Epidemiology of upper limb skin and soft tissue infections requiring surgical intervention in Saskatoon, Canada: A retrospective chart review

doi:10.21203/rs.3.rs-4004749/v1

Background: Skin and soft tissue infections (SSTIs) are a leading cause of hospital admission and engagement with the health care system amongst people who inject drugs (PWID). The current study aims to describe the epidemiology of SSTIs requiring surgical intervention in Saskatoon, Canada.

Methods: This retrospective chart review assessed patients with a primary diagnosis of upper limb SSTIs requiring surgical intervention at St. Paul’s Hospital and Royal University Hospital (Saskatoon, Canada) between January 1 and December 31, 2020.

Results: 38 eligible patients with a median age of 34 years and M:F of 21:17 were identified. 31 (81.6%) smoked cigarettes and 19 (50.0%) used intravenous drugs. A majority of SSTIs were unilateral infections involving the hand 22 (57.9%) or upper arm 11 (28.9%). Ten (26.3%) patients had a prior SSTI requiring surgical management. Necrotizing fasciitis was diagnosed in 7 (18.4%) patients, two of which, required amputation of the affected hand or arm. The median length of hospital stay was 6 days (IQR: 4 – 14.5). Ten patients left the hospital against medical advice, before completion of treatment; of these patients, 8 (80.0%) were PWID.

Conclusion: Harm reduction strategies may help address the rising incidence and recurrence of SSTIs in the injection drug use population. Involvement of addiction services and social work during hospital admission may reduce the rate of patient-directed discharge, facilitating the completion of treatment. Furthermore, increased access to needle exchange programs in the community may reduce the number of SSTIs caused by contaminated injection equipment in the PWID population.

Harm Reduction

Necrotizing Fasciitis

Soft Tissue Infections

Substance Abuse Intravenous

Intravenous drug use (IVDU) is associated with significant morbidity and mortality. In 2016, the national population prevalence of people who inject drugs (PWID) in Canada was reported to be 0.70 per 100 persons aged 15 to 64. In Saskatchewan, however, the provincial population prevalence was much greater at 0.97 per 100 persons aged 15 to 64 years.¹ IVDU is the most common risk factor for the acquisition of both hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in Saskatchewan. Consequently, Saskatchewan has a significantly higher incidence of new HCV and HIV diagnoses compared to the national rate.^2–4

People who inject drugs are at increased risk for the development of bacterial, fungal, and blood-borne infections; often spread via the use of contaminated injection drug supplies, unsanitary conditions, and low vaccination rates in these populations.^5,6 Skin and soft tissue infections (SSTIs) exemplify the infections that contribute to morbidity and mortality in PWID.⁷ Studies in both Canada and the United States have found that SSTIs represent a leading cause of hospitalization and engagement with the healthcare system in PWID.^8,9 The management of SSTIs often requires long hospital admissions, and surgical interventions, resulting in high healthcare associated costs. In addition, several studies report the average cost of hospitalization in PWID to be greater than in patients who do not use injection drugs.^2,10

There is an urgent need to better understand and recognize the characteristics of patients admitted to hospitals with SSTIs in Canada. This study aimed to describe the epidemiology, hospital course, and prevalence of injection drug use in patients with a primary diagnosis of upper limb SSTIs requiring surgical intervention at St. Paul’s Hospital and Royal University Hospital (Saskatoon, Canada) between January 1 and December 31, 2020. Additionally, we sought to describe harm reduction strategies aimed at preventing the development of SSTIs in the PWID population.

Study Design

This retrospective chart review involved patients with upper limb skin and soft tissue infection who were admitted to St. Paul’s Hospital or Royal University Hospital (Saskatoon, SK, CA) between January 1, 2020, and December 31, 2020. Patients were excluded if the soft tissue infection did not involve the upper limb (hand to shoulder) or did not require surgical intervention. The University of Saskatchewan Biomedical Research Ethics Board approved the study protocol (Bio 2875). International Classification of Disease codes (ICD) were used to identify eligible patients from the Saskatchewan Health Authority medical records database.

Data Collection

A pre-determined data abstraction sheet was used for data collection and one researcher (RM) collected the data. Data was organized within 10 predetermined categories: patient demographics (age, gender, smoking, injection drug use, comorbidities), location of infection, prior SSTIs requiring surgical intervention, choice of antibiotic, mode of antibiotic, culture results, time from initial presentation to procedure, length of stay, repeat procedures, and hospital discharge.

Statistical Analysis

Descriptive statistics were performed to summarize the characteristics of the studied population including demographics, course in hospital, antibiotic treatment, culture results, and infection classification. Categorical data was analyzed as frequency and the corresponding proportion using Microsoft Excel.

