Efficacy of antiamebic drugs in a mouse model

Nitroimidazole antibiotics are the mainstay of treatment of invasive amebiasis; however, few comparative studies of applicable antibiotics are available. Evidence of sporadic clinical failure and rare reports of metronidazole resistance have led to the investigation of novel antiamebic therapeutics. The goal of this study was to examine drug efficacy in both in vitro and in vivo models of intestinal amebiasis. We studied six current and three novel drugs. Many drugs, including metronidazole, nitazoxanide, and nitazoxanide derivatives, were shown to be potently inhibitory in vitro. However, metronidazole remained the most effective in vivo, both in preventative and curative regimens, underscoring the value of animal models in evaluating future therapies.     

Metronidazole and amebiasis

Previous reports indicate that metronidazole is highly effective in the therapy of colonic amebiasis and in the treatment of hepatic amebic abscesses when combined with aspiration. A retrospective review of 15 cases of intestinal amebiasis and 12 patients with amebic liver abscesses treated with metronidazole alone is reported. Based on the literature and the clinical response of the patients reported herein, metronidazole is the initial drug of choice in the therapy of amebic colitis because of its ease of administration, efficacy, and low toxicity. In the treatment of hepatic amebic abscesses, metronidazole alone is adequate therapy for most cases, but occasionally there will be progression of the disease despite standard dosages of the drug.     

A case of pulmonary amebiasis

A 57-year-old man was admitted to our hospital because of dyspnea and right abdominal pain. Chest X-ray radiogram showed right massive pleural effusion. Ultrasonic echogram of abdomen showed a unilocular liver cyst. He was treated with intravenous infusion of meropenem, and percutaneous pleural and liver drainage were performed. At the time of drainage, we injected contrast medium into the liver cyst and confirmed a fistula connecting to the right pleural space. Initially we made a diagnosis of bacterial empyema and liver abscess, yet there was no response to the initial treatment. Cultures of pleural effusion and liver abscess were confirmed to be negative. A few days after admission, the patient stated that he was a homosexual. Liver amebiasis and its perforation became the most likely diagnosis, and metronidazole was administered. On admission day 21, tests for anti-amebic antibody were positive. Finally he fully recovered. We must be aware of the rare pulmonary manifestation of amebiasis. We report this case and review the literature.     

Double blind study with a new nitroimidazole derivative, Ro 7-0207, versus metronidazole in symptomatic intestinal amebiasis

Of 115 patients with symptomatic intestinal amebiasis, 56 were treated with Ro 7-0207 and 59 with metronidazole in a double blind study. Results of treatment were similar in the two groups and side effects were of low intensity except in one patient who received Ro 7-0207 and developed numbness of hands and tongue, difficulty in speaking, and headache. These symptoms disappeared after termination of treatment.     

Amebiasis at an evacuation site on the Thai-Cambodian border

Symptomatic intestinal amebiasis was highly endemic among the Cambodians living at Green Hill, an evacuation site on the Thai-Cambodian border between June 1987 through May 1989. Monthly incidence rates of intestinal amebiasis were determined to be inversely proportional to cumulative monthly rainfall. The highest incidence of amebic dysentery was 63/1000 in children 12-23 months old. Behavioral risk factors were investigated by conducting a case-control study. A questionnaire was administered to 73 families, each having at least one member with confirmed intestinal amebiasis within the past 3 months, and to 95 randomly selected control families having no individual with diarrhea for at least 3 months. Individuals from families with greater than 4 members were at higher risk for acquiring intestinal amebiasis. No significant differences in behavioral risk factors were identified between case and control families. Eighty-six percent of 51 water samples drawn from wells where amebiasis patients obtained their drinking water had greater than 10 coliforms/100 ml. The main route of transmission of E. histolytica was not identified, but was most likely via the fecal-oral route.     

Synchronous leiomyosarcoma and ameboma of the Rectum: Report of a Case

Summary A case of leiomyosarcoma of the rectum associated with rectal amebiasis is presented. This is the first case to be reported. Initially, amebiasis obscurred the histologic diagnosis of leiomyosarcoma, but incomplete regression following a course of treatment with metronidazole aroused the suspicion of malignancy, which was confirmed on repeat biopsy. A brief review of the features of leiomyosarcoma was also undertaken. Senior Lecturer and Consultant Surgeon. Department of Surgery. Professor and Consultant Pathologist, Department of Morbid Anatomy.     

