Gentamicin

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Chapter: Essential pharmacology : Aminoglycoside Antibiotics

It was obtained from Micromonospora purpurea in 1964; has become the most commonly used aminoglycoside for acute infections. The properties of gentamicin including plasma t½ of 2–4 hours after i.m. injection are the same as described above for streptomycin, but there are following differences:


GENTAMICIN

 

It was obtained from Micromonospora purpurea in 1964; has become the most commonly used aminoglycoside for acute infections. The properties of gentamicin including plasma t½ of 2–4 hours after i.m. injection are the same as described above for streptomycin, but there are following differences:

 

a)    It is more potent (MIC for most organisms is 4–8 times lower.)

 

b)    It has a broader spectrum of action: effective against Ps. aeruginosa and most strains of Proteus, E. coli, Klebsiella, Enterobacter, Serratia.

 

c)   It is ineffective against M. tuberculosis, Strep. pyogenes and Strep. pneumoniae, but inhibits many Strep. faecalis and some Staph. aureus.


d)     It is relatively more nephrotoxic.

 

Dose: The dose of gentamicin must be precisely calculated according to body weight and level of renal function. For an average adult with normal renal function (creatinine clearance > 100 ml/ min) 3–5 mg/kg/day i.m. either as single dose or divided in three 8 hourly doses is recommended.

 

Because of concentration dependent bactericidal and post-antibiotic effect of aminoglycosides, it was theorised that high plasma concentration attained after the single daily dose will be more effective. It is also likely to be less ototoxic because plasma concentrations will remain subthreshold for ototoxicity for a longer period each day allowing washout of the drug from the endolymph. The efficacy and safety of many aminoglycosides by the conventional (thrice daily) and once daily regimens has been compared in several studies. The data indicate similar efficacy and a trend towards less toxicity. As such, many hospitals now practice once daily dosing of aminoglycosides. It is more convenient as well.

 

The daily dose of gentamicin (and other aminoglycosides) should be reduced in patients with impaired renal function according to measured creatinine clearance. A general guideline is:

 


 

GARAMYCIN, GENTASPORIN, GENTICYN 20, 60, 80, 240 mg per vial inj; also 0.3% eye/ear drops, 0.1% skin cream.

 

Uses

 

Gentamicin is the cheapest (other than streptomycin) and the first line aminoglycoside antibiotic. However, because of low therapeutic index, its use should be restricted to serious gram-negative bacillary infections.

 

1. Gentamicin is very valuable for preventing and treating respiratory infections in critically ill patients; in those with impaired host defence (receiving anticancer drugs or highdose corticosteroids; AIDS; neutropenic), patients in resuscitation wards, with tracheostomy or on respirators; postoperative pneumonias; patients with implants and in intensive care units. It is often combined with a penicillin/cephalosporin or another antibiotic in these situations. However, resistant strains have emerged in many hospitals and nosocomial infections are less amenable to gentamicin now. Another aminoglycoside (tobramycin, amikacin, sisomicin, netilmicin) is then selected on the basis of the local sensitivity pattern. Aminoglycosides should not be used to treat community acquired pneumonias caused by gram-positive cocci and anaerobes.

 

Gentamicin is often added to the peritoneal dialysate to prevent or treat peritonitis.

 

2. Pseudomonas, Proteus or Klebsiella infections: burns, urinary tract infection, pneumonia, lung abscesses, osteomyelitis, middle ear infection, septicaemia, etc. are an important area of use of gentamicin. It may be combined with piperacillin or a third generation cephalosporin for serious infections. Topical use on infected burns and in conjunctivitis is permissible.

 

3. Meningitis caused by gram-negative bacilli: in addition to the usual i.m. dose, 4 mg intrathecal injection may be given daily, but benefits are uncertain. Because this is a serious condition, drug combinations including an aminoglycoside are often used. The third generation cephalosporins alone or with an aminoglycoside are favoured for this purpose.

 

4. SABE: gentamicin is more commonly used in place of streptomycin to accompany penicillin.

 

Gentamicin-PMMA (polymethyl methacrylate) chains (SEPTOPAL) is a special drug delivery system for use in osteomyelitis. It consists of small acrylic beads each impregnated with 7.5 mg gentamicin sulph. and threaded over surgical grade wire. Implanted in the bone cavity after thorough removal of sequestra and left in place for 10 days, it has improved cure rates.

 

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