Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections Research Articles

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study

BackgroundAs limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6–10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. MethodsA retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. ResultsOf 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0–76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01–0.63; P = 0.005). ConclusionShort courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Colistin versus polymyxin B for the treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infections

BackgroundTo assess the effectiveness of colistin (administered as colistimethate sodium-CMS) and polymyxin B (PMB) for the treatment of bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Materials and methodsThis retrospective cohort included hospitalized adult patients with CRKP BSIs from a single tertiary-care hospital. A univariate analysis comparing CMS and PMB groups was carried out and an inverse-probability propensity score (IPPS) was created. An IPPS-adjusted Cox regression model for 30-day mortality was performed including covariates potentially associated with mortality. ResultsA total of 100 patients with CRKP BSI (87 were KPC-producing isolates) were included. The 30-day mortality was 42.0 %:17/46 (38.8 %) and 25/54 (44.6 %) patients of CMS and PMB groups, respectively, P = 0.54 (incidence rate, 18.9 and 21.7/1000 patients-day in CMS and PMB groups, respectively, P = 0.62). No statistically significant difference in 30-day mortality rate was observed in a model adjusted for Pitt bacteremia score, high-risk primary site and IPPS, which included age, intensive care unit admission, minimal inhibitory concentration, previous colonization by CRKP, diabetes mellitus, malignancy, neutropenia, meropenem use before BSI, adjuvant therapy with meropenem and amikacin, and time to start polymyxin. Acute kidney injury (AKI) occurred in 52.0 % of patients, with no significant differences between groups (47.8 % and 57.4 % for CMS and PMB, respectively, P = 0.83). In-hospital mortality was 47,7 % and 50.0 % in CMS and PMB groups, respectively, P = 0.82. ConclusionThere was no difference in 30-day mortality and AKI rates among patients with CRKP BSI treated with PMB or CMS.

Comparison of bloodstream and non-bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae in the intensive care unit: a 9-year respective study.

Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have received much attention. However, few studies have identified risk factors for CRKP BSIs in comparison to CRKP non-bloodstream infections (non-BSIs). This study aimed to compare the epidemiology, risk factors, and outcomes of CRKP BSIs and CRKP non-BSIs. We conducted a retrospective study of patients infected with CRKP in the ICU from January 2012 to December 2020. Clinical characteristics and outcomes were compared between CRKP BSIs and CRKP non-BSIs. Predictors associated with 28-day all-cause mortality in CRKP-infected patients were also evaluated. 326 patients infected with CRKP were enrolled, including 96 patients with CRKP BSIs and 230 with CRKP non-BSIs. The rates of CRKP BSIs in CRKP infections were generally raised from 2012 (12.50%) to 2020 (45.76%). Multivariate logistic analysis indicated that the use of carbapenems within the prior 90 days was an independent risk factor for CRKP BSIs (p = 0.019). Compared to CRKP non-BSIs, CRKP isolates in the CRKP BSI group were found to be non-susceptible to more tested carbapenems (p = 0.001). Moreover, the CRKP BSI group exhibited a higher mortality rate (p = 0.036). The non-susceptibility of CRKP isolates to more tested carbapenems (p = 0.025), a high SOFA score (p = 0.000), and the use of antifungal drugs within the prior 90 days (p = 0.018) were significant factors for 28-day all-cause mortality in CRKP-infected patients. The proportion of CRKP BSI increased progressively in CRKP-infected patients over 9 years. The use of carbapenems within the prior 90 days was an independent risk factor for the development of CRKP BSIs. The non-susceptibility of CRKP isolates to more tested carbapenems and a higher mortality rate were found in the CRKP BSI group.

Risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae bacteraemia in children: a retrospective study

