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Minimum inhibitory concentration (MIC) of some antibiotics against Vibrio cholerae O139 isolates from Pondicherry.

The antibiotic susceptibility pattern of Vibrio cholerae O139, Bengal, an emerging intestinal pathogen has been determined by the Kirby Bauer technique and the MIC values of some antibiotics against these strains by agar dilution technique. All the strains were susceptible to tetracycline, norfloxacin, ciprofloxacin and a majority was susceptible to gentamicin (95.7%) and nalidixic acid (82.9%). Only 51% were susceptible to cefotaxime and most strains were resistant to furazolidone (95.7%), ampicillin (87.3%) and co-trimoxazole (91.5%). The study shows the importance of judicious use of antibiotics in cholera cases and the need for monitoring the susceptibility status of these strains particularly because of their ability to cause extra-intestinal infections like septicaemia.

Ampicillin↗

Effects of pranidipine, a calcium channel antagonist, in an avian model of heart failure.

We have previously demonstrated that turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (DCM) which approximates the human condition [1-3]. We wanted to study the effects of a calcium channel blocker in an animal model with a documented decrease in beta-receptor density, increased levels of circulating catecholamines, and abnormal calcium metabolism. The effects of a third generation calcium channel blocker has not been studied in our model. We hypothesized that the model would be predictive of the human condition and provide additional insights into the potential use of Ca2+ channel blockers in the setting of DCM. In the present study, we examined the effect of pranidipine, a new dihydropyridine calcium antagonist, in the setting of DCM on the gross and microscopic morphology of the heart and the overall contractile performance of the myocardium. A state of symptomatic to mild cardiomyopathy was induced in Broad-Breasted White turkey poults by administration of Fz for three weeks. Blood pressure, heart rate, fractional shortening, and body weight were monitored and compared in DCM animals treated with pranidipine and those given a placebo. After four weeks of treatment or no treatment with pranidipine, animals were euthanized and heart weight, cardiac dimensions, and microscopic morphology were compared. Progressive left ventricular (LV) dilatation and wall thinning was prevented with pranidipine treatment. In addition, microscopic examination demonstrated myocyte hypertrophy regression in DCM animals treated with pranidipine. In DCM animals, treatment with pranidipine resulted in significantly smaller left ventricular dimensions. We conclude that the calcium channel blocker pranidipine was not detrimental to global cardiac function in animals with dilated cardiomyopathy.

Animals↗

A multicentre study on eradication of Helicobacter pylori using four 1-week triple therapies in China.

BACKGROUND: Short-term proton pump inhibitor-based triple therapies for the eradication of Helicobacter pylori are used widely. The eradication rates vary greatly from country to country and from region to region. AIM: To assess the efficacy at eradicating H. pylori of 1-week regimens containing three medications: omeprazole (O) or colloidal bismuth subcitrate (B), furazolidone (F) or metronidazole (M), and amoxicillin (A) or clarithromycin (C). METHODS: A multicentre study involving 20 hospitals in different regions of China. A total of 892 patients with H. pylori-positive non-ulcer dyspepsia or healed duodenal ulcer confirmed by endoscopy were recruited to receive, randomly, one of four regimens: OMC, OFC, OFA, and BFC, b.d. for 7 days. 13C-urea breath test was performed 4-8 weeks after completion of treatment. RESULTS: The eradication rates with per protocol/intention-to-treat analyses were: OMC (n=217/219) 66%/65%; OFC (n=227/229) 69%/69%; OFA (n=223/225) 87%/86%; and BFC (n=214/219) 80%/78%. The eradication rate (per protocol analysis) in duodenal ulcer (79%) was higher than that in non-ulcer dyspepsia (73%, P=0.033). Patient compliance was good. The adverse events of the four regimens were mild, and mainly gastrointestinal. CONCLUSIONS: The omeprazole, furazolidine and amoxicillin regimen achieves a high H. pylori eradication rate in different geographical regions of China.

Adolescent↗

Transfer of nitrofuran residues from parent broiler breeder chickens to broiler progeny.

The use of nitrofuran antibiotics in food-producing animals is prohibited within the EU. Countries in the EU, as well those intending to export food to the EU, must ensure that their products are free from nitrofuran residues. As a result of recent global problems where chicken meat from a wide range of countries has been contaminated with nitrofuran metabolites, an investigation was performed to discover whether or not residues of the nitrofurans might be transferred from parent breeder chickens to their offspring broilers. Four groups of broiler breeders were each treated with one of the nitrofurans: furazolidone, nitrofurazone, nitrofurantoin or furaltadone. Residues of their side-chain metabolites, AOZ, SEM, AHD and AMOZ, were detected in the fertilised eggs at concentrations up to 1567 microg/kg. However, in the chicks that subsequently hatched from these eggs, residue concentrations of SEM, for example, were only found up to 26.6 and 32.5 microg/kg in liver and muscle, respectively, for 1-d-old chicks. Residue concentrations in tissues had fallen below the detection limit of the analytical method for 40-d-old broiler chicks, for all compounds except for semicarbazide (SEM, the nitrofurazone metabolite). Relatively high concentrations of nitrofurans are available to the newly hatched chick through the egg yolk. However, most of these residues are neither utilised nor deposited in the liver or muscle.

Aging↗

Giardiasis: a common cause of diarrheal disease.

Giardiasis has been reported increasingly among visitors to the Soviet Union and is found at epidemic and endemic levels in the United States. The main source of infection is contaminated water. Children, homosexual males, and patients with gastrectomy, achlorhydria, hypogammaglobulinemia, secretory IgA deficiency, or alteration in immune status are particularly susceptible to severe, often chronic, infection. Symptomatic giardiasis can be acute, subacute, or chronic. Symptoms are explosive, watery, foul-smelling stools or semisolid stools with evidence of steatorrhea; flatulence; abdominal distention; and weight loss. Diagnosis usually can be established by examination of stool or duodenal fluid for cysts or trophozoites. Quinacrine hydrochloride is the drug preferred for treatment, but metronidazole and furazolidone are also useful.

Diarrhea↗

Depletion of four nitrofuran antibiotics and their tissue-bound metabolites in porcine tissues and determination using LC-MS/MS and HPLC-UV.

Depletion of the nitrofuran antibiotics furazolidone, furaltadone, nitrofurantoin and nitrofurazone and their tissue-bound metabolites AOZ, AMOZ, AHD and SEM from pig muscle, liver and kidney tissues is described. Groups of pigs were given feed medicated with one of the nitrofuran drugs at a therapeutic concentration (400?mg?kg(-1)) for ten days. Animals were slaughtered at intervals and tissue samples collected for analysis for six weeks following withdrawal of medicated feed. These samples were analysed both for parent nitrofurans (using LC-MS/MS and HPLC-UV), and for tissue-bound metabolites (using LC-MS/MS). The parent drugs were detectable only sporadically and only in pigs subjected to no withdrawal period whatsoever. This confirms the instability of the four major nitrofuran antibiotics in edible tissues. In contrast, the metabolites accumulated to high concentrations in tissues (ppm levels) and had depletion half lives of between 5.5 and 15.5 days. The metabolites of all four drugs were still readily detectable in tissues six weeks after cessation of treatment. This emphasizes the benefits of monitoring for the stable metabolites of the nitrofurans.

Animals↗

Rapid recurrence of Helicobacter pylori infection in Peruvian patients after successful eradication. Gastrointestinal Physiology Working Group of the Universidad Peruana Cayetano Heredia and The Johns Hopkins University.

Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. Since gastric cancer is common in Peru, eradication of H. pylori may help to reduce the occurrence of gastric cancer. This study involved three randomized trials to determine the efficacy of four different triple-drug therapy regimens. The most successful regimen was furazolidone combined with bismuth subsalicylate and amoxicillin, which eradicated infection in 82% of patients. Patients successfully treated were followed every 2-3 months to determine the recurrence rate of H. pylori infection. Of 105 patients with H. pylori eradication documented by pathology and culture, 52% (55) returned for follow-up endoscopy, and in 73% (40) of these 55 the infection recurred during the 8-month follow-up period. Thirty-five patients from whom H. pylori was eradicated and who were tested for antibodies to H. pylori remained consistently seropositive. Rapid recurrence of H. pylori infection after successful eradication suggests that measures other than antimicrobial therapy are needed to fight H. pylori in developing countries.

Adult↗

Pathophysiological and biochemical characterisation of an avian model of dilated cardiomyopathy: comparison to findings in human dilated cardiomyopathy.

OBJECTIVE: With the recent availability of human myocardium, many animal models have been shown to be unsuitable as models of human heart failure. The aim of this study was to describe the pathophysiological changes in a model of dilated cardiomyopathy in turkey poults and to compare them to results obtained from failing human hearts. METHODS: After receiving furazolidone for 2-3 weeks, animals developed cardiomyopathy (Fz-DCM) and were studied at the whole heart and isolated muscle level. Myofibrillar ATPase activity and noradrenaline turnover were determined in tissue homogenates in failing and non-failing control hearts. RESULTS: Fz-DCM animals had greater heart weights, heart weight/body weight ratios, and end diastolic volumes. Fractional shortening of the left ventricle and systolic blood pressures were reduced (p < 0.01) in myopathic animals. Isolated perfused hearts had lower peak developed pressures (p < 0.01). Isolated muscle preparations showed no significant differences in peak twitch forces between control and Fz-DCM muscles at a 1 Hz stimulation rate. The relationship between force and frequency of stimulation was positive in control muscles up to 1.7 Hz, whereas in Fz-DCM muscles the relationship was sharply negative above 1 Hz. Time to 80% relaxation was markedly slower in the Fz-DCM muscles. Although [Ca2+]o responsiveness was similar for Fz-DCM and normal animals, responsiveness to isoprenaline was significantly reduced in Fz-DCM hearts. Cardiomyopathic animals displayed diminished noradrenaline content in the left ventricle. Fractional noradrenaline turnover was higher (p < 0.05) in the cardiomyopathic birds. In skinned fibre preparations from control and Fz-DCM hearts calcium activations were similar. Maximum myofibrillar ATPase activities were, however, significantly lower in myopathic animals and myofibrillar protein content was reduced by 25%. CONCLUSIONS: In this model of dilated cardiomyopathy: (1) relaxation is markedly prolonged; (2) the response to beta adrenergic stimulation is diminished; (3) Mg-ATPase activities and myofibrillar protein content are reduced; and (4) sympathetic activity in the heart is markedly increased with depletion of noradrenaline stores. Furthermore, a reduction in tissue noradrenaline content per se is a misleading index of the dynamic state of cardiac noradrenaline stores. With its similarities to human cardiomyopathy, this model promises to provide new insights into the pathophysiology and progression of dilated cardiomyopathy.

Adenosine Triphosphatases↗

Nitrofurantoin resistance in isolates of Salmonella enteritidis phage type 4 from poultry and humans.

All 38 isolates of Salmonella enteritidis phage type (PT) 4 from chickens and 86 of 89 isolates from human patients were resistant to nitrofurantoin. Resistance to other agents was rare. Thirteen of 16 isolates of S. enteritidis other than PT4 were nitrofurantoin-resistant, and resistance to other agents was slightly more common than with isolates of PT4. Only one third of 83 isolates of other salmonella serotypes were nitrofurantoin-resistant, but resistance to other agents was more common and some isolates were multiply resistant. There was generally cross-resistance between nitrofurantoin and furazolidone although there were discrepancies with isolates that had MICs close to the breakpoint. It may be that use of nitrofurans in the poultry industry has selected for colonization and infection with S. enteritidis PT4. This could explain the prevalence of the organism in poultry and in human enteric infection in the United Kingdom.

Animals↗

Most Helicobacter pylori strains of Kolkata in India are resistant to metronidazole but susceptible to other drugs commonly used for eradication and ulcer therapy.

BACKGROUND: Helicobacter pylori infection is very common in India, as in other developing countries, but few data exist on the susceptibility of H. pylori to antimicrobial agents commonly used for eradication here. AIM: To determine the antimicrobial susceptibility of H. pylori strains from Kolkata, in eastern India. METHODS: A total of 67 H. pylori strains isolated from gastritis and peptic ulcer patients of Kolkata were examined in the study. Minimum inhibitory concentration to the antibiotics was determined by the agar dilution method. RESULTS: Most of the strains (85%) were resistant to at least 8 microg/mL of metronidazole and 7.5% strains were resistant to tetracycline, which was high when compared with other reports in India. All Kolkata strains were highly sensitive to clarithromycin, furazolidone and amoxicillin. CONCLUSIONS: Our results differed significantly from the few available reports on drug sensitivity profile of H. pylori from other parts of India, namely, Hyderabad, Mumbai and Lucknow. This finding supports the need for rigorous susceptibility testing as a guide to empirical treatment and more generally, to define the resistance patterns of H. pylori in particular geographical areas.

Adult↗

Characteristics of some unclassifiable strains of staphylococci isolated from goats and sheep.

Fourteen strains of catalase-positive, Gram-positive and coagulase-negative cocci that were sensitive to 20 micrograms/ml of furazolidone were isolated from goats and sheep. Two of the strains had glycerol with glucose teichoic acids whilst another possessed glycerol, glucose, glucosamine and acetylglucosamine teichoic acids. Six strains had peptidoglycan type L-Lys-Ala-Gly4 peculiar to Staphylococcus sciuri and Staph. lentus but other phenotypic characters were different from those of Staph. sciuri and Staph. lentus. The guanine plus cytosine (G + C) content of the DNA determined for three of the strains examined ranged from 32.9-34.6 mol %. The coagulase-positive staphylococcal strain of caprine origin examined had glycerol and glucosamine teichoic acids in addition to peptidoglycan type L-Lys-Gly5-6. The characteristics of the strains of staphylococci described herein are different from those already described in the literature.

Animals↗

Eradication of Helicobacter pylori: recent advances in treatment.

Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.

Drug Resistance, Bacterial↗

In vitro response of Blastocystis hominis to antiprotozoal drugs.

Ten antiprotozoal drugs were tested in vitro against four axenic strains of the intestinal parasite Blastocystis hominis. Inhibitory drugs in order of effectiveness were emetine, metronidazole, furazolidone, trimethoprim sulfamethoxazole, 5-chloro-8-hydroxy-7-iodo-quinoline (Entero-Vioform), and pentamidine. Moderately inhibitory were two quinolines other than iodochlorhydroxquin. These were chloroquine and 5,7-diiodo-8-hydroxy-quinoline (Floraquin). Diloxanide furoate was not inhibitory. Paromomycin and other antibiotics were not inhibitory. Entero-Vioform and metronidazole have been effective in human and higher primate diarrhea caused by B. hominis.

Animals↗

Treatment of giardiasis.

Giardia lamblia is both the most common intestinal parasite in the United States and a frequent cause of diarrheal illness throughout the world. In spite of its recognition as an important human pathogen, there have been relatively few agents used in therapy. This paper discusses each class of drugs used in treatment, along with their mechanism of action, in vitro and clinical efficacy, and side effects and contraindications. Recommendations are made for the preferred treatment in different clinical situations. The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine.

Animals↗

Characteristics of coagulase-negative staphylococci that help differentiate these species and other members of the family Micrococcaceae.

One hundred reference strains and 1,240 clinical isolates representing 26 species of the family Micrococcaceae were used to evaluate the potential of tests for synergistic hemolysis, adherence to glass, pyroglutamyl-beta-naphthylamide hydrolysis, and susceptibility to a set of five antimicrobial agents for differentiating these species and strains within the species. Sixty-eight percent of the clinical isolates exhibited synergistic hemolysis; 69% of the clinical staphylococci but none of the micrococci or stomatococci were adherence positive, and 92% of the strong positive adherence reactions were produced by strains of Staphylococcus epidermidis. Strains from 15 of the species were pyroglutamyl-beta-naphthylamide positive, but this test separated Staphylococcus xylosus from other novobiocin-resistant staphylococci and Staphylococcus intermedius from other coagulase-positive species. A polymyxin B disk helped differentiate S. epidermidis from most other coagulase-negative staphylococci, and a bacitracin disk (10 U) helped differentiate Staphylococcus haemolyticus from most other novobiocin-susceptible staphylococci. All strains that were susceptible to furazolidone and resistant to Taxo A disks (bacitracin, 0.04 U; BBL Microbiology Systems, Cockeysville, Md.) were staphylococci. We observed a 91% correlation between species identification obtained with the Staph-Ident system (Analytab Products, Plainview, N.Y.) and conventional methods; but the micrococci and stomatococci were incorrectly identified as staphylococci with Staph-Ident, and several isolates of S. epidermidis were misidentified as Staphylococcus hominis because they were alkaline phosphatase negative. Both these problems can be prevented by adding the simple tests we describe to those already recommended when the Staph-Ident system is used to identify isolates of gram-positive, catalase-positive cocci.

Bacitracin↗

A survey of antibiotic resistance of Escherichia Coli isolated from farm animals in Great Britain from 1971 to 1977.

A total of 94,827 Escherichia coli strains isolated from cattle, sheep, pigs and poultry during the years 1971 to 1977 were tested for resistance to six antibiotics using a disc diffusion technique. The percentage of strains resistant to chloramphenicol (10 microgram), streptomycin (10 microgram), tetracycline (10 microgram), neomycin (10 Microgram) and furazolidone (15) were 16.8, 53.9, 42.7, 18 and 10.9 per cent, respectively; 52.2 per cent of strains (1971 and 1972) were resistant to 2 microgram ampicillin and 27.8 per cent of strains (1973 and 1977) were resistant to 10 microgram ampicillin. There was no evidence of an overall increase in antibiotic resistance during the seven year period. The animal species of origin was recorded for each of the 55,494 E coli strains examined during 1974 to 1977; 31,763 strains were isolated from cattle, 15,688 from pigs, 4582 from sheep and 3191 from poultry. Considerable variations in antibiotic resistance were recorded for strains isolated from different species.

Animals↗

Cellular and molecular remodeling in a heart failure model treated with the beta-blocker carteolol.

Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, beta1-receptor density, sarcoplasmic reticulum (SR) Ca2+-ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a beta-adrenergic blocking agent, by administrating two different dosages (0.01 and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased beta-adrenergic receptor density, and the high carteolol dose restored SR Ca2+-ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that beta-blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure.

Adenosine Triphosphate↗

Oxidative metabolites of 5-nitrofurans.

We synthesized the 4-hydroxy derivatives of nitrofurazone, furazolidone and nitrofurantoin. Then we dosed rats orally with these antibiotics and isolated the intensely yellow, polar metabolites from their urine. A comparison of the ultraviolet and nuclear magnetic resonance spectra of these metabolites with the corresponding synthetic derivatives confirmed that the metabolites are 4-hydroxynitrofurazone, 4-hydroxyfurazolidone and 4-hydroxynitrofurantoin.

Animals↗