Cefonicid

Description

Cefonicid has an unesterified D-mandelic acid moiety at C-7 and a methylsulfothiotetrazole group at C-3. The latter is related to the MTT moiety mentioned above under cefamandole nafate; however, the clotting problems and Antabuse-like side effects associated with MTT have not been reported with cefonicid. The extra acid group in the C-3 side chain leads to this molecule being sold as an injectable disodium salt. Pain and discomfort at IM sites is experienced by some patients, as is a burning sensation and phlebitis. Cefonicid has a longer half-life than the other members of its group but achieves this at the price of somewhat lower potency against Gram-positive bacteria and aerobes. The drug is somewhat unstable, needs to be protected from light and heat, and may yellow or darken. If modest, however, this does not necessarily mean that the potency has decreased significantly, but overt precipitation does. Kirby-Bauer disk testing may overestimate the sensitivity of β-lactamase–producing bacteria to this agent, so some extra caution in interpretation of laboratory results is required.

Uses

A semi-synthetic cephalosporin antibiotic related to Cefamandole. Antibacterial

Definition

ChEBI: A cephalosporin bearing {[1-(sulfomethyl)-1H-tetrazol-5-yl]sulfanyl}methyl and (R)-2-hydroxy-2-phenylacetamido groups at positions 3 and 7, respectively, of the cephem skeleton.

Antimicrobial activity

Activity against Gram-positive and Gram-negative organisms in vitro is depressed by the presence of 50% serum. It is highly bound to plasma protein (98%) and has an extended plasma half-life of 4.5–5 h. A 1 g intramuscular dose achieves a mean peak plasma concentration of around 83 mg/L. Following a 1 g intravenous bolus dose, mean peak plasma concentrations of 130–300 mg/L have been reported. In patients treated for community-acquired pneumonia, concentrations of 2–4 mg/L have been found in sputum.
It is predominantly excreted by renal secretion, 83–89% being recovered unchanged in the urine over 24 h. Plasma half-life is linearly related to creatinine clearance. As a result of its high protein binding it is not removed by hemodialysis.
It is generally well tolerated; pain on injection, rash and positive Coombs’ test are reported in some patients. It has been used to treat respiratory, soft tissue and urinary infections. Available in Italy.

Synthesis

Cefonicid, 7-D-mandelamido-3-[[(1-sulfomethyl]-1H-tetrazol-5-yl]thio] methyl]- 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.26), is structurally similar to cefamandole and differs in the presence of a sulfonic acid group in the methyl substituent of the tetrazol ring. It is synthesized by a method analogous to that of the synthesis of cefamandole.