Candidiasis: detection by gas-liquid chromatography of D-arabinitol, a fungal metabolite, in human serum.

D-Arabinitol was identified as a major metabolite of Candida species in human subjects. Gas-liquid chromatography was used to measure the concentration of D-arabinitol in serum. The study included subjects who were healthy and cancer patients who had proven invasive candidiasis or were colonized with Candida. D-Arabinitol concentrations greater than 1.0 microgram per milliliter were found in serum from patients with invasive infection. This technique may prove valuable in the diagnosis of invasive candidiasis.

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.

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.

Fungemia in the immunocompromised host. Changing patterns, antigenemia, high mortality.

Fungemias were reviewed in 110 immunocompromised patients hospitalized between November 1, 1974, and December 31, 1977, a 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.

Bacteremia and fungemia in patients with neoplastic disease.

This study reviewed 431 episodes of septicemia occurring in 356 patients with cancer at Memorial Sloan-Kettering Cancer Center during 1982. The most frequent organisms causing 273 episodes in 239 non-neutropenic patients were Escherichia coli (20 percent), Staphylococcus aureus (13 percent), polymicrobic (12 percent), Pseudomonas species (8 percent), Klebsiella species (7 percent), Candida species (7 percent), Bacteroides species (6 percent), Enterobacter species (4 percent), and Clostridium species (4 percent). The overall mortality was 31 percent (21 percent with adequate therapy; 50 percent with inadequate therapy). The most frequent organisms causing 158 episodes in 117 neutropenic patients were polymicrobic (21 percent), E. coli (16 percent), Klebsiella species (15 percent), Pseudomonas species (8 percent), Candida species (6 percent), S. aureus (6 percent), Streptococcus faecalis (5 percent), S. epidermidis (4 percent), and Corynebacterium CDC-JK (3 percent). The overall mortality was 52 percent (36 percent with adequate therapy; 88 percent with inadequate therapy). Since a review a decade ago, the spectrum of organisms changed in that the gram-positive organisms, S. faecalis, S. epidermidis, and C. CDC-JK, emerged as important pathogens. Neutropenic patients had a high incidence (42 percent) of septicemia due to multiple organisms, occurring concurrently or sequentially. The overall mortality of these patients was exceptionally high (80 percent). In contrast, the overall mortality of neutropenic patients with single-organism septicemia was comparable to that of non-neutropenic patients with single-organism septicemia (37 percent versus 29 percent).

Prospective study of infections in indwelling central venous catheters using quantitative blood cultures.

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-related 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 delineated. PATIENTS AND METHODS: During the year of this study, 488 central venous catheters were implanted. Records were maintained on demographic variables, date of catheter implantation, surgeon, white blood cell count, absolute neutrophil count, and underlying diagnosis. Blood for both aerobic and anaerobic culture was collected from each patient. For patients in whom infection developed, clinical features, white blood cell count, absolute neutrophil 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 episodes (69 percent) were successfully treated with antibiotics and local care. Of the 20 tunnel infections, 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 Pseudomonas species. CONCLUSION: On the basis of these results, compulsory removal of the catheter is not required in cases of catheter-related sepsis. Similarly, exit site infections can often be cured by means of antibiotics and local care. However, catheter removal is required to achieve cure in most tunnel infections, particularly if Pseudomonas species are cultured from the exit sites of patients with tunnel infection.

Catheter-related Malassezia furfur fungemia in immunocompromised patients.

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.

Continuous high-grade mycobacterium avium-intracellulare bacteremia in patients with the acquired immune deficiency syndrome.

Serial quantitative blood cultures were performed before and during treatment in four patients with the acquired immune deficiency syndrome (AIDS) and Mycobacterium avium-intracellulare bacteremia. Initial colony counts were 350 to 28,000 cfu/ml, the counts declined substantially with treatment in two patients, and they declined modestly with treatment but rose when it was stopped in the other two. In one patient who was studied in detail, most of the circulating organisms were within the leukocytes, colony counts in blood subjected to lytic agents were 1.9- to 5.2-fold higher than in unlysed blood, and there were 10(5) to 10(6) times more organisms per gram in several tissue specimens obtained at autopsy than per milliliter of blood. It is concluded that continuous high-grade bacteremia is common in patients with AIDS and severe M. avium-intracellulare infections and that serial quantitative blood cultures provide a potential means for studying treatment in these patients.

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.

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.

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.

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.

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.

The prevalence of yeasts in clinical specimens from cancer patients.

Yeasts recovered from cancer patients during a 15-month period were speciated, and the prevalence of these isolates in various types of clinical specimens was determined. Five species, including Candida albicans, Candida tropicalis, Candida parapsilosis, Candida krusei, and Torulopsis glabrata, accounted for 97.1% of the isolates. Eighteen different species were recovered. Respiratory and urine specimens yielded 75% of the organisms. C. albicans, C. tropicalis, and C. parapsilosis were recovered in about equal frequency from blood cultures. Certain species usually were recovered from one type of specimen: Candida quilliermondii from urine, Trichosporon cutaneum and Candida pseudotropicalis from respiratory sites, and Cryptococcus neoformans from spinal fluid. Pityrosporum orbiculare was isolated only from ear and urine cultures. Most of the yeasts (95.4%) were identified within 48 hours after isolation.

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.

Flavobacterium meningosepticum bacteremia in an adult with acute leukemia. Use of rifampin to clear persistent infection.

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.

Nocardia infection in the acquired immunodeficiency syndrome.

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.

M.I.D.A.S.--an on-line microbiology information system.

The system I have described is the result of several years of study and design. A special thanks is in order to our many friends who shared thoughts, both good and bad, about their own systems. Computerization of clinical microbiology laboratories requires planning that varies considerably from other diagnostic laboratories. As we develop and update our systems it will be very important for us to continue this dialogue. The microbiology Computer Users Group, started by George E. Buck at Texas, is a good example of this effort.

Amplified fragment length polymorphism analysis of human clinical isolates of Mycobacterium haemophilum from different continents.

The role of the species Mycobacterium haemophilum as a pathogenic non-tuberculous microorganism is becoming better defined with the use of specific detection methods. However, epidemiological investigations of this species are still scarce. We analysed the genetic diversity of M. haemophilum by amplified fragment length polymorphism (AFLP) typing and compared isolates from different parts of the world. In total, 128 isolates, including 41 from the USA, 51 from Australia, 28 from Europe and eight from Israel were compared using AFLP methodology. Two restriction enzymes (MseI and EcoRI) and one selective primer were applied and provided a high discriminatory power. Clusters of isolates with identical AFLP patterns, which could indicate a possible common source, were observed from the Netherlands, New York and Australia. No clear clustering on the basis of continental origin was observed; however, types were restricted to geographical areas and not found on other continents. A high genetic stability within the species was demonstrated by the long-term existence of a single type.