Antibiotic Suppression Research Articles

1040. Knee Explant Analysis (KnEA) Using PLG0206 in Periprosthetic Joint Infection (KnEA Study)

BackgroundPLG0206 is a novel engineered cationic antimicrobial peptide being evaluated for treatment of prosthetic joint infections (PJI). This study evaluated the rapid bactericidal activity of PLG0206 to decrease biofilm and planktonic bacteria on ex vivo infected prosthesis following removal from patients with chronic PJI.MethodsDe-identified infected prosthetics were removed from nine patients with PJI, despite chronic suppressive oral antibiotics, during a 2-stage revision procedure. Removed prosthetics were then submersed ex vivo to an expected clinical exposure of PLG0206, 1 mg/mL, for ~15 minutes. Upon completion of the 15-minute exposure, the treated explant was placed into buffer and sonicated. The sonication solution was then plated for bacterial analysis including colony forming unit (CFU) enumeration. Remaining explanted implants from the same patient served as a control and was processed similarly but without exposure to PLG0206.ResultsAs shown in the Table, both Gram-positive and Gram-negative bacteria were identified from removed prosthetics during a 2-stage revision procedure of chronic PJI. Eight of ten infected prosthetics treated ex vivo to PLG0206 1 mg/mL were sterilized (No. 1-5, 8-10). Of the two infected prosthetics that were not sterilized (No. 6 and 7), one was polymicrobial (No. 6) and the other was monomicrobial (No. 7). Collectively, infected prosthetics exposed to PLG0206 demonstrated a mean 4log10 reduction (range 2 to 7).Summary of culture and CFU log reduction among infected prosthetics exposed and not exposed to PLG0206 Table: Summary of culture and CFU log reduction among infected prosthetics exposed and not exposed to PLG0206ConclusionOverall, these findings support the ongoing development of PLG0206 as a local irrigation solution at 1 mg/mL concentration in the wound cavity for 15 minutes in patients undergoing treatment of a PJI occurring after total knee arthroplasty.Disclosures David Huang, MD, PhD, Peptilogics (Employee) Nicholas Pachuda, DPM, Peptilogics (Employee) Despina Dobbins, BS, Peptilogics (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Kenneth Urish, MD, PhD, Peptilogics (Grant/Research Support)

196. Increasing Bacteremia and Endovascular Infections due to Serratia marcescens: Implications for Evaluation and Treatment

Abstract Background While Serratia marcescens can cause bloodstream infections (BSI), endocarditis or other endovascular infections are historically rare and typically due to injection drug use (IDU). Given the rise in IDU nationwide, and limited evidence for managing non-HACEK gram-negative endocarditis, we examined trends in the epidemiology of Serratia BSI and characterized management strategies. Methods Our study was a retrospective analysis of adults admitted to UNC Health, a hospital network in North Carolina, from Apr 2014 to Mar 2021 with Serratia bacteremia. We used EMERSE, a program that searches free text in clinical notes, to identify those with ‘Serratia’ and either ‘bacteremia’ or ‘endocarditis’. This helped identify patients with microbiology obtained at outside hospitals. We performed chart review to confirm the Serratia BSI and collect demographic and clinical data. We tabulated yearly hospitalizations (Apr 1 to Mar 31), proportions of endovascular infections (endocarditis, cardiac device, vascular grafts), and described demographics and treatment approaches. Results We identified 97 patients by EMERSE and included 66 in analysis (Fig 1). 21 (32%) had endovascular infections and 21 (32%) overall were due to IDU (Table). Endovascular infections and BSIs increased over the period (Fig 2). Until 2018-2019, there were 0-10 Serratia BSIs yearly. In the final year, there were 37, 13 (37%) of which were endovascular infections. While we did not limit to S. marcescens, no other species were seen. 59/61 (97%) isolates with 3rd generation cephalosporin susceptibility reported were sensitive. 17/21 endovascular infections were endocarditis. 10/17 (59%) patients underwent valve replacement and 8/21 (38%) received dual antibiotic therapy for ≥ 6 weeks. Of the 10 attending infectious diseases follow-up visit, 6 were prescribed oral suppressive antibiotics after parenteral therapy. Figure 2. Serratia bloodstream infections (2014-2021) Table 1. Characteristics of Serratia bloodstream infections Conclusion Serratia BSI and endovascular infections are markedly increasing, with a large component due to IDU. Given the high proportion of endocarditis, echocardiography may be considered for patients with Serratia BSI, particularly those with IDU or prosthetic material. Further studies are needed to confirm this phenomenon and to establish evidence for optimal management of Serratia endocarditis. Disclosures Asher J. Schranz, MD, United HealthCare (Other Financial or Material Support, Spouse provides scientific review)

