OBJECTIVE:Extended-spectrum β-lactamase-producing Enterobacterales (ESBL-EB) infections are associated with poor outcomes in febrile neutropenia. The early identification of patients at risk during prolonged chemotherapy-induced neutropenia remains challenging. METHODS:This multicentre retrospective cohort study included patients with a first Enterobacterales bacteraemia during neutropenia following induction, consolidation, or stem cell transplantation (2015-2022). ESBL-EB bacteraemia was compared with non-ESBL-EB bacteraemia using multivariable logistic regression. Secondary analysis assessed the association between specific antibiotic classes and ESBL-EB, and the impact of prior antibiotic exposure on phenotypic β-lactam resistance profiles. RESULTS:Amongst 574 patients with Enterobacterales bacteraemia, 74 (12.9%) had ESBL-EB bacteraemia. The mean neutropenia duration was 15.8 ± 10.4 d. Inappropriate empirical therapy (73% vs. 10%, P < 0.001) was more frequent in ESBL-EB bacteraemia. In multivariable analysis, antibiotic exposure within 30 d (aOR 2.46, 95% confidence interval [CI] 1.38-4.38, P = 0.002) and mucosal lesions (aOR 3.20, 95% CI 1.58-7.23, P = 0.002) were associated with ESBL-EB bacteraemia. Prior cefepime exposure (adjusted odds ratio [aOR] 2.91, 95% CI 1.07-8.34; P = 0.04) and exposure to multiple antibiotics (aOR 2.88, 95% CI 1.09-7.99; P = 0.03) were associated with ESBL-EB bacteraemia compared with piperacillin-tazobactam exposure. Cefepime exposure was associated with a higher proportion of ESBL-producing isolates (37.2% vs. 18.6%, P = 0.04), whereas piperacillin-tazobactam exposure was associated with high-level penicillinase producers (37.3% vs. 2.3%, P < 0.001). CONCLUSIONS:Recent antibiotic exposure and mucosal lesions are independent risk factors for ESBL-EB bacteraemia in high-risk neutropenic patients. Prior cefepime exposure was associated with ESBL-EB bacteraemia in comparison with piperacillin-tazobactam exposure; this exploratory finding requires confirmation in prospective studies.

PURPOSE:There may be sex-based disparities in intensive care unit (ICU) management and outcomes. We compared baseline variables, interventions, and outcomes of immunocompromised critically ill men and women. METHODS:We performed a post hoc analysis of the Efraim study, a prospective multinational cohort study of immunocompromised adults with acute hypoxemic respiratory failure admitted to one of 68 ICU in 16 countries between November 2015 and July 2016. We compared in unadjusted and adjusted analyses baseline variables, ICU interventions, and outcomes between men and women. RESULTS:We included 1536 immunocompromised adults (922 men, 614 women) in this study. Women and men had similar age, BMI, and diagnoses leading to immunosuppression; hematopoietic cell transplant was more common in men. On the first ICU day, SOFA score was higher in men vs. women (7 [IQR 4-10] vs 6 [4-10]), p = 0.0005). The use of ICU supportive interventions, including mechanical ventilation, vasopressors, renal replacement, bronchoalveolar lavage, and ARDS adjuncts, were similar between men and women; as were mortality in ICU, in hospital, and at 90 days. After adjustment, female sex (sub-hazard ratio 1.19, 95 % CI 1.05-1.36, p = 0.007), SOFA score on ICU day 1 (sHR 1.16, 95 % CI 1.12-1.19, p < 0.001) and chronic kidney disease (sHR 0.74, 95 % CI 0.59-0.93, p = 0.009) were associated with mechanical ventilation. Age, performance status and SOFA score on ICU day 1 were associated with hospital mortality. CONCLUSIONS:In this post hoc analysis of immunocompromised adult ICU patients with hypoxemic respiratory failure, women and men received similar ICU interventions, and had similar outcomes.

