ArticlePDF Available

Therapeutic uses of metronidazole and its side effects: an update

February 2019
European Review for Medical and Pharmacological Sciences

Authors:

Jesus Carlos Ruvalcaba Ledezma

Autonomous University of Hidalgo State

Luilli Contreras

Ministry of Health, United Arab Emirates

OBJECTIVE: Metronidazole is an antibiotic widely used in different medical conditions such as trichomoniasis, amoebia-sis, and giardiasis among others. Its use has been associated with toxicity; however, it is not well characterized. In this review, we discuss the different therapeutic uses of metronidazole and its side effects in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information , original research articles, clinical trials , and reviews were collected from PubMed to know the state of the art of the different therapeutic uses of metronidazole and the reported side effects. RESULTS: Metronidazole was used by the first time in 1959, to treat an infection caused by Trichomonas vaginalis; subsequently, new therapeutic properties were discovered. Nowadays, Metronidazole is used to treat infections caused by Bacteroides, Fusobacteria and Clostridia, ro-sacea, oral and dental infections, bone and joint infections, gynecologic infections, endocarditis, septicemia, and respiratory tract infections. It also can be used to treat Crohn´s disease or even like prophylaxis, before surgical procedures. Metronidazole is well tolerated with mild to moderate side effects such as nausea, abdominal pain, and diarrhea. Nevertheless, serious neu-rotoxicity, optic neuropathy, peripheral neurop-athy, and encephalopathy have been reported in rare cases. Their genotoxic effects observed in animal models are controversial in humans. CONCLUSIONS: The therapeutic use of metro-nidazole had increased worldwide. Even though it is widely used, metronidazole has been associated with neurotoxicity and genotoxicity; however , its side effects are not well established. Conversely, its veterinary use is restricted in some countries because of its tumor association. Subsequently, further studies are needed to discover the secure use of metronidazole and describe new usages for this drug.

Content uploaded by Luilli Contreras

Content may be subject to copyright.

397

Abstract. – OBJECTIVE: Metronidazole is

an antibiotic widely used in different medical

conditions such as trichomoniasis, amoebia-

sis, and giardiasis among others. Its use has

been associated with toxicity; however, it is not

well characterized. In this review, we discuss

the different therapeutic uses of metronidazole

and its side effects in order to aid future inves-

tigation in this eld.

MATERIALS AND M ETHODS: Relevant infor-

mation, original research articles, clinical tri-

als, and reviews were collected from PubMed to

know the state of the art of the different thera-

peutic uses of metronidazole and the reported

side effects.

RE SU LT S : Metronidazole was used by the

rst time in 1959, to treat an infection caused by

Trichomonas vaginalis; subsequently, new ther-

apeutic properties were discovered. Nowadays,

Metronidazole is used to treat infections caused

by Bacteroides, Fusobacteria and Clostridia, ro-

sacea, oral and dental infections, bone and joint

infections, gynecologic infections, endocarditis,

septicemia, and respiratory tract infections. It al-

so can be used to treat Crohn´s disease or even

like prophylaxis, before surgical procedures.

Metronidazole is well tolerated with mild to mod-

erate side effects such as nausea, abdominal

pain, and diarrhea. Nevertheless, serious neu-

rotoxicity, optic neuropathy, peripheral neurop-

athy, and encephalopathy have been reported in

rare cases. Their genotoxic effects observed in

animal models are controversial in humans.

CONCLUSIONS: The therapeutic use of metro-

nidazole had increased worldwide. Even though

it is widely used, metronidazole has been asso-

ciated with neurotoxicity and genotoxicity; how-

ever, its side effects are not well established.

Conversely, its veterinary use is restricted in

some countries because of its tumor associa-

tion. Subsequently, further studies are needed

to discover the secure use of metronidazole and

describe new usages for this drug.

Key Words:

Metronidazole, Therapeutic uses, Side effects.

Introduction

Metronidazole is a synthetic antibiotic derivat-

ized from azomycin, a nitroimidazole produced

by the genera Actinobacteria and Proteobacteria.

In 1959, this compound was used for trichomonia-

sis treatment, an infection caused by the protozoan

Trichomonas vaginalis. Further, metronidazole has

been effective against dysentery and liver abscess

produced by the intestinal protozoan parasite, En-

tamoeba histolytica. It also was efcacious against

Giardia lamblia, another intestinal parasite that

causes malabsorption and epigastric pain1. Metroni-

dazole is available as orally, intravenously, vaginally

and rectally presentations, although the most clin-

ically used is the oral presentation. Its oral dosage

forms of 250 or 500 mg are rapidly absorbed and

distributed almost to the entire body. The liver is the

main organ responsible for metabolizing metronida-

zole, where this is hydroxylated, acetylated and or

conjugated with glucuronides. The metabolites are

nally excreted mainly by the kidneys2-4.

Metronidazole was introduced in 1959 for

trichomoniasis treatment; however, subsequent-

ly, new pharmacological properties were uncov-

ered5. Due to the high cost and long time needed

for research and development of novel therapeutic

molecules, exploring new uses of existing drugs

is a possible solution to treat infectious diseases6,7.

In this review, we recapitulate the current clini-

cal uses of metronidazole and discuss their side

effects.

Pharmacodynamics

The mechanism of action of metronidazole

has not been fully elucidated. However, its nitro

group reduction by anaerobic organisms appears

to be responsible for the cytotoxic and antimicro-

bial effects. The mechanism described for this

drug is summarized here:

European Review for Medical and Pharmacological Sciences 2019; 23: 397-401

A. HERNÁNDEZ CERUELOS, L.C. ROMERO-QUEZADA, J.C. RUVALCABA

LEDEZMA, L. LÓPEZ CONTRERAS

Área Académica de Medicina, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado

de Hidalgo, Circuito Ex Hacienda, Pachuca de Soto Hidalgo, México

Corresponding Author: Luilli López Contreras, Ph.D; e-mail: luilli_801@yahoo.com.mx

Therapeutic uses of metronidazole and its

side effects: an update

A. Hernández Ceruelos, L.C. Romero-Quezada, J.C. Ruvalcaba Ledezma, L. López Contreras

398

Metronidazole crosses the membrane of the cell

target by passive diffusion; then, its nitro group is

reduced to nitro radicals by ferredoxin or avodoxin.

