Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) disease is the most common infectious complication after solid organ transplantation, frequently affecting the gastrointestinal (GI) tract. There are limited data on quantitative polymerase chain reaction (qPCR) for plasma CMV DNA as an adjunct diagnostic method for GI tract disease in kidney and liver transplant recipients. METHODS: We reviewed all records of adult kidney and liver transplant recipients with a GI tract biopsy and plasma CMV qPCR result within 15 days of biopsy during a 6.5-year period at our center. CMV GI tract disease was defined as histopathologic evidence of CMV on biopsy by immunohistochemistry or visualization of inclusion bodies. RESULTS: GI tract biopsy and qPCR results were available for 81 kidney and liver transplant recipients; 20 cases of confirmed CMV GI tract disease were identified. Overall, the sensitivity of qPCR for diagnosing CMV GI tract disease was 85% (95% confidence interval [CI], 61%-96%), and the specificity was 95% (95% CI, 85%-99%). For CMV-seronegative recipients (R(-)) with CMV-seropositive donors (D(+)), the sensitivity of qPCR was 100% (95% CI, 59%-99%), and the specificity was 80% (95% CI, 30%-99%). The lowest sensitivity was observed in CMV D(+)/R(+) cases (72.7%; 95% CI, 39%-93%). The mean plasma CMV copy number in patients with GI tract disease was 3.84 log10 (38 334 copies/mL). CONCLUSIONS: Plasma CMV qPCR had good sensitivity and excellent specificity for CMV GI tract disease in kidney and liver transplant recipients. Its sensitivity was 100% in CMV D(+)/R(-) cases but 72.7% in CMV D(+)/R(+) cases. This variation in assay performance according to host serostatus may reflect differences in disease pathogenesis.

Clostridium difficile infection after adult autologous stem cell transplantation: a multicenter study of epidemiology and risk factors.

We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto-HSCT) within the first year after HSCT in centers with variable epidemiology of hypertoxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto-HSCT recipients at Johns Hopkins Hospital (JHH) and Hôpital Maisonneuve-Rosemont (HMR) between January 2003 and December 2008. Despite center differences in the prevalence of NAP-1 strains during the study period (21% to 43% at JHH versus 80% to 84% in HMR), the 1-year incidence of CDI was similar in the 2 hospitals (6.2% at JHH versus 5.7% at HMR). The median time to infection was 11 days (interquartile range, 1 to 27 days). In case-control analyses, grade ≥2 mucositis (odds ratio [OR], 3.00; P = .02) and receipt of a fourth-generation cephalosporin (OR, 2.76; P = .04) were identified as predictors for CDI. Mucositis was the strongest predictor of risk for CDI in multivariate analysis (adjusted OR, 2.77; P = .03). CDI is a common and early complication of auto-HSCT. Treatment-related gastrointestinal mucosal damage, along with the potentially modifiable risk of antimicrobial exposure, influence the risk for CDI early after auto-HSCT.

Cunninghamella echinulata causing fatally invasive fungal sinusitis.

We report a fatal case of invasive fungal sinusitis caused by Cunninghamella echinulata in a febrile, neutropenic 15-year-old male with relapsing acute leukemia. The isolate was recovered from a nasal biopsy from the right middle meatus, and microscopic examination of the tissue revealed angioinvasion and necrosis. Human infection caused by this organism has not been well documented; however, this report alerts us to its life-threatening potential.

Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy.

This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (≥50 years; hazard ratio [HR]: 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series.

Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004-2008.

This analysis describes the epidemiology and outcomes of candidemia in patients enrolled in the Prospective Antifungal Therapy Alliance (PATH Alliance®) registry from 2004 to 2008. Overall, 4067 Candida isolates were identified from 3648 patients. The most common Candida spp. were C. albicans (42.1%), C. glabrata (26.7%), C. parapsilosis (15.9%), C. tropicalis (8.7%), and C. krusei (3.4%). The proportion of candidemia caused by non-albicans Candida spp. (57.9%) was higher than that caused by C. albicans (42.1%). Infections with C. albicans were most common in neonatal intensive care unit (54.8%). In total, 3342 patients received antifungal therapy; fluconazole (66.0%) and echinocandins (50.5%) were most frequently administered. The 90-day survival rate for all patients was 61.3%. Among the most common Candida spp., the highest 90-day survival rate was observed for C. parapsilosis (70.0%) and the lowest for C. krusei (53.6%). In conclusion, this study expands the current knowledge of the epidemiology and outcomes of candidemia.

