Timothy E. Kiehn

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.

Mycobacterium avium Complex Infections in Patients with the Acquired Immunodeficiency Syndrome

Disseminated infection with Mycobacterium avium complex developed in 67 patients with the acquired immunodeficiency syndrome (AIDS) who were followed at Memorial Sloan-Kettering Cancer Center. Twenty-nine patients were treated with two or more antimycobacterial drugs for a mean of 6 weeks, and 7 patients received therapy for less than 1 month. Most patients received ansamycin, clofazimine, and ethionamide or ethambutol. Clinical improvement did not occur in treated patients, and microbiologic cure was never obtained. Mycobacterial bacteremia persisted in 24 of 26 treated patients. Colony counts of M. avium complex in sequential blood cultures decreased in 3 patients. Every autopsied patient with M. avium complex infection diagnosed before death, whether treated or not, had disseminated M. avium complex infection at autopsy.

Bacteremia and Fungemia in Patients with the Acquired Immunodeficiency Syndrome

Forty-nine episodes of bacteremia and fungemia occurred in 38 of 336 patients with the acquired immunodeficiency syndrome seen at our institution since 1980. There were five types of infections. Infections commonly associated with a T-cell immunodeficiency disorder comprised 16 episodes and included those with Salmonella species, Listeria monocytogenes, Cryptococcus neoformans, and Histoplasma capsulatum. Infections commonly associated with a B-cell immunodeficiency disorder included those with Streptococcus pneumoniae and Haemophilus influenzae. Infections occurring with neutropenia were caused by Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus faecalis. Other infections occurring in the hospital were caused by Candida albicans, Staphylococcus epidermidis, enteric gram-negative rods, Staphylococcus aureus, and mixed S. aureus and group G streptococcus. Other infections occurring out of the hospital included those with S. aureus, Clostridium perfringens, Shigella sonnei, Pseudomonas aeruginosa, and group B streptococcus. Because two thirds of the septicemias were caused by organisms other than T-cell opportunists, these pathogens should be anticipated during diagnostic evaluation and when formulating empiric therapy.

Treatment of Infections in Patients with the Acquired Immunodeficiency Syndrome

The microorganisms that regularly infect patients with the acquired immunodeficiency syndrome (AIDS) have become well recognized. Most take advantage of defects in T-lymphocyte function, but others, such as Streptococcus pneumoniae and Haemophilus influenzae, take advantage of B-cell defects. Still others, such as Staphylococcus aureus and Shigella species, occur or persist for reasons that are unclear. Infections with organisms associated with hospitalization and medical procedures are also seen and should be anticipated. Among the infections taking advantage of T-cell defects, Pneumocystis carinii pneumonia is the most commonly diagnosed, but cytomegalovirus infection may be equally common. Disseminated Mycobacterium avium-intracellulare infection has been found in one half of our patients at postmortem examination. The retrovirus responsible for AIDS commonly infects the central nervous system, as does Toxoplasma gondii. Although candida infections are common, dissemination is uncommon. Many of the infections respond to appropriate therapy but tend to recur when treatment is stopped. Often treatment courses must be prolonged even beyond those used in other immunocompromised hosts.

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.

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.

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).

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

Abstract: 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.

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.

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.