Alan R. Salkind

Suppressed expression of ICAM-1 and LFA-1 and abrogation of leukocyte collaboration after exposure of human mononuclear leukocytes to respiratory syncytial virus in vitro. Comparison with exposure to influenza virus.

Human mononuclear leukocytes (MNL) exposed to respiratory syncytial virus (RSV) produce net IL-1 inhibitor bioactivity with the anticipated consequences of cell cycle arrest, suppressed virus-specific proliferation, and reduced expression of activation markers. These studies were undertaken to investigate effects of exposure and resultant net IL-1 inhibitor activity on the expression of the intercellular adhesion molecule-1 (ICAM-1), and its ligand the lymphocyte function-associated antigen (LFA-1). MNL collected at 1, 4, and 24 h after exposure to influenza virus (which induces net IL-1 bioactivity) showed enhanced expression of ICAM-1 and LFA-1 relative to sham-exposed MNL and exhibited cell clustering. In contrast, exposure to RSV was associated with suppressed expression of both ICAM-1 and LFA-1 and with minimal detectable cell clustering throughout the culture period. Influenza virus-exposed MNL produced significantly more IL-1 and IFN-gamma (which require cell-cell collaboration for optimal production) than did RSV-exposed MNL. These data raise the possibility that exposure of MNL to RSV fails to elicit or blocks the early events necessary for cellular collaboration, contributing to early suppression of the clonal expansion of RSV-specific lymphocytes.

Fluoroquinolone Treatment of Community-Acquired Pneumonia: A Meta-Analysis

OBJECTIVE: To determine the role of newer fluoroquinolones (FQs) for adults with community-acquired pneumonia (CAP) whose level of illness allows treatment with an oral antibiotic. METHODS: Meta-analysis of randomized controlled trials comparing a macrolide, β-lactam, or doxycycline antibiotic with a newer oral FQ for the treatment of CAP. RESULTS: Patients (5118), most of whom were <60 years of age and free of coexisting diseases, were enrolled in 13 studies comparing an oral macrolide or β-lactam antibiotic with an FQ for the treatment of CAP. No previous study compared doxycycline with an FQ. In the intention-to-treat (ITT) population, no trial demonstrated significant differences between FQs or alternative therapies. Summary estimates showed a statistically significant advantage in favor of the FQs in both the ITT (OR 1.22; 95% CI 1.02 to 1.47; p = 0.03) and evaluable populations (OR 1.37; 95% CI 1.11 to 1.68; p = 0.003). The number needed to treat for an FQ advantage was 33 (95% CI 17 to 362) in the ITT population and 37 (95% CI 22 to 121) in the evaluable population. Treatment failures represented slow symptom resolution; no deaths were reported. CONCLUSIONS: The newer oral FQs showed modest therapeutic benefit compared with the studied alternative antibiotics in adults with CAP. Based on the number needed to treat from the ITT population as a measure of treatment effect, clinicians must decide whether treating 33 patients with an FQ to prevent a single therapeutic failure with another studied antibiotic warrants use of an agent from that class for an illness with a generally favorable outcome regardless of antibiotic selection, and at a time when FQ resistance may be increasing.

Recent observations regarding the pathogenesis of recurrent respiratory syncytial virus infections: implications for vaccine development

Respiratory syncytial virus (RSV) and influenza virus are common pathogens for all age groups. Currently licensed influenza virus vaccines generally provide protection from clinically detectable disease caused by antigenically matched challenging viruses. In contrast, vaccine development for RSV has been hampered by the inability of candidate vaccines to induce protective immunity to naturally occurring infection. The precise mechanism(s) responsible for the RSV vaccine failures have not been determined. We raise the possibility that infection by RSV is associated with attenuation of both proliferative and non-proliferative RSV-specific responses by human mononuclear leucocytes that results in the suppression or delay of host anamnestic defences, allowing development of recurrent clinical illness despite pre-existing immunity.

Economic Burden of Adult Pharyngitis: The Payer's Perspective

OBJECTIVES Although not recommended by practice guidelines, physicians frequently prescribe an antibiotic for adults with viral pharyngitis. The financial burden of this practice, from the payers perspective, has not been previously evaluated. The purpose of this study was to estimate those expenditures. METHODS A cost-of-illness study was performed to estimate annual expenditures of pharyngitis management from the payers perspective. National Ambulatory Care Survey data were used to represent current patterns of ambulatory care visits and antibiotic prescriptions for adult pharyngitis. Direct and antibiotic resistance costs were summed to estimate total expenditures for pharyngitis management. Resistance costs were calculated using a model linking the effect of antibiotic consumption to the cost consequences of resistant Streptococcus pneumoniae infection. Sensitivity analyses compared cost outcomes of current practice, adherence to pharyngitis management guidelines from the Infectious Diseases Society of America (IDSA), and nonantibiotic treatment. RESULTS In the base-case analysis, reflecting current practice patterns, total expenditures were

Acute Rheumatic Fever: Case Report and Review For Emergency Physicians

1.2 billion with antibiotic resistance contributing 36% (

Is This Patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood of Penicillin Allergy

426 million). IDSA guideline adherence decreased costs to

Interleukin-1-Inhibitor Activity Induced by Respiratory Syncytial Virus: Abrogation of Virus-Specific and Alternate Human Lymphocyte Proliferative Responses

559 million with resistance accounting for 6.8% (

What Every Hospitalist Should Know

37.9 million). Guideline adherence plus reducing office visits by 30% decreased costs to

Tuberculosis : What Every Hospitalist Should Know

372 million, with only 1.4% (

Infections of the Central Nervous System, 3rd edition:Infections of the Central Nervous System, 3rd edition

5.3 million) due to resistance. Additional cost-savings of