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PubMed1983

Recurrent urinary tract infections in premenopausal women: prophylaxis based on an understanding of the pathogenesis.

We studied 56 sexually active premenopausal women with a normal genitourinary tract but with persistent introital colonization by enteric gram-negative bacteria who were prone to suffer recurrent urinary tract infections. Sexual intercourse was revealed as a major factor in inducing recurrent urinary tract infections, usually within 24 hours, by transferring the pre-existing introital bacteria into the bladder. Abstention from sexual activity without any additional treatment prevented the development of new urinary tract infections in these women despite persistent introital enteric bacterial flora. Urinary tract infections occurred after onset of sexual activity in all but 2 of the premenopausal women in this study. The 25 premenopausal women with recurrent urinary tract infections were subjected to early postcoital prophylaxis consisting of bladder voiding and the administration of a single tablet of either cotrimoxazole (80 mg. trimethoprim plus 400 mg. sulfamethoxazole), nalidixic acid (500 mg.), nitrofurantoin (50 or 100 mg.) or sulfonamides (500 mg. sulfisoxazole or 250 mg. sulfamethizole). Whereas 70 urinary tract infections occurred during a mean 8-month followup before treatment only 4 occurred during the mean 12.5-month followup after introduction of post-coital prophylaxis (none occurred on co-trimoxazole or nalidixic acid therapy and only 1 infection occurred on nitrofurantoin therapy). Sulfonamides are not recommended as post-coital prophylaxis because of the higher incidence of breakthrough infections. Post-coital prophylaxis with co-trimoxazole, nalidixic acid or nitrofurantoin proved to be simple, economical and efficient, and is recommended in the prevention of recurrent urinary tract infections in otherwise normal premenopausal women.

Adult↗

PubMed1983

[Concentration of antimicrobial agents in male genital organs].

The relationship between the concentrations of various antimicrobial agents in the genital organs of male rats, serum, liver and kidney after oral administration, intramuscular infusion and i.v. infusion were systematically compared and studied. The concentration of Ampicillin in human prostatic tissues after intramuscular infusion was also measured. The drug concentration in the prostatic tissues after oral administration of nalidixic acid (20 mg/kg) was highest 21.5 micrograms/g (2-hour value) which was about 4 times the serum level, followed by chloramphenicol, Cefalexin, Ampicillin, piromidic acid and erythromycin. The concentration of Ampicillin and Cefaloridine in the prostatic tissues after intramuscular infusion was high, but the concentration of Cefazolin, was low after both intramuscular infusion and i.v. infusion. The drug concentration in the prostatic tissues after i.v. infusion of Cefaloridine, Erythromycin, and Ampicillin was high. The concentration of Erythromycin was high only after i.v. infusion. The concentration of both Chloramphenicol and Gentamicin in the blood, and in the prostatic tissues were low. Of the drugs tested, the concentration of Ampicillin in human prostatic tissues was the highest being about 8 micrograms/g at 60 minutes after intramuscular infusion, which was about 40% of its concentration in the blood. The concentrations of antimicrobial agents in the epididymis and testis of the rats were low. Even the relatively high values were only about 10% of the concentration in the blood. The concentration of nalidixic acid in the prostatic tissues was 4 times as high as that of Piromidic acid. In summary, the antimicrobial agents showing high concentrations in the prostatic tissues were nalidixic acid by oral administration, Ampicillin and Cefaloridine by intramuscular infusion, and i.v. infusion, which showed relatively high concentrations in the blood. Irrespective of the route of administration, the concentrations of Chloramphenicol and Gentamicin in the male genitals were low. The drug concentration in the testis was very low irrespective of the chemotherapeutic and administration form. This seems to signify the presence of the so-called blood-testis barrier to protect the important function of spermatogenesis.

Administration, Oral↗

PubMed2005

Antibiotic resistance of Escherichia coli from community-acquired urinary tract infections in relation to demographic and clinical data.

