Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. METHODS: We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. RESULTS: Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). CONCLUSIONS: The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET).

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. METHODS: Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

Vancomycin-resistant enterococcal meningitis in an autologous stem cell transplant recipient cured with linezolid.

Enterococci are an unusual cause of meningitis, with most cases reported in the literature preceded by neurosurgical procedures. Spread to the meninges from an enterococcal bloodstream infection is even more rare, with few cases reported in the literature. We report the first documented case, to our knowledge, of successful treatment of vancomycin-resistant enterococcal (VRE) meningitis with linezolid therapy in an immunosuppressed hematopoietic stem cell transplant recipient. Our case highlights the success of monotherapy with linezolid for VRE meningitis. A literature review is provided, which reveals that there is little evidenced-based data on the optimal therapy for VRE meningitis.

Evolutionary computation and the vega risk of American put options.

While European style options and American call options can be priced using analytical exact valuation models, closed-form solutions for the valuation of American puts have not yet been derived. The American put price as well as the corresponding greeks (e.g., delta, gamma, vega) can be calculated using numerical procedures or analytical approximations. We use a parallel implementation of the genetic programming approach and derive analytical approximations for determining the vega of an American put option because calculating vegas numerically requires even more computational effort than determining deltas or gammas. Applying our approximations to experimental data sets we can show that the genetically derived approximations outperform other approximations based on frequently used American put pricing formulas.

A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer.

PURPOSE: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer. PATIENTS AND METHODS: A total of 317 neutropenic patients (<500 cells/mm3) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the efficacy and safety of each drug by clinical criteria, frequent cultures and radiological procedures, and laboratory values. A response was classified as satisfactory at the end of therapy if the patient was afebrile, had no clinical or microbiological evidence of fungal infection, and did not require study termination due to lack of efficacy, drug toxicity, or death. RESULTS: A satisfactory response occurred in 68% of the patients treated with fluconazole (107 of 158 patients) and in 67% of patients treated with amphotericin B (106 of 159 patients). Progressive or new fungal infections during therapy occurred in 13 (8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and in 10 (6%) patients treated with amphotericin B (5 with Candida, 3 with Aspergillus, 2 with other fungi). Adverse events related to study drug (especially fever, chills, renal insufficiency, electrolyte disturbances, and respiratory distress) occurred more often in patients treated with amphotericin B (128 [81%] of 159 patients) than patients treated with fluconazole (20 [13%] of 158 patients, P = 0.001). Eleven (7%) patients treated with amphotericin B but only 1 (1%) patient treated with fluconazole were terminated from the study owing to an adverse event (P = 0.005). Overall mortality (27 [17%] patients treated with fluconazole versus 34 [21%] patients treated with amphotericin B) and mortality from fungal infection (7 [4%] patients treated with fluconazole versus 5 [3%] patients treated with amphotericin B) were similar in each study group. CONCLUSIONS: Intravenous fluconazole can be an effective and safe alternative to amphotericin B for empiric antifungal therapy in many febrile neutropenic patients. However, because fluconazole may be ineffective in the treatment of Aspergillus, patients at risk for that infection should be evaluated by chest radiograph, computed tomographic scanning, and cultures before the use of empiric fluconazole therapy.

The role of chloramphenicol in the treatment of bloodstream infection due to vancomycin-resistant Enterococcus.

The incidence of bacteremia due to vancomycin-resistant Enterococcus (VRE) has increased markedly in recent years. We investigated the role of chloramphenicol in its treatment. All cases of VRE bacteremia occurring at our facility during a 45-month period were analyzed. The response to chloramphenicol, its effect on mortality, and the incidence of adverse effects were assessed. Fifty-one patients (65.4%) received chloramphenicol. Among patients in whom a response could be assessed, 22 (61.1%) of 36 demonstrated a clinical response, while 34 (79.1%) of 43 showed a microbiological response. Forty-two patients (53.8%) died as a result of the bacteremia. Although the mortality rate was lower for patients treated with chloramphenicol, the difference was not significant (odds ratio = 0.72; 95% confidence interval, 0.28-1.85; P = .49), nor was there an association between earlier initiation of therapy and reduced mortality (P = .45). In cases with central line-related bacteremia, there was no difference in mortality among patients treated with chloramphenicol, line removal, or both (P = .36). Although 16 patients (31.4%) had adverse effects, none could be definitely attributed to chloramphenicol. Although chloramphenicol was well-tolerated, no significant effect of its use on mortality could be demonstrated.

