Anil A. Panackal

Clinical Significance of Azole Antifungal Drug Cross-Resistance in Candida glabrata

ABSTRACT Candida glabrata, which can become resistant to fluconazole, is a common cause of bloodstream infection. This study was performed to determine the significance of cross-resistance to new azole drugs among C. glabrata isolates recovered as a cause of infection in azole-treated hematopoietic stem cell transplant (HSCT) recipients. Seven cases of invasive candidiasis caused by C. glabrata occurred in HSCT recipients who were receiving azole therapy between January 2000 and December 2004 in our institution. Case characteristics were ascertained. Sequential colonizing and invasive isolates were examined to determine susceptibilities to fluconazole, itraconazole, and voriconazole, and molecular relatedness by restriction fragment length polymorphism (RFLP) analysis. Twenty-three C. glabrata isolates were recovered from 4 patients who developed candidemia while receiving fluconazole and three patients who developed candidemia while receiving voriconazole. The mode MICs of fluconazole, itraconazole, and voriconazole for these isolates were ≥64 μg/ml (range, 4 to ≥64 μg/ml), 2 μg/ml (range, 0.25 to ≥16 μg/ml), and 1 μg/ml (range, 0.03 to ≥16 μg/ml), respectively. Kendall tau b correlation coefficients demonstrated significant associations between the MICs of voriconazole with fluconazole (P = 0.005) and itraconazole (P = 0.008). Colonizing and invasive isolates exhibiting variable susceptibilities had similar RFLP patterns. These observations suggest that C. glabrata exhibits considerable clinically significant cross-resistance between older azole drugs (fluconazole and itraconazole) and voriconazole. Caution is advised when considering voriconazole therapy for C. glabrata candidemia that occurs in patients with extensive prior azole drug exposure.

Automatic Electronic Laboratory-Based Reporting of Notifiable Infectious Diseases

Electronic laboratory-based reporting, developed by the University of Pittsburgh Medical Center (UPMC) Health System, was evaluated to determine if it could be integrated into the conventional paper-based reporting system. We reviewed reports of 10 infectious diseases from 8 UPMC hospitals that reported to the Allegheny County Health Department in southwestern Pennsylvania during January 1–November 26, 2000. Electronic reports were received a median of 4 days earlier than conventional reports. The completeness of reporting was 74% (95% confidence interval [CI] 66% to 81%) for the electronic laboratory-based reporting and 65% (95% CI 57% to 73%) for the conventional paper-based reporting system (p>0.05). Most reports (88%) missed by electronic laboratory-based reporting were caused by using free text. Automatic reporting was more rapid and as complete as conventional reporting. Using standardized coding and minimizing free text usage will increase the completeness of electronic laboratory-based reporting.

Fungal Infections among Returning Travelers

Endemic mycoses, such as histoplasmosis, coccidioidomycosis, and penicilliosis, have emerged as important health threats among travelers to regions of the world where these infections are endemic. Travelers have developed fungal infections as a result of a wide range of recreational and work activities, many of which have involved well-recognized risk factors for these diseases. In some instances, infections have been acquired during short trips, whereas, in other instances, infection has been acquired during a longer period of residence in an area where the infection is endemic. Travelers need to be made aware of the risks of acquiring mycotic diseases when visiting such regions. Health care providers need to consider these infections in their differential diagnosis among returning travelers with respiratory illness and should be familiar with the treatment and prevention of these diseases.

