Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown about the basic biology of P. carinii and studies of this infection have been hampered by the lack of cultivation methods. We developed a sensitive and specific assay for P. carinii by utilizing DNA amplification of the P. carinii dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before the onset of histopathological changes. DNA amplification analysis of serum demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected prospectively). Patients with advanced AIDS but without a history of P. carinii pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase chain reaction may facilitate investigations into the natural history and epidemiology of P. carinii infection, provide insight into the pathogenesis of parasite dissemination, and offer a useful, noninvasive diagnostic test for the detection of human pneumocystosis.

Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy.

Respiratory viruses (RV) are a leading cause of infection-related morbidity and mortality for patients undergoing treatment for cancer. This analysis compared duration of RV shedding as detected by culture and PCR among patients in a high-risk oncology setting (adult patients with haematological malignancy and/or stem cell transplant and all paediatric oncology patients) and determined risk factors for extended shedding. RV infections due to influenza virus, parainfluenza virus (PIV), human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) from two study periods-January 2009-September 2011 (culture-based testing) and September 2011-April 2013 (PCR-based testing)-were reviewed retrospectively. Data were collected from patients in whom re-testing for viral clearance was carried out within 5-30 days after the most recent test. During the study period 456 patients were diagnosed with RV infection, 265 by PCR and 191 by culture. The median range for duration of shedding (days) by culture and PCR, respectively, were as follows-influenza virus: 13 days (5-38 days) versus 14 days (5-58 days), p 0.5; RSV: 11 days (5-35 days) versus 16 days (5-50 days), p 0.001; PIV: 9 days (5-41 days) versus 17 days (5-45 days), p ≤0.0001; HMPV 10.5 days (5-29 days) versus 14 days (5-42 days), p 0.2. In multivariable analysis, age and underlying disease or transplant were not independently associated with extended shedding regardless of testing method. In high-risk oncology settings for respiratory illness due to RSV and PIV, the virus is detectable by PCR for a longer period of time than by culture and extended shedding is observed.

Community-based outbreaks of tuberculosis.

Numerous recent reports have detailed outbreaks of tuberculosis in hospitals and other congregate settings. The characteristics of such settings, including high concentrations of infectious patients and immunocompromised hosts, the potential for sustained daily contact for weeks and often months, and improper precautions taken for protection, make them well suited for tuberculosis transmission. However, community-based outbreaks, which are the source of much public concern, have not been reviewed since 1964, when 109 community outbreaks were examined. Since few of the characteristics of institutional settings are present in the community, the lessons learned may not be applicable to community-based outbreaks. Furthermore, recent studies with analysis by restriction fragment length polymorphisms have documented unexpectedly high rates of primary disease in certain urban communities, suggesting that our understanding of community-based transmission may be incomplete. We reviewed all reported community-based outbreaks of tuberculosis occurring in the last 30 years to assess the basis of our current understanding of community-based transmission. More than 70 outbreaks were identified, with schools being the most common site. In most, a delay in diagnosis, sustained contact with the index case, inadequate ventilation, or overcrowding was contributory. We conclude that community-based outbreaks of tuberculosis continue to occur and that well-established risks contribute to most outbreaks. Many outbreaks can be prevented or limited by attention to basic infection control principles.

Fever among outpatients with advanced human immunodeficiency virus infection.

BACKGROUND: Fever is common among persons with human immunodeficiency virus (HIV) infection. However, the clinical implications of fever in this population have not been evaluated. We therefore undertook a prospective study of fever in persons with advanced HIV infection to determine the incidence and etiology of fever in this patient group. METHODS: Prospective natural history study of 176 patients with advanced HIV infection followed up at Memorial Sloan-Kettering Cancer Center, New York, NY, from April 1, 1990, through December 31, 1990. RESULTS: Fever occurred in 46% of patients. A diagnosis was made in 83% of episodes, with acquired immunodeficiency virus-defining illnesses accounting for half of the diagnosed cases. Patients whose conditions required more than 2 weeks to diagnose most often had lymphoma, Mycobacterium avium-intracellulare bacteremia, or Pneumocystis carinii pneumonia. Four patients had persistent unexplained fever without a clear source. Only one patient had fever that clearly responded to antiretroviral therapy. CONCLUSIONS: Fever is common among outpatients with advanced HIV infection. Human immunodeficiency virus itself is rarely the cause of fever in such patients; the cause of the fever should be thoroughly evaluated.

