Treatment

  • ATS/IDSA guidelines recommend empiric treatment strategies as the standard of care, with antibiotic treatment initiated as soon as possible after diagnosis of CAP.1
  • The choice between treatment options requires a risk–benefit assessment for each individual patient and weighing local epidemiological data against specific risk factors.1
  • Patients should be treated with antibiotics for the shortest effective duration;1 clinicians should de-escalate and/or transition from intravenous (IV) to oral antibiotics, as new clinical and microbiological information becomes available and when clinically appropriate.2
Treatment
General Principles
Current Guidelines
Outpatient Therapy Without Comorbidities
Outpatient Therapy With Comorbidities
Inpatient Therapy for Non-Severe CAP
Research Needed for Inpatient Management
Duration

General Principles for Treating Community-Acquired Pneumonia (CAP)

To determine the need for hospitalization in adults with CAP, the ATS/IDSA guidelines recommend that clinicians use clinical judgement and a validated clinical prediction rule for prognosis, such as the Pneumonia Severity Index (PSI) or CURB-65.1 The PSI prediction rule identifies three distinct risk classes (I, II, and III), representing 69% of CAP patients, who are at sufficiently low risk for death and other adverse medical outcomes that physicians can consider outpatient treatment or an abbreviated course of inpatient care for them.3

Site of Care Decision and Management of CAP4

CAP Treatment

Figure adapted from Prina E, Ranzani OT, Torres A. Lancet. 2015; 386(9998):1097-1108.

Antibiotic treatment should be initiated as soon as possible after diagnosis of CAP and preferably started within the first 4–8 hours.4 In the absence of an identified pathogen, initial empiric antibiotic therapy should be used for possible bacterial infection or co-infection, targeting the most common bacterial causes of CAP while taking into consideration local resistance patterns.1

 

The choice of antibiotic depends also on individual risk factors, comorbidities, and allergies to minimize the potential for treatment-related toxicities and collateral damage including Clostridioides difficile infection (CDI).1,5-7 If microbiological testing identifies a pathogen, antibiotic treatment should be re-evaluated, based on culture and sensitivity results.4

Current CAP Guideline Recommendations for Antibiotic Therapy

The ATS/IDSA guidelines suggest empiric treatment strategies as the standard of care, based on whether the patient is treated as an in- or out-patient, comorbidities, severity of CAP and risk factors for MRSA and Pseudomonas aeruginosa.1

 

Initial Antibiotic Treatment Strategies for Outpatients1

 

Empiric Outpatient Regimens  
 Standard outpatient regimenaStrength of recommendationa
No comorbidities or risk factors for MRSA and Pseudomonas aeruginosaa

Amoxicillin
OR

 

Doxycycline
OR

 

Macrolidec (if local pneumococcal resistance is <25%)

Strong recommendation, moderate quality of
evidence

 

Conditional recommendation, low quality of
evidence

 

Conditional recommendation, moderate quality of
evidence

With comorbiditiesb

Option 1
Amoxicillin/clavulanate OR an
oral cephalosporind
PLUS

 

Macrolidec OR doxycycline

 

 

Option 2
Respiratory fluoroquinolonee

Option 1
Strong recommendation, moderate quality of evidence (Amoxicillin/clavulanate OR cephalosphorind PLUS macrolidec)
 

 

Conditional recommendation, low quality of evidence (Amoxicillin/clavulanate OR cephalosporind PLUS doxycycline)
 

Option 2
Strong recommendation, moderate quality of evidence

aRisk factors include prior respiratory isolation of MRSA or P. aeruginosa or recent hospitalization AND receipt of parenteral antibiotics (in the last 90 days).

bComorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia.

cAzithromycin, or clarithromycin.

dCefpodoxime, or cefuroxime.

eLevofloxacin, moxifloxacin or gemifloxacin.

