Dose Of Metronidazole Research Articles

Single-dose Metronidazole ClearsOpalinasp. from JuvenileBufo woodhousii

Protozoans of the family Opalinidae are intestinal commensals in amphibians. To test the hypothesis that these organisms are susceptible to the antiprotozoal antibiotic metronidazole, we randomly assigned 60 juvenile Woodhouse's toads ( Bufo woodhousii ) to receive a single oral dose of metronidazole or water. In pilot trials, the prevalence of opalinids in untreated members of this population was over 70%. One-third of the study population was dissected at each of 3 time points: 18 hr, 1 wk, and 2 wk post-treatment. An examiner blinded to the toad's treatment history determined the presence or absence of opalinids using a dissecting microscope. Opalinids were found in 3/10 toads in the treatment group and 9/10 in the control group after 18 hr (P < 0.02), in none of the treatment group and 8/10 in the control group after 1 wk (P < 0.001), and in none of the treatment group and 10/10 in the control group after 2 wk (P < 0.0001). These results suggest that a single-dose of metronidazole quickly and reliably clears opalinids from juvenile Woodhouse's toads with no evidence of short-term recurrence. The treatment was well tolerated, with no apparent morbidity and no mortality in either group. Future exploration of opalinid-related host fitness consequences may be facilitated by this simple method of developing a protozoan-free host population.

Single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection at Bugando Medical Centre in Mwanza, Tanzania: a randomized, equivalence, controlled trial

BackgroundCaesarean section(C/S) has been found to increase rates of maternal infectious morbidities five times more than vaginal delivery. The provision of intravenous prophylactic antibiotics 30 to 60 minutes prior to C/S has been found to substantially reduce post-caesarean infection. At Bugando Medical Centre, there is no consistent protocol for the administration of antibiotic prophylaxis to patients who are undergoing emergency C/S. Providing repeated dosages of antibiotic prophylaxis after C/S is the common practice. This study aimed to determine the comparative efficacy of a single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection.MethodsFrom October 2011 to May 2012, a randomized, equivalence, non-blinding clinical trial was conducted at Bugando Medical Centre in Mwanza, Tanzania. A total of 500 eligible participants were enrolled in the study and were randomly allocated into two study arms -- “A” and “B”. Participants in “A” received a single dose of gentamicin in combination with metronidazole 30 to 60 minutes prior to the operation, and participants in “B” received the same drugs prior to the operation but continued with for 24 hours. Both groups had 30 days of follow-up and were assessed for signs and symptoms of surgical-site infection as the primary outcome. The equivalence margin was set at 5%. The two-tailed equivalence was analyzed based on intention- to-treat analysis.ResultsThe randomization was proper, as the distribution of various demographic and other baseline characteristics had a p-value of > 0.05. All 500 participants were included in our analysis; of these, no participants were lost to follow-up. Surgical-site infection occurred in 12 out of the 250 (4.8%) receiving single dose compared to 16 out of the 250 (6.4%) receiving multiple doses. There is an absolute proportion difference of 1.6% (95% Confidence interval: -2.4 – 5.6%) which lies outside the pre-specified 5% equivalence margin.ConclusionWe recommend the administration of pre-operative single dose antibiotic prophylaxis for emergency caesarean as this intervention proved to be not equivalent to multiple doses antibiotic prophylaxis in reducing surgical site infection. Single dose therapy also reduces staff workload along with medication costs.Trial registrationCurrent Controlled Trials ISRCTN44462542

Brain MRI evolution of metronidazole intoxication

A 64-year-old woman presented with a 6-month history of intermittent episodes of ataxia and dysarthria. She had been on metronidazole 1,500 mg daily for ulcerative colitis for 10 months. Cranial MRI 3 months before admission revealed hyperintensity in corpus callosum and bilateral dentate nuclei (figure 1, A–C). MRI on admission revealed cystic necrotic degeneration (figure 1, D and E) and cytotoxic edema (figure 2) in corpus callosum, whereas dentate nuclei appeared normal (figure 1F). The cumulative metronidazole dose was 450 g, relatively high,1 which could cause white matter injury by various mechanisms (appendix e-1 on the Neurology® Web site at www.neurology.org). Although early MRI findings are typical for metronidazole toxicity,2 delayed cystic necrosis is unusual.

