John N. Greene

International Retrospective Analysis of 73 Cases of Invasive Fusariosis Treated with Voriconazole

ABSTRACT The outcomes for 73 invasive fusariosis patients treated with voriconazole were investigated. Patients with proven (n = 67) or probable (n = 6) infections were identified from the voriconazole clinical database (n = 39) and the French National Reference Center for Mycoses and Antifungals database (n = 34). Investigator-determined success was a complete or partial response. Survival was determined from day 1 of voriconazole therapy to the last day known alive. Patients were 2 to 79 years old (median, 43 years), and 66% were male. Identified Fusarium species (62%) were F. solani, F. moniliforme, F. proliferatum, and F. oxysporum. Underlying conditions analyzed included hematopoietic stem cell transplant (HSCT; 18%), hematologic malignancy (HM; 60%), chronic immunosuppression (CI; 12%), or other condition (OC; 10%). Infection sites were brain (5%), disseminated excluding brain (67%), lungs/sinus (15%), and other (12%). Most patients (64%) were or had recently been neutropenic (<500 cells/mm3). Therapy duration was 1 to 480 days (median, 57 days), with a 47% success rate. Baseline neutropenia impacted success adversely (P ≤ 0.03). Success varied by underlying condition (HSCT, 38%; HM, 45%; CI, 44%; OC, 71%) and infection site (brain, 0%; disseminated, 45%; other, 56%; lung/sinus, 64%) (P > 0.05). Combination therapy (13 patients) was no better than treatment with voriconazole alone. Overall, 59% of the patients died (49% died of fusariosis), and 90-day survival was 42%. Site of infection influenced survival (P = 0.02). Median survival (in days) by species was as follows: F. solani, 213; F. oxysporum, 112; Fusarium spp., 101; F. proliferatum, 84; F. moniliforme, 76. We conclude that voriconazole is a therapeutic option for invasive fusariosis.

Identification of an Emerging Pathogen, Mycobacterium massiliense, by rpoB Sequencing of Clinical Isolates Collected in the United States

ABSTRACT Mycobacterium massiliense is a rapidly growing mycobacterium that is indistinguishable from Mycobacterium chelonae/M. abscessus by partial 16S rRNA gene sequencing. We sequenced rpoB, sodA, and hsp65 genes from isolates previously identified as being M. chelonae/M. abscessus and identified M. massiliense from isolates from two patients with invasive disease representing the first reported cases in the United States.

Two cases of progressive multifocal leukoencephalopathy after allogeneic hematopoietic cell transplantation and a review of the literature

Progressive multifocal leukoencephalopathy (PML) is a rare subacute demyelinating disorder of the central nervous system (CNS) caused by the DNA JC human polyomavirus. In immunocompromised hosts, PML is caused by reactivation of a latent infection rather than de novo primary exposure. PML in the setting of hematopoietic cell transplantation (HCT) is exceedingly rare. PML should be considered in the differential diagnosis of HCT recipients, autologous or allogeneic, presenting with worsening of neurological symptoms, especially associated with post-transplant neurodegenerative findings. Although DNA polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) has emerged as a promising tool for detecting JC virus, a negative result does not rule out PML. Brain biopsy remains the most reliable and accurate method for diagnosing JC virus-associated PML. Presently, there is no universally effective antiviral therapy against JC virus and outcome is fatal in the majority of cases. We hereby describe two cases of PML developing after allogeneic HCT and provide a comprehensive review of the literature.

Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay®. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. × 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10–21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.

Disseminated Mycobacterium bovis after intravesicular bacillus calmette-Gu rin treatments for bladder cancer.

