Mezlocillin

Mezlocillin is a broad-spectrum penicillin antibiotic. It is active against both Gram-negative and some Gram-positive bacteria. Unlike most other extended spectrum penicillins, it is excreted by the liver, therefore it is useful for biliary tract infections, such as ascending cholangitis.

Mezlocillin

Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	B
Routes of administration	Intravenous, intramuscular
ATC code	J01CA10 (WHO)
Pharmacokinetic data
Protein binding	16–59%
Metabolism	Hepatic (20–30%)
Elimination half-life	1.3–4.4 hours
Excretion	Renal (50%) and biliary
Identifiers
IUPAC name (2S,5R,6R)-3,3-dimethyl-6-[[(2R)-2-[(3-methylsulfonyl- 2-oxo-imidazolidine-1-carbonyl)amino]-2-phenyl-acetyl] amino]-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2- carboxylic acid
CAS Number	51481-65-3^Y
PubChem CID	656511
DrugBank	DB00948^Y
ChemSpider	570894^Y
UNII	OH2O403D1G
KEGG	D05021^Y
ChEBI	CHEBI:6919^Y
ChEMBL	ChEMBL1731^Y
CompTox Dashboard (EPA)	DTXSID1023316
ECHA InfoCard	100.052.013
Chemical and physical data
Formula	C21H25N5O8S2
Molar mass	539.58 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O)[C@@H](c1ccccc1)NC(=O)N2C(=O)N(S(=O)(=O)C)CC2)[C@H]4SC3(C)C
InChI InChI=1S/C21H25N5O8S2/c1-21(2)14(18(29)30)26-16(28)13(17(26)35-21)22-15(27)12(11-7-5-4-6-8-11)23-19(31)24-9-10-25(20(24)32)36(3,33)34/h4-8,12-14,17H,9-10H2,1-3H3,(H,22,27)(H,23,31)(H,29,30)/t12-,13-,14+,17-/m1/s1^Y Key:YPBATNHYBCGSSN-VWPFQQQWSA-N^Y
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Mechanism of action

Like all other beta-lactam antibiotics, mezlocillin inhibits the third and last stage of bacterial cell wall synthesis by binding to penicillin binding proteins. This ultimately leads to cell lysis.

Susceptible organisms

Gram-negative

• Bacteroides spp., including B. fragilis
• Enterobacter spp.
• Escherichia coli
• Haemophilus influenzae
• Klebsiella species
• Morganella morganii
• Neisseria gonorrhoeae
• Proteus mirabilis
• Proteus vulgaris
• Providencia rettgeri
• Pseudomonas spp., including P. aeruginosa
• Serratia marcescens

Gram-positive

• Enterococcus faecalis
• Peptococcus spp.
• Peptostreptococcus spp.

Synthesis

Mezlocillin synthesis:[1][2]

Mezlocillin can be made in a variety of ways including reaction of ampicillin with chlorocarbamate 1 in the presence of triethylamine. Chlorocarbamate 1 itself is made from ethylenediamine by reaction with phosgene to form the cyclic urea followed by monoamide formation with methanesulfonyl chloride and then reaction of the other nitrogen atom with phosgene and trimethylsilylchloride.

The closely related analogue azlocillin is made in essentially the same manner as mezlocillin. but with omission of the methylation step.

References

1. W. Schroeck, H. R. Furtwaengier, H. B. Koenig, and K. G.Metzer, German Offen. 2,318,955 (1973); Chem. Abstr., 82,31313b (1975).
2. H. B. Koenig, K. G. Metzer, H. A. Offe, and W. Schroeck, Eur. J_. Med. Chem., 17, 59 (1982).

External links

• DDB 30377

• Duke
• Kristof R, Clusmann H, Koehler W, Fink K, Schramm J (1998). "Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange". J Neurol Neurosurg Psychiatry. 64 (3): 379–81. doi:10.1136/jnnp.64.3.379. PMC 2170014. PMID 9527154.
• McCormick P, Greenslade L, Kibbler C, Chin J, Burroughs A, McIntyre N (1997). "A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients". Hepatology. 25 (4): 833–6. doi:10.1002/hep.510250408. PMID 9096584.
• Rohde B, Werner U, Hickstein H, Ehmcke H, Drewelow B (1997). "Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure". Eur J Clin Pharmacol. 53 (2): 111–5. doi:10.1007/s002280050347. PMID 9403281.