Treating serious bacterial infections in people who use drugs
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The opioid epidemic in the United States has not only increased the rate of opioid-involved overdose deaths and the transmission of bloodborne viruses but also led to lesser-known consequences, such as increased bacterial infections.
Invasive bacterial infections in people who use drugs (PWUD), especially in people who inject drugs (PWID), are associated with significant morbidity and mortality. This was initially reported with infective endocarditis (IE), of which there was a more than 12-fold increase over a 6-year period (2010 to 2015) in North Carolina, from 0.2 to 2.7 cases per 100,000 persons per year, according to researchers. This trend of increased IE in PWUD was seen nationwide, with the incidence doubling between 2002 and 2016.
Another study found a rise in other serious bacterial infections from 2012 to 2017, including osteomyelitis (OM), central nervous system abscesses, and acute bacterial skin and soft tissue infections (ABSSSI). These serious bacterial infections often require 2 to 6 weeks of therapy with IV antibiotics given as outpatient parenteral antibiotic therapy (OPAT), which is not always feasible for PWUD.
OPAT programs
OPAT programs allow for earlier discharge, minimize risk for hospital-acquired infections and reduce cost. Data on OPAT in PWUD are limited because these individuals are often excluded due to perceived barriers.
Potential barriers to home-based OPAT for PWUD include:
- socioeconomic factors (stable housing, transportation);
- risk of misusing peripherally inserted central catheter (PICC) line;
- lack of tamper-evident mechanism;
- unwillingness of ID physician to follow as outpatient;
- risk of incomplete antibiotic course;
- requirement of behavioral contract or risk to home health care worker safety;
- need for mental health or substance use disorder (SUD) treatment;
- inadequate insurance coverage;
- limited data on outcomes and lack of existing models; and
- legal concerns and risk of being sued.
A review of 10 publications included 800 episodes of OPAT among PWUD. The most common infections treated were OM (37.9%), IE (21%), ABSSSI (16.1%), bacteremia (6.6%) and abscess (5%). The median age ranged from 34.5 to 47 years, with males representing 53% to 89.7% of patients. Most were discharged to home, whereas others were discharged to a facility. The OPAT completion rates among PWUD ranged from 72% to 100%, similar to published data among patients who do not use drugs. Readmission for these individuals was common — greater than 20% in most studies (0.6% to 41%) — and nonadherence to OPAT protocol varied greatly, from 1.2% to 36% of participants.
The studies that compared outcomes between PWID and people who do not inject drugs had comparable outcomes, but PWID were more likely to use after-hour nursing calls and have more frequent noncompliance events (6.4% vs. 0.61%). Four of the studies reported misuse or tampering of the PICC line (incidence ranging from 0% to 2%), and three studies used taper-proof seal or Tegaderm dressing covers to prevent misuse.
SUD treatment was not specified in most studies. The potential to combine SUD treatment and OPAT through a multidisciplinary team is an area that should be explored. A study from the University of Washington evaluated the impact of receiving four interventions of ID consultation, addiction consultation, case management and medications for opioid use disorder. Patients who received all four interventions experienced higher odds of clinical cure (adjusted OR = 3.03; P = .49) and successful retention in addiction care at 30 days (aOR = 6.36; P = .003), suggesting enhanced benefit with the bundled approach.
Complex outpatient antimicrobial therapy with oral antimicrobials is another option in select patients, with data to support the use of oral therapy for the treatment of serious infections such as IE and OM. However, these studies included very few PWUD due to concerns for adherence.
Long-acting lipoglycopeptides
Long-acting lipoglycopeptides (laLGPs) dalbavancin and oritavancin are IV agents with activity against gram-positive organisms, including MRSA, with long half-lives exceeding 1 week. Currently, they are approved by the FDA for ABSSSI only as one- or two-dose regimens. Their ability to penetrate bone, synovial fluid and tissue has led to case reports and series, along with two randomized controlled trials for off-label use, showing positive outcomes in serious infections. One limitation of current data is that the dosing regimens are not standardized for these nonapproved uses. There is a particular interest in using these “lineless” antibiotics for treatment in PWUD as an alternative to completing the entire antibiotic course in the hospital due to not being candidates for OPAT, or in a rehab facility, or for those who leave against medical advice. Additionally, the use of these agents could allow for faster discharge of patients to outpatient or inpatient substance abuse programs that cannot support IV antibiotics.
