Evaluation of Antibiotic Duration after Surgical Debridement of Necrotizing Soft Tissue Infection

Abstract

Background:

Necrotizing soft tissue infection (NSTI) is known to be a medical emergency with high morbidity and mortality. Guidelines do not specify the optimal duration of antibiotic agents after completion of surgical debridements of NSTI, which has created variable practice. It was hypothesized that patients with NSTI who receive 48 hours or less of post-operative antibiotic agents after final debridement have similar rates of subsequent intervention or infection recurrence, suggesting that a shorter duration of antibiotic agents may treat NSTI adequately after final surgical debridement.

Patients and Methods:

This was a retrospective study including adults with NSTI identified through International Classification of Diseases, Ninth Revision (ICD-9), International Classification of Diseases, Tenth Revision (ICD-10), and Current Procedural Terminology (CPT) codes admitted to one academic institution between January 1, 2010 and July 31, 2020. Demographics, surgical practices, antibiotic practices, and clinical outcomes including inpatient mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, total antibiotic days, necrotizing infection clinical composite end point (NICCE) success, and infection recurrence were compared based on the duration of antibiotic agents after final debridement.

Results:

Three hundred twenty-two patients with NSTI were included and baseline characteristics and clinical severity markers were well balanced between the two groups. In 71 patients (22%) who received less than 48 hours of antibiotic agents after final debridement there was no difference in recurrence (1.4% vs. 3.6%; p = 0.697), mortality (1.4% vs. 4.4%; p = 0.476), or ICU LOS (1 vs. 2 days; p = 0.300], but they did have a shorter hospital LOS (7 vs. 10 days; p = 0.011).

Conclusions:

Shorter duration of antibiotic therapy after final surgical debridement of NSTI may be appropriate in patients without another indication for antibiotic agents.

Necrotizing soft tissue infections (NSTI) are a rare group of infections that are a medical emergency, with world-wide mortality rates upwards of 30% [1]. The two major pillars of management including prompt surgical debridement as well as initiation of broad-spectrum antibiotic agents to target gram-positive, gram-negative, and anaerobic organisms [2,3]. Currently, there is no strong evidence within guidelines to drive consensus of antibiotic duration for NSTI. In the absence of clinical trials, practice has been based on expert opinion and has created variable practice among different sites [4]. The Infectious Diseases Society of America (IDSA) 2014 Skin and Soft Tissue Infection (SSTI) guidelines and the Surgical Infection Society (SIS) 2018 SSTI guidelines suggest to continue antibiotic therapy until further debridement has ceased and the patient has clinically stabilized including defervescence for 48–72 hours [5,6].

In 2021, however, the SIS published updated guidelines for the management of complicated SSTIs. They state that “…shorter course antimicrobial therapy (<7 days) appears equivalent to longer therapy and should be considered” [7]. The change in guidelines comes after Lauerman et al. [8] published a single-institution retrospective review of patients with Fournier's gangrene. They reviewed 168 patients and compared patients based on their total duration of antibiotic agents, seven or less days, 8 to 10 days, 11 to 14 days, or 15 or greater days and found no difference in mortality, primary closure, surgical site infection, infection recurrence, or Clostridium difficile infections based on the total duration of antibiotic agents [8]. The authors concluded that this supports that a shorter duration (≤7 days) of antibiotic agents is adequate for patients with Fournier's gangrene, however, the groups may have been influenced by the number of debridements because those who received seven days or less of antibiotic agents had fewer debridements than those who received 15 days or more of antibiotic agents (2.18 vs. 2.97; p = 0.04).

The aim of this study was to compare outcomes of patients with NSTI based on their antibiotic therapy duration after final debridement, which represents source control, with a focus on recurrence of NSTI, antibiotic practices, and operative management among a single institution.

Patients and Methods

Patient identification

This study was approved by the local Institutional Review Board and granted a waiver of the need for informed consent. The study was a retrospective chart review of patients with NSTI admitted to one institution from January 1, 2010 through July 31, 2020. Patients were identified via International Classification of Diseases, Ninth Revision (ICD-9) (728.86, 729.99, 400, 785.4), International Classification of Diseases, Tenth Revision (ICD-10) codes (M72.6, M79.89, N49.3, A48.0), or Current Procedural Terminology (CPT) codes (11004, 11005, 11006, 11008, 49568) for NSTI, Fournier's gangrene, or gas gangrene, respectively. After identification, presence of NSTI was confirmed by findings from surgical debridements, including friability of the superficial fascia, necrotic tissue, dishwater-gray exudate, and absence of pus before the patient was included in the study [2].

