Resistance to Trimethoprim-Sulfamethoxazole

Sulfonamides have a glorious history. In 1935, they were the first class of true antimicrobial agents with life-saving potency. Today, 66 years later, increased bacterial resistance to sulfonamides and to trimethoprim (TMP), a synthetic antimicrobial agent that is 30 years younger than sulfonamides, has limited their use to only a few indications. In the treatment and prophylaxis of patients with urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMZ) or TMP alone is still considered the first-line drug of choice, although increased bacterial resistance to these agents has been linked with treatment failure. TMP-SMZ has a possible role as a second- or third-line treatment for patients who have respiratory tract infections. In the developing world, where this inexpensive drug is widely used as first-line treatment, bacterial resistance has caused problems, especially with regard to the treatment of patients with severe respiratory tract infections. Use of TMP-SMZ as prophylaxis for Pneumocystis carinii infection has rapidly increased the multidrug resistance of bacterial pathogens found in human immunodeficiency virus-infected patients. Today, detailed and reliable knowledge on the resistance of bacterial pathogens to both TMP-SMZ and TMP is an essential requirement for the safe and effective use of these drugs in all clinical settings.