Empiric anti-MRSA therapy is an area of opportunity for antimicrobial stewardship in the treatment of CAP.
Pneumonia is the leading infectious cause of mortality in the United States, with timely antibiotic therapy serving as the foundation of treatment.1
Appropriate risk assessment of patients presenting with community-acquired pneumonia (CAP) is imperative to guide empiric therapy. Given increasing resistance in the community, the term health care-associated pneumonia (HCAP) was created.2,3 This term was accompanied by increased use of broad-spectrum agents. When the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) updated guidelines for treating adults with CAP in 2019, HCAP was eliminated in favor of assessment of local and patient-specific risk factors for Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA).4,5
A recent retrospective cohort study of 88,605 patients with CAP hospitalized within the Veterans Health Administration system sought to examine the addition of empiric anti-MRSA therapy to standard therapy.6 This study included patients typically thought to benefit from anti-MRSA therapy, including individuals admitted to intensive care units, patients with a history of MRSA colonization or infection, or those with a MRSA-positive nasal polymerase chain reaction swab or MRSA found in blood or respiratory cultures within 2 days of admission. Using a weighted propensity score analysis, receipt of anti-MRSA therapy plus standard therapy was associated with a significantly increased adjusted risk of death, acute kidney injury (AKI), and infections due to vancomycin-resistant Enterococcus spp, Clostridioides difficile, and gram-negative rods.6
Investigators concluded that the study questions the assumption that the "benefit of more potent antibiotics during the empirical phase exceeds the harms."6
Empiric anti-MRSA therapy continues to represent an area of opportunity for antimicrobial stewardship in the treatment of CAP.
The 2019 guidelines also removed the recommendation to cover anaerobes when aspiration pneumonia is suspected in favor of covering only in the setting of empyema or lung abscess. Aspiration pneumonia is associated with higher mortality than non-aspiration-related CAP, with anaerobes historically thought of as the primary pathogens.7-9 However, recent data show that anaerobes have a much lower incidence than previously thought. Some studies even postulate harm from administering unnecessary anaerobic therapy.7-9 In a recent, secondary analysis of the international, multicenter, point-prevalence study of adults hospitalized with CAP, 193 patients with aspiration CAP (ACAP) were examined.10 Hospitalized patients with ACAP had similar anaerobic flora to patients without aspiration risk factors. Despite this, a large proportion of CAP patients received antianaerobic therapy, regardless of aspiration or risk factors (72.5% of patients with ACAP, 53.4% of CAP patients with risk factors for aspiration, and 49.8% of CAP patients without risk factors). The study investigators support the guidelines in suggesting limiting antianaerobic therapy to patients with empyema or lung abscess.
The coronavirus disease 2019 (COVID-19) pandemic has affected patient care and provided an additional barrier to antibiotic stewardship. Viral respiratory infections from severe acute respiratory syndrome coronavirus 2 often present with similar signs and symptoms of a bacterial pneumonia, raising the concern for a bacterial coinfection.11 However, the frequency of bacterial coinfections remains low in patients with COVID-19. Study results show that patients presenting from the community have a low prevalence of bacterial coinfections ranging up to 4%.11-14 There is a slightly higher prevalence of secondary bacterial infections in hospitalized patients ranging from 7% to 14.3%.11-14 This rate is lower compared with other prominent viral respiratory infections. By comparison, the prevalence of bacterial coinfections in patients with influenza has been reported to be as high as 30%.11,15-17
Although the frequency of bacterial coinfections is low, there is an increased risk of morbidity and mortality when treatment is delayed, thus creating difficulty in appropriate management of CAP. When there is a strong suspicion of a bacterial coinfection, it is appropriate to start empiric CAP therapy.18 Empiric antibiotic spectrum should correlate with patient-specific risk factors for multidrug-resistant organisms, as stated in the ATS/IDSA CAP guidelines.4,11 For patients with COVID-19 bacterial coinfection, 5 to 7 days of antibiotic therapy with clinical improvement is the typical recommended duration.4,11,18,19 However, coverage for bacterial coinfection is unnecessary in most situations, resulting in antibiotic overuse.
