In vitro activity of ceftobiprole, daptomycin, linezolid, and vancomycin against methicillin-resistant staphylococci associated with endocarditis and bone and joint infection

We tested the in vitro activity of 4 antimicrobial agents against methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci recovered from patients with endocarditis or bone and joint infection. Ceftobiprole, daptomycin, linezolid, and vancomycin MIC(90) values were 1, 1, 2, and 1 microg/mL, respectively. Ceftobiprole, daptomycin, linezolid, and vancomycin MBC(90) values were 2, 4, > or = 128, and 8 microg/mL, respectively. Ceftobiprole MIC and MBC values were < or = 2 microg/mL for all isolates tested, with the exception of one methicillin-resistant coagulase-negative Staphylococcus spp isolate. Vancomycin lacked bactericidal activity (defined as an MBC/MIC ratio of > or = 32) against 2 methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with bone and joint infection; one of these isolates was additionally daptomycin nonsusceptible (daptomycin MIC, 2 microg/mL). There was one additional daptomycin nonsusceptible (daptomycin MIC, 2 microg/mL) isolate (MRSA associated with bone and joint infection). Ceftobiprole demonstrated in vitro bactericidal activity against all MRSA and methicillin-resistant coagulase-negative staphylococci tested.     

In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against Staphylococci and Enterococci, including vancomycin- intermediate and -resistant strains

The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing > or =3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.     

In vitro activities of quinupristin-dalfopristin and cefepime,alone and in combination with various antimicrobials,against multidrug-resistant staphylococci and enterococci in an in vitro pharmacodynamic model

Use of combinations of antimicrobials that together achieve synergistic activities against targeted microorganisms is one potential strategy for overcoming bacterial resistance. As the incidence of infections caused by multidrug-resistant staphylococci and enterococci increases, the importance of devising additional synergistic drug combinations for these bacteria is magnified. We evaluated a number of antimicrobial combinations, with a focus on quinupristin-dalfopristin (Q-D), cefepime, and linezolid, using a previously described in vitro pharmacodynamic model. The combination of Q-D with either linezolid or vancomycin, as well as the combination of cefepime-vancomycin, resulted in enhanced killing (> or =2-log(10) increase in killing versus the most-active single agent) against methicillin-resistant Staphylococcus aureus (MRSA) 494. An improved effect (<2 log(10) kill increase in kill) against MRSA 494 was noted for cefepime plus either Q-D or linezolid, as well as linezolid-vancomycin. Similar relationships were observed for a methicillin-susceptible S. aureus isolate (isolate 1199). Against methicillin-resistant S. epidermidis R444, enhanced killing was achieved with the combination of cefepime-linezolid, while improvement was noted for vancomycin with either cefepime or linezolid. The combination of cefepime and vancomycin also achieved enhanced killing against a glycopeptide-intermediate-susceptible S. aureus isolate (isolate 992). The combination of linezolid and doxycycline achieved an enhanced effect against vancomycin-resistant Enterococcus faecalis (VREFc) and E. faecium. Q-D plus ampicillin or linezolid resulted in similar enhancement of activity against the VREFc isolate. The results of this study suggest a number of novel antimicrobial combinations that may be useful against staphylococci and enterococci. Combination regimens including cefepime, Q-D, and/or linezolid warrant further investigation for the treatment of refractive infections due to multidrug-resistant gram-positive pathogens.     

In vitro activities of a novel cephalosporin, CB-181963 (CAB-175), against methicillin-susceptible or -resistant Staphylococcus aureus and glycopeptide-intermediate susceptible staphylococci

We examined the activity of CB-181963, a novel cephalosporin, against methicillin-resistant Staphylococcus aureus (MRSA) (n = 200), methicillin-susceptible S. aureus (MSSA) (n = 50), glycopeptide-intermediate Staphylococcus species (GISS) (n = 47), and VRSA (n = 2) isolates. CB-181963 exhibited MIC profiles similar to those of linezolid against MRSA and GISS; however, activity against MSSA was similar to that of vancomycin. Time-kill study results of investigations of activity against MRSA, MSSA, and GISS at 24 h were as follows: CB-181963 activity = vancomycin activity > linezolid activity (P < 0.001); CB-181963 = quinupristin-dalfopristin = vancomycin > linezolid (P < 0.05); CB-181963 > linezolid (P = 0.003); and CB-181963 = quinupristin-dalfopristin = vancomycin. CB-181963 may provide an alternative treatment for multidrug-resistant staphylococci.     

