Carbapenem-resistant organisms

Background

• Mechanisms include decreased expression of porins, increased expression of efflux pumps, and carbapenemases

Management

• See also Carbapenem-resistant Enterobacterales and ESCMID guidelines1

Antibiotic	KPC	NDM	OXA-48	CRPsA	CRAB	Stenotrophomonas
New antibiotics
aztreonam-avibactam	+	+	+	±	–	+
cefiderocol	+	+	+	+	+	+
ceftazidime-avibactam	+	–	+	±	–	–
ceftolozane-tazobactam	–	–	–	±	–	±
eravacycline	+	+	+	–	+	+
imipenem-relebactam	+	–	±	+	–	–
meropenem-vaborbactam	+	–	–	–	–	–
plazomicin	+	±	+	±	–	–
Old antibiotics
fosfomycin	±	±	±	±	–	–
colistin	±	±	±	±	±	±
tigecycline	+	+	+	–	+	+
polymixins	+	+	+	+	+
aztreonam	–	±	–	±	–
temocillin	±	–	–	–	–

• For KPC (the most common Class A carbapenemase) consider: ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol
• For AmpCs, consider: ceftazidime-avibactam, meropenem-vaborbactam
• For OXA-48-like producers, consider: ceftazidime-avibactam (preferred), or cefiderocol
• For metallo-β-lactamases, consider: aztreonam-avibactam, or ceftazidime-avibactam plus aztreonam, cefiderocol
• For all of the above, also consider: eravacycline, tigecycline, colistin (though increasing resistance), plazomicin
• For carbapenem-resistant Pseudomonas aeruginosa, consider: ceftolozane-tazobactam (if susceptible), cefiderocol, imipenem-relebactam

Dosing

Antimicrobial	Dose	Targetted Organisms
amikacin	20 mg/kg IV load then per PK monitoring Cystitis: 15 mg/kg IV once	ESBL-E, AmpC-E, CRE, DTR-PA
ampicillin-sulbactam	9 g IV q8h infused over 4 h, or 27 g IV over 24 hours continuous infusion	CRAB
cefepime	2 g IV q8h infused over 2 h Cystitis: 1 g IV q8h	AmpC-E
cefiderocol	2 g IV q8h infused over 3 h	CRE, DTR-PA, CRAB, Stenotrophomonas
ceftazidime-avibactam	2.5 g IV q8h infused over 3 h	CRE, DTR-PA
ceftazidime-avibactam plus aztreonam	2.5 g IV q8h infused over 3 h plus 2 g IV q8h infused over 3 h, infused concurrently if possible	MBL CRE, Stenotrophomonas
ceftolozane-tazobactam	3 g IV q8h infused over 3 h Cystitis: 1.5 g IV q8h infused over 1 h	DTR-PA
ciprofloxacin	400 mg IV q8-12h or 500-750 mg p.o. q12h	ESBL-E, AmpC-E
colistin		CRE cystitis, DTR-PA cystitis, CRAB cystitis
eravacycline	1 mg/kg IV q12h	CRE, CRAB
ertapenem	1 g IV q24h infused over 30 min	ESBL-E, AmpC-E
fosfomycin	Cystitis: 3 g p.o. once	ESBL-E. coli cystitis
gentamicin	7 mg/kg IV load then based on PK Cystitis: 5 mg/kg IV once	ESBL-E, AmpC-, CRE, DTR-PA
imipenem-cilastatin	ESBL-E or AmpC-E: 500 mg IV q6h infused over 30 min CRE and CRAB: 500 mg IV q6h infused over 3 h Cystitis: 500 mg IV q6h infused over 30 min	ESBL-E, AmpC-E, CRE, CRAB
imipenem-cilastatin-relebactam	1.25 g IV q6h infused over 30 min	CRE, DTR-PA
levofloxacin	750 mg p.o./IV q24h	ESBL-E, AmpC-E, Stenotrophomonas
meropenem	ESBL-E or AmpC-E: 1-2 g IV q8h infused over 30 min CRE and CRAB: 2 g IV q8h infused over 30 min Cystitis: 1 g IV q8h, infused over 30 min	ESBL-E, AmpC-E, CRE, CRAB
meropenem-vaborbactam	4 g IV q8h infused over 3 h	CRE
minocycline	200 mg IV/p.o. q12h	CRAB, Stenotrophomonas
nitrofurantoin	cystitis: macrocystals 100 mg p.o. q12h or oral suspension 50 mg p.o. q6h	ESBL-E cystitis, AmpC-E cystitis
plazomicin	15 mg/kg IV load then dosed by PK Cystitis: 15 mg/kg IV once	ESBL-E, AmpC-E, CRE, DTR-PA
polymyxin B		DTR-PA, CRAB
tigecycline	200 mg IV load followed by 100 mg IV q12h	CRE, CRAB, Stenotrophomonas
tobramycin	7 mg/kg IV load then dosed by PK Cystitis: 5 mg/kg IV once	ESBL-E, AmpC-E, CRE, DTR-PA
co-trimoxazole	8-12 mg/kg/day (TMP) p.o./IV divided 18-12h Cystitis: 160 mg (TMP) p.o./IV q12h	ESBL-E, AmpC-E, Stenotrophomonas