Antimicrobial Nonsusceptibility of Gram-Negative Bloodstream Isolates, Veterans Health Administration System, United States, 2003–2013

Emerging Infectious Diseases November 2017 V.23 N.11

Michihiko Goto, Jennifer S. McDanel, Makoto M. Jones, Daniel J. Livorsi, Michael E. Ohl, Brice F. Beck, Kelly K. Richardson, Bruce Alexander, and Eli N. Perencevich

Iowa City Veterans Affairs Health Care System, Iowa City, Iowa, USA (M. Goto, J.S. McDanel, D.J. Livorsi, M.E. Ohl, B.F. Beck, K.K. Richardson, B. Alexander, E.N. Perencevich); University of Iowa Carver College of Medicine, Iowa City (M. Goto, J.S. McDanel, D.J. Livorsi, M.E. Ohl, E.N. Perencevich); Salt Lake City Veterans Affairs Health Care System, Salt Lake City, Utah, USA (M.M. Jones); University of Utah School of Medicine, Salt Lake City USA (M.M. Jones)

Bacteremia caused by gram-negative bacteria is associated with serious illness and death, and emergence of antimicrobial drug resistance in these bacteria is a major concern.

Using national microbiology and patient data for 2003–2013 from the US Veterans Health Administration, we characterized nonsusceptibility trends of community-acquired, community-onset; healthcare-associated, community-onset; and hospital-onset bacteremia for selected gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter spp.).

For 47,746 episodes of bacteremia, the incidence rate was 6.37 episodes/10,000 person-years for community-onset bacteremia and 4.53 episodes/10,000 patient-days for hospital-onset bacteremia.

For Klebsiella spp., P. aeruginosa, and Acinetobacter spp., we observed a decreasing proportion of nonsusceptibility across nearly all antimicrobial drug classes for patients with healthcare exposure; trends for community-acquired, community-onset isolates were stable or increasing.

The role of infection control and antimicrobial stewardship efforts in inpatient settings in the decrease in drug resistance rates for hospital-onset isolates needs to be determined.

PDF

https://wwwnc.cdc.gov/eid/article/23/11/pdfs/16-1214.pdf

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October 18, 2017 at 8:25 am

Emergence of Bordetella holmesii as a Causative Agent of Whooping Cough, Barcelona, Spain

Emerging Infectious Diseases November 2017 V.23 N.11

Alba Mir-Cros, Gema Codina, M. Teresa Martín-Gómez, Anna Fàbrega, Xavier Martínez, Mireia Jané, Diego Van Esso, Thais Cornejo, Carlos Rodrigo, Magda Campins, Tomàs Pumarola, and Juan José González-LópezComments to Author

Hospital Universitari Vall d’Hebron, Barcelona, Spain (A. Mir-Cros, G. Codina, M.T. Martín-Gómez, A. Fàbrega, X. Martínez, T. Cornejo, C. Rodrigo, M. Campins, T. Pumarola, J.J. González-López); Universitat Autònoma de Barcelona, Barcelona (A. Mir-Cros, G. Codina, C. Rodrigo, M. Campins, T. Pumarola, J.J. González-López); Public Health Agency of Catalonia, Barcelona (M. Jané); Primary Care Health Centre Service ‘Muntanya,’ Barcelona (D. Van Esso)

We describe the detection of Bordetella holmesii as a cause of whooping cough in Spain. Prevalence was 3.9% in 2015, doubling to 8.8% in 2016. This emergence raises concern regarding the contribution of B. holmesii to the reemergence of whooping cough and the effectiveness of the pertussis vaccine.

