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an antibiotic (trade name Vancocin) effective against some bacterial infections (同)Vancocin
a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/06/18 06:05:24」(JST)

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Vancomycin is an antibiotic used to treat a number of bacterial infections.^[3] It is recommended intravenously as a first-line treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant S. aureus.^[4] Blood levels may be measured to determine the correct dose.^[5] Vancomycin is also recommended by mouth as a treatment for severe Clostridium difficile colitis. When taken by mouth it is very poorly absorbed.^[3]

Common side effects include pain in the area of injection and allergic reactions. Occasionally problems with hearing, low blood pressure, or bone marrow suppression occur.^[3] Safety in pregnancy is not clear but there is no evidence of harm,^[3]^[6] and it is likely safe for use when breastfeeding.^[7] It is a type of glycopeptide antibiotic and works by blocking the construction of a cell wall.^[3]

Vancomycin was first sold in 1954.^[8] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[9] It is available as a generic medication.^[5] The wholesale cost of an intravenous dose is about 1.70 to 6.00 USD.^[10] In the United States the pills are more expensive than the intravenous solution.^[3] The intravenous solution may be safely taken by mouth for the treatment of Clostridium difficile colitis to reduce costs.^[11] Vancomycin is made by the soil bacterium Amycolatopsis orientalis.^[3]

1 Medical uses
- 1.1 Spectrum of susceptibility
2 Side effects
- 2.1 Nephrotoxicity
- 2.2 Ototoxicity
- 2.3 Interactions with other nephrotoxins
3 Dosing considerations
- 3.1 Intravenous vs oral administration
- 3.2 Red man syndrome
- 3.3 Therapeutic drug monitoring
4 Biosynthesis
5 Total synthesis
6 Pharmacology and chemistry
- 6.1 Mechanism of action
7 Plant tissue culture
8 Antibiotic resistance
- 8.1 Intrinsic resistance
- 8.2 Acquired resistance
9 History
10 Cost
11 See also
12 References

Medical uses

Crystal structure of a short peptide L-Lys-D-Ala-D-Ala (bacterial cell wall precursor, in green) bound to vancomycin (blue) through hydrogen bonds. Reported by Knox and Pratt in Antimicrob. Agents. Chemother., 1990 1342-1347

Vancomycin is indicated for the treatment of serious, life-threatening infections by gram-positive bacteria unresponsive to other antibiotics. In particular, vancomycin should not be used to treat methicillin-sensitive Staphylococcus aureus because it is inferior to penicillins such as nafcillin.^[12]^[13]

The increasing emergence of vancomycin-resistant enterococci has resulted in the development of guidelines for use by the Centers for Disease Control Hospital Infection Control Practices Advisory Committee. These guidelines restrict use of vancomycin to the following indications:^[14]^[15]

Treatment of serious infections caused by susceptible organisms resistant to penicillins (Methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Staphylococcus epidermidis (MRSE)) or in individuals with serious allergy to penicillins
Treatment of pseudomembranous colitis caused by Clostridium difficile; in particular, in cases of relapse or where the infection is unresponsive to metronidazole treatment (for this indication, vancomycin is given orally, rather than by its typical intravenous (IV) route)
For treatment of infections caused by gram-positive microorganisms in patients with serious allergies to beta-lactam antimicrobials.^[15]
Antibacterial prophylaxis for endocarditis following certain procedures in penicillin-hypersensitive individuals at high risk^[15]
Surgical prophylaxis for major procedures involving implantation of prostheses in institutions with a high rate of MRSA or MRSE^[15]
Early in treatment as an empiric antibiotic for possible MRSA infection while waiting for culture identification of the infecting organism
Has shown some success long term in halting the progression of Primary Sclerosing Cholangitis and preventing symptoms; Vancomycin does not cure the patient however

Spectrum of susceptibility

Vancomycin is considered a last resort medication for the treatment of septicemia and lower respiratory tract, skin, and bone infections caused by gram-positive bacteria. The MIC susceptibility data for a few medically significant bacteria are:

Staphylococcus aureus: 0.25 μg/mL to 4.0 μg/mL
Staphylococcus aureus (methicillin resistant or MRSA): 1 μg/mL 138 μg/mL
Staphylococcus epidermidis: ≤0.12 μg/mL to 6.25 μg/mL

^[16]

Side effects

Serum vancomycin levels may be monitored in an effort to reduce side effects, although the value of such monitoring has been questioned.^[17] Peak and trough levels are usually monitored, and, for research purposes, the area under the concentration curve is also sometimes used. Toxicity is best monitored by looking at trough values.^[18]

Common adverse drug reactions (≥1% of patients) associated with IV vancomycin include: local pain, which may be severe, and thrombophlebitis.

