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Netilmicin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria. Netilmicin is not absorbed from the gut and is therefore only given by injection or infusion. It is only used in the treatment of serious infections particularly those resistant to gentamicin.

Available dosage forms

Available dosage forms include:

UK: netilmicin (as sulfate):
- 10 mg/mL (1.5 mL amp)
- 50 mg/mL (1 mL amp)
- 100 mg/mL(1 mL, 1.5 mL, and 2 mL amp)
France: nétilmicin sulfate:
- Amp 25 mg/1 mL
- 50 mg/2 mL
- 100 mg/1 mL
- 150 mg/1.5 mL

Ingredients for 100 mg/mL vial

Netilmicin (as sulfate)	100 mg
Sodium metabisulfite	2.4 mg
Sodium sulfite	0.8 mg
Edetate disodium	0.1 mg
Benzyl alcohol	10 mg
Water for injection	qs 1 mL

FDA approval date : February 28, 1983

Comparison with drugs of the same therapeutic category

According to the British National Formulary (BNF), netilmicin has similar activity to gentamicin, but less ototoxicity in those needing treatment for longer than 10 days. Netilmicin is active against a number of gentamicin-resistant Gram-negative bacteria but is less active against Pseudomonas aeruginosa than gentamicin or tobramycin.

However, according to the below-mentioned studies, the above advantages are controversial:

Netilmicin (Netromycin, Schering-Plough, Netspan- Cipla):
In summary, netilmicin has not been demonstrated to have significant advantages over other aminoglycosides (gentamicin, tobramycin, amikacin), and it is more expensive; thus, its potential value is limited. Drug Intelligence & Clinical Pharmacy: Vol. 17, No. 2, pp. 83-91.
Once-daily gentamicin versus once-daily netilmicin in patients with serious infections—a randomized clinical trial:
We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated. Journal of Antimicrobial Chemotherapy (1994) 33, 823-835.
Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with serious infections. A randomized clinical trial:
We conclude that with once-daily treatment no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated. Clin Otolaryngol Allied Sci. 1995 Apr;20(2):118-23.
Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients:
We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin. Arch Intern Med. 1986 Dec;146(12):2329-34.
Daily single-dose aminoglycoside administration. Therapeutic and economic benefits:
Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens. Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens. Ugeskrift for Lægerer. 1993 May 10;155(19):1436-41.
Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli Meningitis:
Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis. Antimicrob Agents Chemother. 1978 June; 13(6): 899-904.
A comparison of netilmicin and gentamicin in the treatment of pelvic infections:
The microbacteria isolated by standard culture techniques before therapy revealed Neisseria gonorrhoeae in 69% and 51% of the netilmicin and gentamicin groups, respectively; anaerobic organisms were cultured in about 75% of each group. Obstetrics & Gynecology 1979;54:554-557.
Netilmicin: a review of toxicity in laboratory animals:
Presently available data suggest that netilmicin offers distinct advantages over older aminoglycosides. Final conclusions must await prospective randomized double-blind trials in man. J Int Med Res. 1978;6(4):286-99.
Nonparallel nephrotoxicity dose-response curves of aminoglycosides:
Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Antimicrob Agents Chemother. 1981 June; 19(6): 1024–1028.
Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats:
Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear) relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin and gentamicin. Toxicol Appl Pharmacol. 1985 Mar 15;77(3):479-89.
Comparison of Netilmicin and Gentamicin Pharmacokinetics in Humans:
In a crossover study, single doses of netilmicin and gentamicin were administered intramuscularly, each at 1.0 and 2.5 mg/kg. No significant differences were observed between the two drugs in disposition half-life, rate of distribution and elimination, area under the serum concentration-time curve, urinary excretion, total body clearance, and renal clearance. Antimicrobial Agents and Chemotherapy, Feb. 1980, p. 184-187. Schering-Plough Research Division, Bloomfield, New Jersey 07003.

