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Shilpa M Patel

Publications and source records attributed to Shilpa M Patel.

3 recordsLinked to original sources

Monotherapy versus combination therapy.

The science of antibiotic therapy for infectious diseases continues to evolve. In many instances where empiric coverage is necessary, treatment with more than one agent is considered prudent. If an etiology is identified, antibiotics are modified based on culture and susceptibility data. Even when the organism is known, more than one antibiotic may be needed. Decisions about antibiotics should be made after assessments of pertinent clinical information, laboratory and microbiology information, ease of administration, patient compliance, potential adverse effects, cost, and available evidence supporting various treatment options. Clinicians also need to consider synergy and local resistance patterns in selecting therapeutic options. In this article, the authors outline monotherapy and combination therapy options for several common infectious diseases.

Amoxicillin-Potassium Clavulanate Combination↗

Breakthrough Candida infections in patients receiving voriconazole.

OBJECTIVE: To describe 2 instances of breakthrough Candida infection in 2 patients on treatment doses of voriconazole. CASE SUMMARIES: A 27-year-old woman with systemic lupus erythematosus was receiving high-dose voriconazole (400 mg twice daily) for central nervous system lesions of unknown origin and developed oral thrush. The patient was receiving concomitant therapy with phenytoin 400 mg/day. The voriconazole dose was increased to 400 mg 3 times daily, and the thrush resolved. A 50-year-old man with HIV infection was receiving enfuvirtide, lamivudine, tenofovir, and efavirenz 600 mg/day, as well as prophylactic trimethoprim/sulfamethoxazole and azithromycin. He was started on voriconazole 200 mg twice daily for pulmonary aspergillosis and developed esophageal candidiasis. The voriconazole dose was increased to 350 mg twice daily, and the thrush eventually resolved. DISCUSSION: Both reactions were probable according to the Naranjo probability scale. Significant drug interactions may have played a role in the development of breakthrough infections in these patients, specifically with phenytoin and efavirenz. Voriconazole is metabolized primarily by CYP2C19, as well as CYP2C9 and CYP3A4. Voriconazole is also known to inhibit these enzymes, and the manufacturer reports an extensive list of drugs that interact with voriconazole. CONCLUSIONS: Although requiring systematic evaluation, there may be a role for voriconazole serum concentration monitoring to ensure therapeutic efficacy when significant drug interactions are suspected.

Adult↗

Serious adverse cutaneous and hepatic toxicities associated with nevirapine use by non-HIV-infected individuals.

BACKGROUND: Nevirapine is a nonnucleoside reverse transcriptase antiretroviral agent. Among HIV-infected individuals, rare instances (<1%) of serious cutaneous and hepatic toxicity have been reported. Because of its favorable pharmacokinetic profile, non-HIV-infected individuals have received nevirapine-containing postexposure prophylaxis (PEP). OBJECTIVE: To describe the clinical features of cutaneous and hepatic toxicity that occurred when nevirapine was administered to non-HIV-infected individuals. METHODS: Reports of nevirapine-associated cutaneous or hepatic toxicity occurring among non-HIV-infected individuals were obtained from the US Food and Drug Administration's adverse event reporting system, the pharmaceutic manufacturer, occupational health programs in Chicago, physicians, and case reports. The Eastern Cooperative Oncology Group (ECOG) scoring system was used to grade toxicity. RESULTS: Twelve non-HIV-infected individuals developed severe cutaneous toxicity, including 3 with Stevens-Johnson syndrome, after 7 to 12 days of nevirapine-containing PEP regimens. Thirty non-HIV-infected individuals developed hepatotoxicity after 8 to 35 days of single-agent nevirapine (n = 8) or a nevirapine-containing PEP regimen (n = 22). Findings included ECOG grade 3 or 4 hepatotoxicity (n = 14), fevers (n = 11), skin rashes (n = 8), eosinophilia (n = 6), and fulminant hepatic necrosis requiring an orthotopic liver transplant (n = 1). Rates of severe hepatotoxicity (grade 3 or 4) in non-HIV-infected individuals ranged from 10% (4/41) to 62% (5/8). Liver biopsy material from 2 individuals was consistent with a hypersensitivity syndrome. CONCLUSIONS: Serious hepatic and cutaneous toxicities can occur in non-HIV-infected individuals who receive short-term nevirapine therapy. The rate of severe hepatotoxicity appears to be greater in non-HIV-infected individuals than in HIV-infected persons and may be associated with higher CD4 counts. The use of PEP regimens containing nevirapine should be discouraged.

Adult↗