The in-vitro activity of enoxacin, ofloxacin, norfloxacin and nalidixic acid was determined against 1499 Gram-negative and 279 Gram-positive isolates from different clinical institutions in the Federal Republic of Germany. 90% of all Enterobacteriaceae were inhibited by 0.5 mg/l. Glucose non-fermenting Gram-negative rods and staphylococci were less sensitive to all 4-quinolones. All Gram-negative strains selected for resistance to nalidixic acid were significantly less sensitive to the new generation of 4-quinolones tested.
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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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The presence of pharmaceuticals in aquatic environment has become a topic of concern because of their potential adverse effects on human health and wildlife species. A total of 45 dewatered sewage sludge samples were collected throughout China and analyzed for 30 commonly consumed pharmaceutical residues. Ofloxacin was found to be the dominant contaminant with concentrations up to 24760 μg kg(-1), followed by oxytetracycline (5280 μg kg(-1)), norfloxacin (5280 μg kg(-1)) and ketoprofen (4458 μg kg(-1)). The concentration of pharmaceutical residues varied greatly depending on the operation conditions of wastewater treatment plants and sampling locations. Poor agreement was found between the predicted (calculation based on the annual consumption and coefficient of sludge water partition) and detected concentrations of the pharmaceuticals indicating that the occurrence of pharmaceutical residues was affected by various factors such as loading rates, sewage properties and the chemical properties such as the contribution from polar groups. National wide fate and ecotoxicity study is required for the development of control strategies.
Patients were randomly assigned to receive orally every 12 hours norfloxacin, 400 mg, or ciprofloxacin, 500 mg.
We report herein the synthesis of some N-Mannich bases in addition to different N-4 substituents of norfloxacin. The antibacterial activities of the newly synthesized compounds were evaluated and correlated with their physicochemical properties. Results revealed that some of the tested compounds exhibited better inhibitory activities than the reference antibiotic norfloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus strains. Correlation results showed that there is no single physicochemical parameter that can determine the effect of N-4 piperazinyl group on the activity of these fluoroquinolones, where lipophilicity, molecular mass and electronic factors may influence the activity.
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E. coli spontaneous bacterial peritonitis was detected in a 2-year period in three tertiary hospitals. Clinical and bacteriological data were obtained. Phylogenetic group and 15 virulence genes of E. coli strains were analyzed by polymerase gene reaction and compared with 50 isolates from pyelonephritis patients.
To analyse the in-vitro efficacy of commonly used antibacterials against bacterial pathogens from corneal ulcers.
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A recombinant plasmid, pYL-1, containing a tyrosinase gene whose expression is under the control of a phage T5 promoter and 2 lac operators, was constructed. Escherichia coli JM109 harboring pYL-1 was used for production of bacterial melanin. A simple procedure for the isolation and purification of melanin was developed. The ultraviolet (UV)-visible light absorption spectra of melanin prepared by chemical synthesis and derived from different organisms, including bacteria, a plant and an animal source, were determined. Melanins produced by both bacteria and chemical synthesis showed a steady increase of absorption at wavelengths of UV light ranging from approximately 200-400 nm, while melanin derived either from plant or animal sources showed an additional discrete absorption peak at wavelength 280 nm upon a similar steady increase of absorption. This additional absorption peak could be due to the presence of protein-bound melanins in animal and plant sources while a free form of melanin was obtained from bacteria and chemical synthesis. Analysis of the effect of bacterial melanin on the activity of antibiotics against E. coli revealed that the activities of polymyxin B, kanamycin, tetracycline, and ampicillin were markedly reduced in the presence of melanin, whereas the activity of norfloxacin was not affected. The reduction of the antibacterial activity may result directly from the interaction of antibiotics with melanin. However, the mechanism of this interaction remains to be demonstrated.
