In Vitro Activity of a New Antibiotic, NVP-PDF386 (VRC4887), against
            <i>Chlamydia pneumoniae</i>

Roblin, Patricia M.; Hammerschlag, Margaret R.

doi:10.1128/aac.47.4.1447-1448.2003

Cited by 24 publications

(12 citation statements)

References 4 publications

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“…Many of these have shown significant activity against respiratory tract pathogens, including S. pneumoniae and M. catarrhalis, with variable activity against H. influenzae and Chlamydia spp. (4,6,30,33). The PDF inhibitor NVP-PDF386 was recently tested against more than 1,000 clinical isolates for potency and spectrum of activity.…”

Section: Discussionmentioning

confidence: 99%

Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance

Fritsche

Sader

Cleeland

et al. 2005

Antimicrob Agents Chemother

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LBM415 (NVP PDF-713) is the first member of the peptide deformylase (PDF) inhibitor class being developed for clinical trials as a parenteral and oral agent for treatment of community-acquired respiratory tract disease and serious infections caused by antimicrobial-resistant gram-positive cocci. In this study susceptibility testing results from 1,306 recent clinical isolates selected to overrepresent resistance trends among the species were summarized. All staphylococci (153 strains; MIC at which 90% of isolates were inhibited [MIC 90 ], 2 g/ml), Streptococcus pneumoniae (170 strains; MIC 90 , 1 g/ml), other streptococci (150 strains; MIC 90 , 1 g/ml), enterococci (104 strains; MIC 90 , 4 g/ml), Moraxella catarrhalis (103 strains; MIC 90 , 0.5 g/ml), and Legionella pneumophila (50 strains; MIC 90 , 0.12 g/ml) were inhibited at <8 g of LBM415/ml, as were 97% of Haemophilus influenzae isolates (300 strains; MIC 90 , 4 to 8 g/ml). Among other bacterial groups, 100% of gram-positive and -negative anaerobes, including 22 Bacteroides spp. strains (31 strains total; MIC 90 , 1 g/ml), were inhibited by <4 g/ml, whereas Enterobacteriaceae (112 strains) and most nonfermentative bacilli (107 strains) were not inhibited at readily achievable concentrations. The compound was found to have a dominantly bacteriostatic action, and spontaneous single-step mutational rates occurred at low levels (10 ؊6 to <10 ؊8 ). Drug interaction studies failed to identify any class-specific synergistic interactions, nor were antagonistic interactions observed. Variations in broth and agar MIC test conditions demonstrated that, whereas the agar-based method trended towards a 1-log 2 dilution-higher MIC than the broth method and was inoculum dependent, other variations in incubation environment, medium supplements, pH, or calcium concentration had little influence on LBM415 MIC results. Use of the efflux inhibitor phe-arg-␤-naphthylamide showed an average of 1 log 2 dilution decrease in H. influenzae MICs, demonstrating the contribution of efflux pumps in influencing susceptibility to PDF inhibitors. The in vitro activity of LBM415 against targeted bacterial species, including resistant subsets, and other laboratory characteristics of this novel compound demonstrate the potential of PDF inhibitors as a new class of antimicrobial agents.

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Section: Discussionmentioning

confidence: 99%

Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance

Fritsche

Sader

Cleeland

et al. 2005

Antimicrob Agents Chemother

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“…For the pharmacodynamic calculations, the concentrations of levofloxacin required to inhibit 90% (MIC 90 ) of the following potential respiratory pathogens were used: H. influenzae 0.03 g/mL [45], Moraxella catarrhalis 0.06 g/mL [45], C. pneumoniae 0.25 g/mL [11], S. pneumoniae 1.0 g/mL [45] and M. pneumoniae 2.0 g/mL [46]. PK/PD indices, as suggested by Mouton et al [47], were used to calculate the C max /MIC 90 and AUC/MIC 90 ratios.…”

