Suppressive Antibiotic Treatment Research Articles

Effectiveness of temocillin in treatment of non-urinary tract infections caused by ESBL-producing Enterobacterales and risk factors for failure.

To describe the real-life use of temocillin for non-urinary tract infections, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Retrospective multicentric study in 14 tertiary care hospitals, including all patients who received at least one dose of temocillin for ESBL infections from 1 January 2016 to 31 December 2021 for non-urinary tract infections. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. Logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Data on 163 infection episodes were collected; 133 were due to ESBL-producing Enterobacterales and 128 were included in the effectiveness analysis. Median (IQR) age was 61 (53-70) years and 61.7% of patients were male. Main indications were lower respiratory tract infection (LRTI; 28.9%), intra-abdominal infections (IAI; 28.1%) and cutaneous infections (12.5%). The main bacteria involved were Klebsiella pneumoniae (48.4%), Escherichia coli (25.0%) and Enterobacter cloacae (24.2%). Polymicrobial infections occurred in 45.3% of cases. Temocillin was used as monotherapy in 86/128 (67.2%). Failure was found in 36/128 (28.1%) cases. In multivariable analysis, the only factor associated with failure was initial severity of the episode [adjusted OR 3.0 (95% CI: 1.06-8.69)]. During non-urinary tract infections, the main use of temocillin was for LRTIs and IAIs due to ESBL-producing E. coli and K. pneumoniae. The main risk factor for failure was initial severity of the disease.

Enterococcal endocarditis management and relapses.

Enterococcus faecalis is the third micro-organism causing endocarditis and is associated with a significant relapse rate. The objective of this study was to describe the management of patients with Enterococcus faecalis endocarditis (EE) and its implication for relapses. We conducted a monocentric, retrospective analysis of all patients hospitalized for EE including endocarditis or infection of cardiac implantable electronic device defined by the modified ESC 2015 Duke criteria in a referral centre in Paris, France. Between October 2016, and September 2022, 54 patients with EE were included, mostly men (n = 40, 74%) with a median age of 75 [68-80] years. A high risk for infective endocarditis (IE) was found in 42 patients (78%), including 14 (26%) previous histories of IE, and 32 (59%) histories of valvular cardiac surgery. The aortic valve was the most frequently affected (n = 36, 67%). Combination therapy was mainly amoxicillin-ceftriaxone during all the curative antibiotic therapy duration (n = 31, 57%). Surgery was indicated for 40 patients (74%), but only 27 (50%) were operated on, mainly due to their frailty. Among the 17 deaths (32%), six (11%) happened during the first hospitalization for EE. A suppressive antibiotic treatment was initiated in 15 (29%) patients, mostly because of not performing surgery. During the 6-year study period an EE relapse occurred in three (6%) patients. EE is a worrying disease associated with a high risk of relapse and significant mortality. Suppressive antibiotic therapy could be a key treatment to limit the occurrence of relapses.

Early results of a novel modular knee arthrodesis implant after uncontrolled periprosthetic knee joint infection

AimThe aim of this study is to evaluate the functional outcomes and complications after non-fusion knee arthrodesis with a modular segmental intramedullary implant used for infected total knee arthroplasty revisions.MethodsA retrospective review of the patients who had been surgically treated with a modular intramedullary arthrodesis implant for recurrent infection after revision TKA between January 2016 and February 2020 were included. The indications for arthrodesis were failed infected TKA with massive bone loss, deficient extensor mechanism and poor soft tissue coverage that precluded joint reconstruction with revision TKA implants. Clinical outcomes were assesed with visual analogue scale for pain (pVAS), Oxford knee score (OKS) and 12-item short form survey (SF-12). Full-length radiographs were used to verify limb length discrepancies (LLD).ResultsFourteen patients (4 male and 10 female) patients with a mean age of 69.3 (range, 59 to 81) years at time of surgery were available for final follow-up at a mean of 28.8 months (range, 24–35 months). All clinical outcome scores improved at the final follow-up (pVAS, 8.5 to 2.6, p = .01; OKS, 12.6 to 33.8, p = .02; SF-12 physical, 22.9 to 32.1, p = .01 and SF-12 mental, 27.7 to 40.2, p = .01). The mean LLD was 1.0 cm (range, + 15 – 2.3 cm). Re-infection was detected in three patients (21.4%). Two patients were managed with suppressive antibiotic treatment and a third patient required repeat 2-stage revision procedure. In one patient, a periprosthetic femur fracture was observed and treated with plate osteosynthesis.ConclusionUncontrolled infection after total knee arthroplasty can be effectively treated with arthrodesis using a modular intramedullary nail and satisfactory functional results can be obtained.Level of evidenceLevel 4, Retrospective cohort study.

Defibrillator Lead Retention and Suppressive Antibiotic Treatment for Gram-Negative Bacterial Endocarditis.

Defibrillator Lead Retention and Suppressive Antibiotic Treatment for Gram-Negative Bacterial Endocarditis.

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.

Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Temocillin is a β-lactam that is not hydrolysed by ESBLs. To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ± 15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Local antibiotic treatment with calcium sulfate as carrier material improves the outcome of debridement, antibiotics, and implant retention procedures for periprosthetic joint infections after hip arthroplasty - a retrospective study.

Purpose: Debridement, antibiotics, and implant retention (DAIR) is an established treatment modality in periprosthetic joint infections (PJIs), but success rates vary. This study compared the success of DAIR for PJIs after a total hip arthroplasty (THA), with or without local antibiotic delivery with CaSO as the carrier material. Methods: A retrospective review of DAIR for PJIs after THA performed between 2010 and 2018, including 41 patients is conducted. A total of 27 patients were treated by DAIR with local antibiotics with CaSO as the carrier material, and 14 patients were treated by a standard DAIR. The endpoints were treatment failure, defined as the need for a reoperation, either a second DAIR or a prosthesis removal or exchange due to persistent or recurrent infection, the initiation of a long-term suppressive antibiotic treatment, or death related to infection. Results: Considering any reoperation as an outcome, 11 of 14 cases treated without AB-CaSO (79 %) and 4 of the 27 cases treated with AB-CaSO failed (15 %). Considering revision as an outcome, 9 out of 14 cases treated without AB-CaSO (64 %) and 4 of the 27 cases treated with AB-CaSO (15 %) failed. A Kaplan–Meier survival analysis showed that local antibiotic delivery with CaSO as the carrier material led to a significantly longer infection-free survival, considering any surgical revision (; hazard ratio 8.9 (95 % CI 2.8–28.2)) or revision with component exchange (; hazard ratio 5.6 (95 % CI 1.7–18.2)) as the endpoint. Conclusion: The addition of local antibiotics with CaSO as the carrier material to DAIR for PJIs after THA significantly increases success rates, such as infection-free survival, any reoperation, and revision with component exchange in particular.

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.

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.

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.

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.

Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review

Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition. All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed. Seventeen patients were included. Bacteria were identified in 16 cases: Staphylococcus aureus (n=10), including methicillin-resistant S. aureus (n=1); and coagulase-negative staphylococci (n=10), including methicillin-resistant Staphylococcus epidermidis (n=4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0-476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%. Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

Chronic prosthetic joint infections with a draining sinus. Who should receive suppressive antibiotic treatment?

The benefit of suppressive antibiotic treatment in inoperable patients with a chronic periprosthetic joint infection and a sinus tract is unknown. Some physicians prefer to just let the sinus drain, while others prefer antibiotic treatment. In this viewpoint article we discuss the advantages and disadvantages of suppressive antibiotic treatment in this particular patient group.

