Archive for August, 2014

Clinical guidelines in the management of prosthetic joint infection

Journal of Antimicrobial Chemotherapy SEPT 2014 V.69 Suppl.1

 

Angela M. Minassian1, Douglas R. Osmon2 and Anthony R. Berendt1,*

1Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Oxford OX3 7HE, UK

2Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA

*Corresponding author. Tel: +44-1865572415; E-mail: tony.berendt@ouh.nhs.uk

Clinical practice guidelines for the diagnosis and management of prosthetic joint infection have been produced by a range of organizations.

Guidelines stress the importance of multi-disciplinary working and of adopting a methodical approach. This includes careful assessment of the patient’s surgical, medical and psychosocial problems, rational investigation, a decision-making framework for surgery and targeted, sometimes prolonged, use of intravenous or highly bioavailable oral antibiotics.

Despite limited high-quality evidence, adoption of clinical guidelines can improve practice by reducing variation and by establishing conditions for the subsequent conduct of multicentre studies or systematic reviews.

PDF

http://jac.oxfordjournals.org/content/69/suppl_1/i29.full.pdf+html

August 30, 2014 at 8:45 pm

Sofosbuvir for the treatment of chronic hepatitis C: between current evidence and future perspectives.

Hepat Med. 2014 Apr 29;6:25-33.

Degasperi E, Aghemo A.
Division of Gastroenterology and Hepatology, AM and M Migliavacca Center, Fondazione IRCCS Ca’ Granda Maggiore Hospital, University of Milan, Milan, Italy.

Abstract
In recent years, clinical research in the field of new treatments for chronic hepatitis C (HCV) has been devoted to developing regimens based on direct-acting antivirals (DAAs), with the goal of increasing treatment efficacy and improving tolerability and safety.

This can be achieved by Peginterferon (PegIFN)-free anti-HCV regimens, as PegIFN is responsible for many side effects and limits treatment access due to contraindications in some patient categories.

Sofosbuvir (SOF) is the first compound to enter the market with IFN-free combination regimens; it belongs to the nucleotide inhibitors of viral polymerase NS5B and acts as a chain terminator during the HCV replication process, exhibiting pan-genotypic antiviral activity with a high barrier to resistance.

Clinical trials in HCV genotype 2/3 patients have demonstrated optimal efficacy in HCV-2, where the combination SOF/ribavirin (Rbv) for 12 weeks resulted in >90% sustained virological response (SVR) rates, while HCV-3 patients with advanced liver fibrosis and previous failure to PegIFN plus Rbv therapy still require individualized and optimized treatment strategies.

Historically difficult-to-treat genotypes HCV-1, -4-6 can benefit from reduced duration of PegIFN plus SOF and Rbv, while IFN-free regimens in these patients will be based on SOF in combination with other DAA classes.

Due to an optimal tolerability and safety profile with no significant drug-to-drug interactions, SOF is currently undergoing clinical trials in the setting of pre- and post-liver transplantation and HIV-coinfected patients, with the objective to address the until now unmet need for safe and efficient treatment in these populations.

This article provides an overview of SOF features and the main clinical trials, discussing key results and potential future developments.

PDF
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010630/pdf/hmer-6-025.pdf

 

August 30, 2014 at 8:41 pm

Documento de consenso de GeSIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (Actualización enero 2014)

Enfermedades Infecciosas y Microbiología Clínica Agosto-Septiembre 2014 V.32 N.7

2014 – CONSENSO GeSIDA – TARV en adultos -Update

Documento de consenso de GeSIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (Actualización enero 2014)

Panel de expertos de GeSIDA y Plan Nacional sobre el Sida

Objetivo

Actualizar las recomendaciones sobre el tratamiento antirretroviral (TAR) para adultos infectados por el VIH-1.

