Infectious Diseases

Real world utilization of Dalbavancin at a rural community emergency department

a b s t r a c t

Introduction: Acute bacterial skin and skin structure infections (ABSSI) are frequently encountered in the emer- gency department and compromise more than 700,000 hospital admissions annually. Dalbavancin is a single dose long acting semi-synthetic lipogylcopepitde antibiotic with coverage against gram-positive organisms in- cluding methicillin resistant Staphylococcus aureus. Recent data from large Tertiary care centers have shown a de- crease in hospital admissions and repeat emergency department visits for ABSSI’s but little data is available for those who practice in a rural community setting. The primary objective of this study was to describe the use of dalbavancin at a single rural emergency department.

Methods: A retrospective cohort study of all adult patients who received dalbavancin between 2019 and 2021 while in the emergency department was completed. Abstracted data included patient demographics, infection location by body region, emergency department return visits, hospital admissions, and length of stay. Analysis was conducted using descriptive statistics, the Mann-Whitney test for continuous data, and the chi-squared anal- ysis for nominal data.

Results: A total of 125 patients were included in the final analysis with 35.2% being female. The median age of those treated with dalbavancin was 54 years (42.0-64.0) and the most common infection site was the lower ex- tremities. A total of 35 patients re-presented to the emergency department following treatment with dalbavancin within 30 days and 16 were admitted to the hospital. Of those who re-presented to the emergency department, the median age was 56 (40.0-66.0) and the median re-presentation was 9 days (3-17) after dalbavancin admin- istration. A total of 16 patients (12.8%) were subsequently admitted to the hospital with a median length of stay of 5.5 days (3.0-8.0). 30-day readmission rates were 23.9% in those who had an abnormal WBC count at initial presentation, 26.1% for those with congestive heart failure, 20.3% for those with hypertension, and 26.0% in those who had diabetes mellitus.

Conclusion: Following the administration of dalbavancin for ABSSI at a rural emergency department, few patients are subsequently admitted within the following 30 days. To further decrease this number and alleviate the bur- den on emergency departments and hospitals, local treatment algorithms should be developed to minimize the risk of representation and hospitalization following administration.

(C) 2022

  1. Introduction

Acute bacterial skin and skin structure infections (ABSSI) are bacte- rial infections of the muscle layers, fascia and skin that typically present

* Corresponding author.

E-mail addresses: [email protected] (A. Dolan), [email protected] (E. Kuge), [email protected] (E. Bremmer), [email protected] (T. Dietrich), [email protected] (A. Santarelli), [email protected] (J. Ashurst).

with redness, induration, or edema [1]. The most common organisms that cause ABSSI’s include the Gram-positive bacteria Staphylococcus auerues and Streptococcus pyogenes [1]. Over the last decade, however, community acquired methicillin-resistant Staphylococcus aureus has be- come a predominant cause of ABSSIs causing physicians to search for new methods of treatment [2].

Between 1993 and 2005, emergency departments saw a steady rise in the number of presentations due to ABSSIs despite medical advance- ments in pharmacology and the management of infectious diseases [3].

https://doi.org/10.1016/j.ajem.2022.02.006

0735-6757/(C) 2022

In 2009, hospitalizations due to ABSSIs reached 870,000 with an aver- age length stay of 7.3 days costing more than $4.8 billion annually [4,5]. Despite the low incidence of mortality and need for intensive care, many patients are admitted to the hospital for parental antibiotics and further monitoring for progression of the disease [6-10]. Recently, long acting single dose parental antibiotics have been developed that can provide definitive care for ABSSIs and decrease the need for hospital admissions [1].

