The response of Pseudomonas aeruginosa to azlocillin, ticarcillin and cefsulodin.
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The morphological response of Pseudomonas aeruginosa to azlocillin, ticarcillin and cefsulodin was investigated by electron microscopy. Each antibiotic initially caused the formation of filaments. On further incubation in the presence of azlocillin, deposits of dense intracellular material were observed; these were absent from cells exposed to the other two antibiotics. On continued incubation, lysis of the filaments occurred, but the mode of lysis differed between the antibiotics: azlocillin caused breakage at a restricted number of sites in the cell wall, ticarcillin produced breakage at many points and cefsulodin caused extensive cell-wall damage. In addition, ticarcillin and cefsulodin appeared to cause more lysis and spheroplast formation than did azlocillin. The morphological changes correlated with turbidimetric measurements of bacterial response to the three antibiotics, which showed ticarcillin and cefsulodin to act more rapidly than azlocillin. (+info)
Cefsulodin sodium therapy in cystic fibrosis patients.
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Cefsulodin sodium is a narrow-spectrum cephalosporin with marked in vitro activity against clinical isolates of Pseudomonas aeruginosa. We have studied the antibiotic in a clinical trial in 10 patients admitted to the Pediatric Ward of the University of Virginia Medical Center with cystic fibrosis and recurrent acute lower respiratory tract infections with P. aeruginosa isolated from their sputa. The patients received 500 to 1,500 mg of cefsulodin every 6 hours by intravenous infusion for 10 to 22 days. Mean peak drug levels in plasma after 500, 1,000, and 1,500 mg were 46, 71, and 90 micrograms/ml, respectively, and the mean minimal inhibitory concentration of all organisms was 7.5 micrograms/ml. Detectable levels of cefsulodin in sputa were found in approximately half of the random samples and ranged from 2 to 5 micrograms/ml. The clinical response was satisfactory in nine (90%) of the patients. One patient gained weight and had improved pulmonary function tests but showed no reduction in sputum production and no improvement in arterial blood gas values. In pulmonary function tests, four of five patients tested showed an average 43% increase in forced vital capacity after initiation of therapy and five of five had an average 51% increase in forced expired volume in 1 s. No adverse effects were observed. (+info)
Resistance of Pseudomonas aeruginosa mutants with altered control of chromosomal beta-lactamase to piperacillin, ceftazidime, and cefsulodin.
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Examination of beta-lactam susceptibility of mutants altered in the control of chromosomal beta-lactamase of Pseudomonas aeruginosa supports the view that a constitutive level of beta-lactamase is not an adequate explanation for resistance to cefsulodin and ceftazidime but could be for resistance to piperacillin which has an efficiency of hydrolysis ca. 10 times higher than does cefsulodin or ceftazidime. (+info)
Synergistic activities of combinations of beta-lactams, fosfomycin, and tobramycin against Pseudomonas aeruginosa.
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The effects of antibiotic combinations against Pseudomonas aeruginosa infections frequently found in hospitalized patients were investigated. By means of an agar plate dilution checkerboard method, combinations of piperacillin-fosfomycin, cefoperazone-fosfomycin, and cefsulodin-fosfomycin were synergistic against 80.0, 85.0, and 82.6% of the strains tested. The mean fractional inhibitory concentration indices of piperacillin-fosfomycin, cefoperazone-fosfomycin, and cefsulodin-fosfomycin were 0.48, 0.42, and 0.46, respectively. The synergistic activities of these combinations were enhanced by the addition of a small amount of tobramycin, 0.25 micrograms/ml. (+info)
Effect of inoculum size and beta-lactamase production on in vitro activity of new cephalosporins against Haemophilus species.