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly identified in children, but data on the clinical outcomes in this population are limited. The objectives of this study were to characterize the risk factors for 30-day mortality with CRKP bloodstream infection (BSI) in children. We performed a retrospective study from January 2018 to December 2021 at the First Affiliated Hospital of Zhengzhou University. Patients (<18 years old) with CRKP BSI were included. Multivariable Cox and logistic regression were performed to determine risk factors for death and the development of septic shock following CRKP infection, respectively. We identified 33 neonates aged 0-4 weeks and 37 older children. The 30-day mortality rate was 39.4% in neonates and 43.2% in older children. In the neonatal population, a higher Pitt bacteremia score (HR, 1.694; 95% CI, 1.313-2.186; P <0.001) was an independent risk factor for 30-day mortality. In the non-neonatal population, higher platelet count (HR, 0.990; 95% CI, 0.982-0.998; P = 0.010), the use of carbapenems (HR, 0.212; 95% CI, 0.064-0.702; P = 0.011), and appropriate targeted antimicrobial treatment (HR, 0.327; 95% CI, 0.111-0.969; P = 0.044) were associated with decreased 30-day mortality. Monocyte count less than 0.1 × 109 cells/L (OR, 3.615; 95% CI, 1.165-11.444; P = 0.026), and a higher Pitt bacteremia score (OR, 1.330; 95% CI, 1.048-1.688; P = 0.019) were identified as risk factors for the development of septic shock. CRKP BSI was associated with high mortality in children. Appropriate antimicrobial treatment is important to improve survival, but more work is needed to assess the efficacy of specific treatment regimens in children.

Ceftazidime/Avibactam, Polymyxin or Tigecycline as a Rescue Strategy for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae in Bloodstream Infection: A Retrospective Cohort Study.

To analyze the clinical characteristics, outcomes, and risk factors of patients treated with ceftazidime/avibactam, polymyxin, or tigecycline (CPT) compared with those receiving a conventional therapy (CT) (ie, imipenem, levofloxacin, or gentamicin). A single-center retrospective cohort study included patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) treated at one Chinese tertiary hospital between March 2012 and November 2022 was performed. Clinical characteristics, outcomes, and risk factors of patients treated with CPT or CT were compared. Predictors of 30-day mortality of patients with CRKP-BSI were also analysed in our study. Among 184 recruited patients with CRKP-BSI, 39.7% (73/184) were treated with CPT, while 60.3% (111/184) were treated with CT. Compared to patients treated with CT, patients treated with CPT had worse conditions, as evidenced by a higher rate of underlying diseases and invasive procedures; however, they also had a better prognosis and lower rates of 14-day treatment failure (p = 0.024). In addition, univariate analysis and multivariate analysis showed that SOFA score [odds ratio (OR) = 1.310, 95% confidence interval (CI) 1.157-1.483; p < 0.001] and cold weather (OR = 3.658, 95% CI 1.474-9.081; p = 0.005) were independent risk factors for 30-day mortality. Compared to CRKP-BSI patients treated with CT, patients treated with CPT had worse conditions but better prognoses. CRKP-BSI occurred more frequently in hot weather; however, higher 30-day mortality was associated with cold weather. A randomized trial is needed to confirm these observational results.

Cost-effectiveness analysis of ceftazidime-avibactam as definitive treatment for treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infection.

Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic that has been confirmed in the United States and China for use in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). However, the cost-effectiveness of CAZ-AVI is unknown in China. This study aimed to evaluate the cost-effectiveness of CAZ-AVI compared to polymyxin B (PMB) monotherapy or PMB-based therapy for the treatment of CRKP BSI from the Chinese healthcare perspective. A hybrid decision tree and Markov model were constructed for a hypothetical cohort of patients with CRKP BSI. The time horizon of the Markov model was 5 years with an annual discount rate of 5% used in both costs and quality-adjusted life-years (QALYs). The model data was derived from published literature and publicly available database. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the willingness-to-pay (WTP) threshold of $ 11,600 per QALY were considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model analysis. In the base-analysis, CAZ-AVI provided an additional 60 QALYs and reduced the cost by $ 2,218,300, yielding an ICER of $ -36,730.9/QALY, well below the WTP threshold of $ 11,600 per QALY when compared with PMB-based therapy. CAZ-AVI provided an additional 350 QALYs and increased the cost of $ 208,400, producing an ICER of $ 591.7/QALY that was below the WTP threshold compared to PMB monotherapy. At a $ 11,600/QALY threshold, results were sensitive to the cost of PMB-based strategy, the cost of CAZ-AVI strategy, the probability of cure with CAZ-AVI, and the probability of cure with PMB or PMB-based therapy. CAZ-AVI was an optimal regimen in 76.9% and 80.8% of 10,000 Monte Carlo simulations at $ 11,600/QALY and $ 34,800/QALY, respectively. Meanwhile, CAZ-AVI was cost-effective at the WTP thresholds of all 31 Chinese provinces in 61.4% (Gansu) to 83.1% (Beijing) of simulations. Ceftazidime-avibactam is expected to be a cost-effective treatment compared with PMB monotherapy or PMB-based therapy for CRKP BSI from the Chinese healthcare perspective.