Patients aged 18–100 years were included if they were admitted for an NSTI requiring at least one surgical debridement and post-operative antibiotic agents. Patients were excluded if they had an amputation as index procedure, were transferred from an inpatient unit of an outside hospital, died within 48 hours, or participated in a prospective drug trial during index NSTI. Patients were also excluded if they had bacteremia or other concomitant infection (e.g., pneumonia, urinary tract infection, osteomyelitis, etc.) during index NSTI because this could have indicated a longer duration of antibiotic agents than for NSTI alone.

Patients who were transferred from an inpatient unit of an outside hospital to our institution were excluded because antibiotic, culture, and surgical records could not be accurately obtained. Patients who presented to an outside emergency department and were then transferred to our institution were included.

Data collection

Patients were identified utilizing Vizient Clinical Data Base with permission of Vizient Inc. (Irving, TX). Data were obtained from the electronic medical record (Sunrise Clinical Manager, Chicago, IL) and Vizient Clinical Data Base and managed using REDCap electronic data capture tools hosted at the University of Kentucky [9,10]. Variables collected included baseline demographics, surgical course, clinical course including antibiotic practices, and clinical outcomes including inpatient mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, total antibiotic days, necrotizing infection clinical composite end point (NICCE) success, and infection recurrence. Variables collected from Vizient Clinical Data Base (Vizient Inc.) included age, gender, race, hospital LOS, and ICU LOS; the remaining were collected from the electronic medical record. Type 1 NSTI is defined as a polymicrobial infection with at least one anaerobic organism, type 2 is defined as a monomicrobial infection, and type 3 is defined as marine organisms [11]. Antibiotic days were defined as each day that a patient received one or more antibiotic agents, although administration of multiple antibiotic agents only counted as one day.

Success of NICCE was defined as all of the following to be true: alive at 28 days, three or less debridements before day 14, no amputation beyond first debridement, and modified Sequential Organ Failure Assessment (mSOFA) score of one or less at day 14 [12]. Should the patient have been discharged or died before day 14, the last value for each parameter was utilized to calculate the NICCE score. The SOFA score, systemic inflammatory response syndrome (SIRS) score, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score were based on the initial values from the encounter at our institution. If the patient did not have a reported value for a specific component, as a conservative measure it was assumed to be normal and did not contribute to the LRINEC score.

The primary objective was to evaluate the rates of recurrence of NSTI during index hospitalization between individuals who received 48 hours or less of antibiotic agents after final debridement compared with those who received more than 48 hours. Recurrence was defined as unexpected surgical debridement after initial debridements were completed or re-initiation of antibiotic agents for NSTI during index hospitalization. Recurrence was confirmed via independent review of three separate authors, who then had to reach consensus before it was determined that recurrence occurred. Secondary outcomes included inpatient mortality, hospital and ICU LOS, description of antibiotic practices, and NICCE success.

Statistical analysis

Values were reported as median with interquartile range (IQR) or percentage unless otherwise stated. A power calculation was not performed because this study was retrospective in nature and a historical recurrence rate was not previously published in literature. Mann-Whitney U test was utilized for ordinal or non-normally distributed continuous data, Fisher exact test was utilized for binary data, and χ² test was utilized for categorical data. SPSS Statistics, version 27 (IBM Corp., Armonk, NY) was utilized for all analysis and considered a two-sided α of 0.05 as the threshold for statistical significance.

Results

The ICD-9, ICD-10, and CPT codes identified 1,470 patients of whom 1,148 were excluded. Upon chart review, a majority were excluded if the encounter was not for an active NSTI (n = 832), the patient was transferred from an inpatient unit of an outside hospital (n = 186), or the patient had a concomitant infection during index NSTI (n = 85). A total of 322 patients with NSTI admitted to a single site during the review period were included, then stratified into two groups based on the duration of antibiotic therapy after final surgical debridement; 71 patients received less than 48 hours of antibiotic agents and 251 patients received more than 48 hours of antibiotic agents after surgical debridement.

