, *St. Joseph's Hospital and Medical Center, Paterson, New Jersey, and † Wright State University School ofMedicine, Miami Valley Hospital, Dayton, Ohio.

Semin Respir Crit Care Med. 2000;21(1) 

In This Article

Abstract and Introduction

Abstract

There is recent enhanced interest in the potential of medication to produce serious toxicity, and the television media have focused on the serious side effects and drug-drug interactions caused by antibiotics. In fact, a recent hospital study noted that drug-related toxicity was one of the most common causes of death for hospitalized patients. Antibiotic-induced adverse events contribute to host injury diagnostic confusion and excessive medical costs. In addition, however, a "spin-off" of antibiotic-induced adverse events is the emergence and dissemination of drug-resistant organisms.

This chapter will describe the adverse events and drug-drug interactions produced by those antibiotics that are most commonly prescribed to patients to prevent or treat respiratory tract infections. An effort will also be made to focus on those unique settings (the patient with renal insufficiency, the patient receiving immunosuppressive medication, the pregnant patient, the elderly patient, and the HIV-infected patient who is a candidate for primary or secondary prophylaxis for Pneumocystis carinii) that require a knowledge of antibiotic-induced adverse events.

Introduction

Antibiotics are the cornerstone for the prevention and treatment of numerous respiratory infections. Unfortunately, however, these compounds, comparable to other classes of medication, have the potential to cause adverse events. Adverse antibiotic-induced reactions are a concern not only because they cause host injury but also because they interrupt and complicate therapy and often necessitate alternative, more expensive agents that have the ability to foster the emergence and spread of drug-resistant organisms. Adverse antibiotic-related effects can also contribute to excess medical costs and serve as a source of litigation. This chapter reviews the subject of antibiotic-induced untoward events and concentrates on those drugs (penicillins, cephalosporins, imipenem and cilastatin, aztreonam, clindamycin, doxycycline, vancomycin, trimethoprim and sulfamethoxazole, macrolides, and quinolones) that are most frequently prescribed to patients experiencing fungal (Pneumocystis carinii) and bacterial respiratory tract infections.

Adverse events attributed to antibiotics are usually caused by three mechanisms: exaggerated response to the known pharmacological effects of the drug, immunologic reactions to the drug or its metabolites, and toxic effects of the compound or its metabolites. Most antibiotic-related adverse events are precipitated by an extension of the drug's normal pharmacology and are often avoided by appropriate dosage adjustment.

Some antibiotic-induced adverse reactions occur rarely and appear to be unique to the compound administered. Chloramphenicol-induced aplastic anemia and sulfonamide-induced toxic epidermal necrolysis or Stevens-Johnson syndrome are two such examples.[1] In addition to the direct influence of the antibiotic, however, numerous host factors (genetic constitution, integrity of drug elimination mechanisms, concomitant medical disorders) can affect the frequency and severity of antibiotic-related adverse events. A prime example is the HIV-infected patient. There are numerous reports of oxacillin-induced hepatitis and cutaneous reactions occurring in HIV-infected patients who have received trimethoprim-sulfamethoxazole or aminopenicillins.[2,3] Moreover, trimethoprim-sulfamethoxazole causes more non-dose- related gastrointestinal intolerance, fever and altered liver function in patients with AIDS, than in non-HIV-infected patients.

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