Prediction of 30-day mortality after surgery for infective endocarditis using risk scores: Insights from a European multicenter comparative validation study.

BACKGROUND: It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS: Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and 5 specific risk scores for early mortality after surgery for IE-(1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intracardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intracardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa)-was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. RESULTS: A total of 1,012 patients from 5 European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs 0.693 or less, P = .01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. CONCLUSION: EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than 5 established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.

First report of Acinetobacter pittii acute community-acquired pneumonia in an immunocompetent patient in France following a heat wave.

BACKGROUND: In recent years, Acinetobacter baumannii-calcoaceticus complex (ABC) infections have attracted attention, mainly because of the impact of carbapenem-resistant isolates in hospital-acquired infections. However, acute community-acquired ABC infections are not uncommon in warm and humid countries, where they are responsible for community-acquired infections with specific clinical features. To date, such infection has not been reported in France. CASE PRESENTATION: We report the case of a 55-year-old non-immunocompromised patient living in France with no known risk factors for community-acquired ABC infections who presented pneumonia with bloodstream infection due to wild-type A. pittii. The outcome was favorable after 7 days of antibiotic treatment with cefepime. We confirmed bacterial identification with whole-genome sequencing, and we examined the A. pitii core-genome phylogeny for genomic clusters. CONCLUSIONS: This situation is uncommon in Europe and occurred after a heat wave in France with temperatures above 38 °C. Herein, we discuss the possibility that this pneumonia may be emerging in the current context of global warming.

Defining standard and high dosages for ß-lactam agents administered by intermittent, prolonged or continuous infusion: a PK/PD simulation study.

BACKGROUND: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable ß-lactams, standard and high dosages have been proposed for short-infusion regimens only. OBJECTIVES: To evaluate dosages for ß-lactams administered by prolonged infusion (PI) and continuous infusion (CI). METHODS: Monte Carlo simulations were performed for seven injectable ß-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable. RESULTS: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam. CONCLUSIONS: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.

Efficacy of vancomycin lock therapy for totally implantable venous access port-related infection due to coagulase-negative staphylococci in 100 patients with cancer.

OBJECTIVES: Data on the efficacy of vancomycin catheter lock therapy (VLT) for conservative treatment of totally implantable venous access port-related infections (TIVAP-RI) due to CoNS are scarce. The aim of this study was to evaluate the effectiveness of VLT in the treatment of TIVAP-RI due to CoNS in cancer patients. METHODS: This prospective, observational, multicentre study included adults with cancer treated with VLT for a TIVAP-RI due to CoNS. The primary endpoint was the success of VLT, defined as no TIVAP removal nor TIVAP-RI recurrence within 3 months after initiation of VLT. The secondary endpoint was 3 month mortality. Risk factors for VLT failure were also analysed. RESULTS: One hundred patients were included [men 53%, median age 63 years (IQR 53-72)]. Median duration of VLT was 12 days (IQR 9-14). Systemic antibiotic therapy was administered in 87 patients. VLT was successful in 44 patients. TIVAP could be reused after VLT in 51 patients. Recurrence of infection after completion of VLT occurred in 33 patients, among which TIVAP was removed in 27. Intermittent VLT (antibiotic solution left in place in the TIVAP lumen part of the time) was identified as a risk factor for TIVAP-RI recurrence. At 3 months, 26 deaths were reported; 1 (4%) was related to TIVAP-RI. CONCLUSIONS: At 3 months, success of VLT for TIVAP-RI due to CoNS was low. However, removing TIVAP was avoided in nearly half the patients. Continuous locks should be preferred to intermittent locks. Identifying factors of success is essential to select patients who may benefit from VLT.

Viral genomic, metagenomic and human transcriptomic characterization and prediction of the clinical forms of COVID-19.

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper "Th1-Th17" profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19.

Novel SARS-CoV-2 Variant Derived from Clade 19B, France.

We report a novel severe acute respiratory syndrome coronavirus 2 variant derived from clade 19B (HMN.19B variant or Henri Mondor variant). This variant is characterized by the presence of 18 amino acid substitutions, including 7-8 substitutions in the spike protein and 2 deletions. These variants actively circulate in different regions of France.

Risk factors for intra-abdominal fungal infection after simultaneous pancreas-kidney transplantation: A single-center retrospective experience.