Unless otherwise stated, all data that compare the two groups will have the group that received less than 48 hours of antibiotic agents after final debridement reported first. Included patients in the two groups were comparable regarding baseline demographics (Table 1), with the exception that individuals who received less than 48 hours of antibiotic agents had a higher rate of diabetes mellitus (73% vs. 57%; p = 0.014). The two groups were clinically comparable, with similar LRINEC scores, SOFA scores, initial laboratory parameters, size and location of infection, rates of transfer from outside hospital emergency department, time to first debridement, number of debridements, and primary team (Table 1).

Table 1.

Baseline Demographics^a,b

Demographic	≤48 h ABx (n = 71)	>48 h ABx (n = 251)	p
Age (y), mean (SD)	49.7 (11.5)	50.0 (13.9)	0.853
Male	41 (58%)	151 (60%)	0.784
BMI (kg/m²)	37.4 (28.9–45.2)	33.4 (26.9–42.0)	0.105
Past medical history Diabetes mellitus Hypertension Cirrhosis Coronary artery disease	52 (73%) 40 (56%) 6 (9%) 28 (39%)	143 (57%) 126 (50%) 25 (10%) 73 (29%)	0.014 0.420 0.822 0.111
Presented from outside hospital emergency department	58 (82%)	193 (77%)	0.423
ICU status upon admission	47 (66.2%)	169 (67.3%)	0.887
LRINEC score	5 (3–7)	5 (3–7)	0.907
SIRS score	2 (2–3)	2 (1–2)	0.191
SOFA score	7 (2–10)	7 (2–10)	0.806
Initial WBC (k/mcL)	16.5 (12.8–22.1)	17.6 (12.8–22.4)	0.834
Initial base deficit (mmol/L), n = 48; 167	4.4 (1.6–6.4)	4.4 (1.6–7.8)	0.813
Initial lactate (mmol/L), n = 65; 220	1.7 (1.2–2.5)	1.9 (1.4–2.6)	0.256
Size of wound (cm²), n = 60; 198	184 (62.5–442.5)	180 (70–400)	0.708
Location Extremity Truncal Perineal/genital/peri-anal	17 (24%) 36 (51%) 37 (52%)	85 (34%) 111 (44%) 116 (46%)	0.148 0.348 0.420
Antibiotic duration from last debridement (d)	1.2 (0.7–1.7)	5.6 (3.3–9.9)	<0.001
Organism Group A Streptococcus Group B Streptococcus Other Streptococcus spp. Staphylococcus aureus—methicillin sensitive Staphylococcus aureus—methicillin resistant Enterococcus spp. Proteus spp. Bacteroides spp. Escherichia coli Clostridium spp.	1 (1%) 11 (16%) 15 (21%) 6 (9%) 4 (6%) 11 (16%) 1 (1%) 10 (14%) 11 (16%) 0 (0%)	19 (8%) 29 (12%) 42 (17%) 21 (8%) 24 (10%) 45 (18%) 22 (9%) 43 (17%) 53 (21%) 1 (1%)	0.090 0.415 0.384 0.351 1.000 0.858 0.035 0.592 0.399 1.000
Type of NSTI Type 1 Type 2 Type 3 No organism identified	15 (21%) 33 (46%) 2 (3%) 21 (30%)	59 (24%) 141 (56%) 0 (0%) 51 (20%)	0.030
Antibiotics Vancomycin Piperacillin-tazobactam Cefepime Metronidazole Daptomycin Clindamycin Linezolid	67 (94%) 53 (75%) 17 (24%) 14 (20%) 2 (3%) 64 (90%) 2 (3%)	250 (99%) 200 (80%) 57 (23%) 63 (25%) 2 (1%) 230 (92%) 4 (2%)	0.009 0.413 0.873 0.431 0.212 0.641 0.617
Primary team Emergency general surgery or trauma Non-emergency surgery or trauma	59 (83%) 12 (17%)	172 (69%) 79 (31%)	0.017
Time to first debridement (h)	4.0 (2.6–6.2)	4.0 (2.6–6.4)	0.858
Number of debridements	2 (1–3)	2 (1–2)	0.159

ABx = antibiotic; BMI = body mass index; ICU = intensive care unit; LRINEC = Laboratory Risk Indicator for Necrotizing Fasciitis; SIRS = systemic inflammatory response syndrome; SOFA = Sequential Organ Failure Assessment score; WBC = white blood cell count; NSTI = necrotizing soft tissue infection.

