Pneumonia Severity Index Risk Class Research Articles

Omadacycline in the treatment of community-acquired bacterial pneumonia in patients with comorbidities: a post-hoc analysis of the phase 3 OPTIC trial.

The 2019 American Thoracic Society/Infectious Disease Society of America guidelines recommend respiratory fluoroquinolones to treat community-acquired bacterial pneumonia (CABP) in adults with comorbidities. Fluoroquinolones are effective against both typical and atypical pathogens. However, fluoroquinolone treatment has a risk of adverse effects, and the Food and Drug Administration has issued black box safety warnings for their use. Inpatient use of fluoroquinolones has reduced as a result; however, most antibiotic courses are completed as outpatients and discharge prescriptions account for the majority of fluoroquinolone use. As such, a new treatment option is needed to replace fluoroquinolones. Omadacycline is an aminomethylcycline antibiotic with a broad spectrum of activity and is available as a once-daily intravenous or bioequivalent oral formulation. This study assessed the safety and clinical efficacy of omadacycline compared with moxifloxacin for the treatment of adult CABP patients with Pneumonia Severity Index (PSI) risk class II/III and ≥1 comorbidity through a post-hoc analysis of the phase 3 OPTIC study (NCT02531438). In total, 239 omadacycline- and 222 moxifloxacin-treated patients were assessed. The median age was similar between groups (omadacycline: 57 years; moxifloxacin: 58 years), with 26.0% and 26.6%, respectively, ≥65 years of age. Early clinical response was 91.6% for patients with ≥1 comorbidity treated with omadacycline and 91.4% for those treated with moxifloxacin. Post-treatment evaluation results for overall response were 89.1% in the omadacycline group and 87.4% in the moxifloxacin group. Safety warnings have reduced inpatient use of fluoroquinolones; however, outpatient and discharge prescriptions account for the majority of fluoroquinolone use. Outpatients with comorbidities need an efficacious alternative to fluoroquinolones. Omadacycline maintains the similar efficacy and benefits of fluoroquinolones as a once-daily, monotherapy, bioequivalent oral option with potent in vitro activity against the most common CABP pathogens, including S. pneumoniae and atypical pathogens, but offers a materially different safety profile consistent with its tetracycline heritage. In conclusion, both omadacycline and moxifloxacin exhibited similar efficacy in patients with PSI risk class II/III and comorbidities. Omadacycline fulfills an unmet need as an oral monotherapy treatment option for adult patients with CABP, which will further reduce the use of fluoroquinolones. https://www.clinicaltrials.gov/study/NCT02531438, identifer: NCT02531438; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004071-13, identifier: EudraCT #2013-004071-13.

The Impact of Principal Diagnosis on Readmission Risk among Patients Hospitalized for Community-Acquired Pneumonia.

Coding variation distorts performance/outcome statistics not eliminated by risk adjustment. Among 1596 community-acquired pneumonia patients hospitalized from 1998 to 2012 identified using an evidence-based algorithm, the authors measured the association of principal diagnosis (PD) with 30-day readmission, stratified by Pneumonia Severity Index risk class. The 152 readmitted patients were more ill (Pneumonia Severity Index class V 38.8% versus 25.8%) and less likely to have a pneumonia PD (52.6% versus 69.9%). Among patients with PDs of pneumonia, respiratory failure, sepsis, and aspiration, mortality/readmission rates were 3.9/8.5%, 28.8/14.0%, 24.7/19.6%, and 9.0/15.0%, respectively. The nonpneumonia PDs were associated with a greater risk of adjusted 30-day readmission: respiratory failure odds ratio (OR) 1.89 (95% confidence interval [CI], 1.13-3.15), sepsis OR 2.54 (95% CI, 1.52-4.26), and possibly aspiration OR 1.73 (95% CI, 0.88-3.41). With increasing use of alternative PDs among pneumonia patients, quality reporting must account for variations in condition coding practices. Rigorous risk adjustment does not eliminate the need for accurate, consistent case definition in producing valid quality measures.

