Comparative Outcomes of Candida auris Bloodstream Infections: A Multicenter Retrospective Case-Control Study.

BACKGROUND: This study was performed to compare clinical characteristics and outcomes between patients with bloodstream infections (BSIs) caused by Candida auris and those with BSIs caused by other Candida spp. METHODS: A multicenter retrospective case-control study was performed at 3 hospitals in Brooklyn, New York, between 2016 and 2020. The analysis included patients ≥18 years of age who had a positive blood culture for any Candida spp. and were treated empirically with an echinocandin. The primary outcome was the 30-day mortality rate. Secondary outcomes were 14-day clinical failure, 90-day mortality rate, 60-day microbiologic recurrence, and in-hospital mortality rate. RESULTS: A total of 196 patients were included in the final analysis, including 83 patients with candidemia caused by C. auris. After inverse propensity adjustment, C. auris BSI was not associated with increased 30-day (adjusted odds ratio, 1.014 [95% confidence interval, .563-1.828]); P = .96) or 90-day (0.863 [.478-1.558]; P = .62) mortality rates. A higher risk for microbiologic recurrence within 60 days of completion of antifungal therapy was observed in patients with C. auris candidemia (adjusted odds ratio, 4.461 [95% confidence interval, 1.033-19.263]; P = .045). CONCLUSIONS: C. auris BSIs are not associated with a higher mortality risk than BSIs caused by other Candida spp. The rate of microbiologic recurrence was higher in the C. auris group.

Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime-Avibactam.

BACKGROUND: The aim of this study was to evaluate the predictive performance of the INCREMENT-CPE (ICS), Pitt bacteremia score (PBS) and qPitt for mortality among patients treated with ceftazidime-avibactam for carbapenem-resistant Enterobacteriaceae (CRE) infections. METHODS: Retrospective, multicenter, cohort study of patients with CRE infections treated with ceftazidime-avibactam between 2015 and 2019. The primary outcome was 30-day all-cause mortality. Predictive performance was determined by assessing discrimination, calibration and precision. RESULTS: In total, 109 patients were included. Thirty-day mortality occurred in 18 (16.5%) patients. There were no significant differences in discrimination of the three scores [area under the curve (AUC) ICS 0.7039, 95% CI 0.5848-0.8230, PBS 0.6893, 95% CI 0.5709-0.8076, and qPitt 0.6847, 95% CI 0.5671-0.8023; P > 0.05 all pairwise comparisons]. All scores showed adequate calibration and precision. When dichotomized at the optimal cut-points of 11, 3, and 2 for the ICS, PBS, and qPitt, respectively, all scores had NPV > 90% at the expense of low PPV. Patients in the high-risk groups had a relative risk for mortality of 3.184 (95% CI 1.35-8.930), 3.068 (95% CI 1.094-8.606), and 2.850 (95% CI 1.016-7.994) for the dichotomized ICS, PBS, and qPitt, scores respectively. Treatment-related variables (early active antibiotic therapy, combination antibiotics and renal ceftazidime-avibactam dose adjustment) were not associated with mortality after controlling for the risk scores. CONCLUSIONS: In patients treated with ceftazidime-avibactam for CRE infections, mortality risk scores demonstrated variable performance. Modifications to scoring systems to more accurately predict outcomes in the era of novel antibiotics are warranted.

Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections.

Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population (n = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections.

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

BACKGROUND: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). METHODS: Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. RESULTS: In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p < 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024) CONCLUSIONS: V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy.

Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections.

BACKGROUND: We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. METHODS: This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. RESULTS: In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115-4.620 and aOR = 1.234, 95% CI = 1.118-1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180-0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia). CONCLUSIONS: Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.