Antimicrobial Suppression Research Articles

Is there a role for suppression of infection in managing fracture-related infection following intra-medullary nailing?

BackgroundThe management of fracture-related infection has undergone radical progress following the development of international guidelines. However, there is limited consideration to the realities of healthcare in low-resource environments due to a lack of available evidence in the literature from these settings. Initial antimicrobial suppression to support fracture union is frequently used in low- and middle-income countries despite the lack of published clinical evidence to support its practice. This study aimed to evaluate the outcomes following initial antimicrobial suppression to support fracture union in the management of fracture-related infection. MethodsA retrospective review of consecutive patients treated with initial antimicrobial suppression to support fracture healing followed by definitive eradication surgery to manage fracture-related infections following intramedullary fixation was performed. Indications for this approach were; a soft tissue envelope not requiring reconstructive surgery, radiographic evidence of stable fixation with adequate alignment, and progression towards fracture union. ResultsThis approach was associated with successful treatment in 51/55 (93 %) patients. Fracture union was achieved in 52/55 (95 %) patients with antimicrobial suppression alone. Remission of infection was achieved in 54/55 (98 %) patients following definitive infection eradication surgery. Following antibiotic suppression, 6/46 (13 %) pathogens isolated from intra-operative samples demonstrated multi-drug resistance. ConclusionInitial antimicrobial suppression to support fracture healing followed by definitive infection eradication surgery was associated with successful treatment in 93 % of patients. The likelihood of remission of infection increases when eradication surgery is performed in a healed bone. This approach was not associated with an increased risk of developing multi-drug-resistant infections compared to contemporary bone infection cohorts in the published literature. Level of evidenceIV

IS THERE A ROLE FOR ANTIBIOTIC SUPPRESSION IN THE MANAGEMENT OF FRACTURE-RELATED INFECTION FOLLOWING INTRAMEDULLARY NAILING?

IntroductionThe management of fracture-related infection has undergone radical progress following the development of international guidelines. However, there is limited consideration to the realities of healthcare in low-resource environments due to a lack of available evidence in the literature from these settings. Initial antimicrobial suppression to support fracture union is frequently used in low- and middle-income countries despite the lack of published clinical evidence to support its practice. This study aimed to evaluate the outcomes following initial antimicrobial suppression to support fracture union in the management of fracture-related infection.Materials & MethodsA retrospective review of consecutive patients treated with initial antimicrobial suppression to support fracture healing followed by definitive eradication surgery to manage fracture-related infections following intramedullary fixation was performed. Indications for this approach were; a soft tissue envelope not requiring reconstructive surgery, radiographic evidence of stable fixation with adequate alignment, and progression towards fracture union.ResultsThis approach was associated with successful treatment in 51/55 (93%) patients. Fracture union was achieved in 52/55 (95%) patients with antimicrobial suppression alone. Remission of infection was achieved in 54/55 (98%) patients following definitive infection eradication surgery. Following antibiotic suppression, 6/46 (13%) pathogens isolated from intra-operative samples demonstrated multi-drug resistance.ConclusionsInitial antimicrobial suppression to support fracture healing followed by definitive infection eradication surgery was associated with successful treatment in 93% of patients. The likelihood of remission of infection increases when eradication surgery is performed in a healed bone. This approach was not associated with an increased risk of developing multi-drug-resistant infections compared to contemporary bone infection cohorts in the published literature.

Comparison of outcomes between fungal and non-fungal periprosthetic joint infections in total knee arthroplasty.

Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs.

The role of implant retention and conservative management in the management of fracture-related infection

Fracture-related infection (FRI) management has advanced considerably in recent years, offering new possibilities for predictable rates of infection eradication. Debridement, antibiotics, and implant retention (DAIR) procedures have shown promise in the treatment of early FRI. This article provides an overview of the principles and indications of DAIR, including the importance of meticulous debridement and the management of dead space. The outcomes of DAIR are discussed, highlighting the range of fracture union rates reported in the literature. The role of antimicrobial suppression in optimizing host biology and facilitating surgical intervention is also explored. While further research is needed to establish optimal treatment strategies, DAIR offers a valuable treatment approach for FRI when specific criteria are met. Level of evidenceIV.

The fate of fungal periprosthetic joint infection after total knee arthroplasty.

