Pharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary Exacerbation.

Adults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus Because CF patients experience alterations in pharmacokinetics, the optimal dose of telavancin in this population is unknown. Adult CF patients (n = 18) admitted for exacerbations received 3 doses of telavancin 7.5 mg/kg of body weight (first 6 patients) or 10 mg/kg (final 12 patients) every 24 h (q24h). Population pharmacokinetic models with and without covariates were fitted using the nonparametric adaptive grid algorithm in Pmetrics. The final model was used to perform 5,000-patient Monte Carlo simulations for multiple telavancin doses. The best fit was a 2-compartment model describing the volume of distribution of the central compartment (Vc ) as a multiple of total body weight (TBW) and the volume of distribution of the central compartment scaled to total body weight (Vθ) normalized by the median observed value (Vc = Vθ × TBW/52.1) and total body clearance (CL) as a linear function of creatinine clearance (CRCL) (CL = CLNR + CLθ × CRCL), where CLNR represents nonrenal clearance and CLθ represents the slope term on CRCL to estimate renal clearance. The mean population parameters were as follows: Vθ, 4.92 ± 0.76 liters · kg-1; CLNR, 0.59 ± 0.30 liters · h-1; CLθ, 5.97 × 10-3 ± 1.24 × 10-3; Vp (volume of the peripheral compartment), 3.77 ± 1.41 liters; Q (intercompartmental clearance), 4.08 ± 2.17 liters · h-1 The free area under the concentration-time curve (fAUC) values for 7.5 and 10 mg/kg were 30 ± 4.6 and 52 ± 12 mg · h/liter, respectively. Doses of 7.5 mg/kg and 10 mg/kg achieved 76.5% and 100% probability of target attainment (PTA) at a fAUC/MIC threshold of >215, respectively, for MIC of ≤0.12 mg/liter. The probabilities of reaching the acute kidney injury (AKI) threshold AUC (763 mg · h · liter-1) for these doses were 0% and 0.96%, respectively. No serious adverse events occurred. Telavancin 10 mg/kg yielded optimal PTA and minimal risk of AKI, suggesting that this FDA-approved dose is appropriate to treat acute pulmonary exacerbations in CF adults. (The clinical trial discussed in this study has been registered at ClinicalTrials.gov under identifier NCT03172793.).

Levofloxacin-induced rhabdomyolysis in a patient on concurrent atorvastatin: Case report and literature review.

WHAT IS KNOWN AND OBJECTIVE: The combination of HMG-CoA reductase inhibitors (statins) and fluoroquinolones generally is not considered a significant risk factor for rhabdomyolysis. Rhabdomyolysis is a known risk associated with statin therapy but has seldom been described with fluoroquinolone use. We describe a case of acute rhabdomyolysis involving the co-administration of atorvastatin and levofloxacin. CASE DESCRIPTION: A 65-year-old white male presented with clinical and laboratory evidence of rhabdomyolysis after approximately 19 days of levofloxacin therapy for treatment of a prosthetic joint infection. His symptoms resolved after discontinuation of levofloxacin and atorvastatin therapy and did not recur following reintroduction of atorvastatin therapy. WHAT IS NEW AND CONCLUSION: Delayed-onset rhabdomyolysis may occur in patients receiving levofloxacin. Weekly complete metabolic panels along with patient education about symptoms of rhabdomyolysis should be considered, particularly in patients on concurrent medications known to cause rhabdomyolysis.

Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin.