Dalbavancin is single dose long acting semi-synthetic lipogy- lcopepitde antibiotic with coverage against gram-positive organisms including methicillin-resistant S. aureus [1]. Recent data has shown the efficacy of dalbavancin’s use within the emergency department to reduce hospital admissions [11-13]. However, the majority of the data has been produced at large tertiary care facilities [11-13]. Based upon the lack of evidence in the rural setting, the primary aim of the study was to assess 30-day re-admission rates after treatment with dalbavancin in a rural emergency department. Secondary aims were to address baseline demographics of those given dalbavancin in the emer- gency department and determine if any patterns existed for those who either re-presented to the ED or were admitted to the hospital following infusion.

  1. Methods
    1. Setting

BLINDED FOR REVIEW is a 235-bed rural community hospital in BLINDED FOR REVIEW with an annual emergency department census of approximately 50,000 patient visits. The emergency department has a three-year emergency medicine residency that is accredited by the Ac- creditation Council for Graduate Medical Education and is sponsored by BLINDED FOR REVIEW. BLINIDED FOR REVIEW serves hospital district #1 of BLINDED FOR REVIEW county, where the population is 76.7% White, 16.9% Hispanic or Latino, 3.0% American Indian, 1.3% African American or Black, and 1.2% Asian American.

  1. Methods

A retrospective cohort of consecutive adult patients who received dalbavancin under a single dose regiment of 1500 mg administered in- travenously for the treatment of ABSSI between January 1, 2019 to June 1, 2021 were included in analysis. Patients were excluded if dalbavancin was given outside of the emergency department or if given dalbavancin as part of a two-dose protocol. All reported data was abstracted from pa- tient charts in the MEDITECH EXPANSE Platform (Medical Information Technology INC, Westwood, MA). Abstracted data included: patient

demographics, baseline laboratory values, intake vital signs, length of stay, and all cause re-admissions to either the emergency department or hospital within 30 days following infusion. All data was abstracted by a trained research assistant who was blinded to the study’s primary and secondary objectives. The research assistant was trained on proper data abstraction prior to the collection of data by the study team. This was completed by a member of the study team abstracting data for the first two patients with the research assistant. With adherence to a quality-controlled protocol and structured abstraction tool, the research assistant manually collected all data points. Abstractor monitoring and verification of the independent variables was completed by the primary investigator. The primary investigator assessed 10% of all abstracted participants to ensure accuracy. Patients with incomplete data following abstraction were removed from analysis.

    1. Statistical analysis

Statistical analysis was conducted using IBM SPSS statistics version 27 (IBM Corp., Armonk, New York). Continuous data was compared with the Mann-Whitney test presented as the median and interquartile range. Categorical data is presented as frequencies with percentages of the sample and was analyzed using the chi-squared test. A stepwise multivariate binomial logistic regression was used to determine the most influential factors that predict the either re-presentation or re- admission following infusion. Variables selected for regression were de- termined based upon univariate significance with the addition of age and sex as demographic covariates.

  1. Results

A total of 125 dalbavancin infusions for the treatment of ABSSI within the emergency department were included in final analysis. The median age of those infused with dalbavancin was 54 years (42.0-64.0) with 35.2% (44/125) being female. The most common co- morbid condition seen in those treated with dalbavancin was hyperten- sion (51.2%, 64/125) and 48.0%% (60/125) had a history of illicit drug use (Table 1). The most common site of ABSSI infection that was treated with dalbavancin was the lower extremity (68.8%, 86/125).

Within the study cohort, a total of 35 (28.0%) patients re-presented to the emergency department following infusion with dalbavancin. Of those who re-presented to the emergency department, the median age was 56 (40.0-66.0), 31.4% (11/35) were female and the median re-presentation was 9 days (3.0-17.0) after dalbavancin administration. Patients with zero, one, and Multiple comorbidities were equally likely to re-present within 30 day (p = 0.328). The most common site of infec- tion in those who represented to the emergency department was the

Table 1

Comorbidities among patients administered dalbavancin.