To demonstrate the clinical outcomes of patients with fungal periprosthetic joint infections (PJIs) after two-stage exchange arthroplasty combined with antifungal therapy. We retrospectively reviewed the outcomes of 41 patients with fungal PJIs after primary total knee arthroplasty (TKA) in a single centre from January 1999 to October 2017. During the first stage of resection arthroplasty, antifungal-impregnated cement spacers (AICSs) were implanted in all patients. After systemic antifungal treatment during the interval between the two surgeries, delayed reimplantation as part of a two-stage exchange protocol was performed when patients were clinically stable. We defined treatment success as a well-functioning arthroplasty without any signs of PJI after a minimum follow-up of two years without antimicrobial suppression. Successful treatment was confirmed by repeat negative cultures as well as a return of inflammatory markers to normal levels. The treatment success rate was 63.4% at the final follow-up. Thirty-six of 41 patients (87.8%) met the criteria for second-stage revision after confirmation of complete infection control. The mean prosthesis-free interval was 6.6 months (range, 2.0-30.0 months). During follow-up after two-stage exchange arthroplasty, ten patients (27.7% of 36 patients) unfortunately experienced recurrence or relapse of infection after an average of 31.3 months (range, 2.7-135.6 months). The rate of survivorship free from reinfection was 94.4% at six months, 84.8% at one year, and 73.6% at two years. Cox proportional hazard regression analysis demonstrated that the prosthesis-free interval (HR = 1.016, p = 0.037) and mean length of antifungal treatment (HR = 0.226, p = 0.046) were potential risk factors for failure. Fungal PJIs led to devastating clinical outcomes despite even two-stage revision arthroplasty with the use of AICSs and antifungal medications.

Chronic Suppressive Antibiotic Treatment for Staphylococcal Bone and Joint Implant-Related Infections.

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6-max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

Experience with dalbavancin for long-term antimicrobial suppression of left ventricular assist device infections.

Left ventricular assist devices (LVAD) are a common strategy for management of end-stage heart failure. LVADs carry a risk of infection of the implanted device components, and skin flora are commonly implicated. Long-term antibiotics may be needed for management of deep device infection or recurrent superficial infections. In appropriately selected patients, dalbavancin can be a feasible option given its extended dosing interval. This is a retrospective, single-center review of patients presenting with an LVAD infection between January 2011 and November 2022, where management included the use of dalbavancin. Data regarding LVAD placement, details of index infection, dalbavancin use and outcomes was obtained from chart review, and documented in a RedCap database. The mean time from LVAD placement to index infection was 131.6 weeks (standard deviation 87.2 weeks). The most common targeted organism was Corynebacterium striatum in six of 10 patients. Index infection presented as deep driveline infection in four patients and recurrent superficial driveline infection in three patients. Five patients had a concurrent bloodstream infection. Dalbavancin was discontinued in two patients due to breakthrough infection, with one patient requiring surgical intervention. No drug-related adverse events were noted. Dalbavancin is an attractive option in the management of long-term LVAD infection in patients for whom alternative oral or parenteral antibiotics are not a feasible option. Additional studies are needed to determine the optimal dosing of dalbavancin in this setting, and to study adverse events and long-term outcomes of dalbavancin.

985. Practice Patterns of Antimicrobial Suppression Therapy in Total Knee Arthroplasty Infections

Abstract Background There are no current established guidelines for the role of antimicrobial suppression therapy in management of prosthetic joint infection (PJI). In 2013, the IDSA provided initial treatment guidelines for PJI but did not address suppressive therapy. The guidelines do not address suppressive therapy beyond the initial 4-6 weeks for non-staphylococcal infections nor do they address suppressive therapy after 3-6 months of treatment for Staphylococcal infections. Practitioners must delicately balance the risk of PJI recurrence and the negative effects of continued antibiotic therapy including toxicity and resistance. In this study, we surveyed Infectious Disease providers to better understand their antimicrobial suppression practice patterns in different clinical scenarios. Methods We surveyed Infectious Disease providers across the United States from April 2022 to May 2022. We received 78 unique response from 31 different states. Basic demographic data was obtained. Providers presented six multiple choice clinical scenarios and were asked if they would start suppressive therapy and the duration of suppressive therapy. Results The preliminary data revealed that practice patterns vary greatly amongst providers in the management of antibiotic suppressive therapy in PJI. Of the 6 scenarios, only half had greater than 50% consensus (50.6%, 51.3% and 70.1%). Scenario 1 involved a patient who underwent a single stage revision. It was of particular interest as 51.3% of providers indicated they would stop antimicrobial therapy and 48.7% indicated they would extend antimicrobial therapy with 25.6% electing for lifelong suppressive therapy. Conclusion Practice patterns for antimicrobial suppression therapy in knee PJI varies significantly among providers. Even with IDSA guidelines addressing Staphylococcal PJI, the practice patterns among infectious diseases providers still varied greatly especially with regards to single stage revisions. Additional randomized controlled trials examining the best way to manage antimicrobial suppression in PJI would be helpful, and would allow for development of evidence-based guidelines. We also plan to survey orthopedic surgeons using the same clinical scenarios to see if there is a difference in management styles. Disclosures All Authors: No reported disclosures.

