I. Raad

Adenovirus infections in adult recipients of blood and marrow transplants

Adenoviruses are increasingly recognized pathogens that affect blood and marrow transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were reviewed to study the incidence, clinical spectrum, risk factors for dissemination, response to therapy, and outcome of adenovirus infections. Eight-five patients (3%) were diagnosed by means of culture (n=85) or culture and histopathological examination (n=6). Nine patients had asymptomatic viruria, and 76 had symptomatic infections, which included upper respiratory tract infection (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and disseminated disease (n=13). The overall mortality rate was 26%. A higher mortality rate was observed among patients with pneumonia (73%) and disseminated disease (61%). Risk factors for dissemination included receipt of an allogeneic transplant, presence of graft-versus-host disease (GVHD), and receipt of concurrent immunosuppressive therapy. Intravenous ribavirin was not associated with an appreciable benefit among 12 patients who received this treatment. In conclusion, adenovirus infections are an important cause of morbidity and mortality in adult BMT recipients, particularly allogeneic transplant recipients with GVHD who are receiving immunosuppressive therapy. The need for an effective, nontoxic antiviral therapy is apparent.

Rhinovirus Infections in Myelosuppressed Adult Blood and Marrow Transplant Recipients

Scant data are available on the clinical significance of rhinovirus infections in immunocompromised patients. We reviewed the clinical courses of and outcomes for 22 myelosuppressed adult blood and marrow transplant recipients with rhinovirus infections who were hospitalized at the M.D. Anderson Cancer Center (Houston) from January 1992 to January 1997. In 15 patients (68%), illnesses remained confined to the upper respiratory tract. Seven patients (32%) developed fatal pneumonia. These patients had profound respiratory failure a mean of 12 days (range, 3-21 days) after the onset of symptoms. In six of these seven cases, rhinovirus was isolated before death from a bronchoalveolar lavage fluid specimen and/or an endotracheal aspirate. Five patients underwent autopsies, one of which revealed disseminated aspergillosis and four of which revealed interstitial pneumonitis and/or acute respiratory distress syndrome and no other organisms. In conclusion, rhinovirus infections may be associated with considerable pulmonary-related morbidity and mortality in severely myelosuppressed immunocompromised patients.

Pulmonary Candidiasis in Patients with Cancer: An Autopsy Study

For patients who had cancer and autopsy-proven pneumonia, we evaluated whether cultures of respiratory secretions (sputum and/or bronchoalveolar lavage) performed < or =4 weeks before autopsy were a reliable basis for the diagnosis of pulmonary candidiasis. Pulmonary candidiasis was identified at autopsy in 36 patients, but common clinical predictors were insensitive for this diagnosis. For sputum culture, the sensitivity, specificity, and the positive and negative predictive values were 85%, 60%, 42%, and 93%, respectively; for bronchoalveolar lavage culture, these values were 71%, 57%, 29%, and 89%, respectively.

Successful treatment of vancomycin-resistant Enterococcus meningitis with linezolid.

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Influence of type of cancer and hematopoietic stem cell transplantation on clinical presentation of Pneumocystis jiroveci pneumonia in cancer patients

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990–2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.

Outcomes for and risk factors associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium bacteremia in cancer patients

