Antimicrobial agents and chemotherapy
-
Antimicrob. Agents Chemother. · May 2021
Cefepime Population Pharmacokinetics and Target Attainment in Critically Ill Patients on Continuous Renal Replacement Therapy.
Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT), which will affect their antimicrobial exposure. We aimed to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment. ⋯ At MICs of ≤8 mg/liter, intermittent infusion of 2 g cefepime every 8 h achieved good target attainment both early in therapy and at steady state. Only extended- and continuous-infusion regimens achieved good target attainment at MICs of 16 mg/liter. In conclusion, 2 g cefepime infused over 30 min followed by extended infusion of 2 g every 8 h achieved good target attainment at MICs of ≤16 mg/liter with different CRRT flow rates and may be considered in resistant bacterial infections.
-
Antimicrob. Agents Chemother. · Mar 2021
Randomized Controlled TrialRandomized Controlled Trial of the Electrocardiographic Effects of Four Antimalarials for Pregnant Women with Uncomplicated Malaria on the Thailand-Myanmar Border.
Quinoline antimalarials cause drug-induced electrocardiographic QT prolongation, a potential risk factor for torsade de pointes. The effects of currently used antimalarials on the electrocardiogram (ECG) were assessed in pregnant women with malaria. Pregnant women with microscopy-confirmed parasitemia of any malaria species were enrolled in an open-label randomized controlled trial on the Thailand-Myanmar border from 2010 to 2016. ⋯ There was no difference between DP and chloroquine (P = 0.91). QTc prolongation resulted mainly from widening of the JT interval. In pregnant women, none of the antimalarial drug treatments exceeded conventional thresholds for an increased risk of torsade de pointes.
-
Antimicrob. Agents Chemother. · Dec 2020
Observational StudyDecreased Overall and Inappropriate Antibiotic Prescribing in a Veterans Affairs Hospital Emergency Department following a Peer Comparison-Based Stewardship Intervention.
Antibiotic prescribing is very common in emergency departments (EDs). Optimal stewardship intervention strategies in EDs are not well defined. We conducted a prospective, observational cohort study in a Veterans Affairs ED in which clinician education and monthly e-mail-based peer comparisons were directed against all oral antibiotic prescribing for discharged patients. ⋯ Optimal antibiotic prescribing (i.e., antibiotics were indicated, and a guideline-concordant agent was prescribed for guideline-concordant duration) increased by 36% (21.6% to 29.3%, P = 0.12). A peer comparison-based stewardship intervention directed at ED clinicians was associated with reductions in overall and unnecessary oral antibiotic prescribing. There is potential to further improve antibiotic use as suboptimal prescribing remained common.
-
Antimicrob. Agents Chemother. · Nov 2020
Multicenter Study Clinical TrialA Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.
Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. ⋯ During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).
-
Antimicrob. Agents Chemother. · Nov 2020
Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP).
In the phase 3 ASPECT-NP trial (NCT02070757), ceftolozane/tazobactam (C/T) was noninferior to meropenem for treatment of Gram-negative ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we report outcomes in participants from ASPECT-NP with renal impairment (RI). Participants were categorized by their baseline renal function as follows: normal renal function (NRF; creatinine clearance [CLCR], ≥80 ml/min), mild RI (CLCR, >50 to <80 ml/min), moderate RI (CLCR, ≥30 to ≤50 ml/min), and severe RI (CLCR, ≥15 to <30 ml/min). ⋯ Small sample sizes in the RI groups resulted in large 95% confidence intervals (CIs), limiting conclusive interpretation of the analysis. Both drugs were well tolerated across all renal function groups. Overall, these results support the use of the study dosing regimens of C/T for treatment of vHABP/VABP in patients with RI. (This study has been registered at ClinicalTrials.gov under identifier NCT02070757.).