Antibacterial drugs have been administered extensively in clinic, especially in the treatment of ICU patients. However, the widespread use of antibacterial drugs produces further resistant bacteria, which is becoming a serious public health concern [10]. The abuse of this antibacterial drug causes the body to produce multi-drug resistance and the risk of super bacterial infection increases. The rational application of antibacterial drugs in the clinic effectively prevents the spread of drug-resistant strains and more comprehensive understanding of drug resistance mechanisms, and epidemiology of drug-resistant strains has much potential to improve the cure rates of ICU patients [11].
The majority of ICU isolates collected in the participating multicenters consisted of E. coli and Klebsiella pneumoniae in additon to E. cloacae in China [12, 13]. In this study, ESBLs-producing and non-ESBLs-producing strains of E. coli showed significant differences in resistance to cephalosporins with ESBLs-producing strains having significantly higher resistance rates. In contrast, there was no obvious difference between the ESBLs-producing and non-ESBLs-producing strains concerning ciprofloxacin. In the comparison to the sensitivity of cephalosporin antibiotics with sulbactam and tazobactam, the drug resistance was extremely lower than that of cephalosporins alone. This group of studies fully demonstrated that if the production of ESBLs can be reduced as much as possible, the resistance of E. coli can also be greatly reduced.
E. coli and E. cloacae belong to conditional pathogens that are part of the normal intestinal flora but can cause infections of the respiratory and urinary tracts [14, 15]. An epidemiological study has reported that the detection rate of E. coli and E. cloacae producing ESBLs was increasing, 44% in Singapore, 37% in China [16]. Both E. coli and E. cloacae producing ESBLs are closely related to the drug resistance of antibiotics, and the same type of bacteria are likely to carry a variety of ESBLs, leading to multi-drug resistance [17, 18]. Studies have also shown that there are multiple drug resistance mechanisms in E. coli and E. cloacae, which include mutations in Amp C enzymes and porin loss, which has been described in previous literatures [19, 20]. However, we did not explore molucular mechanisms of resistances.
In this study, we collected samples from different parts of the patients and found that E. coli and E. cloacae were most common in infections of the respiratory tract and skin. The resistance of E. cloacae to 17 antimicrobial agents was similar to that of E. coli. All of them exhibited high resistance to cephalosporins, whilst they were highly sensitive to carbapenems. Because the northeast part of China is the most colded region with the highest incurrence of respiratory system diseases, antimicrobial overuse might be an explanation for the antimicrobial agents susceptibility difference in this area.
Clinically, the application of a large number of high-grade cephalosporin antibiotics in the treatment of ICU patients with nosocomial infections and unreasonable use of the third-generation cephalosporins have resulted in a large number of drug-resistant strains [21, 22]. Patients who are ineffectively treated with advanced cephalosporins or β-lactamase inhibitors can only further use carbapenem antibacterial drugs in treating Gram-negative bacteria [23].
Carbapenems have the strongest antimicrobial activity, broadest antimicrobial spectrum and belong to atypical beta-lactam antimicrobial agents. The low toxicity and high stability of beta-lactamase make them one of the best options for the treatment of severe infections when other antimicrobial agents are ineffective [24, 25].
In this study, both E. coli and E. cloacae were highly sensitive to carbapenems, and no significant difference in resistance between ESBLs-producing and non-ESBLs-producing strains was observed, indicating that carbapenems could be used as an option in the treatment of ESBLs-resistant strains. In contrast to data collected from centers in east China, the reduced susceptibilities of E. coli and E. cloacae indicated a local carbapenem resistance [26]. Taken together, the carbapenem overuse might be an explanantion for the difference because of the developed areas with the higher incomes [27].
In the epidemiological analysis of nosocomial infections in the ICU, ERIC-PCR was used to identify isolates EIC-PCR fingerprints. Results of ERIC-PCR in all of ESBLs-producing E. coli isolates exhibited 11 distinct profiles, and one distinct ERIC profiles were observed amongst 46 strains of ESBLs-producing E. cloacae. Since the establishment of ERIC-PCR technique by versalovic et al. in 1991, it has played an important role in the identification and epidemiological investigation of Gram-negative bacteria. In 2001, Matsumoto et al. applied two different methods, ERIC-PCR and PFGE, to detect 23 clinical isolates of Berkholderia onions. The results indicated that two methods have similar detection abilities and reproducibility [28, 29]. ERIC profiles demonstrated an outbreak of nosocomial infection and ESBLs-producing E. coli and E. cloacae prevalent in the ICU of this hospital.
The study found that ESBLs-producing bacteria were resistant to aminoglycoside antibiotics such as levofloxacin, and were more resistant to the above two types of antibacterial drugs than those with high resistance to cephalosporin antibiotics. The resistance to synthetic antibiotics such as sulfonamides was also lower than that of simple ampicillin. In the clinical application of antibiotics, the initial use of advanced cephalosporin antibiotics, especially the unreasonable use of the third generation cephalosporins, is the beginning of habitual therapy. These practices cause us to ignore the role of aminoglycosides and other antibacterial drugs that lead to common clinical drug resistance. In order to control the production and spread of ESBLs from the source, more reasonable use of antibacterial drugs should be followed by limiting the routine empirical application of high-level antibiotics by medical personnel. Publicity and education on the use of antibacterial drugs amongst health care workers should be strengthened along with improvements in the management of pharmacies and hospital ICUs [30, 31]. These measures could effectively cut off the source of infection and a mode of transmission of ESBLs bacteria. In addition, this could guide medical staff to rationally use antimicrobial agents [32]. This study has some limitations. Firstly, the genotypic or molecular data of all strains were not documented. Secondly, the molecular epidemiology was not included. Further studies are needed to confirm the genetic types and the mechanism of transmission.