Antimicrobial Therapy Guidelines

Initial Empiric Therapy

The Infectious Diseases Society of America recommends initial empiric therapy with a β-lactam plus macrolide combination or a respiratory fluoroquinolone for non-ICU patients, and a β-lactam plus either a macrolide or a respiratory fluoroquinolone for ICU patients 1

The American College of Clinical Pharmacy, the World Society of Emergency Surgery, and the American College of Microbiology recommend obtaining blood cultures before initiating antimicrobial therapy and performing antimicrobial susceptibility testing to guide definitive therapy 1, 2
A susceptible range for non-meningeal infections is defined as an MIC ≤1 mg/mL for ceftriaxone 1

The American College of Microbiology recommends Ceftazidime-avibactam 2.5g IV every 8 hours as the first-line treatment for CRE infections, with the specific regimen tailored to the infection site and susceptibility testing results 3
Ceftazidime-avibactam has shown excellent efficacy in treating carbapenem-resistant infections and may be considered as an alternative to carbapenems, as recommended by the Infectious Diseases Society of America and the International Society for Antimicrobial Chemotherapy 4, 3
The following treatment regimens are recommended for specific infections:

Infection Type	Recommended Treatment Duration
Bloodstream infections	10-14 days [3, 5]
Complicated urinary tract infections	7-14 days [3, 5]
Complicated intra-abdominal infections	5-14 days [3, 5]
Hospital-acquired or ventilator-associated pneumonia	7-14 days [3, 5]
Pneumonia	typically 10 days, but may need to be extended in immunocompromised patients or those with severe infection [4, 7]

Clinical response should be monitored within 48-72 hours of initiating therapy, and if no improvement is seen after 72 hours of adequate coverage, catheter removal or source control issues should be considered, as recommended by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America 8, 9

Aminoglycoside-containing combinations are recommended for CRE infections when susceptible, but require close monitoring of renal function and avoidance of other nephrotoxic drugs 5
Fosfomycin-containing combinations are recommended when the CRE isolate is susceptible to fosfomycin or a synergistic effect is demonstrated, but should be avoided in patients with hypernatremia, cardiac or renal insufficiency 5
Polymyxin-based combinations with a carbapenem may be considered for highly resistant strains of bacteria, as recommended by the International Society for Antimicrobial Chemotherapy 4, 3
Therapeutic drug monitoring (TDM) is strongly recommended for polymyxins, aminoglycosides, and carbapenems, particularly in patients with organ dysfunction, difficult-to-reach infection sites, or severe infections like bloodstream infections and sepsis 5
Dosing adjustment is required in patients with renal impairment (CrCl ≤50 mL/min), as recommended by the Infectious Diseases Society of America and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 3, 5
High-dose extended-infusion meropenem (2g IV q8h as 3-hour infusion) is the optimal choice when treating carbapenem-resistant organisms, as recommended by the Infectious Diseases Society of America 10

Third-generation cephalosporins should be avoided as they may induce AmpC β-lactamase production, leading to increased resistance, as warned by the World Health Organization and the Clinical Microbiology and Infection guidelines 7, 9, 11
Tigecycline monotherapy should be avoided for CRE pneumonia due to poor outcomes 3

Infectious disease consultation is highly recommended for the management of CRE infections 3
Therapy should be adjusted based on susceptibility testing results 3, 5