Single Daily Dosing of Ceftriaxone and Metronidazole is as Safe and Effective as Ampicillin, Gentamicin and Metronidazole for Non-operative Management of Complicated Appendicitis in Children

Introduction: Perforated appendicitis very common abdominal emergency in children and nonoperative management with Ampicillin Gentamicin and Metronidazole (AGM) has shown good results. Recent data show that single daily dosing of Ceftriaxone and Metronidazole (CM) is as safe and effective as ampicillin gentamicin and clindamycin for treatment of perforated appendicitis after surgery in children. Treatment of complicated appendicitis in children with once daily CM can decrease the risk of in drug administration’s mistake, require the patient to be connected to the IV line for short time only once a day, may cause less IV line infection and may cost less. The aim of this study was to compare the effectiveness, and safety of CM with the traditional triple antibiotic for conservative treatment of complicated appendicitis children. Methods: A prospective, open, randomized study conducted from July 1st 2008 to June 30th 2009. Included were children younger than 14 years with complicated appendicitis who were randomly assigned to therapy with either CM as a single daily dose or AGM. The outcome variables compared were maximum daily temperature, duration of fever, time return to oral diet, length of antibiotic therapy, results of repeat WBC counts, need for abdominal abscess drainage, length of hospitalization and complication. Results: Overall 22 and 21 children were assigned to CM and AGM regimens respectively. There were no any significant differences in all clinical outcomes parameters between the two groups. Conclusions: Single daily dosing of CM is as safe and effective as the triple antibiotic regimen and has significant advantages for the conservative therapy of complicated appendicitis in children.

Optimum duration of perioperative antibiotic therapy in patients with acute non-perforated appendicitis: a prospective randomized trial

Background: Inappropriate use of antibiotics for perioperative antimicrobial therapy can cause considerable complications including emergence of antibiotic resistance, risk of drug reactions and economic implications. Objective: We assessed the use of antibiotics in patients with acute non-perforated appendicitis. Methods: The study was performed on 317 patients aged 15 to 70 years with non-perforated appendicitis who were undergoing open appendectomy. All patients received intravenous ceftriaxone (1 g) and metronidazole (500 mg) immediately after appendectomy. Patients were randomized into one of the following three treatment protocols; A: no further antibiotics, B: three more doses of antibiotics for 1 day (ceftriaxone 1 g every 12 hours and metronidazole 500 mg every 8 hours), or C: a 3-day course of antibiotics (ceftriaxone 1 g every 12 hours and metronidazole 500 mg every 8 hours) as the postoperative antibiotic regimen. Postoperative infective complication was the primary endpoint within the 10-day postoperative follow-up period. Results: A total of 291 patients (female 37.5%), were subjected to final analysis. This included 97 patients in each group. Twenty-six patients failed to return for wound assessment. The groups were comparable in baseline characteristics including age and gender. The Overall frequency of surgical site infection was 6.25%, with 8.2% in group A, 6.25% in group B and 5.2% in group C. The rate of postoperative surgical infection was not significantly different among all groups. There were no perioperative mortalities. No untreated control group could be included for ethical reasons. Conclusion: A combined preoperative single dose of metronidazole and ceftriaxone appears to be sufficient for the prevention of surgical site infections in patients with uncomplicated appendicitis. Keywords: Acute appendicitis, ceftriaxone, metronidazole, prophylactic antibiotic therapy

Single-dose antibiotic prophylaxis is effective enough in colorectal surgery

The aim of this study was to investigate the hypothesis that prevention of surgical site infection (SSI) is equally effective when patients receive single-dose (SD) or three-dose antibiotic prophylaxis with second-generation cephalosporin and metronidazole in elective colorectal surgery. Ninety-three patients were enrolled from May 2009 to November 2010. The SD group received only one preoperative prophylactic intravenous dose and the three-dose or multiple-dose (MD) group received one preoperative prophylactic and two additional post-operative doses of second-generation cephalosporin and metronidazole. The incidence of infectious complications (SSI of the incision site and organ/space) was compared in the two groups. The overall post-operative infection rate did not differ between the two groups (16.7% in the SD versus 13.3% in the MD, P = 0.653). The incidence of SSI of the incision site and organ/space also did not differ between the groups (6.3% (3/48) versus 4.4% (2/45), P = 0.700; 4.2% versus 6.7%, P = 0.593, respectively). The number of antibiotics administered was not an independent risk factor for SSIs in multivariable analysis. SD antibiotic prophylaxis with second-generation cephalosporin and metronidazole is equivalent to a three-dose prophylaxis for preventing SSI in elective colorectal surgery. But further study would be needed to clarify this because of the small number of participants.

