Clinical Microbiology and Infection最新文献

Objectives: We have developed targeted proteomics in the context of Lyme borreliosis (LM) 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, the diagnosis is indirect and relies mainly on serology.

Methods: We recruited 46 patients with LM and 11 controls and collected two skin biopsies from each patient. One biopsy was used for Borrelia 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: Outer surface protein C (OspC), flagellin, enolase, lipoprotein gi|365823350, decorin binding protein A, and glyceraldehyde-3-phosphate dehydrogenase.

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 nine peptides for the flagellin.

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

Trial registration: clinicaltrials.gov identifier: NCT02414789.

Background: Invasive fungal disease (IFD) causes morbidity and mortality in immunocompromised hosts (ICHs). Based on increasing recognition of the impact of IFD on human disease, a recent WHO priority list identified key areas of need.

Objectives: This review examines changes in the epidemiology of IFD, in particular the emergence of antifungal-resistant pathogens and the current availability of rapid diagnostic tests and antifungal treatment options.

Sources: Literature between 2000 and January 2024 regarding fungal epidemiology, diagnostic tests, antifungal resistance, emerging fungal pathogens, and novel antifungal agents in both adult and paediatric ICH were reviewed.

Content: We describe the changing epidemiology and continued burden and mortality of IFD in ICH. Furthermore, we discuss the emergence of antifungal-resistant organisms driven by new immunosuppressed populations, climate change, and antifungal exposure in the individual and environment. We highlight novel antifungal agents and how they will address current unmet needs.

Implications: The changing epidemiology and increased population at risk for IFD, lack of recognition or quantification of risks for IFD with new therapies, current gaps in the availability of rapid diagnostic tests, and the imminent availability of novel antifungals with distinct spectra of activity argue for improved availability of and access to rapid diagnostics, antifungal stewardship programmes, and global access to antifungal agents.

Objectives: This study aimed to examine the efficacy of whole genome sequencing (WGS) in accurately predicting susceptibility profiles, potentially eliminating the need for conventional phenotypic drug susceptibility testing (pDST) for first-line antituberculosis drugs in routine tuberculosis diagnosis.

Methods: Over the period of 2017 to 2020, 1114 Mycobacterium tuberculosis complex isolates were collected with drug susceptibility testing conducted using the MGIT960 system and WGS performed for predicting drug resistance profiles. In addition, we implemented a new algorithm with an updated WGS workflow, omitting pan-susceptible strains from pDST.

Results: Results showed that out of 1075 analysed isolates, WGS-based genotypic sensitivity predictions for isoniazid, rifampicin, ethambutol, and pyrazinamide were 100% (95% CI, 99.6-100%), 100% (95% CI, 99.62-100%), 99.8% (95% CI, 99.26-99.94%), and 100% (95% CI, 99.63-100%), respectively. In contrast, the WGS-based genotypic resistance prediction, was 98.85% (95% CI, 93.77-99.79%) for isoniazid, 94.74% (95% CI, 82.71-98.54%) for rifampicin, 86.96% (95% CI, 67.87-95.46%) for ethambutol, and 75.7% (95% CI, 59.9-86.63%) for pyrazinamide. Moreover, WGS enabled the implementation of a new testing algorithm that made it unnecessary to perform pDST in 954 of all 1075 samples (88.7%) and in 890 of 901 pan-susceptible samples (98.8%).

Discussion: Integrating WGS into tuberculosis management offers significant potential to replace phenotypic drug susceptibility testing, especially for problematic drugs like pyrazinamide and ethambutol, potentially improving treatment outcomes.

Background: Herpesviruses represent common and significant infectious complications after allogeneic haematopoietic cell transplantation (HCT). In the last decade, major advances in the prevention and treatment of these infections were accomplished.

Objectives: The aim of this paper is to review the recent advances in the prophylaxis and treatment of herpesvirus infections after allogeneic HCT, to assess the persisting challenges, and to offer future directions for the prevention and management of these infections.

Sources: We searched PubMed for relevant literature regarding specific herpesviruses complicating allogeneic HCT through March 2024.

