antibiotics

Article
Multi-Drug Resistant Organisms Infection Impact on Patients
Length of Stay in Respiratory Care Ward
Yi-Ping Chen 1 , Xian-Wen Tasi 2 , Ko Chang 3,4 , Xuan-Di Cao 5 , Jung-Ren Chen 6, * and Chien-Sen Liao 6, *

1 Department of Medical Laboratory, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University,
Kaohsiung 81267, Taiwan; [email protected]
2 Department of Nursing and Medical Quality Management Center, Kaohsiung Municipal Siaogang Hospital,
Kaohsiung Medical University, Kaohsiung 81267, Taiwan; [email protected]
3 Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University,
Kaohsiung 81267, Taiwan; [email protected]
4 College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
5 Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan;
[email protected]
6 Department of Biological Science and Technology, I-Shou University, Kaohsiung 82445, Taiwan
* Correspondence: [email protected] (J.-R.C.); [email protected] (C.-S.L.);
Tel.: +886-7-6151100 (ext. 7320) (J.-R.C.); +886-7-6151100 (ext. 7313) (C.-S.L.)

Abstract: This study aimed to investigate the effects of multi-drug-resistant organism (MDRO)
infection and other factors on the length of hospital stay (LOS) of patients in the respiratory care
ward (RCW) of a regional hospital in Taiwan. In this retrospective study, we collected cases from





 MDRO-infected patients in the RCW from January 2016 to March 2020. The RCW comprises 13 beds
in total. There were 106 infected patients, of which 42 were in the case group (infected with MDROs)
Citation: Chen, Y.-P.; Tasi, X.-W.;
Chang, K.; Cao, X.-D.; Chen, J.-R.;
and 64 were in the control group (not infected with MDROs). Clinical specimens were inoculated in
Liao, C.-S. Multi-Drug Resistant a selective medium to isolate the pathogenic bacteria by standard procedures. The results showed
Organisms Infection Impact on the main factors affecting the LOS were: patients with MDRO infection, patients discharged from
Patients Length of Stay in Respiratory the RCW, and patients who underwent catheterization. The LOS of patients infected with MDROs
Care Ward. Antibiotics 2021, 10, 608. was significantly longer than that of patients without MDRO infection (β = 0.55, 95% CI = 0.02–1.09),
https://doi.org/10.3390/ with the case group and the control group being 479.8 ± 546.5 and 307.3 ± 436.2 days, respectively.
antibiotics10050608 Infection with carbapenem-resistant Pseudomonas aeruginosa (CRPA) was associated with a longer
LOS than other MDRO strains. These findings have important implications for infection control in
Academic Editor: Maria
RCW and in better tracking the health of patients.
Teresa Mascellino

Keywords: length of stay; multi-drug resistant organisms; respiratory care ward; carbapenem-
Received: 30 March 2021
resistant Pseudomonas aeruginosa
Accepted: 17 May 2021
Published: 20 May 2021

Publisher’s Note: MDPI stays neutral

with regard to jurisdictional claims in
1. Introduction
published maps and institutional affil- Airway protection in patients with respiratory distress requires intubation and venti-
iations. lation support via an artificial airway. During intubation, it is easy to damage the natural
defense mechanisms of the oropharynx, causing bacterial infection of the lower respiratory
tract, leading to ventilator-associated pneumonia (VAP) [1,2]. VAP is a serious complica-
tion that significantly impacts the prognosis of patients in RCWs, and it incurs additional
Copyright: © 2021 by the authors. medical expenses [3]. Repeated cases of VAP have been documented in critically ill pa-
Licensee MDPI, Basel, Switzerland. tients having undergone endotracheal intubation and ventilation apparatus support in
This article is an open access article RCWs [4]. These patients require a variety of invasive interventions, and the long-term
distributed under the terms and hospital stay has a huge impact on medical costs. Moreover, antibiotics that are widely
conditions of the Creative Commons used in order to avoid infections in patients drive the generation of multi-drug-resistant
Attribution (CC BY) license (https:// organisms (MDROs): pathogenic bacteria resistant to more than one kind of antibiotic,
creativecommons.org/licenses/by/ which ultimately lead to poor therapeutic control by antibiotics [5,6].
4.0/).

