Gentamicin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Complicated urinary tract infections
• Systemic infections, e.g. septicaemia, peritonitis meningitis
• Bone and soft-tissue infections, e.g. osteomyelitis, wound and soft-tissue infections
• Infected burns
• Respiratory tract infections, e.g pneumonia
• Biliary tract infections
• Eye infections

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Myasthenia gravis

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Elderly
• Risk factors for ototoxicity and nephrotoxicity
  - Renal impairment
  - High doses
  - Prolonged duration of treatment
  - Neonates/infants
  - Elderly
  - Peak concentrations above 10mg/L and troughs above 1mg/L when administering gentamicin 24hrly and 2mg/L when administering gentamicin 12hrly
  - Mitochondrial mutations, particularly m.1555A>G mutation
  - Maternal history of deafness
  - Maternal history of mitochondrial mutation
• Significant obesity
• Conditions characterised by muscular weakness
• May impair ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African Standard Treatment Guideline indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Listeria monocytogenes, Staphylococci,Staphylococcus aureus (MSSA), Campylobacter coli, Campylobacter jejuni, Citrobacter spp.Citrobacter koseri, Enterobacter spp., Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Francisella tularensis, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus spp. (indole positive and indole negative), Proteus vulgaris, Salmonella enterica subsp. enterica, Serratia marcescens, Yersinia enterolitica, Yersinia pseudotuberculosis, Y. pestis, Pseudomonas aeruginosa, Providencia spp., Bartonella spp.

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guideline indications and dosages

Acute pyelonephritis in pregnancy
- Empiric therapy
Diabetic foot ulcers (Additional agent required)
- Severe penicillin allergy
Febrile neutropenia (Additional agent required)
- Within 48hrs of admission
Pelvic inflammatory disease stage II-IV (Additional agent required)
- Severe penicillin allergy
Septic miscarriage (Additional agent required)
- Severe penicillin allergy
Acute pyelonephritis
- Empiric therapy

• IV: 6mg/kg, dly
  (STG, Adult 2019; Adult 2023)

Brucellosis (Additional agent required)

• IV: 6mg/kg, dly; Treatment duration: 3 weeks
  (STG, Adult 2019)

Surgical prophylaxis
- In those with beta-lactam allergies for the following procedures: Gastrointestinal surgery, urology procedures (clean-contaminated), and obstetric/gynaecological surgery (hysterectomy, laparotomy procedures, vaginal repair) (Additional agent required)

• IV: 6mg/kg, within 1hr before incision; Re-dosed in prolonged procedures >6hrs
  (STG, Adult 2019)

Infective endocarditis 
- Empiric therapy (native valve) (Additional agent(s) required)
- Empiric therapy (prosthetic valve) (Additional agents required)
- Directed therapy (native valve) for streptococcal moderately susceptible (MIC: 0.12-0.5mg/l) (Additional agent required)

• IV: 1.5mg/kg, 12hrly; Treatment duration: 2 weeks
  (STG, Adult 2019)

- Directed therapy (native valve) for streptococcal moderately resistant (MIC: 0.5-4mg/l) Enterococci and Abiotrophia spp. (nutritionally variant streptococci) (Additional agent required)

• IV: 1.5mg/kg, 12hrly; Treatment duration: 4 weeks OR 6 weeks of therapy may be required in cases with a history of >3 months, or mitral or prosthetic valve involvement
  (STG, Adult 2019)

- Directed therapy (native valve) for streptococcal fully resistant (MIC>4mg/l) (Additional agent required)

• IV: 1.5mg/kg, 12hrly; Treatment duration: 6 weeks
  (STG, Adult 2019)

- Directed therapy (native valve) for enterococcal moderately resistant  (MIC: 0.5–4mg/l) Enterococci and Abiotrophia spp. (nutritionally variant streptococci) (Additional agents required)

• IV: 1mg/kg, 8hrly; Treatment duration: 2 weeks OR 6 weeks of therapy may be required in cases with a history of >3 months, or mitral or prosthetic valve involvement
  (STG, Adult 2019)

- Directed therapy (native valve) for staphylcoccal (cloxacillin/methicillin-sensitive), as an add-on, if required (Additional agent required)

• IV: 6mg/kg, dly for the first 3–5 days
  (STG, Adult 2019)

