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PubMed1990

[Therapeutic potential of ofloxacin in hospital medicine. A French multicenter study].

Bacteriological studies were carried out on samples taken from 1,824 patients in 12 departments of internal medicine (6 University Hospital Departments and 6 Regional Hospital Departments), over a period of six weeks. Four hundred and twenty-two samples were positive on culture. These included 189 urine samples, 81 samples from the respiratory tract and 71 blood samples for culture. Four hundred and forty-four bacterial strains were isolated (including 290 Gram- organisms, 146 Gram+ organisms, 6 intracellular and 2 anaerobic organisms) 427 of which were tested vis a vis ofloxacin. Seventy-five per cent of identified bacteria were susceptible to ofloxacin including 88% Gram- bacteria, 79% staphylococci and 17.5% streptococci. Bacteria resistant to ofloxacin were responsible for 16 out of 183 of infections originating in the community and 29 out of 116 of infections of nosocomial origin. Enterobacterial strains were tested vis a vis nalidixic acid and staphylococcal strains vis a vis oxacillin: 9 of the 30 strains resistant to nalidixic acid were susceptible to ofloxacin, 4 of the 18 strains resistant to oxacillin were susceptible to ofloxacin. These data confirm the therapeutic potential of ofloxacin in the treatment of common infections encountered in hospital medicine.

Bacteria, Anaerobic↗

PubMed1989

Pharmacokinetic analysis of single- or multiple-dose plasma drug concentration data with a microcomputer using multi-fraction absorption models.

A Basic program for multi-fraction absorption models was developed to link with another microcomputer program, MULTI, and was named MFA-MULTI. A main frame computer program SIMP, based on a simplex method using differential equations, was also operated using a microcomputer equipped with a FORTRAN compiler and a 8087 floating-point coprocessor. These two programs [MFA-MULTI and SIMP (M)] were applied to the analysis of plasma concentration data of several drugs with irregular absorption profiles. The results by MFA-MULTI and SIMP(M) for the single- or multiple-dose data were almost coincident with those obtained by a SIMP program. The result for nalidixic acid estimated using MFA-MULTI or PKM-MULTI was also compared. The plasma nalidixic acid concentration, with irregular absorption profiles due to characteristics of dissolution in the gastrointestinal tract, was found to be described by a two-fraction absorption model. The MFA-MULTI program was applied to the analysis of plasma cimetidine concentration data with double peaks in humans. Pharmacokinetic absorption behavior of a sustained-release preparation of theophylline after repetitive oral administration was adequately evaluated using MFA-MULTI. In addition, application of multi-fraction absorption models to population pharmacokinetics is discussed.

Administration, Oral↗

PubMed2005

Effect of quinolone treatment on selection and persistence of quinolone-resistant Escherichia coli in swine faecal flora.

AIMS: To study the effect of oral administration of a quinolone on emergence of resistance in an indicator bacterial species from faecal flora. METHODS AND RESULTS: Quinolone resistance was studied in Escherichia coli obtained from the faecal contents of pigs housed in nine commercial farrow-to-finish herds in France after administration of flumequine to sows. The percentage of quinolone-resistant E. coli increased in the faeces of sows after administration of flumequine (mean 21.78% at day 7 vs 6.42% before treatment for nalidixic acid) and then decreased (mean 12.6 and 10.4 at days 30 and 60, respectively for nalidixic acid), being not significantly different from initial values 1 month post-treatment. In young pigs, the proportion of resistant strains was lower and decreased over rearing period. Moreover, changes over time of both total E. coli and the proportion of resistant bacteria exhibited great inter-individual variability. CONCLUSIONS: Restoration of susceptible faecal flora occurred within 2 months after flumequine treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Effect of flumequine treatment of sows on the quinolone resistance of faecal E. coli of both sows and their progeny is noticeable but transitory.

Administration, Oral↗

PubMed2004

Analysis of gyrA mutations in quinolone-resistant and -susceptible Campylobacter jejuni isolates from retail poultry and human clinical isolates by non-radioactive single-strand conformation polymorphism analysis and DNA sequencing.

