Török E, Cooke FJ, Moran E: Oxford Handbook of Infectious Diseases and Microbiology, Oxford University Press, Oxford, England, 2009.
Liu C, Bayer A, Cosgrove SE, et al: Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52: e18, 2011.
Lowy FD: Methicillin-resistant Staphylococcus aureus (MRSA) in adults: treatment of skin and soft tissue infections. UpToDate. Available at: https://www.uptodate.com/contents/methicillin-resistant-staphylococcus-aureus-mrsa-in-adults-treatment-of-skin-and-soft-tissue-infections. Accessed August 29, 2020. Published 2020.
Bowen AC, Carapetis JR, Currie BJ, et al: Sulfamethoxazole-trimethoprim (Cotrimoxazole) for skin and soft tissue infections including impetigo, cellulitis, and abscess. Open Forum Infect Dis 4: ofx232, 2017.
Deconinck L, Dinh A, Nich C, et al: Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs). PLoS One 14: e0224106, 2019.
Joseph WS: “Methicillin Resistant Staphylococcus aureus (MRSA),” in Handbook of Lower Extremity Infections, 3rd Ed, p 323, Data Trace Publishing, Brooklandville, MD, 2009.
Kalowski S, Mathew T, Singh Nanra R, et al: Deterioration in renal function in association with co-trimoxazole therapy. Lancet 301: 394, 1973.
Berglund F, Killander J, Pompeius R: Effect of trimethoprim-sulfamethoxazole on the renal excretion of creatinine in man. J Urol 114: 802, 1975.
Myre SA, McCann J, First MR, et al: Effect of trimethoprim on serum creatinine in healthy and chronic renal failure volunteers. Ther Drug Monit 9: 161, 1987.
Gentry CA, Nguyen AT: An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. Ann Pharmacother 47: 1618, 2013.
Rajput J, Moore LS, Mughal N, et al: Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study. Clin Microbiol Infect 26: 1651, 2020.
Alappan R, Perazella MA, Buller GK: Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole. Ann Intern Med 124: 316, 1996.
Velazquez H: Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med 119: 296, 1993.
Cohen SH, Gerding DN, Johnson S, et al: Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 31: 431, 2010.
Peacock WF, Rafique Z, Clark CL, et al: Real World Evidence for Treatment of Hyperkalemia in the Emergency Department (REVEAL–ED): a multicenter, prospective, observational study. J Emerg Med 55: 741, 2018.
Stevens DL, Bisno AL, Chambers HF, et al: Practice guidelines for the diagnosis and management of skin and soft tissue infections: update by the Infectious Diseases Society of America. Clin Infect Dis 59: e10, 2014.
Alappan R, Buller GK, Perazella MA: Trimethoprim-sulfamethoxazole therapy in outpatients: is hyperkalemia a significant problem? Am J Nephrol 19: 389, 1999.
Baethke R, Golde G, Gahl G: Sulphamethoxazole/trimethoprim: pharmacokinetic studies in patients with chronic renal failure. Eur J Clin Pharmacol 4: 233, 1972.
Dijkmans B, Hooff J, Wolff F, et al: The effect of co-trimoxazole on serum creatinine. Br J Clin Pharmacol 12: 701, 1981.
Fraser TN, Avellaneda AA, Graviss EA, et al: Acute kidney injury associated with trimethoprim/sulfamethoxazole. J Antimicrob Chemother 67: 1271, 2012.
Andreev E, Koopman M, Arisz L: A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? J Intern Med 246: 247, 1999.
Eastwood JB, Gower PE: A study of the pharmacokinetics of clindamycin in normal subjects and patients with chronic renal failure. Postgrad Med J 50: 710, 1974.
Ho JMW, Juurlink DN: Considerations when prescribing trimethoprim-sulfamethoxazole. CMAJ 183: 1851, 2011.
Naderer O, Nafziger AN, Bertino JS: Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions. Antimicrob Agents Chemother 41: 2466, 1997.
Nakada T, Kudo T, Kume T, et al: Quantitative analysis of elevation of serum creatinine via renal transporter inhibition by trimethoprim in healthy subjects using physiologically-based pharmacokinetic model. Drug Metab Pharmacokinet 33: 103, 2018.
Paap CM, Nahata MC: Clinical use of trimethoprim/sulfamethoxazole during renal dysfunction. DICP 23: 646, 1989.
Siber GR, Gorham CC, Ericson JF, et al: Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole in children and adults with normal and impaired renal function. Rev Infect Dis 4: 566, 1982.
Parham WA, Mehdirad AA Biermann KM, et al: Hyperkalemia revisited. Tex Heart Inst J 33: 40, 2006.
Joseph WS: Another reason to avoid overuse of trimethoprim/sulfamethoxazole (TMP/SMX). Podiatry Today Blog. Available at: https://www.hmpgloballearningnetwork.com/site/podiatry/blogged/another-reason-avoid-overuse-trimethoprimsulfamethoxazole-tmpsmx. Published August 24, 2010.
Antoniou T, Gomes T, Juurlink DN, et al: Trimethoprim-sulfamethoxazole induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med 170: 1045, 2010.31.
Buffie CG, Jarchum I, Equinda M, et al: Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile–induced colitis. Infect Immun 80: 62, 2012.
The purpose of this article is to familiarize physicians with the risks of prescribing trimethoprim/sulfamethoxazole (TMP/SMX) for patients who have kidney or cardiac pathology, have hyperkalemia, or take other interacting medications. Although TMP/SMX is a drug that is frequently used to treat skin and soft-tissue infections of the leg and foot, particularly if methicillin-resistant Staphylococcus aureus is identified, it is not an innocuous antibiotic. Literature documenting the many adverse effects of TMP/SMX is reviewed. A case history is presented illustrating the association of TMP/SMX with the development of a life-threatening situation. Ways of avoiding these adverse events are discussed, and the use of safer antibiotics is recommended.