Comparative in vitro activities of daptomycin, linezolid, and quinupristin/dalfopristin against Gram-positive bacterial isolates from a large cancer center

Our objective was to evaluate and compare the in vitro activity of daptomycin, linezolid, and quinupristin/dalfopristin against clinical bloodstream isolates of Gram-positive pathogens from a large cancer center in the Northeastern United States. Minimum inhibitory concentrations (MICs) were determined for daptomycin, quinupristin/dalfopristin, and linezolid against 258 isolates; bactericidal activity was evaluated using time-kill experiments against 14 representative pathogens. Vancomycin-resistant enterococci represented the largest proportion of bacteria tested (32% of the isolates), followed by methicillin-resistant coagulase-negative staphylococci (23%), and vancomycin sensitive enterococci (14%). Against staphylococci, the MIC90 was 1 microg/mL for both daptomycin and quinupristin/dalfopristin and 4 microg/mL for linezolid. Against enterococci, the MIC90 for both daptomycin and linezolid was 4 microg/mL and was 16 microg/mL for quinupristin/dalfopristin. The quinupristin/dalfopristin MIC90 for Enterococcus faecium was 2 microg/mL. Two enterococci were linezolid resistant and remained susceptible to daptomycin. In vitro time-kill studies found daptomycin to be rapidly bactericidal against the majority of organisms tested, killing 99.9% of bacteria within 6 h. Quinupristin/dalfopristin was bactericidal against staphylococci and bacteriostatic against most enterococci. Linezolid was bacteriostatic against all organisms evaluated. Daptomycin, quinupristin/dalfopristin, and linezolid each demonstrated in vitro activity against this collection of organisms. Future clinical studies to evaluate a potential role for these agents in the management of infections in cancer patients, including the treatment of febrile neutropenia, appear warranted.     

Comparative activities of daptomycin and several agents against staphylococcal blood isolates. Glycopeptide tolerance

The activity of daptomycin was evaluated against 702 staphylococcal blood isolates (316 methicillin-susceptible Staphylococcus aureus, 187 methicillin-resistant S. aureus [MRSA], and 199 coagulase-negative staphylococci [CoNS]) collected in 41 Spanish hospitals. Glycopeptide tolerance and the incidence of heterogeneous glycopeptide-intermediate (hGISA) isolates were also examined. Vancomycin MICs determined by the Etest were compared with those obtained by the reference broth microdilution method. Daptomycin exhibited good activity, and only 2 isolates were nonsusceptible to this antibiotic. Resistance to linezolid was observed in 2 MRSA isolates and in 16 CoNS. The cfr gene was detected in 7 of these 18 isolates. Vancomycin and teicoplanin tolerance was 9.6% and 21.9%, respectively, in MRSA isolates. We detected the hGISA phenotype in 5.8% of MRSA isolates. Vancomycin MICs by the Etest were slightly higher than those obtained by broth microdilution. Daptomycin retained activity against isolates that were not susceptible to linezolid, teicoplanin, or quinupristin-dalfopristin.     

In-vitro activity of vancomycin, teicoplanin, daptomycin, ramoplanin, MDL 62873 and other agents against staphylococci, enterococci and Clostridium difficile.

