What are Multi-Drug Resistance Organisms (MDROs)?

Definition of Multi-Drug Resistant Organisms (MDROs)

Multi-drug resistant organisms (MDROs) are bacteria that have acquired non-susceptibility to at least one agent in three or more antimicrobial categories, representing a major global health threat with significant implications for morbidity, mortality, and healthcare costs. 1

Standardized Definitions

The international expert consensus provides three tiers of resistance classification 1:

• Multidrug-resistant (MDR): Non-susceptibility to at least one agent in three or more antimicrobial categories 1
• Extensively drug-resistant (XDR): Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (bacterial isolates remain susceptible to only one or two categories) 1
• Pandrug-resistant (PDR): Non-susceptibility to all agents in all antimicrobial categories 1

Key MDRO Pathogens

Gram-Positive MDROs

• Methicillin-resistant Staphylococcus aureus (MRSA): Remains an important pathogen with high levels in several European countries, though percentages have declined 2
• Vancomycin-resistant Enterococcus (VRE): Defined as ampicillin and vancomycin-resistant enterococci with high-level resistance to aminoglycosides 2

Gram-Negative MDROs

The situation is more challenging for Gram-negative bacilli, with alarming increases in resistance 2:

• Carbapenem-resistant Enterobacterales (CRE): Defined as Enterobacterales resistant to doripenem, imipenem, or meropenem, including both carbapenemase-producing and non-producing strains 2

  • More than one-half of E. coli and more than one-third of K. pneumoniae isolates are resistant to at least one antimicrobial group 2
  • K. pneumoniae shows 7.9% carbapenem resistance 3

• Carbapenem-resistant Pseudomonas aeruginosa (CRPA): P. aeruginosa that are non-susceptible to any carbapenem 2

  • 16.5% of P. aeruginosa isolates show carbapenem resistance 3

• Carbapenem-resistant Acinetobacter baumannii (CRAB): Including extensively drug-resistant (XDR-AB) and pandrug-resistant (PDR-AB) strains 2

  • Greater than 30% of A. baumannii isolates demonstrate carbapenem resistance 3

Clinical Significance

MDROs represent a leading cause of healthcare-associated infections worldwide with severe consequences 2:

• Increased mortality: Healthcare-acquired MDRO infections carry an adjusted odds ratio of 2.91 for mortality 4
• Prolonged hospital stays: Contributing to extended healthcare utilization 2
• Higher healthcare costs: Due to complex treatment requirements and extended care 2
• Limited treatment options: Often requiring last-resort antibiotics with high toxicity or poor efficacy 2

Gram-Negative vs. Gram-Positive Mortality Risk

Gram-negative bacteria demonstrate greater mortality risk (adjusted OR 1.63) compared to Gram-positive organisms, with A. baumannii showing the highest prevalence at 30.7% among isolated MDRO organisms 4

Important Clinical Caveats

• Proper testing required: Bacterial isolates should be tested against all or nearly all antimicrobial agents within the antimicrobial categories to correctly apply MDRO definitions 1
• Avoid selective reporting: Suppression of antimicrobial susceptibility results should be avoided to ensure accurate MDRO classification 1
• Infectious disease consultation: Highly recommended for management of MDRO infections due to limited active agents, need for PK/PD optimization, and complex disease evaluation 2