What are the common empiric treatment regimens for adult patients with suspected bacterial infections, including those with respiratory infections and a history of antibiotic resistance?

Empiric Antibiotic Treatment for Suspected Bacterial Infections in Adults

Community-Acquired Respiratory Infections (Non-ICU)

For hospitalized adults with community-acquired pneumonia not requiring ICU admission, use a beta-lactam/beta-lactamase inhibitor (ampicillin-sulbactam or piperacillin-tazobactam) plus a macrolide, OR a respiratory fluoroquinolone (moxifloxacin or levofloxacin 750mg) as monotherapy. 1

Standard Regimens:

• Aminopenicillin/beta-lactamase inhibitor ± macrolide (ampicillin-sulbactam 1.5-3g IV q6h or amoxicillin-clavulanate 875-1000mg PO q8-12h plus azithromycin 500mg day 1, then 250mg daily) 1, 2
• Non-antipseudomonal cephalosporin ± macrolide (ceftriaxone 1-2g IV daily or cefotaxime plus azithromycin or clarithromycin) 1
• Respiratory fluoroquinolone monotherapy (moxifloxacin 400mg daily or levofloxacin 750mg daily) 1, 2

Treatment Duration:

• Maximum 8 days for responding patients 1, 2
• Switch from IV to oral when hemodynamically stable, improving clinically, and able to take oral medications 1

Severe Community-Acquired Pneumonia (ICU)

For ICU patients without risk factors for Pseudomonas, use a non-antipseudomonal cephalosporin III (ceftriaxone or cefotaxime) plus either a macrolide OR a respiratory fluoroquinolone (moxifloxacin or levofloxacin). 1

Risk Factors for Pseudomonas Coverage:

Add antipseudomonal coverage if ANY of the following are present: 1

• Structural lung disease (bronchiectasis, cystic fibrosis)
• Prior IV antibiotic use within 90 days
• Healthcare-associated infection
• Septic shock at presentation
• Five or more days of hospitalization prior to pneumonia

Antipseudomonal Regimen:

Antipseudomonal beta-lactam (piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, ceftazidime 2g IV q8h, or meropenem 1g IV q8h) PLUS a second antipseudomonal agent from different class (ciprofloxacin 400mg IV q8h, levofloxacin 750mg IV daily, or aminoglycoside) 1

MRSA Coverage Indications:

Add vancomycin 15mg/kg IV q8-12h (target trough 15-20 mg/mL) OR linezolid 600mg IV q12h if: 1, 2

• Prior IV antibiotic use within 90 days
• Healthcare setting where MRSA prevalence among S. aureus isolates is >10-20% or unknown
• Prior MRSA colonization or infection
• Septic shock requiring vasopressors

Hospital-Acquired/Ventilator-Associated Pneumonia

For suspected HAP/VAP, empiric coverage must include S. aureus, Pseudomonas aeruginosa, and other gram-negative bacilli in ALL cases. 1

Standard HAP/VAP Regimen (No MDR Risk Factors):

Antipseudomonal beta-lactam monotherapy (piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, or meropenem 1g IV q8h) 1

Add MRSA Coverage When:

• Prior IV antibiotic use within 90 days
• Units where >10-20% of S. aureus isolates are methicillin-resistant
• MRSA prevalence unknown 1

MRSA regimen: Vancomycin 15mg/kg IV q8-12h OR linezolid 600mg IV q12h 1

Add Double Antipseudomonal Coverage When:

Risk factors for MDR Pseudomonas include: 1

• Prior IV antibiotic use within 90 days
• Septic shock at time of VAP
• ARDS preceding VAP
• Five or more days of hospitalization prior to VAP
• Acute renal replacement therapy prior to VAP onset

Double coverage regimen: Antipseudomonal beta-lactam PLUS either a fluoroquinolone (ciprofloxacin or levofloxacin) OR an aminoglycoside (gentamicin, tobramycin, or amikacin) 1

Nosocomial Pneumonia Specific Dosing:

Piperacillin-tazobactam 4.5g IV every 6 hours plus an aminoglycoside for initial presumptive treatment 3

Aspiration Pneumonia

Current guidelines recommend AGAINST routinely adding specific anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is present, as gram-negative pathogens and S. aureus are the predominant organisms, not pure anaerobes. 2

Hospital Ward Patients (From Home):

• Beta-lactam/beta-lactamase inhibitor (ampicillin-sulbactam 1.5-3g IV q6h or amoxicillin-clavulanate 875-1000mg PO q8-12h) 1, 2
• Clindamycin 600-900mg IV q8h 1, 2
• Moxifloxacin 400mg IV/PO daily 1, 2

ICU or Nursing Home Patients:

• Clindamycin plus cephalosporin (clindamycin 600-900mg IV q8h plus ceftriaxone 1-2g IV daily) 1, 2
• Piperacillin-tazobactam 4.5g IV q6h for severe cases 2

Add MRSA/Pseudomonal Coverage:

Use same risk stratification as HAP/VAP above 2

COVID-19 with Suspected Bacterial Co-infection

For patients with proven or high likelihood of COVID-19, do NOT routinely prescribe antibiotics upon admission unless there is strong clinical suspicion of bacterial co-infection. 1

Bacterial Co-infection Upon Admission:

• Bacterial co-infections are uncommon (prevalence <10%) 1
• If antibiotics started, stop after 48 hours if cultures show no pathogens 1
• Use standard community-acquired pneumonia regimens if bacterial infection suspected 1

Secondary Bacterial Infections (>48-72 hours):

Treat as hospital-acquired pneumonia with coverage for: 1

• S. aureus (including MRSA if risk factors present)
• Enterobacterales
• P. aeruginosa
• A. baumannii
• H. influenzae

Treatment duration: 5 days if improving 1

Penicillin Allergy Considerations

For severe penicillin allergy, use aztreonam 2g IV q8h PLUS vancomycin 15mg/kg IV q8-12h OR linezolid 600mg IV q12h for severe cases. 2

For non-severe cases with penicillin allergy, use a respiratory fluoroquinolone (moxifloxacin 400mg daily or levofloxacin 750mg daily) 2

Critical Caveat:

• Aztreonam has negligible cross-reactivity with penicillins and is safe in penicillin allergy 2
• Carbapenems and cephalosporins carry risk of cross-reactivity 2
• Never use ciprofloxacin alone for respiratory infections due to poor S. pneumoniae activity 2

Key Principles for All Empiric Therapy

Timing:

Initiate antibiotics within the first hour without waiting for culture results, as delay in appropriate therapy is consistently associated with increased mortality. 2, 4

De-escalation:

• Reassess at 48-72 hours with culture results 2
• Narrow spectrum based on identified pathogens 1, 4
• Stop antibiotics if cultures negative and clinical improvement 1

Local Antibiogram:

Tailor empiric regimens to local pathogen distribution and antimicrobial susceptibilities, particularly regarding MRSA prevalence thresholds. 1, 2

Common Pitfalls:

• Overuse of broad-spectrum antibiotics when not indicated increases mortality and resistance risk 5
• Inadequate initial therapy also increases mortality 4
• Assuming all aspiration requires anaerobic coverage is incorrect 2
• Underdosing in elderly or critically ill patients leads to treatment failure 2