Epidemiology, Drug Resistance, and Risk Factors for Mortality Among Hematopoietic Stem Cell Transplantation Recipients with Hospital-Acquired Klebsiella pneumoniae Infections: A Single-Center Retrospective Study from China

Figures & data

Table 1 Clinical Characteristics and Laboratory Data of 59 HSCT Recipients with K. pneumoniae Infections

Characteristic	Value
Age, years, median (IQR)	29 (23.5, 49)
Sex, no. of males (%)	41 (69.5%)
Primary disease, n (%)
Acute lymphocytic leukemia	17 (28.8%)
Acute myelogenous leukemia	14 (23.7%)
Myelodysplastic syndrome	10 (16.9%)
Severe aplastic anemia	7 (11.9%)
Lymphoma	3 (5.1%)
Others	8 (13.6%)
Infection sites, n (%)
Lung	38 (64.4%)
Bloodstream	18 (30.5%)
Others	3 (5.1%)
CRKP infections	11 (18.6%)
ESBL infections	41(69.5%)
Time between diagnosis and transplantation, days, median (IQR)	190 (140, 363)
History of relapse/refractory state, n (%)	11 (18.6%)
Identical match, n (%)	19 (32.2%)
Time of engraftment
Granulocyte, days, median (IQR)	14 (11.5, 16)
Platelets, days, median (IQR)	19 (13.5, 26.5)
Umbilical cord blood stem cell infusion, n (%)	13 (22.0)
Mesenchymal stem cell infusion, n (%)	11 (18.6)
Urethral catheterization, n (%)	6 (10.2%)
Acute GVHD (grade I–II), n (%)	36 (61%)
Time from HSCT and infection, days, median (IQR)	30 (14.5, 48)
Multiple times/sites/polymicrobial infections, n (%)	32 (54.2%)
Use of broad-spectrum antibiotics > 5 days one month prior to infection, n (%)	56 (94.9%)
Use of carbapenems > 3 days one month prior to infection, n (%)	41 (69.5%)
Inappropriate empiric antimicrobial treatment, n (%)	24 (40.7%)
Non-use of anti-CMV gamma globulin/rituximab, n (%)	37 (62.7%)
Use of special immunosuppressants^#, n (%)	23(39.0%)
Indicators within 24 hours of infection
Neutrophil count, 10^9/L, median (IQR)	2 (0.1, 3.55)
Lymphocyte count, 10^9/L, median (IQR)	0.3 (0.1, 0.55)
Platelet count, 10^9/L, median (IQR)	34 (14, 63)
PCT, μg/L, median (IQR)	0.3 (0.165, 0.865)
Albumin, g/L, median (IQR)	32.3 (28.85, 37.3)
Total bilirubin, μmol/L, median (IQR)	12.4 (7.55, 20.4)
Creatinine, μmol/L, median (IQR)	63 (49.95, 84.05)
Septic shock, n (%)	12 (20.3%)
Admission to ICU after transplantation, n (%)	15 (25.4%)
Mechanical ventilation, n (%)	4 (6.8%)
Hospital stay, days, median (IQR)	50 (33, 69.5)
Mortality, n (%)	25 (42.4%)

Note: ^#Special immunosuppressants here mainly refer to ruxolitinib, tacrolimus and balliximab.

Abbreviations: HSCT, hematopoietic stem cell transplantation; CRKP, carbapenem-resistant Klebsiella pneumoniae; ESBL, extended-spectrum beta-lactamase; HLA, human leukocyte antigen; GVHD, graft-versus-host disease; CMV, cytomegalovirus; PCT, procalcitonin; ICU, intensive care unit; IQR, interquartile range.

Figure 1 Susceptibility of K. pneumoniae to clinically common antibiotics. (A) Drug resistance rates of K. pneumoniae to twelve antibiotics; (B) drug resistance rates of carbapenem-resistant Klebsiella pneumoniae to twelve antibiotics; (C) comparison of drug resistance rates of K. pneumoniae in two time periods (before 2018 vs after 2018).

Note: *P < 0.05.

Abbreviations: TZP, piperacillin-tazobactam; AMC, amoxicillin-clavulanic acid; CTRX, ceftriaxone; AZT, aztreonam; AN, amikacin; GEN, gentamicin; CPFX, ciprofloxacin; LVF, levofloxacin; TGC, tigecycline; MEM, meropenem; IPM, imipenem; SMZ-TMP, cotrimoxazole.

