Antibiotic, Antifungal, Antiviral Drugs

Another method of combating beta-lactamase-producing organisms has been the development of beta-lactamase inhibitors. Clinical experience with penicillins, especially penicillin G and the aminopenicillins, is extensive. These substances are rarely toxic, even when they are given in an extended range of dosages, making them invaluable for use in pregnant women and children.

High doses of parenteral penicillin can inactivate aminoglycosides. In patients receiving low doses of aminoglycosides because of reduced renal function this can be clinically important.

Embolictoxic reactions to penicillin depot formulations were first described in patients with syphilis. The symptoms include fear of death, confusion, acoustic and visual hallucinations, and possibly palpitation, tachycardia, and cyanosis. Generalized seizures or twitching of the limbs have been observed in children and adults.

Penicillins: Organs and Systems. Respiratory, Nervous system, Gastrointestinal, Urinary tract.

Anaphylactic shock can occur, even after oral administration of penicillin and skin testing. However, anaphylactic shock is less common after oral than parenteral administration. In one study the incidence of anaphylactic shock was 0.04% of all patients treated with penicillin. It is also low in patients receiving long-term benzathine penicillin (1.2 million units every 4 weeks).

Skin reactions are the commonest adverse effects of therapeutically administered penicillins. Penicillin-contaminated milk or meat can cause itching or generalized skin reactions or even anaphylaxis. The overall annual incidence of severe erythema multi-forme (toxic epidermal necrolysis and Stevens-Johnson syndrome) is about one case per million, antibiotics being involved in 30-40%. The clinical differentiation between these syndromes can be difficult.

Penicillin-induced hepatotoxicity may not be as uncommon as has been thought. There have been three reviews. The first was a comparison of the assessment of drug-induced liver injury obtained by two different methods, the Council for International Organizations of Medical Sciences (CIOMS) scale and the Maria & Victorino (M&V) clinical scale. Three independent experts evaluated 215 cases of hepatotoxicity reported using a structured reporting form.

Since the days when chloramphenicol was more commonly used, it has been recognized that many antimicrobial drug are associated with severe blood dyscrasias, such as aplastic anemia, neutropenia, agranulocytosis, throm-bocytopenia, and hemolytic anemia. Information on this association has come predominantly from case series and hospital surveys (38^. Some evidence can be extracted from population-based studies that have focused on aplastic anemia and agranulocytosis and their association with many drugs, including antimicrobial drugs. The incidence rates of blood dyscrasias in the general population have been estimated in a cohort study with a nested case-control analysis, using data from a General Practice Research Database in Spain.