References

Hemsworth S, Nunn A, Selwood K, Osborne C, Jones A, Pizer B (2005). "Once-daily netilmicin for neutropenic pyrexia in paediatric oncology". Acta Paediatr. 94 (3): 268–74. doi:10.1080/08035250510025923. PMID 16028643.
Klingenberg C, Småbrekke L, Lier T, Flaegstad T (2004). "Validation of a simplified netilmicin dosage regimen in infants". Scand J Infect Dis. 36 (6-7): 474–9. doi:10.1080/00365540410020613. PMID 15307571.
Brooks J, Marlow N, Reeves B, Millar M (2004). "Use of once-daily netilmicin to treat infants with suspected sepsis in a neonatal intensive care unit". Biol Neonate. 86 (3): 170–5. doi:10.1159/000079423. PMID 15237240.

UpToDate Contents

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1. アミノグリコシド aminoglycosides
2. 早産児における細菌性敗血症の治療および予防 treatment and prevention of bacterial sepsis in the preterm infant
3. 固有弁心内膜炎の抗菌療法 antimicrobial therapy of native valve endocarditis
4. D群レンサ球菌（Streptococcus bovis、Streptococcus equinus complex）による感染症の臨床症状、診断、および治療 clinical manifestations diagnosis and treatment of infections due to group d streptococci streptococcus bovis streptococcus equinus complex
5. アミノグリコシドによる腎毒性の症状および危険因子 manifestations of and risk factors for aminoglycoside nephrotoxicity

English Journal

Frequency of Aminoglycoside-Modifying Enzymes and ArmA Among Different Sequence Groups of Acinetobacter baumannii in Iran.

Hasani A1,2, Sheikhalizadeh V1,2, Ahangarzadeh Rezaee M1, Rahmati-Yamchi M3, Hasani A3, Ghotaslou R1, Goli HR1.
Microbial drug resistance (Larchmont, N.Y.).Microb Drug Resist.2016 Jul;22(5):347-53. doi: 10.1089/mdr.2015.0254. Epub 2016 Jan 18.
We evaluated aminoglycoside resistance in 87 Acinetobacter baumannii strains isolated from four hospitals located in the North West region of Iran and typed them in sequence groups (SGs) using trilocus sequence-based scheme to compare their clonal relationships with international clones. Resistance
PMID 26779992

Molecular typing and differences in biofilm formation and antibiotic susceptibilities among Prototheca strains isolated in Italy and Brazil.

Morandi S1, Cremonesi P2, Capra E2, Silvetti T3, Decimo M3, Bianchini V4, Alves AC5, Vargas AC6, Costa GM7, Ribeiro MG5, Brasca M3.
Journal of dairy science.J Dairy Sci.2016 May 25. pii: S0022-0302(16)30297-1. doi: 10.3168/jds.2016-10900. [Epub ahead of print]
Bovine mastitis caused by Prototheca is a serious and complex problem that accounts for high economic losses in the dairy industry. The main objective of this study was to identify and characterize at genetic level different Prototheca strains and provide the most complete data about protothecal ant
PMID 27236754

Surveillance of the Activity of Aminoglycosides and Fluoroquinolones Against Ophthalmic Pathogens from Europe in 2010-2011.

Sanfilippo CM1, Morrissey I2, Janes R2, Morris TW1.
Current eye research.Curr Eye Res.2016 May;41(5):581-9. doi: 10.3109/02713683.2015.1045084. Epub 2015 Jul 22.
PURPOSE/AIM: Bacterial infections of the ocular surface are commonly treated empirically with broad spectrum antibiotics. Due to concerns over increasing antibiotic resistance, we evaluated current susceptibility patterns of the ocular bacterial pathogens in Europe.MATERIALS AND METHODS: Non-consecu
PMID 26200173

Japanese Journal

In vitro synergistic effects of double and triple combinations of beta-lactams, vancomycin, and netilmicin against methicillin-resistant Staphylococcus aureus strains

ROCHON-EDOUARD S
Antimicrob Agents Chemother 44, 3055-3060, 2000
NAID 30020629620

アミノ配糖体系抗生物質Arbekacin, Astromicin, IsepamicinとNetilmicinの筋弛緩作用

遠藤和敬
The Japanese journal of antibiotics 52(8), 554-561, 1999-08-25
NAID 10004901492

