Procalcitonin Is Useful for Evaluating Patients with Ambiguous Presentation and for Early Discontinuation of Antibiotics in Community-acquired Pneumonia.
Procalcitonin Is Useful for Evaluating Patients with Ambiguous Presentation and for Early Discontinuation of Antibiotics in Community-acquired Pneumonia.
Project description:Background and objectiveNarrow-spectrum antibiotics are recommended as the first-line agent for children hospitalized with community-acquired pneumonia (CAP). There is little scientific evidence to support that this consensus-based recommendation is as effective as the more commonly used broad-spectrum antibiotics. The objective was to compare the effectiveness of empiric treatment with narrow-spectrum therapy versus broad-spectrum therapy for children hospitalized with uncomplicated CAP.MethodsThis multicenter retrospective cohort study using medical records included children aged 2 months to 18 years at 4 children's hospitals in 2010 with a discharge diagnosis of CAP. Patients receiving either narrow-spectrum or broad-spectrum therapy in the first 2 days of hospitalization were eligible. Patients were matched by using propensity scores that determined each patient's likelihood of receiving empiric narrow or broad coverage. A multivariate logistic regression analysis evaluated the relationship between antibiotic and hospital length of stay (LOS), 7-day readmission, standardized daily costs, duration of fever, and duration of supplemental oxygen.ResultsAmong 492 patients, 52% were empirically treated with a narrow-spectrum agent and 48% with a broad-spectrum agent. In the adjusted analysis, the narrow-spectrum group had a 10-hour shorter LOS (P = .04). There was no significant difference in duration of oxygen, duration of fever, or readmission. When modeled for LOS, there was no difference in average daily standardized cost (P = .62) or average daily standardized pharmacy cost (P = .26).ConclusionsCompared with broad-spectrum agents, narrow-spectrum antibiotic coverage is associated with similar outcomes. Our findings support national consensus recommendations for the use of narrow-spectrum antibiotics in children hospitalized with CAP.
Project description:BackgroundLower procalcitonin (PCT) concentrations are associated with reduced risk of bacterial community-acquired pneumonia (CAP) in adults, but data in children are limited.MethodsWe analyzed serum PCT concentrations from children hospitalized with radiographically confirmed CAP enrolled in the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community (EPIC) Study. Blood and respiratory specimens were tested using multiple pathogen detection methods for typical bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus), atypical bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae), and respiratory viruses. Multivariable regression was used to assess associations between PCT concentrations and etiology and severity.ResultsAmong 532 children (median age, 2.4 years; interquartile range [IQR], 1.0-6.3), patients with typical bacteria had higher PCT concentrations (±viruses; n = 54; median, 6.10; IQR, 0.84-22.79 ng/mL) than those with atypical bacteria (±viruses; n = 82; median, 0.10; IQR, 0.06-0.39 ng/mL), viral pathogens only (n = 349; median, 0.33; IQR, 0.12-1.35 ng/mL), or no pathogen detected (n = 47; median, 0.44; IQR, 0.10-1.83 ng/mL) (P < .001 for all). No child with PCT <0.1 ng/mL had typical bacteria detected. Procalcitonin <0.25 ng/mL featured a 96% negative predictive value (95% confidence interval [CI], 93-99), 85% sensitivity (95% CI, 76-95), and 45% specificity (95% CI, 40-50) in identifying children without typical bacterial CAP.ConclusionsLower PCT concentrations in children hospitalized with CAP were associated with a reduced risk of typical bacterial detection and may help identify children who would not benefit from antibiotic treatment.
Project description:BackgroundRecent trials suggest procalcitonin-based guidelines can reduce antibiotic use for respiratory infections. However, the accuracy of procalcitonin to discriminate between viral and bacterial pneumonia requires further dissection.MethodsWe evaluated the association between serum procalcitonin concentration at hospital admission with pathogens detected in a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia. Systematic pathogen testing included cultures, serology, urine antigen tests, and molecular detection. Accuracy of procalcitonin to discriminate between viral and bacterial pathogens was calculated.ResultsAmong 1735 patients, pathogens were identified in 645 (37%), including 169 (10%) with typical bacteria, 67 (4%) with atypical bacteria, and 409 (24%) with viruses only. Median procalcitonin concentration was lower with viral pathogens (0.09 ng/mL; interquartile range [IQR], <0.05-0.54 ng/mL) than atypical bacteria (0.20 ng/mL; IQR, <0.05-0.87 ng/mL; P = .05), and typical bacteria (2.5 ng/mL; IQR, 0.29-12.2 ng/mL; P < .01). Procalcitonin discriminated bacterial pathogens, including typical and atypical bacteria, from viral pathogens with an area under the receiver operating characteristic (ROC) curve of 0.73 (95% confidence interval [CI], .69-.77). A procalcitonin threshold of 0.1 ng/mL resulted in 80.9% (95% CI, 75.3%-85.7%) sensitivity and 51.6% (95% CI, 46.6%-56.5%) specificity for identification of any bacterial pathogen. Procalcitonin discriminated between typical bacteria and the combined group of viruses and atypical bacteria with an area under the ROC curve of 0.79 (95% CI, .75-.82).ConclusionsNo procalcitonin threshold perfectly discriminated between viral and bacterial pathogens, but higher procalcitonin strongly correlated with increased probability of bacterial pathogens, particularly typical bacteria.