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Duration of therapy is usually a minimum of at least 6 weeks for directed therapy for prosthetic valve endocarditis. Seek expert opinion on antibiotic choice and the need for referral for repeat cardiac surgery early in the course of treatment

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Uncomplicated community acquired cystitis

• IM: 5mg/kg, as a single dose
  (STG, Adult 2019)

Uncomplicated cystitis

• IM: 160mg, as a single dose
  (STG, PHC 2020)

Listeria monocytogenes meningitis (Additional agent required)

• IV: 5mg/kg, dly; Treatment duration: 7 days (may be prolonged if response is poor) 
  (STG, Adult 2019)

Male urethritis syndrome in those with severe penicillin allergy (Additional agent required)
- Severe penicillin allergy
Vaginal discharge syndrome (Additional agent required)
- Persistent cervicitis confirmed on speculum examination, pending results in those with severe penicillin allergy

• IM: 6mg/kg, as a single dose
  (STG, Adult 2019)

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South African registered indications and dosages

Systemic infections, e.g. peritonitis
Bone and soft-tissue infections, e.g. osteomyelitis, wound and soft-tissue infections
Infected burns
Respiratory tract infections, e.g pneumonia
Biliary tract infections 

• IV/IM: 3-5mg/kg/day, in 3 divided (equal) doses, 8hrly; Treatment duration: 7-10 days

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Dose and dosage intervals should be determined for each patient with serum peak and trough levels. Where plasma levels cannot be determined, the above dosage range is recommended

Peak plasma concentrations should not exceed 10-12μg/ml and trough plasma concentrations should not exceed 2μg/ml

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Acute and chronic urinary tract infections
Systemic infections, e.g. meningitis
Eye infections
- Moderate severity

• IV/IM: 2mg/kg/day, as a single dose OR in 3 divided (equal) doses, 8hrly; Treatment duration: 7-10 days

- Severe infections

• IV/IM: 3mg/kg/day, as a single dose OR in 3 divided (equal) doses, 8hrly; Treatment duration: 7-10 days

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Alkalis should be coadministered to raise the urinary pH above 7

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Life-threatening infections
- Sepsis

• IV/IM: Max: 5mg/kg/day, as a single dose OR in 3 divided (equal) doses, 8hrly; Reduce to 3mg/kg/day, as a single dose OR in 3 divided (equal) doses as soon as clinically indicated; Treatment duration: 7-10 days

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Indications and dosages registered in other jurisdictions

Urinary tract infections (upper and lower) 
Respiratory tract infections, including bronchopneumonia 
Intra-abdominal infections
Central nervous system infections 
Bacteraemia 
Septicaemia 
Abscesses 
Subacute bacterial endocarditis 
Gynaecological infections
Accidental and operative trauma 
Burn, wound and serious skin infections or lesions 

• IV/IM: 3-5mg/kg/day, as a single dose OR in 2 divided doses

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The dose should be adjusted according to clinical response and serum concentration levels. Dose calculations should be based on ideal body weight. A dosing frequency of more than twice daily may be adopted for some specific pathogens or some sites of infection as recommended in national and local guidance

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Once daily dosing is not recommended in cases of endocarditis, depending on the responsible pathogens. National and local guidance on treatment with gentamicin and serum level monitoring in endocarditis should be followed

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In patients with normal renal function, 160mg once daily may be used for the treatment of urinary tract infections

Forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African Standard Treatment Guideline indications and dosages
• South African registered indications and dosagesIndications and dosages registered in other jurisdictions

Infections caused by: Listeria monocytogenes, Staphylococci, Staphylococcus aureus (MSSA), Campylobacter coli, Campylobacter jejuni, Citrobacter spp. Citrobacter koseri, Enterobacter spp., Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Francisella tularensis, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus spp. (indole positive and indole negative), Proteus vulgaris, Salmonella enterica subsp. enterica, Serratia marcescens, Yersinia enterolitica, Yersinia pseudotuberculosis, Y. pestis, Pseudomonas aeruginosa, Providencia spp., Bartonella spp.

