Predictors of Acute Kidney Injury and 28-Day Mortality in Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia

Abstract

Colistin is an, antibiotic used to treat carbapenem-resistant Acinetobacter baumannii complex (CRABC) infection. However, colistin is well known for its nephrotoxicity. To accurately assess the effects of colistin on acute kidney injury (AKI) and 28-day mortality, we investigated the risk factors associated with AKI and mortality in patients with CRABC bacteremia who received or never received colistin. Patients with CRABC bacteremia aged ≥18 years were retrospectively identified for 3 years at five tertiary teaching hospitals. AKI was defined by using the Kidney Disease Improving Global Outcomes criteria. AKI developed in 103 (34.9%) of the 295 patients enrolled patients. AKI developed more frequently in patients who received colistin than in patients who did not (46.7% vs. 29.5%, p = 0.004). Multivariate analysis showed that intravenous colistin usage was an independent risk factor for AKI in these patients. Nonfatal disease, catheter-related bloodstream infection, and administration of colistin were protective factors for 28-day mortality. However, the sequential organ failure assessment score and AKI were associated with poor outcomes. In conclusion, colistin may be a double-edged sword; although it causes AKI, it also reduces 28-day mortality in patients with CRABC bacteremia. Therefore, colistin administration as an appropriate antibiotic may improve CRABC bacteremia prognosis, despite its nephrotoxicity.

Introduction

Acinetobacter baumannii complex (ABC) is an important pathogen, that causes health care-associated infections, and results in various diseases, such as pneumonia, catheter-related infections, and urinary tract infections.¹ A rise in infections due to carbapenem-resistant Acinetobacter baumannii complex (CRABC) has been increasingly reported worldwide.^2,3 In the United States, the carbapenem resistance rates among ABC strains range from 33% to 58%.^4–6 In South Korea, the carbapenem resistance rate of ABC identified in hospitals has been reported to reach 90%.^7,8 The reported mortality among patients with ABC infection is high (35–83%), and infection with CRABC is associated with poor outcomes.^9–13

Early appropriate antimicrobial treatment is crucial to improve the clinical outcome of CRABC bacteremia. However, colistin and polymyxin B are often the only effective agents against multidrug-resistant Gram-negative bacteria, including CRABC. Pharmaceutical formulations of colistin and polymyxin B are available for clinical use in many countries, but only parenteral products of colistimethate sodium (CMS) products are approved in South Korea. Colistin and polymyxin B have similar chemical structures and antibacterial activity in vitro.^14,15 Although polymyxin B is administered to patients in its active form, colistin is administered as an inactive prodrug, CMS, and in vivo conversion to colistin is required for activity.^15,16

However, acute kidney injury (AKI) is a notable dose-limiting adverse effect of colistin. It occurs in a substantial proportion of patients receiving colistin, ranging from to 14–76%, and varies depending on the definition of AKI.^11,17–21 To date, no single biomarker or set definitions of colistin-induced AKI have been established. There have been many definitions of AKI, including the Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) classification,²² and the Acute Kidney Injury Network (AKIN) criteria.²³ The latest classification proposed by the Kidney Disease Improving Global Outcomes (KDIGO) AKI Work Group, based on the previous two classifications, aimed at unifying the definition of AKI.²⁴ Currently, only a few have evaluated colistin-associated nephrotoxicity by using KDIGO criteria.²⁵

Here, we present colistin-associated nephrotoxicity by using KDIGO criteria. Although there are numerous studies regarding colistin-associated nephrotoxicity, one limitation is the lack of a control group who did not receive colistin, which has limited the evaluation of the true effect of the drug.^11,18,26 To accurately assess the effects of colistin on AKI, we compared patients who received colistin and did not receive colistin, and we investigated other risk factors associated with AKI in patients with CRABC bacteremia. In addition, we evaluated 28-day mortality outcomes in patients with CRABC bacteremia.

Methods

Study population and design

This retrospective multicenter study was conducted at five tertiary teaching hospitals located in Seoul, Bucheon, Goyang, and Cheonan, Republic of Korea. The medical records of patients with CRABC bacteremia aged ≥18 years identified between April 2012 and March 2015 were reviewed. Bacteremia was defined as one or more blood-positive cultures for CRABC and the presence of clinical features corresponding with the infection. If a patient had undergone recurrent CRABC bacteremia episodes during the study period, only the first episode was considered.