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UTIs were more common in the 0-1 year age group, among males. Among females, UTIs were commonly seen after 2 years of life. The most common isolated pathogen was Escherichia coli spp (45.12%), followed by Klebsiella spp (18.17%) and Enterococcus spp (9.23%). Isolated pathogens were highly resistant to ampicillin, co-trimoxazole, and norfloxacin (82%-98%) and highly sensitive to gentamicin (83%),amikacin (76.5%), and nitrofurantoin (71.5%).
Among recent clinical isolates in Japan, strain CU264 was discovered which formed unusual colonies. This strain was identified as Rahnella aquatilis which is usually found in water. The antibiotic susceptibilities against tetracycline, carbenicillin, chloramphenicol, streptomycin, kanamycin, gentamicin, sulphonamide, neomycin, fosfomycin, rifampicin, norfloxacin and nalidixic acid, were investigated. The result demonstrated that the strain was highly resistant to fosfomycin only. It was further shown that this resistance was transmissible with low frequency to Serratia marcescens whereas it was not transmissible to Escherichia coli.
A DNA fragment responsible for resistance to antimicrobial agents was cloned from the chromosomal DNA of Enterococcus faecalis ATCC 29212 by using drug-hypersensitive mutant Escherichia coli KAM32 as a host cell. Cells of E. coli KAM32 harboring a recombinant plasmid (pAEF82) carrying the DNA fragment became resistant to many structurally unrelated antimicrobial agents, such as norfloxacin, ciprofloxacin, doxycycline, acriflavine, 4',6-diamidino-2-phenylindole, tetraphenylphosphonium chloride, daunorubicin, and doxorubicin. Since the sequence of the whole genome of E. faecalis is known, we sequenced several portions of the DNA insert in plasmid pAEF82 and identified two open reading frames within the insert. We designated the genes efrA and efrB. A search of the deduced amino acid sequences of EfrA and EfrB revealed that they are similar to each other and that they belong to the ATP-binding cassette (ABC) family of multidrug efflux transporters. Transformed E. coli KAM32 cells harboring efrAB showed energy-dependent efflux of acriflavine. The efflux activity was inhibited by reserpine, verapamil, and sodium-o-vanadate, known inhibitors of ABC efflux pumps.
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Three clinically normal pigs were given a single intramuscular injection of an aqueous solution of norfloxacin nicotinate (NFN) at 14 mg/kg body weight. Animals were killed 4 h after treatment and the concentrations of norfloxacin in various biological fluids and tissues were determined by chemical (high performance liquid chromatography, HPLC) and microbiological assay methods. Drug distribution throughout the body was presented as actual concentrations (micrograms/ml and ppm) in each sample and as the ratio of drug concentration in tissue to drug concentration in plasma. Highest concentrations were found in the urine, kidney, liver and bile. The drug was not detected in ocular fluid, brain tissue (by microbiological assay), fat (by HPLC) and skin (by HPLC). Tissue-to-plasma concentrations ratios were near to, or greater than, 1.0 (HPLC assay) for the kidney, liver, spleen, muscle, lung, adrenals, salivary glands, pleural and synovial fluid, and smaller than 1.0 for cerebrospinal fluid, brain tissue and lymph nodes. Agreement between the chemical and microbiological assay results was variable, depending on the type of tissue and biological fluid tested. Binding of norfloxacin to plasma proteins in pig is low (23%-29%). The distribution pattern of the drug in pig, laboratory animals and humans is very similar; it can be characterized as extensive, with tissue-to-serum ratios reaching 2:1 or more in certain non-excretory organs. These values may reflect intracellular concentrations of the drug.
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Emergence of increased antimicrobial resistance of Shigella species is a global challenge, particularly in developing countries where increased misuse of antimicrobial agents occurs. There is no published data in the study area on the prevalence and antimicrobial susceptibility patterns of Shigella among acute diarrheal patients. This study was therefore, under taken to fill this gap.
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By June 1987 worldwide investigators from 37 centres in 12 countries had completed epidemiological susceptibility testing studies comparing the in-vitro activity of fleroxacin with that of ciprofloxacin, norfloxacin and other antibacterials. In this paper the results of these studies, expressed primarily as MIC90S, are reviewed and analysed for centre to centre variability. Twenty thousand eight hundred and seven strains were evaluable for comparative analysis. All three quinolones exhibited high in-vitro activity against Enterobacteriaceae (MIC90 less than or equal to 0.125-2 mg/l), other common aerobic Gram-negative bacilli or coccobacilli (MIC90 less than or equal to 0.125-1 mg/l) and staphylococci, including selected resistant isolates (MIC90 less than or equal to 0.5-4 mg/l), and moderate to weak activity against streptococci and anaerobes (MIC90 = 1- greater than or equal to 8 mg/l). The activity of fleroxacin and norfloxacin was quite similar, but was usually inferior to that of ciprofloxacin. Comparison of data from the various investigating centres showed divergent results for many bacterial species, the MIC90S for the same quinolone varying by two to four dilution steps or more from centre to centre.
There is high antibiotic resistance in children with UTI. The patterns of uropathogen antimicrobial resistance vary in susceptibility to antimicrobials depending on region and time. Thus, the trends of antibiotic susceptibility patterns should be analyzed periodically to select the appropriate regimen for UTI treatment.
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Ciprofloxacin and other newer quinolone antimicrobial agents exhibit increased potency and decreased frequency of spontaneous bacterial resistance in comparison with older analogues such as nalidixic acid. New and published observations on the mechanisms of action of and resistance to ciprofloxacin in Escherichia coli are presented and discussed. Genetic and biochemical studies have identified the A subunit of the essential bacterial enzyme DNA gyrase as a target of ciprofloxacin and other quinolones. For a series of quinolones, inhibition of purified DNA gyrase correlated with antibacterial activity. The bactericidal activity of ciprofloxacin and ofloxacin is, in contrast to that of certain other quinolones, somewhat less affected by rifampin and cell starvation, suggesting the existence of a site of drug action in addition to DNA gyrase. The frequency of selection of spontaneous single-step resistance mutants of E. coli was more than 100-fold lower with ciprofloxacin than with nalidixic acid. Strains highly resistant to ciprofloxacin could, nevertheless, be selected by serial passage on drug-containing agar. Two mutations contributing to this high level of resistance were analyzed. One, designated cfxA, conferred a 16-fold increase in drug resistance and mapped in a location consistent with a gyrA mutation; similar increases in resistance to ciprofloxacin were seen with gyrA mutations selected for resistance to other quinolones. The other mutation, cfxB, conferred pleiotropic resistance to ciprofloxacin, tetracycline, and chloramphenicol and appeared to be an allele of the multiple antibiotic resistance gene marA. The mutation cfxB was associated with a decreased amount of porin outer membrane protein OmpF, suggesting that drug permeation may occur in part through this channel. In summary, the A subunit of DNA gyrase is a target of ciprofloxacin and other quinolones. Ciprofloxacin resistance appears to occur both by mutation in this target and by alteration of drug permeation through the outer membrane of the cell.
When terbium ion (Tb3+)-norfloxacin (NFLX) complex is issued a fluorescent probe, in a buffer solution of pH = 7.6, NADP can remarkably enhance the fluorescence intensity of the Tb3+ -NFLX complex at lambda = 545 nm. The enhanced fluorescence intensity of Tb3+ is in proportion to the concentration of NADP. The dynamic range for the determination of NADP is 1.11 x 10(-7) - 6.16 x 10(-5) mol l(-1), with a detection limit of 4.31 x 10(-8) mol l(-1). This method is simple, practical and relatively free of interference from coexisting substances, so it can be successfully applied to determination of NADP in synthetic water samples.
The clonal relationships among the various strains was established by serotyping and pulsed-field gel electrophoresis. MICs for beta-lactams, quinolones, chloramphenicol and tetracycline were determined. Presence of beta-lactamases was ruled out by a colorimetric assay. Quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes were sequenced, and the relevance of the mutations in these regions was evaluated by complementation assays. Outer membrane protein profiles, the effect of phenylalanyl-arginyl-naphthylamide (PAN, 20 mg/l) on the MICs of several quinolones, and norfloxacin accumulation in the absence and in the presence of a metabolic inhibitor were also determined.