Risk factors and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary-care hospital in China: an eight-year retrospective study

BackgroundThe prevalence of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI.MethodsThis was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China.ResultsAmong the 706 incidences included in this study, 27.4% of them (212/753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies and ICU acquired infection were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P < 0.001). Logistic regression analysis identified severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset as the independent predictors of 28-day mortality of CRKP-BSI patients. However, high dose carbapenem combination therapy was identified as anticipated factors of low 28-day mortality.ConclusionThe occurrence of CRKP-BSI was significantly increased during the study period. Hematologic malignancies and ICU acquired infection were associated with the development of CRKP BSI. Severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset caused significant increase of mortality rates in CRKP-BSI patients. High dose carbapenem combination therapy was associated with better outcome.

Retrospective Analysis of Epidemiology, Risk Factors, and Outcomes of Health Care-Acquired Carbapenem-Resistant Klebsiella pneumoniae Bacteremia in a Chinese Tertiary Hospital, 2010-2019.

In the present study, we aimed to describe the proportion of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) in KP-BSI in one Chinese tertiary hospital over 10years and determine the risk factors and outcomes of CRKP-BSI. We retrospectively analyzed clinical and microbiological data of patients with KP-BSI from January 2010 to December 2019 to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis. KP-BSI only included monomicrobial BSI and health care-acquired BSI. Among the total 687 isolates of KP-BSI in this study, the rate of CRKP was 39.0% (268/687); this rate in the intensive care unit (ICU) was 65.6% and that in seven high-risk departments (including four ICUs, respiratory medicine, gastroenterology medicine, and hepatobiliary surgery) was 74.6%. The annual rate of CRKP in KP-BSI ranged from 0.0% in 2010 to 54.5% in 2019. The 28-day mortality was 36.2% in patients with CRKP-BSI and 11.7% in those with carbapenem-susceptible K.pneumoniae (CSKP) BSI. Multivariable logistic regression analysis showed that prior ICU stay (odds ratio [OR] 2.485, P < 0.001), hospital stay ≥ 30days prior to BSI (OR 1.815, P = 0.007), prior mechanical ventilation (OR 2.020, P = 0.014), prior urinary catheter (OR 1.999, P = 0.003), prior carbapenem use (OR 3.840, P < 0.001), hepatobiliary disease (OR 2.943, P < 0.001), pancreatitis (OR 2.700, P = 0.026), and respiratory disease (OR 2.493, P = 0.009) were risk factors of CRKP-BSI. Patients with a first admission (OR 0.662, P = 0.046) had a lower percentage of CRKP-BSI. The rapidly rising rate of CRKP-BSI in KP with high mortality requires increased attention. Exposure to carbapenems, ICU stay, invasive mechanical ventilation or urinary catheter, prolonged hospital stay, hepatobiliary disease, pancreatitis, and respiratory disease were found to be risk factors for CRKP-BSI. Strict control measures should be implemented to prevent the emergence and spread of CRKP, especially in high-risk departments.

Risk Factors for Mortality and Outcomes in Hematological Malignancy Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

BackgroundThis study aimed to identify risk factors for mortality and outcomes in hematological malignancy (HM) patients with bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).MethodsA retrospective study was conducted at a tertiary teaching hospital in Henan Province, China, between January 2018 and December 2021. All BSIs caused by CRKP in hospitalized HM patients were identified. Data on patient demographics, disease, laboratory tests, treatment regimens, outcomes of infection, and the antimicrobial susceptibility of each isolate were collected from medical records.ResultsA total of 129 patients with CRKP BSI were included in the study, and the 28-day mortality rate was 80.6% (104/129). In Cox analysis an absolute neutrophil count < 500 at discharge (hazard ratio [HR] 6.386, 95% confidence interval [CI] 3.074–13.266, p < 0.001), intensive care unit admission (HR 1.834, 95% CI 1.065–3.157, p = 0.029), and higher Pitt bacteremia score (HR 1.185, 95% CI 1.118–1.255, p < 0.001) were independent risk factors associated with 28-day mortality. Survival curve analysis indicated that compared with ceftazidime-avibactam-based therapy, both polymyxin b (HR 8.175, 95% CI 1.099–60.804, p = 0.040) and tigecycline (HR 14.527, 95% CI 2.000–105.541, p =0.008) were associated with a higher risk of mortality.ConclusionIn HM patients CRKP BSI resulted in high mortality. Intensive care unit admission, higher Pitt bacteremia score, and absolute neutrophil count < 500 at discharge were independently associated with higher mortality. Early initiation of new agents such as ceftazidime-avibactam may improve outcomes.