Lack of benefit of preoperative antimicrobial prophylaxis in children with acute appendicitis: a prospective cohort study

Preoperative antimicrobial prophylaxis is widely used in pediatric patients undergoing appendectomy, but evidence showing a reduction of postoperative infectious complications is lacking. A prospective consecutive cohort study on changing from preoperative antimicrobial prophylaxis to no prophylaxis in children undergoing urgent appendectomy was undertaken. The impact of this change in management on postoperative infectious complications was evaluated by comparing the outcome in 100 patients receiving (group A) and a subsequent 100 patients not receiving prophylaxis (group B), which consisted of a preoperative single dose of intravenous metronidazole (10 mg/kg body weight). Histology confirmed acute appendicitis in 92 patients of group A and 95 patients of group B. In patients with histological simple appendicitis, postoperative infectious complications were noted in 2 (3.0 %) of 69 patients from group A and in none of 70 patients from group B, and in patients with histological perforated appendicitis in 5 (22 %) of 23 and 4 (16 %) of 25 patients from groups A and B, respectively. Postoperative infectious complications were more frequent (p < 0.05) in perforated than in simple appendicitis. These infectious complications included in simple appendicitis two wound infections in group A, and in perforated appendicitis four intraabdominal abscesses and one wound infection in group A and two intraabdominal abscesses and two wound infections in group B. Postoperative infectious complications were seen more often in patients with perforated appendicitis than in those with simple appendicitis. Preoperative antimicrobial prophylaxis with metronidazole did not reduce the rates of postoperative infectious complications.

PTU-101 Drugs used in the treatment of fistulae in Crohn's disease preserve mesenchymal stem cell survival

IntroductionMesenchymal stem cells (MSCs) may enhance tissue healing in fistulae of Crohn's disease, owing to their multilineage differentiation and immunosuppressive capacity. They are currently under investigation in clinical trials in...

Antifertility Potentials of Metronidazole in Male Wistar Rats

There is a growing concern about the decline in the quality of human sperm in recent years. Following reports by previous studies on the toxic effects of metronidazole on testicular functions, this study is designed to investigate further its direct effects on fertility potentials and that of the introduction of vitamin E and testosterone to metronidazole treated rats. A total of 105 adult male and 50 female Wistar rats weighing 170 +/- 10 g (70-90 day old) were used for the experiment. The rats were randomly divided into a control and experimental groups. There were four major groups with 5 subgroups consisting of 5 rats each. Varying doses of metronidazole were used depending on the experiment. Experiment 1; animals were fed with 15 mg kg(-1) of metronidazole, experiment 2, fed with 30 mg kg(-1) of metronidazole, experiment 3, administered with 200 mg kg(-1) of metronidazole and experiment 4, fed with 400 mg kg(-1) of metronidazole. Each experimental group has 5 sub-groups. A: control, B: group fed with the experimental dose, C: experimental dose with vitamin E, D: experimental dose with testosterone, E: fed with experimental dose, vitamin E and testosterone and sub-group F, a reversal group which was left for 8 weeks after cessation of treatment. Parameters assessed were sperm count/motility, hormonal assay, Fertility test for control and treated rats were also carried out. Results showed that metronidazole at the therapeutic dose of 15 mg kg(-1) did not have significant negative effect on the parameters assessed. At the dose of 200 and 400 mg kg(-1), there was reduction in testosterone and follicle stimulating hormone while on the other hand, luteinizing hormone was increased mostly with 400 mg kg(-1) of metronidazole treatment. Body weight was also found to be significantly reduced in rats treated with 200 and 400 mg kg(-1) of metronidazole. The results of this study indicate that metronidazole administration (200 or 400 mg kg(-1)), for 8 weeks, caused a harmful effect on fertility potentials in male rats.

