Temocillin

Temocillin is a β-lactamase resistant penicillin marketed by Eumedica Pharmaceuticals as Negaban® primarily for the treatment of multiresistant Gram negative bacteria.

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Pharmacology

Temocillin is a β-lactamase resistant penicillin. It is not active against Gram positive bacteria or bacteria with altered penicillin-binding proteins.

It is normally active against Moraxella catarrhalis, Brucella abortus, Burkholderia cepacia, Citrobacter species, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Pasteurella multocida, Proteus mirabilis, Salmonella typhimurium and Yersinia enterocolitica. It is also active against some Enterobacter species, Morganella morganii, and Serratia species. Temocillin has no useful activity against Gram positive organisms, Acinetobacter species, or Pseudomonas aeruginosa.

Its primary use is against Enterobacteriaceae, and in particular against strains producing extended spectrum β-lactamase or AmpC β-lactamase (Livermore, 2006).

Dosage

The common dosage is 2g intravenously every 12 hours. There are good theoretical reasons for giving Temocillin as a continuous intravenous infusion in severe disease (De Jongh, 2007): a single loading dose of 2g is given intravenously followed by a 4g infusion over 24 hours. Temocillin for intravenous injection is diluted in 20ml of sterile water; it is diluted in less than 2.7ml of sterile water when being prepared for intramuscular injection; the continuous infusion is diluted in 48ml of sterile water for ease of administration (1ml per half hour). To reduce pain, the intramuscular injection may be made up using sterile 1% lignocaine instead of sterile water.

Temocillin may be given to patient with impaired renal function. No adjustment needs to be made to the dose in mild to moderate renal impairment (creatinine clearance greater than 30ml/min). The manufacturer does not recommend using reduced doses, instead they recommend increasing the duration between doses. In severe renal impairment when it is 10 to 30, the dose is 1g in 24 hours; when less than 10, the dose is 1g every 48 hours. Temocillin is cleared by haemodialysis, which means that in dialysis patients, the dose should be given after dialysis.

There is no licensed oral preparation of Temocillin.

Undesirable effects

The undesirable effects of Temocillin are those of any β-lactam antibiotic. In particular, Temocillin has been associated with angioedema and anaphylaxis in penicillin allergic patients. Animal studies have not shown any induction of Clostridium difficile infection (Boon, 1985). As with any other penicillin, convulsions can occur if very high doses are given.

References

• Eumedica. Eumedica Pharmaceuticals. Retrieved on November 20, 2005.
• Bonacorsi S et al (1999). "Comparative in vitro activities of meropenem, imipenem, temocillin, piperacillin, and ceftazidime in combination with tobramycin, rifampin, or ciprofloxacin against Burkholderia cepacia isolates from patients with cystic fibrosis". Antimicrob Agents Chemother 43 (2): 213–7.
• Boon RJ et al (1985). "Studies with temocillin in a hamster model of antibiotic-associated colitis". Antimicrob Agents Chemother 27 (6): 980–1.
• Livermore DM et al (2006) Activity of temocillin vs. prevalent ESBL- and AmpC-producing Enterobacteriaceae from SE England. J Antimicrob Chemother. 2006 May;57(5):1012-4
• De Jongh R et al (2007) Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. J Antimicrob Chemother. 2007