Antimicrobial activity of ceftobiprole against Gram-negative and Gram-positive pathogens: results from INVITA-A-CEFTO Brazilian study (original) (raw)
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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.
Antipneumococcal activity of ceftobiprole, a novel broad-spectrum cephalosporin.
Antimicrob. Agents Chemother., 2005
Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC(50) and MIC(90) values (µg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1 x and 2 x the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2 x the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2 x the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole.
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.
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.
Microbiologia Medica, 2016
Background and aims: Ceftobiprole is a new cephalosporin characterized by a potent activity against Gram-positive and Gram-negative bacterial pathogens. It is noting that ceftobiprole has a strong affinity for penicillin binding proteins including PBP 2A, which mediates resistance to beta-lactams in methicillin (oxacillin)-resistant coagulase-negative staphylococci and Staphylococcus aureus (MRSA). The aim of the current study was to examine the antimicrobial activity of ceftobiprole against clinical isolates of S. aureus recently collected at our institution. Materials and methods: One hundred and forty blood isolates of S. aureus were evaluated, including methicillin-susceptible (MSSA, n=70) and MRSA (n=70) strains. Twenty additional MRSA isolates obtained from different sites (including skin and soft tissues, blood, and lower respiratory tract) and characterized by borderline susceptibility to vancomycin were also studied to assess the ability of ceftobiprole to overcome this worrisome trait. MIC values of ceftobiprole were determined by Etest strips and results were interpreted according to EUCAST guidelines. Results and conclusions: Study isolates were consistently susceptible to ceftobiprole, with MIC values ranging from 0.125 mg/L to 2 mg/L. Overall, MIC50 and MIC90 were 0.25 mg/L and 0.5 mg/L, respectively. Ceftobiprole showed in vitro activity against all S. aureus isolates, with small differences among groups selected on the basis of resistance to methicillin and/or reduced susceptibility to vancomycin. Thus, ceftobiprole appears a valid choice for treating infections caused by S. aureus, even when susceptibility results are not yet available. Additionally, ceftobiprole may be a valid option in the case of reduced susceptibility to vancomycin.
Antimicrobial Agents and Chemotherapy, 1976
The in vitro activity of cefuroxime, a new cephalosporin derivative, was compared with that of cephaloridine, cephalothin, and cefamandole against strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. Cefuroxime showed very similar activity to cefamandole against Staphylococcus aureus, Haemophilus influenzae , and most members of the Enterobacteriaceae . It was more active than cefamandole against gonococci, pneumococci, and most streptococci. Increasing the inoculum size appeared to have less effect on the minimum inhibitory concentrations of cefuroxime for gram-negative bacilli than has been found with the other cephalosporin derivatives, and minimum bactericidal concentrations of cefuroxime were only marginally greater than minimum inhibitory concentrations.
Antianaerobe activity of ceftobiprole, a new broad-spectrum cephalosporin.
Diagn. Microbiol. Infect. Dis., 2007
Agar dilution testing of 463 anaerobes showed most Gram-positive β-lactamase-negative strains (other than some Clostridium difficile and Peptostreptococcus anaerobius), as well as both β-lactamase-positive and β-lactamase-negative strains of Fusobacterium nucleatum, to have ceftobiprole MIC values of ≤0.016 to 4 µg/mL. Ceftobiprole was less active against β-lactamase-positive Gram-negative bacilli, especially the members of the Bacteroides fragilis group. Like ceftobiprole, piperacillin was active mainly against β-lactamase-negative strains, though MIC values for piperacillin were often 1 to 2 dilutions higher than for ceftobiprole. Carbapenems had MIC values ≤4 µg/mL against all except some C. difficile and 2 strains of B. fragilis. All strains were susceptible to metronidazole, and all bacteria, except C. difficile and a single Bacteroides distasonis strain, were susceptible to chloramphenicol. Clindamycin resistance was seen in most anaerobe groups, whereas high moxifloxacin MICs were found mainly among the B. fragilis and Prevotella groups, and a few C. difficile and F. nucleatum strains.
JPMA. The Journal of the Pakistan Medical Association, 2000
To study the in-vitro antimicrobial activity of Cefpirome: A new fourth generation Cephalosporin in comparison with other agents against clinically significant Gram-negative and Gram-positive bacteria. A multi-center in-vitro study was conducted in 13 centers. Bacterial isolates--A total of 1300 isolates were collected from different clinical laboratories and hospitals at 13 centers. Organisms were identified by the API identification systems (API systems, SA Vericeu, France). The age and sex of each patient, type of hospital unit, source of the isolate and genus and species of the bacteria were recorded on standardized report forms. The sensitivity testing was carried out by the "NCCLS (modified Kirby-Bauer) method"--using Mueller-Hinton agar. The results suggest that Cefpirome has a potential clinical advantage against gram-positive and gram-negative bacteria resistant to other third generation cephalosporins. Cefpirome was active against both gram-negative and gram-posi...