Antibiotics 2021, 10, 608. https://doi.org/10.3390/antibiotics10050608 https://www.mdpi.com/journal/antibiotics

Antibiotics 2021, 10, 608 2 of 10

Healthcare-associated infections (HAIs) also extend the total length of stay in the
hospital. According to a study by Jia et al. [7], HAIs increased the economic burden to
patients in 68 hospitals in China. This difference was statistically significant (p < 0.01).
According to estimates by Zilahi et al. [8], HAIs in the ICU in Iran resulted in a relatively
hefty financial burden related to antibiotics, higher mortality rates, and longer hospital
stays. The extra hospital stay for bloodstream infections (BSIs) was 3.48 days, urinary tract
infections (UTIs) was 3.59 days, surgical site infections (SSIs) was 7.23 days, and VAP was
11.52 days. One study also reported variable LOS for different infection sites: LOS of central
line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP),
and catheter-associated urinary tract infections (CAUTI) were 27.1, 22.2, and 19.2 days,
respectively [9].
MDROs among deceased organ donors are a risk factor for medical-related infec-
tions [10] and one of the risk factors for prolonging LOS. Infection control measures to
reduce cross-spread should include strategies to decrease the infection rate of various parts
of the RCW [11], reduce overuse of medical resources, and reduce LOS, thereby optimizing
antibiotic management [12].
The objectives of this study were to investigate the effects of MDRO infection and other
factors on the LOS of patients in the RCW of a regional hospital in Taiwan. These results
have important implications for infection control in the RCW and may help with devising
prevention and control strategies for multi-drug-resistant bacterial infections. These data
may also provide insight regarding the health of patients and clinical medical staff in
high-acuity medical units through improved infection information.

2. Materials and Methods

2.1. Research Design and Data Collection
This study was conducted in a regional teaching hospital with 496 patient beds.
This hospital is an important tertiary care medical institution in Kaohsiung, Taiwan.
The present study is a retrospective review of hospital-acquired infections due to MDRO
strains collected from patients in the RCW from January 2016 to March 2020. The RCW
comprises 13 beds in total. The positivity rates of MDRO-infected patients over the five-
year period were analyzed by WHONET. Inclusion criteria targeted only patients identified
as having their first confirmed infection of a MDRO strain in a given year. A total of
42 MDRO-infected patients and 64 control patients were enrolled in the study. Ethical ap-
proval for this study was obtained from the Institutional Review Board, Kaohsiung Medical
University, Kaohsiung, Taiwan, approval number KMUHIRB-E(I)-20190148.

2.2. Antibiotic Susceptibility and Species Identification of Bacterial Isolates

Clinical specimens were inoculated in a selective medium to isolate the pathogenic
bacteria by standard procedures. Bacterial isolates were speciated, and antibiotic suscepti-
bility was determined on automated VITEK and VITEK® 2 Compact platforms (bioMérieux,
Inc., Hazelwood, MO, USA). Full traceability and minimization of transcription errors were
ensured using automated bar-coding technology. VITEK® 2 Compact GN (bioMérieux,
VITEK 2 AST-N339 REF419341, Marcy-l’Étoile, France) was used for identifying CRE,
CRAB, and CRPA. Compact GP (bioMérieux VITEK 2 AST-P627 REF414124, Marcy-l’Étoile,
France) was used for identifying vancomycin-resistant Enterococcus faecium (VREfm) and
MRSA. Antibiotic susceptibility was based on the definitions of the 2016 version of CLSI
(Clinical and Laboratory Standards Institute, Wayne, PA, USA). ATCC25922, ATCCBAA-
1705, and ATCCBAA-170 were used as standard strains. The culture medium was provided
by Coning Technology Limited Company (Taichung, Taiwan). The minimum inhibitory
concentration (MIC) of antibiotic susceptibility was determined according to the MCN-6
system (Merlin, Diagnostics, Bornheim-Hersel, Germany) and Clinical and Laboratory
Standards Institute (CLSI, Wayne, PA, USA) specifications. E. coli ATCC 25922, E. coli ATCC
35218, and K. pneumoniae ATCC 700603 were used as positive and negative control strains.
Antibiotics 2021, 10, 608 3 of 10

