A list of all 37 encounters in which a patient received one or more doses of oritavancin within the specified time frame supplied the starting point for review. Thirteen encounters were excluded; the primary reason for exclusion was no known history of injection drug use (n = 9); other reasons included a diagnosis outside of the inclusion criteria (n = 2) and greater than 14 days elapsed between administered doses (n = 2). Twenty four courses, prescribed to 23 different patients, were included in the analysis. One patient (numbers 2 and 22 in Table 1) received 2 separate courses of treatment, with the second course administered 20 months after the final dose of the initial course. At the time of infection diagnosis, 16/24 (67%) encounters were for patients experiencing homelessness. Most patients were male (16/23, 70%) and the average age was 41 years old (range 22–64). The median body mass index (BMI) was 24.3; 8/24 (33%) were considered obese with a BMI of greater than 30. Sixteen of 23 patients (70%) had a history of significant psychiatric illness defined as schizophrenia, bipolar disorder, major depressive disorder, schizoaffective disorder or borderline personality disorder. Nine (39%) patients left AMA during a prior hospitalization for their infection.
MRSA was the most common infecting pathogen occurring in 14/24 (58%) of encounters. Bone or joint was the most frequent infection location occurring in 14/24 (58%) encounters, and the spine was the most common site of bone infection (4/9, 44%). Half of all encounter patients (12/24, 50%) were bacteremic with either MRSA (6/12, 50%) or MSSA (6/12, 50%). Of the two patients diagnosed with infective endocarditis, both involved native tricuspid valves and neither underwent surgical valve replacement.
Patients received a median of 9.5 days of effective gram-positive therapy based on susceptibility, when available, prior to ORI initiation. Number of ORI doses ranged from 1 to 6; initial doses were universally 1200 mg. Subsequent dosing was at the discretion of the clinician and was always administered weekly. Eleven patients received more than one dose. Of those, 4 received 800 mg doses and 7 received 1200 mg doses. The majority of doses were administered in the outpatient infusion center. Twelve patients received 1 dose as inpatient; 3 of these patients received additional outpatient doses thereafter. Twenty three of 24 encounters utilized ORI for therapy completion, having received prior gram-positive treatment for their infections. Patient 8 was the only patient to also receive DAL; the patient received a single dose at an outside hospital prior to transferring care to our institution.
Clinical cure was achieved in 19/24 (79%) encounters and failure in 3/24 (13%); 2/24 (8%) were lost to follow-up after their last infusion. The two patients lost to follow-up were not noted to have any signs of worsening of infection at their final infusion, however, documentation was limited at each of those visits and thus no assessments can be made. Of the 4 patients with osteomyelitis involving the spine, 3/4 (75%) experienced clinical cure and 1/4 (25%) treatment failure. Of the 6 patients who had incomplete adherence to the planned regimen, cure was seen in 5 patients and failure in 1. Three patients received only the first of two planned doses; including the patient deemed to be a clinical failure in the group with partial adherence. The remaining 3 patients with partial adherence experienced an unexpected delay of 14 days between doses, but received all planned doses (3 to 5 doses total).
Two patients (8%) experienced ADRs within 6 weeks of receiving ORI. One patient presented to the Emergency Department (ED) 5 days after receiving ORI complaining of sharp, non-radiating abdominal pain, however, the patient eloped prior to evaluation. Four days after her ED visit she was admitted to the jail medical ward, which is overseen by our institution, without documentation of infection, pain or further antibiotics. One patient experienced an infusion-related reaction becoming visibly flushed and complaining of a headache 20 min into the first dose. After an infusion pause, the remaining drug was administered without symptom recurrence and she received a second dose 1 week later without issue. Employing the NADRPS harm scale, the former patient’s ADR was classified as possible and the latter as probable.
Three patients (patients 11, 21, and 23) were determined to have failed therapy with ORI, with 1 of 3 possibly related to incomplete adherence. Patient 11 was being treated for MRSA ((vancomycin minimum inhibitory concentration (MIC) 2, confirmed by two methods, Vitek and Microscan)) bacteremia with vertebral osteomyelitis and was initially bacteremic for 14 consecutive days. Source control was unable to be achieved due to location of fluid collections and proximity to spinal cord. After blood culture clearance, he was discharged and returned for daily infusions of high-dose daptomycin (> 10 mg/kg) but was transitioned to weekly ORI 3 weeks later due to loss of IV access and inability to receive a peripherally inserted central catheter (PICC). After the second ORI infusion, the patient was readmitted due to ongoing back pain and new spinal cultures were obtained; daptomycin MIC had increased from 0.5 to 4 μg/mL and thus was no longer susceptible. Although the corresponding vancomycin MIC of this isolate was 1 μg/mL, the ID team did not treat with vancomycin due to recent history of MRSA isolate with vancomycin MIC 2 μg/mL and the concern for emergence of resistant subpopulations. At the discretion of the ID physician, the patient remained admitted to complete 6 weeks of ceftaroline.
Patient 21 was treated for MRSA bacteremia and ABSSSI and missed the second of two planned ORI doses. He was admitted 14 days after his ORI infusion (7 days after the missed dose) and found to have recurrent MRSA bacteremia along with a new aortic valve vegetation on transthoracic echocardiography (TTE) that was not seen on TTE during his last admission.
Patient 23 is a paraplegic man with no sensation in his lower extremities, initially treated with IV vancomycin for MRSA bacteremia. On day 7 he planned to leave AMA; oral antibiotics could not be prescribed due to drug interactions so he was given a single ORI dose. The patient was readmitted for inpatient psychiatry care a few weeks later where he experienced a femur fracture while adjusting himself in bed. He was taken to surgery; intraoperative cultures grew MRSA but blood cultures remained negative. Both MRSA isolates, from the pre-ORI blood cultures and post-ORI intraoperative cultures, had a vancomycin MIC of 1 μg/mL via Vitek.