The minimum inhibitory concentrations (MICs) of different antibiotics were determined by a broth microdilution method for staphylococci, enterococci and Clostridium difficile. The antimicrobial agents tested were vancomycin, teicoplanin, daptomycin, ramoplanin, MDL 62873, rifampicin and piperacillin, the latter limited to enterococci. In terms of MIC90S, daptomycin (0.89 mg/l). MDL 62873 (0.99 mg/l), and teicoplanin (1.50 mg/l) were found to be highly active against methicillin-resistant Staphylococcus aureus (MRSA). Daptomycin (MIC90 0.48 mg/l), MDL 62873 (0.95 mg/l) and ramoplanin (1.45 mg/l) were the most active drugs against methicillin-resistant S. epidermidis (MRSE). Teicoplanin (MIC90 0.45 mg/l) was the most active agent against enterococci, followed by MDL 62873 (0.65 mg/l) and daptomycin (1.60 mg/l). MDL 62873 gave the lowest MIC90 (0.17 mg/l) for C. difficile. Teicoplanin (MIC90 0.42 mg/l), daptomycin (0.87 mg/l) and ramoplanin (0.98 mg/l) were also very active. Our results indicate that teicoplanin, daptomycin, ramoplanin and MDL 62873, a teicoplanin derivative, are potentially effective alternative antibiotics for treatment of infections caused by staphylococci, enterococci and C. difficile.     

Recent trend and development of novel antimicrobial agents for MRSA infections]

Gram-positive organisms such as Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, Enterococcus spp., and Streptococcus spp. have in recent years emerged as significant pathogens in hospitals and are now being isolated more frequently than gram-negative bacilli. These organisms are often multidrug resistant. Therefore, alternative agents with potent activity against gram-positive organisms are of considerable interest. In addition to the glycopeptide antibiotic vancomycin and the aminoglycoside antibiotic arbekacin, which can be used in MRSA infections, teicoplanin, RP 59500 and daptomycin are now under basic research in Japan. These antimicrobial agents are very active against gram-positive organisms, including MRSA and appear to be potent agents against infections due to gram-positive cocci, particularly MRSA.     

Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model

We evaluated the impact of high (9.5 log10 CFU/g) and moderate (5.5 log10 CFU/g) inocula of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 +/- 1.1, 3.28 +/- 0.4, and 3.34 +/- 0.8 log10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 +/- 0.10 log10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for nafcillin (MSSA only) (P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.     

Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria

The rising rates of antibiotic resistance accentuate the critical need for new antibiotics. Daptomycin is a new antibiotic with a unique mode of action and a rapid in vitro bactericidal effect against gram-positive organisms. This study examined the kinetics of daptomycin's bactericidal action against peritonitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in healthy and neutropenic mice and compared this activity with those of other commonly used antibiotics. CD-1 mice were inoculated intraperitoneally with lethal doses of MSSA (Xen-29) or MRSA (Xen-1), laboratory strains transformed with a plasmid containing the lux operon, which confers bioluminescence. One hour later, the animals were given a single dose of daptomycin at 50 mg/kg of body weight subcutaneously (s.c.), nafcillin at 100 mg/kg s.c., vancomycin at 100 mg/kg s.c., linezolid at 100 mg/kg via gavage (orally), or saline (10 ml/kg s.c.). The mice were anesthetized hourly, and photon emissions from living bioluminescent bacteria were imaged and quantified. The luminescence in saline-treated control mice either increased (neutropenic mice) or remained relatively unchanged (healthy mice). In contrast, by 2 to 3 h postdosing, daptomycin effected a 90% reduction of luminescence of MSSA or MRSA in both healthy and neutropenic mice. The activity of daptomycin against both MSSA and MRSA strains was superior to those of nafcillin, vancomycin, and linezolid. Against MSSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than nafcillin or linezolid. Against MRSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than vancomycin or linezolid. The rapid decrease in the luminescent signal in the daptomycin-treated neutropenic mice underscores the potency of this antibiotic against S. aureus in the immune-suppressed host.     

The in vitro activity of daptomycin against Staphylococcus aureus and Enterococcus species