AKI was defined according to stages 2 and 3 of the KDIGO criteria²⁴ (Supplementary Table S1). We did not include stage 1 of the KDIGO criteria because of its susceptibility to variable factors during septic conditions. Accordingly, AKI was defined as any of the following: (1) an increase in serum creatinine by ≥2 fold compared with baseline, (2) a urine output of <0.5 mL/(kg·h) for ≥12 hours, and (3) initiation of renal replacement therapy (RRT).

Colistin was administered as CMS and supplied as 150 mg colistin base activity per vial. The dose of colistin recommended by the manufacturer is 2.5–5 mg/(kg·d) in 2–4 separate doses.

Patients with end-stage renal disease (ESRD) who received RRT before developing CRABC bacteremia were excluded. Patients who were transferred to another hospital within 28 days of bacteremia onset were also excluded.

Data collection

Patient demographic characteristics and comorbidities were collected. The severity of comorbidities was classified according to the McCabe and Jackson Classification system.²⁷ The source of infection was determined according to the guidelines issued by the Centers for Disease Control and Prevention.²⁸ For example, pneumonia was defined as the presence of a new pulmonary infiltrate, plus one additional criterion (fever ≥38°C, blood leukocyte count >10,000/mm³, or leukopenia <3,000/mm³), and together with one or more of the following conditions: new cough, change in color of sputum, chest pain, and dyspnea. Catheter-related bloodstream infection (CRBSI) was defined as a positive blood culture, that is, a positive catheter tip culture yielding the same species of microorganisms, or as growth of the same pathogen from blood cultures of the central venous catheter (CVC) and a peripheral vein, with positive values for different times to positivity. If a primary focus of infection could not be determined, it was considered unknown.

Mechanical ventilation, vasopressor use, dialysis, Acute Physiologic Assessment Chronic Health Evaluation (APACHE) II score,²⁹ and Sequential Organ Failure Assessment (SOFA) score³⁰ were chosen indices of severity. Glycopeptide and aminoglycoside usage as nephrotoxic drugs were searched.

The primary end point of the study was to evaluate the potential risk factors for AKI in patients with CRABC bacteremia. Clinical characteristics were compared between patients with and without AKI to identify risk factors associated with it. To accurately assess the effects of colistin on AKI, we also compared the clinical characteristics of patients who received colistin and never received colistin.¹⁹ Finally, risk factors for 28-day mortality were evaluated, including colistin usage.

Microbiological methods

CRABC bacteremia was defined as the presence of at least one blood culture positive for CRABC, in concurrence with clinical features associated with the infection. At least four species, A. calcoaceticus, A. baumannii, A. nosocomialis, and A. pittii, have been invariably reported as A. baumannii by clinical microbiology laboratories because biochemical methods cannot differentiate them at the species level.^31,32 Therefore, these species referred to using the ABC. Bacterial identification of the isolates to the level of ABC was determined by using the Vitek 2 system (bioMérieux) or ASTA MicroIDSys (ASTA, Suwon, Korea). Susceptibility testing was performed by using the microdilution method (MicroScan system; Baxter Health Care, West Sacramento, CA), and the results were interpreted according to the guidelines of the National Committee for Clinical Laboratory Standards.³³ Imipenem resistance was defined as a minimal inhibitory concentration of 8 μg/mL or above. The ABC isolates with imipenem resistance were considered CRABC.

Statistical analyses

Statistical analyses were performed by using IBM SPSS Statistics for Windows (version 20.0; IBM Corp., Armonk, NY). Continuous variables were compared by using the Mann–Whitney U test or Student's t-test, as appropriate. Categorical variables were compared by using Pearson's chi-square test or Fisher's exact test. Univariate and multivariate analyses of risk factors associated with AKI and 28-day mortality were performed by using binary logistic regression models using the stepwise backward method. Variables with a p < 0.1 in the univariate analysis were included in the multivariate analysis. All significance testing was two-tailed, and p < 0.05 was considered statistically significant.

Results

Patient characteristics

A total of 332 patients with CRABC bacteremia were identified. After the exclusion of 22 patients with ESRD and 15 patients transferred to other hospitals within 28 days after the blood culture test was performed, 295 patients with CRABC bacteremia were enrolled in the analysis (Fig. 1). Their median age was 70 years old (interquartile range [IQR, 56–77] years), and 62.7% were males. CRABC bacteremia occurred at a median of 14 (IQR, 7–33) days after hospitalization. The primary source of bacteremia was pneumonia (45.8%). Of the 295 patients, 72.5% developed bacteremia in the intensive care unit. Septic shock developed in 38.3% of the patients. The median APACHE II score was 16 (IQR, 4–24), and the 28-day mortality rate was 59.8%.

