Mortality Associated with Bacteremia Due to Colistin-Resistant Klebsiella pneumoniae with High-Level Meropenem Resistance: Importance of Combination Therapy without Colistin and Carbapenems.

Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing Klebsiella pneumoniae when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing K. pneumoniae is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing K. pneumoniae diagnosed from July 2012 to February 2016 was performed. The impact of combination therapy on crude 30-day mortality was analyzed by Cox regression using a propensity score as a covariate to control for indication bias and in an inverse probability of treatment weighting (IPTW) cohort. The study sample comprised 104 patients, of which 32 (30.8%) received targeted monotherapy and 72 (69.2%) received targeted combination therapy; none of them received either colistin or a carbapenem. The 30-day crude mortality rate was 30.8% (43.8% in patients treated with monotherapy and 25% in patients receiving combination therapy). In the Cox regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (hazard ratio [HR], 6.03; 95% confidence interval [CI], 1.65 to 21.9; P = 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27; P = 0.05). Targeted combination therapy was associated with lower mortality only in patients with septic shock (HR, 0.14; 95% CI, 0.03 to 0.67; P = 0.01). These results were confirmed in the Cox regression analysis of the IPTW cohort. Combination therapy is associated with reduced mortality in patients with bacteremia due to colistin-resistant KPC-producing K. pneumoniae with high-level carbapenem resistance in patients with septic shock.

Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project.

INTRODUCTION: Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood. METHODS AND ANALYSIS: This study will be implemented in two phases. First, a preliminary historical cohort (2017-2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020-2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured. ETHICS AND DISSEMINATION: Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03941951; Pre-results.

Brief Report: Differential Timing of Cholesterol Increase During Successful HCV Therapy: Impact of Type of Drug Combination.

OBJECTIVE: To evaluate factors associated with increased serum cholesterol levels during interferon-free hepatitis C virus (HCV) therapy. DESIGN: Prospective longitudinal study. METHODS: HIV-infected patients who started and successfully completed interferon-free therapy for chronic HCV infection were included. Patients were treated using 2 different regimens, based on the clinician's opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of treatment (EOT), weeks SVR4, SVR12, and SVR24. RESULTS: The study population therefore comprised 85 patients reaching sustained virological response, 42 (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total cholesterol and low-density lipoprotein cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After EOT, no differences were found between SOF/LDV and PrOD with respect to total cholesterol. CONCLUSIONS: Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 coinfected patients achieving sustained virological response is not mediated by HCV clearance but depends on the drug combination used.

Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients.

OBJECTIVES: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. METHODS: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia. A bivariate analysis was performed to compare the clinical variables between the study group and the control group. RESULTS: 31 patients were included. Bacteremia was considered primary in 14 (45%) patients. Overall crude mortality at 30days was 45.2% (n=14). Mortality was more frequent when septic shock (78.6% vs 11.8%; p>0.001) and higher Pitt score (6+14 vs 1.5+4; p<0.01) were present. 8 patients (25.8%) received treatment with ceftazidime/avibactam. No significant differences in crude mortality were found between study and comparator groups (p=0.19). In contrast, patients in study group had higher clinical cure rates than the comparator group within 14days of initiating treatment (85.7% vs. 34.8%, respectively, p=0.031). CONCLUSIONS: CPE bacteremia is associated with high mortality in patients with hematologic malignancies. Ceftazidime/avibactam may be an effective alternative for treating these patients.

Epidemiology and clinical impact of infection in patients awaiting heart transplantation.

OBJECTIVES: The aim of this study was to determine the epidemiology and clinical impact of infections in patients awaiting heart transplantation. METHODS: We evaluated all patients considered for a heart transplant in our center over a period of 18 months over a period of 18 months from 2007 to 2009. The patients were followed up for 8 months or until death, transplant, or loss to follow-up. RESULTS: Ninety patients were included in the study. During follow-up, 25 infections were recorded in 22 heart transplant candidates (24.4%). Respiratory infections were the most frequent infection (12 bronchitis; 48.0%), followed by skin and soft tissue infections (four infections; 16.0%), intra-abdominal infections (four infectious diarrhea; 16.0%), bacteremia (three infections; 12.0%), and urinary tract infections (two infections; 2.0%). Age, comorbidity, sex, and diabetes were not found to be risk factors for infection. Twenty-four patients (26.7%) were transplanted during follow-up. Infection before transplantation was not associated with an increased risk of mortality or a higher rate of infection in the immediate post-transplant period. CONCLUSIONS: Infections are common in heart transplant candidates, affecting almost 25% of them. Respiratory tract infections are the most frequent type of infection. However, they are not associated with increased mortality in the immediate post-transplant period.