What is the preferred Community-Acquired Pneumonia (CAP) treatment for in-patients?

From the Guidelines

For inpatient treatment of community-acquired pneumonia (CAP), the preferred regimen is a combination of a beta-lactam (such as ceftriaxone 1-2g IV daily or ampicillin-sulbactam 1.5-3g IV every 6 hours) plus a macrolide (azithromycin 500mg IV daily), as recommended by the most recent guidelines 1. This approach is supported by the American Thoracic Society and Infectious Diseases Society of America guidelines, which suggest that combination therapy with a beta-lactam and a macrolide is the preferred treatment for inpatients with CAP, especially for those with severe disease or risk factors for drug-resistant pathogens. Some key points to consider when treating inpatients with CAP include:

• Using a respiratory fluoroquinolone like levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily as monotherapy is also an option, especially for patients with mild to moderate disease 1.
• For patients with risk factors for Pseudomonas, coverage should be expanded to include an antipseudomonal beta-lactam (piperacillin-tazobactam 4.5g IV every 6 hours or cefepime 2g IV every 8 hours) plus either a fluoroquinolone or an aminoglycoside 1.
• For MRSA risk, add vancomycin or linezolid to the treatment regimen 1.
• Treatment duration is typically 5-7 days for most patients, with consideration for longer courses in complicated cases 1.
• Patients should be switched from IV to oral therapy when they are hemodynamically stable, showing clinical improvement, able to take oral medications, and have a functioning gastrointestinal tract 1.
• Supportive care including oxygen therapy, fluid management, and early mobilization are also essential components of inpatient CAP management 1.

From the FDA Drug Label

1. 2 Community-acquired Pneumonia Linezolid is indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible isolates only)
2. 5 Community-acquired Pneumonia Piperacillin and Tazobactam for Injection is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae.

The preferred Community-Acquired Pneumonia (CAP) treatment for in-patients is not explicitly stated in the provided drug labels. However, based on the available information:

• Linezolid is indicated for the treatment of CAP caused by Streptococcus pneumoniae or Staphylococcus aureus (methicillin-susceptible isolates only) 2.
• Piperacillin-tazobactam is indicated for the treatment of CAP (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae 3. It is essential to note that the choice of antibiotic therapy should be based on the severity of the disease, the causative pathogen, and local resistance patterns. In the absence of explicit guidance, a conservative approach would be to consider linezolid or piperacillin-tazobactam as potential options for CAP treatment in in-patients, depending on the specific clinical scenario and microbiological data.

From the Research

Community-Acquired Pneumonia (CAP) Treatment

The preferred treatment for in-patients with CAP involves a combination of antibiotics. Key findings from relevant studies include:

• A study published in 2004 4 compared the efficacy and tolerability of intravenous azithromycin plus ceftriaxone and intravenous levofloxacin in hospitalized patients with moderate to severe CAP, finding that both treatments were well tolerated and had favorable clinical outcomes.
• Another study from 2007 5 compared the clinical and bacteriological outcomes of patients with CAP treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin, finding that the combination of ceftriaxone and azithromycin was at least equivalent in efficacy and safety to the comparator regimen.
• A 2012 study 6 compared the clinical efficacy and safety of high-dose levofloxacin with combined ceftriaxone and azithromycin for the treatment of CAP, finding that single-agent, high-dose levofloxacin treatment exhibited excellent clinical and microbiological efficacy with a safety profile comparable to that of ceftriaxone plus azithromycin therapy.
• An open-label, non-comparative multicenter trial from 2008 7 evaluated the efficacy, safety, and tolerability of intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with CAP, finding that this treatment was efficacious and well-tolerated.
• A retrospective cohort study from 2023 8 examined whether 1 g/d of intravenous ceftriaxone is associated with similar clinical outcomes to those of 2 g/d in adults hospitalized with CAP, finding that 1 g/d was associated with similar mortality rates, a decreased rate of C. difficile infection, and shorter length of stay.

Key Treatment Options

Some key treatment options for in-patients with CAP include:

• Intravenous azithromycin plus ceftriaxone, followed by oral azithromycin 4, 5, 7
• High-dose levofloxacin 6
• Intravenous ceftriaxone at a dose of 1-2 g/d, with the addition of macrolide 8

Bacteriological Outcomes

Bacteriological outcomes for these treatments include:

• Equivalent bacteriological eradication rates for both ceftriaxone plus azithromycin and levofloxacin, with the exception of Streptococcus pneumoniae 4
• High microbiological success rates for both high-dose levofloxacin and combined ceftriaxone and azithromycin 6
• Negative cultures obtained from 93.3% of patients at the end of therapy and from 88.9% at the end of the study for intravenous azithromycin plus ceftriaxone followed by oral azithromycin 7