OBJECTIVE Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infection. We sought to compare vancomycin-resistant (VR) Enterococcus faecalis bacteremia and VR Enterococcus faecium bacteremia in cancer patients with respect to risk factors, clinical presentation, microbiological characteristics, antimicrobial therapy, and outcomes. METHODS We identified 210 cancer patients with VRE bacteremia who had been treated between January 1996 and December 2004; 16 of these 210 had VR E. faecalis bacteremia and were matched with 32 patients with VR E. faecium bacteremia and 32 control patients. A retrospective review of medical records was conducted. RESULTS Logistic regression analysis showed that, compared with VR E. faecalis bacteremia, VR E. faecium bacteremia was associated with a worse clinical response to therapy (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.07-0.98]; P=.046) and a higher overall mortality rate (OR, 8.3 [95% CI, 1.9-35.3]; P=.004), but the VRE-related mortality rate did not show a statistically significant difference (OR, 6.8 [95% CI, 0.7-61.8]; P=.09). Compared with control patients, patients with VR E. faecalis bacteremia were more likely to have received an aminoglycoside in the 30 days before the onset of bacteremia (OR, 5.8 [95% CI, 1.2-27.6]; P=.03), whereas patients with VR E. faecium bacteremia were more likely to have received a carbapenem in the 30 days before the onset of bacteremia (OR, 11.7 [95% CI, 3.6-38.6]; P<.001). In a multivariate model that compared patients with VR E. faecium bacteremia and control patients, predictors of mortality included acute renal failure on presentation (OR, 15.1 [95% CI, 2.3-99.2]; P=.004) and VR E. faecium bacteremia (OR, 11 [95% CI, 2.7-45.1]; P<.001). No difference in outcomes was found between patients with VR E. faecalis bacteremia and control patients. CONCLUSIONS VR E. faecium bacteremia in cancer patients was associated with a poorer outcome than was VR E. faecalis bacteremia. Recent receipt of carbapenem therapy was an independent risk factor for VR E. faecium bacteremia, and recent receipt of aminoglycoside therapy was independent risk factor for E. faecalis bacteremia.

In vitro antimicrobial efficacy of silver iontophoretic catheter

A silver iontophoretic catheter was designed consisting of two silver wires connected to an electric power source and disposed in a parallel and helical manner around the proximal subcutaneous segment of a silicone catheter. In an in vitro tunnelled bridge model the silver iontophoretic catheter prevented the migration of Staphylococcus epidermidis from the highly contaminated hub to the sterile tip over a 40-d period. The silver impregnated cuff and electrically charged wires made of aluminium or iron delayed migration for only 72 h. A modified Kirby-Bauer technique, used to test the inhibitory activity of antimicrobial catheters, showed that the silver iontophoretic catheter has a broad spectrum inhibitory activity against Gram-positive bacteria, Gram-negative bacteria and Candida albicans. The silver iontophoretic catheter provides a long-term electrochemical barrier against the migration of organisms from the external contaminated environment into the sterile intravascular compartment.

Prospective, randomized dose-ranging open phase II pilot study of quinupristin/dalfopristin versus vancomycin in the treatment of catheter-related staphylococcal bacteremia

Abstract Two different doses of quinupristin/dalfopristin were compared with intravenous vancomycin with regard to the efficacy and safety in the treatment of catheter-related staphylococcal bacteremia. A total of 39 patients were enrolled from 13 centers. For all treated patients with a baseline pathogen, outcome was comparable for all antibiotic study regimens. Discontinuation of the antibiotic for an adverse clinical event occurred in 12% of patients receiving quinupristin/dalfopristin and in 15% of those receiving vancomycin. Quinupristin/dalfopristin may have the potential to serve as an alternative agent in the treatment of catheter-related staphylococcal bacteremia. However, larger prospective randomized trials are required.

Amphotericin B Lipid Complex as Prophylaxis of Invasive Fungal Infections in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome Undergoing Induction Chemotherapy

The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high‐risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population.

Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients.

The purpose of this prospective randomized study was to compare the efficacy and safety of imipenem and cefoperazone-sulbactam combined with vancomycin for the treatment of fever in neutropenic cancer patients. Patients were assigned to either imipenem 500 mg/m2 (500 mg for bone marrow transplant recipients) every 6 h or cefoperazone (2 g)-sulbactam (1 g) every 8 h. All patients received vancomycin 1 g every 12 h. A total of 457 febrile or infectious episodes occurring in 407 patients were entered in the study. The response rate was 73% for imipenem plus vancomycin and 74% for cefoperazone-sulbactam plus vancomycin among the 369 episodes that could be evaluated. Response rates were comparable for the two regimens with regard to infecting organism, administration of antimicrobial prophylaxis, and neutrophil count and trend. The frequency of side-effects was significantly higher for imipenem plus vancomycin (11 % vs. 5%, p = 0.02), due to therapy-associated nausea and vomiting (5.3% vs. 0%, p = 0.0004). The overall frequency of superinfections was similar with both regimens, butClostridium difficile colitis occurred significantly more often in patients receiving imipenem plus vancomycin (5 vs. 0, p = 0.02). In this study cefoperazone-sulbactam plus vancomycin was an effective alternative to imipenem plus vancomycin for initial therapy of fever in neutropenic patients.