Values reported as median (interquartile range) or n (%) unless otherwise started; p: comparing groups using Mann-Whitney U test for ordinal or non-normally distributed continuous data, Fisher exact test for binary data, and χ² for categorical data. Some variables were not reported for all patients, for which the denominator is reported with the variable name.

The overall infection recurrence rate was not statistically different between the two groups (1.4% vs. 3.6%; p = 0.697) (Table 2). The secondary outcomes can be found in Table 3. Inpatient mortality was not different between the two groups (1.4% vs. 4.4%; p = 0.476). Median hospital LOS was decreased in the group who received less than 48 hours of antibiotic agents (7 [3 –15] vs. 10 [6 –17] days; p = 0.011] whereas ICU LOS was no different (1 [0–5] vs. 2 [0–6]; p = 0.300). There was no difference between NICCE success between the two groups (46.5% vs. 45.0%; p = 0.893). Patients who received more than 48 hours of antibiotic agents had more total antibiotic days (4 [3 –6] vs. 9 [6 –13] days; p < 0.001) and were more likely to be discharged while taking oral antibiotic agents (0% vs. 24.3%; p < 0.001).

Table 2.

Rate of Recurrence^a,b

	≤48 h ABx (n = 71)	>48 h ABx (n = 251)	p
In-hospital recurrence	1 (1.4%)	9 (3.6%)	0.697

ABx = antibiotic.

Values reported as n (%) unless otherwise started; p: comparing groups using Mann Whitney U test for ordinal or non-normally distributed continuous data.

Table 3.

Secondary Outcomes and Complications^a,b

	≤48 h ABx (n = 71)	>48 h ABx (n = 251)	p
Inpatient mortality	1 (1.4%)	11 (4.4%)	0.476
Hospital length of stay (d)	7 (3–15)	10 (6–17)	0.011
ICU length of stay (d)	1 (0–5)	2 (0–6)	0.300
Total inpatient antibiotic days	4 (3–6)	7 (5–10)	<0.001
Total antibiotic days (inpatient and outpatient)	4 (3–6)	9 (6–13)	<0.001
De-escalation of antibiotic agents	26 (37%)	187 (75%)	<0.001
Discharged on oral antibiotic agents	0 (0%)	61 (24%)	<0.001
Duration of oral antibiotic agents (d)	—	7 (6.5–10)	<0.001
NICCE success	33 (47%)	113 (45%)	0.893

ABx = antibiotic; ICU = intensive care unit; NICCE = necrotizing infection clinical composite end point.

The duration of antibiotic agents after final debridement was longer in the group of patients who received more than 48 hours of antibiotic agents (1.2 [0.7–1.7] vs. 5.6 [3.3–9.9] days; p < 0.001) as was the total duration of inpatient antibiotics [4 (3–6) vs. 7 (5–10) days; p < 0.001). The two groups had similar antibiotic selection as shown in Table 1, which depicts all antibiotic agents that a patient received throughout the hospital stay. There was one exception, as the group who received more than 48 hours of antibiotic agents had a higher rate of vancomycin usage (94% vs. 99%; p = 0.009). Of the four patients who received less than 48 hours of antibiotic agents and did not receive vancomycin, two received anti-methicillin–resistant Staphylococcus aureus (MRSA) therapy with linezolid and two received no anti-MRSA therapy. The group who received more than 48 hours of antibiotic agents also had a higher rate of type 1 and type 2 NSTI, and a lower rate of type 3 NSTI or no growth on cultures (p = 0.03; Table 1). Additionally, the two groups had similar organisms grow on sterile wound cultures, exception for the group that received more than 48 hours of antibiotic agents who had a higher rate of Proteus spp. (1% vs. 9%; p = 0.035).

