Dermatology

Effectiveness of oritavancin for management of skin and soft tissue infections in the emergency department: A case series

a b s t r a c t

skin and soft tissue infections, such as cellulitis, are commonly diagnosed in the emergency department and these patients are often admitted to the hospital for Intravenous antibiotic therapy. Oritavancin is a novel antibi- otic approved for the treatment of skin and soft tissue infections that is administered as a one-time infusion. While oritavancin has demonstrated comparable efficacy with multi-dose parenteral antibiotics in clinical trials and has been proposed as an alternative to admission for emergency department patients, there is a paucity of available real world effectiveness data. In this case series, we describe the characteristics and outcomes of ten pa- tients with high-risk skin and soft tissue infections who received oritavancin and were discharged from the emer- gency department.

(C) 2021

  1. Introduction

Skin and soft tissue infections are commonly diagnosed in the emergency department (ED), accounting for ~3% of all ED encoun- ters (3.3 million visits in 2014) [1,2]. SSTI infections such as cellulitis may be treated in the outpatient setting with oral antibiotics; however, patients seeking care in the ED are often admitted due to concerns about illness severity and/or risk of treatment failure [3,4]. During hospitaliza- tion patients typically receive intravenous antibiotic therapy with activ- ity against common pathogens such as methicillin susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus au- reus (MRSA) and group A Streptococcus. The cost of all cellulitis admis- sions in 2013 was estimated at $3.74 billion and the median length of stay and cost per visit was 2.88 days and $5159 and respectively [5].

In 2015, the Food and Drug Administration approved oritavancin for acute bacterial skin and skin structure infections, defined by lesion area of at least 75 cm2. Oritavancin is a semisynthetic glyco- peptide that exhibits extensive tissue distribution. Oritavancin is a 1200 mg infusion given over 3 h that provides a one dose treatment

* Corresponding author.

E-mail addresses: [email protected] (D. Dretske), [email protected]

(L. Schulz), [email protected] (E. Werner), [email protected] (B. Sharp), [email protected] (M. Pulia).

course due to its terminal half-life of 393 h. Oritavancin does not re- quire dose adjustment for hepatic or renal insufficiency and has activ- ity against all common gram positive SSTI pathogens, including MSSA, MRSA, S. pyogenes, S. agalactiae, S. dysgalactiae, S. anginosus group (including S. anginosus, S. intermedius, S. constellatus) and Enterococ- cus faecalis (vancomycin-susceptible isolates only). [6] Oritavancin has shown comparable Clinical effectiveness versus multi-dose stan- dard care antibiotic therapy in the outpatient infusion center setting. In a retrospective observational study of 118 patients, the oritavancin cure rate was 73.2% versus just 48.4% in the Standard care group [7]. Another observational study conducted primarily in the infusion cen- ter setting observed a positive Clinical response in 92.8% of patients treated with oritavancin [8]. These studies are consistent with clinical trial data indicating oritavancin yields similar Treatment failure rates to intravenous vancomycin [9]. However, there is a paucity of real- world data examining the effectiveness of oritavancin for patients pre- senting to the ED.

Current treatment guidelines for SSTIs do not incorporate the use of oritavancin, although algorithms for selecting viable candidates for this novel therapy with the goal of avoiding unnecessary hospital ad- mission have been proposed [10,11]. Available literature indicates these long acting antibiotics may be safely used to reduce hospital ad- missions and generate cost savings compared to inpatient treatment with Intravenous antibiotics [4]. In this case series, we primarily

https://doi.org/10.1016/j.ajem.2021.01.050

0735-6757/(C) 2021

aimed to evaluate the performance and safety of our institutional oritavancin guideline which incorporates ED patient selection criteria proposed by Baxa et al. [10]

  1. Materials and methods

This retrospective chart review was conducted at a midwest quater- nary care academic medical center ED as a Quality improvement project and was thus exempt from IRB review. The detailed chart review was conducted independently by two trained abstractors, a clinical pharma- cist and an emergency medicine physician assistant. Discrepancies in abstracted information were resolved by consensus. Patients were in- cluded if they received oritavancin while in the ED from January 1st, 2018 to December 31st, 2019. Patients were excluded if the treatment indication was not SSTI. A treatment course was defined as an infusion or administration of oritavancin within the ED or ED observation unit. Patients were identified via the electronic health record (EHR, Epic, Ve- rona WI) using medication administration data and patient admission, discharge, transfer data to determine location of infusion.

Patient demographics, indication, suspected organism coverage, ex- clusion criteria for oritavancin and risk factors for oral antibiotic treat- ment failure were collected [10]. The indication was obtained through the institution antibiotic ordering tool defined by the ordering physician [12]. The indication was confirmed by review of the emergency physician’s clinical note within the EHR. Institution specific guideline criteria regarding risk factors for oral antibiotic outpatient treatment failure and exclusion criteria for oritavancin was obtained from the pharmacist note documented in each patient’s chart prior to ordering oritavancin.