Prevalence and impact on outcome of sodium and potassium disorders in patients with community-acquired pneumonia: A retrospective analysis

Introduction: Disorders of sodium and potassium are common and predictors of adverse outcome. Prevalence and impact on outcome of hypokalemia, hyperkalemia, hyponatremia and hypernatremia were investigated in emergency patients with community-acquired pneumonia (CAP). Methods: Patients ≥18 years presenting to our emergency department between January 1st 2017 and December 31st 2018 with on-admission electrolyte measurements were included. Chart reviews were performed to identify patients with CAP. Results: 19.948 cases had measurements of sodium and potassium of which 469 had CAP (2.4%). Prevalence of hypo- and hypernatremia was significantly increased in patients with compared to those without CAP (hyponatremia: 28.8% vs. 10.5% respectively, p<0.0001; hypernatremia: 1.9% vs. 0.6% respectively, p=0.002). The prevalence of hypo- and hyperkalemia was significantly higher in patients with than without CAP (hypokalemia 15.6% vs. 11.4% respectively, p=0.004; hyperkalemia: 4.5% vs. 2.0% respectively, p=0.001). Hyponatremia was significantly associated with longer hospital stay in patients with CAP (regression coefficient 0.194, standard error 0.079, p=0.015). None of the investigated electrolyte disorders were predictive of 30-day re-admission and 180-day pneumonia recurrence rates. Use of loop diuretics was an independent predictor for 30-day re-admission (OR 2.351 (1.099-5.03). p=0.028). Pneumonia Severity Index (PSI) risk class was an independent predictor of 180-day pneumonia recurrence (OR 1.494 (1.022-2.184), p=0.038). Conclusion: Dysnatremias and dyskalemias are common findings complicating CAP in emergency patients. Prevalence of hyponatremia was highest followed by hypokalemia. Hyponatremia was an independent predictor of prolonged length of hospital stay. Loop diuretic use was associated with 30-day readmission and PSI risk class with 180-day pneumonia recurrence.

Hospital Admission Patterns in Adult Patients with Community-Acquired Pneumonia Who Received Ceftriaxone and a Macrolide by Disease Severity across United States Hospitals

(1) Objective: There are limited data regarding community-acquired pneumonia (CAP) admissions patterns in US hospitals. Current expert CAP guidelines advocate for outpatient treatment or an abbreviated hospital stay for CAP patients in pneumonia severity index (PSI) risk classes I–III (low risk); however, the extent of compliance with this recommendation is unclear. This study sought to estimate the proportion of admissions among CAP patients who received ceftriaxone and macrolide therapy, one of the most commonly prescribed guideline-concordant CAP regimens, by PSI risk class and Charlson comorbidity index (CCI) score. (2) Methods: A retrospective cross-sectional study of patients in the Vizient® (MedAssets, Irving, Texas) database between 2012 and 2015 was performed. Patients were included if they were aged ≥ 18 years, had a primary diagnosis for CAP, and received ceftriaxone and a macrolide on hospital day 1 or 2. Baseline demographics and admitting diagnoses were used to calculate the PSI score. Patients in the final study population were grouped into categories by their PSI risk class and CCI score. Hospital length of stay, 30-day mortality rates, and 30-day CAP-related readmissions were calculated across resulting PSI–CCI strata. (3) Results: Overall, 32,917 patients met the study criteria. Approximately 70% patients were in PSI risk classes I–III and length of stay ranged between 4.9 and 6.2 days, based on CCI score. The 30-day mortality rate was <0.5% and <1.4% in patients with PSI risk classes I and II, respectively. (4) Conclusions: Over two-thirds of hospitalized patients with CAP who received ceftriaxone and a macrolide were in PSI risk classes I–III. Although the findings should be interpreted with caution, they suggest that there is a potential opportunity to improve the efficiency of healthcare delivery for CAP patients by shifting inpatient care to the outpatient setting in appropriate patients.

