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An evaluation of current cholera treatment.

Cholera, caused by Vibrio cholerae O1 and O139, is characterised by profuse purging of watery stools, and vomiting and dehydration. The mainstay of therapy of cholera patients is rehydration with oral rehydration salt solution or intravenous Ringer's lactate depending upon the degree of dehydration. Antibiotics such as tetracycline, doxycycline, norfloxacin, ciprofloxacin and furazolidone may be used as an adjunct to rehydration therapy for severely purging cholera patients to reduce the rate of stool output. This shortens the duration of hospital stay, stops excretion of vibrios in the stool and minimises the requirement of fluids. Resistance to many of these drugs has been observed and is a matter of concern. Other antidiarrhoeals are not recommended. Many antisecretory drugs have been tried as an adjunct therapy, unfortunately, until today, none has been found useful in the treatment of cholera. Feeding during and after cholera is emphasised.

Anti-Infective Agents↗

Efficacy of antigiardial drugs.

The flagellated protozoa Giardia duodenalis is the most commonly detected parasite in the intestinal tract of humans. Infections with the parasite result in diarrhoeal disease in humans and animals, with infants at risk from failure-to-thrive syndrome. The incidence of giardiasis worldwide may be as high as 1000 million cases. Current recommended treatments include the nitroheterocyclic drugs tinidazole, metronidazole and furazolidone, the substituted acridine, quinacrine, and the benzimidazole, albendazole. Paromomycin is also used in some situations, and nitazoxanide is proving to be useful. However, treatment failures have been reported with all of the common antigiardial agents, and drug resistance to all available drugs has been demonstrated in the laboratory. In addition, clinical resistance has been reported, including cases where patients failed both metronidazole and albendazole treatments. The identification of new antigiardial drugs is an important consideration for the future, but maintaining the usefulness of the existing drugs is the most cost-effective measure to ensure the continued availability of antigiardial drugs.

Animals↗

Susceptibility of Campylobacter jejuni to twenty-three antimicrobial agents.

Twenty-three antimicrobial agents, including 4 new broadspectrum beta-lactam antibiotics were tested against 50 clinical isolates of Campylobacter jejuni. The activity of metabolites of metronidazole and tinidazole was also tested. Minimum inhibitory concentrations (MIC) were determined by agar dilution. beta-lactamase production was detected by a chromogenic cephalosporin method. All strains were susceptible to erythromycin, clindamycin, chloramphenicol, furazolidone, aminoglycosides (including gentamicin), cefotaxime and NF-thienamycin. All isolates were resistant to penicillin, cephalothin, cefoperazone, vancomycin, rifampicin and trimethoprim; beta-lactamase was detected in 2% of isolates. Some strains were resistant and others sensitive to the other drugs tested, which included ampicillin, moxalactum tetracycline, metronidazole and tinidazole. The 'hydroxy' metabolites of metronidazole and tinidazole were more active than the parent compounds.

Anti-Bacterial Agents↗

In vitro susceptibility of Shigella strains isolated from stool cultures of dysenteric patients.

A reprospective analysis was conducted on the susceptibility by diffusion of 100 Shigella strains to 8 antimicrobial agents. These strains were isolated from 852 stool cultures obtained from dysenteric patients seen between January 1986 and April 1987. Seventy-one per cent of the samples from which Shigella sp were isolated were obtained from children under age 6 years; 86% of these samples revealed pus, with or without blood. The Shigella serotypes isolated most often were S. flexneri (57%) and S. sonnei (38%). The highest susceptibility rates were observed with furazolidone (98%), nalidixic acid (97%), and gentamicin (90%). The same strains were significantly less susceptible to other antimicrobial agents used to treat shigellosis; among them, ampicillin and trimethoprim-sulfamethoxazole, for which susceptibility rates of 40% and 64%, respectively, were observed. Thus, it is important 1) to evaluate regularly the in vitro susceptibility of Shigella sp strains to antimicrobials commonly used to treat shigellosis, and 2) to conduct controlled clinical trials on the efficacy of alternative drugs in treating this disease.

Anti-Bacterial Agents↗

Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response.

