Article

Early in the COVID-19 pandemic, monoclonal antibody (Mab) therapy was the only outpatient therapy for patients with COVID-19 experiencing mild-to-moderate symptoms. The Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) and the REGN-COV2 (Regeneron) clinical trials found participants treated with Mab had a shorter duration of symptoms and fewer hospitalizations compared with those receiving placebo.^1,2 Mab therapy was most efficacious early in the disease course, and the initial US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) of Mab therapies required use within 10 days of symptom onset.³

The impact of the COVID-19 pandemic has been felt disproportionately among marginalized racial and ethnic groups in the US. The COVID-19 Associated Hospitalization Surveillance Network found that non-Hispanic Black persons have significantly higher rates of hospitalization and death by COVID-19 compared with White persons.^4-7 However, marginalized groups are underrepresented in the receipt of therapeutic agents for COVID-19. From March 2020 through August 2021, the mean monthly Mab use among Black patients (2.8%) was lower compared with White patients (4.0%), and Black patients received Mab 22.4% less often than White patients.⁷

The Mab clinical trials BLAZE-1 and REGN-COV2 study populations consisted of > 80% White participants.^1,2 Receipt of COVID-19 outpatient treatments may not align with the disease burden in marginalized racial and ethnic groups, leading to health disparities. Although not exhaustive, reasons for these disparities include patient, health care practitioner, and systems-level issues: patient awareness, trust, and engagement with the health care system; health care practitioner awareness and advocacy to pursue COVID-19 treatment for the patient; and health care capacity to provide the medication and service.⁷

Here, we describe a novel, quality improvement initiative at the Atlanta Veterans Affairs Health Care System (AVAHCS) in Georgia that paired a proactive laboratory-based surveillance strategy to identify and engage veterans for Mab. By centralizing the surveillance and outreach process, we sought to reduce barriers to the Mab referral process and optimize access to life-saving medication.

Implementation

AVAHCS serves a diverse population of more than 129,000 (50.8% non-Hispanic Black veterans, 37.5% White veterans, and 11.7% of other races) at a main medical campus and 18 surrounding community-based outpatient clinics. From December 28, 2020, to August 31, 2021, veterans with a positive COVID-19 nasopharyngeal polymerase chain reaction (PCR) test at AVAHCS were screened daily. A central Mab team consisting of infectious disease (ID) clinical pharmacists and physicians reviewed daily lists of positive laboratory results and identified high-risk individuals for Mab eligibility, using the FDA EUA inclusion criteria. Eligible patients were called by a Mab team member to discuss Mab treatment, provide anticipatory guidance, obtain verbal consent, and schedule the infusion. Conventional referrals from non-Mab team members (eg, primary care physicians) were also accepted into the screening process and underwent the same procedures and risk prioritization strategy as those identified by the Mab team.

Clinic resources allowed for 1 to 2 patients per day to be given Mab, increasing to a maximum of 5 patients per day during the COVID-19 Delta variant surge. We followed our best clinical judgment in prioritizing patient selection, and we aligned our practice with the standards of our affiliated partner, Emory University. In circumstances where patients who were Mab-eligible outnumbered infusion availability, patients were prioritized using the Veterans Health Administration (VHA) COVID-19 (VACO) Index for 30-day COVID-19 mortality.⁸ As COVID-19 variants developed resistance to the recommended Mab infusions, bamlanivimab, bamlanivimab-etesevimab, or casirivimab-imdevimab, local protocols adapted to EUA revisions. The Mab team also adopted FDA eligibility criteria revisions as they were available.^9,10

We describe the outcomes of our centralized screening process for Mab therapy, as measured by screening, uptake, and time to receipt of Mab from screening. We also describe the demographic and clinical characteristics of Mab recipients. Clinical outcomes include postinfusion adverse events (AEs) at day 1 and day 7, emergency department (ED) visits, inpatient hospitalization, and death.

Results

The Mab team screened 2028 veterans who were COVID-19 positive between December 28, 2020, and August 31, 2021, and identified 289 veterans (14%) who met the EUA criteria. One hundred thirty-two veterans (46%) completed Mab infusion, and of the remaining 145 veterans, 124 (86%) declined treatment, and 21 (14%) veterans did not complete Mab infusion largely due to not keeping the appointment. The Mab team active surveillance strategy identified 101 of 132 infusion candidates (77%); 82% had outpatient Mab infusion.

The mean age of veterans who received Mab was 55 years (range, 29-90), and 75% of veterans were aged ≥ 65 years; most were male (84%) and 86 (65%) identified as non-Hispanic Black individuals (Table 1).

Discussion

This novel initiative to optimize access to outpatient COVID-19 treatment demonstrated how the Mab team proactively screened and reached out to eligible veterans with COVID-19 promptly. This approach removed layers in the traditional referral process that could be barriers to accessing care. More than three-quarters of patients who received Mab were identified through this strategy, and the uptake was high at 46%. Conventional passive referrals were suboptimal for identifying candidates, which was also the case at a neighboring institution.

In an Emory University study, referrals to the Mab clinic were made through a traditional, decentralized referral system and resulted in a lower uptake of Mab treatment (4.6%).¹¹ One of the key advantages of the AVAHCS program was that we were able to provide individual education about COVID-19 and counsel on the benefits and risks of therapy. Having a structured, telehealth follow-up plan provided additional reassurance and support to the patient. These personalized patient connections likely helped increase acceptance of the Mab therapy.

Our surveillance and outreach strategy had high uptake among Black patients (65%), which exceeded the proportion of AVAHCS Black veterans (54%).¹² In the Emory study, just 30% of the participants were Black patients.¹¹ In a study of bamlanivimab use in Chicago, Black individuals represented just 11% of the study population. White patients were more likely to receive bamlanivimab compared with others races, and the likelihood of receiving bamlanivimab was significantly worse for Black patients (odds ratio, 0.28) compared with White patients.¹³ These studies highlight the disparity in COVID-19 outpatient treatment that does not reflect the racial and minority group representation of the community at large.

Limitations

The VHA medication allocation system at times created a significant mismatch in supply and demand, which significantly limited the AVAHCS Mab program. VHA facilities nationwide with Mab programs received discrete allocations through the US Department of Health and Human Services via VHA pharmacy benefits management services. Despite our large catchment, AVAHCS was allocated 6 or fewer doses of Mab per week during the evaluated period.

Without formal national guidance in the early period of Mab, the AVAHCS Mab team conferred with Emory University Mab clinicians as well as at other VHA facilities in the country to develop an optimal approach to resource allocation. The Mab team considered all EUA criteria to be as inclusive as possible. However, during times of high demand, our utilitarian approach tried to identify the highest-risk patients who would benefit the most from Mab. The VACO index was validated in early 2021, which facilitated decision making when demand was greater than supply. One limitation of the VACO index is its exclusion of several original Mab EUA criteria, including weight, hypertension, and nonmalignancy-related immunosuppression, into its algorithm.^3,8

Conclusions

Through proactive screening and direct outreach to patients, the AVAHCS was able to achieve timely administration of Mab infusion that was well within the initial EUA time frame of 10 days and comparable with the time frame in the REGN-COV2 and BLAZE-1 trials. Improving access to resources by changing the referral structure helped engage veterans who may have otherwise missed the time frame for Mab therapy. The experience of the Mab infusion program at the AVAHCS provided valuable insight into how a health care system could effectively screen a large population and distribute the limited resource of Mab therapy in a timely and proportionate fashion among its represented demographic groups.

Acknowledgments

The authors acknowledge the Veterans Health Administration VISN 7 Clinical Resource Hub and Tele Primary Care group for their support.

Early in the COVID-19 pandemic, monoclonal antibody (Mab) therapy was the only outpatient therapy for patients with COVID-19 experiencing mild-to-moderate symptoms. The Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) and the REGN-COV2 (Regeneron) clinical trials found participants treated with Mab had a shorter duration of symptoms and fewer hospitalizations compared with those receiving placebo.^1,2 Mab therapy was most efficacious early in the disease course, and the initial US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) of Mab therapies required use within 10 days of symptom onset.³

The impact of the COVID-19 pandemic has been felt disproportionately among marginalized racial and ethnic groups in the US. The COVID-19 Associated Hospitalization Surveillance Network found that non-Hispanic Black persons have significantly higher rates of hospitalization and death by COVID-19 compared with White persons.^4-7 However, marginalized groups are underrepresented in the receipt of therapeutic agents for COVID-19. From March 2020 through August 2021, the mean monthly Mab use among Black patients (2.8%) was lower compared with White patients (4.0%), and Black patients received Mab 22.4% less often than White patients.⁷

The Mab clinical trials BLAZE-1 and REGN-COV2 study populations consisted of > 80% White participants.^1,2 Receipt of COVID-19 outpatient treatments may not align with the disease burden in marginalized racial and ethnic groups, leading to health disparities. Although not exhaustive, reasons for these disparities include patient, health care practitioner, and systems-level issues: patient awareness, trust, and engagement with the health care system; health care practitioner awareness and advocacy to pursue COVID-19 treatment for the patient; and health care capacity to provide the medication and service.⁷

Here, we describe a novel, quality improvement initiative at the Atlanta Veterans Affairs Health Care System (AVAHCS) in Georgia that paired a proactive laboratory-based surveillance strategy to identify and engage veterans for Mab. By centralizing the surveillance and outreach process, we sought to reduce barriers to the Mab referral process and optimize access to life-saving medication.

Implementation

AVAHCS serves a diverse population of more than 129,000 (50.8% non-Hispanic Black veterans, 37.5% White veterans, and 11.7% of other races) at a main medical campus and 18 surrounding community-based outpatient clinics. From December 28, 2020, to August 31, 2021, veterans with a positive COVID-19 nasopharyngeal polymerase chain reaction (PCR) test at AVAHCS were screened daily. A central Mab team consisting of infectious disease (ID) clinical pharmacists and physicians reviewed daily lists of positive laboratory results and identified high-risk individuals for Mab eligibility, using the FDA EUA inclusion criteria. Eligible patients were called by a Mab team member to discuss Mab treatment, provide anticipatory guidance, obtain verbal consent, and schedule the infusion. Conventional referrals from non-Mab team members (eg, primary care physicians) were also accepted into the screening process and underwent the same procedures and risk prioritization strategy as those identified by the Mab team.

