Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis.

Lyme disease has a worldwide distribution and is the most common vector-borne disease in the United States. Incidence, clinical manifestations, and presentations vary by geography, season, and recreational habits. Lyme neuroborreliosis (LNB) is neurologic involvement secondary to systemic infection by the spirochete Borrelia burgdorferi in the United States and by Borrelia garinii or Borrelia afzelii species in Europe. Enhanced awareness of the clinical presentation of Lyme disease allows inclusion of LNB in the imaging differential diagnosis of facial neuritis, multiple enhancing cranial nerves, enhancing noncompressive radiculitis, and pediatric leptomeningitis with white matter hyperintensities on MR imaging. The MR imaging white matter appearance of successfully treated LNB and multiple sclerosis display sufficient similarity to suggest a common autoimmune pathogenesis for both. This review highlights differences in the epidemiology, clinical manifestations, diagnosis, and management of Lyme disease in the United States, Europe, and Asia, with an emphasis on neurologic manifestations and neuroimaging.

Risk factors for nosocomial pneumonia. Focus on prophylaxis.

Despite an increased understanding of the pathogenesis of NP and advances in diagnosis and treatment, the risk, cost, morbidity, and mortality of NP remain unacceptably high. This article has identified strategic areas for primary and secondary prophylaxis that are simple and cost-effective. Realizing that the pathogenesis of NP requires bacterial colonization and the subsequent entry of these bacteria into the lower respiratory tree helps highlight the role of cross-infection and the importance of standard infection control procedures. Similarly the role of sedation and devices as risk factors can be reduced by minimizing the duration and intensity of sedation and length of exposure to invasive devices. Additional low-cost interventions that have been shown to be effective in preventing NP are the positioning of patients in a semirecumbent position and the appropriate use of enteral feeding, antibiotics, and selected medical devices. Prophylaxis of NP and VAP is carried out best by a multidisciplinary management team comprised of physicians (critical care, pulmonary medicine, infectious diseases, and primary care), critical care and infection control nurses, and respiratory therapists, even though this approach may result in decreased professional autonomy and freedom. This group should review the current guidelines, pathways, and standards for short-term and long-term prophylaxis of NP and VAP, then integrate them into and monitor their use for routine patient care. The risk factors and prophylaxis strategies for NP discussed in this article apply primarily to patients in acute care facilities, but also are relevant to alternative health care settings as well as the care of ill patients in ambulatory settings. The routine use of effective team policies for prophylaxis needs to be monitored by the Joint Commission for the Accreditation of Health Care or other agencies. Research to delineate the most effective and feasible strategies for prophylaxis NP has been compromised by insufficient funding and lack of adequate, randomized multicenter studies to enable generalizability of results. Effective strategies for prophylaxis have not been disseminated widely or implemented in hospitals. Successful short-term and long-term strategies for prophylaxis must be evaluated and implemented by a team of physicians, nurses, and respiratory therapists. More than 100 years ago, Sir William Osler warned health care providers, "Remember how much you don't know." The authors would add that clinicians have acquired significant knowledge about risk factors and prophylaxis of NP in the 1980s and 1990s, but prophylaxis as a theory rather than an action. If the tree has not been planted, the time is now.

Guidelines for the management of intravascular catheter-related infections.

