Empiric therapy for the febrile neutropenic patient. Design bias.

Empiric therapy is practical and must be begun promptly; the specific regimen chosen must be based upon local conditions and epidemiology. It must be recalled that subgroups of patients are not necessarily equivalent to the majority, i.e., there are low-risk patients for whom ambulatory and/or oral therapy is appropriate and, conversely, there are high-risk patients who have a potential for a high mortality and who, while perhaps few in number, are of critical importance. Further, many of these patients are very complex, and this leads to a high level of physician concern and insecurity. This physician concern, in turn, leads to a tendency to modify regimens, given that the physician all too often is dealing with inadequate diagnostic information owing to the patient situation. The physician's choice of modification is highly dependent upon knowledge of the regimen the patient is already receiving. There is a need for clear definition of endpoints, and these must be established before the study is initiated. All too many published studies are too small to evaluate the endpoint that has been defined, and many others, although sufficient in size, have all of the problems inherent in studies conducted at multiple sites by multiple individuals with differing degrees of commitment or enthusiasm toward the study at hand. A few implications for study design and evaluation seem evident: it is critical to define endpoints and execute the study accordingly. This means determining the size of the population needed and determining the presence or absence of risk groups. Patients to be excluded e.g., those in whom infection is doubted must be selected on the basis of objective data by an observer blinded to both the outcome and the treatment. Similarly, the classification of response should preferably be done by an observer not influenced by knowledge of the therapy being given. Finally, and similarly, the decision to modify therapy (especially if modification is equivalent to defining failure with the regimen) should not be influenced by knowledge of the therapy being administered.

Ownership and governance of university teaching hospitals: let form follow function.

Under the best of circumstances, the complex decision-making and resource-allocation processes of a state university (and often of a variety of state agencies important to the university) significantly hinder the ability of the university-owned hospital to make changes critical to its financial and, hence, its programmatic success. At worst, as was the case for the University of Maryland Hospital a decade ago, the hospital can become capital-starved and operationally deficient under the bureaucratic mantle of the state and university and find itself unable to respond to the fast-changing market, placing its viability in jeopardy. To remedy this situation at the University of Maryland Hospital, in 1984 the state created a separate not-for-profit corporation, the University of Maryland Medical System ("the Medical system"), governed by its own board of directors, with a mandate to assure sound business practices, outstanding patient care, access to patients from across the state for tertiary care, access for the local disadvantaged community for comprehensive care, and attention to the academic mission of the university and its school of medicine. The results include strong financial performance, the ability to recapitalize outmoded facilities and technology, growth of strong programs, and the recruitment of excellent chairs and faculty. The Medical System's success suggests that university teaching hospitals, which necessarily depend on patient care revenues, may best be served by (1) removing them from university governance, thus allowing them to give primacy to their mission of patient care, and (2) removing them from state ownership, thus allowing them to use sound business practices in the competitive health care environment. The challenge under this arrangement is to ensure that the teaching hospitals can still support the educational and research programs that distinguish them. By establishing its independent, actively involved board of directors, the Medical System has successfully responded to this challenge.

Complementary medicine.

Complementary medicine can be described as additional approaches to care outside of mainstream medical practice but frequently based on traditional practices of nonwestern cultures. These include acupuncture, meditation, massage, diet manipulation, and many others. Recent reviews demonstrate wide and frequent use of these measures, often without concurrent discussion with the patient's physician. One estimate is that more than $13 billion is spent annually on complementary techniques in the United States alone. Many patients with cancer turn to these techniques. Care givers need to recognize this trend, learn about complementary medicine, and guide patients in their proper application when appropriate.

The University of Maryland Medical System invests in its community's minorities.

As a private, non-state-owned teaching hospital adjacent to a predominately low income African American community in Baltimore, the University of Maryland Medical System (hereafter called the Medical System) in partnership with the state's medical school has historically provided excellent medical care to the community's residents regardless of their ability to pay. Nevertheless, executive leadership recognized that the Medical System needed to be even more socially and economically responsible to the minority community by investing more of the system's resources in that community. Doing so would improve the economic strength of the community, and this strength would help the Medical System to continue to thrive and expand its business in Baltimore City. Therefore, in the late 1980s, the Medical System created a program that focuses on greater inclusion of minorities particularly African Americans, in personnel, construction, purchasing, and community outreach. In the area of personnel, recruitment efforts have focused on increasing the representation of minorities, particularly African Americans, in management and residency positions. The result has been the creation of a more supportive environment for minority personnel throughout the organization as well as for minority patients and vendors who have dealings with the medical system. In the area of construction, minority development efforts have included the establishment of a flexible bid-award policy and a partnership with the minority business community. As a result, total construction dollars spent with minority-owned firms increased from $2 million to $18 million over seven years, and the portion of these dollars spent with African American-owned firms increased sixfold. In the area of purchased goods and services, more creative approaches to improving minority participation have been necessary. These have included partnering minority distributors with major suppliers and literally assisting in the creation of new minority firms capable of effectively responding to the competitive marketplace. As a result, purchasing dollars spent with minority-owned firms increased from $1.5 million to $3.2 million in four years, and the portion of these dollars spent with African American-owned firms nearly tripled. In community outreach, a comprehensive program has emerged that includes education, career development, disease prevention, and health promotion activities. The Medical System has encountered many barriers to success in these efforts but fortunately has overcome many of them. This article outlines the methods the system has used to achieve its minority development goals, with particular emphasis on the difficult area of purchasing.

