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Residual antibiotics from aquacultural farming may alter microbial community structure in aquatic environments in ways that may adversely or positively impact microbially-mediated ecological functions. This study investigated 26 ponds (26 composited samples) used to produce fish, razor clam and shrimp (farming and drying) and 2 channels (10 samples) in a saltwater aquacultural farm in southern China to characterize microbial community structure (represented by phospholipid fatty acids) in surface sediments (0-10 cm) with long-term exposure to residual antibiotics. 11 out of 14 widely-used antibiotics were quantifiable at μg kg(-1) levels in sediments but their concentrations did not statistically differ among ponds and channels, except norfloxacin in drying shrimp ponds and thiamphenicol in razor clam ponds. Concentrations of protozoan PLFAs were significantly increased in sediments from razor clam ponds while other microbial groups were similar among ponds and channels. Both canonical-correlation and stepwise-multiple-regression analyses on microbial community and residual antibiotics suggested that roxithromycin residuals were significantly related to shifts in microbial community structure in sediments. This study provided field evidence that multiple residual antibiotics at low environmental levels from aquacultural farming do not produce fundamental shifts in microbial community structure.
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A partial life-cycle study with zebrafish (Danio rerio) was conducted to evaluate the long-term effects of antibiotics, norfloxacin (NOR) and sulfamethoxazole (SMX). A series of bio-endpoints correlated to the growth, development, and reproduction was assessed. The results showed that the body weight and the condition factor were depressed by SMX at 200 μg/L during the growth period. Meanwhile, the activities of metabolic enzyme (ethoxyresorufin O-deethylase, EROD) and antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT) were stimulated in all cases. The consequences of parental exposure to antibiotics for the next generation were also examined. The egg production of parents were depressed by the 200 μg/L NOR and SMX alone or in combination. Similarly, decreased hatching, survival, and enhanced development abnormality of the next generation also occurred after parental exposure to SMX at the highest concentration. The heartbeat however was not altered in all cases. Furthermore, there was no significant difference in the bio-endpoints between the combined and individual treatment in most cases, with the exception of lower EROD activity and egg production in the co-treatment. The results suggest that long-term exposure to NOR and SMX at environmentally relevant concentrations, individually and in a mixture, may not significantly pose a threat to the growth, development, and reproduction of zebrafish, and an adverse effect may be expected at high concentration.
A series of novel 3-quinolinecarboxylic acid derivatives have been prepared and their antibacterial activity evaluated. These derivatives are characterized by fluorine attached to the 6-position and substituted amino groups appended to the 1- and 7-positions. Structure-activity relationship studies indicate that antibacterial potency is greatest when the 1-substituent is methylamino and the 7-substituent is either 4-methyl-1-piperazinyl, 16, or 1-piperazinyl, 21. Derivatives 16 and 21, the 1-methylamino analogues of pefloxacin and norfloxacin, respectively, show comparable in vitro and in vivo antibacterial potency to these two known agents. The activity (vs. Escherichia coli Vogel) of 16 (amifloxacin) is the following: in vitro MIC (microgram/mL) = 0.25; in vivo (mice) PD50 (mg/kg) = 1.0 (po), 0.6 (sc).
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Two novel haptens of ciprofloxacin containing a free amidogen group on the piperazinyl ring were synthesised that were used to produce the monoclonal antibodies. The antibodies obtained simultaneously recognised 12 fluoroquinolones (ciprofloxacin, enrofloxacin, norfloxacin, sarafloxacin, diflocaxin, danofloxacin, ofloxacin, marbofloxacin, pefloxacin, lomefloxacin, amifloxacin and enofloxacin). After evaluation of different coating antigen-antibody combinations, a heterologous competitive indirect ELISA was used to determine the 12 drugs. The cross-reactivities were in the range of 23-120% and the limits of detection were in the range of 1.0-4.5 ng mL(-1). Eight fluoroquinolone drugs licensed as veterinary drugs in China were fortified into blank chicken for analysis. The recoveries were in the range of 61.5-82.5% with coefficients of variation in the range of 7.5-15.2%.
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The selective bone delivery of quinolones conjugated with an acidic oligopeptide may be effective in treating osteomyelitis, although the resulting concentration of antibiotic may be insufficient to completely kill S. aureus.
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This review covers 2346 norfloxacin treated patients in clinical trials world wide. These studies show that 400 mg of norfloxacin b.i.d. was effective and compared favorably with other standard oral agents in the treatment of urinary tract infections, including complicated and recurrent infections in men. This regimen given b.i.d. or t.i.d. was also effective in the treatment of acute gastroenteritis due to common gastrointestinal pathogens such as enterotoxigenic Escherichia coli, Salmonella spp., Shigella spp., Campylobacter spp. as well as less common organisms. A single 800 mg dose was effective in the treatment of gonorrhoea including patients with extra genito-urinary involvement and penicillinase producing strains of Neisseria gonorrhoeae. Preliminary data from ongoing trials have also shown that norfloxacin is effective in the prophylaxis of traveller's diarrhoea and infections in the granulocytopenic patient. These various regimens of norfloxacin were well tolerated with a low incidence (less than 3%) of drug related adverse experiences. The most common adverse experiences were nausea, headache, dizziness, rash, elevation of liver enzymes and eosinophilia.
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Agricultural fields worldwide are being contaminated by the escalating application of veterinary antibiotics (VAs) via animal manure and biosolids applied as fertilizers or of wastewater for irrigation, resulting in soil degradation and damage to the health of terrestrial environments. This paper describes a series of column studies investigating the leaching behavior of five VAs, tetracycline (TC), sulfamethazine (SMZ), norfloxacin (NOR), erythromycin (ERY) and chloramphenicol (CAP), under different simulated rainfall conditions that could occur in agricultural environments. Our aim was to explore the effects of acid rain and torrential rain on the leaching of different VAs and to determine their leaching behaviors along the soil profile. The results showed that acid rain accelerated the accumulation of VAs from animal manure in surface soil while long rainfall durations promoted the downward migration of VAs in soil. Under acid rain conditions, a higher concentration of VAs remained in the animal manure. More VAs were eluted to deeper soil layers and the leachate under extreme rainfall conditions. The leachability of VAs was higher in sandy soil than in clay or loamy soil. SMZ and ERY posed a higher risk to deeper soil layers and groundwater, while NOR and TC tended to persist in surface soil, which can be explained by their different physicochemical properties in soil. Moreover, the general trends from two model assessments and soil column measurements appeared to be in agreement. SMZ had a high leachability, while NOR tended to accumulate in soils. This study provided vital insight into the persistence mechanisms of VAs in terrestrial environments and their potential risks to soils and groundwater.
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The newer quinolones, the fluoroquinolones, are represented by norfloxacin, ciprofloxacin, ofloxacin, and newer agents such as temafloxacin. These agents represent an improvement over their quinolone counterparts in many ways, including a wider spectrum of antimicrobial activity, improved pharmacokinetic properties, clinical efficacy against a wider range of diseases, and fewer and less severe adverse effects. The focus of preclinical evaluation of fluoroquinolone toxicity is guided by earlier data gathered from the quinolones on the juvenile joint, the kidney, the eye, and the central nervous system (CNS). Animal studies with the fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin, and temafloxacin) show similar arthropathic damage to the joints of young animals as did the earlier investigations with quinolones. Effects on the kidney that have been reported with quinolones and fluoroquinolones include mild interstitial nephritis, occult blood in urine, decreased renal function, increased renal weight, and crystalluria. These effects are not believed to be a direct toxic effect, but secondary to precipitation of foreign material in the kidney with a neutral or alkaline urine. Because human urine is not normally alkaline, related toxicities should theoretically not be a problem, and clinical data to date generally support this thesis. Ocular toxicity consisting of lenticular opacities in rats and dogs, electrical and histopathologic changes in cats, and electrical changes in dogs have been reported after fluoroquinolone administration; this toxicity does not appear to be a problem in human use. CNS effects have been noted in both animals and humans. Convulsions have been observed with concomitant administration of enoxacin and fenbufen.
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6-Arylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamides 3 on Vilsmeier-Haak reaction produced 5-formyl-6-arylimidazo[2,1-b]-1,3, 4-thiadiazole-2-[N-(dimethylaminomethino)]sulfonamides 4, while 3 on treatment with potassium thiocyanate in the presence of bromine in acetic acid produced 5-thiocyanato-2-sulfonamides 6. Interaction of 4 with aminoguanidine hydrochloride in ethanol produced the corresponding 5-guanylhydrazone derivatives 5. Compounds 5 and 6 showed a high degree of antibacterial activity against both Escherichia coli and Staphylococcus aureus comparable to that of sulfamethoxazole and Norfloxacin. However, they were found to show moderate activity against Salmonella typhi, Pseudomonas aeruginosa and Pneumococci.
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During 2002 and 1998, 895 and 595 strains of Escherichia coli respectively, isolated from extrahospitalary bacteriurias were collected in ten health centers in Bierzo (León, Spain). Sensitivity to nine most commonly antibiotics used in the clinical practise was determined. The existence of significant differences of susceptibility among years (2002-1998) was analyzed by the chi square test.
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Six hundred and eighty five blood cultures from children clinically diagnosed as enteric fever yielded 176 salmonella strains showing isolation success rate of 25.7%, S. typhi were 164 (93.2%), S. paratyphi A 5 (2.8%), S. choleraesuis 4 (2.3%) and S. typhimurium 3 (1.7%). Antibiogram of 164 isolates of S. typhi showed triple drug resistance (TDR) in 156 strains (95.1%) to chloramphenicol, ampicillin and cotrimoxazole, and sensitivity of 90.2% and 95.1% to norfloxacin and ciprofloxacin respectively. Minimum inhibitory concentrations (MIC) of chloramphenicol were between 360 mcg and 640 mcg per ml. Phage types of 38 strains of TDR S. typhi were predominantly E1 and 0 with prevalences of 47.4% and 36.8% respectively in this region. All children with S. typhi isolates sensitive to quinolones in Vitro responded well to these drugs with almost no relapse and hence, the newer generation of quinolones could be considered as the first choice in the primary treatment of enteric fever.
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Fluoroquinolones are potent antibacterial agents that are active against a wide range of pathogenic organisms and are widely used in veterinary medicine. Fluoroquinolones and their metabolites may reach the soil through animal excreta or manure and may contaminate water and soils. The degree of sorption of these antimicrobials to soils varies widely, as does the mobility of these drugs. In the present study, sorption of norfloxacin in four soils of the state of São Paulo was investigated with batch equilibrium experiments. A strong matrix effect on the chromatographic determination of norfloxacin was verified. Sorption kinetics were best fit by a pseudo second-order model (r>0.99), and sorption/desorption isotherms were well fit by the Freundlich model in log form (r>0.97). Norfloxacin showed high affinity for soil particles, with KF sorption values ranging from 643 to 2410 μg(1-1/n)(cm(3))(1/n)g(-1) and KF desorption values ranging from 686 to 2468 μg(1-1/n)(cm(3))(1/n)g(-1). The high desorption KF values indicate that norfloxacin is highly immobile in the evaluated soils.