scholarly journals Antistaphylococcal Activity of CB-181963 (CAB-175), an Experimental Parenteral Cephalosporin

2004 ◽  
Vol 48 (10) ◽  
pp. 4037-4039 ◽  
Author(s):  
Dianne B. Hoellman ◽  
Glenn A. Pankuch ◽  
Peter C. Appelbaum
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Methicillin Resistant ◽  
Antistaphylococcal Activity ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT Among 265 methicillin-susceptible and -resistant staphylococci, CB-181963 (CAB-175) had a 50% minimum inhibitory concentration of 2 μg/ml and a 90% minimum inhibitory concentration of 4 μg/ml. All strains except two vancomycin-resistant S. aureus and 5 vancomycin-intermediate S. aureus strains were also susceptible to vancomycin and teicoplanin, and all were susceptible to linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin. Most methicillin-resistant strains were levofloxacin resistant. CB-181963 was bactericidal against all six methicillin-resistant strains at four times the MIC after 24 h.

scholarly journals Antistaphylococcal Activity of Dihydrophthalazine Antifolates, a Family of Novel Antibacterial Drugs

2009 ◽  
Vol 53 (4) ◽  
pp. 1353-1361 ◽  
Author(s):  
Catherine Clark ◽  
Lois M. Ednie ◽  
Gengrong Lin ◽  
Kathy Smith ◽  
Klaudia Kosowska-Shick ◽  
...  
Keyword(s):  
Serial Passage ◽  
Single Step ◽  
Coagulase Negative Staphylococcus ◽  
Considerable Variability ◽  
Coagulase Negative Staphylococci ◽  
Resistance Development ◽  
Methicillin Resistant ◽  
Antistaphylococcal Activity ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT For a panel of 153 Staphylococcus aureus clinical isolates (including 13 vancomycin-intermediate or heterogeneous vancomycin-intermediate and 4 vancomycin-resistant strains), MIC50s and MIC90s of three novel dihydrophthalazine antifolates, BAL0030543, BAL0030544, and BAL0030545, were 0.03 and 0.25 μg/ml, respectively, for methicillin-susceptible strains and 0.03 and ≤0.25 μg/ml, respectively, for methicillin-resistant strains. For a panel of 160 coagulase-negative staphylococci (including 5 vancomycin-intermediate and heterogeneous vancomycin-intermediate strains and 7 linezolid-nonsusceptible strains), MIC50s and MIC90s were ≤0.03 and ≤0.06 μg/ml, respectively, for methicillin-susceptible strains and 0.06 and 0.5 μg/ml, respectively, for methicillin-resistant strains. Vancomycin was active against 93.0% of 313 staphylococci examined; linezolid was active against all S. aureus strains and 95.6% of coagulase-negative staphylococcus strains, whereas elevated MICs of clindamycin, minocycline, trimethoprim, and rifampin for some strains were observed. At 4× MIC, the dihydrophthalazines were bactericidal against 11 of 12 staphylococcal strains surveyed. The prolonged serial passage of some staphylococcal strains in the presence of subinhibitory concentrations of BAL0030543, BAL0030544, and BAL0030545 produced clones for which dihydrophthalazines showed high MICs (>128 μg/ml), although rates of endogenous resistance development were much lower for the dihydrophthalazines than for trimethoprim. Single-step platings of naïve staphylococci onto media containing dihydrophthalazine antifolates indicated considerable variability among strains with respect to preexistent subpopulations nonsusceptible to dihydrophthalazine antifolates.

scholarly journals Antistaphylococcal Activity of Ceftobiprole, a New Broad-Spectrum Cephalosporin

2005 ◽  
Vol 49 (10) ◽  
pp. 4210-4219 ◽  
Author(s):  
Tatiana Bogdanovich ◽  
Lois M. Ednie ◽  
Stuart Shapiro ◽  
Peter C. Appelbaum
Keyword(s):  
Active Component ◽  
Serial Passage ◽  
Coagulase Negative Staphylococci ◽  
Low Frequencies ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Antistaphylococcal Activity ◽  
Amoxicillin Clavulanate ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC50 and MIC90 values for ceftobiprole were each 0.5 μg/ml against methicillin-susceptible strains and 2 μg/ml against methicillin-resistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC50 and MIC90 values were, respectively, 0.125 μg/ml and 1 μg/ml against methicillin-susceptible and 1 μg/ml and 2 μg/ml against methicillin-resistant strains. Teicoplanin was less active than vancomycin against coagulase-negative strains. Linezolid, quinupristin-dalfopristin, and daptomycin were active against all strains, whereas increased MICs for amoxicillin-clavulanate, cefazolin, minocycline, gentamicin, trimethoprim-sulfamethoxazole, levofloxacin, rifampin, mupirocin, fusidic acid, and fosfomycin were sometimes observed. At 2× MIC, ceftobiprole was bactericidal against 11 of 12 test strains by 24 h. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to select for clones with MICs >4 times those of the parents; the maximum MIC achieved for ceftobiprole after 50 passages (in 1 of 10 strains) was 8 μg/ml. Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 μg/ml.

Comparison of the in Vitro Activity of Daptomycin and four other Antimicrobial Agents against Staphylococci Associated with CAPD Peritonitis

1988 ◽  
Vol 8 (4) ◽  
pp. 277-279
Author(s):  
Wendy L. Vaudry ◽  
Claudia Gratton ◽  
Kinga Kowalewska ◽  
Wanda M. Wenman
Keyword(s):  
Peritoneal Dialysis ◽  
Minimum Inhibitory Concentration ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Vancomycin Resistant

The minimum inhibitory concentration (MIC) of daptomycin was compared with that of four other antimicrobial agents against clinically relevant staphylococci. Sixtyfive isolates were obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) who contracted peritonitis. These isolates comprised 29 S. Sureus strains (all sensitive to oxacillin); 25 S. epidermidis strains (14 sensitive and 9 resistant to oxacillin); and 11 unspeciated coagulase-negative staphylococci (2 sensitive and 11 resistant to oxacillin). All of the oxacillin susceptible strains were inhibited by ≤2 mg/L of the five antibiotics tested. The oxacillin resistant staphylococci were also resistant to cefuroxime and variably resistant to cefamandole, but were uniformly susceptible to both vancomycin and daptomycin. Daptomycin possesses equivalent in vitro activity to vancomycin against strains of S. Sureus and coagulase negative staphylococci associated with CAPD peritonitis. If vancomycin resistance becomes a significant problem in these patients, and daptomycin is shown to be active against vancomycin resistant organisms, then it would have potential usefulness as an alternative to vancomycin in the treatment of peritonitis caused by multiply -resistant staphylococci.

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