Efficacy of saccharomyces boulardii with antibiotics in acute amoebiasis

AIM: To compare the efficacy of antibiotics therapy alone with antibiotics and saccharomyces boulardii in treatment of acute amebiasis.METHODS: In a double blind, random clinical trial on patients with acute intestinal amoebiasis, 57 adult patients with acute amoebiasis, diagnosed with clinical manifestations (acute mucous bloody diarrhea) and amebic trophozoites engulfing RBCs found in stool were enrolled in the study.Regimen 1 induded metronidazole (750 mg Tid) and iodoquinol (630 mg Tid) for 10 days. Regimen 2 contained capsules of lyophilized saccharomyces boulardii (250 mg Tid) orally in addition to regimen 1. Patients were re-examined at two and four weeks after the treatment, and stool examination was performed at the end of week 4. Student′s t-test, χ2and McNemar′s tests were used for statistical analysis.RESULTS: Three patients refused to participate. The other 54 patients were randomized to receive either regimen 1 or regimen 2 (Groups 1 and 2 respectively, each with 27patients). The two groups were similar regarding their age,sex and clinical manifestations. In Group 1, diarrhea lasted 48.0±18.5 hours and in Group 2,12.0±3.7 hours (P＜0.0001).In Group 1, the durations of fever and abdominal pain were 24.0±8.8 and 24.0±7.3 hours and in Group 2 they were 12.0±5.3 and 12.0±3.2 hours, respectively (P＜0.001).Duration of headache was similar in both groups. At week 4, amebic cysts were detected in 5 cases (18.5 %) of Group 1 but in none of the Group 2 (P＜0.02).CONCLUSION: Adding saccharomyces boulardii to antibiotics in the treatment of acute amebiasis seems to decrease the duration of clinical symptoms and cyst passage.     

Intestinal invasive amebiasis: an experimental model in rodents using axenic or monoxenic strains of Entamoeba histolytica

A new experimental model for the production of early stages of invasive intestinal amebiasis in hamsters or guinea pigs with axenic or monoxenic cultures of Entamoeba histolytica of the HM1:IMSS strain is reported. The model is called the washed-closed cecal loop, because it involves the washing out of the cecum contents of conventionally raised animals and the formation of a closed loop, into which amebas are inoculated. Colonization occurred in all inoculated animals. After 48 hr, macroscopic ulcerations of the cecal mucosa were found in approximately one-half (5/12) of the animals inoculated with axenic amebas and in more than two-thirds (10/12) of those inoculated with monoxenic parasites. The amebic nature of the mucosal ulcerations was confirmed by light and transmission electron microscopy, as well as by scanning electron microscopy (SEM) of fractured samples of cecal mucosa. SEM provided a rapid and reliable technique to assess both the extent and the nature of the lesions. This model is particularly useful for the study of the pathogenesis of early intestinal lesions produced by virulent amebas, and may also be applied to experimental studies on the immunology of invasive intestinal amebiasis.     

Controlled trial of intravenous metronidazole as an adjunct to corticosteroids in severe ulcerative colitis.

A prospective double blind controlled trial was undertaken to examine the role of metronidazole as an adjunct to corticosteroids in the management of severe ulcerative colitis. Thirty nine patients with severe ulcerative colitis were randomised on admission to hospital to receive either intravenous metronidazole 500 mg eight hourly (19 patients) or an identical intravenous placebo (20 patients). The two groups were similar with respect to age, sex, and the extent of colitis. In addition all patients received a standard intravenous regimen consisting of methyl prednisolone 16 mg six hourly and parenteral nutrition together with a twice daily hydrocortisone 100 mg enema. Treatment was continued for five days when the patients were formally assessed. Fourteen of 19 patients (74%) receiving metronidazole and 14/20 (70%) receiving placebo were substantially improved, or in remission at the end of five days. Five patients treated with metronidazole and six with placebo had no improvement and all proceeded to urgent colectomy with no operative mortality. There were three late deaths, one in the metronidazole and two in the placebo group. These results do not support the routine use of intravenous metronidazole in the treatment of severe ulcerative colitis.     

