gentamicin (Garamycin, Genoptic, G-Mycin)

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]

Introduction

antibiotic complex, gentamicins A, C1, C1a & C2.

Tradename: Garamycin.

Indications

adjunct treatment of serious bacterial infections
mainly indicated for serious infections caused by gram negative bacteria, especially Pseudomonas aeruginosa orEnterobacteriaceae
used in combination with penicillin or cephalosporin for systemic enterococcal & streptococcal infections, including bacteremia & endocarditis
- infectious arthritis, osteomyelitis
- skin or soft tissue infection
  - furunculosis, paronychia, folliculitis^[3]^[4]^[5]^[8]
  - ecthyma gangrenosum
  - bacterial infections associated with necrosis
  - bacterial infections associated with burns 3,4,5,8]
- urinary tract infections
- respiratory tract infections
  - pneumonia
- intra-abdominal infections
  - bacterial peritonitis
  - cholangitis
- bacteremia, sepsis
- plague
- bacterial meningitis^[3]^[4]^[5]^[8]
adjunct in empiric therapy for fever of unknown origin^[3]^[4]^[5]^[8]
adjunct in empiric therapy for febrile neutropenia^[3]^[4]^[5]^[8]
prophylaxis for perioperative infection^[10]
eye infections
otitis externa^[3]^[4]^[5]^[8]

Contraindications

anaerobic infections
- aminoglycosides have no anaerobic activity

pregnancy category = d

pregnancy category = c

safety in lactation = ?

Dosage

Adults: 1 mg/kg IV/IM every 8 hours.

Children: 2-2.5 mg/kg every 8 hours.

Alternative: 4.5-5.1 mg/kg IV QD.

Topical agent: Tradename: Garamycin.

0.1% cream/ointment TID/QID.

Ophthalmic agent: Tradenames: Garamycin, Genoptic.

0.3% ointment every 3-4 hours or BID-QID
0.3% drops every 1-6 hours

Therapeutic range:

therapeutic drug monitoring required
- Peak: 4-8 ug/mL.
- Trough: 1-2 ug/mL.

Dosage adjustment in renal failure

Table

creatinine clearance	8-12 hour dosing	24 hour dosing
> 70 mL/min	100%	100%
60-69 mL/min	91%	100%
50-59 mL/min	87%	100%
40-49 mL/min	80%	100%
30-39 mL/min	72%	92%
20-29 mL/min	59%	85%
10-19 mL/min	40%	64%

Post dialysis dose: 1 mg/kg IBW

Continuous arteriovenous hemofiltration: 30-70% every 12 hours

Pharmacokinetics

distributes rapidly to extracellular fluid
volume of distribution = 0.25 L/kg ideal body weight
eliminated by kidney
elimination 1/2life 2-3 hours, increasing with renal insufficiency (20-60 hours ESRD)
concentrated in urine several times that of blood
levels in CSF 25% that of serum
penetration in lung tissue is low

elimination via kidney

1/2life = 2-3 hours

protein binding = <5 %

elimination by hemodialysis = +

elimination by peritoneal dialysis = +/-

Antimicrobial activity

Gram positive

Enterococcus faecalis (synergy with penicillins)
Enterococcus faecium (synergy with penicillins)
Staphylococcus aureus (MSSA)
Staphylococcus epidermidis (+/-)

Gram negative

Neisseria gonorrhoeae
Moraxella catarrhalis
Haemophilus influenzae
Escherichia coli
Klebsiella species
Enterobacter species
Serratia marcescens
Proteus vulgaris
Pseudomonas aeruginosa*
Yersinia enterocolitica
Yerinia pseudotuberculosis
Francisella tularensis
Brucella species
Campylobacter^[10]
- Campulobacter fetus
Citrobacter^[10]

* Less active than tobramycin against Pseudomonas aeruginosa.

Adverse effects

common (> 10%)
- nephrotoxicity
  - diminished creatinine clearance
    - serum creatinine increases 5-7 days after starting gentamicin
  - hypokalemic metabolic alkalosis^[8]^[9]
  - presents as non-oliguric acute tubular necrosis
    - pigmented or brown granular casts & tubular epithelial cells in the urine sediment.
  - urine osmolality is ~300 mOsm/kg H2O
  - FENa is >1%
  - hypokalemia & hypomagnesemia also can occur due to due to K+ & Mg+2 wasting
  - once a day dosing may reduce nephrotoxicity
  - even low-dose aminoglycosides may be nephrotoxic^[4]
- neurotoxicity
- ototoxicity
  - vestibular > auditory^[7]
  - tinnitus
  - vestibular toxicity may occur up to 2-3 months after stopping drug
less common (1-10%)
- pruritus, redness, rash, swelling
uncommon (< 1%)
- difficulty breathing, drowsiness, weakness, headache, tremors, muscle cramps, pseudotumor cerebri, anorexia, nausea/vomiting, weight loss, increased salivation, enterocolitis, granulocytopenia & agranulocytosis, thrombocytopenia, photosensitivity, erythema, paresthesia
ophthalmic (Garamycin, Genoptic)
- ocular irritation

drug adverse effects of aminoglycosides

Drug interactions

neuromuscular blocking agents: aminoglycosides prolong paralysis
aminoglycosides are inactivated with mixed in same IV bag or tubing as penicillins
furosemide by continuous infusion may increase ototoxicity

Laboratory

specimen:
- serum, plasma (EDTA)
- for patients on penicillin, freeze if not analyzed within 4-6 hours
- peak levels obtained 1 hour after IV/IM dose
methods: RIA, MB, HPLC, GLC, REA, EIA, FPIA
interferences:
- MB: coadministration of other antibiotics; penicillins & cephalosporins may be inactivated with commercially available beta lactamase to minimize this interference; heparin may form an inactivating complex with gentamicin
labs with Loincs
- gentamicin in body fluid
  - gentamicin in CSF
  - gentamicin in serum/plasma

Mechanism of action

bactericidal activity, concentration-dependent
ionic cell wall interactions & ribosomal binding

More general terms

aminoglycoside antibiotic

More specific terms

Gentamicin Ophthalmic (Qualamycin)

Additional terms

gentamicin in serum/plasma

Component of

References

↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 163
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 Sanford Guide to antimicrobial therapy 1997, 2001
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 Kaiser Permanente Northern California Regional Drug Formulary, 1998
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
↑ ^7.0 ^7.1 UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
↑ ^8.0 ^8.1 ^8.2 ^8.3 ^8.4 ^8.5 ^8.6 Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
↑ ^9.0 ^9.1 Zietse R, Zoutendijk R, Hoorn EJ. Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol. 2009 Apr;5(4):193-202. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19322184
↑ ^10.0 ^10.1 ^10.2 ^10.3 Cosgrove SE et al. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis 2009 Mar 15; 48:713. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19207079
Bayer AS and Murray BE Initial low-dose aminoglycosides in Staphylococcus aureus bacteremia: Good science, urban legend, or just plain toxic? Clin Infect Dis 2009 Mar 15; 48:722. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19207080

Database

[ref1-1] The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996

[ref2-2] Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 163

[ref3-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 Sanford Guide to antimicrobial therapy 1997, 2001

[ref4-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 Kaiser Permanente Northern California Regional Drug Formulary, 1998

[ref5-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998

[ref6-6] Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995

[ref7-7] 7.0 ^7.1 UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001

[ref8-8] 8.0 ^8.1 ^8.2 ^8.3 ^8.4 ^8.5 ^8.6 Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012

[ref9-9] 9.0 ^9.1 Zietse R, Zoutendijk R, Hoorn EJ. Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol. 2009 Apr;5(4):193-202. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19322184

[ref10-10] 10.0 ^10.1 ^10.2 ^10.3 Cosgrove SE et al. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis 2009 Mar 15; 48:713. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19207079
Bayer AS and Murray BE Initial low-dose aminoglycosides in Staphylococcus aureus bacteremia: Good science, urban legend, or just plain toxic? Clin Infect Dis 2009 Mar 15; 48:722. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19207080

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gentamicin (Garamycin, Genoptic, G-Mycin)

Contents

Introduction

Indications

Contraindications

Dosage

Dosage adjustment in renal failure

Pharmacokinetics

Antimicrobial activity

Adverse effects

Drug interactions

Laboratory

Mechanism of action

More general terms

More specific terms

Additional terms

Component of

References

Database

Navigation menu

gentamicin (Garamycin, Genoptic, G-Mycin)

Introduction

Indications

Contraindications

Dosage

Dosage adjustment in renal failure

Pharmacokinetics

Antimicrobial activity

Adverse effects

Drug interactions

Laboratory

Mechanism of action

More general terms

More specific terms

Additional terms

Component of

References

Database

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