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To compare the bacterial aetiology and their in vitroantibacterial susceptibilities of acute and chronic dacryocystitis.
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In Vietnam's coastal wetlands, fluoroquinolones, a widely used class of antibiotics in shrimp farming, are frequently detected in sediments of former shrimp farms. This phenomenon could lead to negative impacts on the aquatic ecosystem, since the antibiotic residues could induce changes in the microorganism communities of the water body. The potential of native wetland plants (Acrostichum aureum L. and Rhizophora apiculata Blume Fl. Javae) for phytoremediation of fluoroquinolones (ciprofloxacin and norfloxacin) was investigated. The half-life for each antibiotic was estimated at approximately 10 days in the planted sediment. With respect to the accumulation of ciprofloxacin and norfloxacin in plants, these antibiotics were found mainly in roots. Antibiotic translocation from root to stem and leaves occurred at a low rate. The results showed that A. aureum and R. apiculata can be valuable for the phytoremediation of antibiotic-contaminated sediments. Additionally, the initialfindings of the presence of resistant bacteria indicated that bacteria could play a role in facilitating the phytodegradation.
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With the increasing use of herbal remedies by the general public worldwide, there remains a lack of information on the relationship between nutraceutical use and antibiotic resistance. Historically, there have been claims that nutraceuticals possess antibacterial and antiviral activity. However, the claims come with little or no documentation and no information related to the development of resistance to the nutraceutical or the cause of increases in resistance to antibiotics. These studies investigate the ability of nutraceutical exposure to influence the development of antibiotic resistance in bacteria. Two antibiotic-sensitive organisms, Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922, were used as representative of the gram-positive and gram-negative bacteria. These preliminary investigations showed a general increase to the ampicillin marker by the products studied, using Staphylococcus aureus ATCC 29213 as the indicator organism. There were 13 product-related increases in the MIC, 2 decreases, and 7 no changes. All six of the garlic products increased the MIC of the norfloxacin marker to greater than fourfold above baseline. Using E. coli ATCC 25922 as the indicator organism, the greatest product-antibiotic marker interaction was with the ampicillin marker. Garlic, Echinacea, and zinc products all caused large increases in the MIC to ampicillin over baseline values.
DTBN from N. japonicum showed anti-MRSA and anti-VRE activities. DTBN might be involved in the inhibition of DNA topoisomerase IV.
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Parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 4 to 10, of 17 fluoroquinolones, including three congeneric series with systematically varied alkyl chain length at the 4'N-position of the piperazine residue. The permeability values spanned over three orders of magnitude. The intrinsic permeability, P(o), and the membrane permeability, P(m), were determined from the pH dependence of the effective permeability. The pK(a) values were determined potentiometrically. The PAMPA method employed stirring, adjusted such that the unstirred water layer (UWL) thickness matched the 30-100 microm range estimated to be in the human small intestine. The intrinsic permeability coefficients (10(-6)cm/s), representing the permeability of the uncharged form of the drug, are for 4'N-R-norfloxacin: 0.7 (R=H), 49 (Me), 132 (n-Pr), 365 (n-Bu); 4'N-R-ciprofloxacin: 2.7 (H), 37 (Me), 137 (n-Pr), 302 (n-Bu); 4'N-R-3'-methylciprofloxacin: 3.8 (H), 20 (Me), 51 (Et), 160 (n-Pr), 418 (n-Bu). Increasing the alkyl chain length in the congeneric series resulted in increased permeability, averaging about 0.34 log units per methylene group, except that of the first (H-to-Me), which was about 1.2 log units. These results were compared to Caco-2 and rat in situ permeability measurements. The in situ closed loop technique used for obtaining permeability values in rat showed a water layer thickness effect quite consistent with in vivo expectations. The rat-PAMPA correlation (r2=0.87) was better than that of rat-Caco-2 (r2=0.63). Caco-2-PAMPA correlation indicated r2=0.66. The latter correlation improved significantly (r2=0.82) when the Caco-2 data were corrected for the UWL effect.