A case series of 32 PWUD with serious Staphylococcus aureus infections (IE, OM, epidural infection) who were treated with dalbavancin demonstrated a 56% clinical response to treatment. However, most of the lack of clinical response was due to 10 patients (31%) being lost to follow-up. The first dose was administered on the day of hospital discharge, and subsequent weekly infusions were given in ID clinic infusion centers, with an average of 13 days of antibiotics before dalbavancin. PICC line placement was avoided in 47% of patients, and the average length of stay (LOS) was 12.2 days. A total of 17 patients (53%) completed the intended course of therapy.
Another case series of oritavancin — used mostly for bone and joint infections caused by MRSA — involved 23 PWID, with most also experiencing homelessness. It demonstrated favorable outcomes, with clinical cure in 19 cases. This included five individuals whose conditions improved despite nonadherence to the prescribed regimen. A retrospective case series of 56 patients treated with laLGPs for serious gram-positive infections compared outcomes of therapy among 17 PWUD vs. 39 non-PWUD. Clinical failure was seen in 6% in PWUD patients vs. 15% of non-PWUD patients (P = .413), and median hospital LOS reduction was 20 days vs. 11 days (P = .133), respectively. This resulted in an estimated median cost savings of $40,455.08 among PWUD vs. $19,555.08 among non-PWUD (P = .065).
A more conservative approach, used by Denver Health Medical Center, to ensure course completion is to use laLGPs as a single dose to finish the IV antibiotic treatment course. A single dose of dalbavancin was administered 7 to 10 days before planned antibiotic end, allowing for earlier discharge. It was used for 27 patients, among whom 67% were PWID, and the most common indications were uncomplicated S. aureus bacteremia, right-sided IE and bone and joint infection with bacteremia. Clinical success was achieved in 22 (81%) of the patients, clinical failure was confirmed in one patient and four patients were lost to follow-up. A potential adverse event was experienced in 7%, with two patients complaining of dizziness and one of nausea within 1 day of administration. A total of 182 hospital days were averted, with a projected cost avoidance of $246,600, or $9,600 per patient.
The use of laLGPs may serve as a secondary therapy, but it still has limitations, including lack of standardized dosing strategies, drug cost (approximately $3,000 per dose), patient failure to receive repeat doses, loss to follow-up and the risk for adverse drug reactions.
The rate of serious bacterial infections has increased among PWUD over the last decade because of the U.S. opioid epidemic, resulting in increased health care costs from long hospitalization for IV antibiotics. People in this population are often not considered candidates for OPAT therapy, although the limited data available for OPAT in PWUD have shown some success. However, it may require more resources and ideally should be paired with support and treatment of their SUD. Off-label LaLGPs are a potential alternative to traditional OPAT, but further studies to help determine effectiveness and standardized dosing regimens are needed.
- References:
- Ahiskali A, et al. BMC Pharmacol Toxicol. 2020;doi:10.1186/s40360-020-00452-z.
- Beieler AM, et al. Open Forum Infect Dis. 2021;doi:10.1093/ofid/ofab285.
- Bryson-Cahn C, et al. Open Forum Infect Dis. 2019;doi:10.1093/ofid/ofz028.
- Fleischauer AT, et al. MMWR Morb Mortal Wkly Rep. 2017;doi:10.15585/mmwr.mm6622a1.
- Jawa R, et al. J Addict Med. 2021;doi:10.1097/ADM.0000000000000856.
- Kadri AN, et al. J Am Heart Assoc. 2019;doi:10.1161/JAHA.119.012969.
- McCarthy NL, et al. Clin Infect Dis. 2020;doi:10.1093/cid/ciaa008.
- Morrisette T, et al. Open Forum Infect Dis. 2019;doi:10.1093/ofid/ofz274.
- Suzuki J, et al. Open Forum Infect Dis. 2018;doi:10.1093/ofid/ofy194.
- Thomas G, et al. Int J Antimicrob Agents. 2020;doi:10.1016/j.ijantimicag.2020.106069.
- Vazquez Deida AA, et al. Open Forum Infect Dis. 2020;doi:10.1093/ofid/ofaa293.
- For more information:
- Kelly M. Percival, PharmD, BCPS-AQ ID, is a clinical pharmacy specialist in infectious diseases at University of Iowa Hospitals & Clinics. Percival can be reached at kelly-percival@uiowa.edu.
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