Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients.

OBJECTIVES: The most frequent adverse events associated with valganciclovir treatment are hematological disturbances such as neutropenia. However, the consequences of neutropenia are unknown. We investigated the clinical impact of neutropenia during CMV preemptive therapy and its relationship with the length of antiviral therapy. METHODS: An observational, prospective cohort of 67 solid organ transplant recipients receiving CMV preemptive therapy was studied. RESULTS: Severe neutropenia occurred in 21.8% of the patients at a median of three weeks after initiating antiviral therapy. No association was observed between neutropenia and infection risk in these patients. Liver transplant recipients had 6.7 fold increased risk of neutropenia during CMV therapy compared to kidney transplant recipients (p = 0.012). Patients who developed severe neutropenia received antiviral therapy a median of six days longer than patient who did not (p = 0.457). CONCLUSIONS: Despite the frequency of neutropenia during CMV preemptive therapy, the incidence of infections is not increased. Adjusting the length of preemptive therapy during the episodes of viremia may be recommended, especially in patients with concurrent risk factors for neutropenia such as liver recipients. Further trials are warranted to confirm the safety of this approach.

Antimicrobial and immunosuppressive drug interactions in solid organ transplant recipients.

Infections are frequent and can be severe in recipients of solid organ transplantation. Prevention and treatment are priority objectives of multidisciplinary transplant teams. Interactions between antimicrobials (indicated for prevention and therapy) and immunosuppressants (for preventing rejection) make treatment more complex than in the general population. Co-administration of immunosuppressants and antibiotics can cause harmful interactions, modifying the pharmacokinetic and pharmacodynamic characteristics of both groups of drugs. The loss of the transplanted organ due to reduced levels of immunosuppressants is a unique consequence of the often lethal interactions in this group of patients. By contrast, elevated levels of these drugs cause toxicity, and reduced concentrations of antimicrobial treatment fail to contain the infection. Azoles, rifabutin, protease inhibitors, non-nucleoside reverse transcriptase inhibitors and antimicrobial macrolides all interact with immunosuppressants. In this article, we review interactions between antibiotics and immunosuppressants in order to adopt the most appropriate clinical approach (dosage adjustments, close monitoring of plasma levels and organ function) and determine whether they can be used together with any measure of safety.

Antimicrobial and immunosuppressive drug interactions in solid organ transplant recipients

Las infecciones son frecuentes y más graves en receptores de trasplante de órgano sólido. La prevención y tratamiento es una prioridad objetiva de los equipos multidisciplinarios de trasplante. Las interacciones entre el antimicrobiano indicado para prevención y tratamiento y los inmunosupresores para prevenir el rechazo, hacen más complejo al tratamiento que en la población general. La coadministración de inmunosupresores y antibióticos puede causar interacciones perjudiciales, modificando las características farmacocinéticas y farmacodinámicas de ambos grupos de fármacos. La pérdida del órgano trasplantado por los niveles reducidos del inmunosupresor es una consecuencia excepcional de las interacciones en este grupo de pacientes, a menudo letal. Por el contrario, los niveles elevados de estos fármacos causan toxicidad y las concentraciones reducidas de antimicrobianos, fallo del tratamiento de la infección. Los azoles, la rifabutina, los inhibidores de la proteasa, los inhibidores no nucleósidos de la transcriptasa reversa y los antibióticos macrólidos son los fármacos que presentan más interacciones con los inmunosupresores. En este capí-tulo revisamos las interacciones entre los antibióticos y los inmunosupresores para, en consecuencia, adoptar la decisión clínica más conveniente: ajustar las dosis de los fármacos, realizar un control exhaustivo de los niveles plasmáticos o del funcionamiento del órgano o, por el contrario, si pueden ser utilizados con seguridad (AU)

Infections are frequent and can be severe in recipients of solid organ transplantation. Prevention and treatment are priority objectives of multidisciplinary transplant teams. Interactions between antimicrobials (indicated for prevention and therapy) and immunosuppressants (for preventing rejection) make treatment more complex than in the general population. Co-administration of immunosuppressants and antibiotics can cause harmful interactions, modifying the pharmacokinetic and pharmacodynamic characteristics of both groups of drugs. The loss of the transplanted organ due to reduced levels of immunosuppressants is a unique consequence of the often lethal interactions in this group of patients. By contrast, elevated levels of these drugs cause toxicity, and reduced concentrations of antimicrobial treatment fail to contain the infection. Azoles, rifabutin, protease inhibitors, non-nucleoside reverse transcriptase inhibitors and antimicrobial macrolides all interact with immunosuppressants. In this article, we review interactions between antibiotics and immunosuppressants in order to adopt the most appropriate clinical approach (dosage adjustments, close monitoring of plasma levels and organ function) and determine whether they can be used together with any measure of safety (AU)