Gentamicin

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Contents 1 Introduction 2 Indications 3 Dosage 4 Dosage-adjustment-in-renal-failure 5 Pharmacokinetics 6 Antimicrobial-activity 7 Adverse-effects 8 Drug-interactions 9 Laboratory 10 Mechanism-of-action 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Introduction

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

• Tradename: Garamycin.

Indications

• treatment of serious infections of bone/joint, soft tissue urinary tract, respiratory tract, intra-abdominal, bacteremia
• mainly indicated for serious infections caused by gram negative bacteria, especially Pseudomonas aeruginosa or Enterobacteriaceae
• used in combination with penicillin or cephalosporin for systemic enterococcal & streptococcal infections, including bacteremia & endocarditis
• aminoglycosides have no anaerobic activity

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

*  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
• Francisella tularensis
• Brucella species

• * Less active than tobramycin against Pseudomonas aeruginosa.

Adverse-effects

• common (> 10%)

• nephrotoxicity
• neurotoxicity
• ototoxicity

• vestibular > auditory [7]
• tinnitus
• vestibular toxicity may occur up to 2-3 months after stopping drug

• diminished creatinine clearance

• less common (1-10%)

• pruritis, 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)

• occular 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
  
• drug interaction(s) of antibiotics with warfarin

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

Mechanism-of-action

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

More General Terms

• aminoglycoside antibiotic

Additional Terms

• gentamicin in serum/plasma

Internet Database

PubChem: 72396
PubChem: 86483
PubChem: 3467
PubChem: 582362
PubChem: 37569
PubChem: 72397
PubChem: 86474
PubChem: 3034288
PubChem: 72395
PubChem: 588785

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 163
3. Sanford Guide to antimicrobial therapy 1997, 2001
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
6. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
7. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001

gentamicin (Garamycin, Genoptic)