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Biomedical subjects

K A Sepkowitz

Publications and source records attributed to K A Sepkowitz.

At least 37 records · Page 2Linked to original sources

Changing patterns of infections and antimicrobial susceptibilities.

Nosocomial bloodstream infections across the United States and in Europe are increasingly attributable to gram-positive species--a trend that represents a reversal of the gram-negative predominance of the previous decades. Data from Memorial Sloan-Kettering Cancer Center and elsewhere show that patients with hematologic malignancies or patients who are immunocompromised because of anticancer treatments are experiencing this shift in microbial spectrum. Most common among gram-positive species are coagulase-negative Staphylococci. Antimicrobial resistance continues to increase, which makes treatment more difficult for infections caused by some species, especially vancomycin-resistant enterococcal species. The underlying causes of changes in microbial spectrum and drug-resistance patterns are incompletely understood, but it is clear that antibiotic exposure exerts a significant selective pressure on pathogens, resulting in partial or complete resistance. New drugs or drug combinations will be necessary to treat drug-resistant infections in cancer patients.

Adult↗

Resident expectations of morning report: a multi-institutional study.

BACKGROUND: Morning report, a cornerstone of inter nal medicine residency programs for many years, involves a diverse group of teachers and learners with heterogeneous learning goals. METHODS: We distributed a self-administered, cross sectional survey to internal medicine residents to clarify the objectives of the learners at morning report. We selected a convenience sample of internal medicine residents at community- and university-based programs Questions were answered in a Likert scale or multiple-choice format. RESULTS: Residents from 13 residency programs in 7 states participated. We received 356 completed surveys, which represented a 63% response rate. The house staff in our sample preferred that half of the guest attending physicians be generalists. They indicated that the primary function of morning report should be educational, and preferred to discuss the management of a few interesting cases rather than review all patients admitted the previous day. The majority of respondents (60.8%) favored a stepwise presentation of cases to simulate the chronology of receiving information. Disease process, diagnostic workup, and evaluation of tests and procedures were all considered important topics for discussion, while medical ethics and research methods were viewed as less important. Responses varied little when stratified by sex, postgraduate year, type of residency program, subspecialty fellowship plans, or location of medical school. CONCLUSIONS: Residents from a diverse group of programs expressed remarkably similar opinions about morning report. Consistent with the recently increased emphasis on ambulatory care and general internal medicine in residency training, they expressed a desire for about 50% of the guest attending physicians to be generalists. In addition, they preferred a style in which challenging cases were presented in a stepwise manner.

Adult↗

The impact of potent antiretroviral therapy on the characteristics of hospitalized patients with HIV infection.

OBJECTIVE: Despite advances in antiretroviral treatment, a large number of HIV-infected patients still require hospitalization. This study describes the characteristics of HIV patients requiring hospitalization before and after the advent of potent antiretroviral therapies. METHODS: Information was collected on all HIV-positive patients admitted to the New York Hospital-Cornell Medical Center in New York City. Data was collected from 1 January through 30 June 1995, and during the same 6-month interval in 1997. RESULTS: In each time period over 1500 outpatients were receiving treatment for HIV infection. There was a significant decrease in the incidence of admission [60.4 per 100 patient-years (PY) in 1995, 28.8 per 100 PY in 1997], and length of stay (10 versus 8 days). The median CD4 cell count of all HIV-infected patients admitted to the hospital doubled: 37 x 10(6)/l in 1995 versus 80 x 10(6)/l in 1997. However, there was no significant change in the median CD4 cell count of patients diagnosed with opportunistic infections. The incidence of the most common diagnosis (bacterial pneumonia, 8.0 per 100 PY in 1995 versus 3.6 per 100 PY in 1997) and the most common opportunistic infection (Pneumocystis carinii pneumonia 7.6 per 100 PY in 1995 versus 2.4 per 100 PY in 1997) decreased significantly. CONCLUSIONS: Since the introduction of potent antiretroviral therapy, a significant decrease in the incidence of hospital admission and opportunistic infections has occurred. There has been a doubling of the median CD4 cell count of inpatients. There has been no significant change in the median CD4 cell count at which patients present with opportunistic infections.

