Epidemiology and characteristics of antimicrobial resistance in China
Introduction
Antimicrobial resistance is a global public health crisis, with an obvious association between infection and increased morbidity and mortality (Cosgrove and Carmeli, 2003). In particular, nosocomial infections caused by antimicrobial-resistant pathogens pose a serious threat to patient safety. Surveillance and mechanistic studies of bacterial resistance are the most important measures in terms of controlling the spread of resistant bacteria (WHO, 2001). The irrational use of antimicrobial agents is a considerable and serious problem in China leading to severe bacterial resistance (Zhang et al., 2009b). Antimicrobial resistance surveillance began in the 1980s in China, and was initially limited to a few large hospitals and specific antimicrobial-resistant isolates, such as methicillin-resistant Staphylococcus aureus (MRSA). The results of such studies are of limited value as a clinical reference. To obtain data on antimicrobial resistance among Enterobacteriaceae and glucose non-fermenting bacteria, Peking Union Medical College Hospital started surveying intensive care units in 15 hospitals nationwide starting in 1994. Subsequently, the hospital also conducted, albeit on a less regular basis, nationwide surveillance of gram-positive bacteria resistance (Chen and Wang, 2003, Sun et al., 2010a, Sun et al., 2010b). The Shanghai antibacterial resistance surveillance network was established by Fudan University in 1998 and collected routine clinical microbial sensitivity data from more than 10 hospitals annually. The network expanded to about 20 tertiary hospitals nationwide, and in 2005 became CHINET (Wang, 1999, Wang, 2006). Peking University has conducted national antimicrobial resistance surveillance since 1999, and had 15–17 member hospitals, collecting target bacteria every other year and determining minimum inhibitory concentrations (MICs) for antibacterial agents. This program lasted until 2004, when it was replaced by the MOH National Antibacterial Resistance Investigation Net (Mohnarin), which was established by a commission of the Ministry of Health. Since 2010, Zhejiang University has overseen Mohnarin, and the program has gradually developed from an initial group of 50 hospitals to more than 80 member hospitals, representing the widest coverage in China (Li et al., 2001, Xiao et al., 2008a, Xiao, 2008). In addition to the above national surveillance networks, some provinces, such as Zhejiang, Guangzhou, Hubei, Jiangxi, and Beijing, have also established provincial surveillance programs, adding valuable data that can assist in the development of a plan for rational use of antimicrobial agents.
There are differences in hospital coverage and surveillance methods among the different antimicrobial resistance surveillance networks in China. Mohnarin and CHINET mainly collected and analyzed the results of routine bacterial isolation and drug susceptibility testing of isolates from member hospitals, and provided annual training of microbiologists on surveillance protocols and data processing, as well as quality control. They also confirmed particular resistant strains through a central laboratory. The Peking Union Medical College Hospital surveillance program collected mainly target bacteria from member hospitals and determined collective MICs for a relatively small number of strains (Sun et al., 2010a, Sun et al., 2010b, Wang, 2006, Li et al., 2001, Xiao, 2008). Because these programs did not include non-teaching hospitals and primary health centers, their surveillance data do not account for antimicrobial resistance in primary healthcare settings or community infections (Xiao, 2008).
From the early beginning till the present, Clinical Laboratory Standard Institute (CLSI, formerly NCCLS) standard disc diffusion or agar dilution susceptibility testing methods and breakpoints were used in all clinical microbiological laboratories; the susceptible or resistant rates of bacterial isolates to each antimicrobial agent were defined by the criteria of CLSI breakpoints. The quality-control bacterial strains recommended by CLSI were employed in routine examinations in all microbiological laboratories. The unified methodology used in the laboratories guaranteed the comparability of their surveillance data (CLSI, 2005, CLSI, 2008).
During the past decade, the number of studies on antimicrobial resistance in China has grown, as has the number of researchers involved, and the publication of research results in international journals has gradually increased. In-depth studies have elucidated initial resistance phenotypes and molecular mechanisms of resistance, including molecular epidemiology and the underlying biochemical and genetic basis of resistance. These studies have yielded important information on the most prevalent resistant strains in China (e.g., MRSA, and S. pneumoniae), specific mechanisms of resistance (e.g., ESBLs, the KPC enzyme, macrolide resistance in pneumococci, etc.), and the molecular basis of antimicrobial resistance (e.g., plasmid-mediated quinolone resistance). These studies contribute in an important and valuable way to the scientific community involved in the study of antimicrobial resistance mechanisms and help inform strategies for the containment of antimicrobial resistance (Liu et al., 2009a, Fu et al., 2010).
