WordNet

derivative of nitrofuran used as an antibacterial medicine (trade name Macrodantin) effective against a broad range of Gram-positive and Gram-negative bacteria; used to treat infections of the urinary tract (同)Macrodantin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/08 12:57:55」(JST)

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Nitrofurantoin is an antibiotic which is marketed under the following brand names; Niftran, Furadantin, Furabid, Macrobid, Macrodantin, Nitrofur Mac, Nitro Macro, Nifty-SR, Martifur-MR, Uro-Tablinen or Nifuretten (in Germany), Martifur-100 (in India), Urantoin, Nifuran (in Macedonia) and Uvamin (in Middle East). It is usually used in treating urinary tract infection. It is often used against E. coli.

Use[edit]

Resistance to other antibiotics has led to increased interest in this agent.^[2]

It is sometimes described as being appropriate to use in pregnant patients^[3] (along with other agents such as sulfisoxazole or cephalexin).^[4] This is in contrast to agents such as trimethoprim and ciprofloxacin which may not be appropriate for pregnant women.

Pharmacology[edit]

Organisms are said to be susceptible to nitrofurantoin if their minimum inhibitory concentration (MIC) is 32 μg/mL or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis although the patient information leaflet states it is used to prevent and treat infections of the bladder, kidney and other parts of the urinary tract.

At the concentrations achieved in urine (>100 microgm/mL), nitrofurantoin is bacteriocidal. It is bacteriostatic against most susceptible organisms at concentrations less than 32 micrograms per milliliter.^[5]

Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided.

Resistance to nitrofurantoin may be chromosomal or plasmid mediated and involves inhibition of nitrofuran reductase.^[6] Acquired resistance in E. coli continues to be rare.

Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60 mL/min or less. However a retrospective chart review may suggest that nitrofurantoin is not contraindicated in this population.^[7]

Mechanism[edit]

The mechanism of action of nitrofurantoin is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive.^[5] This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA,^[8] respiration, pyruvate metabolism and other macromolecules within the cell. Nitrofurantoin exerts greater effects on bacterial cells than mammalian cells because bacterial cells activate the drug more rapidly.^[5] It is not known which of the actions of nitrofurantoin is primarily responsible for its bactericidal activity.

Clinical uses[edit]

Adult doses of nitrofurantoin for a urinary tract infections can be 100mg two times daily, or 50mg four times daily for seven days. For less severe cases of UTIs, the dosage may be prescribed as shortened to 3 days. The pediatric dose is 5–7 mg/kg/day in four divided doses.^[9] or when in 25 mg/5ml oral suspension then pediatric dose is 3 mg/kg/day in four divided doses.^[10] Nitrofurantoin should be taken with food, as this improves the absorption of the drug by 45%.

Nitrofurantoin is only clinically proven for use against E. coli or Staph. saprophyticus. It may also have in vitro activity against:

Coagulase negative staphylococci
Enterococcus faecalis,
Staphylococcus aureus,
Streptococcus agalactiae,
Citrobacter species, and
Klebsiella species,

and is used in the treatment of infections caused by these organisms. Many or all strains of the following are resistant to nitrofurantoin:

Enterobacter species^[5]
Klebsiella species^[5]
Acinetobacter species,
Morganella species,
Proteus species,^[5]
Providentia species,
Serratia species,
Pseudomonas species.^[5]

Nitrofurantoin must never be used to treat pyelonephritis,^[11] prostatitis,^[5] renal abscess, and pyeloempyema because of extremely poor tissue penetration and low blood levels, although the patient information leaflet states it is used to prevent and treat infections of the bladder, kidney and other parts of the urinary tract. Urinary catheter infections may be treated with nitrofurantoin if there are no systemic features; the catheter must be changed after 48 hours of antibiotics and treatment is ineffective if the catheter is not replaced or removed.

Adverse effects[edit]

The most common side effects with nitrofurantoin are nausea, vomiting, and diarrhea; less common reactions include fever, chills, and various other hypersensitivity reactions.^[5] It can also cause pulmonary fibrosis^[12] and Drug-induced autoimmune hepatitis.^[13] All these side effects are much more common in the elderly hence this antibiotic is strongly not recommended for older adults according to 2012 AGS Beers Criteria.

Patients should be informed that nitrofurantoin colours urine brown;^[5] this is completely harmless.