Métodos

Este documento ha sido consensuado por un panel de expertos de GESIDA y de la Secretaría del Plan Nacional sobre el Sida tras revisar los resultados de eficacia y seguridad de ensayos clínicos, estudios de cohortes y de farmacocinética publicados en revistas biomédicas (PubMed y Embase) o presentados en congresos. La fuerza de cada recomendación y la gradación de su evidencia se basan en una modificación de los criterios de la Infectious Diseases Society of America.

Resultados

Se recomienda el TAR en todos los pacientes infectados por el VIH-1. La fuerza y la gradación de la recomendación varían según la circunstancia clínica: enfermedades B o C de los CDC (A-I), pacientes asintomáticos según número de CD4+ (< 350, A-I; 350-500, A-II; > 500, B-III), comorbilidades (nefropatía por VIH, hepatitis crónica por VHB o VHC, edad superior a 55 años, riesgo cardiovascular elevado, trastornos neurocognitivos o neoplasias, A-II) y prevención de la transmisión del VIH (materno-fetal o heterosexual, A-I; homosexual entre hombres, A-III). El objetivo del TAR es lograr una carga viral plasmática (CVP) indetectable. El TAR de inicio debe ser siempre una combinación de 3 fármacos que incluya una asociación de 2 ITIAN y otro fármaco de distinta familia (ITINN, IP/r o InInt). De las posibles pautas de inicio se han considerado algunas como alternativa. Se exponen las causas y los criterios para cambiar un TAR estando con CVP indetectable, así como en el fracaso virológico en el que en el TAR de rescate se deben usar 3 o 2 fármacos plenamente activos frente al virus. Se actualizan igualmente los criterios específicos del TAR en situaciones especiales (infección aguda, infección por VIH-2, embarazo) o comorbilidades (tuberculosis u otra enfermedad oportunista, afectación renal, hepatopatías y neoplasias).

Conclusiones

Este nuevo documento actualiza las recomendaciones previas respecto a cuándo y con qué regímenes iniciar el TAR, cómo monitorizarlo y qué hacer cuando fracasa o desarrolla toxicidad. Se actualizan los criterios específicos del TAR en pacientes con comorbilidades y en situaciones especiales.

PDF

http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=90340091&pident_usuario=0&pcontactid=&pident_revista=28&ty=107&accion=L&origen=zonadelectura&web=zl.elsevier.es&lan=es&fichero=28v32n07a90340091pdf001.pdf

 

August 30, 2014 at 8:35 pm

Guidelines for the Use of ARV Agents in HIV-1-Infected Adults and Adolescents DHHS MAY, 2014

Developed by the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC)

PDF

http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf

August 30, 2014 at 8:32 pm

The clinical presentation of prosthetic joint infection

Journal of Antimicrobial Chemotherapy SEPT 2014 V.69 Suppl.1

Lucinda Barrett and Bridget Atkins*

Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford, UK

*Corresponding author. Tel: +44-1865-220886; Fax: +44-1865-220890; E-mail: bridget.atkins@ouh.nhs.uk

Prosthetic joint infection (PJI) complicates ∼1% of arthroplasties but accounts for considerable morbidity. Both the timing and features of PJI can vary widely.

Patients may present with early (≤3 months post-operatively), delayed (3–24 months) or late disease (>24 months).

They may be acutely unwell with systemic signs of sepsis or describe only a chronically painful joint with or without sinus formation.

Diagnostic criteria as proposed by the Infectious Diseases Society of America and the Musculoskeletal Infection Society highlight the importance of joint sampling to obtain histological and robust microbiological evidence. Staphylococcus aureus and coagulase-negative staphylococci account for >50% of infections.

Early infections are likely to have been acquired intra- or peri-operatively, whereas late infection is usually haematogenous in origin.

Acute joint inflammation suggests the presence of intra-articular free-living bacteria, whereas chronic infections are associated with the formation of biofilm at the bone–cement or bone–prosthesis interface.

The most significant risk factors predisposing to PJI are previous operation on the index joint, previous arthroplasty at a different site, American Society of Anesthesiologists’ grade 2, 3 or 4, body mass index >25, malignancy and procedure duration <2 or >4 h.

