Gentamicin
Classification: AATC code: J01GB03
Summary
Some studies report that gentamicin-induced nephrotoxicity is more frequent in women compared to men, while other studies have not found any sex difference.
A large study showed that gentamicin and nitrofurantoin were the most suitable treatment options for urinary tract infections in men and women in any age group.
Additional information
Pharmacokinetics and dosing
Gentamicin first-dose pharmacokinetics have been studied in patients with a suspected or documented episode of Gram-negative bacterial sepsis (23 men, 9 women; mean age 68 years). Women had a larger median volume of distribution per kilogram than men (0.50 vs. 0.40 L/kg) and a lower Cmax (15.2 vs. 18.5 mg/L), even though men and women received similar weight adjusted gentamicin doses [2]. No sex differentiation in dosing has been recommended [3].
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].Resistance patterns for pathogens often differ between populations. A Portuguese retrospective analysis of urinary samples (120,691 (78%) from women and 34,898 (22%) from men) gentamicin resistance was more common in male urinary samples positive for E. coli andP. mirabilis[4].
Adverse effects
Studies report contradictory results whether women are more often affected by gentamicin-induced nephrotoxicity than men or not [5]. An analysis of two randomized double-blind controlled clinical trials of aminoglycosides (121 men, 93 women) found that female sex was associated with the development of nephrotoxicity [6]. Also, a multicenter study found a higher risk of gentamicin nephrotoxicity in women [7]. However, another hospital based study found no difference between men and women in risk of developing gentamicin-induced nephrotoxicity [8].
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: 2016-01-08
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
- Gonçalves-Pereira J, Martins A, Póvoa P. Pharmacokinetics of gentamicin in critically ill patients: pilot study evaluating the first dose. Clin Microbiol Infect. 2010;16:1258-63. PubMed
- Gensumycin (gentamicin). Summary of Product Characteristics. Medical Products Agency Sweden; 2015.
- 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
- Ali BH. Gentamicin nephrotoxicity in humans and animals: some recent research. Gen Pharmacol. 1995;26:1477-87. PubMed
- Moore RD, Smith CR, Lipsky JJ, Mellits ED, Lietman PS. Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med. 1984;100:352-7. PubMed
- Prince RA, Ling MH, Hepler CD, Rainville EC, Kealey GP, Donta ST et al. Factors associated with creatinine clearance changes following gentamicin therapy. Am J Hosp Pharm. 1980;37:1489-95. PubMed
- Sweileh WM. Gender differences in aminoglycoside induced nephrotoxicity: a prospective, hospital-based study. Curr Clin Pharmacol. 2009;4:229-32. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-06-30.] Socialstyrelsens statistikdatabas
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson