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Fulltext Pseudomembranous colitis: local experience with 3 cases

Goh KL, Peh SC, Wong NW

Med J Malaysia, 1986 Dec;41(4):347-51.
PMID: 3670159

Three cases of pseudomembranous colitis seen over the past one year in the Medical Unit, University Hospital, Kuala Lumpur, are reported.
The historical background, spectrum of clinical presentation, diagnosis and treatment of the disease are discussed. Early and wider use of sigmoidoscopy in patients with predisposing factors to pseudomembranous colitis have resulted in increased diagnosis of the condition.

Matched MeSH terms: Metronidazole/therapeutic use
Fulltext Resistance towards metronidazole in Blastocystis sp.: A pathogenic consequence

Rajamanikam A, Hooi HS, Kudva M, Samudi C, Kumar S

PLoS One, 2019;14(2):e0212542.
PMID: 30794628 DOI: 10.1371/journal.pone.0212542

Blastocsytis sp. is a protozoan parasite that has been linked to common gastrointestinal illnesses. Metronidazole, the first line therapy, was reported to show frequent inefficacy. Previously, Blastocystis sp. isolated from different population showed varying metronidazole resistance. However, the effect of metronidazole treatment on pathogenic potentials of Blastocystis sp. isolated from different populations, which is known to have different gut environment, is unclear. This study investigates the in vitro effect of metronidazole on the pathogenic potentials of Blastocystis sp. isolated from urban and orang asli individuals. Blastocystis sp. ST 3 isolated from symptomatic and asymptomatic individuals were treated with a range of metronidazole concentration. The parasites' growth characteristics, apoptotic rate, specific protease activity and the ability to proliferate cancer cells were analyzed upon treatment with 0.001 mg/l metronidazole. The study demonstrates that Blastocystis sp. isolates showed increase in the parasite numbers especially the amoebic forms (only in urban isolates) after treating with metronidazole at the concentration of 0.001 mg/ml. High number of cells in post-treated isolates coincided with increase of apoptosis. There was a significant increase in cysteine protease of Blastocystis sp. isolates upon treatment despite the initial predominance of serine protease in asymptomatic isolates. Metronidazole resistant Blastocystis sp. also showed significant increase in cancer cell proliferation. Resistance to metronidazole did not show significant different influence on the pathogenicity between Blastocystis sp. isolated from urban and orang asli individual. However, an increase in parasite numbers, higher amoebic forms, cysteine protease and ability to proliferate cancer cells implicates a pathogenic role. The study provides evidence for the first time, the effect of metronidazole towards enhancing pathogenic potentials in Blastocystis sp. when isolated from different gut environment. This necessitates the need for reassessment of metronidazole treatment modalities.

Matched MeSH terms: Metronidazole/pharmacology*
Metronidazole resistance among Helicobacter pylori strains in Malaysia

Parasakthi N, Goh KL

Am J Gastroenterol, 1992 Jun;87(6):808.
PMID: 1590330
Matched MeSH terms: Metronidazole/pharmacology*
Inhibition of choline kinase as an antiamoebic approach in Entamoeba histolytica infection

Teh ZH, Lim BH, See Too WC, Few LL

Trop Biomed, 2023 Dec 01;40(4):430-438.
PMID: 38308830 DOI: 10.47665/tb.40.4.008

Entamoeba histolytica is the parasite responsible for amoebiasis, which can result in amoebic colitis or amoebic liver abscess. Metronidazole has been the conventional treatment for intestinal amoebiasis, but concerns regarding resistance have emerged due to the identification of resistance pathways in E. histolytica. This study investigates a novel anti-amoebic approach targeting the CDP-choline pathway. Inhibition studies were conducted using potential choline kinase (CK) inhibitors to inhibit the EhCK enzyme, and RNA interference was employed to knock down the EhCK gene. Km and Vmax of purified EhCK and hCKa2 proteins were determined by pyruvate kinase-lactate dehydrogenase (PK-LDH) coupled assay. The IC50 values for EhCK and hCKa2 were determined with several commercial CK inhibitors. Selected inhibitors were incubated with E. histolytica trophozoites for 48 hours to determine the EC50 for each inhibitor. Silencing of gene encoding EhCK was carried out using duplex siRNA and the gene expression level was measured by real-time qPCR. Based on the IC50 values, three of the inhibitors, namely CK37, flavopiridol and H-89 were more potent against EhCK than hCKa2. Trophozoites growth inhibition showed that only HDTAB, H-89 and control drug metronidazole could penetrate and induce cell death after 48-hour incubation. siRNA concentration of 10 µg/mL was used for the transfection of positive control GAPDH, EhCK, and non-targeting GFP siRNAs. RNAi experiment concluded with positive control GAPDH downregulated by 99% while the level of EhCK mRNA was downregulated by 47%. In this study, potential inhibitors of EhCK and siRNA have been identified, paving the way for further refinement and testing to enhance their potency against EhCK while sparing hCK. The utilization of these specific inhibitors and siRNA targeting EhCK represents a novel approach to impede the growth of E. histolytica by disrupting its phospholipid synthesis pathway.