Introduction:Liver cyst infection is a rare and severe complication of the liver cysts associated with autosomal dominant polycystic kidney disease (ADPKD), and evidence-based data for optimal management is lacking. We conducted a multicentric retrospective study to investigate the treatment and outcomes of liver cyst infection. Methods:Liver cyst infection was either defined by (i) C-reactive protein levels ≥ 50 mg/l and suspicion at computed tomography (CT) scan, 18Fluorodeoxyglucose (18FDG) positron-emission tomography (PET) CT, magnetic resonance imaging (MRI); or (ii) proven by cyst puncture. We studied the determinants of treatment failure (persistent infection with requirement for antibiotic therapy change, cyst drainage, and hepatectomy), relapse (< 2 months) and recurrence (> 2 months) of liver cyst infection after antibiotics discontinuation. Results:Sixty-two patients and 112 episodes were included. At least 1 microorganism was identified in 70 of 112 episodes (63%), mainly Escherichia coli in 36 of 70of cases (51%). E coli was resistant to third generation cephalosporin, fluoroquinolone, or cotrimoxazole in 13%, 16%, and 34%, respectively. Treatment failure and relapse occurred in 30 of 112 episodes (27%). Antibiotic therapy duration ≥ 14 days was a protective factor for treatment failure or relapses (odds ratio [OR] = 0.03, 95% confidence interval [CI]: 0-0.23], P = 0.006). Recurrence occurred in 24 of 62 patients (38%), within 1 year for 15 patients (24%) after the first episode. An antibiotic therapy duration ≥ 28 days was identified as a protective factor (OR = 0.12, 95% CI: 0.02-0.65], P = 0.021). Conversely, a history of renal cyst infection significantly increased the risk of recurrence within 1 year (OR = 9.22 95% CI: 1.28-99.55], P = 0.04). Conclusion:Treatment failure or relapse or recurrence of liver cyst infection both occurred in one-third of cases, and are associated with a shorter antibiotic therapy duration < 28 days.

Introduction: The increase in the population of immunocompromised patients due to advances in management of end-stage diseases and transplants poses challenges in treating infections caused by multi-drug resistant (MDR) pathogens. Cefiderocol (FDC), a siderophore cephalosporin, has shown efficacy against carbapenem-resistant Gram-negative bacteria. Methods: This retrospective multicentre study investigated the real-world use of FDC in 114 immunocompromised adults treated for MDR infections in 12 French hospitals (June 2020-November 2023). Clinical and microbiological outcomes, including infection cure, relapse, as well as mortality, and resistance acquisition, were assessed at days 28 and 90. Antibiotic prescription compliance with current guidelines was investigated. Results: At day 28, clinical success was achieved in 53.3% of cases, and overall mortality was 37.7%, consistent with other studies (33-37%). Infection-related mortality accounted for 25.4%. Relapse occurred in 17.5% of patients by day 28, rising by an additional 9.8% among survivors by day 90. Resistance acquisition was observed in two cases at day 28 ( Pseudomonas aeruginosa and Stenotrophomonas maltophilia) and in three additional cases by day 90. FDC was used as monotherapy in 49.1% of cases, with a median treatment duration of 10 days. Nearly 25% of strains collected in FDC-treated patients were susceptible to best-practice alternatives. Conclusion: These findings highlight FDC's utility in difficult-to-treat infections, particularly S. maltophilia, but the high relapse rate and resistance acquisition underscore the need for careful monitoring, adherence to guidelines, and reconsideration of empirical use to prevent resistance and improve outcomes in fragile populations. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Abstract Background Immunocompromised patients account for a large proportion of COVID-19 hospitalizations and deaths, even in the most recent periods, despite having received several COVID-19 vaccine doses. Monoclonal antibodies effectively prevented COVID-19 in the general population in randomized control trials and the immunocompromised population in real-world studies. Unfortunately, the emergence of new variants precluded their use. Sipavibart (AZD3152) is an investigational long-acting monoclonal antibody designed to provide broad coverage across Omicron and ancestral viral variants currently being studied in the SUPERNOVA prevention trial. France was the first country to grant Sipavibart as a COVID-19 pre-exposure prophylaxis treatment in immunocompromised individuals with an early access authorization in December 2023. Methods We performed a retrospective multicentric study in France, including the first consecutive patients to receive one intramuscular dose of Sipavibart in January and February 2024, to collect their characteristics and COVID-19-related medical history. Results Overall, we included 47 patients with a median age of 61 years (IQR:64—69) and 64% male. The three main immunosuppressive conditions were Stem cell transplants (38%), solid organ transplants (32%), and immune-based therapies (mostly Rituximab) (19%) for chronic inflammatory diseases or haematologic malignancies. Nearly half had hypogammaglobulinemia and 71% had at least another key comorbidity (Table 1). 15% and 11% had a history of severe and persistent COVID-19, respectively. The median number of COVID-19 doses was 4 (IQR 3-6), and nearly one-third had previously received previous generation of monoclonal antibodies for COVID-19 prophylaxis (Casirivimab/imdevimab or Tixagevimab/Cilgavimab). SARS-CoV-2 serology results before Sipavibart administration were available in 11 patients (without Immunoglobulins substitution). The median anti-Spike IgG titers was 30 UI/L (IQR 0-179). Conclusion The first patients to receive Sipavibart in France had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions. Disclosures Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant Iliès Benotmane, n/a, Astrazeneca: Advisor/Consultant|Astrazeneca: Board Member

