This article is mainly discussing on hospital acquired infection (example: abdominal infection ) caused by methicillin resistant staphylococcus aureus (MRSA) based on trigger one of my PBL in IMU. The aspect I have chosen for discussion is treatments and drugs.
The treatments involve are pharmacological treatment and non-pharmacological treatment. In pharmacological treatment the drugs involve are vancomycin ,linezolid, and telavancin. The non-pharmacological treatment involve are surgery as well as natural supplement for example, manuka honey, andrographic and garlic. I will discuss mainly on the classes of drugs, mechanism of action ,dosage and route of administration as well as some drug -drug interaction and side effects.
Vancomycin is a kind of tricyclic glycopeptide. It serves as a bactericidal antibiotics .It works by inhibiting the cell wall synthesis of bacterial. It is the first line drug for hospital acquired MRSA infection, perhaps it is only effective against gram positive bacterial. In normal situation, the glycosidic bonds and intercross bridge of old bacterial peptidoglycan are broken down to formed gaps. These gaps allow newly formed peptidoglycan layer to move out from cytoplasm into the outer surface of bacterial cell wall. If there is no drug interference transglycosidase will allow glycosidic bond between N-acetylglucosamine(NAG) and N-acetyltalosaminuronic(NAM) acid of old peptidoglycan to be reformed and that of new peptidoglycan also formed ,besides that the transpeptidase enzyme will allow peptide cross bridge to be formed between the NAM pentapeptides side chains of two adjacent peptidoglycans. These cross bridges between different layers of peptidoglycan provide the strength to the bacterial cell wall. If vancomycin is applied, it will bind to the pentapeptides of peptidoglycan monomers. This will prevent the action of both enzyme transglycosidase and transpeptidase ,as a result the broken glycosidic bond can not be reformed while new glycosideic bond fail to be formed. Besides that the intercross bridge between pentapeptides side chains also can not be formed. When the autolysins keep breaking the “old bonds” while the “new bonds” of peptidoglycan failed to formed, the cell wall will eventually be broken down and this bacterial lysed and killed.
Since vancomycin structure does not have beta lactam ring and therefore it is not affected or resisted by beta lactamase of MRSA. Vancomycin is only effective via intravenous route. Oral administration is not suitable because it is not well absorbed after oral administration. Oral administration is only given for intraluminal gastrointestinal infection. Vancomycin does not cross blood brain barrier and does not penetrate bone, so it has no serious side effect on central nervous system and bone .But it does possess side effect like red man syndrome caused by histamine released. This can be prevented by limiting the infusion rate, this can also prevent severe inflammation at the site of infusion. Besides that ototoxicity and nephrotoxicity are also reported. So dosage adjustment is needed for renal insufficiency patient. This antibiotic is excreted mainly via urine excretion. It may result in teratogenicity because it can cross the placenta to foetus of pregnant woman. The recommended intravenous dose of vancomycin for hospital acquired MRSA infection in adult is 30mg/kg/day in 2 divided doses. For children the recommended intravenous dose is 40mg/kg/day in 4 divided doses. The duration of treatment depends on the severity of infection but should not exceeds 10days to prevent kidney failure and toxicity. Vancomycin can interact with other drugs like furosemide, this interaction can lead to hypokalaemia and cardiac arrest.
