Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial.

Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment's duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s-2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of 'chronic' Q fever. Reinforcing the guidelines' level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.

Invasive Pneumococcal Disease and Long-Term Mortality Rates in Adults, Alberta, Canada.

The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8‒9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio [aHR] 3.75, 95% CI 3.29-4.28), 30‒90 days (aHR 1.56, 95% CI 1.27‒1.93), and >90 days (aHR 1.43, 95% CI 1.33-1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.

Concurrent Infection with Hepatitis C Virus and Streptococcus pneumoniae.

Little is known about concurrent infection with hepatitis C virus (HCV) and Streptococcus pneumoniae, which causes invasive pneumococcal disease (IPD). We hypothesized that co-infection with HCV and S. pneumoniae would increase risk for death and complications. We captured sociodemographic and serologic data for adults with IPD in a population-based cohort study in northern Alberta, Canada, during 2000-2014. IPD patients infected with HCV were compared with IPD patients not infected with HCV for risk of in-hospital deaths and complications by using multivariable logistic regression. A total of 355 of 3,251 patients with IPD were co-infected with HCV. The in-hospital mortality rate was higher for IPD patients infected with HCV. Prevalence of most IPD-related complications (e.g., cellulitis, acute kidney injury, mechanical ventilation) was also higher in HCV-infected patients. Infection with HCV is common in patients with IPD, and HCV is independently associated with an increased risk for serious illness and death.

Rates of, and risk factors for, septic arthritis in patients with invasive pneumococcal disease: prospective cohort study.

BACKGROUND: There are many case reports of septic arthritis complicating invasive pneumococcal disease (IPD); however, no study has compared patients with IPD with septic arthritis to those who didn't develop septic arthritis Thus, we aimed to determine the rates of, and risk factors for, septic arthritis in patients with invasive pneumococcal disease (IPD). METHODS: Socio-demographic, clinical, and serological data were captured on all patients with IPD in Northern Alberta, Canada from 2000 to 2014. Septic arthritis was identified by attending physicians. Descriptive statistics and multivariate analyses were used to compare characteristics of those with septic arthritis and IPD to those who did not. RESULTS: Septic arthritis developed in 51 of 3251 (1.6%) of patients with IPD. Inability to walk independently, male sex, and underlying joint disease were risk factors for developing septic arthritis in patients with IPD. Capsular serotypes 22 and 12F were more common in patients with septic arthritis than those without. CONCLUSIONS: In patients with IPD, septic arthritis is uncommon. Certain risk factors such as walking with or without assistance and underlying joint disease make biological sense as damaged joints are more likely to be infected in the presence of bacteremia. TRIAL REGISTRATION: Not applicable.

Ten-Year Mortality after Community-acquired Pneumonia. A Prospective Cohort.

RATIONALE: Information on the long-term prognosis after community-acquired pneumonia (CAP) is limited. OBJECTIVES: To determine if CAP increases adverse long-term outcomes relative to a control population. METHODS: Between 2000 and 2002, 6,078 adults with CAP from six hospitals and seven emergency departments in Edmonton (AB, Canada) were prospectively recruited and matched on age, sex, and site of treatment with five control subjects without pneumonia (n = 29,402). Mortality, hospitalizations, and emergency department admissions through 2012 were evaluated using multivariable Cox proportional hazards analyses adjusted for socioeconomic status and comorbidities. MEASUREMENTS AND MAIN RESULTS: Average age was 59 years (2,682 [44%] ≥ 65 yr), 3,214 (53%) were men, and 3,425 (56%) were managed as outpatients. Over a median of 9.8 years, 2,858 patients with CAP died compared with 9,399 control subjects (absolute risk difference, 30 per 1,000 patient years [py]; adjusted hazard ratio [aHR], 1.65; 95% confidence interval, 1.57-1.73; P < 0.001). Patients with CAP who were younger than 25 years old had the lowest absolute rate difference for mortality (4 per 1,000 py; aHR, 2.40), and patients older than 80 years old had the highest absolute rate difference (92 per 1,000 py; aHR, 1.42). Absolute rates of all-cause hospitalization, emergency department visits, and CAP-related visits were all significantly higher in patients with CAP compared with control subjects (P < 0.001 for all comparisons). CONCLUSIONS: Our results indicate that an episode of CAP confers a high risk of long-term adverse events compared with the general population who have not experienced CAP, and this is irrespective of age.

Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis.

OBJECTIVE: Some studies suggest better outcomes with macrolide therapy for critically ill patients with community-acquired pneumonia. To further explore this, we performed a systematic review of studies with mortality endpoints that compared macrolide therapy with other regimens in critically ill patients with community-acquired pneumonia. DATA SOURCES: Studies were identified via electronic databases, grey literature, and conference proceedings through May 2013. STUDY SELECTION: Using prespecified criteria, two reviewers selected studies; studies of outpatients and hospitalized noncritically ill patients were excluded. DATA EXTRACTION: Two reviewers extracted data and evaluated bias using the Newcastle-Ottawa Scale. Random effects models were used to generate pooled risk ratios and evaluate heterogeneity (I). DATA SYNTHESIS: Twenty-eight observational studies (no randomized control trials) were included. Average age ranged from 58 to 78 years and 14-49% were women. In our primary analysis of 9,850 patients, macrolide use was associated with statistically significant lower mortality compared with nonmacrolides (21% [846 of 4,036 patients] vs 24% [1,369 of 5,814]; risk ratio, 0.82; 95% CI, 0.70-0.97; p = 0.02; I = 63%). When macrolide monotherapy was excluded, the macrolide mortality benefit was maintained (21% [737 of 3,447 patients] vs 23% [1,245 of 5,425]; risk ratio, 0.84; 95% CI, 0.71-1.00; p = 0.05; I = 60%). When broadly guideline-concordant regimens were compared, there was a trend to improved mortality and heterogeneity was reduced (20% [511 of 2,561 patients] mortality with beta-lactam/macrolide therapy vs 23% [386 of 1,680] with beta-lactam/fluoroquinolone; risk ratio, 0.83; 95% CI, 0.67-1.03; p = 0.09; I = 25%). When adjusted risk estimates were pooled from eight studies, macrolide therapy was still associated with a significant reduction in mortality (risk ratio, 0.75; 95% CI, 0.58-0.96; p = 0.02; I = 57%). CONCLUSIONS: In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines.

Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group.

Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause acute or chronic illness in humans. Transmission occurs primarily through inhalation of aerosols from contaminated soil or animal waste. No licensed vaccine is available in the United States. Because many human infections result in nonspecific or benign constitutional symptoms, establishing a diagnosis of Q fever often is challenging for clinicians. This report provides the first national recommendations issued by CDC for Q fever recognition, clinical and laboratory diagnosis, treatment, management, and reporting for health-care personnel and public health professionals. The guidelines address treatment of acute and chronic phases of Q fever illness in children, adults, and pregnant women, as well as management of occupational exposures. These recommendations will be reviewed approximately every 5 years and updated to include new published evidence.

Inhaled corticosteroids and risk of recurrent pneumonia: a population-based, nested case-control study.

