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Objective: To review the pharmacology, clinical trial data, and clinical implications for the intravenous formulation of zanamivir.Data Sources: MEDLINE, PubMed, EMBASE, and Google Scholar were searched during November 2019 to July 2020. Search terms zanamivirand neuraminidase inhibitorwere used.Study Selection and Data Extraction: All human trials and major reports from compassionate use programs with the intravenous zanamivir (IVZ) formulation were assessed and reviewed here.Data Synthesis: IVZ was found to be similar but not superior to oral oseltamivir in hospitalized patients when studied in populations with very low baseline oseltamivir resistance. IVZ provides an effective alternative for critically ill patients when oral antiviral therapy is not preferred or when oseltamivir resistance is increased.Relevance to Patient Care and Clinical Practice: IVZ was recently authorized for use by the European Medicines Agency, and it is eligible for consideration in emergency use protocols and US stockpile inclusion. It will be of particular interest in critically ill patients especially during influenza seasons with appreciable oseltamivir and peramivir resistance.Conclusions: The available information suggests that the intravenous formulation of zanamivir offers a viable alternative treatment for critically ill patients with influenza, especially when resistance to other agents is present.

The aim of the present study was to see how widespread preventative use of the probiotic Saccharomyces boulardiivia automatic protocol in hospitalised patients receiving antibacterials affected rates of hospital-associated Clostridioides(Clostridium) difficileinfection (HA-CDI). Rates of HA-CDI appeared to be similar between the pre-protocol and protocol periods. Use of CDI treatment antibiotics (oral metronidazole and oral vancomycin) was also similar. Laboratory-confirmed isolation of S. boulardiifrom sterile body sites was identified in five patients during the protocol versus only one case in the pre-protocol years.

ABSTRACTThe current recommendations for intravenous (i.v.) acyclovir dosing in obese patients suggest using ideal body weight (IBW) rather than total body weight (TBW). To our knowledge, no pharmacokinetic analysis has validated this recommendation. This single-dose pharmacokinetic study was conducted in an inpatient oncology population. Enrollment was conducted by 1:1 matching of obese patients (>190% of IBW) to normal-weight patients (80 to 120% of IBW). All patients received a single dose of i.v. acyclovir, 5 mg/kg, infused over 60 min. Consistent with current recommendations, IBW was used for obese patients and TBW for normal-weight patients. Serial plasma concentrations were obtained and compared. Seven obese and seven normal-weight patients were enrolled, with mean body mass indexes of 45.0 and 22.5 kg/m2, respectively. Systemic clearance was substantially higher in the obese than normal-weight patients (mean, 19.4 ± 5.3 versus 14.3 ± 5.4 liters/h; P= 0.047). Area under the concentration-time curve was lower in the obese patients (15.2 ± 2.9 versus 24.0 ± 9.4 mg · h/liter; P= 0.011), as was maximum concentration (5.8 ± 0.9 versus 8.2 ± 1.3 mg/liter; P= 0.031). Utilization of IBW for dose calculation of i.v. acyclovir in obese patients leads to lower systemic exposure than dosing by TBW in normal-weight patients. While not directly evaluated in this study, utilization of an adjusted body weight for dose determination appears to more closely approximate the exposure seen in normal-weight patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01714180.)

Objective:To evaluate and review the literature surrounding the potential protective benefit of tetracyclines, particularly doxycycline, in reducing Clostridium difficileinfection (CDI) acquisition. Data Sources:MEDLINE/PubMed, Google Scholar, and International Pharmaceutical Abstracts were searched through January 2014 using the search terms doxycycline, tetracycline, and Clostridium difficile. Study Selection and Data Extraction:Relevant studies, case reports, and review articles were screened for inclusion. Bibliographies of articles were extensively reviewed for additional sources. Data Synthesis:Doxycycline is a second-generation tetracycline antibiotic indicated for use in a variety of clinical syndromes and has activity against aerobic Gram-positive and -negative, anaerobic, and atypical bacteria as well as protozoan parasites. Although not used therapeutically to treat CDI, doxycycline may prevent or attenuate the virulence factors of toxigenic C difficile. Current literature does not indicate an increased risk of development of CDI with doxycycline use. In 3 retrospective studies, the use of doxycycline was associated with a protective effect. Conclusions:Doxycycline has been shown to have potential protective effects against the development of CDI. Although further randomized placebo-controlled studies are needed, available data suggest that the use of doxycycline in place of alternative antimicrobials, when appropriate, may be a useful antimicrobial stewardship strategy aimed at reducing the incidence of CDI.

