Archive for March, 2016

Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia

Clinical Infectious Diseases April 1, 2016 V.62 N.7 P.817-823

Naomi J. Gadsby, Clark D. Russell, Martin P. McHugh, Harriet Mark, Andrew Conway Morris, Ian F. Laurenson, Adam T. Hill, and Kate E. Templeton

1Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh

2College of Medicine and Veterinary Medicine, University of Edinburgh

3Department of Anaesthesia, University of Cambridge

4Respiratory Medicine, Royal Infirmary of Edinburgh, United Kingdom

Background

The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP.

Methods

Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns.

Results

Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients.

Conclusions

Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.

PDF

http://cid.oxfordjournals.org/content/62/7/817.full.pdf

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March 31, 2016 at 8:05 am

REVIEW ARTICLE – Zika Virus

New England Journal of Medicine March 31, 2016

Lyle R. Petersen, M.D., M.P.H., Denise J. Jamieson, M.D., M.P.H., Ann M. Powers, Ph.D., and Margaret A. Honein, Ph.D., M.P.H.

From the Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO (L.R.P., A.M.P.); and the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (D.J.J), and the Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities (M.A.H), Centers for Disease Control and Prevention, Atlanta.

Address reprint requests to Dr. Petersen at the Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, 3156 Rampart Rd., Fort Collins, CO 80521, or at lxp2@cdc.gov .

In 1947, a study of yellow fever yielded the first isolation of a new virus, from the blood of a sentinel rhesus macaque that had been placed in the Zika Forest of Uganda.1

Zika virus remained in relative obscurity for nearly 70 years; then, within the span of just 1 year, Zika virus was introduced into Brazil from the Pacific Islands and spread rapidly throughout the Americas.2

It became the first major infectious disease linked to human birth defects to be discovered in more than half a century and created such global alarm that the World Health Organization (WHO) would declare a Public Health Emergency of International Concern.3

This review describes the current understanding of the epidemiology, transmission, clinical characteristics, and diagnosis of Zika virus infection, as well as the future outlook with regard to this disease…

FULL TEXT

http://www.nejm.org/doi/full/10.1056/NEJMra1602113?query=TOC

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMra1602113

March 30, 2016 at 10:30 pm

The Zika Challenge

New England Journal of Medicine March 31, 2016

Perspective

Charlotte J. Haug, M.D., Ph.D., Marie Paule Kieny, Ph.D., and Bernadette Murgue, M.D., Ph.D.

Dr. Haug is an international correspondent for the Journal; Dr. Kieny is the assistant director-general for health systems and innovation, and Dr. Murgue the project manager of the WHO R&D Blueprint, at the World Health Organization, Geneva.

“There are many viruses that have similar characteristics to dengue, yellow fever, and Zika that have the potential to emerge. We don’t know why Zika emerged now.

But we know how to develop surveillance systems that will allow us to pick these viruses up if they start to move as Zika has.”

This starting point was outlined by tropical medicine expert Duane Gubler at a World Health Organization (WHO) meeting in Geneva in early March.

Gubler has spent his career studying tropical infectious diseases with an emphasis on dengue virus (DENV), a flavivirus closely related to Zika virus (ZIKV).1

His introductory presentation at the international meeting about the ZIKV challenge emphasized the complexity of the flavivirus–host relationship and the inevitability, thanks to urbanization and globalization, of emergence and spread of viruses that were previously confined to small, remote geographic areas…

FULL TEXT

http://www.nejm.org/doi/full/10.1056/NEJMp1603734

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMp1603734

March 30, 2016 at 10:28 pm

Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities

New England Journal of Medicine March 31, 2016

BRIEF REPORT

Rita W. Driggers, M.D., Cheng-Ying Ho, M.D., Ph.D., Essi M. Korhonen, M.Sc., Suvi Kuivanen, M.Sc., Anne J. Jääskeläinen, Ph.D., Teemu Smura, Ph.D., Avi Rosenberg, M.D., Ph.D., D. Ashley Hill, M.D., Roberta L. DeBiasi, M.D., Gilbert Vezina, M.D., Julia Timofeev, M.D., Fausto J. Rodriguez, M.D., Lev Levanov, Ph.D., Jennifer Razak, M.G.C., C.G.C, Preetha Iyengar, M.D., Andrew Hennenfent, D.V.M., M.P.H., Richard Kennedy, M.D., Robert Lanciotti, Ph.D., Adre du Plessis, M.B., Ch.B., M.P.H., and Olli Vapalahti, M.D., Ph.D.

