Since the beginning of this century, Klebsiella pneumoniae has been prevalent all over the world, and with increasing incidence. It has gained the attention of clinical workers: on the one hand, the increase in the detection rate of drug-resistant bacteria has made it more difficult for clinicians to choose antibiotics; on the other hand, drug-resistant Klebsiella pneumoniae infections have a high mortality rate(2). It has been recommended that a combination of antibiotics be used to treat Klebsiella pneumoniae BSI, but there is still no further clinical evidence. Therefore, we collected the clinical data of patients with Klebsiella pneumoniae bacteremia and statistically analyzed the risk factors for drug-resistant bacterial infection, the risk factors for death, and the mortality of patients with different drug-resistant Klebsiella pneumoniae. The treatment plan was evaluated according to patient prognosis to improve the alertness of clinicians with regard to these cases and to provide guidance for the prevention of drug-resistant bacterial infections and reasonable treatment.
We collected and analyzed the clinical data of patients with Klebsiella pneumoniae BSI during the past five years. Of the 297 patients, S-KP accounted for only 38.4% of the total number of cases. Reviewing data on Klebsiella pneumoniae isolated from blood samples released in Greece, its resistance to carbapenem antibiotics ranged from less than 1% in 2001 to 30–60% in 2008. In 2006, researchers found that the reason for carbapenem resistance of this batch of CRKP was the presence of the blaVIM−1 gene(28,29). In 2008, a number of studies found the blaKPC−2 gene present in CRKP isolates and, at one time, there was an epidemic in two separate hospitals(30,31). Subsequently, CRKP was detected in the United States, Italy, Israel, and other countries around the world, one after another. In this study, we did not explore the molecular epidemiology, but put more emphasis on the clinician perspective. We compared the clinical characteristics of Klebsiella pneumoniae patients with different drug resistance and found that sex and age were not related to susceptibility to drug-resistant bacteria. Patients with recent ICU hospitalization history, recent surgical history, recent antibiotic use history, mechanical ventilation history, and hospitalization more than two weeks before the BSI diagnosis were more likely to be infected with drug-resistant bacteria. It is suggested that clinicians be more vigilant against the possibility of drug-resistant bacterial infections when facing the clinical manifestations of BSIs in these kinds of patients, such as fever, increased procalcitonin (PCT), or even shock. At the same time, several other possible risk factors should not be ruled out, such as patients with a recent history of invasive surgery, patients in the ICU ward, patients with diabetes, and patients with severe clinical symptoms. Mantzarlis et al. found that critically ill patients who received carbapenem or polymyxin antibiotics, patients who received mechanical ventilation, and patients who underwent invasive surgery were more likely to develop CRKP infection(32). However, all the patients included were ICU patients, and the samples included blood and airway secretions, as well as other infectious secretions. Freeman et al. found that patients with a history of ICU hospitalization and transplantation, including hematopoietic stem cell and solid organ transplant, had a higher risk of Extended-Spectrum β-Lactamases Klebsiella pneumoniae (ESBL-KP) infection(33). However, fewer cases were included in this study, and there was no age limit. At the same time, patients who do not have ESBL-KP may also have carbapenem or even a variety of antibiotic-resistant bacteria. In this study, based on the results of the drug sensitivity test that clinicians are typically most concerned about, we analyzed the epidemiological characteristics, high risk factors, and prognosis for drug-resistant bacterial infections.
