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Evaluation of a new agar medium containing cetrimide, kanamycin and nalidixic acid for isolation and enhancement of pigment production of Pseudomonas aeruginosa in clinical samples.

A new selective agar medium (CKNA), containing cetrimide 0.3 g/l, kanamycin sulfate 50 mg/l, and nalidixic acid 5 mg/l, was developed for the isolation of Pseudomonas aeruginosa. It was compared to Nalidixic Acid Cetrimide agar (NAC), Pseudomonas Aeruginosa Selective Agar (PASA) and Pseudosel(TM) agar (CET) using 1,148 clinical specimens. The sensitivities rates of P. aeruginosa with CKNA, NAC, PASA, and CET were 88.2%, 81.3%, 79.2%, and 84.0%, respectively. The specificities of CKNA, NAC, PASA, and CET were 99.2%, 98.4%, 99.2%, and 99.7%, respectively.

Agar↗

[Poisoning by nalidixic acid in children].

A review was made of the clinical histories of 18 children who were admitted to the Emergency Department of the Hospital de Pediatría del C.M.N. (IMSS) with the diagnosis of nalidixic acid intoxication. The study covered a period of 3 years, from 1976 through 1978. There were no differences as to sex; infants under one year were most frequently attached; iatrogenesis was the most frequent mechanism. The clinical manifestations were characterized by neurological disorders of the state of alertness, hypertensive cranial syndrome and neuronal damage; there was metabolic acidosis in other cases. Treatment included gastric lavage, general measures, correction of acid-base unbalance, control of convulsive crises. Indications for the use of nalidixic acid are reviewed stressing that it must be used in urinary infections and as second choice drug.

Accidents, Home↗

Topical treatment of psoriasis with the topoisomerase inhibitors novobiocin and nalidixic acid: a pilot study.

Our studies in human epidermal keratinocytes as a model system have suggested that the antibiotic topoisomerase II inhibitors, novobiocin and nalidixic acid, may be of value for the treatment of hyperproliferative skin disorders. We have therefore conducted a pilot study of the clinical efficacy of these compounds for the treatment of psoriasis. The compounds were administered topically to psoriatic plaques in seven healthy patients over a period of 6 weeks. Nalidixic acid (2%) or novobiocin (2% or 5%) in methylcellulose were applied twice daily under occlusion, and methylcellulose alone was used as a control. In six of the seven patients, one or both compounds effected somewhat greater improvement than in the control within 3 weeks of treatment.

Administration, Topical↗

[Nalidixic acid levels in the serum with restricted renal function (author's transl)].

Simultaneous chemical and microbiological determinations during antibacterial therapy with normal doses of nalidixic acid (4 X 1 g/day) in patients with cystopyelonephritis and restricted renal function (serum creatinine 1.5-14.0 mg%) yielded markedly higher serum levels than in patients with normal kidney function. But no side effects could be observed on longer treatment up to two weeks. The active substance was thus present in the urine in lower concentrations than are found with normal renal function. However, they lie within the range of therapeutically necessary minimal inhibitory concentrations for various gram-negative pathogens. Reduction of the dose of nalidixic acid in severe renal insufficiency seems not to be necessary, and even illogical, because otherwise ineffective plasma and urine levels are obtained. The treatment was effective against sensitive pathogens.

Humans↗

[Increasing incidence and the mechanism of resistance of nalidixic acid resistant Shigella sonnei].

