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Summary Background Human metapneumovirus is a recently discovered RNA virus that typically causes respiratory disease in children. It has been linked to severe lower airway disease in hematopoietic stem cell and solid-organ transplant recipients. hMPV infection in a large population of patients with underlying cancer and varying degrees of immunosuppression has not been reported. We sought to characterize hMPV infection in patients with cancer. Methods Review of all cases of hMPV infection from two seasons (2005–6 and 2006–7) detected by DFA and/or real-time PCR at MSKCC, a tertiary cancer center in New York City. Results Among MSKCC patients with cancer, 51 (2.7%) of 1899 patients were positive for hMPV, including 3.2% with hematologic neoplasm and 1.7% with solid tumors. More children (4.5%) were positive than adults (2.2%). PCR detected twice as many cases as DFA. Cough and fever were common complaints. The longest shedding period was 80 days. 40 patients received radiographic evaluation; of these, 22 showed abnormalities including patchy (11), ground glass (5), and interstitial infiltrates (4). Conclusions hMPV causes a nonspecific respiratory illness and was found in more than 2% of all tested persons with cancer. PCR detected substantially more cases than DFA. Unlike previous reports, we observed no fatalities due to hMPV, including 22 HSCT recipients with the infection.

An unknown virus was isolated from a lung biopsy sample and multiple other samples from a patient who developed a lethal case of pneumonia following a peripheral blood stem cell transplant. A random PCR-based molecular screening method was used to identify the infectious agent as avian paramyxovirus 1 (APMV-1; a group encompassing Newcastle disease virus), which is a highly contagious poultry pathogen that has only rarely been found in human infections. Immunohistochemical analysis confirmed the presence of APMV-1 antigen in sloughed alveolar cells in lung tissue from autopsy. Sequence from the human isolate showed that it was most closely related to virulent pigeon strains of APMV-1. This is the most completely documented case of a systemic human infection caused by APMV-1 and is the first report of an association between this virus and a fatal disease in a human.

Bloodstream infection caused by vancomycin-resistant enterococcus (VRE) is associated with very high mortality among allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. However, it remains unclear whether VRE bloodstream infection directly causes mortality in the early posttransplant period or is simply a marker of poor outcome. To determine the risk factors for VRE bloodstream infection and its effect on outcome, we followed 92 patients screened for stool colonization by VRE upon admission for alloHSCT. Patient records were reviewed to determine outcomes, including mortality and microbiologic failure. Colonization by VRE was extremely common, occurring in 40.2% of patients. VRE bloodstream infection developed in 34.2% of colonized patients by day +35, compared to 1.8% without VRE colonization (P < .01). VRE bloodstream infection was associated with a significant decrement in survival and frequent microbiologic failure, despite treatment with linezolid and/or daptomycin. Five (35.7%) of 14 patients with VRE bloodstream infection had attributable mortality or contributing mortality from the infection. Strain typing by pulsed-field gel electrophoresis identified 9 different VRE strains among the 37 colonized patients and 5 patients with different strains recovered from the stool and the blood. In conclusion, stool screening effectively identified patients at extremely high risk for VRE bloodstream infection. The high mortality of VRE in the early posttransplant period supports the use of empiric antibiotics with activity against VRE during periods of fever and neutropenia in colonized patients.

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.

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, 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.

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.

To the Editor: The immunosuppressive agent alemtuzumab is a DNA-derived, humanized monoclonal antibody directed against the panlymphocyte, cell-surface antigen CD52 (1). The drug is approved for the treatment of refractory B-cell chronic lymphocytic leukemia (2) and also has been used after stem cell (3) and organ transplantations (4). Alemtuzumab causes profound and prolonged lymphocyte depletion, which results in a variety of complications involving infections (5). However, mycobacteria have rarely been reported to cause infection after alemtuzumab treatment. We describe infections with Mycobacterium haemophilum, a fastidious nontuberculous mycobacterium, in 2 patients who experienced cutaneous lesions while they received alemtuzumab.

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.

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.

