All Pharmacy Pearls

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

    Rationale:

    ✓

    Excellent activity against most uropathogens, including drug-resistant Enterobacteriaceae

    ✓

    Eliminated as active drug almost exclusively by the kidneys with concentrations 100-fold greater in the urine 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

    ▪

    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

    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: use undiluted 500 mg/2 mL vial

    IV: Dilute in 100 to 200 mL of NS,

    LR, or D5W and infuse over 30 min

    to 60 min

    IM: use undiluted 80 mL/2 mL vial

    IV: Dilute in 50 to 100 mL of NS, LR

    or D5W and infuse over 20 min 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)

Evidence

    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 x 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 ad comparator arms

    ▪

    Patients with anatomical abnormalities were less likely to have initial microbiologic cure

  • Overall 19% (84/443) 30-day recurrence rate in studies that had minimum 30-day follow-up
  • Only 0.5% (64/13,804) reported adverse effects, mainly due to 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

    ▪

Conclusions

  • Single-dose aminoglycoside therapy may be a plausible treatment option in patients with cystitis.
  • Aminoglycosides can be administered either the IV or IM route, and therefore, does 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.

References

    • 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.

Tags:aminoglycoside urinary tract infection gentamicin stewardship

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single-dose-aminoglycosides-utis.pdf