ANTIBIOTIC SIDE EFFECTS

doi:10.1016/S0025-7125(05)70309-6

Medical Clinics of North America

Volume 85, Issue 1, 1 January 2001, Pages 149-185

https://doi.org/10.1016/S0025-7125(05)70309-6 Get rights and content

Antimicrobial side effects present as adverse drug reactions involving one or more organ systems. Although most antibiotics are safe considering their volume of use, some antimicrobials have the potential for life-threatening side effects. In general, β-lactams have the least frequent and least severe side effects. Although any antibiotic is capable of causing side effects, specific agents from each antibiotic class are more likely to do so than others. Clinicians should be familiar with the side-effect potential of individual antibiotics as well as the likelihood of specific agents being involved in an adverse reaction and should be familiar with the spectrum of organ involvement associated with particular antimicrobials.

Clinicians have a vast armamentarium of antimicrobials effective against a wide variety of pathogens. Most antimicrobials have a good safety profile. Physicians should consider the frequency and severity of potential adverse effects of antimicrobials when selecting agents for therapy.

Section snippets

INDIVIDUAL VERSUS CLASS SIDE EFFECTS

Most antibiotic-related adverse events are related to specific antimicrobial agents and are not related to antimicrobial classes. Clinicians often are misled by considering class side effects of antimicrobials instead of assessing the possibility of individual agents being responsible for the adverse reaction. For example, photosensitizing reactions are common with tetracycline but are rare with minocycline or doxycycline. Similarly, sparfloxacin is associated with photosensitivity reactions

Leukopenia and Thrombocytopenia

Hematologic side effects are common with a wide variety of antimicrobial agents. Isolated cytopenias occur frequently in clinical practice and may present as neutropenia, anemia, and thrombocytopenia. Leukopenia and thrombocytopenia are the most common hematologic side effects related to antimicrobial therapy.³⁴ β-Lactam antibiotics and the sulfamethoxazole component of trimethoprim-sulfamethoxazole (TMP-SMX) are the two most common causes of isolated leukopenia or thrombocytopenia.154, 156, 158

Drug Fever

Drug fevers are the most common antibiotic-mediated hypersensitivity side effect. Drug fevers account for 10% to 15% of unexplained fevers in hospitalized patients in the United States. Drug fevers may occur with any antibiotic but are particularly common with β-lactams and sulfonamides and may occur with any antiviral, antifungal, or antiparasitic medication.154, 155 Drug fevers are defined as hypersensitivity reactions to medications whose primary clinical expression is that of fever without

NEUROLOGIC SIDE EFFECTS

Antimicrobials are responsible for a wide spectrum of neurologic adverse reactions. The most serious neurologic side effects include encephalitis, seizures, neuromuscular blockage, and muscular spasticity.

PULMONARY SIDE EFFECTS

Pulmonary drug reactions are an uncommon side effect of antimicrobial therapy. The presence of drug-induced pulmonary side effects should suggest a nonantimicrobial explanation.

Prolonged QT_c Interval

Ventricular arrhythmias may occur by direct effect of the drug on myocardial irritability. A prolonged QT_c interval may result in ventricular arrhythmias (e.g., torsades de pointes).⁴¹ The antimicrobials most commonly associated with prolongation of the QT_c interval include IV erythromycin, terbinafine, and some quinolones. QT_c prolongation occurs rapidly after an antibiotic is administered, and normalization of the QT_c interval occurs after the drug is withdrawn.¹⁴⁹ Quinolones that prolong the

Nausea and Vomiting

Many drugs are associated with nausea and vomiting, and antimicrobials are no exception. As a group, antiretrovirals commonly are associated with nausea, vomiting, or abdominal discomfort, which may be so severe as to lead to cessation of the medication. Among antibiotics, the macrolides are the least well tolerated when given by the oral route. Clarithromycin is associated with gastric discomfort and taste perversion (i.e., metallic taste). The new formulations of clarithromycin (Biaxin XL)

Drug-Induced Hepatitis

Elevations in the serum transaminases traditionally have been associated with INH in antituberculous therapy. Mild and transient elevations of serum transaminases are common with a wide variety of drugs and are particularly common with antiretroviral therapy.¹²⁶ Oxacillin is the most common β-lactam associated with antibiotic-induced hepatitis, but nafcillin, even with an enterohepatic circulation, is a rare cause of antibiotic-induced hepatitis. Elevations in the serum transaminases secondary