The selectivity of metronidazole for anaerobic

or microaerophilic microorganisms is due to the

redox potential of their electron transport compo-

nents, which are responsible for nitro group re-

duction and generate toxic metabolites.

These metabolites such as N-(2-hydroxyethyl)

oxamic acid and acetamide can react with DNA

and form adducts with guanosine1,5.

Antibiotic and Antiparasitic Uses

Metronidazole is usually, very effective to treat

infections caused by anaerobic or microaerophilic

microorganisms, such as Trichomonas vaginalis,

Giardia lamblia, Entamoeba histolytica, Clostri-

dium difcile, Helicobacter pylori, among others1.

Amoebiasis

Amoebiasis is an infection caused by the protozo-

an Entamoeba histolytica that can result in amebic

colitis or amebic liver abscess. Optimal treatment,

usually effective for intestinal or hepatic infections

by E. histolytica, includes three daily oral doses of

750 mg of metronidazole for 5 or 10 days8-10.

Giardiasis

Giardia lamblia is the most common intesti-

nal parasite as the etiological agent of diarrheal

around the world; its treatment is based on 250

mg of the drug thrice daily for 5 to 7 days11.

Trichomoniasis

Trichomonas vaginalis is a protozoan parasite

responsible for one of the most sexually transmit-

ted diseases, and its management includes a 2 g

single dose of metronidazole. However, if the sin-

gle dose fails, the treatment can be administered

during 7 days12,13.

Bacterial Vaginosis

Metronidazole is useful to treat some bacterial

infections. 500 mg are administered orally twice

a day for a week. There is a second scheme con-

sisting of a single dose of 2 g of metronidazole,

mainly used to treat Gardnerella vaginalis. A gel

presentation of 0.75% metronidazole, administe-

red intravaginally twice a day for ve days is also

effective for bacterial vaginosis13,14.

Helicobacter Pylori

H. pylori causes peptic ulcers disease and it is

associated with stomach cancer. Metronidazole

in combination with bismuth and tetracycline for

two weeks is highly effective for H. pylori era-

dication. Dosage may vary from 200 to 500 mg

three or ve times daily. Metronidazole also has

been combined with bismuth and amoxicillin or

with acid suppression regimens15-17.

Clostridium Difficile

C. difcile colitis is a major cause of nosocomial

infections, causing morbidity and mortality in pa-

tients. Its treatment is based on oral metronidazole,

500 mg three times a day for 10-14 days18-2 0.

Anaerobic Infections

Metronidazole is also effective against anaero-

bic bacteria (for example, Bacteroides fragilis) in

combination with other antibiotics such as cefa-

zolin, cefuroxime, ceftriaxone, quinolone, cefta-

zidime, cefepime, carbapenems, piperacillin or

tazobactam depending on the infection type. Me-

tronidazole dosage varies in anaerobic infections;

however, 500 mg administered intravenously

every 8 h is the most common dose used13, 21.

Crohn’s Disease

Crohn’s disease is a chronic inammatory

bowel disease, which has been hypothesized, is

the result of an abnormal immune response to the

gut microbiome in susceptible subjects. Metroni-

dazole is used for the treatment of Crohn’s disease

and its effectiveness has been evaluated in several

clinical trials, suggesting that metronidazole has

therapeutic benets against the symptoms, such

as perianal discharge and pain. However, control-

led clinical trials are needed to establish the ef-

cacy of metronidazole for Crohn´s disease13,22.

Surgical Prophylaxis

Infections after surgical procedures contribu-

te to higher rates of mortality; however, a single

dose of 500 mg metronidazole reduces the risk of

postoperative anaerobic infections when is used

as a prophylactic treatment in appendicitis, but

also is used in prophylactic treatment in surgical

procedures for the colon, head, and neck13,23-24.

Rosacea

Rosacea is a cutaneous disease of uncertain

etiology characterized by ushing, erythema, pa-

pules, pustules and telangiectasia that affect the

cheeks, nose, eyes, chin and forehead26. There

are various treatments available for rosacea, but

topical metronidazole gel and azelaic acid appe-

ar to be effective and safe according to multiple

Therapeutic uses of metronidazole and its side effects: an update

399

clinical trials. 200 mg of metronidazole, admini-

stered orally twice a day for 12 weeks, is efca-

cious when tetracycline is not effective in rosacea

treatment2 5-27.

Adverse Effects of Metronidazole

Metronidazole is well tolerated with mild to mo-

derate side effects such as nausea, abdominal pain,

and diarrhea. Serious neurotoxicity, optic neuro-

pathy, peripheral neuropathy, and encephalopathy

have been reported in rare cases. Metronidazole

neurotoxicity is not fully elucidated. Rao and col-

leagues suggested that the free radicals damage

nerves, while Alston, proposed the formation of a

thiamine analog derived from the metronidazole

that may result in a nutrition deciency-like neu-

ropathy. On the other hand, Scholars proposed that

the union of metronidazole and its metabolites to

RNA provokes the inhibition of protein synthesis

and axonal degeneration of nerve ber13 ,28 -31.

Peripheral neuropathy is uncommon with short

term-use of metronidazole (4 weeks). Yet, the risk

of peripheral neuropathy increases when the dose

is higher than 42 g; however, this effect is reversi-

ble when discontinuing the drug therapy. Cerebel-

lar dysfunction, visual impairment, vestibulotoxi-

city, cochleotoxicity, ataxic gait, dysarthria, and

seizures also have been reported when metroni-

dazole is used32 -34.

Genotoxicity of Metronidazole

Metronidazole induces single and double DNA

strand breaks, especially in AT clusters. It also

forms adducts and GC-CG transversions. The

clastogenic effect is related to its hydroxylated

derivatives formed during its biotransformation

by cytochrome P45035-36 .

For the mouse micronucleus test and chromo-

somal aberration in bone marrow cells, metroni-

dazole showed a dose-dependent effect, inducing

cytogenetic damage in both models, but did not

show alteration in the rate of polychromatic/ nor-

mochromic erythrocytes as a measure of its cyto-

toxic effect37. In combination with miconazole,

metronidazole was tested for its teratogenic ef-

fect on mice, showing strong potentiation for the

production of skeletal defects when administered

together38.

Few studies have been done on human geno-

toxicity; metronidazole and its analogues did not

induce sister chromatid exchanges in human lym-

phocytes with or without S9 mixture, indicating

that the drug only induced DNA minor ruptures

while its cytotoxic effect was observed only un-

der metabolic activation39. Also, it has been re-

ported, that metronidazole can induce an increase

in chromosomal aberrations and chromatid and

isochromatic breaks in the cell of patients treated

with therapeutic doses of metronidazole40.

In a study41 where patients were treated with me-

tronidazole 4 hours before surgery to remove colon

tumors, a high concentration of the drug and its hy-

droxyl metabolite were found inside the lesion and

metastatic tumors, but not in healthy tissue.

In carcinogenesis, its role is controversial be-

cause metronidazole can induce genotoxic effects

in human cells in vitro and in vivo; however, it

has been established with a carcinogenic role in

mice and rats. According to the IARC (Interna-

tional Agency for Research on Cancer), there is

evidence to consider metronidazole as an animal

carcinogen, but insufcient evidence in humans42.

More studies are needed for clarifying the role of

metronidazole in human cancers.

Conclusions

Metronidazole was rst described in 1959 as a

therapeutic agent to treat Trichomonas vaginalis

infection; over time, metronidazole has been used

against Giardia lamblia, Entamoeba histolytica,

Clostridium difcile, Helicobacter pylori and ana-

erobic bacteria. Metronidazole is also used to tre-

at Crohn´s disease, rosacea, and as a prophylactic

after a surgical procedure. A lot of work must be

performed to elucidate new uses of metronidazo-

le; however, some more studies are also needed to

nd alternatives or variations of this drug because

of the increase of metronidazole-resistant micro-

organisms.

Metronidazole is widely used to treat a variety

of infections due to its high efcacy compared

with others drugs; however, their side effects

must be considered. Genotoxicity and neurotoxi-

city studies on humans should be done to clarify

the role of metronidazole in human health.

Conflict of Interest

The Authors declare that they have no conict of interest.

References

1) SamuelSon J. Why metronidazole is active against

both bacteria and parasites. Antimicrob Agents

Chemother 1999; 43: 1533-1541.

A. Hernández Ceruelos, L.C. Romero-Quezada, J.C. Ruvalcaba Ledezma, L. López Contreras

400

2) Berga n T, arnold e. Pharmacokinetics of metro-

nidazole in healthy volunteers after tablets and

suppositories. Chemother 1980; 26: 231-241.

3) HougHTon gW, SmiTH J, THorne PS, TemPl eTon r. The

pharmacokinetics of oral and intravenous metro-

nidazole in man. J Antimicrob Chemother 1979; 5:

621-623.

4) maTT ila J, männiS Tö PT, män Tyl ä r, ny kanem S, lam-

minSivu u. Comparative pharmacokinetics of me-

tronidazole and tinidazole as inuenced by ad-

ministration route. Antimicrob Agents Chemother

1983; 23: 721-725.

5) müller m. Mode of action of metronidazole on ae-

robic bacteria and protozoa. Surg 1983; 93: 165-

171.

6) CHong Cr, Sullivan dJ. New uses for old drugs.

Nat 2007; 448: 645-646.

7) WrigHT Pm, SeiPle iB, myerS ag. The evolving role

of chemical synthesis in antibacterial drug disco-

very. Angew Chem Int 2014; 53: 8840-8869.

8) BoBBi S, PriTT md, Clark g. Amebiasis. Mayo Clin

Proc 2008; 83: 1154-1160.

9) PeTri Wa Jr. Therapy of intestinal protozoa. Trends

Parasitol 2003; 19: 523-526.

10) maHa Jan rC, CHi Tka ra nl, vin ayak vk. In vitro com-

parative evaluation of tinidazole and metronida-

zole strains of Entamoeba histolytica. Indian J

Pathol Bacteriol 1974; 17: 226-228.

11) gard ner TB. Treatment of giardiasis. Clin Microbiol

Rev 2 001; 14: 114-128.

12) Sea rS Sd, o’Hare J. In vitro susceptibility of Tricho-

monas vaginalis to 50 antimicrobial agents. Anti-

microb Agents Chemother 1988; 32: 144-146.

13) Freeman Cd, kluT man ne, lamP kC. Metronidazole:

a therapeutic review and uptake. Drugs 1997; 54:

679-708.

14) JoneS Bm, geary i, al aWaTTega ma aB, kingHorn gr,

duerden Bi. In vitro and in vivo activity of metroni-

dazole against Gardnerella vaginalis, Bacteroides

ssp and Mobiluncus ssp. in bacterial vaginosis. J

Antimicrob Chemother 1985; 16: 189-197.

15) loPez-Brea m, ma rTin e, loPez-lavid C, Sa nz JC.

Susceptibility of Helicobacter pylori to metroni-

dazole. Eur J Clin Microbiol Infect Dis 1991; 10:

1082-1083.

16) moore ra, BeCkTHold B, Bryan le. Metronidazo-

le uptake in Helicobacter pylori. Can J Microbiol

19 95; 41: 74 6 -74 9.

17) Fra SSer ag, Sim r, Sankey ea, dHillon aP, Pounder

re. Effect of eradication on Helicobacter pylori on

gastric epithelial cell proliferation. Aliment Phar-

macol Ther 1994; 8: 167-173.

18) revele S kr, lee gC, Boyd nk, Frei Cr. The rise in

Clostridium difcile infection incidence among

hospitalized adults in the United States: 2001-

2010. Am J Infect Control 2014; 42: 1028-1032.

19) leSSa FC, BamBerg Wm, BeldavS zg. Burden of Clo-

stridium difcile infection in the United States. N

Engl J Med 2015; 372: 825-834.

