During the pandemic, consider any patient with cough, fever, or any other suggestive symptoms to have COVID-19 until proven otherwise.
When a diagnosis of CAP is established, the next step is to determine whether or not the patient requires outpatient care, hospitalization, or admission to the intensive care unit (ICU). Microbial investigation as well as antimicrobial therapy will depend upon the site of care. Decisions about the site of care can vary widely between hospitals and practice sites and may be based on considerations other than severity.
Outpatient selection and management
Use a validated clinical prediction rule for prognosis, preferably the Pneumonia Severity Index (PSI) over CURB-65, in addition to clinical judgment, to determine whether the patient should be treated as an outpatient.[91]Smith MD, Fee C, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2021 Jan;77(1):e1-e57.
http://www.ncbi.nlm.nih.gov/pubmed/33349374?tool=bestpractice.com
PSI is preferred over CURB-65, as PSI identifies larger proportions of patients as low risk and has a higher discriminative power in predicting mortality.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[91]Smith MD, Fee C, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2021 Jan;77(1):e1-e57.
http://www.ncbi.nlm.nih.gov/pubmed/33349374?tool=bestpractice.com
Outpatient treatment is recommended for the following patients:[88]Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997 Jan 23;336(4):243-50.
http://www.nejm.org/doi/full/10.1056/NEJM199701233360402#t=article
http://www.ncbi.nlm.nih.gov/pubmed/8995086?tool=bestpractice.com
[89]Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003 May;58(5):377-82.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746657
http://www.ncbi.nlm.nih.gov/pubmed/12728155?tool=bestpractice.com
Be aware of the limitations of severity scores and consider other factors when assessing a patient's suitability for outpatient management (e.g., contraindications to outpatient therapy such as inability to maintain oral intake, history of substance abuse, severe comorbid illnesses, cognitive impairment, and impaired functional status, or availability of outpatient support resources). Do not routinely use biomarkers to increase the performance of clinical decision rules when assessing whether to treat the patient as an outpatient.[91]Smith MD, Fee C, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2021 Jan;77(1):e1-e57.
http://www.ncbi.nlm.nih.gov/pubmed/33349374?tool=bestpractice.com
Advise patients not to smoke, to rest, and to stay well hydrated. Also advise them to report any symptoms of chest pain, severe or increasing shortness of breath, or lethargy.
Reassess patients at 48 hours. Symptoms should improve within this time with appropriate treatment. Consider hospital admission in patients who fail to improve within 48 hours. Approximately 10% of outpatients do not respond to antibiotic therapy and require hospitalization.[99]Niederman M. In the clinic: community-acquired pneumonia. Ann Intern Med. 2009 Oct 6;151(7):ITC4-2-ITC4.
http://www.ncbi.nlm.nih.gov/pubmed/19805767?tool=bestpractice.com
Perform a repeat examination after 10-14 days if the patient's response to therapy is satisfactory. Routine follow-up chest imaging is not recommended if symptoms resolve within 5-7 days.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Outpatients who recover without hospitalization are able to resume normal activities more quickly than those who are hospitalized. Hospitalization increases the risk of infection with antibiotic-resistant or more virulent bacteria.[100]Halm EA, Teirstein AS. Clinical practice: management of community-acquired pneumonia. N Engl J Med. 2002 Dec 19;347(25):2039-45.
http://www.ncbi.nlm.nih.gov/pubmed/12490686?tool=bestpractice.com
Empiric antimicrobial treatment in outpatients
The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines recommend the following oral empiric treatment options for outpatients:[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Healthy patients without comorbidities or without risk factors for drug-resistant pathogens:
Amoxicillin
Doxycycline
A macrolide (e.g., azithromycin or clarithromycin).
Only use a macrolide in areas with pneumococcal resistance to macrolides <25% and when there are contraindications to alternative therapies.
Patients with comorbidities (e.g., chronic heart, lung, liver, or renal disease; diabetes mellitus; alcohol abuse; malignancy; asplenia):
Combination therapy with amoxicillin/clavulanate or a cephalosporin (e.g., cefpodoxime, cefuroxime) plus a macrolide or doxycycline
Monotherapy with a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin).
