What is the recommended treatment for hospital-acquired infections (HAIs)?

Treatment for Hospital-Acquired Infections

For hospital-acquired infections, empiric antibiotic selection must be stratified by infection type, risk factors for multidrug-resistant organisms (MDROs), and illness severity, with piperacillin-tazobactam serving as the backbone for most empiric regimens, adding MRSA coverage (vancomycin or linezolid) when risk factors are present. 1

Risk Stratification Framework

Low-Risk Patients (No MDRO Risk Factors)

• Monotherapy options include: 1

  • Piperacillin-tazobactam 4.5 g IV q6h
  • Cefepime 2 g IV q8h
  • Levofloxacin 750 mg IV daily
  • Meropenem 1 g IV q8h or imipenem 500 mg IV q6h

• MDRO risk factors to assess: prior IV antibiotics within 90 days, hospitalization in units where >20% of S. aureus isolates are methicillin-resistant, high APACHE II scores (≥15), or structural lung disease 1

High-Risk Patients (MDRO Risk Factors Present or High Mortality Risk)

• Dual antipseudomonal coverage required (choose two agents from different classes, avoiding two β-lactams): 1

  • β-lactam options: piperacillin-tazobactam 4.5 g IV q6h, cefepime/ceftazidime 2 g IV q8h, or carbapenems
  • Plus one of: aminoglycoside (amikacin 15-20 mg/kg IV daily, gentamicin 5-7 mg/kg IV daily), fluoroquinolone (ciprofloxacin 400 mg IV q8h, levofloxacin 750 mg IV daily), or aztreonam 2 g IV q8h

• Add MRSA coverage when: 1

  • Prior IV antibiotics within 90 days
  • Local MRSA prevalence >20% or unknown
  • Septic shock or requiring ventilatory support
  • Preferred agents: vancomycin 15 mg/kg IV q8-12h (target trough 15-20 mg/mL; consider loading dose 25-30 mg/kg for severe illness) OR linezolid 600 mg IV q12h

Infection-Specific Considerations

Hospital-Acquired Pneumonia (HAP)

• Early-onset (<5 days), low-risk: amoxicillin-clavulanate or cefuroxime 1
• Early-onset with recent antibiotics: third-generation cephalosporin (cefotaxime/ceftriaxone), fluoroquinolone, or piperacillin-tazobactam 1
• Late-onset or Pseudomonas suspected: antipseudomonal β-lactam ± aminoglycoside plus MRSA coverage if risk factors present 1
• Ventilator-associated pneumonia (VAP): piperacillin-tazobactam 4.5 g IV q6h plus aminoglycoside plus vancomycin/linezolid for empiric coverage 1

Complicated Intra-Abdominal Infections

• Community-acquired, mild-moderate: ampicillin-sulbactam, ertapenem, or fluoroquinolone plus metronidazole 1
• Nosocomial/postoperative: broader coverage required for Pseudomonas, Enterobacter, MRSA, enterococci—use piperacillin-tazobactam, meropenem, or imipenem-cilastatin 1
• Add vancomycin if high MRSA suspicion; consider enterococcal coverage for serious nosocomial infections despite limited outcome data 1

Critical Implementation Points

Antibiogram-Guided Therapy

• All hospitals must regularly generate local antibiograms tailored to HAP populations to guide empiric selection 1
• Empiric regimens should reflect local pathogen distribution and susceptibility patterns, updated based on institutional resistance trends 1

De-escalation Strategy

• Narrow therapy at 48-72 hours based on culture results and clinical response 2, 3
• If cultures grow only gram-negative organisms susceptible to monotherapy, discontinue MRSA coverage 2
• Continuing broad-spectrum empirics after susceptibilities are known increases C. difficile risk and antimicrobial resistance without improving outcomes 4, 5

Duration of Therapy

• HAP/VAP: 7-8 days for most patients (shorter courses reduce MDRO recurrence without increasing mortality) 1
• Complicated intra-abdominal infections: 7-10 days 1
• Nosocomial pneumonia: 7-14 days depending on severity 1

Common Pitfalls to Avoid

• Do not use aminoglycosides as sole antipseudomonal agent—always combine with β-lactam for serious infections 1
• Avoid vancomycin for proven methicillin-susceptible S. aureus—β-lactams (nafcillin, oxacillin, cefazolin) have superior efficacy 4
• Do not continue empiric broad-spectrum therapy once susceptibilities confirm narrower options are adequate 4, 5
• Linezolid causes more GI side effects than vancomycin but requires no renal dose adjustment—preferred in severe renal impairment 1, 2
• Monitor for thrombocytopenia and neuropathy with linezolid use beyond 2 weeks 2

Special Populations

Renal Impairment

• Dose-adjust piperacillin-tazobactam: 6
  • CrCl 20-40 mL/min: 2.25 g q6h (3.375 g q6h for nosocomial pneumonia)
  • CrCl <20 mL/min: 2.25 g q8h (2.25 g q6h for nosocomial pneumonia)
  • Hemodialysis: 2.25 g q12h plus 0.75 g after each session

Severe Penicillin Allergy

• Aztreonam provides gram-negative coverage without cross-reactivity to other β-lactams 2
• Consider cephalosporin desensitization if non-anaphylactic allergy, as cross-reactivity is lower than historically believed 2