BACKGROUND: Studies have suggested an increased risk of pneumonia with inhaled corticosteroid (ICS) use, although this association is inconsistent. We evaluated the risk of recurrent pneumonia associated with ICS use in a high-risk population of individuals who survived an episode of pneumonia. METHODS: Clinical and 5-year follow-up data were collected on all adults aged ≥ 65 years with pneumonia over a period of 2 years. Using a nested case-control design, first cases (patients with recurrent pneumonia ≥ 30 days after initial episode) and then controls (free of pneumonia and matched on age, sex, and chronic obstructive pulmonary disease [COPD]) were identified. ICS use was classified as never, past (remote, only before initial pneumonia), or current. Our primary outcome measure was recurrent pneumonia assessed using conditional multivariate logistic regression after adjustment of demographics and clinical data. RESULTS: During 5 years of follow-up, 653 recurrent pneumonia cases were matched with 6244 controls; mean age was 79 (SD, 8) years, 3577 (52%) were male, 2652 (38%) had COPD, and 2294 (33%) ever used ICS. Overall, 123 of 870 (14%) current ICS users had recurrent pneumonia compared to 395 of 4603 (9%) never-users (adjusted odds ratio, 1.90; 95% confidence interval, 1.45-2.50; P < .001; number need to harm = 20). Conversely, there was no association between past (remote) use of ICS and pneumonia: 9% of past users versus 9% never-users (P = .36). CONCLUSIONS: ICS use was associated with a 90% relative increase in the risk of recurrent pneumonia among high-risk pneumonia survivors. This should be considered when prescribing ICS and when deciding which patients might need more intensive follow-up.

Macrolide use in the treatment of critically ill patients with pneumonia: Incidence, correlates, timing and outcomes.

BACKGROUND: Macrolide antibiotics are commonly used to treat pneumonia despite increasing antimicrobial resistance. Evidence suggests that macrolides may also decrease mortality in severe sepsis via immunomodulatory properties. OBJECTIVE: To evaluate the incidence, correlates, timing and mortality associated with macrolide-based treatment. METHODS: A population-based cohort of critically ill adults with pneumonia at five intensive care units in Edmonton, Alberta, was prospectively followed over two years. Data collected included disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score), pneumonia severity (Pneumonia Severity Index score), comorbidities, antibiotic treatments at presentation and time to effective antibiotic. The independent association between macrolide-based treatment and 30-day all-cause mortality was examined using multivariable Cox regression. A secondary exploratory analysis examined time to effective antimicrobial therapy. RESULTS: The cohort included 328 patients with a mean Pneumonia Severity Index score of 116 and a mean APACHE II score of 17; 84% required invasive mechanical ventilation. Ninety-one (28%) patients received macrolide-based treatments, with no significant correlates of treatment except nursing home residence (15% versus 30% for nonresidents [P=0.02]). Overall mortality was 54 of 328 (16%) at 30 days: 14 of 91 (15%) among patients treated with macrolides versus 40 of 237 (17%) for nonmacrolides (adjusted HR 0.93 [95% CI 0.50 to 1.74]; P=0.8). Patients who received effective antibiotics within 4 h of presentation were less likely to die than those whose treatment was delayed (14% versus 17%; adjusted HR 0.50 [95% CI 0.27 to 0.94]; P=0.03). CONCLUSIONS: Macrolide-based treatment was not associated with lower 30-day mortality among critically ill patients with pneumonia, although receipt of effective antibiotic within 4 h was strongly predictive of survival. Based on these results, timely effective treatment may be more important than choice of antibiotics.