Broader-spectrum antibiotic regimens are required in patients with comorbidities as many of these patients have risk factors for drug-resistant pathogens (e.g., prior respiratory isolation of methicillin-resistant Staphylococcus aureus [MRSA] or Pseudomonas aeruginosa, recent hospitalization and administration of parenteral antibiotics in the past 90 days), and they are more vulnerable to poor outcomes if the empiric regimen is inadequate.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Choice of antibiotic requires a risk-benefit analysis for each patient, weighing up local epidemiologic data, specific patient risk factors and comorbidities, contraindications, and possible adverse effects (e.g., cardiac arrhythmias with macrolides; vascular disease, musculoskeletal/neurologic adverse effects with fluoroquinolones). Despite the safety concerns associated with fluoroquinolones (see below), the ATS/IDSA panel believes that fluoroquinolone use is justified in adults with CAP and comorbidities who are managed in the outpatient setting.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Risk factors for drug resistance
Risk factors for penicillin-resistant Streptococcus pneumoniae include use of a beta-lactam in the previous 3 to 6 months, hospitalization in the previous 3 months, aspiration, previous episodes of pneumonia in the past year, age <5 or >65 years, and COPD.[101]Furuya EY, Lowy FD. Antimicrobial-resistant bacteria in the community setting. Nat Rev Microbiol. 2006 Jan;4(1):36-45.
http://www.ncbi.nlm.nih.gov/pubmed/16357859?tool=bestpractice.com
[102]Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin Respir Crit Care Med. 2009 Apr;30(2):210-38.
http://www.ncbi.nlm.nih.gov/pubmed/19296420?tool=bestpractice.com
[103]Fenoll A, Granizo JJ, Aguilar L, et al. Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol. 2009 Apr;47(4):1012-20.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668361
http://www.ncbi.nlm.nih.gov/pubmed/19225097?tool=bestpractice.com
[104]Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008 Dec;8(12):785-95.
http://www.ncbi.nlm.nih.gov/pubmed/19022193?tool=bestpractice.com
[105]Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41.
http://www.ncbi.nlm.nih.gov/pubmed/18201146?tool=bestpractice.com
Risk factors for macrolide-resistant S pneumoniae include use of a macrolide in the previous 3 months, age <5 or >65 years, and recent hospitalization.[101]Furuya EY, Lowy FD. Antimicrobial-resistant bacteria in the community setting. Nat Rev Microbiol. 2006 Jan;4(1):36-45.
http://www.ncbi.nlm.nih.gov/pubmed/16357859?tool=bestpractice.com
[102]Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin Respir Crit Care Med. 2009 Apr;30(2):210-38.
http://www.ncbi.nlm.nih.gov/pubmed/19296420?tool=bestpractice.com
[103]Fenoll A, Granizo JJ, Aguilar L, et al. Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol. 2009 Apr;47(4):1012-20.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668361
http://www.ncbi.nlm.nih.gov/pubmed/19225097?tool=bestpractice.com
[104]Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008 Dec;8(12):785-95.
http://www.ncbi.nlm.nih.gov/pubmed/19022193?tool=bestpractice.com
[105]Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41.
http://www.ncbi.nlm.nih.gov/pubmed/18201146?tool=bestpractice.com
Risk factors for fluoroquinolone-resistant S pneumoniae include previous exposure to fluoroquinolones, residence in a nursing home, penicillin resistance, and COPD.[101]Furuya EY, Lowy FD. Antimicrobial-resistant bacteria in the community setting. Nat Rev Microbiol. 2006 Jan;4(1):36-45.
http://www.ncbi.nlm.nih.gov/pubmed/16357859?tool=bestpractice.com
[102]Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin Respir Crit Care Med. 2009 Apr;30(2):210-38.
