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PubMed1977

Nalidixic acid-induced protein alterations in Escherichia coli.

The effect of nalidixic acid on pulse-labeled protein patterns was analyzed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The drug was found to alter protein patterns in a drug-sensitive strain but not in the isogenic drug-resistant strain of Escherichia coli. The drug-induced alteration of protein patterns was demonstrated by the appearance of some and the disappearance of other pulse-labeled peptides elicited by the drug.

Bacterial Proteins↗
PubMed1984

In-vitro activity of enoxacin against aminoglycoside-resistant gram-negative bacilli and other clinical isolates.

The in-vitro activity of enoxacin was tested against 500 clinical isolates of Gram-negative bacilli that were resistant to one or more of gentamicin, tobramycin and amikacin, and against 1060 recent consecutive clinical isolates of Gram-negative bacilli and Gram-positive cocci. Enoxacin was active against staphylococci (MICs less than or equal to 4 mg/l) but less active against Streptococcus faecalis (MICs mostly 8 mg/l). It was active against Pseudomonas aeruginosa (MICs 0.5-4 mg/l) and very active against Enterobacteriaceae. In the series of consecutive isolates 97% of Enterobacteriaceae had MICs less than or equal to 1 mg/l. The aminoglycoside-resistant series of Enterobacteriaceae included more strains with higher MICs (13% were 2-4 mg/l and 10% were greater than or equal to 8 mg/l); the majority of the isolates with MICs greater than or equal to 8 mg/l); the majority of the isolates with MICs greater than or equal to 8 mg/l were Serratia marcescens and Providencia spp. Among the non-fermenting species the least sensitive were Acinetobacter calcoaceticus and Ps. maltophilia. Enoxacin-resistant strains of Enterobacteriaceae were resistant to nalidixic acid, but nalidixic acid-resistant strains ranged from fully sensitive to highly resistant to enoxacin.

Aminoglycosides↗
PubMedDate not supplied

Antibiotic resistance of Salmonella enterica serovar Paratyphi A in India: emerging and reemerging problem.

BACKGROUND: Antibiotic resistance pattern and R-plasmid of Salmonella enterica serovar Paratyphi A isolates from Kolkata, India are not well documented. AIMS: To determine the trend of antibiotic resistance of S. paratyphi A isolates. SETTINGS AND DESIGN: A retrospective study was carried out using blood culture isolates of S. paratyphi A (1991 to 2005) obtained from patients of enteric fever from Asansol and Kolkata and its suburbs (India). MATERIALS AND METHODS: Antibiotic susceptibility pattern, using seven antibiotics, for the isolates was determined following agar dilution and disk diffusion methods. Transferability of multidrug resistance to ampicillin (Am), chloramphenicol (Chl), cotrimoxazole (Cot) and tetracycline (Tet) among the isolates was determined by in vitro conjugation. The multi-drug resistant (MDR) and antibiotic susceptible S. paratyphi A strains and the trans-conjugants were screened for the presence of plasmid. STATISTICAL ANALYSIS USED: The t test was used to compare the difference between mean minimum inhibitory concentration values of ciprofloxacin (Cp) for nalidixic acid (Nx)-resistant and Nalidixic acid (Nx)-susceptible isolates. RESULTS: Among 13 outbreak causing isolates in 1991, 9 (69.23%) showed AmChlCotTet-resistance, while 4 (30.77%) Cot-resistance only. During 1992-1994, all 13 isolates were susceptible to Am, Chl, Cot and Tet. During 1995-2005, isolates demonstrated different resistance patterns and emergence of nalidixic acid (Nx)-resistance. A transferable plasmid conferring AmChlCotTet-resistance was detected among MDR isolates. All the isolates were susceptible to ceftriaxone (Ctx) and ciprofloxacin (Cp). Association between Nalidixic acid (Nx)-resistance and reduced susceptibility to ciprofloxacin (Cp) among 59 S. paratyphi A isolates was noticed (P < 0.001). CONCLUSION: Vigilance for R-plasmid and surveillance of antibiotic susceptibility among S. paratyphi A isolates in and around Kolkata, India, are mandatory in order to combat antibiotic resistance of the isolates in this part of the world.

Anti-Bacterial Agents↗
PubMed1997

Analysis of the mechanism of quinolone resistance in nalidixic acid-resistant clinical isolates of Salmonella serotype Typhimurium.