Clinic resources allowed for 1 to 2 patients per day to be given Mab, increasing to a maximum of 5 patients per day during the COVID-19 Delta variant surge. We followed our best clinical judgment in prioritizing patient selection, and we aligned our practice with the standards of our affiliated partner, Emory University. In circumstances where patients who were Mab-eligible outnumbered infusion availability, patients were prioritized using the Veterans Health Administration (VHA) COVID-19 (VACO) Index for 30-day COVID-19 mortality.⁸ As COVID-19 variants developed resistance to the recommended Mab infusions, bamlanivimab, bamlanivimab-etesevimab, or casirivimab-imdevimab, local protocols adapted to EUA revisions. The Mab team also adopted FDA eligibility criteria revisions as they were available.^9,10

We describe the outcomes of our centralized screening process for Mab therapy, as measured by screening, uptake, and time to receipt of Mab from screening. We also describe the demographic and clinical characteristics of Mab recipients. Clinical outcomes include postinfusion adverse events (AEs) at day 1 and day 7, emergency department (ED) visits, inpatient hospitalization, and death.

Results

The Mab team screened 2028 veterans who were COVID-19 positive between December 28, 2020, and August 31, 2021, and identified 289 veterans (14%) who met the EUA criteria. One hundred thirty-two veterans (46%) completed Mab infusion, and of the remaining 145 veterans, 124 (86%) declined treatment, and 21 (14%) veterans did not complete Mab infusion largely due to not keeping the appointment. The Mab team active surveillance strategy identified 101 of 132 infusion candidates (77%); 82% had outpatient Mab infusion.

The mean age of veterans who received Mab was 55 years (range, 29-90), and 75% of veterans were aged ≥ 65 years; most were male (84%) and 86 (65%) identified as non-Hispanic Black individuals (Table 1).

Discussion

This novel initiative to optimize access to outpatient COVID-19 treatment demonstrated how the Mab team proactively screened and reached out to eligible veterans with COVID-19 promptly. This approach removed layers in the traditional referral process that could be barriers to accessing care. More than three-quarters of patients who received Mab were identified through this strategy, and the uptake was high at 46%. Conventional passive referrals were suboptimal for identifying candidates, which was also the case at a neighboring institution.

In an Emory University study, referrals to the Mab clinic were made through a traditional, decentralized referral system and resulted in a lower uptake of Mab treatment (4.6%).¹¹ One of the key advantages of the AVAHCS program was that we were able to provide individual education about COVID-19 and counsel on the benefits and risks of therapy. Having a structured, telehealth follow-up plan provided additional reassurance and support to the patient. These personalized patient connections likely helped increase acceptance of the Mab therapy.

Our surveillance and outreach strategy had high uptake among Black patients (65%), which exceeded the proportion of AVAHCS Black veterans (54%).¹² In the Emory study, just 30% of the participants were Black patients.¹¹ In a study of bamlanivimab use in Chicago, Black individuals represented just 11% of the study population. White patients were more likely to receive bamlanivimab compared with others races, and the likelihood of receiving bamlanivimab was significantly worse for Black patients (odds ratio, 0.28) compared with White patients.¹³ These studies highlight the disparity in COVID-19 outpatient treatment that does not reflect the racial and minority group representation of the community at large.

Limitations

The VHA medication allocation system at times created a significant mismatch in supply and demand, which significantly limited the AVAHCS Mab program. VHA facilities nationwide with Mab programs received discrete allocations through the US Department of Health and Human Services via VHA pharmacy benefits management services. Despite our large catchment, AVAHCS was allocated 6 or fewer doses of Mab per week during the evaluated period.

Without formal national guidance in the early period of Mab, the AVAHCS Mab team conferred with Emory University Mab clinicians as well as at other VHA facilities in the country to develop an optimal approach to resource allocation. The Mab team considered all EUA criteria to be as inclusive as possible. However, during times of high demand, our utilitarian approach tried to identify the highest-risk patients who would benefit the most from Mab. The VACO index was validated in early 2021, which facilitated decision making when demand was greater than supply. One limitation of the VACO index is its exclusion of several original Mab EUA criteria, including weight, hypertension, and nonmalignancy-related immunosuppression, into its algorithm.^3,8

Conclusions

Through proactive screening and direct outreach to patients, the AVAHCS was able to achieve timely administration of Mab infusion that was well within the initial EUA time frame of 10 days and comparable with the time frame in the REGN-COV2 and BLAZE-1 trials. Improving access to resources by changing the referral structure helped engage veterans who may have otherwise missed the time frame for Mab therapy. The experience of the Mab infusion program at the AVAHCS provided valuable insight into how a health care system could effectively screen a large population and distribute the limited resource of Mab therapy in a timely and proportionate fashion among its represented demographic groups.

Acknowledgments

The authors acknowledge the Veterans Health Administration VISN 7 Clinical Resource Hub and Tele Primary Care group for their support.

Early in the COVID-19 pandemic, monoclonal antibody (Mab) therapy was the only outpatient therapy for patients with COVID-19 experiencing mild-to-moderate symptoms. The Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) and the REGN-COV2 (Regeneron) clinical trials found participants treated with Mab had a shorter duration of symptoms and fewer hospitalizations compared with those receiving placebo.^1,2 Mab therapy was most efficacious early in the disease course, and the initial US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) of Mab therapies required use within 10 days of symptom onset.³

The impact of the COVID-19 pandemic has been felt disproportionately among marginalized racial and ethnic groups in the US. The COVID-19 Associated Hospitalization Surveillance Network found that non-Hispanic Black persons have significantly higher rates of hospitalization and death by COVID-19 compared with White persons.^4-7 However, marginalized groups are underrepresented in the receipt of therapeutic agents for COVID-19. From March 2020 through August 2021, the mean monthly Mab use among Black patients (2.8%) was lower compared with White patients (4.0%), and Black patients received Mab 22.4% less often than White patients.⁷

The Mab clinical trials BLAZE-1 and REGN-COV2 study populations consisted of > 80% White participants.^1,2 Receipt of COVID-19 outpatient treatments may not align with the disease burden in marginalized racial and ethnic groups, leading to health disparities. Although not exhaustive, reasons for these disparities include patient, health care practitioner, and systems-level issues: patient awareness, trust, and engagement with the health care system; health care practitioner awareness and advocacy to pursue COVID-19 treatment for the patient; and health care capacity to provide the medication and service.⁷

Here, we describe a novel, quality improvement initiative at the Atlanta Veterans Affairs Health Care System (AVAHCS) in Georgia that paired a proactive laboratory-based surveillance strategy to identify and engage veterans for Mab. By centralizing the surveillance and outreach process, we sought to reduce barriers to the Mab referral process and optimize access to life-saving medication.

Implementation

AVAHCS serves a diverse population of more than 129,000 (50.8% non-Hispanic Black veterans, 37.5% White veterans, and 11.7% of other races) at a main medical campus and 18 surrounding community-based outpatient clinics. From December 28, 2020, to August 31, 2021, veterans with a positive COVID-19 nasopharyngeal polymerase chain reaction (PCR) test at AVAHCS were screened daily. A central Mab team consisting of infectious disease (ID) clinical pharmacists and physicians reviewed daily lists of positive laboratory results and identified high-risk individuals for Mab eligibility, using the FDA EUA inclusion criteria. Eligible patients were called by a Mab team member to discuss Mab treatment, provide anticipatory guidance, obtain verbal consent, and schedule the infusion. Conventional referrals from non-Mab team members (eg, primary care physicians) were also accepted into the screening process and underwent the same procedures and risk prioritization strategy as those identified by the Mab team.

Clinic resources allowed for 1 to 2 patients per day to be given Mab, increasing to a maximum of 5 patients per day during the COVID-19 Delta variant surge. We followed our best clinical judgment in prioritizing patient selection, and we aligned our practice with the standards of our affiliated partner, Emory University. In circumstances where patients who were Mab-eligible outnumbered infusion availability, patients were prioritized using the Veterans Health Administration (VHA) COVID-19 (VACO) Index for 30-day COVID-19 mortality.⁸ As COVID-19 variants developed resistance to the recommended Mab infusions, bamlanivimab, bamlanivimab-etesevimab, or casirivimab-imdevimab, local protocols adapted to EUA revisions. The Mab team also adopted FDA eligibility criteria revisions as they were available.^9,10

We describe the outcomes of our centralized screening process for Mab therapy, as measured by screening, uptake, and time to receipt of Mab from screening. We also describe the demographic and clinical characteristics of Mab recipients. Clinical outcomes include postinfusion adverse events (AEs) at day 1 and day 7, emergency department (ED) visits, inpatient hospitalization, and death.

Results

The Mab team screened 2028 veterans who were COVID-19 positive between December 28, 2020, and August 31, 2021, and identified 289 veterans (14%) who met the EUA criteria. One hundred thirty-two veterans (46%) completed Mab infusion, and of the remaining 145 veterans, 124 (86%) declined treatment, and 21 (14%) veterans did not complete Mab infusion largely due to not keeping the appointment. The Mab team active surveillance strategy identified 101 of 132 infusion candidates (77%); 82% had outpatient Mab infusion.

The mean age of veterans who received Mab was 55 years (range, 29-90), and 75% of veterans were aged ≥ 65 years; most were male (84%) and 86 (65%) identified as non-Hispanic Black individuals (Table 1).

Discussion

This novel initiative to optimize access to outpatient COVID-19 treatment demonstrated how the Mab team proactively screened and reached out to eligible veterans with COVID-19 promptly. This approach removed layers in the traditional referral process that could be barriers to accessing care. More than three-quarters of patients who received Mab were identified through this strategy, and the uptake was high at 46%. Conventional passive referrals were suboptimal for identifying candidates, which was also the case at a neighboring institution.

