Macrolide Resistance in Adults with Bacteremic Pneumococcal Pneumonia

We conducted a case-control study of adults with bacteremic pneumococcal pneumonia to identify factors associated with macrolide resistance. Study participants were identified through population-based surveillance in a 5-county region surrounding Philadelphia. Forty-three hospitals contributed 444 patients, who were interviewed by telephone regarding potential risk factors. In multivariable analyses, prior exposure to a macrolide antimicrobial agent (odds ratio [OR] 2.8), prior flu vaccination (OR 2.0), and Hispanic ethnicity (OR 4.1) were independently associated with an increased probability of macrolide resistance, and a history of stroke was independently associated with a decreased probability of macrolide resistance (OR 0.2). Fifty-five percent of patients with macrolide-resistant infections reported no antimicrobial drug exposure in the preceding 6 months. Among patients who reported taking antimicrobial agents in the 6 months preceding infection, failure to complete the course of prescribed drugs was associated with an increased probability of macrolide resistance (OR 3.4)

A hospital-site controlled intervention using audit and feedback to implement guidelines concerning inappropriate treatment of catheter-associated asymptomatic bacteriuria

<p>Abstract</p> <p>Background</p> <p>Catheter-associated urinary tract infection (CAUTI) is one of the most common hospital-acquired infections. However, many cases treated as hospital-acquired CAUTI are actually asymptomatic bacteriuria (ABU). Evidence-based guidelines recommend that providers neither screen for nor treat ABU in most catheterized patients, but there is a significant gap between these guidelines and clinical practice. Our objectives are (1) to evaluate the effectiveness of an audit and feedback intervention for increasing guideline-concordant care concerning catheter-associated ABU and (2) to measure improvements in healthcare providers' knowledge of and attitudes toward the practice guidelines associated with the intervention.</p> <p>Methods/Design</p> <p>The study uses a controlled pre/post design to test an intervention using audit and feedback of healthcare providers to improve their compliance with ABU guidelines. The intervention and the control sites are two VA hospitals. For objective 1 we will review medical records to measure the clinical outcomes of inappropriate screening for and treatment of catheter-associated ABU. For objective 2 we will survey providers' knowledge and attitudes. Three phases of our protocol are proposed: the first 12-month phase will involve observation of the baseline incidence of inappropriate screening for and treatment of ABU at both sites. This surveillance for clinical outcomes will continue at both sites throughout the study. Phase 2 consists of 12 months of individualized audit and feedback at the intervention site and guidelines distribution at both sites. The third phase, also over 12 months, will provide unit-level feedback at the intervention site to assess sustainability. Healthcare providers at the intervention site during phase 2 and at both sites during phase 3 will complete pre/post surveys of awareness and familiarity (knowledge), as well as of acceptance and outcome expectancy (attitudes) regarding the relevant practice guidelines.</p> <p>Discussion</p> <p>Our proposal to bring clinical practice in line with published guidelines has significant potential to decrease overdiagnosis of CAUTI and associated inappropriate antibiotic use. Our study will also provide information about how to maximize effectiveness of audit and feedback to achieve guideline adherence in the inpatient setting.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052545">NCT01052545</a></p

Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism

Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8+ T cells during vaccine immunotherapy

Background: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs correlates with tumor regression. How these potent cells expand with high quality is crucial to the outcome of CTL therapy. However, good markers reflecting the efficacy of DC-target immunotherapy have not been addressed. Methods: Using an EG7 (ovalbumin, OVA-positive) tumor-implant mouse model, we examined what is a good marker for active CTL induction in treatment with Poly(I:C)/OVA. Results: Simultaneous administration of Poly(I:C) and antigen (Ag) OVA significantly increased a minor population of CD8+ T cells, that express CD11c in lymphoid and tumor sites. The numbers of the CD11c+ CD8+ T cells correlated with those of induced Ag-specific CD8+ T cells and tumor regression. The CD11c+ CD8+ T cell moiety was characterized by its high killing activity and IFN-γ-producing ability, which represent an active phenotype of the effector CTLs. Not only a TLR3-specific (TICAM-1-dependent) signal but also TLR2 (MyD88) signal in DC triggered the expansion of CD11c+ CD8+ T cells in tumor-bearing mice. Notably, human CD11c+ CD8+ T cells also proliferated in peripheral blood mononuclear cells (PBMC) stimulated with cytomegalovirus (CMV) Ag. Conclusions: CD11c expression in CD8+ T cells reflects anti-tumor CTL activity and would be a marker for immunotherapeutic efficacy in mouse models and probably cancer patients as well

