The activity of enoxacin against clinical bacterial isolates in comparison with that of five other agents, and factors affecting that activity

The in vitro and in vivo antibacterial activities of a new tricyclic fluoroquinolone, E-4497 [S(-)-9-fluoro-3-methyl-10-(3-amine-3-methyl-azetidin-1 -yl)-7-oxo-2,3-dihydro-7H-pyrido-(1,2,3-de) -1,4-benzoxazine-6-carboxylic acid], were evaluated in comparison with those of DR-3355 [S-(-)-ofloxacin], norfloxacin, and ciprofloxacin. E-4497 was more potent than norfloxacin and as potent as or more potent than DR-3355 and ciprofloxacin against Staphylococcus spp., Streptococcus spp., and Enterococcusfaecalis. With the exception of Providencia spp., E-4497 inhibited 90% of the Enterobacteriaceae at .0.25 ,ug/ml. Against enteric bacteria, E-4497 was similar in potency to norfloxacin but less potent than DR-3355 and ciprofloxacin. For Pseudomonas aeruginosa, the MICs of E-4497, DR-3355, norfloxacin, and ciprofloxacin for 90% of strains were 2, 2, 4, and 0.5 ,ug/ml, respectively. Against Clostridium perfringens and Bacteroides fragilis, E-4497 (MICs for 90% of strains, 2 and 8 ,ug/ml, respectively) was two-to fourfold more active than norfloxacin and ciprofloxacin. E-4497 activity decreased moderately in the presence of 10 mM Mg2+. Urine at pH 5.5 caused a significant decrease in activity compared with urine at pH 7.2. However, the presence of serum either had no effect or increased the activity of E-4497. In general, E-4497 was bactericidal at the MIC. In systemic infections with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa in mice, the protective effect of E-4497 was generally greater than that of norfloxacin and comparable to those of DR-3355 and ciprofloxacin.

Section: Resultsmentioning

confidence: 99%

In vitro and in vivo antibacterial activities of E-4497, a new 3-amine-3-methyl-azetidinyl tricyclic fluoroquinolone

Gargallo-Viola

Esteve

Llovera

et al. 1991

“…Reeves et al (14) and Ratcliffe and Smith (N. T. Ratcliffe and J. T. Smith, 4th Mediterranean Congress of Chemotherapy, abstr. no.…”

mentioning

confidence: 99%

Influence of medium and method on the in vitro susceptibility of Pseudomonas aeruginosa and other bacteria to ciprofloxacin and enoxacin

Blaser¹,

Dudley²,

Gilbert³

et al. 1986

Ciprofloxacin and enoxacin were two-to fourfold less active against Pseudomonas aeruginosa in calcium-and magnesium-supplemented broth compared with unsupplemented broth regardless of inoculum size, presence of serum, or use of inhibitory or bactericidal endpoints (P < 0.01). The effect of cation supplementation was less pronounced and less consistent for Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus.Several new fluorinated piperazinyl quinolone compounds have been shown to have potent antibacterial effects, most notably against gram-negative bacilli (7). However, available pharmacokinetic and microbiological data suggest that the differences between achievable serum or tissue concentrations in vivo and inhibitory or bactericidal concentrations for certain pathogens (e.g., Pseudomonas aeruginosa) may be small. Therefore, relatively small changes in activity found in tests performed by standardized methods in media that more accurately reflect in vivo conditions could be important. The objective of this study was to evaluate the in vitro activities of two new quinolone agents, ciprofloxacin (Miles Pharmaceuticals, West Haven, Conn.) and enoxacin (Warner-Lambert Pharmaceuticals, Ann Arbor, Mich.) in four different media using standardized susceptibility-testing methods.Broth dilution studies were conducted by the microtechnique with two inoculum sizes (8, 11). Three liquid media were used: Mueller-Hinton broth (MHB; Difco Laboratories, Detroit, Mich.), MHB supplemented with calcium (2.5 mM/liter) and magnesium (1.1 mM/liter) (MHB-S), and MHB-S combined 1:1 with fresh heat-inactivated human serum (MHB-S/HS) (18 transformed values) in each medium, the magnitude of increase in MIC or MBC, and the ratios of MBC to MIC for each drug in MHB-S and MHB-S/HS were compared with data obtained in MHB by using the Wilcoxon signed-rank test for matched pairs. Differences were considered significant at the P < 0.05 level for a two-tailed test. The activities of ciprofloxacin and enoxacin against nine strains of P. aeruginosa in the four media tested are summarized in Table 1. Cation supplementation of MHB with or without human serum significantly reduced the activities of both drugs (P < 0.01). MICs and MBCs showed a median two-to fourfold increase at both inoculum sizes tested. The magnitudes of reduction of activity in supplemented broth were similar for ciprofloxacin and enoxacin (P > 0.05). The median MICs obtained by the agar dilution technique were two times higher than in MHB for ciprofloxacin (P < 0.05), whereas no significant difference was found with enoxacin (Table 1).Both quinolones were highly active against non-Pseudomonas strains, with all strains inhibited by 1 ,ug of ciprofloxacin and 2 ,ug of enoxacin per ml. The results obtained with the laboratory reference strains when tested with the larger inocula are presented in Table 2. Compared with P. aeruginosa, the effect of cation supplementation on the activities of the quinolones was quantitatively less pronounced and less consistent among th...

“…Enoxacin is a new naphthyridine fluoroquinolone antibiotic with potent activity in vitro against many gram-positive and gram-negative bacteria (10,18). Studies in normal volunteers have demonstrated that the bioavailabilities of several newer fluoroquinolones, including enoxacin, exceed 70% (12,16,22); however, the pharmacokinetics and bioavailabilities of many of these agents in elderly infected patients are not known.…”

mentioning

confidence: 99%

Pharmacokinetics and bioavailability of intravenous-to-oral enoxacin in elderly patients with complicated urinary tract infections

Marchbanks

Mikolich

Mayer

et al. 1990