In an Emory University study, referrals to the Mab clinic were made through a traditional, decentralized referral system and resulted in a lower uptake of Mab treatment (4.6%).¹¹ One of the key advantages of the AVAHCS program was that we were able to provide individual education about COVID-19 and counsel on the benefits and risks of therapy. Having a structured, telehealth follow-up plan provided additional reassurance and support to the patient. These personalized patient connections likely helped increase acceptance of the Mab therapy.

Our surveillance and outreach strategy had high uptake among Black patients (65%), which exceeded the proportion of AVAHCS Black veterans (54%).¹² In the Emory study, just 30% of the participants were Black patients.¹¹ In a study of bamlanivimab use in Chicago, Black individuals represented just 11% of the study population. White patients were more likely to receive bamlanivimab compared with others races, and the likelihood of receiving bamlanivimab was significantly worse for Black patients (odds ratio, 0.28) compared with White patients.¹³ These studies highlight the disparity in COVID-19 outpatient treatment that does not reflect the racial and minority group representation of the community at large.

Limitations

The VHA medication allocation system at times created a significant mismatch in supply and demand, which significantly limited the AVAHCS Mab program. VHA facilities nationwide with Mab programs received discrete allocations through the US Department of Health and Human Services via VHA pharmacy benefits management services. Despite our large catchment, AVAHCS was allocated 6 or fewer doses of Mab per week during the evaluated period.

Without formal national guidance in the early period of Mab, the AVAHCS Mab team conferred with Emory University Mab clinicians as well as at other VHA facilities in the country to develop an optimal approach to resource allocation. The Mab team considered all EUA criteria to be as inclusive as possible. However, during times of high demand, our utilitarian approach tried to identify the highest-risk patients who would benefit the most from Mab. The VACO index was validated in early 2021, which facilitated decision making when demand was greater than supply. One limitation of the VACO index is its exclusion of several original Mab EUA criteria, including weight, hypertension, and nonmalignancy-related immunosuppression, into its algorithm.^3,8

Conclusions

Through proactive screening and direct outreach to patients, the AVAHCS was able to achieve timely administration of Mab infusion that was well within the initial EUA time frame of 10 days and comparable with the time frame in the REGN-COV2 and BLAZE-1 trials. Improving access to resources by changing the referral structure helped engage veterans who may have otherwise missed the time frame for Mab therapy. The experience of the Mab infusion program at the AVAHCS provided valuable insight into how a health care system could effectively screen a large population and distribute the limited resource of Mab therapy in a timely and proportionate fashion among its represented demographic groups.

Acknowledgments

The authors acknowledge the Veterans Health Administration VISN 7 Clinical Resource Hub and Tele Primary Care group for their support.

Orthopedic implants are frequently used to repair fractures and replace joints. The number of total joint replacements is high, with > 1 million total hip (THA) and total knee (TKA) arthroplasties performed in the United States each year.¹ While most joint arthroplasties are successful and significantly improve patient quality of life, a small proportion become infected.² Prosthetic joint infection (PJI) causes substantial morbidity and mortality, particularly among older patients, and is difficult and costly to treat.³

The historic gold standard treatment for PJI is a 2-stage replacement, wherein the prosthesis is removed in one procedure and a new prosthesis is implanted in a second procedure after an extended course of antibiotics. This approach requires the patient to undergo 2 major procedures and spend considerable time without a functioning prosthesis, contributing to immobility and deconditioning. This option is difficult for frail or older patients and is associated with high medical costs.⁴

In 1998, a novel method of treatment known as debridement, antibiotics, and implant retention (DAIR) was evaluated in a small, randomized controlled trial.⁵ This study used a unique antimicrobial approach: the administration of ciprofloxacin plus either rifampin or placebo for 3 to 6 months, combined with a single surgical debridement. Eliminating a second surgical procedure and largely relying on oral antimicrobials reduces surgical risks and decreases costs.⁴ Current guidelines endorse DAIR with rifampin and a second antibiotic for patients diagnosed with PJI within about 30 days of prosthesis implantation who have a well-fixed implant without evidence of a sinus tract.⁶ Clinical trial data demonstrate that this approach is > 90% effective in patients with a well-fixed prosthesis and acute staphylococcal PJI.^3,7

Thus far, clinical trials examining this approach have been small and did not include veterans who are typically older and have more comorbidities.⁸ The Minneapolis Veterans Affairs Health Care System (MVAHCS) infectious disease section has implemented the rifampin-based DAIR approach for orthopedic device-related infections since this approach was first described in 1998 but has not systematically evaluated its effectiveness or whether there are areas for improvement.

METHODS

We conducted a retrospective analysis of patients who underwent DAIR combined with a rifampin-containing regimen at the MVAHCS from January 1, 2001, through June 30, 2021. Inclusion required a diagnosis of orthopedic device-related infection and treatment with DAIR followed by antimicrobial therapy that included rifampin for 1 to 6 months. PJI was defined by meeting ≥ 1 of the following criteria: (1) isolation of the same microorganism from ≥ 2 cultures from joint aspirates or intraoperative tissue specimens; (2) purulence surrounding the prosthesis at the time of surgery; (3) acute inflammation consistent with infection on histopathological examination or periprosthetic tissue; or (4) presence of a sinus tract communicating with the prosthesis.

All cases of orthopedic device infection managed with DAIR and rifampin were included, regardless of implant stability, age of the implant at the time of symptom onset, presence of a sinus tract, or infecting microorganism. Exclusion criteria included patients who started or finished PJI treatment at another facility, were lost to follow-up, discontinued rifampin, died within 1 year of completing antibiotic therapy due to reasons unrelated to treatment failure, received rifampin for < 50% of their antimicrobial treatment course, had complete hardware removal, or had < 1 year between the completion of antimicrobial therapy and the time of data collection.

Management of DAIR procedures at the MVAHCS involves evaluating the fixation of the prosthesis, tissue sampling for microbiological analysis, and thorough debridement of infected tissue. Following debridement, a course of IV antibiotics is administered before initiating oral antibiotic therapy. To protect against resistance, rifampin is combined with another antibiotic typically from the fluoroquinolone, tetracycline, or cephalosporin class. Current guidelines suggest 3 and 6 months of oral antibiotics for prosthetic hip and knee infections, respectively.⁶

Treatment Outcomes

The primary outcome was treatment success, defined as meeting all of the following: (1) lack of clinical signs and symptoms of infection; (2) absence of radiological signs of loosening or infection within 1 year after the conclusion of treatment; and (3) absence of additional PJI treatment interventions for the prosthesis of concern within 1 year after completing the original antibiotic treatment.

Treatment failure was defined as meeting any of the following: (1) recurrence of PJI (original strain or different microorganism) within 1 year after the completion of antibiotic therapy; (2) death attributed to PJI anytime after the initial debridement; (3) removal of the prosthetic joint within 1 year after the completion of antibiotic therapy; or (4) long-term antibiotic use to suppress the PJI after the completion of the initial antibiotic therapy.

Statistical Analysis

Descriptive statistics were used to define the baseline characteristics of patients receiving rifampin therapy for orthopedic implant infections at the MVAHCS. Variables analyzed were age, sex, race and ethnicity, type of implant, age of implant, duration of symptoms, comorbidities (diabetes and rheumatoid arthritis), and presence of chronic infection. Patients were classified as having a chronic infection if they received previous infection treatment (antibiotics or surgery) for the orthopedic device in question. We created this category because patients with persistent infection after a medical or surgical attempt at treatment are likely to have a higher probability of treatment failure compared with those with no prior therapy. Charlson Comorbidity Index was calculated using clinical information present at the onset of infection.⁹ Fisher exact test was used to assess differences between categorical variables, and an independent t test was used to assess differences in continuous variables. P < .05 indicated statistical significance.

To assess the ability of a rifampin-based regimen to achieve a cure of PJI, we grouped participants into 2 categories: those with an intent to cure strategy and those without intent to cure based on documentation in the electronic health record (EHR). Participants who were prescribed rifampin with the documented goal of prosthesis retention with no further suppressive antibiotics were included in the intent-to-cure group, the primary focus of this study. Those excluded from the intent-to-cure group were given rifampin and another antibiotic, but there was a documented plan of either ongoing chronic suppression or eventual explantation; these participants were placed in the without-intent-to-cure group. Analysis of treatment success and failure was limited to the intent-to-cure group, whereas both groups were included for assessment of adverse effects (AEs) and treatment duration. This project was reviewed by the MVAHCS Institutional Review Board and determined to be a quality improvement initiative and to not meet the definition of research, and as such did not require review; it was reviewed and approved by the MVAHCS Research and Development Committee.

RESULTS

A total of 538 patients were identified who simultaneously received rifampin and another oral antibiotic between January 1, 2000, and June 30, 2021.

Forty-two participants (54%) had Staphylococcus aureus and 31 participants (40%) had coagulase-negative staphylococci infections, while 11 gram-negative organisms (14%) and 6 gram-positive anaerobic cocci (8%) infections were noted. Cutibacterium acnes and Streptococcus agalactiae were each found in 3 participants (4% of), and diphtheroids (not further identified) was found on 2 participants (3%). Candida albicans was identified in a single participant (1%), along with coagulase-negative staphylococci, and 2 participants (3%) had no identified organisms. There were multiple organisms isolated from 20 patients (26%).

Fifty participants had clear documentation in their EHR that cure of infection was the goal, meeting the criteria for the intent-to-cure group. The remaining 28 participants were placed in the without-intent-to-cure group. Success and failure rates were only measured in the intent-to-cure group, as by definition the without-intent-to-cure group patients would meet the criteria for failure (removal of prosthesis or long-term antibiotic use). The without-intent-to-cure group had a higher median age than the intent-to-cure group (69 years vs 64 years, P = .24) and a higher proportion of male participants (96% vs 80%, P = .09). The median (IQR) implant age of 11 months (1.0-50.5) in the without-intent-to-cure group was also higher than the median implant age of 1 month (0.6-22.0) in the primary group (P = .22). In the without-intent-to-cure group, 19 participants (68%) had a chronic infection, compared with 11 (22%) in the intent-to-cure group (P < .001).