AIMS: The aims of this study were to characterize the molecular variations in the quinolone resistance-determining region (QRDR) of gyrA among quinolone-resistant and -susceptible Campylobacter jejuni isolates originating from foods of animal origin and human infections and to evaluate the suitability of the single-strand conformation polymorphism (SSCP) method as a screening method for molecular characterization of fluoroquinolone resistance. METHODS AND RESULTS: Alterations in QRDR of gyrA from 182 C. jejuni isolates were determined by nonradioisotopic SSCP analysis and direct sequencing. A total of 13 types of nucleic acid sequence combinations within the QRDR of the gyrA gene resulted in 11 different SSCP patterns. All nalidixic acid resistant strains possessed nucleotide substitution at either codon Thr-86 or Asp-90. Silent mutations were detected additionally. Thr-86 to Ile mutation was detected in all 139 ciprofloxacin resistant strains, which showed cross-resistance to nalidixic acid. CONCLUSIONS: The SSCP method is suitable for a molecular screening of quinolone resistant C. jejuni isolates and in combination with DNA sequencing suitable to detect genetic variations of the QRDR of gyrA. SIGNIFICANCE AND IMPACT OF STUDY: This study provides data of the genetic variations of the QRDR of gyrA from C. jejuni isolates of foods and human beings.

Animals↗

PubMed1987

In vitro antibacterial activity of irloxacin (E-3432) on clinical isolates.

Irloxacin (E-3432) is a new quinolone derivative. In this study, the activity of irloxacin was compared with that of nalidixic acid, norfloxacin and ciprofloxacin against strains of clinical isolates. Irloxacin showed greater in vitro activity than nalidixic acid, similar activity to norfloxacin and lower activity than ciprofloxacin. Against Staphylococcus, the MIC range of E-3432 was 0.06-1 mg/l, better than the other compounds studied.

Anti-Bacterial Agents↗

PubMed1975

A mutant of Eshcerchia coli K-12, URT-43, with a temperature-sensitive defect at the incision step of the excision repair mechanism.

URT-43, which has a defect in excision repair, exhibits a temperature-dependent ultraviolet survival. It was shown that URT-43 requires protein synthesis but not DNA synthesis for recovery, by examining recovery in a growth medium containing chloramphenicol or nalidixic acid. The recovery of irradiated bacteriophage lambda in URT-43 took place in a medium containing nalidixic acid at 30 degrees, but not at 41 degrees, and chloramphenicol prevented this recovery. These results seem to imply that the product of the mutated gene in URT-43 is labile. URT-43 was confirmed to have a temperature-sensitive mutation at the incision step of the excision repair mechanism by examining the nick formation of parental DNA in alkaline sucrose gradients. The release of pyrimidine dimers was reinvestigated directly by one- and two-dimensional paper-chromatography and indirectly by examining the distribution of DNA molecules synthesized after irradiation. Dimers were excised into the acid-soluble fraction when growing bacteria were incubated, but were not excised when in amino acid starved bacteria. These results suggest that URT-43 is a mutant slowly excising pyrimidine dimers because the product of a mutated gene concerned with the incision step of the excision repair mechanism is unstable.

Centrifugation, Zonal↗

PubMed1999

[Evolution of resistance to quinolones in Salmonella enterica in our setting].

Salmonella enterica is mainly associated with acute gastroenteritis; however, it is also associated with other more severe disease processes, for which quinolones are the treatment of choice. We retrospectively studied the evolution of resistance to nalidixic acid and ciprofloxacin of all the clinical isolates of S. enterica from 1992 to 1998 in our hospital environment. A total of 848 strains from feces, blood and other locations were studied. We detected an increase in the resistance to nalidixic acid from 12% in 1992 to 21.3% in 1998, especially in the Enteritidis and Hadar serotypes. We did not detect resistance to ciprofloxacin, but there was in increase in the MIC in the nalidixic acid-resistant strains. Although this is interpreted as sensitive according the the NCCLS criteria, if we apply the cutoff points established by MENSURA, 89.46% of the strains do not fit into this category (S <0.12 mg/l). This puts into question the utility of quinolones in the long-term treatment of severe disease processes produced by this type of strain.

