Clinical Pharmacology of Mezlocillin

Issell, Brian F.; Bodey, Gerald P.; Weaver, Susanne

doi:10.1128/aac.13.2.180

Cited by 28 publications

(15 citation statements)

References 15 publications

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“…The serum levels reached in the present study correspond to concentrations noted in previous studies (1,5,7,8). The relative volume of distribution, 14% of the body weight, was comparable to 15.2 and 14.4% reported previously.…”

Section: Discussion'supporting

confidence: 90%

“…In normal renal function, the terminal serum half-life after intravenous mezlocillin has been reported to be 1.0 h after 1.0 g (1), 0.8 h after 2.0 and 4.0 g (1, 8), 1.1 h after 3.0 g (5), and 1 and 1.2 h after 5.0 g (1, 7).…”

Section: Discussion'mentioning

confidence: 99%

“…Blood samples were withdrawn from a cubital vein (not same arm as used for injection) at 0, 0.5, 1, 2, 3. 5,6,8,12, and 24 h after medication. The zero-time sample was taken immediately after the injection was completed.…”

mentioning

confidence: 99%

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Mezlocillin pharmacokinetics in patients with normal and impaired renal functions

Bergan¹,

Brodwall²,

Wiik-Larsen³

1979

Antimicrob Agents Chemother

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The pharmacokinetics of intravenous bolus doses of 1.0 g of mezlocillin were studied in 13 persons with normal and reduced renal functions. In renal failure a moderate increase was observed for the terminal serum half-life (t2fl). This changed from a mean of 1.1 h at a glomerular filtration rate of 100 ml/min to 1.6 h at 10 ml/min. The difference was not statistically significant. The excretion of unchanged drug in urine during 24 h was reduced from a mean of 59.4% (range, 52 to 77) in subjects with glomerular filtration rate above 50 ml/min to 10% (range, 7.9 to 12.1) in two patients with glomerular filtration rate of 10 to 20 ml/ min. The volume of distribution during the ,B-phase, Vd, , was 14% of the body weight. Much of the antibiotic was metabolized, and this proportion increased upon reduction in renal function.Mezlocillin is one of the newer penicillins with broad-spectrum activity comprising multiresistant enterobacteria, anaerobes, and Pseudomonas aeruginosa (6). The pharnacokinetics have been studied in subjects with normal renal function (1,5,7,8).The present communication reports on pharmacokinetic changes with reduction in renal function.MATERIALS AND METHODS Antibiotic. Mezlocillin was received from Bayer Chemie AG, Leverkusen, West Germany. One dose of 1.0 g was given as a 10% aqueous solution by intravenous bolus (2-min) injection.Patients. Studied were 13 informed volunteer patients referred to the Medical Department B for assessment of renal function (Table 1). Other antibacterial drugs were not given concomitantly. The patients were supine during the study.Samples. Blood samples were withdrawn from a cubital vein (not same arm as used for injection) at 0, 0.5, 1, 2, 3. 5,6,8, 12, and 24 h after medication. The zero-time sample was taken immediately after the injection was completed. Urine was collected for the periods 0 to 3, 3 to 4, 4 to 8, 8 to 12, and 12 to 24 h postprandially. A permanent urethral catheter and bladder lavage ensured complete recovery of urine for each time interval. Urine volumes were measured, and 10-ml samples were taken from each portion. Serum was separated within 1.5 h. All samples were stored at -20°C to avoid inactivation before assay.Assay. The concentrations were determined by an agar diffusion technique, with well reservoirs filled with 0.5-ml samples and Escherichia coli as the test strain (3). Square plates (16 by 16 cm) with 16 holes and random distibution (Latin square) of standards and samples in triplicate were used. Incubation temperature was 37°C. The assay could measure down to 0.4 ug/ml. The experimental error was 3 to 7% of the observed levels.Calculations. For pharmacokinetic evaluations, curve fitting was done with the AUTOAN 2/NONLIN program of Wagner, Sedman, and Metzler (9). For patients 5, 7, and 12, the best-curve fit was achieved by the first-order, one-compartment open model, whereas the majority of the curve fitting was best with the first-order, two-compartment open model. The values obtained from the two-compartment program were the rate c...