The efficacy of neutralizing SARS-CoV-2 monoclonal antibodies (mAbs) in preventing severe COVID-19 has been hindered by the diversity of viral strains and the complexity of patient populations. In this prospective cohort study, we used regression analyses to identify virological, immunological and clinical factors associated with viral clearance and emergence of escape mutations. We included 114 mainly immunocompromised high-risk patients with mild-to-moderate COVID-19 who received mAbs or direct antivirals to prevent COVID-19 progression. Nasopharyngeal SARS-CoV-2 RNA level at day 7 was independently associated with viral load at day 0, serum neutralization at day 7, and treatment received. The emergence of mutations within Spike was observed in 21.9% of patients, all being immunocompromised treated by Sotrovimab or Tixagevimab/Cilgavimab after Omicron emergence, and was independently associated with higher viral load and serum neutralization at day 7. Our data show that suboptimal neutralizing antibodies should be avoided in immunocompromised individuals, given the risk of emergence of viral escape mutations.

Background Pneumocystis jirovecii pneumonia (PjP) is a rising cause of acute respiratory failure in immunocompromised patients, often requiring Intensive Care Unit (ICU) admission. However, optimal ventilatory strategies remain unclear. Methods For the present study, we conducted an ancillary analysis of the PRONOCYSTIS study, a large multicenter cohort of PjP patients. Patients admitted to the ICUs were compared according to initial respiratory management (High-Flow Nasal Cannula (HFNC), standard Oxygen (SO) or Non-Invasive Ventilation (NIV). A propensity score adjustment [inverse probability of treatment weighting (IPTW) analysis] was implemented to account for potential confounders. The primary outcome was intubation rate. Univariable and multivariable Cox regressions were also used to assess variables associated with survival. Results Over the study period, 248 patients with PjP were included in the present analysis. Of those, 70 were treated by HFNC while 118 and 60 received SO and NIV, respectively. HFNC patients had a decreased intubation rate (28.6% versus 45.0% in NIV and 55.4% in SO patients; p = 0.003). When assessing the impact of respiratory management on intubation by IPTW, HFNC remained an independent protective factor (weighted Hazard Ratio (HR) 0.41 (95% CI 0.24–0.69); p < 0.001). While, NIV was not associated with intubation (HR 0.62 (95% CI 0.37–1.02); p = 0.056). Through adjusted survival analysis, long-term corticosteroids treatment (aHR 4.03 (95% CI 2.01–8.08); p < 0.001), Solid tumor (aHR 3.37 (95% CI 1.45–7.86); p = 0.005) and the Sequential Organ Failure Assessment score (aHR 1.24 (95% CI 1.15–1.35); p < 0.001) were found to be independent predictor for death. Initial respiratory support was not associated with survival either in the Cox multivariable analysis or in the IPTW analysis. Conclusion Through this multicenter observational study of severe PjP patients, although oxygenation strategy was not associated with D90 survival, HFNC support appeared to be associated with a lower intubation rate. Further prospective studies are warranted to refine respiratory management in critically ill PjP patients.

Objectives VEXAS is a recently described acquired auto-inflammatory and haematological syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency. Methods Two of our ten VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or two positive cultures from distinct sites, or one positive culture with two involved sites. Results Patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3vs 38/mm3, P < 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients. Conclusion VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.