Neonates (babies up to the age of one month) have immature enzyme systems in their red blood cells (glutathione instability) and nitrofurantoin must therefore not be used because it can cause haemolytic anaemia. For the same reason, nitrofurantoin should not be given to pregnant women after 38 weeks of pregnancy, or who are about to give birth.

Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60mL/min) due to systemic accumulation and subtherapeutic levels reached in the urinary tract.^[5] However, a retrospective chart review may suggest that nitrofurantoin is not contraindicated in this population.^[7]

Use in animal feed - Unwanted in human food[edit]

Residues from the breakdown of nitrofuran veterinary antibiotics, including nitrofurantoin, have been found in chicken in Vietnam, China, Brazil, and Thailand.^[14] The European Union banned the use of nitrofurans in food producing animals by classifying it in ANNEX IV (list of pharmacologically active substances for which no maximum residue limits can be fixed) of the Council Regulation 2377/90. The Food and Drug Administration (FDA) of the United States has prohibited furaltadone since February 1985 and withdrew the approval for the other nitrofuran drugs (except some topical uses) in January 1992. The topical use of furazolidone and nitrofurazone was prohibited in 2002. Australia prohibited the use of nitrofurans in food production in 1992. Japan did not allocate MRLs for nitrofurans leading to the implementation of a "zero tolerance or no residue standard". In Thailand, the Ministry of Health issued in 2001 Proclamation No. 231 MRL of veterinary drug in food which did not allocate MRL for nitrofurans. The Ministry of Agriculture and Cooperatives had already prohibited importation and use of furazolidone and nitrofurazone in animal feed in 1999 which was extended to all nitrofurans in 2002. Several metabolites of nitrofurans, such as furazolidone, furaltadone and nitrofurazone cause cancer or genetic damage in rats.^[14]

Precautions[edit]

Nitrofurantoin should be taken with food to improve its absorption. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of risk of intravascular hemolysis resulting in anemia.

Trade names[edit]

Furadantin (U.S., UK)
Macrobid (long acting preparation for twice daily dosing available in U.S., Canada, and UK)
Macrodantin (U.S., UK)
Uro-Tablinen, Furadantin, Nifuretten, Nifurantin, Urodin (GER, A, CH)
Macrodantina (Mexico)
Furatin, Niftran(by Ranbaxy), Niftas(by Intas Pharmaceuticals) (India)
Furanit
Uvamin (Middle East)

References[edit]

^ Parrott, E. L.; Matheson Jr, L. E. (1977). "Rectal absorption of nitrofurantoin". Journal of Pharmaceutical Sciences 66 (7): 955–958. doi:10.1002/jps.2600660713. PMID 886458. edit
^ Garau J (January 2008). "Other antimicrobials of interest in the era of extended-spectrum beta-lactamases: fosfomycin, nitrofurantoin and tigecycline". Clin. Microbiol. Infect. 14 Suppl 1: 198–202. doi:10.1111/j.1469-0691.2007.01852.x. PMID 18154548.
^ Lee M, Bozzo P, Einarson A, Koren G (June 2008). "Urinary tract infections in pregnancy". Can Fam Physician 54 (6): 853–4. PMC 2426978. PMID 18556490.
^ "Urinary Tract Infections During Pregnancy - February 1, 2000 - American Academy of Family Physicians".
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Gilman, eds.: Joel G. Hardman, Lee E. Limbird ; consul. ed.: Alfred Goodman (2002). Goodman & Gilman's the Pharmacological Basis of Therapeutics. (12th ed. ed.). New York: McGraw-Hill. pp. Chapter 52. ISBN 0071354697.
^ McCalla DR, Kaiser C, Green MHL (1978). "Genetics of nitrofurazone resistance in Escherichia coli". J Bacteriol 133: 10–16.
^ ^a ^b Bains A, Buna D, Hoag NA (2009). "A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment". Canadian Pharmacists Journal 142 (5): 248–252. doi:10.3821/1913-701X-142.5.248.
^ Tu Y, McCalla DR (1975). "Effect of activated nitrofurans on DNA,". Biochem Biophys Acta 402: 142–49.
^ "Complementary and Alternative Medicine Index (CAM)". Umm.edu. Retrieved 2012-05-29.
^ "Furadantin 25mg/5ml Oral Suspension OR Nitrofurantoin 25mg/5ml Oral Suspension - Summary of Product Characteristics (SPC) - (eMC)". Medicines.org.uk. 2010-11-18. Retrieved 2012-05-29.
^ Richards WA, et al. (1955). "Nitrofurantoin: Clinical and laboratory studies in urinary tract infections". Arch Intern Med 96 (4): 437–50. doi:10.1001/archinte.1955.00250150011001. PMID 13257939.
^ Goemaere NN, Grijm K, van Hal PT, den Bakker MA (2008). "Nitrofurantoin-induced pulmonary fibrosis: a case report". J Med Case Reports 2: 169. doi:10.1186/1752-1947-2-169. PMC 2408600. PMID 18495029.
^ Björnsson, E; Talwalkar, J; Treeprasertsuk, S; Kamath, PS; Takahashi, N; Sanderson, S; Neuhauser, M; Lindor, K (June 2010). "Drug-induced autoimmune hepatitis: clinical characteristics and prognosis.". Hepatology (Baltimore, Md.) 51 (6): 2040–8. doi:10.1002/hep.23588. PMID 20512992. Retrieved 7 September 2012.
^ ^a ^b FAO: Nitrofuran study

External links[edit]

drugs.com for Macrodantin
Meds-Help.com for nitrofurantoin side effects, interactions and information
RxList for Macrobid (Nitrofurantoin)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. ニトロフラントイン誘発性肺損傷 nitrofurantoin induced pulmonary injury
2. 妊娠中の尿路感染症および無症候性細菌尿 urinary tract infections and asymptomatic bacteriuria in pregnancy
3. 急性膀胱炎：2歳以上の小児および思春期におけるマネージメントおよび予後 acute cystitis management and prognosis in children older than two years and adolescents
4. 女性における急性単純性膀胱炎および腎盂腎炎 acute uncomplicated cystitis and pyelonephritis in women
5. 小児における尿路感染症：長期マネージメントおよび予防 urinary tract infections in children long term management and prevention

English Journal

Cystitis: antibiotic prescribing, consultation, attitudes and opinions.

Willems CS1, van den Broek D'Obrenan J, Numans ME, Verheij TJ, van der Velden AW.Author information 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.AbstractBACKGROUND: Despite stable overall antibiotic use between 2007 and 2011 in The Netherlands, use of nitrofurantoin and trimethoprim increased by 32%. The background of this increased antibiotic use against uropathogens is unknown.
Family practice.Fam Pract.2014 Apr;31(2):149-55. doi: 10.1093/fampra/cmt077. Epub 2013 Dec 7.
BACKGROUND: Despite stable overall antibiotic use between 2007 and 2011 in The Netherlands, use of nitrofurantoin and trimethoprim increased by 32%. The background of this increased antibiotic use against uropathogens is unknown.OBJECTIVES: To determine whether increased use of urinary tract infecti
PMID 24317602

Can a simple urinalysis predict the causative agent and the antibiotic sensitivities?

Waseem M1, Chen J, Paudel G, Sharma N, Castillo M, Ain Y, Leber M.Author information 1From the Departments of *Emergency Medicine and †Pediatrics, Lincoln Medical & Mental Health Center, Bronx, NY; and ‡St George's University, Grenada, West Indies.AbstractOBJECTIVES: The objective of this study was (1) to determine the reliability of urinalysis (UA) for predicting urinary tract infection (UTI) in febrile children, (2) to determine whether UA findings can predict Escherichia coli versus non-E. coli urinary tract infection, and (3) to determine if empiric antibiotics should be selected based on E. coli versus non-E. coli infection predictions.
Pediatric emergency care.Pediatr Emerg Care.2014 Apr;30(4):244-7. doi: 10.1097/PEC.0000000000000105.
OBJECTIVES: The objective of this study was (1) to determine the reliability of urinalysis (UA) for predicting urinary tract infection (UTI) in febrile children, (2) to determine whether UA findings can predict Escherichia coli versus non-E. coli urinary tract infection, and (3) to determine if empi
PMID 24651215

Prevalence and antimicrobial resistance among Gram-negative pathogens in Saudi Arabia.

