In vitro activities of RWJ-54428 (MC-02,479) against multiresistant gram-positive bacteria

被引:28
作者
Chamberland, S [1 ]
Blais, J [1 ]
Hoang, M [1 ]
Dinh, C [1 ]
Cotter, D [1 ]
Bond, E [1 ]
Gannon, C [1 ]
Park, C [1 ]
Malouin, F [1 ]
Dudley, MN [1 ]
机构
[1] Microcide Pharmaceut Inc, Mt View, CA 94043 USA
关键词
D O I
10.1128/AAC.45.5.1422-1430.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria, in a broth microdilution susceptibility test against methiciilin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC90) of 2 mug/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIG,, of 2 mug/ml. RWJ-54428 was active against S, aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, less than or equal to0.0625 to 1 mug/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S, aureus (MIC,, 0.5 mug/ml), For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIG(90) of 0.125 mug/ml. RWJ-54428 was also active against Enterococcus faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between less than or equal to0.0625 and 1 mug/ml for ampicillin-susceptible strains and 0.125 and 8 mug/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains of Streptococcus pneumoniae (MIC(90)s, 0.25, 0.125, and less than or equal to0.0625 mug/ml, respectively). RWJ54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae and Moraxella catarrhalis (MIC(90)s, 0.25 and 0.5 mug/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials,
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页码:1422 / 1430
页数:9
相关论文
共 22 条
[1]   METHICILLIN-RESISTANT STAPHYLOCOCCI [J].
BARBER, M .
JOURNAL OF CLINICAL PATHOLOGY, 1961, 14 (04) :385-&
[2]  
Campos JM, 1999, MANUAL CLIN MICROBIO, P604
[3]   Methicillin resistance in staphylococci: Molecular and biochemical basis and clinical implications [J].
Chambers, HF .
CLINICAL MICROBIOLOGY REVIEWS, 1997, 10 (04) :781-+
[4]   Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired respiratory tract infections:: Antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997) [J].
Doern, GV ;
Jones, RN ;
Pfaller, MA ;
Kugler, K .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (02) :385-389
[5]  
FRENAY HME, 1994, J CLIN MICROBIOL, V32, P846
[6]   Mosaic genes and their role in penicillin-resistant Streptococcus pneumoniae [J].
Hakenbeck, R .
ELECTROPHORESIS, 1998, 19 (04) :597-601
[7]   Discovery of RWJ-54428 (MC-02,479), a new cephalosporin active against resistant Gram-positive bacteria [J].
Hecker, SJ ;
Glinka, TW ;
Cho, A ;
Zhang, ZJJ ;
Price, ME ;
Chamberland, S ;
Griffith, D ;
Lee, VJ .
JOURNAL OF ANTIBIOTICS, 2000, 53 (11) :1272-1281
[8]   Epidemiology, laboratory detection, and therapy of penicillin-resistant streptococcal infections [J].
Jones, RN ;
Wilson, WR .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1998, 31 (03) :453-459
[9]   A 1994-95 survey of Haemophilus influenzae susceptibility to ten orally administered agents - A 187 clinical laboratory center sample in the United States [J].
Jones, RN ;
Jacobs, MR ;
Washington, JA ;
Pfaller, MA .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1997, 27 (03) :75-83
[10]   Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci [J].
Kirby, WMM .
SCIENCE, 1944, 99 (2579) :452-453