Lowell S. Young

2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer

Walter T. Hughes, Donald Armstrong, Gerald P. Bodey, Eric J. Bow, Arthur E. Brown, Thierry Calandra, Ronald Feld, Philip A. Pizzo, Kenneth V. I. Rolston, Jerry L. Shenep, and Lowell S. Young St. Jude Children’s Research Hospital, Memphis, Tennessee; Memorial Sloan-Kettering Cancer Center, New York, New York; University of Texas M. D. Anderson Cancer Center, Houston; Harvard Medical School, Boston, Massachusetts; Stanford University School of Medicine, Palo Alto, and Kuzell Institute for Arthritis, San Francisco, California; University of Manitoba, Winnipeg, and Princess Margaret Hospital, Toronto, Canada; and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever

This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are internists, pediatricians, and family practitioners. The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy. Panel members represented experts in adult and pediatric infectious diseases and oncology. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

Aspergillosis complicating neoplastic disease

Abstract From 1964 to June 1971, 93 cases of aspergillosis were encountered at Memorial Sloan-Kettering Cancer Center. The 29 cases diagnosed in 1969–1970 and the 15 cases diagnosed in the first half of 1971 represented, respectively, a doubling and a quadrupling since 1964–1965. The incidence of aspergillosis in patients with leukemia was seven times greater than in patients with Hodgkins disease or lymphoma (p 3 ). Pulmonary involvement was present in 90 of 93 cases, disseminated disease in 23. The commonest clinical pattern was unremitting fever and development of pulmonary infiltrates despite broad-spectrurh antibiotic therapy. In an increasing number of cases aspergillosis followed Pseudomonas aeruginosa infections. When present, serum aspergillus precipitins correlated well with invasive disease, but a negative test result was far less reliable. In one case of acute myelogenous leukemia the patient recovered from pulmonary aspergillosis after surgical excision of the lesion and remission of her leukemia. The incidence of aspergillosis is increasing and should be considered in the setting of progressive pulmonary infiltrates in leukemic and other heavily immunosuppressed patients who respond poorly to antibacterial therapy. Earlier diagnosis may lead to more effective therapy.

Infectious Complications of Neoplastic Disease

Progress has been made in the diagnosis and treatment of infection in patients with neoplastic disease. Among the advances is the appreciation that certain opportunistic infections occur in association with particular host immune defects and epidemiologic factors. Such immune defects are seen secondary to or as a consequence of treatment for the patients basic disease. Improved methods such as serology, open lung biopsy, and fiberoptic bronchoscopy have allowed for earlier diagnosis and treatment of opportunistic infections. The development of empiric antibiotic regimens, particularly aminoglycosides and the antipseudomonal penicillins, have improved the outcome in the febrile neutropenic patient. The benefits of protective environments have been challenged; prophylactic antibiotics and various forms of immunotherapy are of interest but remain investigational.

Nocardia asteroides infection complicating neoplastic disease

Abstract During the decade 1960–1969, Nocardia asteroides was isolated from sputum, abscesses or exudates in twenty-two patients at Memorial Hospital. These patients could be divided into two groups. Group I consisted of thirteen patients with underlying neoplasms receiving radiation or chemotherapy in whom unequivocal evidence of nocardial infection developed. Clinical manifestations included bronchopneumonia, lobar pneumonia, necrotizing pneumonia with single or multiple abscesses, and brain, hepatic or scrotal abscesses. Ten patients had either leukemia or lymphoma. The simultaneous presence of tumor and nocardial infection in the lung was noted in five cases. Sputums or exudates from the patients in group I were positive for organisms simultaneously in both culture and smear in only a third of examinations; this stresses the need for multiple bacteriologic examinations when the diagnosis of nocardiosis is suspected. Although the underlying disease was usually progressively fatal, an excellent response to sulfonamides with resolution of pulmonary disease was noted in several patients who were maintained on anticancer therapy. Group II was composed of nine patients with predominantly respiratory symptoms and fever. Multiple positive cultures were obtained in many of these patients, but all lacked objective pulmonary findings and symptoms usually resolved without treatment. Such cases may represent milder nocardial infections of the upper respiratory tract although a saprophytic role for nocardia cannot be ruled out. These observations indicate that nocardiosis is a significant and often fatal opportunistic infection in patients being treated for cancer, but further studies are needed to define the clinical and epidemiologic spectrum of this disease in man.

