Direct use of eazyplex^® SuperBug CRE assay from positive blood cultures in conjunction with inpatient infectious disease consulting for timely appropriate antimicrobial therapy in Escherichia coli and Klebsiella pneumoniae bloodstream infections

Figures & data

Figure 1 Diagnostic workflow using MALDI BioTyper^TM analysis/eazyplex^® SuperBug CRE assay (direct procedure) or culture-based methods (reference procedure) on positive blood cultures from E. coli or K. pneumoniae bloodstream infections (BSIs). Results from both the diagnostic procedures were notified to an IDCT for streamlining the antimicrobial treatments of BSIs.

Abbreviations: ID, identification; IDCT, infectious disease consultation team.

Table 1 Antimicrobial susceptibilities for 321 Escherichia coli and Klebsiella pneumoniae BSI organisms (151 positive and 170 negative by the eazyplex^® SuperBug CRE assay detection) according to the presence of resistance genes

Type of β-lactamase in the indicated species (no. of isolates)^a	No. (%) of isolates susceptible to the following antimicrobial agents
	CTX	CAZ	FEP	ETP	MEM	TZP	AK	GM	CIP	SXT	TGC	CST
E. coli (214)
blaCTX-M (77)	0 (0.0)	5 (6.5)	0 (0.0)	77 (100)	77 (100)	53 (68.8)	51 (66.2)	47 (61)	6 (7.8)	38 (49.3)	–	–
blaCMY (5)^b	0 (0.0)	0 (0.0)	5 (100)	5 (100)	5 (100)	1 (20.0)	4 (80.0)	3 (60.0)	1 (20.0)	1 (20.0)	–	–
blaKPC/blaVIM (2)	0	0	0	0	0	0	1	1	0	1	2	2
None (130)	130 (100)	130 (100)	130 (100)	130 (100)	130 (100)	114 (87.7)	129 (99.2)	113 (86.9)	95 (73.1)	83 (63.8)	–	–
K. pneumoniae (107)
blaCTX-M (23)	0 (0.0)	0 (0.0)	0 (0.0)	23 (100)	23 (100)	6 (26.1)	17 (73.9)	6 (26.1)	2 (8.7)	3 (13.0)	–	–
blaCMY (1)^b	1	1	1	0	0	0	1	1	1	1	–	–
blaKPC/blaVIM (49)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	12 (24.5)	41 (83.7)	2 (4.0)	9 (18.4)	39 (78.6)	29 (59.2)
None (34)	34 (100)	34 (100)	34 (100)	34 (100)	34 (100)	30 (88.2)	34 (100)	34 (100)	30 (88.2)	31 (91.2)	–	–

Notes: Colistin and tigecycline susceptibility results were available only for carbapenem-resistant isolates. We did not calculate percentages in cases with less than five isolates. ^aWe identified the extended-spectrum β-lactamase (ESBL), plasmidic AmpC β-lactamase, and carbapenemase genes by standard PCR sequencing analysis. Specifically, E. coli isolates harbored bla_CTX-M-15 (n=55), bla_CTX-M-14 (n=9), bla_CTX-M-27 (n=13), bla_CMY-2 (n=5), bla_KPC-3 (n=1), and bla_VIM-1 (n=1); K. pneumoniae isolates harbored bla_CTX-M-15 (n=23), bla_CMY-2 (n=1), bla_KPC-2 (n=2), bla_CTX-M-15+ bla_KPC-3 (n=4), bla_KPC-3 (n=41), and bla_KPC-3+ bla_VIM-1 (n=2). None refers to the isolates not harboring such genes. ^bSix isolates harboring bla_CMY genes had a negative result with the eazyplex^® SuperBug CRE assay.

Abbreviations: CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; ETP, ertapenem; MEM, meropenem; TZP, piperacillin-tazobactam; AK, amikacin; GM, gentamicin; CIP, ciprofloxacin; SXT, trimethoprim-sulfamethoxazole; TGC, tigecycline; CST, colistin.

Table 2 Appropriate empirical or diagnostic-driven antimicrobial treatments stratified by the type of organisms causing bloodstream infections in 321 patients

	No. (%) of appropriate empirical treatments	No. (%) of modifications leading to appropriate treatments, according to the results by
		MALDI BioTyper^TM analysis plus eazyplex^® SuperBug CRE assay	Antimicrobial susceptibility testing
Organisms causing BSI
KPC/VIM-producing E. coli (n=2)	0/2 (0.0)	2/2 (100)	0/2 (0.0)
CTX-M-producing E. coli (n=77)	22/77 (28.6)	48/77 (62.3)	7/77 (9.1)
CMY-producing E. coli (n=5)	1/5 (20.0)	3/5 (60.0)	1/5 (20.0)
ESCS-carbaS E. coli (n=130)	77/130 (59.2)	44/130 (33.8)	9/130 (6.9)
KPC/VIM-producing K. pneumoniae (n=49)	3/49 (6.1)	31/49 (63.3)	14/49 (28.6)^a
CTX-M-producing K. pneumoniae (n=23)	8/23 (34.8)	14/23 (60.9)	1/23 (4.3)
CMY-producing K. pneumoniae (n=1)	1/1 (100)	0/1 (0.0)	0/1 (0.0)
ESCS-carbaS K. pneumoniae (n=34)	20/34 (58.8)	12/34 (35.3)	2/34 (5.9)
Total organisms (n=321)	132/321 (41.1)	154/321 (48.0)	34/321 (10.6)^a

Notes: ^aThe treatment was not appropriate in 1 (0.3%) of 321 BSIs because the infecting KPC/VIM-producing K. pneumoniae organism had an AST-determined pandrug resistance phenotype.

Abbreviations: CRE, carbapenemase-resistant Enterobacteriaceae; BSI, bloodstream infection; ESCS-carbaS, extended-spectrum cephalosporin susceptible-carbapenem susceptible.

Figure 2 Appropriateness of antimicrobial treatments in subgroups defined by the presence of the indicated resistance determinants in 321 patients with Ec or Kp bloodstream infections. Empirical or targeted antimicrobial therapy was the administration of antibiotics before and after the eazyplex^® SuperBug CRE assay results were available, respectively. Definitive antimicrobial therapy was the administration of antibiotics after the antimicrobial susceptibility testing results were available. Overall, antimicrobial therapy was appropriate for any antibiotic with known susceptibility by microbiology report.