Nifuratel Compared with Metronidazole in the Treatment of Trichomonal Vaginitis

Nifuratel (Magmilor) was compared with metronidazole (Flagyl) in the treatment of trichomonal vaginitis by a randomized double-blind trial. Only 18 out of 47 patients (38%) treated with nifuratel were found to be cured, whereas 42 out of 49 patients (85%) treated with metronidazole were cured. Severe reactions, necessitating withdrawal of treatment, occurred in three patients treated with nifuratel. There were no serious side-effects with metronidazole. The results of this trial indicate that nifuratel is not a satisfactory substitute for metronidazole in the treatment of trichomoniasis.     

Methyl jasmonate induces cell death and loss of hydrogenosomal membrane potential in Trichomonas vaginalis

Trichomonas vaginalis is an important human parasite of the urogenital tract. Jasmonates are a group of small lipids that are produced in plants and function as stress hormones. Naturally occurring methyl jasmonate (MJ) has been used to treat several types of cancer cells and it is cytotoxic to protistan parasites. It has been suggested that mitochondria are the target organelles of jasmonates. Here, we tested this drug against T. vaginalis. Although metronidazole has been the drug of choice for trichomoniasis, side effects from this treatment are common, and nausea and dizziness have been reported in up to 12% of patients. In addition, there has been increased recognition of resistance to metronidazole. We demonstrate here using flow cytometry, JC-1 and scanning and transmission electron microscopy that MJ induced the cell death of T. vaginalis parasites. Our results are discussed with previous findings published by others.     

The efficacy of cefepime (Maxipime) in the treatment of abdominal sepsis in surgical patients]

The efficacy of cefepime in the treatment of 46 patients operated for general peritonitis of various genesis and severity (APACHE II not greater than 35) was studied. Cefepime was used in a dose of 2 g administered every 12 hours as slow intravenous infusions in 0.9 per cent sodium chloride solution in combination with metronidazole administered intravenously in a dose of 7.5 mg/kg body weight. The treatment course was 4 to 15 days. 45 patients were given diflucan for the prophylaxis of fungal superinfection, 3 patients were given aminoglycoside antibiotics (netilmicin or amikacin) and 2 patients were given vancomycin per os. The favourable clinical effect of the cefepime therapy was stated in 38 patients (82.6 per cent) including 4 out of 10 patients with initial APACHE II > 15. 101 isolates of aerobic gram-negative and gram-positive microbes from 38 patients treated with cefepime in combination with metronidazole were tested to estimate the bacteriological efficacy of the therapy and it was shown that only 5.9 per cent of them was resistant. The pathogen eradication was stated in 84.2 per cent of the patients.     

Nitrimidazine Compared with Metronidazole in the Treatment of Vaginal Trichomoniasis

A new substituted nitroimidazole, nitrimidazine (Naxogin), is compared with the established drug, metronidazole (Flagyl), for the treatment of vaginal trichomoniasis in a randomized double-blind trial. Nitrimidazine cured 39 (68%) out of 57 patients and showed no undesirable effects other than nausea in one patient. Metronidazole cured 51 (89%) out of 57 patients and also caused nausea in one patient; this cure rate corresponds with that previously reported in other trials. In the recommended dosage nitrimidazine is inferior to metronidazole, but is sufficiently effective to be useful in cases of intolerance to metronidazole.     

Ofloxacin and ciprofloxacin in the treatment of sexually-transmitted diseases]