FIG. 1.

Study flow chart. ESRD, end-stage renal disease; CRBSI, catheter-related bloodstream infection.

AKI in patients with CRABC bacteremia

AKI occurred in 103 (34.9%) patients. The differences in the clinical characteristics of patients with and without AKI are shown in Table 1. Baseline characteristics, including age and sex, were similar between the two groups. However, patients with AKI more often presented with fatal or rapidly fatal McCabe classification than patients without AKI (56.3% vs. 43.2%, p = 0.03).

Table 1.

Comparison of Clinical Characteristics between Patients With and Without Acute Kidney Injury in Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia

	With AKI (N = 103)	Without AKI (N = 192)	p
Median age, years	68 (57–76)	70 (56–77)	0.64
Male gender	69 (67.0)	116 (60.4)	0.27
Actual body weight (kg)	57.9 (48–67)	57 (48–64.8)	0.47
Underlying diseases	96 (93.2)	176 (91.7)	0.64
Diabetes mellitus	32 (31.1)	50 (26)	0.41
Neurologic disease	23 (22.3)	73 (38)	0.006
Chronic lung disease	22 (21.4)	38 (19.8)	0.75
Malignancy	28 (27.2)	39 (20.3)	0.18
Chronic renal insufficiency	7 (6.8)	9 (4.7)	0.44
Liver cirrhosis	9 (8.7)	20 (10.4)	0.64
McCabe classification
Nonfatal	45 (43.7)	109 (56.8)	0.03
Ultimately fatal	42 (40.8)	67 (34.9)	0.32
Rapidly fatal	16 (15.5)	16 (8.3)	0.06
Previous admission days	14.0 (7–32)	14.5 (7–35)	0.44
Acquired infection in ICU	79 (76.7)	135 (70.3)	0.24
Baseline SCr, mg/dL	1.0 (0.6–1.8)	0.9 (0.6–1.5)	0.23
Baseline eGFR (mL/min/1.73 m²)	59.5 (32–98)	65 (35.3–110)	0.10
Severity of infection
Septic shock	42 (40.8)	71 (37.0)	0.52
SOFA score	8 (5–13)	8 (4–13)	0.99
APACHE II	17 (5–24)	16 (3–24)	0.75
Source of bacteremia
Pneumonia	57 (55.3)	78 (40.6)	0.02
Unknown primary	34 (33.0)	60 (31.2)	0.79
CRBSI	7 (6.8)	22 (11.5)	0.20
Intra-abdominal infection	4 (3.9)	14 (7.3)	0.24
Others^a	1 (1.0)	13 (6.8)	0.04
Nephrotoxic drug
Glycopeptide	46 (44.7)	88 (45.8)	0.85
Aminoglycoside	5 (4.9)	9 (4.7)	0.95
Intravenous colistin ≥ 3 days	43 (41.7)	49 (25.5)	0.006
Use of loading dose	4 (2.1)	4 (3.9)	0.46
Treatment duration (day)	7 (4–14)	11.5 (5–16)	0.24
Cumulative dose (mg)	1,200 (720–2,170)	2,016 (600–4,050)	0.09
Dose per ABW [mg/(kg·d)]	3.40 (1.34–5.38)	3.52 (2.21–4.85)	0.75

Continuous variables are presented as n (%), unless otherwise noted. Categorical variables are presented as median (IQR), unless otherwise noted.

Urinary tract infection (7), soft tissue infection (5), endovascular infection (1), and bone & joint infection (1).

ABW, actual body weight; AKI, acute kidney injury; APACHE, acute physiology and chronic health evaluation; CRBSI, catheter-related bloodstream infection; eGFR, estimated glomerular filtration rate; ICU, intensive care unit; IQR, interquartile range; SCr, serum creatinine; SOFA, sequentialorgan failure assessment.

The severity of infection, such as SOFA or APACHE II score, was not different between the two groups at bacteremia onset. Patients with AKI more often had pneumonia as the source of bacteremia (55.3% vs. 40.6%, p = 0.02). Patients who developed AKI received colistin more frequently (41.7% vs. 25.5%, p = 0.006). The 28-day mortality in patients with AKI was higher than in those without AKI (70.9% vs. 52.6%, p = 0.002).