The mean (SD) Charlson Comorbidity Index in the without-intent-to-cure group was 2.5 (1.3) compared with 1.9 (1.4) in the intent-to-cure group (P = .09). There was no significant difference in the type of implant or microbiology of the infecting organism between the 2 groups, although it should be noted that in the intent-to-cure group, 48 patients (96%) had Staphylococcus aureus or coagulase-negative staphylococci isolated.

The median (IQR) dosage of rifampin was 600 mg (300-900). The secondary oral antibiotics used most often were 36 fluoroquinolones (46%) followed by 20 tetracyclines (26%), 6 cephalosporins (8%), and 6 penicillins (8%). Additionally, 6 participants (8%) received IV vancomycin, and 1 participant (1%) was given an oral antifungal in addition to a fluoroquinolone because cultures revealed bacterial and fungal growth. The median (IQR) duration of antimicrobial therapy was 3 months (1.4-3.0). The mean (SD) duration of antimicrobial therapy was 3.6 (2.4) months for TKA infections and 2.4 (0.9) months for THA infections.

Clinical Outcome

Forty-one intent-to-cure group participants (82%) experienced treatment success. We further subdivided the intent-to-cure group by implant age. Participants whose implant was < 2 months old had a success rate of 93%, whereas patients whose implant was older had a success rate of 65% (P = .02).

Secondary Outcomes

The median (IQR) duration of antimicrobial treatment was 3 months (1.4-3.0) for the 38 patients with TKA-related infections and 3 months (1.4-6.0) for the 29 patients with THA infections. AEs were recorded in 24 (31%) of all study participants. Of those with AEs, the average number reported per patient was 1.6. Diarrhea, gastric upset, and nausea were each reported 7 times, accounting for 87% of all recorded AEs. Five participants reported having a rash while on antibiotics, and 2 experienced dysgeusia. One participant reported developing a yeast infection and another experienced vaginitis.

DISCUSSION

Among patients with orthopedic implant infections treated with intent to cure using a rifampin-containing antibiotic regimen at the MVAHCS, 82% had clinical success. Although this is lower than the success rates reported in clinical trials, this is not entirely unexpected.^5,7 In most clinical trials studying DAIR and rifampin for PJI, patients are excluded if they do not have an acute staphylococcal infection in the setting of a well-fixed prosthesis without evidence of a sinus tract. Such exclusion criteria were not present in our retrospective study, which was designed to evaluate the real-world practice patterns at this facility. The population at the US Department of Veterans Affairs (VA) is older, more frail, and with more comorbid conditions than populations in prior studies. It is possible that patients with characteristics that would have caused them to be excluded from a clinical trial would be less likely to receive rifampin therapy with the intent to cure. This is suggested by the significantly higher prevalence of chronic infections (68%) in the without-intent-to-cure group compared with 22% in the intent-to-cure group. However, there were reasonably high proportions of participants included in the intent-to-cure group who did have conditions that would have led to their exclusion from prior trials, such as chronic infection (22%) and implant age ≥ 2 months (40%).

When evaluating participants by the age of their implant, treatment success rose to 93% for patients with implants < 2 months old compared with 65% for patients with older implants. This suggests that participants with a newer implant or more recent infection have a greater likelihood of successful treatment, which is consistent with the results of previous clinical trials.^5,10 Considering how difficult multiple surgeries can be for older adult patients with comorbidities, we suggest that DAIR with a rifampin-containing regimen be considered as the primary treatment option for early PJIs at the MVAHCS. We also note inconsistent adherence to IDSA treatment guidelines on rifampin therapy, in that patients without intent to cure were prescribed a regimen including rifampin. This may reflect appropriate variability in the care of individual patients but may also offer an opportunity to change processes to improve care.

Limitations

Our analysis has limitations. As with any retrospective study evaluating the efficacy of a specific antibiotic, we were not able to attribute specific outcomes to the antibiotic of interest. Since the choice of antibiotics was left to the treating health care practitioner, therapy was not standardized, and because this was a retrospective study, causal relationships could not be inferred. Our analysis was also limited by the lack of intent to cure in 28 participants (36%), which could be an indication of practitioner bias in therapy selection or characteristic differences between the 2 groups. We looked for signs of infection failure 1 year after the completion of antimicrobial therapy, but longer follow-up could have led to higher rates of failure. Also, while participants’ infections were considered cured if they never sought further medical care for the infection at the MVAHCS, it is possible that patients could have sought care at another facility. We note that 9 patients were excluded because they were unable to complete a treatment course due to rifampin AEs, meaning that the success rates reported here reflect the success that may be expected if a patient can tolerate and complete a rifampin-based regimen. This study was conducted in a single VA hospital and may not be generalizable to nonveterans or veterans seeking care at other facilities.

Conclusions

DAIR followed by a short course of IV antibiotics and an oral regimen including rifampin and another antimicrobial is a reasonable option for veterans with acute staphylococcal orthopedic device infections at the MVAHCS. Patients with a well-placed prosthesis and an acute infection seem especially well suited for this treatment, and treatment with intent to cure should be pursued in patients who meet the criteria for rifampin therapy.

Acknowledgments

We thank Erik Stensgard, PharmD, for assistance in compiling the list of patients receiving rifampin and another antimicrobial.

Orthopedic implants are frequently used to repair fractures and replace joints. The number of total joint replacements is high, with > 1 million total hip (THA) and total knee (TKA) arthroplasties performed in the United States each year.¹ While most joint arthroplasties are successful and significantly improve patient quality of life, a small proportion become infected.² Prosthetic joint infection (PJI) causes substantial morbidity and mortality, particularly among older patients, and is difficult and costly to treat.³

The historic gold standard treatment for PJI is a 2-stage replacement, wherein the prosthesis is removed in one procedure and a new prosthesis is implanted in a second procedure after an extended course of antibiotics. This approach requires the patient to undergo 2 major procedures and spend considerable time without a functioning prosthesis, contributing to immobility and deconditioning. This option is difficult for frail or older patients and is associated with high medical costs.⁴

In 1998, a novel method of treatment known as debridement, antibiotics, and implant retention (DAIR) was evaluated in a small, randomized controlled trial.⁵ This study used a unique antimicrobial approach: the administration of ciprofloxacin plus either rifampin or placebo for 3 to 6 months, combined with a single surgical debridement. Eliminating a second surgical procedure and largely relying on oral antimicrobials reduces surgical risks and decreases costs.⁴ Current guidelines endorse DAIR with rifampin and a second antibiotic for patients diagnosed with PJI within about 30 days of prosthesis implantation who have a well-fixed implant without evidence of a sinus tract.⁶ Clinical trial data demonstrate that this approach is > 90% effective in patients with a well-fixed prosthesis and acute staphylococcal PJI.^3,7

Thus far, clinical trials examining this approach have been small and did not include veterans who are typically older and have more comorbidities.⁸ The Minneapolis Veterans Affairs Health Care System (MVAHCS) infectious disease section has implemented the rifampin-based DAIR approach for orthopedic device-related infections since this approach was first described in 1998 but has not systematically evaluated its effectiveness or whether there are areas for improvement.

METHODS

We conducted a retrospective analysis of patients who underwent DAIR combined with a rifampin-containing regimen at the MVAHCS from January 1, 2001, through June 30, 2021. Inclusion required a diagnosis of orthopedic device-related infection and treatment with DAIR followed by antimicrobial therapy that included rifampin for 1 to 6 months. PJI was defined by meeting ≥ 1 of the following criteria: (1) isolation of the same microorganism from ≥ 2 cultures from joint aspirates or intraoperative tissue specimens; (2) purulence surrounding the prosthesis at the time of surgery; (3) acute inflammation consistent with infection on histopathological examination or periprosthetic tissue; or (4) presence of a sinus tract communicating with the prosthesis.

All cases of orthopedic device infection managed with DAIR and rifampin were included, regardless of implant stability, age of the implant at the time of symptom onset, presence of a sinus tract, or infecting microorganism. Exclusion criteria included patients who started or finished PJI treatment at another facility, were lost to follow-up, discontinued rifampin, died within 1 year of completing antibiotic therapy due to reasons unrelated to treatment failure, received rifampin for < 50% of their antimicrobial treatment course, had complete hardware removal, or had < 1 year between the completion of antimicrobial therapy and the time of data collection.

Management of DAIR procedures at the MVAHCS involves evaluating the fixation of the prosthesis, tissue sampling for microbiological analysis, and thorough debridement of infected tissue. Following debridement, a course of IV antibiotics is administered before initiating oral antibiotic therapy. To protect against resistance, rifampin is combined with another antibiotic typically from the fluoroquinolone, tetracycline, or cephalosporin class. Current guidelines suggest 3 and 6 months of oral antibiotics for prosthetic hip and knee infections, respectively.⁶

Treatment Outcomes

The primary outcome was treatment success, defined as meeting all of the following: (1) lack of clinical signs and symptoms of infection; (2) absence of radiological signs of loosening or infection within 1 year after the conclusion of treatment; and (3) absence of additional PJI treatment interventions for the prosthesis of concern within 1 year after completing the original antibiotic treatment.

Treatment failure was defined as meeting any of the following: (1) recurrence of PJI (original strain or different microorganism) within 1 year after the completion of antibiotic therapy; (2) death attributed to PJI anytime after the initial debridement; (3) removal of the prosthetic joint within 1 year after the completion of antibiotic therapy; or (4) long-term antibiotic use to suppress the PJI after the completion of the initial antibiotic therapy.

Statistical Analysis

Descriptive statistics were used to define the baseline characteristics of patients receiving rifampin therapy for orthopedic implant infections at the MVAHCS. Variables analyzed were age, sex, race and ethnicity, type of implant, age of implant, duration of symptoms, comorbidities (diabetes and rheumatoid arthritis), and presence of chronic infection. Patients were classified as having a chronic infection if they received previous infection treatment (antibiotics or surgery) for the orthopedic device in question. We created this category because patients with persistent infection after a medical or surgical attempt at treatment are likely to have a higher probability of treatment failure compared with those with no prior therapy. Charlson Comorbidity Index was calculated using clinical information present at the onset of infection.⁹ Fisher exact test was used to assess differences between categorical variables, and an independent t test was used to assess differences in continuous variables. P < .05 indicated statistical significance.