92. Clinical Decision-Making about Chronic Antibiotic Suppression after Prosthetic Joint Infection Treatment: Qualitative Insights for Antibiotic Stewardship

BackgroundPatients who develop prosthetic joint infections (PJI) may be prescribed chronic antibiotic suppression (CAS) ( > 6 months of antibiotics) after initial antibiotic treatment for the PJI. Patients at low risk of recurrent infection may be good targets for antibiotic stewardship. De-implementation of CAS could potentially reduce the emergence of antibiotic resistant organisms and decrease antibiotic-associated adverse events. Our ongoing study aims to characterize clinical decision-making processes about CAS prescribing and identify points for antibiotic stewardship interventions to stop CAS prescribing for patients who will not benefit.MethodsWe conducted semi-structured interviews with 33 physicians and nurses at 8 Veterans Affairs hospitals, chosen for variation in hospital size, complexity, region, and CAS prescribing. Interviewees included orthopedic surgeons, infectious disease (ID) physicians, hospital epidemiologists, nurses, nurse managers, and primary care physicians (PCPs). We conducted inductive, consensus-based thematic analysis on interview transcripts, using the program MAXQDA.ResultsParticipants reported a complex decision-making process that included a range of collaborative approaches with other clinicians and patients. Their risk-benefit calculation for CAS usually included the type of revision surgery performed, the evidence base, the organism, and patient factors. Surgeons and ID physicians, the primary CAS prescribers, collaborated variably and sometimes consulted pharmacists or antibiotic stewards. Participants emphasized the importance of clinician autonomy and buy-in to order to effect practice change based on evidence, rather than top-down policies. They identified other significant time points that occurred before or after the CAS prescribing decision (initial PJI treatment decisions, follow-up appointments) and identified other decision makers about CAS maintenance (e.g., patients, PCPs). (See Figure 1).Figure 1. Decision Points Relevant to Prescribing or Maintenance of Chronic Antibiotic Suppression after PJI. PJI, prosthetic joint infection; ID, Infectious Diseases physician; PCP, primary care physician; IV, intravenous ConclusionInterventions to optimize CAS prescribing should incorporate clinician concerns about prescriber autonomy and a preference for collaborative decision-making as well as understanding the range of decision makers across time.Disclosures Daniel Suh, MS MPH, General Electric (Shareholder)Merck (Shareholder)Moderna (Shareholder)Smile Direct Club (Shareholder) Bruce Alexander, PharmD, Bruce Alexander Consulting (Independent Contractor) Andrew Pugely, MD, MBA, Globus Medical (Research Grant or Support)Medtronic (Consultant)United Healthcare (Consultant) Marin Schweizer, PhD, 3M (Grant/Research Support)PDI (Grant/Research Support)

235. Outcomes Associated with Extended Oral Antibiotic Prophylaxis After 2-Stage Exchange Surgery to Prevent Recurrent Prosthetic Joint Infection