Toxin synthesis by Shiga toxin-producing Escherichia coli (STEC) appears to be coregulated through induction of the integrated bacteriophage that encodes the toxin gene. Phage production is linked to induction of the bacterial SOS response, a ubiquitous response to DNA damage. SOS-inducing antimicrobial agents, particularly the quinolones, trimethoprim, and furazolidone, were shown to induce toxin gene expression in studies of their effects on a reporter STEC strain carrying a chromosome-based stx2::lacZ transcriptional fusion. At antimicrobial levels above those required to inhibit bacterial replication, these agents are potent inducers (up to 140-fold) of the transcription of type 2 Shiga toxin genes (stx2); therefore, they should be avoided in treating patients with potential or confirmed STEC infections. Other agents (20 studied) and incubation conditions produced significant but less striking effects on stx2 transcription; positive and negative influences were observed. SOS-mediated induction of toxin synthesis also provides a mechanism that could exacerbate STEC infections and increase dissemination of stx genes. These features and the use of SOS-inducing antibiotics in clinical practice and animal husbandry may account for the recent emergence of STEC disease.

Anti-Bacterial Agents↗

Therapeutical trials with antimicrobial agents and cultured cecal microflora in Salmonella infantis infections in chickens.

The efficacy of short antimicrobial therapy was examined in chicks infected with S. infantis on the day of hatching. An attempt was made to prevent the reappearance of salmonellae by treating the chicks with a culture of cecal microflora to re-establish the normal intestinal flora. The following drugs were used: neomycin/polymyxin, oxytetracyline/neomycin, dihydrostreptomycin, furazolidone, and trimethoprim/sulphadiazine. The oxytetracycline/neomycin therapy was most effective, but reappearance of the infection was not avoided. Combined therapy with other antimicrobials and the culture reduced the number of infected chicks compared with the respective control groups. A slight reduction was also found when the culture was used alone without any preceding antimicrobial treatment.

Animals↗

Effect of chemotherapeutic agents on Pasteurella anatipestifer infection in White Pekin ducklings.

In a series of experiments, various chemotherapeutic agents administered in feed were evaluated for their efficacy against experimental Pasteurella anatipestifer (PA) infection in White Pekin ducklings. The feeding of medicated diets was started 3 days prior to challenge and continued throughout each experiment. Novobiocin and lincomycin, when fed at adequate concentrations, were the most effective medicaments tested. Mortality in treated groups was 0-18% compared with 45-92% mortality in controls. Sulfadimethoxine-ormetoprim, sulfaquinoxaline, and lincomycin-spectinomycin were moderately effective. Drugs that were not effective included chlortetracycline, tylosin-sulfamethazine, fosfomycin, furazolidone, nihydrazone, penicillin, bacitracin, and erythromycin. Six antibiotics were tested parenterally against experimental PA infection in another series of experiments. A single dose of an antibiotic was injected subcutaneously 5 to 6 hr after infection except in one experiment in which treatment was delayed until 24 hr after infection. When given 5 to 6 hr after infection, lincomycin-spectinomycin, penicillin-streptomycin, penicillin, oxytetracycline, and spectinomycin significantly reduced mortality. Gentamicin tested under the same conditions was ineffective. Drugs injected 24 hr after infection were not effective.

Animals↗

Effects of diet and antimicrobials on growth, feed efficiency, intestinal Clostridium perfringens, and ileal weight of broiler chicks.