Infections in cancer patients: some controversial issues.

Despite more than two decades of clinical research into the management of infections in the neutropenic cancer patient, many patients still develop serious morbidity from infection and all too many still die. A number of controversies surround (a) the use of combination versus monotherapy for initial empiric administration; (b) the use of vancomycin as part of the initial regimen; (c) the origin of Staphylococcus epidermidis infections (i.e., mostly from vascular catheters or mostly from the alimentary canal); (d) the use of acyclovir for herpes simplex prophylaxis during remission induction for acute leukemia patients not undergoing bone marrow transplantation; (e) the use of alimentary canal microbial suppression or reverse isolation in a room with laminar air flow, or both, as infection prevention techniques. Current recommendations and observations include the following. (a) Monotherapy with ceftazidime or imipenem is effective and appropriate for patients with moderate granulocytopenia at limited risk for infection with a resistant organism. Combination therapy is recommended for patients with profound, persistent granulocytopenia who are at high risk for gram-negative bacteremia; such bacteremic patients have a better prognosis with combined-modality therapy. (b) Vancomycin need not be included in the initial regimen although some centers may choose to do so because of the high prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of indwelling vascular catheters, most S. epidermidis infections among neutropenic patients originate from along the alimentary canal. (d) Herpes simplex infection is much more common following standard remission induction chemotherapy than previously recognized. Acyclovir will reduce these infections and concurrently probably reduce the likelihood of resultant bacterial/fungal co-infections and superinfections. (e) Selective microbial suppression is appropriate for patients expected to experience prolonged (more than 2 weeks) or profound (below 100 granulocytes/microliters) granulocytopenia. Agents chosen should suppress aerobic but not anaerobic flora (maintain colonization resistance) and need to have an effect on both the oral cavity and esophagus as well as the intestines.

Instruction in the techniques and concept of supportive care in oncology.

Cancer education merits a coordinated, vertical curriculum and an integrated planning strategy. It has become clear that it is as important to teach the techniques of supportive care in oncology as it is to teach the concepts of cancer biology, pathology, epidemiology, prevention, detection and aggressive treatments. Our aim is to determine whether the medical school and nursing school curricula give the students an introduction to the concepts of supportive care of the cancer patient. The spectrum of such supportive care encompasses a wide range of issues working towards a common goal of providing overall comfort with an emphasis on quality of life, and runs parallel with specific therapeutic strategies and associated problems. Do the graduate medical student and nursing student understand that cancer management is multidisciplinary and team-based? That the approach to pain management not only includes the administration of pain medications, but should also evaluate pain assessment and anesthetic, neurosurgical and behavioral approaches? That nausea and vomiting associated with chemotherapy can be ameliorated to a certain extent? That infections are common but algorithms exist for prevention and therapy? That certain metabolic complications are unique to cancer patients? That transfusions are vital procedures in patients with neoplasms undergoing aggressive treatments but are associated with certain risks and complications? That there are serious psychosocial, ethical and legal needs to be considered? To address these issues, the American Cancer Society Professors of Clinical Oncology, the American Cancer Society Professors of Oncology Nursing and the United States Cancer Center Directors were surveyed.(ABSTRACT TRUNCATED AT 250 WORDS)

Double beta-lactam regimen compared to an aminoglycoside/beta-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients.

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C +/- T), both agents being administered only if the initial granulocyte count was below 200/microliters, or ceftazidime plus piperacillin (C + P). The overall response rate was 71% (39 of 60 for C +/- T and 45 of 58 for C + P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C + P regimen (P = 0.06), there was no difference in response for patients with bacteremia and profound (< 100/microliters) sustained granulocytopenia. The double beta-lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced excellent serum bactericidal levels (C +/- T geometric mean peak 1:170; C + P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C + P and in 6 of 89 trials in the C +/- T group (P = 0.19). The incidence of secondary infections in patients with profound (< 100/microliters) sustained granulocytopenia was lower in the C +/- T group (P = 0.04). Alimentary canal anaerobic flora preservation with C +/- T, and suppression with C + P, was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Hickman catheters in association with intensive cancer chemotherapy.

