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Antimicrobial Agents and Chemotherapy, January 2006, p. 374-378, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.374-378.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Multicenter Antimicrobial Susceptibility Survey of Gram-Negative Bacteria Isolated from Patients with Community-Acquired Infections in the People's Republic of China

Thomas K. W. Ling,1* Jianhui Xiong,2 Yunsong Yu,3 Ching Ching Lee,1 Huifen Ye,4 Peter M. Hawkey,2 The MK0826 China Study Group

Department of Microbiology, The Prince of Wales Hospital and The Chinese University of Hong Kong, Hong Kong,1 Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom,2 Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, Zhejiang, People's Republic of China,3 Microbiology, The First Municipal People's Hospital of Guangzhou, Guangzhou, People's Republic of China4

Received 15 June 2005/ Returned for modification 12 August 2005/ Accepted 17 October 2005


    ABSTRACT
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A survey of 2,099 gram-negative bacilli from community infections at seven centers in the People's Republic of China is reported. The rates of resistance of 1,615 isolates of the family Enterobacteriaceae were as follows: 40.8% for ciprofloxacin, 32.2% for gentamicin, 0% for imipenem or ertapenem, and 14.7% for cefotaxime. The rates of extended-spectrum ß-lactamase production were 16% for Escherichia coli and 17% for Klebsiella.


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In the People's Republic of China (PRC), the widespread use of antibiotics had led to very high levels of antimicrobial resistance among bacterial isolates from patients with nosocomial infections (3, 11, 13). However, there has been no comprehensive study of the susceptibilities of gram-negative bacilli (GNB) from the community in the PRC. The high prevalence of extended-spectrum ß-lactamase (ESBL)-producing GNB in hospitals (3, 12, 13) suggests that they may be common in the community. Because of the broad spectrum of activity of ertapenem and its potential for the treatment of community-acquired infections (CAIs), it was included with 11 other antibiotics in the first multicenter antimicrobial surveillance study of CAI in the PRC. Gram-negative bacilli isolated from outpatients or patients in the community with clinically significant infections (within 48 h of admission to hospital) in seven geographical areas in the PRC (Beijing, Guangzhou, Hong Kong, Hunan, Shanghai, Wuhan, and Zhejiang) were studied by using 23 collecting laboratories or institutions during 2002 and 2003.

A total of 2,099 nonduplicate clinical isolates of gram-negative bacteria were identified by using the MAST-ID system (Mast Diagnostics, Bootle, United Kingdom) and API 20E/NE strips (bioMérieux, Marcy l'Etoile, France) in both Guangzhou and Hong Kong. Bacterial isolates were collected from urine (38%), tracheal aspirates or sputum (21%), soft tissue (17%), blood (7%), bile (4%), and unspecified sites (13%).

The MICs of the 12 agents tested (Table 1) for all isolates were determined by the CLSI (formerly the NCCLS) agar dilution methodology (9) in the Hong Kong center. ESBL production was confirmed by using ceftazidime (30 µg) and cefotaxime (30 µg) disks with and without clavulanic acid (10 µg) for isolates of the family Enterobacteriaceae with MICs ≥1 µg/ml to ceftazidime or cefotaxime, with a zone diameter difference of ≥5 mm indicating phenotypic confirmation of ESBL production (9).


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TABLE 1. MIC profiles of 12 antibiotics against 2,099 gram-negative bacteria isolated from patients with community acquired infections in the PRC (2002 and 2003)a

 
Table 1 shows the activities of ertapenem and the 11 other antibiotics against the study isolates. The susceptibilities of the Enterobacteriaceae to carbapenems (100%), some broad-spectrum and newer, "fourth-generation" (cefepime) cephalosporins, and amikacin (>90%) were high; but cefotaxime and cefoperazone showed reduced activities (susceptibility rates, 85% and 83%, respectively). High rates of resistance to ciprofloxacin (41%) and gentamicin (32%) were found among the Enterobacteriaceae. No isolate of the Enterobacteriaceae was resistant to ertapenem or imipenem. Ertapenem was the most active agent against all isolates of the Enterobacteriaceae, with an MIC at which 90% of isolates are inhibited (MIC90) of 0.06 µg/ml, followed by imipenem, with an MIC90 of 0.5 µg/ml.

