R. Brigg Turner

National consensus guidelines outline recommendations for best practices in treating patients with candidemia. This study evaluated the impact of receiving care adherent to the best practice recommendations on clinical outcomes in patients with candidemia. This retrospective, multicenter study included patients with candidemia from 2010 to 2015 at 9 hospitals. The primary outcome was the composite of 30-day in-hospital mortality and 90-day candidemia recurrence. Outcomes were compared between those receiving and not receiving care adherent to the guideline recommendations. Inverse probability weights with regression adjustment were utilized to determine the average treatment effect of adherent care on the composite outcome 295 patients were included with 14.2% meeting criteria for the composite outcome (11.9% mortality and 2.4% recurrence). The average treatment effect of adherent care was not significant (P = .75). However, receiving appropriate initial antifungal treatment and central venous catheter removal were both associated with the composite (average treatment effect of −17.5%, P = .011 and −8.8%, P = .013, respectively). In patients with a source of infection other than the central line, central venous catheter removal was not associated with the composite (P = .95). The most common reason for failure to receive appropriate initial antifungal treatment was omission of the loading dose. Central venous catheter removal and appropriate initial antifungal treatment were associated with a lower incidence of the composite of mortality and recurrence. Additional studies are needed to determine the optimal duration of therapy following candidemia clearance.

Background Vancomycin area under the time‐concentration curve (AUC) has been linked to efficacy and safety. An accurate method of calculating the AUC is needed. Methods Bayesian dose optimizing software programs available for clinician use and first‐order pharmacokinetic equations were evaluated for their ability to estimate vancomycin AUC. A previously published rich pharmacokinetic dataset of 19 critically‐ill patients was used for validation of the AUC estimation. The AUC estimated using subsets of the full dataset by Bayesian software and equations was compared with the reference AUC. Accuracy (ratio of estimated AUC to the reference AUC) and bias (percent difference of estimated AUC to reference AUC) were calculated. Results Five Bayesian dose optimizing software programs (APK©, Best Dose^TM, DoseMe^®, Insight‐Rx©, and PrecisePK^TM) and 2 first‐order pharmacokinetic equations were included. Of the Bayesian programs, Insight‐Rx was the most adaptable, visually appealing, easiest to use, and had the most company support. Utilizing only the trough, accuracy (range from 0.79 to 1.03) and bias (range from 5.1% to 21.2%) of the Bayesian dose optimizing software were variable. PrecisePK and Best Dose had the most accurate estimates with the accuracy values of Best Dose exhibiting the most variability of all the programs; however, both programs were more difficult to use. PrecisePK was the least biased (median of 5.1%). Using a single, non‐trough value produced similar results to that of the trough for most programs. The addition of a second level to the trough improved the accuracy and bias for DoseMe and Insight‐Rx but not PrecisePK and Best Dose. APK did not reliably estimate the AUC with input of 2 levels. Using 2 levels, the pharmacokinetic equations produced similar or better accuracy and bias as compared with Bayesian software. Conclusion Bayesian dose optimizing software using 1 or more vancomycin levels and pharmacokinetic equations utilizing 2 vancomycin levels produce similar estimates of the AUC.

Ceftaroline is often used in durations greater than that studied in clinical trials. Several retrospective, non-comparative studies have suggested a higher than anticipated incidence of neutropenia in patients receiving prolonged treatment with ceftaroline. We sought to determine if ceftaroline was associated with neutropenia by comparing the incidence with ceftaroline treatment with treatment with several comparative antibiotics. Patients receiving 14 or more consecutive days of treatment with ceftaroline were compared with patients receiving cefazolin, daptomycin, linezolid, nafcillin or vancomycin (control group). The primary outcome was the development of neutropenia. Multivariate logistic regression and propensity score weighting using inverse probability weights with regression adjustment were used to control for confounding variables. A total of 753 patients were included (53 that received ceftaroline and 700 that received a comparative antibiotic). Ceftaroline was associated with a greater incidence of neutropenia as compared with the control group (17.0% versus 3.9%, P < 0.001). Several covariates were also associated with neutropenia and included younger age, lower baseline absolute neutrophil count, liver disease and bone and joint infections. After controlling for these confounders, receipt of ceftaroline continued to be associated with the development of neutropenia (adjusted OR 3.97, P = 0.003). Analysis after propensity score weighting confirmed this finding. The results of this study suggest that prolonged treatment with ceftaroline is associated with a greater incidence of neutropenia as compared with other antibiotics that are often used for treatment of staphylococcal infections. Careful monitoring of absolute neutrophil count is recommended in patients receiving >14 days of ceftaroline.

Despite limited clinical data, ceftaroline is commonly used for treatment of complicated, invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). A retrospective chart review was conducted of adult patients receiving ceftaroline for MRSA osteomyelitis admitted between April 2011 and March 2016 at a five-hospital system. Twelve patients met the inclusion criteria. All patients received prior antimicrobial therapy with a median time to switch to ceftaroline of 45.5 days. Five of the 12 patients (41.7%) met criteria for ceftaroline failure. Patients with vertebral osteomyelitis (58%) had a longer length of stay, longer ceftaroline treatment, but similar success rates to those with non-vertebral osteomyelitis (57% vs. 60%). Ceftaroline is a viable alternative for a challenging patient population that has failed or are unable to receive other therapies.

Background Pediatric stewardship programs have been successful at reducing unnecessary antibiotic use. Data from nonfreestanding children's hospitals are currently limited. This study is an analysis of antibiotic use after implementation of an antimicrobial stewardship program at a community nonfreestanding children's hospital. Methods In April 2013, an antimicrobial stewardship program that consisted of physician-group engagement and pharmacist prospective auditing and feedback was initiated. We compared antibiotic use in the preintervention period (April 2012 to March 2013) with that in the postintervention period (April 2013 to March 2015) in all units except the neonatal intensive care unit and the emergency department. In addition, drug-acquisition costs, antibiotic-specific use, death, length of stay, and case-mix index were examined. Results Antibiotic use decreased by 16.8% (95% confidence interval, 18.0% to −9.2%; P < .001) in the postintervention period. Vancomycin use decreased by 38% (P = .001), whereas antipseudomonal β-lactam use was unaltered. Drug-acquisition cost savings were estimated to be $67 000/year over the 2-year postintervention period. Lengths of stay and mortality rates were unchanged in the postintervention period after adjusting for case-mix index. Conclusions Implementation of a simple stewardship initiative with limited resources at a community nonfreestanding children's hospital effectively reduced antibiotic use without an overt negative impact on overall clinical outcomes. The results of this study suggest that nonfreestanding children's hospitals can achieve substantial reductions in antibiotic use despite limited resources.