Pneumonia in the ICU: Managing Oral Pathogens for Prevention and Treatment

Since coverage of atypical bacteria by macrolides, fluoroquinolones, or tetracyclines seems to be expandable in mild cases treated as outpatients—most guidelines recommend oral penicillins or aminopenicillins longer half life time, higher bioavailability, and better activity against HI than penicillin V to cover pneumococci—empiric combination treatment of inpatients with beta-lactam plus macrolide remains an issue of debate 79 , A retrospective study revealed a clinical advantage of macrolides even in patients with macrolide-resistant pneumococcal pneumonia.

However, recently, the cardiotoxicity of macrolides has been linked to a slightly increased mortality.

A meta-analysis found that erythromycin carries the greatest risk of QT prolongation and torsades de pointes from all macrolides, followed by clarithromycin and azithromycin A large Danish cohort study estimated 37 cardiac deaths in 1 million treatments with clarithromycin 84 , with an increased risk particularly in women. Whereas the Svanstrom study addressed younger adults and not patients with CAP, the study by Ray et al. The study by Schembri et al.

However, Mortensen et al. However, randomised studies were not available. Finally, in , two randomised studies addressing this question were published. The Swiss study could not prove non-inferiority for beta-lactam monotherapy regarding the proportion of patients reaching clinical stability on day 7, even after exclusion of patients with a positive urine legionella antigen test result. In contrast, the Dutch study found that beta-lactam monotherapy was non-inferior to strategies with a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to day mortality.

The macrolide used in the Dutch study was erythromycin 91 , which has a higher cardiotoxicity than azithromycin or clarithromycin The Swiss study showed that, in particular, patients with atypical pathogens mostly Mycoplasma pneumoniae and patients with a higher severity profited from the macrolide combination. Antibiotic stewardship has become an important strategy to fight the antibiotic resistance crisis. How is antibiotic stewardship implemented in CAP treatment?

First of all, pneumonia has to be differentiated from non-pneumonia entities e. This requires a standard chest X-ray, which is frequently not available in the outpatient setting. Several studies have shown that using a PCT is a useful biomarker to decide for or against empiric antibiotics in inpatients and outpatients presenting with lower respiratory tract infections. Other approaches used a clinical score to predict CAP in outpatients presenting with acute respiratory tract infection in order to identify patients who should be prescribed antibiotics Another strategy to decrease antibiotic consumption without harming the patient is to shorten antibiotic treatment.

A recent prospective before-and-after intervention study from Scotland describes the implementation of a simple CRBbased algorithm for duration of treatment i. Acute exacerbation of COPD: This algorithm was enforced by automatic stop dates and pharmacist feedback to prescribers and resulted in significant reductions of antibiotic consumption and in antibiotic side effects without increasing mortality or length of stay. Vaccines are available against pneumococci and influenza virus, the most frequent bacterial and viral causes of CAP, respectively.

Advances in the prevention, management, and treatment of community-acquired pneumonia

Bacterial-viral co-infections are associated with increased mortality, and synergistic effects have been shown for combined vaccination The standard influenza vaccine is the trivalent split vaccine, containing two influenza A and one influenza B strains, which are annually selected by the World Health Organization. Within the last few years, efforts have been made to improve acceptance, coverage of the vaccine, and particularly its efficacy in the elderly. A central problem of the influenza vaccine is that the elderly, who are at increased risk, exhibit an inferior response to the vaccine because of immunosenescence.

Intradermal vaccination aims to stimulate more antigen-presenting cells, which are found in higher concentration in the dermis than in the subcutis or the muscle. Virions mimic natural viral cell entry, and adjuvants aim to recruit more antigen-presenting cells. High-dose vaccines use four times the amount of antigen.

Whereas studies have shown that most of these approaches increase antibody titres, only high-dose vaccines were tested in a study with a clinically relevant endpoint and showed an increased prevention of laboratory-confirmed influenza cases Other strategies try to improve the influenza vaccine coverage. In contrast to influenza A, influenza B does not undergo antigenic shift and therefore does not cause pandemics. However, as a result of accumulated point mutations, influenza B split into two lines Yamagata and Victoria about 30 to 40 years ago Historically, only one influenza B line was included in the trivalent split vaccine.

Therefore, the coverage of the trivalent split vaccine has depended on the accurate prediction of the dominating B line in the particular season. Recently, quadrivalent influenza vaccines that include both influenza B lines have been made available for clinical use Pneumococcal vaccination of adults is a current issue of debate, since both a valent polysaccharide vaccine and a valent conjugate vaccine are licensed for use in adults.

