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Assignment I, Summarization of Article

October 17, 2009
Link to Article JSTOR Link
The Impact of Novel Immunosuppressive Agents on Infections in Organ Transplant Recipients and the Interactions of These Agents with Antimicrobials
Introduction
Immunotherapy has come a long way in recent years with regards to organ transplants. Various immunosuppressants are now used in the treatment against t The rejection of organ transplants as well as decreasing any toxic side effects.
The article reviews immunosuppressents which are on the market now or in clinical trials.
Methods
Case studies and other clinical trial articles were searched using various key words. The manufactures of both MMF and rapamycin were contacted directly to gain any more revelent unpublished information.
MMF
MMF is produced from a derivative of the Penicillin mold, and is shown to reduce the amount of transplant rejections. It targets the lymphocytes and inhibits the production of purine.
The infection CMV was seen more so in patients receiving MMF after transplants than those whom took azathioprine. There were also increased cases of patients having gastrointestinal side effects because of treatment with MMF.
The way in which MMF induces CMV infection includes the depletion of guanosine triphostphate in the lymphocytes, which in turn decreases the proliferation.
In addition to CMV infection, MMF was seen to cause a type of herpes viral infection in patients having had renal and heart transplants.
In those having had a heart or liver transplant, there were increased incidents of Hepititis B and C infections. The MMF had no effect on the severity of the Hepetitis infection itself.
At concentrations lower than used to treat organ-tranplant patients, MMF is seen to be effective against HIV type 1. Using MMF in the treatment of HIV patients is being studied.
Unlike the cases where CMV infection occured from treatment with MMF, no patients were seen to develop the P.Carinii infection. This is mainly due to MMF's ability to inhibit one of the monophosphate groups in the P.carinii.
MMF is metabolized before treatment of the specific area of organ transplant. There was no difference in effectiveness in patients who were on dialysis compared to healthy patients.
There was no clinical significance seen in healthy patients when MMF was administered along with acyclovir.
There has been no reported interactions between MMF and other drugs including lactam antibiotics, antifungal agents, glycopeptides and other inhibitors.
Rapamycin
Rapamycin works by targeting mTOR, which inhibits the translation process of mRNA to DNA, needed for cell division. The cell cycle is halted because of this.
Rapamycin has been used in conjunction with cyclosporine in an effort to reduce the amount of CMV infection cases.
Herpes-zoster cases have also been seen in patients who have been treated with Rapamycin.
Rapamycin has the ability to inhibit fungal activity in in vitro studies. There are a wide range of fungi which Rapamycin acts against.
Because rapamycin is a substrate for cytochrome P-450 and P-glycoprotiens, metabolism rates may decrease causing the incidental increase in Rapamycin levels.
Rapamycin is just one derivative of many macrolide antibiotics. The various derivatives inhibit different cytochrome and glycoprotein groups.
Rifampin increases metabolism rates which have the ability to lower rapamycin levels in the body.
Other azole antifungal agents also inhibit cytochrome P-3A4 which may increase the levels of Rapamycin. Because of this, it is important to monitor Rapamycin levels if these agents are used in conjuction.
Everolimus
Everolimus is a derivative of Rapamycin with a shorter half-life. In cases where Everolimus was used in patients, only 3% contracted the CMV infection compared to those whom received MMF. Everolimus was also shown to have activity against the proliferation of tumors.
Monoclonal Antibodies
Caustic and fatal infections were seen to arise in patients treated with earlier monoclonal antibodies. In order to prevent this, antibodies working against IL-2R should be used as an effective immunosuppressive treatment.
Although basiliximab has not been seen to have any efficacy for immunosuppressive treatment in kidney transplant patients, it was shown to work against the proliferation of the CMV infection,
Furthermore, patients treated with basiliximab showed to have lower rates of Herpes related virus after transplant.
Basiliximab and the corresponding derivation daclizumab have not shown to have any effect on the HCV infection.
There has been no documented information regarding whether basiliximab or daclizumab have any effect on the prevention of fungal activity.
Conclusions
Immunosuppressive drugs are useful in treating major infections and preventing organ transplant rejection. In the future, immunosuppressive drugs may be able to treat infections at a highly specific location with minimal side effects.

Assignment II

Assignment III