Comparison of patients who received colistin with those who never received colistin

To clarify the effect of intravenous colistin, we performed a subgroup analysis of patients who received intravenous colistin for ≥ 3 days and patients who never received intravenous colistin during hospitalization (Table 2). Ninety-two patients received colistin for ≥ 3 days, and 190 patients never received colistin during hospitalization. Baseline characteristics, including baseline creatinine levels, did not differ between the two groups. However, patients who never received colistin had more rapidly fatal disease (14.7% vs. 2.2%, p = 0.001). CRABC bacteremia was relatively more severe in septic shock and SOFA scores in patients who never received colistin. Thus, patients who received colistin had less severe infections and comorbidities. However, AKI occurred more frequently in patients who received colistin (46.7% vs. 29.5%, p = 0.004). The number of patients who initiated RRT did not differ between the two groups (14.1% vs. 16.8%, p = 0.56). Mortality at 28 days was much higher in patients who never received colistin (64.2% vs. 44.6%, p = 0.002).

Table 2.

Comparison of Clinical Characteristics between Patients with Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia Who Received Colistin and Those Who Never Received Colistin

Variables	With colistin (N = 92)	Without colistin (N = 190)	p
Median age, years	70 (55–76)	69 (57–77)	0.30
Male gender	58 (63.0)	120 (63.2)	0.99
McCabe classification
Nonfatal	54 (58.7)	94 (50.5)	0.20
Ultimately fatal	36 (39.1)	66 (34.7)	0.47
Rapidly fatal	2 (2.2)	28 (14.7)	0.001
Acquired infection in ICU	69 (75.0)	135 (71.1)	0.49
Baseline SCr, mg/dL	0.8 (0.6–1.3)	1.0 (0.6–1.6)	0.10
Baseline eGFR (mL/min/1.73 m²)
AKI	43 (46.7)	56 (29.5)	0.004
Initiation of RRT	13 (14.1)	32 (16.8)	0.56
Severity of infection
Septic shock	23 (25.0)	82 (43.2)	0.003
SOFA score	7 (4–10)	9 (5–14)	0.008
Main treatment
Intravenous colistin ≥ 3 days	92 (100)
Carbapenem		69 (36.3)
β-lactam/β-lactamase inhibitor		40 (21)
Carbapenem + vancomycin		42 (22.1)
Tigecycline	4 (4.3)	9 (4.7)
Others		30 (15.8)
Nephrotoxic drug
Glycopeptide	46 (50.0)	86 (45.3)	0.46
Aminoglycoside	6 (6.5)	8 (4.2)	0.40
28-Day mortality	41 (44.6)	122 (64.2)	0.002

Continuous variables are presented as n (%), unless otherwise noted. Categorical variables are presented as medians (IQRs), unless otherwise noted.

eGFR, estimated glomerular filtration rate; RRT, renal replacement therapy.

When we performed the same analysis including all the patients who received colistin at least once, the number of patients with colistin was 105, and that without was 190. AKI occurred more frequently in the colistin group than in the group that did not receive colistin (44.8% vs. 29.5%, p = 0.008). The other variables showed similar results (data not shown).

Predictors of AKI

We performed multivariate analyses to identify risk factors associated with AKI in CRABC bacteremia, (Table 3). Administration of intravenous colistin for ≥ 3 days was an independent predictor of AKI development (adjusted odds ratio [aOR], 2.36; 95% confidence interval [CI], 1.38–4.06; p = 0.002). As an underlying disease and presence of infections at other sites, such as urinary tract infection, and soft tissue infections, the neurologic disease was considered a protective factor for AKI development among patients with CRABC bacteremia (aOR, 0.4; 95% CI, 0.24–0.78; p = 0.005).

Table 3.

Multivariate Analysis of Risk Factors Associated with Acute Kidney Injury in Patients with Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia

Variables	Univariate analysis		Multivariate analysis
Variables	OR (95% CI)	p	aOR (95% CI)	p
Neurologic disease	0.47 (0.27–0.81)	0.006	0.4 (0.24–0.78)	0.005
Nonfatal diseases	2.02 (0.97–4.24)	0.06	0.64 (0.38–1.08)	0.09
Pneumonia	1.81 (1.12–2.94)	0.02	1.67 (1.0–2.78)	0.05
Other infection site^a	0.13 (0.02–1.05)	0.04	0.18 (0.02–1.45)	0.11
Intravenous colistin ≥ 3 days	2.09 (1.27–3.44)	0.004	2.36 (1.38–4.06)	0.002

Urinary tract infection (7), soft tissue infection (5), endovascular infection (1), and bone & joint infection (1).

aOR, adjusted odds ratio; CI, confidence interval; OR, odds ratio.