HISTORIQUE: Les macrolides sont souvent utilisés pour soigner la pneumonie, malgré une résistance croissante aux antimicrobiens. Selon les données probantes, les macrolides réduiraient également la mortalité en cas de septicémie sévère, en raison de ses propriétés immunomodulatoires. OBJECTIF: Évaluer l'incidence, les corrélats, les délais et la mortalité associés à un traitement fondé sur les macrolides. MÉTHODOLOGIE: Pendant deux ans, les chercheurs ont procédé au suivi rétrospectif d'une cohorte en population d'adultes atteints d'une grave pneumonie, hospitalisés dans cinq unités de soins intensifs d'Edmonton, en Alberta. Ils ont colligé la gravité de la maladie (indice APACHE II d'évaluation de la physiologie aiguë et de la santé chronique), la gravité de la pneumonie (indice de gravité de la pneumonie), les comorbidités, les traitements antibiotiques à la présentation et le délai avant la prise efficace d'antibiotiques. Ils ont examiné l'association indépendante entre le traitement aux macrolides et le décès au bout de 30 jours toutes causes confondues au moyen de la régression de Cox multivariable. Ils ont utilisé une analyse exploratoire secondaire pour examiner le délai avant un traitement antimicrobien efficace. RÉSULTATS: La cohorte se composait de 328 patients dont l'indice moyen de gravité de la pneumonie se situait à 116 et l'indice APACHE II moyen à 17; 84 % d'entre eux ont eu besoin d'une ventilation mécanique. Quatre-vingt-onze patients (28 %) ont reçu des traitements aux macrolides, sans corrélats significatifs du traitement à part le fait d'habiter dans un centre d'hébergement et de soins de longue durée (15 % par rapport à 30 % pour les non-résidents [P=0,02]). La mortalité globale correspondait à 54 cas sur 328 patients (16 %) au bout de 30 jours, soit 14 des 91 patients (15 %) traités aux macrolides par rapport à 40 des 237 (17 %) n'en ayant pas pris (RR rajusté de 0,93 [95 % IC 0,50 à 1,74]; P=0,8). Les patients qui prenaient des antibiotiques efficaces dans les quatre heures suivant leur présentation étaient moins susceptibles de mourir que ceux dont le traitement était retardé (14 % par rapport à 17 %; RR rajusté 0,50 [95 % IC 0,27 à 0,94]; P=0,03). CONCLUSIONS: Le traitement aux macrolides ne s'associait pas à une réduction du taux de mortalité au bout de 30 jours chez les patients atteints d'une grave pneumonie, mais la prise d'antibiotiques efficaces dans les quatre heures était fortement prédictive de la survie. D'après ces résultats, l'administration rapide d'un traitement efficace serait plus importante que le choix d'antibiotique.

Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Macrolides are used to treat pneumonia despite increasing antimicrobial resistance. However, the immunomodulatory properties of macrolides may have a favorable effect on pneumonia outcomes. Therefore, we systematically reviewed all studies of macrolide use and mortality among patients hospitalized with community-acquired pneumonia (CAP). METHODS: All randomized control trials (RCTs) and observational studies comparing macrolides to other treatment regimens in adults hospitalized with CAP were identified through electronic databases and gray literature searches. Primary analysis examined any macrolide use and mortality; secondary analysis compared Infectious Diseases Society of America/American Thoracic Society guideline-concordant macrolide/beta-lactam combinations vs respiratory fluoroquinolones. Random effects models were used to generate pooled risk ratios (RRs) and evaluate heterogeneity (I(2)). RESULTS: We included 23 studies and 137,574 patients. Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (3.7% [1738 of 47,071] vs 6.5% [5861 of 90,503]; RR, 0.78; 95% confidence interval [CI], .64-.95; P = .01; I(2)= 85%). There was no survival advantage and heterogeneity was reduced when analyses were restricted to RCTs (4.6% [22 of 479] vs 4.1% [25 of 613]; RR, 1.13; 95% CI, .65-1.98; P = .66; I(2)= 0%) or to patients treated with guideline-concordant antibiotics (macrolide/beta-lactam, 5.3% [297 of 5574] vs respiratory fluoroquinolones, 5.8% [408 of 7050]; RR, 1.17; 95% CI, .91-1.50; P = .22; I(2)= 43%). CONCLUSIONS: In hospitalized patients with CAP, macrolide-based regimens were associated with a significant 22% reduction in mortality compared with nonmacrolides; however, this benefit did not extend to patients studied in RCTs or patients that received guideline-concordant antibiotics. Our findings suggest guideline concordance is more important than choice of antibiotic when treating CAP.

Epidemic of invasive pneumococcal disease, western Canada, 2005-2009.