PDF

https://wwwnc.cdc.gov/eid/article/23/11/pdfs/17-0960.pdf

October 18, 2017 at 8:24 am

Blood Culture–Negative Endocarditis, Morocco

Emerging Infectious Diseases November 2017 V.23 N.11

Research Letter

Najma Boudebouch, M’hammed Sarih, Abdelfattah Chakib, Salma Fadili, Drissi Boumzebra, Zahira Zouizra, Badie Azamane Mahadji, Hamid Amarouch, Didier Raoult, and Pierre-Edouard Fournier

Institut Pasteur du Maroc, Casablanca, Morocco (N. Boudebouch, M. Sarih); Centre Hospitalier Universitaire Ibn Rochd, Casablanca (A. Chakib, S. Fadili, B.A. Mahadji); Centre Hospitalier Universitaire Ibn Toufail Marrakech, Marrakech, Morocco (D. Boumzebra, Z. Zouizra); Faculté des Sciences Ain Chock, Casablanca (H. Amarouch); Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Marseille, France (D. Raoult, P.-E. Fournier)

We investigated the microorganisms causing blood culture–negative endocarditis (BCNE) in Morocco.

We tested 19 patients with BCNE by serologic methods, molecular methods, or both and identified Bartonella quintana, Staphylococcus aureus, Streptococcus equi, and Streptococcus oralis in 4 patients.

These results highlight the role of these zoonotic agents in BCNE in Morocco.

PDF

https://wwwnc.cdc.gov/eid/article/23/11/pdfs/16-1066.pdf

October 18, 2017 at 8:23 am

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

Clin Infect Dis. 2016 Sep 1;63(5):e61-e111.

Kalil AC1, Metersky ML2, Klompas M3, Muscedere J4, Sweeney DA5, Palmer LB6, Napolitano LM7, O’Grady NP8, Bartlett JG9, Carratalà J10, El Solh AA11, Ewig S12, Fey PD13, File TM Jr14, Restrepo MI15, Roberts JA16, Waterer GW17, Cruse P18, Knight SL18, Brozek JL19.

Author information

1 Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha.

2 Division of Pulmonary and Critical Care Medicine, University of Connecticut School of Medicine, Farmington.

3 Brigham and Women’s Hospital and Harvard Medical School Harvard Pilgrim Health Care Institute, Boston, Massachusetts.

4 Department of Medicine, Critical Care Program, Queens University, Kingston, Ontario, Canada.

5 Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego.

6 Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, State University of New York at Stony Brook.

7 Department of Surgery, Division of Trauma, Critical Care and Emergency Surgery, University of Michigan, Ann Arbor.

8 Department of Critical Care Medicine, National Institutes of Health, Bethesda.

9 Johns Hopkins University School of Medicine, Baltimore, Maryland.

10 Department of Infectious Diseases, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute, Spanish Network for Research in Infectious Diseases, University of Barcelona, Spain.

11 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Veterans Affairs Western New York Healthcare System, New York.

12 Thoraxzentrum Ruhrgebiet, Department of Respiratory and Infectious Diseases, EVK Herne and Augusta-Kranken-Anstalt Bochum, Germany.

13 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.

14 Summa Health System, Akron, Ohio.

15 Department of Medicine, Division of Pulmonary and Critical Care Medicine, South Texas Veterans Health Care System and University of Texas Health Science Center at San Antonio.

16 Burns, Trauma and Critical Care Research Centre, The University of Queensland Royal Brisbane and Women’s Hospital, Queensland.

17 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.

18 Library and Knowledge Services, National Jewish Health, Denver, Colorado.

19 Department of Clinical Epidemiology and Biostatistics and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Abstract

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations.

IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.

These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia.

The panel’s recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981759/pdf/ciw353.pdf

October 13, 2017 at 3:54 pm

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): A double-blind, multicentre, phase 3, randomised controlled non-inferiority trial.

Lancet August 31, 2017    

Joel Gallant, MD, Prof Adriano Lazzarin, MD, Anthony Mills, MD, Chloe Orkin, MD, Daniel Podzamczer, MD, Pablo Tebas, MD, Prof Pierre-Marie Girard, MD, Indira Brar, MD, Eric S Daar, MD, David Wohl, MD, Prof Jürgen Rockstroh, MD, Xuelian Wei, PhD, Joseph Custodio, PhD, Kirsten White, PhD, Dr Hal Martin, MD, Andrew Cheng, MD, Erin Quirk, MD

Background

Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug–drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine.