20) ong gk, reidy TJ, Hu k md, lane Fr. Clostridium

difcile colitis: a clinical review. Am J Surg 2017;

213: 565 -571.

21) PankuCH ga, JaCoBS mr, aPPelB aum PC. Suscepti-

bilities of 428 gram-positive and gram-negative

anaerobic bacteria to Bay y3118 compared with

their susceptibilities to ciprooxacin, clindamycin,

metronidazole, piperacillin, piperacillin-tazobac-

tam and cefoxitin. Antimicrob Agents Chemother

1993; 37: 164 9-1654.

22) Pr anTera C, BerTo e, SCriBano ml, Fala SCo g. Use

of antibiotics in the treatment of active Crohn’s

disease: experience with metronidazole and ci-

prooxacin. Ital J Gastroenterol Hepatol 1998; 30:

602-606.

23) roHWedd er r, Bonadeo F, BenaTi m, oJea QuinTa-

na g, SCHleCker H, vaCC aro C. Single-dose oral

ciprooxacin plus parenteral metronidazole for

perioperative antibiotic prophylaxis in colorectal

surgery. Chemother 1993; 39: 218-224.

24) mor riS WT. Ceftriaxone is more effective than

gentamicin/metronidazole prophylaxis in redu-

cing wound and urinary tract infections after bo-

wel operations. Results of a controlled, randomi-

zed, blind clinical trial. Dis Colon Rectum 1993;

36: 826-833.

25) rainer Bm, kan S, CHienB al. Rosacea: epidemio-

logy, pathogenesis, and treatment. Dermatoloen-

docrinol 2018; 9: 1-10.

26) SaiH an em, BurTon Jl. A double-blind trial of me-

tronidazole versus oxytetracycline therapy for ro-

sacea. Br J Dermatol 1980; 102: 443-445.

27) Py e rJ, Bur Ton Jl. Treatment of rosacea by metro-

nidazole. Lancet 1976; 1: 1211-1212.

28) dingSdag Sa, HunTer n. Metronidazole: an update

on metabolism, structure-cytotoxicity and resi-

stance mechanisms. J Antimicrob Chemother

2017; 73: 265-279.

29) goolSBy Ta, Jakeman B, gayneS rP. Clinical relevan-

ce of metronidazole and peripheral neuropathy:

a systematic review of the literature. Int J Antimi-

crob Agents 2017; 51: 319-325.

30) rao dn, maSon rP. Generation of nitro radical an-

ions of some 5-nitrofurans, 2- and 5- nitroimidazo-

les by norepinephrine, dopamine, and serotonin.

A possible mechanism for neurotoxicity caused

by nitroheterocyclic drugs. J Biol Chem 1987; 262:

117 31 -117 3 6 .

31) al STon Ta, aBeleS rH. Enzymatic conversion of the

antibiotic metronidazole to an analog of thiamine.

Arch Biochem Biophys 1987; 257: 357-362.

32) eren F, aldan ma, dog an vB, gül g, SelCuk HH,

SoySal a. A case with reversible neurotoxicity in-

duced by metronidazole. Ideggyogy Sz 2017; 70:

429-432.

33) aHmed a, loeS dJ, BreSSler el. Reversible reso-

nance imaging in metronidazole-induced ence-

phalopathy. Neurol 1995; 45: 588-589.

34) gri ll mF, ram a km. Neurotoxic effects associated

with antibiotic use: management considerations.

Br J Clin Pharmacol 2011; 72: 381-393.

Therapeutic uses of metronidazole and its side effects: an update

401

35) Tala PaTra Sn, daSguP Ta S, guHa g, auddy m, muk-

HoPadHyay a. Therapeutic efcacies of Coriandrum

sativum aqueous extract against metronidazole-

induced genotoxicity in Channa punctatus peri-

pheral erythrocytes. Food Chem Toxicol 2010; 48:

3458-3461.

36) mudry md, CarBal lo m, la Bal de vinueS a m, gonza-

lez Cid m, larriPa i. Mutagenic bioassay of certain

pharmacological drugs: III. metronidazole (MTZ).

Mutat Res 1994; 305: 127-132.

37) daS roy l, giri S, SingH S, gi ri a. Effects of radiation

and vitamin C treatment on metronidazole geno-

toxicity in mice. Mutat Res 2013; 753: 65-71.

38) TiBoni gm, ma roTTa F, CaSTigliego aP. Teratogenic

effects in mouse fetuses subjected to the concur-

rent in uter o expos ure to miconazol e and metroni-

dazole. Reprod Toxicol 2008; 26: 254-261.

39) gomez-arroyo S, melCHor -CaSTro S, vill aloBoS-

PieTrini r, melendez-Ca margo e, Salgad o-za mora H,

CamPoS-aldr eTe m. Cytogenetic study of metroni-

dazole and three metronidazole analogues in cul-

tured human lymphocytes with and without meta-

bolic acti vation. Toxic ol In vitro 20 04; 18: 319-324.

40) elizondo g, gonSeBaTT me, Sal aza r am, lareS i, San-

Tiago P, Herrera J, Hong e, oSTroSky-Wegman P. Ge-

notoxic effects of metronidazole. Mutat Res 1996;

370: 75-80.

41) SadoWSk a a, kedr a B, CePoWiCz d, rodzieWiCz l, Fie-

doroWiCz a, ProkoPiuk S, milTyk W. Increased con-

centration of metronidazole and its hydroxymeta-

bolite in colon cancer in women. Pharmacol Rep

2012; 6 4: 12 76 -128 0.

42) BendeSky a, menéndez d, oSTroSky-WegmanB P. Is metro-

nidazole carcinogenic? Mut Res 2002; 511: 133-144.