In Canada before 2005, large outbreaks of pneumococcal disease, including invasive pneumococcal disease caused by serotype 5, were rare. Since then, an epidemic of serotype 5 invasive pneumococcal disease was reported: 52 cases during 2005, 393 during 2006, 457 during 2007, 104 during 2008, and 42 during in 2009. Of these 1,048 cases, 1,043 (99.5%) occurred in the western provinces of Canada. Median patient age was 41 years, and most (659 [59.3%]) patients were male. Most frequently representing serotype 5 cases (compared with a subset of persons with non-serotype 5 cases) were persons who were of First Nations heritage or homeless. Restriction fragment-length polymorphism typing indicated that the epidemic was caused by a single clone, which multilocus sequence typing identified as sequence type 289. Large pneumococcal epidemics might go unrecognized without surveillance programs to document fluctuations in serotype prevalence.

Population-based cohort study of outpatients with pneumonia: rationale, design and baseline characteristics.

BACKGROUND: The vast majority of research in the area of community-acquired pneumonia (CAP) has been based on patients admitted to hospital. And yet, the majority of patients with CAP are treated on an ambulatory basis as outpatients, either by primary care physicians or in Emergency Departments. Few studies have been conducted in outpatients with pneumonia, and there is a paucity of data on short and long term morbidity or mortality and associated clinical correlates in this group of patients. METHODS: From 2000-2002, all CAP patients presenting to 7 Emergency Departments in Edmonton, Alberta, Canada were prospectively enrolled in a population-based registry. Clinical data, including pneumonia severity index (PSI) were collected at time of presentation. Patients discharged to the community were then followed for up to 5 years through linkage to the provincial administrative databases. The current report provides the rationale and design for the cohort, as well as describes baseline characteristics and 30-day morbidity and mortality. RESULTS: The total sample included 3874 patients. After excluding patients who were hospitalized, died or returned to the Emergency Department the same day they were initially discharged (n = 451; 12 %), and patients who could not be linked to provincial administrative databases (n = 237; 6 %), the final cohort included 3186 patients treated according to a validated clinical management pathway and discharged back to the community. Mean age was 51 (SD = 20) years, 53 % male; 4 % resided in a nursing home, 95 % were independently mobile, and 88 % had mild (PSI class I-III) pneumonia. Within 30-days, return to Emergency Department was common (25 %) as was hospitalization (8 %) and 1 % of patients had died. CONCLUSIONS: To our knowledge, this represents the largest clinically-detailed outpatient CAP cohort assembled to date and will add to our understanding of the determinants and outcomes in this under-researched patient population. The rich clinical data along with the long term health care utilization and mortality will allow for the identification of novel prognostic indicators. Given how under studied this population is, the findings should aid clinicians in the routine care of their outpatients with pneumonia and help define the next generation of research questions.

The role of atypical pathogens in community-acquired pneumonia.

The term atypical pneumonia was first used in 1938, and by the 1970s it was widely used to refer to pneumonia due to Mycoplasma pneumoniae, Legionella pneumophila (or other Legionella species), and Chlamydophila pneumoniae. However, in the purest sense all pneumonias other than the classic bacterial pneumonias are atypical. Currently many favor abolition of the term atypical pneumonia.This review categorizes atypical pneumonia pathogens as conventional ones; viral agents and emerging atypical pneumonia pathogens. We emphasize viral pneumonia because with the increasing availability of multiplex polymerase chain reaction we can identify the agent(s) responsible for viral pneumonia. By using a sensitive assay for procalcitonin one can distinguish between viral and bacterial pneumonia. This allows pneumonia to be categorized as bacterial or viral at the time of admission to hospital or at discharge from the emergency department and soon thereafter further classified as to the etiology, which should be stated as definite or probable.

Invasive pneumococcal disease and long-term outcomes in children: A 20-year population cohort study.