These guidelines from the Infectious Diseases Society of America (IDSA), the American College of Critical Care Medicine (for the Society of Critical Care Medicine), and the Society for Healthcare Epidemiology of America contain recommendations for the management of adults and children with, and diagnosis of infections related to, peripheral and nontunneled central venous catheters (CVCs), pulmonary artery catheters, tunneled central catheters, and implantable devices. The guidelines, written for clinicians, contain IDSA evidence-based recommendations for assessment of the quality and strength of the data. Recommendations are presented according to the type of catheter, the infecting organism, and the associated complications. Intravascular catheter-related infections are a major cause of morbidity and mortality in the United States. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida albicans most commonly cause catheter-related bloodstream infection. Management of catheter-related infection varies according to the type of catheter involved. After appropriate cultures of blood and catheter samples are done, empirical i.v. antimicrobial therapy should be initiated on the basis of clinical clues, the severity of the patient's acute illness, underlying disease, and the potential pathogen(s) involved. In most cases of nontunneled CVC-related bacteremia and fungemia, the CVC should be removed. For management of bacteremia and fungemia from a tunneled catheter or implantable device, such as a port, the decision to remove the catheter or device should be based on the severity of the patient's illness, documentation that the vascular-access device is infected, assessment of the specific pathogen involved, and presence of complications, such as endocarditis, septic thrombosis, tunnel infection, or metastatic seeding. When a catheter-related infection is documented and a specific pathogen is identified, systemic antimicrobial therapy should be narrowed and consideration given for antibiotic lock therapy, if the CVC or implantable device is not removed. These guidelines address the issues related to the management of catheter-related bacteremia and associated complications. Separate guidelines will address specific issues related to the prevention of catheter-related infections. Performance indicators for the management of catheter-related infection are included at the end of the document. Because the pathogenesis of catheter-related infections is complicated, the virulence of the pathogens is variable, and the host factors have not been well defined, there is a notable absence of compelling clinical data to make firm recommendations for an individual patient. Therefore, the recommendations in these guidelines are intended to support, and not replace, good clinical judgment. Also, a section on selected, unresolved clinical issues that require further study and research has been included. There is an urgent need for large, well-designed clinical studies to delineate management strategies more effectively, which will improve clinical outcomes and save precious health care resources.

The cost effectiveness of combination antiretroviral therapy for HIV disease.

BACKGROUND: Combination antiretroviral therapy with a combination of three or more drugs has become the standard of care for patients with human immunodeficiency virus (HIV) infection in the United States. We estimated the clinical benefits and cost effectiveness of three-drug antiretroviral regimens. METHODS: We developed a mathematical simulation model of HIV disease, using the CD4 cell count and HIV RNA level as predictors of the progression of disease. Outcome measures included life expectancy, life expectancy adjusted for the quality of life, lifetime direct medical costs, and cost effectiveness in dollars per quality-adjusted year of life gained. Clinical data were derived from major clinical trials, including the AIDS Clinical Trials Group 320 Study. Data on costs were based on the national AIDS Cost and Services Utilization Survey, with drug costs obtained from the Red Book. RESULTS: For patients similar to those in the AIDS Clinical Trials Group 320 Study (mean CD4 cell count, 87 per cubic millimeter), life expectancy adjusted for the quality of life increased from 1.53 to 2.91 years, and per-person lifetime costs increased from $45,460 to $77,300 with three-drug therapy as compared with no therapy. The incremental cost per quality-adjusted year of life gained, as compared with no therapy, was $23,000. On the basis of additional data from other major studies, the cost-effectiveness ratio for three-drug therapy ranged from $13,000 to $23,000 per quality-adjusted year of life gained. The initial CD4 cell count and drug costs were the most important determinants of costs, clinical benefits, and cost effectiveness. CONCLUSIONS: Treatment of HIV infection with a combination of three antiretroviral drugs is a cost-effective use of resources.

Epidemiology of ventilator-associated pneumonia.

In summary, the method of diagnosis used for VAP accounts for reported differences in etiology, pathogenesis, and outcomes. Further studies are needed to assess outcomes related to various diagnostic methods rather than to assess the sensitivity and specificity of these methods.

Influenza vaccination of human immunodeficiency virus (HIV)-infected adults: impact on plasma levels of HIV type 1 RNA and determinants of antibody response.

We assessed the effect of influenza vaccination on plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and the impact of age, plasma HIV-1 RNA level, CD4 cell count, and anti-HIV therapy on immune response. Forty-nine adults (mean age, 38.7 years; mean CD4 cell count +/- SD, 190 +/- 169/mL; mean plasma HIV-1 RNA level +/- SD, 154,616 +/- 317,192 copies/mL) were immunized. Elevations of > or = 0.48 log in plasma HIV-1 RNA levels occurred in two (4%) of 49 subjects within 4 weeks of vaccination. A fourfold or greater increase in antibody titer occurred in 13 (45%) of 29 subjects, correlating directly with CD4 cell count (P = .002) and inversely with plasma HIV-1 RNA level (P = .034). By multivariate analysis, CD4 cell count was a stronger predictor of antibody response than was plasma HIV-1 RNA level. We conclude that increases in plasma HIV-1 RNA levels following influenza vaccination are rare and transient and that antibody response is impaired with CD4 cell counts of < 100/mL and plasma HIV-1 RNA levels of > 100,000 copies/mL. Prospective trials are needed to evaluate the impact of highly active therapy on immune response after vaccination.