To demonstrate the full scope of antimicrobial resistance in China, we reviewed data on antimicrobial resistance epidemiology and mechanism of resistance obtained over the past decade, focusing mainly on S. aureus, S. pneumoniae, enterococci, Enterobacteriaceae, P. aeruginosa and Acinetobacter baumannii. Most of the data came from Mohnarin and CHINET, which covered all the regions except Tibet (Fig. 1).
Section snippets
Epidemiology of antimicrobial resistance
The high prevalence of MRSA has been a major problem in China. MRSA was originally detected in China in the 1970s, and the proportion of MRSA among S. aureus increased to approximately 20% after 1980, continuing at that level until 2000 (Li et al., 2001, Zhu et al., 1988). In the 21st century, the prevalence of MRSA rapidly increased, with a greater than 60% of S. aureus being MRSA in hospital isolates in 2008 (Fig. 2). Compared with other countries and regions, the antimicrobial resistance
Penicillin-resistant S. pneumoniae (PRSP)
Penicillin and macrolide resistance in S. pneumoniae have become increasingly common in China, whereas the resistance to fluoroquinolones is still fairly low (Table 2 and Fig. 3) (Xiao et al., 2008a, Shanghai Surveillance of Bacterial Resistance Working Group, 2002, Li et al., 2003b, Li et al., 2005b, Xiao et al., 2008b, Zhu et al., 2005a, Zhu et al., 2005b, Wang and Xiao, 2008, Wang et al., 2010a, Xiao et al., 2010, Sun et al., 2009b, Wang, 2008, Zhu et al., 2004, Wang et al., 2009a, Sun et
Enterococcus resistance
Enterococcus spp. are common pathogen in hospital-acquired infections, and antimicrobial resistance of Enterococcus spp. has been of significant concern, especially the prevalence of vancomycin-resistant enterococcus (VRE). Overall, the incidence of VRE in China is low; however, high-level resistance to aminoglycosides, quinolones resistance and penicillin resistance is quite common (Table 3 and Fig. 2) (Wang, 2006, Li et al., 2001, Xiao et al., 2008a, Shanghai Surveillance of Bacterial
Enterobacteriaceae resistance
Enterobacteriaceae were commonly isolated, with E. coli and Klebsiella pneumoniae among the five most frequently isolated pathogens in hospital-associated infections. The resistance of E. coli and K. pneumoniae to extended-spectrum cephalosporins and fluoroquinolones is high, whereas the resistance to different aminoglycosides varies. Although there has not been a significant change in aminoglycoside-resistance over the past 10 years in China, it is worth noting that the emergence of 16S rRNA
Pseudomonas aeruginosa resistance
The isolation rate of P. aeruginosa increased over the past decade in China, from 9.7–11.2% in 2000, to 10.8–15.8% in 2009, although it could not be excluded to be caused by methodological reasons such as different hospital and specimen distributions. P. aeruginosa has become the second most commonly isolated gram-negative bacillus, second only to E. coli, representing 70% of all strains isolated from sputum and respiratory secretion specimens, particularly from intensive care units (Hu and
Acinetobacter resistance
Acinetobacter has been a significant nosocomial infectious agent over the past decade in China, comprising 7.4–8.8% of clinical isolates in 2000 and 10.6–15.5% in 2009, which was mainly isolated from sputum and other respiratory specimens. It is the third most common gram-negative bacteria. A. baumannii is the predominant species, accounting for about 85% of all Acinetobacter isolates, most of which were identified by routine microbiological methods with VITEK or Phoenix systems. It has mainly
Conclusion
A comprehensive surveillance system for bacterial resistance was established in China that involved tertiary hospitals in distinct regions nationwide. More attention to primary health care institutions and antimicrobial resistance in community-acquired infections is needed, as is timely conduct of active surveillance in the future. Moreover, important antimicrobial-resistant bacteria such as CA-MRSA, multidrug-resistant P. aeruginosa and pan-resistant A. baumannii should be intensively
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