Bacterial and fungal meningitis in patients with cancer.

OBJECTIVE: To analyze cases of bacterial and fungal meningitis in patients with cancer. METHODS: Retrospective chart review from 1993 to 2004 was performed of patients with cancer at our institution who had positive CSF bacterial or fungal culture. RESULTS: We identified 312 positive CSF cultures representing 175 unique presentations. Ninety-six cultures were deemed contaminants, leaving 79 cultures for analysis in 77 patients; 78% had prior neurosurgery. Organisms included 68% gram-positive cocci, 10% gram-positive bacilli, 14% gram-negative bacilli, 7% Cryptococcus, and 1% C. albicans. None had N. meningitidis or H. influenza. Two patients each had S. pneumoniae or L. monocytogenes. Five percent of presentations demonstrated the triad of fever, nuchal rigidity, and mental status changes. Seventy-five percent of presentations demonstrated CSF pleocytosis (> or = 10). Median CSF WBC count was 74 cells/mm(3). CSF protein was elevated and glucose was depressed in 71%. In neutropenic patients (n = 6), 4 had 0 to 1 CSF WBC/mm(3), and 2 had normal CSF. VP shunt infections were more likely to present with mental status changes. Thirty day mortality was 13%. CONCLUSIONS: Patients with cancer do not manifest symptoms of meningitis as often as patients without cancer and display a very different set of CSF organisms compared to a general population. The CSF inflammatory response is muted in patients with cancer with meningitis. Most patients with cancer with meningitis have had prior neurosurgery. Additionally, the organisms causing meningitis in the cancer population have shifted over time, with a decline in the organisms which typically infect immunocompromised hosts and an increase in gram-positive infections.

High rates of infection and colonization by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation.

Nontuberculous mycobacteria (NTM) are essentially ubiquitous and can infect both immunocompetent and immunocompromised hosts. However, NTM infection is surprisingly uncommon in reports from allogeneic hematopoietic stem cell transplant (alloSCT) centers that do not routinely perform allograft T-cell depletion. We reviewed medical records for all adult patients who underwent alloSCT at our center between January 1993 and December 2001. American Thoracic Society and Centers for Disease Control and Prevention guidelines Were used to define definite, probable, and possible NTM infection. Of 571 patients, 36 of 372 (9.7%) T-cell depleted and 14 of 199 (7.0%) conventional alloSCT recipients (P=0.26) had a positive culture for NTM after alloSCT. Of the 50 patients with NTM infection, 16 had definite infection and 34 had probable or possible infection. Rates of NTM infection were 5 to 20-fold higher than rates reported by other centers. Of the 16 definite infections, nine were caused by Mycobacterium haemophilum. Two patients had disseminated M. avium complex (MAC) infection and one had a vascular catheter infected by MAC. Three patients died from complications of NTM infection. Patients with probable or possible NTM infection had markedly different epidemiology, risk factors, site and species of NTM infection, and prognosis than patients with definite NTM infection.

Antibiotic prophylaxis in patients receiving hematopoietic stem cell transplant.

Effective prophylaxis against specific infections has allowed increasingly potent conditioning regimens to be given, thereby prolonging survival in HSCT recipients. The Centers for Disease Control and Prevention, in collaboration with numerous professional societies, has recently published guidelines to codify and advance this approach. Controversy remains in several areas but, curiously, the most intense debate concerns prevention of bacterial infections, the most extensively studied of all of the approaches. Central to this debate are the competing priorities of a potentially ill patient on the one hand vs the long-term consequences of unchecked antibiotic use. The emergence in the 1990s of vancomycin-resistant Enterococcus demonstrated all too vividly how devastating such an end result could be. This article will review the arguments for and against the routine use of antibacterial prophylaxis in HSCT recipients.

Respiratory syncytial virus infection following hematopoietic stem cell transplantation.

Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients of autologous or allogeneic transplants. The incidence of RSV following allogeneic or autologous HSCT was 5.7% and 1.5%, respectively. Of the 58 patients with an RSV infection, 16 of 21 patients identified within the first post-transplant month, developed pneumonia. Seventy-two percent of patients received aerosolized ribavirin and/or RSV-IGIV, including 23 of 25 patients diagnosed with RSV pneumonia. In this aggressively treated patient population, three patients died of RSV disease, each following an unrelated HSCT.

Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond.

This review presents evidence-based guidelines for the prevention of infection after blood and marrow transplantation. Recommendations apply to all myeloablative transplants regardless of recipient (adult or child), type (allogeneic or autologous) or source (peripheral blood, marrow or cord blood) of transplant. In Section I, Dr. Dykewicz describes the methods used to rate the strength and quality of published evidence supporting these recommendations and details the two dozen scholarly societies and federal agencies involved in the genesis and review of the guidelines. In Section II, Dr. Longworth presents recommendations for hospital infection control. Hand hygiene, room ventilation, health care worker and visitor policies are detailed along with guidelines for control of specific nosocomial and community-acquired pathogens. In Section III, Dr. Boeckh details effective practices to prevent viral diseases. Leukocyte-depleted blood is recommended for cytomegalovirus (CMV) seronegative allografts, while ganciclovir given as prophylaxis or preemptive therapy based on pp65 antigenemia or DNA assays is advised for individuals at risk for CMV. Guidelines for preventing varicella-zoster virus (VZV), herpes simplex virus (HSV) and community respiratory virus infections are also presented. In Section IV, Drs. Baden and Rubin review means to prevent invasive fungal infections. Hospital design and policy can reduce exposure to air contaminated with fungal spores and fluconazole prophylaxis at 400 mg/day reduces invasive yeast infection. In Section V, Dr. Sepkowitz details effective clinical practices to reduce or prevent bacterial or protozoal disease after transplantation. In Section VI, Dr. Sullivan reviews vaccine-preventable infections and guidelines for active and passive immunizations for stem cell transplant recipients, family members and health care workers.

Mycobacterium haemophilum in immunocompromised patients.

Mycobacterium haemophilum, a recently described pathogen, can cause an array of symptoms in immunocompromised patients. To date, 90 patients with this infection have been described worldwide. We report our institution's experience with 23 patients who were treated from 1990 through 2000. Fourteen patients had undergone bone marrow transplantation, 5 were infected with human immunodeficiency virus, 3 had hematologic malignancies, and 1 had no known underlying immunosuppression. Clinical syndromes on presentation included skin lesions alone in 13 patients, arthritis or osteomyelitis in 4 patients, and lung disease in 6 patients. Although patients with skin or joint involvement had favorable outcomes, 5 of 7 patients with lung infection died. Prolonged courses of multidrug therapy are required for treatment. A diagnosis of M. haemophilum infection must be considered for any immunocompromised patient for whom acid-fast bacilli are identified in a cutaneous, synovial fluid or respiratory sample or for whom granulomas are identified in any pathological specimen.

Risk for tuberculosis infection among internally displaced persons in the Republic of Georgia.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection and disease among internally displaced persons residing in Tbilisi, Republic of Georgia. DESIGN: Residents of eight refugee hostels were screened for TB infection using a tuberculin skin test (TST) and a symptom questionnaire. Participation was voluntary. TST-positive individuals were referred for chest radiography. Subjects with cough, fever, or night sweats of > 2 weeks duration provided sputum for acid-fast bacilli (AFB) microscopy and culture. RESULTS: Of approximately 4000 potential subjects (internally displaced persons), 988 (24.7%) participated in the screening program. Of these 988, 931 (94.2%) who had a TST placed returned at 48-72 hours to have the skin test examined; 447 (48.0%) were TST-positive (> or = 10 mm induration). In multivariate analysis, risk factors for a positive TST included male sex, ever having received BCG, history of close contact with a case of active tuberculosis, and living in one specific refugee hostel. Risk for a positive TST was greater among subjects > 20 years old, but there was no difference between age groups over the age of 20 years. Five patients with active TB were identified through the screening program, giving a case rate of 537 per 100,000 population. CONCLUSION: Tuberculosis infection and disease were common in this group of internally displaced persons. Screening was a useful mechanism of case finding among this high prevalence population.