One hundred and fourteen Shigella sonnei strains obtained in 1991 to 2000 were tested for their susceptibilities to 12 antimicrobial agents. Nalidixic acid (NA) resistance was found in 2 of 15 strains (13.3%) in 1993, 2 of 8 strains (25%) in 1996, one of 5 strains (20%) in 1998, 7 of 21 strains (33.3%) in 1999 and 6 of 12 strains (50%) in 2000. The incidence of resistance to NA in S. sonnei strains increased significantly during this period. Among those 19 NA resistant strains, 11 strains were derived from patients with traveler's diarrhea and 8 strains were derived from patients who had not traveled abroad before the infection, namely domestic patients. PFGE analysis with Xba I revealed that all strains tested differentiated into two major clonal clusters, one cluster consisted of strains derived from patients who had traveled to India after 1993, and another cluster included strains derived from domestic patients. Mechanism of NA resistance was examined by sequencing the quinolone resistance-determining region (QRDR) of gyrA gene. Among 19 NA resistant strains tested, 11 strains presented a change at Ser-83 to Leu and 7 strains presented a change at Asp-87 to Try (5 strains) or Asn (2 strains), whereas 3 NA sensitive strains had no change in the region. These findings indicated that this mutation in gyrA plays an important role in acquisition of Nalidixic-acid resistance in clinical isolates of S. sonnei.

DNA Gyrase↗

Nalidixic Acid and the Metabolism of Escherichia coli.

Nalidixic acid (NAL) is bactericidal for E. coli B. Synthesis of deoxyribonucleic acid (DNA), ribonucleic acid and protein was necessary to initiate the lethal effect, but only protein synthesis was necessary to sustain it. NAL inhibited DNA synthesis specifically, but this inhibition occurred even under conditions that were not lethal to the bacteria. In contrast to other inhibitors of DNA synthesis, NAL did not cause the solubilization of cellular DNA even when bacteria were exposed to it for 2 hr. A bacterial mutant deficient in DNA polymerase was much more sensitive to the lethal action of NAL than its parent strain. Moreover, inhibition of protein synthesis did not protect this mutant from NAL-induced killing. NAL inhibited neither DNA polymerase, nor thymidine or thymidylate kinases. The data are interpretated as suggesting that NAL altered the structure of DNA or a protein attached to nascent DNA and that this lesion can be partially repaired by DNA polymerase.

Journal Article↗

Resistance to ten different fluoroquinolone antibiotics following in vitro exposures to nalidixic acid.

Ten different fluoroquinolone antibiotics were tested against selected Enterobacteriaceae. Against nalidixic acid-resistant clinical isolates, minimal inhibitory concentrations for all 10 drugs were eightfold to 32-fold greater than those against comparable nalidixic acid-susceptible strains. When the latter strains were serially exposed to increasing concentrations of nalidixic acid, susceptibility to all 10 fluoroquinolones decreased as resistance to nalidixic acid and cinoxacin was acquired in vitro.

Anti-Bacterial Agents↗

Flagellation of Salmonella typhimurium treated with nalidixic acid.

Filamentous cells of Salmonella typhimurium, obtained after treatment with nalidixic acid in the exponential phase of growth, elongated up to 10 micron, corresponding to 4 unit cell lengths, per nucleoid. During elongation, division of nucleoids and septum formation did not occur, but de novo formation of flagella continued. Most of the filamentous cells were motile, and flagella were evenly distributed on their surface.

Cell Movement↗

In vitro activity of norfloxacin in synthetic media and human urine compared to that of cinnoxacin, nalidixic acid and pipemidic acid.

Activity of norfloxacin was compared to that of cinnoxacin, nalidixic acid and pipemidi acid in DST-agar and human urine solidified by adding 1.2% agar. Norfloxacin was the most active compound when tested on DST-agar but the MIC values increased from 64 to 128 fold when tested in urine. Other compounds also showed an increase in MIC in urine-agar, but the increase was less marked. MICs for norfloxacin in DST-agar and Müller-Hinton-Agar were similar. Higher concentrations were required in Müller-Hinton-Broth than in Müller-Hinton-Agar.

Agar↗

Nalidixic acid kinetics in renal insufficiency.