2021. Efficacy of Chronic Antimicrobial Suppressive Therapy in Ventricular Assist Device Infections

Abstract Background Ventricular assist devices (VAD) prolong life expectancy or serve as a bridge to heart transplant in end stage heart failure but are not without risks. These patients are at high risk for device-related infections with a propensity for relapse. Indications and efficacy of chronic antimicrobial suppression (CAS) to prevent relapse are not well defined. Methods We conducted a retrospective study of all adult patients with VAD infections at our institution between 1/1/2013 and 10/31/2020. VAD-specific or VAD-related infections were defined by the International Society for Heart and Lung Transplantation criteria. Patients were stratified by receipt of CAS or no CAS after completing index infection treatment. Relapsed infections were defined as those recurred at the same site caused by the same organism seen in the index infection. Time-to-relapse infection was defined as the time in days between the index infection and first relapse. The primary outcome was CAS efficacy measured by time-to-relapse in VAD-specific or -related infections. Results A total of 83 patients were included with a documented VAD-specific (n = 68) or VAD-related (n = 15) infection. Driveline (n = 66) and bloodstream (n = 13) infections were the most common VAD-specific and VAD-related infections, respectively. For the index infection, all patients received antimicrobial treatment and 16.4% required incision and drainage. Staphylococcus aureus was most frequently isolated in 46 cases. Oral minocycline was the most commonly utilized agent in 22 of 47 patients receiving CAS. Agent-specific CAS efficacy was unable to be assessed due to the small sample. In patients who received CAS, 57% experienced a relapse infection compared to 81% in patients not receiving CAS (p = 0.03). The median time to relapse was 151 days (IQR 78-247) and 57 days (IQR 36-114) in the CAS and non-CAS groups, respectively (p &amp;lt; 0.01). Conclusion The incidence of relapse infection in the setting of CAS was lower compared to those not receiving CAS. Patients receiving CAS were relapse-free for a significantly longer duration. Larger studies are warranted to assess if one agent confers a benefit over another. Disclosures M. Rizwan Sohail, MD, Aziyo Biologics: Honoraria|Boston Scientific Corporation: Honoraria|Medtronic: Grant/Research Support|TRYX: Grant/Research Support.

Chronic Antibiotic Suppression for Nonstaphylococcal Prosthetic Joint Infections Treated with Debridement or Implant Retention

Background: Early postoperative and acute prosthetic joint infection (PJI) may be managed with debridement, antibiotics, and implant retention (DAIR). Among patients with nonstaphylococcal PJI, an initial 4–6-week course of intravenous or highly bioavailable oral antibiotics is recommended in the Infectious Diseases Society of America (IDSA) guidelines, with disagreement among committee members on the need for subsequent chronic oral antimicrobial suppression (CAS). We aimed to characterize patients with nonstaphylococcal PJI who received CAS and to compare them to those who did not receive CAS. Methods: This retrospective cohort study included patients admitted to Veterans’ Affairs (VA) hospitals from 2003 to 2017 who had a PJI caused by nonstaphylococcal bacteria, underwent DAIR, and received 4–6 weeks of antimicrobial treatment. PJI was defined by Musculoskeletal Infection Society (MSIS) 2011 criteria. CAS was defined as at least 6 months of oral antibiotics following initial treatment of the PJI. Patients were followed for 5 years after debridement. We used χ2 tests and t tests were used to compare patients who received CAS with those who did not receive CAS. Results: Overall, 561 patients had a nonstaphylococcal PJI treated with DAIR, and 80.6% of patients received CAS. The most common organisms causing PJI were streptococci. We detected no significant differences between patients who received CAS and those who did not receive CAS, except that modified Acute Physiology and Chronic Health Evaluation (mAPACHE) scores were higher among patients who did not receive CAS (Table 1). Conclusion: Patients not on CAS were more severely ill (by mAPACHE) than those on CAS. Otherwise, the 2 groups were not different. This finding was contrary to our hypothesis that patients with multiple comorbidities or higher mAPACHE scores would be more likely to get CAS. A future analysis will be conducted to assess treatment failure in both groups. We hope to find a specific cohort who may benefit from CAS and hope to deimplement CAS in others who may not benefit from it.Funding: NoDisclosures: None

