Temocillin

{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Watchedfields = changed | verifiedrevid = 447429921 | IUPAC_name = (2''S'',5''R'',6''S'')-6-[(Carboxy-3-thienylacetyl)amino]- 6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid, | image = Temocillin.svg | image_class = skin-invert-image

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| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 66148-78-5 | ATC_prefix = J01 | ATC_suffix = CA17 | PubChem = 171758 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 150149 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 03QB156W6I | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D06064 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 51817

| C=16 | H=18 | N=2 | O=7 | S=2 | smiles = O=C(O)[C@@H]2N3C(=O)[C@@](OC)(NC(=O)C(c1ccsc1)C(=O)O)[C@H]3SC2(C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = BVCKFLJARNKCSS-DWPRYXJFSA-N }}

'''Temocillin''' is a β-lactamase-resistant penicillin<ref name="pmid17550891">{{cite journal | vauthors = Andrews JM, Jevons G, Walker R, Ashby J, Fraise AP | title = Temocillin susceptibility by BSAC methodology | journal = The Journal of Antimicrobial Chemotherapy | volume = 60 | issue = 1 | pages = 185–187 | date = July 2007 | pmid = 17550891 | doi = 10.1093/jac/dkm179 | doi-access = free }}</ref><ref name="pmid7181470">{{cite journal | vauthors = Van Landuyt HW, Pyckavet M, Lambert A, Boelaert J | title = In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic | journal = Antimicrobial Agents and Chemotherapy | volume = 22 | issue = 4 | pages = 535–540 | date = October 1982 | pmid = 7181470 | pmc = 183789 | doi = 10.1128/aac.22.4.535 }}</ref> introduced by Beecham, marketed by Eumedica Pharmaceuticals as Negaban. It is used primarily for the treatment of multiple drug-resistant, Gram-negative bacteria. <br> It is actually a 6-methoxy Ticarcillin; it is also a carboxypenicillin.<ref name="pmid6348653">{{cite journal | vauthors = Chanal M, Sirot J, Cluzel M, Joly B, Glanddier Y | title = [In vitro study of the bacteriostatic and bactericidal activity of temocillin (BRL 17421)] | language = fr | journal = Pathologie-Biologie | volume = 31 | issue = 6 | pages = 467–470 | date = June 1983 | pmid = 6348653 }}</ref>

==Pharmacology== Temocillin is a β-lactamase-resistant penicillin. It is not active against Gram-positive bacteria or bacteria with altered penicillin-binding proteins.{{cn|date=March 2023}}

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''.<ref>{{cite journal | vauthors = Lupia T, De Benedetto I, Stroffolini G, Di Bella S, Mornese Pinna S, Zerbato V, Rizzello B, Bosio R, Shbaklo N, Corcione S, De Rosa FG | title = Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic | journal = Antibiotics | volume = 11 | issue = 4 | pages = 493 | date = April 2022 | pmid = 35453244 | pmc = 9032032 | doi = 10.3390/antibiotics11040493 | doi-access = free }}</ref>

Its primary use is against Enterobacteriaceae, and in particular against strains producing extended-spectrum β-lactamase or AmpC β-lactamase.<ref name="pmid16531428">{{cite journal | vauthors = Livermore DM, Hope R, Fagan EJ, Warner M, Woodford N, Potz N | title = Activity of temocillin against prevalent ESBL- and AmpC-producing Enterobacteriaceae from south-east England | journal = The Journal of Antimicrobial Chemotherapy | volume = 57 | issue = 5 | pages = 1012–1014 | date = May 2006 | pmid = 16531428 | doi = 10.1093/jac/dkl043 | doi-access = free }}</ref> Temocillin is also usually active against KPC-producing ''K. pneumoniae'', and synergistic activity has been demonstrated when administered alongside fosfomycin.<ref>{{Cite journal | vauthors = Costantino V, Principe L, Mehat J, Busetti M, Piccirilli A, Perilli M, Luzzati R, Zerbato V, Meliadò A, La Ragione R, Di Bella S |date=2024-06-04 |title=Synergistic Activity of Temocillin and Fosfomycin Combination against KPC-Producing Klebsiella pneumoniae Clinical Isolates |journal=Antibiotics |language=en |volume=13 |issue=6 |pages=526 |doi=10.3390/antibiotics13060526 |doi-access=free |pmid=38927192 |issn=2079-6382|pmc=11200827 }}</ref>