Related Pictures

★リンクテーブル★

リンク元	「アミノグリコシド系抗菌薬」「ネチルマイシン」
拡張検索	「netilmicin sulfate」

「アミノグリコシド系抗菌薬」

Netilmicin
Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a605011
ATC code	J01GB07 (WHO) S01AA23 (WHO);
Pharmacokinetic data
Bioavailability	~0%
Biological half-life	2.5 hours
Identifiers
	IUPAC name (2R,3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4-Amino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-6-(ethylamino)-2-hydroxycyclohexyl]oxy}-5-methyl-4-(methylamino)oxane-3,5-diol;
CAS Number	56391-56-1 ;
PubChem CID	41859;
DrugBank	DB00955 ;
ChemSpider	38195 ;
UNII	4O5J85GJJB;
KEGG	D08268 ;
ChEMBL	CHEMBL1572 ;
ECHA InfoCard	100.054.661
Chemical and physical data
Formula	C21H41N5O7
Molar mass	475.59 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O[C@]3(C)[C@H](NC)[C@@H](O)[C@@H](O[C@H]2[C@H](NCC)C[C@H](N)[C@@H](OC1O\C(=C/CC1N)CN)[C@@H]2O)OC3 ;
	InChI InChI=1S/C21H41N5O7/c1-4-26-13-7-12(24)16(32-19-11(23)6-5-10(8-22)31-19)14(27)17(13)33-20-15(28)18(25-3)21(2,29)9-30-20/h5,11-20,25-29H,4,6-9,22-24H2,1-3H3/t11?,12-,13+,14-,15+,16+,17-,18+,19?,20+,21-/m0/s1 ; Key:CIDUJQMULVCIBT-KALHTFJLSA-N ;
(what is this?) (verify)

　　[★]

英: aminoglycoside antibiotic
関: 抗菌薬、アミノグリコシド系薬、アミノグリコシド

GOO. chapter.45

タンパク質合成阻害による抗菌薬は静菌的なのもが多いが、アミノグリコシド系抗菌薬は「殺菌的」に作用

構造

amino sugars linked to an aminocyclitol ring by glycosidic bonds (GOO.1155)
名前の通りアミノ基-NH₂を多数有しているため正電荷を帯びる

→経口吸収不良

→脳脊髄液に移行しにくい。

→腎排泄されやすい

動態

内服不可能→外来患者に使いにくい
細胞膜(内膜)の通過は膜電位ポテンシャルに依存している。ここが律速段階となる。　→　細胞内移行性悪

阻害、拮抗要素：二価陽イオン、高浸透圧、pHの低下、嫌気的条件

膿瘍など嫌気的条件、酸性の高浸透圧尿など細菌の膜電位ポテンシャルが低下する場合に薬効低下

作用機序

30Sリボソームに作用してタンパク質合成を阻害

1. 翻訳開始を阻害
2. 翻訳を停止させる
3. 誤ったアミノ酸を取り込ませる

異常蛋白が細胞膜に挿入され、膜の透過性を変えてさらにアミノグリコシド系抗菌薬の取り込みを促す

薬理作用

薬効は迅速。濃度依存的。
post-antibiotic effectがある。

抗菌薬の血漿濃度がminnimum inhibitory concentration以下になっても殺菌活性が残存。殺菌活性の残存時間は濃度依存的

抗菌スペクトル

広い

副作用

腎障害：近位尿細管の壊死変性。用量依存的
耳毒性：CN VIII障害。内耳の有毛細胞を破壊。用量依存的
神経・筋遮断作用：(稀であるが)神経筋遮断作用(およびこれによる無呼吸)を呈する。遮断作用はネオマイシンが一番強く、カナマイシン、アミカシン、ゲンタマイシン、トブラマイシンがこれに続く。通常、胸腔内、腹腔に大量投与した時に生じるが、静脈内、筋肉内、あるいは経口投与でも起こりうる。大抵の発作(神経筋接合部が遮断される発作)は麻酔薬やその他の神経筋接合部遮断薬の投与で生じる(←どういう意味？)。重症筋無力症の患者はアミノグリコシド系抗菌薬による神経筋接合部遮断作用を受けやすい。(GOO.1164)