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Sixty-three strains of Haemophilus species, 38 of which were beta-lactamase producers (37 H. influenzae type b, 1 H. parainfluenzae) and 25 of which were beta-lactamase negative (20 H. influenzae, 5 H. parainfluenzae), were tested for susceptibility to cefoxitin, moxalactam (LY127935) (Lilly), cefsulodin (CGP 7174 E, Ciba), and cefoperazone (T 1551, Pfizer). Cefsulodin was relatively inactive at both low and high inocula. LY127935 and cefoperazone displayed inoculum-dependent bactericidal activity. Cefoxitin displayed little inoculum effect against beta-lactamase-producing strains: 8 and 16 microgram/ml killed at least 90% of those tested at 10(4) and 10(6) colony-forming units per ml, respectively. (+info)
Single-dose pharmacokinetics of cefsulodin in patients with cystic fibrosis.
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The single-dose pharmacokinetics of cefsulodin were evaluated in 12 patients with cystic fibrosis. Each patient received 3 g of cefsulodin intravenously over 30 min. Multiple plasma and urine samples were obtained during the 6-h study period for the determination of cefsulodin. Pharmacokinetic parameters were determined by model-independent methods. Mean values for t1/2, Vss, and CLp were 1.53 h, 0.242 liters/kg, and 117.3 ml/min per 1.73 m2, respectively. Six-hour urine recovery revealed 73.2% of the administered dose with a corresponding cefsulodin urinary clearance of 75.1 ml/min. These pharmacokinetic data in patients with cystic fibrosis appear consistent with data reported for unaffected individuals. (+info)
In vitro antibacterial activity and susceptibility of cefsulodin, an antipseudomonal cephalosporin, to beta-lactamases.
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Cefsulodin sodium (SCE-129, CGP-7174/E), active in minimum inhibitory concentrations (MICs) of 0.5 to 64 microgram/ml, was about 16- to 32-fold more active than carbenicillin against Psuedomonas aeruginosa. It was also active against P. diminuta, P. maltophilia, P. paucimobilis, and P. pseudoalcaligenes (MICs of 1 to 32 microgram/ml) but not against other species of Pseudomonas or other gram-negative bacteria. Except with highly carbenicillin-resistant isolates, MICs of cefsulodin for P. aeruginosa were little affected by an increase in the inoculum. With a small inoculum, minimum bactericidal concentrations (MBCs) were the same as or twice the MIC, but increasing the inoculum had a greater effect on the MBC than on the MIC. Cefsulodin was not hydrolyzed by the beta-lactamase induced in P. aeruginosa by growth in the presence of benzylpenicillin and was a poor substrate for beta-lactamases from Enterobacter cloacae and Proteus morganii. However, it was hydrolyzed, albeit slowly, by the beta-lactamase produced by most of our highly carbenicillin-resistant isolates of P. aeruginosa and by TEM-type beta-lactamases. (+info)
Cefsulodin pharmacokinetics in patients with various degrees of renal function.
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The pharmacokinetics of cefsulodin were characterized in 19 patients with different degrees of renal function after a single 500-mg, 30-min intravenous infusion. Six subjects had a creatinine clearance (Clcr) of greater than 100 ml min-1 (group I), eight had a Clcr of between 12 and 42 ml min-1 (group II), and five had a Clcr of less than 10 ml min-1 (group III). Nine plasma and four urine samples were collected in the first 36 h. The plasma concentration-time data were fitted to a two-compartment open model. The mean beta-phase half-life was 1.77, 6.37, and 10.12 h in groups I, II, and III, respectively. A significant decline in plasma clearance (Clp) was also noted between the three groups: 136 to 49.6 to 27.2 ml min-1 in groups I, II, and III, respectively. Steady-state volume of distribution was 0.26 liter kg-1, regardless of renal function. The observed linear relationship between Clp and Clcr (Clp = 24.09 + 0.765 Clcr; r = 0.9566) can be utilized to revise dosage schedules for patients with any degree of renal impairment. The nonrenal clearance of cefsulodin was also noted to be significantly lower in groups II and III than in group I. Further investigations will be necessary to elucidate the mechanism(s) responsible for the decrease in the nonrenal clearance of cefsulodin. (+info)