Discussion

Necrotizing soft tissue infections are medical emergencies with high morbidity and mortality rates, for which the two pillars of management are surgical debridements and antibiotic therapy [2]. Guidelines do not, however, provide clear guidance on best practices for antibiotic management in these patients, which has created varied clinical practice. Previous research in other surgical disease states have indicated that shorter duration of antibiotic therapy may be appropriate after source control is obtained, as seen in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial in which patients with intra-abdominal infections after adequate source control procedure had similar outcomes regardless of duration of antibiotic agents (4 vs. 8 days) [13]. This trend was also seen in the population with Fournier's gangrene, in which a retrospective analysis found no difference in clinical outcomes in patients who received shorter duration of antimicrobial agents (7 vs. 15 total days) [8]. Our study defined the groups based on duration of antibiotic agents after final debridement, similar to the STOP-IT trial, as the final debridement should be synonymous with source control, not total duration of antibiotic agents as seen in other studies. The authors chose this to avoid the potential confounder of varied number of debridements, as patients who required more debridements would likely be on a longer total duration of antibiotic agents.

Our study indicates that shorter duration of antibiotic agents after final surgical debridement (representing source control) may be appropriate in patients without another indication of antibiotic therapy (i.e., bacteremia, pneumonia, osteomyelitis, etc.). The authors originally were concerned that the patients who had received more than 48 hours of antibiotic agents after final surgical debridement would have an inherently higher acuity and thus required longer duration, however, almost all clinical measures were comparable between the two groups. Additionally, there was no difference in NICCE success, indicating that later in their hospital stay patients had similar clinical acuity based on their mortality, number of debridements, amputations, and mSOFA score.

Our primary outcome was the rate of recurrence between the two groups, which is a critical consideration when determining duration of antibiotics as shorter durations of antibiotics could result in undertreating the infection. Interestingly, the rate of recurrence was actually lower in the group of patients who received less than 48 hours of antibiotic agents after final debridement, however, this difference was not statistically significant. The authors attempted to review re-admission rates for an NSTI recurrence, however, this comes with its own limitations, because patients may have presented to an outside hospital with recurrence and thus their data would not have been available to this study. Ninety-day re-admission has recently been suggested as an important implication after admission with NSTI, mostly because of infection and with increased costs and should be considered for future studies [14].

An important secondary end point to mention is mortality, as it was lower in the group of patients who received less than 48 hours of antibiotic agents after final debridement, however, this difference was also not statistically significant. One theory for the increased rate of mortality in those who received more than 48 hours of antibiotic agents after final debridement is that these patients received more total antibiotic days, thus increasing their potential for acquiring a multi-drug–resistant (MDR) infection. Of the 11 patients who received more than 48 hours of antibiotic agents after final debridement and died, four had newly positive MDR surveillance swabs and two of those four were in septic shock caused by an MDR organism. This is consistent with the literature, as studies have found that the use of antibiotic agents may increase the risk of acquiring MDR organisms, which may increase hospital length of stay and mortality [15 –17].

There were also no cases of Clostridium difficile infections in any of the patients who died during their index hospital stay. Given the higher rate of patients admitted to a trauma or emergency general surgery service who received less than 48 hours of antibiotic agents, another possibility is that the duration was influenced by admitting/operating service and relative comfort with early antibiotic cessation. Certainly, surgeon experience and familiarity with management may have a profound impact on patient outcomes. Kongkaewpaisan et al. [18] recently described their experience with patients with NSTI at a tertiary hospital who were admitted to a non-acute care surgery (ACS) service versus those admitted to an ACS service. They found that those admitted to a non-ACS service had longer time to operation with a non-significant increase in mortality.

At our institution, empiric antibiotic therapy is generally initiated in accordance with IDSA and SIS guidelines, covering broad gram-positive organisms (including MRSA), broad gram-negative organisms (including Pseudomonas spp.), and anaerobic coverage in addition to antitoxin therapy with clindamycin or linezolid. The most common empiric regimen in our study was a combination of vancomycin, piperacillin-tazobactam, and clindamycin. During surgical debridement, sterile cultures are obtained and antibiotic therapy can be de-escalated based on the organisms grown in cultures.