Predictors of 28-day mortality

The 28-day mortality rate was 59.8%. We performed multivariate analyses to identify risk factors for mortality, including colistin and AKI (Table 4). Multivariate analysis showed that nonfatal disease among McCabe Jackson criteria (aOR, 0.15; 95% CI, 0.05–0.38; p < 0.001), CRBSI (aOR, 0.26; 95% CI, 0.08–0.82; p = 0.02), and use of intravenous colistin (aOR, 0.41; 95% CI, 0.20–0.84; p = 0.02) were associated with increased survival of the patients. Meanwhile, the SOFA score (aOR, 1.23; 95% CI, 1.12–1.35; p < 0.001), initiation of RRT (aOR, 6.16; 95% CI, 1.54–24.6; p = 0.01), and development of AKI (aOR, 2.96; 95% CI, 1.43–6.15; p = 0.003 as shown in Table 4) were independent risk factors for 28-day mortality.

Table 4.

Multivariate Analysis of Risk Factors Associated with 28-Day Mortality in Patients with Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia

Variables	Univariate analysis		Multivariate analysis
Variables	OR (95% CI)	p	aOR (95% CI)	p
Nonfatal disease	0.15 (0.06–0.39)	<0.001	0.15 (0.05–0.38)	<0.001
Underlying disease
Malignancy	0.36 (0.13–1.00)	0.05	0.40 (0.14–1.12)	0.08
Neurogenic disorder	0.74 (0.33–1.65)	0.46
Lung disease	1.47 (0.62–3.45)	0.38
Acquired infection in ICU	2.54 (1.06–6.11)	0.04	2.22 (0.98–4.99)	0.05
SOFA score	1.22 (1.10–1.34)	<0.001	1.23 (1.12–1.35)	<0.001
Baseline eGFR	0.99 (0.99–1.0)	0.75
Initiation RRT	7.42 (2.8–19.4)	<0.001	6.16 (1.54–24.62)	0.01
CRBSI	0.37 (0.10–1.28)	0.12	0.26 (0.08–0.82)	0.02
Pneumonia	21.71 (0.778–3.78)	0.18
Intravenous colistin ≥ 3 days	0.40 (0.19–0.84)	0.02	0.38 (0.16–0.69)	0.003
AKI	2.75 (1.30–5.72)	0.007	2.96 (1.43–6.15)	0.003

Discussion

In the current study using the KDIGO criteria, the overall AKI rate was 34.9% (103/295) in patients with CRABC bacteremia, and colistin-associated AKI was 46.7% (43/92). We identified intravenous colistin administration as an independent predictor of AKI. SOFA score and AKI were independent risk factors for 28-day mortality, whereas intravenous colistin administration was a protective factor for poor outcome.

Colistin is well known for its nephrotoxicity. However, the prevalence of nephrotoxicity is highly variable, ranging from 10% to 76%, depending on the different definitions of AKI and patient population heterogeneity.^{11,17–19,34} In another study evaluating colistin-associated nephrotoxicity, the results using the RIFLE and KDIGO criteria were generally consistent.²⁵ The results of the studies on colistin nephrotoxicity to compare the nephrotoxicity rates using standardized international criteria, such as the RIFLE,²² AKIN,²³ and KDIGO criteria,²⁴ were relatively similar.³⁵ Therefore, this finding suggests that the KDIGO criteria could also provide reliable indications of colistin-associated nephrotoxicity.

Although there have been numerous studies on colistin-associated nephrotoxicity, one limitation has been the lack of a control group who did not receive colistin, which has limited the evaluation of the actual effect of this drug.^11,18,26 In the current study, we compared the colistin group and other groups who never received colistin. In our results, 46.7% of patients in the colistin group developed AKI, whereas 29.5% of patients who never received colistin developed AKI. Thirty patients with AKI did not receive other nephrotoxic agents, such as glycopeptide, aminoglycoside, or colistin; these cases might be affected by factors other than colistin, such as sepsis. Many authors agree that the renal effects of sepsis should not be underestimated,^11,19 and the nephrotoxicity of colistin might be overestimated in septic conditions. Nevertheless, colistin is an independent predictor of nephrotoxicity and doubled the incidence of AKI in patients with CRABC bacteremia.