The cost-effectiveness of prophylaxis for Mycobacterium avium complex in AIDS.

OBJECTIVE: To develop a simulation model to project costs, life expectancy, and cost-effectiveness in discounted dollars per quality-adjusted life-year (QALY) saved for clinical strategies to prevent Mycobacterium avium complex (MAC) in patients with AIDS. METHODS: We used natural history data from the Multicenter AIDS Cohort Study, efficacy and toxicity data from randomized clinical trials, and cost data from the AIDS Cost and Services Utilization Survey. The model permits timing of prophylaxis to be stratified by CD4 count (201-300, 101-200, 51-100, and < or = 50/mm3), and allows combinations of prophylaxis, crossover to second- and third-line agents for toxicity, and consideration of adherence, resistance, and quality of life. RESULTS: The model projects that the average HIV-infected patient with a beginning CD4 count between 201 and 300/mm3 has total lifetime costs of approximately $43,150 and a quality-adjusted life expectancy of 42.35 months. If azithromycin prophylaxis for M. avium complex is begun after the CD4 declines to 50/mm3, costs and quality-adjusted survival increase to approximately $44,040 and 42.78 months, respectively, for an incremental cost-effectiveness ratio of $25,000/QALY compared with no M. avium complex prophylaxis. Other prophylaxis options (i.e., rifabutin, clarithromycin, and combination therapies) either cost more but offer shorter survival, or have cost-effectiveness ratios above $260,000/QALY. Sensitivity analysis reveals that, for reasonable assumptions about quality of life, risk of infection, prophylaxis cost, adherence, and resistance, azithromycin remains the most cost-effective prophylaxis option. CONCLUSIONS: Azithromycin prophylaxis, begun after the CD4 count has declined to 50/mm3, is the most cost-effective M. avium complex prophylaxis strategy. Consistent with new United States Public Health Service guidelines, it should be the first-line prophylaxis option.

Ventilator-associated bacterial pneumonia: challenges in diagnosis, treatment, and prevention.

Ventilator-associated pneumonia (VAP) is a common infection in intensive care unit patients that results in high mortality and morbidity and increased duration of hospital stay. Clinical diagnostic methods are sensitive, but lack specificity. Quantitative analysis of specimens from the lower respiratory tract increases specificity. Bacteria causing VAP may originate from the patient's endogenous flora, other patients or hospital personnel, or from environmental sources. Aspiration or direct inoculation are the major routes of bacterial entry into the lower respiratory tract. The bacterial inoculum and host response in the lung are important factors for pathogenesis. Late-onset nosocomial pneumonia is often caused by Pseudomonas aeruginosa, Acinetobacter species, and Staphylococcus aureus. Streptococcus pneumoniae and Haemophilus influenzae, however, are the more common pathogens in early-onset disease. Oropharyngeal and gastric colonization with bacteria, cross-infection, as well as the indiscriminate use of antibiotics or invasive devices substantially increase the risk of VAP. An understanding of the epidemiology and pathogenesis of VAP, along with implementation of appropriate preventive measures, are needed to decrease the incidence, morbidity, and mortality associated with VAP.

A Monte Carlo simulation of advanced HIV disease: application to prevention of CMV infection.