Treatment Recommendations: Outpatient Therapy Without Comorbidities

  • Treatment of CAP in the outpatient setting is usually empiric as blood and sputum cultures are not routinely recommended, as described in the ATS/IDSA guidelines. An ideal oral treatment regimen would have reliable activity against the major bacterial causes of CAP.1
  • For empiric treatment of outpatients without comorbidities the current CAP guidelines recommend amoxicillin, doxycycline, or a macrolide. Non-macrolide alternatives (amoxicillin, doxycycline) are preferred in regions where rates of macrolide resistance in S. pneumoniae are >25%.1
    • Macrolides: In a departure from the prior CAP guidelines, the panel did not give a strong recommendation for routine use of a macrolide antibiotic as monotherapy for outpatient CAP, even in patients without comorbidities. This was based on studies of macrolide failures in patients with macrolide-resistant S. pneumoniae, in combination with a macrolide resistance rate of >30% among S. pneumoniae isolates in the United States (US), most of which is high-level resistance.1
    • Doxycycline: The recommendation for doxycycline was based on limited clinical trial data, but a broad spectrum of action, including against the most common relevant organisms.1
    • Amoxicillin: The recommendation for amoxicillin was based on several studies that showed efficacy of this regimen. Amoxicillin has a long track record of safety but is not appropriate for patients with a history of a serious penicillin allergy or patients needing coverage for atypical pathogens.1
  • The treatment of CAP in the outpatient setting is complicated by antibiotic resistance in Streptococcus pneumoniae; resistance to one or more common antibiotics.8 Across various regions of the United States, macrolide-resistant S. pneumoniae represents 16–59% of S. pneumoniae strains. Resistance to doxycycline (7–31%) and oral penicillin 
    (16–70%) is also common.9

Treatment Recommendation: Outpatient Therapy With Comorbidities

  • Patients with CAP and comorbidities should receive broader-spectrum treatment. The presence of comorbidities in patients with CAP increases the risk for infection with antibiotic-resistant S. pneumoniae.1
  • H. influenzae, S. aureus and Gram-negative bacilli (e.g., K. pneumoniae) are more common causes of CAP in patients with comorbidities, such as COPD.1
  • Initial empiric treatment strategies for outpatients with comorbidities include:
    • Combination therapy: An oral β-lactam (amoxicillin/clavulanate or an oral cephalosporin) plus a macrolide or doxycycline.1
    • Respiratory fluroquinolone: Monotherapy with levofloxacin, moxifloxacin, or gemifloxacin is also recommended.1
  • The choice between these two options requires a risk–benefit assessment for each individual patient, weighing local epidemiological data against specific risk factors such as patient complexities in regards to antibiotic allergies, comorbidities, and history of C. difficile.1
    • A documented penicillin allergy may limit the use of β-lactam antibiotics including amoxicillin, amoxicillin/clavulanate, and oral cephalosporins.1
    • A documented macrolide allergy or the presence of QT prolongation may limit the use of macrolides.1
    • Known safety concerns with fluoroquinolones (QT prolongation, tendon rupture, peripheral neuropathy and central nervous system reactions), in addition to the risk of C. difficile infection (CDI), pose challenges for a subset of patients. Despite these safety concerns, current guidelines recommend treatment with a respiratory fluoroquinolone due to their reliable activity and the convenience of monotherapy.1
    • Tetracyclines, such as doxycycline, should not be used during pregnancy and in children up to the age of 8 years.10

Research Needed for Outpatient Management 1

The ATS/IDSA guidelines also define areas for further research in the outpatient management of CAP. “There is a need for head-to-head prospective randomized controlled trials of outpatient CAP treatment, comparing clinical outcomes, including treatment failure, need for subsequent visits, hospitalization, time to return to usual activities and adverse events. Furthermore, the prevalence of specific pathogens and their antimicrobial susceptibility patterns in outpatients with pneumonia should be monitored.” The guidelines highlight new antibiotics that have been recently approved for the treatment of CAP while also stating that their role in the outpatient management of CAP still needs to be clearly defined.

Treatment Recommendations: Inpatient Therapy for Non-Severe CAP

  • For the management of inpatients with non-severe CAP the ATS/IDSA guidelines recommend
    • Combination therapy with a β-lactam (ampicillin/sulbactam, cefotaxime, ceftaroline, or ceftriaxone) plus a macrolide (azithromycin or clarithromycin)
      OR
    • Monotherapy with a respiratory fluoroquinolone (levofloxacin, moxifloxacin).1
  • In choosing between these two options, the guidelines encourage clinicians to weigh the risks and benefits of the drugs, particularly in light of individual risk factors, such as a history of CDI and risk factors related to FDA warnings for fluoroquinolones.1
  • The ATS/IDSA guidelines also recommend using doxycycline as an alternative to a macrolide in combination with a β-lactam, as a third option in the presence of documented allergies or contraindications to macrolides or fluoroquinolones or clinical failure on one of those agents. The guidelines acknowledge that there is a need for higher quality evidence in support of the use of combination therapy with a β-lactam and doxycycline.1

Initial Antibiotic Treatment Strategies for Inpatients

Inpatient: Non-Severe CAPa  
Standard inpatient regimenStrength of
recommendation		Prior respiratory
isolation of MRSA		Prior respiratory
isolation of P. aeruginosa

β-lactam +
macrolide

OR

 

β-lactam +
doxycycline

OR

Respiratory
fluoroquinolone

Strong recommendation, high quality of evidence

 

 

Conditional recommendation, low quality of evidence

 