Background: Although vaccination against Streptococcus pneumoniae infections (such as invasive pneumococcal disease (IPD)) are available, challenges remain in prevention efforts. Moreover, downstream sequelae in children is relatively unknown. Thus, we aimed to evaluate short and long-term health outcomes among children with IPD. Methods: Analysis of Streptococcus pneumoniae positive isolates from sterile body sites in children (0-17 years) in Alberta (Canada) from 1999 to 2019 was performed retrospectively (n=888). Cases were age and sex-matched to hospitalized population controls. Linkage to administrative health datasets was done to determine comorbidities and healthcare related outcomes. Cox proportional hazards were used to assess differences in time to mortality and hospitalisation between cases and controls in short (<30-day), intermediate (30-90 day), long-term (>90-day) follow-up. Findings: Proportionally more deaths occurred in cases (4.8 deaths/1000 person-years (PY)) than controls (2.7 deaths/1000 PY), leading to a significant adjusted hazard ratio (aHR) of 1.80 (95% CI 1.22-2.64). This increased risk of death was influenced primarily by short-term mortality (319 vs 36 deaths/1000 PY in cases vs controls respectively, aHR 8.78 [95% CI 3.33-23.18]), as no differences were seen in intermediate (14 vs 7 deaths/1000 PY; aHR 2.03, 95% CI 0.41-10.04) or long-term time intervals (2.4 vs 2.3 deaths/1000 PY, aHR 1.03, 95% CI 0.63-1.69). Interpretation: IPD continues to negatively impact survival in children despite vaccination. Although long-term impact on mortality and hospitalisations may not be substantial, the immediate effects of IPD are significant. Funding: This work was supported by grants-in-aid from Pfizer Canada and Wyeth Canada Inc all to GJT.

Oxygen saturations less than 92% are associated with major adverse events in outpatients with pneumonia: a population-based cohort study.

BACKGROUND: patients with hypoxemia (blood oxygen saturation <90%) are usually hospitalized, although validated criteria (eg, the Pneumonia Severity Index [PSI]) suggest outpatient treatment is safe. We sought evidence to support or refute the practice. METHODS: all patients in Edmonton, Alberta, Canada with pneumonia assessed at any of 7 emergency departments (EDs) and then discharged were enrolled in a population-based cohort study. The independent variable of interest was oxygen saturation; the outcome was the composite endpoint of 30-day mortality or hospitalization. RESULTS: the study evaluated 2923 individuals with pneumonia who were treated as outpatients at any of 7 EDs. The patients' mean age (standard deviation [SD])was 52 (20) years; 47% were women; 74% were low risk (PSI Class I-II). The mean blood oxygen saturation (SD) was 95% (3%); 126 patients (4%) had blood oxygen saturations <90%, and 201 patients (7%) had blood oxygen saturations of 90%-92%. Over 30 days, 39 patients (1%) died and 252 (9%) reached the composite endpoint. Compared with patients with higher blood oxygen saturations, those discharged with saturations <90% had significantly (P < .001) higher rates of 30-day mortality (7 [6%] vs 32 [1%]), hospitalization (23 [18%] vs 201 [7%]), and composite endpoints (27 [21%] vs 225 [8%]). Blood oxygen saturation <90% was independently associated with 30-day mortality or hospitalization (adjusted odds ratio (OR), 1.7; 95% confidence interval (CI) 1.1-2.8; P = .032). If the saturation threshold for hospitalization was 92%, then there was no association with adverse events (adjusted OR 1.1, 95% CI 0.8-1.7, P = .48). Raising the admission threshold to 92% entails 1 additional hospitalization for every 14 patients discharged. CONCLUSIONS: among outpatients with pneumonia, oxygen saturations <90% were associated with increased morbidity and mortality. Our results indicate a hospital admission threshold of <92% would be safer and clinically better justified.

Swine outbreak of pandemic influenza A virus on a Canadian research farm supports human-to-swine transmission.

BACKGROUND: Swine outbreaks of pandemic influenza A (pH1N1) suggest human introduction of the virus into herds. This study investigates a pH1N1 outbreak occurring on a swine research farm with 37 humans and 1300 swine in Alberta, Canada, from 12 June through 4 July 2009. METHODS: The staff was surveyed about symptoms, vaccinations, and livestock exposures. Clinical findings were recorded, and viral testing and molecular characterization of isolates from humans and swine were performed. Human serological testing and performance of the human influenza-like illness (ILI) case definition were also studied. RESULTS: Humans were infected before swine. Seven of 37 humans developed ILI, and 2 (including the index case) were positive for pH1N1 by reverse-transcriptase polymerase chain reaction (RT-PCR). Swine were positive for pH1N1 by RT-PCR 6 days after contact with the human index case and developed symptoms within 24 h of their positive viral test results. Molecular characterization of the entire viral genomes from both species showed minor nucleotide heterogeneity, with 1 amino acid change each in the hemagglutinin and nucleoprotein genes. Sixty-seven percent of humans with positive serological test results and 94% of swine with positive swab specimens had few or no symptoms. Compared with serological testing, the human ILI case definition had a specificity of 100% and sensitivity of 33.3%. The only factor associated with seropositivity was working in the swine nursery. CONCLUSIONS: Epidemiologic data support human-to-swine transmission, and molecular characterization confirms that virtually identical viruses infected humans and swine in this outbreak. Both species had mild illness and recovered without sequelae.

Impact of the pneumococcal vaccine on long-term morbidity and mortality of adults at high risk for pneumonia.

BACKGROUND: There is debate surrounding the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV). We determined whether PPV was associated with reduced mortality or additional hospitalization for vaccine-preventable infections in patients previously hospitalized for community-acquired pneumonia (CAP). METHODS: From 2000 through 2002, adults with CAP admitted to the hospital in Edmonton, Alberta, Canada, were enrolled in a population-based cohort. Postdischarge outcomes during 5 years were ascertained using administrative databases. The primary outcome was the composite of all-cause mortality or additional hospitalization for vaccine-preventable infections. Proportional hazards analysis was used to determine the association between PPV use and outcomes. RESULTS: A total of 2950 patients were followed up for a median of 3.8 years. The mean patient age was 68 years; 52% were male. One-third (n = 956) received PPV: 667 (70%) before and 289 (30%) during hospitalization. After discharge, 1404 patients (48%) died, 504 (17%) were admitted with vaccine-preventable infections, and 1626 (55%) reached the composite outcome of death or infection. PPV was not associated with reduced risk of the composite outcome (589 [62%] vs 1037 [52%] for those unvaccinated; adjusted hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.79-1.04). Results were not altered in sensitivity analyses using propensity scores (adjusted HR, 0.91; 95% CI, 0.79-1.04), restricting the sample to patients 65 years or older (adjusted HR, 0.90; 95% CI, 0.77-1.04), or considering only those who received PPV at discharge (adjusted HR, 0.84; 95% CI, 0.71-1.00). CONCLUSIONS: One-half of patients discharged from the hospital after pneumonia die or are subsequently hospitalized with a vaccine-preventable infection within 5 years. PPV was not associated with a reduced risk of death or hospitalization. Better pneumococcal vaccination strategies are urgently needed.

Age still matters: prognosticating short- and long-term mortality for critically ill patients with pneumonia.