Background2-stage exchange (2SE) surgery is often used to treat chronic prosthetic joint infections (PJI). IDSA guidelines do not recommend oral antibiotic suppression after 2SE. However, a recent randomized trial suggested that oral antibiotics for 3 months after arthroplasty reimplantation may prevent recurrent PJI. Objective: To compare rates of treatment failure (i.e., recurrent PJI) and adverse reactions (ARs) among patients who received < 1 month of antibiotics directly after reimplantation to those who received 1-3 months of antibiotics following reimplantation (extended antibiotics). MethodsThis retrospective cohort study included patients with hip, knee, or shoulder PJI who underwent 2SE at 83 VA hospitals between the years 2003-2017. PJI was defined using administrative codes and microbiology data. Patients were followed for 5 years to assess treatment failure (TF) and ARs. TF was defined as recurrent PJI, debridement, or reoperation. ARs included Clostridioides difficile infections (CDI), or antibiotic associated diarrhea (AAD) during or 72 hours after antibiotics. Chi-square tests were used to compare outcomes. Cumulative incidence function curves were created to compare TF rates between those who did and did not receive extended antibiotic treatment, incorporating the competing risks of TF and death.ResultsOf the 433 patients, most (97%) received < 1 month of oral antibiotics and 3% received extended antibiotics. The 15 patients who received extended antibiotics had similar rates of TF and ARs compared with patients who received < 1 month of oral antibiotics (Table). However, there was a trend toward higher rates of CDI (6.7% vs. 3.8%) and AAD (13.3% vs. 9.6%) among those who received extended antibiotics. There was no difference in TF comparing extended antibiotics with < 1 month of antibiotics, accounting for death (Figure). Table: Treatment Failure and Adverse Reactions Among Those Who Did and Did Not Receive Extended Antibiotics ConclusionFew patients received extended oral antibiotics in the study period. There were no statistically significant differences in TF or ARs between the 2 groups. Yet, there was a trend toward higher rates of ARs among the extended antibiotic group. Future prospective studies should assess both the potential benefits and ARs associated with extended antibiotics among patients undergoing 2SE surgery.Disclosures Marin L. Schweizer, PhD, 3M (Grant/Research Support)PDI (Grant/Research Support) Bruce Alexander, PharmD, Bruce Alexander Consulting (Independent Contractor) Daniel Suh, MS MPH, General Electric (Shareholder)Merck (Shareholder)Moderna (Shareholder)Smile Direct Club (Shareholder) Aaron J. Tande, MD, UpToDate.com (Other Financial or Material Support, Honoraria for medical writing) Andrew Pugely, MD, MBA, Globus Medical (Research Grant or Support)Medtronic (Consultant)United Healthcare (Consultant)

254. Excellent Outcomes with Oral Versus Intravenous Antibiotics for Bone and Joint Infections: A Single-Center Experience

Abstract Background The OVIVA trial, published in 2019, demonstrated equivalent efficacy of oral (PO) versus intravenous (IV) antibiotics for bone and joint infections. We report our group’s one-year outcomes in a cohort of such patients who received PO or IV antibiotics. Methods Our orthopedic surgery and orthopedic infectious diseases (ID) groups agreed to employ early switch to PO in patients with a first episode of non-vertebral osteomyelitis (OM), native or prosthetic joint infection (NJA or PJI), or hardware infections when a pathogen susceptible to highly bioavailable antibiotics had been identified and the patient was perceived to be at low risk for medication non-adherence. We reviewed patients 19+ years old seen in the Ortho ID clinic for one of these conditions from July 1st through December 31st, 2019. Data recorded included patient demographics and comorbidities, infection type and site, microbiology, and surgical and antibiotic management. Primary outcome was treatment failure at 1 year, defined as death, unplanned surgery at same site, or chronic antibiotic suppression. Results Forty patients (all IV antibiotics, n=17; initial or switch to PO, n=23) were included. Median IV duration was 15 days. PJI was the most common diagnosis (n=22), followed by other hardware infection and OM (n=7 each). Of the PJIs, 13/22 were managed with 2-stage exchange and 11/13 of these received all-IV therapy. Of the hardware infections, 4/7 underwent debridement and retention or single-stage exchange and all of these received initial or switch to PO therapy. Staphylococci (n=14 S. aureus and n=7 coagulase-negative) and streptococci (n=12) were the most common pathogens. Amoxicillin (n=8), trimethoprim-sulfa (n=6), and levofloxacin (n=3) were the most-used PO antibiotics. The PO group received longer treatment (mean 67 vs 48 days). No treatment failures occurred in the patients who started or switch to PO antibiotics, whereas 35% of patients who received all-IV therapy experienced failure. Conclusion Adopting known risk factors for poor outcome in bone and joint infection such as prior treatment failure and no identified pathogen as exclusion criteria for early switch to PO antibiotic therapy led to excellent one-year treatment outcomes across a range of musculoskeletal infections. Disclosures Angela Hewlett, MD, MS, Mapp Biopharmaceutical (Scientific Research Study Investigator) Angela Hewlett, MD, MS, Mapp Biopharmaceutical, Inc (Individual(s) Involved: Self): Scientific Research Study Investigator Nicolas W. Cortes-Penfield, MD, Nothing to disclose

