The mantra “shorter is better” for antibiotic durations has become a point of importance in the infectious disease and antimicrobial stewardship realms.
It is imperative to determine the minimum duration of antibiotics needed to reduce the risk for adverse reactions, development of resistance and unnecessary costs. There have been numerous studies focusing on shorter antibiotic durations for UTIs that have shown shorter courses are noninferior to longer courses for both cystitis and pyelonephritis. However, these studies were often limited to or predominantly conducted in premenopausal women. This leaves questions about the optimal duration of UTI treatment among men and children, for whom longer durations are still often used and/or recommended.
UTI treatment in men
Currently there is minimal guidance for the optimal treatment duration of UTIs in men, and often longer durations up to 14 days are recommended. The 2011 Infectious Diseases Society of America uncomplicated UTI guideline addresses only women, but it is anticipated that IDSA will be releasing a new complicated UTI guideline this year that will encompass guidance for men.
A randomized clinical trial (RCT) at two Veterans Affairs medical centers compared 7 vs. 14 days of therapy among 272 afebrile men with a median age of 69 years, who were treated with either trimethoprim/sulfamethoxazole or ciprofloxacin. The primary outcome was UTI symptom resolution by 14 days after therapy completion, which occurred in 93.1% of participants in the 7-day group compared with 90.2% in the 14-day group, demonstrating noninferiority of the shorter course.
However, the optimal duration for febrile UTIs in men is still unclear. An RCT of febrile UTIs in the Netherlands in both men and women comparing 7 vs. 14 days showed noninferiority (90% vs. 95%) of the shorter regimen for short-term clinical cure, although not in a subgroup analysis of 86 men in the study. Interestingly, this did not translate to the secondary outcome of long-term clinical cure (70 to 84 days after treatment), which indicated noninferiority, even in the subgroup, indicating that a shorter course of therapy is still reasonable. Further studies focusing just on men are needed.
PROSTASHORT was a noninferiority RCT in France that enrolled 282 men with fever and at least one symptom of UTI to compare 7 days vs. 14 days of antibiotic treatment with ofloxacin 200 mg twice daily. The primary endpoint was treatment success, defined as a negative urine culture and absence of fever and of subsequent antibiotic treatment, between the end of treatment and 6 weeks after day 1. Treatment success occurred in 55.7% in the 7-day group compared with 77.6% in the 14-day group, showing inferiority of the 7-day regimen. This was driven mostly by difference in microbiological success (79.1% vs. 93.6%). There was no difference in the secondary outcome of UTI recurrence between 6 and 12 weeks, and no difference in adverse events or rate of rectal colonization with resistant Enterobacterales. These results led the authors to conclude that febrile UTI in men should not be treated for less than 14 days.
This study should be interpreted with a couple points of caution. The first is that it was not conducted among men with prostatitis, despite the name. Second, the difference in the primary endpoint was primarily driven by microbiological success. The use of microbiological success does not correlate to clinical practice, where follow-up urine cultures are not recommended, and asymptomatic bacteriuria should not be treated. Furthermore, the dose of ofloxacin 200 mg twice daily equates to a levofloxacin dose of 100 mg twice daily — a lower dose than would be most commonly used (levofloxacin 750 mg or 500 mg daily). Given these factors and lack of difference in clinical cure and recurrence, it may still be reasonable to consider 7 days of treatment in men with febrile UTIs.
UTI treatment in pediatrics
In children, upper UTI (pyelonephritis) can lead to the long-term effects of kidney scarring and hypertension. Some data suggest that shorter antibiotic duration in children is effective, although the data are limited and contradictory, and longer durations of 7 to 14 days are endorsed by guidelines.
The SCOUT trial is a noninferiority RCT (5% margin) that evaluated 5 vs. 10 days of therapy among 664 U.S. children with UTIs that were clinically improving at day 5. Most participants were female (96%), and they had a median age of 4 years. At presentation, 38% were febrile. Participants received one of five oral antibiotics, with cefdinir being the most common. The primary outcome was treatment failure, defined as symptomatic UTI at or before the first follow-up visit at day 11 to 14.
The rate of treatment failure was 0.6% in the standard group vs. 4.2% in short-course group, with an upper bound 95% CI for difference in treatment failure of 5.5%, thus not meeting noninferiority. The secondary outcome of asymptomatic bacteriuria was more common in the short-course group. After the first follow-up visit, there was no difference in rates of UTI, incidence of adverse events or gastrointestinal colonization with resistant organisms. Although the study failed to meet noninferiority, the authors concluded that short-course therapy could be considered a reasonable option.
According to a post-hoc analysis, 2.7% of participants who received a short course and 4.2% who received a longer course experienced recurrence 9 days after stopping antibiotics (P = .32), and most recurrences were afebrile.
There were notable limitations to these data, because all UTIs were grouped together with no differentiation between cystitis and pyelonephritis, multiple oral antibiotics were included, and the groups had different times to follow-up (6 to 9 days in short-course therapy vs. 1 to 4 in standard therapy). Based on these limitations, experts recommend that courses no longer than 5 days be given for cystitis in children. However, they would consider courses closer to 10 days for pyelonephritis due to increased risk for long-term complications and recommend the use of shared decision-making with the health care team and caregiver.
The STOP trial was an RCT comparing 5-day vs. 10-day treatment with amoxicillin-clavulanate for febrile UTI, although it excluded children with complicated febrile UTI. The trial enrolled 142 children aged 3 months to 5 years in Italy (median 9 months). The primary outcome was recurrent UTI within 30 days from the end of therapy, which was met by 2.8% in the short group vs. 14.3% in standard group. There was no difference seen in secondary outcomes of febrile UTI recurrence or adverse events between the groups. This trial showed that in uncomplicated febrile UTI, 5 days of treatment was noninferior to 10 days.
These results contrast with those of the SCOUT trial, but this should be interpreted with caution because the studies use different definitions, and the SCOUT trial was a larger, more rigorous study. Based on this, experts again concluded that children with cystitis courses should be limited to 5 days of therapy, but if there is clinical concern of pyelonephritis, continue to use a 10-day course until more data are available.
Conclusion
In men with UTI, 7 days of antibiotic therapy should be used for patients who are afebrile, and this treatment could also be considered for those with febrile UTI because evidence suggests there is no difference in long-term clinical outcomes.
In children, 5 days of therapy should be used for cystitis, but closer to 10 days should be considered for pyelonephritis, along with shared clinical decision-making.
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For more information:
Kelly M. Percival, PharmD, BCPS, BCIDP, is a clinical pharmacy specialist in infectious diseases at the University of Iowa Hospitals & Clinics. Percival can be reached at kelly-percival@uiowa.edu.
