Background: Most COVID‐19‐associated mucormycosis (CAM) cases are reported from India and neighbouring countries. Anecdotally cases from Europe have been presented.Objective: To estimate the disease burden and describe the clinical presentation of CAM in Germany.Methods: We identified cases through German mycology networks and scientific societies, and collected anonymised clinical information via FungiScope®.Results: We identified 13 CAM cases from six tertiary referral hospitals diagnosed between March 2020 and June 2021. Twelve patients had severe or critical COVID‐19, eleven were mechanically ventilated for a median of 8 days (range 1‐27 days) before diagnosis of CAM. Eleven patients received systemic corticosteroids. Additional underlying medical conditions were reported for all but one patient, five were immunocompromised because of malignancy or organ transplantation, three were diabetic. Eleven patients developed pneumonia. Mortality was 53.8% with a median time from diagnosis of mucormycosis to death of 9 days (range 0–214 days) despite treatment with liposomal amphotericin B and/or isavuconazole in 10 of 13 cases. CAM prevalence amongst hospitalised COVID‐19 patients overall (0.67% and 0.58% in two centres) and those admitted to the intensive care unit (ICU) (1.47%, 1.78% and 0.15% in three centres) was significantly higher compared to non‐COVID‐19 patients (P < .001 for respective comparisons).Conclusion: COVID‐19‐associated mucormycosis is rare in Germany, mostly reported in patients with comorbidities and impaired immune system and severe COVID‐19 treated in the ICU with high mortality compared to mainly rhino‐orbito‐cerebral CAM in patients with mild COVID‐19 in India. Risk for CAM is higher in hospitalised COVID‐19 patients than in other patients.

Background: Management of bone and joint infection commonly includes 4–6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. Objective: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. Design: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. Setting: Twenty-six NHS hospitals. Participants: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). Interventions: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. Main outcome measure: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. Results: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was –1.38% (90% confidence interval –4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. Limitations: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. Conclusions: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Future work: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. Trial registration: Current Controlled Trials ISRCTN91566927. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.

Transferable linezolid resistance due to optrA, poxtA, cfr and cfr-like genes is increasingly detected in enterococci associated with animals and humans globally. We aimed to characterize the genetic environment of optrA in linezolid-resistant Enterococcus faecalis isolates from Scotland. Six linezolid-resistant E. faecalis isolated from urogenital samples were confirmed to carry the optrA gene by PCR. Short read (Illumina) sequencing showed the isolates were genetically distinct (>13900 core SNPs) and belonged to different MLST sequence types. Plasmid contents were examined using hybrid assembly of short and long read (Oxford Nanopore MinION) sequencing technologies. The optrA gene was located on distinct plasmids in each isolate, suggesting that transfer of a single plasmid did not contribute to optrA dissemination in this collection. pTM6294-2, BX5936-1 and pWE0438-1 were similar to optrA-positive plasmids from China and Japan, while the remaining three plasmids had limited similarity to other published examples. We identified the novel Tn6993 transposon in pWE0254-1 carrying linezolid (optrA), macrolide (ermB) and spectinomycin [ANT(9)-Ia] resistance genes. OptrA amino acid sequences differed by 0–20 residues. We report multiple variants of optrA on distinct plasmids in diverse strains of E. faecalis . It is important to identify the selection pressures driving the emergence and maintenance of resistance against linezolid to retain the clinical utility of this antibiotic.

Background: Penicillin allergy is the most frequently reported allergy in hospitalized patients, although rarely confirmed. Given the negative outcomes associated with incorrect penicillin allergy diagnoses, implementation of programmatic delabeling strategies is important for successful antibiotic stewardship. This systematic review evaluates the effectiveness of different delabeling strategies and highlights elements and settings that facilitate or constrict their implementation. Methods: Following the PRISMA-statement PubMed/MEDLINE, EMBASE, Cochrane Library, and grey literature databases “Worldcat” and “OpenGrey” were searched for studies reporting on interventions to identify, evaluate, or rule out incorrect penicillin allergy in hospitalized adults. Data extraction included settings, intervention types, and their effectiveness, barriers, facilitators, and regulatory factors. Results: This review included 42 studies, involving 6269 patients undergoing penicillin allergy delabeling, with 5017 (80%) successfully delabeled. Effectiveness varied from 32% to 99%. Skin testing had the highest success rate at 87%, followed by a combination of skin testing and oral challenge (84%), and direct oral challenges (77%). Direct delabeling alone had a lower effectiveness (67%), which improved to 80% when paired with oral challenges. Key facilitators included standardized algorithms and involvement of interdisciplinary teams. Barriers included patient refusal, staff resistance, time constraints, and financial limitations, particularly in smaller hospitals. Conclusion: Dependent on financial and staffing resources, oral challenges and direct delabeling after risk stratification may be alternatives to resource-intensive methods, such as skin testing, for successful delabeling. To address barriers to widespread delabeling implementation, patient and provider education must be improved, interprofessional collaboration enhanced, and standardized protocols developed.