Anti-Infective Agents↗

PubMed1985

Ofloxacin: antibacterial activity, induction of resistance and killing curves.

The antibacterial activity of ofloxacin was compared to that of nalidixic acid, norfloxacin and against various strains. This new quinolone was about 100 times more active than nalidixic acid, and pipemidic acid and generally 2 to 4 fold more active than norfloxacin and pefloxacin except against Pseudomonas aeruginosa. The increase of resistance to ofloxacin, norfloxacin and pefloxacin seems to plateau, usually at about 16 times the initial MIC. The bactericidal activity of ofloxacin also appeared quickly and more rapidly than that of norfloxacin.

Anti-Bacterial Agents↗

PubMed1984

Intraphagocytic bactericidal activity of bacterial DNA gyrase inhibitors against Serratia marcescens.

Addition of phenylbutazone (2 mg/ml) to 55 vol% of fresh defibrinated human blood permitted leukocytic ingestion of Serratia marcescens bacteria, but blocked phagocytic killing activity. The group A (phage tail) bacteriocin bA+ 16 served to kill extraphagocytic test bacteria. Five bacterial DNA gyrase inhibitors (ciprofloxacin, enoxacin, norfloxacin, nalidixic acid and pipemidic acid) revealed intraphagocytic bactericidal activity against ingested S. marcescens bacteria of three test strains; the extent of intraphagocytic activity of these drugs approximated that of rifampin. Following combination with unmodified defibrinated human blood (55 vol%), ciprofloxacin, enoxacin, norfloxacin and pipemidic acid yielded additive effects against 3 assay strains of S. marcescens and Escherichia coli strain ATCC 25922; nalidixic acid was inferior in this regard. These data might guide chemotherapy of parenchymatous urinary tract infections.

Blood Bactericidal Activity↗

PubMed1998

Comparison of NNA agar culture and selective broth culture for detection of group B streptococcal colonization in women.

In 1996, the Centers for Disease Control and Prevention recommended the use of a selective broth culture for the improved detection of genital tract or anorectal carriage of group B streptococci (GBS) in pregnant women. In order to verify this recommendation in our laboratory, we compared the sensitivity of Todd-Hewitt medium with gentamicin and nalidixic acid (SBM) with our current method of direct plating on blood agar medium containing neomycin and nalidixic acid (NNA). Five hundred consecutive cervicovaginal and anorectal specimens submitted for GBS culture were included in the study. Swabs were plated onto NNA and the swabs were immersed in SBM, followed by overnight incubation at 35 degrees C. On the following day, the NNA plates were examined for colonies typical of GBS and the organisms were identified by the CAMP test or by latex agglutination. SBM cultures were subcultured onto blood agar and CNA agar plates, and the plates were reincubated for 24 h. Negative specimens from either medium were incubated for an additional 24 h and were examined again before finalization of the results. GBS were recovered from 78 specimens by both methods; from SBM only for 17 specimens (sensitivity, 86%) and from NNA only for 16 specimens (sensitivity, 85%). A moderate to heavy growth of Enterococcus faecalis was observed on plates containing NNA-positive, SBM-negative specimens. Competitive growth studies suggested that E. faecalis suppressed the growth potential of GBS in SBM. Our study suggests that direct plating on NNA, as a single method, is equivalent in sensitivity to SBM for the recovery of GBS, and the results are often available 24 h sooner. However, it appears that both direct plating and selective broth amplification techniques are required for the maximum level of identification of colonization with GBS in pregnant women.

Carrier State↗

PubMed1988

Differential effects of DNA gyrase inhibitors on the genetic transformation of Neisseria gonorrhoeae.

