Surveillance data from 1998–2017 in Hubei Province showed that the most common BSI-associated Gram-negative and Gram-positive bacteria were E. coli and S. aureus, respectively. This finding was consistent with that of the European Antimicrobial Resistance Surveillance Network (EARS-Net, formerly EARSS) report for 2002–2009  but differed from reports from Malawi, Africa, which showed that non-typhoid Salmonella, S. typhi and Streptococcus pneumoniae were the main BSI-associated pathogens .
Our study showed that S. typhi was also a main BSI-associated pathogen in Hubei Province from 1998–2003. Typhoid fever is a poverty-related disease, mainly occurring in Africa and Asia, with a low incidence in economically developed regions such as Europe and the United States [12-16]. Typhoid fever is transmitted mainly through contaminated food and drinking water . The incidence of S. typhi-related BSIs in rural children was reported to be 2–3 times higher than that in urban children . The different incidences in different areas may be related to local medical and health conditions and vaccination rates. These factors may also have contributed to the high incidence in Hubei Province during 1998–2003. Reports from Africa suggested that S. typhi and non-S. typhi were consistently the most common pathogens of BSIs . Salmonella infections are frequently associated with human immunodeficiency virus infections, very young or elderly patients, clinical malaria and malnutrition, and can be fatal in up to 20–25% of patients [19-20]. Reports from Africa showed that Salmonella was often resistant to first-line antibiotics such as chloramphenicol, sulfonamide and ampicillin [21-22]. In our study, the resistance rate of S. typhi to ampicillin increased from 6.9% in 1998–2002 to 38.5% in 2013–2017, and resistance rates to other antibiotics were lower than 10% in 2013–2017. Resistance to fluoroquinolones and third-generation cephalosporins has also been reported in several African countries [23-24]. Our data showed that S. typhi resistance to third-generation cephalosporins and fluoroquinolones has emerged, but in 1998–2017, the detection rate was less than 5%.
Antibiotic susceptibility tests showed that the resistance rates of E. coli and K. pneumoniae to third-generation cefotaxime were significantly higher than those to ceftazidime, which is consistent with the 30-year data reported from CHINET in China . Wang et al. showed that CTX-M was the most important ESBL type in China and that cefotaxime resistance might be a sign of ESBL-producing bacterial strains . E. coli and K. pneumoniae showed low resistance to amikacin, cefoperazone/sulbactam and imipenem; thus, these antibiotics might be used as empirical treatment options. Notably, in 2013–2017, the rates of K. pneumoniae resistance to imipenem and meropenem reached 15.8% and 17.5%, respectively. Studies have confirmed that mortality rates of patients infected with carbapenem-resistant (CR) K. pneumoniae strains are significantly higher than those of patients infected with carbapenem-sensitive strains [26-27]. CR K. pneumoniae strains often exhibit combined resistance to cephalosporins, fluoroquinolones, aminoglycosides, beta-lactamase inhibitors and other antimicrobial agents . Few antimicrobial agents, including tigecycline and polymyxin, can be used to treat CR K. pneumoniae .
This study revealed that P. aeruginosa and A. baumannii were the most common non-fermentative Gram-negative bacteria that cause BSIs. Susceptibility tests showed that resistance rates of P. aeruginosa to most antibiotics were less than 30%. However, these results differed from those reported in a multicenter epidemiological study on the risk factors and clinical outcomes of nosocomial intra-abdominal infections in China (the Chinese antimicrobial resistance surveillance of nosocomial infections [CARES] 2007–2016), which indicated that P. aeruginosa showed high resistance to a variety of antimicrobial agents, except amikacin, whose susceptibility rate was 83.4% . The antimicrobial susceptibility profiles of A. baumannii isolates from BSIs were similar to those of A. baumannii isolates from abdominal infections. A. baumannii was alarmingly resistant to diverse antibiotics, including third-generation cephalosporins, aminoglycosides, fluoroquinolones and carbapenems . In this study, resistance rates of A. baumannii to common antibiotics increased significantly in 1998–2017. In 2003–2007, the antimicrobial resistance rate of A. baumannii was less than 50%, but by 2013–2017, the resistance rate reached 60–80%. The emergence of multidrug-resistant A. baumannii, especially extensively drug-resistant and fully drug-resistant strains, has made clinical treatment difficult. According to CLSI guidelines, S. maltophilia showed standard resistance levels to minocycline, levofloxacin and trimethoprim/sulfamethoxazole as determined by disk-diffusion tests, but MIC testing showed break points for ticarcillin/clavulanic acid, ceftazidime and chloramphenicol, minocycline, levofloxacin and trimethoprim/sulfamethoxazole . Therefore, some hospitals could increase the drug sensitivity test results of some drugs after changing disk-diffusion tests to MIC tests. For example, for S. maltophilia, disk diffusion method had only three drug break points, while MIC method had six drug break points. As a result, clinicians had more choices in the empirical treatment. However, the disadvantage of the change of drug sensitivity test methodology was that the cumulative drug sensitivity data were inevitably biased when comparing data for many years. In this study, the resistance rate of S. maltophilia to ceftazidime increased to 58.1% in 2013–2017, whereas the resistance rates of S. maltophilia to other antimicrobial agents were less than 25%. Whether the increase in ceftazidime resistance was related to its wide clinical application requires further investigation and analysis.
Surveillance data on BSIs from 1998–2017 showed that the resistance rate of A. baumannii to common antibiotics has reached a high level, and the prevalence of CR K. pneumoniae has increased significantly, resulting in significant difficulties in clinical treatment. Our data show that vancomycin, teicoplanin, linezolid and trimethoprim/sulfamethoxazole can be used to treat MRSA. The resistance rate of MRSA to trimethoprim/sulfamethoxazole has decreased significantly, possibly related to the decreased of use of this drug in recent years. Studies from China, South Korea and France have shown that the antimicrobial resistance rates of S. aureus, K. pneumoniae, E. coli, P. aeruginosa and Candida albicans also decreased with the decreased clinical use of these antimicrobial agents [31-34]. Tigecycline and polymyxin can be used to empirically treat CR K. pneumoniae, E. coli and A. baumannii.
This study had several limitations. The BSI incidence in Hubei Province was often reported from single research centers. We failed to find accurate data on the BSI incidence for all of Hubei Province from 1998–2017. Previous reports lacked demographic data. One shortcoming of this study was that the accurate BSI incidence was not calculated for Hubei Province. Another limitation was that different hospitals used different strain identification methods, including manual biochemical experiments and an IVD-MALDI Biotyper, and these results were undistinguishable once combined. Different hospitals adopted different drug sensitivity test methods, and the same hospital may change the drug sensitivity test method used between 1998 and 2017. Although each hospital strictly followed the CLSI guidelines, the inconsistency of test methods and the difference of drug sensitive consumables may lead to deviation in the analysis of drug resistance. The weakness of the analysis of the resistance mechanism involved in Gram-negative resistance to beta-lactams and more particularly to carbapenems was also a limitation of this study. We will increase the content of drug resistance mechanism research in the future.