e Two mechanisms of resistance to colistin have been described in Acinetobacter baumannii. One involves complete loss of lipopolysaccharide (LPS), resulting from mutations in lpxA, lpxC, or lpxD, and the second is associated with phosphoethanolamine addition to LPS, mediated through mutations in pmrAB. In order to assess the clinical impacts of both resistance mechanisms, A. baumannii ATCC 19606 and its isogenic derivatives, AL1851 ⌬lpxA, AL1852 ⌬lpxD, AL1842 ⌬lpxC, and ATCC 19606 pmrB, were analyzed for in vitro growth rate, in vitro and in vivo competitive growth, infection of A549 respiratory alveolar epithelial cells, virulence in the Caenorhabditis elegans model, and virulence in a systemic mouse infection model. The in vitro growth rate of the lpx mutants was clearly diminished; furthermore, in vitro and in vivo competitive-growth experiments revealed a reduction in fitness for both mutant types. Infection of A549 cells with ATCC 19606 or the pmrB mutant resulted in greater loss of viability than with lpx mutants. Finally, the lpx mutants were highly attenuated in both the C. elegans and mouse infection models, while the pmrB mutant was attenuated only in the C. elegans model. In summary, while colistin resistance in A. baumannii confers a clear selective advantage in the presence of colistin treatment, it causes a noticeable cost in terms of overall fitness and virulence, with a more striking reduction associated with LPS loss than with phosphoethanolamine addition. Therefore, we hypothesize that colistin resistance mediated by changes in pmrAB will be more likely to arise in clinical settings in patients treated with colistin.

Over the last decade vancomycin-resistant enterococci (VRE) have emerged as nosocomial pathogens. The aim of this study was to determine the prevalence of VRE in clinical samples from hospitalized patients in the Canary Islands. From April to November 2000, 437 enterococci were isolated from patients hospitalized at the four main health care centers in those islands. Identification to the species level was performed with the GPS-TA (Vitek 1) or the Wider I system. A PCR assay was used to determine the genotype of glycopeptide resistance ( vanA, vanB, vanC1, and vanC2/C3 genes). Only three (0.7%) VRE were detected: one vanA Enterococcus faecalis, and two vanC1 Enterococcus gallinarum. To our knowledge, this is the first VRE study carried out in the Canary Islands hospitals, and the results showed a low prevalence of VRE.

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Background: Posaconazole prophylaxis in patients with acute myeloid leukaemia (AML) changed the paradigm of fungal infections (FI). Aims: Description of FI and analysis of factors that might predispose to this type of infection in non-allotransplant AML patients in the posaconazole era.Methods: Retrospective analysis of 144 consecutive non-M3 AML patients diagnosed between January 2012 and June 2018 in a tertiary center and treated with intensive chemotherapy regimens with posaconazole prophylaxis, including autologous transplantation when performed in these patients. Multivariate regression analysis was performed to identify characteristics related to FI. Results: Median age at diagnosis was 52 years [19;71], 52% were females and 90% had an age-adjusted Charlson score ≤3. Genetic risk group according to the European Leukemia Net 2017 classification was favourable in 28%, intermediate in 41% and adverse in 22%. Fourteen percent of patients (n = 20) had secondary AML. Patients were included since diagnosis and if completed remission-induction intensive therapy up to transplant referral, the latter which occurred in 52% of patients (n = 75), with a median follow-up of 7 months [1;81]. Only 7 patients had 1 episode of prophylaxis interruption, 3 due to mucositis and 4 out of our protocol. Median time of neutropenia per cycle was 26 days [5;180] and 10% of patients had >2 episodes of prolonged neutropenia (defined as ≥28 consecutive days of <500 neutrophils/microliter). Fungal infections were identified in 25 patients (17.4%) and classified according to EORTC criteria, with 5 proven, 13 probable and 7 possible infections. In 32% of patients FI occurred during remission-induction (n = 8) of which 3 were diagnosed in the first week of neutropenia, 20% during consolidation treatment in first remission and 48% during relapse treatment. Of the confirmed infections, 3 were aspergillosis and 2 candidemia. Probable infections had pulmonary origin with no microbiology isolate or serologic positivity but identified by typical radiologic evidence; of these, broncho-alveolar lavage and/or pulmonary biopsy was performed in 4 patients (31%) with negative results. For possible infections, antifungal therapy was initiated in a pre-emptive manner for high risk patients with persistent fever despite large spectrum antibiotics. In a multivariate analysis, patients with FI had a higher odds of having relapsed AML and >2 episodes of prolonged neutropenia during treatment (p = 0.049 and p = 0.011, respectively). There was no mortality related to FI in this cohort of patients. Summary/Conclusion: Despite posaconazole prophylaxis, FI is still prevalent in AML patients. Infection during salvage treatment for relapsed disease and >2 previous periods of neutropenia exceeding 4 weeks should raise awareness for an increased risk of FI.

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