Emergency contraceptive use of Metronidazole among University female students in Dodoma region of Tanzania: a descriptive cross-sectional study

Article

Full-text available

Aug 2023

Background Metronidazole is known for its therapeutic effect as antibacterial and anti-parasitic. However, its toxicity on the reproductive system remains unclear. Metronidazole use in rodents is associates with toxic effects on the reproductive system, including hormonal alterations, reduced number of fertile cells and reduced sites for implantation, size of the placental disc area, constituent elements of the labyrinth, and spongiotrophoblast layers. Its use at a therapeutic dose among humans has been associated with an increased risk of spontaneous abortion. The effects on the reproductive system in humans may result in misconceptions about contraceptive effects hence sexually active individuals like students who, for any reason, fail to access safe contraceptive services use any possible methods to protect them from conception. This study aims to investigate the unofficial (un-prescribed) use of Metronidazole as an emergency contraceptive and some of its associated factors. Methods This quantitative cross-sectional study involved 470 participants where stratified random sampling technique was used to obtain the sample from three educational institutions in the Dodoma Municipal, Dodoma region. Collected data were analyzed using SPSS version 25, descriptive statistical analysis was done to determine frequencies, percentages, and association, p < 0.05 was used to determine statistical significance. Further analysis using Multivariate binary logistic regression was done to determine the nature of the association between the study variables. Results The finding shows that 169(62.4%) use Metronidazole as an emergency contraceptive. Notably, 345(73.4%) stated that they had ever heard someone use Metronidazole for contraception, especially their peers. Furthermore, an increase in the year of study was significantly associated with reduced use of Metronidazole as an emergency contraceptive (B = [-0.45], p = [0.02]). Furthermore, an increase in age, studying in non-medical college/university, the experience of using contraceptive methods, and hearing someone ever used Metronidazole was found to be positively associated with its use as an emergency contraceptive, although not statistically significant. Conclusion Metronidazole was found to be used as an emergency contraceptive in high doses, different factors associated with its use, and reasons influencing its use. Further research may be done to explore the toxicological effect of high doses of Metronidazole as a contraception and compare the efficiency of Metronidazole over other emergency contraceptives.

Novel 4-nitroimidazole analogues: synthesis, in vitro biological evaluation, in silico studies, and molecular dynamics simulation

Article

Full-text available

Apr 2024
Z NATURFORSCH C

A new series of 4-nitroimidazole bearing aryl piperazines 7–16 , tetrazole 17 and 1,3,4-thiadiazole 18 derivatives was synthesized. All derivatives were screened for their anticancer activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI–H460, DND-41, HL-60, K562, and Z138). Compound 17 proved the most potent compound of the series inhibiting proliferation of most of the selected human cancer cell lines with IC 50 values in the low micromolar range. In addition, compound 11 exhibited IC 50 values ranging 8.60–64.0 μM against a selection of cancer cell lines. These findings suggest that derivative 17 can potentially be a new lead compound for further development of novel antiproliferative agents. Additionally, 17–18 were assessed for their antibacterial and antituberculosis activity. Derivatives 17 and 18 were the most potent compounds of this series against both Staphylococcus aureus strain Wichita and a methicillin resistant strain of S. aureus (MRSA), as well as against Mycobacterium tuberculosis strain mc ² 6230. The antiviral activity of 7–18 was also evaluated against diverse viruses, but no activity was detected. The docking study of compound 17 with putative protein targets in acute myeloid leukemia had been studied. Furthermore, the molecular dynamics simulation of 17 and 18 had been investigated.

MRI Findings and Topographic Distribution of Lesions in Metronidazole-Induced Encephalopathy

Article

Sep 2022

Purpose This study aims to describe the magnetic resonance imaging (MRI) of the brain of five patients diagnosed with metronidazole-induced encephalopathy (MIE). In addition, the aim of our study was to better define the topographic distribution of lesions in MIE. Methods We retrospectively evaluated MRI findings before and after drug cessation in five patients diagnosed with MIE at Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India. The main MRI signal changes and lesion locations were studied. Results Among the patients observed, the average age of the patients with MIE was 55 years (range: 30-70 years). Cerebellar dysfunction, mainly ataxia, and altered mental status were seen in the majority of cases. The most frequently involved sites were the dentate nucleus (cerebellum), brain stem, and corpus callosum (splenium). In diffusion-weighted imaging (DWI), most lesions did not show true restricted diffusion, except for a solitary corpus callosum lesion. Conclusion Although drug-related side effects are more common with long-term use of metronidazole, they may also occur with high doses for short durations. The dentate nucleus, the splenium in the corpus callosum, and the brain stem are the most affected structures. Apart from a solitary lesion of the corpus callosum, all identified lesions were reversible at follow-up MRI after discontinuation of metronidazole. The clinical presentation and characteristic MRI changes are highly specific and can be correlated to make a rapid and more accurate diagnosis of this potentially treatable condition. Prognosis is excellent if detected early.

Antibacterial and anti-Trichomonas Vaginalis effects of Rosa Damascena mill petal oil (a persian medicine product), aqueous and hydroalcoholic extracts

Article

Full-text available

Oct 2021

Background Oils in traditional medicine are important products and used routinely for therapeutic purposes. Rose oil (Rosa damascene Mill), a product of Persian medicine, is advised for the treatment of Infectious diseases related to the female genitourinary tract. In the present study, R. damascena petal oil, aqueous, and hydroalcoholic extracts were evaluated for their in vitro antibacterial and anti-Trichomonas vaginalis effects. Methods Anti-trichomonas activity evaluation of extracts and oil were assayed by the Homocytometery method. Their antibacterial effects against Escherichia coli, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and clinically isolated Group B Streptococcus were assayed by broth microdilution in 96-well plates. Results The MIC of hydroalcoholic and aqueous extracts ranged from 25-50 and 25-100 mg/ml, respectively. Rose oil at all administered doses failed to show any antibacterial activity. Conclusion All extracts and oil concentrations showed some degree of growth inhibition activity on T. vaginalis; however, hydroalcoholic extract was more efficient.

