How often is Covid-19 in hospitalized patients complicated by bacterial infection?

Despite frequent use of empiric antibiotics in hospitalized patients with Covid-19,current data suggests a low rate of documented bacterial co-infection (BCI) in such patients. In fact, the overall reported rate of BCI in hospitalized patients with Covid-19 is generally no greater than 10%.1-3   It’s quite likely that most patients with Covid-19 and chest radiograph changes solely have a coronavirus (SARS-CoV-2) lung infection,4 particularly early in the course of the disease.  

A meta-analysis involving 30 studies (primarily retrospective) found that overall 7% of hospitalized Covid-19 patients had a laboratory-confirmed BCI with higher proportion among ICU patients (14%).Mycoplasma pneumoniae was the most common (42% of BCIs), followed by Pseudomonas aeruginosa and H. influenzae.  Notably, diagnosis of M. pneumoniae infection was based on antibody testing for IgM, which has been associated with false-positive results. Other caveats include lack of a uniform definition of respiratory tract infection among studies and potential impact of concurrent or prior antibiotic therapy on the yield of bacteriologic cultures. 5,6

A low prevalence of BCI was also found in a UK study involving 836 hospitalized Covid-19 patients: 3.2% for early BCI (0-5 days after admission) and 6.1% throughout hospitalization, including hospital-acquired infections.Staphylococcus aureus was the most common respiratory isolate among community-acquired cases, while Pseudomonas spp. was the predominant healthcare associated respiratory isolate.  Similarly, S. aureus. and Streptococcus pneumoniae were the most commonly isolated organisms from blind bronchoalveolar lavage of critically ill patients with Covid-19 during their first 5 days of admission, while gram-negative bacilli became dominant later during the hospitalization.8

The discordance between high rates of antibiotic treatment and confirmed bacterial co-infection in Covid-19 patients is likely a reflection of the difficulty in distinguishing Covid-19 pneumonia from bacterial pneumonia based on clinical or radiographic findings alone.

We need better tests to help distinguish bacterial vs Covid-19 pneumonia. Some have suggested using a low serum procalcitonin to help guide the withholding of or early discontinuation of antibiotics, especially in less severe Covid-19 cases. Formal studies of the accuracy of procalcitonin in Covid-19 are needed to test this hypothesis, given its suboptimal sensitivity in bacterial community-acquired pneumonia. 

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Reference

  1. Stevens RW, Jensen K, O’Horo JC, et al. Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care. Infect Control Hosp Epidemiology 2020. https://reference.medscape.com/medline/abstract/32703323
  2. Lansbury L, Lim B, Baskaran V, et al. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect 2020;81:266-75. https://pubmed.ncbi.nlm.nih.gov/32473235/
  3. Rawson TM, Moore LSP, Zhu N. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020 (Manuscrpit published online ahead of print 2 June ). Doi:10.1093/cid/ciaa530.https://pubmed.ncbi.nlm.nih.gov/32358954/
  4. Metlay JP, Waterer GW. Treatment of community-acquired pneumonia during the coronavirus 2019 (COVID-19) pandemic. Ann Intern Med 2020; 173:304-305. https://pubmed.ncbi.nlm.nih.gov/32379883/
  5. Chang CY, Chan KG. Underestimation of co-infections in COVID-19 due to non-discriminatory use of antibiotics. J Infect 2020;81:e29-30. https://pubmed.ncbi.nlm.nih.gov/32628960/
  6. Rawson TM, Moore LSP, Zhu N, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Reply letter. Clin Infect Dis 2020. https://academic.oup.com/cid/advance-
  7. Hughes S, Troise O, Donaldson H, et al. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clin Microbiol Infect 2020. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30369-4/fulltext
  8. Dudoignon E, Camelena F, Deniau B, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Clin Infect Dis 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337703/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How often is Covid-19 in hospitalized patients complicated by bacterial infection?

When should I consider a switch to oral antibiotics and discharge from hospital in my recently admitted elderly patient with community-acquired pneumonia (CAP)?

A frequently used validated set of clinical stability criteria in patients with CAP and supported by the 2019 ATS/IDSA CAP guidelines consists of a temperature ≤37.8 ᵒC (100.0 ᵒF) AND no more than 1 CAP-related sign of clinical instability as listed below: 1-3

  • Heart rate >100/min
  • Systolic blood pressure <90 mm Hg
  • Respiration rate >24 breaths/min
  • Arterial oxygen saturation <90% or Pa02<60 mm Hg (room air)

Using these criteria, the risk of clinical deterioration serious enough to necessitate transfer to an intensive care unit may be 1% or less, 1 while failure to achieve clinical stability within 5 days is associated with higher mortality and worse clinical outcome. 2 The median time to clinical stability (as defined) for CAP treatment is 3 days.1  

A 2016 randomized-controlled trial involving patients hospitalized with CAP found that implementation of above clinical stability criteria was associated with safe discontinuation of antibiotics after a minimum of 5 days of appropriate therapy.

Potential limitations of the above study include heavy use of quinolones (80%), underrepresentation of patients with severe CAP (Pneumonia Risk Index, PSI, V), and exclusion of nursing home residents, immunosuppressed patients, those with chest tube, or infection caused by less common organisms, such as Staphylococcus aureus or Pseudomonas aeruginosa.

Lack of clinical stability after 5 days of CAP treatment should prompt evaluation for complications of pneumonia (eg, empyema, lung abscess), infection due to  organisms resistant to selected antibiotics, or an alternative source of infection/inflammatory/poor response. 2

References

  1. Halm, EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA 1998;279:279:1452-57. https://reference.medscape.com/medline/abstract/9600479
  2. 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. https://www.ncbi.nlm.nih.gov/pubmed/31573350
  3. Uranga A, Espana PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia. A multicenter randomized clinical trial. JAMA Intern Med 2016;176:1257-65. https://www.ncbi.nlm.nih.gov/pubmed/27455166/
When should I consider a switch to oral antibiotics and discharge from hospital in my recently admitted elderly patient with community-acquired pneumonia (CAP)?