Treatment and Outcomes of Aortic Graft Infections Using a Decision Algorithm

Aortic graft infection (AGI) is a rare but devastating complication requiring both explant of the infected prosthesis and lower extremity revascularization. Despite a variety of methods to treat AGI, there is a paucity of evidence that describes comparative outcomes. Moreover, controversy exists surrounding what the optimal repair strategy is with limited descriptions of how these techniques should be employed in this complex group of patients. Therefore, the purpose of this analysis was to review our experience with AGI management while highlighting a practice philosophy that can achieve acceptable outcomes. All AGI patients between 2002-2019 were reviewed. The primary end-point was 30-day mortality. Secondary end-points included complications, re-infection, unplanned re-operation and all-cause mortality. Kaplan-Meier methodology was used to estimate time to events. Cox regression models were employed to identify association between patient factors and operative strategy with survival. Subgroup analysis included outcome comparison among four different operative approaches(extra-anatomic bypass with aortic ligation [EAB] and in-situ reconstruction [ISR] using either NAIS, cryopreserved allograft [Cryo], or antibiotic-soaked prosthetic grafts [Other]). 142 patients (male-69%, mean age 67 ± 11 years) were reviewed. Median time to AGI presentation was 52 (IQR 16-128) months. ISR was performed in 70% (n = 99)[ISR: NAIS-49% (n = 49), Cryo, 33% (n = 33) and Other-23% (n = 23)]. EAB was used in 26% (n = 37), of which 57% (n = 21) were staged repairs[no reconstruction, 4%: intraoperative death-2, AGI removal without reconstruction-2]. A graft enteric erosion/fistula was identified in 39% (n = 55). Mean follow-up time was 14 ± 27 (median 2.2[IQR 0.1-16]) months. Overall, 30-day mortality was 21% and 69% (n = 98) experienced a complication. The most common complications were pulmonary (35%;n = 50), vascular (28%;n = 39), gastrointestinal (22%;n = 31) and renal (21%;n = 30). Freedom from re-infection at one and three years was 78 ± 5% and 73 ± 6% while freedom from unplanned re-operation was 50 ± 5% and 40 ± 6%, respectively. Corresponding one- and five-year freedom from all-cause mortality was 67 ± 4% and 53 ± 4%. When stratified by the four different repair strategies, unadjusted rates of postoperative complications and mortality were not different. However, EAB patients had more renal complications. All-cause mortality predictors included age (HR 1.04, 95%CI 1.01-1.1; P = 0.003), CHF (HR 2.7, 1.3-5.7; P = 0.01), and graft enteric erosion/fistula (HR 2.2, 1.3-3.8;P = 0.005) while total graft excision was protective (HR 0.34, 0.2-0.7; P = 0.003). AGI repair, regardless of operative strategy, results in significant early morbidity, and mortality. The need for unplanned re-operation is common; however, long-term survival is acceptable in appropriately selected patients. Re-infection risk mandates life-long surveillance and consideration of indefinite anti-microbial suppression in certain subgroups. Due to the complexity and intensity of care, all AGI should be treated, when possible, at centers performing high-volume aortic surgery.

Efficacy and safety of chronic antimicrobial suppression therapy for left ventricular assist device driveline infections: A single-center descriptive experience.

Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short-term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized. To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N=219) receiving care at our tertiary transplant center with continuous-flow LVADs placed between August 2007 and July 2019. A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486days (range 48-2287days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy. Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression.