The influence of smoking on bacterial resistance after vaccine or antibiotic prophylaxis against recurrent urinary tract infections

IntroductionThe influence of tobacco on the microbiological spectrum, resistance-sensitivity pattern and evolution in patients with recurrent urinary tract infections (RUTI) is analyzed. Evaluation of the effect of polyvalent bacterial vaccine on the prevention of RUTI and smoking status. Material and methodsRetrospective multicenter study of 855 women with RUTI receiving suppressive antibiotic treatment or bacterial vaccine between 2009 and 2013. Group A (GA): Antibiotic (n = 495). Subgroups: GA1 non-smoker (n = 417), GA2 smoker (n = 78). Group B (GB): Vaccine (n = 360). Subgroups: GB1 non-smoker (n = 263), GB2 smoker (n = 97). Variables: Age, pre-treatment UTI, disease-free time (DFT), microbial species, sensitivity and resistance. Follow-up at 3, 6 and 12 months with culture and SF-36 questionnaire. ResultsMean age 56.51 years (18–75), similar between groups (p = 0.2257). No difference in the number of pretreatment UTIs (p = 0.1329) or in the distribution of the bacterial spectrum (p = 0.7471). DFT was higher in subgroups B compared with A. Urine cultures in GA1: E. coli 62.71% with 8.10% resistance (33% quinolones; 33% cotrimoxazole; 33% quinolones + cotrimoxazole); in GA2 E. coli 61.53% with 75% resistance (16.66% quinolones; 33.33% quinolones + cotrimoxazole; 16.66% amoxicillin-clavulanate; 16.66% erythromycin + phosphomycin + clindamycin) (p = 0, 0133). There were no differences between patients of GA treated with cotrimoxazole and nitrofurantoin (p = 0.8724). Urine cultures in GB1: E. coli 47.36% with 22.22% resistance (5.55% ciprofloxacin; 5.55% cotrimoxazole; 5.55% ciprofloxacin + cotrimoxazole; 5.55% amoxicillin / clavulanic acid). In GB2 E.coli 70.02% with 61.90% resistances (30.76% quinolones; 30.76% cotrimoxazole; 30.76% quinolones + cotrimoxazole; 17.69% amoxicillin-clavulanic acid) (p = 0,0144). ConclusionsThe development of bacterial resistance is more frequent among women with smoking habits and recurrent urinary infections. This could influence a worse response to preventive treatments, either with antibiotics or vaccines.

Influencia del tabaquismo en la resistencia bacteriana después de la profilaxis frente a infecciones urinarias recurrentes con antibiótico o con vacuna

IntroductionThe influence of tobacco on the microbiological spectrum, resistance-sensitivity pattern and evolution in patients with recurrent urinary tract infections (RUTI) is analyzed. Evaluation of the effect of polyvalent bacterial vaccine on the prevention of RUTI and smoking status. Material and methodsRetrospective multicenter study of 855 women with RUTI receiving suppressive antibiotic treatment or bacterial vaccine between 2009 and 2013. Group A (GA): Antibiotic (n=495); Subgroups: GA1 non-smoker (n=417), GA2 smoker (n=78). Group B (GB): Vaccine (n=360); Subgroups: GB1 non-smoker (n=263), GB2 smoker (n=97). Variables: Age, pre-treatment UTI, disease-free time (DFT), microbial species, sensitivity and resistance. Follow-up at 3, 6 and 12 months with culture and SF-36 questionnaire. ResultsMean age 56.51 years (18-75), similar between groups (P=.2257). No difference in the number of pretreatment UTIs (P=.1329) or in the distribution of the bacterial spectrum (P=.7471). DFT was higher in subgroups B compared with A. Urine cultures in GA1: E. coli 62.71% with 8.10% resistance (33% quinolones; 33% cotrimoxazole; 33% quinolones + cotrimoxazole); in GA2 E. coli 61.53% with 75% resistance (16.66% quinolones; 33.33% quinolones + cotrimoxazole; 16.66% amoxicillin-clavulanate; 16.66% erythromycin + phosphomycin + clindamycin) (P=.0133). There were no differences between patients of GA treated with cotrimoxazole and nitrofurantoin (P=.8724). Urine cultures in GB1: E. coli 47.36% with 22.22% resistance (5.55% ciprofloxacin; 5.55% cotrimoxazole; 5.55% ciprofloxacin + cotrimoxazole; 5.55% amoxicillin/clavulanic acid). In GB2 E. coli 70.02% with 61.90% resistances (30.76% quinolones; 30.76% cotrimoxazole; 30.76% quinolones + cotrimoxazole; 17.69% amoxicillin-clavulanic acid) (P=.0144). ConclusionsThe development of bacterial resistance is more frequent among women with smoking habits and recurrent urinary infections. This could influence a worse response to preventive treatments, either with antibiotics or vaccines.