In this study, the 28-day all-cause mortality rate of the included patients was 42.8%. Patients were divided into groups according to the results of the different drug sensitivity tests. The results showed that the mortality rate of patients with S-KP bacteremia was 21.6%. The mortality rate of patients with MDR-KP bacteremia was 44.8%. And the mortality rate of patients with XDR-KP bacteremia was 67.9%. Studies by Hoxha et al. found that the 30-day attributable mortality rate of CRKP patients was 41%, and the risk of death was three times higher than that of CSKP patients(34). However, the inclusion population included all patients with Klebsiella pneumoniae infection, not limited to BSIs. Studies by Borer et al. found that the crude and attributable mortality rates of patients with drug-resistant Klebsiella pneumoniae were 71.9% and 50%, respectively(35). It was also found that the mortality rate of patients with MODS was 86.9%, and that of patients with septic shock was 100%, which was significantly higher than that of patients with simple sepsis. Nearly 25% of the patients in the study conducted by Borer et al. were from nursing homes and, thus, pertained more to elderly patients. Only adult patients with clinically diagnosed BSI and only Klebsiella pneumoniae blood cultures were included in our study. The mortality data obtained are higher than that in previous studies. On the one hand, because of the large number of critically ill patients, a total of 38% of the patients had a history of living in ICU before hospitalization, and a total of 61.6% of the patients were admitted to ICU during hospitalization. On the other hand, because the outcome index uses a survival condition of 28 days after the BSI diagnosis, this study pertains to all-cause mortality rather than hospital mortality. Unlike other studies that include only CRKP or XDR-KP, this trial includes information on all patients with Klebsiella pneumoniae BSI with different drug sensitivity results.
We analyzed the patients with different clinical prognoses. Through univariate and multivariate analysis, it was clear that tracheal intubation, respiratory failure, hypoalbuminemia, MODS, a SOFA score greater than 6 points, and CRKP were independent risk factors for death within 28 days after diagnosis of Klebsiella pneumoniae infection. Additionally, patients with poor prognosis were more likely to get worse during the course of treatment, such as MODS, acute kidney injury (AKI), mechanical ventilation, and septic shock. The risk factors explored in this study were 28-day risk factors for death in all patients clinically and bacteriologically diagnosed with Klebsiella pneumoniae BSI. Mantzarlis et al. found that older patients and immunodeficient patients were independent risk factors for death in patients with CRKP infection in the ICU(36). Recent studies in southwest China have found that XDR-KP patients with solid tumors and septic shock are independent risk factors for death within 28 days. However, sputum was the main sample and only 13% of the samples were blood. At the same time, the positive culture results of the samples were not combined with the corresponding clinical symptoms. Falcone et al. showed that colistin resistance and intra-abdominal infection were independent risk factors for death in patients with CRKP septic shock(37). Machuca et al. found that septic shock and admission to the ICU are independent risk factors for 30-day death in patients with CRKP, and combined anti-infective therapy can reduce the mortality of septic shock patients with CRKP bacteremia(38). The detection rate of drug-resistant bacteria is increasing day by day, and the 2.9 times higher mortality rate of patients with CRKP infection versus CSKP patients highlights the importance of developing pre-control.
Compared to different treatment schemes, anti-infective combination therapy in patients with S-KP bacteremia did not demonstrate a significant benefit; whereas, monotherapy had a relatively lower cost and greater benefit. Although patients with MDR-KP bacteremia had a lower risk of monotherapy, more patients died in 28 days, and the two antibiotic regimens dominated by tigacycline or carbapenem appeared more frequently. The mortality rate of patients with XDR-KP bacteremia is very high. We found that the 28-day mortality rate of combined therapy was significantly lower than that of monotherapy. It is recommended to avoid anti-infective therapy with single antibiotics in the case of drug-resistant bacterial infections. For patients at high-risk for drug-resistant bacterial infection, if the possibility of Gram-negative bacteremia is considered, whether there is clinical benefit for combination anti-infective treatment to treat Klebsiella pneumoniae infection still needs to be confirmed by further clinical studies.
Our experiment has some limitations. First of all, we only counted the all-cause mortality of patients, but we included only patients with clear Klebsiella pneumoniae at the time of selection, excluding patients who died or were discharged within 24 hours after admission. Second, our sample size is small and retrospective observational studies were conducted. A larger sample is necessary for further randomized controlled trials, but taking into account the changes in drug use and the drug resistance spectrum over time, the patient data from the last five years were selected and no further review was conducted. Third, we did not compare the prognosis of treatment with binary and triple antibiotics. This was due to the fewer number of cases for combined use of three kinds of antibiotics. Thus, the reference value for comparison is small. Finally, and most importantly, our study does not represent the current epidemiological situation in China, let alone other countries. The specific distribution of drug resistance and the corresponding treatment plans still need to be further developed according to the local epidemiological characteristics.