By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Professor of Medicine, Northeast Ohio Medical University, Rootstown, OH
SYNOPSIS: An observational study of adults hospitalized with a complicated urinary tract infection and bacteremia found seven days of therapy was enough for the majority of cases when they received antibiotics with comparable intravenous and oral bioavailability.
SOURCE: McAteer J, Lee JH, Cosgrove SE, et al. Defining the optimal duration of therapy for hospitalized patients with complicated urinary tract infections and associated bacteremia. Clin Infect Dis 2023;76:1604-1612.
Complicated urinary tract infection (cUTI) with bacteremia is one of the most common conditions in clinical practice leading to hospitalization. If the duration of treatment is not long enough, then there is an increased risk of recurrence. However, overtreatment increases the risk of spreading antimicrobial resistance and adverse events like drug side effects and Clostridioides difficile infection. Finding the sweet spot for optimal antibiotic duration for cUTIs has been the goal of several recent studies, including the current one by McAteer and colleagues.
The study was a retrospective cohort analysis that included patients aged 18 years or older with a gram-negative cUTI and associated bacteremia. There were 24 U.S. hospitals from mostly the Northeast (14), with some in the Midwest (6), Mountain states (3), and West (1). The investigators defined a cUTI as a UTI associated with structural or functional abnormalities of the genitourinary tract, or any UTI in a male patient. Furthermore, patients were only included if they had bacteremia caused by the same organism causing the cUTI to assure true infection rather than colonization.
The primary outcome of the study was recurrent UTI due to the same uropathogen within 30 days after discontinuation of antibiotic therapy. The secondary outcome was the development of an antibiotic-resistant UTI (AR-UTI) due to the same uropathogen within 30 days of completing therapy. This was defined as an organism with an antibiotic minimum inhibitory complex (MIC) increase of four-fold or greater to the antibiotic used for treating the index infection.
There were 1,099 patients included in the analysis. Of these, 265 received seven days of treatment (24%), 382 received 10 days of treatment (35%), and 452 received 14 days of treatment(41%). Escherichia coli was the most prevalent uropathogen (59%), followed by Klebsiella pneumoniae (16%), Proteus mirabilis (8%), and Pseudomonas aeruginosa (6%). Extended-spectrum beta-lactamase (ESBL) producers caused 17% of infections.
There was no difference in the rate of recurrent infection for patients who received 10 or 14 days of treatment (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.52-1.87). There was an increased risk of recurrence in the seven-day group compared to the 14-day group (aOR, 2.54; 95% CI, 1.40-4.60). However, when patients were maintained on intravenous (IV) therapy or switched to a highly bioavailable oral antibiotic, this difference disappeared (aOR, 0.76; 95% CI, 0.38-1.52).
A recurrent UTI within 30 days occurred in 18% (76/1,099) of the patients, of whom 14 (1.2%) had an AR-UTI. There was no statistically significant difference between duration of therapy and the development of an AR-UTI (P = 0.10).
COMMENTARY
This is a pragmatic study that should be of great interest to clinicians who take care of hospitalized patients with cUTI and bacteremia. It is notable that seven days of antibiotics was sufficient when IV beta-lactams were used for the entire course of treatment or when antibiotics were transitioned to highly bioavailable oral agents, like fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX). Similar findings also have been reported from clinical trials on UTIs, where patients who received fluoroquinolones or TMP-SMX had better outcomes compared to those who received oral beta-lactams. This likely is due to suboptimal dosing of oral beta-lactams, such as amoxicillin-clavulante 500/125 mg given twice a day. Thus, it is unknown whether a higher dosed beta-lactam would have led to better outcomes in the clinical trials and in the present study. Further investigation of this question is warranted.
Another caveat is that gram-negative uropathogens are becoming increasingly resistant to fluoroquinolones and TMP-SMX, ranging from 20% to 75% in many clinical settings. If the uropathogen causing a cUTI with bacteremia is not susceptible to a fluoroquinolone or TMP-SMX, the clinician must carefully consider whether to continue IV therapy for seven days or transition to another oral agent (like a high-dose beta-lactam) and extend the treatment duration.
The study has several limitations. First, the observational design could have led to unmeasured confounding variables affecting the results in uncertain ways, although the investigators used inverse probability of treatment weighing (IPTW) to try to mitigate this. Second, it is unclear why clinicians chose the duration of therapy they did. For example, therapy could have been extended if a new fever developed on day 5 of treatment. Third, missing data may have led the investigators to underestimate the number of recurrent infections. Finally, differences between the treatment groups beyond day 1 were not addressed.
The “shorter is better” mantra for antibiotic prescribing likely will get louder thanks to the study by McAteer and colleagues. This is a positive development, although physicians still need to take a nuanced approach to treatment duration based on the patient’s clinical response and a careful review of the laboratory data.
