Temocillin

Temocillin
Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	J01CA17 (WHO) ;
Identifiers
	IUPAC name (2S,5R,6S)-6-[(Carboxy-3-thienylacetyl)amino]- 6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid,;
CAS Number	66148-78-5 ;
PubChem CID	171758;
ChemSpider	150149 ;
UNII	03QB156W6I;
KEGG	D06064 ;
ChEBI	CHEBI:51817 ;
CompTox Dashboard (EPA)	DTXSID201009398 ;
ECHA InfoCard	100.060.148
Chemical and physical data
Formula	C16H18N2O7S2
Molar mass	414.45 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(O)[C@@H]2N3C(=O)[C@@](OC)(NC(=O)C(c1ccsc1)C(=O)O)[C@H]3SC2(C)C;
	InChI InChI=1S/C16H18N2O7S2/c1-15(2)9(12(22)23)18-13(24)16(25-3,14(18)27-15)17-10(19)8(11(20)21)7-4-5-26-6-7/h4-6,8-9,14H,1-3H3,(H,17,19)(H,20,21)(H,22,23)/t8?,9-,14+,16-/m0/s1 ; Key:BVCKFLJARNKCSS-DWPRYXJFSA-N ;
	(verify)

Temocillin is a β-lactamase-resistant penicillin^[1]^[2] introduced by Beecham, marketed by Eumedica Pharmaceuticals as Negaban. It is used primarily for the treatment of multiple drug-resistant, Gram-negative bacteria.
It is actually a 6-methoxy Ticarcillin; it is also a carboxypenicillin.^[3]

Pharmacology

Temocillin is a β-lactamase-resistant penicillin. It is not active against Gram-positive bacteria or bacteria with altered penicillin-binding proteins.^{[citation needed]}

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 Acinetobacter species or Pseudomonas aeruginosa.^[4]

Its primary use is against Enterobacteriaceae, and in particular against strains producing extended-spectrum β-lactamase or AmpC β-lactamase.^[5] Temocillin is also usually active against KPC-producing K. pneumoniae, and synergistic activity has been demonstrated when administered alongside fosfomycin.^[6]

Dosage

The common dose is 2 g intravenously every 12 hours and the high dose, notably in critically ill patients, is 2g every 8 hours. Theoretical reasons exist for giving temocillin as a continuous intravenous infusion in severe disease^[7]^[8] a single loading dose of 2 g is given intravenously followed by a 4-g or 6-g infusion over 24 hours. According to the SPC, chemical and physical in-use stability has been demonstrated for 24 hours at 25 °C for the following solvents: water for injection, physiological saline (0.9% sodium chloride), dextrose 5%, sodium chloride compound (Ringer's solution), Hartmann solution (sodium lactate compound + Ringer's lactate solution). Temocillin for intravenous injection is diluted in 10 to 20 ml of sterile water; it is diluted in less than 2 ml of sterile water when being prepared for intramuscular injection; the continuous infusion is diluted in 48 ml of sterile water for ease of administration (2 ml per hour). To reduce pain, the intramuscular injection may be made up using sterile 1% lignocaine instead of sterile water.^{[citation needed]}

Temocillin may be given to patients with impaired renal function after the dose has been adapted:

Creatinine clearance (mL/min)	Dosage per administration	Interval between administrations
More than 60	2 g	12 h
60 to 30	1 g	12 h
30 to 10	1 g	24 h

In case of intermittent high-flux hemodialysis: 1 g (I.V. injection) per 24 h of inter-dialytic session, preferably at the end of the hemodialysis (1 g q24 h, 2 g q48 h, 3 g q72 h). In case of continuous peritoneal dialysis in ambulatory patients: 1 g every 24 hours.

No oral preparation of temocillin is licensed.

Adverse effects

The undesirable effects of temocillin are those of any β-lactam antibiotic. In particular, it has been associated with angioedema and anaphylaxis in penicillin-allergic patients. Animal studies have not shown any induction of Clostridioides difficile infection.^[9] As with any other penicillin, convulsions can occur if very high doses are given.^{[citation needed]}

Synthesis

References

^ Andrews JM, Jevons G, Walker R, Ashby J, Fraise AP (July 2007). "Temocillin susceptibility by BSAC methodology". The Journal of Antimicrobial Chemotherapy. 60 (1): 185–187. doi:10.1093/jac/dkm179. PMID 17550891.
^ Van Landuyt HW, Pyckavet M, Lambert A, Boelaert J (October 1982). "In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic". Antimicrobial Agents and Chemotherapy. 22 (4): 535–540. doi:10.1128/aac.22.4.535. PMC 183789. PMID 7181470.
^ Chanal M, Sirot J, Cluzel M, Joly B, Glanddier Y (June 1983). "[In vitro study of the bacteriostatic and bactericidal activity of temocillin (BRL 17421)]". Pathologie-Biologie (in French). 31 (6): 467–470. PMID 6348653.
^ Lupia T, De Benedetto I, Stroffolini G, Di Bella S, Mornese Pinna S, Zerbato V, et al. (April 2022). "Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic". Antibiotics. 11 (4): 493. doi:10.3390/antibiotics11040493. PMC 9032032. PMID 35453244.
^ Livermore DM, Hope R, Fagan EJ, Warner M, Woodford N, Potz N (May 2006). "Activity of temocillin against prevalent ESBL- and AmpC-producing Enterobacteriaceae from south-east England". The Journal of Antimicrobial Chemotherapy. 57 (5): 1012–1014. doi:10.1093/jac/dkl043. PMID 16531428.
^ Costantino V, Principe L, Mehat J, Busetti M, Piccirilli A, Perilli M, et al. (2024-06-04). "Synergistic Activity of Temocillin and Fosfomycin Combination against KPC-Producing Klebsiella pneumoniae Clinical Isolates". Antibiotics. 13 (6): 526. doi:10.3390/antibiotics13060526. ISSN 2079-6382. PMC 11200827. PMID 38927192.
^ De Jongh R, Hens R, Basma V, Mouton JW, Tulkens PM, Carryn S (February 2008). "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". The Journal of Antimicrobial Chemotherapy. 61 (2): 382–8. doi:10.1093/jac/dkm467. PMID 18070831.
^ Laterre PF, Wittebole X, Van de Velde S, Muller AE, Mouton JW, Carryn S, et al. (March 2015). "Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration". The Journal of Antimicrobial Chemotherapy. 70 (3): 891–8. doi:10.1093/jac/dku465. PMID 25433006.
^ Boon RJ, Beale AS (June 1985). "Studies with temocillin in a hamster model of antibiotic-associated colitis". Antimicrobial Agents and Chemotherapy. 27 (6): 980–981. doi:10.1128/aac.27.6.980. PMC 180203. PMID 3875312.
^ Bentley PH, Clayton JP, Boles MO, Girven RJ (1979). "Transformations using benzyl 6-isocyanopenicillanate". Journal of the Chemical Society, Perkin Transactions 1: 2455. doi:10.1039/P19790002455.