Pharmacokinetic/pharmacodynamic analysis of ceftazidime/avibactam and fosfomycin combinations in an in vitro hollow fiber infection model against multidrug-resistant Escherichia coli.

IMPORTANCE: Mechanistic understanding of pharmacodynamic interactions is key for the development of rational antibiotic combination therapies to increase efficacy and suppress the development of resistances. Potent tools to provide those insights into pharmacodynamic drug interactions are semi-mechanistic modeling and simulation techniques. This study uses those techniques to provide a detailed understanding with regard to the direction and strength of the synergy of ceftazidime-avibactam and ceftazidime-fosfomycin in a clinical Escherichia coli isolate expressing extended spectrum beta-lactamase (CTX-M-15 and TEM-4) and carbapenemase (OXA-244) genes. Enhanced killing effects in combination were identified as a driver of the synergy and were translated from static time-kill experiments into the dynamic hollow fiber infection model. These findings in combination with a suppression of the emergence of resistance in combination emphasize a potential clinical benefit with regard to increased efficacy or to allow for dose reductions with maintained effect sizes to avoid toxicity.

Pharmacokinetic/pharmacodynamic evaluation of tigecycline dosing in a hollow fiber infection model against clinical bla-KPC producing Klebsiella Pneumoniae isolates.

The FDA announced a boxed warning for tigecycline due to progression of infections caused by Gram-negative bacteria and increased risk of mortality during treatment. Plasma exposure of tigecycline might not prevent bacteraemia in these cases from the focuses. Hence, we evaluated intensified dosing regimens and breakpoints that might suppress bloodstream infections, caused by progression of infection by e.g., Gram-negatives. A pharmacometric model was built from tigecycline concentrations (100-600 mg daily doses) against clinical Klebsiella pneumoniae isolates (MIC 0.125-0.5 mg/L). Regrowth occurred at clinically used doses and stasis was only achieved with 100 mg q8h for the strain with the lowest studied MIC of 0.125 mg/L. Stasis at 24 h was related to fAUC/MIC of 38.5. Our study indicates that even intensified dosing regimens might prevent bloodstream infections only for MIC values ≤0.125 mg/L for tigecycline. This indicates an overly optimistic breakpoint of 1 mg/L for Enterobacterales, which are deemed to respond to the tigecycline high dose regimen (EUCAST Guidance Document on Tigecycline Dosing 2022).

Rapid detection of cefiderocol susceptibility/resistance in Acinetobacter baumannii.

PURPOSE: Due to its ability to disseminate worldwide and its multiple resistance trait, Acinetobacter baumannii is becoming a threat for public health worldwide. Cefiderocol (FDC) is a promising broad-spectrum cephalosporin recently approved for treating Gram-negative infection. The aim of this study was to develop a rapid test, namely the rapid FDC Acinetobacter baumannii NP test, for the detection of FDC susceptibility/resistance in A. baumannii since the current FDC susceptibility tests are rather time-consuming (at least 24 h). MATERIALS AND METHODS: The rapid test is based on the reduction of resazurin to resorufin product by bacterial viable cells, thus detecting bacterial growth in the presence of FDC (38.4 mg/L). A color change from blue (resazurin) to violet or pink (resorufin) represents visual detection of bacterial growth. 95 randomly selected A. baumannii isolates were used to evaluate the performance of the rapid FDC Acinetobacter baumannii NP test. RESULTS: The test showed 95.5% (95% CI 78.2-99.2%) and 100.0% (95% CI 95.0-100.0%) of sensitivity and specificity, respectively. All the results were obtained within 4 h30-4 h45 incubation time at 35 °C ± 2 °C, saving virtually one day when compared with currently-used antimicrobial susceptibility tests. The test showed only a single very major error, an isolate with a MIC of 8 mg/L. CONCLUSIONS: The rapid FDC Acinetobacter baumannii NP test can be a valuable method which is easier and faster to interpret when compared with the gold standard broth microdilution method. The test showed remarkable performances; hence, it may be suitable for implementation in clinical microbiology routine laboratories.