2.3. Definition and Data Collection of Risk Factors

Multi-drug-resistant organisms (MDROs) are pathogenic bacteria resistant to more
than one kind of antibiotic. This kind of bacteria is usually resistant to many kinds of antibi-
otics, and often only one or two of the existing antibiotics are effective. Common MDROs in-
clude carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella
pneumoniae (CRKP), CRPA, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-
resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus fae-
cium (VREfm).
Data were collected from the charts of infected patients to identify risk factors, includ-
ing sex (male, female), age (≤18, 19–60, and ≥61 years old), types of specimens (sputum,
urine, abscess, blood, and others), cultured antibacterial-drug-resistant strains (vancomycin-
resistant Enterococcus (VRE), carbapenem-resistant Escherichia coli (CREC), MRSA, CRE,
CRKP, CRAB, and CRPA), cultured antimicrobial susceptibility tests (non-controlled or
controlled drugs), use of catheters (i.e., endoscopes, urinary catheters, ventilators, central
venous catheters, etc.), and the logarithm of the number of days from admission to dis-
charge (or death). Risk factors were categorized and analyzed. Length of hospital stay
(LOS) was defined as the number of days from admission to discharge (or death), and was
the primary outcome variable of this study. The classification of the medications used
by patients before MDRO infection was as follows: anti-Gram-positive bacteria drugs
were erythromycin, moxifloxacin, and amp/sulbactam; anti-Gram-negative bacteria drugs
were cefmetazole and amp/sulbactam; anti-Pseudomonas aeruginosa drugs were cefopera-
zole/sulbactam, ceftazidime, cefepime, piperacillin/tazobactam, meropenem, imipenem,
levofloxacin, ciprofloxacin, colistin, and amikacin; and MRSA drugs were vancomycin,
teicoplanin, tigecycline, daptomycin, and linezolid.

2.4. Statistical Analysis

The data collected were compiled and analyzed with Excel 2016 and SPSS statistical
software version 24.0 (IBM, New York, NY, USA). Descriptive statistical analysis was used
between variables, and LOS was analyzed using the Mann–Whitney U-test [13,14], one-way
ANOVA, and post hoc testing. The relationship between the number of days in hospital
and the variables was analyzed by multivariate regression analysis (two-way ANOVA).
The significance threshold was set to 0.05.

3. Results
3.1. Research Design and Data Collection
As shown in Figure 1, during the study period, a total of 106 cases were collected
and included in this study. Further analysis showed that 42 cases (39.63%) were MDROs
(case group), and the number of non-MDRO cases was 64 (60.37%) (control group). The av-
erage age of patients was 73.21 years old, and 62.0% of them were men. The first objective
of this research was to analyze the risk factors related to HAI in the RCW. The second
objective was to conduct an association study between LOS and RCW MDROs.

3.2. Case Analysis of MDRO-Infected Patients

Figure 2 shows that there were 106 cases of infection in the RCW: 42 patients with
MDROs (case group) and 64 patients without MDROs (control group, 60.37%). MDROs in-
cluded 20 strains of CRPA (18.87%), 9 strains of CRAB (8.49%), 7 strains of MRSA (6.6%),
4 strains of VRE (3.78%), and 2 strains of CREC. KP (1.89%). Comparing the infections
of different MDRO strains, we found that CRPA strains accounted for about 47.62% of
MDRO strains. In a post hoc analysis, we determined that the LOS of MDRO-infected
patients (479.8 ± 546.5 days) was longer than that of the control group (307.3 ± 436.2 days).
The LOS of patients without any bacterial infection was 121.3 ± 65.9 days (Management
office, Kaohsiung Municipal Siaogang Hospital (KMSH), from January 2016 to March 2020).
This difference is statistically significant (p = 0.018).
Antibiotics 2021, 10, 608 4 of 10
Antibiotics 2021, 10, x FOR PEER REVIEW 4 of 11

