Adaptive resistance to cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB): Microbiological and clinical issues.

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.

Clinical manifestations of human leptospirosis: bacteria matter.

Introduction: A high incidence of human leptospirosis is recorded on Mayotte, an oceanic island located in southwestern Indian Ocean, but the severity of the disease appears relatively mild in terms of mortality rate and admission to the intensive care unit. It has been proposed that mild leptospirosis may result from a limited virulence of some of the occurring Leptospira species to which the population is exposed. Methods: Clinical and biological data of patients admitted to the Centre Hospitalier de Mayotte were collected and the infecting Leptospira species were determined through molecular typing. Results: Leptospira interrogans was detected in the minority of admitted patients but most of these patients suffered from severe forms, with 50% admitted to intensive care unit and suffering from organ failures. Nineteen percent of patients infected with Leptospira borgpetersenii were admitted to the intensive care, with 13% displaying organ failures, and one patient died. Leptospira mayottensis was found in 28% of the patients and not a single severe case was observed. Discussion: The distribution of Leptospira species in patients was not different from that reported 10-15 years ago and bacterial genotypes were very closely related to those previously reported. These results highlight the importance of the diversity of pathogenic Leptospira circulating on Mayotte island and are in keeping with distinct outcome of the disease depending on the infecting Leptospira. Altogether, presented data support that the infecting Leptospira species is an important driver of disease severity in humans.

Methodological quality of systematic reviews of the local management of anogenital warts: a systematic review using AMSTAR II, ROBIS and PRISMA.

INTRODUCTION: Anogenital warts (AGWs) are among the most common STDs. Many therapy options are available but are not codified. Systematic reviews (SRs) and meta-analyses (MAs) are helpful to elaborate recommendations on the management of AGWs. The objective of our study was to assess the quality and consistency of SRs for the local management of AGWs using three international tools. METHODS: Seven electronic databases were searched from inception to 10 January 2022 for this SR. The intervention of interest was any local treatment of AGWs. There was no restriction on language and population. The methodological quality, reporting quality and risk of bias (ROB) of the included SRs for the local treatments of AGWs were assessed independently by two investigators with A Measurement Tool to Assess systematic Reviews version II (AMSTAR II), Risk of Bias in Systematic Reviews (ROBIS) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: Twenty-two SRs/MAs met all inclusion criteria. According to the results of the AMSTAR II, nine included reviews were rated critically as being of low quality, and only five were of high quality. Based on the ROBIS tool, only nine SRs/MAs had a low ROB. The domain-assessed 'study eligibility criteria' were mostly rated at a low ROB, unlike the other domains. With PRISMA, the reporting checklist was relatively complete for ten SRs/MAs, but some reporting weaknesses remained in the topics of the abstract, protocol and registration, ROB and funding. DISCUSSION: Several therapy options are available for the local management of AGWs and are widely studied. However, due to the many ROB and low quality of these SRs/MAs, only a few of them have the sufficient methodological quality to support guidelines. PROSPERO REGISTRATION NUMBER: CRD42021265175.