111. Duration of Antibiotic Therapy after Debridement and Implant Retention in Patients with Periprosthetic Joint Infections

BackgroundDebridement, antibiotics, and implant retention (DAIR) is appropriate for select acute postoperative and hematogenous periprosthetic joint infections (PJIs). However, the optimal duration of antimicrobial therapy in patients treated with DAIR has not been defined. Therefore, we aimed to identify the ideal duration of parenteral and oral antibiotics after DAIR. MethodsWe performed a retrospective study of patients >18 years of age with hip or knee PJI managed with DAIR between January 1, 2008, and December 31, 2018, at Mayo Clinic. PJI was defined using criteria adapted from the International Consensus Meeting on PJI. The outcome was defined as either PJI recurrence or unplanned reoperation due to infection. Joint-stratified Cox proportional hazards regression models with time-dependent covariates were used to assess nonlinear effects of antibiotic duration. Hazard ratios were computed based on prespecified time points for comparison, whereas p-values represented the overall effect across the entire range of durations.ResultsThere were 247 unique episodes of PJI in 237 patients during the study period. Parenteral antibiotics were given in 99.2% of cases (n=245). This was followed by chronic oral antibiotic suppression in 92.2% (n=226) with a median duration of 2.2 years (1.0-4.1).DAIR failed in 65 cases over a median follow-up of 4.4 years, with a 5-year cumulative incidence of 28.1%. After adjustment for risk factors, there was no significant association between duration of parenteral antibiotics and treatment failure (p=0.203), with no difference between four versus six weeks (HR 1.11; 95% CI 0.71-1.75) (Figure 1). However, both use and longer duration of oral antibiotic therapy was associated with a lower risk of failure (p=0.006). To account for the possibility that this association was driven by results during early follow-up, conditional analyses at one- and two-year follow-up were performed. Both showed a significantly lower risk for a longer duration of antibiotics (Figure 2). Figure 1. Time-Dependent Analysis of Parenteral Antibiotic Duration Figure 2. Time-Dependent Analysis of Oral Antibiotic Suppression Duration ConclusionAfter DAIR, efficacy from four weeks of parenteral antibiotics was no different from six weeks when followed by chronic oral antibiotic suppression. Our results could not establish an optimal duration but suggested that continuing suppression portends a lower risk of failure of DAIR. Disclosures Elie Berbari, MD, Uptodate.com (Other Financial or Material Support, Honorary unrelated to this work) Matthew P. Abdel, MD, Stryker and AAOS Board of Directors (Board Member, Other Financial or Material Support, Royalties) Aaron J. Tande, MD, UpToDate.com (Other Financial or Material Support, Honoraria for medical writing)

Brucella aortitis managed with debridement, extra-anatomical bypass, and long-term antimicrobial therapy.