http://www.ncbi.nlm.nih.gov/pubmed/19296420?tool=bestpractice.com
[103]Fenoll A, Granizo JJ, Aguilar L, et al. Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol. 2009 Apr;47(4):1012-20.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668361
http://www.ncbi.nlm.nih.gov/pubmed/19225097?tool=bestpractice.com
[104]Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008 Dec;8(12):785-95.
http://www.ncbi.nlm.nih.gov/pubmed/19022193?tool=bestpractice.com
[105]Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41.
http://www.ncbi.nlm.nih.gov/pubmed/18201146?tool=bestpractice.com
Hospital admission
Use a validated clinical prediction rule for prognosis, preferably PSI over CURB-65, in addition to clinical judgment to determine whether the patient should be treated as an inpatient. PSI is preferred over CURB-65, as PSI identifies larger proportions of patients as low risk and has a higher discriminative power in predicting mortality.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[91]Smith MD, Fee C, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2021 Jan;77(1):e1-e57.
http://www.ncbi.nlm.nih.gov/pubmed/33349374?tool=bestpractice.com
Hospital admission is recommended in the following situations:[88]Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997 Jan 23;336(4):243-50.
http://www.nejm.org/doi/full/10.1056/NEJM199701233360402#t=article
http://www.ncbi.nlm.nih.gov/pubmed/8995086?tool=bestpractice.com
[89]Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003 May;58(5):377-82.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746657
http://www.ncbi.nlm.nih.gov/pubmed/12728155?tool=bestpractice.com
Admit patients with hypotension requiring vasopressor therapy or respiratory failure requiring mechanical ventilation to the ICU. In patients who do not require vasopressor therapy or mechanical ventilation, use the ATS/IDSA criteria for defining severe CAP (see Diagnostic criteria section) and clinical judgment to guide the need for higher levels of treatment intensity.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[91]Smith MD, Fee C, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2021 Jan;77(1):e1-e57.
http://www.ncbi.nlm.nih.gov/pubmed/33349374?tool=bestpractice.com
Admit patients with severe CAP (defined as one major criterion or three or more minor criteria) to the ICU.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Administer oxygen therapy as necessary. Monitor oxygen saturation and inspired oxygen concentration with the aim of maintaining SaO₂ above 92%. High concentrations of oxygen can safely be given in uncomplicated pneumonia.
[ ]
What are the effects of noninvasive positive pressure ventilation with supplemental oxygen, when compared with Venturi mask oxygen delivery, in adults with pneumonia?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.73/fullShow me the answer Oxygen therapy in patients with COPD that is complicated by ventilatory failure should be guided by repeated arterial blood gas measurements.[106]O'Driscoll BR, Howard LS, Earis J, et al. British Thoracic Society Guideline for oxygen use in adults in healthcare and emergency settings. BMJ Open Respir Res. 2017;4(1):e000170.
https://www.doi.org/10.1136/bmjresp-2016-000170
http://www.ncbi.nlm.nih.gov/pubmed/28883921?tool=bestpractice.com
Patients with respiratory failure, despite appropriate oxygen therapy, require urgent airway management and possible intubation.
Assess patients for volume depletion. Administer intravenous fluids if needed according to local protocols, and give nutritional support in prolonged illness.
Monitor temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration at least twice daily and more frequently in patients with severe pneumonia and in those requiring regular oxygen therapy. Monitor C-reactive protein (CRP) levels regularly as they are a sensitive marker of progress in pneumonia. Repeat chest x-rays in patients who are not progressing satisfactorily. Routine follow-up chest imaging is not recommended if symptoms resolve within 5-7 days.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Empiric antimicrobial treatment in hospitalized patients not in ICU
The ATS/IDSA guidelines recommend the following intravenous empiric treatment options in inpatients with nonsevere CAP without risk factors for MRSA or P aeruginosa:[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Combination therapy with a beta-lactam (e.g., ampicillin/sulbactam, cefotaxime, ceftriaxone, ceftaroline) plus a macrolide (e.g., azithromycin, clarithromycin). Note that clarithromycin is only available as an oral formulation in the US, and so can only be used if the oral route is feasible
Monotherapy with a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin)
Combination therapy with a beta-lactam plus doxycycline in patients who have contraindications to both macrolides and fluoroquinolones.
