Ertapenem non-susceptibility and independent predictors of the carbapenemase production among the enterobacteriaceae isolates causing intra-abdominal infections in the Asia-Pacific region: results from the study for monitoring the antimicrobial resistance trends (SMART)

Figures & data

Figure 1 The Erta-NS prevalence rates (%) among the isolates of three leading species (Escherichia coli, Klebsiella pneumoniae, and various Enterobacter species; black bars) causing IAI, and the corresponding prevalence rates of CPE (%; gray bars) on the Erta-NS-IAI isolates in the Asia-Pacific countries (or regions) participating in this IAI study, from 2008 through 2014.

Abbreviations: CPE, carbapenemase-producing Enterobacteriaceae; Erta-NS, ertapenem-non-susceptible; IAI, intra-abdominal infections.

Figure 2 The prevalence rates (%) of Erta-NS isolates among the isolates causing IAI validated by testing for presence of the gene(s) encoding β-lactamase(s) (black bars) and the prevalence rates of carbapenemase producing CPE (n>10) among the Erta-NS isolates (gray bars; only isolate numbers >10 per country or region during the study period are included herein) in the Asia-Pacific countries (or regions) participating in this IAI study, from 2008 through 2014.

Abbreviations: CPE, carbapenemase-producing Enterobacteriaceae; Erta-NS, ertapenem-non-susceptible; IAI, intra-abdominal infections.

Figure 3 The prevalence rates (%) of Erta-NS isolates among the isolates that caused IAI (n=1,564) and were positive for harboring gene(s) encoding β-lactamase(s) (black bars), and the prevalence rates of carbapenemase producing CPE among the Erta-NS isolates (gray bars) in the various age populations of patients hospitalized in the Asia-Pacific countries (or regions) participating in this IAI study, from 2008 through 2014.

Abbreviations: CPE, carbapenemase-producing Enterobacteriaceae; Erta-NS, ertapenem-non-susceptible; IAI, intra-abdominal infections.

Figure 4 The prevalence rates of Erta-NS isolates among those causing IAI (n=1,564) and those that were confirmed to possess gene(s) encoding β-lactamase(s) (black bars), and the percentages of carbapenemase producing CPE among the Erta-NS isolates (gray bars) in the ICU and various ward settings in the Asia-Pacific countries (or regions) participating in this IAI study, from 2008 through 2014.

Abbreviations: CPE, carbapenemase-producing Enterobacteriaceae; Erta-NS, ertapenem-non-susceptible; IAI, intra-abdominal infections; ICU, intensive care unit.

Table 1 MICs against imipenem, and the imipenem MIC₅₀, MIC₉₀ levels of diverse carbapenemases on the ertapenem-non-susceptible Enterobacteriaceae isolates causing intra-abdominal infections among patients hospitalized in the Asia-Pacific region from 2008 through 2014

Carbapenemases (isolate number)	Imipenem MIC range (μg/mL)	Imipenem MIC50 value (μg/mL)	Imipenem MIC90 value (μg/mL)
NDM (37)	0.5-32	8	16
KPC (7)	2-32	16	32
OXA-48-like (8)	1-16	4	16
IMP (28)	0.5-16	2	8

Abbreviations: IMP, imipenemases; KPC, Klebsiella pneumoniae carbapenemases; MIC, minimum inhibitory concentration; NDM, New Delhi metallo-β-lactamases; OXA, oxacillinases.

Table 2 Comparison of the variables of demographics of Asia-Pacific patients with IAI, the hospital sampling settings from where the Erta-NS IAI Enterobacteriaceae isolates were collected, types of species (comprising Escherichia coli, Klebsiella pneumoniae, and overall Enterobacter species), detection of the Erta-NS-IAI isolates by culturing samples from the abdominal space, the non-susceptibility rates toward different antimicrobial agents for three leading Erta-NS-IAI Enterobacteriaceae species between the subgroups of CPE and non-CPE isolates collected from 2008 through 2014