This report aims to review the management and outcomes of Brucella-associated mycotic aortic aneurysms. This is a retrospective chart review at a tertiary-level healthcare system. IRB approval was waived per policy. We describe a case of Brucella aortitis acquired from habitual contact with wild hogs. Clinical presentation included lower back pain and elevated white blood cell count. Diagnosis was confirmed with imaging showing an infrarenal abdominal aortic aneurysm and serology revealing elevated Brucella antibodies titers. The patient was initially managed with endovascular aortic repair and combined oral and intravenous antibiotics therapy. He then underwent explanation and extra-anatomical bypass due to symptomatic periaortic infection and interval development of type I endoleak. The patient was asymptomatic after his final operation at 24months of follow-up and remained on suppressive oral antibiotic therapy. An aortic aneurysm secondary to Brucella is a rare entity. A detailed history of long-term exposure to animals may be a clue to obtain serologic testing. Operative debridement and re-establishing of reliable blood flow combined with long-term antibiotic suppression are the mainstay of treatment.

A 73-year-old woman with delayed intra-abdominal and systemic sepsis following complicated aortobifemoral bypass

A 73-year-old woman with delayed intra-abdominal and systemic sepsis following complicated aortobifemoral bypass

Long-term outcome of two-stage revision surgery after hip and knee prosthetic joint infections: an observational study.

Introduction: Two-stage revision surgery is the most frequently performed procedure in patients with a chronic periprosthetic joint infection (PJI). The infection eradication rates in the current literature differ between 54 % and 100 %, which could be attributed to different treatment strategies. The aim of this study was to retrospectively evaluate the infection eradication rate in patients with chronic PJI treated with two-stage revision surgery of the hip or knee in primary and re-revision cases. Methods: All patients treated with a two-stage revision for chronic PJI between 2005 and 2011 were analysed. Patient and infection characteristics were retrieved. Primary outcome was successful infection eradication at last follow-up. Successful eradication is specified as no need for subsequent revision surgery or suppressive antibiotic treatment. Results: Forty-seven patients were treated with a two-stage revision. Infection eradication was achieved in 36 out of 47 cases. Thirty-eight patients had positive cultures: 35 monomicrobial infections and 3 polymicrobial infections. Nine cases of culture-negative infections were identified. Accompanying eradication rates were 26 out of 35 cases, 2 out of 3 cases, and 8 out of 9 cases respectively. Mean follow-up was 128 (27–186) months. For hip and knee revisions the eradication rates were 22 out of 31 cases and 14 out of 16 cases respectively. After primary arthroplasty the infection was eradicated in 29 out of 38 cases and after re-revision in 7 out of 9 cases. Conclusion: In this study, the infection eradication rate for two-stage revision surgery after PJI of the hip and knee in primary and re-revision cases was 77 %. No statistically significant patient, infection and micro-organism characteristics were found which influence the infection eradication rates at long-term follow-up of 128 (27–186) months.

Association between continuous-flow left ventricular assist device infections requiring long-term antibiotic use and post-heart transplant morbidity and mortality.

There exists controversy regarding the impact of infection in patients with a left ventricular assist device (LVAD) on post-heart transplant outcomes. This study evaluated the association between infections during LVAD support and the risk of early and late post-heart transplant infection, rejection, and mortality in transplant recipients bridged with an LVAD. This is a single-center retrospective observational cohort study of consecutive adults supported with a continuous flow LVAD undergoing heart transplant between 2006 and 2019 at the Toronto General Hospital. The grade of LVAD infection was classified as per International Society of Heart and Lung Transplantation guidelines. Patients were divided into three groups: (1) patients with LVAD-specific infection confirmed with positive cultures requiring long-term antibiotic use until the time of transplant; (2) patients with any type of infection in whom antibiotics were stopped at least 1 month before transplant; (3) patients without any infections between LVAD implant and transplant. Logistic regression and Cox proportional hazard models were used to evaluate early- and late-post transplant outcomes, respectively. We included 75 LVAD recipients: 16 (21%) patients had a chronic LVAD-related infection on suppressive antibiotics, 30 (40%) had a resolved infection, and 29 (39%) had no infections. During a median post-transplant follow-up time of 4 (2 to 7) years, 65 (87%) patients developed infections, 43 (64%) rejections, and 17 (23%) deaths. Both short- and long-term risks of infection, rejection, and mortality did not differ significantly among the groups. LVAD patients with infections did not have a significantly higher risk of infection, rejection, or mortality at any time point after transplant.