Pseudomonas aeruginosa Vaccine in Cancer Patients

Abstract During 1969 to 1972, 361 adult patients (176 vaccinees, 185 control patients) at a cancer center were randomized into a prospective study of the lipopolysaccharide vaccine derived from 7 s...

Limitations of current antimicrobial therapy in the immunosuppressed host: Looking at both sides of the coin

During the last twenty years there have been considerable advances in the antimicrobial management of the immunosuppressed host. These include the development of antibiotics with broad-spectrum and high bactericidal activity along with the appreciation of the importance of promptly initiating empiric antibiotic therapy when the granulocytopenic patient becomes febrile and continuing them (in some cases with empiric antifungal therapy) until the resolution of granulocytopenia. Nonetheless, infection still remains a major cause of death in compromised hosts and a number of limitations of therapy persist. Included are a limited repertoire of drugs active against fungi (particularly Aspergillus) as well as certain viruses (for example, cytomegalovirus) and the inability to eradicate certain sites of infection (for example, Pseudomonas pneumonia) even with effective agents. Current investigations are focused on developing new antimicrobial agents as well as methods to improve the altered host defenses of immunosuppressed patients, both as adjuvants to therapy and, eventually, as a means to prevent infectious complications.

Anti-Pseudomonas Heat-Stable Opsonins in Acute Lymphoblastic Leukemia of Childhood.

Heat-stable opsonic activity against Pseudomonas aeruginosa and Staphylococcus epidermidis was measured in sera of 33 children with acute lymphoblastic leukemia at selected times during treatment of their disease. Compared to adults, opsonization of P. aeruginosa was normal in children tested at the time of diagnosis and before chemotherapy. Immediately after achievement of remission, opsonic activity against Pseudomonas was significantly decreased (P smaller than 0.05) compared with pretreatment activity. Activity usually returned to normal and remained so during long-term remission maintenance therapy. In children studied just prior to death from unremitting leukemia, however, anti-Pseudomonas opsonic activity was significantly decreased when compared with that of a group of children before any leukemic treatment (p smaller than 0.005). Anti-S. EPIDERMIDIS OPSONIC ACTIVITY SHOWED NO CHANGES DURING THE PATIENTS COURSE. Decreased serum opsonic activity may significantly contribute to the increased incidence of severe Pseudomonas infections in patients with acute lymphoblastic leukemia.

Antibody Response to a Polyvalent Pseudomonas Vaccine in Children with Leukemia

Pseudomonas aeruginosa infection accounts for 30% of gram-negative bacteremias in children with acute leukemia at Memorial Hospital. There is a mortality rate of 87% despite antimicrobial therapy. Previous studies in animals and man following severe burns suggest that P. aeruginosa infection may be subjected to immunological control. Active immunization of 20 leukemic children in bone marrow remission was attempted with a lipopolysaccharide antigen derived from 7 strains of P. aeruginosa (Fisher-Devlin immunotypes). Vaccination consisted of 4 intramuscular injections at weekly intervals. Febrile and local reactions occurred in all, but were not severe enough to discontinue the procedure. The appearance of antibody was demonstrated by 1 to 5 preipitin bands using the Oucterlony immunodiffusion technique. This was correlated with a rise in hemagglutinating antibody titers. Sixteen children demonstrated antibody response within one month, despite the immunosupressive antileukemic therapy that they were receiving. If this antibody proves to be protective against P. aeruginosa infection by further control studies in progress, vaccination of patients early in the course of leukemia would be indicated.

Immunoprophylaxis of Pseudomonas aeruginosa

Excerpt To the editor: We believe that Dr. Kehl Markleys comments on the immunoprophylaxis ofPseudomonas aeruginosainfections published in the January issue of the ANNALSare too optimistic. None o...