Queen's School of Business Presentation
Issue link: http://invivo.uberflip.com/i/1501332
June 2023 10 A Case-Based Approach to CMV Management In this case, genotyping indicated the presence of a UL97 mutation, conferring resistance to ganciclovir and valganciclovir. Therapeutic options included an increased dose of ganciclovir, foscarnet, maribavir or cidofovir. Additionally, modification of immune suppression may be considered to increase endogenous immune response, based on individual risks and benefits. An increased dose ganciclovir (10 mg/kg BID) has been shown to be an effective therapy in the presence of a UL97 mutation, although it carries an increased risk of myelotoxicity. 7 Foscarnet, a non-competitive inhibitor of the pyrophosphate binding site on the viral DNA polymerase, is the recommended alternative. However, given its intravenous (IV) dosing requirement, potential electrolyte disturbances and renal toxicity, it is difficult to administer it on an outpatient basis, and it o›en requires hospital admission. 8 Maribavir is a novel antiviral that inhibits CMV DNA replication, encapsulation and nuclear egress of viral capsids. In a large, randomized clinical trial of patients with inadequate responses to standard of care therapy, maribavir showed an increased rate of viral clearance and improved clinical outcomes. 9 Cidofovir is a monophosphate nucleoside analog that interferes with DNA polymerase; however, given the potential for renal toxicity, its usage needs to be considered carefully, particularly in patients with ongoing renal gra› dysfunction. 10 Case 2 You are consulted in the case of a 70-year-old female with possible CMV disease with a complex past medical history. She has undergone post-deceased donor lung transplantation due to interstitial lung disease (ILD), with D+/R- CMV serostatus. She was initially managed with ATG and standard triple therapy and was administered six months of valganciclovir. At approximately one month post-transplant she presents with hypoxic respiratory failure and hemoptysis, with a cavitary lung lesion. The patient is intubated and sedated, and a bronchoscopy reveals aspergillus fumigatus; she is initiated on voriconazole. She improves, but then worsens with ongoing fevers. An endotracheal aspirate culture grows Pseudomonas aeruginosa, and the patient is initiated on piperacillin- tazobactam. However, a CMV viral load is also done, and returns at 100,000 IU/mL. She is initiated on ganciclovir. One week later, the patient's neutrophil count declines to 0.5 x 10 9 /L. She remains febrile. What are your next steps? Rationale CMV infection and disease during hospitalization can present complexities for solid organ transplant patients, not only in morbidity and mortality, but also with an increased risk of opportunistic infections and gra› dysfunction. Complications of pharmacotherapy in acutely ill patients add an additional layer of complexity. Patients with viremia during an acute hospitalization should be assessed regularly for signs of underlying disease, which o›en mimic other acute medical issues. Neutropenia associated with post-transplant CMV viremia has a complicated etiology that requires individualized assessment. In the context of this patient who remains critically ill, and has opportunistic infections associated with her immunosuppression, ongoing neutropenia increases the risk of ongoing opportunistic infections and impaired recovery. 11 There may be several factors contributing to this patient's condition. First, CMV infection may lead to ongoing neutropenia through direct bone marrow effects. 12 Second, the treatment, particularly valganciclovir and ganciclovir, carry a risk of myelosuppression. 13 Third, concomitant medications, such as mycophenolate and trimethoprim-sulfamethoxazole may also induce neutropenia. 14 Additionally, in a hospitalized patient, other causes of neutropenia may be present, such as concomitant medications and acute sepsis. Adjusting the patient's medications in this context is important but may carry risks. For example, reduction of antimetabolite therapy may be associated with an increased risk of rejection. In this case, initial management should consider the use of granulocyte colony stimulating factors (G-CSFs), which can lead to temporary reversal of neutropenia. 14 However, these should be administered with caution, as they can lead to immunologic and allergic side effects, as well as significant bone pain following administration. 15 Additionally, their positive effects may be temporary, and if there is ongoing myelosuppression, neutropenia may recur. Therapeutic options for CMV management include lowering the dose of ganciclovir, although there are concerns about inappropriate disease response and the development of resistance. 16 Foscarnet is an alternative option and may be appropriate to treat CMV without introducing the risk of neutropenia. However, in a critically ill patient, electrolyte disturbances and renal injury may worsen the underlying process. 8 Similarly, cidofovir may be a treatment alternative; however, the risk of acute renal dysfunction limits its use. 10 Maribavir may be a reasonable option for the reduction of CMV disease, considering its limited drug toxicity. 9