Prosthetic joint infections: 6 weeks of oral antibiotics results in a low failure rate.

BACKGROUND: Need for parenteral administration and total duration of antibiotic therapy for prosthetic joint infection (PJI) are debated. We report our PJI management, in which outpatient care is privileged. METHODS: This was a retrospective multicentre cohort study of PJI managed from January 2017 to Jun 2021. Microbial diagnosis was based on surgical samples. Surgical procedures and antibiotic treatments were reported. Chronic PJI was defined by a course >1 month. Oral antibiotic therapy (OAT) was defined by exclusive use of oral antibiotics or by ≤3 days of parenteral treatments. Management failure was defined by clinical and/or microbial relapse of PJI over 24 months after surgical treatment. RESULTS: One hundred and seventy-two patients from 13 institutions were included: 103 were male (60%) and mean age was (±SD): 73 ±â€Š12 years. Sites for PJI were mainly hip (50%) and knee (35%), being chronic infections in 70 cases (41%). The main bacterial genus in monomicrobial infections was Staphylococcus spp. (60%). We recorded 41 (24%) implant exchanges. An OAT was prescribed in 76 cases (44%), and the median (range) course for parenteral route was 6 days (4-180) for 96 cases. Median (range) duration of antimicrobials was 42 days (21-180). Management failure was observed in 7/76 (9.2%) cases treated with OAT and 15/96 (15.6%) treated with prolonged parenteral therapy. In multivariate analysis, risk factors for failure were a knee PJI [adjusted OR (95% CI) = 3.27 (1.27-8.40)] and a polymicrobial infection [4.09 (1.46-11.49)]. CONCLUSIONS: OAT for 6 weeks for PJI was associated with a low rate of management failure.

Plasma microparticles of intubated COVID-19 patients cause endothelial cell death, neutrophil adhesion and netosis, in a phosphatidylserine-dependent manner.

COVID-19 has compelled scientists to better describe its pathophysiology to find new therapeutic approaches. While risk factors, such as older age, obesity, and diabetes mellitus, suggest a central role of endothelial cells (ECs), autopsies have revealed clots in the pulmonary microvasculature that are rich in neutrophils and DNA traps produced by these cells, called neutrophil extracellular traps (NETs.) Submicron extracellular vesicles, called microparticles (MPs), are described in several diseases as being involved in pro-inflammatory pathways. Therefore, in this study, we analyzed three patient groups: one for which intubation was not necessary, an intubated group, and one group after extubation. In the most severe group, the intubated group, platelet-derived MPs and endothelial cell (EC)-derived MPs exhibited increased concentration and size, when compared to uninfected controls. MPs of intubated COVID-19 patients triggered EC death and overexpression of two adhesion molecules: P-selectin and vascular cell adhesion molecule-1 (VCAM-1). Strikingly, neutrophil adhesion and NET production were increased following incubation with these ECs. Importantly, we also found that preincubation of these COVID-19 MPs with the phosphatidylserine capping endogenous protein, annexin A5, abolished cytotoxicity, P-selectin and VCAM-1 induction, all like increases in neutrophil adhesion and NET release. Taken together, our results reveal that MPs play a key role in COVID-19 pathophysiology and point to a potential therapeutic: annexin A5.

Therapeutic failures of targeted antibiotic prophylaxis in urology.

