Effects of antiretroviral therapy on immunity in patients infected with HIV.

Drug therapy for human immunodeficiency virus (HIV) is highly effective in suppressing viral replication and restoring immune function in patients with HIV. However, this same treatment can also be associated with immunotoxicity. For example, zidovudine and various other antiretroviral agents are capable of causing bone marrow suppression. Agents used to treat opportunistic infections in these individuals, including ganciclovir, foscarnet, and sulfamethoxazole-trimethoprim, can cause additional hematotoxicity. Drug-drug interactions must also be considered and managed in order to control iatrogenic causes of immunotoxicity. In this review, we examine the normal immune response to HIV, and the benefits of antiretroviral therapy in prolonging immune function. We then discuss immune-related adverse effects of drugs used to treat HIV and the opportunistic infections that are common among these patients. Finally, we address in vitro, animal, and clinical evidence of toxicity associated with various combination use of these agents.

Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria.

BACKGROUND: Polymyxin B sulfate and colistin, also known as colistimethate, have not been used for many years because less toxic antimicrobials are available. Gram-negative bacteria that are resistant to the aminoglycosides, beta-lactams, and fluoroquinolones are becoming more common. These bacteria are often susceptible to the polymyxins. OBJECTIVE: To present a review of the chemistry, antibacterial spectrum, dosing, pharmacokinetics, toxicity, and indications for polymyxin B sulfate and colistin. DATA SOURCE: A MEDLINE search (1966-1998) of the English-language literature was performed to identify primary literature on the polymyxins. Older citations ( 1949-1965) were identified through the bibliographies of these articles. STUDY SELECTION: All available reports of in vitro antibacterial activity, animal and clinical trials, and case reports were reviewed. DATA SYNTHESIS: The polymyxins are amphipathic molecules that interact with lipopolysaccharide in the bacterial outer membrane. They have potent antiendotoxic properties and antibacterial activity against Pseudomonas aeruginosa and many of the Enterobacteriaceae. Polymyxin B and colistin are usually given at a dose of 1.5-2.5 and 5 mg/kg/d, respectively, in two divided doses. Dosing must be altered in renal failure since the kidney is the primary route of elimination. Distribution into pleural fluid, joints, and cerebrospinal fluid is poor. Toxic effects involve the kidney and central nervous system. The polymyxins are recommended for serious systemic infections caused by gram-negative bacteria that are resistant to other agents. CONCLUSIONS: Polymyxin B sulfate and colistin have a role in the therapy of multidrug-resistant gram-negative bacterial infections.