Matched MeSH terms: Metronidazole/pharmacology
Case Report: A Challenging Case of Tetanus Presenting with Headache

Rahim AIA, Azlan EAM, Rahman MR, Pathi NM, Ismail M, Sulaiman WAW

Am J Trop Med Hyg, 2023 Dec 06;109(6):1242-1244.
PMID: 37955309 DOI: 10.4269/ajtmh.23-0035

Tetanus is a life-threatening infectious neurological condition that has become uncommon due to large-scale immunization campaigns. We describe a rare instance of generalized tetanus presenting with a headache on a tropical island in Malaysia. A 43-year-old woman presenting with headaches and generalized body weakness, which progressed into trismus and neck stiffness. Her medical history indicated a wound on the sole of her foot caused by shattered glass in an unhygienic area, but no tetanus prophylaxis had been administered. The patient was subsequently given immunoglobulin, tetanus toxoid, metronidazole, and sedatives in the recommended dosages. Her neurological condition improved remarkably, but she suffered blood pressure fluctuations due to dysautonomia. She was successfully discharged with complete recovery after 6 months of follow-up. The case demonstrates the significance of appropriate identification and care of tetanus, as well as the lethal effects of untreated wounds in vulnerable patients.

Matched MeSH terms: Metronidazole/therapeutic use
Fulltext Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder diffraction

Aina A, Gupta M, Boukari Y, Morris A, Billa N, Doughty S

Saudi Pharm J, 2016 Mar;24(2):227-31.
PMID: 27013917 DOI: 10.1016/j.jsps.2015.03.015

The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide) (PLGA) scaffolds were probed using X-ray Powder Diffraction (XRPD). Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

Matched MeSH terms: Metronidazole
Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis

Pathak M, Turner M, Palmer C, Coombes AG

J Biomater Appl, 2014 Sep;29(3):354-63.
PMID: 24682036 DOI: 10.1177/0885328214528256

Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis.

Matched MeSH terms: Metronidazole/administration & dosage*; Metronidazole/therapeutic use
Single-dose and short course regimens of metronidazole in the treatment of amoebiasis in Malaysia

O'Holohan DR, Hugoe-Matthews J

Ann Trop Med Parasitol, 1972 Jun;66(2):181-6.
PMID: 4338870
Matched MeSH terms: Metronidazole/administration & dosage*; Metronidazole/therapeutic use
Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori

Chua EG, Debowski AW, Webberley KM, Peters F, Lamichhane B, Loke MF, et al.

Gastroenterol Rep (Oxf), 2019 Feb;7(1):42-49.
PMID: 30792865 DOI: 10.1093/gastro/goy048

Background: Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection. Hence, the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals. Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H. pylori. However, metronidazole resistance can also arise in H. pylori strains expressing functional RdxA protein, suggesting that there are other mechanisms that may confer resistance to this drug.
Methods: We performed whole-genome sequencing on 121 H. pylori clinical strains, among which 73 were metronidazole-resistant. Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed. Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H. pylori.
Results: Resistance due to RdxA truncation was identified in 34% of metronidazole-resistant strains. Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance. These sites included R16H/C in RdxA, D85N in the inner-membrane protein RclC (HP0565), V265I in a biotin carboxylase protein (HP0370) and A51V/T in a putative threonylcarbamoyl-AMP synthase (HP0918).
Conclusions: Our approach identified new potential mechanisms for metronidazole resistance in H. pylori that merit further investigation.

Matched MeSH terms: Metronidazole
Fulltext Higher Caspase-like activity in symptomatic isolates of Blastocystis spp

Balakrishnan DD, Kumar SG

Parasit Vectors, 2014;7:219.
PMID: 24886677 DOI: 10.1186/1756-3305-7-219

Biochemical evidence of a caspase-like execution pathway has been demonstrated in a variety of protozoan parasites, including Blastocystis spp. The distinct differences in the phenotypic characterization reported previously have prompted us to compare the rate of apoptosis in Blastocystis spp. isolated from individuals who were symptomatic and asymptomatic. In the current study, we analysed the caspase activation involved in PCD mediated by a cytotoxic drug, (metronidazole) in both symptomatic & asymptomatic isolates.