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.

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.

Antibiotic prophylaxis in patients receiving hematopoietic stem cell transplant.

Effective prophylaxis against specific infections has allowed increasingly potent conditioning regimens to be given, thereby prolonging survival in HSCT recipients. The Centers for Disease Control and Prevention, in collaboration with numerous professional societies, has recently published guidelines to codify and advance this approach. Controversy remains in several areas but, curiously, the most intense debate concerns prevention of bacterial infections, the most extensively studied of all of the approaches. Central to this debate are the competing priorities of a potentially ill patient on the one hand vs the long-term consequences of unchecked antibiotic use. The emergence in the 1990s of vancomycin-resistant Enterococcus demonstrated all too vividly how devastating such an end result could be. This article will review the arguments for and against the routine use of antibacterial prophylaxis in HSCT recipients.

High rates of infection and colonization by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation.

Nontuberculous mycobacteria (NTM) are essentially ubiquitous and can infect both immunocompetent and immunocompromised hosts. However, NTM infection is surprisingly uncommon in reports from allogeneic hematopoietic stem cell transplant (alloSCT) centers that do not routinely perform allograft T-cell depletion. We reviewed medical records for all adult patients who underwent alloSCT at our center between January 1993 and December 2001. American Thoracic Society and Centers for Disease Control and Prevention guidelines Were used to define definite, probable, and possible NTM infection. Of 571 patients, 36 of 372 (9.7%) T-cell depleted and 14 of 199 (7.0%) conventional alloSCT recipients (P=0.26) had a positive culture for NTM after alloSCT. Of the 50 patients with NTM infection, 16 had definite infection and 34 had probable or possible infection. Rates of NTM infection were 5 to 20-fold higher than rates reported by other centers. Of the 16 definite infections, nine were caused by Mycobacterium haemophilum. Two patients had disseminated M. avium complex (MAC) infection and one had a vascular catheter infected by MAC. Three patients died from complications of NTM infection. Patients with probable or possible NTM infection had markedly different epidemiology, risk factors, site and species of NTM infection, and prognosis than patients with definite NTM infection.

Infectious complications of autologous bone marrow and peripheral stem cell transplantation for refractory leukemia and lymphoma.

We aimed to characterize the infectious complications of autologous bone marrow (AuBMT) and peripheral stem cell transplantation (PSCT) in patients with refractory leukemia and lymphoma. We performed a retrospective analysis of all patients (n = 56) with refractory leukemia or lymphoma treated with AuBMT or PSCT at Memorial Sloan-Kettering Cancer Center from January 1993 to July 1994. Records were available in 55, of whom 33 (60%) received AuBMT and 22 (40%) PSCT. Fifteen (27%) developed complicated infections, including 13 (39%) treated with AuBMT and two (9%) with PSCT. Complicated infections were caused by bacterial (11 episodes), fungal (four episodes), and viral (four episodes) pathogens. Five (9%) infections were fatal. In a multivariate model, only duration of neutropenia was significantly associated with development of complicated infection (P = 0.006). Thus, 27% of patients with refractory leukemia or lymphoma treated with AuBMT or PSCT developed complicated infections and 9% died of infection. Prolonged neutropenia was significantly associated with development of infection. Patients receiving PSCT had significantly lower rates of complicated infection, presumably due to the associated shorter duration of neutropenia. Future studies are needed to define the role of PSCT as treatment for refractory neoplastic disease.

Respiratory syncytial virus infection following hematopoietic stem cell transplantation.

Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients of autologous or allogeneic transplants. The incidence of RSV following allogeneic or autologous HSCT was 5.7% and 1.5%, respectively. Of the 58 patients with an RSV infection, 16 of 21 patients identified within the first post-transplant month, developed pneumonia. Seventy-two percent of patients received aerosolized ribavirin and/or RSV-IGIV, including 23 of 25 patients diagnosed with RSV pneumonia. In this aggressively treated patient population, three patients died of RSV disease, each following an unrelated HSCT.

Disseminated toxoplasmosis following T cell-depleted related and unrelated bone marrow transplantation.

More than 95% of reported cases of disseminated toxoplasmosis following BMT have occurred following an unmodified transplant. Most have been fatal, diagnosed at autopsy and without antemortem institution of specific therapy. From 1989 to 1999, we identified 10 cases of disseminated toxoplasmosis, in 463 consecutive recipients of a T cell-depleted (TCD) BMT. Transplants were from an unrelated donor (n = 5), an HLA-matched sibling (n = 4) or an HLA-mismatched father (n = 1). In 40%, both the donor and recipient had positive IgG titers against T. gondii pre-transplant; in 30%, only the recipient was sero-positive. Three recipients of an unrelated TCD BMT developed toxoplasmosis despite both donor and host testing negative pretransplant. All 10 patients presented with high grade fever. CNS involvement ultimately occurred in seven patients, with refractory respiratory failure and hypotension developing in nine. Eight of 10 cases were found only at autopsy, involving the lungs (n = 7), heart (n = 5), GI tract (n = 5), brain (n = 8), liver and/or spleen (n = 5). The only survivor, treated on the day of presentation with fever and headache, was diagnosed by detection of T. gondii DNA by polymerase chain reaction (PCR) performed on the blood and spinal fluid. This study demonstrates the similar incidence of toxoplasmosis following TCD BMT and that reported post T cell-replete BMT, and underscores the need for rapid diagnostic tests in an effort to improve outcome.

Prevalence of PPD positivity among new employees at a hospital in New York City.

OBJECTIVE: To determine the prevalence of tuberculin reactivity among all new employees at a hospital in New York City. DESIGNS: Prospective measurement of purified protein derivative (PPD) status in consecutive new employees at a hospital in New York City from 1991 to 1993. All employees are tested as part of a preemployment physical, assuring complete compliance. Aplisol (Parke-Davis, Morris Plains, NJ) was used in 1991 and 1992, and Tubersol (Connaught, Swiftwater, PA) in 1993. Tests were applied and interpreted by trained employee health personnel. RESULTS: Of 313 consecutive new employees, comprising all job categories, 40% were PPD positive at time of initial hire, including 20% of US-born and 70% of foreign-born employees. Of 114 persons who had received BCG vaccination, 67% were PPD positive. By multivariate regression analysis, age, BCG vaccination history, and foreign country of birth were independent predictors of a reactive PPD test. CONCLUSIONS: The high prevalence of tuberculin reactivity may reflect high rates of Mycobacterium tuberculosis infection and disease in the community, complicating interpretation of the efficacy of Centers for Disease Control and Prevention (CDC) guidelines to prevent the spread of tuberculosis in healthcare facilities.

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.

Control of occupational hepatitis B among healthcare workers in the Czech Republic, 1982 to 1995.

Occupational hepatitis B remains a threat to healthcare workers (HCWs) worldwide, even with availability of an effective vaccine. Despite limited resources for public health, the Czech Republic instituted a mandatory vaccination program for HCWs in 1983. Annual incidence rates of acute hepatitis B were followed prospectively through 1995. Despite giving vaccine intradermally from 1983 to 1989 and intramuscularly as half dose from 1990 to 1995, rates of occupational hepatitis B decreased dramatically, from 177 cases per 100,000 workers in 1982 (before program initiated) to 17 cases per 100,000 in 1995. Among high-risk workers, the effect was even more dramatic (from 587 to 23 per 100,000). We conclude that strong public-health leadership led to control of occupational hepatitis B among HCWs in the Czech Republic, despite limited resources that precluded administering full-dose intramuscular vaccine for much of the program. Application of a similar program should be considered for other countries in regions that currently do not have a hepatitis B vaccination program.