BACKGROUND: Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce. MATERIALS/METHODS: A retrospective monocentric study was conducted on all patients who underwent simultaneous PKT from January 2007 to December 2016. Deep sites positive cultures for fungi during the first post-transplantation year were collected. Clinical, radiological, and microbiological data of proven and probable invasive fungal infections were analysed. RESULTS: Among sixteen PKT patients, 15 were included. Seven patients (47%) developed an invasive fungal infection, exclusively IAFI (six proven, one probable). The proven IAFI included four peritonitis, one pancreatic necrosis with infected hematoma, and one patient with positive preservation fluid only (PF). Candida albicans (n = 4) was the most prevalent species (associated with Galactomyces candidus in one case), C glabrata, C dubliniensis, and C krusei were found in one case each. Three patients had either a positive direct examination and/or culture for renal or pancreatic PF and the culture of PF was positive for the same species that caused IAFI. IAFIs were significantly associated with pancreatic graft arterial thrombosis (5/7 vs 0/8, P = .007) and fungal contamination of PF (3/7 vs 0/8, P = .008). Among patients with IAFI, all required an early surgical revision post-transplantation [1-18 days] and six had early or delayed pancreatic graft removal. One patient died in the first post-transplant year. CONCLUSION: IAFI is a common complication in PKT, associated with pancreatic graft thrombosis or fungal contamination of the graft PF, and can sometimes lead to pancreatic detransplantation.

Diagnostic yield of routine daily blood culture in patients on veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Bloodstream infections (BSIs) are frequent on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Performing routine blood cultures (BCs) may identify early paucisymptomatic BSIs. We investigated the contribution of systematic daily BCs to detect BSIs on V-A ECMO. METHODS: This was a retrospective study including all adult patients requiring V-A ECMO and surviving more than 24 h. Our protocol included routine daily BCs, from V-A ECMO insertion up to 5 days after withdrawal; other BCs were performed on-demand. RESULTS: On the 150 V-A ECMO included, 2146 BCs were performed (1162 routine and 984 on-demand BCs); 190 (9%) were positive, including 68 contaminants. Fifty-one (4%) routine BCs revealed BSIs; meanwhile, 71 (7%) on-demand BCs revealed BSIs (p = 0.005). Performing routine BCs was negatively associated with BSIs diagnosis (OR 0.55, 95% CI [0.38; 0.81], p = 0.002). However, 16 (31%) BSIs diagnosed by routine BCs would have been missed by on-demand BCs. Independent variables for BSIs diagnosis after routine BCs were: V-A ECMO for cardiac graft failure (OR 2.43, 95% CI [1.20; 4.92], p = 0.013) and sampling with on-going antimicrobial therapy (OR 2.15, 95% CI [1.08; 4.27], p = 0.029) or renal replacement therapy (OR 2.05, 95% CI [1.10; 3.81], p = 0.008). Without these three conditions, only two BSIs diagnosed with routine BCs would have been missed by on-demand BCs sampling. CONCLUSIONS: Although routine daily BCs are less effective than on-demand BCs and expose to contamination and inappropriate antimicrobial therapy, a policy restricted to on-demand BCs would omit a significant proportion of BSIs. This argues for a tailored approach to routine daily BCs on V-A ECMO, based on risk factors for positivity.

Clinical relevance and impact of Corynebacterium isolation in lower respiratory tract of critically ill patients requiring mechanical ventilation.

PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007-2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34-60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.

Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers.

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection (n = 15) or as surgical prophylaxis (n = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

De-escalation and discontinuation strategies in high-risk neutropenic patients: an interrupted time series analyses of antimicrobial consumption and impact on outcome.

Febrile neutropenia (FN) is the main reason for antibiotic prescription in hematology wards where, on the other hand, antibiotic stewardship (AS) is poorly explored. The objectives of the present study were to evaluate (1) the impact of an AS intervention on antibiotic consumption and (2) the applicability and acceptance rate of the intervention and its clinical impact. A persuasive AS intervention based on European Conference on Infection in Leukaemia (ECIL) guidelines for FN was implemented in a high-risk hematology ward in a tertiary referral public university hospital. This included the creation and diffusion of flow charts on de-escalation and discontinuation of antibiotics for FN, and the introduction in the team of a doctor dedicated to the implementation of flow charts and to antibiotic prescription revision. All consecutive patients receiving antibiotics during hospitalization were included. A segmented linear regression model was performed for the evaluation of antibiotic consumption, taking into account 1-year pre-intervention period and 6-month intervention period. Overall, 137 consecutive antibiotic prescriptions were re-evaluated, 100 prescriptions were for FN. A significant reduction of the level of carbapenem consumption was observed during the intervention period (level change (estimate coefficient ± standard error) = - 135.28 ± 59.49; p = 0.04). Applicability and acceptability of flow charts were high. No differences in terms of intensive care unit transfers, bacteremia incidence, and mortality were found. A persuasive AS intervention in hematology significantly reduced carbapenem consumption without affecting outcome and was well accepted. This should encourage further applications of ECIL guidelines for FN.