Content: The largest advances in this past decade were witnessed for cytomegalovirus (CMV) with the advent of letermovir for primary prophylaxis and the development of maribavir as an option for refractory and/or resistant CMV infections in transplant recipients. For varicella zoster virus, prevention of reactivation with the recombinant zoster vaccine offers an additional prophylactic intervention. Pritelivir is being explored for the treatment of drug-resistant or refractory Herpes simplex virus infections. Although rituximab is now an established option for preemptive therapy for Epstein-Barr virus, Human Herpesvirus-6 remains the most elusive virus of the herpesvirus family, with a lack of evidence supporting the benefit of any agent for prophylaxis or for optimal preemptive therapy.

Implications: Although considerable advances have been achieved for the treatment and prevention of herpes virus infections, most notably with CMV, the coming years should hold additional opportunities to tame the beast in these herpesviruses postallogeneic HCT, with the advent of new antivirals, cell-mediated immunity testing, and cytotoxic T lymphocytes infusions.

Background: There has been an unprecedented increase in the number of immunocompromised (IC) patients in clinical practice due to various reasons. Bacterial infections are a major cause of morbidity and mortality in this population. Emerging antibacterial resistance poses a significant challenge for prophylaxis and treatment.

Objectives: We aim to provide an update on antibacterial prophylaxis and management, particularly in high-risk IC patients, including those with acute leukaemia and haematopoietic stem cell transplantation.

Sources: We reviewed original articles, systematic reviews, metanalyses, and guidelines using PubMed, Scopus, and Web of Science.

Content: We discussed the pros and cons of fluoroquinolone prophylaxis in neutropenic patients in the context of personalized medicine. We also attempted to give an outline of empirical treatment of presumed bacterial infections and targeted therapy options for documented bacterial infections, considering the recent surge of multiresistant bacteria in haematological cancer patients and local epidemiology. The shortcomings of the current strategies and future needs are discussed in detail.

Implications: Antibacterial prophylaxis with fluoroquinolones may still have a role in preventing bacterial infections in carefully selected patients with high-risk haematology. Empirical treatment algorithms still need to be adjusted according to host and local factors. The use of rapid diagnostic methods may lessen the need for broad-spectrum empirical antibiotic usage. However, these tests may not be easily available due to budget constraints in countries with limited resources but high rates of bacterial resistance. Although new antimicrobials provide opportunities for effective and less toxic treatment of highly resistant bacterial infections, large-scale data from IC patients are very limited. Using data-driven approaches with artificial intelligence tools may guide the selection of appropriate patients who would benefit most from such prophylactic and treatment regimens.

Objectives: To compile the evidence of sub-groups of patients with Pseudomonas aeruginosa (P. aeruginosa) infection from randomized control trials (RCTs) evaluating different definite antipseudomonal monotherapies for severe P.aeruginosa infection.

Methods: Systematic review and meta-analysis of RCTs that assessed monotherapy with an antipseudomonal drug versus another antipseudomonal for definite treatment, and reported on the subgroup of patients with P. aeruginosa infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS and the reference lists of included trials. The primary outcome was 30-day mortality. Results were pooled using fixed-effect and random-effects model as appropriate. Relative risk (RR) and 95% confidence intervals (CI) were calculated.

Results: A total of 76 RCTs and 1,681 patients with pseudomonal infection were included. Due to the low number of studies which reported our outcomes of interest, all subgroups analyses were underpowered. No difference in all-cause mortality was found for any direct antibiotic comparison. Higher clinical failure rates of carbapenems vs piperacillin-tazobactam were observed for pneumonia in 2 RCTs (RR 2.55, 95% CI 1.29-5.03, I²=0%, n=2), and higher microbiological failure rates with carbapenems versus other comparators (RR 1.24, 95% CI 1.02-1.51, I²=0%, n=23). Patients treated with imipenem were more likely to develop resistance to the study drug versus comparators (RR 2.33, 95% CI 1.61-3.38, I² =0%, n=7).

Conclusions: In this systematic review and meta-analysis of definite antipseudomonal monotherapy for P. aeruginosa infection, we found no evidence for clinical benefit differences among direct antibiotic comparisons, but all subgroup analyses were underpowered to detect significant differences.