Combine and Conquer: A Treatment Strategy to Combat Drug-Use Associated Infections - Infectious Disease Advisor
Treatment for substance use disorders (SUD) and infectious disease (ID) has traditionally been viewed as the individual responsibility of mental health professionals and ID physicians, respectively. However, the need for an integrated treatment approach has become clear as rates of infectious diseases related to injection drug use (IDU) continue to surge due to the ongoing opioid epidemic in the United States. Significant increases in HIV, hepatitis C virus (HCV), and various invasive bacterial and fungal infections have been attributed to this surge in IDU.1
Results of a recent study published in the Journal of Infectious Diseases observed increases in hospitalizations for drug-use associated infective endocarditis (DUA-IE; 33%), osteomyelitis (35%), sepsis (24%), and skin, soft tissue, and venous infections (12%) in Michigan between 2016 and 2018, with an associated cost of $1.3 billion.2
In a 2019 study published in the Annals of Internal Medicine, findings showed that the rate of hospitalizations and heart valve procedures related to DUA-IE increased more than 12-fold in North Carolina between 2007 and 2017. Patients with DUA-IE accounted for 42% of heart valve repairs performed during the final year of the study period. "The swell of patients with DUA-IE is reshaping the scope, type, and financing of healthcare resources needed to effectively treat IE," the researchers noted.3
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These findings and those of other recently published studies underscore the importance of a combined treatment approach for patients with opioid use disorder (OUD) who subsequently develop an IDU-related infection. Without addressing both simultaneously, the odds that infection treatment will be unsuccessful decrease, and the risk for recurrent infections and persistent substance use increase.
A meta-analysis published in 2021 in Open Forum Infectious Diseases examined 9 papers on infectious disease outcomes in adults with OUD who received medications to treat OUD (MOUD) compared with those who did not receive MOUD.4 Results showed that MOUD was associated with increased adherence to antiretroviral therapy (ART; odds ratio [OR], 1.55; 95% CI, 1.12-2.15) and an increased likelihood of achieving HIV virologic suppression (OR, 2.19; 95% CI, 1.88-2.56).
"Our results support the importance of integrating HIV and OUD treatment to increase the likelihood of achieving viral suppression" and add to the "existing compelling evidence that it is possible and encouraged to address the intersectionality of the opioid and HIV epidemics," the researchers concluded.4
A study published in 2020 in the Journal of Infectious Diseases compared various MOUD treatment strategies (methadone, buprenorphine, methadone taper for detoxification, and no MOUD) with ID treatment outcomes in 220 patients who were hospitalized for invasive bacterial or fungal infections associated with OUD.5 Findings demonstrated associations between all MOUD and an increased rate of parenteral antibiotic course completion (64.08% vs 46.15%; OR, 2.08; 95% CI, 1.23-3.61).
A multivariate analysis showed that maintenance of MOUD with either buprenorphine (OR, 0.38; 95% CI, 0.17-0.85) or methadone (OR, 0.43; 95% CI, 0.20-0.94), and continuation of MOUD following hospital discharge (OR, 0.35; 95% CI, 0.18-0.67), were associated with a decreased rate of 90-day hospital readmission. However, the use of methadone for detoxification followed by tapering without continuation on discharge was not associated with a decreased risk for readmission (OR, 1.87; 95% CI, 0.62-5.10).5
According to the researchers, "long-term MOUDs, regardless of selection, are an integral component of care in patients hospitalized with OUD-related infections."5 They noted that "patients with OUD should have arrangements made for MOUDs to be continued after discharge, and MOUDs should not be discontinued before discharge."