Population Pharmacokinetics of Metronidazole Evaluated Using Scavenged Samples from Preterm Infants

Pharmacokinetic (PK) studies in preterm infants are rarely conducted due to the research challenges posed by this population. To overcome these challenges, minimal-risk methods such as scavenged sampling can be used to evaluate the PK of commonly used drugs in this population. We evaluated the population PK of metronidazole using targeted sparse sampling and scavenged samples from infants that were ≤ 32 weeks of gestational age at birth and <120 postnatal days. A 5-center study was performed. A population PK model using nonlinear mixed-effect modeling (NONMEM) was developed. Covariate effects were evaluated based on estimated precision and clinical significance. Using the individual Bayesian PK estimates from the final population PK model and the dosing regimen used for each subject, the proportion of subjects achieving the therapeutic target of trough concentrations >8 mg/liter was calculated. Monte Carlo simulations were performed to evaluate the adequacy of different dosing recommendations per gestational age group. Thirty-two preterm infants were enrolled: the median (range) gestational age at birth was 27 (22 to 32) weeks, postnatal age was 41 (0 to 97) days, postmenstrual age (PMA) was 32 (24 to 43) weeks, and weight was 1,495 (678 to 3,850) g. The final PK data set contained 116 samples; 104/116 (90%) were scavenged from discarded clinical specimens. Metronidazole population PK was best described by a 1-compartment model. The population mean clearance (CL; liter/h) was determined as 0.0397 × (weight/1.5) × (PMA/32)²·⁴⁹ using a volume of distribution (V) (liter) of 1.07 × (weight/1.5). The relative standard errors around parameter estimates ranged between 11% and 30%. On average, metronidazole concentrations in scavenged samples were 30% lower than those measured in scheduled blood draws. The majority of infants (>70%) met predefined pharmacodynamic efficacy targets. A new, simplified, postmenstrual-age-based dosing regimen is recommended for this population. Minimal-risk methods such as scavenged PK sampling provided meaningful information related to development of metronidazole PK models and dosing recommendations.

Curcumin Protects the Seminal Vesicles from Metronidazole‑induced Reduction of Secretion in Mice

Seminal vesicle secretion is important for increasing the stability of sperm chromatin, inhibition of the immune activity in the female reproductive tract and so on. Metronidazole (MTZ), a drug used for treatment of infections caused by anaerobic bacteria and protozoa, may have negative effects on the genital gland including the seminal vesicles. Curcumin exhibits antioxidant as well as anti-inflammatory properties. The present study aims to evaluate the negative effects of MTZ on the seminal vesicle structure and ameliorative effects of curcumin using stereological methods. Thirty balb/c mice were divided into six groups. The control group was received distilled water. The second and the third received higher doses of MTZ (500 mg/kg body weight/day) and MTZ (500 mg/kg/day) + 100 mg/kg/day curcumin, respectively. The fourth and the fifth were treated with lower doses of MTZ (165 mg/kg body weight/day) and MTZ (165 mg/kg body weight/day) + curcumin (100 mg/kg body weight/day), respectively. The sixth group received 100 mg/kg body weight/day curcumin. All the administrations were done by oral gavages for 14 days. After 30 days, seminal vesicles were removed. Stereological study of the seminal vesicle structure revealed a significant reduction in gland and vesicular fluid volume in MTZ-treated (higher or lower doses) animals. Curcumin protected the reduction of both parameters in therapeutic-dose treated animals. Metronidazole treatment does not induce structural changes in the seminal gland; however, it can have a significant impact on its secretion ability. Importantly, these deteriorations might be preventable by curcumin co-treatment.

