Comparative in vitro activity of garenoxacin against Chlamydia spp.

Donati, Manuela; Pollini, Gian Matteo; Sparacino, Monica; Fortugno, M. T.; Laghi, E.; Cevenini, Roberto

doi:10.1093/jac/dkf145

Cited by 32 publications

(20 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, C. pneumoniae growing in the polarized Calu-3 cultures appeared to be very resistant to doxycycline exposure (MBC Ͼ 2 g/ml), whereas in the flat Calu-3 cultures, an MBC as low as 0.06 g/ml was detected. The inhibitory concentrations are in accordance with those reported earlier for some C. pneumoniae isolates (10) but are somewhat higher than the more recently reported doxycycline MIC values for C. pneumoniae (2,34), most probably due to the different evaluation methods used.…”

Section: Vol 78 2010 C Pneumoniae Infection In Polarized Epitheliasupporting

confidence: 91%

Chlamydia pneumoniae Infection in Polarized Epithelial Cell Lines

Törmäkangas

Markkula

Lounatmaa³

et al. 2010

Infect Immun

View full text Add to dashboard Cite

We set up a polarized cell culture model to study the pathogenicity of a common respiratory tract pathogen, Chlamydia pneumoniae. Immunofluorescence staining of ZO-1 (a tight junction protein) and Na ؉ K ؉ ATPase (a protein pump localized at the basolateral membrane in the polarized epithelial cells), as well as TER measurements, suggested that the filter-grown Calu-3 cells, but not the A549 cells, were polarized when grown on collagen-coated membranes. Both the flat and the filter-grown cultures were infected with C. pneumoniae. Infection in the polarized Calu-3 cultures produced more C. pneumoniae genome equivalents than infection in the flat cultures. However, this progeny was not as infective as that in the flat cultures. The maximum amount of C. pneumoniae was detected at 6 days postinfection in the filter-grown A549 cells, indicating a slower developmental cycle than that observed in the flat A549 cultures. The effect of cycloheximide on the growth of C. pneumoniae in the polarized cells was negligible. Furthermore, the infection in the polarized Calu-3 cells was resistant to doxycycline, and several cytokines were released mainly on the apical side of the polarized cells in response to C. pneumoniae infection. These findings indicate that the growth of chlamydiae was altered in the filter-grown epithelial culture system. The diminished production of infective progeny of C. pneumoniae, together with the resistance to doxycycline and polarized secretion of cytokines from the infected Calu-3 cells, suggests that this model is useful for examining epithelial cell responses to C. pneumoniae infection, and it might better resemble in vivo infection in respiratory epithelial cells.

show abstract

Section: Vol 78 2010 C Pneumoniae Infection In Polarized Epitheliasupporting

confidence: 91%

Chlamydia pneumoniae Infection in Polarized Epithelial Cell Lines

Törmäkangas

Markkula

Lounatmaa³

et al. 2010

Infect Immun

View full text Add to dashboard Cite

show abstract

“…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%

“…However, their in vitro potency is often inferior to that of the macrolides and fluoroquinolones [15,16,19,23]. Furthermore, there is evidence to suggest that strains of M. pneumoniae are developing resistance to tetracycline [23].…”

Section: In Vitro Susceptibilitymentioning

confidence: 99%

Atypical pathogens and respiratory tract infections

Blasi¹

2004

European Respiratory Journal

109

View full text Add to dashboard Cite

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.

show abstract

“…The methods used in those studies either differed from those used in our study or were not reported, and therefore, a comparison of the results must be made with caution because of possible methodological differences (11,24). However, all garenoxacin MICs reported have ranged from Ͻ0.008 to 0.015 g/ml, and MBCs were equal to the MIC or were 1 twofold dilution higher, while the levofloxacin and moxifloxacin MICs were higher, usually 2 to 5 twofold dilutions for MIC testing (8,9,27).…”

Section: Discussionmentioning

confidence: 57%

“…Three isolates tested in both studies had the same susceptibilities in both studies. Three other studies reported on the garenoxacin MICs for small numbers of C. pneumoniae isolates (8,9,27). The methods used in those studies either differed from those used in our study or were not reported, and therefore, a comparison of the results must be made with caution because of possible methodological differences (11,24).…”

Section: Discussionmentioning

confidence: 78%

In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA

Smith

Baltch

Ritz

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

We studied 20 Chlamydia pneumoniae isolates obtained from respiratory sites and atheroma tissue of patients from various geographic areas to determine the susceptibilities of these isolates to a new desfluoroquinolone, garenoxacin, and to levofloxacin. In addition, we assessed the cultures with these isolates by PCR for the presence or absence of Mycoplasma sp. DNA. Both the MIC at which 90% of isolates are inhibited (MIC 90 ) and the minimal bactericidal concentration at which 90% of isolates are killed (MBC 90 ) for garenoxacin were 0.06 g/ml, and both the MIC 90 and the MBC 90 for levofloxacin were 2.0 g/ml. The activity of garenoxacin against C. pneumoniae was 32-fold greater than that of levofloxacin. Mycoplasma sp. DNA was detected by PCR in 17 of 20 cultures. Mycoplasma amplicons from five Mycoplasma DNA-positive C. pneumoniae cultures were sequenced and found to represent four Mycoplasma species. Our data demonstrate that C. pneumoniae cultures frequently contain Mycoplasma DNA and that its presence in C. pneumoniae cultures does not appear to affect the susceptibility results for the two fluoroquinolones that we tested.Chlamydia pneumoniae is a common cause of acute respiratory illnesses, including pharyngitis, sinusitis, bronchitis, and pneumonia, in children and adults (10). In addition, chronic C. pneumoniae infection is implicated in diseases such as atherosclerosis and its complications (16). C. pneumoniae respiratory infections are usually treated with a macrolide, an azalide, or tetracycline antimicrobials (11). However, fluoroquinolone antibacterial agents are known to be active against C. pneumoniae in vitro. A small number of fluoroquinolones have been moderately successful (70 to 80% bacterial elimination) for the treatment of culture-proven C. pneumoniae infections in humans (12).Garenoxacin (BMS-284756) is a new des-F(6)-quinolone with excellent activity against common respiratory pathogens (9). We studied the in vitro activities of garenoxacin against 20 C. pneumoniae isolates obtained from both respiratory tract and atheroma tissue sources. In addition, because the presence of Mycoplasma is common in reference C. pneumoniae cultures (13, 18) and is known to affect a variety of cell functions (5, 22), we were concerned about the potential effect of the presence of Mycoplasma in HEp-2 cells on antibiotic susceptibility testing with C. pneumoniae (5,18). Therefore, we tested the original cultures, as well as the amplified preparations of C. pneumoniae used for MIC testing, for the presence of Mycoplasma DNA using PCR targeting the 16S rRNA gene (6, 26). We then identified, using DNA sequencing techniques and comparison of the sequences to those in sequence databases, the species of Mycoplasma present in selected cultures. Eleven isolates were obtained from the University of Washington, Seattle: AR388, AR277, AR231, AR427, LR65, Ka50, Ka66, AC14, AC51, ER115, and AR458. Isolate A03SEG was obtained from the University of Louisville, Louisville, Ky. Aliquots of each isolate were prepared for s...

show abstract

Comparative in vitro activity of garenoxacin against Chlamydia spp.

Cited by 32 publications

References 11 publications

Chlamydia pneumoniae Infection in Polarized Epithelial Cell Lines

Chlamydia pneumoniae Infection in Polarized Epithelial Cell Lines

Atypical pathogens and respiratory tract infections

In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA

Contact Info

Product

Resources

About