The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week.

The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation.

At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated….

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1601824

March 30, 2016 at 10:27 pm

DENGUE DURING PREGNANCY: ASSOCIATION WITH LOW BIRTH WEIGHT AND PREMATURITY

Rev. Inst. Med. trop. S. Paulo FEB 2016 V.58                            BLOG

Christiane Fernandes RIBEIRO(1), Vânia Glória Silami LOPES(2), Patricia Brasil(3), Licinio Esmeraldo da Silva(4), Pedro Henrique Fernandes Josephson RIBEIRO(5), Luca Cipriani UGENTI(5), Rita Maria Ribeiro NOGUEIRA(6)

(1)Universidade Federal Fluminense, Departamento Materno-Infantil. Niterói, RJ, Brasil. E-mail: chrisribeiro@vm.uff.br

(2)Universidade Federal Fluminense, Departament of Pathology. Niterói, RJ, Brasil. E-mail: vasilami@oul.com.br

(3)Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, RJ, Brasil. E-mail: patricia.brasil@ini.fiocruz.br

(4)Universidade Federal Fluminense, Institute of Mathematics and Statistics, Department of Statistics. Institute of Mathematics. Rua Mario Braga Santos s/n, 7º andar, Campus Valonguinho 24020-140 Niterói, RJ, Brasil. E-mail: licinio.da.silva@gmail.com

(5)Universidade Federal Fluminense, Faculdade de Medicina, Niterói, RJ, Brasil. E-mails: pedrojosephson@hotmail.com; lucaugenti@hotmail.com

(6)Instituto Oswaldo Cruz, Laboratório de Flavirus, FIOCRUZ, RJ, Brasil. E-mail: rita@ioc.fiocruz.br

The aim of this study was to evaluate the effects of dengue virus infection during pregnancy and its correlation with low birth weight, prematurity, and asphyxia. A non-concurrent cohort study reveals the association of dengue during pregnancy with prematurity and low birth weight, when birth occurred during the maternal-fetal viremia period (p = 0.016 and p < 0.0001, respectively).

PDF

http://www.scielo.br/pdf/rimtsp/v58/0036-4665-rimtsp-S1678-9946201658008.pdf

March 30, 2016 at 8:29 am

Prevalence and risk factors for carriage of ESBL-producing Enterobacteriaceae in Amsterdam

Journal of Antimicrobial Chemotherapy April 2016 V.71 N.4 P.1076-1082

A. Reuland, N. al Naiemi, A. M. Kaiser, M. Heck, J. A. J. W. Kluytmans, P. H. M. Savelkoul, P. J. M. Elders, and C. M. J. E. Vandenbroucke-Grauls

1Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands

2Laboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands

3Medical Microbiology and Infection Control, Ziekenhuisgroep Twente, Almelo, The Netherlands

4Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

5Department of Medical Microbiology and Infection Control, Amphia Hospital, Breda, The Netherlands

6Department of Medical Microbiology, St Elisabeth Hospital, Tilburg, The Netherlands

7EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands

Objectives

The objectives of this study were to determine the prevalence of carriage of ESBL-producing Enterobacteriaceae (ESBL-E) in a representative sample of the general adult Dutch community, to identify risk factors and to gain understanding of the epidemiology of these resistant strains.

Methods

Adults enrolled in five general practices in Amsterdam were approached by postal mail and asked to fill in a questionnaire and to collect a faecal sample. Samples were analysed for the presence of ESBL-E. ESBL genes were characterized by PCR and sequencing. Strains were typed using MLST and amplified fragment length polymorphism (AFLP) and plasmids were identified by PCR-based replicon typing. Risk factors for carriage were investigated by multivariate analysis.

