Carbapenem-Resistant Klebsiella aerogenes Clinical Isolates from a Teaching Hospital in Southwestern China: Detailed Molecular Epidemiology, Resistance Determinants, Risk Factors and Clinical Outcomes

Figures & data

Table 1 Distribution and Corresponding Carbapenem MIC Ranges for Strains with Different Resistance Determinants

Carbapenems Resistance Mechanisms	No. of Isolates	MIC Range(mg/L)
		Imipenem	Meropenem	Ertapenem
Carbapenemase positive
KPC-2+,efflux pump,loss of OMPs	1	128	128	256
NDM-1+,ESBL+,AmpC+,loss of OMPs,efflux pump	1	64	128	256
NDM-1+,ESBL+,AmpC+,efflux pump	1	64	128	256
Carbapenemase negative
ESBL+,AmpC+,loss of OMPs, efflux pump	3	4	2–4	8–64
ESBL+,loss of OMPs, efflux pump	1	8	4	64
ESBL+,AmpC+,efflux pump	8	4–32	0.5–32	4–128
ESBL+,efflux pump	2	4–32	2–32	4–64
AmpC+,efflux pump	8	2–32	0.25–16	4–64
ESBL+,AmpC+	1	4	<0.25	8
ESBL+	1	<0.25	<0.25	2
AmpC+	6	0.25–4	0.25–2	2–4
NONE	3	0.5–2	0.25–1	2

Abbreviations: MIC, minimum inhibitory concentration; OMPs, outer membrane proteins.

Figure 1 PFGE-based dendrogram of CRKA strains. Sample ID, source of initial isolation, and demographic information are included along each PFGE lane.

Abbreviations: ESBLs, Extended-Spectrum Beta-Lactamases; QRD, quinolone resistance determinants; ARD, aminoglycoside resistance determinants; PBRT, PCR-based replicon type; “-”, not detected.

Table 2 Antibiotic Resistance Genes and Susceptibility Profiles in Donor, E. Coli EC600, and Transconjugants

	Donor Strains		Recipient Strain	Transconjugants
	KA8	KA9	EC600	KA8-TC	KA9-TC
Resistance genes	blaNDM-1, blaTEM, blaCTX-M-15, acc(6ʹ)-1b, armA, qnrD, blaEBC, blaACC	blaNDM-1, blaTEM, blaCTX-M-15, acc(6ʹ)-1b, armA, qnrD, blaEBC, blaACC	NA	blaNDM-1,blaTEM, blaCTX-M-15, acc(6ʹ)-1b, armA	blaNDM-1, blaTEM, blaCTX-M-15, acc(6ʹ)-1b, armA
Plasmid replicon type	IncFIIAs	IncFIIAs	NA	IncFIIAs	IncFIIAs
Minimum inhibitory concentration (mg/mL)
Imipenem	64	64	≤1	8	8
Meropenem	128	128	≤1	4	8
Ertapenem	256	256	≤0.5	8	16
Ceftriaxone	≥64	≥64	≤1	≥64	≥64
Ceftazidime	≥64	≥64	≤1	32	32
Cefepime	≥64	≥64	≤1	32	32
Ciprofloxacin	≥4	≥4	≤0.25	≤0.5	≤0.5
Levofloxacin	≥8	≥8	≤0.5	≤0.5	≤0.5
Gentamycin	≥16	≥16	≤1	4	4
Amikacin	≥64	≥64	≤1	16	8
Tobramycin	≥16	≥16	≤1	8	8

Abbreviations: KA, Klebsiella aerogenes; NA, not available; TC, transconjugant.

Table 3 Univariate and Multivariate Analyses of Risk Factors and Outcomes for Patients Infected with CRKA Isolates Compared with CSKA Isolates