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Section: Discussion'supporting

confidence: 90%

Section: Discussion'mentioning

confidence: 99%

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Mezlocillin pharmacokinetics in patients with normal and impaired renal functions

Bergan¹,

Brodwall²,

Wiik-Larsen³

1979

Antimicrob Agents Chemother

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“…While the ureidopenicillins reportedly are more active than carbenicillin and ampicillin against S. marcescens (7,10,21), this finding could not be supported in the present study. Cefoperazone was the least active third generation cephalosporin studied since it exhibited the highest mean MIC (25.09.ug/ml) and showed a striking inoculum effect on bacteriological activity.…”

Section: Discussioncontrasting

confidence: 97%

Comparative Activity of N‐Formimidoyl Thienamycin with Third Generation Cephalosporins and Ureido Penicillins against Multiple Resistant Serratia marcescens

Miller

LeFrock

Vercler

1981

Microbiology and Immunology

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Twenty multiple resistant clinical isolates were tested with N-formimidoyl thienamycin, moxalactam, cefotaxime, cefoperazone, and the three ureidopenicillins: azlocillin, mezlocillin, and piperacillin. A concentration of < 0.97 Itg/ml inhibited 100% of organisms for N:f-thienamycin and cefotaxime, 90% for moxalactam, and 60% for cefoperazone. An increase in inoculum from 10 3 to 10 6 cells reduced activity fourfold for 95% of isolates with cefoperazone, 70% with N-formimidoyl thienamycin, 65% for cefotaxime, but only 15% for moxalactam. For ureidopenicillins, 85% of strains tested had MIC's-c;, 15.6 Itg/m!. An inoculum effect was observed in only 35-50%. At 10 3 , the cidal concentration was the same or twofold greater than the inhibitory level for N:f-thienamycin and cephalosporins in 70% of strains tested and 65% for penicillins. With 10 6 , the 70% value remained for N:f-thienamycin but was reduced to 45% for cefotaxime and 25% for moxalactam; 85% demonstrated>eightfold differences with cefoperazone. Single step high-level resistance was observed to moxalactam (20%). Carbenicillin resistant strains were cross-resistant to the ureidopenicillins. N-fthienamycin and cefotaxime appeared comparable, although important differences between morphological alteration and metabolism may influence their therapeutic effectiveness.

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“…Pharmacological studies of mezlocillin (4,8), azlocillin (1), and piperacillin (S. J. Pancoast, E. Francke, and H. C. Neu, manuscript in preparation) have shown that these new agents produce serum and tissue levels similar to those achieved with carbenicillin and ticarcillin (7). To designate susceptible, intermediate, and resistant organisms, different parameters may be used.…”

Section: Resultsmentioning

confidence: 95%

Agar disk diffusion susceptibility characteristics of azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin

Phaneuf¹,

Neu²

1979

Antimicrob Agents Chemother

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The agar disk diffusion susceptibility of Enterobacteriaceae to mezlocillin and piperacillin was correlated with agar minimal inhibitory concentrations and compared with the susceptibility to carbenicilhin. The agar disk susceptibility of Pseudomonas aeruginosa to azlocillin, mezlocillin, and piperacilhin was correlated with agar minimal inhibitory concentrations and compared with the susceptibility to carbenicillin and ticarcillin. Criteria are offered for the zones of inhibition to provide information about resistant and susceptible isolates that correlate with known serum levels.A number of penicillins with extended antibacterial spectra have been developed in the past few years. A 100-,ug carbenicillin disk has been used to determine the susceptibility of Enterobacteriaceae and Pseudomonas species to carbenicillin and ticarcillin, the antibiotics currently available for general use in the United States. A 75-,tg ticarcillin disk has been evaluated, and zone sizes for resistance have been correlated with the miniimal inhibitory concentration (MIC)(9). Two ureido penicillins, mezlocillin and azlocillin, and a piperazine derivative of ampicillin have been shown by several groups to be more active in vitro than carbenicillin against many bacteria (2,3,5,12 Susceptibility tests. MICs were determined by the agar dilution method, utilizing a replicating device which delivered a drop to agar plates (11). More detailed descriptions of the method have been published (9). The standard inoculum used was 105 colonyforming units. The MICs and the disk diffusion tests were performed at the same time. Organisms were grown overnight in Mueller-Hinton broth and diluted to the proper inoculum in broth. The inoculum for the disk diffusion was adjusted to a 0.5 MacFarland opacity standard. Both agar dilution plates and disk diffusion plates (Muelier-Hinton agar, BBL) were incubated for 18 h at 35°C.The breakpoints used for determination of strains susceptible to carbenicillin were based on the NCCLS recommendations (6). P. aeruginosa were considered susceptible if the inhibition zone size was .-17 mm and resistant if the zone size was c14 mm. When testing Enterobacteriaceae the zone size for susceptibility was >23 mm and that for resistance was c17 mm. The carbenicillin MICs corresponding to these zone sizes were used as criteria to determine susceptibility and resistance with azlocillin, mezlocillin, piperacillin, and ticarcillin.The zone sizes were reported to the nearest 0.5 mm.

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Clinical Pharmacology of Mezlocillin

Cited by 28 publications

References 15 publications

Mezlocillin pharmacokinetics in patients with normal and impaired renal functions

Mezlocillin pharmacokinetics in patients with normal and impaired renal functions

Comparative Activity of N‐Formimidoyl Thienamycin with Third Generation Cephalosporins and Ureido Penicillins against Multiple Resistant Serratia marcescens

Agar disk diffusion susceptibility characteristics of azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin

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