Pseudomonas aeruginosa: Definitions of MDR and DTR
Pseudomonas aeruginosa is considered multidrug-resistant (MDR) when it demonstrates non-susceptibility to at least one agent in three or more antimicrobial categories, while difficult-to-treat resistance (DTR) is defined as non-susceptibility to all first-line, high-efficacy, low-toxicity agents including all of: ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, imipenem/cilastatin, meropenem, levofloxacin and ciprofloxacin. 1, 2
MDR Pseudomonas aeruginosa Definition
The definition of MDR Pseudomonas aeruginosa follows the standardized classification system established by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC):
- MDR: Non-susceptibility to at least one agent in three or more antimicrobial categories 1, 2
- XDR (Extensively drug-resistant): Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
- PDR (Pan drug-resistant): Non-susceptibility to all agents in all antimicrobial categories
This classification helps standardize terminology across healthcare settings and research contexts. The MDR definition has been widely adopted in European guidelines and clinical practice 1.
DTR Pseudomonas aeruginosa Definition
The concept of "difficult-to-treat resistance" (DTR) was proposed to better define P. aeruginosa strains of particular clinical concern and to overcome limitations of the MDR classification. According to the Infectious Diseases Society of America (IDSA) and Italian guidelines:
DTR-PA is defined as P. aeruginosa isolates non-susceptible to ALL of the following 1:
- Ceftazidime
- Cefepime
- Piperacillin/tazobactam
- Aztreonam
- Imipenem/cilastatin
- Meropenem
- Levofloxacin
- Ciprofloxacin
This definition focuses specifically on resistance to all first-line, high-efficacy, low-toxicity agents, making it more clinically relevant than the broader MDR definition.
Clinical Significance and Treatment Implications
MDR P. aeruginosa
- Associated with higher mortality rates compared to non-MDR strains 3, 4
- Increased risk of inappropriate empirical therapy (44% vs. 6% in non-MDR) 4
- Often requires treatment with alternative agents like aminoglycosides
DTR P. aeruginosa
- Requires novel β-lactam agents for effective treatment 1
- First-line treatment options include:
- Ceftolozane/tazobactam
- Ceftazidime/avibactam
- Alternative options include:
- Imipenem/cilastatin–relebactam
- Cefiderocol
- Colistin-based therapy
Common Co-resistance Patterns
Recent research shows that MDR P. aeruginosa frequently demonstrates co-resistance to multiple antibiotic classes 5:
- 42.7% show co-resistance to carbapenems, extended-spectrum cephalosporins, and piperacillin-tazobactam
- 40.7% show co-resistance to carbapenems, extended-spectrum cephalosporins, and fluoroquinolones
Differences Between MDR and DTR
The key differences between MDR and DTR classifications:
- Specificity: DTR is more specific, focusing on resistance to all first-line agents, while MDR is broader (resistance to ≥3 categories)
- Clinical utility: DTR better identifies strains that are truly problematic for treatment
- Treatment approach: DTR strains almost always require newer agents like ceftolozane/tazobactam or ceftazidime/avibactam
Important Clinical Considerations
- DTR P. aeruginosa infections have higher mortality rates and require prompt identification
- Combination therapy is not routinely recommended for DTR-PA but may be considered in specific cases 1
- Novel agents like ceftolozane/tazobactam and ceftazidime/avibactam show the lowest co-resistance rates (5-12%) 5
- Infectious disease consultation is strongly recommended for management of MDR and DTR P. aeruginosa infections 2
It's important to note that the term "DTR" in the question might have been confused with "drug-resistant tuberculosis," which is a different clinical entity. MDR-TB refers specifically to tuberculosis that is resistant to at least isoniazid and rifampin, the two most potent first-line anti-TB drugs 1.