AIDS-Related Opportunistic Infections↗

Seroconversion rates in healthcare workers using a latex agglutination assay after varicella virus vaccination.

OBJECTIVES: To determine the seroconversion rate after varicella immunization of healthcare workers (HCWs) and the effect of seroconversion rate on current cost-based recommendations for universal vaccination. METHODS: A voluntary vaccination program for HCWs was performed at a tertiary-care cancer center in New York City. A commercial latex agglutination assay was used to test postvaccination antibody response. Costs for vaccination and postvaccination serological testing were compared to potential costs of postexposure employee furloughs. RESULTS: Of 263 seronegative HCWs, 96 (36.5%) began the vaccine program. Thirty-nine HCWs received only one dose of vaccine. Seven returned for follow-up antibody testing, of whom 4 were seropositive. Of the 57 HCWs who received two doses, 38 returned for follow-up serology. Thirty-one (81.6%) HCWs were seropositive for varicella-zoster virus antibodies, and seven HCWs (18.4%) remained seronegative. Total cost of vaccination for all 263 seronegative HCWs was estimated and compared to the cost of varicella-related furloughs at our institution. CONCLUSIONS: We found a considerably lower rate of vaccine-induced seroconversion at our hospital compared to that of the published literature. Despite this finding, universal varicella vaccination remained an extremely cost-effective alternative to the furloughing of exposed, seronegative HCWs. Projected hospital savings exceeded $53,000 in the first year after vaccination alone.

Adult↗

Predictors for multidrug-resistant tuberculosis among HIV-infected patients and response to specific drug regimens. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG), National Institutes for Health.

SETTING: Mortality associated with human immunodeficiency virus (HIV) related multidrug-resistant tuberculosis (MDR-TB) is reduced with effective early therapy. Identifying predictors of, and effective regimens for, MDR-TB is critical. OBJECTIVE: A multicenter prospective study was initiated to 1) determine the demographic, behavioral, clinical and geographic risk factors associated with the occurrence of MDR-TB among HIV-infected patients, and 2) to evaluate the overall survival and clinical response of MDR-TB patients treated with specific drug regimens. METHODS: Patients were prospectively evaluated for MDR-TB. Information included history of prior treatment for tuberculosis, close contact with a known case of MDR-TB, and residence in a facility with known or suspected MDR-TB transmission. Patients with known MDR-TB, or those suspected to be at high risk, were offered enrollment in a treatment pilot study. Study drugs included levofloxacin and at least two additional drugs to which the patient's isolate was known, or most likely, to be susceptible. Survival was the primary endpoint. RESULTS: Complete data are available for 156 HIV-infected patients with confirmed tuberculosis. Sixteen (10%) had MDR-TB. Only a history of prior tuberculosis treatment was associated with MDR-TB in multivariate analysis (OR = 4.4, P < 0.02). Twelve patients with MDR-TB enrolled in the treatment pilot had a median CD4 cell count of 51/mm3. The cumulative probability of survival at one year was 75% (95% CI 50.5-99.5) and at 18 months, 65.6% (95% CI 38.1-93.1). Toxicity requiring discontinuation of medications occurred in two patients. CONCLUSIONS: A history of treatment for tuberculosis was the only predictor for MDR-TB in a cohort of HIV-infected patients with tuberculosis. In addition, this prospective study supports the results of prior retrospective studies that effective treatment impacts on mortality. Current second-line treatment, including high dose levofloxacin, appears to be reasonably well tolerated.

AIDS-Related Opportunistic Infections↗

FUO and AIDS.

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AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus infection, Part II.

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.

AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus infection, Part I.