Risk factors for infection and mortality caused by carbapenem-resistant Klebsiella pneumoniae: A large multicentre case–control and cohort study

ObjectivesTo elucidate the predictors of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection and help clinicians better identify CRKP infection at an early stage. MethodsWe conducted a multicentre case–control study of 422 patients with CRKP infection and 948 with carbapenem-susceptible K. pneumoniae (CSKP) infection from March to July 2017. Binary logistic regression was used to identify risk factors for CRKP infection. The subgroups of CRKP respiratory infection, intra-abdominal infection, and bloodstream infection were also evaluated. Patients were followed up for 28 days. Independent risk factors for 28-day crude mortality of CRKP infection were analysed using Cox proportional hazards regression models. ResultsLonger stay of hospitalization, stay in the intensive care unit (ICU), previous exposure to antibacterial agents (especially carbapenems, quinolones, aminoglycosides, and tigecycline), invasive procedures, intravascular catheter use, tracheotomy, and admission to ICU in the preceding 90 days were risk factors for CRKP infection. Carbapenem exposure was the only common predictor of different types of CRKP infection. The 28-day crude mortality of CRKP infection was 24.2% and was independently associated with sex, admitted unit, and type of infection. ConclusionsStrict policies for antibiotic use, cautious decisions regarding the implementation of invasive procedures, and careful management of patients with catheters, especially intravascular catheters, are necessary to handle CRKP infection.

The Value of Neutrophil-To-Lymphocyte Ratio for Evaluating Blood Stream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae: A Retrospective Cohort Study.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a useful marker of inflammation. However, the prognostic function of the NLR in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) blood stream infection (BSI) remains largely unknown. The aim of this study was to explore the potential relationship between the NLR and mortality in these patients.MethodsWe performed a retrospective cohort study based on data retrieved from the computerized patient record system in a tertiary hospital from 1 January 2017 to 31 October, 2020. A total of 134 inpatients with CRKP BSI were enrolled in this study, including 54 fatal cases and 80 survival cases, 28 days after the onset of CRKP BSI. A logistic analysis was performed to assess the association between the NLR on the 4th day and 28-day mortality. Multivariate analyses were used to control for the confounders.ResultsThe overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis of the data of 134 patients and found that the NLR on the 4th day [odds ratio (OR) 1.148, 95% confidence interval (CI) 1.076–1.225, p < 0.001] and antibiotic exposure before BSI onset (OR 3.847, 95% CI 1.322–11.196, p = 0.013) were independent risk factors for 28-day mortality of patients with CRKP BSI, while appropriate initial therapy (AIT, OR 0.073, 95% CI 0.017–0.307, p < 0.001) was an independent protective factor. Among patients treated with AITs, the Cox proportional hazards regression analysis revealed a significant difference in prognosis (p = 0.006) between the ceftazidime/avibactam contained (CAZ) group and non CAZ-AVI groups. After dividing the non CAZ-AVI group into the tigecycline (TGC), colistin (COL), and TGC + COL groups, there were no differences between the CAZ-AVI group and the TGC group (p = 0.093), but CAZ-AVI group showed lower 28-day mortality than COL (p = 0.002) and TGC + COL (p = 0.002) groups. Meanwhile, there was no difference in NLR on the 1st day (p = 0.958) of patients in different groups but significant difference in NLR on the 4th day (p = 0.047).ConclusionsThe NLR on the 4th day is a readily available and independent prognostic biomarker for patients with CRKP BSI. This marker may have the potential for use in evaluating the efficacy of different anti-infection therapy strategies at an early stage.