Ertapenem demonstrated greater antimicrobial activity than imipenem against the Enterobacteriaceae, with the ertapenem MIC90 being eight times lower than that of imipenem. These findings are similar to those from European, Australian, and American studies (4, 6, 7). However, ertapenem was less active against Acinetobacter spp. and Pseudomonas spp., with resistance rates of 52% and 81%, respectively, which were higher than those from a previous report from Europe and Australia (7). Therefore, imipenem would be a better choice than ertapenem for the treatment of CAIs caused by these two organisms, particularly for those cause by Acinetobacter spp. (susceptibility rate, 97%). The percentages of gentamicin-resistant Escherichia coli and Klebsiella spp. were 40% and 19%, respectively, and were higher than those found in 20 European countries (4.3% and 9.1%, respectively) (10). The rate of ciprofloxacin resistance in E. coli (50%) was higher than that found in all Asia-Pacific countries included in a SENTRY study (1 to 30%) (1). Such a high percentage of ciprofloxacin resistance is probably driven by the spread of quinolone-resistant nosocomial E. coli isolates into the community in the PRC (3, 11, 13) and the strong and ubiquitous selection pressure caused by the over-the-counter purchase and community use of fluoroquinolones in the PRC. Isolates from Hong Kong had the lowest rates of resistance to all the antimicrobials tested, except that 17% of the Klebsiella sp. isolates were resistant to ceftazidime; E. coli isolates from Beijing and Shanghai had the highest rates of ciprofloxacin resistance (67% and 63%, respectively). Acinetobacter sp. isolates from these two centers also had the highest rates of resistance to ß-lactams. These differences are probably due to the proliferation of individual strains and differences in prescription policies in the centers.

The prevalence of ESBL production in E. coli was 16% and was higher than that in all Asia-Pacific countries included in the SENTRY study, in which the prevalence of ESBL production in E. coli ranges from 0.5% to 11.3% (5). In contrast, the prevalence of ESBL production in Klebsiella spp. was 17% and was comparable to that among isolates from other Asia-Pacific countries (5). ESBL-producing E. coli and Klebsiella spp. showed coresistance to ciprofloxacin (resistance rates, 76.8% and 67.2%, respectively) and gentamicin (resistance rates, 64.9% and 53.5%, respectively) (Table 1), which is similar to the findings reported in the SENTRY study (5). The prevalence of ESBL production found among community isolates in our study was lower than that detected among nosocomial isolates (40%) in the PRC (3, 11, 13), and the susceptibility patterns of individual antibiotic-species combinations for isolates from both the community and hospitals were quite similar (3). A number of studies have shown that ESBL producers are common among nosocomial isolates in the PRC, particularly CTX-M types, with CTX-M-14 being dominant (2, 8); the genes for CTX-M ESBLs may well have spread into community-associated isolates of the family Enterobacteriaceae. The high levels of resistance found in the gram-negative bacilli in CAIs in the PRC make the choice of empirical antibiotic regimens difficult. Carbapenems such as imipenem and ertapenem are therefore the best choice for the treatment of CAIs in the PRC. The high levels of ESBL-producing isolates of the family Enterobacteriaceae found in this study warrant further genetic characterization of the isolates.


    ACKNOWLEDGMENTS
 
We thank all the contributing laboratories that provided isolates for this study. The members of The MK0826 China Study Group were as follows: in Beijing (X. Z. Zhang), The Beijing Renmin Hospital, The Beijing 301 Hospital, and The Peking Union Medical College Hospital; in Guangzhou (H. F. Ye), The First Municipal People's Hospital of Guangzhou, The Second Affiliated Hospital of Guangzhou Medical College, The First Affiliated Hospital of Sun Yet-San Medical University, The Nanfang Affiliated Hospital of 1st Military Medical University, and The Liuhua General Military Hospital; in Hong Kong (T. K. W. Ling), The Prince of Wales Hospital and The Chinese University of Hong Kong; in Hunan (X. Li), The Xiangya Hospital, The 2nd Affiliated Hospital, The 3rd Affiliated Hospital, and The Hunan Surveillance Net; in Shanghai (B. J. Hu), The Zhongshan Hospital, The Ruijing Hospital, and The Sixth Hospital of Shanghai; in Wuhan (Z. Y. Sun), The Tongji Hospital, The Xiehe Hospital, and The Hubei Surveillance Net; and in Zhejiang (Y. S. Yu), The First Affiliated Hospital of Zhejiang University, The First Hospital of Jiaxing, The Second Hospital of Shaoxing, The First People's Hospital of Hangzhou, and The Hospital of Taizhou.

This study was supported by Merck Medical School Grants.


    FOOTNOTES
 
* Corresponding author. Mailing address: Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, People's Republic of China. Phone: 852-26322307. Fax: 852-26451256. E-mail: lingt{at}cuhk.edu.hk. Back


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Antimicrobial Agents and Chemotherapy, January 2006, p. 374-378, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.374-378.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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