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 g/ml against methicillin-susceptible strains and 2 g/ml against methicillinresistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC 50 and MIC 90 values were, respectively, 0.125 g/ml and 1 g/ml against methicillin-susceptible and 1 g/ml and 2 g/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 g/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 g/ml.The emergence of methicillin-and fluoroquinolone-resistant staphylococci and, more recently, glycopeptide-intermediate staphylococci (6,17,33,46) and the risk of serious infections posed by these strains (10, 42) necessitate alternative therapeutic modalities (9,31,32,44) Ceftobiprole (formerly BAL9141), the active component of the prodrug ceftobiprole medocaril (formerly BAL5788), is a novel parenteral cephalosporin whose broad spectrum of activity includes most clinically important gram-positive and gram-negative bacteria (23,29). Preliminary surveys have indicated that ceftobiprole has excellent in vitro activity against methicillin-resistant staphylococci, vancomycin-intermediate S. aureus (VISA), VRSA, and coagulase-negative staphylococci (8,14,20,23,29). The present study sought to determine (i) the MICs of ceftobiprole and 15 comparators against 303 staphylococci, (ii) the bacteriostatic or bactericidal activities of ceftobiprole and comparators against 12 selected staphylococcal strains, and (iii) the proclivity of ceftobiprole and some comparators to select for endogenous resistance from among 10 staphylococci with diverse resistotypes. .). Most strains studied, including MRSA, were isolated within the 5 years prior to the study. No information on whether strains were community acquired or nosocomial is available. MATERIALS AND METHODS BacteriaAntimicrobial agents and MIC testing. Ceftobiprole powder was obtained from Basilea Pharmaceutica AG (Ba...

We analyzed the emergence of daptomycin nonsusceptibility in a patient with persistent vancomycin-intermediate Staphylococcus aureus (VISA) bacteremia. The daptomycin-nonsusceptible VISA's cell wall demonstrated a reduction in muramic acid O-acetylation, a phenotypic parameter not previously reported for VISA; some isolates also contained a single point mutation in the mprF gene.

Dalbavancin, tested against 146 staphylococci, was more potent than other drugs tested, with an MIC at which 50% of staphylococci were inhibited of 0.03 g/ml and an MIC at which 90% of staphylococci were inhibited of 0.06 g/ml by microdilution. For all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were <4.0 g/ml. Dalbavancin was bactericidal at four times the MIC against all six strains tested.Emergence of staphylococci that are intermediate and resistant to methicillin and quinolone and recently to vancomycin, as well as the propensity of these organisms to cause serious systemic infections in immunocompromised hosts, necessitates other therapeutic modalities (2,3,10,11,15,18,21,25). During 2002, two clinical strains of vancomycin-resistant Staphylococcus aureus (VRSA) carrying van(A), one from Detroit, Mich., and one from our hospital, were isolated (3). Most methicillin-resistant staphylococci are also resistant to available quinolones, such as ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin (2,10,15,18,21). Thus, these last compounds may not be safely used in empirical therapy for patients with methicillin-resistant staphylococcal infections.Dalbavancin is an experimental glycopeptide with a long half-life (4) with excellent activity against gram-positive aerobic and anaerobic bacteria (1,4,8,13,24). This study examined the susceptibilities of 146 staphylococci to dalbavancin compared to susceptibilities to vancomycin, teicoplanin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin by MIC and time-kill analysis. Although dalbavancin activity by MIC is well known, little has thus far been published on its kill kinetics against staphylococci.Twenty-nine methicillin-resistant and 43 methicillin-susceptible S. aureus strains as well as 36 methicillin-resistant and 38 methicillin-susceptible coagulase-negative staphylococci were studied by microdilution, and six strains (three S. aureus strains and three coagulase-negative staphylococci: two methicillin resistant strains and one methicillin-susceptible strain in each group) were subjected to time-kill analysis. Sources of drugs were as follows: dalbavancin, Vicuron Pharmaceuticals, King of Prussia, Pa.; vancomycin, Sigma, Inc., St. Louis, Mo.; oritavancin (as LY 333328), Eli Lilly & Co., Indianapolis, Ind.; teicoplanin and quinupristin-dalfopristin, Aventis Pharma, Romainville, France; linezolid, Pfizer, Inc., Groton, Conn.; ranbezolid, Ranbaxy Laboratories, New Delhi, India; and daptomycin, Cubist Pharmaceuticals, Lexington, Mass. Microdilutions were performed as recommended by NCCLS (17) using commercially prepared trays (TREK, Inc., Westlake, Ohio) with dehydrated dalbavancin and all other drugs in the frozen state. MICs of vancomycin were read after a full 24-h incubation. Calcium was added to daptomycin wells, as recommended by NCCLS (17).For time kills, tubes containing 5 ml of cation-adjusted Mueller-Hinton broth (BBL) with doubling antibiotic concentrations...