Interactions between Bacteria and Aspergillus fumigatus in Airways: From the Mycobiome to Molecular Interactions.

Interactions between different kingdoms of microorganisms in humans are common but not well described. A recent analysis of the mycobiome has described the presence of different fungi and their positive and/or negative interactions with bacteria and other fungi. In chronic respiratory diseases, these different microorganisms form mixed biofilms to live inside. The interactions between Gram-negative bacteria and filamentous fungi in these biofilms have attracted more attention recently. In this review, we analyse the microbiota of the respiratory tract of healthy individuals and patients with chronic respiratory disease. Additionally, we describe the regulatory mechanisms that rule the mixed biofilms of Aspergillus fumigatus and Gram-negative bacteria and the effects of this biofilm on clinical presentations.

Ampicillin-susceptible Enterococcus faecium infections: clinical features, causal clades, and contribution of MALDI-TOF to early detection.

Enterococcus faecium, a common resident of the human gastrointestinal tract, is also a major pathogen. Prompt initiation of appropriate treatment is essential to improve patient outcome in disseminated E. faecium infections. However, ampicillin resistance is frequent in this species, rendering treatment difficult. We used a comprehensive approach, including clinical data review, whole-genome sequencing, and mass spectrometry, to characterize ampicillin-susceptible (EFM-S) and ampicillin-resistant (EFM-R) isolates. We included all patients with culture-confirmed E. faecium infection attending our hospital over a 16-month period. A comparison of 32 patients infected with EFM-S strains and 251 patients infected with EFM-R strains revealed that EFM-R isolates were strongly associated with a longer hospital stay, history of prior hospitalization, and the carriage of multidrug-resistant organisms. An analysis of the genomes of 26 EFM-S and 26 EFM-R isolates from paired patients revealed a population structure almost perfectly matching ampicillin susceptibility, with resistant isolates in clade A1, and susceptible isolates in clades A2 and B. The clade B and A2 isolates mostly came from digestive or biliary tract samples, whereas clade A1 isolates were mostly obtained from urine and blood. Finally, we built a custom database for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which differentiated between clade B and clade A1/A2 strains with high-positive and high-negative predictive values (95.6% and 100%, respectively). This study provides important new insight into the clinical features and clades associated with EFM-S and EFM-R isolates. In combination with MALDI-TOF MS, these data could facilitate the rapid initiation of the most appropriate treatment.IMPORTANCEEnterococcus faecium is an important human pathogen in which the prevalence of ampicillin resistance is high. However, little is known about the clinical characteristics of patients infected with ampicillin-resistant and ampicillin-susceptible strains. Indeed, current knowledge is based on genus-wide studies of Enterococcus or studies of very small numbers of susceptible isolates, precluding robust conclusions. Our data highlight specific clinical features related to the epidemiology of EFM-S and EFM-R strains, such as length of hospital stay, history of prior hospitalization, carriage of multidrug-resistant organisms, and type of sample from which the isolate was obtained. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a custom-built database may make it possible to distinguish clade B isolates, which are typically susceptible to ampicillin, from clade A1/A2 isolates (A1 being typically resistant), thereby facilitating the management of these infections.

An improved PKPD modeling approach to characterize the pharmacodynamic interaction over time between ceftazidime/avibactam and colistin from in vitro time-kill experiments against multidrug-resistant Klebsiella pneumoniae isolates.