Hickman catheters were the major venous access devices utilized at the University of Maryland Cancer Center from November 1978 to 1987. This study provided an opportunity to standardize insertion technique, to manage catheter-related activities and daily maintenance procedures in order to examine the progression of Hickman-catheter-related problems, to identify those factors that may minimize them, and to develop guidelines for the management and prevention of complications and malfunctions. In all, 690 Hickman catheters (368 double lumens) were placed in patients with acute leukemia and other cancers: 401 catheters were placed in patients with leukemia; 269 were placed during neutropenia; and 230 at platelet counts of < 50,000/microliters. Two surgeons inserted 490 catheters, and the remaining 200 were placed by a group of rotating surgeons. All catheters were placed with the intention that they would remain in place as long as clinically necessary. Total Hickman catheter days were 134273. Infectious complications included exit site infections (160), tunnel infections (46) and bacteremias (397). There were 438 instances of noninfectious complications including thrombosis, lack of function, catheter migration, fracture and hemorrhage. Recommendations for prevention and treatment of Hickman-catheter-related complications include the development of a select group committed to placement, daily maintenance and management of problems; prompt removal of catheters with Candida sp. fungemia and bacteremia due to Bacillus sp. or a bacteremia that persists for > 48 h after initiation of appropriate antibiotics, tunnel infections or Hickman-catheter-associated thrombosis. The majority of bacteremias and exit site infections can be effectively treated with antibiotics and local care.

Gram-negative bacteremia.

In the 1960s, almost all patients who developed gram-negative bacteremia during granulocytopenia died; death occurred before blood culture results were available in about 50% of cases; many patients received antibiotics that were, at best, suboptimal and frequently inactive against the invading pathogen. In the early 1970s epidemiological studies demonstrated that more than 50% of gram-negative bacteremias were caused by hospital-acquired strains which colonized along the alimentary canal and caused infection in a limited number of locations, especially the pharynx, lungs, colon, and perianum. Surveillance culture studies have demonstrated that among acquired gram-negative bacilli, Pseudomonas aeruginosa will almost invariably proceed to bacteremia if the patient becomes profoundly neutropenic, with Escherichia coli and Klebsiella pneumoniae leading to bacteremia in only a moderate number of patients and other gram-negative bacilli rarely progressing to bacteremia despite colonization. Hence, the leading causes of bacteremia in the granulocytopenic patient are E. coli, K. pneumoniae and P. aeruginosa. Further investigations demonstrated that gram-negative bacilli were acquired from hands, food, and water, thus leading to approaches to infection prevention which included careful handwashing, low-microbial-content diet, and attention to water sources, including ice machines. Another basic approach to infection prevention has been to suppress gram-negative bacilli colonizing the alimentary canal with oral nonabsorbable antibiotics or, more recently and more effectively, with agents such as the fluoroquinolones which, unlike previous regimens, do not concurrently suppress the anaerobic flora, hence maintaining colonization resistance. The third basic approach to infection prevention is to improve the host defense factors, principally by a more rapid return of circulating granulocytes with the use of colony-stimulating factors such as granulocyte/macrophage colony-stimulating factor or granulocyte colony-stimulating factor. As to therapy, the fundamental approach with presumed gram-negative bacteremia is the prompt institution of empiric antibiotic therapy when fever first develops in the setting of granulocytopenia. There is a short "window of opportunity" after which no therapy will be effective. Combinations of antibiotics such as a beta-lactam and an aminoglycoside are used for multiple reasons: to afford coverage in the event the pathogen, proves resistant to one of the agents, to afford a synergistic activity thus improving and prolonging the serum bactericidal activity, and to reduce the development of resistance. However, patients can be divided into two risk groups: those with granulocytopenia and a regenerating bone marrow and those with an aplastic marrow who will have persistent, profound (< 100 microliters) granulocytopenia.(ABSTRACT TRUNCATED AT 400 WORDS)

University of Maryland Medical System: American medicine's first teaching facility reinvents the academic hospital.

The University of Maryland Medical School, established in 1807, focused on bedside teaching. This emphasis has continued and expanded through the growth of University Hospital and, ultimately, the University of Maryland Medical System, such that Maryland can now boast of a superb medical care system providing excellent medical education and research opportunities in a patient care setting.