Antianaerobe activity of ceftobiprole, a new broad-spectrum cephalosporin. (original) (raw)
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Diagnostic Microbiology and Infectious Disease, 2019
This study investigated the in vitro susceptibility of ceftobiprole and its potential synergistic activity in combination with other antimicrobials against 46 selected Gram-positive pathogens displaying resistance or decrease susceptibility to several drugs. The gradient-cross method was used to assess synergism between ceftobiprole and daptomycin, levofloxacin, linezolid, rifampicin and piperacillin/tazobactam. Time-kill curves were performed for seven representative isolates. Ceftobiprole MICs ranged from 0.25-6 mg/L for staphylococci; 4-≥32 mg/L for Enterococcus faecalis, and 0.38-32 mg/L for E. faecium. Ceftobiprole plus daptomycin was synergistic against all isolates. Ceftobiprole plus linezolid was synergistic against 4 isolates belonging to different species. Ceftobiprole plus levofloxacin was synergistic only against enterococci. In conclusion, ceftobiprole exhibited a potent in vitro antibacterial activity and exhibited synergy with daptomycin against all Gram-positive isolates, despite their antibiotic resistance phenotypes. The use of ceftobiprole in combination may provide a promising alternative therapy for the treatment of resistant Gram-positive infections.
Comparative In Vitro Activity of Newer Cephalosporins Against Anaerobic Bacteria
Antimicrobial Agents and Chemotherapy, 1978
The in vitro susceptibilities of 408 recent clinical isolates of anaerobic bacteria against cefaclor, cephalexin, cephalothin, cefazolin, cefamandole, and cefoxitin were compared by an agar dilution technique. Against gram-positive bacteria, especially peptococci, peptostreptococci, and propionibacteria, cephalexin and cefaclor were significantly less active than cephalothin ( P < 0.05). Cephalexin was also less active than cephalothin against clostridia and lactobacillus ( P < 0.05). Against gram-negative bacteria, major differences were observed primarily with Bacteroides fragilis , against which cephalexin, cefazolin and cefoxitin were all significantly more active than cephalothin ( P < 0.001). At concentrations of 16 μg per ml, however, all cephalosporins showed high in vitro activity, except against Lactobacillus species and B. fragilis . Cephalothin, cefazolin and cefamandole were considerably more active against the former, whereas cefoxitin was distinctly more acti...
Brazilian Journal of Infectious Diseases, 2011
Ceftobiprole is a broad-spectrum cephalosporin with potent activity against staphylococci, including those resistant to oxacillin, as well as against most Gram-negative bacilli including Pseudomonas aeruginosa. In this study, the in vitro activity of ceftobiprole and comparator agents was tested against bacterial isolates recently collected from Brazilian private hospitals. A total of 336 unique bacterial isolates were collected from hospitalized patients between February 2008 and August 2009. Each hospital was asked to submit 100 single bacterial isolates responsible for causing blood, lower respiratory tract or skin and soft tissue infections. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using CLSI microdilution method at a central laboratory. The CLSI M100-S21 (2011) was used for interpretation of the antimicrobial susceptibility results. Among the 336 pathogens collected, 255 (75.9%) were Gram-negative bacilli and 81 (24.1%) were Gram-positive cocci. Although ceftobiprole MIC 50 values for oxacillin resistant strains were twofold higher than for methicillin susceptible S. aureus, ceftobiprole inhibited 100% of tested S. aureus at MICs ≤ 4 μg/mL. Polymyxin B was the only agent to show potent activity against Acinetobacter spp. (MIC 50/90 , 0.5/1 μg/mL), and P. aeruginosa (MIC 50/90 , 1/2 μg/mL). Resistance to broadspectrum cephalosporins varied from 55.3-68.5% and 14.3-28.5% among E. coli and Klebsiella spp. isolates, respectively; with ceftobiprole MIC 50 > 6 μg/mL for both species. Our results showed that ceftobiprole has potent activity against staphylococci and E. faecalis, which was superior to that of vancomycin. Our data also indicates that ceftobiprole demonstrated potency comparable to that of cefepime and ceftazidime against key Gram-negative species.