BACKGROUND: Disagreement exists among decision makers regarding the allocation of limited HIV patient care resources and, specifically, the comparative value of preventing opportunistic infections in late-stage disease. METHODS: A Monte Carlo simulation framework was used to evaluate a state-transition model of the natural history of HIV illness in patients with CD4 counts below 300/mm3 and to project the costs and consequences of alternative strategies for preventing AIDS-related complications. The authors describe the model and demonstrate how it may be employed to assess the cost-effectiveness of oral ganciclovir for prevention of cytomegalovirus (CMV) infection. RESULTS: Ganciclovir prophylaxis confers an estimated additional 0.7 quality-adjusted month of life at a net cost of $10,700, implying an incremental cost-effectiveness ratio of roughly $173,000 per quality-adjusted life year gained. Sensitivity analysis reveals that this baseline result is stable over a wide range of input data estimates, including quality of life and drug efficacy, but it is sensitive to CMV incidence and drug price assumptions. CONCLUSIONS: The Monte Carlo simulation framework offers decision makers a powerful and flexible tool for evaluating choices in the realm of chronic disease patient care. The authors have used it to assess HIV-related treatment options and continue to refine it to reflect advances in defining the pathogenesis and treatment of AIDS. Compared with alternative interventions, CMV prophylaxis does not appear to be a cost-effective use of scarce HIV clinical care funds. However, targeted prevention in patients identified to be at higher risk for CMV-related disease may warrant consideration.

Response of lymphoepithelial parotid cysts to antiretroviral treatment in HIV-infected adults.

BACKGROUND: Surgical resection has been the usual therapy for HIV-infected patients with lymphoepithelial parotid cysts. OBJECTIVE: To study antiretroviral therapy for lymphoepithelial parotid cysts. DESIGN: Case series. SETTING: HIV outpatient clinics. PATIENTS: HIV-infected patients with lymphoepithelial parotid cysts. INTERVENTION: Antiretroviral therapy. MEASUREMENTS: Change in size of the parotid cyst, CD4 lymphocyte count, and HIV viral load. RESULTS: Nine HIV-infected adults presented with chronic, large parotid cysts, eight of which were bilateral. In at least seven patients, the cysts were the initial sign of HIV infection. In six patients, the cysts resolved completely with combination antiretroviral therapy. Four of these patients also received prednisone. Three patients who did not comply with antiretroviral therapy had partial responses followed by relapses. CONCLUSIONS: Parotid cysts are an unrecognized sign of early HIV infection. These cysts respond to combination antiretroviral therapy, with or without corticosteroids. Surgical resection should be reserved for patients in whom medical therapy has failed or those who refuse or are poorly compliant with medical therapy.

The cost-effectiveness of preventing AIDS-related opportunistic infections.

CONTEXT: Multiple options are now available for prophylaxis of opportunistic infections related to the acquired immunodeficiency syndrome (AIDS). However, because of differences in incidence rates as well as drug efficacy, toxicity, and costs, the role of different types of prophylaxis remains uncertain. OBJECTIVE: To determine the clinical impact, cost, and cost-effectiveness of strategies for preventing opportunistic infections in patients with advanced human immunodeficiency virus (HIV) disease. DESIGN: We developed a Markov simulation model to compare different strategies for prophylaxis of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) infection, fungal infections, and cytomegalovirus (CMV) disease in HIV-infected patients. Data for the model were derived from the Multicenter AIDS Cohort Study, randomized controlled trials, and the national AIDS Cost and Services Utilization Survey. MAIN OUTCOME MEASURES: Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) saved. RESULTS: For patients with CD4 cell counts of 0.200 to 0.300 x 10(9)/L (200-300/microL) who receive no prophylaxis, we projected a quality-adjusted life expectancy of 39.08 months and average total lifetime costs of $40288. Prophylaxis for PCP and toxoplasmosis with trimethoprim-sulfamethoxazole for patients with CD4 cell counts of 0.200 x 10(9)/L (200/microL) or less increased quality-adjusted life expectancy to 42.56 months, implying an incremental cost of $16000 per QALY saved. Prophylaxis for MAC for patients with CD4 cell counts of 0.050 x 10(9)/L (50/microL) or less produced smaller gains in quality-adjusted life expectancy; incremental cost-effectiveness ratios were $35000 per QALY saved for azithromycin and $74000 per QALY saved for rifabutin. Oral ganciclovir for the prevention of CMV infection was the least cost-effective prophylaxis ($314000 per QALY saved). Results were most sensitive to the risk of developing an opportunistic infection, the impact of opportunistic infection history on long-term survival, and the cost of prophylaxis. CONCLUSIONS: The cost-effectiveness of prophylaxis against HIV-related opportunistic infections varies widely, but prophylaxis against PCP or toxoplasmosis and against MAC delivers the greatest comparative value. In an era of limited resources, these results can be used to set priorities and explore new alternatives for improving HIV patient care.

