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The causative agents in aspiration pneumonia have shifted from anaerobic to aerobic bacteria. Challenges remain in distinguishing aspiration pneumonia from chemical pneumonitis. Treatment and prevention strategies are discussed.

AbstractSevere pneumonia is associated with high mortality (short and long term), as well as pulmonary and extrapulmonary complications. Appropriate diagnosis and early initiation of adequate antimicrobial treatment for severe pneumonia are crucial in improving survival among critically ill patients. Identifying the underlying causative pathogen is also critical for antimicrobial stewardship. However, establishing an etiological diagnosis is challenging in most patients, especially in those with chronic underlying disease; those who received previous antibiotic treatment; and those treated with mechanical ventilation. Furthermore, as antimicrobial therapy must be empiric, national and international guidelines recommend initial antimicrobial treatment according to the location’s epidemiology; for patients admitted to the intensive care unit, specific recommendations on disease management are available. Adherence to pneumonia guidelines is associated with better outcomes in severe pneumonia. Yet, the continuing and necessary research on severe pneumonia is expansive, inviting different perspectives on host immunological responses, assessment of illness severity, microbial causes, risk factors for multidrug resistant pathogens, diagnostic tests, and therapeutic options.

PurposeSevere community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP.MethodsThe European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations.ResultsRecommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions.ConclusionsIn these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to de-escalation and antimicrobial stewardship. Biomarkers such a procalcitonin can provide decision support for antibiotic use, and may identify patients with a low likelihood of infection, and in some settings, can guide duration of antibiotic therapy. Sepsis can involve drug-resistant pathogens, and this often necessitates consideration of newer antimicrobial agents.

Pneumonia is a common acute respiratory infection that affects the alveoli and distal airways; it is a major health problem and associated with high morbidity and short-term and long-term mortality in all age groups worldwide. Pneumonia is broadly divided into community-acquired pneumonia or hospital-acquired pneumonia. A large variety of microorganisms can cause pneumonia, including bacteria, respiratory viruses and fungi, and there are great geographical variations in their prevalence. Pneumonia occurs more commonly in susceptible individuals, including children of <5 years of age and older adults with prior chronic conditions. Development of the disease largely depends on the host immune response, with pathogen characteristics having a less prominent role. Individuals with pneumonia often present with respiratory and systemic symptoms, and diagnosis is based on both clinical presentation and radiological findings. It is crucial to identify the causative pathogens, as delayed and inadequate antimicrobial therapy can lead to poor outcomes. New antibiotic and non-antibiotic therapies, in addition to rapid and accurate diagnostic tests that can detect pathogens and antibiotic resistance will improve the management of pneumonia. Pneumonia is a respiratory infection of the distal airways; it can be acquired in the community or in the hospital, and it can be caused by several types of bacteria, viruses, fungi and other pathogens.

Introduction Ventilator-associated pneumonia (VAP) is a common cause of nosocomial infection, and is related to significant utilization of health-care resources. In the past decade, new data have emerged about VAP epidemiology, diagnosis, treatment and prevention. Results Classifying VAP strictly based on time since hospitalization (early- and late-onset VAP) can potentially result in undertreatment of drug-resistant organisms in ICUs with a high rate of drug resistance, and overtreatment for patients not infected with resistant pathogens. A combined strategy incorporating diagnostic scoring systems, such as the Clinical Pulmonary Infection Score (CPIS), and either a quantitative or qualitative microbiological specimen, plus serial measurement of biomarkers, leads to responsible antimicrobial stewardship. The newly proposed ventilator-associated events (VAE) surveillance definition, endorsed by the Centers for Disease Control and Prevention, has low sensitivity and specificity for diagnosing VAP and the ability to prevent VAE is uncertain, making it a questionable surrogate for the quality of ICU care. The use of adjunctive aerosolized antibiotic treatment can provide high pulmonary concentrations of the drug and may facilitate shorter durations of therapy for multi-drug-resistant pathogens. A group of preventive strategies grouped as a ‘ventilator bundle’ can decrease VAP rates, but not to zero, and several recent studies show that there are potential barriers to implementation of these prevention strategies. Conclusion The morbidity and mortality related to VAP remain high and, in the absence of a gold standard test for diagnosis, suspected VAP patients should be started on antibiotics based on recommendations per the 2005 ATS guidelines and knowledge of local antibiotic susceptibility patterns. Using a combination of clinical severity scores, biomarkers, and cultures might help with reducing the duration of therapy and achieving antibiotic de-escalation.

Clinical trials of nosocomial pneumonia can include patients with hospital-acquired pneumonia, ventilatorassociated pneumonia, and health care-associated pneumonia. All study participants should meet a clinical definition of infection and have some microbiologic confirmation of infection and its etiology. If the trial is to reflect clinical practice and to be practical to conduct, insistence that all patients have bronchoscopic quantitative cultures performed may not be practical. In designing a clinical trial, patients treated in the intensive care unit are the best group to target for study, including only those with severe pneumonia but allowing those with both ventilator-associated pneumonia and hospital-acquired pneumonia to be enrolled. All trials should include a protocol to control for standards of care, including timing of initial therapy, recent antibiotic use, local microbiology patterns, duration of therapy, and the use of a de-escalation therapy strategy. Blinding of a trial may not be required if studying a new agent that is more active against multidrug-resistant pathogens than against currently available comparators. Any new agent should meet a noninferiority end point for 30-day mortality, but if superiority is a goal of trial design, end points could be microbiologic eradication, time to microbiologic eradication, prolonged duration of therapy, need to modify initial therapy, and serial evaluation of the arterial oxygen tension to fractional inspired oxygen ratio.

Background. Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia. Methods. This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare—associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated. Results. Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). Conclusions. For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.