Treatment of Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Enterobacteriaceae

Introduction to Treatment Options

The American Thoracic Society and the Infectious Diseases Society of America recommend ceftazidime-avibactam combined with aztreonam as the preferred treatment for ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae, particularly when metallo-β-lactamase production is confirmed or suspected, due to significantly lower 30-day mortality (19.2% vs 44%) and superior clinical outcomes compared to colistin-based regimens 1, 2

The European Society of Clinical Microbiology and Infectious Diseases provides a conditional recommendation with moderate-quality evidence for ceftazidime-avibactam 2.5g IV q8h (infused over 2 hours) PLUS aztreonam as the strongly recommended regimen for MBL-producing CRE infections 1, 2, 3
Ceftazidime-avibactam 2.5g IV q8h as monotherapy is preferred for KPC or OXA-48-producing CRE infections, as nearly 100% of KPC-producing and OXA-48-producing CRE strains are susceptible to ceftazidime-avibactam 1, 3

The Infectious Diseases Society of America recommends obtaining carbapenemase genotyping or phenotypic testing immediately, and initiating empiric therapy based on local epidemiology, with ceftazidime-avibactam 2.5g IV q8h PLUS aztreonam if MBL prevalence is high, or ceftazidime-avibactam 2.5g IV q8h alone if predominantly KPC/OXA-48 1, 3

The European Society of Clinical Microbiology and Infectious Diseases provides a conditional recommendation with low-quality evidence for cefiderocol as an alternative treatment option, with clinical cure rates of 75% (12/16) in MBL-producing CRE subgroup from CREDIBLE-CR trial 2

The combination of ceftazidime-avibactam and aztreonam is specifically indicated for severe infections caused by metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (CRE), where it demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to alternative therapies 4, 5
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines suggest this combination therapy for patients with severe CRE infections carrying metallo-β-lactamases and/or resistant to newer antibiotic monotherapies (conditional recommendation, moderate evidence) 6

Aztreonam is not hydrolyzed by metallo-β-lactamases but is susceptible to ESBLs and AmpC enzymes commonly co-produced by these organisms 7

The carbapenemase type should be identified before treatment initiation whenever possible, as this combination is ineffective against non-MBL resistance mechanisms in Pseudomonas aeruginosa 4