Helicobacter Pylori Eradication Therapy: Still a Challenge

Article

Full-text available

May 2021

Introduction Helicobacter pylori (H. pylori) infection is prevalent worldwide. H. pylori therapies' adverse effects can contribute to noncompliance among patients. This study aimed to assess the association between compliance to H. pylori eradication therapy and adverse effects using various drug regimens. Method We conducted an observational study from September 2017 to February 2020 in two tertiary care hospitals in patients with dyspeptic symptoms. H. Pylori detection was done by histopathological examination of gastric mucosa during upper gastrointestinal endoscopy or stool for H. pylori antigen. Patients with positive results were randomly assigned one of the nine different regimens consisting of a combination of proton pump inhibitors along with at least two antibiotics. The antibiotics used in different combinations were amoxicillin, clarithromycin, metronidazole, doxycycline, levofloxacin, and bismuth sulfate. The treatment groups received standard triple therapy with and without probiotics, sequential, concomitant, levofloxacin-based triple therapy, or sequential and bismuth-based quadruple treatments. All treatments were given for two weeks. At the end of the treatment period, patients were interviewed about completing treatment and any adverse effects they may have experienced during therapy. Data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.). Results A total of 250 patients were included in the study (62% males, 38% females) with a mean age of 37 years ± 13 years (range 12-84 years). Most patients completed the treatment regimen (80.4%), and 19.6% did not complete treatment because of adverse effects (p<0.005). The levofloxacin-based, concomitant, and standard triple regimen with probiotic treatments had the highest tolerance (≥85%). Common adverse effects were abdominal and epigastric pain (11%), alteration of taste, and diarrhea (6.5%). Conclusion H. pylori eradication therapy is always a challenge. Patient compliance to the treatment can only be ensured by medicines with fewer adverse effects. In our study, levofloxacin-based triple, concomitant, and standard triple regimens with probiotics are maximally acceptable treatments.

ЕФЕКТИВНІСТЬ РІЗНИХ СПОСОБІВ УВЕДЕННЯ АНТИБІОТИКІВ У КОМПЛЕКСНИХ СХЕМАХ ЛІКУВАННЯ КОРІВ ЗА ПІСЛЯОТЕЛЬНОГО ЕНДОМЕТРИТУ

Article

Mar 2025

О. О. Боднар

Післяотельні захворювання матки є серйозною проблемою молочних корів, оскільки вони можуть вражати значну частку поголів’я і мати серйозні наслідки щодо репродуктивної здатності самок і виробництва молока. Тому профілактику та своєчасне й ефективне лікування пуерперальних ускладнень необхідно розглядати як важливу ланку в системі заходів із ліквідації неплідності та яловості корів. У роботі наведені результати клініко-експериментальних досліджень із реґіонарного застосування антибіотиків і стимулюючих препаратів у комплексних схемах лікування корів за післяотельного ендометриту. В основу раціональної етіотропної та патогенетичної терапії було покладено реґіонарне введення лікарських препаратів: у внутрішню здухвинну артерію, паравагінально та внутрішньопіхвово. Були науково обґрунтовані, розроблені й апробовані комплексно-послідовні схеми лікування хворих на ендометрит корів. Клінічними дослідженнями встановлено, що комбіноване реґіонарне введення енрофлоксацину та метранідазолу в поєднанні із простагландином і утеротонічним препаратом виявилося більш ефективним методом лікування корів за гнійного ендометриту, ніж їх внутрішньом’язові ін’єкції. Ін’єктування антимікробних препаратів у магістральну судину, яка живить матку, дозволяє значною мірою сконцентрувати їхню фармакологічну дію в патологічному вогнищі. Водночас зросла запліднюваність корів, зменшилась частка рецидиву захворювання, скоротився термін лікування. Такий раціональний підхід до вдосконалення протоколів терапії дозволяє зменшити витрати на препарати, що забезпечує його оптимальні фармакоекономічні показники. Установлено, що поєднане введення «броестрофану» та «доцитолу» завдяки синергічності їх дії забезпечило активну евакуацію ексудату з матки та лютеоліз, що позитивно вплинуло на результати лікування та відновлення відтворної функції корів.

Frequency and Risk Factor Analysis for Metronidazole-Associated Neurologic Adverse Events

Article

Dec 2023

Little is known about the risk factors and frequency of metronidazole-associated neurological adverse events. To investigate the risk factors and frequency of metronidazole-associated neurological adverse events. This retrospective study contained two parts. First, we investigated metronidazole treatment-associated neurologic adverse events by performing a population-based cohort study using the Korea Adverse Event Reporting System (KAERS) database from January 2011 to December 2020. Second, we conducted a matched case-control study based on a retrospective cohort of patients treated with metronidazole between January 2006 and July 2021 at a tertiary hospital in South Korea. The data analysis was performed from August 2021 to April 2022. In the case-control study, case patients were defined as those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy during the study period with causal assessment based on the clinical diagnoses and findings from associated tests. In a ratio of 1:3, case patients were compared to a control group of patients prescribed metronidazole without neurologic adverse events matched for age and cumulative dose of metronidazole. Frequency and risk factors for metronidazole-associated neurological adverse events. Overall, 2,309 cases of neurologic adverse events were reported to the KAERS from 2011 to 2020, and the number of reported neurological adverse events showed an increasing trend. Further, 92,838 patients were prescribed metronidazole during the study period at the Severance Hospital; 54 patients were diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy, 40 with central and 28 with peripheral nervous system adverse events. Liver cirrhosis, chronic kidney disease, intravenous administration, and lower body weight were identified as risk factors for these adverse events. The number of reported metronidazole-associated neurological adverse events are increasing. Prolonged metronidazole treatment in patients with the aforementioned factors requires careful examination for neurological adverse events.