Targeted antibiotic prophylaxis (TAP) is required for patients with positive urine culture before urological surgery. Our aim was to determine the efficacy of TAP. This was a prospective single-center study performed in a urology department. All patients who underwent a programmed surgery were included. Urine culture was obtained before surgery requiring a prophylaxis: in the case of sterile urines, antibiotics were used in accordance with national recommendations; for positive urine culture, a TAP was used in accordance with susceptibility testing. The drugs were administered for 2 days before surgery until withdrawal of bladder catheter. The occurrence of healthcare-associated infections was registered until day 30 after surgery. Two hundred three patients were included for 8 non-consecutive weeks in 2020, among whom fifteen were lost of sight before day 30. Among the remaining 188 patients, most frequent surgeries were 75 prostatic diseases (40%), 50 endo-ureteral surgeries for JJ stent insertion (27%), and 23 bladder cancers (12%). One hundred forty-eight (79%) patients required a urine culture before procedure; 142/148 (96%) urine cultures were performed, leading to 74 TAP. The main isolated bacteria were 48 Enterobacteriaceae and 8 Enterococcus spp. TAP was cotrimoxazole (n = 30), aminoglycosides (n = 11), amoxicillin (n = 9), fluoroquinolones (n = 7), and others (n = 17). The rate of healthcare-associated infections was 14.8% (11/74), including six microbiologically documented antibiotic failures. The rate of healthcare-associated infection after urological surgery using TAP was high, implying to discuss the choice and the dosage of the antibiotic molecules.

Real-world effectiveness of casirivimab plus indevimab in a dedicated ambulatory unit created for patients with early COVID-19 during a massive delta variant wave.

Only limited real-life data are available on the effects of neutralizing monoclonal antibodies in high-risk patients who have early COVID-19 and do not require supplemental oxygen. We prospectively studied 217 patients infected by the delta variant who received casirivimab plus indevimab in a dedicated ambulatory unit created during our 4th COVID wave. Mean age was 64 years, 94% had at least one comorbidity, and mean duration of symptoms was 2.9 days. Oxygen requirement, hospitalization, and mortality rates were 10, 6, and 2.8%, respectively. These results suggest benefits of early administration of neutralizing antibodies in high-risk patients infected with the delta variant.

Simplified therapeutic guidelines: the main tool of antimicrobial stewardship programs associated with optimal antibiotic therapy.

Hospitals regularly seek to upgrade their antimicrobial stewardship program (ASP). Our aim was to evaluate the impact of simplified therapeutic guidelines (STGs) compared to various established tools for ASP on the rate of optimal antibiotic therapy (OAT) and antibiotic consumption. Audits of antibiotic prescriptions were carried out over a 24-month period. Feedback information led to STGs (e.g., ≤ 15 drugs). The impact of STGs was based on the rate of OAT, defined as a diagnosis of the infectious disease in the patient's medical records associated with the corresponding therapy indicated in the STGs or in other guidelines. STGs were compared to five other means of ASP: internal or national guidelines, audit, information regarding antibiotic consumption and bacterial resistance, and restricted access to targeted antibiotics. Antibiotic consumption was measured in defined daily doses/1000 days of hospital stay, focusing on third-generation cephalosporins (TGC) and fluoroquinolones (FQ). Twenty-six hospitals were audited from April 2017 to June 2019. A total of 1,028 antibiotic prescriptions were analyzed, including 204 (20%) after STG implementation in seven hospitals. In multivariate analysis, OAT (n = 176, 17%) was associated with STGs, AOR 2.21 [1.51-3.22], and with three tools in place, 1.75 [1.24-2.48]. The relative variations of consumption of TGC and FQ for hospitals with or without STGs were - 13.1 vs. + 9.4% and - 18.5 vs. - 2.7%, respectively, from 2018 to 2019. STGs were more likely than other ASP tools to improve the rate of OAT and to reduce the consumption of antibiotics.

Use of Antibiotic Prophylaxis for Polymicrobial Urine Culture before Urological Surgery: A Pilot Study.