Nephrotoxicity

Nephrotoxicity may be manifested as glomerular or tubular toxicity and may be due to a variety of anti-infectious agents.3, 7, 8, 44, 62, 84, 147 Tubular toxicity is more common and has been associated with multiple-dose aminoglycoside therapy. Nephrotoxic potential is similar among aminoglycosides and varies according to the frequency of intravenous administration.⁷⁴ Aminoglycosides are potentially toxic to the tubules of the nephron. After intravenous administration, aminoglycosides saturate

METABOLIC SIDE EFFECTS

Many antibiotics may cause metabolic abnormalities. Commonly recognized side effects include gonadal and adrenal dysfunction induced by ketoconazole. Lactic acidosis may accompany abacavir therapy. Hyperglycemia frequently is associated with pentamidine administration.

Gynecomastia, lipodystrophy, and other lipid abnormalities are particularly associated with indinavir but may occur with other protease inhibitors. Pathophysiology of lipid abnormalities associated with indinavir is not clear

MISCELLANEOUS SIDE EFFECTS

A variety of other side effects have been ascribed to antimicrobials (Table 12).* Adverse reactions are important from a differential diagnostic and pharmacoeconomic standpoint.

SUMMARY

Antibiotic side effects are approached best from an individual agent perspective rather than from a class-related standpoint. As this article indicates, with the exception of drug fevers and drug rashes, most antibiotic side effects are related to individual agents and not class side effects.75, 76 Clinicians should view antimicrobial side effects as related to each organ system and be aware that more often a nonmicrobial medication is the explanation for the drug side effect rather than the

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: Address reprint requests to Burke A. Cunha, MD, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501

^*: State University of New York School of Medicine, Stony Brook, and the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York

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ANTIBIOTIC SIDE EFFECTS

Section snippets

INDIVIDUAL VERSUS CLASS SIDE EFFECTS

Leukopenia and Thrombocytopenia

Drug Fever

NEUROLOGIC SIDE EFFECTS

PULMONARY SIDE EFFECTS

Prolonged QTc Interval

Nausea and Vomiting

Drug-Induced Hepatitis

Nephrotoxicity

METABOLIC SIDE EFFECTS

MISCELLANEOUS SIDE EFFECTS

SUMMARY

Mayo Clin Proc

Lancet

Lancet

Lancet

Med Clin North Am

Med Clin North Am

Kidney Int

Am J Med

Am J Med

Mayo Clin Proc

Am J Med

Med Clin North Am

Infect Dis Clin North Am

Gastroenterology

Vancomycin and red necks

Ann Intern Med

Adverse reactions to quinolones, potential toxicities, drug interactions, and metabolic effects

Infect Dis Clin Pract

Amphotericin B associated nephrotoxicity

Antibiotics for Clinicians

Hematological toxicities of chloramphenicol

Antibiotics for Clinicians

A decade of pencillin related acute interstitial nephritis—more questions than answers

Clin Nepthrol

The nephrotoxicity of antimicrobial agents

N Engl J Med

The nephrotoxicity of antimicrobial agents

N Engl J Med

Adverse reactions to daily and intermittent rifampicin regimens for pulmonary tuberculosis in Hong Kong

BMJ

Rates of cutaneous reactions to drugs

JAMA

Current concepts: Systemic anaphylaxis in the human being

N Engl J Med

Toxicity

Adverse reactions and interactions of fluoroquinolones

Clin Invest Med

Antibiotic-associated diarrhea

J Infect Dis

Neurological side effects

Antibiotics for Clinicians

Aminoglycosides—50 years on

Br J Clin Pharmacol

Photo-onycholysis caused by demethylchlortetracycline

BMJ

Drug-induced cutaneous reactions

JAMA

Temafloxacin syndrome: Review of 95 cases

Clin Infect Dis

Hypersensitivity syndrome associated with efavirenz therapy

Clin Infect Dis

Hepatoxicity of erythromycin

J Infect Dis

Aztreonam: A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Drugs

Study of the effects of ticarcillin on blood coagulation and platelet function

Antimicrob Agents Chemother

Review of adverse experience and tolerability in the first 2516 patients treated with imipenem-cilastatin

Am J Med

Clinical and laboratory markers of hypersensitivity to trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia and AIDS

J Infect Dis

Use of linezolid, an oxazolidine, in the treatment of multidrug-resistant gram-positive bacterial infections

Clin Infect Dis

Central nervous system toxicity of quinolones: Human and animal findings

J Antimicrob Chemother

Prospective study of ampicillin rash

Prolonged QT_c Interval