OBJECTIVE: To review the pharmacology, mycology, chemistry, pharmacokinetics, efficacy, safety, tolerability, dosage, administration, and economic issues of intravenous itraconazole.DATA SOURCES: A MEDLINE search from 1978 to June 2000 of the English-language literature and an extensive review of meeting abstracts was conducted. Due to the paucity of published information concerning the pharmacokinetics, efficacy, and safety of the intravenous formulation of intravenous itraconazole, additional information was obtained from the manufacturer.DATA EXTRACTION: Data from in vitro and preclinical studies, as well as Phase II and III clinical trials, were included.DATA SYNTHESIS: The triazole antifungal agent itraconazole is available in a cyclodextrin-based intravenous formulation. Intravenous itraconazole is indicated for the treatment of pulmonary and extrapulmonary blastomycosis; histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis; and pulmonary and extrapulmonary aspergillosis in patients who are intolerant of or who are refractory to amphotericin B. This formulation provides quicker and more consistent therapeutic concentrations than the oral formulations. Clinical data comparing the efficacy of intravenous itraconazole with that of amphotericin B are lacking.CONCLUSIONS: Intravenous itraconazole offers a less toxic alternative for patients with pulmonary and extrapulmonary blastomycosis, histoplasmosis, and aspergillosis who cannot receive oral medications or who are intolerant of or refractory to amphotericin B.

The objective of this study was to determine the metabolic profile, routes of elimination, and total recovery of amprenavir and its metabolites after a single oral dose of [14C]‐amprenavir. Six healthy male subjects each received a single oral 630 mg dose of amprenavir containing 95.76 μCi of [14C]‐amprenavir in this Phase I mass balance study. The metabolic disposition of amprenavir was determined through analyses of radiocarbon in whole blood, plasma, urine, and stool samples, collected for a period of 10 to 17 days postdosing. Cerebral spinal fluid (CSF) sampling was conducted on day 1. The ratio of unchanged amprenavir AUC0→∞ to plasma radiocarbon was 27%, suggesting that most of the radiocarbon was metabolites. The median total recovery of the administered dose of radiocarbon was 89% (range: 66%‐93%), with 75% (range: 56%‐80%) recovered in the feces and 14% (range: 10%‐17%) in the urine. Most of the recovered radiocarbon in the feces and urine was excreted within 240 and 48 hours postdose, respectively. Of the 75% of the radiocarbon dose recovered in the feces, 62% wasidentified as a metabolite resulting from dioxidation of the tetrahydrofuran ring (GW549445X) and 32% as a metabolite resulting from subsequent oxidation of the p‐aniline sulfonate group (GW549444X). Unchanged amprenavir was below the limit of quantitation in feces and urine. Therefore, approximately 94% of the dose excreted in the feces was accounted for by these two metabolites. Concentrations of radiocarbon in the CSF were below the limit of quantitation in 5 of 6 subjects sampled. In summary, oral amprenavir is extensively metabolized in humans, with concentrations of unchanged drug below the limits of quantitation in urine and feces. The majority (75%) of administered radiocarbon was excreted in feces.

Study Objectives.To evaluate hepatic cytochrome P450 (CYP) 3A4 activity in patients infected with the human immunodeficiency virus (HIV) using the erythromycin breath test (ERMBT), and to examine the relationship of the ERMBT to plasma concentrations of indinavir and nelfinavir.

The frequency of life‐threatening fungal infections has increased dramatically over the past few decades. For more than 30 years amphotericin B has been the standard treatment for systemic and deep‐seated fungal infections, primarily because of its broad spectrum of activity. Its usefulness is limited by a relatively high frequency of significant adverse events including infusion‐related reactions and nephrotoxicity. In an effort to overcome these side effects, a number of lipid‐based formulations were developed, each with its own composition and pharmacokinetic behavior. The clinical significance of these differences is unknown. Available clinical data suggest the formulations have a reduced propensity for causing nephrotoxicity. However, considering limited efficacy data, they should be reserved as second‐line therapy for patients who cannot tolerate or fail an adequate trial of conventional amphotericin B or cannot benefit from other antifungal agents.