Initially recognized in 1982, acquired immunodeficiency syndrome (AIDS) has been the leading cause of death among young adults in the United States for much of this decade, and it has had a devastating impact on people in the developing world. It is estimated that 42 million people worldwide have been infected with human immunodeficiency virus (HIV), the virus that causes AIDS, and that almost 12 million people have died from AIDS-related diseases through 1997. Among these 12 million are 3 million children. Two thirds of the more than 30 million people with HIV or AIDS reside in sub-Saharan Africa. In the United States, 641,086 patients have been diagnosed with AIDS through 1997, and at least 385,000 have died. However, for the first time, new highly active antiretroviral therapies that include multiple drugs that attack the virus at several sites have slowed the progression from HIV to AIDS and from AIDS to death for those infected with HIV. The cumulative effect of these changes has been a reduction in both AIDS incident cases and AIDS deaths. Recent epidemiologic trends indicate that the proportion of AIDS incident cases and new HIV infections are increasing among women, African-Americans, and Hispanics, and the infections are more likely to be acquired through heterosexual transmission. The clinical management of HIV infection and AIDS has become increasingly complex in recent years. In addition to complete medical and social histories and physical examinations, hematologic, biochemical, serologic, and immunologic laboratory tests are required to predict the likelihood that patients will develop opportunistic infections and other complications related to HIV infection. Among the most important laboratory tests are measurements of HIV in plasma (viral load) in conjunction with peripheral blood CD4+ helper T lymphocyte counts. These tests are potent predictors of disease progression and their results have become markers for clinical response to therapy. The development of highly active antiretroviral therapy has had a profound impact on the epidemiology of AIDS and on the lives of individual patients. Through combinations of antiretroviral drugs, especially protease inhibitors, viral suppression can be achieved. However, adherence to these complex medical regimens and drug interactions have been problems for many patients. In addition, numerous questions remain unanswered, most importantly those regarding the timing of the initiation of treatment, the durability of viral suppression and clinical response, and the optimal "salvage" regimens for patients failing therapy either clinically or virologically.

AIDS-Related Opportunistic Infections↗

Hepatitis B vaccination program at a New York City hospital: seroprevalence, seroconversion, and declination.

BACKGROUND: Despite implementation of hepatitis B vaccination programs, 2 problems have prevented full vaccine-induced protection of health care workers (HCWs). About 10% to 12% of vaccinated HCWs do not develop antibody, and many HCWs continue to decline vaccination. To determine the effectiveness of our hepatitis B vaccine program, we studied rates of postvaccination seroconversion and vaccine declination. METHODS: Employee health service records were used to determine demographic features, hepatitis B surface antibody serostatus at baseline, serologic response to vaccine, and declination or acceptance of vaccine. RESULTS: About 26% of HCWs were seropositive at baseline, including those vaccinated before employment. Higher seroprevalence rates were seen among those born outside the United States, nurses, and laboratory workers. Seroconversion occurred in only 79% of HCWs who completed a 3-vaccine series. Increasing age was the only significant risk for failure to convert. Declination rates overall were about 45% and were lowest in HCWs who have jobs that included potential exposure to blood. CONCLUSION: Hepatitis B seroprevalence among HCWs at our hospital is higher than in many other urban hospitals in the United States; over postvaccination seroconversion rate is substantially lower; and our declination rate of 45% resembles other published series. Declination of vaccine and failure to respond to vaccine continue to thwart achievement of full control of this preventable occupational infection.

Adult↗

Evaluation of an interdisciplinary re-isolation policy for patients with previous Clostridium difficile diarrhea.

BACKGROUND: Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. METHODS: The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. RESULTS: Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. CONCLUSION: Our policy to control the spread of nosocomial C difficile required interdisciplinary cooperation between infection control and the admitting department. By identifying patients who were positive for toxin through admitting, we were able to place all potentially infected patients into isolation. Our positivity rate of 15% on readmission demonstrates the importance of this policy. The cost of controlling C difficile can be significantly lowered by clearing patients who were previously positive for toxin before hospital readmission.

Cancer Care Facilities↗

Effect of prophylaxis on the clinical manifestations of AIDS-related opportunistic infections.