Section: Statistical Pharmacokinetic and Pharmacodynamic Analysesmentioning

confidence: 99%

“…It is active against most strains of Gram-positive organisms such as penicillin-susceptible and -resistant Streptococcus pneumoniae, Enterococcus faecalis, methicillinsusceptible Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes as well as Gram-negative rods such as Haemophilus influenzae, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens and Acinetobacter baumannii. It is also active against causes of atypical respiratory infection such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae [1][2][3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Intrapulmonary pharmacokinetics and pharmacodynamics of high-dose levofloxacin in healthy volunteer subjects

Conte

Golden

McIver

et al. 2006

International Journal of Antimicrobial Agents

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“…Macrolides exhibit excellent in vitro activity against atypical respiratory pathogens, and have traditionally been considered drugs of first choice for infections due to atypical pathogens [15][16][17][18][19][20][21][22][23]. Against contemporary isolates of C. pneumoniae, the minimum inhibitory concentration minimal inhibitory concentration of 90% bacteria values of the macrolides (erythromycin, roxithromycin, clarithromycin and azithromycin) are typically in the range of 0.016-0.5 mg?L -1 [15,21,22,24,25].…”

Section: In Vitro Susceptibilitymentioning

confidence: 99%

“…Against contemporary isolates of C. pneumoniae, the minimum inhibitory concentration minimal inhibitory concentration of 90% bacteria values of the macrolides (erythromycin, roxithromycin, clarithromycin and azithromycin) are typically in the range of 0.016-0.5 mg?L -1 [15,21,22,24,25]. Macrolides are especially potent against strains of M. pneumoniae, with recent studies showing MIC90 values of 0.0019, 0.0019 and 0.0039 mg?L -1 for erythromycin, clarithromycin and roxithromycin respectively [19], and of v0.0005 mg?L -1 for azithromycin [15].…”

Section: In Vitro Susceptibilitymentioning

confidence: 99%

Atypical pathogens and respiratory tract infections

Blasi¹

2004

Eur Respir J

110

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The atypical respiratory pathogens Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila are now recognised as a significant cause of acute respiratory-tract infections, implicated in community-acquired pneumonia, acute exacerbations of chronic bronchitis, asthma, and less frequently, upper respiratory-tract infections.Chronic infection with C. pneumoniae is common among patients with chronic obstructive pulmonary disease and may also play a role in the natural history of asthma, including exacerbations. The lack of a gold standard for diagnosis of these pathogens still handicaps the current understanding of their true prevalence and role in the pathogenesis of acute and chronic respiratory infections.While molecular diagnostic techniques, such as polymerase chain reaction, offer improvements in sensitivity, specificity and rapidity over culture and serology, the need remains for a consistent and reproducible diagnostic technique, available to all microbiology laboratories.Current treatment guidelines for community-acquired pneumonia recognise the importance of atypical respiratory pathogens in its aetiology, for which macrolides are considered suitable first-line agents. The value of atypical coverage in antibiotic therapy for acute exacerbations of chronic bronchitis and exacerbations of asthma is less clear, while there is no evidence to suggest that atypical pathogens should be covered in antibiotic treatment of upper respiratory-tract infections. The term "atypical pathogen" most commonly refers to Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. Once believed to be of little clinical significance, a wealth of data accumulated over the past decade suggests that these are important respiratory pathogens in a wide range of respiratory-tract infections (RTIs) and are capable of causing severe, as well as mild-to-moderate, illness.Although the role of atypical pathogens [1], and of C. pneumoniae in particular [2], has been reviewed previously, there has been little focus on appropriate coverage of these pathogens in treatment decisions for patients with RTIs. In addressing this issue, this review examines the role of atypical pathogens in the aetiology of upper and lower RTIs, in both adults and children, and discusses the value of appropriate coverage of these pathogens in empirical antibiotic prescribing.

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In Vitro Activity of a New Antibiotic, NVP-PDF386 (VRC4887), against Chlamydia pneumoniae

Cited by 24 publications

References 4 publications

Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance

Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance

Intrapulmonary pharmacokinetics and pharmacodynamics of high-dose levofloxacin in healthy volunteer subjects

Atypical pathogens and respiratory tract infections

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