Therapy for ventilator-associated bacterial pneumonia (VAP or VABP, defined as pneumonia that develops ≥ 48 hours of mechanical ventilation), or ventilated hospital-acquired bacterial pneumonia (vHABP).
Important to differentiate colonization from pneumonia. Diagnosis is identified by using a combination of imaging, clinical, and laboratory criteria. 2023 National Healthcare Safety Network guidelines and algorithms here.
Etiologies
Early-onset (<5 days in the hospital, no other risk factors for multi-drug resistant (MDR) organisms)
Strep. pneumoniae
H. influenzae
Enteric gram-negative bacilli
Late-onset (≥ 5 days in the hospital, risk factors of MDR organisms present)
Clinical suspicion and presence of new or progressive pulmonary infiltrates on chest radiograph PLUS two of the following:
Fever
Peripheral leucocytosis
Purulent tracheal secretions
Blood cultures x 2
Culture, gram strain of tracheal aspirate or bronchoalveolar lavage fluid should be performed in all cases of suspected VAP.
PCR of sputum or urine antigen for L. pneumophila particularly in immunocompromised hosts.
Nasopharyngeal swab for PCR detection of respiratory viruses (COVID-19, influenza, RSV and perhaps others), especially in early-onset disease or suspected nosocomial transmission.
Nasal swab culture or PCR for MRSA (good negative predictive value, 76-99%, to rule out MRSA infection; generally poor positive predictive values, as low as 12% [Ann Pharmacother. 2019, 53:627])
Serum procalcitonin (PCT) where available; if negative, repeat in 4-6 hrs (assumes 1-2 hr turn around time)
Negative predictive value for bacterial infection over 95% if PCT < 0.25 ng/mL
Utility of molecular methods (e.g., a pneumonia multiplex PCR panel) to detect potential bacterial pathogens is unproven but may permit detection of pathogens whose growth is suppressed by prior antibiotics, which could result in less empiric therapy and/or better focused antimicrobial therapy.
The suggested diagnostics may not apply or may not be feasible or available in individual clinical settings.
DETECTED PATHOGENS MAY BE EITHER COLONIZING OR INVADING.
Primary Regimens
Low risk of MRSA (ICU prevalence <10-20%), no risk factors for MDR pathogens,
Levofloxacin 750 mg IV/po q24h (not recommended if ESBL-producing organism is suspected)
More severe disease, i.e., sepsis, hypotension, rapid progression of infiltrates on chest radiograph indicating high risk of mortality; MDR risk factor, MRSA prevalence >10-20%
Duration of therapy: See Antimicrobial Stewardship
Alternative Regimens
Linezolid 600 mg IV q12h can be substituted for Vancomycin
Aztreonam 2 gm IV q8h instead of cefepime, piperacillin-tazobactam, or meropenem for patients with severe IgE-mediated hypersensitivity to beta-lactams. However, unlike these other agents, aztreonam is not active against S. aureus or S.pneumoniae and hence should add vancomycin pending culture results.
For suspected carbapenem-resistant Enterobacterales infection: can substitute Ceftazidime-avibactam 2.5 gm IV infused over 2 hours q 8h for Cefepime, Piperacillin-tazobactam or Meropenem (does not cover metallo-beta-lactamase producing organisms)
If S. aureus nares screen is negative for MRSA no need to empirically cover for MRSA, and if coverage initiated, de-escalation is safe with a high negative predictive value (Clin Infect Dis 2020; 71:1142).
Modify the regimen to target the specific pathogen(s) based on results of culture (or molecular testing, if used) and antimicrobial susceptibility testing.
Duration of therapy
In general treat for 7-8 days
Whether a longer duration of therapy should be used for pneumonia caused by non-fermenting organisms (e.g., Pseudomonas aeruginosa) or multiple-drug resistant Gram-negatives continues to be debated (See Clin Infect Disease 2023; 76:745 and Clin Infect Dis 2023; 76:750).
Longer durations of therapy, e.g., 10-14 days, may be appropriate in certain circumstances:
Infections caused by more resistant pathogens (e.g., Pseudomonas,Acinetobacter, Stenotrophomonas, or other multidrug-resistant pathogens), particularly in patients with underlying ARDS or significant structural lung disease
Severely immunocompromised hosts (e.g. recent organ transplantation or treatment for rejection within 3 months, congenital immunodeficiency, etc).
Presence of complications such as bacteremia (e.g., MRSA or MSSA pneumonia with bacteremia probably should be treated for 4 weeks) or empyema.
Delayed improvement of clinical, radiologic, and/or laboratory parameters.
Alternatively, can trend serum procalcitonin levels
Retrospective cohort study found that 1-3 days of therapy was as effective as > 3 days for patients with suspected VAP and minimal and stable ventilator settings defined as daily minimum PEEP of ≤5 cm H2O and daily minimum FiO2 <40% for at least 3 days from the first day of antibiotics (Clin Infect Dis 64:870, 2017).
Multicenter, double-blind, randomized , placebo-controlled trial in adults (where available)
VAP in first 7 days: Placebo: 34%; Amoxicillin-clavulanatae: 19%, p 0.03
Comments
If MDR pathogens are suspected, initial coverage should be broad and then streamlined based on culture and susceptibility results.
Risk factors for MDR organisms:
Antimicrobial therapy in preceding 90 days.
Current hospitalization of 5 days or more.
Septic shock at time of VAP
Acute renal replacement therapy prior to onset of VAP
Antibiotic resistance prevalent in the community or specific hospital unit
Empiric regimen of choice may vary based on local prevalence and susceptibility of pathogens, known prior colonization with MDR organisms, prior treatment history, severity of illness.