Findings from a study published by the same group of researchers in 2022 identified continued MOUD adherence as one of several methods to protect against the risk for hospital readmission (OR, 0.25; 95% CI, 0.09-0.69; P =.004) in persons who inject drugs (PWID) who requested patient-directed discharge while hospitalized with severe DUA infections.6
Additional strategies for protection against readmission included adherence to oral antibiotics provided on discharge (OR, 0.39; 95% CI, 0.15-0.96; P =.041) and ongoing consultation with a multidisciplinary support team (OR, 0.27; 95% CI, 0.10-0.72; P =.009).6
Research published in 2021 in the Annals of Medicine showed favorable results in patients hospitalized with OUD and severe injection-related infections who were treated by an integrated care team. The majority of patients included in the study continued MOUD following discharge, and 95% completed their antibiotic course. Postdischarge follow-up at 90 days showed that readmission rates were 25%, and 70% of patients reported MOUD adherence.7
In a retrospective cohort study published in 2020 in the American Journal of Medicine, results showed that the rate of discharge against medical advice was significantly decreased in patients with infectious complications of IDU who received MOUD compared with those who received supportive care alone (30.0% vs 59.6%). In addition, readmission rates were decreased among those who continued MOUD after discharge vs those who did not (30-day all-cause readmissions, 18.8% vs 35.1%).8
For an in-depth analysis in regard to the overlap between the opioid epidemic and the risk for ID, we interviewed the following experts:
Sandra Springer, MD, associate professor of medicine of ID at Yale University School of Medicine in New Haven, Connecticut, a board-certified physician in internal medicine, ID, and addiction medicine, and co-author of the 2021 meta-analysis4 described above; and Laura Marks, MD, PhD, instructor of medicine in the division of ID at the Washington University School of Medicine in St. Louis, Missouri, and lead author of the 2020 study5 comparing the effect of MOUD strategies with outcomes of treatment for OUD-related infections.
What do these data suggest overall about the importance of a combined treatment approach for ID and addiction?
Dr Springer: First, the reason we focused on this topic in our paper is that IDU, particularly with opioids —heroin and now mainly fentanyl — is leading to an increase in HIV [infection] and other ID epidemics, nationally. I also want to note that while opioids have been the predominant mode of overdose deaths in this country and are fueling new ID epidemics, stimulants are also causing an increase in overdose deaths and fueling these ID epidemics.
The reason we assessed the impact of MOUD (eg, buprenorphine, methadone, and extended-release naltrexone) on ID outcomes is that MOUD are the most effective treatments for OUD, and they reduce overdose deaths and have been shown to also have benefit in reducing poor ID outcomes. In this paper, we sought to evaluate published studies that evaluated the impact of specifically MOUD on improving ID outcomes that are associated with OUD.
Dr Marks: As ID physicians, we are used to thinking critically about the origin of an infection and addressing source control. Most of us would be horrified at the idea of treating a patient with a [central] line infection without discussing with their team if the line could be safely removed. My own work and a growing body of evidence by authors at institutions across the US and Canada have identified that addressing the underlying SUD is a critical component of ID care for persons with IDU-associated infections.
What do your recent findings add to our understanding of this topic?
Dr Springer: Our findings linked OUD to decreased rates of HIV virologic suppression and ART adherence among patients with HIV infection complicated by OUD. This is important, as the US has an Ending the HIV Epidemic (EHE) plan, and the primary goal of those with HIV is to achieve viral suppression.9 However, the EHE plan did not include plans to integrate OUD treatment with HIV treatment. Our study [results] show that integrated treatment for HIV and OUD can help achieve the EHE [plan] and increase rates of treatment as prevention to reduce new HIV infections.
The call for integrated care of infectious diseases and substance use disorders (SUDs), including OUD, is not new. In fact, the National Academy of Sciences Engineering and Medicine (NASEM) convened a special [committee] of experts to conduct a study conferred by the office of ID in the department of health and human services (DHHS) because of the increase in infections (ie, HIV) that were being identified as directly related to the opioid epidemic.
