Arthur E. Brown

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.

Central-Nervous-System Toxoplasmosis in Homosexual Men and Parenteral Drug Abusers

Central-nervous-system toxoplasmosis developed in 7 of 269 patients with the acquired immunodeficiency syndrome reported to the New York City Health Department through July 1982. Focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis, and detectable IgG antibody to Toxoplasma gondii were common; but IgG titers of 1:1024 or more, IgM antibody to T. gondii, and positive open brain biopsies were uncommon. Serologic findings suggested that the disease resulted from recrudescent rather than primary infection. Four of five patients improved when treated with sulfonamides and pyrimethamine, but 2 had relapses. An aggressive diagnostic approach and sometimes even empiric therapy are warranted when central-nervous-system toxoplasmosis is suspected in a seropositive patient with the acquired immunodeficiency syndrome.

Rhodococcus equi: An Emerging Pathogen

More than 100 cases of Rhodococcus equi infection have been reported since the first description of human disease caused by this organism. The vast majority of patients infected with R. equi are immunocompromised, and two-thirds have human immunodeficiency virus infection. The clinical manifestations of R. equi infection are diverse, although 80% of patients have some pulmonary involvement. The organism is easily cultured from specimens of infected tissue or body fluid, but it may be misdiagnosed as a contaminant. Treatment is often prolonged, and relapses at distant sites are common. This article summarizes the history, diagnosis, clinical features, and treatment of infection with this emerging pathogen.

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.

Severe pneumococcal infection in patients with neoplastic disease

A study of pneumococcal bacteremia in 56 patients with neoplastic disease from January 1, 1972 to June 30, 1980 is presented and compared to an earlier study between 1955 and 1971. Patients at highest risk were those with Hodgkin‐s disease who had been splenectomized, multiple myeloma and chronic lymphocytic leukemia showing an attack rate of 15.6/1000, 12.5/1000, and 10.8/1000, respectively. The attack rate was more than three times higher among patients with Hodgkin‐s disease in the present series compared to the previous series. In 32% of cases there was no identifiable source for the infection. Four splenectomized patients with Hodgkin‐s disease developed pneumococcal meningitis and two died. The overall mortality rate was 32% versus a rate of 18% for those treated with appropriate antibiotics for more than 24 hours. There was a significant improvement in overall survival when compared with our previous series. As before, almost one fourth (24%) of our isolates were not among those included in the pneumococcal vaccine presently available. Antibiotic prophylaxis should be considered in high risk patients.

Influenza immunization of children with neoplastic diseases.

During the National Influenza Immunization Program in 1976, 147 children with neoplastic diseases received Wyeth split‐product bivalent influenza vaccine: A/New Jersey/8/76 (Hsw1N1), A/Victoria/3/75 (H3N2). Thirteen normal siblings served as controls. Seventy‐one patients received two doses of the vaccine four weeks apart. After the second injection of A/NJ/8/76, there was a difference between the response of the patients on chemotherapy and those off therapy ⩾30 days—38% vs. 76%, P < 0.01 for four‐fold rise and 26% vs. 57%, P < 0.05 for the attainment of protective (⩾32) hemagglutination inhibition (HI) titers. These differences were observed in both leukemia‐lymphoma and solid tumor patients. There was a difference in HI titers to A/Vic/75 between patients on and off chemotherapy after a single injection, 34% vs. 71%, P < 0.001 for a four‐fold rise. After the second immunization, only 52% on, and 86% off therapy (P < 0.05) had a four‐fold rise in titers. Thirty‐two percent of the patients on treatment who achieved “protective” titers did so only after the second immunization. Immunoglobulin levels and neutropenia did not correlate with the inability to obtain a four‐fold rise in titers. Our findings suggest that patients on chemotherapy cannot be effectively vaccinated by a new antigen, and that single yearly boosters may be insufficient for recall of old antigens. Patients off chemotherapy ⩾30 days respond as normal controls. Cancer 45:750‐756, 1980.

A prospective randomized double-blind trial of bolus urokinase in the treatment of established Hickman catheter sepsis in children

BACKGROUND The incidence of Hickman catheter sepsis is 10% to 40%, with resultant catheter loss in one third of infections. Urokinase causes dissolution of colonized intracatheter fibrin thrombi and may improve salvage. STUDY AIMS To evaluate the efficacy of 12-hour-interval slow-push urokinase infusion in addition to standard antibiotic therapy in the treatment of catheter sepsis in a pediatric oncology population. METHODS A two-arm randomized double-blind trial was undertaken, with catheter salvage rate as the end point. Patients with Hickman catheter sepsis were randomized after culture data confirmed the diagnosis. The study drug was administered by a slow intravenous push and given at 12-hour intervals for a total of four doses. The catheters were aspirated after 1 hour. RESULTS AND CONCLUSIONS The trial was stopped after 41 patients were entered into the study; 18 patients received a placebo, and 23 received the urokinase. In the placebo group, six catheters were lost; in the urokinase group, eight were lost. The rate of bacterial clearance was equivalent for both. After administration of the study drug, each group had three episodes of fever and chills; two of these resulted in hypotension (one in each group). The authors conclude that slow-push urokinase infusion during established Hickman catheter sepsis does not result in improved catheter salvage or bacterial clearance. Slow intravenous push infusions in this setting may provoke hemodynamic instability even after initiation of antibiotics.

A standardized regimen of antibiotics prevents infectious complications in skull base surgery

Objectives/Hypothesis: Craniofacial surgery has been associated with a significant improvement in disease outcome for patients with skull base neoplasms. Despite this improved survival, complications remain considerable. One major source of complications is infectious events. The current study was designed to evaluate a prospectively designed antibiotic regimen and its impact on the incidence and severity of infectious complications. This regimen was compared with a group of historic controls in which antibiotics were administered on an ad hoc basis. The specific objectives/hypothesis were to determine 1) the incidence and severity of infection in a group of patients treated with a nonstandardized antibiotic regimen undergoing craniofacial resection, and 2) whether the use of a prospectively designed, three‐drug, broad spectrum antibiotic is associated with a reduced incidence and severity of infections.