To assess the ability of a rifampin-based regimen to achieve a cure of PJI, we grouped participants into 2 categories: those with an intent to cure strategy and those without intent to cure based on documentation in the electronic health record (EHR). Participants who were prescribed rifampin with the documented goal of prosthesis retention with no further suppressive antibiotics were included in the intent-to-cure group, the primary focus of this study. Those excluded from the intent-to-cure group were given rifampin and another antibiotic, but there was a documented plan of either ongoing chronic suppression or eventual explantation; these participants were placed in the without-intent-to-cure group. Analysis of treatment success and failure was limited to the intent-to-cure group, whereas both groups were included for assessment of adverse effects (AEs) and treatment duration. This project was reviewed by the MVAHCS Institutional Review Board and determined to be a quality improvement initiative and to not meet the definition of research, and as such did not require review; it was reviewed and approved by the MVAHCS Research and Development Committee.

RESULTS

A total of 538 patients were identified who simultaneously received rifampin and another oral antibiotic between January 1, 2000, and June 30, 2021.

Forty-two participants (54%) had Staphylococcus aureus and 31 participants (40%) had coagulase-negative staphylococci infections, while 11 gram-negative organisms (14%) and 6 gram-positive anaerobic cocci (8%) infections were noted. Cutibacterium acnes and Streptococcus agalactiae were each found in 3 participants (4% of), and diphtheroids (not further identified) was found on 2 participants (3%). Candida albicans was identified in a single participant (1%), along with coagulase-negative staphylococci, and 2 participants (3%) had no identified organisms. There were multiple organisms isolated from 20 patients (26%).

Fifty participants had clear documentation in their EHR that cure of infection was the goal, meeting the criteria for the intent-to-cure group. The remaining 28 participants were placed in the without-intent-to-cure group. Success and failure rates were only measured in the intent-to-cure group, as by definition the without-intent-to-cure group patients would meet the criteria for failure (removal of prosthesis or long-term antibiotic use). The without-intent-to-cure group had a higher median age than the intent-to-cure group (69 years vs 64 years, P = .24) and a higher proportion of male participants (96% vs 80%, P = .09). The median (IQR) implant age of 11 months (1.0-50.5) in the without-intent-to-cure group was also higher than the median implant age of 1 month (0.6-22.0) in the primary group (P = .22). In the without-intent-to-cure group, 19 participants (68%) had a chronic infection, compared with 11 (22%) in the intent-to-cure group (P < .001).

The mean (SD) Charlson Comorbidity Index in the without-intent-to-cure group was 2.5 (1.3) compared with 1.9 (1.4) in the intent-to-cure group (P = .09). There was no significant difference in the type of implant or microbiology of the infecting organism between the 2 groups, although it should be noted that in the intent-to-cure group, 48 patients (96%) had Staphylococcus aureus or coagulase-negative staphylococci isolated.

The median (IQR) dosage of rifampin was 600 mg (300-900). The secondary oral antibiotics used most often were 36 fluoroquinolones (46%) followed by 20 tetracyclines (26%), 6 cephalosporins (8%), and 6 penicillins (8%). Additionally, 6 participants (8%) received IV vancomycin, and 1 participant (1%) was given an oral antifungal in addition to a fluoroquinolone because cultures revealed bacterial and fungal growth. The median (IQR) duration of antimicrobial therapy was 3 months (1.4-3.0). The mean (SD) duration of antimicrobial therapy was 3.6 (2.4) months for TKA infections and 2.4 (0.9) months for THA infections.

Clinical Outcome

Forty-one intent-to-cure group participants (82%) experienced treatment success. We further subdivided the intent-to-cure group by implant age. Participants whose implant was < 2 months old had a success rate of 93%, whereas patients whose implant was older had a success rate of 65% (P = .02).

Secondary Outcomes

The median (IQR) duration of antimicrobial treatment was 3 months (1.4-3.0) for the 38 patients with TKA-related infections and 3 months (1.4-6.0) for the 29 patients with THA infections. AEs were recorded in 24 (31%) of all study participants. Of those with AEs, the average number reported per patient was 1.6. Diarrhea, gastric upset, and nausea were each reported 7 times, accounting for 87% of all recorded AEs. Five participants reported having a rash while on antibiotics, and 2 experienced dysgeusia. One participant reported developing a yeast infection and another experienced vaginitis.

DISCUSSION

Among patients with orthopedic implant infections treated with intent to cure using a rifampin-containing antibiotic regimen at the MVAHCS, 82% had clinical success. Although this is lower than the success rates reported in clinical trials, this is not entirely unexpected.^5,7 In most clinical trials studying DAIR and rifampin for PJI, patients are excluded if they do not have an acute staphylococcal infection in the setting of a well-fixed prosthesis without evidence of a sinus tract. Such exclusion criteria were not present in our retrospective study, which was designed to evaluate the real-world practice patterns at this facility. The population at the US Department of Veterans Affairs (VA) is older, more frail, and with more comorbid conditions than populations in prior studies. It is possible that patients with characteristics that would have caused them to be excluded from a clinical trial would be less likely to receive rifampin therapy with the intent to cure. This is suggested by the significantly higher prevalence of chronic infections (68%) in the without-intent-to-cure group compared with 22% in the intent-to-cure group. However, there were reasonably high proportions of participants included in the intent-to-cure group who did have conditions that would have led to their exclusion from prior trials, such as chronic infection (22%) and implant age ≥ 2 months (40%).

When evaluating participants by the age of their implant, treatment success rose to 93% for patients with implants < 2 months old compared with 65% for patients with older implants. This suggests that participants with a newer implant or more recent infection have a greater likelihood of successful treatment, which is consistent with the results of previous clinical trials.^5,10 Considering how difficult multiple surgeries can be for older adult patients with comorbidities, we suggest that DAIR with a rifampin-containing regimen be considered as the primary treatment option for early PJIs at the MVAHCS. We also note inconsistent adherence to IDSA treatment guidelines on rifampin therapy, in that patients without intent to cure were prescribed a regimen including rifampin. This may reflect appropriate variability in the care of individual patients but may also offer an opportunity to change processes to improve care.

Limitations

Our analysis has limitations. As with any retrospective study evaluating the efficacy of a specific antibiotic, we were not able to attribute specific outcomes to the antibiotic of interest. Since the choice of antibiotics was left to the treating health care practitioner, therapy was not standardized, and because this was a retrospective study, causal relationships could not be inferred. Our analysis was also limited by the lack of intent to cure in 28 participants (36%), which could be an indication of practitioner bias in therapy selection or characteristic differences between the 2 groups. We looked for signs of infection failure 1 year after the completion of antimicrobial therapy, but longer follow-up could have led to higher rates of failure. Also, while participants’ infections were considered cured if they never sought further medical care for the infection at the MVAHCS, it is possible that patients could have sought care at another facility. We note that 9 patients were excluded because they were unable to complete a treatment course due to rifampin AEs, meaning that the success rates reported here reflect the success that may be expected if a patient can tolerate and complete a rifampin-based regimen. This study was conducted in a single VA hospital and may not be generalizable to nonveterans or veterans seeking care at other facilities.

Conclusions

DAIR followed by a short course of IV antibiotics and an oral regimen including rifampin and another antimicrobial is a reasonable option for veterans with acute staphylococcal orthopedic device infections at the MVAHCS. Patients with a well-placed prosthesis and an acute infection seem especially well suited for this treatment, and treatment with intent to cure should be pursued in patients who meet the criteria for rifampin therapy.

Acknowledgments

We thank Erik Stensgard, PharmD, for assistance in compiling the list of patients receiving rifampin and another antimicrobial.

Orthopedic implants are frequently used to repair fractures and replace joints. The number of total joint replacements is high, with > 1 million total hip (THA) and total knee (TKA) arthroplasties performed in the United States each year.¹ While most joint arthroplasties are successful and significantly improve patient quality of life, a small proportion become infected.² Prosthetic joint infection (PJI) causes substantial morbidity and mortality, particularly among older patients, and is difficult and costly to treat.³

The historic gold standard treatment for PJI is a 2-stage replacement, wherein the prosthesis is removed in one procedure and a new prosthesis is implanted in a second procedure after an extended course of antibiotics. This approach requires the patient to undergo 2 major procedures and spend considerable time without a functioning prosthesis, contributing to immobility and deconditioning. This option is difficult for frail or older patients and is associated with high medical costs.⁴

In 1998, a novel method of treatment known as debridement, antibiotics, and implant retention (DAIR) was evaluated in a small, randomized controlled trial.⁵ This study used a unique antimicrobial approach: the administration of ciprofloxacin plus either rifampin or placebo for 3 to 6 months, combined with a single surgical debridement. Eliminating a second surgical procedure and largely relying on oral antimicrobials reduces surgical risks and decreases costs.⁴ Current guidelines endorse DAIR with rifampin and a second antibiotic for patients diagnosed with PJI within about 30 days of prosthesis implantation who have a well-fixed implant without evidence of a sinus tract.⁶ Clinical trial data demonstrate that this approach is > 90% effective in patients with a well-fixed prosthesis and acute staphylococcal PJI.^3,7

Thus far, clinical trials examining this approach have been small and did not include veterans who are typically older and have more comorbidities.⁸ The Minneapolis Veterans Affairs Health Care System (MVAHCS) infectious disease section has implemented the rifampin-based DAIR approach for orthopedic device-related infections since this approach was first described in 1998 but has not systematically evaluated its effectiveness or whether there are areas for improvement.

METHODS

We conducted a retrospective analysis of patients who underwent DAIR combined with a rifampin-containing regimen at the MVAHCS from January 1, 2001, through June 30, 2021. Inclusion required a diagnosis of orthopedic device-related infection and treatment with DAIR followed by antimicrobial therapy that included rifampin for 1 to 6 months. PJI was defined by meeting ≥ 1 of the following criteria: (1) isolation of the same microorganism from ≥ 2 cultures from joint aspirates or intraoperative tissue specimens; (2) purulence surrounding the prosthesis at the time of surgery; (3) acute inflammation consistent with infection on histopathological examination or periprosthetic tissue; or (4) presence of a sinus tract communicating with the prosthesis.

