Single-Dose Aminoglycosides for UTIs — Pharmacy Pearl | PACU
Pharmacy Friday Pearl Infectious Disease

Single-Dose Aminoglycosides for Urinary Tract Infections

Evaluating the evidence for single-dose aminoglycoside therapy as an alternative treatment for UTIs — a systematic review of 13 studies spanning 1978–1991.

J

Jimmy Pruitt

Clinical Pharmacist

Apr 14, 2023 6 min

1

Syst. Review

13,804

Patients

13

Included Studies

4

References

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.

Broad-Spectrum Activity

Excellent activity against most uropathogens, including drug-resistant Enterobacteriaceae

Renal Concentration

Urinary concentrations 100-fold greater than plasma levels

Prolonged PAE

Post-antibiotic effect may persist for up to 72 hours

Single-Dose Safety

Toxicities may be limited with one-time administration; prevents 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

Single-Dose Regimens

Gentamicin

5

mg/kg IV/IM once

Amikacin

15

mg/kg IV/IM once

Tobramycin

5

mg/kg IV/IM once

Relative Dosing

Gentamicin 5 mg/kg
Amikacin 15 mg/kg
Tobramycin 5 mg/kg

Weight-Based Dosing

Underweight

[TBW < IBW]: Use TBW

Nonobese

[TBW 1x to 1.25x IBW]: Use IBW or TBW

Obese

[TBW > 1.25x IBW]: Use adjusted body weight

Adverse Effects

Nephrotoxicity Ototoxicity

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.

Evidence at a Glance

94.5%

Microbiologic Cure

19%

30-Day Recurrence

0.5%

Adverse Effects

72%

E. coli Isolates

Safety signal: Only 64/13,804 (0.5%) reported adverse effects — primarily vestibular toxicity (53 pts) and nephrotoxicity (7 pts). No nephrotoxicity reported in studies using single-dose regimens with normal renal function.

Goodlet et al., 2018 Systematic Review n=13,804
Parameter Details
Design Systematic review of 13 studies published from 1978 to 1991 (n=13,804 patients)
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, outpatient setting

72% of isolates were E. coli. Netilmicin most commonly used aminoglycoside.

Efficacy
94.5% microbiologic cure No difference vs comparators

No differences between pediatric- and adult-only studies. Patients with anatomical abnormalities less likely to achieve initial cure.

Recurrence 19% (84/443) 30-day recurrence

In studies with minimum 30-day follow-up

Safety 0.5% adverse effects (64/13,804)

Mainly vestibular toxicity (53 pts) and nephrotoxicity (7 pts)

Limitations

Majority of patients (13,258/13,804) from one study

Questionable generalizability (8 pediatric-only; 3 adult-only)

Only 1 study with renal impairment patients; 2 with pyelonephritis; no sepsis/bacteremia

Older studies not reflecting modern uropathogens; no comparison to nitrofurantoin or IV ceftriaxone

No blinding; symptom data not reported; no assessment of future resistance

Bottom Line

Consider use in patients with:

  • Lower UTI (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
  • History of resistant organisms
  • Unable to take oral medications
1

Single-dose aminoglycoside therapy may be a plausible treatment option in patients with cystitis.

2

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.

3

The risk for adverse events with single-dose aminoglycosides is low, however, there are concerns for nephrotoxicity and ototoxicity.

4

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.

  1. Bonkat G, Bartoletti RR, Bruyere F et al. EAU Guidelines on Urological Infections. Urological Infections. 2019.
  2. Uncomplicated Cystitis and Pyelonephritis (UTI). Clinical Infectious Diseases. 2011;52(5):e103–e120.
  3. 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.
  4. 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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