Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU

Figures & data

Figure 1 Flowchart of patient inclusion.

Table 1 Characteristics of Patients with HAP Caused by KPC with TG in Both Groups

	Effective Group	Failure Group	p-value
	N = 25	N = 27
Characteristic
Age (years) median (IQR)	59.1 (44–74.5)	65.5 (56.2–78)	0.356
BMI	25.36 (20.1–26.9)	23.6 (21.6–27.8)	0.763
Female sex	9	14	0.578
CCI score median (IQR)	2.25	2 (0–3)	0.788
Tumor	5	4	0.621
DM	4	3	0.606
COPD	5	3	0.375
Surgery	7	11	0.335
Mechanical ventilation	16	18	0.840
Length of ICU days (IQR)	41 (31–54)	30 (22–51)	0.077
Days of TG treatment (IQR)	14.5 (9–28.75)	10 (5–16)	0.046
Dose of TG (100mg q12h)	8	12	0.357
Combine therapy
Carbapenems	11	13	0.236
β-Lactamase inhibitors	6	8	0.647
Ceftazidime	1	3	0.317
SMZ	2	5	0.267
Amikacin	5	4	0.621

Abbreviations: BMI, Body Mass Index; CCI, Charlson Comorbidity Index; IQR, Inter-Quartile Range; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; TG, tigecycline; Carbapenems (Imipenem/cilastatin, Meropenem, Biapenem); SMZ, sulfamethoxazole.

Figure 2 Distribution map of drug resistance genes. (1) Multi-drug resistance genes were detected from studied strains, including multidrug resistance efflux pump genes- major facilitator superfamily transporter(MFS), resistance-nodulation-cell division transporter (RND), and β-lactamase genes. Among them, KPC-2, SHV, CTX-M, MFS (mdth, mdtg, mdtk) and RND (acrb, tolc) genes existed in all strains. (2) The number of tetracycline resistance genes contained in the studied strains was different, in which the detection rates of teta, tetd and tetc were 6%, 4% and 100%, respectively.

Figure 3 Distribution map of virulence genes. (1) Multiple virulence genes were detected in the studied strains, among which areo, salmonin and yersinomycin were present in all strains. (2) The detection rates of rmpA, LPS and capsular virulence genes were different among the studied strains, in which rmpA1, rmpA2, LPS-wbbo, capsular-wza and wzc were 67%, 69%, 45%, 82% and 78%, respectively.

Table 2 The Mortality, Clearance of Pathogens and Distribution of Antibiotic Resistance Genes, Virulence Factors in Both Groups

	Effective Group	Failure Group	p-value
	N = 25	N = 27
Mortality
All-cause death in the ICU	6	16	0.010
Clearance of pathogens
At 3 days after stopping TG	12	16	0.416
Virulence factors
rmpA	16	15	0.535
rmpA2	15	18	0.618
AREO-iutA	10	19	0.028
Capsule-wzc	16	20	0.432
Capsule-wza	18	20	0.866
LPS-wbbO	4	14	0.009
Antibiotic Resistance Genes
sul1	17	12	0.087
mpha	7	13	0.136
dfra12	11	10	0.609
aac3iia	6	1	0.046
ant2ia	15	11	0.165

Abbreviations: ICU, Intensive Care Unit; TG, TG, tigecycline.

Table 3 Univariate and Multivariate Analyses of the Risk Factors Associated with Clinical Efficacy in Patients with Klebsiella Pneumoniae Carbapenemase 2-Producing K. Pneumoniae Infections

Univariate Analysis				Multivariate Analysis
Covariate	OR	95% CI	p-value	OR	95% CI	p-value
Age	0.975	0.943–1.008	0.130
Male	0.745	0.248–2.232	0.599
BMI	0.969	0.872–1.076	0.551
CCI	0.921	0.766–1.108	0.382
Mechanical ventilation	0.818	0.267–2.510	0.726
Combined with carbapenems	0.361	0.114–1.145	0.084	0.377	0.211–1.179	0.248
High-dose TG	0.989	0.967–1.012	0.358
Days of TG	1.002	0.963–1.035	0.912
sul1	2.222	0.729–6.777	0.160
mpha		0.132–1.328	0.139
dfra12	1.336	0.44–4.05	0.610
aac3iia	8.221	0.91–73.95	0.060	0.541	0.106–2.758	0.088
ant2ia	2.182	0.72–6.61	0.068	0.740	0.218–2.897	0.024
rmpA	1.422	0.466–4.337	0.536
rmpA2	0.750	0.242–2.325	0.618
AREO-iutA	0.281	0.089–0.887	0.03	0.055	0.004–0.731	0.028
Capsule-wzc	0.142	0.027–0.745	0.021	0.003	0.000–0.262	0.010
Capsule-wza	0.206	0.038–1.108	0.066	3.194	0.196–6.12	0.178
LPS-wbbO	0.177	0.048–0.655	0.009	1.109	0.170–7.217	0.914

Abbreviations: BMI, Body Mass Index; CCI, Charlson Comorbidity Index; TG, tigecycline; Carbapenems (Imipenem/cilastatin, Meropenem, Biapenem).