This prospective study determined the antibiotic susceptibility of 164 isolates of Escherichia coli from the urine of 164 patients (112 female, 52 male; mean age of 54.12 years) with community-acquired urinary tract infection (UTI). Half of the isolates were from uncomplicated UTI and half from complicated UTI (52 males and 34 females). Overall, 57.3% of isolates were resistant to ampicillin, 25% to co-trimoxazole, 20.1% to nalidixic acid, 14% to norfloxacin and ciprofloxacin, and 0% to fosfomycin and nitrofurantoin. Of the 82 isolates from complicated UTI, 16 (19.5%) were resistant to norfloxacin and ciprofloxacin, compared with seven (8.5%) from uncomplicated UTI (p 0.043). Isolates from patients aged >50 years were significantly more resistant than those from patients aged <50 years for nalidixic acid (p 0.007) and the fluoroquinolones tested (p 0.015). Resistance to fluoroquinolones was 25% (13/52) in males and 9% (10/112) in females (p 0.006). For patients with and without previous antimicrobial therapy, there was a significant difference only for resistance to nalidixic acid (p < 0.001) and the fluoroquinolones (p 0.011). There were adequate susceptibility rates to fosfomycin, nitrofurantoin and the fluoroquinolones for empirical use in the treatment of acute uncomplicated UTI. In order to interpret cumulative susceptibility data from the primary healthcare setting, it is necessary to take into account the type of UTI (uncomplicated vs. complicated), previous antimicrobial therapy, and the sex and age of each patient.

Adolescent↗

PubMed1996

Sequence analysis, purification, and study of inhibition by 4-quinolones of the DNA gyrase from Mycobacterium smegmatis.

We determined the nucleotide sequence of a 6-kb DNA region harboring the recF, orf192, gyrB, and gyrA genes from Mycobacterium smegmatis mc(2)155. The amino acid sequences deduced from gyrA and gyrB displayed 89 and 86% identity, respectively, with the DNA gyrase from Mycobacterium tuberculosis, and 67 and 65% identity, respectively, with that from Streptomyces coelicolor. An open reading frame encoding the C-terminal region of the M. smegmatis RecF polypeptide was found upstream from gyrB and was 57% identical to the open reading frame encoding the C-terminal region of the S. coelicolor RecF protein. The gene orf192 was identified between recF and gyrB and was 39% identical to orf191 found in S. coelicolor in the recF-gyrB region. The M. smegmatis DNA gyrase, which was purified by affinity chromatography on novobiocin-Sepharose, consisted of two polypeptides with apparent molecular masses of 98 and 80 kDa. Determination of the N-terminal amino acid sequence of the B subunit confirmed GTG as the start codon in gyrB. Analysis of the supercoiling activity of the enzyme indicated that the M. smegmatis DNA gyrase was characterized by a specific activity equivalent to that of the Escherichia coli DNA gyrase. Inhibition of this activity by 4-quinolones was investigated by determining the 50% inhibitory concentrations (IC50S) of nalidixic acid, ofloxacin, and ciprofloxacin. The results indicated that the inhibitory activities of these drugs against the M. smegmatis DNA gyrase were markedly lower than those previously reported for the E. coli DNA gyrase. The results also suggested that the higher levels of activity of ofloxacin and ciprofloxacin against M. smegmatis (MICs, 0.5 to 1 microgram/ml), in contrast to that of nalidixic acid (MIC, 256 micrograms/ml), could be related to the higher inhibitory activities of fluoroquinolones against the DNA gyrase from this species (IC50S, 7 to 14 micrograms/ml) compared with that of nalidixic acid (IC50, 1,400 micrograms/ml).

4-Quinolones↗

PubMed2006

Antimicrobial susceptibility of clinical isolates of non-jejuni/coli campylobacters and arcobacters from Belgium.