Matched MeSH terms: Metronidazole/pharmacology
Fulltext Lemierre syndrome

Lim AL, Pua KC

Med J Malaysia, 2012 Jun;67(3):340-1.
PMID: 23082433 MyJurnal

Lemierre syndrome is an uncommon disease which commonly arise from acute bacterial oropharyngeal infection. This disease was first described in 1900 by Courmont and Cade Lemierre. It is commonly caused by Fusobacterium necrophorum. Lemierre syndrome has been reported to be serious and potentially fatal in the preantibiotic era. It is characterized by an oropharyngeal infection leading to secondary septic thrombophlebitis of the internal jugular vein with embolization to the lungs and other organs. The incidence has become relatively rare at present and is usually only diagnosed when unsuspected culture results are available. We report a case of Lemierre syndrome which was recently diagnosed in our centre.

Matched MeSH terms: Metronidazole/therapeutic use
Fulltext Modified Field stain - rapid viability test for Trichomonas vaginalis

Afzan MY, Sivanandam S, Suresh K

J Appl Microbiol, 2012 Jan;112(1):132-7.
PMID: 22040369 DOI: 10.1111/j.1365-2672.2011.05185.x

We previously reported that Modified Field Stain (MF) can be used as a rapid stain for diagnosis. In the present study we extend the observation to include the stain as an alternative method to assess viability of the cells.

Matched MeSH terms: Metronidazole/pharmacology
Fulltext Clonorchiasis/opisthorchiasis in Malaysians case reports and review

Shekhar KC, Nazarina AR, Lee SH, Pathmanathan R

Med J Malaysia, 1995 Jun;50(2):182-6.
PMID: 7565193

Clonorchiasis and opisthorchiasis are snail-transmitted trematode infections. The disease is endemic in many parts of Asia. Local case reports have been predominantly in Chinese with a history of travel to endemic countries. Thus far, 20 cases of liver fluke infestation have been reported in this country. This report presents another two cases of clonorchiasis and a case of opisthorchiasis. We also briefly review pertinent aspects of the disease.

Matched MeSH terms: Metronidazole/therapeutic use
Amoebiasis of the cervix uteri

McClatchie S, Sambhi JS

Ann Trop Med Parasitol, 1971 Jun;65(2):207-10.
PMID: 4326239
Matched MeSH terms: Metronidazole/therapeutic use
First case report of paragonimiasis in a Malaysian man

Ponnampalavanar S, Kukreja A, Amir A, Mahmud R

Trop Biomed, 2020 Mar 01;37(1):24-28.
PMID: 33612715

Paragonimiasis is an infection caused by Paragonimus, a lung fluke and is acquired by eating raw or undercooked crustaceans containing the infective metacercariae. Herein, we report a case of paragonimiasis in a Malaysian man who presented with incidental findings from chest radiographs. Examination of his biopsied lung tissue and sputum specimen revealed Paragonimus sp. eggs, whereas stool examination showed the presence of Giardia cysts. Patient was succesfully treated with praziquantel and metronidazole respectively.

Matched MeSH terms: Metronidazole/therapeutic use
Fulltext Granular Formation during Apoptosis in Blastocystis sp. Exposed to Metronidazole (MTZ)

Dhurga DB, Suresh K, Tan TC

PLoS One, 2016;11(7):e0155390.
PMID: 27471855 DOI: 10.1371/journal.pone.0155390

The role and function of the granular life cycle stage in Blastocystis sp, remains uncertain despite suggestions being made that the granules are metabolic, reproductive and lipid in nature. This present study aims to understand granular formation by triggering apoptosis in Blastocystis sp. by treating them with metronidazole (MTZ). Blastocystis sp.cultures of 4 sub-types namely 1, 2, 3 and 5 when treated with 0.01 and 0.0001 mg/ml of metronidazole (MTZ) respectively showed many of the parasites to be both viable and apoptotic (VA). Treated subtype 3 isolates exhibited the highest number of granular forms i.e. 88% (p<0.001) (0.0001 mg/ml) and 69% (p<0.01) (0.01 mg/ml) respectively at the 72 h in in vitro culture compared to other subtypes. These VA forms showed distinct granules using acridine orange (AO) and 4',6-diamino-2-phenylindole (DAPI) staining with a mean per cell ranging from 5 in ST 5 to as high as 16 in ST 3. These forms showed intact mitochondria in both viable apoptotic (VA) and viable non-apoptotic (VNA) cells with a pattern of accumulation of lipid droplets corresponding to viable cells. Granular VA forms looked ultra-structurally different with prominent presence of mitochondria-like organelle (MLO) and a changed mitochondrial trans-membrane potential with thicker membrane and a highly convoluted inner membrane than the less dense non-viable apoptotic (NVA) cells. This suggests that granular formation during apoptosis is a self-regulatory mechanism to produce higher number of viable cells in response to treatment. This study directs the need to search novel chemotherapeutic approaches by incorporating these findings when developing drugs against the emerging Blastocystis sp. infections.