Pleural effusion due to herpes simplex type II infection in an immunocompromised host.

Pleural effusions caused by herpes simplex viruses are rare. We report a case of a young woman with acute lymphocytic leukemia (ALL) and prolonged neutropenia who developed pleural space infection with herpes simplex type II virus (HSV II), as confirmed by cytologic and microbiologic studies. We believe that this is the first report of a pleural effusion caused by HSV II, and suggest that this virus now be considered in the differential diagnosis of an unexplained exudative pleural effusion, especially in an immunocompromised host.

The cause of fever following resolution of neutropenia in patients with acute leukemia.

Many studies have examined the etiology of fever complicating neutropenia. Little is known about the etiology of fever occurring immediately following recovery from myelosuppression. We reviewed 165 episodes of fever in patients who were admitted to the University of Pennsylvania Medical Center (Philadelphia) between 1 August 1992 and 15 August 1994 for the treatment of acute leukemia. We included patients who had episodes of fever (temperature of > or = 38 degrees C) for > or = 48 hours within 10 days after an absolute neutrophil count of < or = 500 cells/mm3 was determined. Twenty-nine (20%) of 145 episodes met these criteria. In 5 (17%) of 29 episodes the cause of fever was a bacterial infection, in 6 (21%) of 29 episodes the cause of fever was noninfectious, and in 12 (41%) of 29 episodes the cause of fever was unknown. Six (21%) of 29 episodes were due to documented or suspected fungal infection, four were due to suspected pulmonary aspergillosis, and two were due to systemic candidal infections. Fever following recovery from chemotherapy-induced neutropenia is common. Fungal infections occur frequently after recovery from myelosuppression despite widespread use of empirical and prophylactic antifungal therapy. Improved strategies for diagnosing and preventing fungal infections in patients who have fever following recovery from myelosuppression are clearly needed.

Chloramphenicol for the treatment of vancomycin-resistant enterococcal infections.

A retrospective study of patients who received chloramphenicol for the treatment of serious vancomycin-resistant enterococcal infections between 1 January 1993 and 31 August 1993 was conducted at the University of Pennsylvania Medical Center (Philadelphia). Antimicrobial susceptibilities as well as the clinical course of infection, adverse events, and response to therapy of 16 patients were reviewed. Forty-seven percent of enterococcal isolates were susceptible only to chloramphenicol, tetracycline, and nitrofurantoin. Types of infection included bacteremias (n = 7), abscesses (n = 7), and others (n = 5). Of 14 patients for whom a clinical response could be ascertained, eight (57%) showed improvement after treatment. Of 11 patients for whom a microbiological response could be ascertained, eight (73%) had sterile cultures after treatment. No lasting adverse effect related to the drug occurred. In-hospital mortality was 56%, but only one death could be directly attributed to vancomycin-resistant enterococcal infection. Chloramphenicol appears to be a useful and well-tolerated agent for the treatment of serious vancomycin-resistant enterococcal infections.

Disseminated cutaneous Pseudallescheria boydii.

As increasingly aggressive chemotherapeutic regimens are used to treat malignancy, more patients will become susceptible to various opportunistic pathogens. Specifically, several fungal organisms previously viewed as relatively non-pathogenic are more frequently causing serious disease in these patients. Identification of these organisms is of paramount importance, as some are relatively resistant to standard antifungal therapies. We report a patient with disseminated cutaneous Pseudallescheria boydii, diagnosed from histopathological examination and culture of a skin biopsy specimen. Identification of the organism was achieved shortly before the patient died. Clinicians must be aware of the numerous emerging opportunistic pathogens, which may require special culture techniques for diagnosis and varied or combined modes of therapy.

Zygomycosis orbital apex syndrome in association with a solitary lung carcinoma.