OBJECTIVE: To determine the association between age and mortality in critically ill patients with pneumonia. We hypothesized that increasing age would be independently associated with both short- and long-term mortality. DESIGN: Prospective population-based cohort study examining the association between age and 30-day (short-term) and 1-yr (long-term) mortality using Cox proportional hazards regression, adjusting for pneumonia severity, mechanical ventilation, sex, functional status, nursing home residence, and having a living will. SETTING: Five intensive care units in Edmonton, Alberta, Canada. PATIENTS: Critically ill adult patients with pneumonia. MEASUREMENTS AND MAIN RESULTS: The cohort included 351 intensive care unit patients; mean age 61 yrs, 59% male, 16% from nursing homes. Mean Pneumonia Severity Index was 115 (73% Pneumonia Severity Index class IV or V), mean Acute Physiology and Chronic Health Evaluation II score 17, and 83% received invasive mechanical ventilation. Overall, 151 (43%) were < 60 yrs old, 64 (18%) were 60-69 yrs old, 82 (23%) were 70-79 yrs old, and 54 (15%) were ≥ 80 yrs old. By 30 days, 58 of 351 (17%) had died; by 1 yr, 112 of 351 (32%) had died. Mortality increased with age, 28 of 151 (19%) in those < 60 yrs, 14 of 64 (22%) in those 60-69 yrs, 39 of 82 (48%) in those 70-79 yrs, and 31 of 54 (57%) in those ≥ 80 yrs. Independent of pneumonia severity and other factors, age (per 10-yr increase) was associated with 30-day mortality (adjusted hazard ratio 1.24, 95% confidence interval 1.03-1.49, p = .026) and 1-yr mortality (adjusted hazard ratio 1.39, 95% confidence interval 1.21-1.60, p < .001). Having a living will was similarly associated with increased mortality (adjusted hazard ratio 3.08, 95% confidence interval 1.61-5.90, p < .001 at 30 days; adjusted hazard ratio 2.00, 95% confidence interval 1.21-3.32, p = .007 at 1 yr). CONCLUSIONS: Increasing age was independently associated with risk-adjusted short- and long-term mortality in critically ill patients with pneumonia. These findings may help elderly patients, their families, and physicians better understand what intensive care unit admission can offer and help them to make more informed decisions.

Willingness of university nursing students to volunteer during a pandemic.

OBJECTIVE: The global threat of an influenza pandemic continues to grow and thus universities have begun emergency preparedness planning. This study examined stakeholder's knowledge, risk-perception, and willingness to volunteer. DESIGN AND SAMPLE: The design of this study is a cross-sectional survey. Questionnaires were sent to 1,512 nursing students and were returned by 484, yielding a response rate of 32% for this subgroup. Nursing students may be a much-needed human resource in the event of an influenza pandemic. MEASURES: The measurement tool was a Web-based questionnaire regarding pandemic influenza designed by a subgroup of researchers on the Public Health Response Committee. RESULTS: Most nursing students (67.9%) said they were likely to volunteer in the event of a pandemic if they were able to do so. An even higher number (77.4%) said they would volunteer if provided protective garments. Overall, 70.7% of students supported the proposition that nursing students have a professional obligation to volunteer during a pandemic. Nursing students indicated that they have had a wealth of volunteer experience in the past and they would apply this service ethic to a pandemic situation. CONCLUSIONS: Emergency preparedness competencies should be integrated into existing nursing curricula and other health science programs. University administrations need to engage in planning to create protocol for recruitment, practice, and protection of volunteers.

Pneumococcal pneumonia: potential for diagnosis through a urinary metabolic profile.

Pneumonia, an infection of the lower respiratory tract, is caused by any of a number of different microbial organisms including bacteria, viruses, fungi, and parasites. Community-acquired pneumonia (CAP) causes a significant number of deaths worldwide, and is the sixth leading cause of death in the United States. However, the pathogen(s) responsible for CAP can be difficult to identify, often leading to delays in appropriate antimicrobial therapies. In the present study, we use nuclear magnetic resonance spectroscopy to quantitatively measure the profile of metabolites excreted in the urine of patients with pneumonia caused by Streptococcus pneumoniae and other microbes. We found that the urinary metabolomic profile for pneumococcal pneumonia was significantly different from the profiles for viral and other bacterial forms of pneumonia. These data demonstrate that urinary metabolomic profiles may be useful for the effective diagnosis of CAP.