OBJECTIVES: To determine the susceptibility of non-jejuni/coli campylobacters and arcobacters isolated from diarrhoeal stool specimens in Belgium. METHODS: The MICs were determined using Etest for six antimicrobial agents including ampicillin, erythromycin, nalidixic acid, ciprofloxacin, gentamicin and tetracycline for the most frequently isolated non-jejuni/coli campylobacter and arcobacter strains in two University Hospital laboratories between 1995 and 2005. RESULTS: In total, 85 Campylobacter upsaliensis, 20 Campylobacter concisus, 11 Campylobacter fetus, 61 Arcobacter butzleri and 10 Arcobacter cryaerophilus isolates were tested. Most C. upsaliensis strains were susceptible to ampicillin (100%), gentamicin (100%), ciprofloxacin (94.1%) and tetracycline (100%), whereas 11.8 and 12.9% were resistant to nalidixic acid and erythromycin, respectively. For A. butzleri, 78.7% of isolates were susceptible to ampicillin and erythromycin. Most A. butzleri isolates were susceptible to ciprofloxacin (96.7%), nalidixic acid (82.0%), gentamicin (100%) and tetracycline (100%). All C. concisus strains were fully susceptible to ampicillin and tetracycline, but 5% of them were resistant to gentamicin, ciprofloxacin and erythromycin. Nearly all C. fetus and A. cryaerophilus strains were susceptible to erythromycin but the results should be interpreted with caution since only a small number of strains were tested. CONCLUSIONS: Fluoroquinolones should be considered in the treatment of severe C. upsaliensis and A. butzleri infection. When clinically indicated, erythromycin remains the first choice for the treatment of intestinal campylobacteriosis caused by C. concisus and C. fetus.

Anti-Bacterial Agents↗

PubMed2004

A European survey of antimicrobial susceptibility among zoonotic and commensal bacteria isolated from food-producing animals.

OBJECTIVE: To study antimicrobial resistance in zoonotic bacteria isolated from food animals in different countries using uniform methodology. METHODS: Samples were taken at slaughter from chickens, pigs and cattle in four EU countries per host. Escherichia coli (indicator organism; n = 2118), Salmonella spp. (n = 271) and Campylobacter spp. (n = 1325) were isolated in national laboratories and MICs tested in a central laboratory against, where appropriate, ampicillin, cefepime, cefotaxime, ciprofloxacin, chloramphenicol, erythromycin, gentamicin, nalidixic acid, streptomycin, tetracycline and trimethoprim/sulfamethoxazole. RESULTS: Isolation rates were high for E. coli, low for Salmonella and intermediate for Campylobacter. MIC results showed resistance prevalence varied among compounds, hosts and countries. For E. coli and Salmonella, resistance to newer compounds (cefepime, cefotaxime, ciprofloxacin) was absent or low, but to older compounds (except gentamicin), resistance was variable and higher. E. coli isolates from Sweden showed low resistance, whereas among isolates from Spain (pigs), resistance to ampicillin, chloramphenicol, streptomycin, tetracycline and trimethoprim/sulfamethoxazole was higher; the UK, France, the Netherlands, Germany, Italy and Denmark were intermediate. For Campylobacter spp. isolates from chickens, nalidixic acid and ciprofloxacin resistance was >30% in France and the Netherlands, >6% in the UK and zero in Sweden. Nalidixic acid resistance was high in cattle (20%-64%), whereas ciprofloxacin resistance was markedly lower in cattle, variable in pigs (3%-21%) and highest in Sweden. Generally, Campylobacter coli was more resistant than Campylobacter jejuni. CONCLUSION: Antimicrobial resistance among enteric organisms in food animals varied among countries, particularly for older antimicrobials, but resistance to newer compounds used to treat disease in humans was generally low.

Animals↗

PubMed1979

Degradation of Escherichia coli DNA: evidence for limitation in vivo by protein X, the recA gene product.

DNA is more extensively degraded after it is damaged in recA mutants of E. coli than in wild type cells. All data presented here are consistent with the recA gene product, protein X, being an inhibitor of nalidixic acid induced degradation of the bulk DNA (but not of newly replicated DNA). Production of protein X also is correlated with appearance of various "S.O.S." repair functions. Evidence was obtained by comparing the rates of protein X synthesis and solubilization of uniformly-labeled DNA in intact cells, incubated in the presence of nalidixic acid. A set of mutants at the lexA locus produced protein X at different rates and degraded their DNA at rates which were inversely correlated to their rates of protein X production. A low concentration of rifampicin quite specifically inhibited protein X production by wild type E. coli, and allowed more rapid DNA degradation. After the DNA was damaged by the incubation of cells in the presence of nalidixic acid, cells preloaded with protein X degraded their DNA more slowly. We propose that protein X could protect DNA against degradation by binding to single-stranded regions, thereby inhibiting nuclease action.

