A Shorter Antibiotic Course for Pyelonephritis?
A Shorter Antibiotic Course for Pyelonephritis?
abstract & commentary
Synopsis: A seven-day course of ciprofloxacin is at least as efficacious as a 14-day course of TMP-SMX for outpatient treatment of uncomplicated pyelonephritis in women, with the quinolone actually demonstrating statistical superiority.
Source: Talan DA, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women. JAMA 2000;283: 1583-1590.
In a multicenter, randomized, double-blind, out-patient trial in women ages 18 or older, the efficacy of a seven-day course of ciprofloxacin (500 mg b.i.d.) was compared to a 14-day course of trimethoprim-sulfamethoxa-zole (TMP-SMX) (160 mg/800 mg b.i.d.) for uncomplicated acute pyelonephritis. The diagnosis was established by the usual clinical findings and substantiated by fixed microscopic pyuric criteria. Of the three hundred seventy-eight patients enrolled, 120 were ultimately excluded from efficacy data analysis because of reasons that included the following: no causative organism on culture; inadequate study drug consumption; lost to follow-up; or other miscellaneous protocol violations. Ultimately, the ciprofloxacin group (n = 128) and TMP-SMX group (n = 127) were found to have similar demographic and clinical characteristics. Treating physicians were allowed discretion regarding whether to administer a first dose of intravenous antibiotics (ciprofloxacin in the 7-day ciprofloxacin group vs ceftriaxone in the 14-day TMP-SMX group). Primary outcome measures included drug efficacy as assessed by bacteriologic and clinical cure both during and after completion of therapy. Secondary measures included adverse drug reactions, organism resistance patterns, continued bacteriologic and clinical cures, and cost analyses.
Not surprisingly, Escherichia coli was the most common causative organism, being isolated in more than 90% of cultures in both study groups. Eighteen percent of all uropathogens isolated were resistant to TMP-SMX, however, including 44 instances of E. coli resistance. Only one isolate was resistant to ciprofloxacin (1 of 3 cultured Proteus mirabilis pathogens). Among the E. coli resistant to TMP-SMX, there was marked regional varia-tion: Eastern sites, 7%; Midwestern, 14%; and Western, 32%.
With respect to bacteriologic cure, 99% of the ciprofloxacin group achieved cure during the 4- to 11-day post-therapy visit, as opposed to 89% of the TMP-SMX group (95% CI, 0.04-0.16; P = 0.004). Regarding clinical outcome, 96% of the ciprofloxacin group had continued clinical cure through the 4- to 11-day post-therapy visit, in contrast to 83% of the TMP-SMX group (95% CI, 0.06-0.22; P = 0.002). In those patients with data available at a second, later point in time (22- to 48-day post-therapy visit), the shorter-course ciprofloxacin again prevailed, although the bacteriologic cure difference did not reach statistical significance. Bacteriologic cure was achieved in 85% of the ciprofloxacin-treated patients vs. 74% of the TMP-SMX-treated patients (95% CI, 0.00-0.21; P = 0.08), whereas clinical cure was found in 91% of the ciprofloxacin group as opposed to 77% of the TMP-SMX group (95% CI, 0.03-0.23; P = 0.02).
The bacteriologic and clinical cure rates of those who did receive an initial intravenous dose of antibiotic were compared to the cure rates of those who did not. Clinical cure rates were similar in both groups regardless of whether a dose of intravenous antibiotic was given. Bacteriologic cure rates were similar for the ciprofloxacin group regardless of intravenous augmentation, but the TMP-SMX group had a higher bacteriologic cure rate at the 4- to 11-day visit, an advantage that was not maintained through the 22- to 48-day encounter.
Adverse events tended to be more common in the TMP-SMX group (33%) than the ciprofloxacin group (24%); this difference persisted when comparing events that led to discontinuation of the study drug (6% in the ciprofloxacin group vs 11% in the TMP-SMX group).
Despite the higher cost of ciprofloxacin, aggregate costs were higher in the TMP-SMX-treated patients because of a greater number of clinical failures.
The authors conclude that a seven-day course of ciprofloxacin is at least as efficacious as a 14-day course of TMP-SMX for outpatient treatment of uncomplicated pyelonephritis in women, with the quinolone actually demonstrating statistical superiority. They caution that these findings cannot be extrapolated to men or to patients who have complicated infections or severe sepsis.
Comment by Richard A. Harrigan, MD, FAAEM
This is an important study conducted by some of the leading researchers in the fields of infectious disease in emergency medicine (Talan and Moran) and urinary tract infection (Stamm and Hooton). As the authors point out, the issue of whether we can treat outpatient pyelonephritis for fewer than 14 days has not been well studied. In that it is a disease not only of the urine but also of medullary renal tissue, adequate serum levels of drug (which correlate with in vitro sensitivity) may, in some cases, be necessary to terminate the infection. This is in contradistinction to simple cystitis, where high levels of drug in the urine may supersede in vitro resistance issues. This study demonstrated that in vitro resistance to TMP-SMX was strongly associated with bacteriologic and clinical treatment failures.
The geographic patterns of resistance found in this study should be noted. Similarly, a high rate of E. coli resistance was noted in another recent study of cystitis conducted in the Northwest.1,2 Fluoroquinolones should be considered the treatment of choice in regions demonstrating significant resistance (i.e., > 10% of isolates) to TMP-SMX.3 Treatment with TMP-SMX, if used, should be conducted with particular attention to urine culture and sensitivity results. Complicated pyelonephritis (e.g., in diabetics, males, structural/functional urologic abnormalities, nursing home patients) is a different entity; the treating physician must be wary of polymicrobial infection and related issues of antibiotic resistance.3 (Dr. Harrigan is Associate Professor of Medicine, Temple University School of Medicine, Associate Research Director, Division of Emergency Medicine, Temple University Hospital, Philadelphia, Pa.)
References
1. Gupta K, et al. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA 1999;281:736-738;
2. Harrigan RA. Antibiotic resistance in uncomplicated UTIs. Emerg Med Alert 1999;12:90-91.
3. Talan DA. New concepts in antimicrobial therapy for emergency department infections. Ann Emerg Med 1999;34:503-516.
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