A resurgence of tuberculosis has occurred in recent years in the United States and abroad. Deteriorating public health services, increasing numbers of immigrants from countries of endemicity, and coinfection with the human immunodeficiency virus (HIV) have contributed to the rise in the number of cases diagnosed in the United States. Outbreaks of resistant tuberculosis, which responds poorly to therapy, have occurred in hospitals and other settings, affecting patients and health care workers. This review covers the pathogenesis, epidemiology, clinical presentation, laboratory diagnosis, and treatment of Mycobacterium tuberculosis infection and disease. In addition, public health and hospital infection control strategies are detailed. Newer approaches to epidemiologic investigation, including use of restriction fragment length polymorphism analysis, are discussed. Detailed consideration of the interaction between HIV infection and tuberculosis is given. We also review the latest techniques in laboratory evaluation, including the radiometric culture system, DNA probes, and PCR. Current recommendations for therapy of tuberculosis, including multidrug-resistant tuberculosis, are given. Finally, the special problem of prophylaxis of persons exposed to multidrug-resistant tuberculosis is considered.

Mycobacterium haemophilum is emerging as a pathogen of immunocompromised patients particularly those with AIDS and organ transplants. Infection has also occurred in healthy children. Adults usually present with cutaneous manifestations, septic arthritis or occasionally pneumonia. Children have perihilar, cervical or submandibular adenitis. The organism grows on mycobacterial media supplemented with ferric ammonium citrate or hemin, incubated at 30 degrees C to 32 degrees C, two to three weeks after inoculation. The most active antimicrobial agents in vitro are amikacin, ciprofloxacin, clarithromycin, rifabutin and rifampin. Development of resistance to the rifamycins has been demonstrated after patients were treated for several months with several antimycobacterial agents, including the rifamycins. Treatment for several months with at least two agents demonstrated to have low MICs for the organism has been shown to be effective.

In May 1991, an article in a New York newspaper was entitled "HIV Victims' New Foe--Haemophilum: Rare but Deadly Microbe Remains a Mystery" (1). The article noted that "Marie, a once-beautiful 32-yr-old New Jersey suburbanite with AIDS, is covered from head to toe with huge purple scars that occasionally erupt in painful oozing sores. She routinely has fevers of more than 101°F. She walks with a limp because a deadly organism has eaten a hole in a bone in her left leg." The purple sores, originally thought to be the lesions of Kaposi's sarcoma, were eventually found to be caused by infection with Mycobacterium haemophilum Pus from lesions in the left leg contained the mycobacterium. During 1990 and 1991 at Memorial Sloan-Kettering Cancer Center (MSKCC), we observed four cases of M. haemophilum infection and presented them at Intercity Infectious Disease Rounds. Physicians from two other hospitals in New York City described their own cases. Laboratory directors in the greater New York area were called, and a total of five additional cases were disclosed. In May 1991, we received a call from Dr. Robert C. Good, Chief of the Respiratory Diseases Branch of the Centers for Disease Control (CDC), who stated that he had received a call from a New York reporter who wondered what the "haemophilum" organism was. Investigations by the New York City Health Department and the CDC were begun. In addition to the four cases of M. haemophilum infection seen at MSKCC (2), at least nine additional cases of suspected M. haemophilum infection occurred in the New York City area within the past 2 yr (3), and 17 additional cases of M. haemophilum infection were reported in journals between 1976 and 1991 (4, 5). A summary of the four MSKCC cases and the 17 previously reported culture proven cases is presented in Table 1.

Four cases of meningitis due to beta-hemolytic non-A, non-D streptococci among adult patients with neoplastic disease are reported. All four patients had head or neck tumors for greater than or equal to 4 years, and all had undergone surgery for these tumors. Three of four patients had received local radiation therapy. None of the patients were neutropenic. One patient died. A review of the literature revealed that most patients with non-A, non-D streptococcal meningitis had disruption of the normal barrier protecting the CNS due to trauma, surgery, or the presence of a tumor, or had extensive exposure to animals or an underlying medical disease. Infection with non-A, non-D streptococci should be considered in any patient with meningitis who has a tumor of the head or neck and who has undergone surgery and/or radiation therapy.

