Introduction
Urinary tract infections are most commonly caused by Enterobacteriaceae (E. coli, Proteus spp., Klebsiella spp., etc.) and other Gram-negative organisms. Barriers to traditional oral antibiotic therapy include increasing bacterial resistance, nonadherence rates approaching 60%, and medication access issues.
Why Consider Single-Dose Aminoglycosides?
- Excellent activity against most uropathogens, including drug-resistant Enterobacteriaceae
- Eliminated as active drug almost exclusively by the kidneys with concentrations 100-fold greater in urine than plasma
- Post-antibiotic effect may persist for up to 72 hours
- Toxicities may be limited with one-time administration
- Prevents medication access and adherence concerns
Key Definitions
Uncomplicated UTI
Non-pregnant women with no known anatomical/functional urinary tract abnormalities or comorbidities
Complicated UTI
All men, pregnant women, anatomical/functional abnormalities, indwelling catheters, renal diseases, diabetes
Cystitis
Infection confined to the bladder; symptoms of increased urinary urgency, frequency, and dysuria
Pyelonephritis
Infection extends beyond the bladder; cystitis symptoms plus fever, chills, flank and pelvic pain
Pharmacology & Dosing
| Parameter | Gentamicin | Amikacin | Tobramycin |
|---|---|---|---|
|
Dose
|
5 mg/kg IV/IM once |
15 mg/kg IV/IM once |
5 mg/kg IV/IM once |
Weight-Based Dosing Considerations
[TBW < IBW]: Use TBW (total body weight)
[TBW 1x to 1.25x IBW]: Use IBW or TBW
[TBW > 1.25x IBW]: Use adjusted body weight
Adverse Effects
Considerations
Caution in renal impairment
Large volume for IM administration
Clinical Pearl
Aminoglycosides achieve urinary concentrations 100-fold greater than plasma levels. The post-antibiotic effect may persist up to 72 hours, making single-dose therapy a pharmacokinetically rational approach for uncomplicated lower UTIs.
Overview of Key Evidence
| Parameter | Details |
|---|---|
| Study | Goodlet et al., 20184 |
| Design |
Systematic Review
n=13,804 patients across 13 studies (1978–1991) |
| Inclusion |
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 72% of isolates were E. coli Netilmicin was the most commonly used aminoglycoside, followed by amikacin and gentamicin 7 studies with a comparator arm (single-dose oral fosfomycin; oral TMP-SMX, amoxicillin, or cephalosporin x 5–10 days) |
|
Outcomes
|
Efficacy
Overall microbiologic cure rate of 94.5% ± 4.3%
Parity
No differences between pediatric- and adult-only studies; no differences between aminoglycosides and comparator arms
Recurrence
Overall 19% (84/443) 30-day recurrence rate in studies with minimum 30-day follow-up
Safety
Only 0.5% (64/13,804) reported adverse effects, mainly vestibular toxicity (53 pts) and nephrotoxicity (7 pts) |
|
Limitations
|
Majority of patients (13,258/13,804) were from one study Generalizability is questionable — 8 pediatric-only and 3 adult-only studies 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 reported Older studies — did not study modern uropathogens or compare to commonly used agents (nitrofurantoin, IV ceftriaxone) Did not assess for future uropathogen resistance Symptom data not reported; patients could have been treated for asymptomatic bacteriuria No studies were blinded; unknown drug dosing of comparator arms |
Clinical Conclusions
Bottom Line
Consider use in patients with:
- Lower urinary tract infection (cystitis)
- No systemic signs/symptoms
- Normal renal function
- No urinary tract abnormalities
AND multiple of the following:
- Medication access issues
- Known medication nonadherence
- Multiple antibiotic allergies
- Known history of resistant organisms
- Unable to take oral medications
Single-dose aminoglycoside therapy may be a plausible treatment option in patients with cystitis.
Aminoglycosides can be administered via either the IV or IM route and 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 aminoglycoside should NOT be recommended as first-line therapy. It can be considered in patients with acute cystitis with normal renal function and multiple barriers to the standard of care.
Full Reference List
- Bonkat G, Bartoletti RR, Bruyere F et al. EAU Guidelines on Urological Infections. Urological Infections. 2019.
- Uncomplicated Cystitis and Pyelonephritis (UTI). Clinical Infectious Diseases. 2011;52(5):e103–e120.
- Clinical Practice Guideline for the management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2019;68(10):e83–75.
- 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.
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