Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Three-day trimethoprim-sulfamethoxazole was best for acute cystitis

ACP J Club. 1995 July-Aug;123:15. doi:10.7326/ACPJC-1995-123-1-015


Source Citation

Hooton TM, Winter C, Tiu F, Stamm WE. Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women. JAMA. 1995 Jan 4;273:41-5.


Abstract

Objective

To compare the efficacy, safety, and total costs of 3-day trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin, nitrofurantoin, and cefadroxil for acute uncomplicated cystitis in women.

Design

Randomized controlled trial with cost analyses.

Setting

University student health center in the United States.

Patients

180 women (mean age 24 y, 87% white) ≥ 18 years old with symptoms of acute cystitis (dysuria, frequency, urgency, suprapubic pain) for ≤ 7 days. Exclusion criteria were pregnancy, lactation, evidence of upper urinary tract infection, abnormal urinary tract anatomic findings, or allergy to study medications. Follow-up was 88%.

Intervention

Treatment duration was 3 days. 46 women were assigned to receive TMP-SMX, 160/800 mg 2 times/d; 52 women were assigned to receive amoxicillin, 500 mg 3 times/d; 42 women were assigned to receive macrocrystalline nitrofurantoin, 100 mg 4 times/d; and 40 women were assigned to receive cefadroxil, 500 mg 2 times/d. Follow-up was 4 to 6 days, 12 to 16 days, and 4 to 6 weeks after treatment.

Main outcome measures

Urinary symptoms, microbiological treatment failure, and adverse effects. Cost calculations included diagnostic tests and treatment for the initial episode, recurrences (treatment with ciprofloxacin, 250 mg 2 times/d for 3 d), and antibiotic-induced fungal vaginitis (treatment with clotrimazole for 7 d).

Main results

Escherichia coli was the most common pathogen (85%); others were Enterobacteriaceae (5%), Staphylococcus saprophyticus (3%), and other gram-positive cocci (6%). At 4 to 6 days, the rates of treatment failures were lower with TMP-SMX (3%) and cefadroxil (0%) than with nitrofurantoin (16%) (P = 0.05 for comparison with TMP-SMX) and showed a trend toward fewer failures than with amoxicillin (14%). At the end of the study, nitrofurantoin had a higher failure rate (39%) than TMP-SMX (18%) (P = 0.04) (Table). Failure rates did not differ for cefadroxil (34%) and amoxicillin (33%). The groups did not differ for adverse effects (35% for TMP-SMX, 43% for nitrofurantoin, 30% for cefadroxil, and 25% for amoxicillin). Total costs per patient were lower for TMP-SMX (U.S. $114) and amoxicillin ($131) than for nitrofurantoin and cefadroxil (both $155).

Conclusion

A 3-day course of trimethoprim-sulfamethoxazole was more effective and less expensive than 3-day courses of amoxicillin, nitrofurantoin, and cefadroxil for treatment of uncomplicated cystitis in young women.

Source of funding: Not stated.

For article reprint: Dr. T.M. Hooton, Harborview Madison Clinic, 325 - 9th Avenue, #359930, Seattle, WA 98104-2499, USA. FAX 206-731-5109.


Table. Trimethoprim-sulfamethoxazole (TMP-SMX) vs nitrofurantoin, amoxicillin, or cefadroxil for women with uncomplicated cystitis*

Treatment failure Comparison Rates RRR (95% CI) NNT (CI)
At 4 to 6 d TMP-SMX vs nitrofurantoin 3% vs 16% 84% (6 to 97) 8 (4 to 156)
At 4 to 6 d TMP-SMX vs amoxicillin 3% vs 14% 82% (-6 to 97) Not significant
At 6 wk TMP-SMX vs nitrofurantoin 18% vs 39% 54% (2 to 79) 5 (2 to 212)
At 6 wk TMP-SMX vs cefadroxil 18% vs 34% 48% (-16 to 77) Not significant

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

The study by Hooton and colleagues addresses cystitis in young women and extends previous work by the same authors and by others (1, 2). Patients with cystitis expect a good outcome with minimal cost and inconvenience. Although clinical practice does not require 3 follow-up visits for cystitis, morbidity and expense may not appear for weeks. Cefadroxil was effective at initial eradication of the infection, but recurrences were common. The cost of incapacity or time off from work was not calculated but would offer a multiplier effect for adequate treatment (enhancing the superiority of TMP-SMX). Drug acquisition cost composed only 4% to 11% of total treatment expense.

Treatment was started before culture results were available. Several patients with "resistant" strains were cured, as were almost all with "intermediate" strains. Nitrofurantoin frequently failed with "susceptible" organisms. These results confirm the lack of utility of cultures in uncomplicated cystitis. The outcome with β-lactams suggests that these agents are less useful than TMP-SMX in urinary tract infection therapy.

Although researchers in a large Scandinavian study (2) prematurely stopped assigning patients to receive TMP-SMX because they feared that TMP-SMX could cause rare but life-threatening complications, such as toxic epidermal necrolysis, TMP-SMX is still widely used in the United States. Although increasing bacterial resistance to TMP-SMX is worrisome (3), the clinical implication is uncertain. A comparison between 3-day courses of TMP-SMX and a fluoroquinolone would probably show similar cost and outcome (1). The biggest objection to fluoroquinolone therapy is ecologic—fear of selecting resistant bacteria. Given the existing level of abuse of fluoroquinolones when they are marginally indicated, it is unclear whether using them for urinary tract infections would hasten the emergence of resistance.

Thomas Fekete, MD
Temple University School of MedicinePhiladelphia, Pennsylvania, USA


References

1. Hooton TM, Johnson C, Winter C, et al. Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women. Antimicrob Agents Chemother. 1991; 35:1479-83.

2. Coordinated multicenter study of norfloxacin versus trimethoprim-sulfamethoxazole treatment of symptomatic urinary tract infections. The Urinary Tract Infection Study Group. J Infect Dis. 1987;155:170-7.

3. Gupta K, Scholes D, Stamm WE. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA. 1999;281:736-8.