Antibiotics 2021, 10, x FOR PEER REVIEW 5 of 11

Figure 1. Experimental Experimental
Figure 1. flow chart. flow chart.
3.2. Case Analysis of MDRO-Infected Patients
Figure 2 shows that there were 106 cases of infection in the RCW: 42 patients with
MDROs (case group) and 64 patients without MDROs (control group, 60.37%). MDROs
included 20 strains of CRPA (18.87%), 9 strains of CRAB (8.49%), 7 strains of MRSA (6.6%),
4 strains of VRE (3.78%), and 2 strains of CREC. KP (1.89%). Comparing the infections of
different MDRO strains, we found that CRPA strains accounted for about 47.62% of
MDRO strains. In a post hoc analysis, we determined that the LOS of MDRO-infected
patients (479.8 ± 546.5 days) was longer than that of the control group (307.3 ± 436.2 days).
The LOS of patients without any bacterial infection was 121.3 ± 65.9 days (Management
office, Kaohsiung Municipal Siaogang Hospital (KMSH), from January 2016 to March
2020). This difference is statistically significant (p = 0.018).

Figure 2. Strain percentages comprising all HAI.

Figure 2. Strain percentages comprising all HAI.
3.3. Risk Factor Data Collection
3.3. Risk Factor Data Collection
Patient demographic information is shown in Table 1, and includes: age, sex, previ-
Patient
ous ward, demographic
type of ward wheninformation
discharged, lastis shown in Table
departure, 1, and
nutritional includes:
score, age,
antibiotic use,sex, previous
ward, typedrugs,
controlled of ward when
anti-PsA discharged,
drugs, last departure,
anti-MRSA drugs, nutritional
use of catheters, score, antibiotic use,
use of endoscopes,
controlled
use of CVC,drugs, anti-PsA
use of FOLEY, usedrugs, anti-MRSA
of respirators, drugs,
and LOS. use ofshowed
The results catheters,
that use of endoscopes,
the use
of anti-MRSA
use of CVC, usedrugs
ofmay increase
FOLEY, usetheofproduction
respirators,of and
andinfection
LOS. Thewithresults
MDROs compared
showed that the use of
with anti-PsAdrugs
anti-MRSA drugs may
(p = 0.006). We found
increase that the average
the production LOSinfection
of and in the MDRO group
with MDROswas compared
479.8 ± 546.5 days, resulting in a mean additional LOS of 172 more days than that of the
with anti-PsA drugs (p = 0.006). We found that the average LOS in the MDRO group was
non-MDROs group (307.3 ± 436.2, p = 0.018). There was no statistically significant differ-
ence in±the
479.8 546.5
otherdays,
relatedresulting
risk factorsin(pa> mean
0.05). additional LOS of 172 more days than that of
the non-MDROs group (307.3 ± 436.2, p = 0.018). There was no statistically significant
difference
Table in the otherstatistical
1. Descriptive relatedanalysis
risk factors (p > 0.05).
of risk factors.

Overall (n = 106) Non-MDROs (n = 64) MDROs (n = 42)

Variable p-Value
n (%)/Mean ± SD n (%)/Mean ± SD n (%)/Mean ± SD
Age (years)
>65 71 (67.0) 40 (62.5) 31 (73.8)
0.226
other 35 (33.0) 24 (37.5) 11 (26.2)
Sex
Male 55 (51.9) 32 (50.0) 23 (54.8)
0.631
Female 51 (48.1) 32 (50.0) 19 (45.2)
Sample
Sputum 47 (44.3) 24 (37.5) 23 (54.8)
Urine 31 (29.2) 24 (37.5) 7 (16.7)
0.110
Antibiotics 2021, 10, 608 5 of 10

Table 1. Descriptive statistical analysis of risk factors.