Prolonged antibiotic suppression therapy for infected hip and knee arthroplasty: is this a viable option?

Prolonged antibiotic suppression therapy for infected hip and knee arthroplasty: is this a viable option?

IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice

AbstractAging is associated with impaired hematopoietic and immune function caused in part by decreased fitness in the hematopoietic stem cell (HSC) population and an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. Here we demonstrate that older specific pathogen free (SPF) wild-type (WT) mice in contrast to young SPF mice produce more interleukin-1a and interleukin-1b (IL-1a/b) in steady-state bone marrow (BM), with most of the IL-1a/b being derived from myeloid BM cells. Furthermore, blood from steady-state older SPF WT mice contains higher levels of microbe-associated molecular patterns, specifically TLR4 and TLR8 ligands. In addition, BM myeloid cells from older mice produce more IL-1b in vitro, and older mice show higher and more durable IL-1a/b responses upon stimulation with lipopolysaccharide in vivo. To test whether HSC aging is driven by IL-1a/b, we evaluated HSCs from IL-1 receptor 1 (IL-1R1) knockout (KO) mice. Indeed, older HSCs from IL-1R1KO mice show significantly mitigated aging-associated inflammatory signatures. Moreover, HSCs from older IL-1R1KO and from germ-free mice maintain unbiased lymphomyeloid hematopoietic differentiation upon transplantation, thus resembling this functionality of young HSCs. Importantly, in vivo antibiotic suppression of microbiota or pharmacologic blockade of IL-1 signaling in older WT mice was similarly sufficient to reverse myeloid-biased output of their HSC populations. Collectively, our data define the microbiome/IL-1/IL-1R1 axis as a key, self-sustaining and also therapeutically partially reversible driver of HSC inflammaging.

Congenital Hepatic Fibrosis as a Cause of Recurrent Cholangitis: A Case Report and Review of the Literature

Rare liver diseases caused by ductal plate malformation, such as congenital hepatic fibrosis (CHF), Caroli syndrome, and polycystic liver disease, can have clinical manifestations such as recurrent cholangitis—frequently involving multidrug-resistant microorganisms—leading to difficulties in selecting the optimal antimicrobial treatment. Without prompt recognition, these infections severely hamper the patient’s quality of life and can develop into life-threatening complications. We report here the case of a 50-year-old woman with a history of recurring cholangitis with occasional systemic involvement leading to bloodstream infection, who ultimately received a diagnosis of CHF and was put on chronic suppressive antibiotic therapy while on the waiting list for a liver transplant. We also reviewed the literature collecting cases of recurrent infections occurring in patients with ductal plate malformation.

The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus.

Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of 6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; .68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; .14), and a higher resolution of pain was observed (35 % vs. 14 %; .22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed.

Plant Growth-Promoting Microbe Mediated Uptake of Essential Nutrients (Fe, P, K) for Crop Stress Management: Microbe–Soil–Plant Continuum