Candida dubliniensis at a cancer center.

Candida dubliniensis, a germ tube-positive yeast first described and identified as a cause of oral candidiasis in patients with acquired immunodeficiency syndrome in Europe in 1995, has an expanding clinical and geographic distribution that appears to be similar to that of the other germ tube-positive yeast, Candida albicans. This study determined the frequency, clinical spectrum, drug susceptibility profile, and suitable methods for identification of this emerging pathogen at a cancer center in 1998 and 1999. Twenty-two isolates were recovered from 16 patients with solid-organ or hematologic malignancies or acquired immunodeficiency syndrome. Two patients with cancer had invasive infection, and 14 were colonized with fungus or had superficial fungal infection. All isolates produced germ tubes and chlamydospores at 37 degrees C, did not grow at 45 degrees C, and gave negative reactions with d-xylose and alpha-methyl-d-glucoside in the API 20 C AUX and ID 32 C yeast identification systems. Phenotypic identification was confirmed by molecular beacon probe technology. All isolates were susceptible to the antifungal drugs amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, and ketoconazole.

Control of influenza A on a bone marrow transplant unit.

In January 1998, an outbreak of influenza A occurred on our adult bone marrow transplant unit. Aggressive infection control measures were instituted to halt further nosocomial spread. A new, more rigorous approach was implemented for the 1998/99 influenza season and was extremely effective in preventing nosocomial influenza at our institution.

Rotavirus outbreak on a pediatric oncology floor: possible association with toys.

BACKGROUND: Several outbreaks of rotavirus gastroenteritis have occurred in hospitals and day care centers. In the spring of 1997, an outbreak of rotavirus occurred on our pediatric unit. Aggressive infection control measures were instituted, and potential lapses in infection control were assessed. METHODS: Memorial Sloan-Kettering Cancer Center is a 434-bed cancer hospital in New York City. The pediatric unit is a 42-bed ward with both bone marrow transplant patients and non-bone marrow transplant oncology patients. Nosocomially acquired rotavirus was defined as diarrhea, vomiting, or gastrointestinal upset with onset 48 hours or more after hospital admission, accompanied by a positive enzyme immunoassay for rotavirus antigen. RESULTS: Between February 24 and April 4, 1997, 8 patients on the pediatric unit had nosocomial rotavirus. Aggressive infection control measures were instituted. Patients with rotavirus were cohorted and placed on contact precautions (strict handwashing, gloves, and gown). Investigation by the infection control team revealed that communal toys in the playroom were not being cleaned according to the weekly protocol. CONCLUSIONS: An outbreak of nosocomial rotavirus occurred on our pediatric oncology unit. Shared toys may have served as fomites in the transmission of rotavirus.

Coronary artery disease and human immunodeficiency virus infection.

Recent reports of myocardial infarctions in young persons infected with human immunodeficiency virus (HIV) who are receiving protease inhibitor therapy have raised concerns about premature coronary artery disease in this population. Endothelial dysfunction, hypercoagulability, hypertriglyceridemia, and abnormal coronary artery pathology were in fact associated with HIV infection prior to the availability of protease inhibitor therapy. Newly recognized risk factors, such as insulin resistance, hypercholesterolemia, and fat redistribution syndrome, may exacerbate underlying atherosclerotic risk for patients receiving protease inhibitors. Data on the incidence of myocardial infarction among these patients are largely limited to case reports but are of concern. Pending the availability of further data, it is prudent to monitor these patients for hyperlipidemia and consider interventions to modify cardiac risk factors.

Changing patterns of infections and antimicrobial susceptibilities.

