The Microbial Etiology of Community-Acquired Pneumonia in Adults: from Classical Bacteriology to Host Transcriptional Signatures.

All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Enterobacteriaceae, Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying Legionella and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized ("typical") bacterial pathogens as well as a role for commensal bacteria ("normal respiratory flora"). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.

Contributions of Animal Studies to the Understanding of Infectious Diseases.

Experiments in animals have played an integral role in furthering basic understanding of the pathophysiology, host immune response, diagnosis, and treatment of infectious diseases. However, competing demands of modern-day clinical training and increasingly stringent requirements to perform animal research have reduced the exposure of infectious disease physicians to animal studies. For practitioners of infectious diseases and, especially, for contemporary trainees in infectious diseases, it is important to appreciate this historical body of work and its impact on current clinical practice. In this article, we provide an overview of some major contributions of animal studies to the field of infectious diseases. Areas covered include transmission of infection, elucidation of innate and adaptive host immune responses, testing of antimicrobials, pathogenesis and treatment of endocarditis, osteomyelitis, intra-abdominal and urinary tract infection, treatment of infection associated with a foreign body or in the presence of neutropenia, and toxin-mediated disease.

Procalcitonin to Distinguish Viral From Bacterial Pneumonia: A Systematic Review and Meta-analysis.

Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37-.71; I2 = 95.5%) and 0.76 (95% CI, .62-.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP.

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

Physician Integrity, Templates, and the 'F' Word.

The medical profession is increasingly dependent upon electronic health records. Along with documented benefits, a number of potential ethical abuses have been outlined. Herein, we describe an ethical abuse that has received almost no attention, namely falsified medical records. We present three cases in which the medical record cited facts from history that were not elicited and findings from physical examination that was not performed. This is fraud. Prepopulated templates were almost certainly responsible. If a template is used, it must begin free of results-a skeleton onto which flesh is placed. If coders and third-party payers insist on having information than health care providers think relevant, then we, as a profession should "push back," but a template that has been prepopulated puts fraudulent data into electronic health record, seriously damaging physician integrity.

Evolving Understanding of the Causes of Pneumonia in Adults, With Special Attention to the Role of Pneumococcus.

Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia in adults. After 1950, the proportion of pneumonia caused by pneumococcus began to decline. Pneumococcus has continued to decline; at present, this organism is identified in fewer than fewer10%-15% of cases. This proportion is higher in Europe, a finding likely related to differences in vaccination practices and smoking. Gram-negative bacilli, Staphylococcus aureus, Chlamydia, Mycoplasma, and Legionella are each identified in 2%-5% of patients with pneumonia who require hospitalization. Viruses are found in 25% of patients, up to one-third of these have bacterial coinfection. Recent studies fail to identify a causative organism in more than 50% of cases, which remains the most important challenge to understanding lower respiratory infection. Our findings have important implications for antibiotic stewardship and should be considered as new policies for empiric pneumonia management are developed.

The Ongoing Genetic Adaptation of Streptococcus pneumoniae.

Streptococcus pneumoniae has demonstrated a remarkable ability to adapt during the conjugate vaccine era. The increasing incidence of serotype 35B disease and emergence of a multidrug-resistant clone reported in this issue of the Journal of Clinical Microbiology (L. Olarte et al., J Clin Microbiol 55:724-734, 2017, https://doi.org/10.1128/JCM.01778-16) underscore the limitations of pneumococcal vaccines that target the polysaccharide capsule.

Postobstructive Pneumonia: An Underdescribed Syndrome.

