Intravenous Gentamicin Use in Adults (HARTFORD Guidance)

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Kerry Rodgers
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Bacrund This plicy cvers the use f intravenus (IV) gentamicin in adults using the HARTFORD dsing guidance. Evidence fr this dsing regimen is prvided belw.

The guidance des nt apply t gentamicin use in the fllwing: synergistic treatment f endcarditis r Staphylcccal bne infectin patients treated in Renal units r receiving haemdialysis r haemfiltratin

myasthenia gravis Cautins t gentamicin therapy: Patients with decmpensated liver disease - aminglycsides are assciated with an increased risk f renal failure.

1 Bacrund This plicy cvers the use f intravenus (IV) gentamicin in adults using the HARTFORD dsing guidance. Evidence fr this dsing regimen is prvided belw. The plicy is fr the use f gentamicin fr the treatment f infectin nly. SAPG recmmendatins n gentamicin dsing fr surgical prphylaxis are prvided elsewhere. The guidance des nt apply t gentamicin use in the fllwing: synergistic treatment f endcarditis r Staphylcccal bne infectin patients treated in Renal units r receiving haemdialysis r haemfiltratin majr burns ascites age < 16 years cystic fibrsis (refer t lcal guidelines) pregnancy (refer t lcal guidelines) Cntra-indicatins and cautins Cntra-indicatins t gentamicin therapy hypersensitivity, myasthenia gravis Cautins t gentamicin therapy: Patients with decmpensated liver disease - aminglycsides are assciated with an increased risk f renal failure. Cncurrent administratin f neurtxic and / r nephrtxic agents increases the risk f gentamicin txicity. Review therapy and cnsider amending r withhlding nephrtxic drugs during gentamicin treatment. Avid c-administratin with the fllwing: neurmuscular blckers ther ptentially nephrtxic (e.g. NSAIDs and ACE Inhibitrs) r ttxic drugs ptent diuretics ther aminglycsides This list is nt exhaustive cnsult the Summary f Prduct Characteristics (espc) fr a full list ( Chrnic Kidney Disease (CKD) Stage 4 r mre, knwn r suspected acute kidney injury in the previus 48 hurs ( 50% increase in baseline serum creatinine r liguria > 6 hurs). If gentamicin is clinically indicated, give ne dse as per guidance and check with micrbilgy r an infectin specialist befre giving a secnd dse. Prescribing and dcumentatin T imprve the prescribing f gentamicin, ensure cnsistency and reduce risk, standardised charts (agreed natinally) shuld be used t dcument the prescriptin, administratin and mnitring f gentamicin. These shuld be used fr prescribing treatment dses f gentamicin in cnjunctin with the existing inpatient prescribing chart (e.g. kardex) and medical / nursing dcumentatin. These charts cntain a step-wise apprach t safe and effective prescribing and key pints f advice n mnitring, interpreting and re-prescribing. An Antimicrbial app and/r an nline calculatr is available in all bards and shuld be used t calculate the initial dse. Reference: Niclau DP, Freeman CD, Belliveau PP, et al. Experience with a nce-daily aminglycside prgram administered t 2,184 adult patients. Antimicrb Agents Chemther. 1995; 39:

2 STEP 1: Calculate, prescribe and administer the first dse T reduce the risk f mrtality, cmmence gentamicin administratin within 1 hur f recgnising sepsis. If creatinine is knwn use the nline calculatr r app (preferred methd). The guidelines in Bx 2 (belw) can be used if the nline calculatr is nt available. The dse amunt is based n estimated creatinine clearance (Bx 1) and actual bdy weight r a crrected dsing weight (CDW) if the patient is bese (Bx 2). If creatinine is nt knwn give 7 mg/ gentamicin (maximum 600 mg) r, if Chrnic Kidney Disease (CKD) 5, give 2.5 mg/ (maximum 180 mg) n advice f senir staff. Calculate the dse using actual bdy weight r crrected bdy weight if the patient is bese. Give the recmmended dse by infusin in 100 ml sdium chlride 0.9% ver 1 hur and ensure the time f administratin is nted n the medicine chart. Bx 1: Estimatin f creatinine clearance (CrCl) The fllwing Cckcrft Gault equatin can be used t estimate creatinine clearance (CrCl) [140 age (years)] x weight () x 1.23 (male) OR x 1.04 (female) CrCl = (ml/min) serum creatinine (micrml/l) Cautins: Use actual bdy weight r maximum bdy weight, whichever is lwer. Fr maximum bdy weight see In patients with lw creatinine (< 60 micrml/l), use 60 micrml/l. Nte: Use f estimated glmerular filtratin rate (egfr) is nt recmmended. Bx 2: Initial GENTAMICIN dses If creatinine clearance is > 20 ml/min and the patient is nt bese, calculate the dse by multiplying actual bdy weight by 7 (i.e. 7 mg/) t a maximum dse f 600 mg. Rund this t the nearest 40 mg fr ease f administratin. (see Table 1) If creatinine clearance is > 20 ml/min and the patient is bese (actual weight is >20% abve their Ideal bdy weight) calculate the gentamicin dse by multiplying their crrected dsing weight (CDW) by 7 (i.e. 7 mg/ CDW) t a maximum dse f 600 mg. Rund this t the nearest 40 mg fr ease f administratin (see Table 1). CDW = ideal bdy weight (actual bdy weight ideal bdy weight) Fr ideal bdy weight see If creatinine clearance 20 ml/min, first cnfirm that gentamicin is the mst apprpriate treatment. Calculate the initial dse by multiplying the patient s actual bdy weight (r crrected dsing weight if the patient is bese) by 2.5 (i.e. 2.5 mg/) t a maximum f 180 mg. Alternatively, a SINGLE dse f 7 mg/ may be cnsidered (d nt repeat this dse). 2