1 A pharmacokinetic study of nalidixic acid (NA) and metabolites was carried out in 23 patients with differing renal function so as to determine the influence of renal insufficiency on the excretion and biotransformation rate of this antibacterial agent. Plasma and urine concentration of NA and of its 7-hydroxy (HNA) and 7-carboxy (CNA) derivatives were measured after a single oral administration. 2 Renal insufficiency did not markedly affect the renal clearance of NA while it significantly decreased the elimination rate of HNA, a compound which largely excreted into the urine. 3 Interestingly, CNA which could never be detected in the plasma of patients with normal renal function appeared in that of patients with renal insufficiency. Plasma concentrations of CNA and creatinine were positively related, and the amount of urinary CNA increased with the renal impairment. 4 These results suggest that HNA can still be biotransformed into CNA by the impaired kidney. Since CNA cannot be easily excreted in the urine of patients with renal insufficiency it is hypothesized that this compound back diffuses into the plasma. 5 Finally, the study of the urinary concentrations of NA and metabolites shows that a standard NA dosage can be used, at least in patients with mild renal insufficiency.

Adult↗

[Antibacterial activity of norfloxacin, ofloxacin and ciprofloxacin according to resistance phenotypes to nalidixic acid and pefloxacin].

In vitro antibacterial activity of 5 quinolones: nalidixic acid (NAL), pefloxacin (PEF), norfloxacin (NOR), ofloxacin (OFL) and ciprofloxacin (CIP) was evaluated by agar diffusion (disks Diagnostics Pasteur) for 1,253 bacterial strains (767 Enterobacteriaceae: E 164 P. aeruginosa: PA, 90 A. baumannii: AB and 232 S. aureus: SA) isolated during the last three months of 1988. Strains were ranged in susceptible (S) intermediate (I) and resistant (R) according to recommendations of Comité Français de l'Antibiogramme; in addition, activity of NOR, OFL and CIP was precised according to susceptibility to NAL and PEF. Frequencies of strains R + I observed for NAL, PEF, NOR, OFL and CIP were (%): E: 14.4; 13.4; 7.3; 7.6; 2.4 - PA: 100; 68.5; 18.4; 36.8; 8.9 - AB: 78.9; 57.8; 75.5; 54.4; 50 - SA: 100; 27.5; 28.9; 28.5; 28.7. For E and AB, analysis according to resistance phenotypes to NAL and PEF showed reduction of activity of NOR, OFL and CIP, on strains RI and particularly RR by comparison with strains SS and RS. Activity of PEF, NOR, OFL and CIP is similar on PA, belonging to RS and RR phenotypes. On RI strains, only CIP showed activity practically identical to that on RS strains. For SA, NOR, OFL and CIP were inactive on PEF R strains. Analysis of populations of strains according to resistance phenotypes to NAL and PEF permitted to show reduction of activity of other compounds on strains with an acquired resistance character to quinolones; currently, only test of PEF is presently sufficient for susceptibility testing of other fluoroquinolones (NOR, OFL and CIP) on E, AB and SA; however for PA, test of CIP is also necessary.

Ciprofloxacin↗

Nalidixic acid resistance influences sensitivity to ionizing radiation among Salmonella isolates.

Nalidixic acid (Nal) resistance has been used as a selective marker for studies of pathogen-inoculated fruits and vegetables. A collection of 24 Salmonella isolates were screened for natural resistance to Nal (50 microg/ml). The resistance to ionizing radiation was determined and compared for i) three naturally Nal-resistant (Nal(R)) strains, ii) three naturally Nal-sensitive (Nal(S)) strains, and iii) three strains derived from Nals strains that were made resistant to Nal (Nal(Ri)) by successive culturing and selection in Nal-amended broth. The radiation D10-values (the radiation dose required to achieve a 1-log reduction in population) were determined in buffer solution and in orange juice. D10-values were significantly (P < 0.05) different among the Salmonella isolates tested. When considered as a group, Nal(R) isolates were significantly more sensitive to ionizing radiation than Nals isolates in both media tested. In buffer, D10 of Nal(R) was 0.210 kGy versus 0.257 kGy for Nals. In orange juice, D10 of Nal(R) was 0.581 versus 0.764 for Nals. Inducing resistance to Nal altered the response to irradiation. D10-value of Nal(Ri) was 0.234 kGy in buffer, a 9% reduction relative to Nals parents. In orange juice, the D10-value of Nal(Ri) was 0.637 kGy, a reduction of 17% relative to Nals parents. These results suggest that natural and/or induced resistance to Nal may predispose Salmonella isolates to greater sensitivity to ionizing radiation,and that this effect is influenced by the suspending medium and by the nature of the isolates evaluated.