Bacterial Proteins↗

PubMed1994

Association between double mutation in gyrA gene of ciprofloxacin-resistant clinical isolates of Escherichia coli and MICs.

The mutations in the quinolone resistance-determining region of the gyrA and gyrB genes from 27 clinical isolates of Escherichia coli with a range of MICs of ciprofloxacin from 0.007 to 128 micrograms/ml and of nalidixic acid from 2 to > 2,000 micrograms/ml were determined by DNA sequencing. All 15 isolates with ciprofloxacin MICs of > or = 1 micrograms/ml showed a change in Ser-83 to Leu of GyrA protein, whereas in clinical isolates with a MIC of > or = 8 micrograms/ml (11 strains), a double change in Ser-83 and Asp-87 was found. All isolates with a MIC of nalidixic acid of > or = 128 micrograms/ml showed a mutation at amino acid codon Ser-83. Only 1 of the 27 clinical isolates of E. coli analyzed showed a change in Lys-447 of the B subunit of DNA gyrase. A change in Ser-83 is sufficient to generate a high level of resistance to nalidixic acid, whereas a second mutation at Asp-87 in the A subunit of DNA gyrase may play a complementary role in developing the strain's high levels of ciprofloxacin resistance.

Amino Acid Sequence↗

PubMed1980

Four proteins synthesized in response to deoxyribonucleic acid damage in Micrococcus radiodurans.

Four proteins, alpha beta, gamma, and delta, preferentially synthesized in ultraviolet light-treated cells of Micrococcus radiodurans, were characterized in terms of their molecular weights and isoelectric points. Within the sublethal-dose range, the differential rate of synthesis for these proteins increased linearly with the inducing UV dose. The degree of induction reached 100-fold, and the most abundant protein beta, amounted to approximately 2% of the total newly synthesized protein after irradiation. Damage caused by ionizing radiation or by treatment with mitomycin C also provoked the synthesis of the four proteins. The proportions between the individual proteins, however, varied strikingly with the damaging agent. In contrast to treatments which introduced damage in the cellular deoxyribonucleic acid, the mere arrest of deoxyribonucleic acid replication, caused by nalidixic acid or by starvation for thymine, failed to elicit the synthesis of either protein. Repair of deoxyribonucleic acid damage requires that a number of versatile and efficient processes by employed. It is proposed that the induced proteins participate in deoxyribonucleic acid repair in M. radiodurans. Mechanisms are discussed which would allow a differentiated cellular response to damages of sufficiently distinctive nature.

Bacterial Proteins↗

PubMed1986

DNA synthesis inhibitors suppress expression of Epstein-Barr virus in chemically activated human lymphoblastoid cells.

Of the DNA synthesis inhibitors tested, novobiocin, nalidixic acid, coumermycin A1, mitomycin C, hydroxyurea, and bleomycin effectively inhibited Epstein-Barr virus (EBV)-related early antigen (EA) synthesis induced in human lymphoblastoid cells by 12-O-tetradecanoyl-phorbol-13-acetate and n-butyrate, but did not inhibit EA synthesis in 12-O-tetradecanoyl-phorbol-13-acetate and n-butyrate, but did not inhibit EA synthesis in cells superinfected with EBV. Inhibition of EA synthesis by treatment with novobiocin, nalidixic acid, or coumermycin A1 paralleled that of total cellular DNA synthesis, whereas mitomycin C, hydroxyurea, and bleomycin prevented EA synthesis at higher concentrations than those required for DNA inhibition. Inhibition of EA and total RNA synthesis was not in parallel. The inhibition by novobiocin, nalidixic acid, bleomycin, and hydroxyurea was reversible. Our results suggest that DNA synthesis inhibitors prevent the synthesis of EA in a manner independent of their inhibitory effects on cellular DNA synthesis and that these inhibitors act on a common process of EBV genome activation by different inducing agents.

Alkylating Agents↗

PubMed1971

Nature of the penetration barrier in Escherichia coli K-12: effect of macromolecular inhibition of penetrability in strains containing the envA gene.