One intriguing finding in our study was that only 37% of the patients who received less than 48 hours of antibiotics after final surgical debridement had their antibiotic agents de-escalated to a narrower regimen versus 75% of the patients who received more than 48 hours of antibiotic agents after final surgical debridement. On review of these patients, it was deemed that this was likely because when the patients who received less than 48 hours of antibiotic agents after final surgical debridement were at the point of potential de-escalation: they had their antibiotic agents discontinued compared with the group who received more than 48 hours of antibiotic agents had them de-escalated and continued. At our institution, it would likely not be feasible to de-escalate antibiotic agents within 48 hours after final debridement because culture data with organism identification and susceptibility information may not be available until 48–72 hours after culture collection. Because most patients had a median of two debridements, generally 24–48 hours apart, those with culture data collected during an index operation would not have results until post-operative day three to four, which would be the same time that antibiotic agents are generally discontinued. Another concern at our institution for early de-escalation had been the concern for delayed identification of polymicrobial or anaerobic pathogens.

Conversely, some patients at our institution were discharged while taking oral antibiotic agents for NSTI, with a median duration of seven days. All of these patients were in the group that received more than 48 hours of antibiotic agents after final debridement, because both inpatient and outpatient antibiotic orders and prescriptions were summed to determine the duration of antibiotic agents after final debridement. Fewer patients were discharged while taking oral antibiotic agents if they were admitted to an emergency general surgery or trauma service (36.1% vs. 63.9%; p < 0.001). One concern was that the patients who were discharged while taking oral antibiotic agents would be an inherently sicker population, however, these patients actually had a lower LRINEC Score (2 vs. 8; p = 0.038), lower SOFA score (2 vs. 8; p < 0.001), and smaller wound size (120 vs. 200 cm²; p < 0.001).

Limiting antibiotic duration for these patients can have multiple important benefits. First, our study showed a decreased hospital LOS (7 vs. 10 days; p = 0.011). Previous literature has shown that prolonging a patient's hospital LOS has been shown to increase the probability of acquiring a nosocomial infection, which then can further prolong LOS [19]. Additionally, previous studies have shown that decreasing the duration of antibiotic therapy may reduce the development of resistance [20,21] and thus, the development of MDR infections or sepsis, which was seen in our study as noted above. The reduction in hospital length also has important financial implications, as the adjusted expenses per day in hospital ranges from $1,000 to $3,000 based on type and location of hospital, patient acuity, and procedures [22].

The strengths of this study include the large patient population compared with previous NSTI studies. Additionally, this study was the first to define and document NSTI recurrence in the literature. Limitations of this study include its retrospective nature, because variables not included in this data set were unable to be accounted for, and some factors were assumed from documentation. Although this study excluded those who transferred from an inpatient unit of another hospital, patients transferred from an outside hospital emergency department were included but any antimicrobial or culture data was not available. Additionally, although a large number of patients were included, it was at a single institution and surgical and antimicrobial practices may differ at other institutions thus reducing the external validity. The authors attempted to combat this weakness by including patients who were not treated by an emergency surgery or trauma team, to increase generalizability. With the improvement in NSTI management some of the clinical outcomes, including recurrence and mortality, are rare and would be better studied with a larger patient population. Additionally, this study spanned almost 10 years, which could represent a potential temporal confounder. Upon further review of the data, however, the authors found no changes in rates of patients who received less than 48 hours of antibiotic agents after final debridement or in the rate of NSTI recurrence from those treated in 2010–2015 versus 2016–2020.

Another weakness is that sensitivities for organisms that grew on cultures were not collected in this study. The authors, however, believe that the rate of MDR organisms would be similar between the two groups as there were no significant differences in organisms present on cultures or types of antibiotics utilized. Antibiotic exposure is a known risk factor for the development of MDR organisms, however, information on the isolation of MDR organisms or development of superinfections for all patients was unavailable, as those who survived to discharge might have been seen at or re-admitted to an outside institution. Finally, it is important to note that this study was underpowered to identify differences in all clinical outcomes.

Conclusions

In this study, patients with NSTI and without another indication for antibiotic agents who were treated with less than 48 hours of antibiotic agents after final debridement did not have worse outcomes, including recurrence and death, but did have a shorter hospital LOS. Future directions should include prospective research to confirm these findings, with the potential to include cost as an outcome.

Funding Information

The project described was supported by the National Institutes of Health National Center for Advancing Translational Sciences through grant number UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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