Trimethoprim + sulfamethoxazole
Classification: AATC code: J01EA01, J01EE01
Summary
A large study has shown that trimethoprim-sulfamethoxazole susceptibility was similar in male and female urinary isolates with E. coli. Some studies report more resistance to trimethoprim-sulfamethoxazole in urinary samples from boys/men while other studies find no sex differences.
Additional information
Trimethoprim-sulfamethoxazole is also known as co-trimoxazolein English literature.
Pharmacokinetics and dosing
No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of trimethoprim-sulfamethoxazole have been found.
Effects
In some settings urine cultures to identify pathogens and resistance pattern cannot always be obtained and therapy of urinary tract infections then has to be empirical. A Brazilian study analyzed urine isolates to identify suitable empirical therapy options for cystitis and urinary tract infections in relation to patient’s sex and age (1098 men, 8700 women). Drug classes analyzed was ampicillin, nitrofurantoin, fluoroquinolones (ciprofloxacin and levofloxacin), trimethoprim-sulfamethoxazole, gentamicin, and ceftriazone/cefotaxime. Women exhibited higher susceptibility values for all drug classes studied than men. For women in any age group, only nitrofurantoin and gentamicin provided adequate activity for empirical therapy (> 80% susceptibility). For men in any age group, only gentamicin was suitable for empirical therapy. In women aged over 60 years, few suitable empirical treatment options were identified [1].Another study of urinary E. coliisolates (2274 men, 32265 women) has described age- and sex-specific antibiotic susceptibility patterns for ampicillin, amoxicillin clavulanate, ciprofloxacin, nitrofurantoin and trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole susceptibility was similar in men and women. Age-specific susceptibilities differed between men and women for all antibiotics studies except trimethoprim-sulfamethoxazole. However, the magnitude of the observed differences was generally less than 5% and the authors suggest that they may not represent clinically meaningful differences [2].
Resistance patterns for pathogens often differ between populations. A Dutch study [3, 4] did not find any difference in E. colisusceptibility to trimethoprim. However a Portuguese study [5] and a British study [6] found that resistance to trimethoprim or trimethoprim-sulfamethoxazole was more common in bacteria isolated from men than women. Similarly in a US study in children, E. coliand Proteusresistance to trimethoprim-sulfamethoxazole was higher in boys than in girls, but Enterobacterhad a higher level of resistance to trimethoprim-sulfamethoxazole in girls than in boys [7]. Another study in children (494 boys, 512 girls; <2 years old) found that trimethoprim resistance increased over a 10-year period only in girls [8].
Adverse effects
A randomized controlled study has evaluated the effect of recommended gonorrhea-treatment regimens on simultaneous chlamydial infection (46 men and 44 women on trimethoprim-sulfamethoxazole). Cure rates for trimethoprim-sulfamethoxazole in treating gonorrhea were similar in men and women. However, side effects from trimethoprim-sulfamethoxazole were more frequent in women (36% vs. 8.7%). The administrated dose trimethoprim-sulfamethoxazole was unspecified [9].
Among reported cases of thrombocytopenia after administration of trimethoprim-sulfamethoxazole in the Australian Adverse Drug Reactions Registry, 68% of the cases were in women [10]. Similarly, a study of adverse reactions among hospitalized medical patients (292 men, 357 women) receiving trimethoprim-sulfamethoxazole 80/400 mg showed that reactions were reported more often in women. The largest sex difference was observed for rashes (4.6% vs. 2.1%) [11].
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Updated: 2020-08-28
Date of litterature search: 2016-01-28
References
- Rocha JL, Tuon FF, Johnson JR. Sex, drugs, bugs, and age: rational selection of empirical therapy for outpatient urinary tract infection in an era of extensive antimicrobial resistance. Braz J Infect Dis. 2012;16:115-21. PubMed
- McGregor JC, Elman MR, Bearden DT, Smith DH. Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients. BMC Fam Pract. 2013;14:25. PubMed
- den Heijer CD, Donker GA, Maes J, Stobberingh EE. Antibiotic susceptibility of unselected uropathogenic Escherichia coli from female Dutch general practice patients: a comparison of two surveys with a 5 year interval. J Antimicrob Chemother. 2010;65:2128-33. PubMed
- den Heijer CD, Penders J, Donker GA, Bruggeman CA, Stobberingh EE. The importance of gender-stratified antibiotic resistance surveillance of unselected uropathogens: a Dutch Nationwide Extramural Surveillance study. PLoS One. 2013;8:e60497. PubMed
- Linhares I, Raposo T, Rodrigues A, Almeida A. Frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections: a ten-year surveillance study (2000-2009). BMC Infect Dis. 2013;13:19. PubMed
- Amyes SG, Doherty CJ, Young HK. High-level trimethoprim resistance in urinary bacteria. Eur J Clin Microbiol. 1986;5:287-91. PubMed
- Edlin RS, Shapiro DJ, Hersh AL, Copp HL. Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol. 2013;190:222-7. PubMed
- Swerkersson S, Jodal U, Åhrén C, Hansson S. Urinary tract infection in small outpatient children: the influence of age and gender on resistance to oral antimicrobials. Eur J Pediatr. 2014;173:1075-81. PubMed
- Stamm WE, Guinan ME, Johnson C, Starcher T, Holmes KK, McCormack WM. Effect of treatment regimens for Neisseria gonorrhoeae on simultaneous infection with Chlamydia trachomatis. N Engl J Med. 1984;310:545-9. PubMed
- Dickson HG. Trimethoprim-sulphamethoxazole and thrombocytopenia. Med J Aust. 1978;2:5-7. PubMed
- Lawson DH, Jick H. Adverse reactions to co-trimoxazole in hospitalized medical patients. Am J Med Sci. 1978;275:53-7. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-06-30.] Socialstyrelsens statistikdatabas
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson