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Drug resistance in Salmonellae isolated at Chandigarh (India) during 1972-1978.

A total of 1316 strains of Salmonella belonging to 20 serotypes isolated at P.G.I. Chandigarh (India) were tested for drug resistance. Drug resistance was noticed in 494 (38.3%) of the strains; 194 (14.8%) of these strains were resistant to one drug, while 300 (23.5%) had multiple drug resistance. All isolated strains were sensitive to gentamicin, furazolidone and nalidixic acid. Resistance to streptomycin was observed in 233 (17.7%), chloramphenicol 197 (14,9%), tetracycline 293 (22.3%), ampicillin 428 (32.5%), kanamycin 206 (15.7%), neomycin 206 (15.7%) and sulphadiazine 215 (19.9%). Multiple drug resistance was most common in S. bareilly, S. typhimurium and S. anatum serotypes. Increase in incidence of drug resistance in Salmonellae has been noticed during 1972-1978.

Anti-Bacterial Agents↗

Evidence that a system similar to the recA system of Escherichia coli exists in Vibrio cholerae.

Two lines of evidence suggest that a gene analogous to the recA gene of Escherichia coli exists in Vibrio cholerae and that its product serves a proteolytic function in the SOS response. Firstly, Southern blot hybridization using the recA gene of E. coli as a probe revealed a genomic sequence in V. cholerae which hybridized with the probe. Secondly, the SOS-like response in V. cholerae (as measured by beta phage induction) triggered by DNA damaging agents like Furazolidone could be blocked by Antipain, a protease inhibitor known to inhibit RecA protease action in E. coli. Maximal blocking effect of Antipain on beta phage induction occurred at 1 mM. At this concentration neither the viability of the host bacterium nor the lytic growth of a clear plaque mutant of the phage was affected by Antipain.

Antipain↗

[Multi-method for determining residues of chemotherapeutics, antiparasitics and growth promotors in foods of animal origin. 2. Determination of nitrofurans and nicarbazin (dinitrocarbanilide components)].

Nitrofurans and dinitrocarbanilide are extracted from food according to the multiresidue method and detected by Reversed-phase-HPLC with UV-detection at 360 nm. Records of the UV-spectra confirm the results qualitatively. Possibilities for further confirmation are discussed. Substances in amounts below 0.01 mg/kg can only be determined with particular care. Statistical confirmation of this method and possible problems are mentioned. An interlaboratory collaborative study confirmed the method: furazolidone, furaltadone, nitrofurazone, nitrofurantoin, and nicarbazin (the dinitrocarbanilide containing component) were added to homogenized eggs in amounts of 0.005-0.150 mg/kg. The procedure can be standardized as an official analytical method at a detection limit of 0.005 mg/kg for nitrofurans and 0.01 mg/kg for nicarbazin.

Animals↗

The short-term toxicity of some feed additives to different freshwater organisms.

The short-term toxicity (EC50 respectively LC50 after 2 or 4 days) of 13 feed additives was determined to 4 freshwater organisms of different trophical levels: Chlorella pyrenoidosa, Daphnia magna, Lebistes reticulatus and Salmo gairdneri. The most toxic (LC(EC)50 less than 1 mg/1) were robenidine (to all tested organisms) and stenorol (to Daphnia); moderately toxic (1 less than LC(EC)50 less than 10 mg/1) was pyrimethamine. Amprolium, ethopabate, furazolidone and zoalene proved to be little toxic (LC(EC)50 greater than 10 mg/1); whereas buquinolate, carbadox, clopidol, decoquinate, grofas and sulfaquinoxaline were under the experimental conditions not toxic for the tested organisms.

Animals↗

Multi-drug resistant typhoid fever in hospitalised children. Clinical, bacteriological and epidemiological profiles.

A total of 592 children with clinical diagnosis of typhoid fever admitted to the Dr B. C. Roy Memorial Hospital for Children, Calcutta, India during the period between February 1990 and January 1992, were screened for Salmonella typhi by blood culture. S. typhi was isolated from 221 (37.3%) cases. The majority of the strains (92.3%) showed multi-drug resistant (MDR). They were resistant to chloramphenicol, ampicillin, tetracycline and trimethoprim-sulphamethoxazole. However, all the strains were uniformly (100%) susceptible to gentamicin, amikacin, furazolidone, norfloxacin and ciprofloxacin. Minimum inhibitory concentration of the antimicrobial agents against the resistant strains of S. typhi ranged between 200 and > 1600 micrograms/ml. Phage type 0 was most frequently encountered. The rate of isolation of S. typhi was more or less the same in all the pediatric age groups. The majority of the cases came from lower socio-economic classes with poor personal hygiene. Fever was the main presenting feature in all the cases. Other associated features of the MDR typhoid fever cases, who were uncomplicated during admission, were headache (36.0%), chill and rigor (23.2%), diarrhea (37.2%), anorexia (26.2%), vomiting (23.8%), cough (18.0%) and abdominal pain (19.8%). Hepatosplenomegaly was present in 42.4% cases. However, complications were less frequently encountered among the MDR typhoid fever cases who were uncomplicated during admission and treated as in-patients. Fourteen bacteriologically-confirmed MDR typhoid fever cases had jaundice and another 18 cases had an abnormal state of consciousness during admission. Four (2.0%) bacteriologically-confirmed MDR typhoid fever patients died during the period of observation.

Age Distribution↗

Sensitivity of strains of enteropathogenic Escherichia coli to tobramycin and other antibiotics.

The sensitivity patterns of strains of enteropathogenic Escherichia coli associated with diarrhoeal disease of infants to tobramycin and other antibiotics were estimated. The activity of tobramycin and of gentamicin alone and in combinations against recent isolates of enteropathogenic Escherichia coli was investigated. It was found that all the strains included in the present study were sensitive to tobramycin and gentamicin and most of them were sensitive to colistin and furazolidone. No significant differences in minimal inhibitory concentrations (MICs) and rates of killing were found between tobramycin and gentamicin, and they acted in an additive manner against most of the strains tested.

Anti-Bacterial Agents↗

Advantages of LC-MS-MS compared to LC-MS for the determination of nitrofuran residues in honey.

In the framework of developing analyses for exogenous contaminants in food matrices such as honey, we have compared data obtained by high-performance liquid chromatography coupled with mass spectrometry (LC-MS) to those provided by high-performance liquid chromatography and tandem mass spectrometry (LC-MS-MS). Initial results obtained with LC-MS showed that the technique lacked selectivity, which is why the method was validated by LC-MS-MS. This method involves a solid-phase extraction (SPE) of nitrofuran metabolites and nitrofuran parent drugs, a derivatization by 2-nitrobenzaldehyde for 17 h, and finally a clean-up by SPE. The data obtained show that the limits of detection varied between 0.2 and 0.6 microg kg(-1) for the metabolites and between 1 and 2 microg kg(-1) for nitrofuran parent drugs. The method was applied to different flower honeys. The results showed that nitrofurans (used as antibiotics) are consistently present in this matrix, the predominant compound being furazolidone. Figure Working bees.

Chromatography, Liquid↗

Intracellular calcium and the relationship to contractility in an avian model of heart failure.

Global contractile heart failure was induced in turkey poults by furazolidone feeding (700 ppm). Abnormal calcium regulation appears to be a key factor in the pathophysiology of heart failure, but the cellular mechanisms contributing to changes in calcium fluxes have not been clearly defined. Isolated ventricular myocytes from non-failing and failing hearts were therefore used to determine whether the whole heart and ventricular muscle contractile dysfunctions were realized at the single cell level. Whole cell current- and voltage-clamp techniques were used to evaluate action potential configurations and L-type calcium currents, respectively. Intracellular calcium transients were evaluated in isolated myocytes with fura-2 and in isolated left ventricular muscles using aequorin. Action potential durations were prolonged in failing myocytes, which correspond to slowed cytosolic calcium clearing. Calcium current-voltage relationships were normal in failing myocytes; preliminary evidence suggests that depressed transient outward potassium currents contribute to prolonged action potential durations. The number of calcium channels (as measured by radioligand binding) were also similar in non-failing and failing hearts. Isolated ventricular muscles from failing hearts had enhanced inotropic responses, in a dose-dependent fashion, to a calcium channel agonist (Bay K 8644). These data suggest that changes in intracellular calcium mobilization kinetics and longer calcium-myofilament interaction may be able to compensate for contractile failure. We conclude that the relationship between calcium current density and sarcoplasmic reticulum calcium release is a dynamic process that may be altered in the setting of heart failure at higher contraction rates.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Nitroheterocyclic drugs with broad spectrum activity.

The group of biologically active nitroheterocyclic compounds includes various 5- and 2-nitroimidazoles and 5-nitrofurans, which can be used as therapeutic agents against a variety of protozoan and bacterial (anaerobic) infections of humans and animals. The current status in the the treatment of giardiasis, trichomoniasis, balantidiasis, histomoniasis, and amebiasis (including infections due to opportunistic amebas) is presented. The most relevant drugs (benznidazole, furazolidone, metronidazole, misonidazole, nifurtimox, nimorazole, nitazoxanide, ornidazole, secnidazole, and tinidazole) are characterized with regard to their chemical, chemotherapeutic, toxicological, pharmacokinetic, and pharmacological properties, including the mechanism of action and resistance in certain parasitic protozoa.

Animals↗

Rescue Therapy for Helicobacter pylori.

Up to 35% of patients infected with Helicobacter pylori fail to respond to standard anti-H. pylori therapy. With the rising prevalence antimicrobial resistance, the failure rates of conventional proton pump inhibitor-containing triple therapy are expected to increase. Pretreatment antibiotic resistance testing should be done whenever possible to allow for tailoring of the treatment regimens. The data on second-line or rescue therapy are limited and usually are subjected to various biases and confounding factors. Switching between clarithromycin and metronidazole should be considered if repeated courses of proton pump inhibitor-containing triple therapy are used as second-line therapy in the absence of antimicrobial sensitivity testing. The prolongation of therapy duration with proton pump inhibitor, amoxicillin, and clarithromycin is ineffective for clarithromycin-resistant strains. The bismuth-containing quadruple therapy is the best salvage treatment in the absence of pretreatment antibiotic susceptibility. Furazolidone quadruple therapy (where available) and rifabutin triple therapy are salvage therapies of last resort. If these regimens fail, culture and susceptibility testing is required.

Journal Article↗

Diagnosis and Treatment of Helicobacter pylori.

Helicobacter pylori infection remains a ubiquitous infection, especially in populations with poor socioeconomic conditions. Severe clinical outcomes of chronic infection include peptic ulcer disease and gastric cancer. Consensus meetings have developed guidelines for diagnosis, treatment, and management of H. pylori infection and related disorders in various populations. Clear benefits are obtained for H. pylori eradication in peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma. Most authorities agree that first-degree relatives of gastric cancer patients should undergo testing for H. pylori infection. H. pylori eradication in dyspepsia remains controversial. Global investigations continue to identify specific host and bacterial factors that are responsible for H. pylori-related inflammatory processes and development of clinical disease. Effective eradication regimens have been identified. The proton pump inhibitor (PPI)-based triple therapies are considered first-line therapy because of high patient compliance and good eradication rates. "Quadruple therapy" with bismuth-metronidazole-tetracycline plus a PPI is another first-line therapy with a similar eradication rate. This therapy is preferred in patients with penicillin allergy or prior exposure to clarithromycin. Rescue regimens are being developed because of rising antimicrobial resistance to metronidazole and clarithromycin in H. pylori strains. Emerging rescue combination therapies include furazolidone, rifabutin, and quinolones. These combination regimens are still preliminary and should be reserved for patients who have failed first-line therapies. Vaccine development remains elusive.

Journal Article↗

Treatment of Giardiasis.

Tinidazole is the first-line drug treatment of giardiasis, as it requires only a single dose to cure infection in most individuals. The related drug metronidazole is as effective, but it requires 5 to 7 days of three times a day therapy. Nitazoxanide appears in limited studies to be as effective as tinidazole or metronidazole, and it does not have the bitter taste of nitroimidazoles. A good alternate for use during pregnancy is paromomycin. Cure of infection varies between 60% and 100% with one course of treatment. Less effective and/or less well-tolerated drugs for the treatment of giardiasis include albendazole, quinacrine, and furazolidone; the use of these agents should be reserved for giardiasis refractory to treatment with the first-line agents.