Colony Count, Microbial↗

Effects of nalidixic acid on hamster knee cartilage morphology and synovial fluid composition.

Quinolone-induced changes were studied in the knee joints of 4-wk-old female hamsters given intraperitoneal doses of either nalidixic acid (400 mg/kg body weight) or vehicle on days 0 and 1. After euthanasia on day 4, synovial fluid was collected for cytologic evaluation and for analysis of concentrations of hyaluronan, proteoglycans, total protein, and collagen as hydroxyproline. Slides of formalin-fixed decalcified tissues were stained with hematoxylin-eosin or safranin O for histologic scoring of lesion severity. Nine of 10 hamsters treated with nalidixic acid had fissures within articular cartilage of the femur and reduced safranin O staining of matrix indicative of loss of proteoglycans. Synovial membranes from affected joints, however, were not inflamed. Synovial fluid cell counts and cytomorphology were unaffected by treatment. In synovial fluid from 5 of 10 treated hamsters, proteoglycans were elevated by more than 2 SDs above the control group, and individual animal levels correlated with the histologic severity score (r2 = 0.36; p = 0.02). The hyaluronan content of the synovial fluid from treated hamsters was mildly but significantly elevated (p = 0.005), and the histologic severity score again correlated with individual animal levels (r2 = 0.42; p = 0.01). Hydroxyproline was unaffected by treatment. Although synovial fluid changes and histologic changes were correlated on a group basis, interanimal variability was significant and the magnitude of biochemical changes were far smaller than those that occur during inflammation. Changes in synovial fluid composition are not sufficiently robust to predict cartilage changes in individual animals.

Animals↗

The comparative in-vitro activity of norfloxacin, ciprofloxacin, enoxacin and nalidixic acid against 423 strains of gram-negative rods and staphylococci isolated from infected hospitalised patients.

The in-vitro activities of four quinolone carboxylic acids against 423 clinical isolates of Gram-negative rods and staphylococci from infected hospitalised patients were compared. The antibiotics included nalidixic acid and the newer compounds, norfloxacin (MK-0366), ciprofloxacin (Bay 09867) and enoxacin (AT 2266 or CI919). Norfloxacin showed slightly more activity than enoxacin, but both agents had markedly greater potencies and broader antibacterial spectrums than nalidixic acid. Ciprofloxacin was the most active quinolone tested against both gentamicin-susceptible and gentamicin-resistant stains, having an MIC90 equal or less than 1 mg/l for all species studied.

Acinetobacter↗

Determination of nalidixic acid and its two major metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography.

This paper describes a precise and sensitive method for analysis of nalidixic acid and its two major metabolites in plasma and urine following the oral administration of a therapeutic dose in humans. After addition of an internal standard (oxolinic acid), 1-ml samples of plasma or urine are extracted at acidic pH with chloroform. The extracts are purified by re-extraction with sodium hydroxide solution and then chloroform. The final extracts are evaporated to dryness, reconstituted in mobile phase and injected into a high-performance liquid chromatograph equipped with RP-8 column and UV detector operating at 254 nm. The limit of sensitivity of the method is lower than 0.5 micrograms/ml of plasma or urine for each compound. The applicability of the method to pharmacokinetic studies of nalidixic acid in humans is demonstrated.

Chromatography, High Pressure Liquid↗