The PATH (Prospective Antifungal Therapy) Alliance® registry and invasive fungal infections: update 2012.

The Prospective Antifungal Therapy Alliance (PATH Alliance®) performed prospective surveillance of invasive fungal infections (IFIs) among patients hospitalized at 25 medical centers in North America between 2004 and 2008, collecting information on the epidemiology, diagnosis, treatment, and mortality rates of IFIs. In total, 7526 IFIs were identified in 6845 patients. Candida spp. (73.4%) were the most common pathogens, followed by Aspergillus spp. (13.3%), and other yeasts (6.2%). Culture was the most frequently used diagnostic test in the majority of IFI categories. Most patients with invasive candidiasis were treated with fluconazole (48.3%) and the echinocandins (34.0%), while voriconazole (45.5%) was the main antifungal agent for invasive aspergillosis. The 12-week survival rate ranged from 37.5% for hematopoietic stem cell transplant recipients to ~75.0% for those with HIV/AIDS. In summary, the findings of the PATH Alliance® registry provide a better understanding of the epidemiology of a vast variety and large numbers of IFIs.

Diagnostic and therapeutic challenges in a liver transplant recipient with central nervous system invasive aspergillosis.

This is a case report of central nervous system (CNS) invasive aspergillosis (IA) in a liver transplant recipient, which illustrates the utility of enzyme-based diagnostic tools for the timely and accurate diagnosis of IA, the treatment challenges and poor outcomes associated with CNS IA in liver transplant recipients.

An outbreak of human parainfluenza virus 3 infection in an outpatient hematopoietic stem cell transplantation clinic.

BACKGROUND: Parainfluenza viruses cause respiratory tract infections in adults and children, with peak activity during the spring and summer months. Human parainfluenza virus type 3 (hPIV-3) can contribute to significant morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Automated surveillance software was used to identify an hPIV-3 outbreak in an HSCT clinic. Active surveillance for respiratory illness and infection control measures were instituted. A retrospective molecular investigation of outbreak viral strains was performed by direct sequencing. RESULTS: Twelve of 196 HSCT recipients attending the clinic during the outbreak period had hPIV-3; one of these patients died. Sequencing demonstrated highly related strains in 9 of 10 patients studied. Despite the ongoing presence of hPIV-3 outside the inpatient/outpatient care continuum clinic, only 2 cases were observed after institution of respiratory season infection control measures. CONCLUSIONS: This investigation demonstrates the utility of surveillance software in the identification of respiratory virus outbreaks and the importance of rapid implementation of infection control/prevention measures for containment of outbreaks.

Epidemiology and outcomes of Clostridium difficile infections in hematopoietic stem cell transplant recipients.

Background. Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population. Methods. We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results. The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n = 999). The median time to diagnosis of CDI was short among both autologous and allogeneic HSCT recipients (6.5 days and 33 days, respectively). Risk factors for CDI in allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54-12.84; P = .006). There was a strong relationship between early CDI and subsequent development of gastrointestinal tract GVHD in the year following allogeneic HSCT (P < .001). Gastrointestinal GVHD was also strongly associated with an increased risk for recurrent CDI (AOR, 4.23 [95% CI, 1.20-14.86]; P = .02). Conclusions. These results highlight the high incidence and early timing of CDI after HSCT. Early timing, coupled with the noted risk of pretransplant chemotherapy, suggests that the natural history of disease in some patients may involve colonization prior to HSCT. A potentially important interplay between CDI and GVHD involving the gastrointestinal tract was observed.

Administration of voriconazole in patients with renal dysfunction.

BACKGROUND: The intravenous use of voriconazole requires coadministration with sulphobutylether-ß-cyclodextrin, which may accumulate in patients with impaired renal function. METHODS: All adult patients treated with the same formulation of voriconazole for a minimum of 3 consecutive days were included. Renal function was assessed based on the creatinine level and the calculated creatinine clearance (CrCl). Change in renal function was calculated on days 3, 7, and end of treatment (EOT) and was defined based on the RIFLE criteria. RESULTS: Among 166 patients in whom baseline renal function was assessed, 42 (25.3%) had a CrCl <50 mL/min and received intravenous voriconazole, 77 (46.4%) had a CrCl ≥50 mL/min and received intravenous voriconazole, and 47 (28.3%) had a CrCl <50 mL/min and were treated with oral voriconazole. Renal function changed on days 3, 7, and EOT in 19 (11.4%), 14 (8.4%), and 28 (16.9%) patients, respectively. Multivariate analyses identified significant predictors of renal dysfunction: (1) day 3, hematologic malignancy (odds ratio [OR], 5.09, P = .01), fluconazole use within 30 days prior to voriconazole (OR, 6.21; P = .008), coadministration of penicillins (OR, 6.12; P = .03), and immunosuppressants (OR, 7.00; P = .002); (2) day 7, baseline liver impairment (OR, 5.30; P value = .004); (3) EOT, administration of penicillins (OR, 2.39; P = .04). CONCLUSIONS: Voriconazole route of administration and baseline renal function were not predictors of worsening renal dysfunction on days 3, 7, and EOT. Underlying disease, baseline liver impairment, and concomitant administration of other drugs (eg, penicillins, fluoroquinolones, immunosuppressants) were the strongest predictors of renal dysfunction.

Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections.

There has been an increase in the number of patients susceptible to invasive fungal infections (IFIs) leading to a greater need for effective, well tolerated, and easily administered antifungal agents. The advent of triazoles has revolutionized the care of patients requiring treatment or prophylaxis for IFIs. However, triazoles have been associated with a number of adverse events and significant drug-drug interactions. While commonly used, physicians and patients should be aware of the distinct properties of these agents in order to ensure that patients are optimally treated with the least amount of toxicity possible. Clinicians should have a full understanding of the basic pharmacokinetics, absorption, and bioavailability of triazoles. Moreover, knowledge of the drug-drug interactions and potential toxicities of each agent is critical prior to administering a triazole. Careful history taking, thorough review of the patient's medication list, and detailed discussion with the patients and their families about the efficacy, safety, and tolerability of these agents should be performed. Clinicians treating patients with triazoles should closely follow them, monitor pertinent laboratory tests, and consider measuring drug levels as needed. This article will review the basic pharmacokinetic properties and most frequently encountered adverse events and pitfalls associated with triazoles in clinical practice.

Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry.

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P=.002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. CONCLUSIONS: The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.

Initial treatment and outcome of Candida glabrata versus Candida albicans bloodstream infection.

Candida glabrata is a common cause of bloodstream infection (BSI) and exhibits decreased susceptibility to fluconazole. We sought to determine whether patients with C. glabrata infection were at increased risk of inappropriate initial therapy and mortality compared with the more fluconazole-susceptible species Candida albicans by performing a matched case-control study using the Prospective Antifungal Therapy Alliance registry of invasive fungal infections. C. glabrata BSI patients were matched to those with C. albicans BSI by age, sex, and underlying illness after screening all C. glabrata patients entered into the registry from March 2004 through September 2007. Of 161 patients with C. glabrata BSI included and matched to 161 C. albicans patients, those with C. glabrata were less likely to receive an adequate dose of fluconazole as initial therapy (12% versus 52%, P < 0.05) and more likely to receive an echinocandin (44% versus 26%, P < 0.05) or inadequately dosed fluconazole (32% versus 8%, P < 0.05) as initial therapy. Although time to initiation of therapy did not differ by species (P = 0.2), time to receipt of adequate therapy was longer for those with C. glabrata BSI (P < 0.001). Overall, C. glabrata patients were more likely to receive inadequate initial therapy (34% versus 11%, P < 0.05), but 4-week mortality was no different between groups (30% for C. glabrata versus 29% for C. albicans, P = 0.80). We found hematologic malignancy, age greater than 60, the presence of a central venous catheter at diagnosis, mechanical ventilation, and dialysis dependence to be independent predictors of 4-week mortality. The lack of difference in mortality between species may reflect the overriding importance of host variables and/or a difference in virulence by species: further study is needed to investigate these hypotheses.

Epidemiology and outcome of multiple-species candidemia at a tertiary care center between 2004 and 2007.

The incidence of multiple-species candidemia (MSC) among cases of candidemia ranges between 2.8% and 8.0%. We sought to study the epidemiology and outcome of MSC at a tertiary care center. A retrospective analysis of MSC episodes occurring between 2004 and 2007 was performed. MSC was defined as > or =2 different Candida spp. growing concomitantly within the same blood culture bottle or within 72 h of each other. Information on demographics, comorbidities, antifungal use, and survival was collected. Forty MSC patients with 81 Candida isolates were identified. Non-albicans Candida spp. (54 of 81 isolates, 66.7%) were more frequently identified. The most common combinations observed were Candida albicans/Candida glabrata (15 of 40 patients, 37.5%), C. albicans/Candida parapsilosis (8, 20.0%), and C. glabrata/Candida krusei (5, 12.5%). The overall crude 4- and 12- week mortality, excluding patients lost to follow-up, was 41.9% and 66.7%, respectively. In this contemporary sampling of patients with MSC, the combination of C. albicans/C. glabrata was most frequently observed and mortality was high.