FluA-p score: a novel prediction rule for mortality in influenza A-related pneumonia patients

BackgroundThe pneumonia severity index (PSI) and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) score have been shown to predict mortality in community-acquired pneumonia. Their ability to predict influenza-related pneumonia, however, is less well-established.MethodsA total of 693 laboratory-confirmed FluA-p patients diagnosed between Jan 2013 and Dec 2018 and recruited from five teaching hospitals in China were included in the study. The sample included 494 patients in the derivation cohort and 199 patients in the validation cohort. The prediction rule was established based on independent risk factors for 30-day mortality in FluA-p patients from the derivation cohort.ResultsThe 30-day mortality of FluA-p patients was 19.6% (136/693). The FluA-p score was based on a multivariate logistic regression model designed to predict mortality. Results indicated the following significant predictors (regression statistics and point contributions toward total score in parentheses): blood urea nitrogen > 7 mmol/L (OR 1.604, 95% CI 1.150–4.492, p = 0.040; 1 points), pO2/FiO2 ≤ 250 mmHg (OR 2.649, 95% CI 1.103–5.142, p = 0.022; 2 points), cardiovascular disease (OR 3.967, 95% CI 1.269–7.322, p < 0.001; 3 points), arterial PH < 7.35 (OR 3.959, 95% CI 1.393–7.332, p < 0.001; 3 points), smoking history (OR 5.176, 95% CI 2.604–11.838, p = 0.001; 4 points), lymphocytes < 0.8 × 109/L (OR 8.391, 95% CI 3.271–16.212, p < 0.001; 5 points), and early neurominidase inhibitor therapy (OR 0.567, 95% CI 0.202–0.833, p = 0.005; − 2 points). Seven points was used as the cut-off value for mortality risk stratification. The model showed a sensitivity of 0.941, a specificity of 0.762, and overall better predictive performance than the PSI risk class (AUROC = 0.908 vs 0.560, p < 0.001) and the CURB-65 score (AUROC = 0.908 vs 0.777, p < 0.001).ConclusionsOur results showed that a FluA-p score was easy to derive and that it served as a reliable prediction rule for 30-day mortality in FluA-p patients. The score could also effectively stratify FluA-p patients into relevant risk categories and thereby help treatment providers to make more rational clinical decisions.

Incidence and risk factors for cardiovascular events in patients hospitalized with community-acquired pneumonia

Objective: To explore the incidence, risk factors of cardiovascular events (CVE) and their impact on 30-day mortality in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a multicenter, retrospective study. Patients hospitalized with CAP from 5 teaching hospitals in Beijing, Shandong and Yunnan provinces during 1 January 2013 to 31 December 2015 were included and clinical data were retrieved from the Hospital Information System (HIS), and patients were divided into CVE group and non-CVE group. Age, sex, comorbidities, pneumonia severity index(PSI)/CURB-65 score, routine blood test, biochemical examinations, radiological findings on admission and mortality on 30-day after admission were analyzed. The primary endpoint was acute CVE during hospitalization, the secondary endpoint was 30-day death after admission. Multivariate Cox regression analysis was used to explore the risk factors for CVE. Kaplan-Meier survival curve was used to compare the difference on 30-day mortality between CVE patients and non-CVE patients by Log-rank test. Multivariate Cox regression model was used to assess the impact of CVE on the 30-day mortality among CAP patients after adjustment with age, sex, comorbidities, PSI/CURB-65 score. Results: A total of 3 561 CAP patients were included into the final analysis, including 210 (5.9%) patients in CVE group and 3 351 (94.1%) patients in non-CVE group. Compared with patients in non-CVE group, patients in CVE group were older (P<0.001), prevalence of hypertension, coronary heart disease, chronic heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, aspiration risk and bedrid were significantly higher (all P<0.001); prevalence of CURB-65 score 3-5 and PSI risk class Ⅳ/Ⅴ were also significantly higher (both P<0.001). The proportion of axillary temperature<36 ℃, respiratory rate≥30 beats/minutes, confusion, leukocytes>10×10(9)/L, hemoglobin<100 g/L, platelets>300×10(9)/L, albumin<35 g/L, blood urea nitrogen>7 mmol/L, fasting blood glucose>11 mmol/L, serum C-reaction protein>100 mg/L, serum procalcitonin≥2 μg/L, arterial pH<7.35, arterial PO(2)/FiO(2)≤300 mmHg (1 mmHg=0.133 kPa), and multilobar infiltrates and pleural effusion on chest X-ray or CT scan were significantly higher in CVE group than in non-CVE group(all P<0.05); the 30-day mortality was significantly higher in CVE group than in non-CVE group(P<0.001). The incidence of CVE was significantly higher in patients with cardiovascular and cerebrovascular disease(CVD) than in patients without CVD (13.9%(150/1 079) vs. 2.4%(60/2 482), χ(2)=178.737, P<0.001). Meanwhile, the incidence of CVE increased with PSI in patients with Ⅰ/Ⅱ, Ⅲ and Ⅳ/Ⅴ class, respectively(χ(2)=228.350, P<0.001); and CURB-65 score 0-1, 2 and 3-5, respectively (χ(2)=387.154, P<0.001). Cox regression analysis revealed that age (HR=1.05, 95%CI 1.02-1.09, P=0.002), coronary heart disease (HR=1.88, 95%CI 1.01-3.51, P=0.048), chronic heart failure (HR=4.25, 95%CI 1.89-9.52, P<0.001), PSI risk class (HR=1.66, 95%CI 1.50-2.62, P=0.029) and serum procalcitonin≥ 2 μg/L (HR=3.72, 95%CI 1.60-8.66, P=0.002) were independent risk factors for CVE in CAP patients. Kaplan-Meier curve showed that the survival probability of patients with CVE was significantly lower than patients without CVE (P<0.001). After adjustment for age, sex, comorbidities and PSI/CURB-65 score, Cox regression model showed that CVE was associated with increased 30-day mortality in CAP patients (HR=6.05, 95%CI 3.11-11.76, P<0.001). Conclusions: Although the incidence of CVE is not high in Chinese patients hospitalized with CAP, CVE is common in patients with severe pneumonia and in patients with CVD. Age, cardiovascular disease, PSI risk class and serum procalcitonin are the risk factors for CVE in this patient cohort. CVE is related to increased 30-day mortality in CAP patients.

