Archive for June, 2018

Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.

Sci Rep. June 25, 2018 V.8 N.1 P.9633.      doi: 10.1038/s41598-018-27890-4.

Omoto S1, Speranzini V2, Hashimoto T3, Noshi T3, Yamaguchi H3, Kawai M3, Kawaguchi K3, Uehara T3, Shishido T3, Naito A3, Cusack S4.

Author information

1 Shionogi & Co., Ltd., Osaka, Japan. shinya.oomoto@shionogi.co.jp

2 European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France.

3 Shionogi & Co., Ltd., Osaka, Japan.

4 European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France. cusack@embl.fr

Abstract

Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. In clinical trials, single doses of BXM profoundly decrease viral titers as well as alleviating influenza symptoms. Here, we characterize the impact on BXA susceptibility and replicative capacity of variant viruses detected in the post-treatment monitoring of the clinical studies. We find that the PA I38T substitution is a major pathway for reduced susceptibility to BXA, with 30- to 50-fold and 7-fold EC50 changes in A and B viruses, respectively.

The viruses harboring the I38T substitution show severely impaired replicative fitness in cells, and correspondingly reduced endonuclease activity in vitro. Co-crystal structures of wild-type and I38T influenza A and B endonucleases bound to BXA show that the mutation reduces van der Waals contacts with the inhibitor. A reduced affinity to the I38T mutant is supported by the lower stability of the BXA-bound endonuclease. These mechanistic insights provide markers for future surveillance of treated populations.

FULL TEXT

https://www.nature.com/articles/s41598-018-27890-4

PDF

https://www.nature.com/articles/s41598-018-27890-4.pdf

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June 30, 2018 at 5:47 pm

Approved: Baloxavir marboxil

WHO Drug Information 2018 V.32 N.1 P.32

One-dose treatment for influenza

Product name: Xofluza®

Dosage form: Tablet

Class: cap-dependent endonuclease inhibitor

Approval: Ministry of Health, Labour and Welfare (MHLW) of Japan

Use: Treatment of influenza types A and B

Benefits: Treatment requires only a single oral dose regardless of age.

Shionogi & Co. Ltd Press

PDF

http://www.who.int/medicines/publications/druginformation/issues/WHO_DI_32-1.pdf

 

June 30, 2018 at 5:45 pm

Back to basics: hand hygiene and isolation

Current Opinion in Infectious Diseases: August 2014 – Volume 27 – Issue 4 – p 379–389

Huang, Gene K.L.a; Stewardson, Andrew J.a,b,d; Grayson, Michael L.a,b,c,d

Purpose of review

Hand hygiene and isolation are basic, but very effective, means of preventing the spread of pathogens in healthcare. Although the principle may be straightforward, this review highlights some of the controversies regarding the implementation and efficacy of these interventions.

Recent findings

Hand hygiene compliance is an accepted measure of quality and safety in many countries. The evidence for the efficacy of hand hygiene in directly reducing rates of hospital-acquired infections has strengthened in recent years, particularly in terms of reduced rates of staphylococcal sepsis. Defining the key components of effective implementation strategies and the ideal method(s) of assessing hand hygiene compliance are dependent on a range of factors associated with the healthcare system. Although patient isolation continues to be an important strategy, particularly in outbreaks, it also has some limitations and can be associated with negative effects. Recent detailed molecular epidemiology studies of key healthcare-acquired pathogens have questioned the true efficacy of isolation, alone as an effective method for the routine prevention of disease transmission.

Summary

Hand hygiene and isolation are key components of basic infection control. Recent insights into the benefits, limitations and even adverse effects of these interventions are important for their optimal implementation.

FULL TEXT

https://journals.lww.com/co-infectiousdiseases/Fulltext/2014/08000/Back_to_basics___hand_hygiene_and_isolation.13.aspx?WT.mc_id=HPxADx20100319xMP

PDF (CLIC en ARTICLE as PDF)

June 30, 2018 at 10:54 am

Zika virus infection: epidemiology, clinical manifestations and diagnosis

Current Opinion in Infectious Diseases: October 2016 – Volume 29 – Issue 5 – p 459–466

Calvet, Guilherme Amaral; Santos, Flavia Barreto dos; Sequeira, Patricia Carvalho

Purpose of review

Zika virus (ZIKV) is an arbovirus previously believed to cause only a mild and self-limiting illness. Recently, it has emerged as a new public health threat that caused a large outbreak in French Polynesia in 2013–2014 and since 2015 an explosive outbreak in Brazil, with an increase in severe congenital malformations (microcephaly) and neurological complications, mainly Guillain–Barré syndrome (GBS). Since then, it has spread through the Americas. On 1 February 2016, the WHO declared the ZIKV epidemic in Brazil a Public Health Emergency of International Concern. We reviewed the epidemiology of ZIKV infection, clinical presentations and diagnosis. We highlighted the clinical features and nonvector borne transmission of the virus.

Recent findings

Association between ZIKV infection and severe foetal outcomes, including microcephaly and other birth defects; increased rate of GBS and other neurological complications due to the ongoing ZIKV outbreak; increased evidence to date of ZIKV being the only arbovirus linked to sexual transmission; the challenge of ZIKV diagnosis; and the need for a specific point-of care test in epidemic scenarios.