Five experiments were conducted to evaluate the effects of diet and antimicrobials on weight gain, feed efficiency, ileal weight, and Clostridium perfringens in the ileum of broiler chicks. In the first experiment, glucose, sucrose, and fructose were added to a semipurified diet and the results were compared with those from a practical corn and soybean meal diet. All of the diets were fed with and without bacitracin at a level of 55 ppm. Fructose resulted in the greatest depression in weight gain, followed by sucrose. Bacitracin significantly improved weight gain and feed efficiency of chicks fed the fructose, sucrose, and practical diets. Highly significant inverse correlations were obtained between ileal weight and weight gain and the number of C. perfringens in the ileum and weight gain. In other experiments bacitracin, penicillin, chlortetracycline, oxytetracycline, erythromycin, tylosin, virginiamycin, lincomycin, bambermycins, and carbadox, all at a level of 55 ppm, improved weight gain and feed efficiency and significantly reduced the weight of the ileum and the number of C. perfringens in the ileum of chicks fed the practical diet. The antibacterial agents 3-nitro-4-hydroxy-phenylarsonic acid, arsanilic acid, furazolidone, and sulfathiazole had little to no effect on the 4 parameters evaluated. Virginiamycin and lincomycin at 16.5 and 4.4 ppm, respectively, were shown to be effective. In vitro activities of the antimicrobials against C. perfringens did not directly relate to in vivo activities and the effects on growth and feed efficiency. The results of these experiments support the concept of antimicrobials as growth permittants and provide further evidence for C. perfringens as a causative bacteria for growth depression.

Animal Feed↗

Acute diarrhea during army field exercise in southern China.

AIM: During emergency period, infectious diseases can be a major threat to military forces. During field training in southern China, diarrhea is the main cause of nonbattle injury. To evaluate the causes of and risk factors for diarrhea in emergency period, we collected clinical and epidemiological data from the People's Liberation Army (PLA) during field training in southern China. METHODS: From September 25 to October 2 1997, 2636 military personnel were investigated. Fecal sample cultures for lapactic pathogens were obtained from 103 military personnel with diarrhea. In addition, a questionnaire was administered to 103 cases and 206 controls to evaluate the association between illness and potential risk factors. At the same time, another questionnaire of 1:4 case-case control was administered to 22 severe cases (each severe case paired 4 mild cases). RESULTS: The training troop's diarrhea incidence rate was significantly higher than that of garrison. The diarrhea incidence rate of officers was significantly lower than that of soldiers. A lapactic pathogen was identified in 63.1% (65/103) of the troops with diarrhea. Enterotoxigenic Escherichia coli (35.0%) and plesiomona shigelloides (16.5%) were the most common bacterial pathogens. All bacterial isolates were sensitive to norfloxacin and ceftazidine. However, almost all of them were resistant to sulfamethoxazole, trimethoprim-sulfamethoxazole, oxytetracycline, doxycycline, furazolidone, ampicillin and cloromycetin to a different degree. Risk factors associated with diarrhea included drinking raw water, eating outside, contacting diarrhea patients, lacking sanitation, depression, lacking sleep, which were established by multiple-factor logistic regression analysis. In addition, the unit incidence rate was associated with the density of flies and the average daily boiled water available by regression and discriminate analysis. CONCLUSION: A series of risk factors are associated with the incidence rate of diarrhea. Our results may provide a useful basis for prevention and cure of diarrhea in emergency period of PLA.

Acute Disease↗

Activity of oral drugs against Leishmania tropica in human macrophages in vitro.

Because of the need for orally active antileishmanial agents, orally administrable drugs have sometimes been used to treat human leishmaniases without prior demonstration of efficacy in experimental models. The antileishmanial activity of such agents was tested against Leishmania tropica (a cause of cutaneous leishmaniasis) within human macrophages in vitro. Although trimethoprim + sulfamethoxazole and isoniazid + rifampin have been reported as efficacious orally in certain human studies of cutaneous disease, these drugs were ineffective in vitro (less than or equal to 40% parasite elimination) at peak achievable serum levels. The combination of allopurinol and Pentostam is being tested in humans. In vitro, allopurinol (5 micrograms/ml) augmented the antileishmanial effect of a low concentration of Pentostam (5 micrograms/ml) but not of a higher concentration of Pentostam (20 micrograms/ml). Nifurtimox is a nitrofuran which has questionable activity against human cutaneous disease. Nifurtimox was similarly only 50% effective in vitro at peak achievable serum levels (1.0-3.0 micrograms/ml). However, furazolidone, another orally administered nitrofuran, eliminated 92% of parasites at 1.0 micrograms/ml. Chlorpromazine and quinacrine are concentrated in tissues that are susceptible to infection by Leishmania. Chlorpromazine and quinacrine eliminated only 15% and 35% of organisms in vitro at achievable serum levels (less than or equal to 0.3 microgram/ml), but eliminated virtually all organisms in vitro at possible achievable tissue levels. Both the negative and the positive data of this report may aid in selection of effective orally active agents for in vivo trials.

