Michael Saccente

Clinical and Laboratory Update on Blastomycosis

SUMMARY Blastomycosis is endemic in regions of North America that border the Great Lakes and the St. Lawrence River, as well as in the Mississippi River and Ohio River basins. Men are affected more often than women and children because men are more likely to participate in activities that put them at risk for exposure to Blastomyces dermatitidis. Human infection occurs when soil containing microfoci of mycelia is disturbed and airborne conidia are inhaled. If natural defenses in the alveoli fail to contain the infection, lymphohematogenous dissemination ensues. Normal host responses generate a characteristic pyogranulomatous reaction. The most common sites of clinical disease are the lung and skin; osseous, genitourinary, and central nervous system manifestations follow in decreasing order of frequency. Blastomycosis is one of the great mimickers in medicine; verrucous cutaneous blastomycosis resembles malignancy, and mass-like lung opacities due to B. dermatitidis often are confused with cancer. Blastomycosis may be clinically indistinguishable from tuberculosis. Diagnosis is based on culture and direct visualization of round, multinucleated yeast forms that produce daughter cells from a single broad-based bud. Although a long course of amphotericin B is usually curative, itraconazole is also highly effective and is the mainstay of therapy for most patients with blastomycosis.

Detecting bacterial colonization of implanted orthopaedic devices by ultrasonication.

Glycocalyx-producing bacteria have been observed on orthopaedic devices that were removed for reasons other than infection. It has been suggested that the bacteria adhere to foreign surfaces within a biofilm and elude standard culture techniques. The authors adapted previously used ultrasonication protocols that disrupt the surface biofilm before culturing removed orthopaedic devices from patients without clinical evidence of infection. Patients having revision total joint arthroplasty of the hip or knee who lacked current or prior clinical evidence of infection were studied prospectively. During surgery, the femoral component and a corresponding control femoral implant were placed in separate sterile bags of saline. The implant and saline combination was placed in an ultrasonication bath for 30 minutes at 60 Hz. The saline solution was passed through a 0.45-μm pore filter, and the filter residue was cultured on sheep blood agar. None of the 21 implants yielded positive culture on routine microbiologic testing. However, using the ultrasonication protocol, a coagulase-negative Staphylococcus grew from one of the removed implants. Numerous total joint implant failures that are attributed to aseptic loosening may be a result of subclinical infection from bacteria within a biofilm. The current study supports the concept that biofilm-protected bacterial colonization of implants may occur without overt signs of infection and ultrasonication can be used to enhance identification of these bacteria.

Klebsiella pneumoniae Liver Abscess, Endophthalmitis, and Meningitis in a Man with Newly Recognized Diabetes Mellitus

resolved. The dorsum of his right foot had only small, red macules, and erythema in the pretibial region had resolved. BCG vaccine has been used for decades for the prevention of tuberculosis. More recently, BCG has been used as immunotherapy for various tumors. Importantly, the dosing of BCG is much higher when given as cancer immunotherapy [5]. As a result, BCG immunotherapy is often complicated by systemic side effects. Although BCG has been recovered from blood immediately after subcutaneous injection [6], attempts at isolating the organism from skin specimens from patients with chronic cutaneous changes have been futile [7]. Therefore, the cause of the cutaneous granulomatous lesions has remained controversial. Even though some investigators have postulated a hypersensitivity reaction to BCG as the underlying etiology, others have pointed to the rapid response of patients to antituberculosis treatment as evidence for direct invasion [5]. To our knowledge, we report the first case of culture-proven BCG infection of a chronic cutaneous lesion. When combined with the granulomatous changes seen during pathological evaluation and an excellent clinical response to antituberculosis therapy, it appears that direct BCG infection is the etiology of at least some of the postimmunization cutaneous abnormalities in our patient. Stephen L. Moff, G. Ralph Corey, and Magnus Gottfredsson Department of Internal Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina

Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers

The systemic availability of itraconazole capsules may be reduced secondary to elevated gastric pH and possibly by presystemic intestinal metabolism via CYP3A4. Grapefruit juice is acidic and an inhibitor of intestinal CYP3A4. To determine the effect of grapefruit juice on the systemic availability of itraconazole capsules, serum itraconazole and hydroxy-itraconazole concentrations were determined in eleven healthy volunteers studied in a randomized, two-way crossover design. Concurrent grapefruit juice resulted in a 43% decrease in the mean itraconazole AUC0-48 (2507 ng x hr/mL versus 1434 ng x hr/mL, p = 0.046) and a 47% decrease in the mean hydroxy-itraconazole AUC0-72 (7264 ng x hr/mL versus 3880 ng x hr/mL, p = 0.025). Grapefruit juice also significantly increased the mean itraconazole Tmax (5.5 versus 4 hours). We conclude that concomitant grapefruit juice does not enhance the systemic availability of itraconazole capsules, but rather appears to impair itraconazole absorption. Therefore, concomitant grapefruit juice will not likely be useful in improving the oral availability of itraconazole capsules.