Geoclimatic Influences on Invasive Aspergillosis after Hematopoietic Stem Cell Transplantation

BACKGROUND Aspergillus species are ubiquitous. We hypothesized that climatic variables that affect airborne mold counts affect the incidence of invasive aspergillosis (IA). METHODS Patients who received hematopoietic stem cell transplants (HSCTs) in geographically and climatically diverse regions (Seattle, WA, and Houston, TX) were examined. Cumulative incidence function, Kaplan-Meier analysis, and Cox proportional hazards regression were performed to examine the association between IA and season. Poisson regression analysis was performed to evaluate the seasonal patterns in IA rates and association with spore counts and climate. RESULTS In Seattle, the 3-month incidence of IA was 4.6% (5.7% in allograft recipients and 0.8% in autograft recipients). During the 10-year study period, there was a decrease in the incidence of IA among allogeneic HSCT recipients, corresponding to decreased risks during the nonsummer months; receipt of HSCTs during the summer months was associated with an increased hazard for IA (hazard ratio, 1.87; 95% confidence interval, 1.25-2.81) after adjustment for other known risks. The person-month IA rate in Seattle was positively associated with environmental spore counts, which increased with high temperature and low precipitation. No seasonal effect on IA was observed in Houston, where total spore counts were lower and not variable by climate. CONCLUSIONS Climatic variables differentially affect airborne spore counts and IA risk in geographically disparate centers.

Aspergillus ustus Infections among Transplant Recipients

This is the first report of clustered Aspergillus ustus causing systemic disease in transplant patients.

Coccidioidomycosis among workers at an archeological site, northeastern Utah.

In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9–12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, extending northward its known geographic distribution in Utah by approximately 200 miles.

Outbreak of invasive aspergillosis among renal transplant recipients.

Invasive aspergillosis (IA) is rare among renal transplant recipients (RTRs). We investigated a cluster of IA among RTRs at a California hospital from January to February 2001, when construction was ongoing. We conducted a cohort study among RTRs who were hospitalized between January 1 and February 5, 2001, to determine risk factors for IA. IA was defined using established guidelines. Four IA cases occurred among 40 RTRs hospitalized during the study period. Factors associated with an increased risk of IA included prolonged hemodialysis, lengthy corticosteroid treatment posttransplant, and use of sirolimus alone or with mycophenolate (P<0.05). After the study period, three additional RTRs developed IA; two Aspergillus isolates recovered from these patients had indistinguishable profiles by DNA fingerprinting, suggesting common-source exposure. This study suggests that immunosuppressed RTRs can be at an increased risk for IA. Measures to prevent IA in these patients should be taken during hospital construction.

Cutaneous fungal infections in the United States: analysis of the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS), 1995-2004.

Background  Dermatophyte infections lead to high costs and differentially affect certain groups. Previous population studies have been limited in size, duration, and representativeness.

Prosthetic Joint Infection Due to “Helcococcus pyogenica”

ABSTRACT Helcococci have previously been associated with the colonization of ulcers and infections of the skin and soft tissues. We describe a case of prosthetic joint infection due to a previously undescribed organism that is genetically most closely related to Helcococcus.

Optimizing Containment and Control of Candida parapsilosis Fungemia among Neonates in the Outbreak Setting Using a Mathematical Modeling Approach

Candida is the second leading cause of sepsis related death in the neonatal intensive care unit (NICU). Using the C. parapsilosis paradigm, the endogenous and exogenous routes of infection were simulated in order to enhance prevention among neonates at highest risk. A deterministic model was constructed with transmission parameters calculated from the basic reproductive number (), derived from the mean serial interval from two published outbreaks. Uncertainty and sensitivity analyses were performed via Latin hypercube sampling. Prevention measure effects were ascertained by incorporating percent coverage and efficacies into the existing model. The colonized and infected neonatal prevalence peaked at 17.4% and 39.4%, respectively, and reduction was achieved by compartmental replacement with susceptibles. Containment of greater than 60% of the cohort had minimal effect on the effective reproductive number () unless hand hygiene compliance dropped below 40% at a fixed ratio of nurses to neonates. Antifungal prophylaxis in combination with hand hygiene and cohorting extinguished an outbreak 14 days sooner than baseline. The critical proportion () requiring prophylaxis in order to stop an outbreak increases, as rises, and the prophylaxis efficacies decrease. Internal and external sources of Candida lead to invasive disease in neonates differentially. Optimal prevention is dependent upon understanding the dynamics of this disease process under diverse circumstances.