Clinical Edge Journal Scan Commentary: CAP January 2022

The practitioner’s primary responsibility in managing respiratory infection is to determine which patients with community acquired pneumonia (CAP) warrant hospitalization and more aggressive management. Standard practice for mild infection dictates empiric administration of 5 days of antimicrobial agents¹ particularly for the youngest, oldest and patients with underlying comorbid conditions, usually on an outpatient basis with careful follow-up.

Variables for hospitalization and for the selection of antibiotic therapy include the likelihood of a bacterial etiology, epidemiologic considerations, clinical symptoms, predisposing host factors, age, and radiographic findings. Patients who have viral processes generally have low-grade fever and are usually uncomfortable, although they may not appear toxic. However, it is not possible to distinguish between viral and bacterial pneumonia on clinical grounds alone, particularly with the emergence of COVID-19 (SARS-CoV-2), as rapid progression of an initially mild viral upper respiratory infection may become life threatening, particularly in patients with comorbid conditions, such as pulmonary disease, diabetes, and immunodeficiency. All patients with severe CAP should be tested for this viral agent. A recent study of 96 patients with chronic obstructive pulmonary disease (COPD) and COVID-19 infection showed they had higher intensive care unit (ICU) admissions, ventilation requirements, cardiovascular events, and mortality as compared to 1,129 hospitalized patients with COPD and non-COVID-19 infection.² In addition to COVID-19, type 2 diabetes mellitus must also be considered, as such patients developing severe CAP from all causes have a higher mortality and poorer clinical outcomes than those without diabetes.³

      Predicting which patients are likely to progress to severe disease from CAP is a challenging task. In the past clinicians relied on clinical assessment, along with some inflammatory lab studies such as the complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin. Newer tests have recently been studied for their ability to inform prognosis and likely mortality. A very simple test is the admission blood glucose level, which, if increased at hospital admission, is associated with a higher mortality.⁴ More recently the quick sequential organ failure assessment (qSOFA) score was shown to be better than the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) minor criteria score in predicting mortality.⁵ A potential new laboratory test, serum IL-17 concentrations, demonstrated a positive correlation with CAP severity, ICU admission, longer hospital stay, mechanical ventilation, and mortality.⁶

Current studies have identified some potential advantages of newer antibiotics. Cefoperazone-sulbactam was shown to be equivalent to piperacillin-tazobactam (PIP-TAZO) for treating severe CAP in elderly patients, thereby avoiding the potential acute kidney injury (AKI) of the PIP-TAZO – vancomycin combination.⁷ This benefit of reduced AKI was supported by a retrospective cohort study that included 449,535 hospitalized adult patients with CAP.⁸

In a phase 3 study, lefamulin was as effective as moxifloxacin in treating bacterial CAP, including drug-resistant strains and typical, atypical, and polymicrobial infections.⁹  Of 1,289 study patients, a pathogen was identified in 709. Side effects were minor. This antibiotic has a unique mechanism of action through inhibition of protein synthesis, preventing the binding of transfer RNA.

Adjunctive oral dexamethasone therapy for CAP has been advocated by some experts. In a study of 354 non-ICU patients, a shorter hospital stay was seen in patients who received dexamethasone vs. placebo (4 vs. 6 days) but only in patients who had elevated neutrophil or WBC counts, or high neutrophil-lymphocyte ratios; otherwise there was no difference.¹⁰

References

1. Vaughn VM et al. a statewide collaborative quality initiative to improve antibiotic duration and outcomes in patients hospitalized with uncomplicated community-acquired pneumonia. Clin Infect Dis. 2021(Nov 13):ciab950 (Nov 13). 
2. Sheikh D et al. Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non-SARS-CoV-2 community-acquired pneumonia. Respir Med. 2021(Dec 8);191:106714.
3. Huang D et al. Clinical characteristics and risk factors associated with mortality in patients with severe community-acquired pneumonia and type 2 diabetes mellitus. Crit Care. 2021(Dec 7);25:419.
4. Shen Y et al. Association of admission blood glucose level with all-cause mortality according to age in patients with community acquired pneumonia. Int J Gen Med. 2021(Nov 6);14:7775-7781.
5. Guo Q et al. qSOFA predicted pneumonia mortality better than minor criteria and worse than CURB-65 with robust elements and higher convergence. Am J Emerg Med. 2022(Feb);52:1-7.
6. Feng CM et al. Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study. BMC Pulm Med. 2021(Dec 2);21:393.
7. Huang CT et al. Clinical effectiveness of cefoperazone-sulbactam versus piperacillin-tazobactam for the treatment of pneumonia in the elderly population. Int J Antimicrob Agents. 2021(Dec 4);106491.
8. Le P et al. Association of antibiotic use and acute kidney injury in patients hospitalized with community-acquired pneumonia. Curr Med Res Opin. 2021 (Nov 15).   
9. Paukner S et al. Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin. J Glob Antimicrob Resist. 2021 (Nov 14).
10. Wittermans E et al. Neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio in relation to response to adjunctive dexamethasone treatment in community-acquired pneumonia. Eur J Intern Med. 2021 (Nov 12).