Over a period of 2.5 years, 42 cases of gastro-enteritis caused by nalidixic acid-resistant Salmonella serotype Typhimurium occurred in Malaga. The epidemiological relationship among the strains involved was investigated by analysis of plasmid profile and of chromosomal DNA by pulsed-field gel electrophoresis (PFGE). Despite having different plasmid profiles, all 42 nalidixic-acid resistant Typhimurium isolates had evolved from one clone as shown by analysis of chromosomal DNA by PFGE. The mechanism of quinolone resistance in these Typhimurium isolates was also investigated. Analysis of outer-membrane proteins and lipopolysaccharide from quinolone-susceptible and resistant clinical isolates tested showed no differences. All nalidixic acid-resistant isolates had MICs for ciprofloxacin of 0.25 mg/L and for nalidixic acid of 1024 mg/L. Polymerase chain reaction fragments of 285 bp, containing the quinolone resistance-determining region of the gyrA gene, and of 237 bp, containing the region of parC homologous to the quinolone resistance-determining region of the gyrA gene, were sequenced. All resistant isolates presented a change at Ser-83 to Phe in the GyrA protein, but no changes were observed in the ParC protein. These findings indicated that this mutation in gyrA plays a major role in the acquisition of nalidixic-acid resistance in clinical isolates of Typhimurium.

Amino Acid Sequence↗
PubMed1981

Nalidixic acid-induced photodermatitis after minimal sun exposure.

More than 30 cases of bullous photodermatitis have already been associated with the administration of nalidixic acid. This reaction is reported in a 57-year-old woman whose sun exposure was minimal. Nalidixic acid-induced photoreactions generally occur in females; they affect mainly the dorsal surfaces of the hands, feet, and legs, and usually do not involve the face. Blistering is always reported, and erythema is common. Dosage regimen and duration of treatment have little influence on the onset and severity of the reaction, which is probably of allergic nature. Its duration may be long, from three to six weeks, reexposure to the sun may trigger the reappearance of blistering for several months, even in the absence of a drug rechallenge.

Female↗
PubMed1990

Effects of mutations altering SOS regulation on a nalidixic acid-inducible system for the production of heterologous proteins in Escherichia coli.

The major leftward early promoter of phage lambda pL, has frequently been used to drive expression of heterologous genes in Escherichia coli. pL is typically maintained fully repressed by the lambda cl protein. When induction of heterologous protein synthesis is desired, one of several potential mechanisms of destroying cl function is employed and the expression of the foreign gene commences. One method of derepressing pL involves exposing cells to nalidixic acid, which results in the "activation" of RecA protein and the subsequent RecA-mediated proteolytic cleavage of cl. Activated RecA also mediates the cleavage of the E. coli LexA protein, resulting in induction of the SOS regulon (at least 15 E. coli genes, including recA). We have examined the effect of two chromosomal mutations on the productivity of nalidixic acid inductions. One of the tested mutations (recA o) increased the intracellular concentration of RecA prior to induction; the other (lexAind-) resulted in a mutated lexA protein insensitive to RecA-mediated cleavage. These mutations were introduced into a strain carrying a cl+ defective lysogen. Synthesis of two heterologous proteins, human alpha 1-antitrypsin and a fusion protein partially derived from the Plasmodium falciparum circumsporozoite surface antigen, was examined in the wild-type and mutant strains. The maximum alpha-1 antitrypsin concentration achieved was improved by 50% when the recA o strain was used rather than the wild-type; however, only smaller changes (20% or less) in the maximum concentration of the malaria fusion protein were observed. Use of the lexAind- strain resulted in a decrease in the maximum concentration attained for both heterologous products.

Animals↗
PubMed1983

In vitro antibacterial activity of norfloxacin compared with eight other antimicrobial agents.

The antibacterial activity of norfloxacin, an organic acid structurally related to nalidixic acid, was compared with that of the oral cephalosporins cefaclor and cephalexin, and with that of nalidixic acid, cinoxacin, amikacin, ampicillin, trimethoprim alone and the combination of trimethoprim and sulfamethoxazole. Agar dilution studies were performed with a total of 398 clinical isolates of gram-negative bacteria. Norfloxacin was found to be the most active drug studied against each of the different groups of organisms tested. MIC90 values for norfloxacin were as follows: Citrobacter spp., 2 micrograms/ml; Enterobacter spp., 0.13 micrograms/ml; Escherichia coli, 0.06 micrograms/ml; Klebsiella spp., 0.13 micrograms/ml; Proteus spp., 0.06 micrograms/ml; Salmonella spp., 1 microgram/ml; Serratia spp., 0.13 micrograms/ml; and Pseudomonas spp., 2 micrograms/ml. MIC90 values for the other drugs were 4 micrograms/ml or greater and many organisms were totally resistant to one or more of the other drugs (MIC greater than 128 micrograms/ml). Cross resistance between norfloxacin and the related drugs nalidixic acid and cinoxacin was not observed.

