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.

Preemptive diagnosis and treatment of Epstein-Barr virus-associated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development.

Hematopoietic stem cell transplant (HSCT) recipients are at risk for Epstein-Barr virus (EBV)-associated, post transplant lymphoproliferative disorder (PTLD). Studies have suggested that early treatment may improve the outcome of patients with PTLD. Thus, significant attention has been focused on PCR-based approaches for preemptive (i.e., prior to clinical presentation) diagnosis. Reports from several transplant centers have demonstrated that HSCT recipients with PTLD generally have higher concentrations of EBV DNA in the peripheral blood than patients without PTLD. However, the PCR values of patients with PTLD typically span multiple orders of magnitude and overlap significantly with values from patients without PTLD. Thus, questions remain about the sensitivity and predictive value of these assays. Preemptive strategies using rituximab and/or EBV-specific cytotoxic T lymphocytes have been evaluated in patients with elevated EBV viral loads. We review the current literature, discuss our institutional experience and identify several areas of future research that could improve the diagnosis and treatment of this life-threatening disorder in HSCT recipients.

Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients.

We report on bloodstream infection (BSI) rates, risk factors, and outcome in a cohort of 298 adult and pediatric hematopoietic stem cell transplantation (HSCT) recipients at Memorial Sloan-Kettering Hospital from September 1999 through June 2003. Methods. Prospective surveillance study. BSI rates are reported per 10,000 HSCT days. Date of engraftment is defined as the first of at least 3 consecutive dates of absolute neutrophil count >500/mm(3) after stem cell infusion. BSI severity grades: severe (intravenous antibiotics), life threatening (sepsis), or fatal (caused or contributed to death). Results. The incidence of pre- and post-engraftment BSI was 22% and 19.5%, respectively. Pre-engraftment highest rates were observed for viridans streptococci (58), Enterobacteriaceae (39), and Enterococcus faecium (34). Post-engraftment rates ranged from 0.2 to 2.9 without any predominant pathogen. In multivariate analyses, pre-engraftment BSI was associated with diagnosis of chronic myelogenous leukemia, age >18 years and peripheral blood stem cell graft; post-engraftment BSI was associated with acute graft-versus-host disease, neutropenia, and liver or kidney dysfunction. Attributable mortality was 12.5% and 1.7% for pre- and post-engraftment BSI, respectively. BSI fatality rates were 24% for viridans streptococci, 8% for E. faecium, 11% for Staphylococcus aureus, and 67% for Candida. Conclusions. Pre-engraftment BSI, especially by viridans streptococci and E. faecium, was associated with substantial attributable mortality. Post-engraftment BSI was a marker of post-transplant complications and rarely the primary cause of death.

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.

Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance.

We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.

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.

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.

Disseminated toxoplasmosis following T cell-depleted related and unrelated bone marrow transplantation.

More than 95% of reported cases of disseminated toxoplasmosis following BMT have occurred following an unmodified transplant. Most have been fatal, diagnosed at autopsy and without antemortem institution of specific therapy. From 1989 to 1999, we identified 10 cases of disseminated toxoplasmosis, in 463 consecutive recipients of a T cell-depleted (TCD) BMT. Transplants were from an unrelated donor (n = 5), an HLA-matched sibling (n = 4) or an HLA-mismatched father (n = 1). In 40%, both the donor and recipient had positive IgG titers against T. gondii pre-transplant; in 30%, only the recipient was sero-positive. Three recipients of an unrelated TCD BMT developed toxoplasmosis despite both donor and host testing negative pretransplant. All 10 patients presented with high grade fever. CNS involvement ultimately occurred in seven patients, with refractory respiratory failure and hypotension developing in nine. Eight of 10 cases were found only at autopsy, involving the lungs (n = 7), heart (n = 5), GI tract (n = 5), brain (n = 8), liver and/or spleen (n = 5). The only survivor, treated on the day of presentation with fever and headache, was diagnosed by detection of T. gondii DNA by polymerase chain reaction (PCR) performed on the blood and spinal fluid. This study demonstrates the similar incidence of toxoplasmosis following TCD BMT and that reported post T cell-replete BMT, and underscores the need for rapid diagnostic tests in an effort to improve outcome.

Histologic reactions to cutaneous infections by Mycobacterium haemophilum.