However, the majority of pneumococcal pneumonia is non-bacteraemic, and it remains controversial whether this vaccine is protective against non-invasive pneumococcal pneumonia To date, only one RCT in Japanese nursing home residents showed a clear reduction of pneumococcal pneumonia , whereas several other studies and a respective meta-analysis revealed no effect The coverage of valent pneumococcal conjugate vaccine PCV13 in adults is supposed to decrease because of herd protection effects of the PCV13 infant vaccination program that has led to a substantial decrease of the 13 vaccine serotypes in countries with such a program.

Nevertheless, it remains unclear whether the herd protection effects on invasive pneumococcal disease seen after implementing PCV7 can be extrapolated to the additional six serotypes of PCV13 or non-invasive pneumococcal pneumonia or both. Recent data from Sweden, the US, and Germany suggest that there is only minor or no herd protection for serotype 3, one of the most frequent serotypes causing pneumonia in adults — Considering these data, the Advisory Committee on Immunization Practices has suggested a sequential vaccination PCV13 followed by PPV23 after 6 to 12 months for all adults older than Within the next few years, intensive surveillance on serotype distribution in pneumococcal pneumonia is needed in order to estimate the extension of herd protection and to evaluate the use of PCV13 vaccination in adults.

CAP is the infectious disease with the highest number of deaths worldwide. Nevertheless, the importance of this disease is often underestimated. It is diagnosed too late, severity scoring is not appropriate, so that patients are too seldom admitted to intermediate care or ICUs, and antibiotic therapy is often not in accordance with guidelines.

Therefore, current guidelines are much more evidence based than ever before. The challenge for the future is to implement current knowledge into clinical practice to reduce the number of CAP cases by vaccination and the number of deaths by adequate diagnostics and treatment. National and international societies should establish CAP audits to oversee the management of CAP and to give clinicians feedback about their daily clinical practice.

I confirm that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. F Faculty Reviews are commissioned from members of the prestigious F Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions any comments will already have been addressed in the published version.

National Center for Biotechnology Information , U. Journal List FRes v. Published online Mar 8. Pletz , a, 1 Gernot G. Author information Article notes Copyright and License information Disclaimer. The authors declare that they have no competing interests. Accepted Mar 3. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC. Abstract Community-acquired pneumonia CAP is the infectious disease with the highest number of deaths worldwide. Introduction and epidemiology Community-acquired pneumonia CAP remains a burden in the modern world. Predicting low risk of complications in the outpatient setting To assist clinical risk assessment, different score systems have been recommended by guidelines. Low-risk identification in the outpatient setting. Clinical assessment, supplemented by evaluation of the following criteria: Open in a separate window.

Identifying high-risk patients in need of intensified management in the emergency department Acute pulmonary or extra-pulmonary organ dysfunction due to sepsis or decompensating especially cardiovascular comorbidities determines early prognosis in CAP 41 , 47 — Antibiotic treatment Most major guidelines suggest an empiric treatment stratified according to severity of disease 79 , Antibiotic stewardship Antibiotic stewardship has become an important strategy to fight the antibiotic resistance crisis.

Vaccination Vaccines are available against pneumococci and influenza virus, the most frequent bacterial and viral causes of CAP, respectively. Implications for clinical practice CAP is the infectious disease with the highest number of deaths worldwide. Notes [version 1; referees: The referees who approved this article are: Approaches to estimate the population-based incidence of community acquired pneumonia. New perspectives on community-acquired pneumonia in patients. Results from a nationwide mandatory performance measurement programme in healthcare quality.

Invasive pneumococcal disease in the Netherlands: Syndromes, outcome and potential vaccine benefits. Global, regional, and national age-sex specific all-cause and cause-specific mortality for causes of death, Clinical and economic burden of community-acquired pneumonia among adults in Europe. Pneumococcal infection in adults: Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: How deadly is seasonal influenza-associated pneumonia?

Etiology of community-acquired pneumonia: Mycoplasma pneumoniae and Chlamydia spp. Importance of Legionella pneumophila in the etiology of severe community-acquired pneumonia in Santiago, Chile. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP: Inflammatory response in mixed viral-bacterial community-acquired pneumonia. Prognostic value of procalcitonin in community-acquired pneumonia.

Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB classes. Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia. Clin Chem Lab Med. Assessment of inflammatory markers in patients with community-acquired pneumonia--influence of antimicrobial pre-treatment: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan.

Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: Performance of pro-adrenomedullin for identifying adverse outcomes in community-acquired pneumonia.

Dysnatremia, vasopressin, atrial natriuretic peptide and mortality in patients with community-acquired pneumonia: Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: Serum cortisol predicts death and critical disease independently of CRB score in community-acquired pneumonia: Admission hypoglycemia and increased mortality in patients hospitalized with pneumonia.