Methods

We did this double-blind, multicentre, active-controlled, randomised controlled non-inferiority trial at 122 outpatient centres in nine countries in Europe, Latin America, and North America. We enrolled HIV-1 infected adults (aged ≥18 years) who were previously untreated (HIV-1 RNA ≥500 copies per mL); HLA-B*5701-negative; had no hepatitis B virus infection; screening genotypes showing sensitivity to emtricitabine, tenofovir, lamivudine, and abacavir; and an estimated glomerular filtration rate of 50 mL/min or more. Participants were randomly assigned (1:1), via a computer-generated allocation sequence (block size of four), to receive coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg, with matching placebo, once daily for 144 weeks. Randomisation was stratified by HIV-1 RNA (≤100 000 copies per mL, >100 000 to ≤400 000 copies per mL, or >400 000 copies per mL), CD4 count (<50 cells per μL, 50–199 cells per μL, or ≥200 cells per μL), and region (USA or ex-USA). Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to group assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 48, as defined by the US Food and Drug Administration snapshot algorithm, with a prespecified non-inferiority margin of −12%. All participants who received one dose of study drug were included in primary efficacy and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02607930.

Findings

Between Nov 13, 2015, and July 14, 2016, we randomly assigned 631 participants to receive coformulated bictegravir, emtricitabine, and tenofovir alafenamide (n=316) or coformulated dolutegravir, abacavir, and lamivudine (n=315), of whom 314 and 315 patients, respectively, received at least one dose of study drug. At week 48, HIV-1 RNA less than 50 copies per mL was achieved in 92·4% of patients (n=290 of 314) in the bictegravir, emtricitabine, and tenofovir alafenamide group and 93·0% of patients (n=293 of 315) in the dolutegravir, abacavir, and lamivudine group (difference −0·6%, 95·002% CI −4·8 to 3·6; p=0·78), demonstrating non-inferiority of bictegravir, emtricitabine, and tenofovir alafenamide to dolutegravir, abacavir, and lamivudine. No individual developed treatment-emergent resistance to any study drug. Incidence and severity of adverse events was mostly similar between groups except for nausea, which occurred less frequently in patients given bictegravir, emtricitabine, and tenofovir alafenamide than in those given dolutegravir, abacavir, and lamivudine (10% [n=32] vs 23% [n=72]; p<0·0001). Adverse events related to study drug were less common with bictegravir, emtricitabine, and tenofovir alafenamide than with dolutegravir, abacavir, and lamivudine (26% [n=82] vs 40% [n=127]), the difference being driven by a higher incidence of drug-related nausea in the dolutegravir, abacavir, and lamivudine group (5% [n=17] vs 17% [n=55]; p<0·0001).

Interpretation

At 48 weeks, coformulated bictegravir, emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent resistance. Bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine. Because coformulated bictegravir, emtricitabine, and tenofovir alafenamide does not require HLA B*5701 testing and provides guideline-recommended treatment for individuals co-infected with HIV and hepatitis B, this regimen might lend itself to rapid or same-day initiation of therapy in the clinical setting.

Funding

Gilead Sciences.

FULL TEXT

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32299-7/fulltext

PDF

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)32299-7.pdf

October 11, 2017 at 7:53 am

Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): A randomised, double-blind, multicentre, phase 3, non-inferiority trial.

Lancet August 31, 2017     

Prof Paul E Sax, MD, Anton Pozniak, MD, M Luisa Montes, MD, Ellen Koenig, MD, Edwin DeJesus, MD, Hans-Jürgen Stellbrink, MD, Andrea Antinori, MD, Prof Kimberly Workowski, MD, Jihad Slim, MD, Jacques Reynes, MD, Will Garner, PhD, Joseph Custodio, PhD, Kirsten White, PhD, Dr Devi SenGupta, MD, Andrew Cheng, MD, Erin Quirk, MD

Background

Integrase strand transfer inhibitors (INSTIs) coadministered with two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are recommended as first-line treatment for HIV, and coformulated fixed-dose combinations are preferred to facilitate adherence. We report 48-week results from a study comparing initial HIV-1 treatment with bictegravir—a novel INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug interactions—coformulated with the NRTI combination emtricitabine and tenofovir alafenamide as a fixed-dose combination to dolutegravir administered with coformulated emtricitabine and tenofovir alafenamide.

