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Antimicrobial Agents and Chemotherapy Dec 1978Mezlocillin in doses of 1.0, 2.0, and 5.0 g and carbenicillin in doses of 2.0 g were given as bolus injections intravenously to 10 healthy volunteers. For mezlocillin,...
Mezlocillin in doses of 1.0, 2.0, and 5.0 g and carbenicillin in doses of 2.0 g were given as bolus injections intravenously to 10 healthy volunteers. For mezlocillin, dose-dependent pharmacokinetics was detected. This is reflected by a more than proportional rise in serum concentrations and a decreased total body clearance as doses were increased. Per dose unit, the areas under serum concentration curves to infinity were 33.5 mug.h/ml for the 1.0-g dose, 47.2 mug.h/ml for the 2.0-g dose, and 54.8 mug.h/ml for the 5.0-g dose. The body clearance fell from 31.2 liters/h with the 1.0-g dose to 17.0 liters/h with the 5.0-g dose. This can be explained mainly by a marked depression of nonrenal clearance, which fell from 12.2 to 3.8 liters/h, compared with a parallel change in renal clearance from 19.0 to 13.2 liters/h. Contributing to the non-linearity may be biotransformation, evacuation via bile, or another process. With dose increments, rising amounts are recovered unchanged in the urine-61% after a 1.0-g dose compared with 69% after a 5.0-g dose. This clearly defines metabolism as a major factor of elimination. Carbenicillin, for which the first-order, two-compartment open model was applicable here as in previous studies, had a longer serum half-life than did mezlocillin. For the 2.0-g doses, the former had a half-life of 1.4 h, compared with 0.8 h for the latter (calculated as if the two-compartment model were fully valid). The relative area under the curve (see above) was 76.1 mug.h/ml after the 2.0-g dose.
Topics: Adult; Drug Evaluation; Humans; Injections, Intravenous; Penicillins
PubMed: 742869
DOI: 10.1128/AAC.14.6.801 -
Antimicrobial Agents and Chemotherapy Jul 1985The activity of cefpimizole (formerly U-63196E) was compared with that of other broad-spectrum cephalosporins and penicillins. Overall, cefpimizole exhibited limited... (Comparative Study)
Comparative Study
The activity of cefpimizole (formerly U-63196E) was compared with that of other broad-spectrum cephalosporins and penicillins. Overall, cefpimizole exhibited limited activity against gram-positive cocci and members of the family Enterobacteriaceae as compared with the other cephalosporins tested. The activity of cefpimizole against Pseudomonas aeruginosa was similar to that of cefoperazone and mezlocillin (90% MIC, 32 micrograms/ml) but poorer than that of ceftazidime (90% MIC, 8 micrograms/ml). Cefpimizole appears to have no in vitro advantage over the cephalosporins with which it was compared.
Topics: Cephalosporins; Enterobacteriaceae; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa
PubMed: 3929676
DOI: 10.1128/AAC.28.1.133 -
Antimicrobial Agents and Chemotherapy Apr 1978The activities of azlocillin and mezlocillin were compared with those of carbenicillin, ticarcillin, and pirbenicillin against a wide range of gram-negative organisms.... (Comparative Study)
Comparative Study
The activities of azlocillin and mezlocillin were compared with those of carbenicillin, ticarcillin, and pirbenicillin against a wide range of gram-negative organisms. The two new drugs were considerably more active than carbenicillin against Klebsiella species and Escherichia coli. Carbenicillin was twice as active against Proteus mirabilis as mezlocillin and four times as active as azlocillin. Against Pseudomonas aeruginosa, azlocillin was eight times as active as carbenicillin. Azlocillin and mezlocillin were twice as active as carbenicillin against Bacteroides fragilis, and these drugs showed a high degree of activity against Haemophilus influenzae and Neisseria gonorrhoeae.
Topics: Bacteria; Bacteroides fragilis; Enterobacteriaceae; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Penicillins; Protein Binding
PubMed: 96726
DOI: 10.1128/AAC.13.4.559 -
Saudi Journal of Biological Sciences Nov 2019Antibiotic-resistant strains including extended-spectrum β-lactamase (ESBL) isolates are globally widespread in medical, food, and environmental sources. Some of these...
Antibiotic-resistant strains including extended-spectrum β-lactamase (ESBL) isolates are globally widespread in medical, food, and environmental sources. Some of these strains are considered the most pathogenic bacteria in humans. The present work examined the predominance of antibiotic resistance in strains in wound infections comparing with strains isolated from a raw milk as a potential source of those strains. The wound infections included abdomen, anus, arm, back, buttock, chest, foot, hand, head, leg, lung, mouth, neck, penis, thigh, toe, and vagina infections. In total, 161 and 153 isolates identified as were obtained from wound infections and raw milk, respectively. A Vitek 2 system innovated by bioMérieux, France was applied to perform the identification and susceptibility tests. The isolates that have ability to produce ESBL were detected by an ESBL panel and NO45 card (bioMérieux). Over half of the were from abdomen, back, and buttock wound infections. More than 50%of the isolates obtained from wound infections were resistant to cefazolin, ampicillin, cefuroxime, ciprofloxacin, mezlocillin, moxifloxacin, piperacillin, and tetracycline; 70% of the isolates from wound infections and 0% of the isolates from raw milk were isolates produced ESBL. The data showed that the strains resistance to multi-antibiotic and produced ESBL are more widespread among wound infections than in raw milk.