Antimicrobial evaluation of the Cynara cardunculus extract in Helicobacter pylori cells using mid‐infrared spectroscopy and chemometric methods

Article

Jun 2022

Aims: The treatment effectiveness of gastric diseases caused by the bacteria Helicobacter pylori is failing due to high resistance to some antibiotics. Consequently, it is urgent to develop an accurate methodology to screen new antimicrobial agents. Methods and results: A preliminary assay, using both therapeutic-based antibiotics (clarithromycin and metronidazole), was conducted to optimize experimental conditions in terms of the sensibility of the Fourier Transform Mid-Infrared spectroscopy (MIR-FTIR) associated with chemometric methods. Principal component analysis was applied to understand how the Cynara extract concentration acts differentially against H. pylori bacteria. The partial least squares model, characterized by R2 = 0.98, and root mean square error cross-validation, 0.011, was developed for the spectral regions (3600 - 2500 cm-1 , and 2000 - 698 cm-1 ). Conclusions: MIR-FTIR spectroscopy associated with chemometric methods can be considered a suitable approach to discover and analyze the promissory antimicrobial agents based on the biomolecular changes observed according to the Cynara extract. Significance and impact of the study: MIR-FTIR spectroscopy and chemometric methods allowed to register the biomolecular changes due to the potential antimicrobial drugs at reduced concentrations comparatively to the conventional assay based on an agar-dilution method, being considered a useful approach to develop a platform to discover new bioactive molecules, allowing to reduce time and costs related to the exploratory step.

In vitro effects of the 4-[(10H-phenothiazin-10-yl)methyl]-N-hydroxybenzamide on Giardia intestinalis trophozoites

Article

Full-text available

Apr 2022
ACTA TROP

Giardiasis is an intestinal disease caused by the parasite protozoan Giardia intestinalis. For more than five decades, the treatment of this disease has been based on compounds such as nitroimidazoles and benzimidazoles. The parasite's adverse effects and therapeutic failure are largely recognized. Therefore, it is necessary to develop new forms of chemotherapy treatment against giardiasis. Lysine deacetylases (KDACs), which remove an acetyl group from lysine residues in histone and non-histone proteins as tubulin, are found in the Giardia genome and can become an interesting option for giardiasis treatment. In the present study, we evaluated the effects of 4-[(10H-phenothiazin-10-yl)methyl]-N-hydroxybenzamide, a new class I/II KDAC inhibitor, on G. intestinalis growth, cytoskeleton, and ultrastructure organization. This compound decreased parasite proliferation and viability and displayed an IC50 value of 179 nM. Scanning electron microscopy revealed the presence of protrusions on the cell surface after treatment. In addition, the vacuoles containing concentric membranous lamella and glycogen granules were observed in treated trophozoites. The cell membrane appeared deformed just above these vacuoles. Alterations on the microtubular cytoskeleton of the parasite were not observed after drug exposure. The number of diving cells with incomplete cytokinesis increased after treatment, indicating that the compound can interfere in the late steps of cell division. Our results indicate that 4-[(10H-phenothiazin-10-yl)methyl]-N-hydroxybenzamide should be explored to develop new therapeutic compounds for treating giardiasis.

A sensitive electrochemical detection of metronidazole in synthetic serum and urine samples using low-cost screen-printed electrodes modified with reduced graphene oxide and C60

Article

Full-text available

Mar 2021

Monitoring the concentration of antibiotics in body fluids is essential to optimize the therapy and minimize the risk of bacteria resistance, which can be made with electrochemical sensors tailored with appropriate materials. In this paper, we report on sensors made with screen-printed carbon electrodes coated with fullerene (C60), reduced graphene oxide (rGO) and nafion (NF) (C60-rGO-NF/SPE) to determine the antibiotic metronidazole (MTZ). Under optimized conditions, the C60-rGO-NF/SPE sensor exhibited a linear response in square wave voltammetry for MTZ concentrations from 2.5 × 10⁻⁷ to 34 × 10⁻⁶ mol/L, with detection limit of 2.1 × 10⁻⁷ mol/L. This sensor was also capable of detecting MTZ in serum and urine, with recovery between 92 and 100% which are similar to the standard chromatographic method (HPLC-UV). Because the C60-rGO-NF/SPE sensor is amenable to mass production and allows for MTZ determination with simple principles of detection, it fulfills the requirements of therapeutic drug monitoring programs.

Metronidazole: an update on metabolism, structure–cytotoxicity and resistance mechanisms

Article

Full-text available

Oct 2017
J ANTIMICROB CHEMOTH

Metronidazole, a nitroimidazole, remains a front-line choice for treatment of infections related to inflammatory disorders of the gastrointestinal tract including colitis linked to Clostridium difficile. Despite >60 years of research, the metabolism of metronidazole and associated cytotoxicity is not definitively characterized. Nitroimidazoles are prodrugs that are reductively activated (the nitro group is reduced) under low oxygen tension, leading to imidazole fragmentation and cytotoxicity. It remains unclear if nitroimidazole reduction (activation) contributes to the cytotoxicity profile, or whether subsequent fragmentation of the imidazole ring and formed metabolites alone mediate cytotoxicity. A molecular mechanism underpinning high level (>256 mg/L) bacterial resistance to metronidazole also remains elusive. Considering the widespread use of metronidazole and other nitroimidazoles, this review was undertaken to emphasize the structure–cytotoxicity profile of the numerous metabolites of metronidazole in human and murine models and to examine conflicting reports regarding metabolite–DNA interactions. An alternative hypothesis, that DNA synthesis and repair of existing DNA is indirectly inhibited by metronidazole is proposed. Prokaryotic metabolism of metronidazole is detailed to discuss new resistance mechanisms. Additionally, the review contextualizes the history and current use of metronidazole, rates of metronidazole resistance including metronidazole MDR as well as the biosynthesis of azomycin, the natural precursor of metronidazole. Changes in the gastrointestinal microbiome and the host after metronidazole administration are also reviewed. Finally, novel nitroimidazoles and new antibiotic strategies are discussed.

Rosacea: Epidemiology, pathogenesis, and treatment

Article

Full-text available

Sep 2017

Rosacea is a chronic relapsing inflammatory skin disease with a high prevalence among adults of Northern European heritage with fair skin. Symptoms present in various combinations and severity, often fluctuating between periods of exacerbation and remission. Based on morphological characteristics, rosacea is generally classified into four major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Diverse environmental and endogenous factors have been shown to stimulate an augmented innate immune response and neurovascular dysregulation; however, rosacea's exact pathogenesis is still unclear. An evidence-based approach is essential in delineating differences between the many available treatments. Because of the diverse presentations of rosacea, approaches to treatment must be individualized based on the disease severity, quality-of-life implications, comorbidities, trigger factors, and the patient's commitment to therapy.

