By Samuel Nadler, MD, PhD
Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle; Clinical Instructor, University of Washington, Seattle
Dr. Nadler reports no financial relationships relevant to this field of study.
Community-acquired pneumonia (CAP) is a common cause for hospital admission. Many patients will require intensive care unit (ICU) admission for mechanical ventilation and vasopressor support. A review of hospital- and ventilator-acquired pneumonia was previously published in Critical Care Alert.1 This article serves to summarize new updates in the definition, prognosis, and treatment, specifically of bacterial, severe community-acquired pneumonia (SCAP).
PROGNOSIS AND RISK STRATIFICATION OF SEVERE COMMUNITY-ACQUIRED PNEUMONIA
Many definitions of SCAP have been proposed. The most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines reiterated previously published criteria from 2007.2 These include the presence of one major or at least three minor criteria due to pulmonary infection. (See Table 1.) The two major criteria include septic shock with the need for vasopressor support and respiratory failure necessitating mechanical ventilation. There are nine minor criteria, including: respiratory rate (RR) ≥ 30 breaths/minute, PaO2/FiO2 ≤ 250, multi-lobar infiltrates on imaging, encephalopathy/confusion, uremia (blood urea nitrogen ≥ 20 mg/dL), white blood cell count < 4,000 cells/µL, platelet count < 100,000/µL, hypothermia (core temperature < 36°C), and hypotension requiring fluid resuscitation.
Septic shock requiring vasopressors and respiratory failure requiring mechanical ventilation clearly suggest severe CAP. Combinations of the minor criteria also are predictive of the need for mechanical ventilation or vasopressor support (MV/VS). A meta-analysis of 5,696 and 6,240 patients evaluated the predictive value of minor criteria for mortality and ICU admission, respectively.3 The ATS/IDSA minor criteria predicted 30-day mortality with a receiver operating characteristic (area under the curve, or AUC) of 0.78, ICU admission AUC of 0.85, and requirement for MV/VS AUC of 0.85. Simplified criteria omitting leukopenia, thrombocytopenia, and hypothermia were similarly predictive, with AUCs of 0.77, 0.85, and 0.85 for 30-day mortality, MV/VS, and ICU admission, respectively, when at least two minor criteria were present.
Other systems to predict pneumonia severity exist. They include the pneumonia severity index (PSI), CURB-65 score, SMART-COP criteria, and SCAP score, among others. A prospective study of 1,062 patients comparing these scoring systems showed that for MV/VS, the ATS/IDSA criteria were most predictive, with a positive likelihood ratio (PLR) of 4.3, negative likelihood ratio (NLR) of 0.26, sensitivity of 78.6%, specificity of 81.9%, and AUC of 0.85.4 Similarly, to predict ICU admission, the ATS/IDSA fared best with a PLR of 4.2, NLR of 0.3, sensitivity of 75.3%, specificity of 82.2%, and AUC of 0.85. For the prediction of 30-day mortality, the ATS/IDSA criteria again outperformed other scoring systems: PLR 2.9, NLR 0.52, sensitivity 58.3%, specificity 79.6%, and AUC 0.78. Thus, the ATS/IDSA criteria not only define severe CAP but are predictive of ICU admission, the need for MV/VS, and 30-day mortality. Other scoring systems are more useful for triaging inpatient vs. outpatient management.
There is ongoing interest in biomarkers for prognostication of patients with pneumonia. Two of the most widespread are procalcitonin (PCT) and C-reactive peptide (CRP). Procalcitonin is a 116 amino-acid peptide produced by the liver, thyroid, and lung K cells as an acute phase reactant that is cleaved into calcitonin, katacalcin, and an N-terminal fragment.5 Although studies have shown that PCT-guided algorithms may reduce antibiotic exposure, IDSA/ATS guidelines strongly recommend against using PCT to diagnose SCAP or make decisions regarding initiation of antibiotics.2 The rationale for this stems from difficulties establishing a clear cut-off to initiate antibiotics, highly variable sensitivities, and concern for delays in elevation of PCT leading to delays in antibiotic administration. As described earlier, ATS/IDSA clinical criteria alone performed well to predict the need for ICU admission. In contrast, PCT-guided protocols may have a role in guiding antibiotic therapy, as will be discussed later.
