ArticleAntimicrobial agents and chemotherapy2002
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.
Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 23 citations in OpenAlex.
- Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria.International journal of molecular sciences · 2021Article
- Bactericidal activity of besifloxacin against staphylococci, Streptococcus pneumoniae and Haemophilus influenzae.The Journal of antimicrobial chemotherapy · 2010Article
- Multidrug-resistant Streptococcus pneumoniae infections: current and future therapeutic options.Drugs · 2007Review
- Postantibiotic, postantibiotic sub-MIC, and subinhibitory effects of PGE-9509924, ciprofloxacin, and levofloxacin.Antimicrobial agents and chemotherapy · 2003Article
- In vitro antibacterial activity and pharmacodynamics of new quinolones.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2003Review
- National athletic trainers' association position statement: skin diseases.Journal of athletic trainingReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 microg/ml) than those of moxifloxacin (MIC(90), 0.12 microg/ml), gatifloxacin (MIC(90), 0.25 microg/ml), levofloxacin (MIC(90), 0.25 microg/ml), and ciprofloxacin (MIC(90), 1 microg/ml). Against S. pneumoniae isolates with WT sequences at gyrA and parC, the NFQs PGE 9262932 (MIC(90), 0.03 microg/ml) and PGE 9509924 (MIC(90), 0.12 microg/ml) were 8- to 64-fold and 2- to 16-fold more potent, respectively, than moxifloxacin (MIC(90), 0.25 microg/ml), gatifloxacin (MIC(90), 0.5 microg/ml), levofloxacin (MIC(90), 2 microg/ml), and ciprofloxacin (MIC(90), 2 microg/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 > or =32 microg/ml, whereas the MICs of the NFQs for strains with these double alterations were 4 to 8 microg/ml. The PGE 9262932 and PGE 9509924 MICs for the S. pneumoniae isolates did not exceed 0.5 and 1 microg/ml, respectively, even for isolates with GyrA (Ser81Phe) and ParC (Ser79Phe) alterations, for which levofloxacin MICs were > 16 microg/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.
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