OBJECTIVE: The purpose of this study was to examine the in vitro activity of daptomycin using an optimal calcium (Ca2+) concentration (50 mg/L) against a diverse collection of enterococcal and Staphylococcus aureus clinical isolates, including glycopeptide-resistant enterococci (GRE) and methicillin-resistant S. aureus (MRSA). METHODS: The activity of daptomycin was compared with the activities of seven other agents against 1483 enterococcal and S. aureus clinical isolates, including 303 GRE and 193 methicillin-resistant S. aureus (MRSA) strains. Susceptibility testing was performed by the NCCLS broth microdilution method, with one exception: Mueller-Hinton (MH) broth was supplemented to a physiological level of 50 mg/L Ca2+ when testing daptomycin. Daptomycin zone diameters were determined by disc diffusion with MH agar plates containing Ca2+ 50 mg/L. RESULTS: All staphylococcal isolates tested, and the majority of enterococcal isolates (96.5%), would be considered susceptible to daptomycin if the breakpoint previously proposed of or = 20 mm, and all of the enterococcal isolates had daptomycin zone diameters > or = 17 mm. CONCLUSIONS: Overall, daptomycin showed potent activity against S. aureus and enterococcal isolates, comparable to quinupristin-dalfopristin and linezolid.     

In vitro activities of dalbavancin and 12 other agents against 329 aerobic and anaerobic gram-positive isolates recovered from diabetic foot infections

Tests of dalbavancin's in vitro activity against 209 aerobic and 120 anaerobic isolates from pretreatment diabetic foot infections showed an MIC(90) of < or =0.125 microg/ml against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and 120 anaerobes (Clostridium perfringens, other clostridia, Peptoniphilus asaccharolyticus, Finegoldia magna, and Anaerococcus prevotii), compared to respective MIC(90)s for MSSA and MRSA of 0.5 and 1 microg/ml for vancomycin, 4 and 4 microg/ml for linezolid, 0.5 and 0.5 microg/ml for daptomycin, and 0.25 and >8 microg/ml for clindamycin.     

Comparative In Vitro Activities and Postantibiotic Effects of the Oxazolidinone Compounds Eperezolid (PNU-100592) and Linezolid (PNU-100766) versus Vancomycin against Staphylococcus aureus, Coagulase-Negative Staphylococci, Enterococcus faecalis, and Enterococcus faecium

The activities of the oxazolidinone antibacterial agents eperezolid (PNU-100592) and linezolid (PNU-100766) were compared with that of vancomycin against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (n = 200), coagulase-negative staphylococci (n = 100), and vancomycin-susceptible and -resistant Enterococcus faecalis and Enterococcus faecium (n = 50). Eperezolid and linezolid demonstrated good in vitro inhibitory activity, regardless of methicillin susceptibility for staphylococci (MIC at which 90% of the isolates are inhibited [MIC₉₀] range, 1 to 4 μg/ml) or vancomycin susceptibility for enterococci (MIC₉₀ range, 1 to 4 μg/ml). In time-kill studies, eperezolid and linezolid were bacteriostatic in action. A postantibiotic effect of 0.8 ± 0.5 h was demonstrated for both eperezolid and linezolid against S. aureus, S. epidermidis, E. faecalis, and E. faecium.     

Multicentre surveillance of antimicrobial resistance in enterococci and staphylococci from Colombian hospitals, 2001-2002

Invasive isolates of staphylococci and enterococci were collected from 15 tertiary care centres in five Colombian cities from 2001 to 2002. A total of 597 isolates were available for analysis. Identification was confirmed by both automated methods and multiplex PCR assays in a central laboratory. Staphylococcus aureus and coagulase-negative staphylococci (CoNS) corresponded to 49.6% and 29.6% of isolates, respectively, and 20.8% were identified as enterococci. MICs of ampicillin, ciprofloxacin, chloramphenicol, erythromycin, gentamicin, linezolid, oxacillin, rifampicin, teicoplanin, tetracycline, trimethoprim/sulfamethoxazole (SXT) and vancomycin were determined using an agar dilution method as appropriate. Screening for vancomycin-resistant S. aureus was also carried out on brain-heart infusion agar plates supplemented with vancomycin. The presence of mecA and van genes was investigated in methicillin-resistant staphylococci and glycopeptide-resistant enterococci (GRE), respectively. All staphylococci were susceptible to vancomycin, teicoplanin and linezolid. No VISA isolates were found. In S. aureus and CoNS, the lowest rates of resistance were found for SXT (7.4%) and chloramphenicol (10.7%), respectively. Resistance to oxacillin in S. aureus and CoNS was 52% and 73%, respectively. The mecA gene was detected in 97.5% of methicillin-resistant S. aureus isolates. In enterococci, resistance to glycopeptides was 9.7%: vanA (58.3%) and vanB (41.7%) genes were found. Pulsed-field gel electrophoresis indicated that the GRE isolates were closely related. Rates of resistance to ampicillin, ciprofloxacin, chloramphenicol, rifampicin and high levels of gentamicin and streptomycin were 9.7%, 27.4%, 8.9%, 43%, 17% and 28.2%, respectively. All enterococci were susceptible to linezolid.     