Methods

In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were screened and enrolled at 126 outpatient centres in 10 countries in Australia, Europe, Latin America, and North America. Participants were previously untreated adults (HIV-1 RNA ≥500 copies per mL) with estimated glomerular filtration rate of at least 30 mL/min. Chronic hepatitis B virus or hepatitis C co-infection was allowed. We randomly assigned participants (1:1) to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo, once a day for 144 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received at least one dose of study drug were included in primary efficacy and safety analyses. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of −12%. This study is registered with ClinicalTrials.gov, number NCT02607956.

Findings

Between Nov 11, 2015, and July 15, 2016, 742 participants were screened for eligibility, of whom 657 were randomly assigned to treatment (327 with bictegravir, emtricitabine, and tenofovir alafenamide fixed-dose combination [bictegravir group] and 330 with dolutegravir plus emtricitabine and tenofovir alafenamide [dolutegravir group]). 320 participants who received the bictegravir regimen and 325 participants who received the dolutegravir regimen were included in the primary efficacy analyses. At week 48, HIV-1 RNA <50 copies per mL was achieved in 286 (89%) of 320 participants in the bictegravir group and 302 (93%) of 325 in the dolutegravir group (difference −3·5%, 95·002% CI −7·9 to 1·0, p=0·12), showing non-inferiority of the bictegravir regimen to the dolutegravir regimen. No treatment-emergent resistance to any study drug was observed. Incidence and severity of adverse events were similar between groups, and few participants discontinued treatment due to adverse events (5 [2%] of 320 in the bictegravir group and 1 [<1%] 325 in the dolutegravir group). Study drug-related adverse events were less common in the bictegravir group than in the dolutegravir group (57 [18%] of 320 vs 83 [26%] of 325, p=0·022).

Interpretation

At 48 weeks, virological suppression with the bictegravir regimen was achieved and was non-inferior to the dolutegravir regimen in previously untreated adults. There was no emergent resistance to either regimen. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen.

Funding

Gilead Sciences Inc.

FULL TEXT

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32340-1/fulltext

PDF

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)32340-1.pdf

October 11, 2017 at 7:52 am

The triumph of HIV treatment: Another new antiretroviral.

Lancet August 31, 2017   

Comment

Boffito M and Venter F.

Since the approval of the first integrase strand inhibitor (INSTI) raltegravir for the treatment of HIV 10 years ago, INSTIs have become agents of choice in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) in many international guidelines.1, 2 This was driven by the sound real-world experience of this antiretroviral class, especially following the introduction of the most recently licensed INSTI, dolutegravir.

Dolutegravir has shown superiority to other major alternative third agents belonging to the classes of protease inhibitors and non-NRTIs, and it has become the gold standard against which other drugs need to prove their efficacy. It is dosed once daily in most patients, and it is coformulated with either abacavir and lamivudine or tenofovir disoproxil fumarate and lamivudine. Importantly, dolutegravir does not require the coadministration of a pharmacoenhancer and is characterised by a low potential for drug–drug interactions, unlike elvitegravir. The high barrier to the development of resistance3 might go some way to address the recent concern over rising resistance to efavirenz (the current primary recommendation for low-income and middle-income countries), resulting in WHO looking for alternative treatments, with dolutegravir appearing to be the current leading cost-effective candidate.4, 5, 6 The tide is changing and middle-income countries like Brazil, Botswana, and South Africa are starting to adopt INSTIs for first-line treatment.5 …

FULL TEXT

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32297-3/fulltext

PDF

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)32297-3.pdf

October 11, 2017 at 7:52 am

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