Variable	CRKA	CSKA	Univariate Analysis		Multivariate Analysis
	(N=36)	(N=131)	OR (95% CI)	P-value	OR (95% CI)	P-value
Demographics, n (%)
Elderly (≥ 60 years)	17(47.2%)	68(51.9%)	0.829(0.396–1.735)	0.618
Male gender	26(77.2%)	88(67.2%)	1.270(0.562–2.871)	0.564
Surgical units	17(47.2%)	62(47.3%)	0.996(0.476–2.871)	0.991
Transfer from another hospital	14(38.9%)	51(38.9%)	0.998(0.468–2.127)	0.996
Admission to ICU	13(36.1%)	42(32.1%)	1.198(0.553–2.594)	0.647
Comorbid conditions, n (%)
Hypertension	9(25%)	36(27.5%)	0.880(0.277–2.050)	0.766
Malignant disease	11(30.6%)	37(28.2%)	1.118(0.500–2.500)	0.786
Cardiovascular disease	6(16.7%)	17(13.0%)	1.341(0.487–3.697)	0.504
Chronic kidney disease	6(16.7%)	23(17.6%)	0.939(0.351–2.516)	0.901
Hepatobiliary disease	15(41.7%)	26(19.8%)	2.885(1.31–6.35)	0.007
Gastrointestinal disease	14(38.9%)	28(21.4%)	2.341(1.063–5.156)	0.032
Respiratory diseases	15(41.7%)	39(29.8%)	1.69(0.79–3.61)	0.177
Neurological disease	4(11.1%)	25(19.1%)	0.53(0.172–1.636)	0.263
Endocrine, metabolic disease	2(5.6%)	2(1.5%)	3.794(0.516–27.924)	0.203
Vascular, hematological disease	10(27.8%)	20(15.3%)	2.135(0.893–5.10)	0.083
Hypoalbuminaemia	29(80.6%)	61(46.6%)	4.754(1.945–11.622)	<0.001	3.569(1.036–12.481)	0.044
Urinary tract infection	9(25%)	15(11.5%)	2.578(1.021–6.510)	0.04
skin infection	8(22.2%)	10(7.6%)	3.457(1.252–9.554)	0.028
Respiratory infection	16(44.4%)	41(31.3%)	1.756(0.826–3.733)	0.141
Invasive procedures within prior 4 weeks, n (%)
Surgery in the past 6 months	19(52.8%)	53(40.5%)	1.645(0.784–3.453)	0.186
Receipt of total parenteral nutrition	0(0%)	1(0.8%)	0.783(0.723–0.848)	1
Mechanical ventilation	10(27.8%)	30(22.9%)	1.295(0.562–2.986)	0.544
Bladder irrigation	4(11.1%)	4(3.1%)	3.969(0.941–16.736)	0.067
Drainage tube	25(69.4%)	44(33.6%)	4.494(2.026–9.966)	<0.001	5.777(1.807–18.468)	0.003
Urinary catheter	27(75.0%)	51(38.9%)	4.706(2.048–10.815)	<0.001	3.321(1.032–10.684)	0.044
Tracheal cannula	16(44.4%)	42(32.1%)	1.695(0.798–3.590)	0.167
Nasal catheter	0(0%)	7(5.3%)	0.775(0.713–0.842)	0.348
Central venous catheter	10(27.8%)	10(7.6%)	4.654(1.758–12.320)	0.003
Antimicrobial exposure within 3 months, n (%)
Penicillins	14(38.9%)	23(17.6%)	2.988(1.33–6.698)	0.006
Cephalosporins	23(63.9%)	64(48.9%)	1.852(0.865–3.966)	0.11
Carbapenems	13(36.1%)	18(13.7%)	3.55(1.53–8.24)	0.002	5.007(1.292–19.406)	0.02
Fluoroquinolones	5(13.9%)	4(3.1%)	5.121(1.298–20.196)	0.023
Aminoglycosides	3(8.3%)	2(1.5%)	5.864(0.941–36.538)	0.068
Glycopeptides	7(19.4%)	11(8.4%)	2.633(0.929–7.382)	0.071
Clinical outcomes n (%)
In-hospital mortality	4(11.1%)	5(3.8%)	3.15(0.80–12.41)	0.102
Functional status deterioration	6(16.7%)	9(25%)	2.711(0.896–8.206)	0.095
Post-culture length of stay, median (IQR), days	19(6.75–30)	9(4–18)	NA	0.003
Total length of hospital stay, median (IQR), days	52.5 (31.25–101.75)	24(14–42.5)	NA	<0.001	1.008(1.001–1.014)	0.016

Notes: Data are expressed as n (%) of patients for categorical variables and median (IQR) for continuous variables as appropriate. Bold face indicates values that are significant (P<0.05).

Abbreviations: CRKA, carbapenems-resistant K. aerogenes; CSKA, carbapenems-sensitive K. aerogenes; ICU, intensive care unit; OR, odds ratio; CI, confidence interval; IQR, interquartile range; NA, not available.