Additional empiric antibiotic cover is required in patients with risk factors for MRSA or P aeruginosa if locally validated risk factors for either pathogen are present:[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
MRSA: add vancomycin or linezolid
P aeruginosa: add piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, meropenem, or imipenem/cilastatin.
The strongest risk factors for infection with MRSA or P aeruginosa are prior isolation of these organisms from the respiratory tract, and/or recent hospitalization and exposure to parenteral antibiotics in the past 90 days. Based on this, ATS/IDSA recommend the following:[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
If the patient has a prior history of respiratory isolation of MRSA or P aeruginosa: add appropriate antibiotic cover and obtain cultures (or nasal polymerase chain reaction [PCR] for MRSA if available) to guide de-escalation or to confirm the need to continue additional cover.
If the patient has had a recent hospitalization and parenteral antibiotics in the past 90 days and has been locally validated for risk factors for MRSA: obtain cultures and nasal PCR. If PCR or cultures are negative, withhold additional cover. If PCR or cultures are positive, start additional cover.
If the patient has had a recent hospitalization and parenteral antibiotics in the past 90 days and has been locally validated for risk factors for P aeruginosa: obtain cultures but only initiate cover if cultures are positive.
Consider de-escalation to standard antibiotic therapy at 48 hours provided cultures do not reveal a drug-resistant pathogen and the patient is clinically improving.
Additional empiric antibiotic cover is required in patients with risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae. Consult an infectious disease specialist for guidance on an appropriate antibiotic regimen. Additional anaerobic cover for patients with suspected aspiration pneumonia is not recommended unless lung abscess or empyema is suspected.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
The recommendation to cover atypical pathogens in the empiric antibiotic regimen is debated;[107]Naucler P, Strålin K. Routine atypical antibiotic coverage is not necessary in hospitalised patients with non-severe community-acquired pneumonia. Int J Antimicrob Agents. 2016 Aug;48(2):224-5.
http://www.ncbi.nlm.nih.gov/pubmed/27374746?tool=bestpractice.com
[108]Postma DF, van Werkhoven CH, Oosterheert JJ. Community-acquired pneumonia requiring hospitalization: rational decision making and interpretation of guidelines. Curr Opin Pulm Med. 2017 May;23(3):204-10.
http://www.ncbi.nlm.nih.gov/pubmed/28198726?tool=bestpractice.com
[109]File TM Jr, Marrie TJ. Does empiric therapy for atypical pathogens improve outcomes for patients with CAP? Infect Dis Clin North Am. 2013 Mar;27(1):99-114.
http://www.ncbi.nlm.nih.gov/pubmed/23398868?tool=bestpractice.com
however, the recommendation is supported by current data.[110]File TM Jr, Eckburg PB, Talbot GH, et al. Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point. Int J Antimicrob Agents. 2017 Aug;50(2):247-51.
http://www.ncbi.nlm.nih.gov/pubmed/28599867?tool=bestpractice.com
[111]Eljaaly K, Alshehri S, Aljabri A, et al. Clinical failure with and without empiric atypical bacteria coverage in hospitalized adults with community-acquired pneumonia: a systematic review and meta-analysis. BMC Infect Dis. 2017 Jun 2;17(1):385.
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2495-5
http://www.ncbi.nlm.nih.gov/pubmed/28576117?tool=bestpractice.com
[ ]
In hospitalized adults with community-acquired pneumonia, is there randomized controlled trial evidence to support the use of empiric atypical antibiotic coverage over typical antibiotic coverage?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.306/fullShow me the answer
Empiric antimicrobial treatment in ICU patients
The ATS/IDSA guidelines recommend the following intravenous empiric treatment options in inpatients with severe CAP without risk factors for MRSA or P aeruginosa:[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Combination therapy with a beta-lactam (e.g., ampicillin/sulbactam, cefotaxime, ceftriaxone, ceftaroline) plus a macrolide (e.g., azithromycin, clarithromycin); there is stronger evidence for this regimen compared with the regimen below. Although ATS/IDSA recommend clarithromycin in these patients, it is only available as an oral formulation in the US so is unlikely to be useful in this setting
Combination therapy with a beta-lactam plus a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin).