Adipose tissue is a predictor of 30-days mortality in patients with bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae

BackgroundPrevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection with high mortality has attached physicians' attention. High visceral adipose tissue (VAT) and high subcutaneous adipose tissue (SAT) were confirmed by previous studies that were closely related to increased pneumonia severity, more complications, and higher mortality in COVID-19. Thus, we speculate that CT-quantified body composition may also be connected to all-cause mortality and bacterial clearance in patients with CRKP bloodstream infection (BSI).MethodsWe investigated the associations of CT-quantified body composition with the mortality of CRKP bloodstream infectious patients. All CT images were obtained at the level of the L3/4 spinal level. The prognostic value of the body composition was analyzed using the Cox regression model, and precise clinical nomograms were established.Results72 eligible patients both suffered from CRKP bloodstream infection and performed abdominopelvic CT were included. Factors associated with 30-day all-in hospital mortality included total adipose tissue (TAT) [adjusted hazard ratio (HR) = 1.028, 95% confidence interval (CI), 1.003–1.053; P = 0.025], age [HR = 1.030, 95% CI, 1.000–1.061; P = 0.047] and SOFA scores [HR = 1.138, 95% CI 1.049–1.263; P = 0.002]. Compared with low-VAT, patients with high-VAT show a strikingly poor prognosis in both 30-day all-cause mortality (P = 0.0108, Fig. 2A) and 30-day CRKP BSI mortality (P = 0.0049, Fig. 2C). The results of TAT were similar to VAT.ConclusionsOur study suggested that CT-derived body composition could be a credible and effective alternative to assess the prognosis of patients with BSI owing to CRKP. CT-quantified TAT, age, and SOFA scores were independently associated with 30-day all-cause mortality in these severe infectious patients, while skeletal muscle did not have obvious statistical significance.

A retrospective observational cohort study of the clinical epidemiology of bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae in an OXA-48 endemic setting

This study aimed to characterize the epidemiology and clinical outcomes of patients with bloodstream infections (BSIs) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in an OXA-48-predominant environment. This was a retrospective single-centre cohort study including all consecutive patients with CRKP BSIs treated between 1 January 2014 and 31 December 2018. Multivariate analysis, subgroup analysis and propensity-score-matched analysis were employed to analyse 30-day mortality as the primary outcome. Clinical cure at day 14 was also analysed for the whole cohort. In total, 124 patients with unique isolates met all the inclusion criteria. OXA-48 was the most common type of carbapenemase (85.5%). Inappropriate therapy was significantly associated with 30-day mortality [70.6% vs 39.7%, adjusted odds ratio (aOR) 4.65, 95% confidence interval (CI) 1.50-14.40, P=0.008] and 14-day clinical failure (78.5% vs 56.2%, aOR 3.14, 95% CI 1.09-9.02, P=0.033) in multivariate analyses. Among those treated appropriately, the 30-day mortality rates were similar in monotherapy and combination therapy arms (OR 2.85, 95% CI 0.68-11.95, P=0.15). INCREMENT CPE mortality score (aOR 1.16, 95% CI 1.01-1.33, P=0.029), sepsis at BSI onset (aOR 2.90, 95% CI 1.02-8.27, P=0.046), and inappropriate therapy (aOR 4.65, 95% CI 1.50-14.40, P=0.008) were identified as independent risk factors for 30-day mortality. Colistin resistance in CRKP had no significant impact on 30-day mortality. These results were also confirmed in all propensity-score-matched analyses and sensitivity analyses. Appropriate regimens were associated with better clinical outcomes than inappropriate therapies for BSIs with CRKP predominantly possessing OXA-48.

Risk Factors for a Hospital-Acquired Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection: A Five-Year Retrospective Study.

PurposeThis study aimed to describe trends in Klebsiella pneumoniae (KP) resistance in bloodstream infections (BSI) and to identify risk factors for a hospital-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI and 28-day mortality from a hospital-acquired KP BSI.Patients and MethodsWe recorded the results of antimicrobial susceptibility testing of 396 KP-positive blood cultures from January 2016 to December 2020. A total of 277 patients with a KP BSI were included in this study, of which 171 had a hospital-acquired infection and 84 had a hospital-acquired CRKP BSI. Multivariate logistic regression analysis was used to identify risk factors for a hospital-acquired CRKP BSI and 28-day mortality from a hospital-acquired KP BSI.ResultsThe proportion of hospital-acquired infections among KP BSI patients increased from 53.1% in 2016 to 72.8% in 2020. The detection rate of CRKP among KP BSI patients increased from 18.8% in 2016 to 37.7% in 2020. Multivariate logistic regression showed that β-lactam/β-lactamase inhibitor combinations (BLBLIs) exposure (P = 0.022, OR 2.863), carbapenems exposure (P = 0.007, OR 3.831) and solid organ transplantation (P <0.001, OR 19.454) were independent risk factors for a hospital-acquired CRKP BSI. Risk factors for a 28-day mortality from hospital-acquired KP BSI were CRKP BSI (P =0.009, OR 5.562), septic shock (P =0.002, OR 4.862), mechanical ventilation>96 hours (P =0.020, OR 8.765), and platelet counts <100×109/L (P =0.003, OR 4.464).ConclusionThe incidence of hospital-acquired KP BSI continues to rise and the proportion of CRKP BSI is also increasing. We believe that the use of the BLBLIs needs to be carefully evaluated in hospital-acquired infection. Hospital-acquired KP BSI Patients with CRKP BSI, septic shock, mechanical ventilation and deficiency of platelets are more likely to have a poor prognosis.

