Infectious Diseases I
Definitive antibiotic therapy should be focused on the causative pathogen(s) identified on lower
respiratory tract culture.
Pathogen-specific definitive antibiotic choices should be based on antibiotic susceptibilities and, if
possible, available evidence supporting efficacy and safety in patients with VAP.
MRSA: Vancomycin or linezolid; daptomycin is not indicated for pneumonia because of direct
inhibition by pulmonary surfactant. Although not included in the guidelines, ceftaroline is
also a potential treatment of MRSA HAP/VAP.
ii.
P. aeruginosa
| (a) | Monotherapy with a Ξ²-lactam listed below and found to be susceptible on final culture |
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results is recommended in immunocompetent patients not in septic shock and not at a
high risk of dying. Concomitant aminoglycoside or antipseudomonal fluoroquinolone is
recommended in immunocompromised patients and those in septic shock or at a high risk
of dying. Combination therapy can be de-escalated to monotherapy Ξ²-lactam once septic
shock resolves.
| (b) | Ξ²-Lactams: Cefepime, ceftazidime (has minimal activity against MSSA and should |
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not be used to for both P. aeruginosa and MSSA), piperacillin/tazobactam, imipenem,
meropenem, ceftolozane-tazobactam, ceftazidime-avibactam, or cefiderocol
| (c) | Aminoglycosides: Amikacin, gentamicin, or tobramycin |
|---|---|
| (d) | Fluoroquinolones: Ciprofloxacin or levofloxacin |
iii.
Acinetobacter spp.: Sulbactam-durlobactam, ampicillin-sulbactam (sulbactam is active agent),
carbapenems (eg, imipenem or meropenem), minocycline, or cefiderocol
iv.
Stenotrophomonas maltophilia: The combination of 2 of the following agents:
sulfamethoxazole-trimethoprim, levofloxacin, minocycline, or cefiderocol. For cultures
exhibiting metallo-Ξ²-lactamase, the combination of ceftazidime-avibactam and aztreonam
can be used.
Extended-spectrum Ξ²-lactamase (ESBL)-producing organisms: Carbapenem (e.g., ertapenem;
imipenem; meropenem)
vi.
Since the 2016 IDSA guidelines, cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam,
imipenem/cilastatin/relebactam, and sulbactam/durlobactam have been FDA approved for
the treatment of VAP. These agents can be considered for certain multidrug-resistant (MDR)
pathogens (e.g., ESBL; specific carbapenemases) in concert with an antimicrobial stewardship
program.
vii.
In 2024, IDSA updated its guidance document in the treatment of antimicrobial-resistant
gram-negative infections (Clin Infect Dis. 2024 Aug 7:ciae403).
Duration of definitive antibiotic therapy is recommended to be 7 days for all patients rather than
longer durations. Pathogen-based recommendations for duration of definitive antibiotic are no
longer indicated in VAP guidelines.
The PneumA trial was a pivotal noninferiority study that evaluated 8 days (7 full treatment
days) versus 15 days (14 full treatment days) for duration of definitive antibiotic therapy in
patients with bacteriologically diagnosed VAP. The primary noninferiority outcome was VAP
recurrence. All patients included in the study received appropriate empiric antibiotic therapy
| (a) | Definitive antibiotic therapy for 8 days was noninferior to 15 days in patients with VAP |
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not caused by nonβlactose-fermenting gram-negative bacilli (e.g., P. aeruginosa).
| (b) | Patients with VAP caused by nonβlactose-fermenting gram-negative bacilli in the |
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8-day group more often had VAP recurrence. This was primarily seen in patients with
P. aeruginosa, but also included other lactose-non-fermenters (e.g., Acinetobacter,
Stenotrophomonas, and Burkholderia spp.).