Damage to the kidneys and to the hearing were a side effect of the early impure versions of vancomycin, and these were prominent in the clinical trials conducted in the mid-1950s.^[19]^[20] Later trials using purer forms of vancomycin found nephrotoxicity is an infrequent adverse effect (0.1% to 1% of patients), but this is accentuated in the presence of aminoglycosides.^[21]

Rare adverse effects (<0.1% of patients) include: anaphylaxis, toxic epidermal necrolysis, erythema multiforme, red man syndrome, superinfection, thrombocytopenia, neutropenia, leukopenia, tinnitus, and dizziness and/or ototoxicity

Vancomycin can induce platelet-reactive antibodies in the patient, leading to severe thrombocytopenia and bleeding with florid petechial hemorrhages, ecchymoses, and wet purpura.^[22]

Vancomycin has traditionally been considered a nephrotoxic and ototoxic drug, based on observations by early investigators of elevated serum levels in renally impaired patients who had experienced ototoxicity, and subsequently through case reports in the medical literature. However, as the use of vancomycin increased with the spread of MRSA beginning in the 1970s, the previously reported rates of toxicity were recognized as not being observed. This was attributed to the removal of the impurities present in the earlier formulation of the drug, although those impurities were not specifically tested for toxicity.^[19]

Nephrotoxicity

Subsequent reviews of accumulated case reports of vancomycin-related nephrotoxicity found many of the patients had also received other known nephrotoxins, in particular, aminoglycosides. Most of the rest had other confounding factors, or insufficient data regarding the possibility of such, that prohibited the clear association of vancomycin with the observed renal dysfunction.

In 1994, the use of vancomycin monotherapy was clearly documented in only three of 82 available cases in the literature.^[23] Prospective and retrospective studies attempting to evaluate the incidence of vancomycin-related nephrotoxicity have largely been methodologically flawed and have produced variable results. The most methodologically sound investigations indicate the actual incidence of vancomycin-induced nephrotoxicity is around 5% to 7%. To put this into context, similar rates of renal dysfunction have been reported for cefamandole and benzylpenicillin, two reputedly non-nephrotoxic antibiotics.

In addition, evidence to relate nephrotoxicity to vancomycin serum levels is inconsistent. Some studies have indicated an increased rate of nephrotoxicity when trough levels exceed 10 µg/mL, but others have not reproduced these results. Nephrotoxicity has also been observed with concentrations within the "therapeutic" range, as well. In essence, the reputation of vancomycin as a nephrotoxin is overstated, and it has not been demonstrated that maintaining vancomycin serum levels within certain ranges will prevent its nephrotoxic effects, when they do occur.

Ototoxicity

Attempts to establish rates of vancomycin-induced ototoxicity are even more difficult due to the scarcity of quality evidence. The current consensus is that clearly related cases of vancomycin ototoxicity are rare. The association between vancomycin serum levels and ototoxicity is also uncertain. While cases of ototoxicity have been reported in patients whose vancomycin serum level exceeded 80 µg/mL, cases have been reported in patients with therapeutic levels, as well. Thus, whether therapeutic drug monitoring of vancomycin for the purpose of maintaining "therapeutic" levels will prevent ototoxicity also remains unproven.

Interactions with other nephrotoxins

Another area of controversy and uncertainty concerns the question of whether, and, if so, to what extent, vancomycin increases the toxicity of other nephrotoxins. Clinical studies have yielded variable results, but animal models indicate some increased nephrotoxic effect probably occurs when vancomycin is added to nephrotoxins such as aminoglycosides. However, a dose- or serum level-effect relationship has not been established.