Does a cheaper mask save money? The cost of implementing a respiratory personal protective equipment program.

OBJECTIVE: To determine the annual cost of implementing and maintaining a respiratory personal protective equipment (PPE) program at an urban hospital. SETTING: St Clare's Hospital and Health Center, a 250-bed hospital in Manhattan that treats 60 to 100 cases of tuberculosis annually. METHODS: Review of Purchasing Department records for all masks acquired by the hospital from 1992 to 1995, and an estimate of administrative time spent developing and implementing the guidelines recommended by various agencies during the study interval. RESULTS: Respiratory isolation was provided for 6,360 to 10,883 days annually during the 4-year interval. Yearly costs for the PPE program ranged from $86,560 to $175,690. Of note, the daily cost for a respiratory isolation day decreased dramatically between 1994 and 1995 ($25/day to $13/day), when the high-efficiency particulate air-filter (HEPA) respirator was used by all staff. The decrease occurred because of lower administrative costs and a sharp decrease in the numbers of HEPA units purchased. Objective measures of worker compliance with HEPA respirators demonstrated the decrease was not due to less HEPA use but rather that employees were using each HEPA unit for several weeks, as recommended. CONCLUSION: We found a significant decrease in cost in the second year of our HEPA program due to increasing employee familiarity with the program. Newly approved, cheaper, but less durable, N-95 masks are unlikely to withstand multiple wearings and may be discarded after a few uses. Thus, cheaper masks may result in a more expensive PPE program.

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.

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.

Dramatic decrease in tuberculin skin test conversion rate among employees at a hospital in New York City.

BACKGROUND: The Centers for Disease Control and Prevention recently issued updated guidelines for preventing the transmission of tuberculosis in health care facilities. Many recommendations, including the use of high-efficiency particulate air filter respirators, are expensive to implement and of unproven efficacy. We therefore reviewed the tuberculin skin test conversion rate among our employees from 1991 to 1993, before introduction of high-efficiency particulate air filter respirators. During this period, several other improvements in tuberculosis control were implemented. METHODS: Employee tuberculin test conversion rates were reviewed by 6-month interval from 1991 to 1993. RESULTS: Throughout the study period, several tuberculosis control measures were implemented, including early isolation of patients with suspected cases of tuberculosis in rooms with negative-pressure ventilation, placement of germicidal UV light fixtures into patient rooms and common areas, and use of Technol shields (Technol, Inc., Fort Worth, Texas) (1991), particulate respirators (1992), and dust-mist-fume respirators (1993). With these improvements, the conversion rate among employees fell from 20.7% in the first 6 months of 1991 to 5.8% in the latter half of 1993. CONCLUSIONS: The rate of skin test conversion among our employees decreased before introduction of high-efficiency particulate air filter respirators. This suggests that nosocomial spread of tuberculosis can be decreased by means of previously established, less costly methods.

Benefit of two-step PPD testing of new employees at a New York City hospital.

BACKGROUND: Recent concern about nosocomial transmission of tuberculosis has led hospitals to scrutinize employee tuberculin conversion rates. The Centers for Disease Control and Prevention recommends two-step testing of new employees to limit the booster phenomenon. The cost of such a program and its subsequent yield have not recently been examined. METHODS: Employee health records were retrospectively reviewed of persons hired from 1993 and 1994 at St. Clare's Hospital in New York City, all of whom received two-step testing at time of initial employment. RESULTS: Of 262 new employees, 107 (41%) had positive tuberculin results on initial testing. The results of 15 (9.7%) of the remaining 155 patients became positive on two-step testing administered 1 week later. Persons with a positive second test result were significantly more likely to be male or foreign born or to have received previous bacille Calmette-Guérin vaccination. Identification of these 15 persons and exclusion of them from probable subsequent conversion prevented an almost 50% increase in the annual conversion rate at our hospital, from 3.2% to 4.7%. CONCLUSION: Two-step tuberculin testing is an essential means of identifying persons with a baseline positive tuberculin test result, thus allowing accurate reporting of subsequent employee tuberculin conversions.

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.