Comparative in vitro activity of DU-6859a, a new fluoroquinolone agent, against gram-positive cocci

Abstract

The in vitro activity of DU-6859a (DU), a new fluoroquinolone agent, was evaluated against 233 gram-positive cocci and was compared with those of ciprofloxacin, vancomycin, nafcillin, and ampicillin. The MICs of DU for 90% of the staphylococci tested were <0.06 ,ug/ml. All of the groups A and B and viridans group streptococci were inhibited by sO.125 ,ug of DU per ml, which was 32-fold more active than ciprofloxacin. On T-3761 (10), OPC-17116 (14), AM-1155 (13), E-4497 (11), CP-74667 (16), and CP-99219 (6). DU appears to be one of the most active of these agents (25). In the present study, the antibacterial activity of DU was investigated and compared with the activities of ciprofloxacin, vancomycin, nafcillin, and ampicillin against gram-positive cocci representing a broad range of antimicrobial resistance patterns. DU in powder form was provided by Daiichi Pharmaceutical Co., Tokyo, Japan; ciprofloxacin was provided by Miles Pharmaceuticals, West Haven, Conn.; and vancomycin, nafcillin, and ampicillin were purchased from Sigma Chemical Co., St. Louis, Mo. All staphylococci and streptococci were collected from hospitals in Houston, Tex., between 1989 and The bactericidal activity of DU against 7 E. faecalis and 3 E. faecium isolates was determined. Overnight cultures were diluted to yield a final inoculum of _107 CFU/ml in flasks containing brain heart infusion broth. The concentration of DU (2 ,ug/ml) used in the time-kill assays was recommended by the manufacturer to represent levels achievable in human serum. Samples (100 ,ul each) were withdrawn from flasks following 0, 4, and 24 h of incubation at 37°C with agitation. Undiluted and serially diluted samples were plated onto brain heart infusion agar plates. The lowest detectable number of organisms was 10 CFU/ml. The agar plates were incubated at 37°C for 24 h before CFU were counted. Bactericidal activity was defined as a reduction in CFU of >3 loglo. A drug carryover effect was excluded by showing that there was less than 5% difference in colony counts when 100 ,ul of 103 to 104 CFU/ml was plated onto antibiotic-free plates in the absence or presence of DU (2 ,ug/ml).The results of susceptibility testing with DU and a comparison of these results with the results of testing with other antibiotics are shown in Table 1. Fifty percent of the staphylococcal isolates tested were inhibited by .0.03 ,ug of DU per ml, and 90% were inhibited by .0.06 ,ug/ml (Table 1). The MICs for 90% of strains tested (MIC90s) were higher for the methicillin-resistant subgroups of S. aureus and coagulasenegative staphylococci than for the methicillin-susceptible sub-

New Directions in Antibacterial Research

“…faecalis , 0.5 μg/mL against E . faecium , and 1 μg/mL against MRSA . A recent study provided a possible explanation for DU-6859a being more active than other currently available quinolones against quinolone-resistant clinical isolates of P .…”

“…85 The in vitro activity of DU-6859a was evaluated and the MIC 90 values were found to be e0.06 µg/mL against staphylococci, e0.125 µg/mL against all groups A and B streptococci, 1 µg/mL against E. faecalis, 0.5 µg/mL against E. faecium, and 1 µg/mL against MRSA. 86 A recent study provided a possible explanation for DU-6859a being more active than other currently available quinolones against quinolone-resistant clinical isolates of P. aeruginosa. The authors suggest that this activity is due to strong inhibitory effects against mutant quinolone-resistant DNA gyrases.…”

Antimicrobial susceptibility of coagulase-negative staphylococci

“…However, although many of the newer fluoroquinolones have more potent antistaphylococcal activities, fluoroquinolone-resistant mutants have emerged following exposure to the drugs. In addition, ciprofloxacin-resistant CoNS have markedly reduced susceptibility to most of the newer quinolones (40, 47,74) and an increased frequency of mutation to resistance (74). Increasing levels of resistance to older agents may preclude the use of these newer compounds.…”

Studies on 6-Aminoquinolones: Synthesis and Antibacterial Evaluation of 6-Amino-8-methylquinolones

“…In addition, the majority of methicillin-resistant staphylococci (especially Staphylococcus aureus ) are now resistant to all of the currently available quinolones . Therefore, recent efforts have been directed toward the synthesis of compounds which have greater activities against these organisms, such as tosufloxacin, , clinafloxacin, , DU 6859, , Bay 3118, PD 138312, and PD 140248 . On the basis of these considerations, we hoped that with the new series of 6-aminoquinolones, we could obtain compounds with strong activity against all Gram-positives and which would also be effective against resistant strains such as methicillin-resistant staphylococci.…”