A total of 132 patients were identified. Of these, 94 patients were excluded due to the anatomic location of the SSTI or lack of surgical intervention. Of the 38 patients included in the study, the median patient age was 34 years (IQR: 28 to 49 years) and the male: female ratio was 21:17. Among these, 31 (81.6%) smoked cigarettes and 19 (50.0%) used intravenous drugs. The most common comorbidity reported was type 2 diabetes mellitus in 7 (18.4%) patients. One patient was noted to be taking immunosuppressive medication and one patient had end-stage renal disease. Ten (26.3%) patients had a prior soft tissue infection requiring surgical management.

A majority of the skin and soft tissue infections assessed in this study were unilateral infections; either involving the hand 22 (57.9%) or the upper arm 11 (28.9%). Three cases involved the bilateral hands (7.9%) and two cases involved the unilateral wrist (5.3%). There were no bilateral upper arm or bilateral wrist infections diagnosed in the study population (Table 1).

Necrotizing fasciitis was diagnosed in 7 (18.4%) patients in this sample and was most commonly associated with Streptococcus pyogenes (GAS) (Fig. 1). The most common microbe cultured in all assessed SSTIs was GAS 17 (44.7%). Methicillin-resistant Staphylococcus aureus (MRSA) was cultured in 5 (13.2%) patients and Methicillin-susceptible Staphylococcus aureus (MSSA) in 4 (10.5%) cases. Four of the patients (11%) had culture-negative results and 6 (15.7%) grew multiple organisms; of these, four grew both Streptococcus pyogenes and Streptococcus agalactiae (GBS) (Fig. 2).

All patients were started on broad-spectrum antibiotics intravenously; 18 (47.4%) patients received one antibiotic, 10 (26.3%) received two different antibiotics, 8 (21.1%) received three different antibiotics, and two patients (5.3%) received four different antibiotics. Twenty-three (60.5%) patients received Vancomycin alone or in combination with other antibiotics. Piperacillin/Tazobactam was used in 17 (44.7%) cases and Ceftriaxone and Clindamycin were used in 10 (26.3%) and 8 (21.1%) cases respectively. Other antibiotics used included Penicillin G in 3 (7.9%) patients and Trimethoprim/sulfamethoxazole in 2 (5.3%) patients. Metronidazole, Ertapenem, and Meropenem were each used only once, in three different patients (Fig. 3).

Upon initial presentation to the emergency department (ED), the majority of patients were in the operating room within at least 24 hours of presentation 22 (57.9%). Eleven (28.9%) patients were taken to the operating room within 48 hours and three (7.9%) patients, were in the operating room 72 or more hours after initial presentation. Two patients left the hospital, against medical advice, prior to surgical intervention. As it relates to the type of surgical procedure required for patients in this sample, 26 patients (68.4%) underwent incision and drainage and 10 (26.3%) underwent irrigation and debridement. Two patients underwent amputation of the infected hand or arm. In 26 (68.4%) cases, repeat surgical intervention was required.

The most common investigations completed in the study population included wound culture 36 (94.7%), complete blood count 35 (94.6%), and a metabolic panel 34 (89.5%). Other investigations included a lactate level 23 (60.5%) and C-reactive protein 21 (55.3%). In 16 (42.1%) patients, blood cultures were obtained. Imaging was not routinely utilized for the investigation of SSTIs in this study population; ultrasound and computed tomography (CT) were completed in 6 (15.8%) and 4 (10.5%) cases, respectively. Two patients (5.2%) underwent magnetic resonance imaging (MRI). The median length of hospital stay was 6 days (IQR: 4–14.5). Eighteen (47.4%) patients were discharged to home or community, and 10 (26.3%) discharges were patient-directed (left against medical advice). Of the 10 patients who left the hospital against medical advice, 8 (80.0%) were PWID (Table 2).

Areas of increased vascularity, such as the groin and antecubital fossa, are among the most common sites of injection for intravenous drug users.¹¹ These findings are consistent with other studies in the literature, which found the most common sites of infection in PWID to be the antecubital fossa, arm, and hand.^12,13

Prior studies have typically demonstrated that females are more likely to be affected by SSTIs than males, especially in injection drug use related cases.^14,15 With a male-to-female ratio of 21:17 in our study population, this trend was not observed. However, the number of male and female patients in this study was roughly equal and the discrepancy with prior studies may be in part explained by the small sample size of our study. The average age of patients in our study is equally consistent with findings in prior studies of SSTIs secondary to IVDU.²

The microbiology of SSTIs in PWID is generally predictable; Staphylococcus aureus and Streptococcus pyogenes are the most common culture isolates of SSTIs associated with IVDU.^16–19 In addition, one of the strongest risk factors associated with MRSA positive SSTIs is IVDU.²⁰

While Staphylococcus aureus is also a common culprit in SSTIs of persons who do not inject drugs, Streptococcus pyogenes is more prevalent in PWID.²¹ In addition, PWIDs are more likely to present with anaerobic and polymicrobial infections as compared to those who do not inject drugs.²² Culture results in our patient population are consistent with these findings, with the vast majority of cases isolating Streptococcus pyogenes, Staphylococcus aureus (including MRSA), and polymicrobial organisms.

