Note: Antibiotic prescribing is best deferred to local antibiograms. If your institution or practice area has data local resistance patterns, you should prioritize the use of this information when deciding appropriate antibiotic therapy.
Recommended Citation: Reyes J. The Cheese - Considerations in the Treatment of Urinary Tract Infections[Internet]. Cook County Emergency Medicine Residency;Available from: https://cookcountyem.com/blog/2023/9/25/the-cheese-considerations-in-the-treatment-of-urinary-tract-infections
I remember the first time I heard it. It sounded like a myth, or a game of telephone gone wrong. Then I looked it up, and veni, vidi, vici, it was true. Cephalexin, in certain conditions, can be dosed BID, and that condition is uncomplicated UTIs. Here, we will discuss some tips and tricks for antibiotic guidance for urinary tract infections.
Are there any resistance patterns for urinary tract infections I should know about?
Data produced in 2016 found rates of increasing fluoroquinolone-resistant organisms and extended-spectrum beta-lactamase (ESBL) producing organisms in patients with UTI from 2013-2014, with rates of 6.3%-19.9% for fluoroquinolone resistance and 2.6% to 12.2% for ESBL (1). Notably, they also found that approximately 75% of ESBL cases and 45% of fluoroquinolone-resistant cases occurred in patients without previous antimicrobial exposure. Similar data was found in a multi-center cohort of emergency department patients in the US. This observational trial between 2018-2020 included 3779 adult patients with cystitis, pyelonephritis, and UTI and found fluoroquinolone-resistant organisms in 22.1% of cases and ESBL-producing organisms in 7.4% of cases (2). Previous antimicrobial in the past 90 days was associated with an odds ratio of 2.68 (95% CI:2.04-3.51), close to tripling the likelihood of someone having fluoroquinolone resistance. Nearly 37% of all patients infected with drug-resistant organisms had no documented risk factors for such an occurrence.
Answer: Of the first-line agents, augmentin will remain my first choice compared to a fluoroquinolone like ciprofloxacin or levofloxacin. If a patient is penicillin allergic and has risk factors for severe disease or recent anti-microbial exposure, I will consider trimethoprim-sulfamethoxazole more highly.
How and when should I give cephalexin for urinary tract infections?
The US Food and Drug Administration package insert for Cephalexin currently states cephalexin is approved for the treatment of uncomplicated urinary tract infections due to E. coli, Klebsiella, and Proteus, and, additionally, can be administered at 500 mg BID as opposed to 250 mg QID. The physiologic reason for this relates to first-generation cephalosporins' high renal clearance, which can create 0.5-1 mg/mL in urine (3). The use of cephalexin in the form of BID dosing is supported in the literature (4), including an article published in 2023 in Open Forum Infectious Diseases (5) under the umbrella of Infectious Diseases Society of America, which retrospectively compared patients with susceptible UTIs treated 5-7 days with either Cephalexin 500 mg BID and 500 mg QID and found no differences in treatment failure (BID Group 12.7% vs QID Group 17%). Notably, this is in patients with uncomplicated lower urinary tract infections.
Answer: In patients with an uncomplicated urinary tract infection without a history of recent antibiotics or drug-resistant UTI who have a contraindication to nitrofurantoin (recommended by our antibiogram), I will consider this narrow spectrum agent alternatively.
Do I really need to treat acute bacterial prostatitis for 4 weeks?
The Journal of Clinical Infectious Diseases in 2010 and the European Association of Urology have endorsed a shorter antimicrobial course, 14 days, in treating acute bacterial prostatitis in individuals who are not clinically ill or have evidence of bacteremia (6, 7). Although this feels like a strong endorsement, in the New England Journal in 2016, an expert opinion article with guidelines from Prostate Cancer UK that acute bacterial prostatitis should be treated 4 weeks given approximately 1 in 4 patients with prostatitis are bacteremic, and 5-10% have a concomitant prostate abscess, further worsened by poor antimicrobial penetration into prostatic tissue (8). Therefore, when and if at all we should treat individuals for prostatitis with a shorter course is unclear.
Answer: Short answer is yes. In most to all patients, I will continue to give 4 weeks of antibiotics for acute bacterial prostatitis. If a patient has close PCP or urological follow up, is young without risk factors, and has no evidence of systemic illness, I may very selectively consider a patient-centered discussion regarding trialing a 2 week course of antibiotics only at the preference of these very select patients.
SUMMARY: Fluoroquinolone resistance is outpacing the rate of ESBL, including in patients with community-acquired urinary tract infections without recent antimicrobial exposures. An alternative agent narrow-spectrum agent with relatively good resistance profiles is cephalexin, which can be dosed 500 mg BID. Prostatitis treatment length is currently contentious, and uniformity among both urologic and infectious disease societies suggesting a shorter course does not currently exist.
Authored by Jose Reyes, MD
References:
Talan, D.A., et al., Fluoroquinolone-Resistant and Extended-Spectrum β-Lactamase-Producing Escherichia coli Infections in Patients with Pyelonephritis, United States(1). Emerg Infect Dis, 2016. 22(9): p. 1594-603.
Faine, B.A., et al., High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020. Acad Emerg Med, 2022. 29(9): p. 1096-1105.
Griffith, R.S., The pharmacology of cephalexin. Postgrad Med J, 1983. 59 Suppl 5: p. 16-27.
Nguyen, H.M. and C.J. Graber, A Critical Review of Cephalexin and Cefadroxil for the Treatment of Acute Uncomplicated Lower Urinary Tract Infection in the Era of "Bad Bugs, Few Drugs". Int J Antimicrob Agents, 2020. 56(4): p. 106085.
Yetsko, A., et al., Two times versus four times daily cephalexin dosing for the treatment of uncomplicated urinary tract infections in females. Open Forum Infectious Diseases, 2023.
Lipsky, B.A., I. Byren, and C.T. Hoey, Treatment of Bacterial Prostatitis. Clinical Infectious Diseases, 2010. 50(12): p. 1641-1652.
EAU Guidelines. Edn. presented at the EAU Annual Congress Milan, Italy 2023. ISBN 978-94-92671-19-6
Schaeffer, A.J. and L.E. Nicolle, CLINICAL PRACTICE. Urinary Tract Infections in Older Men. N Engl J Med, 2016. 374(6): p. 562-71.