I was one of the members of that committee, and the results of this study were published in January 2020 on the NASEM website.10 [Our committee] also published an abbreviated report in JAMA in March 2020 to demonstrate the need and what we recommended.11
Dr Marks: We found that it is critical to consider what the postdischarge plans for ongoing [SUD] care will be. [The use of] MOUD is incredibly effective for patients with OUD. However, they are most effective when patients have ongoing access to them after discharge.
We identified that patients who had a plan in place for where they would continue to receive MOUD after discharge, such as an appointment at a methadone clinic or a bridge script for buprenorphine-naloxone along with an appointment with a provider who would be continuing that medication, did better than patients who had no plan in place for how MOUD would be continued after discharge.
We would never discharge a patient from the hospital who was newly diagnosed with HIV infection and [was well maintained] on ART and say, "staying on ART is important and I hope you find an HIV doctor soon," but not link them with a HIV clinic. We need to provide the same linkage to care efforts for patients with SUD as we would for patients with any other chronic disease. Our medical system is fragmented and challenging for patients to navigate under the best of circumstances, and a little bit of discharge planning for patients goes a long way in this population.
What are the potential reasons as to why this combined approach is not more common?
Dr Springer: As shown in our NASEM study, the top reason is stigma from healthcare providers (HCP) and organizations not wanting to treat SUDs. Other reasons include buprenorphine restrictions, lack of detailed plans, and lack of insurance coverage, as well as overlooking patients who cannot seek regular care (eg, due to lack of transportation and lack of insurance), structural racism, and housing instability. We need to think about how to bring services to people, including HIV prevention and treatment and OUD/SUD treatment to those who cannot access routine care.
Dr Marks: I think the largest reason is that many areas lack adequate resources. At our institution, we have been really lucky to have a dedicated addiction medicine consult service, as well as case managers and health coaches, who can help patients identify HCPs following hospital discharge. However, this is not the case at most institutions across the US.
What are recommendations for clinicians about how to better address these dual needs in practice?
Dr Springer: The best approach is to ask every patient about substance use and to be able to quickly screen and diagnose and rapidly initiate or refer [them] to treatment in any setting, but those of us who treat infections should include routine screening and treatment.
Dr Marks: If you are an ID physician in an area without addiction medicine physicians, get X-waivered.12 It is incredibly easy and will increase the number of tools you have to help patients with injection opioid-related infections.
Harm reduction is also something we should be routinely talking about with our patients. We would never feel comfortable caring for a younger patient with their first sexually transmitted infection without having an open discussion about safer sex practices, and we should apply this same lens to taking care of patients with IDU-related infections.
Not every patient is going to have abstinence as a goal, so make sure that you feel knowledgeable and comfortable describing best practices for patients to [decrease] the risk of developing another infection. Leah Harvey, MD, MPH, an infectious disease and addiction medicine fellow at Boston Medical Center, had a fantastic piece in Open Forum Infectious Diseases recently that went over 6 moments of infection prevention that ID physicians can use to counsel patients on safer injection practices.13
What are the most pressing needs in this area in terms of clinician education?
Dr Springer: We need more education of students as well as treating clinicians on the importance of SUD and how to treat OUD and other SUDs in clinical practice, including in hospitals as well as penal settings. We should encourage clinicians to not be afraid to treat these issues. We would never not treat diabetes or hypertension, for example, and OUD should not be any different. We should also think of how to integrate OUD and SUD treatment with prevention similar to that of HIV pre-exposure prophylaxis.
I recently coauthored an article in which the Infectious Diseases Society of America (IDSA) and the HIV Medicine Association subgroup requested federal and state policy changes to end these dueling epidemics.14 Drug overdoses continue to increase, with over 100,000 deaths reported in the US for the 12-month period ending in April 2021.15 There is no end in sight, and the drug crisis is fueling new HIV epidemics across the country, as well as increasing rates of HCV, IE, and other infections. We need all hands on deck to address these problems.
Disclosures: Dr Springer disclosed receipt of consultation honoraria, as well as in-kind drug donations for NIH-sponsored research, from Alkermes, Inc.