Hepato-pulmonary amebiasis: a case report

Infections with Entamoeba histolytica are seen worldwide and are more prevalent in the tropics. About 90% of infections are asymptomatic, and the remaining 10% produce a spectrum of clinical syndromes, ranging from dysentery to abscesses of the liver or other organs. Extra-intestinal infection by E. histolytica most often involves liver. Pleuro-pulmonary involvement, seen as the second most common extra-intestinal pattern of infection, is frequently associated with amebic liver abscess. Pulmonary amebiasis occurs in about 2-3% of patients with invasive amebiasis. We report herein the case of a 45-year-old male presenting with hepato-pulmonary amebiasis. The diagnosis was established from direct examination of sputum, in which trophozoites of E. histolytica were detected, and by serology. Following treatment with metronidazole and chloroquine, the clinical evolution improved significantly. On regular follow-up visits, the patient was asymptomatic. This case report reiterates the need for collaboration between clinicians and microbiologists for timely diagnosis of such infections.     

溃疡性结肠炎合并阿米巴肠病临床特点探讨

目的 探讨溃疡性结肠炎合并阿米巴肠病的临床特点.方法 回顾性分析2003～2010年共104例溃疡性结肠炎患者诊治资料,其中15例确诊合并阿米巴肠病(A组),单纯性溃疡性结肠炎患者89例(B组),统计各患者的腹泻次数、贫血程度、低白蛋白血症程度及结肠病变范围.结果 A、B组患者中腹泻＞6次/d者分别为13例、40例,血红蛋白＜90 g/L患者分别为8例、16例,血清蛋白＜30 g/L患者分别为10例、23例,结肠病变范围超过1/2的患者分别为12例、31例,两组存在统计学差异;15例溃疡性结肠炎合并阿米巴肠病患者中7例为先确诊溃疡性结肠炎,后获得阿米巴感染并致病,其余8例患者无法判断两种疾病的发病先后顺序.所统计病例中溃疡性结肠炎并发阿米巴肠病发病率为14.4％(15/104),高于阿米巴肠病在普通人群中发病率(同地区平均为0.44％,最高2.43％).结论 溃疡性结肠炎合并阿米巴肠病病情较单纯性溃疡性结肠炎患者严重;溃疡性结肠炎患者较普通人群更容易获得溶组织内阿米巴感染并致病.     

BRIEF COMMUNICATIONS: A quantity survey of intravenous administration of metronidazole in its different forms in a tertiary teaching hospital

The aim of this paper is to examine the prescribing patterns and cost of various formulations of metronidazole in a hospital setting over a 3‐month period. Oral metronidazole has high bioavailability (98.9%) with peak plasma concentrations averaged at 2.3 h after dosing. Despite the high bioavailability of oral metronidazole, many patients continue to receive metronidazole intravenously when they are suitable for oral preparation. An audit of 120 consecutive patients prescribed metronidazole was conducted at the Liverpool Hospital, NSW, from March to July 2005. There were 65 men and 55 women (age 18–93). Of the 120 patients, 16 were on oral, 1 on rectal and 103 were on intravenous metronidazole. Treatment was initiated based on clinical diagnoses. Potential pathogens were subsequently identified on only 21 occasions. The use of metronidazole as an oral preparation was contraindicated in 27 patients (22.5%) who were nil‐by‐mouth. Of these, rectally administered metronidazole was contraindicated in only eight patients. The average course of intravenous metronidazole was 8.0 ± 9.7 days (mean ± SD). The total number of intravenous metronidazole treatment days was 824. Oral metronidazole would have been possible in 618 out of the 824 days. The estimated cost to administer each dose of oral, suppository and intravenous forms of metronidazole is $A0.11, $A1.34 and $A6.09 respectively. Thus, substantial savings could be achieved if oral metronidazole were to be administered whenever possible. The early use of oral or rectal metronidazole should be encouraged when there are no clinical contraindications.     