A retrospective analysis of 57 pediatric oncology patients with a baseline positive vancomycin-resistant enterococcus (VRE) culture who subsequently received chemotherapy and/or radiation therapy was performed. The incidence of subsequent VRE infection was calculated using a competing risk analysis accounting for death from non-VRE causes as a competing risk. Ten patients had subsequent VRE infection. The cumulative incidence of subsequent infection was 14% (7–27%, 95% confidence interval) at 1 year and 16% (9–29%, 95% confidence interval) at 2 years. None of the hypothesized risk factors appeared to differ between patients who developed a subsequent infection and those who did not. Pediatr Blood Cancer 2009;52:300–302. © 2008 Wiley-Liss, Inc.

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 (≥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.

A significant increase in the use of vascular access devices has changed the spectrum of organisms causing bacteremia and fungemia at Memorial Sloan-Kettering Cancer Center. This paper documents the 1988 laboratory experience with bacteremia and fungemia and contrasts some of that data with information obtained in 1984. In 1988, 439 tunnelled-catheters and 355 ports were inserted in patients; 2,778 organisms were subsequently recovered from 933 episodes of bacteremia and fungemia. Fifty-percent of the episodes of bacteremia and fungemia were vascular access device-related. Compared to 1984, the relative incidence of bacteremia due to gram-positive organisms increased from 33 to 43%, polymicrobic cultures increased from 24 to 27%, and the number of organisms with colony counts greater than 100 cfu/ml increased from 24 to 44%. In 1988, device-related sepsis was often caused by Acinetobacter spp., Bacillus spp., Corynebacterium spp., pseudomonads other than Pseudomonas aeruginosa, and coagulase-negative staphylococci. Infection was also caused by species of flavobacteria, Micrococcus, and Rhodotorula. Efforts required for identification of many of the newer pathogens have escalated material and personnel costs.

We describe a 12-year-old boy with acute myeloid leukemia who developed pleuropericarditis while he was neutropenic and was receiving intravenously administered antibiotic and antifungal therapy for pneumonia. A KOH preparation of the purulent material from an extensive diagnostic and therapeutic pleuropericardial drainage procedure revealed multiple irregularly septate hyphae, and cultures yielded the organism Pythium insidiosum. After completing a 12-month course of intravenously administered liposomal amphotericin B (AmBisome; Fujisawa Healthcare) and itraconazole, the patient remained alive, in clinical remission, and symptom free.

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, 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.

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.

Bordetella bronchiseptica is a Gram-negative coccobacillus that frequently causes infections in animals, including atrophic rhinitis in swine, snuffles in rabbits and kennel cough in dogs.1 The most common symptom of kennel cough is a dry ‘honking’ cough. B. bronchiseptica belongs to the same genus as the causative agent of whooping cough in humans, Bordetella pertussis, an organism that infects only humans. Most infections with B. bronchiseptica occur in immunocompromised individuals exposed to farm or companion animals, although infections have been reported in immunocompetent patients.1, 2, 3 The organism is usually susceptible in vitro to the aminoglycosides, antipseudomonal penicillins, quinolones, tetracycline, third-generation cephalosporins and trimethoprim–sulfamethoxazole. Effective treatment is often difficult because of the patient's underlying disease and the ability of the organism to invade and persist in epithelial cells. The two veterinary vaccines currently marketed are an avirulent live intranasal vaccine and a s.c. antigen extract vaccine. Although data suggest that the intranasal route may be effective within 72 h, there is less data on the efficacy of the s.c. vaccine.

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.

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 tuberculosis was isolated from the eyelid, skin, tongue, and lungs of a green-winged macaw ( Ara chloroptera ). Two persons living in the same household were culture positive for pulmonary tuberculosis 3 to 4 years before tuberculosis was diagnosed in the bird. Although humans have not been shown to acquire tuberculosis from birds, an infected bird may be a sentinel for human infection.

Mycobacterium genavense, a recently reported cause of a wasting illness in patients with AIDS, was isolated from a cervical lymph mode from a dog with severe hind limb weakness and from trachael tissue from a parrot with acute onset respiratory distress. Physicians caring for immunocompromised patients should consider birds and dogs potential sources of M. genavense infection and submit appropriate specimens for culture.

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.