Overall (n = 106) Non-MDROs (n = 64) MDROs (n = 42)

Variable p-Value
n (%)/Mean ± SD n (%)/Mean ± SD n (%)/Mean ± SD
Age (years)
>65 71 (67.0) 40 (62.5) 31 (73.8)
0.226
other 35 (33.0) 24 (37.5) 11 (26.2)
Sex
Male 55 (51.9) 32 (50.0) 23 (54.8)
0.631
Female 51 (48.1) 32 (50.0) 19 (45.2)
Sample
Sputum 47 (44.3) 24 (37.5) 23 (54.8)
Urine 31 (29.2) 24 (37.5) 7 (16.7)
0.110
Blood 16 (15.1) 10 (15.6) 6 (14.3)
Other 12 (11.3) 6 (9.4) 6 (14.3)
Previous ward
None 65 (61.3) 39 (60.9) 26 (61.9)
0.920
Yes 41 (38.7) 25 (39.1) 16 (38.1)
Type of ward
discharged
General ward 26 (24.5) 17 (26.6) 9 (21.4)
0.548
RCW 80 (75.5) 47 (73.4) 33 (78.6)
Nutritional score 2.2 ± 1.2 2.1 ± 1.2 2.1 ± 1.2 0.407
Antibiotics
None 20 (18.9) 15 (23.4) 5 (11.9)
0.138
Yes 86 (81.1) 49 (76.6) 37 (88.1)
Controlled drugs
None 24 (22.6) 18 (28.1) 6 (14.3)
0.096
Yes 82 (77.4) 46 (71.9) 36 (85.7)
Anti- PsA drugs
None 32 (30.2) 23 (35.9) 9 (21.4)
0.111
Yes 74 (69.8) 41 (64.1) 33 (78.6)
Anti-MRSA drugs
None 65 (61.3) 46 (71.9) 19 (45.2)
0.006 *
Yes 41 (38.7) 18 (28.1) 23 (54.8)
Catheterization
None 20 (18.9) 13 (20.3) 7 (16.7)
0.639
Yes 86 (81.1) 51 (79.7) 35 (83.3)
Use of endoscope
None 67 (63.2) 40 (62.5) 27 (64.3)
0.852
Yes 39 (36.8) 24 (37.5) 15 (35.7)
Use of CVC
None 90 (84.9) 55 (85.9) 35 (83.3)
0.714
Yes 16 (15.1) 9 (14.1) 7 (16.7)
Use of FOLEY
None 61 (57.5) 38 (59.4) 23 (54.8)
0.638
Yes 45 (42.5) 26 (40.6) 19 (45.2)
Use of ventilator
None 47 (44.3) 29 (45.3) 18 (42.9)
0.803
Yes 59 (55.7) 35 (54.7) 24 (57.1)
LOS a 375.6 ± 487.9 307.3 ± 436.2 479.8 ± 546.5 0.018 *
*: The mean difference is significant at the 0.05 level. a: Logarithm of the number of days in hospital.

3.4. Factors Affecting the Length of Hospital Stay

As shown in Table 2, we explored factors affecting the LOS in terms of demographic
variables and clinical treatment characteristics with statistically significant influence of age
and MDRO status.
Antibiotics 2021, 10, 608 6 of 10

3.4.1. Analysis of Variance (One-Way ANOVA)

The statistical results showed that the main factors affecting the LOS in the RCW
were: presence of MDRO infection (β = 0.62, 95% CI = 0.05–1.18, p = 0.033), age (β = 0.68,
95% CI = 0.10–1.27, p = 0.023), having left the nursing station in the RCW last (β = 1.52,
95% CI = 0.94–2.11, p < 0.0001), use of catheters (β = 1.37, 95% CI = 0.07–2.04, p < 0.0001),
and use of a respirator (β = 0.99, 95% CI = 0.46–1.53, p < 0.0001). There were no statistically
significant differences in the other variables (p > 0.05).

3.4.2. Multivariate Regression Analysis (Two-Way ANOVA)

The data from Section 3.4.1 were also subjected to multivariate analysis (Table 2).
The main factors influencing the LOS included patients with MDRO infection, patients who
left the nursing station in the RCW, and patients who underwent catheterization. Patients
with MDRO infection had significantly greater LOS than those without MDRO infection
(β = 0.55, 95% CI = 0.02–1.09, p = 0.037). The LOS of patients who were discharged from the
RCW was significantly longer than the LOS of patients discharged from the general ward
(β = 1.16, 95% CI = 0.52–1.80, p < 0.001). There was significantly greater LOS in patients
with catheters than without catheters (β = 0.86, 95% CI = 0.03–1.70, p = 0.043). There were
no statistically significant differences between the other variables (p > 0.05).

