIC) breakpoints of oral penicillin, the percentages of penicillin-resistant, penicillin-intermediate and penicillin-susceptible S. pneumoniae were 44.1%, 13.7%, and 42.2%, respectively. The rates of penicillin-non-susceptible S. pneumoniae ranged from 27.9% to 72.2% in different cities, with the highest rate in Nanchang. Macrolides, including azithromycin, clarithromycin and erythromycin, showed the lowest activities against S. pneumoniae isolates, with resistance rates of 90.5%, 92.2% and 93.0%, respectively. However, 98% of these strains were susceptible to levofloxacin and moxifloxacin. For H. influenzae isolates, most of the antimicrobials agents exhibited good activities. However, ampicillin and trimethoprim/sulfamethoxazole showed relatively lower activity against H. influenzae, with resistance rates of 35.0% and 54.4%, respectively. β-lactamase production rates amongst H. influenzae and M. catarrhalis were 31.0% and 87.1%, respectively. In addition, a total of 15 β-lactamase-negative ampicillin-resistant (BLNAR) strains identified in this study were resistant to ampicillin, amoxicillin/clavulanic acid, cefaclor and cefuroxime. Most of the antimicrobial agents showed excellent activity against M. catarrhalis, with susceptibility rates of >90%. The results from the current study confirmed the regional variations in antimicrobial susceptibility of major CARTI pathogens and provided some choices for the treatment of these organisms. Continuous national surveillance of the epidemiology of CARTIs is strongly warranted in China.

In Vitro Analysis of Activities of 16 Antimicrobial Agents against Gram-Negative Bacteria from Six Teaching Hospitals in China

To evaluate the in vitro antimicrobial activities of biapenem, arbekacin, and cefminox against different gram-negative bacterial isolates in China, a total of 100 non-duplicated Escherichia coli, 100 Acinetobacter baumannii, 100 Pseudomonas aeruginosa, and 99 Klebsiella pneumoniae isolates were collected from 6 teaching hospitals in China in 2012. The minimal inhibitory concentrations (MICs) of biapenem, arbekacin, cefminox and 13 other antibiotics were determined by the broth microdilution method. The carbapenems (biapenem, meropenem, and imipenem) exhibited high antimicrobial activity against E. coli (98%) and K. pneumoniae (≥95%), followed by colistin and amikacin. The MIC50 and MIC90 of biapenem against E. coli were ≤0.06 mg/L and 0.25 mg/L, respectively. For K. pneumoniae, the MIC50 and MIC90 of biapenem were 0.25 mg/L and 1.0 mg/L, respectively. The MIC50 and MIC90 of cefminox against E. coli were 1.0 mg/L and 4.0 mg/L, respectively. The resistance rates of A. baumannii to most of the antibiotics were more than 50%, except for colistin. Amikacin was the most active antibiotic against P. aeruginosa (97%), followed by colistin (93%). The MIC50 and MIC90 of arbekacin against P. aeruginosa were 2.0 mg/L and 8.0 mg/L, respectively. In conclusion, carbapenems, colistin, amikacin, and arbekacin exhibited high antimicrobial activities against gram-negative bacteria, except A. baumannii.

Prospective Multicenter Study of Pathogen Distributions in Early-Onset and Late-Onset Hospital-Acquired Pneumonia in China

Hospital-acquired pneumonia (HAP) is among the most common of nosocomial infections and is associated with prolonged hospitalizations, increased medical expenses, and increased mortality (1, 2).…