Antiprotozoal Agents↗

Improved agar diffusion method for detecting residual antimicrobial agents.

The improved agar diffusion method for determination of residual antimicrobial agents was investigated, and the sensitivities of various combinations of test organisms and assay media were determined using 7 organisms, 5 media, and 31 antimicrobial agents. Bacillus stearothermophilus and synthetic assay medium (SAM) showed the greatest sensitivity for screening penicillins (penicillin G and ampicillin). The combination of Bacillus subtilis and minimum medium (MM) was the most sensitive for tetracyclines (oxytetracycline and chlortetracycline), B. stearothermophilus and SAM or Micrococcus luteus and Mueller-Hinton agar (MHA) for detecting tylosin and erythromycin, B. subtilis and MHA for aminoglycosides (streptomycin, kanamycin, gentamicin, and dihydrostreptomycin), B. stearothermophilus and SAM for polyethers (salinomycin and lasalocid), and B. subtilis and MM or Clostridium perfringens and GAM for polypeptides (thiopeptin, enramycin, virginiamycin, and bacitracin). However, gram-negative bacterium Escherichia coli ATCC 27166 and MM were better for screening for colistin and polymixin-B. For detecting the synthetic drugs tested, the best combination was B. subtilis and MM for sulfonamides, E. coli 27166 and MM for quinolones (oxolinic acid and nalidixic acid), B. subtilis and MM for furans (furazolidone), and the bioluminescent bacterium Photobacterium phosphoreum and luminescence assay medium for chloramphenicol and oxolinic acid. The results showed that the use of four assay plates, B. stearothermophilus and SAM, B. subtilis and MM, M. luteus and MHA, and E. coli 27166 and MM, was superior to the currently available techniques for screening for residual antimicrobial agents in edible animal tissues.

Agar↗

Prevalence of multidrug-resistant Salmonella on ready-to-eat betel leaves (Paan) and in water used for soaking betel leaves in North Indian cities.

The purpose of this study was to determine the prevalence of Salmonella in the water used by Paan vendors in 11 North Indian cities. The analysis of 776 water samples and 120 samples each of preprocessed Paan (from vendor stock) and ready-to-eat Paan collected from Bareilly revealed that four of the ready-to-eat Paan and 34 of the water samples contained multidrug-resistant Salmonella strains. The isolates belonged to five different serovars, i.e., Salmonella Newport (1), Salmonella Paratyphi B (1), Salmonella Teko (1), Salmonella Virchow (3), and Salmonella Saintpaul (32), and could also be classified into 18 different resistotypes. All of the isolates were sensitive to cotrimoxazole, and 97.27% of the isolates were sensitive to chloramphenicol, imipenem, ciprofloxacin, ceftriaxone, and neomycin. Multidrug resistance (against 5 to 18 antibiotics) was common, particularly for nalidixic acid (65.79%), cephalothin (68.42%), cefoperazone (57.89%), sulfamethizole (52.63%), furazolidone (65.79%), kanamycin (68.42%), doxycycline (50.00%), and cefotaxime (44.74%). Bacteriological analysis of 16 Salmonella-positive and 23 Salmonella-negative samples revealed that the presence of Salmonella in water samples had a negative correlation (r = -0.35) with coliform counts and a positive correlation (r = 0.55) with nonlactose fermenter counts. We determined that centrifugation was a rapid and cheap method for concentrating large samples of Salmonella. The presence of multidrug-resistant strains of zoonotic Salmonella on ready-to-eat Paan is a public health concern and may be one of the factors responsible for the hyperendemic status of salmonellosis in India.

Anti-Bacterial Agents↗

Identification and semiquantitative estimation of antibiotics added to complete feeds, premixes, and concentrates.