Use of diagnostic stewardship tools provides opportunities to optimize patient care. In patients with COVID-19 with a mild severity of illness, a normal procalcitonin level (<0.5 μg/L) correlates with a low likelihood of a bacterial infection and may guide clinicians toward discontinuing antibiotics.18 However, patients critically ill with COVID-19 may have an elevated procalcitonin level (>0.5 μg/L). Procalcitonin levels can be elevated, because of noninfectious causes, including acute respiratory distress, AKI, cardiogenic shock, and end-stage renal disease.18 An additional stewardship tool is MRSA nasal swabs, which can be used for patients with risk factors to reduce unnecessary MRSA coverage. These tools allow for prompt antibiotic cessation or deescalation to reduce exposure to unnecessary antibiotic therapy and decrease potential patient harm.18,20
The January 15, 2021, episode of Breakpoints, a podcast by the Society of Infectious Diseases Pharmacists, has more information on controversies in the treatment of CAP.21
1. Kochanek KD, Murphy SL, Xu J, Arias E. Deaths: final data for 2017. National Vital Statistics Reports. CDC. June 24, 2019. Accessed January 11, 2021. https://www.cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_09_508.pdf
2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416. doi:10.1164/rccm.200405-644ST
3. 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):27-72. doi:10.1086/511159
4. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia: an official clinical practice guidelines of the American Thoracic Society and the Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST
5. Berger A, Edelsberg J, Oster G, Huang X, Weber DJ. Patterns of initial antibiotic therapy for community-acquired pneumonia in US hospitals, 2000 to 2009. Am J Med Sci. 2014;347(5):347-356. doi:10.1097/MAJ.0b013e318294833f
6. Jones BE, Ying J, Stevens V, et al. Empirical anti-MRSA vs standard antibiotic therapy and risk of 30-day mortality in patients hospitalized for pneumonia. JAMA Intern Med. 2020;180(4):552-560. doi: 10.1001/jamainternmed.2019.7495
7. Lanspa MJ, Jones BE, Brown SM, Dean NC. Mortality, morbidity, and disease severity of patients with aspiration pneumonia. J Hosp Med. 2013;8(2):83-90. doi: 10.1002/jhm.1996
8. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest 1999;115(1):178-183. doi:10.1378/chest.115.1.178
9. El-Solh AA, Pietrantoni C, Bhat A, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003;167(12):1650-1654. doi: 10.1164/rccm.200212-1543OC
10. Marin-Corral J, Pascual-Guardia S, Amati F, et al. Aspiration risk factors, microbiology, and empiric antibiotics for patients hospitalized with community-acquired pneumonia. Chest. 2021:159(1):58-72. doi:10.1016/j.chest.2020.06.079
11. Langford BJ, So M, Raybardhan S, et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin Microbiol Infect. 2020;26(12):1622-1629. doi:10.1016/j.cmi.2020.07.016
12. Garcia-Vidal C, Sanjuan G, Moreno-Garcia E, et al; COVID-19 Researchers Group. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021;27(1):83-88. doi:10.1016/j.cmi.2020.07.041
13. Buehrle DJ, Decker BK, Wagener MM, et al. Antibiotic consumption and stewardship at a hospital outside of an early coronavirus disease 2019 epicenter. Antimicrob Agents Chemother. 2020;64(11):e01011-e01020. doi:10.1128/aac.01011-20
14. Rawson TM, Moore LSP, Zhu N, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis. 2020;71(9):2459-2468. doi:10.1093/cid/ciaa530
15. Estenssoro E, Rios FG, Apezteguia C, et al. Pandemic 2009 influenza A in Argentina: a study of 337 patients on mechanical ventilation. Am J Respir Crit Care Med. 2010;182(1):41-48. doi:10.1164/201001-0037OC
16. Martin-Loeches I, Sanchez-Corral A, Diaz E, et al; H1N1 SEMICYUC Working Group. Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus. Chest. 2011;139(3):555-562. doi:10.1378/chest.10-1396
17. Rice TW, Rubinson L, Uyeki TM, et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med. 2012;40(5):1487-1498. doi:10.1097/ccm.0b013e3182416f23
18. Wu CP, Adhi F, Highland K. Recognition and management of respiratory co-infection and secondary bacterial pneumonia in patients with COVID-19. Cleve Clin J Med. 2020;87(11):659-663. doi:10.3949/ccjm.87a.ccc015
19. Spellberg B. The new antibiotic mantra-"shorter is better." JAMA Intern Med. 2016;176(9):1254-1255. doi:10.1001/jamainternmed.2016.3646
20. Parente DM, Cunha CB, Mylonakis E, Timbrook TT. The clinical utility of methicillin-resistant staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: a diagnostic meta-analysis with antimicrobial stewardship implications. Clin Infect Dis. 2018;67(1):1-7. doi:10.1093/cid/ciy024
21. Society of Infectious Disease Pharmacists. Breakpoints. Accessed February 22, 2021. https://sidp.org/Podcasts
The Society of Infectious Diseases Pharmacists (SIDP) is an association of pharmacists and other allied healthcare professionals who are committed to promoting the appropriate use of antimicrobial agents and supporting practice, teaching, and research in infectious diseases. We aim to advance infectious diseases pharmacy and lead antimicrobial stewardship in order to optimize the care of patients. To learn more about SIDP, visit sidp.org.