Temocillin is a b-lactamase resistant penicillin [1-2] belonging to the class of carboxypenicillins primarily used for the treatment of multiresistant Gram-negative bacteria.
Temocillin 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 b-lactamase or AmpC b-lactamase .
Respiratory tract infections
38 episodes of Burkholderia cepacia infections in 23 patients were treated with temocillin and reported favorable outcome .
Clinical cure was achieved in 21 of 22 patients with acute peritonitis . Of 25 patients who had had biliary tract surgery and developed infections, 23 were cured, one developed a staphylococcal pneumonia, and one had defective wound healing . In a group of 22 patients with culture-positive septicemia, clinical cure was reported in 15, improvement in four, and failure in three . Among patients with acute gonorrhoea, temocillin given as a single intramuscular dose of 0.5 or 1 g resulted microbiologic cure in 248 of 267 patients (93%) .
Temocillin is administered parenterally
at doses of 1 or 2 g intramuscularly or intravenously twice or three times daily
or up to
Newborn infants and children
No ofﬁcial information is available. In one trial of the use of temocillin for the treatment of pyelonephritis in children, a dose of 25 mg/kg. twice-daily was given to 22 children aged three months to 13 years .
The manufacturer recommends no dose
reduction in patients with a creatinine clearance >30 ml/min. In patients with
The undesirable effects of temocillin are those characteristic of b-lactam antibiotics. 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 . As with any other penicillin, convulsions can occur if very high doses are given.
The animal toxicology studies showed a high degree of safety . Since temocillin is rather highly protein bound, displacement of bilirubin from cord serum was studied . Displacement was found only at concentrations far higher than those achieved clinically.
Since biliary concentrations of temocillin are very high, a hamster model of antibiotic-associated colitis was used to test the potential of temocillin to cause colitis . It was reported that temocillin did not cause antibiotic-associated colitis, whereas that was the case when cefoxitin or clindamycin was administered as positive controls.
The volume of distribution increases disproportionately with increasing temocillin doses, as does extrarenal clearance (from 6 ml/min at 0.5 g to 14 ml/min at 2 g). These ﬁndings could be due to a high and dose-dependent binding of temocillin to plasma proteins. In a study the protein binding was 88% , 83%, and 63% at concentrations of 50, 100, and 200 mg/ml . Similar results were reported by other authors [18-19].
Temocillin is not orally available.
The penetration of temocillin into various tissues has been assayed and the tissue concentrations varied between 9% and 39% of concurrent serum concentrations [20-21]. In peripheral lymph, the maximal concentrations and areas under the serum concentration curve were reported to be approximately 50% of those in serum . In bile, very high temocillin concentrations have been reported by several groups [23-25]. The cerebrospinal ﬂuid penetration of temocillin was was found to be highly variable .
Temocillin is primarily excreted by renal mechanisms. Urinary excretion accounted for 38% of the total dose given after 6 hours in six healthy volunteers, and total biliary excretion was recorded as 2.2% of the given dose (0.5 or 1 g) . Seventy-one percent of the administered dose is excreted by 12 hours . The mean concentration of temocillin in gallbladder bile was 314.7 (±273.2) mg/ml after the 0.5-g dose and 474.5 (±307.3) mg/ml after the 1-g dose. Thus, temocillin is highly concentrated in the normal gallbladder in man .
Mechanism of Action
Similar to other b-lactam antibiotics, temocillin acts by inhibiting penicillin-binding proteins (PBPs). A higher afﬁnity of PBP 3 and 1 for temocillin than for ticarcillin and cefoxitin was observed. The afﬁnity for PBP 2 of temocillin was low.
The antibacterial spectrum of temocillin is shown in Table 1 . Similar results were reported by other authors [2, 18, 29-30]. Temocillin lacks activity against Gram-positive organisms and against Pseudomonas spp. Against B. cepacia, temocillin displays relatively high activity, with 82% of strains from patients with cystic ﬁbrosis being susceptible if a breakpoint for susceptibility of ≤16 mg/ml was used . Temocillin has a high activity against Neisseria gonorrhoeae, Branhamella catarrhalis, and Haemophilus inﬂuenzae irrespective of pencillinase production [32-33].
Emerging resistance and cross-resistance
Temocillin has a high degree of stability to b-lactamases, including extended-spectrum b-lactamases [3, 28, 34]. Temocillin has therefore kept most of its activity over the years .
Table 1. In vitro activity of temocillin.
CAS number: 66148-78-5 EINECS: 266-184-1
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13. Boon R.J. et al., "Studies with temocillin in a hamster model of antibiotic-associated colitis". Antimicrob. Agents Chemother. 27 (6), 980–1, (1985).
14. Cockburn A., Mellows G., Jackson D., White D.J. "Temocillin. Summary of safety studies". Drugs 29, (Suppl 5): 103, (1985).
15. Davies B.E. "Displacement of bilirubin from cord serum by sulphadimethoxine, amocycillin, clavulanic acid, temocillin and cloxacillin". Br. J. Clin. Pharmacol. 20: 345, (1985).
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19. Overbosch D., van Gulpen C., Mattie H. "Renal clearance of temocillin in volunteers". Drugs 5, (Suppl 5): 128, (1985).
20. Cowan W., Baird A., Sleigh J.D. et al. "Lung tissue penetration of temocillin". Drugs 29, (Suppl 5): 151, (1985).
21. Gould J.G., Meikle G., Cooper D.L., Horton R. "Temocillin concentrations in human tissues". Drugs 29, (Suppl 5): 167, (1985).
22. Bergan T., Olszewski W.L., Engeset A. "Temocillin penetration of peripheral lymph". Drugs 29, (Suppl 5): 114, (1985).
23. Maudgal D.P., Lanzini A., Northﬁeld T.C. et al. "Quantiﬁcation of temocillin biliary excretion and gallbladder bile concentration". Drugs 29, (Suppl 5): 146, (1985).
24. Poston G.J., Greengrass A., Moryson C.J. "Biliary concentrations of temocillin". Drugs 29, (Suppl 5): 140, (1985).
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28. Jules K., Neu H.C. "Antibacterial activity and b-lactamase stability of temocillin". Antimicrob. Agents Chemother. 22: 453, (1982).
29. Greenwood D., Cowlishaw A., Eley A. "In vitro activity of temocillin, a new b-lactamase-stable penicillin active against enterobacteria". Antimicrob. Agents Chemother. 22: 198, (1982).
30. Verbist L. "In vitro activity of temocillin (BRL 17421). A novel beta-lactamase-stable penicillin". Antimicrob. Agents Chemother. 22: 157, (1982).
31. Bonacorsi S., Fitoussi F., Lhopital S., Bingen E. "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: 213, (1999).
32. Piot P., van Dyck E. "In vitro activity of BRL 17421 against Haemophilus inﬂuenzae, Neisseria gonorrhoeae, and Branhamella catarrhalis. Antimicrob. Agents Chemother. 21: 166, (1982).
33. Jephcott A.E., Egglestone S.I. "In vitro activity of temocillin against Neisseria gonorrhroea, including penicillinase-producing strains". Drugs 5, (Suppl 5): 18, (1985).
34. Rodriguez-Villalobos H., Malaviolle V., Frankard J. et al. "In vitro activity of temocillin against extended spectrum b-lactamase-producing Escherichia coli". J. Antimicrob. Chemother. 57: 771, (2006).
35. Livermore D.M., Tulkens
P.M. "Temocillin revived". J. Antimcrob. Chemother. 63: 243, (2009).
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