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!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"
!Target group
!Loading Dose
|-
!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>
There is large interpatient variability in vancomycin pharmacokinetics <ref name="[19]">Carter, B.L., Damer, M.K., Walroth, T.A., Buening, N.R., Foster, D.R. (2015). A systematic Review of Vancomycin Dosing and Monitoring in Burn Patients. ''Journal of Burn Care & Research, 36'', 641-650. [https://doi.org/10.1097/BCR.0000000000000191 doi:10.1097/BCR.0000000000000191]</ref>. The rate of clearance of vancomycin depends on the following factors; pathogen susceptibility to the drug, disease severity, the site of the infection, patient weight, age, gender and renal function <ref name="[18]" />. As vancomycin is largely cleared through the kidneys, the effect of renal function is especially great. Groups of patients demonstrating rapid clearance, such as young children with naturally high renal function and burn patients, require significantly more frequent dosing than patients with normal renal function to achieve the same target trough concentrations <ref name="[17]" /><ref name="[18]" /><ref name="[19]" />. In contrast, patients with impaired renal function may require dose reductions or extended dosing intervals in order to stay within the therapeutic range <ref name="[17]" /><ref name="[18]" />.
The SensUs competition wants to stimulate the development of molecular biosensing devices, which are small devices that can be used at the bedside of patients or even at home. Currently no handheld or table-top point-of-care devices for detecting vancomycin are available on the market. The devices listed below in Table 2 are all large instruments which can only be found in laboratory environments.
{| class="wikitable" style="margin-bottom:0"
!Company
!Product
|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.
|}<div style="margin-bottom:1em"><sub>''Table 2: Selection of currently available systems for measuring vancomycin.''</sub></div>
All products in Table 2 make use of enzyme immunoassays to detect vancomycin in blood plasma or serum, these are explained in more detail in the next section. Almost all plasma stabilising anticoagulants are compatible with the assays - EDTA K2 or K3, Li -heparin, etc. - as vancomycin does not react with any of these reagents <ref name="[24]" /><ref name="[25]" /><ref name="[26]" />.
The cost of running a single vancomycin assay on the Abbott Architect is €3.50 <ref name="[24]" /><ref name=”[40]”>This list price was received by email from Abbott, The Netherlands.</ref>.
== Past, Present and Future Sensing Methods ==