Variables	Yes or no	CPE (n=80), no (%)	Non-CPE (n=404), no (%)	OR	95% CI	P-value
Gender, male	Yes	45 (56.3)	240 (59.4)	0.879	0.541, 1.426	0.620
	No	35 (43.8)	164 (40.6)
Age (years)
<14 years (pediatric)	Yes	4 (5.0)	9 (2.2)	2.244	0.708, 7.110	0.244
	No	76 (95.0)	395 (97.8)
15-64 years (adult)	Yes	47 (58.8)	162 (40.1)	1.465	1.177, 1.824	0.003
	No	33 (41.3)	242 (59.9)
>65 years (geriatric)	Yes	29 (36.3)	233 (57.7)	0.417	0.254, 0.686	0.001
	No	51 (63.8)	171 (42.3)
Sites of acquisition of isolates
ICU setting acquisition	Yes	18 (22.5)	59 (14.6)	1.698	0.938, 3.072	0.08
	No	62 (77.5)	345 (85.4)
Surgical ICU patients	Yes	14 (17.5)	35 (8.7)	2.236	1.141, 4.383	0.024
	No	66 (82.5)	369 (91.3)
Medical ICU patients	Yes	3 (3.8)	22 (5.4)	0.677	0.198, 2.316	0.782
	No	77 (96.3)	382 (94.6)
Surgical ward patients	Yes	34 (42.5)	140 (34.7)	1.116	0.686, 1.814	0.659
	No	46 (57.5)	264 (65.3)
Medical ward patients	Yes	22 (27.5)	157 (38.9)	0.597	0.351, 1.014	0.058
	No	58 (72.5)	247 (61.1)
Bacterial species
Escherichia coli	Yes	15 (18.8)	83 (20.5)	0.892	0.484, 1.644	0.763
	No	65 (81.3)	321 (79.5)
Klebsiella pneumoniae	Yes	49 (61.3)	91 (22.5)	5.437	3.275, 9.024	<0.001
	No	31 (38.8)	313 (77.5)
Enterobacter spp.	Yes	13 (16.3)	210 (52.0)	0.179	0.096, 0.335	<0.001
	No	67 (83.8)	194 (48.0)
Source of isolates
Peritoneal space	Yes	54 (67.5)	145 (35.9)	3.710	2.227, 6.179	<0.001
	No	26 (32.5)	259 (64.1)
Hepatobiliary system	Yes	14 (17.5)	193 (47.8)	0.232	0.126, 0.426	<0.001
	No	66 (82.5)	211 (52.2)
LGI tract	Yes	3 (3.8)	16 (4.0)	0.945	0.269, 3.321	1.000
	No	77 (96.3)	388 (96.0)
Phenotype of isolates (μg/mL)
Imipenem NS (MIC >1)	Yes	74 (92.5)	62 (15.3)	68.032	28.365, 163.175	<0.001
	No	6 (7.5)	342 (84.7)
Amikacin NS (MIC >16)	Yes	51 (63.8)	91 (22.5)	6.049	3.625, 10.095	<0.001
	No	29 (36.3)	313 (77.5)
Cefepime MIC >8	Yes	77 (96.3)	150 (37.1)	43.462	13.477, 140.167	<0.001
	No	3 (3.8)	254 (62.9)
Cefepime MIC >16	Yes	69 (86.3)	107 (26.5)	17.411	8.877, 34.148	0.003
	No	11 (13.8)	297 (73.5)
Piperacillin-tazobactam NS	Yes	74 (92.5)	327 (80.9)	2.904	1.219, 6.920	0.010
	No	6 (7.5)	77 (19.1)
Ciprofloxacin NS (MIC >1)	Yes	67 (83.8)	193 (47.8)	5.635	3.015, 10.529	<0.001
	No	13 (16.3)	211 (52.2)
Levofloxacin NS (MIC >2)	Yes	55 (68.8)	155 (38.4)	3.534	2.115, 5.906	<0.001
	No	25 (31.3)	249 (61.6)
ceftriaxone NS (MIC >1)	Yes	80 (100)	388 (96.0)	1.041	1.021, 1.062	0.087
	No	0 (0)	16 (4.0)
cefoxitin NS (MIC >8)	Yes	78 (97.5)	395 (97.8)	0.889	0.188, 4.192	1.000
	No	2 (2.5)	9 (2.2)
ESBL positivity	Yes	76 (95)	176 (43.6)	24.614	8.836, 68.566	<0.001
	No	4 (5)	228 (56.4)
AmpC positivity	Yes	22 (27.5)	255 (63.1)	0.222	0.130, 0.377	<0.001
	No	58 (72.5)	149 (36.9)

Abbreviations: LGI, lower gastrointestinal tract; NS, non-susceptibility; CPE, carbapenemase-producing Enterobacteriaceae; IAI, intra-abdominal infections; Erta-NS, ertapenem-non-susceptible; ICU, intensive care unit; ESBL, extended-spectrum β-lactamase; MIC, minimum inhibitory concentration.

Table 3 Independent predictors of carbapenemase producers among the ertapenem-non-susceptible Enterobacteriaceae isolates causing intra-abdominal infections in patients hospitalized in the Asia-Pacific region from 2008 through 2014

Variables	OR	95% CI	P-value
Imipenem non-susceptibility	56.4	19.8, 161.1	<0.0001
Cefepime MIC >8 μg/mL	4.4	1.0, 19.2	0.047
Cultured from the peritoneal space (tissue, abscess)	3.3	1.4, 7.9	0.008
Positivity of the ESBL encoding allele(s) by multiplex PCR test	11.5	2.8, 47.1	0.001
Positivity of the AmpC encoding allele(s) by multiplex PCR test	0.26	0.10, 0.66	0.004

Abbreviations: ESBL, extended-spectrum β-lactamase; MIC, minimum inhibitory concentration.