Quality of care in elder emergency department patients with pneumonia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The goals of the study were to assess the relationship between age and processes of care in emergency department (ED) patients admitted with pneumonia and to identify independent predictors of failure to meet recommended quality care measures.</p> <p>Methods</p> <p>This was a prospective cohort study of a pre-existing database undertaken at a university hospital ED in the Midwest. ED patients ≥18 years of age requiring admission for pneumonia, with no documented use of antibiotics in the 24 hours prior to ED presentation were included. Compliance with Pneumonia National Quality Measures was assessed including ED antibiotic administration, antibiotics within 4 hours, oxygenation assessment, and obtaining of blood cultures. Odds ratios were calculated for elders and non-elders. Logistic regression was used to identify independent predictors of process failure.</p> <p>Results</p> <p>One thousand, three hundred seventy patients met inclusion criteria, of which 560 were aged ≥65 years. In multiple variable logistic regression analysis, age ≥65 years was independently associated with receiving antibiotics in the ED (odds ratio [OR] = 2.03, 95% CI 1.28–3.21) and assessment of oxygenation (OR = 2.10, 95% CI, 1.18–3.32). Age had no significant impact on odds of receiving antibiotics within four hours of presentation (OR 1.10, 95% CI 0.84–1.43) or having blood cultures drawn (OR 1.02, 95%CI 0.78–1.32). Certain other patient characteristics were also independently associated with process failure.</p> <p>Conclusion</p> <p>Elderly patients admitted from the ED with pneumonia are more likely to receive antibiotics while in the ED and to have oxygenation assessed in the ED than younger patients. The independent association of certain patient characteristics with process failure provides an opportunity to further increase compliance with recommended quality measures in admitted patients diagnosed with pneumonia.</p

Replication of Norovirus in Cell Culture Reveals a Tropism for Dendritic Cells and Macrophages

Noroviruses are understudied because these important enteric pathogens have not been cultured to date. We found that the norovirus murine norovirus 1 (MNV-1) infects macrophage-like cells in vivo and replicates in cultured primary dendritic cells and macrophages. MNV-1 growth was inhibited by the interferon-αβ receptor and STAT-1, and was associated with extensive rearrangements of intracellular membranes. An amino acid substitution in the capsid protein of serially passaged MNV-1 was associated with virulence attenuation in vivo. This is the first report of replication of a norovirus in cell culture. The capacity of MNV-1 to replicate in a STAT-1-regulated fashion and the unexpected tropism of a norovirus for cells of the hematopoietic lineage provide important insights into norovirus biology

The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo

BACKGROUND: The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV). METHODS: Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c(+ )CD8(+ )and CD11c(- )CD8(+ )T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8(+ )T cells was assessed by quantitative PCR. RESULTS: Following RSV infection CD11c(+ )CD8(+ )T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8(+ )T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8(+ )T cells in the absence of RSV infection, its mRNA was expressed in CD8(+ )T cells of both naïve and RSV infected mice. CD11c(+), but not CD11c(-), CD8(+ )T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c(+ )CD8(+ )T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo. CONCLUSION: CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo

"I really should've gone to the doctor": older adults and family caregivers describe their experiences with community-acquired pneumonia

BACKGROUND: Responding to acute illness symptoms can often be challenging for older adults. The primary objective of this study was to describe how community-dwelling older adults and their family members responded to symptoms of community-acquired pneumonia (CAP). METHODS: A qualitative study that used face-to-face semi-structured interviews to collect data from a purposeful sample of seniors aged 60+ and their family members living in a mid-sized Canadian city. Data analysis began with descriptive and interpretive coding, then advanced as the research team repeatedly compared emerging thematic categories to the raw data. Searches for disconfirming evidence and member checking through focus groups provided additional data and helped ensure rigour. RESULTS: Community-acquired pneumonia symptoms varied greatly among older adults, making decisions to seek care difficult for them and their family members. Both groups took varying amounts of time as they attempted to sort out what was wrong and then determine how best to respond. Even after they concluded something was wrong, older adults with confirmed pneumonia continued to wait for days, to over a week, before seeking medical care. Participants provided diverse reasons for this delay, including fear, social obligations (work, family, leisure), and accessibility barriers (time, place, systemic). Several older adults and family members regretted their delays in seeking help. CONCLUSION: Treatment-seeking delay is a variable, multi-phased decision-making process that incorporates symptom assessment plus psychosocial and situational factors. Public health and health care professionals need to educate older adults about the potential causes and consequences of unnecessary waits. Such efforts may reduce the severity of community-acquired pneumonia upon presentation at clinics and hospitals, and that, in turn, could potentially improve health outcomes