To evaluate the activity of posaconazole for treatment of zygomycosis, a disease for which therapeutic options are limited, we conducted a retrospective study including 91 patients with zygomycosis (proven zygomycosis, 69 patients; probable zygomycosis, 22 patients). Patients had infection that was refractory to prior antifungal treatment (n=81) or were intolerant of such treatment (n=10) and participated in the compassionate-use posaconazole (800 mg/day) program. The rate of success (i.e., either complete or partial response) at 12 weeks after treatment initiation was 60%, and 21% of patients had stable disease. The overall high success and survival rates reported here provide encouraging data regarding posaconazole as an alternative therapy for zygomycosis.

Our objective was to prospectively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone. Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h (total dose, 750 mg). For patients with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus, a second drug was added (ceftazidime or piperacillin/tazobactam for P. aeruginosa and vancomycin for methicillin-resistant S. aureus). Population pharmacokinetic studies of 58 patients demonstrated that this population handled the drug differently from populations of volunteers. Multivariate logistic regression analysis (n=47 patients) demonstrated that only the age of the patient and the achievement of an area under the curve: minimum inhibitory concentration ratio of > or =87 had a significant effect on eradication of the pathogen (P<.001). Achieving the breakpoint made the patient 4 times more likely to achieve eradication. The effect was greatest in patients > or =67 years old.

Quantitative cultures were done on 149 intravenous catheters and 40 additional intravascular inserts. Intradermal and intravascular segments of the insert were cultured separately. The inserts were immersed in broth and flushed. The number of colony-forming units (cfu) per insert was estimated by surface culture of serial dilution of the broth. Nonquantitative culture of undiluted broth was also done. Since all inserts associated with bacteremia had at least 10(3) cfu, inserts greater than 10(3) cfu were considered infected. Staphylococcus epidermidis was more likely than more virulent organisms to colonize an insert without causing bacteremia. The inserts in one bacteremic patient were infected from a distant bloodstream focus; however, in the majority of patients, quantitative intradermal cultures suggested that the insertion site was the portal of entry. In bacteremic patients, either a positive quantitative or a nonquantitative culture identified an infected insert. However, only 33% of positive nonquantitative insert cultures from nonbacteremic patients were confirmed by quantitative insert culture.

Therapeutics for the treatment of pathogenic orthopoxvirus infections are being sought. In the absence of patients with disease, animal models of orthopoxvirus disease are essential for evaluation of the efficacies of antiviral drugs and establishment of the appropriate dose and duration of human therapy. Infection of nonhuman primates (NHP) by the intravenous injection of monkeypox virus has been used to evaluate a promising therapeutic drug candidate, ST-246. ST-246 administered at 3 days postinfection (which corresponds to the secondary viremia stage of disease) at four different doses (from 100 mg/kg of body weight down to 3 mg/kg) once a day for 14 days was able to offer NHP 100% protection from a lethal infection with monkeypox virus and reduce the viral load and lesion formation. In NHP, the administration of ST-246 at a dose of 10 mg/kg/day for 14 days resulted in levels of blood exposure comparable to the levels attained in humans administered 400 mg in the fed state. These results suggest that administration of an oral dosage of 400 mg once daily for 14 days will be effective for the prevention or treatment of smallpox or monkeypox infections in humans.