In vitro activities of ramoplanin, selected glycopeptides, fluoroquinolones, and other antibiotics against clinical bloodstream isolates of gram-positive cocci.

The susceptibilities of 316 gram-positive bacteremic isolates to ramoplanin, vancomycin, and teicoplanin and seven other antibiotics were tested. Ramoplanin demonstrated MICs of < or = 0.25 microgram/ml for at least 99% of Staphylococcus aureus isolates and 100% of coagulase-negative staphylococci tested. For both oxacillin-susceptible and oxacillin-resistant S. aureus and coagulase-negative staphylococci, the activity of ramoplanin surpassed those of both vancomycin and teicoplanin. Ramoplanin and teicoplanin had comparable activities against enterococci and Streptococcus pneumoniae and were superior to vancomycin.     

In vitro activities of linezolid against important gram-positive bacterial pathogens including vancomycin-resistant enterococci.

The emergence of resistance in gram-positive bacteria has necessitated a search for new antimicrobial agents. Linezolid is an oxazolidinone, a new class of antibacterial agents with enhanced activity against pathogens. We compared the activity of linezolid to those of other antimicrobial agents against 3,945 clinical isolates. Linezolid demonstrated potent activity against all isolates tested. For all vancomycin-susceptible enterococci, staphylococci, and streptococci, the activity of linezolid was comparable to that of vancomycin. Against oxacillin-resistant staphylococci and vancomycin-resistant enterococci, linezolid was the most active agent tested. In summary, linezolid appears to be a promising new antimicrobial agent for the treatment of gram-positive infections.     

In Vitro Activity and Microbiological Efficacy of Tedizolid (TR-700) against Gram-Positive Clinical Isolates from a Phase 2 Study of Oral Tedizolid Phosphate (TR-701) in Patients with Complicated Skin and Skin Structure Infections

Tedizolid (TR-700, formerly torezolid) is the active moiety of the prodrug tedizolid phosphate (TR-701), a next-generation oxazolidinone, with high potency against Gram-positive species, including methicillin-resistant Staphylococcus aureus (MRSA). A recently completed randomized, double-blind phase 2 trial evaluated 200, 300, or 400 mg of oral tedizolid phosphate once daily for 5 to 7 days in patients with complicated skin and skin structure infections. This report examines the in vitro activity of tedizolid and Zyvox (linezolid) against Gram-positive pathogens isolated at baseline and describes the microbiological and clinical efficacy of tedizolid. Of 196 isolates tested, 81.6% were S. aureus, and of these, 76% were MRSA. The MIC(50) and MIC(90) of tedizolid against both methicillin-susceptible S. aureus (MSSA) and MRSA were 0.25 μg/ml, compared with a MIC(50) of 1 μg/ml and MIC(90) of 2 μg/ml for linezolid. For coagulase-negative staphylococci (n = 7), viridans group streptococci (n = 15), and beta-hemolytic streptococci (n = 3), the MICs ranged from 0.03 to 0.25 μg/ml for tedizolid and from 0.12 to 1 μg/ml for linezolid. The microbiological eradication rates at the test-of-cure visit (7 to 14 days posttreatment) in the microbiologically evaluable population (n = 133) were similar in all treatment groups, with overall eradication rates of 97.7% for all pathogens, 97.9% for MRSA, and 95.7% for MSSA. The clinical cure rates for MRSA and MSSA infections were 96.9% and 95.7%, respectively, across all dose groups. This study confirms the potent in vitro activity of tedizolid against pathogenic Gram-positive cocci, including MRSA, and its 4-fold-greater potency in comparison with linezolid. All dosages of tedizolid phosphate showed excellent microbiological and clinical efficacy against MRSA and MSSA.     

