Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

Anaerobes have been considered a major cause of aspiration pneumonia (AP) based on studies published in 1970’s (1-3). More recent data, however, suggest that anaerobes no longer play an important role in most cases of AP (4-7) and routine inclusion of specific anti-anaerobic drugs in their treatment is no longer necessary.

 
An important reason for anaerobes not playing an important role in AP in the current era is the change in the demographics of patients who may be affected. Patients reported in older studies often suffered from alcohol use disorder, drug ingestion, seizure disorders and acute cerebrovascular accident. In contrast, more recent data show that AP often occurs in nursing home residents, the elderly with cognitive impairment, and those with dysphagia, gastrointestinal dysmotility or tube feeding (8,9).

 
In addition, many cases of AP reported in older studies involved delay of 4 or more days before seeking medical attention and, not surprisingly, often presented with lung abscess, necrotizing pneumonia, empyema, or putrid sputum, features that are relatively rare in the current era.

 
Further supporting the diminishing role of anaerobes in AP, are recent microbiological studies of the respiratory tract in AP revealing the infrequent isolation of anaerobes and, even when isolated, often coexisting with aerobic bacteria. The latter observation is important because, due to the alteration in the redox potential (9,10), treatment of aerobic bacteria alone may lead to less oxygenation consumption and less favorable environment for survival of anaerobes in the respiratory tract.

 
We should also always consider the potential adverse effects of unnecessary antibiotics with anaerobic activity in our frequently debilitated patients, including gastrointestinal dysbiosis (associated with Clostridiodes difficile infections and overgrowth of antibiotic-resistant pathogens such as vancomycin-resistant enterococci (VRE), hypersensitivity reactions, drug interactions, and central nervous system toxicity (11,12).
Thus, the weight of the evidence does not justify routine anaerobic coverage of AP in today’s patients.

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References
1. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Am J Med. 1974;56(2):202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
2. Bartlett JG, Finegold SM. Anaerobic pleuropulmonary infections. Medicine (Baltimore). 1972;51(6):413-50. https://www.ncbi.nlm.nih.gov/pubmed/4564416
3. Bartlett JG, Gorbach SL. The triple threat of aspiration pneumonia. Chest. 1975;68(4):560-6. https://www.ncbi.nlm.nih.gov/pubmed/1175415
4. Finegold SM. Aspiration pneumonia. Rev Infect Dis. 1991;13 Suppl 9:S737-42. https://www.ncbi.nlm.nih.gov/pubmed/1925318
5. Bartlett JG. How important are anaerobic bacteria in aspiration pneumonia: when should they be treated and what is optimal therapy. Infect Dis Clin North Am. 2013;27(1):149-55. https://www.ncbi.nlm.nih.gov/pubmed/23398871
6. El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003;167(12):1650-4. https://www.ncbi.nlm.nih.gov/pubmed/12689848
7. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999;115(1):178-83. https://www.ncbi.nlm.nih.gov/pubmed/9925081
8. Bowerman TJ, Zhang J, Waite LM. Antibacterial treatment of aspiration pneumonia in older people: a systematic review. Clin Interv Aging. 2018;13:2201-13. https://www.ncbi.nlm.nih.gov/pubmed/30464429
9. Mandell LA, Niederman MS. Aspiration Pneumonia. N Engl J Med. 2019 Feb 14;380(7):651-663. doi: 10.1056/NEJMra1714562. https://www.ncbi.nlm.nih.gov/pubmed/30763196
10. Walden, W. C., & Hentges, D. J. (1975). Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria. Applied microbiology, 30(5), 781–785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC187272/
11. Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1(2):101-14. https://www.ncbi.nlm.nih.gov/pubmed/11871461
12. Bhalla A, Pultz NJ, Ray AJ, Hoyen CK, Eckstein EC, Donskey CJ. Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol. 2003;24(9):644-9. https://www.ncbi.nlm.nih.gov/pubmed/14510245

 

Contributed by Amar Vedamurthy, MD, MPH, Mass General Hospital, Boston, MA

Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)?

Since the primary reason for obtaining a sputum culture in a patient with pneumonia is to sample the lower respiratory tract, you should first verify that the sputum was “adequate” by reviewing the gram stain. Absence of neutrophils (unless the patient is neutropenic) with or without epithelial cells on gram stain of sputum suggests that it may not be an adequate sample (ie, likely saliva)1, and therefore growth of normal respiratory flora (NRF) should not be surprising in this setting.  

Other potential explanations for NRF on sputum culture in patients with CAP include:2-5

  • Delay in sputum processing with possible overgrowth of oropharyngeal flora.
  • Pneumonia caused by pathogens that do not grow on standard sputum culture media (eg, atypical organisms, viruses, anaerobes).
  • Pneumonia caused by potential pathogens such as as Streptococcus mitis and Streptococcus anginosus group that may be part of the NRF.
  • Initiation of antibiotics prior to cultures (eg, in pneumococcal pneumonia).

Of note, since 2010, several studies have shown that over 50% of patients with CAP do not have an identifiable cause.3 So, growing NRF from sputum of patients with CAP appears to be common.

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References

  1. Wong LK, Barry AL, Horgan SM. Comparison of six different criteria for judging the acceptability of sputum specimens. J Clin Microbiol 1982;16:627-631. https://www.ncbi.nlm.nih.gov/pubmed/7153311
  2. Donowitz GR. Acute pneumonia. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (2010). Churchill Livingstone, pp 891-916.
  3. Musher DM, Abers MS, Bartlett JG. Evolving understanding of the causes of pneumonia in adults, with special attention to the role of pneumococcus. Clin Infect Dis 2017;65: 1736-44. https://www.ncbi.nlm.nih.gov/pubmed/29028977
  4. Abers MS, Musher DM. The yield of sputum culture in bacteremic pneumococcal pneumonia after initiation of antibiotics. Clin Infect Dis 2014; 58:1782. https://www.ncbi.nlm.nih.gov/pubmed/24604901
  5. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Bartlett JG, Gorbach SL, Finegold SM. Am J Med 1974;56:202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)?