What changes should I consider in my diagnostic approach to hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA)?

Compared to 2007,1 the 2019 ATS/IDSA guidelines2 have 2 major “Do’s” and 2 major “Dont’s” in the diagnostic approach to CAP in hospitalized patients:

  • DO order sputum and blood cultures in patients empirically treated for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa—in addition to those with severe CAP as in 2007.  
  • DO order rapid influenza molecular assay—in preference to antigen test— when influenza viruses are circulating in community, irrespective of pneumonia severity
  • DON’T routinely order urine antigens for pneumococcal or Legionella antigens, except in severe CAP or in the presence of suggestive epidemiological factors (eg. Legionella outbreak, recent travel)
  • DON’t routinely order serum procalcitonin to determine need for initial antibacterial therapy

Patients at risk of MRSA or P. aeruginosa include those with prior infection with the same pathogens as well as those with hospitalization and treated with parenteral antibiotics—in or out of the hospital— in the last 90 days; HCAP is no longer recognized as an entity.

The definition of severe CAP is unchanged: 1 of 2 major criteria (septic shock or respiratory failure requiring mechanical ventilation) or 3 or more of the following minor criteria or findings listed below:

  • Clinical
    • Respiratory rate ≥30 breath/min
    • Hypotension requiring aggressive fluid resuscitation
    • Hypothermia (core temperature <36 ᵒC, 96.8 ᵒF)
    • Confusion/disorientation
  • Radiographic 
    • Multilobar infiltrates
  • Laboratory 
    • Leukopenia (WBC <4,000/ul)
    • Thrombocytopenia (platelets <100,000/ul)
    • BUN ≥20 mg/dl
    • Pa02/FI02 ratio ≤250

Keep in mind that these guidelines focus on adults who are not immunocompromised or had recent foreign travel and are often based on expert opinion but low or very low quality evidence due to the dearth of properly designed studies.

Bonus Pearl: Did you know that the urine Legionella antigen only tests for L. pneumophila type I, with an overall sensitivity ranging from 45% to 100%!3,4

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References

  1. Mandell LA, Wunderink RG, Anzueto A. Infectious Disease Society of America/American Thoracic Society Consensus Guidelines on the Management guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72. https://www.ncbi.nlm.nih.gov/pubmed/17278083
  2. 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. https://www.ncbi.nlm.nih.gov/pubmed/31573350
  3. Blazquez RM, Espinosa FJ, Martinez-Toldos CM, et al. Sensitivity of urinary antigen test in relation to clinical severity in a large outbreak of Legionella pneumonia in Spain. Eur J Clin Microbiol Infect Dis 2005;24:488-91. https://www.ncbi.nlm.nih.gov/pubmed/15997369
  4. Marlow E, Whelan C. Legionella pneumonia and use of the Legionella urinary antigen test. J Hosp Med 2009;4:E1-E2. https://www.ncbi.nlm.nih.gov/pubmed/19301376

 

 

What changes should I consider in my diagnostic approach to hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA)?

When should I consider Pseudomonas aeruginosa as a cause of respiratory tract infection in my hospitalized patient with COPD exacerbation?

The most consistent risk factor for isolation of P. aeruginosa from sputum of adults with COPD is the presence of more advanced pulmonary disease (eg, FEV-1 <35%-50% of predicted value) or functional impairment (1-5).

 

Chronic corticosteroid use is also frequently cited as an important predictor of respiratory tract colonization/infection due to P. aeruginosa in patients with COPD, while the data on antibiotic use during the previous months have been conflicting (2,4). Other risk factors may include prior isolation of P. aeruginosa and hospital admission during the previous year (1).
A prospective study of patients hospitalized for COPD exacerbation found P. aeruginosa to be the most frequently isolated organism, growing from 26% of validated sputum samples at initial admission, followed by Streptococcus pneumoniae and Hemophilus influenzae. In the same study, bronchiectasis (present in up to 50% of patients with COPD) was not shown to be independently associated with the isolation of P. aeruginosa (1).
Of interest, compared to the patients without P. aeruginosa, patients hospitalized for acute exacerbation of COPD and isolation of P. aeruginosa from sputum have significantly higher mortality: 33% at 1 year, 48% at 2 years and 59% at 3 years (5).

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References
1. Garcia-Vidal C, Almagro P, Romani V, et al. Pseudomonas aeruginosa in patients hospitalized for COPD exacerbation: a prospective study. Eur Respir J 2009;34:1072-78. https://www.ncbi.nlm.nih.gov/pubmed/19386694
2. Murphy TF. Pseudomonas aeruginosa in adults with chronic obstructive pulmonary disease. Curr Opin Pulm Med 2009;15:138-42. https://www.ncbi.nlm.nih.gov/pubmed/19532029
3. Miravitlles M, Espinosa C, Fernandez-Laso E, et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999;116:40-6. https://www.ncbi.nlm.nih.gov/pubmed/10424501
4. Murphy TF, Brauer AL, Eschberger K, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:853-60. https://www.ncbi.nlm.nih.gov/pubmed/18202344
5. Almagro P, Silvado M, Garcia-Vidal C, et al. Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease. Respiration 2012;84:36-43. https://www.karger.com/Article/FullText/331224

 

 

When should I consider Pseudomonas aeruginosa as a cause of respiratory tract infection in my hospitalized patient with COPD exacerbation?