Table 2. Factors affecting the length of hospital stay.

Univariate Multivariate
Variable
β (95% CI) p-Value β (95% CI) β (95% CI)
MDROs (Yes vs. None) 0.62 (0.05, 1.18) 0.033 * 0.55 (0.02, 1.09) 0.037 *
Age (>65 years vs. other) 0.68 (0.10, 1.27) 0.023 * 0.25 (−0.34, 0.84) 0.410
Sex (Female vs. Male) −0.36 (−0.92, 0.20) 0.207 −0.05 (−0.60, 0.50) 0.857
Sample
Other Ref. Ref.
Sputum 0.81 (−0.12, 1.74) 0.087 0.86 (−0.01, 1.73) 0.052
Urine 0.48 (−0.50, 1.46) 0.331 0.82 (−0.17, 1.81) 0.102
Blood 1.01 (−0.09, 2.11) 0.071 1.12 (0.11, 2.14) 0.031
Previous ward (Yes vs. None) 0.002 (−0.58, 0.58) 0.993 0.26 (−0.35, 0.86) 0.403
Type of ward discharged
1.52 (0.94, 2.11) <0.001 * 1.16 (0.52, 1.80) <0.001 *
(RCW vs. General ward)
Nutritional score 0.16 (−0.08, 0.40) 0.196 −0.06 (−0.30, 0.18) 0.616
Antibiotics (Yes vs. None) 0.59 (−0.12, 1.30) 0.104 0.31 (−0.66, 1.28) 0.530
Controlled drug (Yes vs. None) 0.60 (−0.07, 1.26) 0.077 −0.03 (−1.48, 1.42) 0.966
Anti-PsA drugs (Yes vs. None) 0.52 (−0.09, 1.13) 0.093 0.11 (−0.99, 1.21) 0.844
Anti-MRSA drugs (Yes vs. None) 0.19 (−0.38, 0.77) 0.507 −0.28 (−0.93, 0.37) 0.400
Catheterization (Yes vs. None) 1.37 (0.70, 2.04) <0.001 * 0.86 (0.03, 1.70) 0.043 *
Use of endoscope (Yes vs. None) −0.20 (−0.78, 0.39) 0.507 −0.22 (−0.90, 0.45) 0.513
Use of CVC (Yes vs. None) 0.47 (−0.32, 1.25) 0.242 −0.18 (−0.95, 0.60) 0.651
Use of FOLEY (Yes vs. None) 0.15 (−0.42, 0.72) 0.597 −0.37 (−0.93, 0.19) 0.189
Use of ventilator (Yes vs. None) 0.99 (0.46, 1.53) <0.001 * 0.54 (−0.18, 1.25) 0.139
*: The mean difference is significant at the 0.05 level. Note: β is an unstandardized coefficient (converted by natural log). The coefficient
that affects the length of hospitalization was adjusted for other variables (such as MDRO, age, sex, sample, previous ward, last departure,
nutrition score, antibiotics, controlled medication, and PsA drugs), MRSA drugs, use of catheters, use of endoscopes, use of CVC, use of
FOLY, and use of respirators).

3.5. Analysis of Variance (ANOVA) of log LOS of Different Drug-Resistant MDROs

As shown in Table 3, a one-way ANOVA found that there was a significant difference
between the log LOS for bacteria with different MDROs (p < 0.018). Post hoc testing
using log LOS as the dependent variable comparing different MDROs is presented in
Table 4. The results showed that log LOS was significantly different between CRPA and
CRAB of MDROs (p < 0.037). Scheffe’s post hoc test found that the log LOS of CRPA
was greater than CRAB, representative of the strains of MDROs in the RCW during the
research period. In other words, the CRPA and CRAB of MDROs affected the difference in
Antibiotics 2021, 10, 608 7 of 10

log LOS days (p < 0.037 *). CRPA was associated with a longer LOS than other strains of
MDROs. The other strains of MDROs did not affect the increase in LOS, and there was no
statistically significant difference (p > 0.005). Further analysis of these MDRO infections in
RCW revealed that the average LOS increase was 158.90 days. Comparing different MDRO
infections, we found that CR-PA-induced LOS was an average of 643.30 days, which is
longer than that of other MDRO infections. For example, the average LOS of VRE was
112.00 days, the average LOS of MRSA was 484.86 days, and the average LOS of CREC.
KP was 415.50 days. The CRAB average LOS was 272.40 days.