Transitional-cell carcinoma of the bladder is an aggressive and potentially fatal malignancy. In 1990, the US Food and Drug Administration approved the use of intravesicular bacillus CalmetteGuérin (BCG) for the treatment of superficial bladder cancer.1 BCG is a live, attenuated strain of Mycobacterium bovis (M. bovis) that has been used to treat transitional-cell carcinoma since 1976 and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease.2 The precise mechanism by which BCG acts is unknown, but a local granulomatous inflammation, centered on a T-cell–mediated immunity response, is thought to play a role.3 While the majority of patients tolerate BCG intravesicular treatments well, a number of adverse reactions (eg, fever, hematuria, dysuria, nausea, and malaise) have been reported.4,5 More serious complications include granulomatous prostatitis, pneumonitis, and hepatitis. We report a case of disseminated BCG infection causing pneumonitis that required corticosteroids and antitubercular therapy for cure.

Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment

Klebsiella producing carbapenemase is an emerging pathogen. We report transmission of this organism by contaminated endoscopic instruments. Quick identification of source, staff education, contact precautions, and emphasis on hand and environmental hygiene led to case control and prevention of outbreak.

Sirolimus for treatment of steroid-refractory acute graft-versus-host disease

Acute GVHD (aGVHD) is a major cause of morbidity and mortality in hematopoietic allograft recipients. The best therapy for patients failing to respond, or not tolerating, systemic glucocorticoids remains undefined. We evaluated the efficacy of sirolimus in 34 patients, median age of 49 (23–67) years, with steroid-refractory (n=31) or steroid-intolerant (n=3) aGVHD. aGVHD was diagnosed at a median of 34 (7–1042) days post allografting, and confirmed by biopsy in all cases. Initial aGVHD treatment consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1–255) days after glucocorticoid initiation. A sirolimus loading dose was administered to 19 (56%) of 34 patients, median 6 (3–8) mg, followed by maintenance of 1–2 mg/day to target therapeutic trough levels between 4 and 12 ng/ml. Overall response rate was 76%. Fifteen (44%) of 34 patients achieved CR, defined as complete resolution of aGVHD sustained for at least 1 month, after sirolimus initiation without additional immunosuppressive agents. CR was achieved in 11 (42%) of 31 steroid-refractory and 2 (67%) of 3 steroid-intolerant patients. Median OS after initiation of sirolimus was 5.6 months, and 1-year OS was 44% (95% CI: 27–60%). Sirolimus is effective in controlling steroid-refractory aGVHD.

Detection of airborne cytomegalovirus in hospital rooms of immuncompromised patients

Human cytomegalovirus (CMV) is a major pathogen in immunocompromised patients. Transmission in this population is known to occur by fomites, but the potential for airborne spread is unknown. In this study, air from the rooms of two immunosuppressed patients with CMV pneumonia and one patient with latent infection was filtered and examined by a polymerase chain reaction assay. CMV-DNA was easily detected in the rooms of the patients with pneumonia and a weak positive signal was detected in the room of the patient with latent CMV infection. This technique permits the detection of aerosolized CMV-DNA and could possibly be adapted to detect other airborne pathogens.

Infectious complications of cutaneous t-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is the most common primary lymphoma of the skin. As with most cancers, survival depends on the stage of disease. Infection is a common complication of CTCL, contributing significant morbidity and mortality. We report a patient with severe, generalized mycosis fungoides (MF) complicated by recurrent skin infections,and we review the infectious complications of patients with CTCL.

Mucormycosis in immunochallenged patients

Mucorales species are deadly opportunistic fungi with a rapidly invasive nature. A rare disease, mucormycosis is most commonly reported in patients with diabetes mellitus, because the favorable carbohydrate-rich environment allows the Mucorales fungi to flourish, especially in the setting of ketoacidosis. However, case reports over the past 20 years show that a growing number of cases of mucormycosis are occurring during treatment following bone marrow transplants (BMT) and hematological malignancies (HM) such as leukemia and lymphoma. This is due to the prolonged treatment of these patients with steroids and immunosuppressive agents. Liposomal amphotericin B treatment and posaconazole are two pharmacologic agents that seem to be effective against mucormycosis, but the inherently rapid onset and course of the disease, in conjunction with the difficulty in correctly identifying it, hinder prompt institution of appropriate antifungal therapy. This review of the literature discusses the clinical presentation, diagnosis, and treatment of mucormycosis among the BMT and HM populations.