Classical microbiological methods for determining antimicrobial compounds in feeds are nonspecific. Thus, there is a need to identify biological activity, and bioautography is used for this purpose. A routine method for detecting the following antimicrobial substances in feeds is described: avilamycin, avoparcin, Zn-bacitracin, erythromycin, flavomycin, furazolidone, lasalocid, monensin, narasin, penicillin, salinomycin, spiramycin, tetracyclines, tylosin, and virginiamycin. Carbadox can be detected by UV light examination of the plates prior to bioautography. Semiquantitative estimations of antibiotic content are compared with quantitative determinations of the above mentioned substances in feeds, except erythromycin, penicillin, and tetracyclines. Detection limits range from 0.1 mg/kg (chlortetracycline) to 20 mg/kg (lasalocid). The method involves agar diffusion of buffered samples, a neutral extraction of polyether antibiotics followed by thin-layer chromatography (TLC), and an acid extraction for other antibiotics followed by TLC. Five test bacteria were used for the main detection by agar diffusion: Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 6538P, Corynebacterium xerosis NCTC 9755, Bacillus cereus ATCC 11778, and B. subtilis ATCC 6633. Identification after TLC was achieved by bioautography with the most sensitive microorganism(s). This method allows one laboratory technician to analyze up to 30 feed samples within 2.5 working days, provided that feeds of the same category are analyzed in the same run, and that labels of additives are available. Qualitative and semiquantitative information are valuable when performing a quantitative antibiotic determination and it provides proof that the activity determined is due to the tested substance. This last feature is essential from the perspective of quality assurance of results.

Animal Feed↗

Antimicrobial drug use and related management practices among Ontario swine producers.

A mail survey of swine producers in Ontario was undertaken during 1991 to describe the types, frequency, and motives for antimicrobial use. Two hundred operations that marketed fewer than 350 hogs per year, and 800 that marketed more than 350 per year were sent questionnaires, 63% of which were completed and returned. Most operations (86%) added antimicrobials to starter (weanling pig) rations, while fewer (29%) added these drugs to finisher pig rations. The most commonly used antimicrobials were tylosin, carbadox, and furazolidone in weanling pigs, and tylosin, lincomycin, and tetracycline in finishers. Water medication of grower-finisher pigs was practised on 25% of farms; 80% of farms had injected at least some grower-finisher pigs with antimicrobials in the 12 mo preceding the survey. Approximately 20% of operations that added antimicrobials to finisher rations did so for growth promotion purposes only, while others used them for disease treatment, prevention, control, or a combination of reasons. Among those not using antimicrobials in finisher rations, 83% did not believe they were necessary and 37% were concerned about the potential for residues in marketed hogs.

Animal Husbandry↗

Antibiotic resistance pattern of foodborne Salmonella isolates in Addis Ababa (Ethiopia).

A total of 39 Salmonella cultures isolated from raw minced beef and chicken (gizzard, liver, and heart) samples in Addis Ababa were examined for susceptibility to a group of 10 selected antimicrobials. 34 isolates (87.2%) were resistant to one or more antibiotics. The antibiotics to which isolated Salmonella strains were most often fully resistant included nitrofurantoin (48.7%), furazolidone (48.7%) and streptomycin (46.2%). Only 4 antimicrobials (gentamycin, kanamycin, rifampicin and sulphamethoxazole-trimethoprim) were effective against all Salmonella isolates with the exception of 2 which were intermediate in resistance to kanamycin (1) and sulphamethoxazole-trimethoprim (1). 77.8% of the S. Enteritidis strains showed multiple resistance to up to four antibiotics followed by S. Typhimurium (60.0%) and S. Dublin (33.3%). The high level of antibiotic resistance of foodborne Salmonella isolates in the study area is an indication of indiscriminate and continuous use of subtherapeutic doses of antibiotics in animals.

Animals↗

An analysis of the chronic oral toxicity of polyether ionophore antibiotics in animals.

