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Resistance to nalidixic acid. A misconception due to underdosage
JAMA
|October 18, 1976
Summary
Full-dose nalidixic acid (4 gm/day) effectively treats infections, with low resistance development in patients and minimal fecal resistance. Underdosing is the likely cause of observed resistance to this antibiotic.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Nalidixic acid is an antibiotic used for urinary tract infections.
- Concerns exist regarding the development of resistance to nalidixic acid.
- Understanding resistance mechanisms is crucial for effective antibiotic use.
Purpose of the Study:
- To evaluate the clinical development of resistance to nalidixic acid.
- To compare resistance development with nalidixic acid to other antibiotics.
- To identify factors contributing to nalidixic acid resistance.
Main Methods:
- Clinical treatment of 27 patients with 4 gm/day of nalidixic acid.
- Monitoring resistance in bacteriuric populations.
- Assessing fecal reservoir resistance.
- In vitro studies on 100 Enterobacteriaceae strains at varying concentrations and inoculum sizes.
Main Results:
- Only 7% of patients developed resistance when treated with 4 gm/day.
- Fecal resistance was minimal compared to sulfonamides, tetracyclines, and ampicillin.
- Resistance development in vitro was inversely proportional to nalidixic acid concentration.
- Extrachromosomal R-factor resistance to nalidixic acid was not observed.
Conclusions:
- Full dosage (4 gm/day) of nalidixic acid is effective in preventing resistance.
- Underdosing is the probable cause of excessive nalidixic acid resistance.
- Nalidixic acid remains a viable option, especially for multiply-resistant Enterobacteriaceae.