INTRODUCTION: Preoperative polymicrobial urine cultures are common, but the associated risk of nosocomial infection is currently unknown. We aimed to analyze the risk of postoperative infection in patients with preoperative polymicrobial urine cultures. METHODS: This was a prospective cohort study conducted from November 2018 to October 2020. Polymicrobial urine cultures were defined by at least the presence of 3 bacteria without leukocyturia threshold on two consecutive samples in the month preceding the surgical procedure. Data on postoperative infections were collected during hospitalization until day 30. A postoperative infection was defined by the occurrence of clinical signs (fever, chills, and suppurated process on the surgical site) associated with the prescription of an antibiotic therapy. RESULTS: Sixty-eight patients were included, and seven developed a postoperative infection with a microbe identified in blood or urine cultures. There was a significant association between leukocyturia ≥104 (p = 0.02) and the administration of intraoperative antibiotic prophylaxis (p < 0.001). In contrast, there was no significant association between postoperative infections for patients with polymicrobial preoperative urine cultures and having received or not an empirical antibiotic therapy. CONCLUSION: The rate of postoperative infection in patients with polymicrobial urine culture before urological procedure was 10.2%. Further studies are needed to assess the antibiotic prophylaxis to be used in this situation.

A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint Infections.

Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare the plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover trial, patients were randomly assigned to receive either 3 days of CI (two 75-mg/kg 12-h cloxacillin infusions per day) and then 3 days of ItI (four 37.5-mg/kg 1-h cloxacillin infusions per day) or vice versa. The drug concentration measurement was performed on day 3 of each type of administration at 1, 6, and 11 h and at 1, 2, 3, 4, and 6 h after the beginning of CI and ItI, respectively. We used the nonparametric algorithm NPAG to estimate population pharmacokinetic (PK) parameters. The final model was used to perform pharmacokinetic/pharmacodynamic (PK/PD) simulations and calculate the probabilities of target attainment (PTA) for several ItI and CI dosing regimens. We considered two PK/PD targets of time spent above the MIC for free cloxacillin concentrations (fT>MIC): 50 and 100%. Eighty-four concentrations from 11 patients were analyzed. A two-compartment model adequately described the data. ItI with q6h regimens and short 1-h infusions of 2,000 or 3,000 mg were associated with low PTA, even for the low target (50% fT>MIC) while 3-h infusions and continuous infusions (6 to 12 g/day) were associated with a PTA of >90% for an MIC up to 0.5 mg/liter. These results support the use of prolonged or continuous infusion of cloxacillin in patients with BJI.

Impact of simplified therapeutic guidelines on antibiotic prescriptions: a prospective multicentre comparative study.

OBJECTIVES: We studied the impact of simplified therapeutic guidelines (STGs) associated with accompanied self-antibiotic reassessment (ASAR) on antibiotic use. METHODS: Prospective antibiotic audits and feedback took place at 15 hospitals for 12 months, allowing STGs with ≤15 drugs to be devised. STGs were explained to prescribers through sessions referred to as ASAR. Optimal therapy was defined by the conjunction of a diagnosis and the drug specified in the STGs. Analysis of consumption focused on critical drugs: amoxicillin/clavulanic acid, third-generation cephalosporins and fluoroquinolones. RESULTS: We compared prescriptions in five hospitals before (n = 179) and after (n = 168) the implementation of STGs + ASAR. These tools were associated with optimal therapies and amoxicillin/clavulanic acid prescriptions [adjusted odds ratio (AOR) 3.28, 95% CI 1.82-5.92 and 2.18, 95% CI 1.38-3.44, respectively] and fewer prescriptions for urine colonization [AOR 0.20 (95% CI 0.06-0.61)]. Comparison of prescriptions (n = 1221) from 10 departments of three clinics with STGs + ASAR for the first quarters of 2018 and 2019 revealed that the prescriptions by 23 ASAR participants more often complied with STGs than those by 28 other doctors (71% versus 60%, P = 0.003). STGs alone were adopted by 10 clinics; comparing the prescriptions (n = 311) with the 5 clinics with both tools, we observed fewer unnecessary therapies in the latter [AOR 0.52 (95% CI 0.34-0.80)]. The variation in critical antibiotic consumption between 2017 and 2018 was -16% for the 5 clinics with both tools and +20% for the other 10 (P = 0.020). CONCLUSIONS: STGs + ASAR promote optimal antibiotic therapy and reduce antibiotic use.