In contrast to the checkerboard method, bactericidal experiments [time-kill curves (TKCs)] allow an assessment of pharmacodynamic (PD) interactions over time. However, TKCs in combination pose interpretation problems. The objective of this study was to characterize the PD interaction over time between ceftazidime/avibactam (CZA) and colistin (CST) using TKC against four multidrug-resistant Klebsiella pneumoniae susceptible to both antibiotics and expressing a widespread carbapenemase determinant KPC-3. In vitro TKCs were performed and analyzed using pharmacokinetic/pharmacodynamic (PKPD) modeling. The general pharmacodynamic interaction model was used to characterize PD interactions between drugs. The 95% confidence intervals (95%CIs) of the expected additivity and of the observed interaction were built using parametric bootstraps and compared to evaluate the in vitro PD interaction over time. Further simulations were conducted to investigate the effect of the combination at varying concentrations typically observed in patients. Regrowth was observed in TKCs at high concentrations of drugs alone [from 4 to 32× minimum inhibitory concentrations (MIC)], while the combination systematically prevented the regrowth at concentrations close to the MIC. Significant synergy or antagonism were observed under specific conditions but overall 95%CIs overlapped widely over time indicating an additive interaction between antibiotics. Moreover, simulations of typical PK profile at standard dosages indicated that the interaction should be additive in clinical conditions. The nature of the PD interaction varied with time and concentration in TKC. Against the four K. pneumoniae isolates, the bactericidal effect of CZA + CST combination was predicted to be additive and to prevent the emergence of resistance at clinical concentrations.

Evaluation of in vitro pharmacodynamic drug interactions of ceftazidime/avibactam and fosfomycin in Escherichia coli.

BACKGROUND: Combination therapy can increase efficacy of antibiotics and prevent emergence of resistance. Ceftazidime/avibactam and fosfomycin may be empirically combined for this purpose, but a systematic and quantitative evaluation of this combination is needed. OBJECTIVES: In this study, a systematic analysis of the pharmacodynamic interactions of ceftazidime/avibactam and fosfomycin in clinical and isogenic Escherichia coli strains carrying genes coding for several carbapenemases or ESBLs was performed and pharmacodynamic interactions were quantified by modelling and simulations. METHODS: Pharmacodynamic interactions were evaluated in 'dynamic' chequerboard experiments with quantification of viable bacteria in eight isogenic and six clinical E. coli strains. Additionally, supplemental time-kill experiments were performed and genomic analyses were conducted on representative fosfomycin-resistant subpopulations. Models were fitted to all data using R and NONMEM®. RESULTS: Synergistic drug interactions were identified for 67% of the clinical and 75% of the isogenic isolates with a mean EC50 reduction of >50%. Time-kill experiments confirmed the interactions and modelling quantified EC50 reductions up to 97% in combination and synergy prevented regrowth of bacteria by enhanced killing effects. In 9 out of 12 fosfomycin-resistant mutants, genomic analyses identified previously reported mutations. CONCLUSIONS: The broad synergistic in vitro activity of ceftazidime/avibactam and fosfomycin confirms the potential of the application of this drug combination in clinics. The substantial reduction of the EC50 in combination may allow use of lower doses or treatment of organisms with higher MIC values and encourage further research translating these findings into the clinical setting.

A Selective Culture Medium for Screening Cefiderocol Resistance in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Cefiderocol (FDC) is a siderophore cephalosporin with a broad spectrum of activity against many multidrug-resistant Gram-negative bacteria. Acquired resistance to FDC has been already reported among Gram-negative isolates, thus highlighting the need for rapid and accurate identification of such resistant pathogens, in order to control their spread. Therefore, the SuperFDC medium was developed to screen FDC-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. After testing several culture conditions, a selective medium was set up by supplementing an iron-depleted agar medium with 8 µg/mL of FDC and evaluated with a collection of 68 FDC-susceptible and 33 FDC-resistant Gram-negative isolates exhibiting a variety of ß-lactam resistance mechanisms. The sensitivity and specificity of detection of this medium were evaluated at 97% and 100%, respectively. In comparison with the reference broth microdilution method, only 3% very major errors were found. In addition, excellent detection performances were obtained by testing spiked stools with a lower limit of detection ranging between 100 and 103 CFU/mL. The SuperFDC medium allows detection of FDC-resistant Gram-negative isolates regardless of their corresponding resistance mechanisms.

Volunteers, religious communities and users representatives as an alternative for visiting hospitalized patients: The importance of an infection control training.