Additional empiric antibiotic cover is required in patients with risk factors for MRSA or P aeruginosa if locally validated risk factors for either pathogen are present:[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
MRSA: add vancomycin or linezolid
P aeruginosa: add piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, meropenem, or imipenem/cilastatin.
Add additional antibiotic cover and obtain cultures (or nasal PCR for MRSA if available) to guide de-escalation of therapy or confirm the need to continue therapy. Consider de-escalation to standard antibiotic therapy at 48 hours provided cultures do not reveal a drug-resistant pathogen and the patient is clinically improving.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Additional empiric antibiotic cover is required in patients with risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae. Consult an infectious disease specialist for guidance on an appropriate antibiotic regimen. Additional anaerobic cover for patients with suspected aspiration pneumonia is not recommended unless lung abscess or empyema is suspected.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Safety of fluoroquinolone antibiotics
Consider safety issues before prescribing fluoroquinolones. The Food and Drug Administration (FDA) has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[112]Food and Drug Administration. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. Jul 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-reinforces-safety-information-about-serious-low-blood-sugar-levels-and-mental-health-side
[113]Food and Drug Administration. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Dec 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics
The European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with fluoroquinolones in 2018. These adverse effects included tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid are at a higher risk of tendon damage. Coadministration of a fluoroquinolone and a corticosteroid should be avoided if possible. This review resulted in prescribing restrictions in Europe, limiting the use of fluoroquinolones to severe infections only.[114]European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. Mar 2019 [internet publication].
https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products
Despite these concerns, ATS/IDSA guidelines recommend fluoroquinolones as a treatment option, including patients with comorbidities who are treated in the outpatient setting, nonsevere CAP in the hospital setting, and severe CAP.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Route of antibiotic therapy
Start empiric antibiotic treatment as soon as possible, and give in the emergency department to avoid delay. Delayed administration has been associated with an increased risk in mortality in patients with severe CAP.[115]Garnacho-Montero J, Barrero-García I, Gómez-Prieto MG, et al. Severe community-acquired pneumonia: current management and future therapeutic alternatives. Expert Rev Anti Infect Ther. 2018 Sep;16(9):667-77.
http://www.ncbi.nlm.nih.gov/pubmed/30118377?tool=bestpractice.com
The initial route for antibiotic therapy depends on severity, the patient’s condition, and the site of care. Guidelines recommend that oral antibiotics be used for outpatients while intravenous treatment is preferred for hospitalized patients. However, intravenous treatment should always be given in patients with severe CAP (at least within the initial hours following admission), with daily evaluation for switching to oral medication as soon as possible. Consider switching the patient to oral therapy when they are hemodynamically stable and improving clinically, can ingest oral medications, and have a normally functioning gastrointestinal tract. Switch to an oral formulation of the same drug or an oral formulation of a drug within the same drug class.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Duration of antibiotic therapy
Treat for a minimum of 5 days. Duration of treatment should be guided by a validated measure of clinical stability (e.g., resolution of vital sign abnormalities, normal cognitive function, ability to eat).[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[116]Uranga A, España PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med. 2016 Sep 1;176(9):1257-65.
http://www.ncbi.nlm.nih.gov/pubmed/27455166?tool=bestpractice.com
[117]Lee RA, Centor RM, Humphrey LL, et al. Appropriate use of short-course antibiotics in common infections: best practice advice from the American College of Physicians. Ann Intern Med. 2021 Jun;174(6):822-7.
https://www.doi.org/10.7326/M20-7355
http://www.ncbi.nlm.nih.gov/pubmed/33819054?tool=bestpractice.com
Consider discontinuing therapy when the patient has been afebrile for 48-72 hours and there are no signs of complications (endocarditis, meningitis). A retrospective cohort study found that two-thirds of hospitalized patients with CAP received excess antibiotic therapy, and each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse effects after discharge.[118]Vaughn VM, Flanders SA, Snyder A, et al. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: a multihospital cohort study. Ann Intern Med. 2019 Aug 6;171(3):153-63.