To evaluate infectious morbidity associated with long-term use of venous access devices.Prospective, observational study.Comprehensive cancer center at a university hospital.1431 consecutive patients with cancer requiring 1630 venous access devices for long-term use inserted between 1 June 1987 and 31 May 1989.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.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 (Por = 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 (Por = 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.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.

The diagnostic mycobacterial laboratory of the 1990s must respond to a change in the clinical spectrum of mycobacterial infections brought about by an increase in the number of patients who are immunocompromised, are indigent, or have temporary or permanent implanted devices. Emerging pathogens such as Mycobacterium haemophilum and Mycobacterium genavense, multidrug-resistant strains of Mycobacterium tuberculosis, and catheter infections with rapidly growing mycobacteria are examples of new issues. Fortunately, new methods for detection and identification of microbes have been or are being developed. Procedures that, when applied directly to clinical specimens or actively growing cultures, dramatically reduce the time to diagnosis of mycobacterial infections include radiometric broth, lysis-centrifugation, and biphasic systems for specimen culture, and DNA probes, high-performance liquid chromatography, DNA hybridization, restriction fragment length polymorphism, and gene amplification for organism detection and identification. At present, in vitro antimicrobial susceptibility tests are most helpful in guiding treatment of infections caused by M. tuberculosis and rapidly growing mycobacteria.

purpose, patients, and methods: Malassezia furfur has usually been described as a cause of catheter-related sepsis in neonates receiving intravenous lipid emulsion. We report seven cases of catheter-related M. furfur fungemia that occurred in seven immunocompromised patients including four adults and three children who were not neonates. Only two of these patients were receiving concurrent intravenous lipid emulsion. results: All positive blood cultures were obtained from a central venous access device, one of which was a port device. Quantitative M. furfur colony counts ranged from 50 cfu/mL to greater than 1,000 cfu/mL. All seven patients were treated with amphotericin B. Blood drawn through the central lines of three patients yielded additional organisms. One central venous access device required removal due to persistently positive M. furfur blood cultures despite treatment with amphotericin B. conclusion: We conclude that catheter-related M. furfur fungemia occurs in immunocompromised patients with central venous access devices whether or not they are receiving intravenous lipids. Prompt, aggressive treatment with amphotericin B (1 mg/kg/d) may spare patients removal of their central venous access device. Further studies are needed to determine the role of endogenous lipids in the development of catheter-related M. furfur fungemia and to determine if there is a seasonal incidence in populations other than neonates, since all of our cases occurred between late March and July.

Four cases of infection with Mycobacterium haemophilum occurred at a single hospital in a seven-month period. Only 22 cases have been reported since 1976. All four patients were immunocompromised; two had AIDS and two were the first known recipients of allogeneic bone marrow transplants (BMT) to develop the infection. One BMT recipient died of Mycobacterium haemophilum pneumonia. The organism requires hemin or ferric ammonium citrate and incubation of media at 30 degrees C for optimum growth. Clinicians and microbiologists should consider infection with Mycobacterium haemophilum, particularly when specimens are from immunocompromised patients with unexplained illness and/or when acid-fast bacilli are seen on smear.

An unusual case of disseminated Nocardia brasiliensis infection is presented. The patient, who had been receiving chronic dexamethasone therapy for 4 years, had pneumonia and septic arthritis of the left knee due to N. brasiliensis. To our knowledge, this is the first report from the United States of a synovial joint infection with this organism. Disseminated disease due to N. brasiliensis is infrequently reported; it is most often seen in the immunocompromised patient and is often unresponsive to therapy.

With increased use of surgically implanted silastic central venous catheters, there has been an increase in the recovery from blood cultures at Memorial Sloan-Kettering Cancer Center (New York) of environmental and skin organisms including the red yeast Rhodotorula. From 1985 through 1989, 23 patients had catheter-related Rhodotorula sepsis. All 23 patients had indwelling central venous catheters that had been in place from 1 to 22 months (average, 9.3 months) prior to the detection of fungemia. All patients had blood drawn both through the catheter and from a peripheral source, and only one patient had a peripheral blood culture positive for Rhodotorula. Colony counts of yeast from the catheter cultures often exceeded 100 (15 patients) and even 1,000 (seven patients) cfu/mL of blood. Thirteen of the patients were treated with antifungal therapy and had the catheter removed, and five patients received antifungal therapy without catheter removal (suggesting that compulsory removal of the catheter may not always be required). Five patients had the catheter removed without antifungal therapy. All patients survived the fungemic episode and experienced no recurrence of the infection.