Burden of Clostridium difficile Infection in the United States

Article

Full-text available

Feb 2015
NEW ENGL J MED

The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥ 1 year of age). Cases were classified as community-associated or health care-associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care-associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care-associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001). C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).

Increased concentration of metronidazole and its hydroxy metabolite in colon cancer in women

Article

Full-text available

Sep 2012

Background: Metronidazole (MTZ) is indicated in the prevention of infections during surgical procedures. However, some data have shown that metronidazole has carcinogenic potential. Methods: In the present work, we determined concentrations of metronidazole and its hydroxy metabolite (MTZOH) in colorectal cancer patients. MTZ and MTZOH were measured in tumor tissue and surrounding healthy tissue by LC-ESI-MS-MS method. Results: We found different concentration of MTZ and MTZOH in colorectal cancer and healthy tissue. Interestingly, we noted a higher level of the above substances in women vs. men, both in healthy and cancerous gut. Conclusion: We suggest that women are more exposed to a potential carcinogenic effect of metronidazole than men.

Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature

Article

Sep 2017
INT J ANTIMICROB AG

The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy with the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks).

The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010

Article

Oct 2014
AM J INFECT CONTROL

Background Clostridium difficile infection (CDI) incidence is a growing concern. This study provides national estimates of CDI over 10 years and identifies trends in mortality and hospital length of stay (LOS) among hospitalized adults with CDI. Methods We conducted a retrospective analysis of the US National Hospital Discharge Surveys from 2001-2010. Eligible cases included adults aged ≥18 years discharged from a hospital with an ICD-9-CM diagnosis code for CDI (008.45). Data weights were used to derive national estimates. CDI incidence rates were depicted as CDI discharges per 1,000 total adult discharges. Results These data represent 2.2 million adult hospital discharges for CDI over the study period. CDI incidence increased from 4.5 CDI discharges per 1,000 total adult discharges in 2001 to 8.2 CDI discharges per 1,000 total adult discharges in 2010. The overall in-hospital mortality rate was 7.1% for the study period. Mortality increased slightly over the study period, from 6.6% in 2001 to 7.2% in 2010. Median hospital LOS was 8 days (interquartile range, 4-14 days), and remained stable over the study period. Conclusions The incidence of CDI among hospitalized adults in the United States nearly doubled from 2001-2010. Furthermore, there is little evidence of improvement in patient mortality or hospital LOS.

ChemInform Abstract: The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery

Article

Nov 2014
Angew Chem

The discovery and implementation of antibiotics in the early twentieth century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within pathogenic bacteria, made worse by widespread misuse of antibiotics. For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but economic factors have led to a subsidence of this effort, which places society on the precipice of a disaster. We believe that the strategic application of modern chemical synthesis to antibacterial drug discovery must play a critical role if a crisis of global proportions is to be averted.

Effects of radiation and vitamin C treatment On metronidazole genotoxicity in mice

Article

Feb 2013
MUTAT RES-FUND MOL M

The impact of exposure to low dose radiation (LDR) on human health is not clear. Besides, cross adaptation or sensitization with pharmaceutical agents may modify the risk of LDR. In the present study, we analyzed the interaction of radiation and metronidazole (MTZ) in inducing chromosome aberration (CA) and micronucleus (MN) in the bone marrow cells of Balb/C mice in vivo. Further, we evaluated the efficacy of vitamin C to reduce MTZ induced genotoxicity. We found that 10, 20 and 40mg/kg of MTZ induced dose dependent increase in the frequency of CA (r=0.9923, P<0.01) as well as MN (r=0.9823, P<0.05) in polychromatic erythrocytes. However, MTZ did not affect the ratio of polychromatic erythrocytes to normochromatic erythrocytes indicating lack of cytotoxicity. Supplementation with vitamin C prior to MTZ treatment significantly reduced the frequency of CA (P<0.001) as well as MN (P<0.001). Radiation (0.5Gy) exposure prior to MTZ treatment produced a less than additive (for CA) to additive (for MN) effects. However, radiation exposure following MTZ treatment produced additive (for CA) and synergistic (for MN) effects. Further, vitamin C pre-treatment also reduced the genotoxicity indices following the combined treatment of MTZ and radiation. Our findings suggest that MTZ may sensitize bone marrow cells to radiation exposure and enhances genotoxicity. We recommend more studies on the interaction of LDR and marketed pharmaceuticals to minimize possible harmful outcomes through appropriate precautionary measures.

Susceptibility ofHelicobacter pylori to metronidazole

Article

Dec 1991

Neurotoxic effects associated with antibiotic use: Management considerations

Article

Apr 2011
BRIT J CLIN PHARMACO

The clinical manifestations of antibiotic-induced neurotoxic effects, the underlying mechanisms and management strategies have been reviewed. PubMed and OVID searches (January 1960-June 2010) were conducted using search terms such as antibiotics, side effects, neurotoxicity and encephalopathy which yielded approximately 300 articles. All relevant case reports, case series, letters and retrospective reviews describing neurotoxic effects and those discussing mechanisms of neurotoxicity were included. Antibiotic-induced neurotoxic side effects can have a myriad of neurologic presentations. Patients with prior central nervous system (CNS) disease, renal insufficiency and advanced age may be particularly vulnerable. Treatment consists of discontinuation of the offending agent, use of antiepileptic drugs in the case of seizures or status epilepticus and haemodialysis in certain cases. The risk of CNS toxicity may be reduced via dosage adjustments in high risk populations. Awareness of the potential neurotoxic clinical manifestations of various antibiotics and high degree of vigilance in critically ill patients is essential in identifying a potentially serious, though reversible complications of antibiotic therapy particularly with the advent of newer antimicrobial agents.

Therapeutic uses of metronidazole and its side effects: an update

Abstract

Recommended publications

Therapeutic uses of metronidazole and its side effects: An update

Isolated involvement of corpus callosum in metronidazole-induced encephalopathy with concomitant per...

The effect of metronidazole on the histology of the cerebellum and pituitary gland in female wistar...

Neurotoxicity induced by metronidazole