Background A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae (CRE). Methods We retrospectively analyzed observational data on the use and outcomes of CAZ-AVI therapy for infections caused by KPC-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens vs. CAZ-AVI monotherapy. Results The cohort comprised 577 adults with bloodstream infections (BSIs) (n=391) or non-bacteremic infections (nBSIs) involving mainly the urinary tract, lower respiratory tract, intra-abdominal structures. All received treatment with CAZ-AVI alone (n=165) or with one or more other active antimicrobials (n=412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no statistically significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs. 25.0%, P=0.79). In multivariate analysis, mortality was positively associated with the presence at infection onset of septic shock (P=0.002), neutropenia (P <0.001), or an INCREMENT score >8 (P=0.01); with LRTI (P=0.04); and with CAZ-AVI dose adjustment for renal function (P=0.01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P=0.006). All associations remained significant after propensity score adjustment. Conclusions CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug’s seemingly more limited efficacy in LRTIs and the potential survival benefits of prolonging CAZ-AVI infusions to 3 hours or more.
Background Patients colonized with carbapenem resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT) with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. Methods Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray sub-distribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. Results 840 LT recipients found to be colonized with CRE before (n=203) or after (n=637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (IQR 9-42) days after LT. Pre-and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical re-intervention were retained in the prediction model. Median 30 and 60-day predicted risk was 15% (IQR 11-24%) and 21% (IQR 15-33%), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (AUC 74.6, Brier index 16.3) and bootstrapped validation dataset (AUC 73.9, Brier index 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. Conclusions Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
The pandemic caused by the COVID-19 virus has required major adjustments to healthcare systems, especially to infection control and antimicrobial stewardship. The objective of this study was to describe the incidence of multidrug-resistant (MDR) hospital-acquired infections (HAIs) and antibiotic consumption during the three waves of COVID-19 and to compare it to the period before the outbreak at Molinette Hospital, located in the City of Health and Sciences, a 1200-bed teaching hospital with surgical, medical, and intensive care units. We demonstrated an increase in MDR infections: particularly in K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp), A. baumannii, and MRSA. Fluoroquinolone use showed a significant increasing trend in the pre-COVID period but saw a significant reduction in the COVID period. The use of fourth- and fifth-generation cephalosporins and piperacillin–tazobactam increased at the beginning of the COVID period. Our findings support the need for restoring stewardship and infection control practices, specifically source control, hygiene, and management of invasive devices. In addition, our data reveal the need for improved microbiological diagnosis to guide appropriate treatment and prompt infection control during pandemics. Despite the infection control practices in place during the COVID-19 pandemic, invasive procedures in critically ill patients and poor source control still increase the risk of HAIs caused by MDR organisms.
Background: CORACLE is a retrospective and prospective, regional multicenter registry, developed to evaluate risk factors for mortality in a cohort of patients admitted with SARS-CoV-2 infection within non-intensive wards. Methods: The primary objective was to estimate the role of several prognostic factors on hospital mortality in terms of adjusted Odds Ratios (aOR) with multivariable logistic regression models. Results: A total of 1538 patients were enrolled; 42% were female, and 58% were >70 years old. Deceased patients were 422 (27%), with a median age of 83 years (IQR (Inter Quartile Range) 76–87). Older age at admission (aOR 1.07 per year, 95%CI 1.06–1.09), diabetes (1.41, 1.02–1.94), cardiovascular disease (1.79, 1.31–2.44), immunosuppression (1.65, 1.04–2.62), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (3.53, 2.26–5.51), higher C-reactive protein values and a decreased PaO2/FiO2 ratio at admission were associated with a higher risk of hospital mortality. Amongst patients still alive on day 7, only hydroxychloroquine (HCQ) treatment was associated with reduced mortality (0.57, 0.36–0.90). Conclusions: Several risk factors were associated with mortality in SARS-CoV-2 positive patients. Although HCQ seems to be the only factor significantly associated with reduced mortality, this result is in contrast with evidence from randomized studies. These results should be interpreted in light of the study limitations.
Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028–1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572–18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.
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