P1456 Pacemaker and percutaneous aortic valve endocarditis - a complex decision

Abstract CASE REPORT We describe the case of a 64-year-old man who was referred because of a fever. He had history of hypertension, dyslipidemia, atrial fibrillation, chronic obstructive pulmonary disease and a right lung pneumectomy due to epidermoid lung cancer diagnosed twenty-five years ago. He implanted dual-chamber definite pacemaker ten years ago and had a transcatheter aortic valve implantation (TAVI) in the previous year due to severe aortic stenosis and a high surgical risk. He was hospitalized 2 months ago because of a respiratory infection. Blood cultures were positive for an Enterococcus faecalis. A transthoracic echocardiogram was performed and had no evidence of vegetations. After one month, he had recurrence of fever and was again admitted. On physical examination he was hemodynamically stable, with signs of peripheral congestion and no heart murmur on cardiac auscultation. Blood cultures were again positive for Enterococcus faecalis. The transesophageal echocardiogram (TEE) showed a biologic aortic valve with thickened leaflets and small nodular structures suggestive of vegetations. There was a small periprosthetic leak and no obstruction or suspected perivalvular abscesses. There was also a small vegetation with 0,45*0,3 cm in the auricular pacemaker lead. A thoraco-abdomino-pelvic computed tomography scan showed no embolic complications. A diagnosis of pacemaker and TAVI endocarditis was made. The patient started directed antibiotic therapy (ceftriaxone and ampicillin). The case was discussed in Heart Team and because of high surgical risk, medical treatment was decided. The patient completed antibiotic treatment with negative blood cultures and apyrexia. A repeated TEE showed persistence of vegetations, without development of local complications. It was decided to discharge the patient under palliative suppressive antibiotic treatment with levofloxacin after discussion with the infectious disease doctor. In a follow-up evaluation, he remained clinically stable, without recurrence of fever. DISCUSSION As TAVI procedures are performed more frequently, a higher number of late complications are expected. Prosthetic valve endocarditis after TAVI is a complex situation, whose treatment strategy is not well-defined, particularly because these patients are usually of high surgical risk. This case describes a complex clinical picture and highlights the difficulty in decision-making in these situations. Also, it pretends to reinforce the need to discuss in a Heart Team the best treatment options.

The Role of Long-Term Antibiotic Suppression in the Management of Peri-Prosthetic Joint Infections Treated With Debridement, Antibiotics, and Implant Retention: A Systematic Review