A comparative study of oral single dose of metronidazole, tinidazole, secnidazole and ornidazole in bacterial vaginosis

Objective:To compare the cure rates of oral single dose of metronidazole (2 g), tinidazole (2 g), secnidazole (2 g), and ornidazole (1.5 g) in cases of bacterial vaginosis.Materials and Methods:This was a prospective, comparative, randomized clinical trial on 344 Indian women (86 women in each group) who attended a gynecology outpatient department with complaint of abnormal vaginal discharge or who had abnormal vaginal discharge on Gynecological examination but they did not complaint of it. For diagnosis and cure rate of bacterial vaginosis, Amsel's criteria were used. Statistical analysis was done by Chi-square test of proportions. The cure rate was compared considering metronidazole cure rate as gold standard.Results:At 1 week, the cure rate of tinidazole and ornidazole was 100% and at 4 weeks, it was 97.7% for both drugs (P<0.001). Secnidazole had cure rate of 80.2% at 4 weeks (P=NS). Metronidazole showed a cure rate of 77.9% at 4 weeks, which is the lowest of all four drugs.Conclusion:Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis.

A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on antiretroviral therapy.

BackgroundTrichomonas vaginalis has been associated with increased vaginal HIV-1 RNA shedding in antiretroviral therapy (ART)-naïve women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that T. vaginalis infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels.MethodsWe conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g). Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation.ResultsAmong 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI 4% - 30%]), 4 (13% [95% CI 4% - 30%]), and 5 (16% [95% confidence interval {CI} 5% - 34%]) women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7). In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45), p = 0.6).ConclusionDetection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection.

Metronidazole-induced Mania: Recurrence with Re-challenge

Purpose: Antimicrobial-induced mania, termed “antibiomania”, is exceptional and only reported in isolated case reports. Assigning causation of a rare adverse event to a particular therapy or condition is challenging. Definite cause-and-effect relationships are commonly absent. We report a case of metrondiazole-induced mania, reappearing with drug re-administration to alert physicians to a very rare adverse effect of a common medication. Case: A 57 year old man developed watery, non-bloody diarrhea a few days after taking levofloxacin for upper respiratory complaints. He was 3 years post-stem cell transplant for acute myelogenous leukemia and was being treated for graft versus host disease. Medications included prednisone 15 mg/day, tacrilomus, insulin, and long-term sulfamethoxazole- trimethoprim, fluconazole and acyclovir prophylaxis. Metronidazole was begun for symptoms. After 2 doses, he was noted by family, including a physician-daughter, to be hyperactive, expansive, talking excessively, grandiose - claiming special intuition about people with disordered thought processes. The next morning, his mood and thought processes had returned to normal baseline function. Because diarrhea persisted, he took another dose of metronidazole, but not levofloxacin. One hour later, disordered mood and thought reappeared. He went to the Emergency Department, where mania was diagnosed. He was treated with one dose of olanzapine and was normal the next day. Levofloxacin was restarted to finish a 5 day course and vancomycin was used with success for the diarrhea. There was no recurrence of the mania or diarrhea over a 2-year follow-up. Conclusion: Antibiomania is quite rare, most commonly attributed to clarithromycin, isoniazid and fluroquinolones. Less than 10 possible instances have incriminated metronidazole. We postulate that our patient had metronidazole-induced mania, perhaps potentiated by low-dose steroids and other antimicrobials. Further assessment difficulty exists because of single case reports of mania possibly induced by both acyclovir and sulfamethoxazole. Our case is highly unusual because documented recrudescence of symptoms occurred with drug re-administration; thus, this case may satisfy WHO criteria for definite rather than probable or possible causality, rare in single cases of putative drug reactions. Symptoms were of acute onset, temporally related to metronidazole use and self-limited with drug discontinuation. Prompt recurrence with re-challenge is striking. Antibiomania is rare, but should be considered with new onset of acute mania. Contribution of other medications is unclear and the mechanism is speculative.

Murine Models of Vaginal Trichomonad Infections

Trichomonas vaginalis and Tritrichomonas foetus cause common sexually transmitted infections in humans and cattle, respectively. Mouse models of trichomoniasis are important for pathogenic and therapeutic studies. Here, we compared murine genital infections with T. vaginalis and T. foetus. Persistent vaginal infection with T. foetus was established with 100 parasites but T. vaginalis infection required doses of 10(6), perhaps because of greater susceptibility to killing by mouse vaginal polymorphonuclear leukocytes. Infection with T. vaginalis persisted longest after combined treatment of mice with estrogen and dexamethasone, whereas infection was only short-lived when mice were given estrogen or dexamethasone alone, co-infected with Lactobacillus acidophilus, and/or pretreated with antibiotics. Infection rates were similar with metronidazole-resistant (MR) and metronidazole-sensitive (MS) T. vaginalis. High dose but not low dose metronidazole treatment controlled infection with MS better than MR T. vaginalis. These murine models will be valuable for investigating the pathogenesis and treatment of trichomoniasis.