Influence of grapefruit juice on the systemic availability of itraconazole oral solution in healthy adult volunteers

Study Objective. To evaluate the effect of repeated ingestion of grapefruit juice on the systemic availability of itraconazole (ITZ) and hydroxy‐itraconazole (OHITZ) serum concentrations in subjects administered hydroxypropyl‐β‐cyclodextrin‐ITZ (HP‐β‐CD ITZ) oral solution.

Cerebral histoplasmosis in the azole era: Report of four cases and review

We report four cases of cerebral histoplasmosis and discuss features of six additional cases reported in the medical literature in the past 10 years, when azoles have been available for therapy. Most patients with this disease are immunocompromised or have a history that suggests heavy exposure to Histoplasma capsulatum. Fever and other clinical findings of systemic toxicity caused by disseminated histoplasmosis may be absent; 5 of 10 patients did not manifest these findings. Although the mainstay of treatment for central nervous system histoplasmosis remains amphotericin B, 9 of the 10 patients received itraconazole or fluconazole either as initial therapy or after a course of treatment with amphotericin B.

CLINICAL APPROACH TO INFECTIVE ENDOCARDITIS

The epidemiology of IE has evolved over the past 50 years. Mitral valve prolapse and degenerative valvular disease have replaced rheumatic heart disease as the most common predisposing conditions. The average age of patients with IE has increased, and nosocomially acquired cases are becoming more common. Although viridans streptococci are currently responsible for a smaller proportion of cases than previously, this group of bacteria remains the most common cause of prosthetic value and native valve endocarditis. Staphylococci are the most important cause in some community hospitals, in nosocomial IE, and in IVDUs. IE is a multisystem disease, and patients may present with diverse clinical features. In the absence of direct histopathologic and microbiologic examination of valvular vegetations, the diagnosis of IE depends on the detection of endocardial abnormalities and the isolation of a pathogen from blood. Blood culture remains the most important laboratory test and yields the causative microorganism in 95% of patients. Echocardiography has become an important tool for detecting endocardial lesions. The clinical features of IE in IVDUs are somewhat different than those in other populations. The microbiology is distinctive, and right-sided involvement with septic pulmonary emboli is the most common clinical scenario in this group.

Candida lusitaniae septic arthritis: case report and review of the literature

Candida lusitaniae is an infrequently encountered Candida species that has been associated with resistance to amphotericin B. We present a case of septic arthritis with C. lusitaniae and provide a brief review of the organism, especially in regard to current information about its pattern of resistance to antifungal agents.

Mycobacterium fortuitum group periprosthetic joint infection.

The Mycobacterium fortuitum group of rapidly growing mycobacteria is recognized infrequently as a cause of periprosthetic joint infection. This report describes a case of periprosthetic joint infection due to a member of the M. fortuitum group where failure to consider this pathogen caused months of diagnostic delay. Aggressive surgery and 6 months of combination antimicrobial therapy eradicated the infection.

Geographic distribution of endemic fungal infections among older persons, United States.

To the Editor: We read with interest the article by Baddley et al. (1) and appreciate their efforts to characterize incidence rates of mycoses. We agree that histoplasmosis, blastomycosis, and coccidioidomycosis are differential diagnoses for patients with consistent symptoms but who reside outside mycosis-endemic areas. However, we believe that the methods of Baddley et al. probably do not determine the true incidence of these mycoses in sparsely populated states such as Arkansas. Their estimates contrast markedly with surveillance data from the Arkansas Department of Health (Table) and with our clinical experience as infectious disease physicians. We characterize Arkansas as a state in which histoplasmosis and blastomycosis incidence is high and coccidioidomycosis incidence is low; however, Baddley et al. indicate that in Arkansas, incidence of blastomycosis is relatively low and incidence of coccidioidomycosis is high. Table Reported cases of fungal diseases in Arkansas, by year* To investigate whether this finding might be associated with their small 5% sample of Medicare beneficiaries, we used data from the Arkansas census to determine that in 2008 the population of adults >65 years of age was ≈407,014, and during 1999–2008, there were ≈3,840,896 person-years for persons in this age group. A 5% sample would account for ≈192,045 person-years. Using their rate ranges (7.84–12.3 cases/100,000 person-years for histoplasmosis, 3.97–6.71 for coccidioidomycosis, and 0.39–0.86 for blastomycosis), we calculated the approximate numbers of cases in their sample: 15–23 histoplasmosis cases, 7–12 coccidioidomycosis cases, and only 1 blastomycosis case. Compared with rates from surveillance averaged over the 10 years, the midpoints of the Baddley et al. estimates are ≈6-fold higher for histoplasmosis, ≈60-fold higher for coccidioidomycosis, and ≈0.4-fold lower for blastomycosis. Only their estimate for blastomycosis incidence falls within the 10-year 95% CIs from surveillance data. We believe that the small cell sizes require that the rate estimates of Baddley et al. be interpreted with care, especially with respect to less populous states.