Mezlocillin

Description

Mezlocilin is an acylaminopenicillin, which has been shown to cause both immediate and delayed hypersensitivity in a nurse.

Originator

Baypen,Bayer,W. Germany,1977

Uses

Like azlocillin, mezlocillin is used for infections of the urinary tract, gynecological infections, intraabdominal infections, skin infections, and respiratory tract infections. Synonyms of this drug are baypen, mezlin, and optocillin.

Uses

Antibacterial.

Uses

Mezlocillin is a broad spectrum penicillin antibiotic.

Definition

ChEBI: A penicillin in which the substituent at position 6 of the penam ring is a (2R)-2-[3-(methanesulfonyl)-2-oxoimidazolidine-1-carboxamido]-2-phenylacetamido group.

Manufacturing Process

9.3 parts by weight of ampicillin were suspended in 80% strength aqueous tetrahydrofuran (140 parts by volume) and sufficient triethylamine (approximately 6.3 parts by volume) was added dropwise while stirring at 20°C, just to produce a clear solution and to give a pH value of between 7.5 and 8.2 (glass electrode). The mixture was cooled to 0°C and 5.1 parts by weight of 3-methylsulfonyl-imidazolidin-2-one-1-carbonyl chloride were added gradually in portions over the course of 30 minutes, while the mixture was stirred and kept at a pH value of between 7 and 8 by simultaneous addition of triethylamine.
The carbonyl chloride reactant was prepared by reacting 2-imidazolidone with methanesulfonyl chloride then that product with phosgene. The mixture was stirred for 10 minutes at 0°C and subsequently further stirred at room temperature until no further addition of triethylamine was necessary to maintain a pH value of 7 to 8. 150 parts by volume of water were added andthe tetrahydrofuran was largely removed in a rotary evaporator at room temperature.
The residual aqueous solution was extracted once by shaking with ethyl acetate, covered with 250 parts by volume of fresh ethyl acetate and acidified to pH 1.5 to 2.0 with dilute hydrochloric acid while being cooled with ice. The organic phase was separated off, washed twice with 50 parts by volume of water at a time and dried for 1 hour over anhydrous MgSO4 in a refrigerator. After filtration, about 45 parts by volume of a 1 molar solution of sodium 2- ethylhexanoate in ether containing methanol were added to the solution of the penicillin. The mixture was concentrated on a rotary evaporator until it had an oily consistency and was dissolved in a sufficient amount of methanol by vigorous shaking, and the solution was rapidly added dropwise, with vigorous stirring, to 500 parts by volume of ether which contained 10% of methanol.
The precipitate was allowed to settle for 30 minutes, the solution was decanted from the precipitate, and the latter was again suspended in ether, filtered off and washed with anhydrous ether. After drying over P2O5 in a vacuum desiccator, the sodium salt of the mezlocillin was obtained in the form of a white solid substance.

brand name

Multocillin (Bayer).

Therapeutic Function

Antibiotic

Antimicrobial activity

A semisynthetic acylureidopenicillin supplied as the sodium salt for parenteral administration.
Ampicillin-susceptible strains of H. influenzae and Neisseria spp. are very susceptible, but β-lactamase-producing organisms are usually resistant. It is less active than azlocillin and piperacillin against Ps. aeruginosa and has variable activity against B. fragilis, independent of β-lactamase production. It exhibits typical β-lactam synergy with aminoglycosides against Ps. aeruginosa and enterobacteria.
It attains peak concentrations of 250 mg/L after a 2 g intravenous infusion, with a plasma half-life of 55 min. Protein binding is 20–30%. It distributes into multiple tissues and human body fluids at therapeutically useful concentrations. Up to 60% of the dose is recoverable unchanged from the urine, with up to 2.5% excreted in the bile.
Toxicity and side effects are similar to those associated with carboxypenicillins. Its clinical use is for serious infections with susceptible organisms, including lower respiratory tract, intra-abdominal, urinary tract and gynecological infections. Commercial availability is quite limited.

General Description

Mezlocillin was synthesized by Bayer in 1974. The NH2 residue of ampicillin was acylated. Mezlocillin is a member of the so-called ureidopenicillins and shows two- to eightfold greater activity against Citrobacter, Enterobacter, Klebsiella, Escherichia coli, and Haemophilus influenzae than ampicillin, carbenicillin, or sulbenicillin. Its activity against gram-positive bacteria is almost the same as that of carbenicillin. Mezlocillin is used by intravenous administration for therapy of sepsis, meningitis, and respiratory tract, urinary tract, and abdominal infections.

Synthesis

Mezlocillin, (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(R)-2-[(3-methylsulfonyl)-2- oxoimidazolidin-1-carboxamido]-2-phenylacetamido]-4-thia-1-azabicyclo[3.2.0]-heptan-2- carboxylic acid (32.1.1.27), is synthesized by acylating ampicillin (32.1.1.16) with 3-chlorocarbonyl-1-methansulfonyl-2-imidazolidinone (32.1.1.26) in the presence of triethylamine. The necessary 3-chlorocarbonyl-1-methansulfonyl-2-imidazolidinone (32.1.1.26) is synthesized by sulfonating 2-imidazolidinone with methanesulfonyl chloride, which forms 1-methanesulfonyl-2-imidazolidinone (32.1.1.25) and its subsequent reaction with phosgene.