Nosocomial bloodstream infections across the United States and in Europe are increasingly attributable to gram-positive species--a trend that represents a reversal of the gram-negative predominance of the previous decades. Data from Memorial Sloan-Kettering Cancer Center and elsewhere show that patients with hematologic malignancies or patients who are immunocompromised because of anticancer treatments are experiencing this shift in microbial spectrum. Most common among gram-positive species are coagulase-negative Staphylococci. Antimicrobial resistance continues to increase, which makes treatment more difficult for infections caused by some species, especially vancomycin-resistant enterococcal species. The underlying causes of changes in microbial spectrum and drug-resistance patterns are incompletely understood, but it is clear that antibiotic exposure exerts a significant selective pressure on pathogens, resulting in partial or complete resistance. New drugs or drug combinations will be necessary to treat drug-resistant infections in cancer patients.

Seroconversion rates in healthcare workers using a latex agglutination assay after varicella virus vaccination.

OBJECTIVES: To determine the seroconversion rate after varicella immunization of healthcare workers (HCWs) and the effect of seroconversion rate on current cost-based recommendations for universal vaccination. METHODS: A voluntary vaccination program for HCWs was performed at a tertiary-care cancer center in New York City. A commercial latex agglutination assay was used to test postvaccination antibody response. Costs for vaccination and postvaccination serological testing were compared to potential costs of postexposure employee furloughs. RESULTS: Of 263 seronegative HCWs, 96 (36.5%) began the vaccine program. Thirty-nine HCWs received only one dose of vaccine. Seven returned for follow-up antibody testing, of whom 4 were seropositive. Of the 57 HCWs who received two doses, 38 returned for follow-up serology. Thirty-one (81.6%) HCWs were seropositive for varicella-zoster virus antibodies, and seven HCWs (18.4%) remained seronegative. Total cost of vaccination for all 263 seronegative HCWs was estimated and compared to the cost of varicella-related furloughs at our institution. CONCLUSIONS: We found a considerably lower rate of vaccine-induced seroconversion at our hospital compared to that of the published literature. Despite this finding, universal varicella vaccination remained an extremely cost-effective alternative to the furloughing of exposed, seronegative HCWs. Projected hospital savings exceeded $53,000 in the first year after vaccination alone.

Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS.

We compared the efficacy of a 400-mg once-weekly dosage versus a 200-mg daily dosage of fluconazole for the prevention of deep fungal infections in a multicenter, randomized, double-blind trial of 636 human immunodeficiency virus-infected patients to determine if a less intensive fluconazole regimen could prevent these serious but relatively infrequent complications of AIDS. In the intent-to-treat analysis, a deep fungal infection developed in 17 subjects (5.5%) randomly assigned to daily fluconazole treatment and in 24 (7.7%) given weekly fluconazole during 74 weeks of follow-up (risk difference, 2.2%; 95% confidence interval [CI], -1.7% to 6.1%). Thrush occurred twice as frequently in the weekly versus daily fluconazole recipients (hazard ratio, 0.59; 95% CI, 0.40-0.89), and in a subset of patients evaluated, fluconazole resistance was infrequent. Fluconazole administered once weekly is effective in reducing deep fungal infections in patients with AIDS, but this dosage is less effective than the 200-mg-daily dosage in preventing thrush.

Evaluation of an interdisciplinary re-isolation policy for patients with previous Clostridium difficile diarrhea.

BACKGROUND: Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. METHODS: The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. RESULTS: Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. CONCLUSION: Our policy to control the spread of nosocomial C difficile required interdisciplinary cooperation between infection control and the admitting department. By identifying patients who were positive for toxin through admitting, we were able to place all potentially infected patients into isolation. Our positivity rate of 15% on readmission demonstrates the importance of this policy. The cost of controlling C difficile can be significantly lowered by clearing patients who were previously positive for toxin before hospital readmission.

Human immunodeficiency virus infection, Part II.

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.