Summary

The findings illustrate the emergence of a viral disease with the identification of new associated disorders, new modes of transmission, including maternal–foetal and sexual transmission.

FULL TEXT

https://journals.lww.com/co-infectiousdiseases/Fulltext/2016/10000/Zika_virus_infection___epidemiology,_clinical.6.aspx?WT.mc_id=HPxADx20100319xMP

PDF (CLIC en ARTICLE as PDF)

June 30, 2018 at 10:51 am

Sexually transmitted infections in older populations

Current Opinion in Infectious Diseases. 26(1):80-85, February 2013.

Poynten, I. Mary; Grulich, Andrew E.; Templeton, David J.

Purpose of review

People are living longer and healthier lives. In recent years, there has been a focus on recognition of ongoing sexual activity among older adults and leading from this, the potential for an increase in diagnoses of sexually transmitted infections (STIs). Data on STI rates, sexual behaviour and factors affecting susceptibility to STIs are discussed.

Recent findings

There is limited published literature in this field and few recent longitudinal studies of STI acquisition in people older than 50 years. Although there is evidence of an increase in incidence, STIs remain rare in older compared with younger populations. Compared with their heterosexual counterparts, older men who have sex with men are at higher risk of incident HIV and some other STIs. The HIV epidemic is ageing as a result of increasing life span and acquisition of HIV at older ages. Improved longevity, evolving societal norms and physiological changes may place older people at risk of HIV and other STIs.

Summary

Routine STI screening is not warranted in all older people. Education and prevention strategies for all people at greater risk of HIV, regardless of age are required. Age-appropriate interventions designed to impart knowledge and provide the requisite skills needed to reduce STI risk in older age would be beneficial.

FULL TEXT

https://journals.lww.com/co-infectiousdiseases/Fulltext/2013/02000/Sexually_transmitted_infections_in_older.12.aspx?WT.mc_id=HPxADx20100319xMP

PDF (CLIC en ARTICLE as PDF)

June 30, 2018 at 10:49 am

Antibiotic therapy of pneumonia in the obese patient: dosing and delivery

Current Opinion in Infectious Diseases. 27(2):165-173, April 2014.

Al-Dorzi, Hasan M.; Al Harbi, Shmylan A.; Arabi, Yaseen M.

Purpose of review

Obesity has been shown to be associated with antibiotic underdosing and treatment failure. This article reviews the recent literature on antibiotic dosing in obese patients with pneumonia.

Recent findings

Obesity is associated with several alterations in antibiotic pharmacokinetics and pharmacodynamics, including increases in the antibiotic volume of distribution and clearance. These alterations necessitate changes in the dosing of certain antibiotics. However, data on antibiotic dosing for pneumonia in obese patients are limited and come mainly from observational studies. Additionally, dosing recommendations are often extrapolated from healthy obese volunteers and from the studies of antibiotics given for other indications.

Summary

Recognizing obesity-related pharmacokinetic and pharmacodynamic alterations is important in treating obese patients with pneumonia. Studies that evaluate such alterations and assess the impact of antibiotic dosing and delivery on the clinical outcomes of this patient population are needed.

FULL TEXT

https://journals.lww.com/co-infectiousdiseases/Fulltext/2014/04000/Antibiotic_therapy_of_pneumonia_in_the_obese.9.aspx?WT.mc_id=HPxADx20100319xMP

PDF (CLIC en ARTICLE as PDF)

June 30, 2018 at 10:47 am

The role of the surface environment in healthcare-associated infections

Current Opinion in Infectious Diseases. 26(4):338-344, August 2013.

Weber, David J.; Anderson, Deverick; Rutala, William A.

Purpose of review

This article reviews the evidence demonstrating the importance of contamination of hospital surfaces in the transmission of healthcare-associated pathogens and interventions scientifically demonstrated to reduce the levels of microbial contamination and decrease healthcare-associated infections.

Recent findings

The contaminated surface environment in hospitals plays an important role in the transmission of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), Clostridium difficile, Acinetobacter spp., and norovirus. Improved surface cleaning and disinfection can reduce transmission of these pathogens. ‘No-touch’ methods of room disinfection (i.e., devices which produce ultraviolet light or hydrogen peroxide) and ‘self-disinfecting’ surfaces (e.g., copper) also show promise to decrease contamination and reduce healthcare-associated infections.

Summary

Hospital surfaces are frequently contaminated with important healthcare-associated pathogens. Contact with the contaminated environment by healthcare personnel is equally as likely as direct contact with a patient to lead to contamination of the healthcare provider’s hands or gloves that may result in patient-to-patient transmission of nosocomial pathogens. Admission to a room previously occupied by a patient with MRSA, VRE, Acinetobacter, or C. difficile increases the risk for the subsequent patient admitted to the room to acquire the pathogen. Improved cleaning and disinfection of room surfaces decreases the risk of healthcare-associated infections.

FULL TEXT

https://journals.lww.com/co-infectiousdiseases/Abstract/2013/08000/The_role_of_the_surface_environment_in.8.aspx?WT.mc_id=HPxADx20100319xMP

PDF (CLIC en ARTICLE as PDF)

June 30, 2018 at 10:43 am

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