Sur ces 20 dernières années, la pneumonie à Pneumocystis jirovecii (PcP) a émergé chez de nouveaux hôtes, apparus avec l'avènement des traitements antirétroviraux hautement actifs contre le VIH et des nouvelles thérapies immunomodulatrices chez les patients greffés d'organes et en hématologie/oncologie. Ces nouveaux patients présentent des profils de PcP très distincts de ceux associés à l'infection par le VIH, avec des formes plus graves et des taux de mortalité supérieurs. Compte tenu des progrès de la médecine personnalisée basée sur le profilage immunologique individuel, ces profils de patients non infectés par le VIH représentent de nouveaux défis pour améliorer le diagnostic, le traitement et le pronostic de la PcP. Pour étudier les facteurs impliqués dans les différents sous-types de PcP, une analyse non supervisée des manifestations cliniques, des caractéristiques biologiques et des données pronostiques de 481 patients atteints de PcP a été réalisée. Cette étude est une sous-étude de la cohorte PRONOCYSTIS, un réseau multicentrique rétrospectif impliquant trois hôpitaux français de janvier 2011 à décembre 2021, incluant des patients avec un diagnostic de PcP prouvée ou probable selon la definition de l'Organisation Européenne pour la Recherche et le Traitement du Cancer (EORTC). Au total, 481 patients ont été inclus, tous étaient immunodéprimés (hémopathies malignes n = 118, infection par le VIH n = 114, transplantation d'organe solide n = 103, maladies auto-inflammatoires et auto-immunes n = 87, oncologie solide n= 56 et autres immunodéficiences n = 3). Trois groupes stables présentant des caractéristiques cliniques et des pronostics significativement différents ont été identifiés. Le groupe 1 était principalement associé aux patients infectés par le VIH. Le groupe 2 était associé aux patients atteints d'hémopathies malignes, de maladies auto-inflammatoires et auto-immunes (IMID) et de tumeurs solides. Le groupe 3 correspondait aux patients ayant reçu une transplantation d'organe solide, ayant été exposés à une corticothérapie au long cours et présentant des comorbidités respiratoires et rénales. Chacun de ces groupes était associé à un pronostic spécifique de la PcP et à des caractéristiques cliniques et biologiques spécifiques. Le groupe 1 présentait le taux de survie le plus élevé, tandis que le groupe 2 présentait le pronostic le plus défavorable. Le phénotype de la PcP est fortement associé à la maladie sous-jacente et à un pronostic précis. Les caractéristiques clinico-biologiques, ainsi que le pronostic de la PcP, semblent étroitement liés aux profils de déficits immunitaires des patients. Une évaluation plus poussée des profils immunologiques associés à ces phénotypes pourrait permettre d'améliorer l'identification des patients à haut risque et de s'orienter vers des stratégies thérapeutiques personnalisées. Aucun lien d'intérêt

La neutropénie fébrile (NF) est une complication fréquente chez les patients atteints d'hémopathies malignes, avec un risque élevé de progression rapide vers une infection sévère. En cas de NF chez un patient à haut risque, une antibiothérapie à large spectre doit être initiée en urgence et associée à une approche diagnostique et thérapeutique structurée. L'émergence croissante de bactéries multirésistantes chez ces patients sévèrement immunodéprimés souligne la nécessité de mettre en œuvre des stratégies d'épargne antibiotique afin de limiter la propagation de ces germes. Les recommandations européennes (ECIL-4) préconisent en ce sens une antibiothérapie courte chez les patients présentant une fièvre d'origine inconnue (FUO) lorsque celle-ci évolue favorablement. Lorsqu'une infection par un germe multirésistant est documentée, une antibiothérapie ciblée utilisant des molécules récemment disponibles peut être nécessaire. Cette mise au point vise à actualiser les stratégies de gestion de la NF, notamment quand elles sont à haut risque, en intégrant les pratiques d'utilisation raisonnée d'antibiotiques de dernière génération.

BACKGROUND: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. RESEARCH QUESTION: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? STUDY DESIGN AND METHODS: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. RESULTS: Overall, 481 patients were included in the study; 180 (37.4%) were de fi ned as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated in fl ammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose >= 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010). INTERPRETATION: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs. CHEST 2024; 165(6):1319-1329

ObjectivesThe empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin versus other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis.MethodsA post-hoc analysis of a prospective cohort study of patients hospitalized in a French reference center with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteremia under treatment.ResultsOf the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteremia compared to other treatments (3.6 days versus 4.6 days, p=0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 days versus 4.7 days, p<0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteremia ≤72 hours (p=0.02), whereas endocarditis on native valves (p=0.01), and intracardiac abscess were associated with longer duration of bacteremia (p=0.01).ConclusionsEmpirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides. Text