MRSA bacteraemia after caesarean section wound infection: when screening is missed and things go wrong

A 30-year-old woman, originally from Romania, was admitted to the Delivery Suite of our unit as a transfer from a neighbouring trust with a history of preterm premature rupture of membranes (PPROM) and low lying placenta at 29 weeks. She had had one previous miscarriage at 8 weeks and one previous caesarean section for breech presentation at 40 weeks whilst resident in Romania. Otherwise she had no previous medical history of note. In the UK, she had previously been admitted twice to her booking hospital for vaginal bleeding at around 25 weeks, at which time she was given two doses of steroids. She then ruptured her membranes at 28 weeks and 5 days. An ultrasound scan (USS) showed oligohydramnios, anterior low lying placenta, normal growth (EFW 1,350 g) and breech presentation. She was transferred to our unit in view of the risk of early delivery. Although initially stable, the patient required a grade 2 emergency caesarean section at 29 weeks and 3 days for a rising CRP and suspected chorioamnionitis. The caesarean section was uneventful. She received our routine antibiotic prophylaxis with a single dose of cefuroxime (1.5 g) and metronidazole (500 mg) at the time of surgery and she recovered well, being discharged 2 days later. The baby was admitted to our Neonatal Unit for management of prematurity and suspected infection. The second day following discharge she attended our Accident and Emergency Department complaining of fever, generalised abdominal pain and distension. She had no urinary or bowel symptoms. On examination, her temperature was 37.4°C with a tachycardia of 121 bpm; the examination was otherwise unremarkable and the caesarean scar was clean and dry. Her blood tests showed a raised white cell count at 21 £ 10/L (reference range 3.5–9 £ 10/L), neutrophils 17.6 £ 10/L (reference range 1.3–5.4 £ 10/L) and CRP of 476 mg/L (reference range <5 mg/L). She was admitted to the maternity ward for close observation with an initial diagnosis of sepsis of unknown source and intravenous cefuroxime (1.5 g three times daily) and metronidazole (500 mg three times daily) were started, along with pain relief. The following day her temperature was 38.5°C with worsening abdominal distension and clinical examination revealed rebound tenderness. The CRP was found to be 573 mg/L. Blood cultures were taken. On day 2 post-admission, the patient continued to show no signs of improvement and developed a large area of erythema around the scar site up to the navel, with induration of the skin. A transabdominal U/S was performed by the Consultant in the ward. This showed a large collection (174 £ 100 £ 62 mm), likely to be intraabdominal in origin. Given the suspicion of the above, a CT scan of the abdomen and pelvis was ordered. Free Xuid was noted in the abdomen and pelvis along with generalised oedema of the intraabdominal fat consistent with secondary signs of sepsis. However, no collection was seen. J. Melendez (&) · A. Claxton · K. Erskine Homerton University Hospital, Homerton Row, London E9 6SR, UK e-mail: joan.melendez@gmail.com

Metronidazole-induced encephalopathy in a patient with liver cirrhosis

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

The effects of an investigational antimalarial agent, NIPRD-AM1 on the single dose pharmacokinetics of metronidazole in healthy human volunteers

The effect of concurrent administration of a novel phytomedicine, NIPRD-AM1 used for the treatment of malaria on the pharmacokinetics of metronidazole was investigated in healthy volunteers. The study was a completely randomized one, crossover involving administration of single dose metronidazole tablets (200 mg×2) concomitantly with NIPRD-AM1 capsules (250 mg×2) to 11 healthy volunteers. Blood samples were collected before and at pre-determined time intervals following administration of the drugs. Serum concentrations of the unchanged metronidazole were analyzed using a modified simple and sensitive reversed phase high performance liquid chromatography (HPLC) method. The method showed good precision for metronidazole with coefficient of variation less than 10%. The Pharmacokinetic parameters (AUC, Cmax, and Tmax) were generated using GraphPad Prism software version 2. The derived pharmacokinetic parameters (AUC, Cmax) following the administration of metronidazole alone and co-administration with NIPRD-AM1 were 76.12 μg/ml per hour, 7.94 μg/ml and 73.52 μg/ml per hour, 7.83 μg/ml, respectively. This differences were not statistically significant (P<0.05) and the relative bioavailability was found to be about 96%. The comparable relative bioavailabilty value obtained shows that there is little or no interaction between NIPRD-AM1 and metronidazole. The findings, therefore, showed that metronidazole can be administered with the phytomedicine NIPRD-AM1 without any significant effect on the pharmacokinetic profiles of metronidazole.

