Spontaneous bacterial peritonitis due to carbapenemase-producing Enterobacteriaceae: Etiology and antibiotic treatment

Table 1 Synthesis of a selection of the studies published on spontaneous bacterial peritonitis due to carbapenem-resistant Enterobacteriaceae producing pathogens

Ref.	Total number SBP/CRE SBP	CRE	CRE N-SBP/Total SBP	Not-N-SBP/Total SBP
Piano et al[14], 2012	1/1	K. pneumoniae	1/1	0/1
Li et al[27], 2015	31/6	K. pneumoniae, E. coli	2/4, 2/2	2/4, 0/2
Alexopoulou et al[28], 2016	130/6	K. pneumoniae, E. coli	5/5, 1/1	0/5, 0/1
Lutz et al[29], 2016	92/3	E. faecium	3/3	0/3
Tudorascu et al[30], 2016	64/3	K. pneumoniae, E. coli, Enterobacter	1/1, 1/1, 1/1	0/1, 0/1, 0/1
Salerno et al[31], 2016	56/8	K. pneumoniae, E. coli	5/7, 0/1	7/2, 1/1
Béjar-Serrano et al[32], 2019	22/1	E. cloacae	1/1	0/1

CRE: Carbapenem-resistant Enterobacteriaceae; N: Nosocomial; SBP: Spontaneous bacterial peritonitis; CRE SBP: Spontaneous bacterial peritonitis due to carbapenem-resistant Enterobacteriaceae; CRE N-SBP: Nosocomial spontaneous bacterial peritonitis due to carbapenem-resistant Enterobacteriaceae; Not-N-SBP: Not nosocomial spontaneous bacterial peritonitis; K. pneumoniae: Klebsiella pneumoniae; E. coli: Escherichia coli; E. cloacae: Enterobacter cloacae; E. faecium: Enterococcus faecium.

Table 2 Class A carbapenemase asset found in each pathogen

Pathogens	Class A carbapenemase
	KPC-1	KPC-2	KPC-3	GES-4	GES-5	GES-6	SME-1	SME-2	SME-3	NMC-A
K. pneumoniae	+	+	+	+	+	+
S. marcescens							+	+	+
E. coli					+
E. cloacae			+							+

KPC: Klebsiella pneumoniae; GES: Guiana-Extended-Spectrum; SME: Serratia marcescens enzyme; K. pneumoniae: Klebsiella pneumoniae; E. coli: Escherichia coli; E. cloacae: Enterobacter cloacae; S. marcescens: Serratia marcescens.

Table 3 Class B carbapenemase asset found in each pathogen

Pathogens	Class B carbapenemase
	IMP-1	IMP-1-like	IMP-4	IMP-8	VIM-1	VIM-1-like	VIM-2	VIM-2-like	VIM-4	VIM-5
K. pneumoniae	+	+	+		+		+		+	+
S. marcescens		+				+	+	+
E. coli		+	+			+
E. cloacae		+	+	+	+		+	+	+	+
C. freundii	+	+					+

IMP: Imipenemase; VIM: Verona imipenemase; K. pneumoniae: Klebsiella pneumoniae; E. coli: Escherichia coli; E. cloacae: Enterobacter cloacae; S. marcescens: Serratia marcescens; C. freundii: Citrobacter freundii.

Table 4 Class D carbapenemase asset found in each pathogen

Pathogens	Class D carbapenemase
	OXA-48	OXA-163	OXA-181	OXA-244
K. pneumoniae	+	+	+
S. marcescens	+
E. coli	+		+	+
E. cloacae	+

OXA: Oxacillin-hydrolyzing; K. pneumoniae: Klebsiella pneumoniae; E. coli: Escherichia coli; E. cloacae: Enterobacter cloacae; S. marcescens: Serratia marcescens.

Table 5 Advantages and disadvantages of the antimicrobials used to treat spontaneous bacterial peritonitis due to gram-negative bacteria producing carbapenem-resistant Enterobacteriaceae

Antimicrobial agent	Advantages	Disadvantages	Ref.
Aminoglycosides (i.e. Plazomicin)	Good activity against GNB producing ESβL, KPC, AmpC but not MβL enzymes	Heterogeneous susceptibility high dose (toxicity)	[49]
Polimixins (i.e. Colistin)	Low resistance emergence	Low efficacy for Klebsiella spp. producing KPC enzymes	[56]
Fosfomicyn	Moderate activity against MDR–CRE	Rapid emergence of antibiotic resistance	[59]
Glycylcycline (i.e. Tigecycline)	Good activity against MDR–CRE	High dose (toxicity)	[62]
Fluorocycline (i.e. Eravacycline)	Broad spectrum activity (even if MDR and XDR pathogens). Active against the most common tetracycline-resistance mechanisms. High oral bioavailability. Safety and tolerability	Not active on Pseudomonas spp. and Burkholderia spp.	[63- 65]
β-lactams/β-lactamase inhibitors (i.e. ceftazidime/avibactam)	Good activity against GNB producing ESβL, KPC, AmpC, OXA-48 and MβL. Safety and tolerability	Frequent emergence of antibiotic resistance	[67]
Carbapenem/β-lactamase inhibitors (i.e. meropenem/vaborbactam or Imipenem/cilastatin/relebactam)	Good activity against GNB producing ESβL, KPC and AmpC. Outcome improvement	Not active on GNB producing OXA-48 and MβL	[79]
Monobactam/β-lactamase inhibitor (i.e. aztreonam/avibactam)	Good activity against GNB producing ESβL, KPC, AmpC and OXA-48	Recently approved	[50- 52]
Siderophore cephalosporin (i.e. Cefidecol)	Broad spectrum of activity against GNB, including MDR Enterobacteriaceae, Pseudomonas aeruginosa and A. baumannii	Recently approved	[50]

GNB: Gram-negative bacteria; ESβL: Extended-spectrum β-lactamase; CRE: Carbapenem-resistant Enterobacteriaceae, KPC: Klebsiella pneumoniae; MβL: Molecular class B β-lactamases; MDR: Multidrug resistant; XDR: Extensively resistant.