Oritavancin was deemed effective if the patient was prescribed no further antibiotics for their SSTI within 14 days. Cases involving addi- tional antibiotics within 7 days of oritavancin administration were con- sidered early treatment failures and those occurring between 8 and 14 days were considered late failures. Rescue antibiotic administration and follow-up dates were determined using ordering and medication administration data in the EHR, which included review of clinical docu- mentation from outside institutions via sharing tools within the EHR.

  1. Results

Eleven treatment courses (cases) of oritavancin from 10 unique pa- tients were identified in the study period (Table 1). One of the 10 pa- tients received oritavancin on two separate occasions ~5 months apart. Five patients were female and five patients were male. The me- dian age at the time of diagnosis was 45 years (SD +- 16.97). Nine pa- tients had cellulitis of either a lower or upper extremity and one patient had facial cellulitis. Two patients underwent an incision and drainage procedure during their ED visit.

Oritavancin was deemed effective in 7 of the 11 cases (63.3%) be- cause no additional antibiotics were required. Four cases involved res- cue antibiotics, three of which were considered early failures. The median time to administer rescue antibiotics was 4 days (range 1 to 11 days). Two of the patients with early failure required an additional ED visit and one patient was admitted. No patients in the failure group were considered septic or died as a result of their infection. One case was lost to follow-up as they had no clinical documentation within the EHR following administration.

The most commonly selected risk factors for potential oral antibi- otic Outpatient therapy for SSTIs by the pharmacist included psycho- social concerns for adherence, previous oral treatment failure (>24 h of appropriate therapy) and an infection duration of greater than 7 days. The average number of selected indications per case was

3.4 (SD +- 1.88).

  1. Discussion

This case series represents the first to examine the real-world ef- fectiveness of oritavancin for ED patients with SSTI. There are many options available to ED providers when managing SSTI patients, in- cluding various oral and parenteral antibiotic therapies and outpa- tient or inpatient disposition depending on the clinical scenario. While low risk SSTI patients are typically managed with outpatient enteral antibiotic therapy, available data suggest most patients admitted for parenteral therapy could be safely managed in the outpatient setting [3,13]. While the cost of oritavancin is high, several health economic analyses support its cost effectiveness as compared to the expenses associated with hospital admission for SSTI [4,14,15]. Oritavancin offers several specific benefits over traditional paren- teral treatment modalities, most notably its broad spectrum activity, elimination of need for invasive intravenous access (e.g. peripherally inserted central catheter for outpatient parenteral antimicrobial ther- apy th) [16] and it addresses adherence and lack of adequate follow up concerns with a single dose regimen. Baxa et al. identified that the only justification for admission in ~10% of ED patients admitted for SSTIs is the presence of a risk factor for treatment failure (e.g. concern for non-adherence, diabetes mellitus) [10]. These ‘high risk’ but clini- cally stable patients are ideal candidates for oritavancin therapy. These risk factors were incorporated into our institutional oritavancin guide- line allowing pharmacists to document risk factors for each patient as part of the approval process. It is important to note that oritavancin is not approved for all types of SSTIs (e.g. diabetic foot infections, bite wounds) and allergy to lipopeptides is a contraindication [10]. Although concerns have been raised about potential interactions between warfa- rin and oritavancin, a pharmacokinetics study concluded that they can

be safely co-administered [17].

Of the eleven identified cases, oritavancin was successful in treating the SSTI, specifically avoiding additional antibiotics and hospital admis- sion, in 63.3% of cases. This suggests that in carefully selected popula- tions, oritavancin can be an effective tool in managing high-risk patients with SSTIs in the ED. In terms of the treatment failure cases, none of the patients suffered a serious adverse event, specifically sepsis or death, following oritavancin therapy. All rescue antibiotics were pre- scribed in the outpatient setting except for one patient who required subsequent admission.

A more detailed review of the treatment failure cases suggests the success rate of oritavancin might be even higher than determined using our established definition of Rescue therapy. For example, in one of these cases, an outpatient provider initiated additional antibi- otics 4 days after the ED visit despite documenting, “Left lower leg cellulitis clinically receding now after 1 intravenous dose oritavancin in ED”. This suggests some providers may not be aware of the long du- ration of action and potential for single dose cure with oritavancin. Regarding the patient who returned 1 day after his ED visit and was subsequently admitted for treatment failure, we identified that the patient’s return visit may have been related to secondary gain and not due to actual progression of disease. Unfortunately, the clinical documentation of the SSTI characteristics from the initial ED visit was not complete and available for the second physician to reference due to the close proximity of the visits (<24 h). This highlights the importance of timely documentation or preferably, entry of clinical photographs in the chart to assist downstream providers in gauging the objective progression as they attempt to make a determination regarding treatment failure. If these two cases do not represent true treatment failures, the success rate of oritavancin in this case series would reach 81.8%.