The practitioner’s primary responsibility in managing respiratory infection is to determine which patients with community acquired pneumonia (CAP) warrant hospitalization and more aggressive management. Standard practice for mild infection dictates empiric administration of 5 days of antimicrobial agents¹ particularly for the youngest, oldest and patients with underlying comorbid conditions, usually on an outpatient basis with careful follow-up.

Variables for hospitalization and for the selection of antibiotic therapy include the likelihood of a bacterial etiology, epidemiologic considerations, clinical symptoms, predisposing host factors, age, and radiographic findings. Patients who have viral processes generally have low-grade fever and are usually uncomfortable, although they may not appear toxic. However, it is not possible to distinguish between viral and bacterial pneumonia on clinical grounds alone, particularly with the emergence of COVID-19 (SARS-CoV-2), as rapid progression of an initially mild viral upper respiratory infection may become life threatening, particularly in patients with comorbid conditions, such as pulmonary disease, diabetes, and immunodeficiency. All patients with severe CAP should be tested for this viral agent. A recent study of 96 patients with chronic obstructive pulmonary disease (COPD) and COVID-19 infection showed they had higher intensive care unit (ICU) admissions, ventilation requirements, cardiovascular events, and mortality as compared to 1,129 hospitalized patients with COPD and non-COVID-19 infection.² In addition to COVID-19, type 2 diabetes mellitus must also be considered, as such patients developing severe CAP from all causes have a higher mortality and poorer clinical outcomes than those without diabetes.³

      Predicting which patients are likely to progress to severe disease from CAP is a challenging task. In the past clinicians relied on clinical assessment, along with some inflammatory lab studies such as the complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin. Newer tests have recently been studied for their ability to inform prognosis and likely mortality. A very simple test is the admission blood glucose level, which, if increased at hospital admission, is associated with a higher mortality.⁴ More recently the quick sequential organ failure assessment (qSOFA) score was shown to be better than the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) minor criteria score in predicting mortality.⁵ A potential new laboratory test, serum IL-17 concentrations, demonstrated a positive correlation with CAP severity, ICU admission, longer hospital stay, mechanical ventilation, and mortality.⁶

Current studies have identified some potential advantages of newer antibiotics. Cefoperazone-sulbactam was shown to be equivalent to piperacillin-tazobactam (PIP-TAZO) for treating severe CAP in elderly patients, thereby avoiding the potential acute kidney injury (AKI) of the PIP-TAZO – vancomycin combination.⁷ This benefit of reduced AKI was supported by a retrospective cohort study that included 449,535 hospitalized adult patients with CAP.⁸

In a phase 3 study, lefamulin was as effective as moxifloxacin in treating bacterial CAP, including drug-resistant strains and typical, atypical, and polymicrobial infections.⁹  Of 1,289 study patients, a pathogen was identified in 709. Side effects were minor. This antibiotic has a unique mechanism of action through inhibition of protein synthesis, preventing the binding of transfer RNA.

Adjunctive oral dexamethasone therapy for CAP has been advocated by some experts. In a study of 354 non-ICU patients, a shorter hospital stay was seen in patients who received dexamethasone vs. placebo (4 vs. 6 days) but only in patients who had elevated neutrophil or WBC counts, or high neutrophil-lymphocyte ratios; otherwise there was no difference.¹⁰

References

1. Vaughn VM et al. a statewide collaborative quality initiative to improve antibiotic duration and outcomes in patients hospitalized with uncomplicated community-acquired pneumonia. Clin Infect Dis. 2021(Nov 13):ciab950 (Nov 13). 
2. Sheikh D et al. Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non-SARS-CoV-2 community-acquired pneumonia. Respir Med. 2021(Dec 8);191:106714.
3. Huang D et al. Clinical characteristics and risk factors associated with mortality in patients with severe community-acquired pneumonia and type 2 diabetes mellitus. Crit Care. 2021(Dec 7);25:419.
4. Shen Y et al. Association of admission blood glucose level with all-cause mortality according to age in patients with community acquired pneumonia. Int J Gen Med. 2021(Nov 6);14:7775-7781.
5. Guo Q et al. qSOFA predicted pneumonia mortality better than minor criteria and worse than CURB-65 with robust elements and higher convergence. Am J Emerg Med. 2022(Feb);52:1-7.
6. Feng CM et al. Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study. BMC Pulm Med. 2021(Dec 2);21:393.
7. Huang CT et al. Clinical effectiveness of cefoperazone-sulbactam versus piperacillin-tazobactam for the treatment of pneumonia in the elderly population. Int J Antimicrob Agents. 2021(Dec 4);106491.
8. Le P et al. Association of antibiotic use and acute kidney injury in patients hospitalized with community-acquired pneumonia. Curr Med Res Opin. 2021 (Nov 15).   
9. Paukner S et al. Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin. J Glob Antimicrob Resist. 2021 (Nov 14).
10. Wittermans E et al. Neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio in relation to response to adjunctive dexamethasone treatment in community-acquired pneumonia. Eur J Intern Med. 2021 (Nov 12).