Anti-Bacterial Agents↗
PubMed1990

Toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals.

A toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals was undertaken using nalidixic acid as a standard drug. Norfloxacin and nalidixic acid were subcutaneously administered to rats and rabbits, orally administered to dogs, and norfloxacin was orally dosed to monkeys once a day for 7 consecutive days. Of the dose levels tested, the minimum arthropathic doses of norfloxacin were 100, 25, and 50 mg/kg/day in rats, rabbits, and dogs, respectively. At these doses, the peak serum concentrations (Cmax) on Day 6 were 16.1, 9.73, and 5.11 micrograms/ml, and the areas under the serum concentration/time curve (AUC0----infinity) were 31.9, 22.9, and 26.2 micrograms.hr/ml, in respective animals. Monkeys showed no arthropathy with norfloxacin at doses of less than 500 mg/kg/day, at which the Cmax and AUC0----infinity were 15.6 micrograms/ml and 103 micrograms.hr/ml, respectively. The minimum arthropathic doses of nalidixic acid were 50, 100, and 25 mg/kg/day in rats, rabbits, and dogs, respectively. The Cmax and AUC0----infinity of nalidixic acid were higher than those of norfloxacin in all animals. Joint tissues took up more norfloxacin than nalidixic acid, but when arthropathy was present the articular cartilage concentrations of the two drugs were in the same range. The penetration of norfloxacin into the articular cartilage was the same regardless of the joint's anatomical locations, but differed among species, being highest in rats and lowest in monkeys. The Cmax and AUC0----infinity of norfloxacin in animals at their arthropathic doses were far higher than those measured clinically in children, whereas those of nalidixic acid in animals did not differ much from its clinical parameters.

Administration, Oral↗
PubMed1995

Effect of PANTA on growth of Mycobacterium kansasii in BACTEC 12B medium.

Mycobacterium kansasii isolates from two patients showed relatively slow growth in BACTEC 12B medium (12B) (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) compared with the more rapid growth of these isolates on solid media. This finding prompted an evaluation of the effect of PANTA (Becton Dickinson) on the growth rate of these isolates. Suspensions of one isolate from each of these two patients (A and B), six additional isolates from six other patients (C through H), and one M. kansasii American Type Culture Collection isolate were inoculated into 12B with PANTA, 12B with reconstituting fluid only, and Middlebrook 7H11 agar plates (Remel, Lenexa, Kans.). For the isolates from patients A and B, the average times to detection for 12B with PANTA, 12B with reconstituting fluid, and Middlebrook 7H11 agar were 12.3, 7.4, and 9.0 days, respectively. For the remaining six patient isolates and the American Type Culture Collection strain, the average times to detection for these media were 9.2, 8.1, and 9.6 days. Susceptibility tests performed with the isolates from patients A and B with the individual component antibiotics of PANTA and testing of four of the other isolates with nalidixic acid alone suggested that nalidixic acid exerts some degree of inhibition on the growth of M. kansasii. The eight patient isolates were also inoculated onto Lowenstein Jensen medium (Remel) and onto a variety of selective mycobacterial media containing nalidixic acid and other antimicrobial agents. All isolates showed some degree of inhibition on at least one of these selective media.

Amphotericin B↗
PubMed2003

Mutations in gyrA and parC genes in nalidixic acid-resistant Escherichia coli strains from food products, humans and animals.

