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Vancomycin

23 bytes removed, 14:22, 11 January 2018
m
Changed units to mg/L
|-
!style="text-align:left;"|Solubility
|0.225 gmg/L <ref name="[1]" /> in water
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!style="text-align:left;"|Half life
Resistance to vancomycin and other GPAs (glycopeptide antibiotics) took over three decades to develop <ref name="[10]" /><ref name="[7]" />. This exceptionally large delay between introduction into the clinic and the emergence of resistance, is due in part to the relatively low clinical use of vancomycin during the period following its introduction <ref name="[7]" />. Indeed, once the first large outbreaks of β-lactam resistant strains of bacteria such as MRSA appeared in the 80s - causing a marked increase in vancomycin usage - vancomycin resistant bacterial strains quickly appeared as well <ref name="[10]" /><ref name="[7]" />.
Two distinct forms of vancomycin resistance exist. The milder form of vancomycin resistance, exhibited for example by VISA (vancomycin intermediate staphylococcus aureus) strains, develops in patients undergoing prolonged vancomycin therapy. The prolonged exposure to vancomycin puts selective pressure on the pathogens. The treatment turns a heterogenous colony of bacteria with only a small subpopulation having a vancomycin MIC (minimum inhibitory concentration) greater than 2 µgmg/mLL, into a homogenous colony with a MIC of 8 µgmg/mLL. The resulting colony becomes very difficult to eradicate with vancomycin therapy <ref name="[12]">Gardete, S. & Tomasz, A. (2014). Mechanisms of vancomycin resistance in Staphylococcus aureus. ''The Journal of Clinical investigation, 124''(7), 2836-2840. [https://doi.org/10.1172/JCI68834 doi:10.1172/JCI68834]</ref>.
The second, more serious form of vancomycin resistance, demonstrated by bacterial strains such as VRSA (vancomycin resistant staphylococcus aureus), is not due to spontaneous mutations of pathogens upon continued exposure to the drug <ref name="[10]" />. Instead, pathogenic microorganisms appear have directly copied the defense mechanisms of the antibiotic producing actinomycetes. This defense mechanism is used by the actinomycetes to avoid suicide during antibiotic production <ref name="[10]" /><ref name="[7]" /><ref name="[14]">Binda, E., Marinelli, F., Marcone, G.L. (2014). Old and New Glycopeptide Antibiotics: Action and Resistance. ''Antibiotics, 3''(4), 572-594. [https://doi.org/10.3390/antibiotics3040572 doi:10.3390/antibiotics3040572]</ref>. Pathogens resistant to GPAs obtain resistance through plasmid-borne copies of transposons coding for genes named ''van'', which reprogram the biosynthesis of cell walls, replacing the D-Ala-D-Ala peptide terminus with a D-alanyl-D-lactate (D-Ala-D-Lac) terminus <ref name="[14]" /><ref name="[10]" /><ref name="[13]">Miller, W.R., Munita, J.M., Arias, C.A. (2014). Mechanisms of antibiotic resistance in enterococci. ''Expert Review of Anti-Infective Therapy, 12''(10), 1221-1236. [https://doi.org/10.1586/14787210.2014.956092 doi:10.1586/14787210.2014.956092]</ref>. This small change reduces the binding affinity of vancomycin to the target around a 1000-fold, resulting in a vancomycin MIC ≥ 100 µgmg/mL L making treatment with vancomycin impossible and effectively rendering the organism resistant <ref name="[10]" /><ref name="[7]" /><ref name="[13]" />.
== Medical Use and TDM ==
Vancomycin is a glycopeptide antibiotic used as a last resort to treat severe, life-threatening infections caused by multidrug-resistant gram-positive bacteria, such as methicillin-resistant ''Staphylococcus aureus'' (MRSA) <ref name="[14]" />. Vancomycin can be administered intravenously or orally. When taken orally, vancomycin is absorbed very poorly into the bloodstream <ref name="[3]" />. Therefore, oral intake is only used for infections within the gastrointestinal tract, such as diarrhea caused by ''Clostridium difficile'', and to treat enterocolitis caused by certain types of bacteria <ref name="[15]">PubMed Health (2017). Vancomycin (By mouth). Accessed on 17 October 2017, at ''https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0012602/?report=details''.</ref>. In all other cases vancomycin is administered intravenously <ref name="[16]">PubMed Health (2017). Vancomycin (By injection). Accessed on 17 October 2017, at ''https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0012603/?report=details''.</ref>. Care must be taken to not administer the drug too fast, as this may lead to the patient developing red man syndrome <ref name="[6]" />. Most hospital protocols recommended a minimum vancomycin infusion time of 60 minutes <ref name="[6]" />.
For patients with severe, deep-seated infections (including but not limited to meningitis, pneumonia osteomyelitis, endocarditis, bacteremia and prosthetic joint infection) a serum trough concentration of 15 to 20 µgmg/mL L is recommended <ref name="[17]">Consgrove, S.E., Avdic, E., Dzintars, K. & Smith, J. (2015). Antibiotic Guide. ''Johns Hopkins Medicine, The Johns Hopkins Hospital Antimicrobial Stewardship Program.''</ref><ref name="[18]">Drew, R.H. & Sakoulas, G. (2017). Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults. Accessed on 26 September 2017, at ''https://www.uptodate.com/contents/vancomycin-parenteral-dosing-monitoring-and-adverse-effects-in-adults.''</ref>. To achieve this concentration more rapidly an initial loading dose of 20-25 mg/kg is often given, followed by intermittent maintenance dosing of typically around 15-20 mg/kg every 8 to 12 hours <ref name="[17]" />. Patients with less severe infections (soft tissue infections) do not require a loading dose, and are started immediately on intermittent dosing with the aim of achieving a minimum serum trough concentration of 10-15 µgmg/mL L <ref name="[18]" />. Trough concentrations are measured as these constitute the most practical and accurate indicator for treatment effectiveness and toxicity. Peak levels are rarely measured and are not clinically relevant <ref name="[17]" />.
{| class="wikitable" style="margin-bottom:0"
|-
!Patients with deep-seated infections
|20 – 25 mg / kg|15 – 20 µgmg/mLL
|-
!Patients without severe infections
| -
|10 – 15 µgmg/mLL
|}<div style="margin-bottom:1em"><sub>''Table 1. Vancomycin dosing for different classes of patients with normal renal function <ref name="[17]" />.''</sub></div>
|iVancomycin
|20 μL
|3 - 100 μgmg/mLL
|CV <10%
|16 min.
|VANC3
|2 μL
|4 - 80 μgmg/mLL
|CV <11%
|10 min.
|Emit ® 2000 Vancomycin Assay
|2.4 μL
|2 - 50 μgmg/mLL
|CV <5%
|8-9 min.

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