Single-dose metronidazole versus 5-day multi-drug antibiotic regimen in excision of pilonidal sinuses with primary closure: a prospective randomised controlled double-blinded study

BACKGROUND AND AIMS: This pilot study examines whether single-dose intravenous metronidazole preoperatively is at least as effective as a broad-spectrum multi-drug regimen in preventing infection-related wound complications following excision of pilonidal sinuses with primary closure. PATIENTS AND METHODS: A double-blinded study with 50 patients randomised to receiving either a single drug (intravenous metronidazole 500 mg) prophylaxis preoperatively or multi-drug cover (intravenous cefuroxime 1.5 g and metronidazole 0.5 g preoperatively, and oral co-amoxiclav 375 mg 8-hourly postoperatively). They will be reviewed 1, 2 and 4 weeks postoperatively. The wound will be graded as: I, healthy; II, redness and swelling of edges; III, abscess related to a suture; IV, spreading wound infection; V, wound breakdown. Other factors considered are the distance from the lowest wound margin to the anal verge, and previous pilonidal sinus surgery. RESULTS: Results awaited. CONCLUSION: Single-dose metronidazole seems an appropriate and low-cost antibiotic to consider for prophylaxis in pilonidal sinus surgery. This study will form the base for a trial to be conducted in larger numbers as a randomised controlled trial in order to have statistical power.     

Intravenous metronidazole for the treatment of Clostridium difficile colitis

PURPOSE: SevereClostridium difficile colitis may produce abdominal distention and ileus, precluding oral antibiotic therapy. Stimulated by several case reports in which intravenous metronidazole was used, we reviewed our experience. METHODS: Using pharmacy and microbiology laboratory records, we retrospectively identified patients withC. difficile colitis who received intravenous metronidazole as initial monotherapy. To be included, patients had to fulfill the following criteria: 1) at least six doses (equivalent to two days of therapy) of intravenous metronidazole were administered, 2) no other potential cause for colitis was found, and 3) the diagnosis ofC. difficile colitis was firmly established. For eligible patients, five clinical parameters were assessed before and after intravenous metronidazole. RESULTS: Our patient group (n=10) received an average of 13.7 (range, 6–24) doses of intravenous metronidazole as initial therapy forC. difficile colitis. All received a dose of 500 mg three times daily. The majority of patients with vomiting, fever, and/or abdominal pain present at the beginning of therapy had resolution with intravenous metronidazole. Only one patient developed a symptom (vomiting) while on therapy; however, this eventually resolved when oral metronidazole was instituted. No patient required colectomy for refractory colitis or developed toxic megacolon. No patient, including those on prolonged courses, developed toxicity related to intravenous metronidazole such as peripheral neuropathy. CONCLUSIONS: Intravenous metronidazole may be effective therapy in patients withC. difficile colitis. A randomized, prospective study appears warranted.     

High-frequency ultrasound imaging of the duodenum and colon in patients with symptomatic giardiasis in comparison to amebiasis and healthy subjects

Aim:  The application of ultrasound may be suitable for evaluating the effects of intestinal cytoskeletal rearrangement of the duodenum and colon as a result of exposure to live Giardia lamblia trophozoites. We studied the sonographic appearance of the duodenum and colon in giardiasis compared with amebiasis and healthy subjects.
Methods:  Sonographic images obtained from 100 consecutive patients with symptomatic giardiasis were compared to those taken from 40 patients with amebiasis and 40 healthy subjects. B-mode ultrasound examination of the duodenum and colon was performed using a 7.5 MHz annular array transducer. Gray scale images with water contrast were acquired.
Results:  Normal duodenum and colon echoanatomy were demonstrated. Giardial lesions of the duodenum and colon were associated with increased wall thickness when compared with healthy subjects ( P  < 0.05). Furthermore, giardial lesions were characterized by increased wall echogenicity, flattening or loss of duodenal folds and/or colonic haustration, hyperechoic floating foci (HFF) demonstrating chaotic motility, increased peri-lesional tissue echogenicity, and altered colonic peristalsis. In amebiasis, focal hyperechoic wall thickening was seen at lesion sites identified as amebomas with increased wall echogenicity, but otherwise normal duodenal folds and colonic haustration. There were no HFF with chaotic motility, rather intestinal contents showed bulk motility in patients with amebiasis. There was no focal colonic wall motion abnormality observed.
Conclusion:  B-mode imaging with water contrast demonstrated details of duodenal and colonic echoanatomy. There were sonographic features of giardial lesions of the duodenum and colon that were distinct from those in amebiasis and healthy subjects.     