Molecular Epidemiology and Risk Factors of Carbapenem-Resistant Klebsiella Pneumoniae Bloodstream Infections in Wuhan, China

The clinical characteristics and microbiological data of patients with K. pneumoniae bloodstream infections (BSI) from January 2018 to December 2020 were retrospectively analyzed to study the molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae (CRKP). We also aimed to identify the risk factors for the development of CRKP BSI. This retrospective study was conducted at Renmin Hospital of Wuhan University from January 2018 to December 2020. The date of non-duplicate K. pneumoniae isolates isolated from blood samples was identified using the microbiology laboratory database. The data from patients diagnosed with K. pneumoniae BSI were collected and analyzed. From 2018 to 2020, there were 510 non-duplicated K. pneumoniae blood isolates, mainly distributed in the intensive care unit (ICU) (28.4%), that were identified in our research. These cases included 77 strains of CRKP and 433 strains of carbapenem-susceptible K. pneumoniae (CSKP). The resistance rate of K. pneumoniae to meropenem and imipenem increased from 11.2% in 2018 to 27.1% in 2020. Moreover, Compared with CSKP, all CRKP isolates showed multi-resistance to tested antibiotics. The phylogenetic analysis showed that the CRKP isolates could be grouped into four major clades, and multilocus sequence typing revealed that the isolates had considerable clonality. Overall, 8 sequence types (STs) of CRKP were detected, of which ST11 comprised the majority and clustered into clade 3. The most prevalent carbapenemase gene was blaKPC (87%) among the CRKP isolates, followed by blaNDM (9.1%) and blaIMP (1.3%). A total of 74 (16.6%) patients with CRKP BSI and 373 (83.4%) patients with CSKP BSI were categorized as the case and control groups. The mortality in the CRKP group was 44.6%, and 11.5% in CSKP group (P<0.001). A multivariate analysis that a long hospital stay before BSI (OR=1.42, 95% CI 1.02-4.31, P=0.011), ICU hospitalization history (OR=3.30, 95% CI 1.35-8.05, P=0.002), and prior use of carbapenems (OR=3.33, 95% CI 1.29-7.27, P=0.001) and antifungals (OR=2.81, 95% CI 1.24-6.04, P<0.001) were independent risk factors for CRKP BSI. ST11 is the predominant type of CRKP mediating inter-hospital transmission, and blaKPC is the main carbapenemase gene harboured by CRKP blood isolates. ICU stay, prolonged hospitalization before BSI, and prior use of carbapenems and antifungals were independent risk factors for acquiring CRKP BSI. Our study may provide insights into early infection control practices.

Risk Factors of 30-Day All-Cause Mortality in Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection.

An optimal antimicrobial regimen for the treatment of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is currently unavailable. This study aimed to identify the appropriate antibiotics and the risk factors of all-cause mortality for CRKP BSI patients. This retrospective cohort study included the hospitalized patients with CRKP BSI. Primary outcome was 30-day all-cause mortality. Cox regression analysis was used to evaluate the risk factors of 30-day mortality. A total of 89 patients were included with a 30-day mortality of 52.1%. A total of 52 (58.4%) patients were treated with appropriate antimicrobial regimens and 58 (65.2%) isolates carried blaKPC-2 genes. Microbiologic eradication within 7 days (adjusted hazard ratio [HR] = 0.09, p < 0.001), platelet count (per 1 × 104/mm3, adjusted HR = 0.95, p = 0.002), and Pitt bacteremia scores (adjusted HR = 1.40, p < 0.001) were independently associated with 30-day all-cause mortality. No effective antimicrobial regimens were identified. In conclusion, risk factors of 30-day mortality in patients with CRKP BSI included microbiologic eradication > 7 days, lower platelet count, and a higher Pitt bacteremia score. These findings render a new insight into the clinical landscape of CRKP BSI.