Omadacycline for Community-Acquired Bacterial Pneumonia

BackgroundOmadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia.MethodsIn a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used.ResultsThe intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, −1.6 percentage points; 95% confidence interval [CI], −7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, −2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial.ConclusionsOmadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438.)

Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey

ObjectivesTo describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China.DesignThis was a multicentre, retrospective, observational study.Setting13 teaching hospitals in northern, central and southern China...

Community-Acquired Pneumonia Due to Multidrug- and Non–Multidrug-Resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa is not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosa can be the etiology in 1.8%to 8.3%of patients, with a case-fatality rate of 50%to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa. Prospective observational study of 2,023 consecutive adult patients with CAP with definitive etiology. P aeruginosa was found in 77 (4%) of the 2,023 cases with microbial etiology. In 22 (32%) of the 68 cases of P aeruginosa with antibiogram data, the isolates were MDR. Inappropriate therapy was present in 49 (64%) cases of P aeruginosa CAP, including 17/22 (77%) cases of MDR P aeruginosa CAP. Male sex, chronic respiratory disease, C-reactive protein<12.35mg/dL, and pneumonia severity index risk class IV to V were independently associated with P aeruginosa CAP. Prior antibiotic treatment was more frequent in MDR P aeruginosa CAP compared with non-MDR P aeruginosa (58%vs29%, P= .029), and was the only risk factor associated with CAP resulting from MDR P aeruginosa. In the multivariate analysis, age≥65 years, CAP resulting from Paeruginosa, chronic liver disease, neurologic disease, nursing home, criteria of ARDS, acute renal failure, ICU admission, and inappropriate empiric treatment were the factors associated with 30-day mortality. P aeruginosa is an individual risk factor associated with mortality in CAP. The risk factors described can help clinicians to suspect P aeruginosa and MDR P aeruginosa.

A novel method for rapid detection of Streptococcus pneumoniae antigens in blood.