PDF

http://jac.oxfordjournals.org/content/69/suppl_1/i25.full.pdf+html

August 26, 2014 at 8:12 pm

Has the time come to abandon efavirenz for first-line antiretroviral therapy?

Journal of Antimicrobial Chemotherapy JUL 2014 V.69 N.7 P.1742-1747

 

Francois Raffi1,*, Anton L. Pozniak2 and Mark A. Wainberg3

1Division of Infectious Diseases, Nantes University Hospital, Nantes, France

2HIV Department, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

3Departments of Medicine and of Microbiology, Jewish General Hospital, McGill University, Montreal, Canada

*Corresponding author. Tel: +33-240-083-372; E-mail: francois.raffi@wanadoo.fr

Abstract

Efavirenz has been recommended as a preferred third agent together with two nucleos(t)ides for first-line combination antiretroviral therapy (ART) for >15 years.

The availability of efavirenz in a fixed-dose combination makes it very attractive.

However, because of (i) adverse events associated with efavirenz, (ii) a poorer overall efficacy of efavirenz compared with newer antiretrovirals, (iii) the ranking of efavirenz as FDA Pregnancy Category D and (iv) the relatively high prevalence of transmitted drug-resistance mutations, there is a need to reconsider the role of efavirenz in first-line ART.

We review the available evidence that challenges efavirenz’s current position in first-line HIV treatment guidelines.

Apart from its animal teratogenic potential, and moderate neuropsychiatric adverse events associated with its use, efavirenz has recently been associated with an increased risk of suicidality when compared with other antiretroviral drugs.

Most importantly, efavirenz has demonstrated overall inferior efficacy to various comparator drugs, which include rilpivirine, raltegravir and dolutegravir, in antiretroviral-naive patients.

Furthermore, epidemiological data indicate that the prevalence of non-nucleoside reverse transcriptase inhibitor resistance has reached 5%–8% in various parts of the world, and minority transmitted non-nucleoside reverse transcriptase inhibitor resistance-associated mutations can have a negative impact on the outcome of first-line efavirenz-based ART.

Based on considerations of efficacy, toxicity and resistance, it is time to reconsider the routine use of efavirenz in ART. This, of course, presupposes that other antiretrovirals will be available in place of efavirenz, and may not be applicable in certain developing country settings where this is not the case.

PDF

http://jac.oxfordjournals.org/content/69/7/1742.full.pdf+html

August 26, 2014 at 8:08 pm

Zero tolerance for healthcare-associated MRSA bacteraemia: is it realistic?

Journal of Antimicrobial Chemotherapy AUG 2014 V.69 N.8 P.2238-2245

 

  1. Estée Török1,2,3,*,†, Simon R. Harris4,†, Edward J. P. Cartwright1,3, Kathy E. Raven1, Nicholas M. Brown2,3, Michael E. D. Allison5, Daniel Greaves2, Michael A. Quail4, Direk Limmathurotsakul6, Matthew T. G. Holden4, Julian Parkhill4 and Sharon J. Peacock1,2,3,4,6

1Department of Medicine, University of Cambridge, Cambridge, UK

2Department of Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

3Public Health England, Clinical Microbiology and Public Health Laboratory, Cambridge, UK

4Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

5Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

6Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand

*Corresponding author. University of Cambridge, Department of Medicine, Box 157, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK. Tel: +44-(0)1223-336845; Fax: +44-(0)1223-336846; E-mail: et317@medschl.cam.ac.uk

Background

The term ‘zero tolerance’ has recently been applied to healthcare-associated infections, implying that such events are always preventable. This may not be the case for healthcare-associated infections such as methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia.

Methods

We combined information from an epidemiological investigation and bacterial whole-genome sequencing to evaluate a cluster of five MRSA bacteraemia episodes in four patients in a specialist hepatology unit.