PubMed: 31762626
DOI: 10.1016/j.sjbs.2018.11.016 -
Antimicrobial Agents and Chemotherapy Aug 1980Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients.... (Clinical Trial)
Clinical Trial
Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients. Patients known to be colonized with an organism resistant to 100 micrograms of mezlocillin per mol were excluded. The initial 25 cases (23 patients) received intravenous mezlocillin, 260 mg per kg per day in six divided doses; the mean 1-h-postinfusion serum level was 69 micrograms/ml. Because of the low serum level, the next 25 cases (22 patients) received 450 mg/kg per day, also in six divided doses, resulting in a mean 1-h-postinfusion serum level of 161 micrograms/ml. Both dosage regimens provided similar efficacy. Combined results show that 11 of 21 microbiologically documented infections and 7 of 13 clinically documented infections improved. Instances of bacteremia (number of cases in parentheses) were caused by Pseudomonas aeruginosa (two), Staphylococcus epidermidis (two), Clostridia perfringens (one), and Bacillus species (one); only one case improved. A rise in granulocyte count to > 500/microliters, a serum bactericidal activity of greater than or equal to 1:8 against the infecting pathogen, or both were indicators of a good therapeutic response. Despite exclusion of patients known to be previously colonized with mezlocillin-resistant organisms, 7 of 23 pathogens required a minimal concentration of greater than or equal to 100 micrograms of mezlocillin per ml for inhibition. In addition, surveillance cultures from 18 cases showed resistant organisms colonizing the gingiva, rectum, or both. Side effects of mezlocillin were minimal and included pseudoproteinuria, asymptomatic transient rise in bilirubin, and easily reversible kypokalemia. Mezlocillin, a new semisynthetic penicillin with little toxicity, was found to be inadequate as a single-agent empiric antibiotic therapy for febrile, granulocytopenic cancer patients.
Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Female; Fever; Humans; Leukocyte Count; Male; Mezlocillin; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Penicillins
PubMed: 6449902
DOI: 10.1128/AAC.18.2.299 -
Antimicrobial Agents and Chemotherapy Jan 1984Most penicillin-resistant staphylococci release a considerable portion of their beta-lactamase into the surrounding medium. Accumulation of this exoenzyme in...
Most penicillin-resistant staphylococci release a considerable portion of their beta-lactamase into the surrounding medium. Accumulation of this exoenzyme in conventional susceptibility test systems may result in a rapid inactivation of hydrolyzable antibiotics. Since under in vivo conditions the concentration of extracellular beta-lactamase should depend on the site of infection, susceptibility of Staphylococcus aureus to mezlocillin, a broad-spectrum penicillin, was measured in an open test model which prevented build-up of exoenzyme. The staphylococcal cells were immobilized and incubated between two membrane filters, and the excreted beta-lactamase was washed out by a constant flow of broth containing the antibiotic. Two test strains which produced large amounts of extracellular beta-lactamase and which were found to be resistant in the broth dilution test proved to be susceptible to mezlocillin in the open test model. This indicates that resistance to mezlocillin as measured by the broth dilution method was mediated predominantly by the extracellular enzyme fraction. Experiments performed with small infective doses in a model of peritoneal infection in leukopenic mice suggest that mezlocillin exhibits a therapeutic effect against beta-lactamase-producing staphylococci under certain in vivo conditions in which build-up of extracellular beta-lactamase does not occur.
Topics: Animals; Male; Mezlocillin; Mice; Penicillin Resistance; Penicillinase; Staphylococcus aureus
PubMed: 6608314
DOI: 10.1128/AAC.25.1.125 -
Antimicrobial Agents and Chemotherapy Apr 1981The effects of combining the new broad-spectrum penicillins piperacillin and mezlocillin with cefoxitin, cefamandole, or cephalothin on the antibacterial activities of...
The effects of combining the new broad-spectrum penicillins piperacillin and mezlocillin with cefoxitin, cefamandole, or cephalothin on the antibacterial activities of these antibodies were determined in vitro against 50 to 109 bacterial strains and in six experimental infections in mice. Against strains of Escherichia coli, Klebsiella, Proteus mirabilis, Salmonella, Acinetobacter, Enterococcus, and Staphylococcus, the combinations exhibited synergistic, indifferent, or additive effects, but no antagonism. Against strains of four groups of organisms (Pseudomonas, Serratia, Enterobacter, and indole-positive Proteus), a high incidence of antagonism was observed, particularly with combinations containing cefoxitin (60 to 100%). The penicillins were antagonized by the cephalosporin antibiotics. In vitro effects were reflected in vivo. Mice infected with cultures associated with synergistic or additive in vitro effects were protected with lower doses of piperacillin when this antibiotic was administered with ineffective doses of cefoxitin than when piperacillin was used alone. Infections with cultures associated with in vitro antagonism required two- to eightfold higher doses of piperacillin and mezlocillin when these antibiotics were used in combination with the cephalosporins. The clinical implications of these effects should be considered.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cephalosporins; Drug Interactions; Male; Mezlocillin; Mice; Penicillins; Piperacillin; beta-Lactams
PubMed: 6454388
DOI: 10.1128/AAC.19.4.634 -
Infectious Diseases in Obstetrics and... 1993This study evaluated the blood and uterine tissue concentration of mezlocillin, a broadspectrum penicillin.