The envA mutation in Escherichia coli K-12, which maps at 1.5 min, was previously shown to mediate sensitivity to gentian violet as well as to several antibiotics. Moreover, strains containing the envA gene were recently found to be lysed by lysozyme in the absence of ethylenediaminetetraacetate. It is here reported that the envA mutation mediates an increased uptake of gentian violet. The uptake of the dye was markedly affected by growth with different antibiotics interfering with macromolecular synthesis. Amino acid starvation of a strain containing envA with a stringent control of ribonucleic acid (RNA) synthesis resulted in a decreased uptake of gentian violet. However, no decrease in dye uptake was found during starvation in an envA transductant with a relaxed control of RNA synthesis. Inhibition of deoxyribonucleic acid (DNA) synthesis by nalidixic acid decreased the uptake of gentian violet of envA cells and, in addition, rendered the cells insensitive to the lytic action of lysozyme. Chloramphenicol treatment increased penetrability in wild-type and starved envA cells. In most instances, this effect of chloramphenicol was prevented by selectively interfering with DNA or RNA synthesis. A coordinate regulation of nucleic acid synthesis and penetrability is suggested.

Amino Acids↗

PubMed2003

Resistance to quinolones in Campylobacter jejuni and Campylobacter coli from Danish broilers at farm level.

AIMS: To investigate the prevalence of quinolone resistance among Campylobacter jejuni and Camp. coli isolates from Danish poultry at the farm level, as well as for the whole country. METHODS AND RESULTS: Data and isolates were collected from a national surveillance of Campylobacter in poultry. Quinolone resistance was investigated by determination of minimum inhibitory concentration (MIC) to nalidixic acid and enrofloxacin. Among Camp. jejuni and Camp. coli combined, 7.5% were resistant to nalidixic acid. Quinolone resistance varied considerably from farm to farm, with 0% on some farms and almost 100% on others, but the resistance was evenly distributed geographically. With respect to isolates from farms where resistance was detected, quinolone resistance was higher among Camp. coli (28.7%) than among Camp. jejuni (11.3%). PFGE typing of quinolone-resistant and quinolone-susceptible isolates from four farms indicated that certain resistant isolates belonged to specific clones that were able to persist on the farms during several rotations, even in the absence of selective pressure. Some clones were present and repeatedly isolated in both a quinolone-susceptible and quinolone-resistant variant. CONCLUSIONS: Overall, quinolone resistance among Campylobacter isolates from Danish broilers was 7.5% in 1998 and 1999; it was higher among Camp. coli than Camp. jejuni. Genetic diversity among resistant isolates was lower than among susceptible isolates, and certain clones existed in both a resistant and a susceptible variant. Some resistant clones appeared to persist on the farms and were repeatedly isolated from poultry flocks. SIGNIFICANCE AND IMPACT OF THE STUDY: The study is important for the understanding of persistence and dynamics of Campylobacter in broiler houses. It also highlights the extent, farm-to-farm variation and persistence of quinolone-resistant Campylobacter in broiler houses.

Animals↗

PubMed2005

Survival of Listeria monocytogenes on fresh and frozen strawberries.

Cut or intact surfaces of fresh strawberries were spot inoculated with a five-strain cocktail of nalidixic-acid resistant Listeria monocytogenes (10(6) (low inoculum) and 10(8) (high inoculum) CFU per three-berry sample). Inoculated strawberries were dried for 1 h at 24 degrees C and were stored in loosely closed containers at 4 or 24 degrees C. An initial population reduction of approximately 0.6 and 1.2 log cycles, high and low inoculum, respectively, was observed on intact but not cut berries after the 1-h drying period. A decrease of 1.4 and 3.3 log cycles per intact sample was observed over 48 h for the high and low inoculum, respectively, when stored at 24 degrees C. When held at 4 degrees C, a reduction of approximately 3 log cycles per intact-berry sample was observed for both inocula over the 7-day storage period. Populations on cut surfaces remained constant at both temperatures and both inoculum densities throughout the storage period. Sliced, inoculated strawberries (6.7 log CFU/25-g sample) with or without 20% sucrose were frozen at -20+/-2 degrees C. After 28 days of frozen storage, populations of L. monocytogenes determined on tryptose phosphate agar supplemented with nalidixic acid (TPAN) had declined by 0 to 1.2 log cycles, with and without 20% sucrose, respectively. Counts on modified Oxford agar supplemented with nalidixic acid were significantly (P< or =0.05) lower (0.5 to 1.8 log CFU/g) than on TPAN indicating that some cell injury had occurred. Results of this study indicate that L. monocytogenes is capable of survival but not growth on the surface of fresh intact or cut strawberries throughout the expected shelf life of the fresh fruit and can survive on frozen strawberries for periods of at least 4 weeks. On whole strawberries held at 24 degrees C, significantly faster declines (P< or =0.05) of L. monocytogenes were observed when lower rather than higher inoculum levels were applied.