CRB predicts death from community-acquired pneumonia. Prediction of in-hospital death from community-acquired pneumonia by varying CRB-age groups. Why do nonsurvivors from community-acquired pneumonia not receive ventilatory support? A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. Defining community acquired pneumonia severity on presentation to hospital: Value of severity scales in predicting mortality from community-acquired pneumonia: Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia.

Systematic review and meta-analysis. Assessment of oxygenation and comorbidities improves outcome prediction in patients with community-acquired pneumonia with a low CRB score. Improvement of CRB as a prognostic tool in adult patients with community-acquired pneumonia. Cardiac complications in patients with community-acquired pneumonia: Acute myocardial infarction versus other cardiovascular events in community-acquired pneumonia. Validity of severity scores in hospitalized patients with nursing home-acquired pneumonia. Physician judgement is a crucial adjunct to pneumonia severity scores in low-risk patients.

Improvement of CRB as a prognostic scoring system in adult patients with bacteraemic pneumococcal pneumonia. Scand J Infect Dis. Community-acquired pneumonia as medical emergency: Incidence, etiology, timing, and risk factors for clinical failure in hospitalized patients with community-acquired pneumonia. Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis.

Severe sepsis in community-acquired pneumonia: The impact of a delay in intensive care unit admission for community-acquired pneumonia. Ewig S, Torres A: Community-acquired pneumonia as an emergency: Management-based risk prediction in community-acquired pneumonia by scores and biomarkers. Severity assessment tools to guide ICU admission in community-acquired pneumonia: An effective strategy should target infection control from several vantage points: All healthcare providers involved in the care of patients requiring mechanical ventilation should be educated about and take an active role in VAP prevention, as multidisciplinary teams, who are well educated about infection control measures, are more successful in VAP prevention 37 , However, the translation of decades of research showing the effectiveness of VAP-prevention strategies into clinical practice has proven to be challenging.

Advances in the prevention, management, and treatment of community-acquired pneumonia

Studies conducted amongst ICU physicians and nurses reveal that only 37 and Care bundles have been proposed to address this gap in implementation of guidelines but studies to date have been inconclusive. Prevention of colonization of the upper airway and gastrointestinal tracts has also been targeted as a means to prevent VAP.

Here we discuss the relative utility of oral decontamination, selective digestive decontamination, and the use of probiotics. Selective digestive tract decontamination: Selective digestive tract decontamination SDD and selective oropharyngeal decontamination SOD are measures in which antibiotic therapy is used to eradicate potentially pathogenic microorganisms in oral, gastric, and intestinal flora. These techniques have been studied for decades and have been the subjects of reviews and meta-analysis showing modest reductions in mortality 41 , In this trial, SDD consisted of four days of intravenous cefotaxime and topical application of tobramycin, colistin and amphotericin B in the oropharynx and stomach.

SOD consisted of oropharyngeal application only of the same antibiotics. While rigorous, a significant limitation to this study was that it did not address the impact of antibiotic resistance. Chlorhexidine is the oral antiseptic most rigorously studied with regards to VAP 45 ; its use has been associated with a reduction in the rates of VAP in recent systematic reviews and meta-analysis 46 , 47 , Unfortunately, the results in non cardiac patients were not as clear and there was no benefit in terms of mortality, number of mechanical ventilation days, or other outcomes.

Iseganan and povidone iodine have also been investigated for oral decontamination. Iseganan is a topical antimicrobial with activity against Gram-positive and gram-negative bacteria, and yeast. However, topical oropharyngial administration failed to show any reduction in VAP when compared to placebo in a multicenter randomized trial Povidone iodine has demonstrated a benefit in VAP rates in patients with severe head trauma, but this has yet to be investigated in other patient populations Probiotics are living microorganisms that confer a health benefit when administered in adequate dosages.

A pilot study found that critically ill patients at high risk for VAP who received Lactobacillus rhamnosus had significantly fewer microbiologically confirmed cases of VAP and significantly fewer episodes of Clostridium difficile -associated diarrhoea compared to patients who did not receive the probiotics However, larger multi-center trials with more liberal inclusion criteria are needed to evaluate the generalizability of this finding. VAP-prevention strategies have recently been grouped together into care bundles with hopes that routine, co-ordinated practice of a select number of interventions in concert will result in better outcomes than any intervention in isolation.

Improvements in VAP rates have been reported by several authors through the use of bundles that include measures such as head of bed elevation, oral cleansing with chlorhexidine, sedation holidays, weaning protocols, and care provider education 54 , 55 , 56 , 57 , 58 , 59 , 60 , However, it has yet to be clearly shown which interventions are most crucial to include in such bundles and precisely how to go about implementation so has to improve clinical outcomes.