The indiscriminate and intensive use of agrochemicals in developing nations to enhance crop productivity has posed an alarming threat to soil quality, fertility, biodiversity, food safety, agricultural sustainability, and groundwater quality, thus critically affecting planetary health and food productivity. Additionally, both abiotic and biotic stresses and developmental disorders, i.e., disease susceptibility, hormonal imbalance, and nutritional deficiency, are the major constraints on crop productivity. In this context, the use of soil–plant associated microbiomes “phytomicrobiome,” especially rhizospheric microbiota, in combination with agronomic practices (nutrient, water, and resource management, as integrated management options: INM/IPM/IWM) is the most promising alternative for managing soil health and crop productivity. The global recognition of plant/soil-associated microbiome has generated substantial investment of public and private bodies to grow microbe-based food products. However, understanding the molecular, genetic, physiological, and ecological aspects of phytomicrobiome toward sustainable agriculture would require broad attention along with associated environmental/physico-chemical control points. The underpinning mechanisms of plant–microbe interactions are of immense significance for strategizing host selection (single culture/consortia) and its field application. Taxa such asRhizobium, Pseudomonas, Alcaligenes, Burkholderia, Sphingomonas, Stenotrophomonas, Arthrobacter, Bacillus, andRhodococcushave emerged as promising plant growth-promoting (PGP) candidates with diverse beneficial traits, such as, producing phyto-hormones, volatile organics, antibiotics for disease suppression, N2-fixation, Fe uptake, and extracellular enzymes, but several physico-chemical constraints/extremities limit the field application (on-site) of such microbes. Hence, a detailed overview on genomic, physiological, metabolic, cellular, and ecological aspects is necessitated. Thorough insights into nutrient acquisition (especially limiting nutrients like Fe and P) during abiotic stress are still under-studied, so the use OMICS, robust bioinformatics pipeline/tools, might greatly revolutionize the field of PGP microbial ecology (complex plant–microbe interactions) for application in agricultural sustainability, nutritional security, and food safety. This review focusses on critical aspects of mechanisms of Fe and P transport-uptake (nutrient acquisition) by various PGP microbes, and their metabolism, genetics, and physiology relevant for managing stress and better crop production.

The role of chronic suppressive antibiotics therapy in superficial drive line infection relapse of left ventricular assist devices: A retrospective cohort from a tertiary care center.

Drive line infections (DLIs) are common complications of left ventricular assist devices (LVADs). Data on use of suppression antibiotic therapy are limited. We performed a retrospective review of 451 patients who underwent LVAD placement from January 2009 to May 2015. First superficial DLIs were included for analysis. We examined factors associated with the use of chronic suppressive antibiotics (CSAs) therapy. Cox proportional hazards models were performed to identify factors associated with DLI relapse with the same organism as the initial DLI. A total of 69 patients developed a superficial DLI within a median of 195 (interquartile range [IQR] 98-348) days of LVAD insertion. The median age was 57years, 87% were males, and 74% were White. Gram positive bacteria caused 61% of infections, with Staphylococcus aureus being the most common (35%). Forty-three (62%) patients received suppressive antibiotic therapy. Relapse DLI occurred in 29 (42%) patients. Independent risk factors for relapse infection in multivariable analysis were sepsis (aHR 5.94 [CI 1.42-24.92]), and MRSA DLI (aHR 4.19 [CI 1.37-12.79]). There was no difference in the proportion of patients with relapse among those who were treated with antibiotic suppression therapy versus not (44%vs. 38%, p=0.64), although relapse occurred at a later time in those who received suppression (185vs. 69 days, p<0.01). CSA therapy was associated with delayed time to DLI relapse but no significant difference in the proportion of patients with relapse. A prospective study is needed to examine the effect of suppression on relapse rates.

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis.

To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team. This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up. Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE. The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team.

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

Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective

The treatment of prosthetic joint infections (PJIs) is a complex matter in which surgical, microbiological and pharmacological aspects must be integrated and, above all, placed in the context of each patient to make the best decision. Sometimes it is not possible to offer curative treatment of the infection, and in other cases, the probability that the surgery performed will be successful is considered very low. Therefore, indefinite administration of antibiotics with the intention of “suppressing” the course of the infection becomes useful. For decades, we had little information about suppressive antibiotic treatment (SAT). However, due to the longer life expectancy and increase in orthopaedic surgeries, an increasing number of patients with infected joint prostheses experience complex situations in which SAT should be considered as an alternative. In the last 5 years, several studies attempting to answer the many questions that arise on this issue have been published. The aim of this publication is to review the latest published evidence on SAT.

Results of debridement, antibiotics, and implant retention for periprosthetic knee joint infection supplemented with the use of intraosseous antibiotics.

Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J2021;103-B(6 Supple A):185-190.