P153 MET642, AN ORAL FXR AGONIST, IMPROVES COLITIS INDUCED BY ADOPTIVE T-CELL TRANSFER

Abstract Introduction Farnesoid X receptor (FXR) is a ligand-activated nuclear hormone receptor expressed in the gastrointestinal tract, with high expression levels in the intestinal epithelium. Previously we have shown that FXR agonists with sustained activity decreased colitis in multiple chronic IBD models (i.e. Adoptive transfer colitis, Mdr1a-/- colitis, and SAMP1/YitFc ileitis). Because FXR agonists are dosed orally and do not have systemic immunosuppressive properties, they represent a novel and differentiated therapeutic approach for IBD. MET642 is an optimized, potent non-bile acid FXR agonist with sustained FXR activation. In this study, we examined the efficacy of MET642 in therapeutic treatment mode in adoptive T-cell transfer model. Methods Colitis was induced by transplanting CD4+CD45RBhi T-cells to recipient C.B-17 SCID mice. Body weights were monitored throughout study duration. Staring 21 days after T-cell transfer, mice were treated with vehicle (n=10), MET642 (0.1, 0.3 or 1 mg/kg p.o., daily, n=10), or anti-IL-12p40 (neutralizing both IL-12 and IL-23, 0.5mg/mouse, i.p., weekly, n=5) for 4 weeks. Terminal endpoints included colon weight to length ratio (W/L), colon histopathology and gene expression. Histopathology scores were determined for inflammation, erosion, gland loss and hyperplasia, each with a score of 0–5, and cumulative sum score of 0–20. Results CD4+CD45RBhi T-cell transfer led to a significant reduction in body weight and increase in colon W/L ratio; both were reversed by MET642 and anti-IL-12p40. All dose levels of MET642 significantly improved the histopathology sum score relative to vehicle treatment, with maximal efficacy reached at 0.3mg/kg. Similar to anti-IL-12p40, MET642 showed improvements across all individual histopathology endpoints. Gene expression analysis suggests FXR activation increases anti-microbial activity, improves gut barrier and transporter function, and suppresses inflammation. Conclusion MET642, an oral once daily FXR agonist, significantly improved colitis in the adoptive T-cell transfer model. Activation of FXR by MET642 potentially promotes pathways of gut anti-microbial function, barrier function, and suppression of inflammation. These findings support further development of MET642 as a novel oral therapeutic for treating IBD.

Epidemiology of Left Ventricular Assist Device Infections: Findings From a Large Nonregistry Cohort.

Infection is a major complication during circulatory support with a left ventricular assist device (VAD). Changes in device characteristics and treatment practices in the last decade can affect the epidemiology of infection. The International Society for Heart and Lung Transplantation (ISHLT) has published recommendations on the prevention and management of VAD infections, but data to support these recommendations remain sparse. We performed a retrospective review of 455 patients who underwent VAD placement from 2009 to 2015. Infection episodes were defined using ISHLT criteria and were also grouped as endovascular or local. Analysis included descriptive statistics. There were 174 patients (38.6%) with a VAD infection. Infection incidence was 36.9 cases per 100 person-years of VAD support. The driveline was the most common infection site (67.2%). Systemic inflammatory response syndrome (SIRS) criteria were not satisfied in 29.2% of patients with endovascular infections, and computed tomography (CT) examinations were normal in 37.7% of cases. Gram-positive bacteria caused 65.6% of infections in patients with an available culture. Antimicrobial suppression was used in 72.3% of patients who survived treatment. Median survival after infection was 35 months for patients with VAD-related infections versus 14 months for patients with VAD-specific infections. VAD infections continue to be a major complication after implantation. Clinical criteria alone were not predictive of serious infections, and many patients with confirmed infection had normal CTs. Patients with VAD-specific infections had lower median survival than patients with VAD-related infections.

The direct anterior approach: treating periprosthetic joint infection of the hip using two-stage revision arthroplasty.