To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.
This is the first report of the El Tor variant of V. cholerae O1 Ogawa having the ctxB gene of the classical strain with altered antibiogram causing epidemics of cholera in Orissa, India.
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S. typhimurium AlhR, S. enteritidis OulR, and S. hadar GueR resistant to fluoroquinolones (QR), ciprofloxacin MICs, 0.25 to 1 microgram/ml; norfloxacin MICs, 0.5 to 4 micrograms/ml; nalidixic acid MIC, 256 micrograms/ml were isolated from urinary tract infections (AlhR and OulR) during FQ therapy in immunocompromised patients infected by the parent FQ-susceptible strains (AlhS and OulS) (ciprofloxacin MICs, 0.032-0.063; norfloxacin MICs, 0.125-0.25; nalidixic acid MICs, 4-8) or from intestinal infection (GueR). Transformation of AlhR, OulR, and GueR by plasmid pJSW101 carrying the wild-type gyrA gene of Escherichia coli resulted in complementation (nalidixic acid MICs, 4 to 8), proving that these strains had a gyrA mutation. A 800-bp fragment of gyrA from the five strains was amplified by PCR. Direct DNA sequencing of 252-bp region of this fragment identified a single point mutation leading to a substitution Ser-83 to Tyr in AlhR and to a substitution Ser-83 to Phe in OulR and in GueR. These results emphasize the potential risk of selection of FQ-resistant Salmonella during FQ therapy in immunocompromised patients and suggest that these strains differ from the parent strains at least by one mutation in the gyrA gene. They also confirm the role of substitutions in position 83 of gyrA in FQ-resistant clinical isolates of Salmonella.
Ascites is a common clinical problem in children with liver disease. The peripheral arterial vasodilation hypothesis is mostly accepted as the pathophysiological basis of ascites. The most important complication is spontaneous ascitic fluid infection in the form of spontaneous bacterial peritonitis (SBP) and its variants. Aerobic gram-negative bacteria, primarily Escherichia coli, are the most common isolates. Diagnostic paracentesis is done in patients with ascites when diagnosed first time and at the beginning of each admission to hospital. Ascitic fluid is evaluated for cell count with differential, albumin level, total protein and culture. Serum-ascites albumin gradient (SAAG) is the best single test for classifying ascites into portal hypertensive (SAAG> 1.1 g/dL) and non-portal hypertensive (SAAG < 1.1 g/dL) causes. In patients with tense ascites LVP should be performed. A neutrophil count of > 250 cells/mm3 is highly suggestive of bacterial peritonitis. Intravenous cefotaxime is the empiric antibiotic of choice. Long-term administration of oral norfloxacin 5-7.5 mg/Kg once a day in cirrhotic patients with ascitic fluid protein content of < 1g/dL or prior episode of SBP is recommended for prevention of SBP. Oral dual diuretic therapy of single morning dose of spironolactone along with furosemide in the ratio of 5:2 is recommended. While obtaining satisfactory diuretic response dual diuretic therapy can be changed over to monotherapy with spironolactone. Patients should be on sodium restricted diet. Management of ascites might ultimately require liver transplantation.
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TA displayed a weak inhibitory effect (MIC 512 μg/ml) against S. aureus SA-1119, while no inhibitory effect was displayed by GA (MIC >512 μg/ml). However, when TA was tested at a subinhibitory concentration in combination with Nor, the MIC of Nor against S. aureus SA-1119 decreased from 128 to 4 μg/ml (32-fold); this effect was not observed for GA. In the checkerboard assay, the MIC of TA and Nor decreased from 512 to 128 μg/ml (4-fold) and from 128 to 8 μg/ml (16-fold), respectively. The combination of TA and Nor presented an FICI as low as 0.31, which indicates a synergistic interaction.