Inhibitors of DNA gyrase in Escherichia coli exerted differential effects on the genetic transformation of Neisseria gonorrhoeae. When competent cells of the gonococcus were exposed to novobiocin before the uptake of transforming antibiotic resistance DNA, there was a 50 to 60% reduction in the number of transformants compared with the number of control untreated cells. Norfloxacin, a more potent inhibitor of DNA gyrase and an analog of nalidixic acid, nearly abolished the production of transformants by recipient cells. On the contrary, exposure of competent cells to nalidixic acid had no effect on transformant yield. The target of these inhibitors appears to be at the level of recombination. Possible mechanisms are discussed.

Nalidixic Acid↗

PubMed1996

Sister-chromatid exchanges (SCE) induction by inhibitors of DNA topoisomerases in cultured human lymphocytes.

The induction of sister-chromatid exchanges (SCE) in cultured human lymphocytes by four inhibitors of DNA topoisomerases: m-amsacrine, camptothecin, etoposide and nalidixic acid has been evaluated. Although the four compounds apparently increase the frequency of SCE, the effect of nalidixic acid is weak because only a statistically significant positive response was found in one donor at the highest concentration (500 microM). The other compounds tested act as SCE inducers in both donors, camptothecin being the most effective. In addition, the influence of these four topoisomerase inhibitors on the SCE frequency induced by MMC was also analysed. The results reveal that less than additive SCE effect was induced by the combined treatments which could suggest that the process leading to SCE induction by MMC and the four inhibitors of DNA topoisomerases are not totally independent.

Amsacrine↗

PubMed1990

The use of sensitivity discs in the identification of Campylobacter species.

Filter paper discs were impregnated with a solution containing 20 mg of triphenyltetrazolium chloride per millilitre, and used in the typing of catalase-positive Campylobacter species. Also used were filter paper discs impregnated with cephalothin at 30 micrograms/ml, 60 micrograms/ml and 3 mg/ml and nalidixic acid at the same concentrations, as well as commercially available discs containing 30 micrograms of, respectively, cephalothin and nalidixic acid. Results obtained proved the technique to be reliable and easier to interpret than previously used methods, and laboratory prepared filter paper discs compared favourably with commercial discs.

Animals↗

PubMedDate not supplied

Emerging quinolone-resistant Salmonella in the United States.

We conducted a national survey of antimicrobial resistance in human clinical isolates of Salmonella between July 1, 1994, and June 30, 1995. Every tenth nontyphoidal Salmonella isolate received at state public health laboratories in the United States during this period was tested for resistance to 12 antimicrobial agents, including two quinolones, nalidixic acid, and ciprofloxacin. Emerging quinolone resistance was detected; of 4,008 isolates tested, 21 (0.5%) were resistant to nalidixic acid, and one (0.02%) was resistant to ciprofloxacin. Continued surveillance for quinolone-resistant Salmonella is necessary, particularly after the recent approval of a fluoroquinolone for use in animals intended for food in the United States.

Animal Feed↗

PubMed2007

Prevalence of antimicrobial resistance among Salmonella on midwest and northeast USA dairy farms.

The objective of this study was to determine the prevalence of antimicrobial resistance among Salmonella isolated from dairy herds in New York, Minnesota, Michigan, and Wisconsin, USA. Serogroup and antimicrobial susceptibility characteristics were determined for Salmonella from cattle and environmental samples collected during August 2000-October 2001 as part of a longitudinal study where 129 herds were visited at 2-month intervals. Salmonella isolates were tested (using a broth microdilution method) for susceptibility to amoxicillin/clavulanic acid, ampicillin, ceftiofur, ceftriaxone, cephalothin, chloramphenicol, ciprofloxacin, gentamicin, kanamycin, nalidixic acid, streptomycin, sulfamethoxazole, tetracycline, and trimethoprim/sulfamethoxazole. Of the 1506 isolates tested for minimum inhibitory concentrations to these 14 antimicrobial agents, 81.2% were pan-susceptible and for most herds (81.6%) the predominant antimicrobial resistance pattern was pan-susceptible. At least 1 Salmonella isolate resistant to 5 or more antimicrobial agents was found on 23.6% of herds. This resistance phenotype was most common among serogroups B and E1 and among samples from calves and farmer-designated sick cows. Resistant samples most frequently exhibited resistance to tetracycline, streptomycin, and/or ampicillin. No samples were resistant to ceftriaxone (though 13 were in the intermediate range), and very few samples were resistant to ciprofloxacin (n=1), nalidixic acid (n=5), or trimethoprim/sulfamethoxazole (n=7).

