Single-Dose Aminoglycosides for UTIs Jimmy April 14, 2023 0 Comments Introduction UTIs are most commonly caused by Enterobacteriaceae (E. coli, Proteus spp., Klebsiella spp., etc.) and other Gram-negative organisms.UTIs are most commonly caused by Enterobacteriaceae (E. coli, Proteus spp., Klebsiella spp., etc.) and other Gram-negative organisms. UTIs are most commonly caused by Enterobacteriaceae (E. coli, Proteus spp., Klebsiella spp., etc.) and other Gram-negative organisms.UTIs 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. Pharmacology Rationale: Excellent activity against most uropathogens, including drug-resistant EnterobacteriaceaeEliminated 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 hoursToxicities may be limited with one-time administration✓Prevents medication access & adherence concerns Dosing Gentamicin Amikacin Tobramycin Dosing 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 TBWObese [TBW >1.25x IBW]: use adjusted body weight Administration Pharmacokinetics/ Pharmacodynamics Adverse Effects Nephrotoxicity Ototoxicity Considerations Caution in renal impairment Large volume for IM administration *Definitions Uncomplicated – non-pregnant women with no known anatomical and functional abnormalities of the urinary tract or comorbiditiesComplicated – all men, pregnant women, anatomical or functional abnormalities of the urinary tract, indwelling urinary catheters, renal diseases, and/or other immunocompromising diseases such as diabetesCystitis – infection confined to the bladder; symptoms of increased urinary urgency, frequency & dysuriaPyelonephritis – infection extends beyond the bladder; cystitis symptoms + fever, chills, flank & pelvic pain Overview of Evidence Study Goodletet al. 2018Design Systematicreview (n=13,804 patients across 13 studies published from 1978 to 1991)IncludedStudies -Single-dose aminoglycoside with no concomitant antibiotic therapy-Averagepatient: 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 andgentamicinOutcomes-Overall microbiologic cure rate of 94.5% ± 4.3% No differences between pediatric- and adult-only studiesNo differences between aminoglycosides ad comparator armsPatients 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-dayfollow-up -Only 0.5% (64/13,804) reported adverse effects, mainly dueto 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 (10/44patients) Only 2 studies included patients with pyelonephritisNo cases of sepsis or bacteremia were reported-Older studies Did not study against modern uropathogensDid not compare to commonly used agents, such as nitrofurantoin or IV ceftriaxone-Did not assess for future uropathogen resistance-Symptom data was not reportedPatients could have been treated for asymptomatic bacteriuriaLack of assessment of clinical cure rate for majority of studies-No studies were blinded-Unknown drug dosing of comparator armsThe Bottom Line Consider use in patients with:· Lower urinary tract infection (cystitis), · No systemic signs/symptoms,· Normal renal function, and· 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 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.