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Showing 1 - 200 of 370 Journals sorted alphabetically
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 6, SJR: 0.881, h-index: 38)
Adaptation     Hybrid Journal   (Followers: 8, SJR: 0.111, h-index: 4)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.538, h-index: 35)
African Affairs     Hybrid Journal   (Followers: 57, SJR: 1.512, h-index: 46)
Age and Ageing     Hybrid Journal   (Followers: 82, SJR: 1.611, h-index: 107)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 15, SJR: 0.935, h-index: 80)
American Entomologist     Full-text available via subscription   (Followers: 6)
American Historical Review     Hybrid Journal   (Followers: 130, SJR: 0.652, h-index: 43)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 41, SJR: 1.441, h-index: 77)
American J. of Epidemiology     Hybrid Journal   (Followers: 158, SJR: 3.047, h-index: 201)
American J. of Hypertension     Hybrid Journal   (Followers: 18, SJR: 1.397, h-index: 111)
American J. of Jurisprudence     Hybrid Journal   (Followers: 15)
American J. of Legal History     Full-text available via subscription   (Followers: 4, SJR: 0.151, h-index: 7)
American Law and Economics Review     Hybrid Journal   (Followers: 26, SJR: 0.824, h-index: 23)
American Literary History     Hybrid Journal   (Followers: 12, SJR: 0.185, h-index: 22)
Analysis     Hybrid Journal   (Followers: 24)
Annals of Botany     Hybrid Journal   (Followers: 35, SJR: 1.912, h-index: 124)
Annals of Occupational Hygiene     Hybrid Journal   (Followers: 26, SJR: 0.837, h-index: 57)
Annals of Oncology     Hybrid Journal   (Followers: 47, SJR: 4.362, h-index: 173)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 8, SJR: 0.642, h-index: 53)
Annals of Work Exposures and Health     Hybrid Journal  
AoB Plants     Open Access   (Followers: 4, SJR: 0.78, h-index: 10)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 19, SJR: 0.884, h-index: 31)
Applied Linguistics     Hybrid Journal   (Followers: 51, SJR: 1.749, h-index: 63)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 0.779, h-index: 11)
Arbitration Intl.     Full-text available via subscription   (Followers: 21)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 12)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 27, SJR: 0.96, h-index: 71)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 20)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 47, SJR: 0.144, h-index: 15)
Behavioral Ecology     Hybrid Journal   (Followers: 47, SJR: 1.698, h-index: 92)
Bioinformatics     Hybrid Journal   (Followers: 238, SJR: 4.643, h-index: 271)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 9, SJR: 1.646, h-index: 149)
Biometrika     Hybrid Journal   (Followers: 19, SJR: 2.801, h-index: 90)
BioScience     Hybrid Journal   (Followers: 28, SJR: 2.374, h-index: 154)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 1, SJR: 0.213, h-index: 9)
Biostatistics     Hybrid Journal   (Followers: 16, SJR: 1.955, h-index: 55)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 142, SJR: 2.314, h-index: 133)
BJA Education     Hybrid Journal   (Followers: 66, SJR: 0.272, h-index: 20)
Brain     Hybrid Journal   (Followers: 61, SJR: 6.097, h-index: 264)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 45, SJR: 4.086, h-index: 73)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 50)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 33, SJR: 1.267, h-index: 38)
British J. of Aesthetics     Hybrid Journal   (Followers: 25, SJR: 0.217, h-index: 18)
British J. of Criminology     Hybrid Journal   (Followers: 511, SJR: 1.373, h-index: 62)
British J. of Social Work     Hybrid Journal   (Followers: 79, SJR: 0.771, h-index: 53)
British Medical Bulletin     Hybrid Journal   (Followers: 7, SJR: 1.391, h-index: 84)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 27)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.474, h-index: 31)
Cambridge J. of Economics     Hybrid Journal   (Followers: 56, SJR: 0.957, h-index: 59)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 9, SJR: 1.067, h-index: 22)
Cambridge Quarterly     Hybrid Journal   (Followers: 10, SJR: 0.1, h-index: 7)
Capital Markets Law J.     Hybrid Journal  
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.439, h-index: 167)
Cardiovascular Research     Hybrid Journal   (Followers: 11, SJR: 2.897, h-index: 175)
Cerebral Cortex     Hybrid Journal   (Followers: 39, SJR: 4.827, h-index: 192)
CESifo Economic Studies     Hybrid Journal   (Followers: 16, SJR: 0.501, h-index: 19)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.436, h-index: 76)
Children and Schools     Hybrid Journal   (Followers: 6, SJR: 0.211, h-index: 18)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 3)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 21, SJR: 0.737, h-index: 11)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 8, SJR: 1.238, h-index: 15)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 11, SJR: 0.191, h-index: 8)
Classical Receptions J.     Hybrid Journal   (Followers: 17, SJR: 0.1, h-index: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 58, SJR: 4.742, h-index: 261)
Clinical Kidney J.     Open Access   (Followers: 4, SJR: 0.338, h-index: 19)
Community Development J.     Hybrid Journal   (Followers: 24, SJR: 0.47, h-index: 28)
Computer J.     Hybrid Journal   (Followers: 7, SJR: 0.371, h-index: 47)
Conservation Physiology     Open Access   (Followers: 2)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.111, h-index: 3)
