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Objectives: This study aimed to assess the frequency of co-resistance to antibiotics recommended in acute pyelonephritis among Escherichia coli clinical strains isolated from urinary tract infections (UTIs) acquired in community or nursing homes (NHs), and to identify situations without alternatives to fluoroquinolones (FQs)., Methods: All antimicrobial susceptibility test (AST) results of E. coli culture-positive urine samples from females living in the community or in NHs, collected through a large network of clinical laboratories in 2020 in France, were included. The percentages of strains resistant to amoxicillin alone or combined with a resistance to one to four alternatives among amoxicillin/clavulanic acid, trimethoprim/sulfamethoxazole, cefixime and FQs were calculated and compared between age categories and settings., Results: Among 291 367 E. coli strains from community-acquired UTIs, 60.3% were susceptible to amoxicillin (<65-year-olds: 61.8% versus ≥65-year-olds: 58.8%; P < 0.001), and 99.1% to oral alternatives to FQs. Co-resistance to amoxicillin and trimethoprim/sulfamethoxazole was higher among females ≥65 years old versus <65 years old (7.1% versus 6.1%; P < 0.01), as well as co-resistance to amoxicillin, amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole (8.6% versus 10%; P < 0.001). Among 11 340 strains from NH UTIs, 51.2% were susceptible to amoxicillin, and 98% to oral alternatives to FQs. Co-resistance to amoxicillin, amoxicillin/clavulanic acid and/or cefixime was higher in isolates from females ≥65 years old living in NHs versus in the community (respectively 11.9% versus 15.3%, P < 0.001; 0.8% versus 2.8%, P < 0.01; 1.7% versus 4.4%, P < 0.01)., Conclusions: Based on AST results, prescribing oral alternatives to FQs for females may be possible in ≥99% of E. coli acute pyelonephritis cases in the community, and ≥98% in NHs., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Determining the best available therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is a challenge. Cefiderocol is an attractive alternative drug effective against many resistance mechanisms in Gram-negative bacteria. However, its place in the treatment of Acinetobacter baumannii infections remains unclear and much debated, with contradictory results., Methods: We describe here the case of a 37-year-old man with ventilator-associated bacteraemic CRAB pneumonia in an intensive care unit. He was initially treated with a combination of colistin and tigecycline, and was then switched onto colistin and cefiderocol. We then used a new accessible protocol to test 30 CRAB isolates (OXA-23/OXA-24/OXA-58/NDM-1) for adaptive resistance to cefiderocol (ARC) after exposure to this drug., Results: After clinical failure with the initial combination, we noted a significant clinical improvement in the patient on the second combination, leading to clinical cure. No ARC was detected in the two OXA-23 case-CRAB isolates. All NDM-1 CRAB isolates were resistant to cefiderocol in standard tests; the OXA-23, OXA-24 and OXA-58 CRAB isolates presented 84.2 %, 50 % and 0 % ARC, respectively., Conclusions: ARC is not routinely assessed for CRAB isolates despite frequently being reported in susceptible isolates (69.2 %). Subpopulations displaying ARC may account for treatment failure, but this hypothesis should be treated with caution in the absence of robust clinical data. The two main findings of this work are that (i) cefiderocol monotherapy should probably not be recommended for OXA-23/24 CRAB infections and (ii) the characterisation of carbapenemases in CRAB strains may be informative for clinical decision-making., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Pseudomonas aeruginosa (PA) remains one of the leading causes of nosocomial acute pneumonia. The array of virulence factors expressed by PA and the intense immune response associated with PA pneumonia play a major role in the severity of these infections. New therapeutic approaches are needed to overcome the high resistance of PA to antibiotics and to reduce the direct damage to host tissues. Through its immunomodulatory and anti-virulence effects, azithromycin (AZM) has demonstrated clinical benefits in patients with chronic PA respiratory infections. However, there is relatively little evidence in PA acute pneumonia. We investigated the effects of AZM, as an adjunctive therapy combined with ceftazidime (CAZ), in a murine model of PA acute pneumonia. We observed that the combined therapy (i) reduces the weight loss of mice 24 h post-infection (hpi), (ii) decreases neutrophil influx into the lungs at 6 and 24 hpi, while this effect is absent in a LPS-induced pneumonia or when PA is pretreated with antibiotics and mice do not receive any antibiotics, and that (iii) AZM, alone or with CAZ, modulates the expression of PA quorum sensing regulators and virulence factors (LasI, LasA, PqsE, PhzM, ExoS). Our findings support beneficial effects of AZM with CAZ on PA acute pneumonia by both bacterial virulence and immune response modulations. Further investigations are needed to clarify the exact underlying mechanisms responsible for the reduction of the neutrophils influx and to better discriminate between direct immunomodulatory properties of AZM, and indirect effects on neutrophilia resulting from bacterial virulence modulation., (© 2023 The Societies and John Wiley & Sons Australia, Ltd.)