We describe a patient who presented with orbital apex syndrome. Sphenoidectomy and biopsy revealed invasive zygomycosis. The patient had no obvious risk factors for the development of zygomycosis, but was subsequently found to have a solitary, occult lung carcinoma. The unusual clinical features of this case are discussed, and the English language literature on zygomycoses in patients with solid tumours is reviewed. Possible predisposing factors are discussed.

Community-acquired Pseudomonas aeruginosa pneumonia in patients with HIV infection.

OBJECTIVE: To describe the clinical and radiographic presentation, risk factors, response to therapy and outcome of 16 patients with HIV infection and pulmonary infections caused by Pseudomonas aeruginosa. DESIGN: Retrospective review of medical records. SETTING: An academic tertiary-care hospital. PATIENTS: Sixteen patients who met the case definition were included for retrospective review. RESULTS: P. aeruginosa pneumonia was community-acquired in 15 patients (94%). The majority of patients (94%) had a diagnosis of AIDS with a mean CD4 cell count of 27 x 10(6)/l cells. Traditional risk factors for the development of P. aeruginosa were missing in most patients. Cavitary infiltrates were present on admission chest radiograph in eight patients (50%). An additional three patients (19%) presented with pulmonary infiltrates that cavitated subsequently. Clinical course was extremely varied with an in-hospital mortality of only 19%, but with an additional 25% of patients developing chronic or recurrent disease. CONCLUSIONS: Community-acquired pneumonia caused by P. aeruginosa occurs in patients with end-stage HIV infection. The presence of cavitary pulmonary infiltrates on chest radiograph in a patient with a low CD4 count should raise suspicion of P. aeruginosa infection. Obvious risk factors for P. aeruginosa infection may be absent. While the initial mortality rate is lower than that observed in other immunocompromised hosts, the potential for chronic or recurrent infection should be recognized and patients should be followed closely.

Persistent bacteremia with Erysipelothrix rhusiopathiae in a hospitalized patient.

A patient with a history of alcohol abuse and pancreatitis presented with a pleural effusion resulting from a fistula between the pancreatic duct and left pleural space. Two weeks into her hospitalization, fever and persistent bloodstream infection with Erysipelothrix rhusiopathiae and Candida albicans developed. The patient had no history of exposure to animals. To our knowledge this is the first report of an E. rhusiopathiae infection presenting during hospitalization. This case suggests the possibility of a carrier state of infection and illustrates that a high index of suspicion is necessary for identification of unusual pathogens in hospitalized patients.

Regulation of neutrophil superoxide by antichymotrypsin-chymotrypsin complexes.

The ability of neutrophils to generate free radicals is a crucial component of host defense (Babior, B. M. (1978) N. Engl. J. Med. 298, 659-668, 721-725. Neutrophil oxidants, however, can cause significant host tissue destruction (Weiss, S. J. (1989) N. Engl. J. Med. 320, 365-376), and the regulation of free radical production is not well understood. We have previously shown that recombinant antichymotrypsin (rACT), a serine protease inhibitor, inhibits superoxide production in intact neutrophils (Kilpatrick, L., Johnson, J. L., Nickbarg, E. B., Wang, Z., Clifford, T. F., Banach, M., Cooperman, B. S., Douglas, S. D., and Rubin, H. (1991) J. Immunol. 146, 2388-2393). Using a cell-free NADPH oxidase preparation, we now demonstrate that rACT alone has no effect on superoxide production and that antichymotrypsin-chymotrypsin (rACT.CT) complexes are required to inhibit superoxide, suggesting that neutrophil chymotrypsin-like proteases produce conformational changes in ACT, allowing it to become active in regulating superoxide production. Additionally, we have identified NADPH oxidase itself as the target for rACT.CT and have demonstrated that rACT.CT interferes specifically with activation of the NADPH oxidase without changing the Km for NADPH or the rate constant describing the rate-limiting step in activation. These observations suggest an important role for antichymotrypsin in the regulation of NADPH-oxidase activation, which is a prerequisite for neutrophil superoxide production, and predict possible therapeutic uses for rACT in conditions where unregulated neutrophil-free radical production has been implicated in the mechanism of tissue destruction.