Management of Gram-Negative Multi-Drug Resistant Infections

Patient Risk Stratification

The World Health Organization and other guideline societies recommend risk stratification for appropriate empiric therapy selection, helping to avoid both undertreatment and overuse of broad-spectrum antibiotics, with key risk factors including prior infection/colonization with MDR organisms, antibiotic therapy within past 90 days, poor functional status, hospitalization >2 days in past 90 days, current hospitalization ≥5 days, hemodialysis, and immunosuppression 1
Prior receipt of carbapenems, broad-spectrum cephalosporins, and fluoroquinolones specifically increases risk for MDR Pseudomonas aeruginosa, according to the Infectious Diseases Society of America 1

The European Society of Clinical Microbiology and Infectious Diseases recommends newer β-lactam/β-lactamase inhibitor combinations like ceftazidime-avibactam and meropenem-vaborbactam as first-line options for KPC-carbapenemase-producing pathogens 2
Ceftolozane-tazobactam is the preferred agent for MDR Pseudomonas aeruginosa infections, as recommended by the American Thoracic Society 2
Double-covering therapy might be considered for severe infections, though evidence is of very low certainty, according to the Infectious Diseases Society of America 2

The Centers for Disease Control and Prevention recommend implementing strong hand hygiene education programs with monitoring and feedback to healthcare workers, as well as performing active screening cultures at hospital admission for high-risk patients, followed by contact precautions 4, 5
Cohorting patients with MDR gram-negative bacteria in designated areas and ensuring proper environmental cleaning with specific protocols for disinfection are also recommended by the World Health Organization 5

The Infectious Diseases Society of America recommends implementing in-ward antimicrobial stewardship programs to reduce selection pressure for resistance, as well as using procalcitonin-guided therapy to reduce unnecessary antibiotic exposure in respiratory infections and sepsis 1
Preserving carbapenems by using carbapenem-sparing options for susceptible organisms when possible is recommended by the European Society of Clinical Microbiology and Infectious Diseases, to delay resistance development 3

Obtaining microbiological cultures before initiating therapy to guide targeted treatment is recommended by the American Society for Microbiology, as well as considering periodic screening cultures for patients at high risk of MDR-GNB carriage due to ICU stay, prolonged antibiotic therapy, or presence of devices 3, 4

Relying on monotherapy for highly resistant pathogens when combination therapy may be needed is a common pitfall, according to the Infectious Diseases Society of America, and neglecting source control can also lead to poor outcomes 2
Overlooking infection control measures is critical for preventing transmission of MDR organisms, as recommended by the Centers for Disease Control and Prevention 4, 5