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Concurrent administration of fluconazole probably causes increased exposure to amitriptyline. Three reports of adults have shown increased amitriptyline plasma concentrations with concurrent administration of fluconazole; in one patient, a 57-year-old woman, the QT interval was prolonged and torsade de pointes occurred. In vitro studies and experiments in animals have given conflicting results relating to potential antagonism between the effects of fluconazole and amphotericin on Candida species.

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Torsade de pointes and cardiorespiratory arrest have been reported in a patient with congenital long QT syndrome who took azithromycin. In a prospective study of 47 previously healthy people, there was a modest statistically insignificant prolongation of the QTC interval without clinical consequences after the end of a course of azithromycin 3 g/day for 5 days. Azithromycin can cause ototoxicity. In one study, 8 (17%) of 46 HIV-positive patients had probable (n = 6) or possible (n = 2) ototoxicity with azithromycin.

Treatment of HIV / AIDS

The goal of antiretroviral therapy is to achieve the maximum suppression of HIV replication (HIV RNA level that is less than the lower limit of quantitation). Secondary goals include an increase in CD4 lymphocytes and an improved quality of life. The ultimate goal is decreased morbidity and mortality.

Antimicrobial Regimen Selection

A generally accepted systematic approach to the selection and evaluation of an antimicrobial regimen is shown in Table Systematic Approach for Selection of Antimicrobials. An «empiric» antimicrobial regimen is begun before the offending organism is identified, while a «definitive» regimen is instituted when the causative organism is known. The use of combinations to prevent the emergence of resistance is widely applied but not often realized. The only circumstance where this has been clearly effective is in the treatment of tuberculosis.

Infectious disorders

Infectious diseases comprise those illnesses that are caused by microorganisms or their products. Clinical manifestations of infection occur only when sufficient tissue injury has been inflicted directly by microbial products (e.g., endotoxins and exotoxins), or indirectly by host responses (e.g., cytokines and hydrolytic enzymes released by polymorphonuclear leukocytes). Despite the extraordinary recent advances that have occurred in therapeutics for infectious diseases, a number of basic principles should be followed to prescribe antimicrobials and vaccines is an optimal manner.

Antimicrobial therapy: general principles

A wide variety of antimicrobial agents is available to treat established infections caused by bacteria, fungi, viruses, or parasites. This section will cover the general principles of antimicrobial therapy and will also include illustrative clinical problems to emphasize proper decision-making in using antimicrobials.

Toxicity of Antimicrobial Therapy

The mechanisms associated with common adverse reactions to antimicrobials include dose-related toxicity that occurs in a certain fraction of patients when a critical plasma concentration or total dose is exceeded, and toxicity that is unpredictable and mediated through allergic or idiosyncratic mechanisms. For example, certain classes of drugs such as the aminoglycosides are associated with dose-related toxicity.

Antiretroviral Agents General Statement

Decisions regarding when to initiate or modify antiretroviral therapy should be guided by monitoring plasma HIV-1 RNA levels (viral load), CD4+ T-cell counts, and the clinical condition of the patient. Although various other surrogate markers and laboratory parameters were used in the past to assess the risk of progression of HIV infection and evaluate efficacy of antiretroviral agents.

Patient Compliance and Issues Related to Dosage and Administration

Patient compliance with recommended regimens (even when asymptomatic) is essential to the potential benefits of antiretroviral therapy. Adherence to antiretroviral regimens is an important determinant of both the degree and duration of virologic suppression. Excellent adherence has been shown to increase the likelihood of sustained virologic control, which is important for reducing HIV-associated morbidity and mortality. Poor adherence has been shown to increase the likelihood of virologic failure and can lead to the development of resistance and limit the effectiveness of antiretroviral therapy.