Administration of targeted prophylaxis for AIDS-related opportunistic infections has contributed significantly to the recent decrease in mortality among patients with AIDS in the United States. Most reported prophylaxis trials have focused on determining (a) the percentage of cases prevented and (b) the effect of widespread antibiotic use on drug susceptibility. A third phenomenon that is seldom reported on is the attenuating effect of failed prophylaxis on the clinical presentation of opportunistic infections (OIs). With the increasingly widespread use of prophylaxis for OIs, more atypical "breakthrough" cases of opportunistic infections will be seen. Reports of clinical changes are reviewed below. Investigators should routinely report the clinical manifestations of breakthrough cases in all articles pertaining to prophylaxis for opportunistic infections in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS.

We compared the efficacy of a 400-mg once-weekly dosage versus a 200-mg daily dosage of fluconazole for the prevention of deep fungal infections in a multicenter, randomized, double-blind trial of 636 human immunodeficiency virus-infected patients to determine if a less intensive fluconazole regimen could prevent these serious but relatively infrequent complications of AIDS. In the intent-to-treat analysis, a deep fungal infection developed in 17 subjects (5.5%) randomly assigned to daily fluconazole treatment and in 24 (7.7%) given weekly fluconazole during 74 weeks of follow-up (risk difference, 2.2%; 95% confidence interval [CI], -1.7% to 6.1%). Thrush occurred twice as frequently in the weekly versus daily fluconazole recipients (hazard ratio, 0.59; 95% CI, 0.40-0.89), and in a subset of patients evaluated, fluconazole resistance was infrequent. Fluconazole administered once weekly is effective in reducing deep fungal infections in patients with AIDS, but this dosage is less effective than the 200-mg-daily dosage in preventing thrush.

AIDS-Related Opportunistic Infections↗

Postexposure prophylaxis for human immunodeficiency virus: frequency of initiation and completion of newly recommended regimen.

Recent evidence demonstrating the efficacy of zidovudine, as well as experience with protease inhibitors, led to revision of recommendations for occupational exposures to human immunodeficiency virus-infected blood. At our hospital, this resulted in significant increases in rates of reported exposures and prophylaxis initiation. Among 10 healthcare workers given three-drug, protease-inhibitor-containing regimens, five completed 4 weeks, two completed 4 weeks of two drugs, and three stopped due to intolerance. Three workers missed work due to side effects.

Anti-HIV Agents↗

A national survey of immunization practices following allogeneic bone marrow transplantation.

OBJECTIVES: To describe the frequency and patterns of use of routine childhood and hepatitis B, pneumococcal, influenza, and meningococcal vaccines following allogeneic bone marrow transplantation (BMT). DESIGN, SETTING, AND PARTICIPANTS: Survey of all US transplantation centers participating in the National Marrow Donor Program (NMDP) during 1994. MAIN OUTCOME MEASURES: Use, timing, and total doses of selected vaccines given to patients younger than 7 years and patients aged 7 years or older following allogeneic BMT. RESULTS: Of 66 centers associated with the NMDP, 45 (68%) responded. A total of 97% of centers performing transplants on patients younger than 7 years and 88% of centers performing transplants on patients aged 7 years or older gave either the diphtheria-tetanus vaccine or the diphtheria-tetanus-pertussis vaccine compared with 77% and 58% usage, respectively, of Haemophilus influenza type b conjugate vaccine (P=.03 and .003, respectively). Centers were more likely to administer inactivated poliovirus and measles-mumps-rubella vaccines to patients younger than 7 years than to the older age group (94% vs 73% for poliovirus, P=.02; and 94% vs 70% for measles-mumps-rubella, P=.01). About one half of centers routinely administer hepatitis B vaccine and approximately three quarters immunize with pneumococcal and influenza vaccines. Few programs, regardless of age of bone marrow recipient, use multiple vaccine (> or =2) doses. The number of schedules reported for specific vaccines varied widely (3-11 schedules per vaccine). CONCLUSIONS: Despite convincing evidence that patients lose protective antibodies to vaccine-preventable diseases following allogeneic BMT and accumulating data showing the safety and efficacy of many vaccines after BMT, vaccines are underutilized and schedules vary widely at US transplant centers. National guidelines for optimal doses and timing of vaccines after BMT are warranted.

Adolescent↗