Hospital-Acquired, Health Care-Associated, and Ventilator-Associated Pneumonia Organism-Specific Therapy

Organism-specific therapeutic regimens for hospital-acquired pneumonia (HAP), health care–associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP) are provided below, including those for Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S aureus (MSSA), Legionella pneumophila, Acinetobacter baumannii, and Stenotrophomonas maltophilia.[1]

Definitions are as follows:

• HAP: Diagnosis made more than 48 hours after admission
• VAP: Diagnosis made 48-72 hours after endotracheal intubation
• HCAP: Per the 2016 IDSA/ATS guidelines, this is no longer a subset of HAP, as isolated organisms are more consistent with CAP. Instead, individual risk factors for multidrug-resistant organisms (MDROs) should be assessed on a case-by-case basis.

Regimens for P aeruginosa pneumonia include the following:

• Piperacillin/tazobactam 4.5 g IV q6h (standard infusion) or 4.5 g IV q8h (infused over 4 hours) or
• Cefepime 2 g IV q8h or
• Ceftazidime/avibactam 2.5 g (2 g ceftazidime, 0.5 g avibactam) IV q8h infused over 2 hours or
• Imipenem/cilastatin 1 g q6-8h or
• Meropenem 2 g IV q8h (standard infusion or infused over 3 hours) or
• Cefiderocol 2 g IV q8h or
• Aztreonam 2 g IV q8h or
• Ceftolozane/tazobactam 3 g (2 g ceftolozane, 1 g tazobactam) infused over 1 hour (reserved for only carbapenem-resistant isolates) ^[2] or
• Meropenem/vaborbactam 4 g IV (2 g meropenem, 2 g vaborbactam) q8h infused over 3 hours (reserved for only carbapenem-resistant isolates) or
• Imipenem/cilastatin/relebactam 1.25 g IV q6h ^[3]
• Duration of therapy: 7 days
• Data are limited concerning the benefit of combination therapy for pseudomonal infections; when antimicrobial drug susceptibility results are known, it is reasonable to continue a single active beta-lactam agent and to discontinue the accompanying fluoroquinolone or aminoglycoside
• For empiric therapy, an aminoglycoside (gentamicin 7 mg/kg/day IV, tobramycin 7 mg/kg/day IV, or amikacin 20 mg/kg/day IV) or fluoroquinolone (ciprofloxacin 400 mg IV q8h or levofloxacin 750 mg IV q24h) may be added for empiric coverage if organism resistance to local isolate is 10% or more as per local antibiogram or local resistance is unknown.

Regimens for K pneumoniae pneumonia include the following:

• Ceftriaxone 2g IV q24h
• Cefepime 2 g IV q8h or
• Ceftazidime 2 g IV q8h or
• Piperacillin-tazobactam 4.5 g IV q6h or
• Cefiderocol 2 g IV q8h

Regimens for an extended-spectrum beta-lactamase (ESBL)–producing K pneumoniae strain include the following:

• Imipenem/cilastatin 500 mg IV q6h or
• Meropenem 1 g IV q8h or
• Cefiderocol 2 g IV q8h or
• Ceftolozane/tazobactam 3 g IV q8h or
• Imipenem/cilastatin/relebactam 1.25 g IV q6h or
• Ertapenem 1g q24h (if hemodynamically stable)

Regimens for carbapenem-resistant K pneumoniae (CRKP) strain pneumonia include the following:

• Colistin 5 mg/kg/day IV divided q12h or
• Polymyxin B 15,000-25,000 units/kg/day IV divided q12h (preferred over colistin) or
• Consider addition of meropenem 2 g IV q8h to colistin or polymyxin (based on limited data) or
• Imipenem/cilastatin/relebactam 1.25 g IV q6h or
• Ceftazidime/avibactam 2.5 g (2 g ceftazidime, 0.5 g avibactam) IV q8h infused over 2 hours or
• Meropenem-vaborbactam 4 g IV (2 g meropenem, 2 g vaborbactam) q8h infused over 3 hours; reserved for highly resistant organisms
• Duration of therapy: 7 days

Regimens for MRSA pneumonia include the following:

• Linezolid 600 mg IV or PO q12h for 7 days or
• Vancomycin 15 mg/kg IV q12h for 7 days or
• Telavancin 10mg/kg IV once daily for 7-21 days (reserved for use when alternative treatments are not suitable)

Regimens for MSSA pneumonia include the following:

• Oxacillin 2 g IV q4h for 7 days or
• Nafcillin 2 g IV q6h for 7 days (consider midline or peripherally inserted central catheter [PICC] owing to high incidence of phlebitis when given via peripheral intravenous [PIV] catheter) or
• Cefazolin 2 g IV q8h for 7 days
• Drugs listed for MRSA treatment may be used as alternatives if no beta-lactam drug is available

Regimens for L pneumophila pneumonia include the following:

• Levofloxacin 750 mg IV q24h, then 750 mg/day PO for 7 days or
• Moxifloxacin 400 mg IV or PO q24h for 7 days or
• Azithromycin 500 mg IV q24h for 7 days

Regimens for A baumannii pneumonia include the following:

• Imipenem 1 g IV q6h or
• Meropenem 2 g IV q8h (standard infusion or extended over 3 hours) or
• Cefiderocol 2 g IV q8h or
• Ampicillin/sulbactam 3 g IV q6h or
• Tigecycline 100 mg IV in a single dose, then 50 mg IV q12h or
• Minocycline 100 mg PO q12h or
• Colistin 5 mg/kg/day IV divided q12h or
• Polymyxin B 15,000-25,000 units/kg/day IV divided q12h
• Duration of therapy: 14-21 days

Regimens for S maltophilia pneumonia include the following:

• Trimethoprim/sulfamethoxazole 15-20 mg/kg/day of TMP IV or PO divided q8h or
• Ciprofloxacin 750 mg PO or 400 mg IV q12h or
• Moxifloxacin 400 mg PO or IV q24h
• Duration of therapy: Uncertain, but usually 14 days or more