Risk Factors and Molecular Mechanism of Polymyxin B Resistance in Carbapenem-Resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Fujian, China

Figures & data

Table 1 Comparison of Demographic Factors Among of the Case and Control Groups

Variable	Case Group (n = 12)	Control Group (n = 24)	P-value
Age (years) [median (IQR)]	66 (13–79)	68.5 (20–88)	0.509
Male sex	9 (75.0)	19 (79.2)	0.777
LOS before first CRKP isolation (days) [median (IQR)]	17 (2–169)	18 (2–55)	0.110
Co-morbidities
Hypertension	9 (75.0)	7 (29.2)	0.013
Diabetes	5 (41.7)	3 (12.5)	0.059
Coronary heart disease	7 (58.3)	2 (8.3)	0.004
Heart failure	1 (8.3)	0 (0)	0.998
Kidney disease	3 (25)	10 (41.7)	0.331
Liver disease	5 (41.7)	10 (41.7)	1
ECOG score [median (IQR)]	5 (2–5)	3 (1–4)	0.0125
Medical devices
Tracheostomy	11 (91.7)	12 (50)	0.032
Lumbar puncture	1 (8.3)	0 (0)	0.998
Chest puncture	3 (25.0)	5 (20.8)	0.777
Abdominal puncture	1 (8.3)	1 (4.2)	0.614
Number of admissions [median (IQR)]	2 (1–9)	1 (1–7)	0.252
Number of days in hospital stay	36 (2–365)	35.5 (12–169)	0.166

Note: P = test significance.

Abbreviations: IQR, interquartile range; LOS, length of hospital stay; CRKP, carbapenem-resistant Klebsiella pneumoniae; ECOG, Eastern Cooperative Oncology Group.

Table 2 Molecular Characterization of Resistance-Related Genes in 239 CRKP Isolates

Gene	Number	Proportion (%)
blaKPC	217	90.79
blaNDM	16	6.69
blaVIM	0	0
blaIMP	1	0.42
blaOXA-48	0	0
mcr-1	0	0
OmpK35	230	96.23
OmpK36	234	97.90
OmpK37	235	98.33

Abbreviation: CRKP, carbapenem-resistant Klebsiella pneumoniae.

Figure 1 Susceptibility of CRKP isolates to different antimicrobial agents.

Figure 2 Distribution of MIC values of polymyxin B by broth micro-dilution method.

Abbreviations: MIC, minimal inhibitory concentration; µg/mL, micrograms per milliliter.

Table 3 Univariate and Multivariate Analyses of Risk Factors for the Emergence of Polymyxin Resistance in Carbapenem-Resistant Klebsiella pneumoniae (CRKP)

Variable	Univariate or (95% CI)	P-value	Multivariate or (95% CI)	P-value
Hypertension	7.286 (1.508–35.211)	0.013	4.602 (0.711–29.764)	0.109
Coronary heart disease	15.400 (2.428–97.674)	0.004	7.822 (1.040–58.819)	0.046
Tracheostomy	11.000 (1.221–99.071)	0.032	8.316 (0.678–102.014)	0.098
Polymyxin use	4.600 (0.373–56.752)	0.234
Carbapenem use	1.429 (0.335–6.083)	0.629
Cephalosporins use	3.000 (0.648–13.885)	0.16
Aminoglycosides use	3.400 (0.800–14.441)	0.097
Quinolones use	1.735 (0.408–7.368)	0.455

Note: P = test significance.

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; OR, odds ratio; 95% CI, confidence interval.

Table 4 Mechanisms of Polymyxin Resistance in 12 PR-CRKP Strains

Strain	Carbapenemase	Polymyxin MIC (PR-CRKP)	mRNA Expression PmrB PmrK		Amino Acid Substitutions in PR-CRKP Strains pmrb
PR-1	blaKPC	32	2.489±0.539	34.51±3.207
PR-2	blaKPC; blaNDM	64	37.62±6.898	21.59±3.586	Arg766Gly, Ile149Ala
PR-3		32	1.394±0.047	4.104±1.279	Arg766Gly
PR-4	blaKPC	4	1.434±0.059	4.524±1.035
PR-5	blaKPC; blaNDM	32	1.977±0.773	3.099±1.916
PR-6	blaKPC; blaNDM	32	2.147±0.073	2.814±0.503
PR-7	blaKPC; blaNDM	64	5.414±1.091	2.342±0.580
PR-8	blaKPC	64	1.967±0.265	3.586±0.321
PR-9	blaKPC	8	1.465±0.02	3.309±0.47
PR-10	blaKPC	8	4.292±0.813	9.470±1.146
PR-11	blaKPC	8	1.515±0.262	2.083±0.585	Arg766Gly
PR-12	blaKPC	32	2.745±0.302	8.592±1.302

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; MIC, Minimum Inhibitory Concentration; Arg, arginine; Gly, glycine; Ile, isoleucine; Ala, alanine.

Figure 3 ERIC-PCR dendrogram of all PR-CRKP clinical isolates.