Dosing considerations

Intravenous vs oral administration

Vancomycin must be given intravenously (IV) for systemic therapy, since it is not absorbed from the intestine. It is a large hydrophilic molecule that partitions poorly across the gastrointestinal mucosa. Due to short half-life, it is often injected twice-daily.^[24]

The only approved indication for oral vancomycin therapy is in the treatment of pseudomembranous colitis, where it must be given orally to reach the site of infection in the colon. Following oral administration, the fecal concentration of vancomycin is around 500 µg/mL^[25] (sensitive strains of C. difficile have a mean inhibitory concentration of ≤2 µg/mL^[26])

Inhaled vancomycin has also been used (off-label), via nebulizer, for treatment of various infections of the upper and lower respiratory tract.

The caustic nature of vancomycin makes IV therapy using peripheral lines a risk for thrombophlebitis. Ideally, central lines or infusion ports should be used.^[27]

Red man syndrome

Vancomycin is recommended to be administered in a dilute solution slowly, over at least 60 min (maximum rate of 10 mg/min for doses >500 mg)^[14] due to the high incidence of pain and thrombophlebitis and to avoid an infusion reaction known as the "red man syndrome" or "red neck syndrome". This syndrome, usually appearing within 4 min to 10 min after the commencement or soon after the completion of an infusion, is characterized by flushing and/or an erythematous rash that affects the face, neck, and upper torso. These findings are due to nonspecific mast cell degranulation and are not an IgE-mediated allergic reaction. Less frequently, hypotension and angioedema may also occur. Symptoms may be treated or prevented with antihistamines, including diphenhydramine, and are less likely to occur with slow infusion.^[28]^[29]^:120–1

Therapeutic drug monitoring

Plasma level monitoring of vancomycin is necessary due to the drug's biexponential distribution, intermediate hydrophilicity, and potential for ototoxicity and nephrotoxicity, especially in populations with poor renal function and/or increased propensity to bacterial infection. Vancomycin activity is considered to be time-dependent; that is, antimicrobial activity depends on the duration that the serum drug concentration exceeds the minimum inhibitory concentration of the target organism. Thus, peak serum levels have not been shown to correlate with efficacy or toxicity; indeed, concentration monitoring is unnecessary in most cases. Circumstances in which therapeutic drug monitoring is warranted include: patients receiving concomitant aminoglycoside therapy, patients with (potentially) altered pharmacokinetic parameters, patients on haemodialysis, patients administered high-dose or prolonged treatment, and patients with impaired renal function. In such cases, trough concentrations are measured.^[14]^[23]^[30]^[31]

Target ranges for serum vancomycin concentrations have changed over the years. Early authors suggested peak levels of 30 mg/L to 40 mg/L and trough levels of 5 mg/L to 10 mg/L,^[32] but current recommendations are that peak levels need not be measured and that trough levels of 10 mg/L to 15 mg/L or 15 mg/L to 20 mg/L, depending on the nature of the infection and the specific needs of the patient, may be appropriate.^[33]^[34]

Biosynthesis

Vancomycin is made by the soil bacterium Amycolatopsis orientalis.^[3]

Figure 1: Modules and domains of vancomycin assembly

Vancomycin biosynthesis occurs via different nonribosomal protein synthases (NRPSs).^[35] The enzymes determine the amino acid sequence during its assembly through its 7 modules. Before vancomycin is assembled through NRPS, the amino acids are first modified. L-tyrosine is modified to become the β-hydroxychlorotyrosine (β-hTyr) and 4-hydroxyphenylglycine (HPG) residues. On the other hand, acetate is used to derive the 3,5 dihydroxyphenylglycine ring (3,5-DPG).^[36]

Figure 2: Linear heptapeptide, which consists of modified aromatic rings

Nonribosomal peptide synthesis occurs through distinct modules that can load and extend the protein by one amino acid through the amide bond formation at the contact sites of the activating domains.^[37] Each module typically consists of an adenylation (A) domain, a peptidyl carrier protein (PCP) domain, and a condensation (C) or elongation domain. In the A domain, the specific amino acid is activated by converting into an aminoacyl adenylate enzyme complex attached to a 4'phosphopantetheine cofactor by thioesterification^[38]^[39] The complex is then transferred to the PCP domain with the expulsion of AMP. The PCP domain uses the attached 4'-phosphopantethein prosthetic group to load the growing peptide chain and their precursors.^[40] The organization of the modules necessary to biosynthesize Vancomycin is shown in Figure 1. In the biosynthesis of Vancomycin, additional modification domains are present, such as the epimerization (E) domain, which isomerizes the amino acid from one stereochemistry to another, and a thioesterase domain (TE) is used as a catalyst for cyclization and releases of the molecule via a thioesterase scission.