A complex clinico-laboratory++ examination and treatment were made of 76 women with inflammatory processes in the urogenital tract. Gonorrhea, trichomoniasis, chlamydiosis and Ureaplasma infection were detected in 60, 31.4, 41 and 14 per cent of the cases, respectively. There were affections of the rectum by gonococci, chlamydia, ureaplasmas and Trichomonas in 55, 32, 10.6 and 6.6 per cent of the cases, respectively. The frequency of chlamydia in the oropharynx amounted to 30 per cent whereas gonococci and ureaplasma were less frequent i.e. 9 and 1.2 per cent, respectively. The combination of the above pathogens in the rectum were the following: gonococci and chlamydia (15 per cent of the cases), gonococci, chlamydia and Trichomonas (7.3 per cent), gonococci and ureaplasma (7.3 per cent), ureaplasma and chlamydia (7.8 per cent). In the throat the association of gonococci and chlamydia was detected in 3.7 per cent of the cases. It should be indicated that the signs of sex-transmitted diseases were few, which required careful clinico-laboratory examination of the extragenital foci in the patients with inflammatory urogenital diseases. Ofloxacin showed a high efficacy in the treatment of patients with gonorrhea and ureaplasmosis. Its use in treatment of chlamydiosis proved inexpedient while ciprofloxacin was effective in the treatment of the infection.     

Paraendocervical route for metronidazole administration in complex treatment of chronic Trichomonas endocervicitis]

The data on paraendocervical administration of metronidazole in the treatment of patients with relapsing Trichomonas endocervicitis are presented. Metronidazole was administered as 0.5% solution in a dose of 0.04 g once a day for 8-10 days in complex traditional therapy including oral use of metronidazole and immunocorrigating and local treatment. It was shown that paraendocervical administration of the protistocidal agent provided earlier regression of the urogenital symptoms and 2.8 times lower frequency of the relapses.     

Trichomonosis of the oral cavity complicated by mycosis.

Protozoa and fungi of the oral cavity, although frequently occurring and connected to considerable clinical adverse effects, are as yet insufficiently known. The aims of the study were (i) to estimate the prevalence of common invasions of Trichomonas tenax and fungi, (ii) to associate the symptoms with the diagnosis of trichomonosis complicated by mycosis, and (iii) to determine trichomonacidal properties of ornidazole, tinidazole and metronidazole. A sample of 936 dentist patients with different diagnoses were included in the study. The collected material consisted of rinsings, with simultaneous application of selective media, different for protozoa or fungi cultures. Using ornidazole, tinidazole and metronidazole, we examined in vitro their influence on 30 strains of T. tenax. Among the examined patients T. tenax was found in 90 cases including 85 cases where it occurred together with fungi, on the basis of which diagnosis of trichomonosis complicated by mycosis of the oral cavity was established. It was the most frequent in patients with leukoplakia and lichen Wilsoni. We recorded a statistically significant association for T. tenax with fungi and xerostomia, burning sensation, periodontal pockets and denuded teeth. T. tenax was never found in patients with caries and with aphtha recidivans. The curves of ornidazole activity were obtained within the solution range of 130-4350 micrograms/ml; the curves of tinidazole activity within the concentration range of 500-16870 micrograms/ml; metronidazole in the highest concentration killed from 5 to 100% of the population of all strains.     

The use of ampicillin/sulbactam (Unasyn) in treating inflammatory urological diseases

Unasyn is a combination of ampicillin, a bactericidal antibiotic, and sulbactam, an inhibitor of beta-lactamases. It was used in treatment of 36 patients with urogenital infections. The combination was administered intravenously and in the main intramuscularly. The treatment course amounted to 7-10 days. The average daily dose was 6 to 9 g. 22 patients with acute nonocclusive pyelonephritis were treated with the combination and its clinical and bacteriological efficacy was stated in 95 per cent of the cases. An excellent clinical effect of the combination was observed in 6 patients with acute epididymitis. A clinical improvement was also observed in the treatment of the patients with acute prostatitis and chronic renal infections. Unasyn proved to be a highly efficient antibacterial combination with regard to gram-positive flora and colon bacilli as representatives of gram-negative organisms. Satisfactory results were also stated in the treatment of infections caused by Proteus spp. Complete elimination of the pathogen was achieved in 57.7 per cent of the cases. No adverse reactions to Unasyn except pain in the site of the injection were recorded.     

TRICHOMONIASIS—Clinical Trial of Metronidazole (Flagyl?)

Metronidazole was given in various dosage regimens to 97 patients having microscopically diagnosed trichomoniasis.At the first examination after treatment all 97, including 76 to whom metronidazole had been given orally only, were found by culture and wet smear to be free of trichomonads.Reexamination of the 65 patients followed up for periods ranging from two weeks to 14 months revealed reappearance of trichomonads in eight cases.Nineteen husbands were treated. No patient had a recurrence after treatment of the husband.No effect of metronidazole on pregnancy or on fetal development was seen. Side effects, noted in 19 cases (20 per cent), generally were mild and transient and in no case were severe enough to terminate therapy before cure was effected.     

Efficacy of pefoxacin (abactal) in the complex treatment of patients with pancreonecrosis]

The efficacy of pefloxacin in the complex treatment of 28 patients with pancreatonecrosis of various etiology was estimated in a prospective trial. The diagnosis of pancreatonecrosis was verified by the data of the disease clinical progress, laboratory findings and instrumental examination. Pefloxacin (Abactal; LEK) was administered intravenously in a dose of 400 mg every 8 hours (1200 mg) in combination with metronidazole in a dose of 1.5-2.0 g a day intravenously. When indicated 3 days after the start of the pefloxacin therapy, the treatment was switched to the oral use of the drug in the same dosage. The positive clinical effect (cure and improvement) at the end of the treatment with pefloxacin was stated in 78 per cent of the patients in spite of the initial severity state of above 15 APACHE II. It was shown that in the treatment of patients with pancreatonecrosis when the severity state was not above 12 APACHE II the antibacterial therapy with pefloxacin in combination with metronidazole was optimal.     

Enteric trichomonads of squirrel monkeys (Saimiri sp): Natural infestation and treatment

In a large breeding colony of squirrel monkeys, a previous study demonstrated apparent universal infestation of adult animals with enteric trichomonads. The potential of these organisms to act as a source of experimental variability and the potential pathogenic effects of parasitism in this species stimulated this study of organism acquisition and treatment. Age of natural infestation with trichomonads was determined from results of microscopic examination and culture of fecal samples from infants of different ages. A majority of squirrel monkey infants showed first evidence of trichomoniasis at 2 to 4 weeks of age, with apparent 100% infestation by 8 weeks of age. Treatment of adult monkeys was investigated. In vitro techniques were utilized to determine sensitivity to metronidazole of a number of isolates. An effective regimen for treatment of adult monkeys was determined to be 25 mg/kg body weight of metronidazole given orally, twice daily for 5 days.     

Metronidazole Susceptibility in Clostridium difficile Isolates Recovered from Cases of C. difficile -associated Disease Treatment Failures and Successes

Despite high clinical efficacy, a small number of patients with Clostridium difficile -associated disease (CDAD) do not respond to treatment with metronidazole. We looked for evidence of metronidazole resistance in human C. difficile isolates from 632 patients with CDAD treated with metronidazole, 14(2%) of whom failed treatment. C. difficile isolates were available from 10 of the metronidazole-failure cases and were matched with isolates from 20 contemporary control CDAD patients who responded to treatment with metronidazole. The mean (±SD) MIC of metronidazole-failure-associated C. difficile isolates was similar to the mean (±SD) MIC of isolates from metronidazole-success cases (E-test; 0.23±0.21 vs 0.29±0.19μg/mL, P=0.4). Restriction endonuclease analysis typing revealed that no particular C. difficile strain was associated with metronidazole treatment failure. Clinical CDAD treatment failures with metronidazole could not be attributed to decreased susceptibility of the causativeC. difficle isolate to metronidazole.     

S-Adenosylhomocysteine hydrolase of the protozoan parasite Trichomonas vaginalis: potent inhibitory activity of 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine

In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 μM compared to 0.72 μM for metronidazole.     

