Adverse Effects of Single Dose Gentamicin in Adults - A Systematic Review Hayward R S, Harding J, Molloy R, Land L, Longcroft-Neal K, Moore D, Ross J D C

Background N. gonorrhoeae - Increasing resistance to antibiotics Gentamicin –aminoglycoside –lower incidence of resistance compared to other antibiotics –known for toxicities - nephrotoxicity and ototoxicity –most toxicity information based on multi-dose regimens

Objective: To review the frequency and type of adverse events associated with a single dose of intravenous or intramuscular gentamicin in adults, for any indication, when a comparator group is used.

Methods: Protocol developed and registered with PROSPERO. Studies eligible for review; - recruited human participants >16 years old - gentamicin IM or IV as a single one-off dose - compared to a control group (placebo, no treatment, an antimicrobial regimen where gentamicin is used in combination with other antibiotics or an antimicrobial regimen that does not include gentamicin) - adverse events were monitored

Methods: Following databases searched; MEDLINE, EMBASE, British Nursing Index and Cumulative Index Nursing and Allied Health Literature (CINAHL), The Cochrane Library. National Guideline Clearinghouse, NICE and SIGN. Trial registers, conference abstracts and proceedings, dissertations and theses. Pharmacovigilance data from regulatory authorities and a specific drug bibliographic database TOXLINE. The National Technical Information Service (NTIS) and OpenGrey were searched Citation searching carried out on included articles.

Records identified through database searching n = Titles and abstracts screened for relevance n = 5840 Records excluded n = 4907 Full-text articles assessed for eligibility n = 933 Studies included in qualitative synthesis n = 22 Full-text articles excluded n = 911 Results: PRISMA Flow Diagram Duplicates removed n = 6276

Results: - 22 studies 18 journal articles 3 trial protocols (2 not currently reported - excluded) 1 thesis 20 studies included in final analysis 20 studies - 12 randomised controlled trials - 2 cohort studies - 3 pharmacokinetic studies - 3 quasi experimental studies

Results: participants across all studies received a single one-off dose of gentamicin Ages yr old Gentamicin dose 1mg/kg to 280mg Indications: neurosurgical prophylaxis, gonorrhoea treatment, UTI treatment, prophylaxis prior to emergency abdo surgery, prophylaxis prior to cystogram, prophylaxis prior to prostatectomy, acute pyelonephritis treatment Adverse events not the primary outcome measure in any study Meta analysis not possible due to heterogeneity

Results: participants across all studies received a single one-off dose of gentamicin Reversible nephrotoxicity/creatinine rise Gentamicin – 37 reports Control – at least 4 reports (incomplete reporting) Irreversible renal impairment Gentamicin – 1 report Control – incomplete reporting Ototoxicity Gentamicin – 3 reports Control – 7 reports Dizziness Gentamicin – 7 reports Control – 7 reports

Discussion: - Gentamicin is an infrequent cause of adverse events Limitation - limited and low quality adverse event reporting in published studies

Questions?