Urinary tract infection and antibiotic use around ureteral stent insertion for urolithiasis.

Urolithiasis is the main indication for a ureteral JJ stent. Our aim was to determine the incidence of urinary tract infections (UTIs) after a JJ stent for urolithiasis, with an emphasis on antibiotic use. Prospective, multicenter, cohort study over a 4-month period including all of the patients with urolithiasis requiring JJ stent insertion. The clinical and microbiological data and therapeutic information were recorded until removal of the JJ stent. Two hundred twenty-three patients at five French private hospitals were included. A urine culture was performed for 187 patients (84%) prior to insertion of a JJ stent, 36 (19%) of which were positive. One hundred thirty patients (58%) received an antibiotic therapy during surgery: 74 (33%) prophylaxis and 56 (25%) empirical antibiotic therapy, comprising 17 different regimens. The rate of prophylaxis varied according to the center, from 0 to 70%. A total of 208 patients were followed-up until removal of the first stent. The rate of UTIs was 6.3% (13/208); 8.1% of the patients who did not receive a prophylaxis had a UTI versus 1.4% of those who did receive a prophylaxis (p = 0.057). Seven empirical antibiotic regimens were used to treat these 13 patients. Another large panel of antibiotic prescriptions was observed at the time of JJ stent removal. The incidence of a UTI after JJ stent insertion for urolithiasis was 6.3%, in part due to a lack of prophylaxis. An unwarranted diversity of antibiotic use was observed at each step of care.

Risk Factors for Unnecessary Antibiotic Therapy: A Major Role for Clinical Management.

BACKGROUND: Assessment of antimicrobial use places an emphasis on therapeutic aspects of infected patients. Our aim was to determine the risk factors for unnecessary antibiotic therapy (UAT). METHODS: This was a prospective, multicenter study evaluating all curative antibiotic therapies prescribed over 2 consecutive days through the same electronic medical records. Each item that could participate in these prescriptions was collected from the computerized file (reason for hospitalization, comorbid conditions, suspected or definitive diagnosis of infection, microbial analyses). UAT was defined as the recognition of noninfectious sydromes (NIS), nonbacterial infections, use of redundant antimicrobials, and continuation of empirical broad-spectrum antimicrobials. RESULTS: Four hundred fifty-three antibiotic therapies were analyzed at 17 institutions. An infectious disease was the reason for hospitalization in 201 cases (44%). An unspecified diagnosis of infection was observed in 104 cases (23%). Microbial samples were taken in 296 cases (65%), allowing isolation of a pathogen in 156 cases (53%). Unspecified diagnosis was associated with the absence of a microbial sample compared to patients with a diagnosis: (56/104 [54%] vs 240/349 [69%]; P = .005). A total of 158 NIS were observed (35%). UAT was observed in 169 cases (37%), due to NIS in 106 cases. In multivariate analysis, the modifiable risk factors for UAT were unspecified diagnosis (adjusted odds ratio [AOR], 1.83; 95% confidence interval [CI], 1.04-3.20) and absence of a blood culture (AOR, 5.26; 95% CI, 2.56-10.00). CONCLUSIONS: UAT is associated with an unspecified diagnosis and the absence of microbial testing. Antimicrobial stewardship programs should focus on diagnostic difficulties and microbial testing, the latter facilitating antibiotic reassessment and therapeutic interruption.

Amoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertainty.

Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (n = 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (p = 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16-0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.

Adherence to antibiotic guidelines for erysipelas or cellulitis is associated with a favorable outcome.

