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gentamicin (Garamycin, Genoptic, G-Mycin)

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 - blepharoconjunctivitis - meibomitis - dacryocystitis - otitis externa [3,4,5,8] Contraindications: - anaerobic infections - 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. 1) 0.3% ointment every 3-4 hours or BID-QID 2) 0.3% drops every 1-6 hours Therapeutic range: - therapeutic drug monitoring required a) Peak: 4-8 ug/mL. b) 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: 1) distributes rapidly to extracellular fluid 2) volume of distribution = 0.25 L/kg ideal body weight 3) eliminated by kidney 4) elimination 1/2life 2-3 hours, increasing with renal insufficiency (20-60 hours ESRD) 5) concentrated in urine several times that of blood 6) levels in CSF 25% that of serum 7) penetration in lung tissue is low 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: 1) common (> 10%) a) 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] b) neurotoxicity c) ototoxicity - vestibular > auditory [7] - tinnitus - vestibular toxicity may occur up to 2-3 months after stopping drug 2) less common (1-10%) - pruritus, redness, rash, swelling 3) 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 4) ophthalmic (Garamycin, Genoptic) - ocular irritation Drug interactions: 1) neuromuscular blocking agents: aminoglycosides prolong paralysis 2) aminoglycosides are inactivated with mixed in same IV bag or tubing as penicillins 3) furosemide by continuous infusion may increase ototoxicity Laboratory: 1) specimen: a) serum, plasma (EDTA) b) for patients on penicillin, freeze if not analyzed within 4-6 hours c) peak levels obtained 1 hour after IV/IM dose 2) methods: RIA, MB, HPLC, GLC, REA, EIA, FPIA 3) 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 4) labs with Loincs - gentamicin in body fluid - gentamicin in CSF - gentamicin in serum/plasma - gentamicin in serum/plasma peak - gentamicin in serum/plasma trough - gentamicin in serum/plasma random Mechanism of action: 1) bactericidal activity, concentration-dependent 2) ionic cell wall interactions & ribosomal binding

Interactions

drug interactions drug adverse effects of aminoglycosides

Related

gentamicin in serum/plasma

Specific

Gentamicin Ophthalmic (Qualamycin)

General

aminoglycoside antibiotic

Properties

MISC-INFO: elimination route KIDNEY 1/2life 2-3 HOURS therapeutic-range 5-10 UG/ML <2 UG/ML toxic-range >12 NG/ML >4 NG/ML protein-binding <5% elimination by hemodialysis + peritoneal dialysis +/- pregnancy-category D C safety in lactation ?

Database Correlations

PUBCHEM correlations

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
  8. Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
  9. 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: 19322184
  10. 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: 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: 19207080

Component-of

betamethasone/clotrimazole/gentamicin betamethasone/gentamicin betamethasone/gentamicin/isopropanol clotrimazole/gentamicin/mometasone cortisol/gentamicin/miconazole gentamicin/prednisolone