Journal of Antimicrobial Chemotherapy, 2010
To assess the in vitro activity of ceftobiprole and comparators against a recent collection of Grampositive and Gram-negative pathogens, in order to detect potential changes in susceptibility patterns, and to evaluate the Etest assay for ceftobiprole susceptibility testing. Methods: Contemporary Gram-positive and Gram-negative isolates (excluding extended-spectrum b-lactamase-producing isolates) from across Europe and the Middle East were collected, and their susceptibility to ceftobiprole, vancomycin, teicoplanin, linezolid, ceftazidime and cefepime was assessed using the Etest method. Quality testing [using Etest and broth microdilution (BMD)] was conducted at a central reference laboratory. Results: Some 5041 Gram-positive and 4026 Gram-negative isolates were included. Against Gram-positive isolates overall, ceftobiprole had the lowest MIC 50 (0.5 mg/L), compared with 1 mg/L for its comparators (vancomycin, teicoplanin and linezolid). Against methicillin-resistant Staphylococcus aureus, all four agents had a similar MIC 90 (2 mg/L), but ceftobiprole had a 4-fold better MIC 90 (0.5 mg/L) against methicillin-susceptible strains. Only 38 Gram-positive isolates were confirmed as ceftobiprole resistant. Among Gram-negative strains, 86.9%, 91.7% and 95.2% were susceptible to ceftobiprole, ceftazidime and cefepime, respectively. Pseudomonas aeruginosa was less susceptible to all three antimicrobials than any other Gram-negative pathogen. There was generally good agreement between local Etest results and those obtained at the reference laboratory (for ceftobiprole: 86.8% with Gram-negatives; and 94.7% with Gram-positives), as well as between results obtained by BMD and Etest methods (for ceftobiprole: 98.2% with Gram-negatives; and 98.4% with Gram-positives). Conclusions: Ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.
Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin.
Antimicrob. Agents Chemother., 2005
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, MIC(50) and MIC(90) values for ceftobiprole were each 0.5 microg/ml against methicillin-susceptible strains and 2 µg/ml against methicillin-resistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC(50) and MIC(90) 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 x 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.
Antimicrobial Agents and Chemotherapy, 1980
A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephalothin, chloramphenicol, and ampicillin. Their susceptibility to three new broad-spectrum f-lactams, LY127935 (a 1-oxa-p-lactam), cefotaxime (HR 756), and cefoperazone (T 1551), was compared with the susceptibility of random strains of nine species of aerobic gram-negative bacilli collected in the same hospital in 1979. Susceptibility to cefamandole and ticarcillin was also determined. Strains of staphylococci and streptococci from that hospital and two nearby city-county hospitals were also compared for the three new cephalosporins and other effective antibiotics. The agar dilution method was used to measure the minimum inhibitory concentration for each antibiotic. The multiply resistant strains (minimum inhibitory concentration for gentamicin 2 8 ,ug/ml) usually were as susceptible to the three new broad-spectrum ,B-lactams as were non-multiply resistant strains.
Journal of Antimicrobial Chemotherapy
Background Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB). Objectives To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain. Methods Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth micro...
Journal of clinical microbiology, 1988
The six species of the Bacteroides fragilis group are potent pathogens and commonly have different susceptibility patterns. We determined the relative annual isolation rate of anaerobic bacteria and the susceptibility of B. fragilis group species isolated during 1987 at two community hospitals. The relative frequencies of isolation of 261 strains were as follows: B. fragilis, 61%; B. thetaiotaomicron, 17%; B. distasonis, 7%; B. vulgatus, 6%; B. ovatus, 5%; and B. uniformis, 4%. A total of 234 recent clinical isolates were tested against cefmetazole, cefotetan, cefoxitin, ceftizoxime, clindamycin, imipenem, and piperacillin by a brucella agar dilution method. Imipenem was the most active agent tested with all but three isolates (two B. vulgatus and one B. distasonis) susceptible to less than 2 micrograms/ml. Of the cephalosporins tested, cefoxitin, cefotetan, and cefmetazole were relatively equal against B. fragilis, with 93 to 98% of strains susceptible to 32 micrograms/ml. Ceftizox...