Outside areas of S. aureus strains resistant to methicillin (MRSA) in the community, no studies showed a relationship between the treatment for erysipelas or cellulitis and the outcome. We aimed to measure the impact of an internal therapeutic protocol, based on national guidelines on patients' outcome. This study was based on the dashboard of the infectious diseases department, which prospectively includes 28 parameters for all admitted patients. We included community-acquired erysipelas and cellulitis; exclusion criteria were abscesses at admission; ear, nose, throat, or dental cellulitis; pyomyositis; and length of stay ≤ 2 days. Adherence to guidelines was defined by the use of amoxicillin, amoxicillin/clavulanic acid, clindamycin, or pristinamycin, alone or in combination or successively. A poor outcome was defined by surgical procedure or intensive care requirement or death occurring after 5 days or more of antibiotic therapy. From July 2005 to June 2017, 630 cases of erysipelas or cellulitis were included. Blood cultures performed in 567 patients (90%) were positive in 39 cases (6.9%). Adherence rate to guidelines was 65% (410 cases). A poor outcome was recorded in 54 (8.5%) patients, less frequently in case of adherence to guidelines: 26/410 (6.3%) vs 28/220 (12.7%), p = 0.007. In logistic regression analysis, two risk factors were associated with a poor outcome: peripheral arterial disease, AOR 4.80 (2.20-10.49); and bacteremia, AOR 5.21 (2.31-11.76), while guideline adherence was the only modifiable protective factor, OR 0.48 (0.26-0.89). In erysipelas and cellulitis, adherence to guidelines was associated with a favorable outcome.

Antibiotic therapy for Enterococcus bacteraemia: warning for the antimicrobial stewardship team.

Enterococci are a significant cause of bacteraemia in healthcare-associated infections (HCAI), being resistant to cephalosporins and aminoglycosides often used in this setting. Our aim was to measure the rate of inefficient antimicrobial therapy and its impact on the outcome. We conducted a retrospective multicentre cohort study in 6 French institutions. Patients were identified through the laboratory's database, which extracted all positive blood cultures for Enterococcus spp. in 2016. Patients' data were gathered by reviewing hospital records. Efficient antimicrobial therapy was defined as any therapy containing at least one antibiotic compound with in vitro efficacy against Enterococcus spp.: amoxicillin, amoxicillin/clavulanic acid, piperacillin, piperacillin/tazobactam, imipenem, meropenem, vancomycin, daptomycin, linezolide, tigecycline. A short-term unfavourable outcome was defined as intensive care requirement and/or in-hospital death at least 48 h after positive blood culture. One hundred thirty-one patients were included; the main diagnosis was a urinary tract infection (46%) and a HCAI was observed in 54% of the cases. Four patients did not receive any antibiotic. Forty-three per cent of empirical antibiotic therapies and 17% of documented ones were inefficient for enterococcal bacteraemia. Sixty patients (46%) received amoxicillin as a documented therapy. Twenty-three per cent of the patients presented a short-term unfavourable outcome. Univariate and multivariate analyses showed that not receiving amoxicillin as a documented antibiotic therapy was associated with an unfavourable short-term outcome (p = 0.001). In conclusion, Enterococcal bacteraemia was associated with a high proportion of inefficient antimicrobial therapy. In multivariate analysis, amoxicillin use was associated with a better outcome.

Factors associated with unfavorable outcome in a multicenter audit of 100 infective endocarditis.

We aimed to identify factors associated with unfavorable outcome in patients treated for infective endocarditis (IE), with a focus on departure from European guidelines. We conducted a retrospective audit of all adult patients treated for endocarditis during a 1-year period across a regional network of nine care centers in the south-east of France. Medical records were reviewed regarding patient and infection characteristics, antibiotic therapy, outcome, and compliance to the European Society of Cardiology guidelines. Antibiotic treatment appropriateness was evaluated regarding molecule, dosage, and duration, according to guidelines. Primary endpoint was the assessment of factors associated with unfavorable outcome, defined as in-hospital mortality or IE relapse at 1-year follow-up. Secondary endpoints were intensive care admission, iatrogenic events, and nosocomial infections that occurred during hospital stay. One hundred patients were included. Median age was 71 years old. Twenty-two patients died and IE relapse occurred in two patients, representing 24 patients with unfavorable outcome. Overall, antibiotic treatment was deemed appropriate in 28 cases. Thirty-three patients required intensive care, 34 iatrogenic events were found, including 19 acute kidney injuries, and 13 nosocomial infections occurred during care. Using a logistic regression, factors associated with unfavorable outcome were admission in the intensive care unit (adjusted odd ratio 7.26 [1.8-29.28]; p = 0.005), new-onset nosocomial infection (adjusted odd ratio 8.83 [1.42-54.6]; p = 0.019), and age > 71 years old (adjusted odd ratio 11.2 [2.76-46.17]; p < 0.001). Departure from guidelines was frequent but not related to unfavorable outcome in our study. Only intensive care, age, and nosocomial infections were associated with mortality and relapse. Iatrogenic events were numerous, with no impact on outcome.