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guideline indications and dosages

Infective endocarditis (Additional agent required)
- Empiric therapy if culture is not yet available or remains negative

• IV: 3mg/kg, dly; Treatment duration: 2 weeks
  (STG, Paed. 2017)

Respiratory distress in the newborn (Additional agent required)
- Suspected infection, e.g., bronchopneumonia

First week of life: <32 weeks gestation

• IV: 5mg/kg/36hrs; Treatment duration: 5-7 days; Review after 72hrs if infection confirmed or very strongly suspected continue for 10 days

First week of life: ≥32 weeks gestation

• IV: 5mg/kg/24hrs; Treatment duration: 5-7 days; Review after 72hrs if infection confirmed or very strongly suspected continue for 10 days

After first week of life: All gestations

• IV: 5mg/kg/24hrs; Review after 72hrs if infection confirmed or very strongly suspected; Treatment duration: 10 days
  (STG, Paed 2017)

Septicaemia of the newborn (Additional agent required)
- Empiric therapy (first line)

First week of life: <32 weeks gestation

• IV: 5mg/kg/36hrs; Treatment duration: 10 days

First week of life: ≥32 weeks gestation

• IV: 5mg/kg/24hrs; Treatment duration: 10 days
  (STG, Paed. 2017)

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Reconsider choice of antibiotic when the results of blood and CSF cultures become available or the child does not improve within 72-96hrs

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Severe acute malnutrition (SAM) (Additional agent required)
- For infection, commencing on the first day of admission

• IV: 6mg/kg, dly; Treatment duration: 7 days 
  (STG, Paed. 2017)

Acute diarrhoea (Additional agent required)
- Severe malnutrition
- Very young infants <2 months

• IV: 6mg/kg, dly; Treatment duration: 5 days
  (STG, Paed. 2017)

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Confirm normal renal function before admin. of second dose

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Acute liver failure

• Oral (inj): 12.5mg/kg/dose, 6hrly; Treatment duration: 5 days
  (STG, Paed. 2017)

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IV formulation should be given orally for this indication

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Acute osteomyelitis/ osteitis (Additional agent required)
- Penetrating foot bone injury

• IV: 6mg/kg, dly; Treatment duration: 4-6 weeks, inclusive of transition to oral therapy once there is sustained clinical improvement, resolution of fever and CRP<30mg/l
  (STG, Paed. 2017)

Necrotising enterocolitis (Additional agent required)
- Empiric therapy

• IV: 5mg/kg, dly; Treatment duration: 7 days
  (STG, Paed. 2017)

Hypoxia/ischaemia of the newborn with infection (Additional agent required)
- If infection is suspected or confirmed
Perinatal hypoxia/ hypoxic-ischaemic encephalopathy (Additional agent required)
- If infection is suspected or confirmed

• IV: 5mg/kg, dly
  (STG, Paed. 2017)

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Where available, gentamicin doses should be adjusted on the basis of therapeutic drug levels. Trough levels (taken immediately prior to next dose), target plasma level<1mg/l. Peak levels (measured 1 hour after commencement of IV infusion or IM/IV bolus dose), target plasma level>8mg/l

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South African registered indications and dosages

Acute and chronic urinary tract infections
Severe systemic infections, e.g. sepsis, peritonitis, meningitis
Bone and soft tissue infections, e.g. acute osteomyelitis, wound and soft tissue infections
Infected burns
Respiratory tract infections
Eye infections

 Younger than 1 week (neonates and infants)

• IV: 6mg/kg/day, in 2 divided (equal) doses, 12hrly; Treatment duration: 7-10 days

Older than 1 week (infants)

• IV: 3-6mg/kg/day, in 2 divided (equal) doses, 12hrly; Treatment duration: 7-10 days

OR 

• IV: 3-6mg/kg/day, as a single dose OR in 3 divided (equal) doses, 8hrly; Treatment duration: 7-10 days

Children

• IV: 3-6mg/kg/day, in 3 divided doses, 8hrly; Treatment duration: 7-10 days

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The dosing interval of gentamicin in paediatric patients may vary from every 4-24hrs depending on the medical condition of the patient (cystic fibrosis, burns, renal dysfunction). Serum levels of gentamicin must be monitored

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Indications and dosages registered in other jurisdictions