Feeding well-mixed ionophores to adapted cattle improves ruminal fermentation and growth rates. In nonruminants, growth is improved by reducing competing gastrointestinal microorganisms. Interactions of monensin with other drugs may be beneficial or toxic. Tiamulin and furazolidone potentiate monensin's negative effects. For example, monensin produces positive inotropy and cardiomyopathy dependent on calcium and extracellular sodium. Based on available toxicity data and derived no observable effect levels (NOEL) in the same species and across species, monensin was more toxic than salinomycin, lasalocid or narasin. Lasalocid was 5- to 10-fold less toxic to horses than is monensin. Based on available toxicity data and derived NOEL, lasalocid was less toxic than all ionophores except salinomycin. Very high levels of narasin caused death in sows, leg muscle weakness in turkeys, and cardiopulmonary clinical signs in 15% of the rabbits from Brazilian rabbit farms. Only salinomycin and lasalocid were less toxic than narasin. Salinomycin was the least toxic of all the ionophores. Maduramicin was the most toxic of all the ionophores. Nearly all maduramicin fed to poultry persists in litter (manure), making this poultry litter toxic if fed to cattle as a nitrogen source. While ionophore comparative toxicity was difficult to estimate, most cross-comparisons utilized NOEL within and across species. The relative toxicities of the ionophores from lowest to highest were salinomycin < lasalocid < or = narasin < or = monensin (but lasalocid < monensin) < maduramicin.

Administration, Oral↗

Occurrence of Salmonella enteritidis in pooled table eggs and market-ready chicken carcasses in Zambia.

The level of Salmonella enteritidis contamination in Zambian table eggs and ready market chicken carcasses was studied. Nine of the 240 (3.8%) pooled samples of table eggs and 18 of 382 (4.7%) chicken carcasses were contaminated with S. enteritidis. All the isolates from the table eggs belonged to the enteropathogenic invasive phage type 4, whereas seven isolates from the chicken carcasses belonged to phage type 4, three were phage type 7, and eight were untypable (rough type). All the isolates were sensitive to gentamycin, ampicillin, tetracycline, cotrimoxazole, amoxycillin, furazolidone, and chloramphenicol.

Animals↗

Comparison of five different treatment regimens for H. pylori eradication.

AIM: Treatment response to five different H. Pylori eradication regimens were evaluated to see which is the best regimen in our setup. METHODS: Patients presenting with upper GI symptoms of acid peptic disease underwent upper GI endoscopy and an antral CLO test. All those with a positive CLO test were included in the study. The study was carried out over a year and one trial was followed by another. The treatment regimens comprised of (1) Omeprazole 20 mg once a day, colloidal bismuth subcitrate 120 mg three times a day, Metronidazole 200 mg three times a day (18 cases). (2) Colloidal bismuth subcitrate three times a day, furazolidone 100 mg three times a day, metronidazole 200 mg three times a day (28 cases). (3) Omeprazole 20 mg once a day, Clarithromycin 500 mg twice a day (21 cases). (4) Lansoprazole 30 mg once a day, Amoxycillin 500 mg three times a day (21 cases). (5) Lansoprazole once a day, Amoxycillin 500 mg three times a day and Roxithromycin 150 mg twice a day (14 cases). Therapy for all 5 groups comprised of 14 days. Endoscopy and CLO test were done prior to the entry in the trial and at 28 days to see the response. RESULTS: Meta analysis was done for all the 5 regimens. For the purpose of analysis patients were divided into 2 groups, i.e., those with peptic ulcer and positive CLO (peptic ulcer disease (PUD) and those without peptic ulcer but positive CLO test (Non ulcer dyspepsia (NUD). PUD was seen in 14 of 18 cases in group 1, 18 of 28 cases in group 2, 16 of 21 cases in group 3, 6 of 21 cases in group 4 and 3 of 14 cases in group 5. In PUD after 14 days of therapy, lesions healed and CLO became negative in 50% cases each in group 1 and 2, 56% in group 3, 83% in group 4 and all in group 5, while in NUD, 25%, 60%, 80%, 47% and 82% respectively showed H. Pylori eradication. CONCLUSION: Of the different therapies one proton pump inhibitor with two antibiotics gave best results in ulcer healing and H. pylori eradication in ulcer and non ulcer dyspepsia.

Anti-Bacterial Agents↗