Figure 3: Modifications necessary for vancomycin to become biologically active

A set of multienzymes (peptide synthase CepA, CepB, and CepC) are responsible for assembling the heptapeptide. (Figure 2). The organization of CepA, CepB, and Cep C closely resembles other peptide synthases such as those for surfactin (SrfA1, SrfA2, and SrfA3) and gramicidin (GrsA and GrsB).^[37] Each peptide synthase activates codes for various amino acids to activate each domain. CepA codes for modules 1, 2, and 3. CepB codes for modules 4, 5, and 6, and CepC codes for module 7. The three peptide synthases are located at the start of the region of the bacterial genome linked with antibiotic biosynthesis, and span 27 kb.^[37]

After the linear heptapeptide molecule is synthesized, vancomycin has to undergo further modifications, such as oxidative cross-linking and glycosylation, in trans^{[clarification needed]} by distinct enzymes, referred to as tailoring enzymes, to become biologically active (Figure 3). To convert the linear heptapeptide, eight enzymes, open reading frames (ORFs) 7, 8, 9, 10, 11, 14, 18, 20, and 21 are used. The enzymes ORF 7, 8, 9, and 20 are P450 enzymes. ORF 10 and 18 show to nonheme haloperoxidases^{[clarification needed]}. And ORF 9 and 14 are identified as putative hydroxylation enzymes.^[41] With the help of these enzymes, β-hydroxyl groups are introduced onto tyrosine residues 2 and 6, and coupling occurs for rings 5 and 7, rings 4 and 6, and rings 4 and 2. In addition, a haloperoxidase is used to attach the chlorine atoms onto rings 2 and 6 via an oxidative process.^[37] Some of the glycosyltransferases capable of glycosylating vancomycin and related nonribosomal peptides display notable permissivity and have been employed for generating libraries of differentially glycosylated analogs through a process known as glycorandomization.^[42]^[43]^[44]

Total synthesis

Vancomycin has been a successful target in total synthesis.^[45]^[46]^[47]

Pharmacology and chemistry

Vancomycin is a branched tricyclic glycosylated nonribosomal peptide produced by the Actinobacteria species Amycolatopsis orientalis (formerly designated Nocardia orientalis).

Vancomycin exhibits atropisomerism — it has multiple chemically distinct rotamers owing to the rotational restriction of some of the bonds. The form present in the drug is the thermodynamically more stable conformer, so has more potent activity.^{[citation needed]}

Mechanism of action

Vancomycin acts by inhibiting proper cell wall synthesis in gram-positive bacteria. Due to the different mechanism by which gram-negative bacteria produce their cell walls and the various factors related to entering the outer membrane of gram-negative organisms, vancomycin is not active against gram-negative bacteria (except some nongonococcal species of Neisseria).

The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Under normal circumstances, this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents cell wall synthesis of the long polymers of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) that form the backbone strands of the bacterial cell wall, and it prevents the backbone polymers that do manage to form from cross-linking with each other.^[48]

Mechanism of vancomycin action and resistance: This diagram shows only one of two ways vancomycin acts against bacteria (inhibition of cell wall cross-linking) and only one of many ways that bacteria can become resistant to it.

Vancomycin is added to the bacterial environment while it is trying to synthesize new cell wall. Here, the cell wall strands have been synthesized, but not yet cross-linked.
Vancomycin recognizes and binds to the two D-ala residues on the end of the peptide chains. However, in resistant bacteria, the last D-ala residue has been replaced by a D-lactate, so vancomycin cannot bind.
In resistant bacteria, cross-links are successfully formed. However, in the nonresistant bacteria, the vancomycin bound to the peptide chains prevents them from interacting properly with the cell wall cross-linking enzyme.
In the resistant bacteria, stable cross links are formed. In the sensitive bacteria, cross-links cannot be formed and the cell wall falls apart.