Either one- or two-stage revision arthroplasties can be used for the treatment of chronic periprosthetic joint infection (PJI) after total hip arthroplasty (THA). We report our results following two-stage revision surgery performed through the direct anterior approach (DAA) interval using a custom-made articulating spacer. Between 2009 and 2014, 49 patients (49 consecutive procedures) had surgery through either a DAA or extended DAA approach. Each patient received perioperative intravenous administration of antibiotics. A custom-made spacer was implanted after explanting cup and stem and following extensive debridement. Broad-spectrum antibiotics were administered during the immediate perioperative period and then adjusted according to the infecting organism. Complication rates and eradication rates were observed. WOMAC patient assessments were administered preoperatively and one-year postoperatively. Of the 49 study patients, five had a recurrence of the infection after the second-stage revision, five had a proximal periprosthetic fracture during the first stage procedure and one patient had a transient femoral nerve palsy that resolved fully within the first postoperative year. 30 different microorganisms were identified on intraoperative specimens. The average time between first and second stage procedure was 65.7days (range 21-132days). Eradication of infection was defined as healed wound without fistula, no drainage, no recurrence of the infection, no subsequent surgical intervention for persistent or perioperative infection after second stage revision and no long-term (> 6months) antimicrobial suppression therapy. Eradication rate of infection in our study was 89.8%. Postoperative WOMAC scores improved significantly CONCLUSION: The preliminary clinical results for the custom-made spacer technique implanted through the DAA are promising. Therefore, we believe the DAA can be used safely as a standard operative approach for two-stage revision procedures.

New Molecules for Treating Resistant Hypertension: a Clinical Perspective.

To review the findings of trials evaluating pharmacological treatment approaches for hypertension in general, and resistant hypertension (RH) in particular, and propose future research and clinical directions. RH is defined as blood pressure (BP) that remains above target levels despite adherence to at least three antihypertensive medications, including a diuretic. Thus far, clinical trials of pharmacological approaches in RH have focused on older molecules, with spironolactone being demonstrated as the most efficacious fourth-line agent. However, the use of spironolactone in clinical practice is hampered by its side effect profile and the risk of hyperkalaemia in important RH subgroups, such as patients with moderate-severe chronic kidney disease (CKD). Clinical trials of new molecules targeting both well-established and more recently elucidated pathophysiologic mechanisms of hypertension offer a multitude of potential treatment avenues that warrant further evaluation in the context of RH. These include selective mineralocorticoid receptor antagonists (MRAs), aldosterone synthase inhibitors (ASIs), activators of the counterregulatory renin-angiotensin-system (RAS), vaccines, neprilysin inhibitors alone and in combined formulations, natriuretic peptide receptor agonists A (NPRA-A) agonists, vasoactive intestinal peptide (VIP) agonists, centrally acting aminopeptidase A (APA|) inhibitors, antimicrobial suppression of central sympathetic outflow (minocycline), dopamine β-hydroxylase (DβH) inhibitors and Na+/H+ Exchanger 3 (NHE3) inhibitors. There is a paucity of data from trials evaluating newer molecules for the treatment of RH. Emergent novel molecules for non-resistant forms of hypertension heighten the prospects of identifying new, effective and well-tolerated pharmacological approaches to RH. There is a glaring need to undertake RH-focused trials evaluating their efficacy and clinical applicability.

Long-term antimicrobial suppression prevents treatment failure of streptococcal periprosthetic joint infection

To evaluate the effect of oral antimicrobial suppression on the outcome of streptococcal periprosthetic joint infection (PJI). Consecutive patients with streptococcal PJI receiving antimicrobial suppression for >6 months were prospectively included and compared to a retrospective control group without suppression. Outcome was assessed with Kaplan-Meier analysis and compared by the log-rank Mantel-Cox test. Multivariate analysis was used to identify factors associated with treatment failure. Of 69 streptococcal PJI episodes (37 knee, 31 hip and one shoulder PJI), 43 (62%) were caused by beta-hemolytic streptococci and 26 (38%) by viridans group streptococci. Debridement and prosthesis retention was performed in 27 (39%), one-stage exchange in 5 (7%), multi-stage exchange in 31 (44%) and prosthesis removal in 6 patients (9%). 24 patients (35%) were treated with antimicrobial suppression receiving oral amoxicillin (n = 22), doxycycline (n = 1) or clindamycin (n = 1). After a median follow-up of 13 months (range, 0.5-111 months), 38 of 65 patients (58%) were infection-free. Suppressive antimicrobial treatment was associated with higher success rate compared with no suppression (93% vs. 57%, p = 0.002), representing the only significant independent factor preventing treatment failure. Long-term antimicrobial suppression was associated with significantly better treatment outcome and should be strongly considered in streptococcal PJI.

