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Azithromycin: Organs and Systems Cardiovascular 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. Sensory systems Ears 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. The effects were hearing loss (88%), tinnitus (37%), plugged ears (37%), and vertigo (25%), developing at a mean of 7.6 weeks …

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Treatment of HIV / AIDS

Goals of treatment 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. General approach to treatment of HIV infection Regular, periodic measurement of plasma HIV RNA levels and CD4 cell counts is necessary to determine the risk of disease progression in an HIV-infected individual and to determine when to initiate or modify antiretroviral treatment regimens. Treatment decisions should be individualized by level of risk indicated by plasma HIV RNA levels and CD4 …

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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. This chapter addresses the broader issues of treating infectious diseases and provides a number of practical clinical examples to demonstrate rational therapeutics. A rational therapeutic strategy in the management of proved or suspected …

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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. Determinants of Antimicrobial Efficacy Measurement of antimicrobial activity in vitro Susceptibility testing is indicated for any bacterial pathogen warranting chemotherapy. Drugs that irreversibly destroy the ability of an organism to replicate, and perhaps in the process destroy the structural integrity of the organism, are microbicidal. Drugs that reversibly impair replicating ability, with this function being restored when drug concentrations fall below critical inhibitory levels, are microbiostatic. In quantitative …

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Toxicity of Antimicrobial Therapy

Mechanisms of toxicity 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. In contrast, the major toxicity of the penicillins and cephalosporins is due to allergic reactions. These differences are explained in part by the relative ability of specific drugs to inhibit enzymatic pathways in the host versus their stimulation of specific immune response. Not included in these lists is mention of the …

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Nucleoside analogs

Nucleoside analog reverse transcriptase inhibitors have formed the backbone of anti-human immunodeficiency virus therapy for the last decade (see Table Characteristics of Nucleoside Reverse Transcriptase Inhibitors). Reverse transcription is necessary for human immunodeficiency virus RNA to be used as a template to produce viral DNA, which can be integrated into the cellular genome. In order for reverse transcription to take place, deoxynucleotide must be added to the end of the elongating DNA. A 3′-hydroxyl group is present on the sugar moiety of deoxynucleotides that can form a 3′,5′-phosphodiester bond allowing further addition of nucleotide triphosphates. Several deoxynucleotide analogs have been synthesized that differ from normal deoxynucleotides in that the 3′-hydroxyl group …

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Antiretroviral Agents General Statement

Abacavir Sulfate, Amprenavir, Atazanavir Sulfate, Delavirdine Mesylate, Didanosine, Efavirenz, Emtricitabine, Enfuvirtide, Indinavir Sulfate, Lamivudine, Lopinavir and Ritonavir, Nelfinavir Mesylate, Nevirapine, Ritonavir, Saquinavir, Stavudine, Tenofovir Disoproxil Fumarate, Zalcitabine, Zidovudine • Laboratory Monitoring • Plasma HIV-1 RNA Levels and CD4+ T-cell Counts 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 (e.g., peripheral blood mononuclear cell [PBMC] HIV-1 titers, plasma concentrations or levels of …

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Patient Compliance and Issues Related to Dosage and Administration

• Patient Compliance 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. There is evidence that nonadherence in patients receiving HAART is the strongest predictor of failure to achieve suppression of viral load to levels below the …

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HIV Protease Inhibitors

The fact that hyperglycemia, new-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and diabetic ketoacidosis have occurred in HIV-infected individuals receiving HIV protease inhibitors should be considered when these drugs are used during pregnancy. Because pregnancy is itself a risk factor for hyperglycemia and it is not known whether use of an HIV protease inhibitor exacerbates this risk, glucose concentrations should be monitored closely in pregnant women receiving these drugs and these women should be advised about the warning signs of hyperglycemia and diabetes (e.g., increased thirst and hunger, unexplained weight loss, increased urination, fatigue, dry or itchy skin). Because hyperbilirubinemia (generally reported as an increase in indirect bilirubin) has been …

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CDC Recommendations for Postexposure Prophylaxis following Occupational Exposure to HIV

Since most occupational exposures to HIV do not result in transmission of the virus, the potential toxicity of PEP regimens must be considered carefully and, whenever possible, prophylaxis should be implemented in consultation with clinicians who have expertise in antiretroviral therapy and HIV transmission. Modification of the recommended regimens may be appropriate based on factors such as whether the source patient is known or suspected of being infected with drug-resistant strains of HIV; the local availability of antiretroviral agents; and the medical condition, concurrent drug therapy, and drug toxicity in the exposed health-care worker. The CDC has made the following recommendations for PEP following occupational exposure to HIV:126 • The recommended …

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