http://www.ncbi.nlm.nih.gov/pubmed/31284301?tool=bestpractice.com
In patients with bacterial CAP, one systematic review and meta-analysis showed a 5 day course of antibiotics to lead to similar clinical outcomes, with a similar safety profile, to longer courses (≥ 7 days).[119]Lan SH, Lai CC, Chang SP, et al. Five-day antibiotic treatment for community-acquired bacterial pneumonia: a systematic review and meta-analysis of randomized controlled trials. J Glob Antimicrob Resist. 2020 Dec;23:94-9.
https://www.doi.org/10.1016/j.jgar.2020.08.005
http://www.ncbi.nlm.nih.gov/pubmed/32866643?tool=bestpractice.com
One RCT found that in patients with moderately severe CAP who met clinical stability criteria, discontinuing beta-lactam treatment after 3 days was non-inferior to 8 days of treatment, suggesting that 3 days of antibiotics may be sufficient in immunocompetent, non-severely ill patients that are clinically improved at day 3.[120]Dinh A, Ropers J, Duran C, et al. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet. 2021 Mar 27;397(10280):1195-203.
http://www.ncbi.nlm.nih.gov/pubmed/33773631?tool=bestpractice.com
Longer treatment courses are recommended in patients with complications and in cases of pneumonia due to less common pathogens. A treatment course of 7 days is recommended in patients with MRSA or P aeruginosa.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Consult with an infectious diseases expert in these cases.
Microbiologically directed therapy
Consider switching patients to an organism-specific antimicrobial therapy guided by antibiotic sensitivity in patients in whom laboratory tests have revealed a causative organism.
Antiviral treatment in patients with influenza
Add antiviral treatment (e.g., oseltamivir) to antimicrobial treatment in patients with CAP who test positive for influenza in the inpatient setting, independent of duration of illness before diagnosis. Consider antiviral treatment in outpatients who test positive for influenza virus.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Corticosteroid therapy in hospitalized patients
The use of corticosteroids in patients with severe CAP has been a long-debated issue. Current ATS/IDSA guidelines generally recommend against the use of corticosteroids in patients with nonsevere or severe CAP, although acknowledge that they may be considered in patients with refractory septic shock according to Surviving Sepsis Campaign guidelines, and can be used as clinically appropriate for comorbid conditions (e.g., COPD, asthma, autoimmune diseases). This recommendation is based on the fact that there are no data suggesting benefit in patients with nonsevere CAP with respect to mortality or organ failure, and only limited data to support their use in patients with severe CAP.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Meta-analyses of studies of hospitalized adults with CAP found that the use of corticosteroids was associated with reduced need for mechanical ventilation, reduced hospital stay, lower clinical failure rates, fewer complications (including septic shock), decreased CRP levels, and reduced all-cause mortality. However, it appears that the reduction in mortality applies to only patients with severe CAP. In patients with nonsevere disease, adjunctive corticosteroids reduce morbidity, but not mortality.[121]Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163(7):519-28.
http://www.ncbi.nlm.nih.gov/pubmed/26258555?tool=bestpractice.com
[122]Bi J, Yang J, Wang Y, Yao C, et al. Efficacy and safety of adjunctive corticosteroids therapy for severe community-acquired pneumonia in adults: an updated systematic review and meta-analysis. PLoS One. 2016 Nov 15;11(11):e0165942.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165942
http://www.ncbi.nlm.nih.gov/pubmed/27846240?tool=bestpractice.com
[123]Briel M, Spoorenberg SMC, Snijders D, et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Jan 18;66(3):346-54.