In this study, we used "RAPIRUN(®)Streptococcus pneumoniae HS (otitis media/sinusitis) (RAPIRUN-HS)," a rapid S. pneumoniae antigen detection kit, to investigate methods for detecting S. pneumoniae antigens in blood of 32 bacterial pneumonia patients. We simultaneously performed PCR to detect S. pneumoniae in blood samples. The results of these tests were compared based on pneumonia severity, determined using the Pneumonia Severity Index (PSI) score classification. Four S. pneumoniae PCR-positive patients of the six severe pneumococcal pneumonia patients (PSI risk class IV/V) also tested positive using RAPIRUN-HS. Twenty-four mild to moderate pneumonia patients (PSI risk class I-III) were S. pneumoniae PCR-negative; of these, 21 tested negative using RAPIRUN-HS. The pneumococcal pneumonia patients testing positive using RAPIRUN-HS had low leukocyte counts and elevated C-reactive protein and procalcitonin levels, indicating that RAPIRUN-HS results were correlated with pneumonia severity. The time course evaluations of the laboratory tests for severe pneumococcal pneumonia patients showed that RAPIRUN-HS and S. pneumoniae PCR yielded positive results earlier than the changes in procalcitonin and IL-6. Thus, concomitant pneumococcal bacteremia was strongly suspected in patients testing positive using RAPIRUN-HS. In conclusion, RAPIRUN-HS may be useful for determining whether to admit patients into hospitals and selecting the appropriate antimicrobial agents.

Validity of pneumonia severity index/pneumonia outcome research trial and Curb-65 severity scoring systems in community acquired pneumonia in Indian setting

Background: The symptoms of CAP begin outside the hospital or within 48 hours of admission into the hospital in patients who has not resided in a health care facility for at least 14 days before the onset of the symptoms. Pneumonia severity index (PSI) and the CURB-65 rule for CAP have been developed to identify the relevant prognostic factors might be useful for early identification of patients at high risk requiring intensive care treatment. This study was conducted to determine prognostic factors associated with mortality in and to test the validity of PSI/PORT (pneumonia outcome research trial) and CURB-65 severity scoring systems in community acquired pneumonia (CAP) in Indian setting. Methods: Complete detailed clinical history was taken from 150 patients suspected of community acquired pneumonia patients and they were subjected to thorough physical examination, including X rays, ECG blood tests for various parameters. PSI and CURB-65 scores were taken for all the patients. Results: Maximum no. of patients, i.e.33.33% were in the age group of 60-69. Of 150 patients, 16 died accounting for a mortality rate of 10.7%. This group included 12 (8%) patients who died in hospitals and four (2.67%) who died within 30 days of discharge. All 16 patients (100%) in death group were of PSI risk class ≥IV. Mortality in PSI class I to III was 0% in class IV 14.04% and Class V 34.78%. Mortality in CURB-65 risk class 0 to II was 0%, in risk class III it was 9.52%, 47.82% in Class IV and 50% in Class V. Conclusions: PSI and CURB-65 have excellent sensitivity for predicting death but low specificity albeit specificity of CURB-65 was better than that of PSI. Because of its simplicity and ease of use, in addition to higher specificity, CURB-65 may be better suited than PSI as a severity scoring system in CAP in developing countries with limited resources.

Intensive Care Unit Admission With Community-Acquired Pneumonia

There has been a dramatic increase in the use of intensive care units (ICUs) over the past 25 years. Greater use of validated measures of illness severity may better inform ICU admission decisions in patients with community-acquired pneumonia. This article examined predictors of ICU admission and hospitalization costs, including the pneumonia severity index (PSI) and CURB-65 (confusion, uremia, respiratory rate, blood pressure, age ≥65 years) scores. The study identified 422 patients hospitalized for community-acquired pneumonia, ascertaining patient characteristics by chart review and extraction of administrative data. Multivariate logistic regression was performed to quantify the association of the PSI, CURB-65 and comorbidities with ICU admission. The predictors of cost were estimated using a generalized linear model. Compared to 194 general medicine patients, certain clinical and radiographic findings were more common among 228 ICU patients. Compared to PSI reference group I/II/III, ICU admission was strongly associated with risk class IV (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.63-5.72) and V (OR, 4.84; CI, 2.44-9.62), and also CURB-65 ≥3 (OR, 2.90; CI, 1.51-5.56). The relative increase in mortality among PSI risk class V (compared to IV) patients was 2.68 times higher in general medicine, compared with the ICU. Among ICU admissions, risk class V was associated with an additional cost of $14,548 (95% CI, $4,232 to $24,864). Illness severity and chronic pulmonary disease are strong predictors of ICU admission. More extensive use of the PSI may optimize site-of-care decisions, thereby minimizing mortality and unnecessary resource utilization.

Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia.

BackgroundWe aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.MethodsAdult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/or culture of respiratory secretions and/or urinary antigen test.ResultsOf 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log10 DNA copies/mL (range 1.79–9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration ≥2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient’s own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54–82% and positive predictive values of 37–56%, indicating suboptimal performance.ConclusionsPneumonia severity, symptom duration ≥2 days, and a medium/high serum immunoglobulin titer against the patient’s own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia: risk and prognosis.

The sensitivity of blood cultures in the diagnosis of bacteraemia for community-acquired pneumonia is low. Recommendations, by guidelines, to perform blood cultures are discordant. We aimed to determine the incidence, microbial aetiology, risk factors and outcomes of bacteraemic patients with community-acquired pneumonia, including cases with antibiotic-resistant pathogens (ARP). A prospective, observational study was undertaken on consecutive adult patients admitted to the Hospital Clinic of Barcelona (Barcelona, Spain) with community-acquired pneumonia and blood cultures were obtained. Of the 2892 patients included, bacteraemia was present in 297 (10%) patients; 30 (10%) of whom had ARP (multidrug-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and an extended spectrum of beta-lactamase producing Enterobacteriaceae). In multivariate analyses, pleuritic pain, C-reactive protein ≥21.6 mg·dL(-1) and intensive care unit admissions were independently associated with bacteraemia, while prior antibiotic treatment and pneumococcal vaccine were protective factors. The risk factors for ARP bacteraemia were previous antibiotics and C-reactive protein <22.2 mg·dL(-1), while pleuritic pain was the only protective factor in the multivariate analysis. Bacteraemia (excluding ARP), appropriate empiric treatment, neurological disease, arterial oxygen tension/inspiratory oxygen fraction <250, pneumonia severity index risk classes IV and V, and intensive care unit admission were independently associated with a 30-day hospital mortality in the multivariate analysis. Inappropriate therapy was more frequent in ARP bacteraemia, compared with other bacteraemias (27% versus 3%, respectively, p<0.001). Antibiotic therapy protected against bacteraemia, but increased specifically the risk of bacteraemia from ARP due to the inappropriate coverage of these pathogens. Identifying patients at risk of ARP bacteraemia would help in deciding appropriate empiric antimicrobial therapy. The results from this study provide evidence concerning community-acquired pneumonia patients in whom blood cultures should not be performed.

Mortality of Community-Acquired Pneumonia in Korea: Assessed with the Pneumonia Severity Index and the CURB-65 Score

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.

Bacterial co-infection with H1N1 infection in patients admitted with community acquired pneumonia

SummaryBackgroundBacterial co-infection is an important contributor to morbidity and mortality during influenza pandemics .We investigated the incidence, risk factors and outcome of patients with influenza A H1N1 pneumonia and bacterial co-infection.MethodsProspective observational study of consecutive hospitalized patients with influenza A H1N1 virus and community-acquired pneumonia (CAP). We compared cases with and without bacterial co-infection.ResultsThe incidence of influenza A H1N1 infection in CAP during the pandemic period was 19% (n, 667). We studied 128 patients; 42(33%) had bacterial co-infection. The most frequently isolated bacterial pathogens were Streptococcus pneumoniae (26, 62%) and Pseudomonas aeruginosa (6, 14%). Predictors for bacterial co-infection were chronic obstructive pulmonary disease (COPD) and increase of platelets count. The hospital mortality was 9%. Factors associated with mortality were age ≥65 years, presence of septic shock and the need for mechanical ventilation. Although patients with bacterial co-infection presented with higher Pneumonia Severity Index risk class, hospital mortality was similar to patients without bacterial co-infection (7% vs. 11%, respectively, p = 0.54).ConclusionBacterial co-infection was frequent in influenza A H1N1 pneumonia, with COPD and increased platelet count as the main predictors. Although associated with higher severe scales at admission, bacterial co-infection did not influence mortality of these patients.