Genetically different clonal isolates of Trichomonas gallinae, obtained from the same bird, can vary in their drug susceptibility, an in vitro evidence

Trichomonas gallinae is a flagellated protozoon which parasitizes in the upper digestive tract of different birds, especially columbiformes (doves and pigeons) and falconiformes. The parasite is also a common inhabitant of the crop of psittacine birds and is frequently detected in budgerigars. The lesions associated with T. gallinae infection of the upper digestive tract range from mild inflammation of the mucosa to large caseous lesions that block the lumen of the oesophagus. Nitroimidazoles are considered to be the drugs of choice for the treatment of trichomonosis. However, only a few studies report the existence of resistant strains of T. gallinae to these drugs. Thus, in the present investigation cloned cultures of T. gallinae obtained from budgerigars and pigeons were analysed for the first time for their in vitro susceptibilities against four 5′-nitroimidazole derivates, including metronidazole, dimetridazole, ronidazole and ornidazole. Significantly different minimal lethal concentrations (MLCs) were observed for them against all four drugs. The lowest MLCs revealed the Trichomonas isolates obtained from two budgerigars, ranging from 2.0 ± 0.3 to 3.0 ± 0.7 μg/ml for metronidazole and dimetridazole, and from 2.0 ± 0.6 to 6.7 ± 1.7 μg/ml for ornidazole and ronidazole. Contrary to this, the highest MLCs were recorded for one Trichomonas isolate obtained from a pigeon, ranging from 83.3 ± 6.7 (for dimetridazole and ronidazole) to 103.3 ± 3.3 μg/ml (for metronidazole and ornidazole). The data obtained for the resistance testing were further compared with already available genetic data of the small subunit rRNA gene sequences and ITS-1, 5.8S rRNA and ITS-2 sequences, indicating a certain correlation between in vitro results and strain relationships.     

Efficacy of 2-week, second-line Helicobacter pylori eradication therapy using rabeprazole, amoxicillin, and metronidazole for the Japanese population

Background: Following the failure of first‐line Helicobacter pylori eradication therapy using a proton pump inhibitor, amoxicillin, and clarithromycin, second‐line therapy is conducted for 1 week using metronidazole instead of clarithromycin in Japan. Recent studies indicate that metronidazole‐containing therapy has a higher eradication rate with prolonged treatment duration, even with metronidazole resistance. The aim of this study was to reveal the efficacy of 2‐week metronidazole‐containing second‐line therapy. Methods: Eighty‐two consecutive outpatients who had failed in the first‐line eradication therapy were enrolled and second‐line therapy was initiated with 10 mg rabeprazole, 750 mg amoxicillin, and 250 mg metronidazole twice daily. After they had been screened by hematological examination 1 week after initiation, the treatment was continued for 2 weeks after initiation in patients without hematological abnormality. Cure was essentially confirmed by the urea breath test. Results: After one patient was lost, hematological examination showed elevated serum aminotransferase in 14 of 81 patients. Although it was mild without clinical issues, they were ethically excluded from this study. In the remaining 67 patients and the lost patient, the eradication rate with 2‐week therapy was 65/68 (96%, 95% confidence interval: 88–98%) by intention to treat analysis and 65/65 (100%, 94–100%) by per protocol analysis. The main adverse event was soft stools (39%), and no serious adverse event was observed. Conclusion: This 2‐week metronidazole‐containing second‐line therapy provides high efficacy in Japan where metronidazole resistance is rare.     

Seven-Day Triple Therapy with Lansoprazole, Clarithromycin, and Metronidazole for the Cure of Helicobacter pylori Infection: A Short Report

Background To refine our understanding of anti- Helicobacter pylori treatment regimens further, we evaluated the efficacy and safety of lansoprazole given in combination with clarithromycin and metronidazole for 7 days in an open-label, multicenter study.
Materials and Methods. H. pylori -positive patients self-administered lansoprazole, 30 mg; clarithromycin, 500 mg; and metronidazole, 500 mg bid for 7 days. Patients were assessed at pretreatment, at which time the presence of H. pylori was documented by rapid urease test or histology and culture, following study drug administration (week 1) for a brief evaluation only, and at least 4 weeks posttreatment (week 5), including endoscopy with collection of biopsy specimens for culture and histology testing.
Results. Of the 60 patients enrolled in the study, 59 had confirmed H. pylori infection, and 51 were included in an intent-to-treat analysis of efficacy. Primary metronidazole and clarithromycin resistance were observed in 84% and 8% of study patients, respectively. One month after the end of therapy, H. pylori infection was cured in 40 of 51 patients (78%); 95% confidence interval, 65%–89%). The triple-therapy regimen was well-tolerated, with only 2 patients (4%) requiring premature withdrawal from the study due to treatment-related adverse events. Taste perversion (15.0%) and diarrhea (11.7%) were the most frequently reported adverse events possibly or probably related to study medication during the treatment period.
Conclusion. Despite a high prevalence of metronidazole resistance, a 1-week, triple-drug combination of lansoprazole, clarithromycin, and metronidazole is effective treatment for and well-tolerated by patients with H. pylori infection.     

Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis

Trichomoniasis is the most common, sexually transmitted infection.It is caused by the flagellated protozoan parasite Trichomonas vagina/is. Symptoms include vaginitis and infections have been associatedwith preterm delivery, low birth weight and increased infant mortality, as well as predisposing to HIV/AIDSand cervical cancer. Trichomoniasis has the highest prevalence and incidence of any sexually transmitted infection. The 5-nitroimidazole drugs, of which metronidazole is the most prescribed, are the only approved,effective drugs to treat trichomoniasis. Resistance against metronidazole is frequently reported and cross-resistance among the family of 5-nitroimidazole drugs is common, leaving no alternative for treatment, withsome cases remaining unresolved. The mechanism of metronidazole resistance in T. Vagina/is from treatment failures is not well understood, unlike resistance which is developed in the laboratory under increasingmet ronidazole pressure. In the latter situation, hydrog enosomal function which is involved in activationof the prodrug, metronidazole, is down-regulated. Reversion to sensitivity is incomplete after removal ofdrug pressure in the highly resistant parasites while clinically resistant strains, so far analysed, maintaintheir resistance levels in the absence of drug pressure. Although anaerobic resistance has been regarded asa laboratory induced phenomenon, it clearly has been demonstrated in clinical isolates. Pursuit of both approaches will allow dissection of the underlying mechanisms. Many alternative drugs and treatments have been tested in vivo in cases of refractory trichomoniasis, as well as in vitro with some successes including the broad spectrum anti-parasitic drug nitazoxanide. Drug resistance incidence in T. Vagina/is appears to be on the increase and improved surveillance of treatment failures is urged.     

凝结芽孢杆菌活菌片联合甲硝唑栓治疗细菌性阴道病的临床观察

目的观察凝结芽孢杆菌活菌片(商品名:爽舒宝)联合甲硝唑栓治疗细菌性阴道病的临床疗效。方法选取细菌性阴道病患者108例随机分为观察组和对照组,每组54例。两组患者均以甲硝唑栓放入阴道治疗,观察组在此基础上,口服凝结芽孢杆菌活菌片,首次6片,以后3片/次,3次/d,连用14d。观察两组患者用药后的临床疗效及不良反应,并比较治疗后随访半年内的复发率。结果观察组患者临床总有效率(90.7%)明显高于对照组(74.1%)(P0.05),治疗期间均未见明显的药物不良反应。治疗后随访半年,观察组的复发率(14.3%)明显低于对照组(32.5%)(P0.05)。结论凝结芽孢杆菌活菌片联合甲硝唑栓治疗细菌性阴道病疗效显著,能降低复发率,值得临床推广应用。     

阴道毛滴虫铁氧还蛋白与甲硝唑抵抗的研究进展

氢化酶体是阴道毛滴虫重要的代谢器官,该器官内存在的铁氧还蛋白不仅是虫体代谢过程中主要的电子传递介体,而且也在甲硝唑的激活中起关键作用。近年来阴道毛滴虫的甲硝唑抵抗株在临床和实验室都有报道,实验研究发现活化药物的铁氧还蛋白减少或缺失,因此对铁氧还蛋白与甲硝唑抵抗的相关性研究越来越受到医学及药学界的重视。本文总结近年来该领域的研究成果及发展动态,以期对滴虫药物抵抗的发生机制以及滴虫病防治的研究提供有价值的资料。