Protective immunity to amebiasis: new insights and new challenges

Amebiasis, infection with the protozoan parasite Entamoeba histolytica, is the third leading cause of death from parasitic diseases. Despite its importance, we know little about protective immunity to amebiasis. Now, studies from a cohort of children in Bangladesh have provided some critical insights into immunity to intestinal amebiasis. Children with mucosal IgA antibodies to the amebic adherence lectin were found to be resistant to reinfection with E. histolytica. However, immunity was short-lived, and approximately 20% of children in the cohort had a second episode of E. histolytica infection during the study period. Theses findings indicate that immunity to amebiasis can develop in some children after intestinal infection, but protective immunity may be transient, and its importance in preventing disease remains to be established.     

Varioliform mucosal polypoid lesions in intestinal tract in a patient with adult T-cell leukemia

We describe a case of adult T-cell leukemia (ATL) with intestinal infiltration. In the early clinical stage, the endoscopic findings for the intestine were similar to those of amebic enterocolitis, i.e., varioliform mucosal polypoid lesions, and amebic cyst was detected with stool examination. Although no specific pathological factor could be identified on biopsy, the patient was treated for amebiasis as a diagnostic therapy. the findings of varioliform mucosal polypoid lesions were detected in the duodenum on endoscopic examination, but the lesions eventually disappeared during the treatment for amebiasis. We then suspected lymphoma partially masked by, the amebiasis. Immunological staining of a specimen of the colonic mucosa revealed T cell invasion and Southern blotting demonstrated adult T-cell leukemia provirus invasion. Thus, ATL cell infiltration of the intestinal tract was confirmed It is suggested that systemic disease should also be considered when varioliform mucosal polypoid lesions are found on colonoscopic examination.     

Combination Therapy for Intestinal Amebiasis Using an Anti-amebic Drug and Total Parenteral Nutrition —Report of Two Cases—

Abstract: In this study we report on two cases of amebic colitis treated in our hospital. On admission both patients were in a severe state of malnutrition due to intermittent diarrhea which had continued for one month. Both patients suffered from amebic colitis presumably transmitted by homosexual intercourse. A definite diagnosis of amebic colitis was made from both fecal examination and colonoscopic biopsy. After the diagnosis was made, the patients were treated with metronidazole. This medication can eliminate Entamoeba histolytica, although it was insufficient for the treatment of the patients’malnutrition. Therefore we used total parenteral nutrition to treat their malnutrition. It was successful and resulted in their recovery and discharge. These two cases indicate that total parenteral nutrition therapy is useful for supporting the recovery of patients with amebiasis.     

Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile.

Faecal metronidazole and hydroxymetronidazole concentrations measured by high pressure liquid chromatography are reported during 10 episodes of Clostridium difficile colitis in nine patients. Bactericidal faecal concentrations were present in all patients with acute disease receiving oral or intravenous metronidazole, and all responded to therapy. Metronidazole and hydroxymetronidazole concentrations fell as the diarrhoea improved and neither substance was detectable in the faeces of five patients after recovery. This demonstration of intracolonic therapeutic concentrations of metronidazole supports the clinical experience of oral metronidazole being effective in the treatment of antibiotic associated diarrhoea caused by C difficile and also suggests a potential role for intravenous metronidazole in this disease.     

Topical ampicillin in addition to a systemic antibiotic prophylaxis in elective colorectal surgery. A prospective randomized study

Prophylactic use of topical ampicillin in addition to intravenous ampicillin and metronidazole was studied in a randomized trial including 203 consecutive patients undergoing elective colorectal surgery. All received ampicillin, 1 g X 3, and metronidazole, 0.5 g X 3, intravenously for at least three days from induction of anesthesia, and 105 also received topical ampicillin, 1 g, in each of the surgical wounds. Deep wound infection or dehiscence was seen in 12 of 105 having both administrations of antibiotics, and in nine of 98 having only intravenous antibiotics. The two groups were similar according to distribution of sex, age, type of surgery, and efficiency of bowel preparation. Topical ampicillin should be omitted in elective colorectal surgery when systemic prophylaxis with ampicillin and metronidazole is used.