Occupational exposure to HIV: experience at a tertiary care center.

We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers.

Hospital-acquired pneumonia: perspectives for the healthcare epidemiologist.

Nosocomial pneumonia is defined as an infection of lung parenchyma that was neither present nor incubating at the time of the patient's admission to the hospital. In the United States, hospital-acquired pneumonia is the second most common nosocomial infection and accounts for the most deaths from nosocomial infection. We describe how infection control personnel can use targeted surveillance to identify clusters of cases and to prevent pneumonia. We also discuss common pathogens that cause nosocomial pneumonia; ventilator-associated pneumonia; and strategies for prevention of hospital-acquired pneumonia.

The Boston AIDS Survival Score (BASS): a multidimensional AIDS severity instrument.

OBJECTIVES: This study developed a new acquired immunodeficiency syndrome (AIDS) severity system by including diagnostic, physiological, functional, and sociodemographic factors predictive of survival. METHODS: Three-hundred five persons with AIDS in Boston were interviewed; their medical records were reviewed and vital status ascertained. RESULTS: Overall median (+/- SD) survival for the cohort from the first interview until death was 560 +/- 14.4 days. The best model for predicting survival, the Boston AIDS Survival Score, included the Justice score (stage 2 relative hazard [RH] = 1.25, 95% confidence interval [CI] = 0.80, 1.96; stage 3 RH = 1.76, 95% CI = 1.15, 2.70), a newly developed opportunistic disease score (Boston Opportunistic Disease Survival Score; stage 2 RH = 1.35, 95% CI = 0.90, 2.02; stage 3 RH = 2.10, 95% CI = 1.38, 3.18), and measures of activities of daily living (any intermediate limitations, RH = 1.84, 95% CI = 1.05, 3.21; any basic limitations, RH = 2.60, 95% CI = 1.44, 4.69). This model had substantially greater predictive power (R2 = .17, C statistic = .68) than the Justice score alone (R2 = .09, C statistic = .61). CONCLUSIONS: Incorporating data on clinically important events and functional status into a physiologically based system can improve the prediction of survival with AIDS.

Race, gender, drug use, and participation in AIDS clinical trials. Lessons from a municipal hospital cohort.

OBJECTIVES: To determine whether participation rates of women, persons of color, and injection drug users in AIDS clinical trials are similar to those of other HIV/AIDS patients, and to examine whether differences in patients' knowledge of clinical trails or reasons for not participating explain differences in participation rates by gender, race, or drug use. DESIGN: Cross-sectional survey of patients with HIV disease. SETTING: Ambulatory practice of a municipal teaching hospital. PATIENTS: Two hundred sixty patients receiving primary care for HIV disease. MEASUREMENTS AND MAIN RESULTS: Overall, 22.3% of patients had participated in a clinical trail. Women, patients of color, and drug users were significantly less likely to have ever participated in an AIDS clinical trial (p < .05). Multiple logistic regression confirmed being a person of color (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.12-4.08) and injection drug use (OR 2.09; 95% CI 1.08-4.04) as significant predictors of nonparticipation in AIDS clinical trials (p < .05). Patients of color and women reported less knowledge of clinical trials, and were less likely to have been told about clinical trials for which they were eligible (p < .05). Patients of color were half as likely as whites to cite ineligibility as their reason for not participating (10.4% vs 22.4%). and more likely to hold unfavorable opinions of clinical research (50.7% vs. 40.5%). Reasons for nonparticipation did not differ by gender. CONCLUSIONS: Even when AIDS clinical trials are available on-site, persons of color, women, and drug users are less likely to participate. Educational efforts for patients and providers are needed to remedy continuing disparities in participation by race, gender, and risk factor group in AIDS clinical trials.