Disease relevance of carbenicillin

• Carbenicillin-associated hypokalemic alkalosis [1].
• Eight strains of three genera (Proteus, Escherichia, Pseudomonas) isolated at Boston City Hospital or Institut Pasteur, Paris, showed antagonism of carbenicillin or ampicillin by cephaloridine, cloxacillin, or 6-aminopenicillanic acid [2].
• Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis [3].
• Carbenicillin-induced haemorrhagic cystitis [4].
• Carbenicillin and pseudomembranous enterocolitis [5].

High impact information on carbenicillin

• From these organisms, the good inducers of a beta-lactamase that acted on benzylpenicillin did not induce enzymes that inactivated carbenicillin [2].
• 52% of pseudomonas isolates were carbenicillin-resistant, and 31% gentamicin-resistant [6].
• Carbenicillin was used for a longer period among cases and patients with predictive nose cultures than among patients without aspergillosis [7].
• Conditions optimal for the transformation of Pseudomonas putida and E. coli with a drug-resistance factor (RP 1) DNA, which specifies resistance to carbenicillin, tetracycline, kanamycin, and neomycin, are described [8].
• In a randomized control trial, five treatment regimens were compared: no antibiotics or granulocytes (controls), gentamicin (5 mg/kg/day), carbenicillin (500 mg/kg/day), gentamicin and carbenicillin (same dosages), and daily granulocyte transfusion (minimum 5 x 10(9) cells/day) plus gentamicin (5 mg/kg/day) [9].

Chemical compound and disease context of carbenicillin

• For Pseudomonas infections, ticarcillin, carbenicillin, the ureidopenicillins, and the aminoglycosides are indicated [10].
• Cure was achieved with piperacillin in patients infected with carbenicillin-resistant P aeruginosa and Klebsiella organisms [11].
• Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae [12].
• A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias [13].
• Piperacillin sodium, a semisynthetic penicillin that inhibits many Klebsiella and Pseudomonas aeruginosa organisms resistant to carbenicillin, was used to treat 41 episodes of infection in 35 patients [11].

Biological context of carbenicillin

• Kinetics of mezlocillin and carbenicillin [14].
• Ticarcillin vs carbenicillin: clinical pharmacokinetics [15].
• Protein binding in 100 percent human serum was 50 percent and 65 percent for carbenicillin and ticarcillin, respectively [15].
• Pseudomonas aeruginosa strain isolated in France that carries a plasmid determining carbenicillin resistance [16].
• Carbenicillin was stable to hydrolysis (kcat, less than 0.1/min) and induced weakly at low concentrations [17].

Anatomical context of carbenicillin

• We found that beta-lactamase fusion proteins carrying a eukaryotic signal peptide at its N-terminus were able to direct their export into the periplasm in E. coli to confer survival upon challenge with carbenicillin [18].
• One hundred seven patients were treated with either piperacillin (56) or carbenicillin (51) in an open randomized trial of hospitalized patients with pleuropulmonary (40), urinary tract (26), gynecologic (21), skin and soft-tissue (eight), joint (five), bone (three), and miscellaneous other infections (four) [19].
• This killing was shown to be unaffected by treatment with carbenicillin, an inhibitor of bacterial cell wall biosynthesis and, indirectly, replication [20].
• The intrinsic-resistance phenotype becomes further enhanced in "intrinsically carbenicillin-resistant" isolates, which were often assumed to produce outer membranes of even lower permeability [21].
• In the first study, corneas still contained Pseudomonas after 4 days of continual topical therapy with either tobramycin 400 mg/ml, amikacin 250 mg/ml, ticarcillin 400 mg/ml, or carbenicillin 400 mg/ml [22].

Associations of carbenicillin with other chemical compounds

• Isolated case reports of in vivo inactivation of gentamicin by either carbenicillin or ticarcillin exist [23].
• Following an intravenous infusion of 4 gm in 5 min to 8 normal men there was an average serum level of 294 microgram/ml for mezlocillin and 365 microgram/ml for carbenicillin [14].
• In a pharmacolinetic study on a new semisynthetic penicillin, alpha-sulfobenzylpenicillin, sulbenicillin, serum level, serum half-life, apparent distribution volume, renal clearance, urinary excretion, and metabolism were determined after a 4-gm intravenous dose and compared to that of carbenicillin in 5 patients with normal renal function [24].
• Analysis of the percentage of functional enzymes revealed that the hydrolysis of ampicillin was more affected than hydrolysis of carbenicillin by amino acid substitutions at positions 162 to 164 and 165 to 167 [25].
• Immediate radioimmunoassay demonstrated that carbenicillin reduced in vivo serum half-lives of gentamicin and tobramycin by 40% (P < 0.05) [26].

Gene context of carbenicillin

• Both TEM-1 and TEM-E2 beta-lactamases were encoded by a transferable 103 kb plasmid; these two enzymes also had similar molecular weights, were inhibited by clavulanic acid, and hydrolysed ampicillin, carbenicillin and cephaloridine at similar rates [27].
• Two beta-lactamase-producing strains of Pseudomonas aeruginosa remained resistant to carbenicillin in the presence of clavulanic acid [28].
• Unlike cefamandole, cefoperazone, carbenicillin, and piperacillin, cefoxitin was not hydrolyzed by the common plasmid beta-lactamases, TEM-1, TEM-2, OXA-2, and SHV-1 [29].
• A fragment of Tn1331 including tnpR, aac, aadA, and a bla gene which encodes lower levels of resistance to ampicillin and carbenicillin as compared to those mediated by the TEM beta-lactamase was sequenced [30].
• pWW53-4 is a cointegrate between RP4 and the catabolic plasmid pWW53 from Pseudomonas putida MT53, which contains 36 kbp of pWW53 DNA inserted close to the oriV gene of RP4; it encodes the ability to grow on toluene and the xylenes, characteristic of pWW53, as well as resistance to tetracycline, kanamycin and carbenicillin, characteristic of RP4 [31].

Analytical, diagnostic and therapeutic context of carbenicillin

• Of special interest was the finding of liver function test abnormalities in 17/78 (21%) carbenicillin recipients (evaluative and nonevaluative cases) [19].
• Following an intravenous infusion of 2 gm in 5 min, there was a lower average serum level for ticarcillin (218 mug/ml) than for carbenicillin (301 mug/ml), but after 2 hr the differences were not significant [15].
• Moxalactam was the least active of the new beta-lactams, with activity equivalent to that of carbenicillin; each had a minimum inhibitory concentration for 90% of isolates of 64 micrograms/ml and a minimum bactericidal concentration for 90% of isolates of 128 microgram/ml [32].
• Piperacillin, ticarcillin, and carbenicillin were administered intravenously to 10 healthy volunteers in a three-way, crossover study [33].
• The rates at which the esters were hydrolyzed in vitro to carbenicillin by animal and human tissues were compared and the carbenicillin serum levels arising after oral administration of the esters were measured in squirrel monkeys and human volunteer subjects [34].

References