Table 3. One-way ANOVA of log LOS for different anti-drug MDROs.

Sum of Squares Degrees of Freedom Mean Sum of Squares F Significance (p)

Between Group 21.665 4 5.416 3.412 0.018
Within Group 58.741 37 1.588
Sum 80.406 41

Table 4. Table of post hoc tests of log LOS of different anti-drug MDROs.

Dependent Variable MDRO a Mean Difference Standard Error Significance (p) Post-Hoc Test
2 −1.24785 0.86948 0.725
3 −1.21241 1.15022 0.890
Log LOS 1
4 0.29371 0.82943 0.998
5 −1.35252 0.78011 0.563
1 1.24785 0.86948 0.725
3 0.03545 1.01025 1.000
Log LOS 2
4 1.54156 0.62093 0.211
5 −0.10467 0.55333 1.000
1 1.21241 1.15022 0.890
2 −0.03545 1.01025 1.000
Log LOS 3
4 1.50612 0.97599 0.668
5 −0.14012 0.93444 1.000
1 −0.29371 0.82943 0.998
2 −1.54156 0.62093 0.211 5>4
Log LOS 4
3 −1.50612 0.97599 0.668
5 −1.64623 * 0.48800 0.037 *
1 1.35252 0.78011 0.563
2 0.10467 0.55333 1.000
Log LOS 5
3 0.14012 0.93444 1.000 5>4
4 1.64623 * 0.48800 0.037 *
*: The mean difference is significant at the 0.05 level. Scheffe’s post hoc test; a : 1: VRE; 2: MRSA; 3: CREC. KP; 4: CRAB; 5: CRPA.

4. Discussion
4.1. MDRO Infection Is a Risk Factor for Prolonged LOS
The present study focused on LOS related to infection by MDROs, because patients
in the RCW tend to be older, immunocompromized, and have catheter-related issues.
The LOS in the RCW is longer than that of the outpatient and emergency departments
or general and surgical wards. For example, the LOS for patients with MDROs such as
CRAB and CRPA is significantly longer, as evidenced by statistical analysis (p < 0.037).
Taking a similar approach to one study comparing different MDRO infections in mainland
China [7], we found that the increase in LOS associated with HAI due to CRPA was
significantly longer than other MDRO infections, other than VRE and CR-E. coli infection
(p < 0.05). There was no significant difference between other MDRO infections (p > 0.05).
In line with the findings of several previous studies [15–17], the present study also
found the increase in LOS of HAI to be more than that of uninfected patients. This evidence
suggests that MDROs are a risk factor for prolonged LOS.
Antibiotics 2021, 10, 608 8 of 10

4.2. Risk Factors Affecting LOS

The risk factors for MDRO infection are well-documented: (1) patients with a his-
tory of hospitalization for more than 2 days in the past 90 days; (2) patients in nursing
homes or long-term care centers; (3) patients who received antibiotic treatment in the past
90 days [18]. Among hospitalized patients in Athens, Greece, long-term hospitalization
and age were independent risk factors for carrying VRE, while infection with CRGN was
associated with an increased risk of acquiring drug-resistant pathogens, prolonged hospital
stays, and increased mortality [19]. Patients suffering from ICU-acquired paresis (ICUAP)
due to MDROs have a higher ICU mortality rate than non-MDRO patients. Patients with-
out microbiological confirmation are more often treated with antibiotics than those with
positive cultures [20]. In addition to local epidemiology, the risk factors of MDROs may
also be important for the choice of initial antibacterial therapy. We found that the univariate
risk factors associated with LOS were MDROs (yes vs. none), age (>65 years vs. other),
use of catheters (yes vs. none), respirators (yes vs. none), and final discharge station status
(severe vs. general). The analysis of multivariate ANOVA found that MDROs (yes vs.
no), use of catheters (yes vs. no), and final departure (severe vs. general) affected the
LOS. These results are slightly different from previous studies [18,21]. Further studies are
needed to settle this discrepancy.
Our results show the main factors affecting LOS in patients are MDRO infection,
hospitalization in the RCW, and catheterization. The results of this study provide relevant
data to supplement existing medical care-related infection data and provide insights into
how to better maintain the health of patients and clinical medical staff through the exchange
of infection information related to the RCW. Our study underscores the considerable health
burden of MDRO infections and addresses the urgent need for improved antimicrobial
stewardship to improve public health in Taiwan.