Journal Article↗

Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi.

Eleven types/classes of compound with antifilarial activity were comparatively evaluated in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi or B. pahangi. The paper deals with the efficacy of (i) predominantly microfilaricidal compounds [diethylcarbamazine, levamisole, avermectins (ivermectin, milbemycin), nitrofurans (nitrofurantoin, hydroxymethylnitrofurantoin, nifurtimox, furazolidone, furapyrimidone), organophosphorals (metrifonate, haloxon), and aminophenyl-amidines], (ii) predominantly macrofilaricidal compounds [suramin, benzimidazoles (flubendazole, mebendazole, oxfendazole, ciclobendazole, albendazole, cambendazole, fenbendazole), and arsenicals (thiacetarsamide, Mel PH, R7/45)], and (iii) micro- and macrofilaricidal compounds [benzazole derivatives (CGP 20376 and other benzothiazoles) and nitrophenylamines (amoscanate, CGP 6140)]. Minimum effective doses against microfilariae and minimum curative doses against adult filariae as well as detailed data on dose-efficacy relationships are reported for the various drugs. The results obtained in M. coucha are compared with those published for other experimental in vivo filarial systems, thus attempting to describe a general status of in vivo antifilarial activity of the compounds.

Animals↗

Nonfluid therapy and selected chemoprophylaxis of acute diarrhea.

Various available forms of therapy can decrease morbidity and mortality associated with acute diarrhea. Oral fluids represent the cornerstone of therapy of all cases. A variety of agents acting nonspecifically can decrease diarrhea and improve other worrisome symptoms associated with enteric infection. Kaopectate makes the stool more formed but has little additional effects. Bismuth subsalicylate, an antisecretory agent, reduces the number of stools passed by about 50 percent and improves other associated symptomatology. The drugs that affect motility such as loperamide and diphenoxylate are the most active of the nonspecifically acting drugs. They must be avoided in patients with significant fever and dysentery. Trimethoprim/sulfamethoxazole is now considered the drug of choice for shigellosis due to the presence of ampicillin-resistant Shigella strains in most regions of the world. Trimethoprim/sulfamethoxazole is also an effective form of therapy for enterotoxigenic Escherichia coli infection and for traveler's diarrhea without definable cause. Erythromycin, although not proved to be effective against Campylobacter, probably shortens the disease. Furazolidone, although not dramatically effective, has a spectrum of activity that includes Shigella, enterotoxigenic E. coli, Campylobacter, and Giardia lamblia. It may not be effective in severely ill (hospitalized) patients with diarrhea. The various forms of available therapy can be administered empirically, depending on symptomatology. Mildly ill patients (one to three unformed stools in 24 hours with minimal additional symptoms) probably are best treated with fluids only. Mild to moderately ill persons (three to six unformed stools in 24 hours) can be treated with a drug that acts nonspecifically, such as bismuth subsalicylate or loperamide. Those with severe diseases (six or more unformed stools with moderate to severe associated symptoms), particularly when associated with fever and the passage of bloody mucoid stools, may be given an antimicrobial agent. The antimicrobial drug given will be determined by ancillary laboratory tests (dark-field examination or examination of a wet-mount preparation for motile Campylobacter or stool culture for Shigella, Campylobacter, or Salmonella) or may be administered on an empiric basis. Traveler's diarrhea can be eliminated in selected persons by the administration of a pharmacologic agent. Liquid bismuth subsalicylate is effective in large doses, which may be impractical. Studies with the tablet formulation suggest that it is partially effective in preventing the illness. Doxycycline and trimethoprim/sulfamethoxazole are more effective, particularly when admini

Acute Disease↗

A survey of antimicrobial resistance in Salmonellae isolated from animals in England and Wales during 1984-1987.