It is interesting to note that only eleven ED administrations were identified in a two year time period, suggesting ongoing provider (e.g. familiarity) and systems level barriers to oritavancin use (e.g. patient cost concerns and cumbersome insurance coverage verification

Table 1

Patient demographics, clinical factors and outcomes.

Patient

Age/Gender

Infection type

Suspected

Previous Antibiotic Treatment

Oritavancin Criteria (Risk

Rescue Therapy – Antibiotic(s)

Adverse

#

and Location

Organism Covered

Factors for Treatment Failure)

and

Days Post Oritavancin

Effects from Oritavancin

1

57 y/o F

Lower left

MSSA, MRSA,

Doxycycline

1. Concern for adherence

Sulfamethoxazole-Trimethoprim

Diarrhea

extremity cellulitis

Streptococcus

2. Duration of infection

(4)

>7 days

    1. History of ABSSI at same site within last

3 months

4. Oral treatment failure

5. Diabetes mellitus

2

44 y/o M

Facial cellulitis

MSSA

Topical Clindamycin

1. Duration of infection

N/A

None

MRSA

>7 days

reported

2. Oral treatment failure

3

44 y/o M

Upper left

MRSA

Sulfamethoxazole-Trimethoprim

1. Concern for adherence

N/A

None

extremity

& Cephalexin

2. intravenous drug user

reported

cellulitis+

3. Duration of Infection

>7 days

4. Oral treatment failure

4

86 y/o F

Lower right

MSSA

Ceftriaxone &Doxycycline

1. Concern for adherence

N/A

None

extremity cellulitis

MRSA

2. Cognitively impaired

reported

Streptococcus

3. Duration of infection

>7 days

4. Oral treatment failure

5. Diabetes mellitus

5

73 y/o F

Lower left

MSSA

Dicloxacillin

1. Lymphedema

Dicloxacillin (4)

None

extremity cellulitis

MRSA

2. Oral treatment failure

reported

Streptococcus

6?

29 y/o F

Bilateral upper

MSSA

Sulfamethoxazole-Trimethoprim

1. Concern for adherence

N/A

None

Visit #1

extremity

MRSA

& Cephalexin

2. Intravenous drug user

reported

cellulitis+

Streptococcus

3. Duration of infection

7? 29 y/o F Visit #2

Bilateral upper extremity cellulitis

MSSA MRSA

Streptococcus

>7 days

    1. History of ABSSI at same site within last

3 months

    1. Oral treatment failure

None 1. Concern for adherence

  1. Intravenous drug user
  2. History of ABSSI at same site within last

3 months

  1. Incarcerated

N/A Hives

  1. 47 y/o M Lower left extremity cellulitis

MSSA MRSA

Streptococcus

None 1. Incarcerated

2. Diabetes mellitus

Cefazolin (1) Headache

  1. 46 y/o F Bilateral lower extremity cellulitis

MSSA MRSA

None 1. Chronic Edema None Nausea

  1. 42 y/o M Lower left extremity cellulitis

MSSA Amoxicillin & Doxycycline

  1. Concern for adherence
  2. Chronic edema
  3. Lymphedema
  4. Chronic leg ulcers
  5. Duration of infection

>7 days

  1. History of ABSSI at same site within last

3 months

  1. Oral treatment failure

Ceftriaxone (11) Itching,

flushing

  1. 39 y/o M Upper right extremity cellulitis

MSSA MRSA

Streptococcus

Sulfamethoxazole-Trimethoprim & Cephalexin

1. Oral treatment failure None None reported

* Same patient, visits separated by ~5 months.

+ Patient underwent incision and drainage procedure.

process). One limitation of this case series is the potential for missed ad- ministration of additional antibiotics and adverse clinical outcomes for patients who did not present for follow up within our healthcare sys- tem. In the future, we plan to continue tracking Treatment outcomes for patients who receive this novel therapy and will examine ways to in- crease oritavancin utilization at our institution (e.g. formal barrier analysis).

  1. Conclusions

This case series of ED patients with risk factors for outpatient SSTI treatment failure treated with oritavancin appears consistent with prior trial data suggesting oritavancin may be a safe and effective alter- native for patients with planned admission due to concern of being high-risk for treatment failure with outpatient therapy. Further large-

scale reports assessing the real-world effectiveness of oritavancin in the ED, including relevant clinical outcomes, are necessary to inform proto- col optimization and dissemination efforts.

Disclosures

Lucas Schulz, Medicines Company advisory board. All other authors have nothing relevant to disclose.

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