In this study, we reported the rates and changing trends of CRKP infections, compared patient sources, specimen types and infection sources with CSKP and CRKP, and investigated the risk factors and outcomes for CRKP infections. Since reported studies have explored trends, characteristics and risk factors of CRKP which were isolated from blood culture in the ICU or the whole hospital, it was worth noting that we conducted the study among patients with all types of KP infections in the ICU. And changing trends of patient sources, specimen types and infection sources for critical care patients with KP infections were not reported before. So many findings in our study were reported firstly, and they provided a basis for the control of KP infections in ICU.
Few study explored changing trends of resistance rates of KP to carbapenems in the ICU, we found a study from an intensive care unit of Southern Italy that carbapenem resistant KP rates rose from 0% in 2008 to 59.2% in 2013[19], and multicenter data from CHINET described that resistance change of KP to imipenem and meropenem increased from 3.0% in 2005 to 26.3% in 2018[4]. Considering the trends of China and abroad, we predicted that the prevalence of CRKP also rose in our ICU. Here we found that an impressive increase of CRKP numbers and rates from 2012 to 2017. It showed that carbapenem resistance rate increased from 11.11% in 2012 to 63.48% in 2017. Notably, the resistance rate decreased from 2018(51.52%), and our unpublished data also revealed that the incidence of CRKP decreased further in 2019. It may be related to the implementation of antimicrobial stewardship(AMS) in our hospital.
Uwe Koppe et al.[20] reported the number of KP isolates tested non-susceptible to 3 carbapenems (imipenem, meropenem, and ertapenem). In our study, we explored the changing trends of KP isolates resistance to 1, 2, and 3 carbapenems. We discovered that the rates of resistance to 1 and 2 carbapenems dropped significantly, and the rate of resistance to 3 carbapenems continuously increased from 0 to 98.04%. Obviously, it posed a much more difficult challenge for the treatment of CRKP infections.
Specimen types may associate with the rates of CRKP. Among KP patients with bloodstream infection, wound infection, urinary infection, and pleural infection, the rates of CRKP were significantly higher than that of CSKP. This suggests that, the treatment regimen for CRKP infection may be necessary when KP is suspected to be the pathogen of these infections. Although bloodstream infection with CRKP were most reported, as the amount of respiratory specimen was more than the sum of other specimen types, it suggests that pulmonary infection with KP should not be ignored.
The incidences of CRKP in patients from different sources were not reported before. We found that the incidence of CRKP in patients from external hospitals had increased to 65%, which was more than the incidence of CSKP in the last 3 years. It indicated that when patients from external hospitals infected with KP, CRKP would be more likely. So effective antibiotic treatment that keeping a low rate of carbapenem –resistance, should be implemented.
In the study, we found that CRKP infection was mainly ICU acquired. It demonstrated that ICU admission was an important risk factor for acquiring CRKP. CSKP infection was mainly ICU acquired and normal wards in our hospital acquired. Although these findings were firstly reported and they need to be verified, it helps us tailor our surveillance actions to our circumstance, and an intensification of ICU-acquired CRKP infection control measure may be considered desirable.
Several risk factors associated with CRKP infection have been identified in previous studies. According to a CRKP BSI study, independent risk factors were ICU acquired infection, skin and tissue[14]. For a study of patients with CRKP BSI in the ICU, indwelling central venous catheter was the only independent risk factor for CRKP bacteremia[12]. Another study of a teaching hospital on CRKP infections only found that use of sputum suction was an independent risk factor[21]. In our study, we observed that previous ICU stay, gastric tube, previous use of carbapenems and β‑lactams and β‑lactamase inhibitor combination were risk factors for ICU patients infected with CRKP. As the scope and infection types were different among studies, the risk factors are not completely consistent, they all provided a basis for the control of CRKP in their own ICU or hospital.
In addition, we investigated the outcomes of patients with CRKP infections. Compared with CSKP, patients with CRKP had longer length of ICU stay, a higher rate of bloodstream infection, and a lower rate of improved and cured. Since the mortality was based on the number of patients who died in our ICU, we did not measure the mortality of patients transferred out of ICU who abandoned treatment due to deterioration. Therefore, the mortality in this study was lower than the actual value. We found the crude 30-day mortality in patients with CRKP infections was 7.81%,and the rate increased to 14% in patients with CRKP bloodstream infections which was also lower to studies in both China and other countries[9, 22]. So we analyzed the risk factors associated with failure and mortality of patients with CRKP infections. The result displayed that ages, bloodstream infection, and the previous use of antifungal agents were risk factors. Age, bloodstream infection were also confirmed in other studies[23, 24].
Our study has limitations. Firstly, as our hospital is a tertiary hospital that admit different kinds of critical ill patients, changing trends of patient sources and other epidemiology data maybe not suitable for specialized hospitals. Secondly, as a retrospective analysis, clinical data were obtained from electronic medical records, missing information may have potential effects on results. Nevertheless, the sample size of our study was not small and it would not hamper the statistical power of our analysis.