STEP 1: Creatinine Clearance (ml/min) 20 Calculate, prescribe and administer the first dse 40-44 Table 1: Initial GENTAMICIN dses Actual bdy weight (use crrected dsing weight if the patient is bese)

3 STEP 1: Creatinine Clearance (ml/min) 20 Calculate, prescribe and administer the first dse Table 1: Initial GENTAMICIN dses Actual bdy weight (use crrected dsing weight if the patient is bese) mg/ (max 180 mg) then take a bld sample after 24 hurs > 20 mg mg mg mg mg mg mg mg mg If actual bdy weight is < 40 and creatinine clearance is > 20 ml/minute, use a dse f 7 mg/ and rund t the nearest 20 mg Nte that patients wh have unusual clinical characteristics, e.g. weight < 40, weight >120, age >90 years may require dse adjustments and require clse mnitring. Cntact pharmacy fr advice. STEP 2: Mnitr creatinine and gentamicin cncentratins and establish the dsage regimen Cncentratins are meaningless unless the dse & sample times are recrded accurately If creatinine clearance is > 20 ml/min Take a bld sample 6-14 hurs after the start f the first gentamicin infusin. Recrd the exact time f all gentamicin samples using the gentamicin prescribing chart AND n the sample request frm. Recrd the serum cncentratin n the gentamicin prescribing chart. Plt the gentamicin cncentratin n the nmgram belw & reassess the dse/dsing interval as indicated. If the result is n the line, chse the lnger interval. If the level is abve the 48 hurly line (Q48h), stp therapy and reassess the dsage regimen. D nt give a further dse until the cncentratin is <1 mg/l. 3

4 STEP 2: Mnitr creatinine and gentamicin cncentratins and establish the dsage regimen If creatinine clearance is 20 ml/min Take a bld sample 24 hurs after the start f the gentamicin infusin. Recrd the exact time f all gentamicin samples using the gentamicin prescribing chart AND n the sample request frm. If therapy is t cntinue, give a further dse nce the measured cncentratin is < 1 mg/l. General pints Dcument the actin taken in the medical ntes and n the gentamicin prescribing chart. Undertake pre-prescribing checks (Bxes 3 & 4 n p.5) t assess the risk f renal txicity and ttxicity. Prescribe the next dse as apprpriate. If a bld sample is nt taken, is lst r is taken at wrng time and if there is any cncern abut patient s renal functin, take a sample hurs after the start f the gentamicin infusin and wait fr the result befre giving the next dse. Otherwise, take a bld sample after next dse. If the measured cncentratin is unexpectedly HIGH r LOW, cnsider the fllwing: Were dse and sample times recrded accurately? Was the crrect dse administered? Was the sample taken frm the line used t administer the drug? Was the sample taken during drug administratin? Has renal functin declined r imprved? Des the patient have edema r ascites? If in dubt, take anther sample befre re-prescribing and / r cntact pharmacy fr advice STEP 3: Assess daily the nging need fr gentamicin and signs f txicity Take a further sample 6-14 hurs after the dse at least every 2 days. If the cncentratin is unexpectedly high, r if renal functin alters, daily sampling may be necessary. If the patient is receiving 36 r 48 hurly dsing, a level shuld be checked after each infusin. T minimise the risk f txicity, duratin f treatment shuld nrmally be limited t 72 hurs. All gentamicin prescriptins that cntinue beynd 3-4 days f treatment must be discussed with micrbilgy r an infectin specialist. Cnsider changing t an ral alternative - refer t the IV t Oral switch plicy. Bx 3: Renal txicity Mnitr creatinine daily. Seek advice if renal functin is unstable (e.g. change in creatinine f > 15-20%) Signs f renal txicity include increase in creatinine r decrease in urine utput / liguria Cnsider an alternative agent if creatinine is rising r the patient becmes liguric. 4

5 Bx 4: Ottxicity Ottxicity secndary t gentamicin is independent f drug cncentratin. It is suggested by any f the fllwing: new tinnitus, dizziness, pr balance, hearing lss r scillating visin. Txicity is assciated with prlnged aminglycside use (usually > 10 days but may be > 72 hurs) and is secndary t drug accumulatin within the inner ear. Stp treatment if ttxicity is suspected and refer t micrbilgy/infectin specialist fr advice n future therapy. If gentamicin cntinues fr > 7 days, cnsider referral t audilgy fr assessment. 5

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