Aspergillus osteomyelitis: review of 12 cases identified by the Prospective Antifungal Therapy Alliance registry.

A review of 12 patients with proven Aspergillus osteomyelitis was undertaken between July 2004 and October 2007. Aspergillus fumigatus was most commonly identified (n = 9). Voriconazole was commonly administered (11/12; 91.7%), and 9 (75.0%) underwent surgery. Seven (58.3%) responded to treatment, and 12-week mortality was 25.0% (3/12). Survival was improved with surgical intervention (P = 0.05).

Peripheral subcutaneous stimulation for the treatment of intractable postherpetic neuralgia: two case reports and literature review.

Postherpetic neuralgia (PHN) is a common cause of chronic pain in the elderly. Antidepressants, anticonvulsants, and opioids may reduce discomfort in many patients, while others have pain intractable to all forms of therapy. We present a novel treatment approach for intractable PHN utilizing percutaneous peripheral nerve stimulation. Two cases are described in which an 80-year-old man and a 67-year-old woman with intractable PHN, lasting 2 and 10 years, respectively, were effectively treated with implantation of two octapolar leads in the lateral thoracic region. These cases suggest that peripheral nerve stimulation may offer an alternative treatment option for intractable pain associated with PHN especially in the elderly where treatment options are limited because of existing comorbidities.

Candidemia in the 21st century.

The 21st century has brought forth vast innovations in the healthcare field. The availability and use of aggressive chemotherapeutic and immunosuppressive agents as well as broad-spectrum antibacterial agents has created a large population of patients who are at increased risk of acquiring infections with fungal organisms, especially Candida species. This review will focus on the changing epidemiology of candidal bloodstream infections, its impact on healthcare and new advances in the diagnosis and treatment of candidemia.

Presentation of the PATH Alliance registry for prospective data collection and analysis of the epidemiology, therapy, and outcomes of invasive fungal infections.

Randomized clinical trials for patients with invasive fungal infections (IFIs) are often limited or precluded, necessitating alternate sources of information. The Prospective Antifungal Therapy Alliance (PATH Alliance) is a registry that collects data on patients with IFIs at medical centers in North America. Patients with a diagnosis of proven or probable IFI are enrolled and followed prospectively for 12 weeks. Using a Web-based electronic data capture and reporting system, the registry collects anonymous data to address end points in epidemiology, diagnosis, treatment, and outcome of IFIs. As of October 2006, 1892 IFIs were observed in 1710 patients enrolled at 22 sites. The most commonly encountered IFIs were caused by Candida spp. (73.0%), presenting predominantly as candidemia, followed by Aspergillus spp. (14.8%). A small number of IFIs with uncommon and emerging moulds were observed. Culture remains the main diagnostic tool for most IFIs (91.8%). Antifungal agent choice depended on the fungal species isolated, with fluconazole being the most frequently administered agent (58.2%). The overall crude 12-week mortality, excluding the patients lost to follow-up, was 43.9%. PATH Alliance is a network of medical institutions gathering significant information about IFIs in North America. Significant trends and treatment practices concerning yeasts and moulds were observed. As enrollment continues, additional data will be analyzed and published, which will provide valuable information concerning the epidemiology, therapy, and outcomes of IFIs.

Rhodotorula mucilaginosa catheter-related fungemia in a patient with sickle cell disease: case presentation and literature review.

Rhodotorula mucilaginosa (formerly Rhodotorula rubra) is a ubiquitous, environmental, urease-positive yeast that does not ferment sugars and can assimilate various carbohydrates. Characterized by the salmon-pink to coral-red color of its colonies, Rhodotorula mucilaginosa can disseminate and cause significant disease. We present a case of sustained Rhodotorula mucilaginosa catheter-related fungemia in a patient with sickle cell anemia who refused removal of the implanted port. The patient remained clinically stable, with blood cultures persistently growing Rhodotorula mucilaginosa, despite appropriate antifungal therapy. An extensive literature review revealed a wide range of clinical manifestations in immunocompromised patients. Susceptibility patterns to different antifungal agents and therapeutic considerations are thoroughly discussed. Rhodotorula mucilaginosa can be a significant, recalcitrant pathogen in immunocompromised patients and prompt treatment should be instituted.