PCR monitoring for EBV reactivation is commonly used to confirm the diagnosis of EBV-LPD in alloSCT recipients. Previous studies using multiple PCR approaches have suggested a correlation between high EBV copy number and impending EBV-LPD, potentially allowing for the administration of preemptive rituximab and/or donor leukocytes prior to disease onset. However, subpopulations of alloSCT recipients with EBV reactivation at higher risk for EBV-LPD remain incompletely defined. We sought to determine the demographic factors among alloSCT recipients that affect the predictive value of our EBV PCR assay. Quantitative real-time PCR was performed on serum samples obtained from alloSCT recipients using primers that amplify a portion of the BNRF1-p143 locus. Clinical patient information was retrieved from institutional research databases. Patients who did not undergo appropriate EBV PCR screening (n=13), had a history of EBV-LPD prior to alloSCT (n=1) or received rituximab for prophylaxis against EBV-LPD (n=2) were excluded. 187 alloSCT recipients underwent EBV PCR monitoring between 7/03–7/05, of whom 58 (31.0%) were 500 copies/mL) at some point after alloSCT. The prevalence of EBV reactivation was similar in recipients of TCD and conventional allografts (28.8% vs. 31.5%). Among patients with EBV reactivation, the risk for EBV-LPD did not differ based on age, sex, underlying disease, donor relation or HLA disparity. However, of the 56 patients with EBV reactivation, 5/32 (15.6%) recipients of TCD allografts and 0/24 (0.0%) recipients of conventional allografts developed EBV-LPD (p500 for >6 months and 3 had ≥1 PCR value >100K. In our study population, the utility of the EBV PCR was maximized in recipients of TCD allografts with PCR values >500 (Table). In conclusion, EBV reactivation is common among recipients of both conventional and T cell depleted allografts, but preemptive therapy guided by EBV PCR should be primarily directed toward the latter. The effects of in vivo TCD with agents such as alemtuzumab on EBV reactivation and EBV-LPD are under investigation. Utility of the EBV PCR for predicting EBV-LPD and for guiding preemptive therapy in all patients and in only those who received T cell depleted allografts Patient group PCR cutoff (copies/mL) Sensitivity Specificity Positive predictive value Negative predictive value Number needed to treat The highest PCR value within 1 year prior to LPD presentation was used for patients with LPD. All patients >500 100% 72% 9% 100% 11.2 >1,000 80% 77% 9% 99% 12.5 >5,000 40% 85% 7% 98% 20 >10,000 40% 88% 9% 98% 14.6 >100,000 20% 98% 25% 98% 4.4 T cell depleted >500 100% 75% 16% 100% 6.4 >1,000 80% 77% 14% 99% 7.6 >5,000 40% 85% 11% 97% 12.7 >10,000 40% 89% 14% 97% 8.9 >100,000 20% 98% 33% 96% 3.4

To describe 13 infections caused by Mycobacterium haemophilum.Identification of patients by microbiologic record review, followed by medical record review and a case-control study.Seven metropolitan hospitals in New York.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.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.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.

A case of Flavobacterium meningosepticum bacteremia complicating the course of a patient with leukemia is described. The patient was treated successfully when rifampin was added to the antibiotic therapy. Unusual organisms should be considered as agents of infection in immunocompromised hosts and susceptibility testing with drugs not commonly employed for gram-negative rods should be performed in complicated cases.

