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In vitro activities of PD 117,596 and reference antibiotics against 448 clinical bacterial strains
R P Smith1, A L Baltch, M C Hammer
1Department of Medicine, Veterans Administration Medical Center, Albany, New York.
Abstract:
The in vitro activity of PD 117,596, a new fluoroquinolone antibiotic, was tested against 448 bacterial isolates (15 genera) by agar dilution (inoculum, 10(4) CFU per spot). The activity of PD 117,596 was compared with that of 15 antibiotics against 327 gram-negative strains and with that of 8 other antibiotics against 121 gram-positive strains. PD 117,596 demonstrated the best activity against Klebsiella spp., Enterobacter spp., Acinetobacter spp., Serratia marcescens, and Branhamella catarrhalis (MICs for 90% of the isolates [MIC90S], 0.008 to 0.25 microgram/ml). PD 117,596 (MIC90, 0.25 microgram/ml) was at least twofold more active than ciprofloxacin against Pseudomonas aeruginosa and Pseudomonas spp. PD 117,596 and ciprofloxacin were similar in activity against Escherichia coli, Proteus mirabilis, Haemophilus influenzae, H. parainfluenzae, Neisseria gonorrhoeae, Legionella pneumophila, and Campylobacter jejuni (MIC90, 0.002 to 0.125 microgram/ml). PD 117,596 was more active than ciprofloxacin against streptococcal groups A, B, C, and G, S. pneumoniae, and enterococci (MIC90S, 0.06 to 0.125 microgram/ml). Against Staphylococcus aureus, including methicillin-resistant isolates, PD 117,596 (MIC90S, 0.03 to 0.06 microgram/ml) was 4- to 16-fold more active than ciprofloxacin and was most active against Corynebacterium spp. PD 117,596 appears to be the most active fluoroquinolone to date, with excellent activity against gram-positive bacteria and enhanced activity against gram-negative aerobic-facultative bacteria.
Insights
PD 117,596, a novel fluoroquinolone antibiotic, shows potent in vitro activity against a wide range of bacteria. This new antibiotic demonstrates superior efficacy against both gram-positive and gram-negative pathogens compared to existing treatments.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Fluoroquinolones are a critical class of antibiotics used to treat bacterial infections.
- The emergence of antibiotic resistance necessitates the development of new agents with improved efficacy.
- Understanding the in vitro activity spectrum of novel fluoroquinolones is essential for guiding clinical use.
Purpose of the Study:
- To evaluate the in vitro antibacterial activity of PD 117,596 against a diverse collection of bacterial isolates.
- To compare the activity of PD 117,596 with established antibiotics, including ciprofloxacin, against both Gram-negative and Gram-positive bacteria.
- To determine the spectrum of activity and potency of PD 117,596.
Main Methods:
- Agar dilution method was employed to determine the minimum inhibitory concentrations (MICs).
- A total of 448 bacterial isolates from 15 genera were tested.
- The activity of PD 117,596 was compared against 15 other antibiotics for Gram-negative strains and 8 for Gram-positive strains.
Main Results:
- PD 117,596 exhibited potent activity against Klebsiella spp., Enterobacter spp., Acinetobacter spp., Serratia marcescens, and Branhamella catarrhalis (MIC90s, 0.008 to 0.25 µg/ml).
- It demonstrated superior activity against Pseudomonas aeruginosa and Pseudomonas spp. compared to ciprofloxacin (MIC90, 0.25 µg/ml).
- PD 117,596 showed enhanced activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MIC90s, 0.03 to 0.06 µg/ml), and Corynebacterium spp.
Conclusions:
- PD 117,596 represents a highly active fluoroquinolone with broad-spectrum efficacy.
- The compound demonstrates excellent activity against Gram-positive bacteria and enhanced activity against Gram-negative aerobic-facultative bacteria.
- PD 117,596 shows promise as a valuable therapeutic agent for treating various bacterial infections.