There are no well-designed, controlled trials addressing this question to date. VAP continues to be a commonly encountered challenge amongst critically ill patients and carries significant burdens of morbidity, antibiotic utilization and cost. Studies on prevention strategies directed towards the pathophysiologic mechanisms of VAP have shown variable success.

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However, certain measures as described in this review have been shown to improve patient outcomes and, therefore, we recommend care providers consider a multidisciplinary strategy incorporating the following: NPPV when able; sedation and weaning protocols for those patients who do require mechanical ventilation; mechanical ventilation protocols including head of bed elevation and oral care; and removal of subglottic secretions. National Center for Biotechnology Information , U.

Indian J Med Res. Author information Article notes Copyright and License information Disclaimer. Received Jul This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. This article has been cited by other articles in PMC. Abstract Ventilator-associated pneumonia VAP is one of the most commonly encountered hospital-acquired infections in intensive care units and is associated with significant morbidity and high costs of care. Intensive care unit, mechanical ventilation, morbidity, non-invasive positive pressure ventilation, prevention, ventilator-associated pneumonia.

Introduction Ventilator-associated pneumonia VAP is one of the most commonly encountered hospital-acquired infections seen in the critical care setting and can be linked to several adverse clinical outcomes. How VAP happens Patients at risk: Reducing the time at risk As discussed above, any intubated patient is at risk for development of VAP and the longer the duration of mechanical ventilation, the higher the risk. Targeting endotracheal tube colonization and microaspiration The presence of the endotracheal tube contributes to VAP via two mechanisms: Infection control in the ICU The goal of infection control is to prevent cross transmission of pathogens, which has been shown to play an important role in the development of nosocomial infections including VAP.

Reducing colonization Prevention of colonization of the upper airway and gastrointestinal tracts has also been targeted as a means to prevent VAP. Conclusions VAP continues to be a commonly encountered challenge amongst critically ill patients and carries significant burdens of morbidity, antibiotic utilization and cost.

Disclosure statement Dr M. Chastre J, Fagon JY. Attributable mortality of ventilator-associated pneumonia: Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies. Risk factors for ICU-acquired pneumonia. Clinical and economic consequences of ventilator-associated pneumonia: Epidemiology and risk factors for nosocomial pneumonia. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Changing pharyngeal bacterial flora in hospitalized patients: Emergence of gram-negative bacilli.

N Engl J Med. Molecular analysis of oral and respiratory bacterial species associated with ventilator-associated pneumonia. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure.

Noninvasive positive-pressure ventilation and ventilator-associated pneumonia. Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: A randomized, controlled trial.

Introduction and epidemiology

Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: Evidence-based clinical practice guidelines.

Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Nurse-staffing levels and the quality of care in hospitals. A prospective, randomized study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation delayed tracheotomy in critically ill medical patients. Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: A randomized controlled trial.

Tracheotomy tubes with suction above the cuff reduce the rate of ventilator-associated pneumonia in intensive care unit patients. Ann Otol Rhinol Laryngol. Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: Subglottic secretion drainage for preventing ventilator-associated pneumonia: J Trauma Acute Care Surg. Pneumonia in intubated patients: A low-volume, low-pressure tracheal tube cuff reduces pulmonary aspiration.

Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: Supine body position as a risk factor for nosocomial pneumonia in mehcnically ventilated patients: Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: Technologic advances in endotracheal tubes for prevention of ventilator-associated pneumonia.

Endotracheal tubes coated with antiseptics decrease bacterial colonization of the ventilator circuits, lungs and endotracheal tube. A randomized crossover study of silver-coated urinary catheters in hospitalized patients. Silver-coated endotracheal tubes and the incidence of ventilator-associated pneumonia: Cost-effectiveness analysis of a silver-coated endotracheal tube to reduce the incidence of ventilator-associated pneumonia.

Infect Control Hosp Epidemiol. A rapid method of impregnating endotracheal tubes and urinary catheters with gendine: Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Am J Infect Control. Effects of staff training on the care of mechanically ventilated patients: Reducing ventilator-associated pneumonia rates through a staff education programme.

Why do physicians not follow evidence-based guidelines for preventing ventilator-associated pneumonia? A survey based on the opinions of an international panel of intensivists. Nursing adherence with evidence-based guidelines for preventing ventilator-associated pneumonia. Selective decontamination of the digestive tract. Curr Opin Infect Dis. Selective decontamination of the digestive tract reduces bacterial bloodstream infection and mortality in critically ill patients. Systematic review of randomized, controlled trials. Decontamination of the digestive tract and oropharynx in ICU patients.

Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Chlorhexidine decreases the risk of ventilator-associated pneumonia in intensive care unit patients: