In Vitro Antianaerobic Activity of DX-619, a New Des-Fluoro(6)Quinolone

Abstract

The in vitro activity of DX-619, a new des-F(6) quinolone, against anaerobic bacteria was evaluated. DX-619 showed potent activity against Bacteroides, Prevotella, Fusobacterium, Micromonas, Actinomyces, and Clostridium spp., with MIC 50 s/MIC 90 s of <0.03 to 0.25/<0.03 to 1 g/ml, respectively. DX-619 was also active against imipenem-resistant Bacteroides spp., with MIC 50 s/MIC 90 s of 0.25/1 g/ml, respectively.Older fluoroquinolones, such as ciprofloxacin and ofloxacin, are inactive or only partially active against anaerobic bacteria (7,11,12,15,20,23,25,26). Newer quinolones, such as sparfloxacin and levofloxacin (LVX), have improved in vitro activities against anaerobic bacteria but still have limited activities against certain gram-positive and gram-negative anaerobic bacilli (3,7,8,11,12,15,23,25). Some of the newer fluoroquinolones are much more active to both gram-positive and gram-negative anaerobic bacteria (3,8,11,12,15,20,26). DX-619 is a new derivative of quinolone, defined as a des-F(6) quinolone that lacks the six-position fluorine characteristic of the previous generation of fluoroquinolones. It has potent antibacterial activity against multidrug-resistant, gram-positive aerobic bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (2, 5). Other compounds of this new type of quinolone showed potent activities against gram-positive and gram-negative aerobic and anaerobic bacteria (23, 25). There have been few reports on the antibacterial activity of DX-619 against anaerobic bacteria (16). We evaluated the in vitro activity of DX-619 against anaerobic gram-positive and gram-negative species in comparison with that of several reference agents.For the investigation of the anaerobic antibacterial spectrum, a total of 71 gram-positive and gram-negative reference strains (64 species in 25 genera) of anaerobic bacteria and some fastidious microaerophilic anaerobes were examined. Those reference strains include strains obtained from the American Type Culture Collection (ATCC; Virginia), the German Collection of Microorganisms and Cell Cultures (DSMZ; Braunschweig, Germany), the Japan Collection of Microorganisms (JCM; Saitama, Japan), the National Collection of Type Cultures (NCTC; Wiltshire, United Kingdom), and VPI (Virginia Polytechnic Institute and State University, Virginia) and some characteristic clinical strains belong to GAI (the culture collection of our laboratory). A total of 268 clinical strains isolated from various sources (including intra-abdominal infection, head and neck space infection, pleuropulmonary infection, and soft-tissue infection) between 1994 and 2004 were also studied. Isolates were identified by standard criteria (9, 10, 22). In addition, the activities of DX-619 against 11 stock strains of the imipenem (IPM)-resistant Bacteroides fragilis group (10 Bacteroids fragilis and 1 B. thetaiotaomicron strain) were also studied.The antibacterial agents used in this study were obtained as powders of known potency from their respective m...

Persistent microbial dysbiosis in preterm premature rupture of membranes from onset until delivery

“…The transient nature of the PPROM microbiome is consistent with the idea of an ecology that is out of equilibrium. Prevotella and Peptoniphilus emerge as taxa of particular interest in PPROM given their prevalence at presentation and persistence throughout treatment, evidence of prominent role in persistent bacterial vaginosis and preterm labor ( Marrazzo et al, 2008 ; Smayevsky et al, 2001 ; Wang et al, 2013 ; Mikamo et al, 1999 ) and display of broad-spectrum antibiotic resistance ( Sherrard et al, 2013 ; Tanaka et al, 2006 ). The highly variable placental microbiome recovered and the weak correlation with the maternal microbiome raises the possibility that the uterine microbiome may be an independent driver of the placental microenvironment.…”

Peer Review #2 of "Persistent microbial dysbiosis in preterm premature rupture of membranes from onset until delivery (v0.1)"

“…The transient nature of the PPROM microbiome is consistent with the idea of an ecology that is out of equilibrium. Prevotella and Peptoniphilus emerge as taxa of particular interest in PPROM given their prevalence at presentation and persistence throughout treatment, evidence of prominent role in persistent bacterial vaginosis and preterm labor (Marrazzo et al 2008); (Smayevsky et al 2001); (Wang et al 2013); (Mikamo et al 1999) and display of broadspectrum antibiotic resistance (Sherrard et al 2013); (Tanaka et al 2006). The highly variable placental microbiome recovered and the weak correlation with the maternal microbiome raises the possibility that the uterine microbiome may be an independent driver of the placental microenvironment.…”