Plant tissue culture

Vancomycin is one of the few antibiotics used in plant tissue culture to eliminate gram-positive bacteria infection. It has relatively low toxicity to plants.^[49]^[50]

Antibiotic resistance

Intrinsic resistance

A few gram-positive bacteria are intrinsically resistant to vancomycin: Leuconostoc and Pediococcus species, but these organisms rarely cause diseases in humans.^[51] Most Lactobacillus species are also intrinsically resistant to vancomycin,^[51] with the exception of L. acidophilus and L. delbruekii, which are sensitive.^[52] Other gram-positive bacteria with intrinsic resistance to vancomycin include Erysipelothrix rhusiopathiae, Weissella confusa, and Clostridium innocuum.^[53]^[54]^[55]

Most gram-negative bacteria are intrinsically resistant to vancomycin because their outer membrane is impermeable to large glycopeptide molecules^[56] (with the exception of some non-gonococcal Neisseria species).^[57]

Acquired resistance

Evolution of microbial resistance to vancomycin is a growing problem, in particular, within healthcare facilities such as hospitals. While newer alternatives to vancomycin exist, such as linezolid (2000) and daptomycin (2003), the widespread use of vancomycin makes resistance to the drug a significant worry, especially for individual patients if resistant infections are not quickly identified and the patient continues the ineffective treatment. Vancomycin-resistant Enterococcus emerged in 1987. Vancomycin resistance evolved in more common pathogenic organisms during the 1990s and 2000s, including vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA).^[58]^[59] Agricultural use of avoparcin, another similar glycopeptide antibiotic, may have contributed to the evolution of vancomycin-resistant organisms.^[60]^[61]^[62]^[63]

One mechanism of resistance to vancomycin involves the alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits, under normal conditions, D-alanyl-D-alanine, to which vancomycin binds. The D-alanyl-D-lactate variation results in the loss of one hydrogen-bonding interaction (4, as opposed to 5 for D-alanyl-D-alanine) possible between vancomycin and the peptide. This loss of just one point of interaction results in a 1000-fold decrease in affinity. The D-alanyl-D-serine variation causes a six-fold loss of affinity between vancomycin and the peptide, likely due to steric hindrance.^[64]

In enterococci, this modification appears to be due to the expression of an enzyme that alters the terminal residue. Three main resistance variants have been characterised to date among resistant Enterococcus faecium and E. faecalis populations:

VanA - Enterococcal resistance to vancomycin and teicoplanin; inducible on exposure to these agents
VanB - lower-level enterococcal resistance; inducible by vancomycin, but strains may remain susceptible to teicoplanin
VanC - least clinically important; enterococci resistant only to vancomycin; constitutive resistance

2011: A variant of vancomycin has been tested at the Scripps Research Institute that binds to the resistant D-lactic acid variation in vancomycin-resistant bacterial cell walls, and also binds well to the original target (vancomycin-susceptible bacteria), and thus reinstates potent antimicrobial activity.^[65]

History

Vancomycin was first isolated in 1953 by Edmund Kornfeld (working at Eli Lilly) from a soil sample collected from the interior jungles of Borneo by a missionary.^[66] The organism that produced it was eventually named Amycolatopsis orientalis.^[19] The original indication for vancomycin was for the treatment of penicillin-resistant Staphylococcus aureus.^[19]^[20]

The compound was initially called compound 05865, but was eventually given the generic name vancomycin, derived from the term "vanquish".^[19] One advantage that was quickly apparent is that staphylococci did not develop significant resistance despite serial passage in culture media containing vancomycin. The rapid development of penicillin resistance by staphylococci led to the compound's being fast-tracked for approval by the Food and Drug Administration in 1958. Eli Lilly first marketed vancomycin hydrochloride under the trade name Vancocin^[20]

Vancomycin never became the first-line treatment for S. aureus for several reasons:

It possesses poor oral bioavailability; it must be given intravenously for most infections.
β-Lactamase-resistant semisynthetic penicillins such as methicillin (and its successors, nafcillin and cloxacillin) were subsequently developed, which have better activity against non-MRSA staphylococci.
Early trials used early impure forms of vancomycin ("Mississippi mud"), which were found to be toxic to the ears and to the kidneys;^[67] these findings led to vancomycin's being relegated to the position of a drug of last resort.^[20]

In 2004, Eli Lilly licensed Vancocin to ViroPharma in the U.S., Flynn Pharma in the UK, and Aspen Pharmacare in Australia. The patent expired in the early 1980s; the FDA authorized the sale of several generic versions in the USA, including from manufacturers Bioniche Pharma, Baxter Healthcare, Sandoz, Akorn Strides, and Hospira.^[68]