Urinary tract infections (upper and lower) 
Respiratory tract infections, including bronchopneumonia 
Intra-abdominal infections
Central nervous system infections 
Bacteraemia 
Septicaemia 
Abscesses 
Subacute bacterial endocarditis 
Gynaecological infections
Accidental and operative trauma 
Burn, wound and serious skin infections or lesions 
Neonatal infections 

Between 0-4 weeks (neonates and pre-term infants)

• IV/IM: 4-7mg/kg/day

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Due to the longer half-life, newborns are given the required daily dose in one single dose

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Serum concentration monitoring of gentamicin is recommended in newborns

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Between 4 weeks-1 year

• IV/IM: 4.5-7.5mg/kg/day, as a single dose OR in 2 divided doses

1 year and older

• IV/IM: 3-6mg/kg/day, as a single dose OR in 2 divided doses

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Once daily dosing should only be administered through the IV route

Pregnancy

• Caution
• There are no proven cases of intrauterine damage caused by gentamicin. However, in common with most drugs known to cross the placenta, usage in pregnancy should only be considered in life threatening situations where expected benefits outweigh possible risks. Gentamicin should only be used in pregnancy if considered essential by the physician

Breastfeeding

• Caution
• In the absence of gastro-intestinal inflammation, the amount of gentamicin ingested from breastmilk is unlikely to result in significant blood levels in breastfed infants

Renal Impairment

• Caution; dose adjustment recommended
  Loading dose: No adjustment necessary
  Maintenance dose: Dose adjustments should be based on current calculated CrCl (eGFR) and trough plasma aminoglycoside concentration (See additional prescribing points)

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  There is some evidence that elderly patients may be more susceptible to aminoglycoside toxicity whether secondary to previous auditory/vestibular impairment or borderline renal dysfunction. Accordingly, therapy should be closely monitored by frequent determination of gentamicin serum levels, assessment of renal function and ototoxicity

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Hallucinations
• Confusion
• Central neuropathy
  - Convulsions
  - Lethargy
  - Encephalopathy
• Peripheral neuropathy

Gastrointestinal Disorders

• Stomatitis
• Antibiotic-associated colitis
• Nausea and vomiting

Hepatobiliary Disorders

• Abnormal hepatic function
• Increased transaminases

Genitourinary Disorders

• Acute renal failure
• Fanconi-like syndrome (prolonged, high-dose treatment)
• Nephrotoxicity

Endocrine and Metabolic Disorders

• Hypomagnesaemia (on prolonged therapy)

Skin and Subcutaneous Tissue Disorders

• Rash
• Purpura
• Urticaria
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Anaphylaxis/anaphylactic reaction (including anaphylactic shock)
• Anaemia
• Blood dycrasias

Sensory Disorders

• Vestibular damage
• Hearing loss (transitory as well as irreversible)
• Deafness

• Ototoxic agents
• Potent diuretics
• Etacrynic acid
• Furosemide
• Nephrotoxic agents
• Amphotericin B
• Cisplatin
• Ciclosporin
• Cephalosporins
• Cephaloridine
• Curare-type muscle relaxants
• Indomethacin
• Oral anticoagulants
• Bisphosphonates
• Botulinum toxin
• Neostigmine
• Pyridostigmine

• Renal function
• Hearing tests (including monitoring of the vestibule and cochlea)
• Plasma gentamicin levels (typically obtained before and after the third dose in conventional dosing)

Specific cases may require

• Urinalysis
• Urine output
• Blood urea nitrogen (BUN)

Injection 20mg/2ml, Injection 40mg/ml, Injection 80mg/2ml, Injection 80mg/2ml - EML (Primary)

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Administration directions

• The recommended dose and precautions for IM and IV administration are identical
• IV administration: Gentamicin should be injected directly into a vein or into the drip set tubing over no less than 3 minutes
• Infusion: Infusion should be done over 20-30mins and in no greater volume of fluid than 100ml. Longer infusion times of up to 60mins may be used, in particular for a once daily dosing regimen
• Once daily dosing should be administered through the IV route

Incompatibilities

• In general, gentamicin injection should not be mixed
• In particular, the following are incompatible in mixed solution with gentamicin injection:
  - Penicillins
  - Cephalosporins
  - Erythromycin
  - Heparins
  - Sodium bicarbonate
• Dilution in the body will obviate the danger of physical and chemical incompatibility and enable gentamicin to be given concurrently with the agents listed above either as a bolus injection into the drip tubing, with adequate flushing, or at separate sites. In the case of carbenicillin, administration should only be at a separate site
• Carbon dioxide may be liberated on addition of the two solutions. Normally this will dissolve in the solution but under some circumstances, small bubbles may form