Serum arabinitol concentrations and arabinitol/creatinine ratios were determined in 25 cancer patients with invasive candidiasis, 73 severely ill cancer patients who did not have invasive candidiasis, and 15 uninfected patients with chronic renal failure. Elevated arabinitol concentrations were found in patients with renal failure and invasive candidiasis. Serum arabinitol concentrations exceeded 1.19 micrograms/ml in 13 of 18 patients with invasive candidiasis who were studied when renal function was normal and in three of 52 control patients. Among patients with renal failure, 10 of 14 with invasive candidiasis but only four of 36 control patients had serum arabinitol concentrations of greater than 5.85 micrograms/ml. Serum arabinitol and creatinine concentrations were strongly correlated. The arabinitol/ creatinine ratio exceeded 1.5 in 16 of 25 patients with invasive candidiasis but in only three of 88 control patients. Increased serum arabinitol concentrations appear to reflect increased production of arabinitol by yeast in individuals with invasive candidiasis.

Blood cultures obtained with a lysis-centrifugation (L-C) system and a conventional two-bottle broth system were compared for the recovery of bacteria and yeasts from 7,000 cultures. The L-C system recovered significantly more total organisms, Escherichia coli, and Candida spp. and detected more patients with bacteremia and fungemia due to members of the family Enterobacteriaceae and yeasts. The broth system recovered significantly more streptococci and detected significantly more low-level Pseudomonas bacteremias. Polymicrobic bacteremia and fungemia were detected equally well by either culture system. Aerobic organisms grew equally well on blood, chocolate, or brain heart infusion agar plates used for L-C inoculation. A total of 82% of colony counts measured no more than 10 CFU/ml of blood, and it was at these low levels that enhanced detection of organisms by either system was observed. The L-C system isolated organisms and detected yeasts more rapidly than did the broth system. Contaminants occurred in 8.2% of L-C cultures and 1.9% of broth cultures. Low colony counts on L-C plates occurred for both Staphylococcus epidermidis contamination and septicemia.

The Mycobacterium avium complex, only rarely described as an invasive pathogen in humans, has recently been reported to frequently cause disseminated disease in patients with the acquired immune deficiency syndrome. Between February 1981 and February 1984 at Memorial Sloan-Kettering Cancer Center, 30 patients with acquired immune deficiency syndrome, 3 patients with leukemia, and 2 patients with congenital severe combined immunodeficiency syndrome developed disseminated M. avium complex infection. Mycobacteria were often found in multiple sites both antemortem and postmortem. Blood cultures were a reliable method for detecting disseminated infection, and the new lysis blood culture systems provided an efficient technique for determining the number of organisms per milliliter of blood. Acid-fast stains and cultures of fecal specimens were also helpful in diagnosing infection. Most of the mycobacteria were serovar 4 (77%), and most (86%) produced a deep yellow pigment. All isolates were susceptible to standard concentrations of clofazimine, cycloserine, and ansamycin, but tended to be resistant to isoniazid, streptomycin, ethambutol, ethionamide, and rifampin.

A case of pneumonia caused by Cunninghamella bertholletiae is described in a patient with chronic lymphatic leukemia. The species of Cunninghamella, a genus in the order Mucorales, are characterized by the formation of conidia on the surface of an inflated conidiophore (vesicle). C. bertholletiae, not C. elegans, is the most appropriate name for this fungus. This zygomycete was resistant by in vitro sensitivity testing to amphotericin B. The source of the infection is not known.

The potential clinical value of colony counts determined by the lysis-centrifugation blood culture method was studied by reviewing the records of eight patients with persistent septicemia in whom colony counts were available on at least 3 days. Colony counts of the five patients who survived decreased steadily as the patients improved. One of the three patients who died had counts repeatedly below 1.0 CFU/ml while she was clinically stable and higher counts when her condition deteriorated. Two patients died despite decreasing colony counts. One was improving and died unexpectedly of an unrelated cause; the other died of candidiasis, but declining serial arabinitol/creatinine ratios suggested a partial response to therapy. In addition, septicemia related to infected intravenous catheters was documented by demonstrating large differences in colony counts determined simultaneously from two different sites in two patients and by demonstrating a precipitous drop in CFU per milliliter after removal of the infected catheter in one patient. Routine availability of colony counts appears to be an important advantage of the lysis-centrifugation method.

Fungemias were reviewed in 110 immunocompromised patients hospitalized between November 1, 1974, and December 31, 1977, at Memorial Sloan-Kettering Cancer Center (MSKCC). The incidence of Candida tropicalis fungemia increased each year. Seventy-six percent of the patients with C. tropicalis fungemia and 32.5 percent of those with C. albicans fungemia had either leukemia or lymphoma. Seventy-seven percent of the C. parapsilosis fungemias were related to total parenteral nutrition. Thirty-seven percent of the patients with C. albicans fungemia were receiving oral prophylactic nystatin therapy. The source of fungemia was often difficult to determine: in 60 percent of the patients, only blood cultures were positive for C. tropicalis or Torulopsis glabrata; no cultures were positive for the fungus from any other site before the episode occurred. Serologic tests, including a highly sensitive passive hemagglutination test, showed fourfold increases in titer only inconsistently. A passive hemagglutination-inhibition test for circulating antigen was positive in 50.9 percent of 57 patients with fungemia who were tested and may be a valid indication for treatment. Fungemia usually represented a severe and often fatal disease. The over-all mortality of the 110 patients with fungemia was 79 percent whereas only 23 percent of the patients with C. parapsilosis fungemia died. Among the patients who received more than 200 mg of amphotericin B, 71 percent died despite treatment.

Purpose Surgically implanted central venous catheters are widely used in cancer patients in whom there is a need for prolonged venous access for chemotherapy, parenteral nutrition, antibiotics, and blood sampling. This study evaluated catheter infectious complications, including catheter-relat- ed sepsis, exit site infection, and tunnel infection. Specifically, an evaluation of the incidence, type, and response to treatment of indwelling catheter infections was performed, and conditions under which the catheter should be removed were delin- eated. Patients and methods During the year of this study, 488 central venous catheters were implant- ed. Records were maintained on demographic vari- ables, date of catheter implantation, surgeon, white blood cell count, absolute neutrophil count, and un- derlying diagnosis. Blood for both aerobic and an- aerobic culture was collected from each patient. For patients in whom infection developed, clinical features, white blood cell count, absolute neutro- phil count, and microbiologic data were noted, as were the clinical course and response to treatment. Results A total of 142 episodes of infectious complications were documented. There were 88 episodes of catheter-related sepsis, and 33 of 54 evaluable episodes (61 percent) were successfully treated with antibiotics. There were 34 episodes of exit site infection, and 20 of the 29 evaluable epi- sodes (69 percent) were successfully treated with antibiotics and local care. Of the 20 tunnel infec- tions, only five (25 percent) were successfully treated with antibiotics, and the other 15 required catheter removal for cure. Twelve of the 15 cases requiring catheter removal were caused by Pseu- domonas species. Conclusion On the basis of these results, com- pulsory removal of the catheter is not required in cases of catheter-related sepsis. Similarly, exit site infections can often be cured by means of antibiot- ics and local care. However, catheter removal is re- quired to achieve cure in most tunnel infections, particularly if Pseudomonas species are cultured from the exit sites of patients with tunnel infection.

A case of catheter-associated fungemia caused by Fusarium chlamydosporum is described in a patient with lymphocytic lymphoma. The fungus, which has been isolated from soil but not reported to cause human infection, characteristically produces microconidiophores that are polyphialides bearing microconidia that are spindle-shaped but never globose. Results of in vitro antimicrobial susceptibility tests depended on the test conditions used.