Animals↗

PubMed1986

In vitro activity of DJ-6783 (a keto carboxylic acid) compared with six other orally administered antimicrobial agents.

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.

Anti-Bacterial Agents↗

PubMed1988

Autogenous regulation and kinetics of induction of Pseudomonas aeruginosa recA transcription as analyzed with operon fusions.

A promoterless chloramphenicol acetyltransferase gene (cat) was used to construct recA-cat operon fusions to quantitatively examine the transcriptional regulation of the Pseudomonas aeruginosa recA gene in P. aeruginosa PAO. Wild-type P. aeruginosa containing the recA8-cat fusion was treated with methyl methanesulfonate (MMS) and showed immediate induction of chloramphenicol acetyltransferase (CAT) specific activity, whereas a recA::Tn501 mutant of P. aeruginosa containing recA8-cat showed no induction with MMS. This indicated that a functional copy of recA was required for derepression of recA transcription and that P. aeruginosa recA protein was a positive regulatory factor promoting its own expression. Compared with that in the wild type, the uninduced level of CAT in recA8-cat-containing cells was reduced by approximately one-half in the recA::Tn501 mutant, indicating that recA+-dependent spontaneous induction contributes to the uninduced levels of recA expression in P. aeruginosa. MMS (0.012%) caused recA-directed CAT synthesis to increase almost immediately, with maximum CAT activity, fourfold higher than uninduced levels, attained at 60 min postinduction. The kinetics of recA8-cat fusion activity were shown to be directly related to the MMS doses used. Another fusion called recAa1-cat, where cat was located between the two transcriptional terminators of the P. aeruginosa recA gene, also showed dose-dependent induction by MMS, but the CAT activity from recAa1-cat was only one-half of that obtained with recA8-cat under the same conditions. Treatment of recA+ P. aeruginosa containing recA8-cat with UV irradiation produced an immediate effect on recA8-cat transcription and showed little UV dose dependency at doses of 5 J/m2 or greater. Treatment with 10 J/m2 produced peak levels of recA-directed CAT activity, fivefold higher than background levels, by 60 min postirradiation; CAT activity remained at peak levels during the 120 min of the experiment. In contrast, nalidixic acid had a weak effect on recA8-cat expression in P. aeruginosa, although the response was dose dependent. Nalidixic acid (800 micrograms/ml) produced maximal CAT activity that was only twofold higher than background levels.

DNA Damage↗

PubMedDate not supplied

Sythesis and turnover of phospholipids in Escherichia coli cells with inhibited DNA synthesis.

The relative amounts of individual phospholipids are not greatly affected in E. coli B cells inhibited with mitomycin C, nalidixic acid or hydroxyurea. Turnover and synthesis of phospholipids continue in the first 40 minute period of treatment with nalidixic acid and then cease. Arrest of phospholipid synthesis is not coupled with protein synthesis since beta-galactosidase is still induced after cessation of phospholipid metabolism. The cells, washed free of drug, resume growth as well as synthesis and turnover of phospholipids. During the lag phase preceding the renewal of cell division, a decrease in phosphatidylglycerol content and an increase in cardiolipin content are observed. The ratio of these phospholipids is then comparable with that found in normal non-dividing cells. We suggest that the variation in the relative contents of cardiolipin and phosphatidylglycerol might be related to the cell division process.

Bacterial Proteins↗