OBJECTIVE
This study evaluated the blood and uterine tissue concentration of mezlocillin, a broadspectrum penicillin.
METHODS
We adapted a liquid chromatographic method to measure mezlocillin in serum and tissue. Mezlocillin reference standard was diluted in water, chromatographed on a reversed phase C18 column eluted at 1.5 ml/min with acetonitrile and phosphate buffer (1:3 v:v), and detected spectrophotometrically at 210 nm. Mezlocillin was administered to 14 premenopausal women scheduled to undergo vaginal hysterectomy. Each patient received a 4 g IV infusion of the drug 30 to 60 min prior to surgery. During surgery, tissue was removed from the uterine cervix and blood was obtained for assay of mezlocillin content.
RESULTS
Chromatography of the mezlocillin standard furnished a discrete peak with a retention time of 2.4 min. The sensitivity of the assay was 0.1 microg/ml with a linear response up to 100 microg/ml. The correlation coefficient for the standard curve was 0.9997. When reference standard was diluted in pooled human serum, the assay was complicated by interfering compounds. These were removed by ether extraction. The sensitivity of the assay performed in serum was 3 microg/ml. Serum samples contained from 81.2 to 358 microg of mezlocillin/ml with an average serum concentration of 207.5 microg/ml. When serum containing a known amount of mezlocillin was homogenized for a period of time similar to that required to homogenize tissue samples, a deteatable loss of drug was observed and was applied as a correction factor to the measured tisulevels. After correction, the average tissue level was 117.2 microg/ml and ranged from 27% to 98% of the serum levels.
CONCLUSIONS
The serum concentration of mezlocillin after IV infusion of 4 g was greater than that required to inhibit the majority of the most significant organisms responsible for post-hysterectomy sepsis. Although tissue levels appeared to be consistently lower than serum levels, they could be expected to provide an inhibitory effect against many of the bacterial strains that contaminate the surgical site.
PubMed: 18476212
DOI: 10.1155/S1064744993000171 -
Antimicrobial Agents and Chemotherapy Mar 1982The dose dependence of mezlocillin pharmacokinetics was examined in relation to renal function after intravenous doses of 1 and 5 g in 16 subjects with various degrees...
The dose dependence of mezlocillin pharmacokinetics was examined in relation to renal function after intravenous doses of 1 and 5 g in 16 subjects with various degrees of renal impairment. Dose and time-average model-independent physiological parameters were calculated from plasma concentration and urinary excretion data. Lack of superimposition of plasma concentration profiles occurred between dosage levels with a twofold exaggeration of areas under the curve produced between doses of 1 and 5 g. Decreased plasma clearances at the higher dose were caused partly by nonlinear renal clearance, but more markedly by dose dependence in nonrenal clearances. At each dosage level, these parameters were examined in relation to creatinine clearances. Plasma and renal clearances exhibited a typical linear correlation with creatinine clearance for each dose level. However, nonrenal clearances demonstrated a linear relationship with creatinine clearance at the 1-g dose, but apparent saturation of this pathway produced lower and relatively constant nonrenal clearance values at the 5-g dose. Mezlocillin pharmacokinetics are thus influenced by both dose and renal function over the dosage range of 1 to 5 g. Saturation in renal clearance and probably in biliary clearance explains the unusual disposition characteristics of mezlocillin observed in this and previously reported studies.
Topics: Adult; Aged; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Kidney Diseases; Kinetics; Male; Mezlocillin; Middle Aged; Penicillins
PubMed: 6213190
DOI: 10.1128/AAC.21.3.428 -
Antimicrobial Agents and Chemotherapy Jan 1991A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic dose of either a cephalosporin or... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic dose of either a cephalosporin or mezlocillin. Stool samples were cultured for Clostridium difficile the day before the operation and later on postoperative days 4, 7, and 14. C. difficile was detected in 23.0% of patients who received a cephalosporin (cefoxitin, 8.3%; cefazolin, 14.3%; cefotetan, 20.0%; ceftriaxone, 25.0%; cefoperazone, 43.7%), in 3.3% of patients given mezlocillin, and in none of 15 control volunteers given no antimicrobial agent. No patient experienced diarrhea.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cephalosporins; Clostridioides difficile; Enterocolitis, Pseudomembranous; Female; Humans; Intestines; Male; Middle Aged; Premedication; Prospective Studies; Surgical Procedures, Operative
PubMed: 2014978
DOI: 10.1128/AAC.35.1.208