Project description:To develop and validate a model to predict resistance to community-acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare-associated pneumonia (HCAP), and to compare the model's predictive performance to a model including only guideline-defined criteria for HCAP.Retrospective cohort study.Six Veterans Affairs Medical Centers in the northwestern United States.Culture-positive inpatients with HCAP.Patients were identified based upon guideline-defined criteria for HCAP. Relevant cultures obtained within 48 hours of admission were assessed to determine bacteriology and antibiotic susceptibility. Medical records for the year preceding admission were assessed to develop predictive models of CAP-resistance with logistic regression. The predictive performance of cohort-developed and guideline-defined models was compared.CAP-resistant organisms were identified in 118 of 375 culture-positive patients. Of guideline-defined criteria, CAP-resistance was associated (odds ratio (OR) [95% confidence interval (CI)]) with: admission from nursing home (2.6 [1.6-4.4]); recent antibiotic exposure (1.7 [1.0-2.8]); and prior hospitalization (1.6 [1.0-2.6]). In the cohort-developed model, CAP-resistance was associated with: admission from nursing home or recent nursing home discharge (2.3 [1.4-3.8]); positive methicillin-resistant Staphylococcus aureus (MRSA) history within 90 days of admission (6.4 [2.6-17.8]) or 91-365 days (2.3 [0.9-5.9]); cephalosporin exposure (1.8 [1.1-2.9]); recent infusion therapy (1.9 [1.0-3.5]); diabetes (1.7 [1.0-2.8]); and intensive care unit (ICU) admission (1.6 [1.0-2.6]). Area under the receiver operating characteristic curve (aROC [95% CI]) for the cohort-developed model (0.71 [0.65-0.77]) was significantly higher than for the guideline-defined model (0.63 [0.57-0.69]) (P = 0.01).Select guideline-defined criteria predicted CAP-resistance. A cohort-developed model based primarily on prior MRSA history, nursing home residence, and specific antibiotic exposures provided improved prediction of CAP-resistant organisms in HCAP.
Project description:BackgroundSevere community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT).MethodsWe conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a β-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality.ResultsAmong the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis.ConclusionLegionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.
Project description:Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.
Project description:Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality both in the USA and globally. As the burden of CAP continues to increase due to several factors, the advances in its diagnosis, prevention, and treatment have taken on even greater interest and importance. The majority of CAP patients are treated empirically, and selection of appropriate antibiotic treatment is increasingly difficult because the epidemiology of CAP is changing, in part due to antimicrobial resistance, and the causative CAP pathogens differ between countries and regions. There is also an increasing prevalence of chronic co-morbid diseases among CAP patients. Treatment of CAP has become challenging because of these factors along with the varying safety profiles and efficacy of well-established antibiotics, as well as limited new therapeutic options. Recently, however, new antibiotics have been approved, which will expand the treatment options for CAP, particularly in those patients with underlying complications. Recently approved delafloxacin, an anionic fluoroquinolone, has a unique structure and distinct chemical characteristics; it demonstrated non-inferiority to moxifloxacin in a phase III clinical trial, but was shown to be superior to moxifloxacin at early clinical response in CAP patients who also have chronic obstructive pulmonary disease (COPD) or asthma as a co-morbidity, and in CAP patients who may have severe illness. Delafloxacin could offer an additional therapy against resistant isolates and among these difficult-to-treat patients. This review summarizes the development, latest research, and safety profile of the new antibiotic delafloxacin, and its potential future role in the treatment of CAP.
Project description:Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection. Biomarkers that can identify bacterial infections may reduce antibiotic prescription. We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008. Demographics, clinical data, and blood samples were collected. Procalcitonin and CRP concentrations were measured from available sera.Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied. Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001). Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]). The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00). A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma. CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness.
Project description:BackgroundCommunity-acquired pneumonia (CAP) is often accompanied by changes in lipid metabolism. This study aimed to examine the changes in serum phospholipids (PLs) that may be useful for early disease stratification and as potential therapeutic targets in patients with CAP.MethodsSerum samples from 58 patients hospitalized with CAP and 11 control samples were collected during admission between January 2017 and October 2018. Targeted lipidomic analysis was used to determine the concentrations of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), and lysophosphatidylethanolamine (LPE). The Gene Expression Omnibus (GEO) database was used to evaluate the gene expression levels of key enzymes in the Lands cycle, and quantitative real-time polymerase chain reaction (qRT-PCR) was used for further verification.ResultsA significant decrease in LPC levels and an increase in PE levels, PC/LPC and PE/LPE ratios were observed in patients with CAP (P<0.05). The area under the curve (AUC) of PE serum concentrations combined with CURB-65 scores (confusion, uremia, respiratory rate, blood pressure, and age ≥65 years) was 0.848 for discriminating disease severity, which was significantly higher than the discriminating disease severity of CURB-65 (P<0.05). The efficiency of predicting 30-day mortality using PC, LPC, or PC/LPC ratio combined with CURB-65 scores (AUC =0.811, AUC =0.854, AUC =0.838, respectively) was better than CURB-65 alone (P<0.05). Gene expression analysis revealed the upregulation of LPC acyltransferase 2.ConclusionsLPC or PE serum levels as well as PC/LPC ratios combined with CURB-65 are effective biomarkers for predicting the disease severity and 30-day mortality of patients with CAP. Further investigations of phospholipid metabolism will improve our understanding and treatment of CAP.