La durée de traitement des endocardites infectieuses (EI) est basée sur des études anciennes analysant les cultures de valve de patients opérés. Les recommandations préconisent une durée d'antibiothérapie de 2 à 6 semaines en fonction du germe et du type de valve. L'objectif de cette étude était de déterminer les facteurs associés à la culture de valve positive dans une cohorte de patients ayant une EI opérée. Analyse post-hoc d'une cohorte prospective monocentrique ayant inclus les patients consécutifs ayant une EI confirmée par la réunion de concertation pluridisciplinaire et ayant été opéré d'une chirurgie valvulaire entre juillet 2013 et décembre 2022. Les patients ayant une endocardite à germe intracellulaire, fongique ou non documentée, ainsi que les patients dont la valve n'a pas été envoyée en culture ont été exclus. Le critère de jugement principal était la culture bactériologique de valve. Parmi les 930 patients ayant une EI inclus dans notre cohorte, 292 patients (31,4%) ont été opérés d'une chirurgie valvulaire dont 43 patients ont été exclus : 18 pour une absence d'analyse microbiologique de la valve, 15 en raison de l'absence de documentation microbiologique de l'endocardite, 8 en raison d'une endocardite à germe intracellulaire et 2 car il s'agissait d'endocardites fongiques. Parmi les 249 patients inclus, 75 patients (30,1%) avaient une culture de valve positive. Le taux de valve positive était de : • 34,9% (29/83) pour les Staphylococcus sp • 11,6% (13/112) pour les Streptococcus sp • 66,6% (26/39) pour les Enterococcus sp • 46,6% (7/15) pour les autres germes. Le délai médian [IQR] entre le début de l'antibiothérapie et la chirurgie était similaire selon le type de germe : 11 jours [6-18] pour les Staphylococcus sp, 12 [5-26] pour les Streptococcus sp, 12 jours [6-22] pour les Enterococcus sp, 8 jours [4-26] pour les autres germes. Le délai entre le début de l'antibiothérapie et la chirurgie pour stériliser 95% des valves était de 18 jours, 7 jours et 24 jours respectivement pour les Staphylococcus sp, Streptococcus sp et Enterococcus sp. Les facteurs significativement associés au fait d'avoir une culture de valve positive étaient : (i) un délai <10 jours entre le début de l'antibiothérapie et la chirurgie (p<0,01), (ii) une EI à Enterococcus sp (p<0,01) (iii) une végétation supérieure à 20 mm (p=0,05). Inversement, le fait que l'endocardite survienne sur une valve prothétique n'était pas significativement associé à un sur-risque de culture de valve positive (p=0,20). (i) Le taux de stérilisation des valves cardiaques des EI à Enterococcus sp est le plus faible, y compris à distance de l'antibiothérapie. (ii) La durée de traitement des EI à Streptococcus sp pourrait probablement être réduite y compris chez les patients recevant une monothérapie de bétalactamine. (iii) D'autres paramètres tels que la taille de la végétation pourraient être pris en compte pour individualiser la durée de traitement des EI. Aucun lien d'intérêt

France was the first country to grant Sipavibart (AZD3152, an investigational long-acting monoclonal antibody) as a COVID-19 pre-exposure prophylaxis treatment in immunocompromised individuals in December 2023. The first patients to receive Sipavibart had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions. No adverse event was reported.

Objective: Acute graft pyelonephritis (AGPN) is the most frequent infectious complication in kidney transplant recipients (KTR). The treatment of acute community-acquired (CA) pyelonephritis is based on third-generation cephalosporins (3GC) and fluoroquinolones. Cefepime or a piperacillin-tazobactam combination are more often used in healthcare-associated (HCA) infections. However, these recommendations do not consider the resistance observed in KTRs. The objective of our study was to define the most appropriate empirical antibiotherapy for AGPN in KTRs according to the CA and HCA settings. To answer this question, we assessed the prevalence of resistance to different antibiotics usually recommended for urinary tract infections (UTIs) in the general population. Methods: Observational, retrospective, multicenter study covering all episodes of AGPN occurring in hospitalized KTRs in 2019. Results: A total of 210 patients were included in 7 centers and 244 episodes of AGPN were analyzed (158 CAAGPN and 86 HCA-AGPN). The prevalence of 3GC and fluoroquinolone resistance was 23 % (n = 36) and 30 % (n = 50) in CA infections (n = 158), and 47 % (n = 40) and 31 % (n = 27) in HCA infections (n = 86), respectively. Cefepime resistance rate was 19 % (n = 30) in CA-AGPN and 29 % (n = 25) in HCA-AGPN. Piperacillin-tazobactam combination had resistance rates > 15 % in both CA and HCA infections. The only antimicrobials with resistance rates < 10 % were aminoglycosides and carbapenems. Conclusion: None of the antibiotics recommended in empirical treatment in UTIs has shown a resistance rate of less than 10% with regard to AGPN. Therefore, none of them should be used as monotherapy. A combination therapy including amikacin could be an appropriate strategy in this setting.

Background. We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).Methods. This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15.Results. Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29.Conclusions. Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.