Mycobacterium haemophilum is an emerging pathogen in immunocompromised patients. We report the clinical and histologic findings of 16 skin biopsies from 11 patients with culture-proven infections by M. haemophilum. The patients had leukemia or non-Hodgkin's lymphoma. Ten of them had undergone bone marrow transplantation. When the skin biopsy specimens were taken, a portion of the skin was simultaneously submitted to a microbiology laboratory for cultures. The remaining skin was processed routinely. Acid-fast bacilli were found in 11 of 16 lesions. The number of histologically detectable organisms was typically low: nine biopsies had fewer than three bacilli per 50 oil immersion fields. The most common histologic pattern was a mixed suppurative and granulomatous reaction (7 of 16 biopsies). Four biopsies showed well-formed epithelioid granulomas. Two showed necrosis, one of which was ulcerated. One lesion was a subcutaneous abscess. Two biopsies showed a mixed lichenoid and granulomatous dermatitis. In one of them, the granulomatous reaction was focal and small. One biopsy lacked a granulomatous tissue reaction altogether; it showed an interface dermatitis, a perivascular and periadnexal lymphocytic infiltrate, and necrotizing lymphocytic small vessel vasculitis. A subsequent biopsy from the same patient additionally showed a focal granulomatous reaction. Our observation that infections by M. haemophilum can present with nongranulomatous or pauci-granulomatous reactions without necrosis is of note. Failure to suspect mycobacterial infection in such reactions contributes to probable underreporting of M. haemophilum and to misdiagnoses. Furthermore, our findings emphasize the importance of simultaneous biopsies for culture and histology in immunocompromised patients.

Pulmonary nodule due to Mycobacterium haemophilum in an immunocompetent host.

We present a case of a pulmonary nodular lesion in an immunocompetent patient documented at open lung biopsy to be due to Mycobacterium haemophilum. This organism has recently been recognized as a cause of disease in immunocompromised patients, presenting predominantly as skin lesions, arthritis, and rarely pneumonia. Because this mycobacterium is fastidious and difficult to grow without the use of special media and conditions, our case raises the possibility that M. haemophilum could be an underrecognized cause of granulomatous pulmonary lesions and should be considered particularly in cases where smears for acid-fast bacteria are positive but cultures are negative.

Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans.

Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.

Mycobacterium haemophilum infections in bone marrow transplant recipients.

The purpose of this study was to describe the clinical presentation, treatment, and outcome of Mycobacterium haemophilum infection in patients undergoing bone marrow transplantation at a cancer center. Bone marrow transplant recipients with M haemophilum infection were identified upon culture of the organism by implementing the organism's unique requirements for growth. This report of the patients' clinical and immunologic course is based on a retrospective chart review. Two distinctly different presentations of M haemophilum infection were observed. Three patients presented with cutaneous lesions, typical of those seen in previous reports of the infection. Two others developed pulmonary disease only. All patients received directed therapy against M haemophilum, but respiratory failure developed in the patients with pneumonia and they died. The remaining 3 patients survived and are free of infection. These are the only reported cases of M haemophilum infection in bone marrow transplant recipients. Early diagnosis obtained through biopsy and special request for culture conditions conducive to the growth of the organism may decrease morbidity and mortality, particularly in patients with pulmonary disease.

Direct observations of surgical wound infections at a comprehensive cancer center.

OBJECTIVES: To identify the rate of surgical site infection and risk factors for surgical site infection in patients with cancer and to evaluate antibiotic use patterns on surgical oncology services. DESIGN: Criterion standard. SETTING: Memorial Sloan-Kettering Cancer Center, a comprehensive cancer center at a university hospital. PATIENTS: Over a 15-month period, 1226 patients undergoing 1283 surgical procedures performed by the Breast, Colorectal, and Gastric-Mixed Tumor surgical services. MAIN OUTCOME MEASURE: Direct observation of surgical sites was performed by a single, surgeon-trained member of the hospital's Infection Control Section, adhering to an established protocol for grading of the surgical site. RESULTS: Operative procedures accounted for the following traditional wound class distributions: class I (clean), 630 cases; class II (clean-contaminated), 577 cases; class III (contaminated), 29 cases; and class IV (dirty-infected), 47 cases. Surgical site infection rates were 3.8% in class I; 8.8% in class II; 20.7% in class III; and 46.9% in class IV procedures. The mean (+/- SD) age was 57.7 +/- 14.3 years and the Anesthesiology Society of America physical assessment score, 2.3 +/- 0.7. The mean (+/- SD) operation time was 145 +/- 104.9 minutes. Logistic regression analysis demonstrated several risk factors for surgical site infection: obesity (P < .0001); a contaminated or dirty-infected surgical procedure category (P < .0001); operation time greater than 4 hours (P = .0004); Anesthesiology Society of America physical assessment score of 3 or greater (P < .01); and preoperative length of stay of 3 or more days (P = .03). CONCLUSIONS: Risk factors for surgical site infection in patients with cancer are similar to those found in the National Nosocomial Infections Surveillance System. However, as an individual risk factor among our patient population, obesity contributed as strongly as the surgical procedure category to a patient's likelihood of acquiring a surgical site infection. In addition to Anesthesiology Society of America status, length of the surgical procedure, and surgical procedure category, obesity should warrant consideration as an individual risk factor for surgical site infection.