All cases of orthopedic device infection managed with DAIR and rifampin were included, regardless of implant stability, age of the implant at the time of symptom onset, presence of a sinus tract, or infecting microorganism. Exclusion criteria included patients who started or finished PJI treatment at another facility, were lost to follow-up, discontinued rifampin, died within 1 year of completing antibiotic therapy due to reasons unrelated to treatment failure, received rifampin for < 50% of their antimicrobial treatment course, had complete hardware removal, or had < 1 year between the completion of antimicrobial therapy and the time of data collection.

Management of DAIR procedures at the MVAHCS involves evaluating the fixation of the prosthesis, tissue sampling for microbiological analysis, and thorough debridement of infected tissue. Following debridement, a course of IV antibiotics is administered before initiating oral antibiotic therapy. To protect against resistance, rifampin is combined with another antibiotic typically from the fluoroquinolone, tetracycline, or cephalosporin class. Current guidelines suggest 3 and 6 months of oral antibiotics for prosthetic hip and knee infections, respectively.⁶

Treatment Outcomes

The primary outcome was treatment success, defined as meeting all of the following: (1) lack of clinical signs and symptoms of infection; (2) absence of radiological signs of loosening or infection within 1 year after the conclusion of treatment; and (3) absence of additional PJI treatment interventions for the prosthesis of concern within 1 year after completing the original antibiotic treatment.

Treatment failure was defined as meeting any of the following: (1) recurrence of PJI (original strain or different microorganism) within 1 year after the completion of antibiotic therapy; (2) death attributed to PJI anytime after the initial debridement; (3) removal of the prosthetic joint within 1 year after the completion of antibiotic therapy; or (4) long-term antibiotic use to suppress the PJI after the completion of the initial antibiotic therapy.

Statistical Analysis

Descriptive statistics were used to define the baseline characteristics of patients receiving rifampin therapy for orthopedic implant infections at the MVAHCS. Variables analyzed were age, sex, race and ethnicity, type of implant, age of implant, duration of symptoms, comorbidities (diabetes and rheumatoid arthritis), and presence of chronic infection. Patients were classified as having a chronic infection if they received previous infection treatment (antibiotics or surgery) for the orthopedic device in question. We created this category because patients with persistent infection after a medical or surgical attempt at treatment are likely to have a higher probability of treatment failure compared with those with no prior therapy. Charlson Comorbidity Index was calculated using clinical information present at the onset of infection.⁹ Fisher exact test was used to assess differences between categorical variables, and an independent t test was used to assess differences in continuous variables. P < .05 indicated statistical significance.

To assess the ability of a rifampin-based regimen to achieve a cure of PJI, we grouped participants into 2 categories: those with an intent to cure strategy and those without intent to cure based on documentation in the electronic health record (EHR). Participants who were prescribed rifampin with the documented goal of prosthesis retention with no further suppressive antibiotics were included in the intent-to-cure group, the primary focus of this study. Those excluded from the intent-to-cure group were given rifampin and another antibiotic, but there was a documented plan of either ongoing chronic suppression or eventual explantation; these participants were placed in the without-intent-to-cure group. Analysis of treatment success and failure was limited to the intent-to-cure group, whereas both groups were included for assessment of adverse effects (AEs) and treatment duration. This project was reviewed by the MVAHCS Institutional Review Board and determined to be a quality improvement initiative and to not meet the definition of research, and as such did not require review; it was reviewed and approved by the MVAHCS Research and Development Committee.

RESULTS

A total of 538 patients were identified who simultaneously received rifampin and another oral antibiotic between January 1, 2000, and June 30, 2021.

Forty-two participants (54%) had Staphylococcus aureus and 31 participants (40%) had coagulase-negative staphylococci infections, while 11 gram-negative organisms (14%) and 6 gram-positive anaerobic cocci (8%) infections were noted. Cutibacterium acnes and Streptococcus agalactiae were each found in 3 participants (4% of), and diphtheroids (not further identified) was found on 2 participants (3%). Candida albicans was identified in a single participant (1%), along with coagulase-negative staphylococci, and 2 participants (3%) had no identified organisms. There were multiple organisms isolated from 20 patients (26%).

Fifty participants had clear documentation in their EHR that cure of infection was the goal, meeting the criteria for the intent-to-cure group. The remaining 28 participants were placed in the without-intent-to-cure group. Success and failure rates were only measured in the intent-to-cure group, as by definition the without-intent-to-cure group patients would meet the criteria for failure (removal of prosthesis or long-term antibiotic use). The without-intent-to-cure group had a higher median age than the intent-to-cure group (69 years vs 64 years, P = .24) and a higher proportion of male participants (96% vs 80%, P = .09). The median (IQR) implant age of 11 months (1.0-50.5) in the without-intent-to-cure group was also higher than the median implant age of 1 month (0.6-22.0) in the primary group (P = .22). In the without-intent-to-cure group, 19 participants (68%) had a chronic infection, compared with 11 (22%) in the intent-to-cure group (P < .001).

The mean (SD) Charlson Comorbidity Index in the without-intent-to-cure group was 2.5 (1.3) compared with 1.9 (1.4) in the intent-to-cure group (P = .09). There was no significant difference in the type of implant or microbiology of the infecting organism between the 2 groups, although it should be noted that in the intent-to-cure group, 48 patients (96%) had Staphylococcus aureus or coagulase-negative staphylococci isolated.

The median (IQR) dosage of rifampin was 600 mg (300-900). The secondary oral antibiotics used most often were 36 fluoroquinolones (46%) followed by 20 tetracyclines (26%), 6 cephalosporins (8%), and 6 penicillins (8%). Additionally, 6 participants (8%) received IV vancomycin, and 1 participant (1%) was given an oral antifungal in addition to a fluoroquinolone because cultures revealed bacterial and fungal growth. The median (IQR) duration of antimicrobial therapy was 3 months (1.4-3.0). The mean (SD) duration of antimicrobial therapy was 3.6 (2.4) months for TKA infections and 2.4 (0.9) months for THA infections.

Clinical Outcome

Forty-one intent-to-cure group participants (82%) experienced treatment success. We further subdivided the intent-to-cure group by implant age. Participants whose implant was < 2 months old had a success rate of 93%, whereas patients whose implant was older had a success rate of 65% (P = .02).

Secondary Outcomes

The median (IQR) duration of antimicrobial treatment was 3 months (1.4-3.0) for the 38 patients with TKA-related infections and 3 months (1.4-6.0) for the 29 patients with THA infections. AEs were recorded in 24 (31%) of all study participants. Of those with AEs, the average number reported per patient was 1.6. Diarrhea, gastric upset, and nausea were each reported 7 times, accounting for 87% of all recorded AEs. Five participants reported having a rash while on antibiotics, and 2 experienced dysgeusia. One participant reported developing a yeast infection and another experienced vaginitis.

DISCUSSION

Among patients with orthopedic implant infections treated with intent to cure using a rifampin-containing antibiotic regimen at the MVAHCS, 82% had clinical success. Although this is lower than the success rates reported in clinical trials, this is not entirely unexpected.^5,7 In most clinical trials studying DAIR and rifampin for PJI, patients are excluded if they do not have an acute staphylococcal infection in the setting of a well-fixed prosthesis without evidence of a sinus tract. Such exclusion criteria were not present in our retrospective study, which was designed to evaluate the real-world practice patterns at this facility. The population at the US Department of Veterans Affairs (VA) is older, more frail, and with more comorbid conditions than populations in prior studies. It is possible that patients with characteristics that would have caused them to be excluded from a clinical trial would be less likely to receive rifampin therapy with the intent to cure. This is suggested by the significantly higher prevalence of chronic infections (68%) in the without-intent-to-cure group compared with 22% in the intent-to-cure group. However, there were reasonably high proportions of participants included in the intent-to-cure group who did have conditions that would have led to their exclusion from prior trials, such as chronic infection (22%) and implant age ≥ 2 months (40%).

When evaluating participants by the age of their implant, treatment success rose to 93% for patients with implants < 2 months old compared with 65% for patients with older implants. This suggests that participants with a newer implant or more recent infection have a greater likelihood of successful treatment, which is consistent with the results of previous clinical trials.^5,10 Considering how difficult multiple surgeries can be for older adult patients with comorbidities, we suggest that DAIR with a rifampin-containing regimen be considered as the primary treatment option for early PJIs at the MVAHCS. We also note inconsistent adherence to IDSA treatment guidelines on rifampin therapy, in that patients without intent to cure were prescribed a regimen including rifampin. This may reflect appropriate variability in the care of individual patients but may also offer an opportunity to change processes to improve care.

Limitations

Our analysis has limitations. As with any retrospective study evaluating the efficacy of a specific antibiotic, we were not able to attribute specific outcomes to the antibiotic of interest. Since the choice of antibiotics was left to the treating health care practitioner, therapy was not standardized, and because this was a retrospective study, causal relationships could not be inferred. Our analysis was also limited by the lack of intent to cure in 28 participants (36%), which could be an indication of practitioner bias in therapy selection or characteristic differences between the 2 groups. We looked for signs of infection failure 1 year after the completion of antimicrobial therapy, but longer follow-up could have led to higher rates of failure. Also, while participants’ infections were considered cured if they never sought further medical care for the infection at the MVAHCS, it is possible that patients could have sought care at another facility. We note that 9 patients were excluded because they were unable to complete a treatment course due to rifampin AEs, meaning that the success rates reported here reflect the success that may be expected if a patient can tolerate and complete a rifampin-based regimen. This study was conducted in a single VA hospital and may not be generalizable to nonveterans or veterans seeking care at other facilities.

Conclusions

DAIR followed by a short course of IV antibiotics and an oral regimen including rifampin and another antimicrobial is a reasonable option for veterans with acute staphylococcal orthopedic device infections at the MVAHCS. Patients with a well-placed prosthesis and an acute infection seem especially well suited for this treatment, and treatment with intent to cure should be pursued in patients who meet the criteria for rifampin therapy.

