多重抗藥性GNB治療建議

Pathogen	Preferred Treatment	Alternative Options	Agents to Avoid	Notes (MIC, PK, Resistance)
ESBL-Producing Enterobacterales	Carbapenems (meropenem/imipenem)	TMP-SMX, Ciprofloxacin, Levofloxacin (if susceptible)	Piperacillin-tazobactam, Cefepime (for serious infections)	MIC ≥2 for ceftriaxone suggests ESBL Carbapenems remain reliable first-line Confirm TMP-SMX activity via AST Avoid cefepime if MIC ≥4 µg/mL Fluoroquinolone resistance common in high-burden areas
AmpC-Producing Enterobacterales	Cefepime (preferred), Carbapenems	TMP-SMX, Fluoroquinolones, Aminoglycosides	3rd-gen cephalosporins, Piperacillin-tazobactam (serious infections)	AmpC is inducible; avoid ceftazidime, ceftriaxone Cefepime stable to AmpC hydrolysis High-dose cefepime or carbapenem improves PK/PD Inoculum effect may reduce cephalosporin efficacy
Carbapenem-Resistant Enterobacterales (CRE)	Ceftazidime-avibactam, Meropenem-vaborbactam, Imipenem-cilastatin-relebactam	Cefiderocol, Tigecycline, Colistin (limited)	Polymyxin or carbapenem monotherapy	Resistance via KPC, OXA-48, NDM Avibactam active vs KPC/OXA-48, not MBL Cefiderocol effective against MBL (NDM, VIM) MIC ≤8 µg/mL for ceftazidime-avibactam Tigecycline: poor urine levels, bacteriostatic
CRAB (A. baumannii)	Sulbactam-durlobactam + meropenem/imipenem, or High-dose ampicillin-sulbactam	Minocycline, Cefiderocol, Polymyxin B	Tigecycline monotherapy, Meropenem, Rifampin, Fosfomycin	Common resistance: OXA-type enzymes, ADC Sulbactam targets PBP1a/3; durlobactam protects it High-dose sulbactam (9g/day) often needed MIC >8 µg/mL often predicts treatment failure Cefiderocol: good *in vitro*, mixed clinical data
DTR P. aeruginosa	Ceftolozane-tazobactam, Ceftazidime-avibactam, Imipenem-cilastatin-relebactam	Cefiderocol, Aminoglycosides (for UTI)	Fluoroquinolones, β-lactam monotherapy without AST	DTR = resistant to ≥6 traditional agents Mechanisms: AmpC, efflux, OprD loss Cefiderocol: ~99% susceptible in surveillance Aminoglycosides preferred in UTI due to renal excretion Monotherapy sufficient if active β-lactam confirmed
Stenotrophomonas maltophilia	TMP-SMX + Minocycline or Cefiderocol	Ceftazidime-avibactam + Aztreonam (in severe cases)	Monotherapy before improvement, Omadacycline	Intrinsic resistance via L1/L2 β-lactamases TMP-SMX: only bacteriostatic even at high doses Minocycline: CLSI MIC ≤1 µg/mL preferred Cefiderocol: high susceptibility, limited trials Rapid fluoroquinolone resistance via qnr, efflux

Abbreviations:

• MIC: Minimum Inhibitory Concentration
• PK: Pharmacokinetics
• PD: Pharmacodynamics
• AST: Antimicrobial Susceptibility Testing
• CLSI: Clinical and Laboratory Standards Institute
• TMP-SMX: Trimethoprim-sulfamethoxazole
• CZA: Ceftazidime-avibactam
• C/TZ: Ceftolozane-tazobactam
• IMR: Imipenem-cilastatin-relebactam
• MBL: Metallo-β-lactamase
• OXA: Oxacillinase-type carbapenemase
• KPC: Klebsiella pneumoniae carbapenemase
• NDM: New Delhi Metallo-β-lactamase
• VIM: Verona Integron-encoded Metallo-β-lactamase
• DTR: Difficult-to-Treat Resistance
• CRAB: Carbapenem-Resistant Acinetobacter baumannii