Inflammatory biomarkers and prediction for intensive care unit admission in severe community-acquired pneumonia*

Increased inflammatory response is related to severity and outcome in community-acquired pneumonia, but the role of inflammatory biomarkers in deciding intensive care unit admission is unknown. We assessed the relationship between inflammatory response, prediction for intensive care unit admission, delayed intensive care unit admission, and outcome in patients with community-acquired pneumonia. Prospective clinical study. Intensive care units of two university hospitals. We included 627 ward and 58 intensive care unit patients with community-acquired pneumonia, 36 with direct and 22 with delayed intensive care unit admission. Serum levels of C-reactive protein, procalcitonin, tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-8, and interleukin-10 at admission. We assessed the prediction for intensive care unit admission of biomarkers and the Infectious Diseases Society of America/American Thoracic Society guidelines minor criteria for severe community-acquired pneumonia. Procalcitonin (p=.001), C-reactive protein (p=.005), tumor necrosis factor-α (p=.042), and interleukin-6 (p=.003) levels were higher in intensive care unit-admitted patients; however, the Infectious Diseases Society of America/American Thoracic Society guidelines minor severity criteria predicted better intensive care unit admission (odds ratio, 12.03; 95% confidence interval, 5.13-28.20; p<.001). No patient with severe community-acquired pneumonia by three or more minor severity criteria and procalcitonin levels below the optimal cutoff (0.35 ng/mL) needed intensive care unit admission compared with 14 (23%) with levels above the cutoff (p=.032). In patients initially admitted to wards, procalcitonin (p=.012) and C-reactive protein (p=.039) were higher in those 22 patients subsequently transferred to the intensive care unit after adjusting for age, comorbidities, and Pneumonia Severity Index risk class. Despite initially admitted to wards, 14 (64%) patients with delayed intensive care unit admission had already criteria for severe community-acquired pneumonia at admission compared with 73 (12%) ward patients (p<.001). Inflammatory biomarkers identified patients needing intensive care unit admission, including those with delayed intensive care unit admission. Patients with severe community-acquired pneumonia by minor criteria and low levels of procalcitonin may be safely admitted to wards. Correctly applying the Infectious Diseases Society of America/American Thoracic Society guidelines would reduce substantially delayed intensive care unit admission.

A clinical pathway for community-acquired pneumonia: an observational cohort study

BackgroundSix hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost.MethodsData were collected for adults from six U.S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost.ResultsOverall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p < 0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean pharmacy costs ($356 vs. $442, p = 0.11).ConclusionsPathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP.

Prognostic value of procalcitonin in community-acquired pneumonia

The prognostic value of procalcitonin (PCT) levels to predict mortality and other adverse events in community-acquired pneumonia (CAP) remains undefined. We assessed the performance of PCT overall, stratified into four predefined procalcitonin tiers (< 0.1, 0.1-0.25, > 0.25-0.5, >0.5 μg·L⁻¹) and stratified by Pneumonia Severity Index (PSI) and CURB-65 (confusion, urea >7 mmol·L⁻¹, respiratory frequency ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 yrs) risk classes to predict all-cause mortality and adverse events within 30 days follow-up in 925 CAP patients. In receiver operating characteristic curves, initial PCT levels performed only moderately for mortality prediction (area under the curve (AUC) 0.60) and did not improve clinical risk scores. Follow-up measurements on days 3, 5 and 7 showed better prognostic performance (AUCs 0.61, 0.68 and 0.73). For prediction of adverse events, the AUC was 0.66 and PCT significantly improved the PSI (from 0.67 to 0.71) and the CURB-65 (from 0.64 to 0.70). In Kaplan-Meier curves, PCT tiers significantly separated patients within PSI and CURB-65 risk classes for adverse events prediction, but not for mortality. Reclassification analysis confirmed the added value of PCT for adverse event prediction, but not mortality. Initial PCT levels provide only moderate prognostic information concerning mortality risk and did not improve clinical risk scores. However, PCT was helpful during follow-up and for prediction of adverse events and, thereby, improved the PSI and CURB65 scores.