Yezli S, Shibl AM, Livermore DM, Memish ZA.AbstractAntimicrobial resistance among Gram-negative bacteria is a worldwide problem, including in the Kingdom of Saudi Arabia, with major concerns regarding Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. Although over half of the isolates of P. aeruginosa remain susceptible to carbapenems, quinolones, and aminoglycosides in most reports from Saudi Arabia, resistance is on increase, with a worrying high prevalence of multidrug resistance. Ceftazidime, ciprofloxacin, and aminoglycosides remain active against A. baumannii isolates in some studies from the Kingdom, but recent data suggest increased resistance. Carbapenems are now the treatment of choice for Acinetobacter infections but their activity too is being eroded. Among Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. are the most clinically relevant species. Rates of extended-spectrum beta-lactamase (ESBL) production by these species vary among studies but are generally high in Saudi Arabia, with many ESBL-producing isolates multiresistant to other agents, except carbapenems and nitrofurantoin. A similar pattern is seen for Klebsiella, although with more resistance to quinolones, aminoglycosides, and to nitrofurantoin than in E. coli. Enterobacter is commonly resistant to penicillins, monobactams, and cephalosporins but mostly susceptible to carbapenems. Carbapenemases are beginning to emerge in Enterobacteriaceae.
Journal of chemotherapy (Florence, Italy).J Chemother.2014 Mar 27:1973947814Y0000000185. [Epub ahead of print]
Antimicrobial resistance among Gram-negative bacteria is a worldwide problem, including in the Kingdom of Saudi Arabia, with major concerns regarding Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. Although over half of the isolates of P. aeruginosa remain susceptible to car
PMID 24669827

Changing epidemiology of infections due to extended spectrum beta-lactamase producing bacteria.

Kassakian SZ, Mermel LA.AbstractBACKGROUND: Community-associated infections caused by extended-spectrum beta-lactamase (ESBL) producing bacteria are a growing concern.
Antimicrobial resistance and infection control.Antimicrob Resist Infect Control.2014 Mar 25;3(1):9. [Epub ahead of print]
BACKGROUND: Community-associated infections caused by extended-spectrum beta-lactamase (ESBL) producing bacteria are a growing concern.METHODS: Retrospective cohort study of clinical infections due to ESBL-producing bacteria requiring admission from 2006-2011 at a tertiary care academic medical cent
PMID 24666610

Japanese Journal

A TLC bioautographic assay for the detection of nitrofurantoin resistance reversal compound

SHAHVERDI Ahmad R.,ABDOLPOUR Farid,MONSEF-ESFAHANI Hamid R.,FARSAM Hasan
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 850(1), 528-530, 2007-05-01
NAID 10025798908

Phenolic Constituents of Galla Rhois with Hepatoprotective Effects on Tacrine- and Nitrofurantoin-Induced Cytotoxicity in Hep G2 Cells(Pharmacognosy)

AN Ren Bo,OH Hyuncheol,KIM Youn Chul
Biological & pharmaceutical bulletin 28(11), 2155-2157, 2005-11-01
… values of 70.39±5.4 and 29.51±0.7μM, respectively, against tacrine-induced cytotoxicity, and 150.9±6.4 and 23.81±0.5μM, respectively, against nitrofurantoin-induced cytotoxicity in Hep G2 cells. …
NAID 10016783881

台湾におけるサルモネラとカンピロバクターによるアヒルの汚染とそれら細菌の薬剤感受性(公衆衛生学)

TSAI Hsiang-Jung,HSIANG Pi-Hung
The journal of veterinary medical science 67(1), 7-12, 2005-01-25
… 分離率は,他の週齢のアヒルに比して有意に低かった(P<0.05).ディスク法で薬剤感受性を試験した結果,サルモネラの菌株は全てamikacin,amoxicillin/clavulanic acid,ceftraxone,cephalothin,ciprofloxacin,norfloxacinおよびpolymyxin Bに対して感受性を示した.カンピロバクターの菌株は,amoxicillin,florfenicol,flumequine,josamicin/trimethoprim,nalidixic acid,nitrofurantoin,norfloxacin,ofloxacin,polymyxin B,sulfamethoxazole/trimethoprimおよびtetracvclineに対して著しく高い耐性を示した. …
NAID 110003963665