Total

(N = 125)

Male

(n = 81)

Female (n = 44)

Coronary Artery Disease

15.2%

13.6%

18.2%

(19/125)

(11/81)

(8/44)

Congestive Heart Failure

18.4%

17.3%

20.5%

(23/125)

(14/81)

(9/44)

Hypertension

51.2%

50.6

52.3%

(64/125)

(41/81)

(23/44)

Chronic Obstructive Pulmonary Disease

20.8%

23.5%

15.9%

(26/125)

(19/81)

(7/44)

Diabetes Mellitus

40.0%

35.8%

47.7%

(50/125)

(29/81)

(21/44)

Chronic Kidney Disease

13.6%

12.3%

15.9%

(17/125)

(10/81)

(7/44)

Liver Cirrhosis

8.0%

8.6%

6.8%

(10/125)

(7/81)

(3/44)

Drug Abuse

48.0%

53.1%

38.6%

(60/125)

(43/81)

(17/44)

lower extremity (60%, 21/35). No patients represented to the emer- gency department for an adverse event following dalbavancin infusion during the study period or had an adverse event during infusion. A total of 60% (21/35) of patients re-presenting to the emergency depart- ment had a white blood cell workup upon return. These patients exhib- ited no significant reduction in White blood cell counts from 9.9 K/ul to

9.4 K/ul on average (p = 0.42).

Within the sample, 12.8% (16/125) were admitted to the hospital within 30 days. In those admitted to the hospital, the median age was

52.0 (45.5-60.0) and 43.8% (7/16) were female. The median length of stay within the hospital was 5.5 days (3.0-8.0), no patient required in- tensive care transfer, and no in-hospital deaths were reported. A total of 41 days of hospitalization was noted for the cohort of patients who were admitted (2.56 days per admitted participant).

Patients with comorbid diabetes mellitus (81.3%, 13/16) and/or hy- pertension (81.3%, 13/16) comprised the greatest proportion of 30- day admittances following infusion. An increased likelihood to require admission was detected among patients with comorbid congestive heart failure (26.1%; 6/23, p = 0.035), hypertension (20.3%; 13/64, p = 0.01), and diabetes mellitus (26.0%; 13/50, p < 0.001) (Table 2). Patients with an abnormal white blood cell count were additionally more likely to require hospitalization after discharge (23.9%; 11/46, p = 0.02). No significant differences were detected for the admittance rates between men and women (p = 0.44) nor age (p = 0.36). A step- wise regression revealed three factors to be significantly associated with readmittance within 30-days: initial white blood cell fraction (p = 0.001), comorbid congestive heart failure (p = 0.026), and comorbid di- abetes mellitus (p = 0.002) (Table 3). Only a single patient (6.3%; 1/16) was re-admitted with intake lab values and comorbidities outside this classification.

  1. Discussion

To date, this is the first study assessing the use of dalbavancin at a rural community emergency department. In the current study, no ad- verse events were reported and 12.8% of patients were admitted at 30 days following dalbavancin administration for ABSSIs. As compared to

Table 3

Logistic Model of patients readmitted within 30 days of dalbavancin administration

Factor

Wald X2

Beta

S.E

Significance

Initial WBC count

10.723

0.293

0.089

0.001

Congestive Heart Failure

4.951

1.651

0.742

0.026

Diabetes Mellitus

9.504

2.643

0.857

0.002

previous literature from larger healthcare institutions, the adverse event and hospitalization rates after dalbavancin administration in the emergency department appear to be similar [ 11-13]. Given that the demographics of patients included in prior studies appear similar to the current study, re-presentation rates are most likely related to the underlying comorbidities of those receiving treatment [11-13].