Mutations in quinolone targets were analysed in 80 unrelated nalidixic acid-resistant (NALR) Escherichia coli strains whose nalidixic acid and ciprofloxacin MICs ranged from 32 to >256 mg/L and 0.03-64 mg/L, respectively. These strains were isolated from food products (23) and faecal samples from humans (15) and healthy animals (42). Thirteen nalidixic acid-susceptible (NALS) E. coli strains were also analysed. Mutations in gyrA and parC genes were studied by PCR and sequencing. No amino acid changes were detected in GyrA or ParC proteins of the 13 NALS strains. A single change in the GyrA protein was detected in all 61 NALR strains with ciprofloxacin MICs </= 2 mg/L with the following substitutions (number of strains): Ser-83-->Leu (54), Ser-83-->Ala (one), Ser-83-->Val (one), Asp-87-->Asn (two), Asp-87-->Tyr (two) and Asp-87-->Gly (one). A double change in GyrA was found in 18 of 19 NALR strains with ciprofloxacin MICs >/= 4 mg/L. Amino acid substitutions were Ser-83-->Leu, with an additional change [Asp-87-->Asn (15), Asp-87-->Tyr (two) or Asp-87-->His (one)]. The remaining strain (ciprofloxacin MIC 4 mg/L) showed a single Ser-83-->Leu substitution. In respect of the ParC protein, a single change at Ser-80 or Glu-84 was found in 25 of 42 strains, with ciprofloxacin MICs ranging from 0.5 to 32 mg/L. A double substitution (Ser-80-->Ile and Glu-84-->Gly) was found in one strain (ciprofloxacin MIC 64 mg/L). No amino acid changes were detected in the GyrB protein of 18 NALR strains.

Animals↗
PubMed2000

A randomized controlled comparison of azithromycin and ofloxacin for treatment of multidrug-resistant or nalidixic acid-resistant enteric fever.

To examine the efficacy and safety of short courses of azithromycin and ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with Salmonella enterica serovar Typhi and 2 with S. enterica serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC(90) (range) of azithromycin was 8 (4 to 16) microgram/ml for the isolates. The MIC(90) (range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) microgram/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) microgram/ml. There was no significant difference in the overall clinical cure rate with ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%]; P = 0.27) or in the patients infected with nalidixic acid-resistant typhoid (17 of 21 [81.0%] versus 24 of 25 [96.0%]; P = 0.16). However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 264] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains.

Adolescent↗
PubMed1978

Synergistic effects of chlorpromazine and perphenazine on several chemotherapeutic agents. I. General profile of the effects measured by the filter paper strip-agar diffusion method with Escherichia coli and Pseudomonas aeruginosa.

The combination effects of chlorpromazine (CPZ) and periphenazine (PPZ) with beta-lactam antibiotics (ampicillin, carbenicillin, cefazolin) and nalidixic acid group compounds (nalidixic acid, piromidic acid and pipemidic acid) have been estimated to be synergistic by the filter paper strip-agar diffusion method (Dye's method) with Escherichia coli and Pseudomonas aeruginosa as test organisms. The observed synergism might be associated with their inhibition of various enzymes including ATPase and DNAase as well as with their specific binding to DNA. Similar synergistic effects of CPZ and PPZ have been shown by the broth dilution method. Based on these findings, it seems to be a fascinating project to devise a new phenothiazine drug without influence in mental disease that will have a greater measure of synergistic effect when combined with the above-studied antibacterial agents.

Adenosine Triphosphatases↗
PubMed1983

In vitro antibacterial properties of AT-2266, a new pyridonecarboxylic acid.

AT-2266, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3 -carboxylic acid, is a new pyridonecarboxylic acid derivative with broad and potent antibacterial activity. It inhibited some gram-positive bacteria, such as staphylococci and Bacillus subtilis, and most gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, Haemophilus influenzae, and Campylobacter jejuni, at concentrations of 0.1 to 0.78 microgram/ml, and most gram-positive bacteria, glucose-nonfermenters, and Mycoplasma pneumoniae at concentrations of 1.56 to 12.5 micrograms/ml. Most of the clinical isolates tested were as susceptible to AT-2266 as were laboratory strains. The antibacterial potency of AT-2266 was higher than those of pipemidic acid and nalidixic acid and similar to that of norfloxacin. AT-2266 was not cross-resistant with antibiotics and inhibited most highly nalidixic acid-resistant bacteria at concentrations of 1.56 to 3.13 micrograms/ml. Its activity was barely affected by the addition of horse serum or sodium cholate but weakened by lowering the medium pH or increasing the inoculum size. AT-2266 was bactericidal at concentrations near its minimal inhibitory concentrations. Frequencies of mutants resistant to 10 micrograms of AT-2266 per ml were lower than 4.0 x 10(-9).

Anti-Bacterial Agents↗
PubMed1994

Determination of pyridonecarboxylic acids in plasma by reverse-phase high-performance liquid chromatography.

