To our knowledge, few studies have evaluated the risk factors for the acquisition of CREC infections, with most reports describing the mechanisms of carbapenem resistance of CRE (17, 18, 19, 20). Therefore, the aim of our matched case‒control study was to assess the potential risk factors for CREC infections.
In our study, we found that CREC infections were mainly concentrated in the ICU, followed by the emergency department in the general medical ward and the neurosurgical ward in the surgical department. Patients in the ICU have serious underlying diseases and require life-support systems and the usage of broad-spectrum antibiotics (21). Patients with various infectious diseases are often treated in the emergency department, and patients undergoing craniocerebral surgery need to have the drainage tube in place for a long time and use broad-spectrum antibiotics due to intracranial infection.
All of the CREC strains were resistant to ampicillin, cefazolin, cefuroxime, ceftriaxone, and ciprofloxacin.The antibiotic resistance of the CREC group was more severe than that of the CSEC group, and the differences between most antibiotics in two groups was statistically significant. However, the strains remained relatively susceptible to amikacin. There was no better way to treat CREC infections considering the above results and according to individual clinical conditions.
Our results show that antibiotics exposure (3rd- or 4th-generation cephalosporin and carbapenem), glucocorticoid exposure, and surgical history were risk factors for CREC infection.
Studies have reported that there is close association between CREC infection and antibiotic use, especially carbapenem exposure (22, 23, 24, 25). Our study showed that the prior use of carbapenem was an independent risk factor for CREC infections, which is consistent with most previous studies. The acquisition of the ability to produce carbapenemase is the main cause of carbapenem resistance, which can easily result in nosocomial spread (26). Tian et al demonstrated that the most prevalent carbapenemase gene in CREC was blaNDM, followed by blaKPC-2 in China (9). However, Dagher C et al found that the predominant detected carbapenemase was OXA-48 in Lebanon (27), and carbapenem exposure may induce the emergence of these resistance-conferring genes. In our study, 3rd- or 4th-generation cephalosporin exposure within 3 months was also a risk factor for CREC infections, which indicates that CREC infection occurrence can be induced not only by the usage of carbapenem, but also by the use of other drugs. Thus, we need to strengthen the management of antibiotics for inpatients, and treatment with high doses and controlled durations is also a better way to limit the risk of infections(24).
Unlike in other studies, our study revealed that previous usage of glucocorticoids was also a risk factor for CREC infections, possibly because patients with CREC infections have serious underlying diseases and are treated with glucocorticoids. Second, the use of glucocorticoids destroyed the intestinal microenvironment, killed sensitive strains, and then promoted the overgrowth of drug-resistant strains, which promoted the shift of opportunistic pathogens to pathogenic bacteria.
It is not surprising that surgical history is a risk factor for CREC infection, which is consistent with previous studies (28), emphasizing the importance of aseptic operation in patient care. Aseptic technique is an important strategy for the prevention of CREC infections .
In this study, we found that gastric tube insertion was an independent risk factor for 30-day mortality. Meta-analyses have shown that the use of medical devices (including gastric tubes) had the highest pooled estimate (29). Some studies have shown that CREC can colonize the gastrointestinal tract, patients with CREC colonization of the gastrointestinal tract are more likely to develop CREC infections (30). The majority of patients with gastric tubes have gastrointestinal dysfunction and poor nutritional status and have a higher risk of intestinal translocation of bacteria, including that of CREC. CREC infections and carbapenem exposure were also found to be independent risk factors for 30-day mortality. Therefore, judicious use of carbapenem with antibiotic stewardship programs, reduction of invasive procedures and prevention of CREC infections are effective ways to reduce 30-day mortality.
Patients with CREC infections who died were significantly older than surviving patients with CREC infections. Possible reasons for this might have included more frequent health care and antibiotics exposure among older adults (31). Central venous catheter insertion was an independent risk factor for in-hospital mortality in nosocomial CREC infections. The most likely reason is that invasive procedures can lead to damage to the mucosa, and increase the incidence of CREC infections since the majority of the bacteria are able to pass through the mucosal barrier into other sites (32). Carbapenem exposure was also a risk factor for in-hospital mortality in patients with CREC infection, and the possible reasons are the same as above.
This study has several limitations that should be taken into consideration. First, a molecular epidemiological investigation of CREC was not carried out; thus, we could not assess whether there were any outbreaks during the study period, and different drug resistance mechanisms may result in different clinical outcomes. Therefore, we will perform molecular epidemiological investigations in future studies. In addition, there may have been bias during our control group selection, because the assessment of patients harboring antibiotic‒susceptible organisms might lead to an overestimation of the risk of antibiotics exposure (33).Finally, it was a single‒center study with a small sample size. Prospective, multicenter and large-sample clinical trials are needed.