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Objectives: To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing. Data Sources: A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus. Study Selection and Data Extraction: Articles assessing Clcr under non–steady-state conditions and studies evaluating predictive equations were selected. Data Synthesis: When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcr are appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcr in patients with unstable SCr. Relevance to Patient Care and Clinical Practice: Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcr and most important for estimating glomerular filtration rate. However, standard methods of estimating Clcr for medication dosing are not accurate under non–steady-state conditions. Conclusion: The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations.

This article critically evaluates commonAn extensive PubMed, Google Scholar, and ClinicalTrials.gov search was conducted (January 1995 to July 2020) to identify relevant literature on epidemiology, resistance mechanisms, antipseudomonal agents, newer β-lactam agents, and clinical data available pertaining toRelevant published articles and package inserts were reviewed for inclusion.Therapeutic options to treatMultidrug-resistant (MDR)Newer agents, including ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and cefiderocol, are useful for the treatment of MDR

OBJECTIVE: To describe the use of high-dose posaconazole in 2 pediatric patients who received bone marrow transplant (BMT) and highlight concerns regarding posaconazole absorption. CASE SUMMARY: We present 2 pediatric BMT patients in whom prescribed high doses of posaconazole (120-300 mg/kg/day for >3 months) provided serum concentrations less than 1 μg/mL. Both patients received posaconazole with other antifungal therapy and surgical debridement for Rhizopus spp. infections after allogeneic BMTs. Various alternative dosing strategies to potentially enhance posaconazole absorption to increase serum concentrations were attempted, including higher daily doses, frequent or continuous oral administration via feeding tube, use of enteral nutrition, and limiting use of acid-blocking agents. During high-dose therapy, frequent posaconazole serum concentration measurement and other monitoring techniques, such as continuous telemetry, were used. While the fungal infections resolved in both patients and no serious adverse effects could be attributed to high-dose posaconazole administration, posaconazole therapy may have contributed to nausea and vomiting in 1 of the patients. DISCUSSION: These 2 cases describe complex circumstances, with several reasons that may have affected the patients' posaconazole serum concentrations. Both patients received significantly higher doses than those recommended in the posaconazole prescribing information, but potentially serious adverse events were not observed since serum concentration measurements were rarely more than 0.5 μg/mL. CONCLUSIONS: The safety of high-dose posaconazole therapy was not determined in these 2 patients. However, given that limited alternative therapy options are available for severely ill patients with suspected posaconazole malabsorption, research regarding dosing strategies should be considered.

BACKGROUND: The rate of methicillin-resistant Staphylococcus aureus (MRSA) has increased significantly over the last decade. Previous cohort studies of patients with MRSA bacteremia have reported higher mortality rates, increased morbidity, longer hospital length of stay (LOS), and higher costs compared with patients with methicillin-susceptible S. aureus (MSSA) bacteremia. The clinical and economic impact of MRSA involving other sites of infection has not been well characterized. OBJECTIVE: To determine the clinical and economic implications of MRSA compared with MSSA infections across a variety of infection sites and severity of illnesses. METHODS: A retrospective, case—control analysis comparing differences in clinical and economic outcomes of patients with MRSA and MSSA infections was conducted at an academic medical center. Case patients with MRSA infection were matched (1:1 ratio) to control patients with MSSA infection according to age, site of infection, and type of care. RESULTS: Thirty-six matched pairs of patients with S. aureus infection were identified. Baseline characteristics of patients with MSSA and MRSA infection were similar. Patients with MRSA infections had a trend toward longer hospital LOS (15.5 vs 11 days; p = 0.05) and longer antibiotic-related LOS (10 vs 7 days; p = 0.003). Median hospital cost associated with treatment of patients with MRSA infections was higher compared with patients with MSSA infections ($16 575 vs $12 862; p = 0.11); however, this difference was not statistically significant. Treatment failure was common in patients with MRSA infection. Among patients with MSSA infections, treatment failure was associated with vancomycin use. CONCLUSIONS: Patients with MRSA infections had worse clinical and economic outcomes compared with patients with MSSA infections.

OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 ± 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5–fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.