Other biomarkers have been studied for prognostication of patients with SCAP. CRP is a pentameric protein produced by the liver in response to infection or inflammation.2 Although not discussed in the 2019 recommendations, previous IDSA/ATS guidelines recommended against its use for diagnosis and in the decision to initiate antibiotics.6 This was because of several studies showing similar CRP levels in patients with and without ventilator-associated pneumonia (VAP), since both infection and inflammation led to elevated levels. Overall, this was a weak recommendation based on low-quality evidence. Other biomarkers include soluble triggering receptor expressed on myeloid cells (sTREM), pro-adrenomedullin (Pro-ADM), lactate, and neutrophil to lymphocyte ratio (NTLR). Although small studies have shown promise, these are not widely available and have not found their way into widespread use.
ANTIBIOTIC THERAPY FOR SEVERE COMMUNITY-ACQUIRED PNEUMONIA
Antibiotic therapy is foundational for the treatment of SCAP. Updated ATS/IDSA guidelines for antibiotic therapy are summarized in Table 2. Although many studies were observational or retrospective, two meta-analyses did favor macrolide-containing regimens.7,8 These guidelines also suggested not routinely adding anaerobic coverage for suspected aspiration pneumonia since anaerobic coverage seemed to have led to a higher incidence of Clostridioides difficile infection without improved outcomes from pneumonia. Additionally, the concept of hospital-acquired pneumonia (HCAP) was removed. The designation of HCAP led to use of overly broad antibiotic regimens and an increased concern for the development of drug-resistant organisms. The updated guidelines suggest identifying specific risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa to guide treatment. Specifically, they recommend using antibiotics directed at these organisms if there is a history of prior respiratory isolation or if there are local data indicating a high prevalence of these organisms. Furthermore, if these organisms are not detected within 48 hours, recommendations are to de-escalate the broad antibiotic therapies. The duration of therapy was suggested to be guided by evidence of clinical stability but no less than five days, unless MRSA or P. aeruginosa is present, in which case a seven-day course was recommended.
Empiric antibiotic choices are designed to cover the most common bacterial pathogens. A prospective observational study of 2,149 adults ages 65 years and older diagnosed with pneumonia showed that Streptococcus pneumoniae remains the most common identified pathogen (41.5%), although a microbial cause was only identified in 39.8% of patients.9 Mixed infections were seen in 13.8%. After pneumococcus, the most common pathogens included Legionella pneumophila (7.4%), Haemophilus influenzae (6.4%), and P. aeruginosa (4.7%). A more recent study of 664 patients specifically diagnosed with SCAP showed similar results.10 A pathogen was identified in 50.6% of cases, with S. pneumoniae (55.4%), L. pneumophila (7.4%), P. aeruginosa (7.4%), and Staphylococcus aureus (5.9%) being most common. Although randomized trials have not shown a benefit for routine testing for Pneumococcus and Legionella urinary antigens, observational studies have suggested reduced mortality; thus, ATS/IDSA guidelines recommend this testing for patients admitted with SCAP (conditional recommendation, low quality of evidence).2
Procalcitonin-guided cessation of antibiotics has shown promise. Townsend et al demonstrated reduced exposure to antibiotics from seven to six days using such an algorithm.11 However, the ProACT trial failed to demonstrate a reduction in antibiotic duration in a more general CAP population.12 A recent meta-analysis including 2,447 ICU patients with respiratory infections concluded that procalcitonin-guided cessation of antibiotics reduced exposure (9.5 vs. 8.1 days, 95% confidence interval [CI], -1.99 to -0.88; P < 0.0001) without increased mortality.13 It is notable that these antibiotic exposure durations exceed recommended duration. Thus, following ATS/IDSA guidelines for antibiotic duration may be as effective as biomarker-driven protocols.