Cost

It is available as a generic medication.^[5] The wholesale cost of an intravenous dose is about 1.70 to 6.00 USD.^[10] In the United States the pills are very expensive.^[3] The intravenous solution may be taken by mouth for C. dif. to reduce costs.^[11]

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UpToDate Contents

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1. バンコマイシン過敏症 vancomycin hypersensitivity
2. バンコマイシン：成人への非経口投与と血清濃度のモニタリング vancomycin parenteral dosing and serum concentration monitoring in adults
3. バンコマイシン低感受性黄色ブドウ球菌による菌血症 staphylococcus aureus bacteremia with reduced susceptibility to vancomycin
4. バンコマイシン耐性腸球菌の疫学、予防および管理 epidemiology prevention and control of vancomycin resistant enterococci
5. コアグラーゼ陰性ブドウ球菌による感染症の治療 treatment of infections due to coagulase negative staphylococci

English Journal

Reversible detection of vancomycin using peptide-functionalized cantilever array sensor.

Bai X1, Lu B1, Chen X1, Zhang B2, Tang J3.
Biosensors & bioelectronics.Biosens Bioelectron.2014 Dec 15;62:145-50. doi: 10.1016/j.bios.2014.06.024. Epub 2014 Jun 18.
A reversible detection method for vancomycin was developed utilizing the cantilever array sensor functionalized by a designed peptide consisting of a cysteine (Cys-), a space linker (-Gly-Gly-Gly-Gly-) and a molecular recognition ligand (-l-Lys-d-Ala-d-Ala). It was found that the peptide space linke
PMID 24997368

Prospective validation of neonatal vancomycin dosing regimens is urgently needed.

Vandendriessche A1, Allegaert K1, Cossey V1, Naulaers G1, Saegeman V2, Smits A1.
Current therapeutic research, clinical and experimental.Curr Ther Res Clin Exp.2014 Jul 14;76:51-7. doi: 10.1016/j.curtheres.2014.06.001. eCollection 2014.
BACKGROUND: Although vancomycin is frequently used to treat neonatal late-onset sepsis, there is no consensus on the optimal dosing regimen. Because many neonates needed dosing adaptation due to suboptimal trough values, the vancomycin dosing regimen in our neonatal department was changed during 201
PMID 25061483

Isolation and characterization of multidrug-resistant bacteria from minced meat in Austria.

Petternel C1, Galler H2, Zarfel G2, Luxner J2, Haas D2, Grisold AJ2, Reinthaler FF2, Feierl G2.
Food microbiology.Food Microbiol.2014 Dec;44:41-6. doi: 10.1016/j.fm.2014.04.013. Epub 2014 May 6.
INTRODUCTION: Resistant bacteria are a well-known public health problem. This study was conducted to investigate the prevalence and genetic characteristics of extended spectrum β-lactamase (ESBL) producing enterobacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant E
PMID 25084643