Sepsis caused by Flavimonas oryzihabitans.

Previous reports of F. oryzihabitans sepsis involving central venous access devices reveal a relatively high rate of complications, including device removal, despite a course of broad-spectrum anti-microbials with compatible in vitro susceptibility results. In the present report of 22 cases of F. oryzihabitans sepsis treated at Memorial Sloan-Kettering Cancer Center from February 1986 through September 1993, the majority of CVAD-related infections with F. oryzihabitans were successfully treated with a 14-day course of antimicrobials with antipseudomonal activity, and removal of the device was usually not required. Factors that may complicate successful treatment of CVAD-related sepsis caused by F. oryzihabitans include polymicrobial infections and premature discontinuation of antibiotic therapy.

Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients.

OBJECTIVE: To describe 13 infections caused by Mycobacterium haemophilum. DESIGN: Identification of patients by microbiologic record review, followed by medical record review and a case-control study. SETTING: Seven metropolitan hospitals in New York. PATIENTS: All patients with M. haemophilum infections diagnosed between January 1989 and September 1991 and followed through September 1992. Surviving patients were enrolled in the case-control study. RESULTS: Infection with M. haemophilum causes disseminated cutaneous lesions, bacteremia, and diseases of the bones, joints, lymphatics, and the lungs. Improper culture techniques may delay laboratory diagnosis, and isolates may be identified incorrectly as other mycobacterial species. Persons with profound deficits in cell-mediated immunity have an increased risk for infection. These include persons with human immunodeficiency virus infection or lymphoma and those receiving medication to treat immunosuppression after organ transplant. Various antimycobacterial regimens have been used with apparent success to treat M. haemophilum infection. However, standards for defining antimicrobial susceptibility to the organism do not exist. CONCLUSIONS: Clinicians should consider this pathogen when evaluating an immunocompromised patient with cutaneous ulcerating lesions, joint effusions, or osteomyelitis. Microbiologists must be familiar with the fastidious growth requirements of this organism and screen appropriate specimens for mycobacteria using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be considered as the infecting organism as well as other mycobacteria, and appropriate media and incubation conditions should be used.

Infectious morbidity associated with long-term use of venous access devices in patients with cancer.

OBJECTIVE: To evaluate infectious morbidity associated with long-term use of venous access devices. DESIGN: Prospective, observational study. SETTING: Comprehensive cancer center at a university hospital. PARTICIPANTS: 1431 consecutive patients with cancer requiring 1630 venous access devices for long-term use inserted between 1 June 1987 and 31 May 1989. MEASUREMENTS: Quantitative microbiologic tests to identify device-related bacteremia and fungemia, catheter tunnel infection, pocket infection in implantable port devices, and site infections; number of days the device remained in situ and time until infectious morbidity; vessel or device thrombosis and device breakage. RESULTS: At least one device-related infection occurred with 341 of 788 (43% [95% CI, 39% to 47%]) catheters compared with 57 of 680 (8% [CI, 6% to 10%]) completely implanted ports (P < or = 0.001). Device-related bacteremia or fungemia is the predominant infection occurring with catheters, whereas ports have a more equal distribution of pocket, site, and device-related bacteremia. The predominant organisms isolated in catheter-related bacteremia were gram-negative bacilli (55%) compared with gram-positive cocci (65.5%) in port-related bacteremia. The number of infections per 1000 device days was 2.77 (95% CI, 2.48 to 3.06) for catheters compared with 0.21 (CI, 0.16 to 0.27) for ports (P < or = 0.001). Based on a parametric model of time to first infection, devices lasted longer in patients with solid tumors than in those with hematopoietic tumors. Ports lasted longer than catheters across all patient groups. CONCLUSIONS: The incidence of infections per device-day was 12 times greater with catheters than with ports. Patients with solid tumors were the least likely to have device-related infectious morbidity compared with those with hematologic cancers. The reasons for the difference in infectious complications is uncertain but may be attributable to type of disease, intensity of therapy, frequency with which devices are accessed, or duration of neutropenia.