Measurement of Serum Procalcitonin

THE ADVENT OF ANTIBIOTICS LED TO DRAMATIC REductions in mortality and medical complications from bacterial respiratory tract infections. Although the armamentarium of diagnostic and therapeutic approaches has increased exponentially since that time, the effect of these advances on patient outcomes is less dramatic. Nevertheless, the goal of care remains constant: to match the patient’s illness with a treatment approach that optimizes recovery while causing no harm. Harm exists in at least 2 forms: patient-specific, from an adverse event due to a diagnostic test or a treatment, and population-based, from the development of bacterial resistance promoted by the misuse or overuse of antibiotics. Lower respiratory tract infections (LRTIs) are a pervasive public health problem and cause more disease and death in the United States than any other infection. Patients and their physicians share a goal of improving symptoms from LRTIs as quickly as possible, often viewing antibiotics as the most expeditious intervention to achieve this goal. This one-sizefits-all approach for patients with illnesses ranging from acute bronchitis to community-acquired pneumonia (CAP) fails to consider the basic questions of who would benefit (or be harmed) from antibiotic therapy, and if treated, what is the optimal duration. Answering these questions requires an accurate assessment of which patients have bacterial infections and how their illness might progress with or without treatment. Many conventional bacterial detection techniques used in LRTIs, such as sputum Gram stains and cultures, lack sufficient diagnostic accuracy and turnaround time to inform real-time decisions. In the setting of a severe LRTI with evidence of organ derangement, assessing the benefits and risks of treatment often favors empirical antibiotic therapy. However, such clinical scenarios are uncommon; the vast majority of patients have mild to moderate illness, rendering this assessment of cause and response more challenging. Clinical decision rules based on bedside clinical and laboratory data could help physicians improve antibiotic management for such patients and optimize the duration of therapy. The ultimate clinical value of such rules is a function of diagnostic accuracy, effectiveness in changing clinician behavior, safety for patients, and both individual and societal cost. In this issue of JAMA, Schuetz and colleagues build on prior work bystudyingtheeffectivenessandsafetyofusinganovel decision rule to guide antibiotic therapy of patients diagnosed with LRTIs ranging from acute bronchitis to exacerbationofchronicobstructivepulmonarydisease(COPD)toCAP. In their current study, theauthors evaluated1359patientspresenting to emergency departments in 6 tertiary care hospitals who were randomized to receive care guided by evidencebased LRTI guidelines (control group) or by an experimental algorithm that used serum procalcitonin (PCT) to quantify the likelihood of a bacterial infection and gauge the response to therapy. PCT is released in response to bacterial infection and correlates with illness burden and severity; furthermore, it is rarely elevated in patients with viral infection. The algorithm specified 1 of 4 antibiotic treatment recommendations, rangingfromstronglydiscouragetostronglyrecommend,based on the measured PCT levels. For hospitalized patients, repeat PCT measurements guided continuation of antibiotic therapy. In contrast to many effectiveness trials that seek to change clinician behavior through the implementation of decision rules, compliance with treatment recommendations in this trial were commendably high (79.4% in the control group and 90.8% in the PCT group). Overall, the PCT-guided strategy led to reduced antibiotic exposure by an average of 3 days (8.7 vs 5.7 days) and led to 8.2% less antibioticrelated adverse effects (28.1% vs 19.8%), with slightly lower overall adverse event rates in the PCT group (15.4% vs 18.9%). Although similar outcomes were observed for patients with acute bronchitis, COPD exacerbation, and CAP, the paths to reducing antibiotic exposure differed in a predictable fashion. For acute bronchitis, decreased antibiotic exposure was principally from nontreatment, whereas for CAP it was principally from reduction in duration of therapy. Even though this PCT-guided decision rule holds promise for the management of patients with LRTI, several issues must be carefully considered before broadly translating this research into clinical practice. First, the study had a high proportion of patients with pneumonia (68.1%), more than half of whom were considered high risk (pneumonia severity index risk classes IV or V). In such patients, the high likelihood of bacterial disease and high disease acuity render PCT guidance unlikely to alter the decision to initiate antibiotic