BACKGROUND: During the COVID-19 pandemic, the suspension of relatives' visits was a common measure in healthcare facilities to prevent the spread of the virus among patients. This measure caused significant adverse consequences for hospitalized patients. Volunteers' intervention was an alternative but could also lead to cross transmission events. AIMS: in order to secure their intervention with patients, we implemented an infection control training to evaluate and to improve the knowledge of volunteers about infection control measures. METHOD: We performed a before-after study in a group of five tertiary referral teaching hospitals in the suburbs of Paris. A total of 226 volunteers from three groups (religious representatives, civilian volunteers and users' representatives) were included. Basic theoretical and practical knowledge about infection control, hand hygiene, and glove and mask use were evaluated just before and immediately after a three-hour training program. The contribution of the characteristics of the volunteers to the results was studied. FINDINGS: The initial conformity rate for theoretical and practical infection control measures ranged from 53% to 68%, depending on the participants' activity status and education level. Some critical shortcomings in hand hygiene as well as mask and glove wearing putatively endangered the patients and volunteers. Surprisingly, serious gaps were also identified among volunteers who experienced care activities. Regardless of their origin, the program significantly improved both their theoretical and practical knowledge (p<0.001). Real-life observance and long-term sustainability should be monitored. CONCLUSIONS: To become a secure alternative to relatives' visits, volunteers' interventions must be preceded by the assessment of their theoretical knowledge and practical skills in infection control. Additional study, including practice audit, must confirm the implementation of the acquired knowledge in the real-life.

The Relative Contributions of Occupational and Community Risk Factors for COVID-19 among Hospital Workers: The HOP-COVID Cohort Study.

The relative contributions of occupational and community sources of COVID-19 among health-care workers (HCWs) are still subject to debate. In a cohort study at a 2814-bed tertiary medical center (five hospitals) in the Paris area of France, we assessed the proportion of hospital-acquired cases among staff and identified risk factors. Between May 2020 and June 2021, HCWs were invited to complete a questionnaire on their COVID-19 risk factors. RT-PCR and serology test results were retrieved from the virology department. Mixed-effects logistic regression was used to account for clustering by hospital. The prevalence of COVID-19 was 15.6% (n = 213/1369 respondents) overall, 29.7% in the geriatric hospitals, and 56.8% of the infections were hospital-acquired. On multivariable analyses adjusted for COVID-19 incidence and contact in the community, a significantly higher risk was identified for staff providing patient care (especially nursing assistants), staff from radiology/functional assessment units and stretcher services, and staff working on wards with COVID-19 clusters among patients or HCWs. The likelihood of infection was greater in geriatric wards than in intensive care units. The presence of significant occupational risk factors after adjustment for community exposure is suggestive of a high in-hospital risk and emphasizes the need for stronger preventive measures-especially in geriatric settings. Clinicaltrials.gov NCT04386759.

Biobased polymer resources and essential oils: a green combination for antibacterial applications.

To fight nosocomial infections, the excessive use of antibiotics has led to the emergence of multidrug-resistant microorganisms, which are now considered a relevant public health threat by the World Health Organization. To date, most antibacterial systems are based on the use of petro-sourced polymers, but the global supplies of these resources are depleting. Besides, silver NPs are widely accepted as the most active biocide against a wide range of bacterial strains but their toxicity is an issue. The growing interest in natural products has gained increasing interest in the last decade. Therefore, the design of functional antibacterial materials derived from biomass remains a significant challenge for the scientific community. Consequently, attention has shifted to naturally occurring substances such as essential oils (EOs), which are classified as Generally Recognized as Safe (GRAS). EOs can offer an alternative to the common antimicrobial agents as an inner solution or biocide agent to inhibit the resistance mechanism. Herein, this review not only aims at providing developments in the antibacterial modes of action of EOs against various bacterial strains and the recent advances in genomic and proteomic techniques for the elucidation of these mechanisms but also presents examples of biobased polymer resource-based EO materials and their antibacterial activities. Especially, we describe the antibacterial properties of biobased polymers, e.g. cellulose, starch, chitosan, PLA PHAs and proteins, associated with EOs (cinnamon (CEO), clove (CLEO), bergamot (BEO), ginger (GEO), lemongrass (LEO), caraway (CAEO), rosemary (REO), Eucalyptus globulus (EGEO), tea tree (TTEO), orange peel (OPEO) and apricot (Prunus armeniaca) kernel (AKEO) essential oils). Finally, we discuss the influence of EOs on the mechanical strength of bio-based materials.

The Population Genomics of Increased Virulence and Antibiotic Resistance in Human Commensal Escherichia coli over 30 Years in France.

Escherichia coli is a commensal species of the lower intestine but is also a major pathogen causing intestinal and extraintestinal infections that is increasingly prevalent and resistant to antibiotics. Most studies on genomic evolution of E. coli used isolates from infections. Here, instead, we whole-genome sequenced a collection of 403 commensal E. coli isolates from fecal samples of healthy adult volunteers in France (1980 to 2010). These isolates were distributed mainly in phylogroups A and B2 (30% each) and belonged to 152 sequence types (STs), the five most frequent being ST10 (phylogroup A; 16.3%), ST73 and ST95 (phylogroup B2; 6.3 and 5.0%, respectively), ST69 (phylogroup D; 4.2%), and ST59 (phylogroup F; 3.9%), and 224 O:H serotypes. ST and serotype diversity increased over time. The O1, O2, O6, and O25 groups used in bioconjugate O-antigen vaccine against extraintestinal infections were found in 23% of the strains of our collection. The increase in frequency of virulence-associated genes and antibiotic resistance was driven by two evolutionary mechanisms. Evolution of virulence gene frequency was driven by both clonal expansion of STs with more virulence genes ("ST-driven") and increases in gene frequency within STs independent of changes in ST frequencies ("gene-driven"). In contrast, the evolution of resistance was dominated by increases in frequency within STs ("gene-driven"). This study provides a unique picture of the phylogenomic evolution of E. coli in its human commensal habitat over 30 years and will have implications for the development of preventive strategies. IMPORTANCE Escherichia coli is an opportunistic pathogen with the greatest burden of antibiotic resistance, one of the main causes of bacterial infections and an increasing concern in an aging population. Deciphering the evolutionary dynamics of virulence and antibiotic resistance in commensal E. coli is important to understand adaptation and anticipate future changes. The gut of vertebrates is the primary habitat of E. coli and probably where selection for virulence and resistance takes place. Unfortunately, most whole-genome-sequenced strains are isolated from pathogenic conditions. Here, we whole-genome sequenced 403 E. coli commensals isolated from healthy French subjects over a 30-year period. Virulence genes increased in frequency by both clonal expansion of clones carrying them and increases in frequency within clones, whereas resistance genes increased by within-clone increased frequency. Prospective studies of E. coli commensals should be performed worldwide to have a broader picture of evolution and adaptation of this species.

Evidence of Sexual Transmission of Extended-Spectrum ß-Lactamase-Producing Enterobacterales: A Cross-sectional and Prospective Study.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) represent a major threat to public health. Little is known on their potential for sexual transmission. METHODS: We recruited individuals at a sexually transmitted infection and human immunodeficiency virus (HIV) outpatient clinic in Paris, France, in whom we evaluated the prevalence of ESBL-E intestinal carriage and, among those testing positive, the proportion with clearance 6 months thereafter. We compared carriage prevalence between groups using logistic regression adjusted for age, geographic origin, travel outside Europe, and antibiotic use in the past 6 months. RESULTS: A total of 2157 individuals participated, of whom 226 (10.5%) were ESBL-E carriers. The proportions of ESBL-E carriers varied across sexual groups and were as follows: HIV-negative men who have sex with men (MSM) and who were on preexposure prophylaxis (PrEP), 16.3% (41 of 251); HIV-negative MSM not on PrEP, 9.7% (47 of 487); HIV-positive MSM, 12.2% (61 of 500); HIV-negative men who have sex exclusively with women, 10.0% (44 of 439); and HIV-negative women who have sex with men, 6.9% (n = 33 of 480). After adjustment, ESBL-E prevalence was significantly higher in HIV-negative MSM on PrEP (P < .001) and HIV-positive MSM (P = .01) than in women who have sex with men. A higher number of sexual partners in the past 6 months was associated with ESBL-E carriage after adjustment (P = .004). Escherichia coli sequence type 14 and blaSHV-12-producing ESBL-E were observed only in MSM. Of 102 individuals with ESBL-E returning for testing, 26 (25%) had carriage at 6 months. CONCLUSION: ESBL-E carriage is more frequent in MSM undergoing PrEP or living with HIV and with increasing number of sexual partners. More research is warranted to understand the consequences of ESBL-E carriage in these populations and how transmission can be reduced.