Acknowledgments

We thank Erik Stensgard, PharmD, for assistance in compiling the list of patients receiving rifampin and another antimicrobial.

The psychological and moral comfort of a presence at once humble and understanding—this is the greatest benefit that the dog has bestowed upon man. Percy Bysshe Shelley

Ever since their domestication about 20,000 years ago, dogs have been cherished for their indomitable and generous spirit, ability to assist humans in myriad ways, and unconditional love. August heralds National Dog Month, and September honors the loyal companionship and dedicated work of service dogs so valuable to service members and veterans.

The nature of their special training to perform specific tasks for the safety and well-being of veterans distinguishes service dogs from pets or emotional support animals. Most of us recognize the happiness and meaning animals bring to our lives. What we may not appreciate is the impressive contribution service dogs make to the health and rehabilitation of those who have served their country. Veteran patients with neurologic conditions such as seizures know the difference a service dog trained to warn them of an emerging seizure makes for their freedom of movement and peace of mind. Veterans with diabetes have described times when their service dogs sought help before they realized their blood sugar was dangerously low.

Patients, friends, and neighbors who have been paired with service dogs describe ways their new companion helped them transition from a life in which even surviving was a struggle to one of holistic thriving. A Vietnam veteran neighbor with a significant tremor due to Parkinson disease benefitted from the ability of his dog to fetch and bring, retrieve, and carry. His dog has learned to hold essential items still, which would otherwise be too shaky in human hands, enabling the veteran to open his closet door and dress independently each morning. One veteran classmate avoided all forms of public transportation due to memories of a traumatic mobile-based mass evacuation she assisted with during her military service. She dreaded her long, inconvenient daily drive back and forth to work. She was then partnered with a large dog breed that was trained to stand a short distance from her to protect her sense of space and open air. The dog would stretch out his body to claim more space for her among crowds. This veteran started to ride the bus to campus each morning and appreciated the interaction with other riders as well as the saved travel time, mileage, gasoline expense, and parking stress.

A veteran brought his sweet retriever to the neighborhood weekly “Paws-itive Reading” program for children in the local public library. When MW’s daughter was busy reading to his furry friend, the veteran shared that for at least 5 years after his combat tours, he rarely left his window-shuttered home. His dog’s steady comfort re-established his ability to participate in his community. He now generously shares his dog’s patient affection with children learning to read.

MW recently witnessed the profound and protective presence of a service dog in comforting a veteran during a posttraumatic stress disorder (PTSD)–related crisis. The service dog offered a lean and reassuring paw pressure on the veteran’s shoulder if he was reexperiencing trauma. The dog’s steady breathing and familiar warmth helped to reorient their human companion to the safety of his present physical surroundings. Bearing witness to the dog’s trained interaction with the veteran left MW speechless. The trust between them was therapeutic in a way that transcended her ability to articulate what she experienced. This compelled MW to investigate whether this was a rare relationship or whether there was existing data on the impact of trained service dogs and PTSD.

Service dog placement with veterans with PTSD has been shown to have a positive influence on both physiological (arousal-related functioning and cortisol awakening response) and psychosocial well-being, including decreased isolation and increased physical activity.^1,2 Veterans with PTSD paired with service dogs showed significantly fewer PTSD-related symptoms, better sleep quality, and improved well-being, compared with those with just a pet.³ A recent meta-analysis revealed that veteran partnerships with a service dog had a clinically meaningful, significant, and large effect on PTSD severity scores (P < .001).² The mechanism for impact is thought to be not only the dog’s working role but also the transcendent loyalty of the canine-veteran bond.

Many accredited dog training programs describe a certain reciprocity to the dog-human relationship. Some use rescue puppies to give the dogs a new life and purpose. Dogs who have undergone challenges often need patience, time, safe relationships, and trustworthy new experiences to maximize their potential. Reciprocally, trained service dogs have the potential to foster access to these same emotional, relational, existential, and physical safety needs for veterans exposed to trauma.

Recent legislation has made progress in recognizing the role of service dogs for veterans and improving access. The Puppies Assisting Wounded Servicemembers (PAWS) for Veterans Therapy Act (38 USC §1705, 1714) was passed in 2021. The PAWS Act implemented a policy and 5-year pilot program to connect trained canines to eligible veterans diagnosed with PTSD as an element of an integrative health program, regardless of whether the veteran has a mobility impairment. The PAWS Act gives federal funding to accredited dog training organizations to help pair eligible veterans with service dogs by covering veteran travel expenses for the training, training program participation, and relevant veterinary expenses. The bipartisan Service Dogs Assisting Veterans Act (SAVES) Act was introduced this summer to award grants to nonprofit organizations Assistance Dog International has accredited to help these groups provide service dogs to veterans.

The US Department of Veterans Affairs (VA) has made strides in welcoming service dogs. Trained service dogs of all breeds under the control of a human companion are now allowed in VA facilities other than in areas where safety and infection control standards would be compromised (ie, sterile equipment rooms).⁴ A prescribing clinician can now evaluate eligible veterans to determine their ability, resources, and goals for having a service dog.⁵ An assessment of the veteran’s ability to care for a dog and education on expectations for the partnership is critical to success and animal welfare. Those veterans approved for a service dog are then referred to accredited agencies. The VA Veterinary Health Insurance Benefit includes aspects of coverage for the veteran to attend service dog training, veterinary wellness (preventive care, immunizations, dental cleanings, certain prescriptions, etc), and care for the dog’s illnesses when treatment enables the dog to perform duties in service to the veteran.⁶

The productive purpose and friendship of a service dog become a formidable force in a veteran’s life. Veterans spent an average of 82% of their time with service dogs (assessed via Bluetooth proximity between collar and smartphone).⁷ Human partners of veterans with service dogs may experience improved quality of life and relationship functioning with the inclusion of a service dog in the family unit.⁸ Veterans depict increased community engagement, social connectedness, and personal confidence as a result of the canine companionship.^9,10 Veterans with service dogs often speak of the ways the dog’s presence transformed their lives and many speak of the dog literally saving their lives.¹¹ Meta-analyses showed improved mental health treatment engagement, medication adherence, and decreased suicidality.^2,12

A story was recently shared with us about the compassion and competence of VA staff in a perioperative unit. A veteran was scheduled for a life-altering surgery and yet was anxious about entering the room for his scheduled pre-anesthesia check-in, knowing his service dog could not accompany him through the entire procedure. The staff recognized that the veteran was increasingly nervous and even started to question whether he would stay for the scheduled procedure they deemed would benefit his health. The perioperative team then proactively worked together to safely walk the veteran through the preparation processes in a sterile setting while keeping the dog within sight of the veteran. They then ensured that the veteran’s service dog was by his side early in the recovery room so that the veteran woke to wags and licks. In these months of canine recognition, we honor the ways the VA has fostered companionship and courage in veterans’ lives through the inclusion of service dogs in so many aspects of their care and life.

The psychological and moral comfort of a presence at once humble and understanding—this is the greatest benefit that the dog has bestowed upon man. Percy Bysshe Shelley

Ever since their domestication about 20,000 years ago, dogs have been cherished for their indomitable and generous spirit, ability to assist humans in myriad ways, and unconditional love. August heralds National Dog Month, and September honors the loyal companionship and dedicated work of service dogs so valuable to service members and veterans.

The nature of their special training to perform specific tasks for the safety and well-being of veterans distinguishes service dogs from pets or emotional support animals. Most of us recognize the happiness and meaning animals bring to our lives. What we may not appreciate is the impressive contribution service dogs make to the health and rehabilitation of those who have served their country. Veteran patients with neurologic conditions such as seizures know the difference a service dog trained to warn them of an emerging seizure makes for their freedom of movement and peace of mind. Veterans with diabetes have described times when their service dogs sought help before they realized their blood sugar was dangerously low.

Patients, friends, and neighbors who have been paired with service dogs describe ways their new companion helped them transition from a life in which even surviving was a struggle to one of holistic thriving. A Vietnam veteran neighbor with a significant tremor due to Parkinson disease benefitted from the ability of his dog to fetch and bring, retrieve, and carry. His dog has learned to hold essential items still, which would otherwise be too shaky in human hands, enabling the veteran to open his closet door and dress independently each morning. One veteran classmate avoided all forms of public transportation due to memories of a traumatic mobile-based mass evacuation she assisted with during her military service. She dreaded her long, inconvenient daily drive back and forth to work. She was then partnered with a large dog breed that was trained to stand a short distance from her to protect her sense of space and open air. The dog would stretch out his body to claim more space for her among crowds. This veteran started to ride the bus to campus each morning and appreciated the interaction with other riders as well as the saved travel time, mileage, gasoline expense, and parking stress.

A veteran brought his sweet retriever to the neighborhood weekly “Paws-itive Reading” program for children in the local public library. When MW’s daughter was busy reading to his furry friend, the veteran shared that for at least 5 years after his combat tours, he rarely left his window-shuttered home. His dog’s steady comfort re-established his ability to participate in his community. He now generously shares his dog’s patient affection with children learning to read.

MW recently witnessed the profound and protective presence of a service dog in comforting a veteran during a posttraumatic stress disorder (PTSD)–related crisis. The service dog offered a lean and reassuring paw pressure on the veteran’s shoulder if he was reexperiencing trauma. The dog’s steady breathing and familiar warmth helped to reorient their human companion to the safety of his present physical surroundings. Bearing witness to the dog’s trained interaction with the veteran left MW speechless. The trust between them was therapeutic in a way that transcended her ability to articulate what she experienced. This compelled MW to investigate whether this was a rare relationship or whether there was existing data on the impact of trained service dogs and PTSD.

Service dog placement with veterans with PTSD has been shown to have a positive influence on both physiological (arousal-related functioning and cortisol awakening response) and psychosocial well-being, including decreased isolation and increased physical activity.^1,2 Veterans with PTSD paired with service dogs showed significantly fewer PTSD-related symptoms, better sleep quality, and improved well-being, compared with those with just a pet.³ A recent meta-analysis revealed that veteran partnerships with a service dog had a clinically meaningful, significant, and large effect on PTSD severity scores (P < .001).² The mechanism for impact is thought to be not only the dog’s working role but also the transcendent loyalty of the canine-veteran bond.