Nafcillin and oxacillin are used interchangeably in clinical practice, yet few studies have evaluated the safety of these two agents. Our objective was to compare the differential tolerabilities of nafcillin and oxacillin among hospitalized patients. We conducted a retrospective cohort study of all patients who received 12 g/day of nafcillin or oxacillin for at least 24 h. Two hundred twenty-four patients were included. Baseline characteristics and comorbidities were similar among patients receiving nafcillin (n = 160) and those receiving oxacillin (n = 64). Hypokalemia, defined as a potassium level of ≤3.3 mmol/liter or ≤2.9 mmol/liter or as a ≥0.5-mmol/liter decrease from the baseline level, occurred more frequently among patients who received nafcillin (51%, 20%, and 56%, respectively) than among those who received oxacillin (17%, 3%, and 34%, respectively; P < 0.0001, P = 0.0008, and P = 0.005, respectively). By multivariate logistic regression analysis, receipt of nafcillin was an independent predictor of severe hypokalemia (odds ratio [OR] = 6.74; 95% confidence interval [CI], 1.46 to 31.2; P = 0.02). Rates of hepatotoxicity did not differ between groups; however, acute kidney injury occurred more commonly with nafcillin than with oxacillin (18% versus 6%; P = 0.03). Overall, 18% of patients who received nafcillin discontinued therapy prematurely due to adverse events, compared to 2% of patients who received oxacillin (P = 0.0004). Nafcillin treatment is associated with higher rates of adverse events and treatment discontinuation than oxacillin among hospitalized adult patients. These findings have important implications for patients in both inpatient and outpatient settings, particularly patients who require long-term therapy and cannot be monitored routinely. Future randomized controlled studies evaluating the efficacy, costs, and tolerability of nafcillin versus oxacillin are warranted.

Diagnostic stewardship for Clostridioides difficile testing in an acute care hospital: A quality improvement intervention.

Objective: To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI). Design: Quality improvement study. Setting: Two urban acute care hospitals. Interventions: All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention. Results: The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022-October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021-January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73-1.05; P = .13). Conclusions: A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs.

A cost-minimization analysis of dalbavancin compared to conventional therapy for the outpatient treatment of acute bacterial skin and skin-structure infections.

INTRODUCTION: Acute bacterial skin and skin-structure infections (ABSSSI) are common infectious diseases (ID) that often require intravenous (IV) antibiotics. Dalbavancin is a novel lipoglycopeptide antibiotic administered once that is FDA-approved for the treatment of ABSSSI. No literature is available for real-world cost-comparability relative to conventional therapy. METHODS: This retrospective chart review examined adults diagnosed with ABSSSI and treated with IV antibiotics at an outpatient ID clinic after hospital discharge from January 2015 to August 2016. Patients received either dalbavancin or conventional therapy. In-hospital baseline demographics as well as outpatient clinical variables and outcomes were assessed. The primary outcome was the total ID-related cost of care per patient. A Monte Carlo probalistic sensitivity analysis was conducted. RESULTS: One hundred and fifty-eight patients were included: 64 received dalbavancin and 94 received conventional therapy. The total ID-related cost of care per patient was greater with dalbavancin (mean $4,561) vs conventional (mean $1,668), p < 0.01. In the subset of patients treated with daptomycin, the total ID-related cost (mean $5,218) was comparable to dalbavancin (mean $4,561). CONCLUSIONS: Dalbavancin was more costly than conventional therapy for the outpatient treatment of ABSSSI. This greater overall cost was likely driven by the higher acquisition cost of dalbavancin. Dalbavancin may be comparable to the daily use of daptomycin for ABSSSI.

Vancomycin-resistant enterococci in acute myeloid leukemia and myelodysplastic syndrome patients undergoing induction chemotherapy with idarubicin and cytarabine.

We conducted a retrospective study to determine the risk factors associated with vancomycin-resistant enterococci (VRE) acquisition/infection in newly diagnosed acute myeloid leukemia and myelodysplastic syndrome patients undergoing chemotherapy with the 7 + 3 regimen of cytarabine and idarubicin. Although only 2.5% (6/235) patients were colonized with VRE on admission, 59% (134/229) of patients acquired VRE during their hospitalization. Multivariable analysis identified the use of intravenous vancomycin (p = .024; HR: 1.548) and cephalosporin (p = .009; HR: 1.596) as the risk factors for VRE acquisition. VRE infection developed in 14% (33/229) of patients, with bloodstream infections accounting for 82% (27/33) of cases. VRE infection occurred in 25/126 (20%) of the VRE-colonized patients, but only 8/103 (8%) of those who were not (p = .01). Our study provides the evidence for the role of intravenous cephalosporin and vancomycin in VRE acquisition and highlights the clinical significance of VRE colonization in these patients.