Colony Count, Microbial↗

PubMed1990

Reduction of Chloroplast DNA Content in Solanum nigrum Suspension Cells by Treatment with Chloroplast DNA Synthesis Inhibitors.

Suspension cell cultures of Solanum nigrum were grown in the presence of six different chloroplast DNA synthesis inhibitors in order to determine whether the pool size of chloroplast DNA (cpDNA) could be selectively reduced relative to the nuclear DNA content. One of the effects of the inhibitors was a reduction in cell growth and viability. Cell growth (fresh weight) was reduced 50% (in 8 day cultures) by: 100 micromolar bisbenzimide, 8 micromolar ethidium bromide, 0.3 micromolar 5-fluordeoxyuridine (Fudr), 200 micromolar nalidixic acid, 30 micromolar novobiocin, or 10 micrograms per milliliter rifampicin. At these concentrations, three of the inhibitors, ethidium bromide, Fudr, and rifampicin, also substantially reduced the viability of the cultures. Analyses of the chloroplast and nuclear DNA content per gram fresh weight by dot blot hybridizations indicated that the reduction of cpDNA content was greatest at inhibitor concentrations which reduced cell growth by more than 50% but this depended on the culture conditions. For example, the two DNA gyrase inhibitors, nalidixic acid and novobiocin, were more effective in lowering cpDNA content in cultures which were transferred (2 x 4 days) once during the eight day incubation. Because several inhibitors were toxic to cell growth, the DNA content of treated cells was also determined on the basis of cell (protoplasts) number. Analyses of nuclear and cpDNA content per cell for each treatment indicated that only the DNA gyrase inhibitors, nalidixic acid, and novobiocin reduced cpDNA content. Neither inhibitor reduced nuclear DNA content. These results suggest that DNA gyrases participate in cpDNA replication. The selective reduction of cpDNA content in regeneratable cultures may facilitate the generation and selection of cpDNA mutants or transformants from higher plants.

Journal Article↗

PubMed1991

Campylobacter butzleri sp. nov. isolated from humans and animals with diarrheal illness.

Seventy-eight aerotolerant Campylobacter isolates were characterized phenotypically and by DNA hybridization (hydroxyapatite method at 50 and 65 degrees C). Two DNA relatedness groups were found. (i) Sixty-four strains belonged to aerotolerant Campylobacter DNA hybridization group 2. These organisms were isolated from humans, primarily with diarrheal illness, and animals on several continents. Strains were aerotolerant at 30 and 36 degrees C and catalase negative or weakly catalase positive, grew in media containing glycine and on MacConkey agar, were susceptible to nalidixic acid, and were resistant to cephalothin. The name Campylobacter butzleri sp. nov. is proposed for this group. (ii) DNA hybridization group 1 consisted of the type strain of Campylobacter cryaerophila and 13 additional strains isolated from 10 animals outside the United States and from three humans within the United States. This group was genetically diverse; five strains were closely related to the type strain of C. cryaerophila (DNA hybridization group 1A), and eight strains were more closely related to one another (DNA hybridization group 1B). Strains in DNA hybridization group 1B were phenotypically diverse, with two of eight strains resembling C. cryaerophila. The seven strains from DNA hybridization groups 1A and 1B which resembled C. cryaerophila and the C. cryaerophila type strain were aerotolerant only at 30 degrees C and catalase positive, did not grow in glycine or on MacConkey agar, were generally susceptible to nalidixic acid, and were resistant to cephalothin. The remaining six strains of DNA hybridization group 1B phenotypically resembled C. butzleri; however, they were generally catalase positive and susceptible to nalidixic acid and cephalothin. DNA hybridization group 1B is not designated as a separate species at this time since it cannot, with certainty, be separated genetically from C. cryaerophila or phenotypically from C. butzleri.