Temocillin has also been reported in the management of urinary tract, bloodstream and intra-abdominal infections, with a favorable safety and ecological profile. It has additionally been used in outpatient parenteral antimicrobial therapy (OPAT), including administration by the subcutaneous route.<ref>{{Cite journal | vauthors = Cosimi L, Zerbato V, Grasselli Kmet N, Oliva A, Cogliati Dezza F, Geremia N, Cattaneo D, Nadrah K, Pirs M, Saletinger R, Nunnari A, Mearelli F, Di Girolamo FG, Avena G, Russo R, Fabiani C, Venturini S, Principe L, Nicolò GM, Di Bella S |date=2025-08-26 |title=Temocillin: A Narrative Review of Its Clinical Reappraisal |journal=Antibiotics |language=en |volume=14 |issue=9 |pages=859 |doi=10.3390/antibiotics14090859 |doi-access=free |issn=2079-6382|pmc=12466873 }}</ref>

==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<ref name="pmid18070831">{{cite journal | vauthors = De Jongh R, Hens R, Basma V, Mouton JW, Tulkens PM, Carryn S | title = 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 | journal = The Journal of Antimicrobial Chemotherapy | volume = 61 | issue = 2 | pages = 382–8 | date = February 2008 | pmid = 18070831 | doi = 10.1093/jac/dkm467 | url = | doi-access = free | hdl = 2078.1/36857 | hdl-access = free }}</ref><ref name="pmid25433006">{{cite journal | vauthors = Laterre PF, Wittebole X, Van de Velde S, Muller AE, Mouton JW, Carryn S, Tulkens PM, Dugernier T | title = Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration | journal = The Journal of Antimicrobial Chemotherapy | volume = 70 | issue = 3 | pages = 891–8 | date = March 2015 | pmid = 25433006 | doi = 10.1093/jac/dku465 | url = | doi-access = free }}</ref> 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.{{cn|date=March 2023}} Subcutaneous administration of temocillin, although off-label, has been investigated in selected patients, showing lower peak concentrations but sustained plasma exposure above pharmacokinetic/pharmacodynamic targets over the dosing interval, with limited clinical data suggesting feasibility and tolerability in outpatient parenteral antimicrobial therapy (OPAT) settings.<ref>{{cite journal | vauthors = Di Bella S, Geremia N, Pea F, Zeitlinger M, Sanson G, Monticelli J, Bergmann F, Motet C, Lambotte-Buffet C, Zerbato V, Gatti M | title = When and How to Use Subcutaneous Antibiotics | journal = Clinical Infectious Diseases | date = January 2026 | pmid = 41556663 | doi = 10.1093/cid/ciaf691 | doi-access = free }}</ref>

Temocillin may be given to patients with impaired renal function after the dose has been adapted: {| class="wikitable" |- ! 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.<ref>{{cite journal | vauthors = Boon RJ, Beale AS | title = Studies with temocillin in a hamster model of antibiotic-associated colitis | journal = Antimicrobial Agents and Chemotherapy | volume = 27 | issue = 6 | pages = 980–981 | date = June 1985 | pmid = 3875312 | pmc = 180203 | doi = 10.1128/aac.27.6.980 }}</ref> As with any other penicillin, convulsions can occur if very high doses are given.{{citation needed|date=December 2018}}

==Synthesis== thumb|center|700px|Temocillin synthesis:<ref>{{Cite journal | doi = 10.1039/P19790002455| title = Transformations using benzyl 6-isocyanopenicillanate| journal = Journal of the Chemical Society, Perkin Transactions 1| pages = 2455| year = 1979| vauthors = Bentley PH, Clayton JP, Boles MO, Girven RJ }}</ref>

== References == {{reflist}}

== Further reading == * {{cite journal | vauthors = Livermore DM, Tulkens PM | title = Temocillin revived | journal = The Journal of Antimicrobial Chemotherapy | volume = 63 | issue = 2 | pages = 243–245 | date = February 2009 | pmid = 19095679 | doi = 10.1093/jac/dkn511 | doi-access = free | hdl = 2078.1/35864 | hdl-access = free }}

Category:Penicillins Category:Thiophenes