Table 2 Univariate and Multivariate Analysis of Risk Factors Associated with CRKP Acquisition Among HSCT Recipients

Variable	Univariate Analysis			Multivariable Analysis
	CRKP (-)	CRKP (+)	P	OR (95% CI)	P
Age > 50 years, n (%)	7 (14.6%)	4 (36.4%)	0.106
Male, n (%)	34 (70.8%)	7 (63.6%)	0.641
Interval from diagnosis to transplantation > 180 days, n (%)	21 (43.8%)	8 (72.7%)	0.095
An infection 3 months before transplant, n (%)	3 (6.2%)	4 (36.4%)	0.013*	10.981(1.474, 81.809)	0.019*
Use of carbapenems > 3 days 1 month prior to infection, n (%)	34 (70.8%)	7 (63.6%)	0.641
Urethral catheterization, n (%)	2 (4.2%)	4 (36.4%)	0.007*	5.819(0.674, 50.271)	0.109
Use of special immunosuppressants, n (%)	19 (39.6%)	4 (36.4%)	0.844
Indicators within 24 hours of infection, n (%)
Neutrophil count < 0.5×10^9/L	12 (25.0%)	4 (36.4%)	0.448
PCT > 5 μg/L	6 (12.5%)	2 (18.2%)	0.622
Creatinine > 177 μmol/L	8 (16.7%)	5 (45.5%)	0.047*	4.225(0.694, 25.726)	0.118

Note: *P values are statistically significant.

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; HSCT, hematopoietic stem cell transplantation; CMV, cytomegalovirus; PCT, procalcitonin; OR, odd ratio; CI, confidence interval.

Table 3 Univariate and Multivariate Analysis of Risk Factors Associated with Mortality of K. pneumoniae Infection in HSCT Recipients

Variable	Univariate Analysis		Multivariable Analysis
	HR (95% CI)	P	HR (95% CI)	P
Age > 50 years	0.132 (0.018–0.974)	0.047*
Interval from diagnosis to transplantation > 180 days	4.276 (1.699–10.761)	0.002*	3.963(1.25–12.561)	0.019*
HLA non-identical	1.664 (0.665–4.168)	0.277
Engraftment period > 20 days	3.26 (1.358–7.827)	0.008*	8.015 (2.355–27.279)	0.001*
CRKP infections	2.613 (1.122–6.082)	0.026*
Non-use of anti-CMV gamma globulin/rituximab	4.051 (1.389–11.821)	0.010*	10.720 (2.390–48.089)	0.002*
Inappropriate empiric antimicrobial treatment	1.625 (0.740–3.566)	0.226
Indicators within 24 hours of infection
Neutrophil count < 1.5×10^9/L	1.885 (0.855–4.159)	0.116
Albumin < 30 g/L	1.31 (0.578–2.967)	0.518
Total bilirubin > 34.2 μmol/L	3.98 (1.571–10.080)	0.004*
Creatinine > 177 μmol/L	2.525 (1.112–5.735)	0.027*
PCT > 5 μg/L	6.589 (2.665–16.291)	0.000*	5.906 (1.623–21.500)	0.007*
Mechanical ventilation	11.743 (3.542–38.932)	0.000*
Septic shock	6.741 (2.945–15.429)	0.000*

Note: *P values are statistically significant.

Abbreviations: HSCT, hematopoietic stem cell transplantation; HLA, human leukocyte antigen; CMV, cytomegalovirus; PCT, procalcitonin; HR, hazard ratio; CI, confidence interval.

Figure 2 Survival comparison of patients with independent risk factors (Kaplan-Meier curve). (A) Engraftment period > 20 days vs ≤ 20 days (37.9% vs 76.7%, P=0.005); (B) procalcitonin > 5 μg/L vs ≤ 5 μg/L (12.5% vs 64.7%, P<0.001); (C) interval from diagnosis to transplantation > 180 days vs ≤ 180 days (34.5% vs 80.0% P=0.001) (D) non-use of anti-CMV immunoglobulin/rituximab vs use of (43.2% vs 81.8%, P=0.005).

Abbreviations: CMV, cytomegalovirus; HR, hazard ratio.