In Vitro Antimicrobial Activity of Doripenem, a New Carbapenem

The doripenem MICs at which 90% of the tested strains were inhibited ranged from 0.03 to 1 μg/ml for 10 species of Enterobacteriaceae (n = 351), from 0.03 to 0.12 μg/ml for oxacillin-susceptible staphylococci (n = 119), from 4 to 32 μg/ml for oxacillin-resistant staphylococci (n = 64), from ≤0.008 to 0.06 μg/ml for penicillin-susceptible streptococci (n = 132), and from 1 to 4 μg/ml for penicillin-resistant streptococci (n = 51). Overall, doripenem demonstrated in vitro activity similar to that of meropenem against gram-negative pathogens and to that of imipenem against gram-positive pathogens

In Vitro Activities of Novel Nonfluorinated Quinolones PGE 9262932 and PGE 9509924 against Clinical Isolates of Staphylococcus aureus and Streptococcus pneumoniae with Defined Mutations in DNA Gyrase and Topoisomerase IV

Two 8-methoxy nonfluorinated quinolones (NFQs), PGE 9262932 and PGE 9509924, were tested against contemporary clinical isolates of Staphylococcus aureus (n = 122) and Streptococcus pneumoniae (n = 69) with genetically defined quinolone resistance-determining regions (QRDRs). For S. aureus isolates with wild-type (WT) sequences at the QRDRs, the NFQs demonstrated activities 4- to 32-fold more potent (MICs at which 90% of isolates are inhibited [MIC(90)s], 0.03 μg/ml) than those of moxifloxacin (MIC(90), 0.12 μg/ml), gatifloxacin (MIC(90), 0.25 μg/ml), levofloxacin (MIC(90), 0.25 μg/ml), and ciprofloxacin (MIC(90), 1 μg/ml). Against S. pneumoniae isolates with WT sequences at gyrA and parC, the NFQs PGE 9262932 (MIC(90), 0.03 μg/ml) and PGE 9509924 (MIC(90), 0.12 μg/ml) were 8- to 64-fold and 2- to 16-fold more potent, respectively, than moxifloxacin (MIC(90), 0.25 μg/ml), gatifloxacin (MIC(90), 0.5 μg/ml), levofloxacin (MIC(90), 2 μg/ml), and ciprofloxacin (MIC(90), 2 μg/ml). The MICs of all agents were elevated for S. aureus isolates with alterations in GyrA (Glu88Lys or Ser84Leu) and GrlA (Ser80Phe) and S. pneumoniae isolates with alterations in GyrA (Ser81Phe or Ser81Tyr) and ParC (Ser79Phe or Lys137Asn). Fluoroquinolone MICs for S. aureus strains with double alterations in GyrA combined with double alterations in GrlA were ≥32 μg/ml, whereas the MICs of the NFQs for strains with these double alterations were 4 to 8 μg/ml. The PGE 9262932 and PGE 9509924 MICs for the S. pneumoniae isolates did not exceed 0.5 and 1 μg/ml, respectively, even for isolates with GyrA (Ser81Phe) and ParC (Ser79Phe) alterations, for which levofloxacin MICs were >16 μg/ml. No difference in the frequency of selection of mutations (<10(−8) at four times the MIC) in wild-type or first-step mutant isolates of S. aureus or S. pneumoniae was detected for the two NFQs. On the basis of their in vitro activities, these NFQ agents show potential for the treatment of infections caused by isolates resistant to currently available fluoroquinolones

Antimicrobial Surveillance of Haemophilus influenzae in the United States during 2000-2001 Leads to Detection of Clonal Dissemination of a β-Lactamase-Negative and Ampicillin-Resistant Strain

A 2000-2001 U.S. Haemophilus influenzae surveillance study (n = 1,434) detected nine (0.6%) β-lactamase-negative and ampicillin-resistant (BLNAR) isolates collected from two different hospitals. The MICs of ampicillin for all nine isolates were 4 μg/ml, with results being reproducible; and all nine isolates were susceptible to amoxicillin-clavulanate, cefuroxime, cefprozil, macrolides, and fluoroquinolones. Pulsed-field gel electrophoresis of genomic DNA following SmaI digestion demonstrated identical patterns for each of the nine isolates, suggesting intra- and interhospital dissemination of a BLNAR clone