Although healthcare institutions may have a treatment protocol for the administration of dalbavancin, emergency medicine providers should also consider the patients clinical status and past medical history prior to administration to minimize the need for re-presentation or hos- pitalization. As healthcare institutions look to decrease re-presentations and hospitalizations for ABSSIs, treatment algorithms that include pa- tient characteristics should be developed for the administrations of long-acting Intravenous antibiotics. In the current study, patients with an abnormal white blood cell count and the comorbid conditions of con- gestive heart failure and diabetes mellitus were all more likely to re- quire hospitalization following treatment. However, none required intensive care admission or expired during the study period. As com- pared to the prior literature, abnormal imaging [e.g., gas, abscess, osteo- myelitis], systemic inflammatory response syndrome, diabetes, prior SSTI at the same location, age > 65 years, and hand location have all been associated with the need for a high level of care in those with ABSSI [14]. Moving forward, institutions should not only develop proto- cols for administration but also to risk stratify patients based upon laboratory values and demographics to decrease the burden of re-presentation rates to the emergency department.

The location of the infection may also play a role in those who represent to the emergency department. In the current study, the most common site of infection was located in the lower extremities.

Table 2

Readmittance characteristics of Patients receiving dalbavancin

Lost to Follow-up 87.2% (109/125)

30d Re-Admit 12.8% (16/125)

Significance

Females

84.1%

15.9%

0.44

(n = 44)

(37/44)

(7/44)

Coronary Artery Disease

73.7%

26.3%

0.06

(n = 19)

(14/19)

(5/19)

Congestive Heart Failure

73.9%

26.1%

0.04

(n = 23)

(17/23)

(6/23)

Hypertension

79.7%

20.3%

0.01

(n = 64)

(51/64)

(13/64)

Chronic Obstructive Pulmonary Disease

84.6%

15.4%

0.66

(n = 26)

(22/26)

(4/26)

Diabetes Mellitus

74.0%

26.0%

<0.01

(n = 50)

(37/50)

(13/50)

Chronic Kidney Disease

88.2%

11.8%

0.89

(n = 17)

(15/17)

(2/17)

Liver Cirrhosis

90.0%

10.0%

0.78

(n = 10)

(9/10)

(1/10)

Drug Abuse

83.4%

11.7%

0.72

(n = 60)

(53/60)

(7/60)

Comorbidities Absent

100.0%

0.0%

0.02

(n = 40)

(40/40)

(0/40)

Single Comorbidity

88.9%

11.1%

0.77

(n = 27)

(24/27)

(3/27)

Two or More Comorbidities Present

77.6%

22.4%

0.03

(n = 58)

(45/58)

(13/58)

Abnormal WBC on Initial Presentation

76.1%

23.9%

0.02

(n = 46)

(35/46)

(11/46)

Previous data has shown that one third of all patients who are admitted from the emergency department with lower extremity cellulitis have a different diagnosis upon discharge from the hospital [15]. This leads to not only unnecessary risks from antibiotic exposure but also increased Healthcare costs. Much like the prior literature, the number of patients who represented to the emergency department for lower extremity ABSSI probably had another diagnosis such as worsening peripheral vascular disease or vasculitis. Further research is needed to correctly di- agnose and treat those with lower extremity ABSSIs to prevent the over- use of antibiotics and Healthcare resources.

  1. Limitations

This was a single site retrospective cohort study from a fairly homog- enous patient population. Results may not be generalizable across all Rural communities or patient populations across the nation. Although KRMC is the one of the largest healthcare providers in the county, patients may have presented to other healthcare facilities for re-presentations or hospitalizations. If this occurred, these numbers were not captured in the current data. Treatment decisions for both dalbavancin administration and hospitalization were provider depen- dent and may have altered the final results. The study is also limited by the study design and lack of a control group to determine superiority or inferiority to prevent re-presentations or admissions.

  1. Conclusion

The administration of dalbavancin in a rural emergency department for the treatment of ABSSI appears to be a safe treatment option with no adverse events reported both during infusion and within 30 days of treatment and few hospitalizations noted at 30 days. healthcare systems should develop algorithms for the usage of dalbavancin based upon risk factors targeting those who are at low risk of re-presentation and hospitalization within 30 days of administration.

Reprint requests

None.

Source of support

None.

Article presentations

None.

Declaration of Competing Interest

None to Report.

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