Evaluation of <i>in vitro</i> activity of ceftolozane-tazobactam against recent clinical bacterial isolates from Brazil - the EM200 study

Tuon, Felipe Francisco; Cieslinski, Juliette; Rodrigues, Suellen da Silva; Serra, Fernando Brandão; Paula, Marina Della-Negra de

doi:10.1016/j.bjid.2020.04.004

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Original articles • Braz J Infect Dis 24 (2) • Mar-Apr 2020 • https://doi.org/10.1016/j.bjid.2020.04.004 copy

Evaluation of in vitro activity of ceftolozane-tazobactam against recent clinical bacterial isolates from Brazil - the EM200 study

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Background:

The emergence of antibiotic resistance is increasing and there are few effective antibiotics to treat infections caused by resistant and multidrug resistant bacterial pathogens. This study aimed to evaluate the in vitro activity of ceftolozane-tazobactam against clinical bacterial isolates from Brazil.

Methods:

A total of 673 Gram-negative bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and other Enterobacterales collected from 2016 to 2017 were tested, most of them isolated from patients in intensive care units. Minimum inhibitory concentrations (MIC_50/90) were determined by broth microdilution for amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftolozane-tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam using dried panels. Antimicrobial susceptibility results were interpreted according to Clinical and Laboratory Standards Institute criteria.

Results:

Susceptibility rates to ceftolozane-tazobactam ranged from 40.4% to 94.9%. P. aeruginosa susceptibility rate to ceftolozane-tazobactam was 84.9% (MIC_50/90, 1/16 µg/mL) and 99.2% to colistin. For E. coli, ceftolozane-tazobactam inhibited 94.9% (MIC_50/90, 0.25/1 µg/mL) of the microorganisms. The susceptibility rate of K. pneumoniae to ceftolozane-tazobactam was 40.4% (MIC_50/90, 16/>32 µg/mL). Other Enterobacterales have shown susceptibility rates of 81.1% (MIC_50/90, 0.5/16 µg/mL) to ceftolozane-tazobactam, 93.9% to meropenem, 90.9% to amikacin (90.9%), and 88.6% to ertapenem. In non-carbapenemase producing isolates, AmpC mutations were found three isolates.

Conclusions:

Ceftolozane-tazobactam has shown relevant activity against a large variety of the analyzed microorganisms collected from multiple centers in Brazil, showing promising results even in multidrug resistant strains.

Keywords:
Ceftolozane; tazobactam; Pseudomonas aeruginosa; Enterobacterales; Drug Resistance; Antimicrobial Resistance; Antimicrobial Susceptibility Test

Compound	Test range (mg/L)
Amikacin	4-32
Aztreonam	1-16
Cefepime	1-32
Cefotaxime	1-32
Cefoxitin	2-16
Ceftolozane-tazobactam	0.06-32
Ceftazidime	1-32
Ceftriaxone	1-32
Ciprofloxacin	0.25-2
Colistin	1-4
Ertapenem	0.06-4
Imipenem	0.5-32
Levofloxacin	1-4
Meropenem	0.12-16
Piperacillin-tazobactam	2-64

Species	N	Percent (%)
Escherichia coli	216	32.1
Klebsiella pneumoniae	193	28.7
Pseudomonas aeruginosa	132	19.6
Proteus mirabilis	72	10.7
Enterobacter cloacae	38	5.6
Klebsiella oxytoca	11	1.6
Klebsiella variicola	4	0.6
Klebsiella aerogenes	3	0.4
Enterobacter asburiae	1	0.1
Morganella morganii	1	0.1
Proteus vulgaris	1	0.1
Providencia rettgeri	1	0.1
Total	673	100

Organism (n)	Antimicrobial	%S	%I	%R	MIC ₅₀	MIC₉₀	Range
Pseudomonas aeruginosa (132)	Ceftolozane-tazobactam	84.9	4.6	10.6	1	16	0.5->32
	Amikacin	84.9	3.0	12.1	≤4	>32	≤4->32
	Aztreonam	50.0	15.9	34.1	8	>16	2->16
	Cefepime	61.4	12.9	25.8	8	>32	≤1->32
	Ceftazidime	59.9	9.9	30.3	8	>32	≤1->32
	Ciprofloxacin	68.9	6.8	24.2	≤0.25	>2	≤0.25->2
	Colistin	99.2	-	0.8	≤1	≤1	≤1-4
	Imipenem	53.0	6.1	40.9	2	32	≤0.5->32
	Levofloxacin	62.9	7.6	29.6	≤1	>4	≤1->4
	Meropenem	58.3	9.9	31.8	2	>16	≤0.12->16
	Piperacillin-tazobactam	55.3	14.4	30.3	16	>64	≤2->64
Escherichia coli (216)	Ceftolozane-tazobactam	94.9	2.3	2.8	0.25	1	≤0.06->32
	Amikacin	97.7	0.9	1.4	≤4	8	≤4->32
	Aztreonam	67.1	7.4	25.5	≤1	>16	≤1->16
	Cefepime	65.3	7.9	26.9	≤1	>32	≤1->32
	Cefotaxime	60.7	1.4	38.0	≤1	>32	≤1->32
	Cefoxitin	68.5	14.8	16.7	8	>16	≤2->16
	Ceftazidime	70.4	9.7	19.9	≤1	16	≤1->32
	Ceftriaxone	59.7	1.4	38.9	≤1	>32	≤1->32
	Ciprofloxacin	47.7	1.9	50.5	>2	>2	≤0.25->2
	Colistin	98.2	-	1.9	≤1	≤1	≤1-4
	Ertapenem	94.0	0.5	5.6	≤0.06	0.12	≤0.06->4
	Imipenem	97.2	1.9	0.9	≤0.5	≤0.5	≤0.5-8
	Levofloxacin	49.5	3.7	46.8	4	>4	≤1->4
	Meropenem	97.2	1.4	1.4	≤0.12	≤0.12	≤0.12->16
	Piperacillin-tazobactam	91.7	3.7	4.6	≤2	16	≤2->64
Klebsiella pneumoniae (193)	Ceftolozane-tazobactam	40.4	3.6	56.0	16	>32	0.25->32
	Amikacin	91.2	1.6	7.3	≤4	16	≤4->32
	Aztreonam	23.8	3.1	73.1	>16	>16	≤1->16
	Cefepime	25.4	7.8	66.8	>32	>32	≤1->32
	Cefotaxime	21.8	2.1	76.2	>32	>32	≤1->32
	Cefoxitin	39.9	10.4	49.7	16	>16	≤2->16
	Ceftazidime	28.5	2.1	69.4	>32	>32	≤1->32
	Ceftriaxone	20.7	1.6	77.7	>32	>32	≤1->32
	Ciprofloxacin	25.9	2.1	72.0	>2	>2	≤0.25->2
	Colistin	90.2	-	9.8	≤1	2	≤1->4
	Ertapenem	53.4	1.0	45.6	0.5	>4	≤0.06->4
	Imipenem	61.1	4.7	34.2	≤0.5	32	≤0.5->32
	Levofloxacin	28.5	4.7	66.8	>4	>4	≤1->4
	Meropenem	60.1	2.1	37.8	≤0.12	>16	≤0.12->16
	Piperacillin-tazobactam	30.6	14.0	55.4	>64	>64	≤2->64
Other Enterobacterales ^a a Other Enterobacterales consist of (n): Klebsiella aerogenes (3); Enterobacter asburiae (1); E. cloacae (38); Klebsiella oxytoca (11); K. variicola (4); Morganella morganii (1); Proteus mirabilis (72); P. vulgaris (1); Providencia rettgeri (1). (132)	Ceftolozane-tazobactam	81.1	3.0	15.9	0.5	16	0.12->32
	Amikacin	90.9	2.3	6.8	≤4	16	≤4->32
	Aztreonam	72.0	0.8	27.3	≤1	>16	≤1->16
	Cefepime	62.1	10.6	27.3	≤1	>32	≤1->32
	Cefotaxime	52.3	3.0	44.7	≤1	>32	≤1->32
	Cefoxitin	56.1	6.1	37.9	8	>16	≤2->16
	Ceftazidime	72.7	2.3	25.0	≤1	>32	≤1->32
	Ceftriaxone	52.3	5.3	42.4	≤1	>32	≤1->32
	Ciprofloxacin	63.6	2.3	34.1	≤0.25	>2	≤0.25->2
	Colistin	40.9	-	59.1	>4	>4	≤1->4
	Ertapenem	88.6	3.8	7.6	≤0.06	1	≤0.06->4
	Imipenem	72.0	18.9	9.1	≤0.5	2	≤0.5->32
	Levofloxacin	68.9	4.6	26.5	≤1	>4	≤1->4
	Meropenem	93.9	0	6.1	≤0.12	0.25	≤0.12->16
	Piperacillin-tazobactam	80.3	7.6	12.1	≤2	>64	≤2->64

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[1] *Corresponding author. E-mail address: felipe.tuon@pucpr.br (F.F. Tuon).