Cystic Fibrosis Patients May Experience Anti-Viral Drug Resistance After Lung Transplantation

Ana Pamplona, PhD avatar

by Ana Pamplona, PhD |

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CF lung transplant viral drug resistance

CF lung transplant viral drug resistanceLung transplantation patients who are treated with immune-suppressing drugs after surgery to prevent rejection of the lung are susceptible to contracting life-threatening viruses such as cytomegalovirus (CMV). In order to protect against this, lung transplant patients are normally treated with an anti-viral drug called ganciclovir, which decreases mortality caused by viruses from 34% to 3- 6% in patients.

A recent study entitled “Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients” was published in the journal Transplant Infectious Disease by Dr. James Gagermeier, first author of the study. Dr. Gagermeier, along with colleagues from Loyola University Medical Center, found that resistance against ganciclovir seems to occur more often in cystic fibrosis patients. The authors found lower levels of the ganciclovir in circulation in patients with cystic fibrosis, permitting continuous replication of the virus. This increases the probability of mutations appearing that favor the development of drug resistance.

Dr. Gagermeier and colleagues analyzed the clinical reports of 51 lung transplant patients from Loyola University Medical Center,  21 of whom had CMV infection. The response to ganciclovir was variable with the infected lung transplant patients, among which 5 patients had very low levels of ganciclovir not responding to the drug and had drug-resistant strains of the CMV virus. Four of the five patients had cystic fibrosis. Cystic fibrosis patients do not possess the pancreatic enzymes that facilitate absorption of food and therapeutic drugs, and these patients also metabolize the drugs very quickly.

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Dr. James Gagermeier stated that therapeutic levels of ganciclovir should be controlled in the blood circulation of cystic fibrosis patients.

The authors recognize that the study has some limitations since is a retrospective study with a small number of patients, and the patient agreement with antiviral drugs was not systematically well evaluated. The poor antiviral drug fulfillment may have contributed to CMV infection and/or resistance to ganciclovir. Notably, a genetic analysis was not done on all CMV infected patients and thus the cases of resistance against ganciclovir may not have been detected.