K. pneumoniae is an opportunistic pathogen that causes a wide range of infections, including pneumonia, urinary tract infection, bacteremia, cholecystitis, and meningitis, especially in immunocompromised individuals. CHINET shows that both the K. pneumoniae isolation rate and drug resistance rate are steadily increasing [2]. Data from 66 hospitals in Shanghai show that the separation rate of ESBLs-KP derived from sputum, blood, and urine increased year by year from 2015 to 2017 [9]. The change in antibiotic resistance rates over 17 years (2000–2016) from EARSNet was becoming more and more serious, and that the resistance rates to third-generation cephalosporins, fluoroquinolones, and aminoglycosides showed a significant upward trend, and the analysis was related to ambient temperature [10].
The results of this study show that, except for SMCH, mainly from middle-aged and elderly patients, and with increasing age, the detection rate of K. pneumoniae gradually increases; the detection rate of K. pneumoniae isolated from men is higher than that of women, and K. pneumoniae isolated from males is more resistant to antibiotics than females. These findings suggest that elderly men are facing a more severe situation of K. pneumoniae resistance. Population-based surveillance is essential for monitoring the emergence and trends of antimicrobial resistance and guiding the development of rational antibiotic treatment recommendations[11].
Compared with the meta-analysis results of multiple studies in Asia, the overall resistance rates of amikacin, aztreonam, and meropenem were 40.8%, 73.3%, and 62.7%, respectively[12], the drug resistance rate in this study area is generally low. In our study, the resistance rate of amikacin was the lowest at 4.42%, followed by tigecycline, meropenem, imipenem, ertapenem, piperacillin/tazobactam, and the resistance rates were 5.76%, 6.83%, 9.42%, 9.02%, 9.95%, respectively. The resistance rate of the remaining antibiotics is greater than 10%, and the highest resistance rate is ciprofloxacin, with a resistance rate of 28.72%, which was generally lower than the CHINET average[13]. The high resistance rate of ciprofloxacin mainly comes from the urinary tract. The resistance rates of K. pneumoniae isolated from urine in this study to ciprofloxacin and levofloxacin were 42.45% and 32.34%, respectively, which were much higher than those of K. pneumoniae isolated from other specimens. This may be because fluoroquinolones are the first-line treatment of empirical medication in urinary tract infections[14, 15].
The production of ESBLs is one of the main resistance mechanisms of K. pneumoniae. ESBLs genes are mostly mediated by plasmids, which can spread between bacteria, including TEM, OXA, CTX-M, and SHV, etc, among which CTX-M is the main type contribution of the epidemiologic evolution of human ESBL infections[16]. An epidemiological survey in Zhejiang Province shows that the ESBLs rate is slightly higher than 20% in recent years[17]. The results in 2019 in the Shaoxing region are consistent with it. However, the ESBLs rate of each hospital is different. Among them, the ESBLs rate of TCM Hospital is the lowest, at only 11.80%. Whether it is related to the different disease composition of the patients admitted to this hospital or maybe because Chinese medicine is mainly used and antibiotics are used less is unknown, which is limited study on epidemiology and mechanism in TCM hospitals. A retrospective surveillance study in a TCM hospital in Hangzhou, Zhejiang Province, showed that 11.2% of hospital-acquired bloodstream infections were caused by K. pneumoniae, and 57.1% stains produced ESBLs, which is significantly higher than the average level of ESBLs in this study[18]. In our study, SUH has the highest ESBLs rate, which was converted from an infectious disease hospital to a general hospital in July 2018. The patients are mainly immunosuppressed people such as liver disease and HIV. The long hospital stay and repeated hospitalization history of these patients may be the main reasons.
K. pneumoniae may have become one of the important pathogens of childhood infections, and also is one of the vital cause of mortality[19]. A systematic review suggests that K. pneumoniae is the most frequent etiology of community-acquired pneumonia among children in China[20]. In our study, the detection rate of K. pneumoniae in the ≦ 17y group was 5.32%, much lower than previous reports[21]. Previous study has shown that children with bloodstream infections have the highest isolation rate and are mainly isolated from the ICU[22]. The K. pneumoniae isolated from the SMCH has the lowest resistance rate to carbapenems, β-lactam-β-lactamase inhibitor combinations, fourth-generation cephalosporins, amikacin, tobramycin, and sulfamethoxazole. However, the detection rate of ESBL strains in ≦ 17y group is 23.08%. Among them, up to 83.33% (20/24) of the strains were isolated from the neonatal ICU of the hospital (data not shown), which was higher than the adult group in this study. Children infected with ESBLs strains had a significantly longer length of hospital stays and required more ICU care days than those without such infection. At the same time, it increases the risk of further acquisition and transmission with resistant bacteria[23]. But the separation rate of ESBL is lower than that of large tertiary children's hospitals in our country[24]. And fortunately, no carbapenem resistance strain was found in ≦ 17y group in this study.
CHINET surveillance showed that the national average CRKP isolation rate in 2019 was 27.6%[13]. The 2014–2018 survey in Zhejiang Province indicated that the CRKP prevalence rate in Shaoxing was 9.72%, the detection rate by our study is slightly higher than that, which is far lower than the national average level[17]. However, the hospitals covered by the above-mentioned research studies are completely different, and there are also certain differences from the six hospitals covered by this research.
The detection rate of CRKP in different specimen sources is varied. In our study, the detection rate in non-sterile body fluids is the lowest at 2.63%, and except for cefoperazone/sulbactam and Sulfamethoxazole, K. pneumoniae isolated from non-sterile body fluids has the lowest resistance rate to antibiotics, while the detection rate of CRKP in the blood group is the highest at 23.86%. In our study, the resistance rate of K. pneumoniae isolated from blood to imipenem, cefepime, piperacillin/tazobactam is higher than that of strains isolated from other specimen sources. Previous research of bloodstream infections by Yang et al. found that K. pneumoniae was the second most infectious pathogen, and both adults and children showed an increasing trend between 2012 and 2017, and resistance to carbapenems and amikacin was on the rise [25]. Bloodstream infections are often combined with infections of other sites, and the most common sites are the respiratory tract and urinary tract[26]. There is also a study that intra-abdominal infection is an important source[27].Carbapenems have been considered to be the last line of defense against K. pneumoniae infection. With increasing drug resistance makes clinical anti-infective treatment has become a more difficult problem. Especially carbapenem-resistant K. pneumoniae bloodstream infections are accompanied by higher mortality[10].