BackgroundA number of clinical trials have been conducted, assessing the role of long-term (>1 year) suppressive antibiotic treatment (SAT) combined with Debridement, Antibiotics, and Implant Retention (DAIR) for the management of peri-prosthetic joint infection (PJI). However, no systematic review of the literature has been published to date to evaluate complications associated with long-term antibiotic treatment and overall survivorship free from re-operation and revision for infection after DAIR for total hip and total knee PJI. MethodsThe US National Library of Medicine (PubMed/MEDLINE), EMBASE, and the Cochrane Database of Systematic Reviews were queried for publications from January 1980 to December 2018 utilizing keywords pertinent to total knee arthroplasty, total hip arthroplasty, PJI, and antibiotic suppression. ResultsOverall, 7 articles of low quality (level III or IV) were included in this analysis. The studies included in this systematic review included 437 cases of PJI treated surgically with DAIR and then with SAT. The overall mean infection-free rate of SAT following DAIR was 75% (318/424 patients), while the all-cause re-operation rate was 6.7%. Overall, the mean rate of adverse effects associated with long-term antibiotic use was 15.4% and the mean rate of adverse effects leading to discontinuation of SAT was 4.3%. There was no study to show significant differences between acute (either post-operative or hematogenous, with onset of symptoms ≤4 weeks) and chronic (onset of symptoms >4 weeks) infections and failure rates of DAIR with SAT. The literature is inconclusive on the influence of anatomic location (hip vs knee) as well as microorganism on the success rate of DAIR with SAT. ConclusionThe results of this systematic review demonstrate that there is still only low-quality evidence regarding the therapeutic effect of DAIR combined with SAT, which is not enough to draw definitive conclusions. Furthermore, high-quality prospective studies are needed to better understand SAT’s efficacy and safety in a controlled fashion. Although discontinuation of antibiotic treatment due to side effects was found to be low, the high rates of adverse effects noted after DAIR with SAT demonstrate the underlying frailty and complexity of many patients with PJI, and the imperfect therapies available. Although Staphylococcus aureus appears to be a risk factor for increased risk of SAT failure, there are not enough data to establish which patients would benefit most from DAIR with post-operative SAT.

384. Denosumab-Related Osteonecrosis of the Jaw: an Emergent and Potentially Complex Bone and Joint Infection

BackgroundOsteonecrosis of the jaw is a known complication of antiresorptive treatment, like bisphosphonate. More recently, denosumab was validated as a treatment in the osteoporosis and bone metastasis. Its mechanism is different from bisphosphonate but induces also a decrease of bone resorption and a risk of osteonecrosis of the jaw. In case of treatment failure by a dental surgeon or in complex cases, patients could be addressed to a bone and joint infection (BJI) reference center. The aim of this study was to analyze microbiology, as well as surgical and medical care of patients who present denosumab-related osteonecrosis of the jaw (DRONJ) and who were treated in a bone and join reference center.MethodsAll patients managed in our BJI reference center between January 2013 and December 2018 for a DRONJ were included in our retrospective observational monocentric cohort.ResultsTwelve patients (median age 71; ratio M/W 0.7) with a DRONJ (metastatic cancer, n = 10 (83%)) in grade 3 (n = 5), 2 (n = 4), 1 (n = 3) were included. Only 3 patients (25%) had a dental health control before initiating the treatment by denosumab and 7 patients (58%) had a dental surgical procedure done before the DRONJ. Eleven patients had a bone exposure, treated at least with a scaling and mucosal closure at the same time. All infections with bacterial cultures (n = 11 (91%)) were polymicrobial, including 8 (72%) with Streptococcus spp; 8 (72%) with anaerobia including 2 (18%) with Actinomyces; 5 (45%) with Staphylococcus spp; 5 (45%) with enterobacteria; 3 (27%) with Candida spp; 2 (17%) with a non-fermentative Gram-negative bacilli and 7 (64%) with others bacteria. All patients (n = 12) received a betalactam, 8 (66%) a lincosamide or a synergistin, 5 (41%) an antifungal, 5 (41%) metronidazole, 4 (33%) a fluoroquinolone, 3 (25%) a glycopeptide and 2 (17%) other antibiotics. The median follow-up was 6 months. Eight patients were cured after a medico-surgical care and a median duration of antibiotics of 97 days (including 28.5 days in intravenous). 2 patients required a suppressive antibiotic treatment, 1 relapsed at a distance of the treatment and 1 died from some other causes.ConclusionDRONJ is a potential complex BJI, for which some patients could benefit from medical care in a BJI reference center.Disclosures All authors: No reported disclosures.

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study

ObjectivesThe aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. MethodsThis was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. ResultsIn total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75–59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan–Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1–2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09–2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5–3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). ConclusionsSAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.

French national cohort of first use of dalbavancin: A high proportion of off-label use

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.