Many accredited dog training programs describe a certain reciprocity to the dog-human relationship. Some use rescue puppies to give the dogs a new life and purpose. Dogs who have undergone challenges often need patience, time, safe relationships, and trustworthy new experiences to maximize their potential. Reciprocally, trained service dogs have the potential to foster access to these same emotional, relational, existential, and physical safety needs for veterans exposed to trauma.

Recent legislation has made progress in recognizing the role of service dogs for veterans and improving access. The Puppies Assisting Wounded Servicemembers (PAWS) for Veterans Therapy Act (38 USC §1705, 1714) was passed in 2021. The PAWS Act implemented a policy and 5-year pilot program to connect trained canines to eligible veterans diagnosed with PTSD as an element of an integrative health program, regardless of whether the veteran has a mobility impairment. The PAWS Act gives federal funding to accredited dog training organizations to help pair eligible veterans with service dogs by covering veteran travel expenses for the training, training program participation, and relevant veterinary expenses. The bipartisan Service Dogs Assisting Veterans Act (SAVES) Act was introduced this summer to award grants to nonprofit organizations Assistance Dog International has accredited to help these groups provide service dogs to veterans.

The US Department of Veterans Affairs (VA) has made strides in welcoming service dogs. Trained service dogs of all breeds under the control of a human companion are now allowed in VA facilities other than in areas where safety and infection control standards would be compromised (ie, sterile equipment rooms).⁴ A prescribing clinician can now evaluate eligible veterans to determine their ability, resources, and goals for having a service dog.⁵ An assessment of the veteran’s ability to care for a dog and education on expectations for the partnership is critical to success and animal welfare. Those veterans approved for a service dog are then referred to accredited agencies. The VA Veterinary Health Insurance Benefit includes aspects of coverage for the veteran to attend service dog training, veterinary wellness (preventive care, immunizations, dental cleanings, certain prescriptions, etc), and care for the dog’s illnesses when treatment enables the dog to perform duties in service to the veteran.⁶

The productive purpose and friendship of a service dog become a formidable force in a veteran’s life. Veterans spent an average of 82% of their time with service dogs (assessed via Bluetooth proximity between collar and smartphone).⁷ Human partners of veterans with service dogs may experience improved quality of life and relationship functioning with the inclusion of a service dog in the family unit.⁸ Veterans depict increased community engagement, social connectedness, and personal confidence as a result of the canine companionship.^9,10 Veterans with service dogs often speak of the ways the dog’s presence transformed their lives and many speak of the dog literally saving their lives.¹¹ Meta-analyses showed improved mental health treatment engagement, medication adherence, and decreased suicidality.^2,12

A story was recently shared with us about the compassion and competence of VA staff in a perioperative unit. A veteran was scheduled for a life-altering surgery and yet was anxious about entering the room for his scheduled pre-anesthesia check-in, knowing his service dog could not accompany him through the entire procedure. The staff recognized that the veteran was increasingly nervous and even started to question whether he would stay for the scheduled procedure they deemed would benefit his health. The perioperative team then proactively worked together to safely walk the veteran through the preparation processes in a sterile setting while keeping the dog within sight of the veteran. They then ensured that the veteran’s service dog was by his side early in the recovery room so that the veteran woke to wags and licks. In these months of canine recognition, we honor the ways the VA has fostered companionship and courage in veterans’ lives through the inclusion of service dogs in so many aspects of their care and life.

The psychological and moral comfort of a presence at once humble and understanding—this is the greatest benefit that the dog has bestowed upon man. Percy Bysshe Shelley

Ever since their domestication about 20,000 years ago, dogs have been cherished for their indomitable and generous spirit, ability to assist humans in myriad ways, and unconditional love. August heralds National Dog Month, and September honors the loyal companionship and dedicated work of service dogs so valuable to service members and veterans.

The nature of their special training to perform specific tasks for the safety and well-being of veterans distinguishes service dogs from pets or emotional support animals. Most of us recognize the happiness and meaning animals bring to our lives. What we may not appreciate is the impressive contribution service dogs make to the health and rehabilitation of those who have served their country. Veteran patients with neurologic conditions such as seizures know the difference a service dog trained to warn them of an emerging seizure makes for their freedom of movement and peace of mind. Veterans with diabetes have described times when their service dogs sought help before they realized their blood sugar was dangerously low.

Patients, friends, and neighbors who have been paired with service dogs describe ways their new companion helped them transition from a life in which even surviving was a struggle to one of holistic thriving. A Vietnam veteran neighbor with a significant tremor due to Parkinson disease benefitted from the ability of his dog to fetch and bring, retrieve, and carry. His dog has learned to hold essential items still, which would otherwise be too shaky in human hands, enabling the veteran to open his closet door and dress independently each morning. One veteran classmate avoided all forms of public transportation due to memories of a traumatic mobile-based mass evacuation she assisted with during her military service. She dreaded her long, inconvenient daily drive back and forth to work. She was then partnered with a large dog breed that was trained to stand a short distance from her to protect her sense of space and open air. The dog would stretch out his body to claim more space for her among crowds. This veteran started to ride the bus to campus each morning and appreciated the interaction with other riders as well as the saved travel time, mileage, gasoline expense, and parking stress.

A veteran brought his sweet retriever to the neighborhood weekly “Paws-itive Reading” program for children in the local public library. When MW’s daughter was busy reading to his furry friend, the veteran shared that for at least 5 years after his combat tours, he rarely left his window-shuttered home. His dog’s steady comfort re-established his ability to participate in his community. He now generously shares his dog’s patient affection with children learning to read.

MW recently witnessed the profound and protective presence of a service dog in comforting a veteran during a posttraumatic stress disorder (PTSD)–related crisis. The service dog offered a lean and reassuring paw pressure on the veteran’s shoulder if he was reexperiencing trauma. The dog’s steady breathing and familiar warmth helped to reorient their human companion to the safety of his present physical surroundings. Bearing witness to the dog’s trained interaction with the veteran left MW speechless. The trust between them was therapeutic in a way that transcended her ability to articulate what she experienced. This compelled MW to investigate whether this was a rare relationship or whether there was existing data on the impact of trained service dogs and PTSD.

Service dog placement with veterans with PTSD has been shown to have a positive influence on both physiological (arousal-related functioning and cortisol awakening response) and psychosocial well-being, including decreased isolation and increased physical activity.^1,2 Veterans with PTSD paired with service dogs showed significantly fewer PTSD-related symptoms, better sleep quality, and improved well-being, compared with those with just a pet.³ A recent meta-analysis revealed that veteran partnerships with a service dog had a clinically meaningful, significant, and large effect on PTSD severity scores (P < .001).² The mechanism for impact is thought to be not only the dog’s working role but also the transcendent loyalty of the canine-veteran bond.

Many accredited dog training programs describe a certain reciprocity to the dog-human relationship. Some use rescue puppies to give the dogs a new life and purpose. Dogs who have undergone challenges often need patience, time, safe relationships, and trustworthy new experiences to maximize their potential. Reciprocally, trained service dogs have the potential to foster access to these same emotional, relational, existential, and physical safety needs for veterans exposed to trauma.

Recent legislation has made progress in recognizing the role of service dogs for veterans and improving access. The Puppies Assisting Wounded Servicemembers (PAWS) for Veterans Therapy Act (38 USC §1705, 1714) was passed in 2021. The PAWS Act implemented a policy and 5-year pilot program to connect trained canines to eligible veterans diagnosed with PTSD as an element of an integrative health program, regardless of whether the veteran has a mobility impairment. The PAWS Act gives federal funding to accredited dog training organizations to help pair eligible veterans with service dogs by covering veteran travel expenses for the training, training program participation, and relevant veterinary expenses. The bipartisan Service Dogs Assisting Veterans Act (SAVES) Act was introduced this summer to award grants to nonprofit organizations Assistance Dog International has accredited to help these groups provide service dogs to veterans.

The US Department of Veterans Affairs (VA) has made strides in welcoming service dogs. Trained service dogs of all breeds under the control of a human companion are now allowed in VA facilities other than in areas where safety and infection control standards would be compromised (ie, sterile equipment rooms).⁴ A prescribing clinician can now evaluate eligible veterans to determine their ability, resources, and goals for having a service dog.⁵ An assessment of the veteran’s ability to care for a dog and education on expectations for the partnership is critical to success and animal welfare. Those veterans approved for a service dog are then referred to accredited agencies. The VA Veterinary Health Insurance Benefit includes aspects of coverage for the veteran to attend service dog training, veterinary wellness (preventive care, immunizations, dental cleanings, certain prescriptions, etc), and care for the dog’s illnesses when treatment enables the dog to perform duties in service to the veteran.⁶

The productive purpose and friendship of a service dog become a formidable force in a veteran’s life. Veterans spent an average of 82% of their time with service dogs (assessed via Bluetooth proximity between collar and smartphone).⁷ Human partners of veterans with service dogs may experience improved quality of life and relationship functioning with the inclusion of a service dog in the family unit.⁸ Veterans depict increased community engagement, social connectedness, and personal confidence as a result of the canine companionship.^9,10 Veterans with service dogs often speak of the ways the dog’s presence transformed their lives and many speak of the dog literally saving their lives.¹¹ Meta-analyses showed improved mental health treatment engagement, medication adherence, and decreased suicidality.^2,12

A story was recently shared with us about the compassion and competence of VA staff in a perioperative unit. A veteran was scheduled for a life-altering surgery and yet was anxious about entering the room for his scheduled pre-anesthesia check-in, knowing his service dog could not accompany him through the entire procedure. The staff recognized that the veteran was increasingly nervous and even started to question whether he would stay for the scheduled procedure they deemed would benefit his health. The perioperative team then proactively worked together to safely walk the veteran through the preparation processes in a sterile setting while keeping the dog within sight of the veteran. They then ensured that the veteran’s service dog was by his side early in the recovery room so that the veteran woke to wags and licks. In these months of canine recognition, we honor the ways the VA has fostered companionship and courage in veterans’ lives through the inclusion of service dogs in so many aspects of their care and life.