Results

The five MRSA bacteraemia isolates were highly related by multilocus sequence type (ST) (four isolates were ST22 and one isolate was a single-locus variant, ST2046). Whole-genome sequencing demonstrated unequivocally that the bacteraemia cases were unrelated. Placing the MRSA bacteraemia isolates within a local and global phylogenetic tree of MRSA ST22 genomes demonstrated that the five bacteraemia isolates were highly diverse. This was consistent with the acquisition and importation of MRSA from the wider referral network. Analysis of MRSA carriage and disease in patients within the hepatology service demonstrated a higher risk of both initial MRSA acquisition compared with the nephrology service and a higher risk of progression from MRSA carriage to bacteraemia, compared with patients in nephrology or geriatric services. A root cause analysis failed to reveal any mechanism by which three of five MRSA bacteraemia episodes could have been prevented.

Conclusions

This study illustrates the complex nature of MRSA carriage and bacteraemia in patients in a specialized hepatology unit. Despite numerous ongoing interventions to prevent MRSA bacteraemia in healthcare settings, these are unlikely to result in a zero incidence in referral centres that treat highly complex patients.

PDF

http://jac.oxfordjournals.org/content/69/8/2238.full.pdf+html

August 26, 2014 at 8:04 pm

Sofosbuvir: a new oral once-daily agent for the treatment of hepatitis C virus infection.

P T. 2014 May;39(5):345-52.

Cha A, Budovich A.
PDF
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029125/pdf/ptj3905345.pdf

 

August 26, 2014 at 8:00 pm

Emerging antivirals for the treatment of hepatitis B.

World J Gastroenterol. 2014 Jun 28;20(24):7707-17.

Wang XY, Chen HS.
Author information
Xue-Yan Wang, Hong-Song Chen, Peking University Hepatology Institute, Peking University People’s Hospital, Beijing 100044, China.
Abstract
Chronic infection with hepatitis B virus (HBV) constitutes a major global public health threat, causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma, thus representing high unmet medical needs.

Currently available therapies are safe, well tolerated, and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral resistance. However, long-term management remains a clinical challenge, mainly due to the slow kinetics of HBV surface antigen clearance.

In this article, we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry, viral replication, viral assembly, and the host immune response, leading to preclinical and clinical trials for possible future therapeutic intervention.

The recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.
PDF
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069299/pdf/WJG-20-7707.pdf

August 26, 2014 at 7:57 pm

Molecular techniques for diagnosing prosthetic joint infections

Journal of Antimicrobial Chemotherapy SEPT 2014 V.69 Suppl.1

 

John C. Hartley* and Kathryn A. Harris

Department of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK

*Corresponding author. Tel: +44-(0)20-7829-7930; Fax: +44-(0)20-7813-8268; E-mail: john.hartley@gosh.nhs.uk

Prosthetic joint infections (PJI) can be broadly classed into two groups: those where there is a strong clinical suspicion of infection and those with clinical uncertainty, including ‘aseptic loosening’.

Confirmation of infection and identification of the causative organism along with provision of antibiotic susceptibility data are important stages in the management of PJI.

Conventional microbiological culture and susceptibility testing is usually sufficient to provide this. However, it may fail due to prior antimicrobial treatment or the presence of unusual and fastidious organisms.

Molecular techniques, in particular specific real-time and broad-range PCR, are available for diagnostic use in suspected PJI. In this review, we describe the techniques available, their current strengths, limitations and future development.

Real-time pathogen-specific and broad-range PCR (with single sequence determination) are suitable for use as part of the routine diagnostic algorithm for clinically suspected PJI.

Further development of broad-range PCR with high-throughput (next-generation) sequencing is necessary to understand the microbiome of the prosthetic joint further before this technique can be used for routine diagnostics in clinically unsuspected PJI, including aseptic loosening.

PDF

http://jac.oxfordjournals.org/content/69/suppl_1/i21.full.pdf+html

 

2014-09 Molecular techniques for diagnosing prosthetic joint infections JAC

August 23, 2014 at 6:27 pm

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