Japanese Journal

重症難治性Clostridium difficile感染症に対して便移植（fecal microbiota transplantation）が著効した1例

日本消化機病學會雜誌. 乙 113(1), 55-62, 2016
NAID 130005118424

予後不良であった肺炎球菌性髄膜炎の1剖検例

東京女子医科大学雑誌 85(1), 16-21, 2015-02-25
NAID 110009883331

バンコマイシン塩酸塩点滴静注用製剤の生理食塩液に対する溶解性比較

日本環境感染学会誌 30(1), 29-32, 2015
NAID 130005064062

Related Pictures

★リンクテーブル★

リンク元	「バンコマイシン」
関連記事	「hydrochloride」「vancomycin」

「バンコマイシン」

Vancomycin
Systematic (IUPAC) name
	(1S,2R,18R,19R,22S,25R,28R,40S)- 48- {[(2S,3R,4S,5S,6R)- 3- {[(2S,4S,5S,6S)- 4- amino- 5- hydroxy- 4,6- dimethyloxan- 2- yl]oxy}- 4,5- dihydroxy- 6- (hydroxymethyl)oxan- 2- yl]oxy}- 22- (carbamoylmethyl)- 5,15- dichloro- 2,18,32,35,37- pentahydroxy- 19- [(2R)- 4- methyl- 2- (methylamino)pentanamido]- 20,23,26,42,44- pentaoxo- 7,13- dioxa- 21,24,27,41,43- pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta- 3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49- pentadecaene- 40- carboxylic acid
Clinical data
Pronunciation	/væŋkəˈmaɪsᵻn/
Trade names	Vancocin
AHFS/Drugs.com	Monograph
MedlinePlus	a604038
License data	US FDA: Vancocin;
Pregnancy; category	AU: B2; B (PO) / C (IV)(US);
Routes of; administration	IV, oral
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	Negligible (oral)
Metabolism	Excreted unchanged
Biological half-life	4 h to 11 h (adults); 6 d to 10 d (adults, impaired renal function)
Excretion	Renal
Identifiers
CAS Number	1404-90-6
ATC code	A07AA09 (WHO) J01XA01 (WHO)
PubChem	CID 14969
DrugBank	DB00512
ChemSpider	14253
UNII	6Q205EH1VU
KEGG	D00212
ChEBI	CHEBI:28001
ChEMBL	CHEMBL262777
Chemical data
Formula	C66H75Cl2N9O24
Molar mass	1449.3 g.mol−1
	SMILES C[C@H]1[C@H]([C@@](C[C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2Oc3c4cc5cc3Oc6ccc(cc6Cl)[C@H]([C@H](C(=O)N[C@H](C(=O)N[C@H]5C(=O)N[C@@H]7c8ccc(c(c8)-c9c(cc(cc9O)O)[C@H](NC(=O)[C@H]([C@@H](c1ccc(c(c1)Cl)O4)O)NC7=O)C(=O)O)O)CC(=O)N)NC(=O)[C@@H](CC(C)C)NC)O)CO)O)O)(C)N)O ;
	InChI InChI=1S/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1 ; Key:MYPYJXKWCTUITO-LYRMYLQWSA-N ;
(verify)

　　[★]

英: vancomycin, VCM
化: 塩酸バンコマイシン vancomycin hydrochloride
商: Vancocin, Luphocin、バンマイシン
関: 抗菌薬一覧、テイコプラニン、メトロニダゾール

first aid step1 2006 p.140,165,166,169,173,207

抗菌薬

グリコペプチド系抗生物質

特徴

Streptomyces orientalisから分離
経腸管的に吸収されないため骨髄移植時の消化管内消毒に用いられる。

構造

作用機序

細胞壁合成阻害作用(block peptidoglycan synthesis)
細胞内で作られたmurein monomerの重合を妨げる？

薬理作用

抗菌スペクトル

MRSAを含むほとんどのグラム陽性菌と一部の嫌気性菌に抗菌作用を示す
殺菌的に作用(bactericidal antibiotics)

動態

腸管からほとんど吸収されない→腸管殺菌のための経口投与、点滴静注による全身投与で用いられる

適応

感染性腸炎
骨髄移植時の消化管内殺菌

[US?]MRSA(methicillin-resistant Staphylococcus aureus), penicillin-resistant Sreptococcus pneumoniae

適応菌種

メチシリン耐性黄色ブドウ球菌、クロストリジウム・ディフィシル

注意

禁忌

副作用

nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing(red man syndrome) (first aid step1 2006 p.169)

重大な副作用

添付文書

1)ショック：0.1%未満(血圧低下、不快感、口内異常感、喘鳴、眩暈、便意、耳鳴り、発汗等)
2)注射用塩酸バンコマイシン製剤：アナフィラキシー様症状、急性腎不全、間質性腎炎、汎血球減少、無顆粒球症、血小板減少、皮膚粘膜眼症候群(Stevens-Johnson症候群)、中毒性表皮壊死症(Lyell症候群)、剥脱性皮膚炎、第8脳神経障害、偽膜性大腸炎、肝機能障害、黄疸

その他

1)過敏症(発熱、発疹、潮紅、悪寒、蕁麻疹、そう痒)
2)血液(好酸球増多、白血球減少、血小板減少)
3)肝臓(AST・ALT・Al-P上昇)
4)消化器(下痢：48%、悪心：28%、嘔吐：34%、食欲不振)　←骨髄移植時の消化管内殺菌における発現頻度
5)腎臓(BUN・クレアチニンの上昇)
6)その他(口内炎、舌炎)

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

「vancomycin」

　　[★] バンコマイシン VCM 　

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vancomycin hydrochloride