Single-Dose Aminoglycosides for UTIs

Introduction

UTIs are most commonly caused by Enterobacteriaceae (E. coli, Proteus spp., Klebsiella spp., etc.) and other Gram-negative organisms.
UTIs are classified based on risk factors (uncomplicated vs. complicated) and the area of the urinary tract affected (cystitis vs. pyelonephritis).
Treatment of asymptomatic bacteriuria is often not beneficial and only supported by guidelines in pregnant women and before urological procedures that compromise the mucosa.
Inappropriate antibiotic use has led to increased resistance in uropathogenic bacteria.
Barriers to traditional oral antibiotic therapy include increasing bacterial resistance, nonadherence rates approaching 60%, and medication access issues.

Clinical Detail

Pharmacology

Rationale for single-dose aminoglycosides:

Excellent activity against most uropathogens, including drug-resistant Enterobacteriaceae.
Eliminated as active drug almost exclusively by the kidneys, with urine concentrations ~100-fold greater than plasma.
Post-antibiotic effect of aminoglycosides may persist for up to 72 hours.
Toxicities may be limited with one-time administration.
Prevents medication access & adherence concerns.

	Gentamicin	Amikacin	Tobramycin
Dose	5 mg/kg IV/IM once	15 mg/kg IV/IM once	5 mg/kg IV/IM once
Weight basis	Underweight [TBW < IBW]: use TBW Nonobese [TBW 1× to 1.25× IBW]: use IBW or TBW Obese [TBW > 1.25× IBW]: use adjusted body weight
Administration	IM: undiluted 40 mg/mL vial IV: dilute in 50 to 200 mL of NS, LR, or D5W and infuse over 30 min to 2 h	IM: undiluted 500 mg/2 mL vial IV: dilute in 100 to 200 mL of NS, LR, or D5W and infuse over 30 to 60 min	IM: undiluted 80 mg/2 mL vial IV: dilute in 50 to 100 mL of NS, LR, or D5W and infuse over 20 to 60 min
PK/PD	IM: rapid & complete absorption No CYP-mediated metabolism Urine (70% unchanged drug)	IM: rapid & complete absorption No CYP-mediated metabolism Urine (94–98% unchanged drug)	IM: rapid & complete absorption No CYP-mediated metabolism Urine (90–95% unchanged drug)
Adverse Effects	Nephrotoxicity Ototoxicity
Considerations	Caution in renal impairment Large volume for IM administration

Single-dose aminoglycoside regimens above apply to lower UTI (cystitis); doses use the weight basis shown. IM administration may require a large injection volume.

Definitions

Uncomplicated – non-pregnant women with no known anatomical and functional abnormalities of the urinary tract or comorbidities.
Complicated – all men, pregnant women, anatomical or functional abnormalities of the urinary tract, indwelling urinary catheters, renal diseases, and/or other immunocompromising diseases such as diabetes.
Cystitis – infection confined to the bladder; symptoms of increased urinary urgency, frequency & dysuria.
Pyelonephritis – infection extends beyond the bladder; cystitis symptoms + fever, chills, flank & pelvic pain.

Evidence

Overview of Evidence

Parameter	Detail
Study	Goodlet et al., 2018
Design	Systematic review (n=13,804 patients across 13 studies published from 1978 to 1991)
Included studies	Single-dose aminoglycoside with no concomitant antibiotic therapy Average patient: *pediatric female with acute uncomplicated cystitis secondary to E. coli* with normal renal function treated in the outpatient setting** 7 studies with a comparator arm: Single-dose oral fosfomycin Oral trimethoprim-sulfamethoxazole, amoxicillin, or cephalosporin × 5–10 days 72% of isolates were E. coli Netilmicin was the most commonly used aminoglycoside, followed by amikacin and gentamicin
Outcomes	Overall microbiologic cure rate of 94.5% ± 4.3% No differences between pediatric- and adult-only studies No differences between aminoglycosides and comparator arms Patients with anatomical abnormalities were less likely to have initial microbiologic cure Overall 19% (84/443) 30-day recurrence rate in studies with a minimum 30-day follow-up Only 0.5% (64/13,804) reported adverse effects, mainly vestibular toxicity (53 patients) and nephrotoxicity (7 patients)
Limitations	Majority of patients (13,258/13,804) were from one study Generalizability is questionable 8 studies (pediatric only) & 3 studies (adults only) Only 1 study included patients with moderate or severe renal impairment (10/44 patients) Only 2 studies included patients with pyelonephritis No cases of sepsis or bacteremia were reported Older studies Did not study against modern uropathogens Did not compare to commonly used agents, such as nitrofurantoin or IV ceftriaxone Did not assess for future uropathogen resistance Symptom data was not reported Patients could have been treated for asymptomatic bacteriuria Lack of assessment of clinical cure rate for the majority of studies No studies were blinded Unknown drug dosing of comparator arms