One interesting finding is that physicians hesitated to administer colistin in patients with more severe underlying disease and more severe infection. As a result, most of the patients in the group who did not receive colistin also did not receive in vitro susceptible antibiotics. These findings suggest that physicians still consider colistin a suboptimal drug with a high risk of adverse events, such as nephrotoxicity. However, colistin is often the only treatment option for CRABC infection. In addition, administration of colistin was a protective factor against 28-day mortality in the present study. Early administration of colistin was associated with improved survival in patients with pneumonia¹⁰ and CRABC bacteremia.³⁶ Therefore, our study suggests that despite the increased AKI rate in the colistin group, colistin has clinical benefit in treating CRABC bacteremia, and it is therefore an appropriate antibiotic to treat CRABC infection.

Another protective factor for 28-day mortality was nonfatal disease among the McCabe Jackson classified diseases and CRBSI as a site of infection. The presence of severe comorbidities could result in a high severity of illness, causing higher mortality. We used the McCabe Jackson classification to evaluate the severity of the underlying disease.²⁷ The classic McCabe Jackson criteria was developed to predict the likelihood of survival of patients with Gram-negative bacteremia, based on the underlying disease. Therefore, nonfatal disease might be a predictor of survival, as shown in a previous report.³⁷ The outcome of CRBSI was favorable in this study. This might be explained by the fact that the short duration of antibiotic therapy in CRBSI due to Gram-negative bacilli was not associated with therapeutic failure once the CVC had been removed.^38,39

In our study, SOFA score and AKI were independently associated with 28-day mortality. This is in line with the fact that higher SOFA scores are related to mortality at the onset of ABC bacteremia.^40,41 AKI defined by KDIGO and RIFLE criteria has demonstrated significant predictive utility for mortality risk in critically ill patients.^42,43 AKI has long been recognized as a complication of critical illness independently associated with mortality.^35,44

This study had several limitations. First, this study had a retrospective design; therefore, a hidden bias may have resulted in an under- or overestimation of the proper relationship between colistin and nephrotoxicity. For example, nephrotoxic medication contributes to a substantial proportion of AKI in hospitalized patients other than colistin, glycopeptide, and aminoglycosides.⁴⁵ However, because of the study's retrospective nature, we could not search every nephrotoxic medication administered to the study patients. Since colistin is the only treatment option for many infections, a prospective randomized trial would inevitably be associated with ethical problems. Second, the attending physician's preference could be a potential confounding factor for prescribing colistin or other drugs. An institutionally standardized dosing protocol for intravenous colistin was not dictated during the study period. Therefore, prescriber preference could have contributed to potential confounding through higher doses in patients perceived as more severely ill. Besides colistin dose, physicians hesitated to administer colistin in patients with CRABC bacteremia with more severe underlying disease and more severe infection. Finally, some may argue that it is inappropriate to compare the clinical characteristics of patients with colistin or without colistin because patients in the group who did not receive colistin also did not receive an in vitro susceptible drug for the treatment of CRABC bacteremia. However, our scope is to evaluate the risk factors for AKI. Thus, to accurately evaluate the effect of colistin on AKI, we compared colistin and no-colistin groups, as shown in another report.¹⁹

In conclusion, AKI occurred in more than one-third of patients with CRABC bacteremia. Intravenous colistin was an independent predictor of AKI, and it doubled the incidence of AKI in CRABC bacteremia. Despite its limitations due to nephrotoxicity, colistin usage was a protective factor for 28-day mortality. Therefore, prompt and accurate administration of these drugs should be considered for the treatment of CRABC bacteremia.

Footnotes

Authors' Contributions

S.N.Y., T.K., and S.Y.P. designed the study. S.N.Y., T.K., S.Y.P., Y.M.L., K.H.P., E.J.L., M.H.J., E.J.C., T.H.K., M.S.L., and S.Y.P. collected and assembled the data. S.N.Y. and T.K. performed statistical analyses. S.N.Y. and S.Y.P. drafted the article. All authors read and approved the final article.

Ethical Approval

Dongguk University Ilsan Hospital institutional review board approved this study (IRB number 2015-65). All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Disclosure Statement

The authors declare that they have no conflicts of interest. The corresponding author had full access to all data and had final responsibility for the decision making to submit the article for publication.

Funding Information

This work was supported by the Soonchunhyang University Research Fund (2020).

Supplementary Material

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