Related Pictures

★リンクテーブル★

リンク元	「ニトロフラントイン」

「ニトロフラントイン」

Nitrofurantoin
Systematic (IUPAC) name
	(E)-1-[(5-nitro-2-furyl)methylideneamino]imidazolidine-2,4-dione
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682291
Pregnancy cat.	B
Legal status	Rx, PoM
Routes	oral, rectal
Pharmacokinetic data
Bioavailability	40%
Metabolism	liver (75%)
Half-life	20 minutes
Excretion	urine and bile
Identifiers
CAS number	67-20-9
ATC code	J01XE01
PubChem	CID 6604200
DrugBank	DB00698
ChemSpider	5036498
UNII	927AH8112L
KEGG	D00439
ChEBI	CHEBI:71415
ChEMBL	CHEMBL572
Chemical data
Formula	C8H6N4O5
Mol. mass	238.16
	SMILES O=[N+]([O-])c2oc(/C=N/N1C(=O)NC(=O)C1)cc2;
	InChI InChI=1S/C8H6N4O5/c13-6-4-11(8(14)10-6)9-3-5-1-2-7(17-5)12(15)16/h1-3H,4H2,(H,10,13,14)/b9-3+ ; Key:NXFQHRVNIOXGAQ-YCRREMRBSA-N ;
(what is this?) (verify);

　　[★]

英: nitrofurantoin
ラ: nitrofurantoinum
商: Furadantin, Furan, Macrodantin
関

尿路感染症の治療薬

[parrott1976-1] Parrott, E. L.; Matheson Jr, L. E. (1977). "Rectal absorption of nitrofurantoin". Journal of Pharmaceutical Sciences 66 (7): 955–958. doi:10.1002/jps.2600660713. PMID 886458. edit

[pmid18154548-2] Garau J (January 2008). "Other antimicrobials of interest in the era of extended-spectrum beta-lactamases: fosfomycin, nitrofurantoin and tigecycline". Clin. Microbiol. Infect. 14 Suppl 1: 198–202. doi:10.1111/j.1469-0691.2007.01852.x. PMID 18154548.

[pmid18556490-3] Lee M, Bozzo P, Einarson A, Koren G (June 2008). "Urinary tract infections in pregnancy". Can Fam Physician 54 (6): 853–4. PMC 2426978. PMID 18556490.

[urlUrinary_Tract_Infections_During_Pregnancy_-_February_1.2C_2000_-_American_Academy_of_Family_Physicians-4] "Urinary Tract Infections During Pregnancy - February 1, 2000 - American Academy of Family Physicians".

[PharmBasisTherap-5] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Gilman, eds.: Joel G. Hardman, Lee E. Limbird ; consul. ed.: Alfred Goodman (2002). Goodman & Gilman's the Pharmacological Basis of Therapeutics. (12th ed. ed.). New York: McGraw-Hill. pp. Chapter 52. ISBN 0071354697.

[6] McCalla DR, Kaiser C, Green MHL (1978). "Genetics of nitrofurazone resistance in Escherichia coli". J Bacteriol 133: 10–16.

[Bains_A.2C_Buna_D.2C_Hoag_NA_2009_248.E2.80.93252-7] Bains A, Buna D, Hoag NA (2009). "A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment". Canadian Pharmacists Journal 142 (5): 248–252. doi:10.3821/1913-701X-142.5.248.

[8] Tu Y, McCalla DR (1975). "Effect of activated nitrofurans on DNA,". Biochem Biophys Acta 402: 142–49.

[9] "Complementary and Alternative Medicine Index (CAM)". Umm.edu. Retrieved 2012-05-29.

[10] "Furadantin 25mg/5ml Oral Suspension OR Nitrofurantoin 25mg/5ml Oral Suspension - Summary of Product Characteristics (SPC) - (eMC)". Medicines.org.uk. 2010-11-18. Retrieved 2012-05-29.

[11] Richards WA, et al. (1955). "Nitrofurantoin: Clinical and laboratory studies in urinary tract infections". Arch Intern Med 96 (4): 437–50. doi:10.1001/archinte.1955.00250150011001. PMID 13257939.

[pmid18495029-12] Goemaere NN, Grijm K, van Hal PT, den Bakker MA (2008). "Nitrofurantoin-induced pulmonary fibrosis: a case report". J Med Case Reports 2: 169. doi:10.1186/1752-1947-2-169. PMC 2408600. PMID 18495029.

[13] Björnsson, E; Talwalkar, J; Treeprasertsuk, S; Kamath, PS; Takahashi, N; Sanderson, S; Neuhauser, M; Lindor, K (June 2010). "Drug-induced autoimmune hepatitis: clinical characteristics and prognosis.". Hepatology (Baltimore, Md.) 51 (6): 2040–8. doi:10.1002/hep.23588. PMID 20512992. Retrieved 7 September 2012.

[fao-14] FAO: Nitrofuran study

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案内

nitrofurantoin