Animals↗

PubMed2004

Mechanism of resistance to several antimicrobial agents in Salmonella Clinical isolates causing traveler's diarrhea.

The evolution of antimicrobial resistance in Salmonella isolates causing traveler's diarrhea (TD) and their mechanisms of resistance to several antimicrobial agents were analyzed. From 1995 to 2002, a total of 62 Salmonella strains were isolated from stools of patients with TD. The antimicrobial susceptibility to 12 antibiotics was determined, and the molecular mechanisms of resistance to several of them were detected as well. The highest levels of resistance were found against tetracycline and ampicillin (21 and 19%, respectively), followed by resistance to nalidixic acid (16%), which was mainly detected from 2000 onward. Molecular mechanisms of resistance were analyzed in 16 isolates. In these isolates, which were resistant to ampicillin, two genes encoding beta-lactamases were detected: oxa-1 (one isolate) and tem-like (seven isolates [in one strain concomitantly with a carb-2]). Resistance to tetracycline was mainly related to tetA (five cases) and to tetB and tetG (one case each). Resistance to chloramphenicol was related to the presence of the floR and cmlA genes and to chloramphenicol acetyltransferase activity in one case each. Different genes encoding dihydrofolate-reductases (dfrA1, dfrA12, dfrA14, and dfrA17) were detected in trimethoprim-resistant isolates. Resistance to nalidixic acid was related to the presence of mutations in the amino acid codons 83 or 87 of the gyrA gene. Further surveillance of the Salmonella spp. causing TD is needed to detect trends in their resistance to antimicrobial agents, as we have shown in our study with nalidixic acid. Moreover, such studies will lead to better treatment and strategies to prevent and limit their spread.

Anti-Bacterial Agents↗

PubMed1993

Radiosensitization of human lung fibroblasts by chemical that decrease ATP levels.

Radiosensitization by lactate, pyruvate, nalidixic acid and novobiocin was studied in exponentially growing SH-18L human lung fibroblasts. All the chemicals had a slight radiosensitizing effect at a low concentration and a definite effect at a higher one. Decreases in the D0 and/or Dq values were present in each dose survival curve. Fibroblasts incubated with the low concentration of each chemical for 24 hrs after X irradiation showed no reduction in intracellular ATP content, whereas, the higher concentration produced a significant decrease. These observations suggest that the decrease in the ATP content may be involved in the radiosensitization of human fibroblasts at high concentrations of these chemicals. In contrast, radiosensitization at a low concentration is not explained by a relationship to ATP content. Different mechanisms may be involved in radiosensitization at low and high concentrations of these chemicals.

Adenosine Triphosphate↗

PubMed2002

Diarrhoeagenic bacterial pathogens in HIV-positive patients with diarrhoea in rural communities of Limpopo Province, South Africa.

Potential enteric bacterial pathogens in 60 HIV-positive patients with chronic diarrhoea in rural communities of the Limpopo Province, South Africa, were identified using standard microbiological methods. The Kirby-Bauer disk-diffusion method was employed to determine antibiograms of isolated bacteria. Results revealed that diarrhoeagenic bacterial agents were isolated from 48 (80%) of the 60 HIV-positive patients with diarrhoea. Forty-four (73.3%) and 16 (26.7%) of the 60 patients were female and male respectively in the age range of 17-55 years with a mean of 34 years. Bacterial pathogens isolated comprised Campylobacter species (20.0%), Plesiomonas shigelloides (16.6%), Aeromonas species (13.3%), and Escherichia coli, Shigella and Salmonella species (10.0% each). No attempts were made to isolate parasites, fungi, or viruses. Antibiotic susceptibility profiles revealed resistance of the isolates to ampicillin, cephalothin, chloramphenicol, erythromycin, and streptomycin. However, all (100%) of P. shigelloides and Salmonella species were sensitive to nalidixic acid and ciprofloxacin. Most isolates were susceptible to nalidixic acid, ciprofloxacin, and gentamicin, indicating the usefulness of these drugs, although antibiograms may not always correlate with clinical usefulness.

Adolescent↗