4.3. Advantages
The advantages of the present research are: (1) there was a paucity of current literature
addressing specific analysis of MDROs in RCW; (2) risk factors impacting LOS have not
been previously analyzed with such rigor in the RCW hospital care setting in Taiwan.

4.4. Limitations
The present study only shows that the presence of MDROs is a risk factor for pro-
longed LOS. In order to establish a causal relationship between MDRO infection and LOS,
we would have needed to take an approach similar to the study by Barrasa-Villar (2017)
who looked only at LOS after diagnosis of MDRO infection and controlled for hospital LOS
prior to the infection. However, the causal relationship between MDRO infection and LOS
was beyond the scope of their investigation.
This study is also limited by being conducted in a single regional hospital, with a lim-
ited number of cases and MDRO strains, and the time encompassed was limited to a 5-year
period. If coordinated data can be collected from more hospitals with relevant MDRO
strains in RCW patients, and pertinent clinical data can be provided for further analysis,
this would allow a more representative and comprehensive conclusion to be drawn and be
applied to more hospitals.

5. Conclusions
We investigated the effects of MDRO infection and other factors on the LOS of patients
in the RCW of a regional hospital in Taiwan. The results showed that infection by multi-
drug-resistant organisms impacted the LOS of patients in the RCW, and that CRPA strains
were the most common MDROs in the RCW, comprising 47.62% of MDRO infections.
ANOVA and post hoc testing of log LOS found that different MDROs, specifically CRPA
and CRAB, have a significant impact on log LOS days (p < 0.037). The main factors affecting
LOS achieving statistical significance (p < 0.05) were MDRO infection, hospitalization in
the RCW, and catheterization. The findings of this study provide useful information for
Antibiotics 2021, 10, 608 9 of 10

the hospital RCW about the impact of MDROs on LOS of patients. These findings may also
improve the level of clinical medical care and provide holistic health care service strategies,
which can be used to improve infection control in the future.

Author Contributions: Conceptualization, Y.-P.C. and C.-S.L.; data curation, Y.-P.C., X.-D.C. and
C.-S.L.; formal analysis, Y.-P.C., X.-W.T. and X.-D.C.; funding acquisition, C.-S.L.; investigation,
Y.-P.C.; methodology, Y.-P.C., X.-W.T., K.C., X.-D.C. and J.-R.C.; project administration, K.C. and
C.-S.L.; resources, K.C. and J.-R.C.; software, X.-W.T. and K.C.; supervision, J.-R.C. and C.-S.L.;
writing—original draft, Y.-P.C., J.-R.C. and C.-S.L.; writing—review & editing, J.-R.C. and C.-S.L.
All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted according to the guidelines of
the Declaration of Helsinki and approved by the Institutional Review Board of Kaohsiung Medical
University, Kaohsiung, Taiwan (approval number KMU-HIRB-E(I)-20190148).
Informed Consent Statement: Not applicable.
Data Availability Statement: The data presented in this study are available on request from the
corresponding author. The data are not publicly available due to privacy restrictions.
Acknowledgments: The authors would like to thank the patients and their families, without whom
this study would not have been possible. The authors owe their sincere gratitude to Roni J. Bollag at
Augusta University, Medical Center, Augusta, GA, USA, for their critical review of the manuscript.
Conflicts of Interest: The authors declare no conflict of interest.

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