Paul J. Deziel

Emergence of drug‐resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes

Abstract:  Background:  Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir‐resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug‐resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis.

Fluoride excess and periostitis in transplant patients receiving long-term voriconazole therapy.

BACKGROUND We describe a heart transplant patient with painful periostitis and exostoses who was receiving long-term therapy with voriconazole, which is a fluoride-containing medication. Elevated plasma and bone fluoride levels were identified. Discontinuation of voriconazole therapy led to improvement in pain and reduced fluoride and alkaline phosphatase levels. METHODS To determine whether voriconazole is a cause of fluoride excess, we measured plasma fluoride levels in 10 adult post-transplant patients who had received voriconazole for at least 6 months and 10 post-transplant patients who did not receive voriconazole. To assess the effect of renal insufficiency on fluoride levels in subjects receiving voriconazole, half were recruited on the basis of a serum creatinine level of ≥1.4 mg/dL on their most recent measurement, whereas the other 5 subjects receiving voriconazole had serum creatinine levels <1.4 mg/dL. All control subjects had serum creatinine levels of ≥1.4 mg/dL. Patients were excluded from the study if they received a fluorinated pharmaceutical other than voriconazole. RESULTS All subjects who received voriconazole had elevated plasma fluoride levels, and no subjects in the control group had elevated levels (14.32 μmol/L ± 6.41 vs 2.54 ± 0.67 μmol/L; P<.001). Renal function was not predictive of fluoride levels. Plasma fluoride levels remained significantly higher in the voriconazole group after adjusting for calcineurin inhibitor levels and doses. Half of the voriconazole group subjects had evidence of periostitis, including exostoses in 2 patients. Discontinuation of voriconazole therapy in patients with periostitis resulted in improvement of pain and a reduction in alkaline phosphatase and fluoride levels. CONCLUSIONS Voriconazole is associated with painful periostitis, exostoses, and fluoride excess in post-transplant patients with long-term voriconazole use.

Clinical predictors of relapse after treatment of primary gastrointestinal cytomegalovirus disease in solid organ transplant recipients.

Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R− SOT recipients with biopsy‐proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40–70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean ± SD, 33.8 ± 19.3 days) followed by valganciclovir (27.5 ± 13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6 ± 28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5–30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0–33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p = 0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse.

Phaeohyphomycosis due to Alternaria species in transplant recipients.

R.D. Boyce, P.J. Deziel, C.C. Otley, M.P. Wilhelm, A.J. Eid, N.L. Wengenack, R.R. Razonable. Phaeohyphomycosis due to Alternaria species in transplant recipients.
Transpl Infect Dis 2010: 12: 242–250. All rights reserved

The impact of invasive fungal diseases on survival after lung transplantation.

Arthurs SK, Eid AJ, Deziel PJ, Marshall WF, Cassivi SD, Walker RC, Razonable RR. The impact of invasive fungal diseases on survival after lung transplantation.
Clin Transplant 2010: 24: 341–348.

Donor-transmitted HTLV-1-associated myelopathy in a kidney transplant recipient--case report and literature review.

Clinical disease due to human T cell lymphotropic virus type 1 (HTLV‐1), a retrovirus endemic in certain regions of the world, is rarely reported after solid organ transplantation. In 2009, universal deceased donor organ screening for HTLV‐1 was discontinued in the United States. We report the first case of donor‐derived HTLV‐1‐associated myelopathy in a kidney transplant recipient from the United States. The patient, who was HTLV‐1‐seronegative prior to transplantation, likely acquired HTLV‐1 infection from a seropositive organ donor. In this era when screening of donors and recipients for HTLV infection is not mandatory, clinicians should be vigilant in recognizing the risk and potential occurrence of this donor‐derived infection in recipients with epidemiologic exposures.

Majocchi's granuloma in solid organ transplant recipients

F.A. Romero, P.J. Deziel, R.R. Razonable. Majocchis granuloma in solid organ transplant recipients.
Transpl Infect Dis 2011: 13: 424–432. All rights reserved

Disseminated coccidioidomycosis in a liver transplant recipient with negative serology: use of polymerase chain reaction.

Coccidioidomycosis has been previously described in recipients of solid organ transplantation, especially in patients who have lived in or have visited areas endemic for Coccidioides spp. We present a case of coccidioidomycosis in a liver transplant recipient with several unique aspects, including negative serology and positive polymerase chain reaction results. Liver Transpl 12:1290–1292, 2006.

Gordonia Bacteremia: A Case Series and Review of the Literature

ABSTRACT Gordonia species are ubiquitous aerobic actinomycetes that rarely cause infection in humans. We report the second known case of Gordonia otitidis catheter-related bacteremia in an immunocompromised patient and review four additional cases of Gordonia bacteremia seen at our institution over the past 14 years. In addition, the existing literature on Gordonia infections is reviewed.

Misidentification of Neosartorya pseudofischeri as Aspergillus fumigatus in a Lung Transplant Patient

ABSTRACT We present a case of disseminated Neosartorya pseudofischeri infection in a bilateral lung transplant patient with cystic fibrosis. The organism was originally misidentified from respiratory specimens as Aspergillus fumigatus using colonial and microscopic morphology. DNA sequencing subsequently identified the organism correctly as N. pseudofischeri.