For 260 pneumococcal and 266 staphylococcal strains, ranbezolid MICs ranged from <0.06 to 4 g/ml. The MICs for pneumococci were similar irrespective of the strains' ␤-lactam, macrolide, or quinolone susceptibilities, and ranbezolid MICs for coagulase-negative staphylococci were lower than those for Staphylococcus aureus. Ranbezolid was bacteriostatic against pneumococci. Ranbezolid MICs were similar to or lower than those of linezolid. Vancomycin and quinupristin-dalfopristin were also very active.The incidence of pneumococci being resistant to penicillin G and other ␤-lactams and non-␤-lactams has increased worldwide at an alarming rate, including in the United States (1, 5, 9). There is an urgent need for oral compounds for outpatient treatment of respiratory tract infections caused by resistant pneumococci (1,5,8). The emergence of methicillin-and quinolone-intermediate, and recently glycopeptide-intermediate, staphylococci, as well as the propensity of these organisms to cause serious systemic infections in immunocompromised hosts, also necessitates other therapeutic modalities (7,12,21).The MICs of linezolid, an oxazolidinone which has been available clinically for the past few years, for pneumococci and staphylococci range between 0.5 and 4 g/ml, irrespective of the organisms' resistance to other agents (2-4, 6, 10, 15, 18). Ranbezolid (RBX 7644; Ranbaxy Research Laboratories, New Delhi, India) is a new parenteral oxazolidinone with enhanced activity against gram-positive aerobes and gram-positive and gram-negative anaerobes.The present study compared (i) the antipneumococcal activity of ranbezolid with those of linezolid, vancomycin, teicoplanin, quinupristin-dalfopristin, amoxicillin-clavulanate, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and erythromycin by using MIC and time-kill studies and (ii) the antistaphylococcal activity of ranbezolid with those of linezolid, vancomycin, teicoplanin, and quinupristin-dalfopristin by using an MIC study.The pneumococci tested comprised 89 penicillin-susceptible, 89 penicillin-intermediate, and 82 penicillin-resistant strains. Of these, 107 were erythromycin resistant. Twenty-six strains were quinolone resistant (levofloxacin MICs of Ն8 g/ml). For time-kill studies, 12 penicillin-susceptible, -intermediate, and -resistant strains (four of each), including six macrolide-resistant and two quinolone-resistant strains, were tested. Sixtyeight methicillin-resistant and 65 methicillin-susceptible Staphylococcus aureus strains and 69 methicillin-resistant and 64 methicillin-susceptible coagulase-negative staphylococci were examined.Ranbezolid susceptibility powder was obtained from Ranbaxy Research Laboratories. Other antimicrobials were obtained from their respective manufacturers. For testing with pneumococci, agar dilution was performed by using MuellerHinton agar (BBL Microbiology Systems, Cockeysville, Md.) supplemented with 5% sheep blood (11). Methicillin MIC plates for staphylococci were incubated for a full 24 h (11).For time-kill studies, tubes con...