Comparative in vitro activity of PD 127391, a new fluoroquinolone agent, against susceptible and resistant clinical isolates of gram-positive cocci

Miranda, Abraham G.; Wanger, Audrey; Singh, Kavindra V.; Murray, Barbara E.

doi:10.1128/aac.36.6.1325

Cited by 23 publications

(10 citation statements)

References 16 publications

(28 reference statements)

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“…A number of broad-spectrum quinolones possess activity against gram-positive bacterial species and display pharmacokinetic parameters indicating potential utility for therapy of systemic infections. The data presented in this report reveal high levels of in vitro activities (MIC 90 s, Յ0.5 g/ml) against E. faecalis for the new fluoroquinolones clinafloxacin, CI-990, and PD 138312, and our values are consistent with those reported earlier (1,7,12). In vitro clinafloxacin, CI-990, and PD 138312 activities were consistently severalfold higher than those of ciprofloxacin and ofloxacin.…”

supporting

confidence: 82%

In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD 138312 versus enterococci

Cohen¹,

Yoder²,

Huband³

et al. 1995

Antimicrob Agents Chemother

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Certain new fluoroquinolones have high activity against enterococci. Against Enterococcus faecalis (n ‫؍‬ 18), MICs at which 90% of the isolates were inhibited were as follows (in micrograms per milliliter): clinafloxacin, 0.125; CI-990, 0.5; and PD 138312, 0.25 (compared with 1 g/ml for ciprofloxacin and 2 g/ml for ofloxacin). Strains producing ␤-lactamase or that were vancomycin resistant or resistant to high-level gentamicin were not quinolone cross-resistant. The drugs were bactericidal and were unaffected by 50% human serum. Oral efficacies (in milligrams per kilogram of body weight for 50% protective doses) in lethal mouse infections with quinolone-susceptible strains were 4.3 to 24 for clinafloxacin, 7.2 to 39 for CI-990, 7.2 to 76 for PD 138312, and 41 to >100 for ciprofloxacin; when the drugs were given subcutaneously, the order was similar and values ranged from 1.1 to 12.5. Clinafloxacin, CI-990, and PD 138312 may have therapeutic potential in systemic enterococcal infections in humans.Enterococci have gained increasing recognition as primary human pathogens. Resistance to penicillins, aminoglycosides, and glycopeptides (6,13,14,(20)(21)(22) and to quinolones such as ciprofloxacin (18) Frequencies of single-step spontaneous mutations were determined in duplicate by spreading ϳ10 11 CFU onto MuellerHinton agar (Difco Laboratories) containing drugs; colonies were counted after 24 to 72 h of incubation. Multistep resistance selection measured increases in MICs over daily transfers in 5-ml volumes (0.1-ml inoculum harvested from a tube

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supporting

confidence: 82%

In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD 138312 versus enterococci

Cohen¹,

Yoder²,

Huband³

et al. 1995

Antimicrob Agents Chemother

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“…When the ciprofloxacin-resistant strains are removed from our analysis, the MIC90 for both gentamicin-susceptible and gentamicin-resistant strains is 0.125 p,g/ml. This MIC90 is equivalent to that previously reported with WIN 57273 for ciprofloxacin-susceptible E. faecalis (7) and comparable with or below the MIC90s for other new fluoroquinolones (1,5,8,15,19). Time-kill experiments were performed with three phenotypically distinct isolates.…”

mentioning

confidence: 91%

Bactericidal activity of the fluoroquinolone WIN 57273 against high-level gentamicin-resistant Enterococcus faecalis

Noskin

Mehl

Warren

1993

Antimicrob Agents Chemother

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The fluoroquinolone WIN 57273 showed identical bactericidal activities (MBC for 90%v of the strains = 0.25 ug/ml) for bacteremic strains ofEnterococcusfaecalis with and without high-level gentamicin resistance. WIN 57273 was bactericidal in time-kill measurements with highly gentamicin-resistant, ciprofloxacin-susceptible strains of E. faecalis. However, WIN 57273 was indifferent with penicillin for gentamicin-resistant E. faecalis and was not bactericidal for ciprofloxacin-resistant E. faecalis. antimicrobial agent which inhibits visible growth. The MBC is defined as the lowest concentration of antibiotic that kills .99.9% of the original inoculum. For our study, MBCs were determined by subculturing clear culture broths onto antibiotic-free Mueller-Hinton agar plates. Three E. faecalis strains were used for time-kill measurements: LS-31, which demonstrated high-level gentamicin resistance, high-level streptomycin resistance, and ciprofloxacin susceptibility (Gmr Smr Cips); LS-45, which demonstrated high-level gentamicin resistance, streptomycin susceptibility, and ciprofloxacin susceptibility (Gmr Sms Cips); and LS-49, which demonstrated high-level gentamicin resistance, streptomycin susceptibility, and ciprofloxacin resistance (Gmr Sm, Cipr). Time-kill measurements (10) were performed in triplicate with each strain to determine the extents and rates of killing by WIN 57273 alone or with penicillin and by penicillin with and without an aminoglycoside. Antibiotics were tested at the following concentrations: penicillin, 10 U/ml; WIN 57273, 2 jig/ml; gentamicin, 5 ,ug/ml; and streptomycin, 25 p,g/ml. Antibiotic carryover was eliminated by the use of a minimum dilution factor of at least 100. Organisms were diluted in 20 ml of cation-supplemented Mueller-Hinton broth to give a final inoculum of 5 x 105 CFU/ml and incubated with mechanical shaking at 35°C. At 0, 4, 8, and 24 h after inoculation, 0.5-ml samples were taken from the broth and passed through serial 10-fold dilutions. From each dilution, a 0.1-ml sample was spotted and spread over the entire surface of antibiotic-free agar. A 0.1-ml sample of undiluted broth was also directly inoculated to antibioticfree agar. Colonies were counted after 24 h of incubation. The minimum accurately countable bacterial population was 50 CFU/ml. Bactericidal activity in time-kill measurements is defined as a .3 log10 increase in bacterial killing at 24 h of incubation. Synergy is defined as a .2 logl0 increase in killing by a combination of two antibiotics compared with the killing by the active antibiotic alone, with the other antibiotic present in a concentration which does not affect the growth curve of the organism. If the result of using two drugs in time-kill measurements equals the effect of the more active antibiotic used alone (s1 loglo increase), the antibiotic combination is considered to be indifferent (2).The activity of WIN 57273 was compared with those of other fluoroquinolones, as shown in

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“…Most new fluoroquinolones are at least fourfold more active than ciprofloxacin against staphylococci, including methicillinresistant strains, regardless of susceptibility to unrelated drugs (Table 1 [ciprofloxacin is shown as the progenitor fluoroquinolone, as it is widely used in the United States and Europe]) (2,4,6,8,9,21,25,39). All of the new agents described in Table 1 inhibit 90% of staphylococci at concentrations of <0.…”

Section: Staphylococcimentioning

confidence: 99%

New quinolones and gram-positive bacteria

Piddock

1994

Antimicrob Agents Chemother

108

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Comparative in vitro activity of PD 127391, a new fluoroquinolone agent, against susceptible and resistant clinical isolates of gram-positive cocci

Cited by 23 publications

References 16 publications

In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD 138312 versus enterococci

In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD 138312 versus enterococci

Bactericidal activity of the fluoroquinolone WIN 57273 against high-level gentamicin-resistant Enterococcus faecalis

New quinolones and gram-positive bacteria

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