http://www.ncbi.nlm.nih.gov/pubmed/29020323?tool=bestpractice.com
[124]Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007720.pub3/abstract;jsessionid=E97F2D0357B4F74EC5C27A9A56E8D2D3.f03t02
http://www.ncbi.nlm.nih.gov/pubmed/29236286?tool=bestpractice.com
[125]Wu WF, Fang Q, He GJ. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: a meta-analysis. Am J Emerg Med. 2018 Feb;36(2):179-84.
http://www.ncbi.nlm.nih.gov/pubmed/28756034?tool=bestpractice.com
[126]Huang J, Guo J, Li H, et al. Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: a systematic review and meta-analysis. Medicine (Baltimore). 2019 Mar;98(13):e14636.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456091
http://www.ncbi.nlm.nih.gov/pubmed/30921179?tool=bestpractice.com
[127]Jiang S, Liu T, Hu Y, et al. Efficacy and safety of glucocorticoids in the treatment of severe community-acquired pneumonia: a meta-analysis. Medicine (Baltimore). 2019 Jun;98(26):e16239.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616855
http://www.ncbi.nlm.nih.gov/pubmed/31261585?tool=bestpractice.com
[ ]
How do corticosteroids compare with placebo in adults with pneumonia?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1978/fullShow me the answer
Patients treated with corticosteroids have an increased risk for hyperglycemia.[123]Briel M, Spoorenberg SMC, Snijders D, et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Jan 18;66(3):346-54.
http://www.ncbi.nlm.nih.gov/pubmed/29020323?tool=bestpractice.com
[124]Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007720.pub3/abstract;jsessionid=E97F2D0357B4F74EC5C27A9A56E8D2D3.f03t02
http://www.ncbi.nlm.nih.gov/pubmed/29236286?tool=bestpractice.com
[ ]
How do corticosteroids compare with placebo in adults with pneumonia?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1978/fullShow me the answer Other adverse effects include super infection and upper gastrointestinal bleeding.
Nonresponding pneumonia
Nonresponding CAP describes the clinical situation where there is an inadequate response after antibiotic treatment as assessed at day 3 to day 5. The causes of nonresponding pneumonia are classified as infectious, noninfectious, and of unknown origin. Multicenter studies have shown that between 6% and 24% of CAP cases will not respond to antibiotic treatment, and in cases of severe pneumonia, this rate can reach 31%.[19]Torres A, Barberán J, Falguera M, et al. Multidisciplinary guidelines for the management of community-acquired pneumonia [in Spanish]. Med Clin (Barc). 2013 Mar 2;140(5):223.e1-223.e19.
http://www.ncbi.nlm.nih.gov/pubmed/23276610?tool=bestpractice.com
[128]Aliberti S, Blasi F. Clinical stability versus clinical failure in patients with community-acquired pneumonia. Semin Respir Crit Care Med. 2012 Jun;33(3):284-91.
http://www.ncbi.nlm.nih.gov/pubmed/22718214?tool=bestpractice.com
One study has described two different clinical patterns of nonresponding pneumonia:[129]Menendez R, Torres A. Treatment failure in community-acquired pneumonia. Chest. 2007 Oct;132(4):1348-55.
http://www.ncbi.nlm.nih.gov/pubmed/17934120?tool=bestpractice.com
Progressive pneumonia that follows a course of clinical deterioration with respiratory failure or septic shock
The situation where clinical stability is not achieved and no other patient characteristics are responsible.
Biomarkers such as CRP and procalcitonin (PCT) have been found to be useful for predicting inadequate host response. High levels of CRP or PCT at initial presentation represent a risk factor for inadequate response,[80]Menéndez R, Cavalcanti M, Reyes S, et al. Markers of treatment failure in hospitalised community acquired pneumonia. Thorax. 2008 May;63(5):447-52.
http://thorax.bmj.com/content/63/5/447.long
http://www.ncbi.nlm.nih.gov/pubmed/18245147?tool=bestpractice.com
whereas low levels are protective. The use of procalcitonin to guide initiation and duration of antibiotic treatment results in a lower risk of mortality, lower antibiotic consumption, and lower risk for side effects.[130]Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017 Oct 12;(10):CD007498.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007498.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/29025194?tool=bestpractice.com
[131]Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018 Jan;18(1):95-107.