Reduced Chlorhexidine Susceptibility Is Associated with Tetracycline Resistance tet Genes in Clinical Isolates of Escherichia coli.

Chlorhexidine is a widely used antiseptic in hospital and community health care. Decreased susceptibility to this compound has been recently described in Klebsiella pneumoniae and Pseudomonas aeruginosa, together with cross-resistance to colistin. Surprisingly, few data are available for Escherichia coli, the main species responsible for community and health care-associated infections. In order to decipher chlorhexidine resistance mechanisms in E. coli, we studied both in vitro derived and clinical isolates through whole-genome sequence analysis. Comparison of strains grown in vitro under chlorhexidine pressure identified mutations in the gene mlaA coding for a phospholipid transport system. Phenotypic analyses of single-gene mutants from the Keio collection confirmed the role of this mutation in the decreased susceptibility to chlorhexidine. However, mutations in mlaA were not found in isolates from large clinical collections. In contrast, genome wide association studies (GWAS) showed that, in clinical strains, chlorhexidine reduced susceptibility was associated with the presence of tetA genes of class B coding for efflux pumps and located in a Tn10 transposon. Construction of recombinant strains in E. coli K-12 confirmed the role of tetA determinant in acquired resistance to both chlorhexidine and tetracycline. Our results reveal that two different evolutionary paths lead to chlorhexidine decreased susceptibility: one restricted to in vitro evolution conditions and involving a retrograde phospholipid transport system; the other observed in clinical isolates associated with efflux pump TetA. None of these mechanisms provide cross-resistance to colistin. This work demonstrates the GWAS power to identify new resistance mechanisms in bacterial species.

Spontaneous and postsurgical/traumatic Klebsiella pneumoniae meningitis: two distinct clinico-microbiological entities.

OBJECTIVES: To analyze and compare the characteristics and outcomes of spontaneous meningitis (SM) versus postsurgical/traumatic meningitis (PSTM) due to Klebsiella pneumoniae. METHODS: A retrospective multicentric cohort study of all K. pneumoniae meningitis cases managed between January 2007 and May 2018 was carried out in seven university hospitals in the Paris area. The microbiological characteristics of 16 available K. pneumoniae isolates were further analyzed, and the genomes of seven of those isolated from SM were sequenced. RESULTS: Among 35 cases, 10 were SM and 25 were PSTM. SM cases more severe than PSTM cases, with higher septic shock (p = 0.004) and in-hospital mortality rates (p = 0.004). In contrast, relapse occurred in five patients from the PSTM group versus no patients from the SM group. All K. pneumoniae strains recovered from SM but none of those recovered from PSTM displayed hypervirulent phenotypic (positive string test) and genotypic (genes corresponding to capsular serotypes K1 or K2; virulence genes rmpA and iutA) characteristics (p < 0.0001). PSTM tended to be more frequently polymicrobial (p = 0.08) and caused by an extended-spectrum ß-lactamase producing strain (p = 0.08) than SM. CONCLUSIONS: SM and PSTM are two entities differing both from a clinical and a microbiological standpoint. SM appears to be a more serious infection, induced by hypervirulent K. pneumoniae strains.

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.