Renal impairment

• Its important to:
  - Avoid adopting 'fixed percentage' dosage reduction practice
  - Avoid adopting 'estimated' low dosages (based on another antimicrobial therapy)
  -Maintenance dose adjustments should be according to eGFR-TDM (therapeutic drug monitoring)

Ototoxicity and nephrotoxicity

• Ototoxicity has been reported following the use of aminoglycosides, including gentamicin. Symptoms include loss of balance and hearing loss, which may be irreversible
• Important risk factors include renal impairment, high doses, prolonged duration of treatment and age (neonates/infants and possibly the elderly). Due to the potential for ototoxicity and nephrotoxicity, monitoring of vestibule, cochlea and renal function is recommended before, during and shortly after treatment
• Serum levels are determined so as to avoid peak concentrations above 10mg/L and troughs above 1mg/L when administering gentamicin once daily and 2mg/L when administering gentamicin twice daily
• As there is some evidence that risk of both ototoxicity and nephrotoxicity is related to the level of total exposure, duration of therapy should be the shortest possible compatible with clinical recovery. In some patients with impaired renal function there has been a transient rise in blood-urea-nitrogen which has usually reverted to normal during or following cessation of therapy. It is important to adjust the frequency of dosage according to the degree of renal function
• There have been observed cases of an increased risk of ototoxicity with aminoglycosides administered to patients with mitochondrial mutations, particularly the m.1555A>G mutation, including cases where the patient's aminoglycoside serum levels were within the recommended range. Some cases were associated with a maternal history of deafness and/or mitochondrial mutation. Mitochondrial mutations are rare, and the penetrance of this observed effect is unknown

Gentamicin is a mixture of antibiotic substances produced by the growth of micromonospora purpurea. It is bactericidal with greater antibacterial activity than streptomycin, neomycin or kanamycin. Gentamicin exerts a number of effects on cells of susceptible bacteria. It affects the integrity of the plasma membrane and the metabolism of RNA, but its most important effects is inhibition of protein synthesis at the level of the 30s ribosomal subunit.

Spectrum of activity: Listeria monocytogenes, Staphylococci, Staphylococcus aureus (MSSA), Campylobacter coli, Campylobacter jejuni, Citrobacter spp., Citrobacter koseri, Enterobacter spp., Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Francisella tularensis, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus spp. (indole positive and indole negative), Proteus vulgaris, Salmonella enterica subsp. enterica, Serratia marcescens, Yersinia enterolitica, Yersinia pseudotuberculosis, Y. pestis, Pseudomonas aeruginosa, Providencia spp., Bartonella spp.

Injection (per ml) 10mg

• Garamycin (Schering-Plough)
• Gentamycin Fresenius (Fresenius Kabi)
• Micro-Gentamicin (Micro Healthcare)
• Pharma Q Gentamicin (Pharma Q)

Injection (per 2ml) 20mg

• Gentamycin Fresenius ampoule (Fresenius)
• Micro-Gentamicin (Micro Healthcare)
• Pharma-Q Gentamycin 20 (Pharma-Q)

Injection (per 2ml) 20mg

• Gentamycin Fresenius vial (Fresenius Kabi)

Injection (per ml) 40mg

• Aspen Gentamicin (Aspen)
• Garamycin (Schering-Plough)
• Gentamycin Fresenius ampoule (Fresenius Kabi)
• Micro-Gentamicin (Micro Healthcare)
• Mylan Gentamicin (Mylan)
• Pharma Q Gentamicin (Pharma Q)
• Sandoz Gentamicin (Sandoz)

Injection (per 2ml) 80mg

• Aspen Gentamicin (Litha Pharma)
• Gentamycin Fresenius (Fresenius Kabi)
• Micro-Gentamicin (Micro Healthcare)
• Pharma-Q Gentamicin (Pharma Q)

Injection (per 50ml) 80mg

• Sabax Gentamix (Adcock-Ingram) originator

Also available in the following forms: Bone cement, implant and beads & chains.