# Empiric Antibiotic Therapy for Community-Acquired Pneumonia — ATS/IDSA 2019

## General Principles

- Empiric antibiotic therapy should be initiated as soon as CAP is diagnosed, regardless of initial serum procalcitonin level (Strong recommendation, Moderate quality of evidence).
- Antibiotic selection is stratified by treatment setting (outpatient, inpatient non-ICU, inpatient ICU) and risk factors for resistant organisms.
- Routine anaerobic coverage for suspected aspiration pneumonia is **not** recommended unless lung abscess or empyema is suspected (Conditional recommendation, Very low quality of evidence).

## Outpatient Treatment

### Healthy Adults Without Comorbidities or Risk Factors for Resistant Pathogens

(Strong recommendation, Moderate quality of evidence)

- **Amoxicillin** 1 g orally three times daily; OR
- **Doxycycline** 100 mg orally twice daily; OR
- **Azithromycin** 500 mg on day 1, then 250 mg daily on days 2-5 (only in areas with pneumococcal macrolide resistance < 25%)

### Adults With Comorbidities

Comorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia. (Strong recommendation, Moderate quality of evidence)

**Option A — Combination Therapy:**
- **Amoxicillin/clavulanate** 500 mg/125 mg orally three times daily OR 875 mg/125 mg orally twice daily OR 2,000 mg/125 mg orally twice daily; OR
- **Cefpodoxime** 200 mg orally twice daily; OR
- **Cefuroxime** 500 mg orally twice daily

**PLUS one of:**
- **Azithromycin** 500 mg on day 1, then 250 mg daily; OR
- **Doxycycline** 100 mg orally twice daily

**Option B — Monotherapy:**
- **Levofloxacin** 750 mg orally once daily; OR
- **Moxifloxacin** 400 mg orally once daily; OR
- **Gemifloxacin** 320 mg orally once daily

## Inpatient Treatment (Non-Severe CAP, General Ward)

### Without Risk Factors for MRSA or Pseudomonas aeruginosa

(Strong recommendation, High quality of evidence)

**Option A — Combination Therapy (Preferred):**
- Beta-lactam PLUS macrolide:
  - **Ampicillin/sulbactam** 1.5-3 g IV every 6 hours; OR
  - **Cefotaxime** 1-2 g IV every 8 hours; OR
  - **Ceftriaxone** 1-2 g IV once daily; OR
  - **Ceftaroline** 600 mg IV every 12 hours

  PLUS:
  - **Azithromycin** 500 mg IV/PO once daily; OR
  - **Clarithromycin** 500 mg orally twice daily

**Option B — Monotherapy:**
- **Levofloxacin** 750 mg IV/PO once daily; OR
- **Moxifloxacin** 400 mg IV/PO once daily

## Inpatient Treatment (Severe CAP, ICU)

### Without Risk Factors for MRSA or Pseudomonas aeruginosa

(Strong recommendation, Moderate quality of evidence)

- Beta-lactam PLUS either a macrolide or a respiratory fluoroquinolone:
  - **Ceftriaxone** 1-2 g IV once daily; OR
  - **Cefotaxime** 1-2 g IV every 8 hours; OR
  - **Ampicillin/sulbactam** 3 g IV every 6 hours

  PLUS:
  - **Azithromycin** 500 mg IV once daily; OR
  - **Levofloxacin** 750 mg IV once daily; OR
  - **Moxifloxacin** 400 mg IV once daily

**Note:** For severe CAP, monotherapy with a respiratory fluoroquinolone is NOT recommended. A beta-lactam must be part of the regimen.

### Penicillin Allergy (Severe CAP)

- A respiratory fluoroquinolone **plus** aztreonam can be considered.

## Empiric Coverage for MRSA

When locally validated risk factors for MRSA are present (Conditional recommendation, Very low quality of evidence):

- **Vancomycin** 15 mg/kg IV every 12 hours (adjust based on trough levels or AUC/MIC); OR
- **Linezolid** 600 mg IV/PO every 12 hours

**Risk factors for MRSA in CAP:**
1. Prior respiratory isolation of MRSA (within the prior year)
2. Recent hospitalization AND receipt of parenteral antibiotics (in the last 90 days)

**De-escalation:** Obtain cultures (sputum, blood) before or at time of initiating empiric MRSA coverage. If cultures negative at 48 hours and/or MRSA nasal PCR is negative, de-escalate by discontinuing MRSA coverage (Strong recommendation, Low quality of evidence).

## Empiric Coverage for Pseudomonas aeruginosa

When locally validated risk factors for P. aeruginosa are present (Conditional recommendation, Very low quality of evidence):

Use one of the following antipseudomonal beta-lactams:
- **Piperacillin/tazobactam** 4.5 g IV every 6 hours; OR
- **Cefepime** 2 g IV every 8 hours; OR
- **Ceftazidime** 2 g IV every 8 hours; OR
- **Aztreonam** 2 g IV every 8 hours; OR
- **Meropenem** 1 g IV every 8 hours; OR
- **Imipenem** 500 mg IV every 6 hours

**Risk factors for P. aeruginosa in CAP:**
1. Prior respiratory isolation of P. aeruginosa (within the prior year)
2. Recent hospitalization AND receipt of parenteral antibiotics (in the last 90 days)

**De-escalation:** Obtain cultures (sputum, blood) before or at time of initiating empiric antipseudomonal coverage. If cultures negative at 48 hours, de-escalate to standard CAP therapy (Strong recommendation, Very low quality of evidence).

## Duration of Therapy

- Antibiotic therapy should be guided by clinical stability and should be continued for **no less than 5 days** (Strong recommendation, Moderate quality of evidence).
- Antibiotics may be discontinued when the patient meets **all** of the following clinical stability criteria AND has been treated for at least 5 days:

### Clinical Stability Criteria

| Parameter | Threshold |
|-----------|-----------|
| **Temperature** | < 37.8 degrees C (100 degrees F) for >= 48 hours |
| **Heart rate** | < 100 beats/min |
| **Respiratory rate** | < 24 breaths/min |
| **Systolic blood pressure** | >= 90 mmHg |
| **Oxygen saturation** | >= 90% on room air or PaO2 >= 60 mmHg |
| **Mental status** | Return to baseline |
| **Oral intake** | Ability to maintain adequate oral intake |

## Escalation and Treatment Failure

- **Non-response definition:** Failure to achieve clinical stability after 48-72 hours of appropriate empiric therapy.
- **Actionable steps for non-response:**
  1. Review microbiologic data; broaden coverage if warranted.
  2. Consider alternative diagnoses (PE, heart failure, organizing pneumonia, empyema, lung abscess).
  3. Repeat imaging (CXR or CT chest) to assess for complications.
  4. Consider de novo cultures (including for resistant organisms).
  5. Escalate level of care if clinical deterioration (reassess IDSA/ATS severity criteria).