From Crosstalk between Immune and Bone Cells to Bone Erosion in Infection.

Bone infection and inflammation leads to the infiltration of immune cells at the site of infection, where they modulate the differentiation and function of osteoclasts and osteoblasts by the secretion of various cytokines and signal mediators. In recent years, there has been a tremendous effort to understand the cells involved in these interactions and the complex pathways of signal transduction and their ultimate effect on bone metabolism. These crosstalk mechanisms between the bone and immune system finally emerged, forming a new field of research called osteoimmunology. Diseases falling into the category of osteoimmunology, such as osteoporosis, periodontitis, and bone infections are considered to have a significant implication in mortality and morbidity of patients, along with affecting their quality of life. There is a much-needed research focus in this new field, as the reported data on the immunomodulation of immune cells and their signaling pathways seems to have promising therapeutic benefits for patients.

Improved quality of care for patients infected or colonised with ESBL-producing Enterobacteriaceae in a French teaching hospital: impact of an interventional prospective study and development of specific tools.

The increasing incidence of ESBL-producing Enterobacteriaceae (ESBL-E) in France prompted the publication of national recommendations in 2010. Based on these, we developed a toolkit and a warning system to optimise management of ESBL-E infected or colonised patients in both community and hospital settings. The impact of this initiative on quality of care was assessed in a teaching hospital. The ESBL toolkit was developed in 2011 during multidisciplinary meetings involving a regional network of hospital, private clinic and laboratory staff in Southeastern France. It includes antibiotic treatment protocols, a check list, mail templates and a patient information sheet focusing on infection control. Upon identification of ESBL-E, the warning system involves alerting the attending physician and the infectious disease (ID) advisor, with immediate, advice-based implementation of the toolkit. The procedure and toolkit were tested in our teaching hospital. Patient management was compared before and after implementation of the toolkit over two 3-month periods (July-October 2010 and 2012). Implementation of the ESBL-E warning system and ESBL-E toolkit was tested for 87 patients in 2010 and 92 patients in 2012, resulting in improved patient management: expert advice sought and followed (16 vs 97%), information provided to the patient's general practitioner (18 vs 63%) and coding of the condition in the patient's medical file (17 vs 59%), respectively. Our multidisciplinary strategy improved quality of care for in-patients infected or colonised with ESBL-E, increasing compliance with national recommendations.

Bacteraemia in emergency departments: effective antibiotic reassessment is associated with a better outcome.

