Management and prevention of bacterial diarrhea.

The etiology, pathogenesis, transmission and communicability, diagnosis, and management of infectious diarrhea are reviewed. Infectious diarrhea is common in both industrialized and unindustrialized areas of the world. Better understanding of the etiology and pathogenesis and identification of "new" enteric pathogens has resulted in the use of a variety of drugs to relieve symptoms or to effect a clinical cure. Both host and microbial virulence factors are key in the acquisition of diarrheal illness. Host factors such as extreme age, a dysfunctional gastrointestinal tract, or underlying immunodeficiency enhance the risk of illness after ingestion of a pathogen or its toxins. Microbial virulence factors (the pathogen's ability to invade or produce enterotoxins, neurotoxins, or cytotoxins) characterize the type of illness manifested and the symptom complex (e.g., acute watery diarrhea versus chronic dysentery). Supportive care is indicated in the majority of cases of infectious enteritis, and rehydration is considered the mainstay of therapy in any diarrheal illness accompanied by dehydration. Antimicrobial therapy is beneficial in the treatment of severe diarrhea caused by Shigella, Campylobacter spp., Vibrio cholerae, Escherichia coli, and Clostridium difficile. Infectious diarrhea is common but is often self-limited and of short duration. Therapy frequently consists of symptomatic relief and fluid replacement.

Clinical pharmacology of antibiotics. Sulbactam/ampicillin.

Sulbactam/ampicillin appears to be effective in the treatment of gynecologic and intra-abdominal infections, and infections of skin and skin structures. However, until more data is available from well-controlled, comparative studies, it is difficult to determine the most appropriate place of sulbactam/ampicillin in the therapy of these and other infections. Sulbactam/ampicillin is similar to other agents in the prophylaxis of infectious complications secondary to gastrointestinal and gynecologic surgery, and may have a role in surgical prophylaxis as it is well tolerated by most patients and is cost-effective. Indeed, the discovery of sulbactam provides us with yet another useful compound. Additional study is clearly needed so as to best use sulbactam to its fullest advantage.

Update on pentamidine for the treatment of Pneumocystis carinii pneumonia.

The chemistry, spectrum of activity, mechanism of action, pharmacokinetics, adverse effects, and dosage and administration of pentamidine are reviewed, and the role of the drug in treating Pneumocystis carinii infections in immunocompromised patients is discussed. Pentamidine isethionate, an aromatic diamidine compound, is active against certain protozoan organisms. Used extensively in the tropics in the treatment of Trypanosoma and Leishmania infections, its value in the management of Pneumocystis carinii infections has been demonstrated in infected immunosuppressed children and adults. Recently, interest in pentamidine has increased with the rising number of patients with acquired immunodeficiency syndrome (AIDS) who have P. carinii pneumonia. Pentamidine's mechanism of action and pharmacokinetic profile are not completely understood. Pentamidine is distributed extensively after i.v. or i.m. administration, with a volume of distribution of 3 L/kg. Appreciable quantities of pentamidine concentrate in the urine, and drug levels are detectable for up to six to eight weeks after cessation of therapy. After aerosol administration, the drug is almost exclusively recovered from the lung, with little extrapulmonary distribution. Available data suggest that approximately 50% of patients who receive the drug by the i.v. or i.m. route will experience some drug toxicity (local pain, sterile abscesses at the intramuscular injection site, hypoglycemia, hypotension, or azotemia), while adverse effects after aerosol therapy include bronchial irritation but little systemic toxicity. Regardless of the route of administration, pentamidine has emerged as a mainstay of therapy in the management of P. carinii pneumonitis in AIDS patients, especially in those who are allergic to the sulfa component of trimethoprim-sulfamethoxazole.

Naloxone.

Naloxone hydrochloride, a synthetic N-allyl derivative of oxymorphone, is an effective agent for the reversal of the cardiovascular and respiratory depression associated with narcotic and possibly some non-narcotic overdoses. It is essentially a pure narcotic antagonist, is relatively safe, and is a useful diagnostic and therapeutic agent. Due to naloxone's pharmacokinetic profile, a continuous infusion protocol is recommended when prolonged narcotic antagonist effects are required. The complex pharmacodynamics of naloxone, specifically relating to endorphin receptor sites, focus its potential use in a variety of clinical situations as continuing research illustrates the association of endogenous opioid compounds with various disease states.