Mupirocin (pseudomonic acid A), an antibiotic produced by Pseudomonasfluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria, including Haemophilus influenzae and Neisseria gonorrhoeae, but was much less active against most gram-negative bacilli and anaerobes. Nearly all clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, including multiply resistant strains, were susceptible (mupirocin MIC, o0.5 ,ug/ml). There was no cross-resistance between mupirocin and clinically available antibiotics, and the selection of resistant variants in vitro occurred at a low frequency. Mupirocin was highly bound (95% bound) to the protein of human serum, and activity was reduced 10-to 20-fold in the presence of human serum. The activity of mupirocin was not greatly influenced by inoculum size but was significantly enhanced in acid medium. In tests of bactericidal activity, MBCs were 8-to 32-fold higher than MICs and the antibiotic demonstrated a slow bactericidal action in time-kill tests, resulting in 90 to 99% killing after 24 h at 37°C.The isolation and characterization of a group of antibacterial substances produced by Pseudomonas fluorescens was reported by Fuller et al. (7), and the name pseudomonic acid was ascribed to the major metabolite, which accounted for most of the antibacterial activity observed. Subsequent investigations revealed, in addition, the presence of three chemically related compounds as minor metabolites; for convenience, the substances were termed pseudomonic acids A (the major metabolite), B, C, and D (3-5, 11) ( Fig. 1). More recently, the term mupirocin has been adopted as the approved name for pseudomonic acid A.Pharmacokinetic studies in animals and in human volunteer subjects showed that mupirocin was well absorbed after oral and parenteral administration but serum antibiotic concentrations were short-lived as a result of extensive degradation to the antibacterially inactive metabolite, monic acid A (1; Beecham research laboratories, unpublished data), which is formed by hydrolysis of the ester linkage between the nucleus and the side chain of mupirocin (Fig. 1). Accordingly, the studies reported here were designed to investigate the antibacterial properties of mupirocin as an antibiotic for topical usage.MATERIALS AND METHODS Antibiotics. Mupirocin was used as the sodium salt in these studies. Standard antibiotics were obtained from the following manufacturers: benzylpenicillin, cloxacillin, and methicillin, Beecham Pharmaceuticals; erythromycin, Eli Lilly & Co.; fusidic acid, Leo Laboratories Ltd.; gentamicin, Nicholas Laboratories Ltd.; neomycin, the Upjohn Co.Bacteria. Most of the cultures tested were clinical strains of bacteria isolated from infections of the skin and other sources.MICs. Serial dilutions of mupirocin were added to 18-ml volumes of molten Mueller-Hinton agar (Difco Laboratories) in petri dishes. The medium was supplemented with horse blood for tests with streptococci (5% [vol/vol] for ...

Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.

New and previously reported analyses of the data from a placebo-controlled trial of famciclovir are reviewed in light of recently proposed recommendations for the analysis of pain in herpes zoster trials. The analyses examined the effect of famciclovir treatment on the duration of postherpetic neuralgia (PHN), which was defined as pain persisting after rash healing, pain persisting > 30 days after study enrollment, or pain persisting > 3 months after study enrollment; the baseline characteristics of patients in the famciclovir and placebo groups who developed PHN; the impact of famciclovir treatment on the duration of PHN, while controlling for significant covariates; and the prevalence of PHN at monthly intervals from 30 to 180 days after enrollment. The results of these analyses indicated that greater age, rash severity, and acute pain severity are risk factors for prolonged PHN. In addition, they demonstrated that treatment of acute herpes zoster patients with famciclovir significantly reduces both the duration and prevalence of PHN.

Antiviral chemotherapy with famciclovir results in clinically and statistically significant reductions in the symptoms associated with HSV infection and the symptomatic and asymptomatic shedding of HSV among HIV-positive persons.