The practitioner’s primary responsibility in managing respiratory infection is to determine which patients with community acquired pneumonia (CAP) warrant hospitalization and more aggressive management. Standard practice for mild infection dictates empiric administration of 5 days of antimicrobial agents¹ particularly for the youngest, oldest and patients with underlying comorbid conditions, usually on an outpatient basis with careful follow-up.

Variables for hospitalization and for the selection of antibiotic therapy include the likelihood of a bacterial etiology, epidemiologic considerations, clinical symptoms, predisposing host factors, age, and radiographic findings. Patients who have viral processes generally have low-grade fever and are usually uncomfortable, although they may not appear toxic. However, it is not possible to distinguish between viral and bacterial pneumonia on clinical grounds alone, particularly with the emergence of COVID-19 (SARS-CoV-2), as rapid progression of an initially mild viral upper respiratory infection may become life threatening, particularly in patients with comorbid conditions, such as pulmonary disease, diabetes, and immunodeficiency. All patients with severe CAP should be tested for this viral agent. A recent study of 96 patients with chronic obstructive pulmonary disease (COPD) and COVID-19 infection showed they had higher intensive care unit (ICU) admissions, ventilation requirements, cardiovascular events, and mortality as compared to 1,129 hospitalized patients with COPD and non-COVID-19 infection.² In addition to COVID-19, type 2 diabetes mellitus must also be considered, as such patients developing severe CAP from all causes have a higher mortality and poorer clinical outcomes than those without diabetes.³

      Predicting which patients are likely to progress to severe disease from CAP is a challenging task. In the past clinicians relied on clinical assessment, along with some inflammatory lab studies such as the complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin. Newer tests have recently been studied for their ability to inform prognosis and likely mortality. A very simple test is the admission blood glucose level, which, if increased at hospital admission, is associated with a higher mortality.⁴ More recently the quick sequential organ failure assessment (qSOFA) score was shown to be better than the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) minor criteria score in predicting mortality.⁵ A potential new laboratory test, serum IL-17 concentrations, demonstrated a positive correlation with CAP severity, ICU admission, longer hospital stay, mechanical ventilation, and mortality.⁶

Current studies have identified some potential advantages of newer antibiotics. Cefoperazone-sulbactam was shown to be equivalent to piperacillin-tazobactam (PIP-TAZO) for treating severe CAP in elderly patients, thereby avoiding the potential acute kidney injury (AKI) of the PIP-TAZO – vancomycin combination.⁷ This benefit of reduced AKI was supported by a retrospective cohort study that included 449,535 hospitalized adult patients with CAP.⁸

In a phase 3 study, lefamulin was as effective as moxifloxacin in treating bacterial CAP, including drug-resistant strains and typical, atypical, and polymicrobial infections.⁹  Of 1,289 study patients, a pathogen was identified in 709. Side effects were minor. This antibiotic has a unique mechanism of action through inhibition of protein synthesis, preventing the binding of transfer RNA.

Adjunctive oral dexamethasone therapy for CAP has been advocated by some experts. In a study of 354 non-ICU patients, a shorter hospital stay was seen in patients who received dexamethasone vs. placebo (4 vs. 6 days) but only in patients who had elevated neutrophil or WBC counts, or high neutrophil-lymphocyte ratios; otherwise there was no difference.¹⁰

References

1. Vaughn VM et al. a statewide collaborative quality initiative to improve antibiotic duration and outcomes in patients hospitalized with uncomplicated community-acquired pneumonia. Clin Infect Dis. 2021(Nov 13):ciab950 (Nov 13). 
2. Sheikh D et al. Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non-SARS-CoV-2 community-acquired pneumonia. Respir Med. 2021(Dec 8);191:106714.
3. Huang D et al. Clinical characteristics and risk factors associated with mortality in patients with severe community-acquired pneumonia and type 2 diabetes mellitus. Crit Care. 2021(Dec 7);25:419.
4. Shen Y et al. Association of admission blood glucose level with all-cause mortality according to age in patients with community acquired pneumonia. Int J Gen Med. 2021(Nov 6);14:7775-7781.
5. Guo Q et al. qSOFA predicted pneumonia mortality better than minor criteria and worse than CURB-65 with robust elements and higher convergence. Am J Emerg Med. 2022(Feb);52:1-7.
6. Feng CM et al. Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study. BMC Pulm Med. 2021(Dec 2);21:393.
7. Huang CT et al. Clinical effectiveness of cefoperazone-sulbactam versus piperacillin-tazobactam for the treatment of pneumonia in the elderly population. Int J Antimicrob Agents. 2021(Dec 4);106491.
8. Le P et al. Association of antibiotic use and acute kidney injury in patients hospitalized with community-acquired pneumonia. Curr Med Res Opin. 2021 (Nov 15).   
9. Paukner S et al. Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin. J Glob Antimicrob Resist. 2021 (Nov 14).
10. Wittermans E et al. Neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio in relation to response to adjunctive dexamethasone treatment in community-acquired pneumonia. Eur J Intern Med. 2021 (Nov 12).