Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects
- Stephen B Calderwood, MD
Stephen B Calderwood, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine (Microbiology and Immunobiology)
- Harvard Medical School
Beta-lactam antibiotics are among the most commonly prescribed drugs, grouped together based upon a shared structural feature, the beta-lactam ring. Beta-lactam antibiotics include:
- Spratt BG, Cromie KD. Penicillin-binding proteins of gram-negative bacteria. Rev Infect Dis 1988; 10:699.
- Novak R, Charpentier E, Braun JS, Tuomanen E. Signal transduction by a death signal peptide: uncovering the mechanism of bacterial killing by penicillin. Mol Cell 2000; 5:49.
- Gold HS, Moellering RC Jr. Antimicrobial-drug resistance. N Engl J Med 1996; 335:1445.
- Pitout JD, Sanders CC, Sanders WE Jr. Antimicrobial resistance with focus on beta-lactam resistance in gram-negative bacilli. Am J Med 1997; 103:51.
- Tomasz A. Antibiotic resistance in Streptococcus pneumoniae. Clin Infect Dis 1997; 24 Suppl 1:S85.
- Mulligan ME, Murray-Leisure KA, Ribner BS, et al. Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. Am J Med 1993; 94:313.
- Jacobson KL, Cohen SH, Inciardi JF, et al. The relationship between antecedent antibiotic use and resistance to extended-spectrum cephalosporins in group I beta-lactamase-producing organisms. Clin Infect Dis 1995; 21:1107.
- Tamma PD, Girdwood SC, Gopaul R, et al. The use of cefepime for treating AmpC β-lactamase-producing Enterobacteriaceae. Clin Infect Dis 2013; 57:781.
- Katsanis GP, Spargo J, Ferraro MJ, et al. Detection of Klebsiella pneumoniae and Escherichia coli strains producing extended-spectrum beta-lactamases. J Clin Microbiol 1994; 32:691.
- Wiener J, Quinn JP, Bradford PA, et al. Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 1999; 281:517.
- Papanicolaou GA, Medeiros AA, Jacoby GA. Novel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 1990; 34:2200.
- Bratu S, Landman D, Haag R, et al. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch Intern Med 2005; 165:1430.
- Bratu S, Brooks S, Burney S, et al. Detection and spread of Escherichia coli possessing the plasmid-borne carbapenemase KPC-2 in Brooklyn, New York. Clin Infect Dis 2007; 44:972.
- Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010; 10:597.
- Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: A systematic review. Neurology 2015; 85:1332.
- Asbel LE, Levison ME. Cephalosporins, carbapenems, and monobactams. Infect Dis Clin North Am 2000; 14:435.
- FDA Drug Safety Communication: Cefepime and risk of seizure in patients not receiving dosage adjustments for kidney impairment, June 26, 2012. http://www.fda.gov/Drugs/DrugSafety/ucm309661.htm (Accessed on June 27, 2012).
- Gillies M, Ranakusuma A, Hoffmann T, et al. Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication. CMAJ 2015; 187:E21.
- Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med 1994; 330:257.
- Onorato IM, Axelrod JL. Hepatitis from intravenous high-dose oxacillin therapy: findings in an adult inpatient population. Ann Intern Med 1978; 89:497.
- Shiffman ML, Keith FB, Moore EW. Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility. Gastroenterology 1990; 99:1772.
- Ditlove J, Weidmann P, Bernstein M, Massry SG. Methicillin nephritis. Medicine (Baltimore) 1977; 56:483.
- Tan JS, File TM Jr. Antipseudomonal penicillins. Med Clin North Am 1995; 79:679.
- Bush LM, Johnson CC. Ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations. Infect Dis Clin North Am 2000; 14:409.
- Sattler FR, Weitekamp MR, Ballard JO. Potential for bleeding with the new beta-lactam antibiotics. Ann Intern Med 1986; 105:924.
- MECHANISM OF ACTION
- MECHANISMS OF BACTERIAL RESISTANCE
- Decreased penetration to the target site
- Alteration of the target site
- Inactivation by a bacterial enzyme
- - Chromosomal beta-lactamases
- - Plasmid-mediated beta-lactamases
- ADVERSE EFFECTS
- IgE-mediated allergic reactions
- Serum sickness
- Dermatologic reactions
- Neurologic reactions
- Pulmonary reactions
- Gastrointestinal reactions
- Hepatobiliary reactions
- Renal reactions
- Hematologic reactions
- INFORMATION FOR PATIENTS