Knowledge of specific microbes implicated in the pathogenesis of SSTIs in PWID is essential to direct the choice of antibiotic therapy for these infections. Recent landmark trials out of the United States have found improved outcomes and higher cure rates with the combination of empiric antibiotic therapy and incision and drainage for the treatment of SSTIs.^23,24 Both studies selected antibiotics covering GAS, GBS, and MRSA (Trimethoprim–Sulfamethoxazole and Clindamycin).^23,24 Similarly, in our study, a majority of patients (60.5%) received a course of Vancomycin, a broad-spectrum antibiotic covering the most commonly implicated microbes including MSSA, MRSA, and Streptococcus species.

Necrotizing fasciitis (NF) is a rapidly progressive infection of the subcutaneous fat and fascia. Although rare, NF is a life-threatening infection, with mortality rates reaching 50%.^22,23 Given this, prompt diagnosis, surgical intervention, and initiation of broad-spectrum antibiotic therapy are essential in the management of NF. In our patient population, NF was diagnosed in 7 (18.4%) patients, three of which, were known injection drug users. Streptococcus pyogenes was isolated in 6 (85.7%) of the necrotizing fasciitis cases in our study. This is consistent with previous findings in the literature demonstrating Streptococcus pyogenes as the most common cause of mono-bacterial necrotizing soft tissue infections.²⁵

It has been frequently reported in the literature that injection drug use is a significant risk factor for the development of necrotizing soft tissue infections.^19,26,27 There are several possible reasons for this, including the direct inosculation of bacteria from contaminated drug products or injection equipment, increased rates of Staphylococcus aureus colonization in PWID, and non-vascular injection into the skin.¹⁹

Although IVDU appears to be a significant risk factor for the development of NF, the mortality rate of NF in PWID tends to be lower than in the non-injection drug use population. Waldron et al. found in patients diagnosed with NF, the mortality rate for PWID was 17% as compared to the overall mortality rate of 29%.²⁸ Similarly, Chen et al. found a mortality rate of 10% for PWID diagnosed with NF, as opposed to 21% among those who do not inject drugs.²⁹ These discrepancies may be explained by a higher index of clinical suspicion in PWID resulting in surgical intervention within 24 hours of presentation to the hospital. ^22,24

Necrotizing fasciitis in PWID has also been associated with an increased risk of requiring amputation of the infected area and the development of deep vein thrombosis.^30,31 In our study, two patients underwent amputation; both patients had a primary diagnosis of Necrotizing fasciitis and were PWID. In addition, PWID are at increased risk for recurrent SSTIs, leading to re-admissions to hospital and additional surgical procedures. Chan et al. found that of PWID presenting with NF, 32% of these patients had a prior abscess or cellulitis.²⁹ Similarly, nearly one-third of patients in our study had a prior soft tissue infection requiring surgical management.

In our patient cohort, the median length of hospital stay was 6 days (IQR: 4–14.5). A previous study evaluating hospital admissions amongst the PWID population in Regina, Saskatchewan found the median length of hospital stay to be 7.7 days. In addition, of the 149 patients included in that study, 30% of all admissions were due to SSTIs. They determined the average cost of stay for the PWID population to be $24,982 CAD, which is significantly more than the standard cost of hospital stay in the region.5 In keeping with this, several other Canadian studies found the average hospital stay for the PWID population to be greater than those without a history of substance use.^10,32

In the current study, 26% of all patient discharges from the hospital were patient-directed (against medical advice). Patient-directed discharge is three times more common in patients with substance use disorder compared to those without.³³ Factors such as perceived stigma from healthcare staff, uncontrolled pain, and untreated withdrawal contribute to patients leaving the hospital before the completion of treatment.³³ Leaving the hospital before the completion of treatment contributes to higher rates of readmission, negative health outcomes, and higher rates of mortality.^34–36 These findings underscore the importance of strategies that reduce premature patient-directed discharge and promote completion of treatment.

We propose that harm reduction strategies initiated during hospital admission may reduce the rate of patients leaving the hospital before the completion of treatment. Inpatient opioid agonist therapy such as methadone, and the involvement of social supports including family and friends, are mitigating factors that may reduce the rate of patient-directed hospital discharge.³⁷ In one study, initiation of methadone during the patient's hospital admission was found to reduce the rate of discharge against medical advice by 50%.³⁷

In Saskatoon hospitals, harm reduction strategies may include the involvement of addiction medicine services and social work during the patient's hospital admission. In the community, increased access to needle syringe programs and supervised consumption sites has proven to reduce SSTIs in the PWID population.³⁸ This data suggests that the uptake of harm reduction strategies in hospitals and the community would greatly benefit the PWID population from a morbidity and mortality standpoint.