In vitro activity of sparfloxacin and six reference antibiotics against gram-positive bacteria.

The in vitro activity of sparfloxacin, a new fluoroquinolone, was assessed against 234 gram-positive bacterial isolates by agar dilution (10(4) CFU/spot). Sparfloxacin activity was compared with that of ciprofloxacin and five other antibiotics. Sparfloxacin was the most active drug tested against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MIC90, 0.125-0.25 mg/l). Sparfloxacin was also the most active drug tested against Enterococcus faecalis (MIC90, 1 mg/l) and showed equal activity against gentamicin-susceptible and gentamicin-resistant (MIC greater than 2,000 mg/l) enterococci. Sparfloxacin was the most active quinolone tested against Streptococcus pneumoniae and S. pyogenes (MIC90, 1 mg/l). Most Corynebacterium jeikeium showed exquisite susceptibility to sparfloxacin (MIC, 0.06-0.25 mg/l). For MRSA, time-kill curves showed sparfloxacin to be rapidly bactericidal at the MIC of the organism. Sparfloxacin showed greater and more sustained bactericidal activity than ciprofloxacin and vancomycin at 1x and 2x the MIC. Reduction in the activity of sparfloxacin occurred with decreased agar pH (from 7.0 to 6.0) and increased bacterial inoculum. Sparfloxacin showed superior activity compared to reference drugs against most gram-positive bacteria.     

Quinupristin-dalfopristin resistance among gram-positive bacteria in Taiwan

To understand quinupristin-dalfopristin resistance among clinical isolates of gram-positive bacteria in Taiwan, where this agent is not yet available for clinical use, we evaluated 1,287 nonduplicate isolates recovered from January 1996 to December 1999 for in vitro susceptibility to quinupristin-dalfopristin and other newer antimicrobial agents. All methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to quinupristin-dalfopristin. High rates of nonsusceptibility to quinupristin-dalfopristin (MICs, >/=2 microg/ml) were demonstrated for the following organisms: methicillin-resistant S. aureus (MRSA) (31%), coagulase-negative staphylococci (CoNS) (16%), Streptococcus pneumoniae (8%), viridans group streptococci (51%), vancomycin-susceptible enterococci (85%), vancomycin-resistant Enterococcus faecalis (100%), vancomycin-resistant Enterococcus faecium (66%), Leuconostoc spp. (100%), Lactobacillus spp. (50%), and Pediococcus spp. (87%). All isolates of MSSA, MRSA, S. pneumoniae, and viridans group streptococci were susceptible to vancomycin and teicoplanin. The rates of nonsusceptibility to vancomycin and teicoplanin were 5 and 7%, respectively, for CoNS, ranging from 12 and 18% for S. simulans to 0 and 0% for S. cohnii and S. auricularis. Moxifloxacin and trovafloxacin had good activities against these isolates except for ciprofloxacin-resistant vancomycin-resistant enterococci and methicillin-resistant staphylococci. In Taiwan, virginiamycin has been used in animal husbandry for more than 20 years, which may contribute to the high rates of quinupristin-dalfopristin resistance.     

Comparative activity of linezolid and other new agents against methicillin-resistant Staphylococcus aureus and teicoplanin-intermediate coagulase-negative staphylococci.

The activity of linezolid was determined against 225 recently isolated methicillin-resistant Staphylococcus aureus (MRSA) and 20 methicillin-resistant coagulase-negative staphylococci (CoNS) with decreased levels of susceptibility to teicoplanin. Linezolid activity was compared with other new agents (quinupristin-dalfopristin, trovafloxacin, moxifloxacin, levofloxacin and telithromycin) and six other antimicrobials (erythromycin, clindamycin, gentamicin, vancomycin, teicoplanin and rifampicin). The in vitro activity of linezolid was similar to that of vancomycin. Linezolid inhibited all MRSA strains at between 0.1 and 2 mg/L and all CoNS strains tested at between 0.2 and 0.5 mg/L. These results suggest that linezolid would be useful for the treatment of infections involving these organisms.