Confronting UTI Antimicrobial Resistance: What’s Up Our Sleeve?

One of the greatest challenges of modern medicine is antimicrobial resistance. Most clinicians exercise discretion when writing antibiotic prescriptions for patients in front of us. However, many of our practices have disease-specific intervention protocols that decrease clinician burden and facilitate patient care, but that put antibiotic prescribing on autopilot. One common protocolized intervention addresses urinary tract infections. Ciprofloxacin has been the UTI workhorse for many of us because it is effective and well-tolerated. However, increasing resistance and calls to put ciprofloxacin “on reserve” have prompted changes in our UTI protocols.

Last week, the Journal of the American Medical Association published a comparative evaluation of cefpodoxime and ciprofloxacin to see if we could expand our UTI treatment armamentarium (JAMA. 2012;307:583-9). Cefpodoxime has broad spectrum antimicrobial activity and would provide a useful alternative to fluoroquinolones for cystitis treatment if demonstrated to be similar in efficacy. In this study, three hundred women with acute cystitis were randomized to cefpodoxime or ciprofloxacin given for 3 days. The primary outcome was clinical cure at 30 days. E. coli caused most cystitis (75%). Overall, 4% of isolates (4% of E. coli and 8% of non−E. coli) were nonsusceptible to ciprofloxacin and 8% (4% of E. coli and 36% of non−E. coli) were nonsusceptible to cefpodoxime. The overall cure rate at 30 days using an intent-to-treat approach in which patients lost to follow-up were considered having had a clinical cure, was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%). The investigators had pre-determined that a greater than 10% lower rate of cure for cefpodoxime was clinically inferior, so they concluded that cefpodoxime did not meet criteria for noninferiority for achieving clinical cure. The authors speculated that cephalosporins probably fail because fewer women achieved eradication of vaginal E. coli colonization with cefpodoxime than with cirprofloxacin.

The Infectious Diseases Society of America suggested that fluoroquinolones be reserved for important uses other than acute cystitis, and thus should be considered alternative antimicrobials for acute cystitis. Nitrofurantoin could be used, but insurance companies currently are mailing “information letters” about the dangers of using this drug in older patients due to concerns about drug accumulation in people with less than optimal renal function. Fosfomycin could be used, but we have had some trouble finding it in our local pharmacies.

The take-home message is that current studies do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. More research needs to be conducted on the efficacy of narrow-spectrum cephalosporins to increase our options. Most importantly, we need to be continually reviewing our local resistance patterns, guideline panel recommendations, and the emerging evidence to intelligently update our disease-specific treatment protocols.

Dr. Ebbert reported having no relevant conflicts of interest.  

One of the greatest challenges of modern medicine is antimicrobial resistance. Most clinicians exercise discretion when writing antibiotic prescriptions for patients in front of us. However, many of our practices have disease-specific intervention protocols that decrease clinician burden and facilitate patient care, but that put antibiotic prescribing on autopilot. One common protocolized intervention addresses urinary tract infections. Ciprofloxacin has been the UTI workhorse for many of us because it is effective and well-tolerated. However, increasing resistance and calls to put ciprofloxacin “on reserve” have prompted changes in our UTI protocols.

Last week, the Journal of the American Medical Association published a comparative evaluation of cefpodoxime and ciprofloxacin to see if we could expand our UTI treatment armamentarium (JAMA. 2012;307:583-9). Cefpodoxime has broad spectrum antimicrobial activity and would provide a useful alternative to fluoroquinolones for cystitis treatment if demonstrated to be similar in efficacy. In this study, three hundred women with acute cystitis were randomized to cefpodoxime or ciprofloxacin given for 3 days. The primary outcome was clinical cure at 30 days. E. coli caused most cystitis (75%). Overall, 4% of isolates (4% of E. coli and 8% of non−E. coli) were nonsusceptible to ciprofloxacin and 8% (4% of E. coli and 36% of non−E. coli) were nonsusceptible to cefpodoxime. The overall cure rate at 30 days using an intent-to-treat approach in which patients lost to follow-up were considered having had a clinical cure, was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%). The investigators had pre-determined that a greater than 10% lower rate of cure for cefpodoxime was clinically inferior, so they concluded that cefpodoxime did not meet criteria for noninferiority for achieving clinical cure. The authors speculated that cephalosporins probably fail because fewer women achieved eradication of vaginal E. coli colonization with cefpodoxime than with cirprofloxacin.

The Infectious Diseases Society of America suggested that fluoroquinolones be reserved for important uses other than acute cystitis, and thus should be considered alternative antimicrobials for acute cystitis. Nitrofurantoin could be used, but insurance companies currently are mailing “information letters” about the dangers of using this drug in older patients due to concerns about drug accumulation in people with less than optimal renal function. Fosfomycin could be used, but we have had some trouble finding it in our local pharmacies.

The take-home message is that current studies do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. More research needs to be conducted on the efficacy of narrow-spectrum cephalosporins to increase our options. Most importantly, we need to be continually reviewing our local resistance patterns, guideline panel recommendations, and the emerging evidence to intelligently update our disease-specific treatment protocols.

Dr. Ebbert reported having no relevant conflicts of interest.  

One of the greatest challenges of modern medicine is antimicrobial resistance. Most clinicians exercise discretion when writing antibiotic prescriptions for patients in front of us. However, many of our practices have disease-specific intervention protocols that decrease clinician burden and facilitate patient care, but that put antibiotic prescribing on autopilot. One common protocolized intervention addresses urinary tract infections. Ciprofloxacin has been the UTI workhorse for many of us because it is effective and well-tolerated. However, increasing resistance and calls to put ciprofloxacin “on reserve” have prompted changes in our UTI protocols.

Last week, the Journal of the American Medical Association published a comparative evaluation of cefpodoxime and ciprofloxacin to see if we could expand our UTI treatment armamentarium (JAMA. 2012;307:583-9). Cefpodoxime has broad spectrum antimicrobial activity and would provide a useful alternative to fluoroquinolones for cystitis treatment if demonstrated to be similar in efficacy. In this study, three hundred women with acute cystitis were randomized to cefpodoxime or ciprofloxacin given for 3 days. The primary outcome was clinical cure at 30 days. E. coli caused most cystitis (75%). Overall, 4% of isolates (4% of E. coli and 8% of non−E. coli) were nonsusceptible to ciprofloxacin and 8% (4% of E. coli and 36% of non−E. coli) were nonsusceptible to cefpodoxime. The overall cure rate at 30 days using an intent-to-treat approach in which patients lost to follow-up were considered having had a clinical cure, was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%). The investigators had pre-determined that a greater than 10% lower rate of cure for cefpodoxime was clinically inferior, so they concluded that cefpodoxime did not meet criteria for noninferiority for achieving clinical cure. The authors speculated that cephalosporins probably fail because fewer women achieved eradication of vaginal E. coli colonization with cefpodoxime than with cirprofloxacin.

The Infectious Diseases Society of America suggested that fluoroquinolones be reserved for important uses other than acute cystitis, and thus should be considered alternative antimicrobials for acute cystitis. Nitrofurantoin could be used, but insurance companies currently are mailing “information letters” about the dangers of using this drug in older patients due to concerns about drug accumulation in people with less than optimal renal function. Fosfomycin could be used, but we have had some trouble finding it in our local pharmacies.

The take-home message is that current studies do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. More research needs to be conducted on the efficacy of narrow-spectrum cephalosporins to increase our options. Most importantly, we need to be continually reviewing our local resistance patterns, guideline panel recommendations, and the emerging evidence to intelligently update our disease-specific treatment protocols.

Dr. Ebbert reported having no relevant conflicts of interest.