STEROIDS FOR SEVERE COMMUNITY-ACQUIRED PNEUMONIA
The use of corticosteroids for SCAP remains controversial. ATS/IDSA guidelines suggest not routinely using steroids in adults with SCAP, although this is a conditional recommendation with moderate quality of evidence. A 2017 Cochrane review of corticosteroids for pneumonia noted a reduction in mortality for the subset of adults with SCAP treated with steroids (relative risk [RR] 0.58; 95% CI, 0.4-0.84), with moderate quality of evidence for a number needed to treat of 18.14 Two subsequent meta-analyses focused specifically on SCAP similarly concluded that adjunctive steroids for SCAP had benefit.15-16 Wu et al reviewed 10 studies of varying quality containing 729 patients.16 They concluded that the administration of corticosteroids reduced in-hospital mortality (RR 0.49; 95% CI, 0.29-0.85) and decreased hospital length of stay (LOS) (-4.21 days; 95% CI, -6.61 to -1.81), although there was no difference in mechanical ventilation duration. Huang et al published a systematic review and meta-analysis of similar but non-overlapping studies that found steroids led to decreased mortality (odds ratio [OR] 0.63; 95% CI, 0.42-0.95), decreased LOS (-2.52 days; 95% CI, -4.88 to -0.15), as well as a trend toward decreased mechanical ventilation.15 In that analysis, corticosteroids did not lead to increased hyperglycemia, gastrointestinal hemorrhage, or adverse cardiac events. The ATS/IDSA summary of this evidence cited heterogeneity in studies with differing definitions of SCAP, steroid dosing regimens, and lack of large randomized controlled studies in making the recommendation against steroids, but also noted there were no studies indicating excess mortality. There are data about hyperglycemia, increased complications, and re-hospitalization rates that further prevented the ATS/IDSA from recommending steroids, although these data vary as well. With additional investigations, the recommendations regarding steroids for SCAP may change.
Although viral pneumonia due to COVID-19 has received much attention recently, bacterial infections leading to SCAP remain a common reason for ICU admission. New guidelines regarding the definition, diagnosis, and treatment of SCAP have been published. Clinical factors seem most predictive of the need for ICU admission, although the development of predictive biomarkers is ongoing. Antibiotic recommendations have been narrowed to minimize unnecessary coverage leading to antibiotic resistance and complications. The concept of healthcare-associated pneumonia has been removed from the guidelines. Finally, steroid therapy for SCAP remains controversial and likely an area of further research.
- Thompson W. Ventilator-associated pneumonia and hospital-acquired pneumonia: Prevention and treatment. Critical Care Alert 2019;27:9-13.
- Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. Am J Respir Crit Care Med 2019;200:e45-e67.
- Salih W, Schembri S, Chalmers JD. Simplification of the IDSA/ATS criteria for severe CAP using meta-analysis and oberservational data. Eur Respir 2014;43:842-851.
- Chalmers JD, Taylor JK, Mandal P, et al. Validation of the Infectious Diseases Society of America/American Thoracic Society minor criteria for intensive care unit admission in community-acquired pneumonia patients without major criteria or contraindications to intensive care unit care. Clin Infect Dis 2011;53:503-511.
- Sungurlu S, Balk RA. The role of biomarkers in the diagnosis and management of pneumonia. Clin Chest Med 2018;39:691-701.
- Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin infect Dis 2016;63:e61-e111.
- Sligl WI, Asadi L, Eurich DT, et al. Macrolides and mortality in critically ill patients with community-acquired pneumonia: A systematic review and meta-analysis. Crit Care Med 2014;42:420-432.
- Vardakas KZ, Trigkidis KK, Falagas ME. Fluoroquinolones or macrolides in combination with b-lactams in adult patients hospitalized with community acquired pneumonia: A systematic review and meta-analysis. Clin Microbiol Infect 2017;23:234-241.
- Cilloniz C, Polverino E, Ewig S, et al. Impact of age and comorbidity on cause and outcome in community-acquired pneumonia. Chest 2013;144:999-1007.
- Ferrer M, Travierso C, Cilloniz C, et al. Severe community-acquired pneumonia: Characteristics and prognostic factors in ventilated and non-ventilated patients. PLoS One 2018;13:e0191721.
- Townsend J, Adams V, Galiatsatos P, et al. Procalcitonin-guided antibiotic therapy reduces antibiotic use for lower respiratory tract infections in a United States medical center: Results of a clinical trial. Open Forum Infect Dis 2018;5:1-9.
- Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med 2018;379:236-249.
- 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;18:95-107.
- Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev 2017;12:CD007720.
- 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 2019;98:e14636.
- Wu WF, Fang Q, He GJ. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med 2018;36:179-184.