Clinical Microbiology and Infection最新文献

Objectives: We have developed targeted proteomics in the context of Lyme borreliosis as a new direct diagnostic tool for detecting Borrelia proteins in the skin of patients with erythema migrans. If satisfactory, this proteomic technique could be used in addition to culture and/or PCR for disseminated infections, where Borrelia detection is essential to demonstrate active infection. In these infections, diagnosis is indirect and relies mainly on serology.

Methods: We recruited 46 patients with Lyme borreliosis and 11 controls and collected two skin biopsies from each patient. One biopsy was used for B. burgdorferi sensu lato PCR and culture and the other one was for targeted mass-spectrometry based proteomics. Six markers of infection were selected for proteomics: OspC, flagellin, enolase, lipoprotein gi|365823350, DpbA, and GAPDH.

Results: Culturing Borrelia from the biopsies increased the sensitivity of the methods. Among the patients included for analysis, 61% (28 patients), 61% (28), and 46% (21) were detected as positive, by proteomics, PCR, and culture respectively. PCR and proteomics were complementary. OspC and flagellin were the most frequently detected protein markers of infection by proteomics, which in some patients, detected up to 9 peptides for the flagellin.

Conclusions: It is possible to identify bacterial makers from the skin by proteomics. Our approach can be used to diagnose tick-borne diseases such as Lyme borreliosis.

Trial registration: ClinicalTrials.gov Identifier: NCT02414789.

Objectives: Data are lacking regarding the long-term consequences of SARS-CoV-2 and COVID-19 mRNA vaccine on infants exposed in utero. We aimed to evaluate the neurodevelopment of infants exposed prenatally to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy at 12 months after birth.

Methods: Infants born from mothers exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy, or unexposed to either the virus or the vaccine were enrolled from 2021 to 2023. Infants with prenatal exposure to the virus or vaccine were compared to infants without prenatal exposure to the virus and/or vaccine. Parents received a neurodevelopmental questionnaire (ASQ-3) at 12 months after birth assessing 5 subdomains: communication, gross motor, fine motor, problem solving and personal social development. A low score was defined as <2 standard deviations below the normative mean in at least one of the subdomains.

Results: A total of 330 infants were included (76 in the SARS-CoV-2 group; 153 in the mRNA-COVID-19 vaccine group; 101 in the reference group). In utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine were not associated with an increased risk of a low score for at least one subdomain compared to the reference group. The crude odds ratios were 1.16 (95% confidence interval [CI] 0.59-2.28) and 1.04 (95% CI 0.58-1.86), respectively. Results remained consistent in the multivariate analysis, showing no increased risk of a low score for at least one subdomain for infants exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine, compared to the reference group. The adjusted odds ratios were 1.74 (95% CI 0.76-3.99) and 0.76 (95% CI 0.39-1.49), respectively.

Conclusion: In utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one ASQ-3 subdomain at 12 months after birth. Additional studies are needed to confirm our results, especially longer-term evaluation of infant development.

Objectives: The efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia.

Methods: We performed a randomised, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50, 75 and 100%ƒ_uT_>MIC, and 30-day mortality.

Results: Between November 19, 2019 and June 22, 2022, 295 patients we screened for eligibility, of whom 150 were randomly assigned to receive EI (n=77) or II (n=73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference -12.4%; 95% confidence interval, -29.4 to 4.7, p=0.17). The pharmacokinetic/pharmacodynamic targets of 75 and 100% ƒ_uT_>MIC for empirical treatment were achieved more frequently in the EI group. No statistically-significant differences were found between groups in terms of adverse events or 30-day mortality.

Conclusions: Our findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis/septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.

Objectives: Reported amphotericin B resistance rates for Candida auris vary considerably. This may reflect clinically relevant differences in susceptibility, technical issues with testing or adoption of a clinical breakpoint (BP) that bisects the wild-type population. We compared reference methods and two gradient diffusion strips using a shared C. auris strain collection.

Methods: Forty C. auris strains from nine US states and ≥3 clades were included. Fourteen MIC data sets were generated using EUCAST E.Def 7.4, CLSI M27Ed4, Etest and MTS (Liofilchem) strip MICs. MICs ≤1 mg/L were classified as susceptible.

Results: EUCAST and CLSI amphotericin B MIC testing were robust across included method variables. The modal MIC was 1 mg/L, distributions unimodal and narrow with similar GM-MICs (0.745-1.072); however, susceptibility classification varied (0-28% resistance). Gradient diffusion strip testing resulted in wider and bimodal distributions for 8/9 data sets. If adopting, per manufacturer's protocol, double inoculation for the Etest method, the modal MIC increased to 2-4 mg/L and resistance rates to 45-63% versus 25-30% with the single inoculation. The EUCAST, CLSI, Etest and MTS strip MICs correlated to the OD of drug-free control EUCAST wells suggesting that some isolates grew better than others and that this was associated with MIC.

Conclusions: The EUCAST and CLSI MIC results were in close agreement, whereas the strip test showed wider and bimodal distributions with reader to reader and centre to centre variation. Our study adds to the concern for commercial MIC testing of amphotericin B against C. auris and suggest the current breakpoint leads to random susceptibility classification.