The next drug which is effective against hospital acquired MRSA infection is linezolid. Linezolid is an oxazolidinones drug with heterocyclic ketone. It can be classified under protein inhibitor group of antibiotic. Linezolid will prevent translation to be carried out by bacterial. This will stop the growth and reproduction of bacterial like MRSA. Some scholar discovered that despite its’ bacteriostatic activity, linezolid showed some bactericidal activity in vivo, this is because it inhibits the production of toxins produced by bacterial, it also have pro-antibiotic effect ,this is because its’ antibacterial effect remains for 4hours even after the discontinue usage of it. No evidence shows that it is effective against gram negative bacterial. Linezolid inhibits the translation of essential protein of bacterial by binding to the 50s ribosomal subunit .This will prevent it complex with the 30s ribosomal subunit which already pre-bind with the synthesized mRNA. Therefore, essential protein translation fail to occur. The growth and reproduction of bacterial are inhibited, bacterial population stop growing and eventually declined. It is available in oral form and intravenous form. For adult intravenous route it is recommended to give 600mg every 12 hours or 600mg twice per day for oral route. For children the recommended dose for intravenous and oral route are both 10mg/kg every12 hours ususally the duration of treatment is over a period of 10 to 28 days. The possible side effect of linezolid is. Vancomycin oral bioavailability is almost 100%. Its’ plasma protein binding is low and it is distributed to almost all body tissue including the brain (low amount) except white adipose tissue and bone tissue. It is mostly distributed to lower respiratory tract(sometime the level in it is higher than that in blood plasma), so it is best choice of drug to fight MRSA infection in lungs, example pneumonia. The adverse drug effect of linezolid is nausea ,vomiting, lost of taste perception and constipation. Linezoid is a kind of monoamine oxidase inhibitor should not be used concomitantly with other MAOIs and serotonin, this is to prevent serotonin toxicity and hypertension.
Telavancin is a new type rapid bacteriacidal antibiotic effective against hospital aquired-MRSA infection. It is a modified form of vancomycin with an additional lipophilic and hydrophilic side chain. It is also named as lipoglycopeptide drug. It has dual mechanism in fighting MRSA. The first mechanism is to inhibit bacterial cell wall formation just like what vancomycin done. The second mechanism is to dissipate the cell membrane potential(cell membrane no longer selective) and increases the membrane permeability. These caused the leakage of cellular materials like ATP and potassium ions. The dual mechanisms and lipophilic side group provide a faster onset of bactericidal effect than vancomycin. Telavancin is also used to fight against vancomycin resistant bacterial. Televancin is usually administered via intravenous route. The recommended dose for adult is 10mg/kg once every 24 hours for 7 to 14 days. This drug is not suitable for children due to the weaker physiology of children and there is no enough study of the safeness of telavancin on children. The adverse drug effects are constipation, lost of taste sensation, nausea and vomiting. If used together with moxifloxacin or sulfamethoxazole it may causes arrhythmias(prolong the QT interval).
The non -pharmacological treatments include surgery as well as natural supplement for example, manuka honey, andrographic and garlic. The culprit bacterias can be drained out of body via surgery and the pus also can be removed the same way. Manuka honey is produced by bees from nectar of manuka tree in New Zealand. It is used in wound care product. It can reverse the MRSA resistance, making penicillin antibiotic to be effective again. This bees used glucose oxidase enzyme in the saliva to convert nectar of manuka flower to manuka honey. This honey consist strong antibacterial agents which are effective against MRSA infection. These agents include unique manuka factors (UMF) and hydrogen peroxide. This UMF kill MRSA bacterials by destroying the proteins FaB 1 of MRSA bacterials, these proteins are needed for biosynthesis of fatty acids and for MRSA cell integrity. On the other hands, hydrogen peroxide will produce free oxygen radicals to bind to bacterial macromolecules like DNA, inhibiting the growth and reproduction of MRSA bacterial. It can penetrate the deep tissue ,treating deep tissue infection. It can be applied topically or orally. Andrographics can treat and prevent MRSA infection by boosting up body immune system. This is because it caused the increased of CD4 lymphocytes cell counts, this in turn rises the production of T cell (natural killer) and B cells(antibodies production). It also can relief the pain and inflammation at the site of infection. It can also be used to treat virus infection. Garlic also can be used to treat and prevent MRSA infection due to its’ antibacterial property. But blood thinning can be resulted upon prolong use of it , so it is not suitable to be used together with other blood thinning agent like aspirin and warfarin.
These are the treatments for hospital acquired or nosocomial MRSA infection.
:D
REFERENCES
Drug benefits books
http://en.wikipedia.org/wiki/Linezolid
http://www.globalrph.com/linezolid_dilution.htm
http://www.drugs.com/drug-interactions/bactrim-with-telavancin-2128-1386-3173-0.html
No comments:
Post a Comment