Definitions and Key Distinctions
Multidrug-resistant (MDR) bacteria retain susceptibility to at least one or two antimicrobial classes, whereas pan-drug-resistant (PDR) bacteria are non-susceptible to all agents in all antimicrobial categories, leaving essentially no treatment options. 1
Multidrug-Resistant (MDR) Bacteria
- MDR organisms demonstrate resistance to multiple antimicrobial classes but remain susceptible to at least one or two categories of antibiotics. 1
- For example, carbapenem-resistant Acinetobacter baumannii (CRAB) that remains susceptible to colistin or sulbactam qualifies as MDR but not PDR. 1
- MDR Pseudomonas aeruginosa may still respond to newer beta-lactam/beta-lactamase inhibitor combinations like ceftolozane-tazobactam or ceftazidime-avibactam. 2
Extensively Drug-Resistant (XDR) Bacteria
- XDR represents an intermediate category: non-susceptibility to carbapenem and at least one agent in all but two antimicrobial categories. 1
- XDR Acinetobacter baumannii (XDR-AB) typically retains susceptibility to only polymyxins (colistin) and possibly tigecycline or sulbactam. 1
Pan-Drug-Resistant (PDR) Bacteria
- PDR is defined as non-susceptibility to all agents in all antimicrobial categories, representing the most extreme resistance phenotype. 1
- PDR Acinetobacter baumannii (PDR-AB) demonstrates resistance to all tested antibiotics including polymyxins, carbapenems, tigecycline, and sulbactam. 1
Treatment Approach Differences
MDR Bacterial Infections
Available Treatment Options
- For MDR carbapenem-resistant Enterobacterales (CRE), novel beta-lactam combinations are first-line: ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h. 1
- For MDR Pseudomonas aeruginosa, ceftolozane-tazobactam 3g IV q8h (for pneumonia) or ceftazidime-avibactam 2.5g IV q8h are preferred. 2
- Colistin-based combination therapy remains an option for CRAB pneumonia: colistin 5mg CBA/kg IV loading dose, then 2.5mg CBA×(1.5×CrCl+30) IV q12h, with or without carbapenem. 1
Monotherapy vs. Combination
- Monotherapy with highly active novel beta-lactams is preferred when susceptibility is confirmed for MDR organisms. 2
- Combination therapy is recommended for polymyxin-based regimens due to inferior outcomes with polymyxin monotherapy. 1, 2
- For CRAB bloodstream infections, colistin-carbapenem combination therapy is recommended over monotherapy. 1
PDR Bacterial Infections
Severely Limited Options
- For PDR organisms, treatment selection must be based on the least resistant antibiotic(s) relative to MIC breakpoints, with primary emphasis on optimal source control. 1
- When all antibiotics show resistance, clinicians must select agents with the lowest MICs even if technically "resistant" by breakpoint criteria. 1
Source Control is Paramount
- Surgical source control becomes the most critical intervention for PDR infections, as antimicrobial therapy alone has minimal efficacy. 1
- Drainage of abscesses, removal of infected devices, debridement of necrotic tissue, and elimination of anatomic sources of infection are mandatory. 1
Experimental Approaches
- Infectious disease consultation is highly recommended (strong recommendation) for all MDRO infections, and is essentially mandatory for PDR organisms. 1
- Consider combination therapy with 2-3 agents showing the lowest MICs, even if all are technically "resistant." 1
- Prolonged infusion of beta-lactams (3-4 hours) may optimize pharmacokinetics for pathogens with high MICs. 1, 2
Specific Treatment Algorithms
For MDR CRAB Infections
Pneumonia:
- First-line: Colistin 5mg CBA/kg IV loading + maintenance dosing, with or without carbapenem (imipenem 500mg IV q6h or meropenem 2g IV q8h), plus adjunctive inhaled colistin. 1
- Alternative: Sulbactam 6-9g/day IV in 3-4 divided doses. 1
- Do NOT use tigecycline monotherapy for pneumonia (strong recommendation). 1
Bloodstream Infections:
For MDR CRE Infections
KPC-producing CRE:
- Ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h are first-line (strong recommendation). 1
- Imipenem-relebactam 1.25g IV q6h is an alternative. 1
MBL-producing CRE:
- Ceftazidime-avibactam 2.5g IV q8h PLUS aztreonam is strongly recommended. 1
- Cefiderocol may be considered as an alternative (conditional recommendation). 1
OXA-48-producing CRE:
- Limited data; ceftazidime-avibactam shows promise but requires further study. 1
For PDR Organisms
- Obtain infectious disease consultation immediately. 1
- Prioritize aggressive source control (drainage, debridement, device removal). 1
- Select 2-3 antibiotics with lowest MICs, even if all show "resistance." 1
- Use prolonged infusions and optimize dosing based on therapeutic drug monitoring when available. 1
- Consider experimental agents or compassionate use protocols if available. 1
Critical Pitfalls to Avoid
- Never use aminoglycoside monotherapy for severe infections; reserve for uncomplicated UTI only. 2
- Tigecycline monotherapy should not be used for pneumonia or bloodstream infections due to poor outcomes. 1, 3
- Do not assume carbapenem activity in MDR strains without susceptibility testing. 2
- Avoid empiric use of last-resort agents (colistin, new beta-lactams) without considering local resistance patterns and antibiotic stewardship. 1
- For PDR infections, do not rely solely on antimicrobial therapy—source control is the primary determinant of outcome. 1