The retrospective nature of this study poses several limitations. Firstly, of the 38 patients included in this study, 10 left against medical advice, two of which left prior to planned surgical intervention. Secondly, in comparison to other similar studies, a total of 38 patients in the current study met the inclusion criteria, making our sample size relatively small. In addition, many patients do not disclose injection drug use, due to associated stigma and other factors. Therefore, the number of patients reported to use injection drugs in this study may be underestimated.

This study highlights the need to address harm-reduction strategies aimed at reducing the development, and recurrence, of SSTIs in the PWID population. People who inject drugs experience a disproportionate burden of recurrent SSTIs, prolonged hospital admissions, and repeat surgical interventions. Furthermore, the increased risk of developing necrotizing fasciitis associated with injection drug use underscores the critical need for healthcare providers to maintain a high index of clinical suspicion when caring for this patient population. By implementing harm reduction strategies during patients' hospital admission, we anticipate a decrease in patient-directed discharge, facilitating the completion of treatment. In addition, by expanding access to needle syringe programs in the community, we expect a reduction in SSTIs requiring surgical intervention and hospital admission in the injection drug use population.

IVDU – Intravenous Drug Use

PWID – People Who Inject Drugs

SSTI – Skin and Soft Tissue Infections

NF – Necrotizing Fasciitis

Ethics Approval and Consent

Under the guidance of the Biomedical Research Ethics Board at the University of Saskatchewan, obtaining patient consent was waived due to it being impossible or impractical to seek individual consent given the retrospective nature of this study. All portions of this research including data collection and statistical analysis, did not involve direct or indirect patient contact. The investigators have taken the appropriate measures to ensure the protection of the personal information of the individuals included in this study. The data was collected and deidentified, and only aggregate data are published.

IRB Approval Statement: The University of Saskatchewan Biomedical Research Ethics Board approved the study protocol (Bio 2875).

Consent for Publication

Not applicable.

Availability of Data and Materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing Interests

The authors declare that they have no competing interests.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author Contributions

Conceptualization, R.M., C.T., G.G..; methodology, R.M., C.T., G.G..; validation, R.M., C.T., G.G..; data curation, R.M.; formal analysis, E.Y.; writing—original draft preparation, E.Y., R.M., R.R.; writing—review and editing, E.Y., R.M., R.R., C.T., G.G.; supervision, C.T.; project administration, E.Y., R.M., R.R., C.T., G.G.; All authors have read and agreed to the published version of the manuscript.

Acknowledgements

Not applicable.

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Table 1: Patient Characteristics

Characteristic	Data
Number of patients	38
Patient age (years), median, [interquartile range]	34 [28 - 49]
Patient sex, n (%)
Male	21 (55.3)
Female	17 (44.7)
Location of infection, n (%)
Unilateral hand	22 (57.9)
Unilateral upper arm	11 (28.9)
Bilateral hands	3 (7.9)
Unilateral wrist	2 (5.3)
Bilateral upper arm	0 (0)
Bilateral wrists	0 (0)
Comorbidities, n (%)
Cigarette smoking	31 (81.6)
Intravenous drug use	19 (50)
Type 2 diabetes mellitus	7 (18.4)
End-stage renal disease	1 (2.6)
Taking immunosuppressive medication	1 (2.6)
Past medical history, n (%)
Previous soft tissue infection requiring surgical management	10 (26.3)

Table 2: Course in Hospital

Characteristic	Data
Length of stay, median [interquartile range], days	6 [4-14.5]
Time from presentation to operation, n (%)
Within 24 hours	22 (57.9)
24 – 48 hours	11 (28.9)
Over 48 hours	3 (7.9)
Type of procedure, n (%)
Incision and drainage	26 (68.4)
Irrigation and debridement	10 (26.3)
Amputation	2 (5.3)
Imaging investigations, n (%)
US	6 (15.8)
CT	4 (10.5)
MRI	2 (5.3)
Laboratory investigations, n (%)
Wound culture	36 (94.7)
CBC	35 (94.6)
Metabolic panel	34 (89.5)
Lactate	23 (60.5)
CRP	21 (55.3)
Blood culture	16 (42.1)
LFT	16 (42.1)
CK	13 (34.2)
Disposition, n (%)
Home or community	18 (47.4)
Left against medical advice	10 (26.3)

No competing interests reported.

Epidemiology of upper limb skin and soft tissue infections requiring surgical intervention in Saskatoon, Canada: A retrospective chart review

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Abstract

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BACKGROUND

METHODS

Statistical Analysis

RESULTS

DISCUSSION

CONCLUSION

Abbreviations

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Additional Declarations

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