The Bottom Line

Consider use in patients with	AND multiple of the following
Lower urinary tract infection (cystitis) No systemic signs/symptoms Normal renal function No urinary tract abnormalities	Medication access issues Known medication nonadherence Multiple antibiotic allergies Known history of resistant organisms Unable to take oral medications

Recent Evidence (2024–2025)

Author, year	Design / sample size	Intervention & comparison	Outcome
Peyko et al., 2025	Randomized, open-label trial N = 57 at 7 days (30 gentamicin, 27 standard care)	Single-dose gentamicin vs. standard oral care for acute uncomplicated cystitis in premenopausal women	Self-reported symptom resolution at 7 days was 83.3% (25/30) with gentamicin vs. 48.1% (13/27) with standard care (P=0.005). A dedicated randomized comparison of single-dose gentamicin for uncomplicated cystitis — but open-label, single-center, and small; hypothesis-supporting, not definitive.
Jenrette et al., 2024	Multicenter, prospective study N = 13 (complicated cystitis discharged from the ED)	Single-dose aminoglycoside for complicated cystitis at ED discharge	10/13 (77%) reported resolved urinary symptoms and 11/13 (85%) reported no new symptoms; no patient required admission for treatment failure and no adverse events were reported. Extends the single-dose concept to complicated cystitis, but very small and pilot-grade.

Conclusions

Single-dose aminoglycoside therapy may be a plausible treatment option in patients with cystitis.
Aminoglycosides can be administered by either the IV or IM route and therefore do not necessarily require IV access. Gentamicin may be considered the preferred aminoglycoside based on frequency of use in studies.
The risk for adverse events with single-dose aminoglycosides is low; however, there are concerns for nephrotoxicity and ototoxicity.
Single-dose aminoglycosides should NOT be recommended as first-line therapy. They can be considered in patients with acute cystitis, normal renal function, and multiple barriers to the standard of care.
Since this pearl’s original publication, newer evidence has begun to test the strategy prospectively: a small 2025 open-label randomized trial (n=57) found higher 7-day symptom resolution with single-dose gentamicin vs. standard care in premenopausal women with uncomplicated cystitis (83.3% vs. 48.1%, P=0.005), and a 2024 prospective ED cohort (n=13) extended the approach to complicated cystitis with no treatment-failure admissions. Both are small and single-/few-center. Current broad guidance (2024 WikiGuidelines consensus; 2024 EAU) still centers first-line cystitis therapy on nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin and does not yet endorse single-dose aminoglycosides.

References

Bonkat G, Bartoletti RR, Bruyere F, et al. EAU Guidelines on Urological Infections. Urological Infections. 2019.
Gupta K, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257
Nicolle LE, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019;68(10):e83-e110. doi:10.1093/cid/ciy1121
Goodlet KJ, Benhalima FZ, Nailor MD. A Systematic Review of Single-Dose Aminoglycoside Therapy for Urinary Tract Infection: Is It Time To Resurrect an Old Strategy? Antimicrob Agents Chemother. 2018 Dec 21;63(1):e02165-18. doi:10.1128/AAC.02165-18
Peyko V, et al. Single-Dose Gentamicin vs Standard Care for Treatment of Acute Uncomplicated Cystitis in Premenopausal Women: A Randomized Trial. J Pharm Pract. 2025;38(6):518-524. doi:10.1177/08971900251322368
Jenrette JE, et al. Prospective evaluation of single-dose aminoglycosides for treatment of complicated cystitis in the emergency department. Acad Emerg Med. 2024;31(7):649-655. doi:10.1111/acem.14886
Nelson Z, et al. Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement. JAMA Netw Open. 2024;7(11):e2444495. doi:10.1001/jamanetworkopen.2024.44495
Kranz J, et al. European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines. Eur Urol. 2024;86(1):27-41. doi:10.1016/j.eururo.2024.03.035

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