Results

ESBL-E were found in 145/1695 (8.6%) samples; 91% were Escherichia coli. Most ESBL genes were of the CTX-M group (blaCTX-M-1 and blaCTX-M-15). MLST ST131 was predominant and mainly associated with CTX-M-15-producing E. coli. One isolate with reduced susceptibility to ertapenem produced OXA-48. In multivariate analyses, use of antimicrobial agents, use of antacids and travel to Africa, Asia and Northern America were associated with carriage of ESBL-E, in particular strains with blaCTX-M-14/15.

Conclusions

This study showed a high prevalence of ESBL-E carriage in the general Dutch community. Also, outside hospitals, the use of antibiotics was a risk factor; interestingly, use of antacids increased the risk of carriage. A major risk factor in the general population was travel to countries outside Europe, in particular to Asia, Africa and Northern America.

PDF

http://jac.oxfordjournals.org/content/71/4/1076.full.pdf

 

March 30, 2016 at 8:18 am

A Randomized Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin and Skin Structure Infection

Clinical Infectious Diseases March 1, 2016 V.62 N.5 P.545-551

Editor’s Choice

Michael W. Dunne, Sailaja Puttagunta, Philip Giordano, Dainis Krievins, Michael Zelasky, and James Baldassarre

1Allergan plc, Branford, Connecticut

2Orlando Health, Florida

3Stradins University Hospital, Riga, Latvia

4Janssen Pharmaceuticals, Springhouse, Pennsylvania

Dalbavancin when delivered as a single 1500-mg infusion is noninferior to the same total dose given as a 2-dose regimen, removing the logistical constraints related to the second dose while improving compliance and patient convenience.

Background

Acute bacterial skin and skin structure infections (ABSSSIs) are a cause of significant morbidity and therapy can be a burden to the healthcare system. New antibiotics that simplify treatment and avoid hospitalization are needed. This study compared the safety and efficacy of a single intravenous infusion of 1500 mg of dalbavancin to the 2-dose regimen.

Methods

This study was a randomized, double-blind trial in patients aged >18 years with ABSSSIs. Patients were randomized to dalbavancin 1500 mg either as a single intravenous (IV) infusion or 1000 mg IV on day 1 followed 1 week later by 500 mg IV. The primary endpoint was a ≥20% reduction in the area of erythema at 48–72 hours in the intent-to-treat population. Noninferiority was to be declared if the lower limit of the 95% confidence interval (CI) on the difference in the outcomes was greater than −10%. Clinical outcome was also assessed at days 14 and 28.

Results

Six hundred ninety-eight patients were randomized. Demographic characteristics were similar on each regimen, although there were more patients with methicillin-resistant Staphylococcus aureus (MRSA) at baseline on the 2-dose regimen (36/210 [17.1%] vs 61/220 [27.7%]). Dalbavancin delivered as a single dose was noninferior to a 2-dose regimen (81.4% vs 84.2%; difference, −2.9% [95% CI, −8.5% to 2.8%]). Clinical outcomes were also similar at day 14 (84.0% vs 84.8%), day 28 (84.5% vs 85.1%), and day 14 in clinically evaluable patients with MRSA in a baseline culture (92.9% vs 95.3%) in the single- and 2-dose regimens, respectively. Treatment-emergent adverse events occurred in 20.1% of the single-dose patients and 19.9% on the 2-dose regimen.

Conclusions

A single 1500-mg infusion of dalbavancin is noninferior to a 2-dose regimen, has a similar safety profile, and removes logistical constraints related to delivery of the second dose.

Clinical Trials Registration.NCT02127970.

abstract

http://cid.oxfordjournals.org/content/62/5/545.abstract

PDF

http://cid.oxfordjournals.org/content/62/5/545.full.pdf

 

March 28, 2016 at 3:05 pm

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