http://www.ncbi.nlm.nih.gov/pubmed/29037960?tool=bestpractice.com
However, one review found no difference in short-term mortality in critically ill patients specifically,[132]Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med. 2018 May;46(5):684-90.
http://www.ncbi.nlm.nih.gov/pubmed/29293146?tool=bestpractice.com
while another study found that PCT-guided therapy did not result in decreased use of antibiotics.[133]Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018 Jul 19;379(3):236-49.
https://escholarship.org/uc/item/9bd679z6
http://www.ncbi.nlm.nih.gov/pubmed/29781385?tool=bestpractice.com
The American College of Emergency Physicians does not recommend the routine use of biomarkers when deciding on administration of antibiotics in the emergency department.[91]Smith MD, Fee C, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2021 Jan;77(1):e1-e57.
http://www.ncbi.nlm.nih.gov/pubmed/33349374?tool=bestpractice.com
Consensus algorithms that include PCT cut-off points for deciding when to initiate or discontinue antibiotics may help to facilitate safe and efficient implementation of PCT-guided therapy.[134]Schuetz P, Bolliger R, Merker M, et al. Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials. Expert Rev Anti Infect Ther. 2018 Jul;16(7):555-64.
http://www.ncbi.nlm.nih.gov/pubmed/29969320?tool=bestpractice.com
The first response to nonresponse or deterioration should be to re-evaluate the initial microbiology results.[18]Metlay JP, Waterer GW, Long AC, et al. 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. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Results of cultures and sensitivity testing that were not available at presentation may now make the cause of clinical failure obvious. In addition, a further history of any risk factors for infection with unusual microorganisms, including viruses and fungi, should be sought if this has not already been done. Further diagnostic testing may also be warranted.
Specifically, if the patient with nonresponding pneumonia lives in or has recently traveled to regions either endemic for blastomycosis or coccidioidomycosis or where there has been a recent outbreak of these infections, enzyme immunoassay-based diagnostic testing for these fungal infections should be considered.[135]Centers for Disease Control and Prevention. Valley fever: testing algorithm for coccidioidomycosis. May 2024 [internet publication].
https://www.cdc.gov/valley-fever/hcp/testing-algorithm
Similarly, if a patient with nonresponding CAP lives in or has traveled to regions endemic for histoplasmosis, or has had significant exposure to bat or bird droppings, or x-ray shows new nodules or lymphadenopathy, enzyme immunoassay based diagnostic tests for detection of histoplasmosis infection should be considered.[136]Centers for Disease Control and Prevention. Testing algorithm for histoplasmosis. May 2024 [internet publication].
https://www.cdc.gov/histoplasmosis/hcp/algorithm
For more information on areas that would raise suspicion of these infections please refer to CDC guidance.[135]Centers for Disease Control and Prevention. Valley fever: testing algorithm for coccidioidomycosis. May 2024 [internet publication].
https://www.cdc.gov/valley-fever/hcp/testing-algorithm
[136]Centers for Disease Control and Prevention. Testing algorithm for histoplasmosis. May 2024 [internet publication].
https://www.cdc.gov/histoplasmosis/hcp/algorithm
Bundled interventions
While efficacy of individual interventions may demonstrate efficacy in clinical trials, a bundled intervention, which included adjunct corticosteroids, as well as early mobilization, nutrition screening, and early switch to oral antibiotics, was not found to have a significant effect on hospital stay length, mortality, or complications, but was found to increase the risk of gastrointestinal bleeding when compared with normal care. Therefore, the efficacy of individual interventions may not translate into effectiveness when these interventions are bundled and given in combination, and may even result in net harm.[137]Lloyd M, Karahalios A, Janus E, et al. Effectiveness of a bundled intervention including adjunctive corticosteroids on outcomes of hospitalized patients with community-acquired pneumonia: a stepped-wedge randomized clinical trial. JAMA Intern Med. 2019;179(8):1052-60.
http://www.ncbi.nlm.nih.gov/pubmed/31282921?tool=bestpractice.com