Patients with bacteraemia constitute an useful population for an audit of antibiotic treatments. Empirical antibiotic therapy (EAT) and its reassessment must take into account clinical data and microbiological results. Our aim was to determine the impact of these sequential steps of the therapy on survival. This was a retrospective multicentre study which included patients admitted to emergency departments (ED) for whom blood cultures were positive over a 4-month period. Microbial results were compiled from the database of the laboratories. The relevant information was extracted from the computerized patient's chart. An efficient EAT was based on antibiotic susceptibility of the bacteria. An effective antibiotic reassessment (AR) was defined as any modification of the EAT. Unfavorable outcome was defined as death of the patient during in-hospital care. Three hospitals and two clinics took part in this study, 169 patients with bacteraemia being included. The diagnosis in ED was undetermined in 21 cases (12%), 35 patients (21%) required intensive care, and 23 died (14%). One hundred and thirty-six patients (80%) received an EAT, the latter being efficient in 107 cases (63%). An effective AR was performed in 116 cases (69%). In multivariate analysis, risks factors for death were: ongoing cancer AOR (adjusted odds ratio) 3.34, undetermined diagnosis in ED: AOR 9.34 and severe sepsis or shock: AOR 6.98. Effective AR was a protective factor: AOR 0.28 [0.09-0.81]. One third of bacteraemic patients in ED did not benefit from AR. Improvement of antimicrobial stewardship should be associated with a higher rate of survival.

Patients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort study.

Bacteremia of unknown origin (BUO) are associated with increased mortality compared to those with identified sources. Microbiological data of those patients could help to characterize an appropriate empirical antibiotic treatment before bloodcultures results are available during sepsis of unknown origin. Based on the dashboard of our ward that prospectively records several parameters from each hospitalization, we report 101 community-acquired BUO selected among 1989 bacteremic patients from July 2005 to April 2016, BUO being defined by the absence of clinical and paraclinical infectious focus and no other microbiological samples retrieving the bacteria isolated from blood cultures. The in-hospital mortality rate was 9%. We retrospectively tested two antibiotic associations: amoxicillin-clavulanic acid + gentamicin (AMC/GM) and 3rd generation cephalosporin + gentamicin (3GC/GM) considered as active if the causative bacteria was susceptible to at least one of the two drugs. The mean age was 71 years with 67% of male, 31 (31%) were immunocompromised and 52 (51%) had severe sepsis. Eleven patients had polymicrobial infections. The leading bacterial species involved were Escherichia coli 25/115 (22%), group D Streptococci 12/115 (10%), viridans Streptococci 12/115 (10%) and Staphylococcus aureus 11/115 (9%). AMC/GM displayed a higher rate of effectiveness compared to 3GC/GM: 100/101 (99%) vs 94/101 (93%) (p = 0.04): one Enterococcus faecium strain impaired the first association, Bacteroides spp. and Enterococcus spp. the second. In case of community-acquired sepsis of unknown origin, AMC + GM should be considered.

Staphylococcus lugdunensis: a neglected pathogen of infections involving fracture-fixation devices.

PURPOSE: Cases of fracture-fixation device infection involving Staphylococcus lugdunensis are not frequent. The clinical characteristics and the choice of treatment strategies of these infections are not obviously known to date. METHODS: We performed a review of fracture-fixation device infection involving S. lugdunensis managed by our centres. RESULTS: Among the 38 cases of fracture-fixation device infection involving S. lugdunensis, 53% were located in the tibia. Most of our cases (87%) were chronic infections. Purulent discharge, which occurred in 79% of cases, was the most frequent clinical symptom, followed by pain in 63%, local inflammation in 55%, and fever in 37%. Bacteremia and severe sepsis occurred in 10% and 18% of cases, respectively. Four cases (10%) were treated exclusively with antimicrobial treatment alone. Thirty-four cases (89%) were treated with a combination of surgery with antimicrobial therapy including surgical debridement, antibiotics and osteosynthesis device retention in six cases (16%), and osteosynthesis device removal in 27 cases (71%). The mean length of antibiotic treatment was 119 days. The relapse rate was high that was not related to selection of resistant strains. Polymicrobial infection had no impact on clinical outcome. A combination of surgery with antimicrobial therapy was identified as a significant prognostic factor associated with remission (p = 0.042). CONCLUSIONS: S. lugdunensis is probably involved in more infections than has been reported. Using appropriate microbiological methods laboratories should routinely identify the species of all coagulase-negative Staphylococci isolates involved in fracture-fixation device infection to better achieve the treatment strategies of fracture-fixation device infection involving S. lugdunensis.