Strong recommendation, high quality of evidence

Add MRSA coverage if locally validated risk factors are present

 

Obtain cultures/ nasal PCR to justify continued therapy

Add coverage for P. aeruginosa if locally validated risk factors are present

 

Obtain cultures to justify continued therapy

 

 

Inpatient: Severe CAPa  
Standard inpatient regimenStrength of
recommendation		Prior respiratory
isolation of MRSA		Prior respiratory
isolation of P. aeruginosa

β-lactam +
macrolide

OR

β-lactam + respiratory
fluoroquinolone

Strong recommendation, moderate quality of evidence

 

 

Strong recommendation, low quality of evidence

Add MRSA coverage if locally validated risk factors are present

 

Obtain cultures/ nasal PCR to justify continued therapy

Add coverage for P.aeruginosa if locally validated risk factors are present

 

Obtain cultures to justify continued therapy

aAs defined by 2007 ATS/IDSA CAP severity criteria guidelines.

Research Needed for Inpatient Management

  • The ATS/IDSA guideline authors define areas for further research in the inpatient management of CAP, stating that “given concerns over increasing drug resistance (macrolides) and safety issues (macrolides, fluoroquinolones), there is a need for research on new therapeutic agents for adults with CAP”.1
  • The need for safer, new alternative antibiotics for CAP treatment is further highlighted by IDSA guidelines on the prevention and management of CDI. This guideline recommends minimizing the frequency and duration of high-risk antibiotics including third-generation cephalosporins (e.g., ceftriaxone) and fluoroquinolones to reduce rates of CDI.7
  • Newer antimicrobial agents are approved for CAP; however, experience with these agents in the outpatient setting was too limited to be recommended in the current IDSA CAP guideline but are recommended in the IDSA inpatient clinical pathway.1,11
Learn about the current treatment challenges in CAP

Duration of Therapy and Transition of Care

The ATS/IDSA guidelines recommend that patients should be treated with antibiotics for the shortest effective duration to minimize the potential for treatment-related adverse effects.1 Treatment should be continued until the patient achieves clinical stability and for no less than a total of 5 days, with clinical stability defined as resolution of vital sign abnormalities, ability to eat and normal mentation. 1,12 Approved prescribing information should be consulted for dosing recommendations on individual agents.

Criteria for Clinical Stability12

  • Temperature ≤37.8 °C
  • Heart rate ≤100 beats/min
  • Respiratory rate ≤24 breaths/min
  • Systolic blood pressure ≥90 mmHg
  • Arterial saturation ≥90% or pO₂ ≥60 mmHb on room air
  • Ability to maintain oral intake
  • Normal mental status

Clinicians should routinely re-evaluate the empiric antibiotic regimen and de-escalate and/or transition from IV to oral antibiotics, as new clinical and microbiological information becomes available and when clinically appropriate.2 Timely transition to oral antibiotics therapy may shorten the length of hospitalization without compromising efficacy or safety.2,5,6

Learn about the symptoms and diagnosis of CAP
Learn more about the treatment challenges in CAP

References

  1. 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;200(7):e45–e67.
  2. Morency-Potvin P, Schwartz DN, Weinstein RA. Antimicrobial Stewardship: How the Microbiology Laboratory Can Right the Ship. Clin Microbiol Rev. 2017;30(1):381–407.
  3. 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;336(4):243–250.
  4. Prina E, Ranzani OT, Torres A. Community-acquired pneumonia. Lancet. 2015;386(9998):1097–1108.
  5. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–77.
  6. Centers for Disease Control and Prevention. The core elements of hospital antibiotic stewardship programs: 2019. Available from: https://www.cdc.gov/antibiotic-use/healthcare/pdfs/hospital-core-elements-H.pdf ( accessed October 04 2020).
  7. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1–e48.
  8. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States 2019. Available from: https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf  (accessed October 09 2020).
  9. Lalitagauri M Deshpande, Michael D Huband, Sarah Charbon, Mariana Castanheira, Rodrigo E Mendes, 2139. High Rates of Non-Susceptibility to Common Oral Antibiotics Among Streptococcus pneumoniae Clinical Isolates from the United States (2019-2021), Open Forum Infectious Diseases, Volume 10, Issue Supplement_2, December 2023, ofad500.1762, https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.1762/7446724 
  10. Tetracycline prescribing information. Available from: https://www.drugs.com/pro/tetracycline.html (accessed January 08 2021).
  11. Infectious Disease Society of America. CAP Clinical Pathway. Available from:  https://www.idsociety.org/globalassets/idsa/practice-guidelines/community-acquired-pneumonia-in-adults/cap-clinical-pathway-final-online.pdf  (Accessed March 21, 2024
  12. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 (Suppl 2):S27–72.
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