Laparoscopy-Assisted Single-Port Appendectomy in Children: Is the Postoperative Infectious Complication Rate Different?

In childhood, laparoscopy-assisted single-port appendectomy (SPA), including the advantages of open and laparoscopic surgery, is not widely used. However, there is debate whether the retrieval of the infected appendix via the umbilicus results in a higher infection rate compared with other laparoscopic or open techniques. The aim of the study was to determine the postoperative infection rate and possible risk factors for infection after SPA in children. For this retrospective study, case notes of all children (n = 262) who underwent SPA between August 2005 and December 2008 were reviewed. Those children in whom the preoperative ultrasonography revealed suspected perforation were excluded from SPA and subsequently underwent open surgery. SPA was performed using a 12-mm trocar with one 5-mm working channel, introduced through a sub-umbilical incision. After grasping the appendix with atraumatic forceps, the appendix was exteriorized through the umbilicus and dissected outside the abdominal cavity as in open surgery. Preoperatively, each patient received one dose of Metronidazole and Cefuroxime, and the umbilicus was cleaned in particular. Of the 262 children who underwent SPA, 146 were boys (55.7%) and 116 girls (44.3%). Median age at operation was 11.4 years (range, 1.1-15.9). Six obese (with a body mass index greater than the 95th percentile) children (2.3%) developed intra-abdominal abscess after perforated appendicitis that was treated with a course of antibiotics. One child required revisional surgery and drainage. The median length of antibiotic treatment was 3 days (range, 0-15). In our institution, SPA is the method of choice for appendectomy in children with acute appendicitis, in whom preoperative ultrasound does not reveal signs of perforation. The infection rate (2.7%) after SPA is not increased compared with other laparoscopic or open techniques. Overweight (body mass index greater than the 95th percentile) and perforated appendicitis seem to increase the risk of postoperative infectious complications.

Trichomonas vaginalis Prevalence, Incidence, Risk Factors and Antibiotic-Resistance in an Adolescent Population

To determine the prevalence and incidence of trichomoniasis, risk factors for infection, and the prevalence of metronidazole and tinidazole-resistant Trichomonas vaginalis (T. vaginalis) in female adolescents. Nonpregnant, HIV-seronegative, sexually active females (13-19 years) visiting an inner city public primary care clinic were tested for T. vaginalis by wet mount and culture, and interviewed about risk-taking behavior every 6 months. Infected patients were treated with a 2 g oral dose of metronidazole. Isolates from positive T. vaginalis cultures were tested for in vitro resistance to metronidazole and tinidazole. Among 467 study participants, 67 (14.4%; 95% confidence interval, 11.3-17.5) were diagnosed with trichomoniasis at first T. vaginalis culture. Significant risk factors for T. vaginalis infection were having an older sex partner and concurrent Neisseria gonorrhoeae infection. The incidence was 22.1 cases per 100 person-years. Among 42 participants who had a prevalent infection and returned for followup, 13 (31.0%) had at least 1 more episode of trichomoniasis. Resistance testing was completed for 78 isolates: 37 at first visit and 41 during follow-up. One (2.7%; 95% confidence interval, 0.07-14.2) of the 37 first-visit isolates was moderately resistant to metronidazole (minimal lethal concentration = 200 microg/mL). Of the 41 follow-up visit isolates, 1 was moderately resistant to metronidazole and 2 had borderline resistance (minimal lethal concentration = 50 microg/mL). The prevalence of tinidazole resistance was 0% (0.0%-9.5%). The study population had high prevalence and incidence of trichomoniasis. The prevalence of antibiotic-resistant T. vaginalis among female adolescents was low.