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End-organ cytomegalovirus (CMV) disease can be life threatening to solid organ transplant recipients. Diagnosis is often complicated by variation in amount of CMV DNA in plasma and the need for an invasive procedure to obtain a biopsy of the suspected affected organ, which can delay recognition and treatment. Several inflammatory cytokines are elevated in CMV disease, and the purpose of this study was to determine if they could be used to distinguish solid organ transplant recipients with CMV DNAemia alone from those with possible end-organ CMV disease. We found that regardless of pre-transplant CMV serostatus, plasma interleukin (IL)-18, tumor necrosis factor-α (TNF-α), and amount of CMV DNA in plasma were increased in possible end-organ CMV disease, with elevated IL-18 associated with increased odds of possible end-organ CMV disease even after adjusting for amount of CMV DNA. These findings highlight IL-18 and TNF-α as potential non-invasive markers of possible end-organ CMV disease regardless of transplanted organ or serostatus in solid organ transplant recipients.

Background Treatment of ganciclovir-resistant (GCV-R)/refractory cytomegalovirus (CMV) infections in blood/marrow transplant (BMT) and solid organ transplant (SOT) recipients remains suboptimal. Cidofovir (CDV), a nucleotide analogue with anti-CMV activity, is nephrotoxic and oculotoxic. Methods We retrospectively evaluated the outcomes of SOT and BMT patients with GCV-R/refractory CMV treated with CDV between 1/1/2008 and 12/31/2017. Data collected baseline demographics, CMV serostatus, clinical and virologic presentations and outcomes, UL97 and UL54 genotype mutations, drug toxicities, and cause of death. Descriptive statistics were used. Results 16 patients received CDV for treatment of CMV: six BMT and 10 SOT. Seven (47%) of the patients had high-risk donor/recipient serostatus: six (60%) SOT were D+/R-; one (16.7%) BMT was D-/R+. Median time to CMV DNAemia was 131 days post-transplant (IQR, 37.5-230.3). Proven tissue invasive disease was present in three patients (18.8%). Twelve (75%) had genotype testing; 10 (83.3%) of those had antiviral resistance mutations. While on CDV, six (37.5%) developed nephrotoxicity, and four (25%) developed uveitis (two had both uveitis and nephrotoxicity). Eight (50%) had failure to clear CMV DNAemia despite CDV treatment. Eight (50%) of the patients died; median time to death, after initiation of CDV, was 33.5 days [IQR22-988]. Conclusions In the absence of good therapeutic alternatives, CDV is used in GCV-R/refractory CMV infection. However, it is associated with a substantial risk of toxicity and failure to clear CMV DNAemia, highlighting the need for development of newer and less toxic therapies. The high mortality in this group of patients underscores the severity of illness in this population.