Matched MeSH terms: Metronidazole/pharmacology*
Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance

Bujanda L, Nyssen OP, Ramos J, Bordin DS, Tepes B, Perez-Aisa A, et al.

Am J Gastroenterol, 2024 Apr 01;119(4):646-654.
PMID: 37983769 DOI: 10.14309/ajg.0000000000002600

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance.
METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included.
RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results.
DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Matched MeSH terms: Metronidazole/pharmacology
Increase number of mitochondrion-like organelle in symptomatic Blastocystis subtype 3 due to metronidazole treatment

Raman K, Kumar S, Chye TT

Parasitol Res, 2016 Jan;115(1):391-6.
PMID: 26481491 DOI: 10.1007/s00436-015-4760-0

Blastocystis sp., an intestinal organism is known to cause diarrhea with metronidazole regarded as the first line of treatment despite reports of its resistance. The conflicting reports of variation in drug treatment have been ascribed to subtype differences. The present study evaluated in vitro responses due to metronidazole on ST3 isolated from three symptomatic and asymptomatic patients, respectively. Symptomatic isolates were obtained from clinical patients who showed symptoms such as diarrhea and abdominal bloating. Asymptomatic isolates from a stool survey carried out in a rural area. These patients had no other pathogens other than Blastocystis. Ultrastructural studies using transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed drug-treated ST3 from symptomatic patients were irregular and amoebic with surface showing high-convoluted folding when treated with metronidazole. These organisms had higher number of mitochondrion-like organelle (MLO) with prominent cristae. However, the drug-treated ST3 from asymptomatic persons remained spherical in shape. Asymptomatic ST3 showed increase in the size of its central body with the MLO located at the periphery.

Matched MeSH terms: Metronidazole/pharmacology*; Metronidazole/therapeutic use
Fulltext Significant reduction of brain cysts caused by Toxoplasma gondii after treatment with spiramycin coadministered with metronidazole in a mouse model of chronic toxoplasmosis

Chew WK, Segarra I, Ambu S, Mak JW

Antimicrob Agents Chemother, 2012 Apr;56(4):1762-8.
PMID: 22271863 DOI: 10.1128/AAC.05183-11

Toxoplasma gondii is a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and the in vitro reactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n = 9), which received vehicle only; (ii) a spiramycin-only group (n = 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n = 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n = 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n = 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC(0-∞)) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC(0-∞) values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P < 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reduced in vitro reactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction of T. gondii brain cysts, with potential clinical translatability for chronic toxoplasmosis treatment.

Matched MeSH terms: Metronidazole/pharmacokinetics; Metronidazole/therapeutic use*
Omeprazole 40 mg o.m. combined with amoxycillin alone or with amoxycillin and metronidazole in the eradication of Helicobacter pylori

Goh KL, Peh SC, Parasakthi N, Wong NW, Tan KK, Lo YL

Am J Gastroenterol, 1994 Oct;89(10):1789-92.
PMID: 7942668

OBJECTIVES: Our objectives were to determine the effect of dual therapy with omeprazole and amoxicillin and of triple therapy with omeprazole, amoxicillin, and metronidazole in the eradication of Helicobacter pylori (HP) and to study the long-term results of eradication in these patients.
METHODS: A prospective, randomized, controlled trial was performed. Patients who were recruited had unequivocal evidence of HP infection based on culture, histology, rapid urease test, and Gram's stain of a tissue smear. Eradication was defined as the absence of bacteria in all tests performed on both corpus and antral biopsies.
RESULTS: The infection was eradicated in 15 of 19 (78.9%) patients randomized to receive dual therapy and in 19 of 22 (86.4%) patients who received triple therapy. We followed the course of 30 patients in whom HP had been eradicated for a prolonged term (up to 12 months). All remained clear of HP. Twenty-five of 28 patients (89.3%) with duodenal ulcers in whom HP was successfully eradicated remained healed at 12 months. Fewer side effects were reported among patients who received the dual therapy.
CONCLUSIONS: Combination therapy with omeprazole and amoxicillin with or without metronidazole is effective in the eradication of HP. In particular, the dual therapy regimen with amoxicillin is not only effective but is also well tolerated by patients.

Matched MeSH terms: Metronidazole/administration & dosage*; Metronidazole/adverse effects

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