[How to read new antimicrobial susceptibility testing results?] / Comment lire les nouveauxComment lire les nouveaux.

HOW TO READ NEW ANTIMICROBIAL SUSCEPTIBILITY TESTING RESULTS? Antimicrobial susceptibility testing (AST) results (formerly 'susceptible', 'intermediate' and 'resistant') are now expressed with the new susceptibility categories 'susceptible, standard dosing regimen', 'susceptible, increased exposure' and 'resistant'. These new categories introduce a paradigm shift in the way clinicians have to interpret AST results: uncertainties (previously embedded in the 'intermediate' category) now have to be dealt with exclusively by the laboratory, independently from the clinical categorization itself, and both 'susceptible, standard dosing regimen' and 'susceptible, increased exposure' categories are associated with a high likelihood of therapeutic success if appropriate dosing regimen is used. To help clinicians, a dosing table (fitting dosing regimens usually recommended in France, and consistent with clinical breakpoints) is now available as an appendix to the CA-SFM document (Comité de l'antibiogramme de la Société française de microbiologie), and can also be downloaded from the SPILF website (Société de pathologie infectieuse de langue française).

COMMENT LIRE LES NOUVEAUX ANTIBIOGRAMMES ? Les résultats d'antibiogramme, auparavant rendus avec les catégories cliniques « sensible ¼, « intermédiaire ¼ et « résistant ¼, sont désormais exprimés avec les catégories « sensible à posologie standard ¼, « sensible à forte posologie ¼ (ou SFP) et « résistant ¼. Plus qu'une simple évolution terminologique, il s'agit d'une modification profonde de la façon d'apprécier les résultats d'antibiogramme, car les notions d'incertitude (antérieurement associées à la catégorie « intermédiaire ¼) sont désormais exclusivement gérées par le laboratoire, indépendamment de la catégorisation clinique elle-même ; un antibiotique catégorisé « sensible à forte posologie ¼ offre dorénavant la même garantie d'efficacité clinique qu'un antibiotique catégorisé « sensible à posologie standard ¼ dès lors que la posologie prescrite est adaptée. Pour aider les cliniciens, un tableau des posologies (adapté aux schémas posologiques utilisés en France et en adéquation avec les concentrations et diamètres critiques qui permettent de déterminer la catégorisation clinique des antibiotiques) est désormais disponible en annexe du communiqué annuel du comité de l'antibiogramme de la Société française de microbiologie (CA-SFM) et disponible sur le site internet de la Société de pathologie infectieuse de langue française (SPILF).

Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption.

Background: The advent of anti-tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα. Methods: This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure. Results: Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery). Conclusions: TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy.

Value of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Identifying Osteoarticular Septic Grafts in Suspected Infective Endocarditis: Results from a Large Monocentric Cohort.

Background: 18F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET/CT) is useful for identifying infective endocarditis (IE) but also the detection of other concomitant septic foci. Previously, we found that FDG-PET/CT identified an osteoarthritic septic graft (OASG) in 19.1% of IE patients, frequently asymptomatic. These preliminary results encouraged us to extend our analyses to a larger population, including all patients initially explored for suspected IE, to assess the prevalence, characteristics, and OASG locations brought out by FDG-PET/CT and to identify predictive factors. Methods: From a single-center cohort of patients referred for a clinical and/or biological suspicion of IE, we included all patients who underwent FDG-PET/CT, mainly performed to confirm a prosthesis heart valve or a foreign cardiac device infection. We excluded those who did not meet the 2015 modified Duke Criteria and those for whom another infectious diagnosis was finally retained or for whom all bacterial samples were negative. Demographic, clinical, bacteriological, imaging, and therapeutic data were collected. FDG-PET/CT images were retrospectively analyzed by three blinded nuclear medicine specialists to identify OASGs. Results: We identified 72 distinct OASG locations by FDG-PET/CT in 48 of 174 patients (27.6%), mainly located in the spine (21 OASGs in 20 patients); 14 patients (8.0%) had several OASG locations. In total, 43.8% of OASG locations were asymptomatic. In multivariate analysis, the presence of OASGs was associated with musculoskeletal pain (p < 0.001) and tricuspid valve involvement (p = 0.002). Conclusions: FDG-PET/CT is useful for identifying OASGs in patients with suspected IE, especially those with tricuspid IE or musculoskeletal pain. The identification of OASGs could impact antibiotic therapy and would allow adapted orthopedic management to be proposed.

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial.

BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.