Resistance to 14 antimicrobial substances was tested in 18,647 salmonella strains isolated from animals, their environment and from animal feeds during the period 1984-1987. Of the 2284 Salmonella dublin strains the percentage sensitive to all the antimicrobial substances ranged from 18.1 to 26.8. Resistance to the higher concentration of streptomycin (S25) ranged from 1.9 to 6.4%, whereas the corresponding figures when the lower concentration (S10) was used were 32.3 and 63.8%. Resistance to the higher sulphonamide concentration (Su500) never exceeded 3.3%, although in 1987 70.3% of strains showed resistance to the lower concentration. In general, less than 1% of strains showed resistance to the other antibacterial substances. No strains resistant to amikacin (AK), apramycin (Apr), gentamicin (CN) and colistin (CT) were detected. Of the 8677 S. typhimurium strains the percentage sensitive to all the antimicrobial agents ranged from 6.6 in 1985 to 13.6 in 1987. Resistance to tetracycline (T), ampicillin (PN), trimethoprim (TM) and chloramphenicol (C) ranged from 36.5 to 58.8%, the highest percentages being detected with tetracyclines. Less than 1% of strains showed resistance to furazolidone and none was resistant to amikacin and colistin. Resistance to apramycin ranged from 3.1% in 1984 to 11.6% in 1985; the figures for gentamicin were approximately half that of apramycin. In 1984, 41.6% of strains showed resistance to neomycin but only 8.5% in 1987. The fall in neomycin resistance was associated with the epidemic spread of the commonest phage-type DT204C becoming sensitive to neomycin. Of the 7687 strains of serotypes other than S. typhimurium and S. dublin the percentage sensitive to all antimicrobial agents ranged from 23.7 in 1985 to 14.7 in 1987. Resistance to tetracyclines and sulphonamides (Su500) ranged from 5.2 to 12.1% and 5.8 to 13.3% respectively. Resistance to the other antimicrobial agents was usually less than 5%.

Animal Feed↗

Cytotoxicity and DNA damage to mammalian cells by nitrofurans.

Nitrofurazone, nitrofurantoin, furazolidone, furaltadone and N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) were toxic to cultured mouse L cells. The extent of toxocity and the rate of reduction of nitrofurazone increased markedly as the oxygen content of the incubation medium was lowered. The toxic effect of nitrofurans was decreased by addition of serum and was much greater in phosphate-buffered saline containing glucose (PSG) than in medium. Damage to L cell DNA by nitrofurans increased as the oxygen concentration decreased from 21% to 0%. The concentration of nitrofurazone and duration of exposure also determined the number of DNA single-strand breaks. It is suggested that toxicity and DNA damage may result from the actions of toxic intermediates in the metabolic reduction of nitrofurans.

Cell Survival↗

Redox behaviour of nifuroxazide: generation of the one-electron reduction product.

The electrochemical properties of nifuroxazide have been investigated in aqueous and aqueous-DMF mixed solvents. In aqueous media, a single, irreversible four-electron reduction occurs to give the hydroxylamine derivative. In mixed media, a reversible one-electron reduction to form a nitro radical anion takes place. Cyclic voltammetric studies show that the anion radical product is stable, although the nitro radical anion intermediate shows a tendency to undergo further chemical reactions. A comparison with the voltammetric behaviour of other nitrofurans such as nifurtimox, nitrofurazone and furazolidone is made. The electrochemically-obtained parameters are correlated with the in vivo studies of oxygen consumption on Trypanosoma cruzi cell suspensions.

Animals↗

Collagenous gastritis.

Subepithelial fibrosis has previously been reported in the small intestine (collagenous sprue) and colon (collagenous colitis). We report a 15-yr-old girl with chronic gastritis and subepithelial fibrosis of the gastric corpus who presented with recurrent abdominal pain and acute upper gastrointestinal bleeding. Nodularity and erythema of the gastric corpus were persistent endoscopic findings. Biopsies revealed patchy chronic active gastritis with a striking focal thick band of collagen immediately beneath the surface epithelial cells that did not extend to deeper portions of the lamina propria. Contrast radiography demonstrated an abnormal mucosa of the gastric corpus with a mosaiclike surface pattern. Numerous studies have failed to elucidate the etiology. Despite treatment with ranitidine, sucralfate, and furazolidone, there has been no clinical or pathologic improvement. The pathogenesis and prognosis of collagenous gastritis, and its relationship to collagenous sprue and collagenous colitis, remain to be defined.

Adolescent↗