Τετάρτη 17 Αυγούστου 2022

Evolution and transmission of cefiderocol-resistant Acinetobacter baumannii during an outbreak in the burn intensive care unit

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Abstract
We report 11 critically-ill burn patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. Clinical success was achieved in 36% and complicated by treatment-emergent resistance and inter-patient transmission of cefiderocol-resistant A. baumannii between patients. Resistant isolates harbored disrupted pirA and piuA gen es that were not disrupted among susceptible isolates.
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Novel mutations in antiviral multiresistant HSV‐2 genital lesion: a case report

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ABSTRACT

Introduction

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management.

Objective

To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion.

Results

Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still prese nt, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage.

Conclusions

This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

This article is protected by copyright. All rights reserved.

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Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE

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Publication date: Available online 17 August 2022

Source: Annals of Diagnostic Pathology

Author(s): Elizabeth Arslanian, Kamaljeet Singh, Katrine Hansen, M. Ruhul Quddus

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Onkolytische Virotherapie bei Kopf-Hals-Karzinomen

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Laryngorhinootologie
DOI: 10.1055/a-1901-9214

Ziel Onkolytische Viren (OV) infizieren und töten Krebszellen und lösen eine antitumorale Immunantwort aus. Durch ihr Potenzial, die Immunresistenz von Tumoren zu durchbrechen, könnten OV eine zukünftige zusätzliche Behandlungsoption bei Patient*innen mit fortgeschrittenen Kopf-Hals-Karzinomen (HNC) sein. Wirkungsweise und Modifikationen der OV zur Behandlung von HNC werden erläutert, ebenso die Risiken bei der Anwendung. Ergebnisse präklinischer und klinischer Studien werden vorgestellt. Methoden Präklinische und klinische Studien zu OV und HNC wurden in der PubMed-Literaturdatenbank und internationalen Studienregistern analysiert. Untersuchungen zum onkolytischen Herpes-Simplex-Virus (HSV), Adenovirus, Vacciniavirus und Reovirus wurden ausgewählt. Ergebnisse In jüngsten präklinischen Studien wurde eine verstärkte Infektion und Abtötung von Tumorzellen durch OV mit Kapsid- und Genommodifikationen beschrieben. Die meisten klinischen Studien waren Phase-I/II-Studien. In Phase-III-Studien wurden nach Behandlung mit onkolytischem HSV, Adenoviren und Reoviren eine partielle Tumorregression und ein verlängertes Überleben beobachtet. In den meisten Studien wurden OV mit Radiochemotherapie oder Immuntherapie kombiniert. Schlussfolgerung In den vorliegenden Studien war die OV-Therapie zur Behandlung von Patient*innen mit HNC sicher, oft gut verträglich und zeigte vielversprechende Ergebnisse in Hinsicht auf Ansprechen und Überleben, insbesondere in Kombination mit einer Radiochemotherapie oder Checkpoint-Inhibitoren.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Tension pneumocephalus: case report and review

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This report presents a case of traumatic tension pneumocephalus associated with an anterior and posterior table frontal sinus fracture in a patient with pneumosinus dilatans and osteogenesis imperfecta. (Source: International Journal of Oral and Maxillofacial Surgery)
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