A simple qualitative and quantitative determination for pyridonecarboxylic acids including nalidixic acid (NA), oxolinic acid (OA) and pipemidic acid (PPA) in chicken plasma was carried out by microbiological, spectrophotometric, thin-layer chromatographic (TLC) and reverse-phase high-performance liquid chromatographic (HPLC) methods. As a test organism for bacteriological bioassay, Bacillus subtilis ATCC-6633 was the most sensitive of seven organisms investigated. Using the cup and the disc methods, a standard curve was obtained by determining the relationship between various drug concentrations and the diameter of the inhibition zone. The three drugs had two strong UV absorbance wavelengths (257 and 330 nm) on spectrophotometry. TLC analysis using a silica gel 60 F254 plate was investigated, and a solution of methanol:chloroform:acetic acid (3:1:1, v/v/v) was found to be the most suitable solvent for separation. The minimum concentration of drug detectable by this method was 0.5 microgram/ml for NA, 0.075 microgram/ml for OA and 0.39 microgram/ml for PPA. For HPLC analysis, a solution of acetonitrile:0.2 M phosphoric acid (1:1, v/v) was superior, and simultaneous determination of all three drugs was possible under the HPLC conditions used. The lowest measurable amount of drug in chicken plasma was 0.01 microgram/g. Recovery from extracts spiked with each drug at a known concentration was close to 100% for NA and OA, but only about 50% for PPA.

Animals↗
PubMed1980

Improved medium for selective isolation and enumeration of Bifidobacterium.

Petuely's selective medium for Bifidobacterium was improved by addition of riboflavin, nucleic acid bases, pyruvic acid, and nalidixic acid. The modified medium, when examined under strictly anaerobic conditions for efficient isolation of Bifidobacterium from human fecal samples, exhibited selective and high viable counts that were close to those found on the usual nonselective medium.

Actinomycetaceae↗
PubMed1985

Occurrence of gram negative bacteria in midstream bladder urine and their sensitivity to quinoline derivatives.

326 gram negative bacteria have been isolated and quantitative bacteria counts performed from midstream urine of as many patients affected with symptomatic and non symptomatic urinary tract infections. Susceptibility of bacteria to four quinoline derivatives (Norfloxacin, Oxolinic acid, Pipemidic acid and Nalidixic acid) was studied determining the minimal inhibitory concentrations (MICs) of each drug by a miniaturized dilution broth method. The frequency of bacterial species isolated, the frequency of symptoms and the frequency of bacterial counts were studied to establish a possible relationship between these data. It has been observed that patients affected with pyuria without any other subjective symptoms demonstrate a colony count ranging between less than 10(4) and greater than 10(5) bacterial/ml of urine and these bacteriuria were determined by several different bacterial species. E. coli was much more frequently responsible for low or high count bacterial infections of the urinary tract than other species. In fact E. coli was detected in 64.4% of patients, P. mirabilis in 15.9%, E. agglomerans in 5.2%, P. aeruginosa in 4.9. Other species were detected in much lower percentages. Norfloxacin proved to be the most effective drug in vitro, out of those under examination. Its MIC50 never exceeded 8 mcg/ml even against Pseudomonas and Serratia strains, which were resistant to all the other antimicrobial agents.

Adolescent↗
PubMed2003

Antimicrobial-resistant Salmonella serovars isolated from imported foods.

A total of 187 Salmonella isolates representing 82 serotypes recovered from 4072 imported foods in the year 2000 by the U.S. Food and Drug Administration field laboratories were tested for their susceptibility to 17 antimicrobials of human and veterinary importance. Fifteen (8%) isolates were resistant to at least one antimicrobial, and five (2.7%) were resistant to three or more antimicrobials. Most of the isolates (n=9) exhibited resistance to tetracycline. Four isolates from catfish or tilapia from Taiwan or Thailand also demonstrated resistance to nalidixic acid. These nalidixic acid-resistant Salmonella isolates possessed a point mutation at the Ser83 or Asp87 position in DNA gryase, resulting in amino acid substitutions to phenylalanine, tyrosine, or asparagine. One Salmonella Derby isolated from frozen anchovies imported from Cambodia was resistant to six antimicrobials including ampicillin, amoxicillin/clavulanic acid, chloramphenicol, sulfamethoxazole, tetracycline, and trimethoprim/sulfamethoxazole. Of seven isolates displaying resistance to sulfonamides, only one S. Derby and one Salmonella Agona contained class 1 integrons that were further shown to possess the aadA and pse-1 genes conferring resistance to streptomycin and ampicillin, respectively. This study indicates that antimicrobial-resistant Salmonella are present in imported foods, primarily of seafood origin, and stresses the need for continued surveillance of foodborne zoonotic bacterial pathogens from imported foods entering the United States.

Anti-Bacterial Agents↗