The first report describing a blood culture technique based on lysis and centrifugation appeared in 1976 (6). During the next few years improvements were made in the system, and in the early 1980s the Isolator system was introduced by DuPont Co. (Wilmington, Del.). There has since been a number of evaluations of the Isolator 7.5 ml, 10 ml, and 1.5 ml systems (2-5, 8, 13, 19). The evaluations have included comparisons of the Isolator to broth systems for the recovery and time to detection of bacteria and fungi, and the interpretation of colony counts from the Isolator system. The various Isolator systems have been compared to a variety of broth systems including conventional broth bottles with 50mL, 100 mL, and biphasic fills with Columbia, tryptic soy, and Brain Heart Infusion broth; the Roche Septi-Chek (Roche Diagnostics, Nutley, N.J.) bottles; and BACTEC (Johnston Laboratories, Towson, Md.) resin and nonresin broth media. I would like to summarize these findings and include my own opinion as to our observations and those of others. The evaluations represent a wide variety of study protocols, patient populations, media, etc., thus they must be interpreted with some caution. For example, at this institution, many of our patients are immunosuppressed, approximately 50% are receiving antibiotics at the time the blood culture is taken, and approximately 50% of blood cultures are taken through indwelling catheters. These circumstances may predispose our studies to different results from those of a large general hospital. A summary of the studies suggests, in general, that neither Isolator nor broth has consistently provided the greatest sensitivity for all organism groups. Thus for optimal recovery of a variety of aerobic and anaerobic bacteria, yeasts and molds, at least two blood culture systems should be used. In several studies, Isolator recovered more yeast and staphylococci, and the broth systems recovered more streptococci and anaerobes. We have compared Isolator to conventional Columbia broth, BACTEC 6B-7D, and BACTEC 16B-17D media. Of the three broth media combinations, the BACTEC resin media was the most effective and recovered aerobic and facultative anaerobic bacteria and yeasts as efficiently as did the Isolator system. Both Isolator and resin media remove antibiotics, thus in a hospital where many patients have received antibiotics before culture, these systems may be preferred. Recovery of yeasts has often been favored by the Isolator system, and Streptococcus pneumoniae has been recovered more often by the broth systems. Several large studies referenced earlier and individual case reports (18, 20) also showed that Candida spp., Histoplasma capsulatum, and Cryptococcus neoformans were detected more often and sooner on an agar surface from the Isolator system or broth subcultures than from broth media alone. Perhaps increased yeast recovery on agar is due to the aerobic metabolism of the yeast. Thus when fungemia is suspected, the Isolator system may be the blood culture system of choice. For those using only broth systems for detecting fungemia, terminal subcultures of the broth should be performed. Decreased yield of S. pneumoniae by the Isolator system may be caused by lysis of the bacteria by saponin in the Isolator tube. Saponin, used to lyse red blood cells in the Isolator system, was shown in 1933 to lyse pneumococci that had been sensitized with cholesterol and ergosterol (16). Organisms have been detected at approximately the same time with both the Isolator and broth systems. Colonies on Isolator plates may more readily provide inoculum for identification and antibiotic tests, and the presence of different colonial morphologies on Isolator plates may indicate polymicrobic infection earlier than would a broth system. These potential advantages, however, may not necessarily translate to earlier reports of important information. The availability of blood culture information depends, in addition to the system used, on the hours of operation of the laboratory, culture sampling times, the use of rapid procedures for organism identification, and the timely ability to communicate the results to the clinician. In our laboratory, initially more contaminants were recovered from the Isolator than by broth systems. These results suggested that cultures should be processed with minimum air flow and that hooded environments should be used. We now inoculate Isolator sediment to agar plates and examine those plates daily inside a SteriLGARD biosafety hood. We do not routinely report the presence of one or two staphylococci colonies on Isolator plates if these organisms are present only in that culture. The number of colony-forming units of organism per milliliter of blood (CFU/ml) can readily be determined by the Isolator system. How important is this information? Interest in quantifying organisms in the blood as an aid in the diagnosis and management of septicemia is not new. In 1985 I reviewed 52 years of blood culture quantitation (14) and found that many papers showed that colony counts have been used in studies of the diagnosis and treatment of endocarditis, the relationship between magnitude of bacteremia and mortality, and the identification of sites of infection in adults, children, and neonates. In most of these studies, labor-intensive pourplate techniques have been used for quantitation of organisms, and these cumbersome procedures have tended to discourage routine determinations of colony counts in septicemia. Introduction of the Isolator system has caused a renewed interest in the quantitation of bacteria and fungi in

A case of Nocardia asteroides pneumonia in a patient with the acquired immunodeficiency syndrome who was intolerant of sulfadiazine is described. On cefuroxime, the patient had a complete resolution of his Nocardia pneumonia. Disk-diffusion and broth microdilution antibiotic susceptibility testing (MIC less than or equal to 2 micrograms/ml) strongly supported the use of cefuroxime as treatment in this patient. Susceptibility testing with newer cephalosporins should be considered for all significant Nocardia isolates.