BACKGROUND: Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP). METHODS: We prospectively studied patients hospitalized for CAP; 5.4% had PO-CAP, defined as a pulmonary infiltrate occurring distal to an obstructed bronchus. Sputum and blood cultures, viral polymerase chain reaction, urinary antigen tests, and serum procalcitonin (PCT) were done in nearly all cases. Clinical and laboratory characteristics of patients with PO-CAP were compared to those of patients with B-CAP. RESULTS: In a 2-year period, we identified 30 patients with PO-CAP. Compared to patients with B-CAP, patients with PO-CAP had longer duration of symptoms (median, 14 vs 5 days;P< .001). Weight loss and cavitary lesions were more common (P< .01 for both comparisons) and leukocytosis was less common (P< .01) in patients with PO-CAP. A bacterial pathogen was implicated in only 3 (10%) PO-CAP cases. PCT was <0.25 ng/mL in 19 (63.3%) patients. Although no differences were observed in disease severity or rates of intensive care unit admissions, 30-day mortality was significantly higher in PO-CAP vs B-CAP (40.0% vs 11.7%;P< .01). CONCLUSIONS: Although there is substantial overlap, PO-CAP is a clinical entity distinct from B-CAP; a bacterial cause was identified in only 10% of patients. Our study has important implications for the clinical recognition of patients with PO-CAP, the role of microorganisms as etiologic agents, and the use of antibiotic therapy.

Predictive and prognostic factors in patients with blood-culture-positive community-acquired pneumococcal pneumonia.

In patients with pneumococcal community-acquired pneumonia (CAP), the risk factors for bacteraemia and its impact on outcomes are not fully elucidated. We aimed to compare characteristics of patients with blood-culture-positive versus blood-culture-negative pneumococcal CAP, and to characterise bacteraemic serotypes.We describe a prospective, observational study on nonimmunocompromised patients with pneumococcal CAP, from 1996 to 2013. We define severe pneumonia according to American Thoracic Society/Infectious Diseases Society of America guidelines.Of a total of 917 patients with pneumococcal CAP, 362 had blood-culture-positive pneumococcal pneumonia (BCPPP; 39%). High C-reactive protein (CRP) (≥20 mg·dL(-1)) (odds ratio (OR) 2.36, 95% CI 1.45-3.85), pleural effusion (OR 2.03, 95% CI 1.13-3.65) and multilobar involvement (OR 1.69, 95% CI 1.02-2.79) were independently associated with bacteraemic CAP, while nursing home resident (OR 0.12, 95% CI 0.01-1.00) was found as a protective factor. Despite the clinical differences, BCPPP showed similar outcomes to blood-culture-negative pneumococcal pneumonia (BCNPP). 14% of the serotypes (period 2006-2013) causing bacteraemia are included in pneumococcal conjugate vaccine PVC7, 74% in pneumococcal conjugate vaccine PVC13 and 83% in pneumococcal polysaccharide vaccine PPSV23.Pleural effusion, a high level of CRP and multilobar involvement predicted an increased risk of BCPPP. Although BCPPP patients were more severely ill at admission, mortality was not significantly greater than in BCNPP patients.

Clinical Diagnosis, Viral PCR, and Antibiotic Utilization in Community-Acquired Pneumonia.

We evaluated the intensity of antibiotic therapy in patients in whom the etiology of community-acquired pneumonia (CAP) was determined using newly available diagnostic techniques. For 1 year, we studied all patients admitted for findings consistent with CAP. Sputum and blood cultures, urinary pneumococcal and Legionella antigens, and viral polymerase chain reaction (PCR) were studied prospectively. Patients were stratified based on the final diagnoses: proven bacterial, presumptive bacterial, viral, fungal, undetermined, and uninfected. We determined the number of antibiotics given, duration of antibiotic therapy, and intensity of antibiotic use determined by antibiotic-days defined as the sum, in each patient, of all antibiotics given for CAP and the number of days given. Median duration and intensity of antibiotics were 12 and 18 days for proven, and 13 and 16.5 days for presumed bacterial CAP (P > 0.9). When positive viral PCR results were not disclosed to primary care physicians, antibiotic use was similar to that in bacterial CAP. However, in 11 cases, when positive viral PCR results were disclosed, duration and intensity of antibiotic use were reduced to 7 and 9 days, respectively (P = 0.05 and 0.08, respectively). Antibiotic use was similar in patients with bacterial pneumonia and those judged on clinical grounds to have likely nonbacterial infection. Despite obvious differences in clinical syndromes and final diagnoses, the intensity of antibiotic therapy was similar in all groups of patients admitted for CAP with the exception of those who were uninfected and whose primary care physicians were informed of a positive viral PCR.