Approach Considerations
Challenges of diagnosing and managing of opioid use disorder infective endocarditis (OUD-IE) in the age of COVID-19 are immense. There has been a movement toward establishing multidisciplinary endocarditis teams to better coordinate care and post-hospitalization follow-up. [22, 26] The European Society of Cardiology has published guidelines for multidisciplinary endocarditis teams, which have lowered mortality rates. [26] In the United States, two teams (at the University of Michigan and The Massachusetts General Hospital) have lowered in-hospital mortality by expediting consults and post-hospitalization adverse events by engaging addiction medicine services and early initiation of medications for OUDs. [26, 27] Furthermore, with a multidisciplinary endocarditis team in place, consults and work-up are streamlined owing to established protocols that can improve diagnostic capabilities. Successful IE management requires collaboration among specialties not limited to infectious disease, cardiology, cardiac surgery, neurology, neurosurgery, and addiction medicine providers.
Medical Care
Empiric antibiotic treatment for OUD-IE should cover for methicillin-resistant S aureus (MRSA), methicillin-sensitive S aureus (MSSA), and streptococcal species. Two important points of therapeutic considerations are that vancomycin should no longer be considered empiric treatment and that ampicillin and cefotaxime should be the preferred treatment for E faecalis.
Prolonged use of empiric antibiotics due to decreased diagnostic certainty has risen in the COVID-19 era and led to heightened concern regarding antimicrobial resistance. [28] Excessive IV antibiotic use during COVID-19 has led to shifts in multi-drug resistant organisms (MDROs), especially against coagulase-negative S aureus species (CoNS). [19] This has had a particular effect on cephalosporins and fluoroquinolones. [29]
A 4- to 6-week course of IV antibiotics is recommended for OUD-IE. The need for long-term hospitalizations for therapy and disease severity can unnecessarily increase the risk for nosocomial infections. [23, 28, 30, 31, 32, 33, 34] A single-center retrospective study at a tertiary center identified a rise in MDROs and positive blood cultures on admission for hospitalized patients with COVID-19 at 8.6% compared with 2.5% to 2.9% previously. [35, 36] A newer glycopeptide, dalbavancin, permits weekly IV antibiotic therapy outside of healthcare facilities for off-label treatment of OUD-IE, which may be beneficial in the COVID-19 era. [35, 36] If the patient is clinically improving, repeat one to two blood cultures daily for 5 days to ensure clearance of bacteremia. If clearance does not occur, a complete reassessment is required. A steady downward trending CRP indicates improvement in the inflammatory processes of either or both the COVID-19 and OUD-IE to guide the antibiotic course. Hospitalized patients with OUD-IE should be followed by a multidisciplinary team on a regular basis.
The role of antibiotics has not yet been established in the treatment of OUD-IE. In 2019, the “POET” trial compared a partial oral antibiotic regimen with a full course of IV antibiotic treatment for endocarditis showing non-inferiority between the two treatment arms for left sided IE. [11, 37] A newer study revealed limited evidence in the efficacy of oral antibiotics due to issues with 7% documented failure, 23% lost to follow-up, and 67% with presumed success. [38] This study does not support the use of oral antibiotics in treating OUD-IE because only 67% of patients were proven to respond to oral therapy. On the basis of current evidence, switching over to oral therapy should be avoided.
See Infective Endocarditis for details on antibiotic therapy.
Surgical Care
Insertion of any prosthetic material among patients with OUD should be avoided as it may lead to increased rates of cardiac or recurrent valvular infection. Right-sided IE accounts for 5% to 10% of all IE cases though it is no longer pathognomonic for OUD-IE. [39] If a tricuspid valve OUD-IE does not respond adequately to antibiotic therapy, it would be preferable to remove the vegetation and repair the valve instead of inserting a prosthetic valve. Repair may lead to development of a pulsatile liver due to tricuspid regurgitation. Most patients tolerate these conditions. For the same reasons, valve repair is preferred among OUDs who are prone to relapse or continue to use drugs. [39, 40] Avoid implants if at all possible among OUDs because of injection drug use relapse (eg, pacemakers, cardiac defibrillators, transcatheter aortic valve replacement). This is where a multidisciplinary team approach would be helpful in formulating appropriate plans for patients and risk stratifying based on risk for relapse in high risk patients. An example would be the involvement of the infectious disease team to determine if a patient might benefit from complete valve removal as opposed to valve replacement in a high risk patient where hardware might be promote recurrent IE. [41, 42]
Complications
Choosing to anti-coagulate patients with a coinfection of COVID-19 and OUD-IE is a difficult decision and is best handled via a multidisciplinary team approach. Although both harbor prothrombotic properties, as described above, the risks versus benefits for intracranial bleeding due to previously unidentified cerebral lesions is not trivial. Among patients with IE, 8% develop hemorrhagic lesions whereas 60% develop single or multiple microbleeds. [1, 42]
Personalized Therapy
Garcia -Vidal et al published a report describing their experience employing "personalized therapy" of 75 hospitalized patients with COVID-19 infection. [7] Specific therapy was based on the immune markers presented in Table 1. At the 14th day of treatment, the mortality rate of the study group was 20% as compared with 43.6% for those receiving usual care. At the 28th day of treatment, the mortality rates were 20% and 44.2%, respectively. None of the personalized patients had evidence of OUD-IE; however, this study is notable in providing a framework on which to base initial therapeutic approaches.
Prognosis
The outlook of OUD-IE with concurrent COVID-19 infection is quite variable. Timely identification of the active disease process and institution of appropriate treatment is the most beneficial approach. The overlapping clinical symptomatology of both conditions has led to marked delays in providing appropriate treatment. In addition, infrastructural disarray during the COVID-19 pandemic resulted in delays to the delivery of healthcare (eg, limited follow-up appointments), exacerbated safety nets in place for mental health support, and decreased community-sponsored support groups (eg, food pantries, shelter space).
Patient Education
Patient education, especially for those suffering from OUD-IE, should focus on key warning signs of OUD-IE with and without concurrent COVID-19 infection. Such signs include persistent fever, worsening fatigue, and signs of congestive failure such as leg swelling and dyspnea. Patients should be told to avoid taking “street antibiotics” because this will usually delay arriving at the correct diagnosis and treatment. Of course, the COVID-19 vaccine should be made easily available in trying to establish or re-establish psychiatric or psychological housing in addition to other community programs.
Tables
Major Pathological Mechanisms |
Definitions |
Targeted Pathogenic Pathway |
Onset of Symptoms (Days) |
Coinfection |
Bacterial, fungal, viral co-infection |
Interaction of viral specific proteins with host receptors leading to endothelial activation and dysfunction [7] | 6-12 |
Inflammatory |
Endothelitis due to platelet activation [7] | ||
|
↑ CRP ↓ ferritin |
IL-6 |
8-13 |
|
↑ CRP ↑ ferritin |
IL-1, IL-6 |
10-13 |
|
↓ CRP ↑ ferritin |
IL- 1 |
11-16 |
Thrombotic |
DVT, PE |
Hypercoagulable state induced by COVID-19 infection [7] | 10-18 |
Differential Diagnoses of OUD-IE during the COVID-19 Pandemic |
|