Epidemiological and clinical features of prosthetic joint infections caused by gram-negative bacteria.

To review the clinical literature focusing on epidemiology, clinical presentation and outcomes of prosthetic joint infections (PJIs) due to gram-negative bacteria (GNB) and to report the experience of a multicentric cohort. A retrospective, observational, cohort study was performed in three Italian hospitals. All consecutive PJIs caused by GNB over a 12-year period (from May 2007 to March 2018) were enrolled. Epidemiological, clinical, microbiological and therapeutic features were described. Factors related to treatment failure (defined as the occurrence of death, amputation or starting long-term antimicrobial suppression therapy) were analysed with a Cox regression model. A total of 82 PJIs due to GNB (42.7% men; median age 73 years) were studied. The implants included 65 (79.3%) hip, 16 (19.5%) knee and one (1.2%) shoulder. An early PJI was diagnosed in 16.2% of patients, a delayed PJI in 29.4% and a late PJI in 54.4%. The most common isolated organisms were Escherichia coli (21.7%) and Pseudomonas spp. (20.9%). 13.4% of the isolates were carbapenem-resistant bacteria (CRB). In 53.8% of cases a two-stage exchange arthroplasty was performed and in 32.5% a Girdlestone excision arthroplasty. The average therapeutic failure occurred in 17.7% of cases. The therapeutic failure rate of the two-stage was 10%. PJI due to CRB was identified as a potential risk factor for failure (aHR 4.90; IC 95%, 0.96-25.08; p=0.05). The therapeutic failure rate in the CRB group was 50%. The treatment with the two-stage procedure for PJIs caused by GNB seems to be associated with a low rate of failure, while PJI due to CRB seems to be related to the worst outcome.

Destination Joint Spacers, Reinfection, and Antimicrobial Suppression

In this cohort of 51 patients managed with retained "destination spacers" after the resection of infected joint prostheses, the presence of preoperative sinus drainage was significantly associated with reinfection. Chronic antimicrobial suppression after destination-spacer retention did not significantly prevent reinfections.

322. Joint Spacer Retention, Antimicrobial Suppression, and Risk of Re-infection

BackgroundTwo-stage exchange is the standard treatment of periprosthetic joint infection in the United States. Occasionally, for selected patients, temporary antibiotic-loaded spacers are retained “permanently” instead of proceeding with prosthesis re-implantation. It is unclear whether the “retained” spacer represents a nidus for re-infection, and would require secondary antibiotic suppression to prevent recurrence of infection. We aim to determine the risk of re-infection among patients with retained knee and hip spacers, and assess the role of antibiotic suppression.MethodsWe identified 51 patients with retained static or articulating knee (n = 34) and hip (n = 17) spacers between 1996 and 2014 using the Mayo Clinic Hospital Orthopedic database. Medical records were reviewed to collect clinical data, including antibiotic use and offending organisms. We compared the cumulative incidence of reinfection between those with or without suppression using a competing risk model, with death and revision for mechanical failure as competing risks.ResultsThe median age was 77 years (range, 48–94). Gender distribution was equal. The median Charlton Comorbidity Index (CCI) was 3 (1–11), while median BMI was 30.1 (17.8–59.5). Eleven of 51 patients received antibiotic suppression after spacer retention. A history of prior antibiotic suppressive therapy was the only variable associated with being placed back on antibiotic suppression after spacer retention [OR 18 (95% CI 3.2–100)]. During the median follow-up period of 31.3 months, there were five re-infections. The cumulative incidence of re-infection was not significantly different between suppressed and unsuppressed groups (P = 0.89). The re-infecting pathogens were different from the index offending organisms. Only the presence of preoperative draining sinus was significantly associated with re-infection [OR 10 (95% CI 1–99.6)].ConclusionIn selected patients where a second-stage prosthesis re-implantation is not an option, and retention of “temporary” antibiotic loaded spacer is surgically preferred, the risk of re-infection was not prevented by prolonged antibiotic suppression. The presence of a draining sinus was significantly associated with re-infection, often with new pathogens.Disclosures All authors: No reported disclosures.