Shift in the Dominant Sequence Type of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection from ST11 to ST15 at a Medical Center in Northeast China, 2015-2020.

ObjectiveTo investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection at a medical center in northeast China, especially after coronavirus disease (COVID-19) pandemic.MethodsFifty-one patients were diagnosed with CRKP bloodstream infection between January 2015 and December 2020, among which 42 isolates were available for further study. Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. Carbapenemase genes, virulence genes and MLST genes were detected by polymerase chain reaction. Moreover, the string test and serum killing assay were performed to evaluate the virulence of the CRKP isolates.ResultsDuring the six-year period, the detection rate of CRKP in bloodstream infection showed an increasing trend, with the intensive care unit, hematology and respiratory medicine wards mainly affected. Molecular epidemiology analyses showed that KPC-2 was the dominant carbapenemase gene. In addition, the dominant sequence type (ST) of CRKP shifted from ST11 to ST15 strains, which were all sensitive to amikacin in contrast to the ST11 stains. Furthermore, ST15 CRKP strains were positive for the KfuB virulence gene and more resistant to serum killing compared to the ST11 CRKP strains. Nonetheless, the mortality rate of patients infected with ST11 and ST15 CRKP did not show any significant differences.ConclusionA shift in the dominant sequence type of CRKP bloodstream infections from ST11 to ST15 was observed during the years 2015–2020. Compared to ST11, the ST15 CRKP strains showed amikacin sensitivity, positivity for KfuB gene, and serum resistance, which may indicate stronger virulence.

The Impact of Carbapenem Resistance on Mortality in Patients With Klebsiella Pneumoniae Bloodstream Infection: An Individual Patient Data Meta-Analysis of 1952 Patients

IntroductionAvailable evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined.MethodsWe updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256).ResultsIPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56–3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24–2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70–4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36–3.59; I2 = 58%).ConclusionResistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00408-8.

Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia

The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR)=12.89, 95% confidence interval (CI) 3.88-42.83; P < 0.001], pneumonia (aOR=5.97, 95% CI 1.65-21.76; P=0.007) and rapidly fatal underlying disease (aOR=6.43, 95% CI 1.30-31.09; P=0.02). In contrast, cefepime-based therapy (aOR=0.03, 95% CI 0.003-0.38; P=0.006) and combination therapy (aOR=0.09, 95% CI 0.02-0.36; P=0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.

Polymyxin monotherapy versus polymyxin-based combination therapy against carbapenem-resistant Klebsiella pneumoniae: A systematic review and meta-analysis

ObjectivesThis meta-analysis was performed to compare polymyxin monotherapy and polymyxin-based combination therapy for carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections. MethodsWe conducted searches on MEDLINE, Embase and Cochrane Collaborative database for both observational studies and randomised controlled trials (RCTs) comparing polymyxin monotherapy with polymyxin-based combination therapy in patients with CR-KP infection. The primary outcome was mortality. We divided all included studies into several groups according to different combination-combination and different infection types. The odds ratio (OR) and 95% confidence intervals (CI) were calculated for outcome analysis. ResultsTen studies with 481 patients were included. Polymyxin monotherapy was associated with higher mortality than polymyxin-based combination therapy in treatment of CR-KP bloodstream infections (BSI) (OR 1.93, 95% CI 1.14–3.27, P = 0.01) and ventilator-associated pneumonia (VAP)/hospital-acquired pneumonia (HAP) (OR 3.82, 95% CI 1.15–12.71, P = 0.03). In subgroup analysis of different combinations, mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline (OR 1.88, 95% CI 1.05–3.37, P = 0.03), or with cabapenem (OR 3.11, 95% CI 1.25–7.74, P = 0.01), but no differences were found in combinations with aminoglycosides (OR 1.29, 95% CI 0.72–2.29, P = 0.38). Three-drug combination therapy including polymyxin was also associated with significant survival benefit (OR 3.86, 95% CI 1.60–9.32, P = 0.003). ConclusionsPolymyxin-based combination therapy provides significant survival benefit in treatment of CR-KP, which appears to be more pronounced when a carbapenem or tigecycline is included in the regimen.