Antibiotic Resistance and Treatment

Definitions and Classification

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
MDR organisms demonstrate resistance to multiple antimicrobial classes but remain susceptible to at least one or two categories of antibiotics 1
XDR represents an intermediate category: non-susceptibility to carbapenem and at least one agent in all but two antimicrobial categories 1
PDR is defined as non-susceptibility to all agents in all antimicrobial categories, representing the most extreme resistance phenotype 1

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 5, 6
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 3, 7
Monotherapy with highly active novel beta-lactams is preferred when susceptibility is confirmed for MDR organisms 4
Combination therapy is recommended for polymyxin-based regimens due to inferior outcomes with polymyxin monotherapy 8, 4

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 9
Surgical source control becomes the most critical intervention for PDR infections, as antimicrobial therapy alone has minimal efficacy 9
Infectious disease consultation is highly recommended (strong recommendation) for all MDRO infections, and is essentially mandatory for PDR organisms 1

For MDR CRAB infections, first-line treatment for pneumonia is colistin 5mg CBA/kg IV loading + maintenance dosing, with or without carbapenem, plus adjunctive inhaled colistin 3, 7
For MDR CRE infections, ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h are first-line (strong recommendation) 6
For PDR organisms, obtain infectious disease consultation immediately, prioritize aggressive source control, select 2-3 antibiotics with lowest MICs, and use prolonged infusions and optimize dosing based on therapeutic drug monitoring when available 1, 9

Never use aminoglycoside monotherapy for severe infections; reserve for uncomplicated UTI only 4
Tigecycline monotherapy should not be used for pneumonia or bloodstream infections due to poor outcomes 1, 3, 11
Do not assume carbapenem activity in MDR strains without susceptibility testing 4
Avoid empiric use of last-resort agents (colistin, new beta-lactams) without considering local resistance patterns and antibiotic stewardship 9
For PDR infections, do not rely solely on antimicrobial therapy—source control is the primary determinant of outcome 9