References
1. Levitt A, Mermin J, Jones CM, See I, Butler JC. Infectious diseases and injection drug use: Public health burden and response. J Infect Dis. 2020;222(Suppl 5):S213-S217. doi:10.1093/infdis/jiaa432. PMID: 32877539
2. Coyle JR, Freeland M, Eckel ST, Hart AL. Trends in morbidity, mortality, and cost of hospitalizations associated with infectious disease sequelae of the opioid epidemic. J Infect Dis. 2020;222(Suppl 5):S451-S457. doi:10.1093/infdis/jiaa012
3. Schranz AJ, Fleischauer A, Chu VH, Wu LT, Rosen DL. Trends in drug use-associated infective endocarditis and heart valve surgery, 2007 to 2017: A study of statewide discharge data. Ann Intern Med. 2019;170(1):31-40. doi:10.7326/M18-2124
4. McNamara KF, Biondi BE, Hernández-RamÃrez RU, Taweh N, Grimshaw AA, Springer SA. A systematic review and meta-analysis of studies evaluating the effect of medication treatment for opioid use disorder on infectious disease outcomes. Open Forum Infect Dis. 2021;8(8):ofab289. doi:10.1093/ofid/ofab289
5. Marks LR, Munigala S, Warren DK, et al. A comparison of medication for opioid use disorder treatment strategies for persons who inject drugs with invasive bacterial and fungal infections. J Infect Dis. 2020;222(Suppl 5):S513-S520. doi:10.1093/infdis/jiz516
6. Lewis S, Liang SY, Schwarz ES, et al. Patients with serious injection drug use-related infections who experience patient-directed discharges on oral antibiotics have high rates of antibiotic adherence but require multidisciplinary outpatient support for retention in care. Open Forum Infect Dis. 2022;9(2):ofab633. doi:10.1093/ofid/ofab633
7. Serota DP, Tookes HE, Hervera B, et al. Harm reduction for the treatment of patients with severe injection-related infections: description of the Jackson SIRI Team. Ann Med. 2021;53(1):1960-1968. doi:10.1080/07853890.2021.1993326
8. Wang SJ, Wade E, Towle J, et al. Effect of inpatient medication-assisted therapy on against-medical-advice discharge and readmission rates. Am J Med. 2020;133(11):1343-1349. doi:10.1016/j.amjmed.2020.04.025
9. Office of Infectious Disease and HIV/AIDS policy, HHS. What is Ending the HIV Epidemic in the US? Accessed online February 18, 2022.
10. National Academies of Sciences, Engineering, and Medicine. 2020. Opportunities to improve opioid use disorder and infectious disease services: Integrating responses to a dual epidemic. Washington, DC: The National Academies Press. doi:10.17226/25626
11. Springer SA, Merluzzi AP, Del Rio C. Integrating responses to the opioid use disorder and infectious disease epidemics: A report from the National Academies of Sciences, Engineering, and Medicine. JAMA. 2020;324(1):37-38. doi:10.1001/jama.2020.2559
12. Substance Abuse and Mental Health Services Administration. Become a buprenorphine waivered practitioner. Updated January 3, 2022. Accessed online February 18, 2022.
13. Harvey L, Boudreau J, Sliwinski SK, et al. Six moments of infection prevention in injection drug use: An educational toolkit for clinicians. Open Forum Infect Dis. 2022;9(2):ofab631. doi:10.1093/ofid/ofab631
14. Centers for Disease Control and Prevention. Drug overdose deaths in the U.S. top 100,000 annually. November 17, 2021. Accessed online February 18, 2022.
15. Springer SA, Barocas JA, Wurcel A, et al. Federal and state action needed to end the infectious complications of illicit drug use in the United States: IDSA and HIVMA's advocacy agenda. J Infect Dis. 2020;222(Suppl 5):S230-S238. doi:10.1093/infdis/jiz673
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