Antibacterial Spectrum of a Novel Des-Fluoro(6) Quinolone, BMS-284756

Fung‐Tomc, Joan; Minassian, Beatrice; Kolek, B; Huczko, E; Aleksunes, Lauren M.; Stickle, Terry M.; Washo, Thomas; Gradelski, Elizabeth; Valera, Lourdes; Bonner, Daniel P.

doi:10.1128/aac.44.12.3351-3356.2000

Cited by 161 publications

(126 citation statements)

References 6 publications

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“…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: Discussioncontrasting

confidence: 40%

“…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: 50%

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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

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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...

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Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 50%

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

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“…It has been shown to have activity against a wide range of clinical isolates (1,7,12,34), and in particular, garenoxacin has been shown to have good activity against Staphylococcus aureus, both methicillin sensitive and resistant (6), and the respiratory pathogens Streptococcus pneumoniae (26), Haemophilus influenzae, and Moraxella catarrhalis (8). The activity of garenoxacin has been further assessed against strains of S. aureus with specific topoisomerase mutations (21), and more recently, it has been shown that garenoxacin has similar potency against both topoisomerase IV and gyrase (16) (dual-targeting quinolone), thus requiring mutations in both topoisomerases for resistance to occur (29).…”

mentioning

confidence: 99%

Antimicrobial Activities of Garenoxacin (BMS 284756) against Asia-Pacific Region Clinical Isolates from the SENTRY Program, 1999 to 2001

Christiansen

Bell

Turnidge

et al. 2004

Antimicrob Agents Chemother

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Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin. Garenoxacin was four-to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 g/ml. Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin. For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA). Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 g/ml for only 9% of them. For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries. No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 g/ml. There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 g/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated. No mutations conferring high-level resistance were detected. Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region. In particular, it has good activity against S. aureus and S. pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance.

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“…Moraxella catarrhalis is of particular importance as a cause of CAP in patients with chronic bronchitis. 4,5 Since, organisms express themselves in a stereotypical fashion, an etiologic classification of pneumonia correlates with the patient's signs and symptoms. Elderly patients will often have only the infiltrate, which is not always accompanied by fever or leukocytosis.…”

Section: Discussionmentioning

confidence: 99%