Contributions to Political Economy     Hybrid Journal   (Followers: 6, SJR: 0.313, h-index: 10)
Critical Values     Full-text available via subscription  
Current Legal Problems     Hybrid Journal   (Followers: 25)
Current Zoology     Full-text available via subscription   (SJR: 0.999, h-index: 20)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 11, SJR: 1.068, h-index: 24)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 12)
Diplomatic History     Hybrid Journal   (Followers: 18, SJR: 0.296, h-index: 22)
DNA Research     Open Access   (Followers: 4, SJR: 2.42, h-index: 77)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 3)
Early Music     Hybrid Journal   (Followers: 14, SJR: 0.124, h-index: 11)
Economic Policy     Hybrid Journal   (Followers: 54, SJR: 2.052, h-index: 52)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 1.26, h-index: 23)
English Historical Review     Hybrid Journal   (Followers: 46, SJR: 0.311, h-index: 10)
English: J. of the English Association     Hybrid Journal   (Followers: 13, SJR: 0.144, h-index: 3)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.791, h-index: 66)
Environmental Epigenetics     Open Access   (Followers: 1)
Environmental History     Hybrid Journal   (Followers: 25, SJR: 0.197, h-index: 25)
EP-Europace     Hybrid Journal   (Followers: 2, SJR: 2.201, h-index: 71)
Epidemiologic Reviews     Hybrid Journal   (Followers: 10, SJR: 3.917, h-index: 81)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 15, SJR: 0.1, h-index: 6)
European Heart J.     Hybrid Journal   (Followers: 47, SJR: 6.997, h-index: 227)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 9, SJR: 2.044, h-index: 58)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 1)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. Supplements     Hybrid Journal   (Followers: 8, SJR: 0.152, h-index: 31)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 8, SJR: 1.568, h-index: 104)
European J. of Intl. Law     Hybrid Journal   (Followers: 151, SJR: 0.722, h-index: 38)
European J. of Orthodontics     Hybrid Journal   (Followers: 4, SJR: 1.09, h-index: 60)
European J. of Public Health     Hybrid Journal   (Followers: 22, SJR: 1.284, h-index: 64)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 12, SJR: 1.549, h-index: 42)
European Review of Economic History     Hybrid Journal   (Followers: 27, SJR: 0.628, h-index: 24)
European Sociological Review     Hybrid Journal   (Followers: 39, SJR: 2.061, h-index: 53)
Evolution, Medicine, and Public Health     Open Access   (Followers: 11)
Family Practice     Hybrid Journal   (Followers: 12, SJR: 1.048, h-index: 77)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 8, SJR: 1.687, h-index: 115)
Fems Microbiology Letters     Hybrid Journal   (Followers: 20, SJR: 1.126, h-index: 118)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 25, SJR: 7.587, h-index: 150)
Fems Yeast Research     Hybrid Journal   (Followers: 13, SJR: 1.213, h-index: 66)
Foreign Policy Analysis     Hybrid Journal   (Followers: 21, SJR: 0.859, h-index: 10)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 16, SJR: 0.903, h-index: 44)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.108, h-index: 6)
French History     Hybrid Journal   (Followers: 30, SJR: 0.123, h-index: 10)
French Studies     Hybrid Journal   (Followers: 19, SJR: 0.119, h-index: 7)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.102, h-index: 3)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 10, SJR: 3.22, h-index: 39)
Geophysical J. Intl.     Hybrid Journal   (Followers: 31, SJR: 1.839, h-index: 119)
German History     Hybrid Journal   (Followers: 25, SJR: 0.437, h-index: 13)
GigaScience     Open Access   (Followers: 3)
Global Summitry     Hybrid Journal  
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.692, h-index: 101)
Health and Social Work     Hybrid Journal   (Followers: 46, SJR: 0.505, h-index: 40)
Health Education Research     Hybrid Journal   (Followers: 12, SJR: 0.814, h-index: 80)
Health Policy and Planning     Hybrid Journal   (Followers: 21, SJR: 1.628, h-index: 66)
Health Promotion Intl.     Hybrid Journal   (Followers: 20, SJR: 0.664, h-index: 60)
History Workshop J.     Hybrid Journal   (Followers: 27, SJR: 0.313, h-index: 20)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 23, SJR: 0.115, h-index: 13)
Human Molecular Genetics     Hybrid Journal   (Followers: 9, SJR: 4.288, h-index: 233)
Human Reproduction     Hybrid Journal   (Followers: 78, SJR: 2.271, h-index: 179)
Human Reproduction Update     Hybrid Journal   (Followers: 19, SJR: 4.678, h-index: 128)
Human Rights Law Review     Hybrid Journal   (Followers: 58, SJR: 0.7, h-index: 21)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 54, SJR: 1.233, h-index: 88)
ICSID Review     Hybrid Journal   (Followers: 9)
ILAR J.     Hybrid Journal   (Followers: 1, SJR: 1.099, h-index: 51)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.329, h-index: 26)
IMA J. of Management Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.351, h-index: 20)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.661, h-index: 28)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 2.032, h-index: 44)
Industrial and Corporate Change     Hybrid Journal   (Followers: 8, SJR: 1.37, h-index: 81)
Industrial Law J.     Hybrid Journal   (Followers: 29, SJR: 0.184, h-index: 15)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 8, SJR: 1.911, h-index: 90)
Interacting with Computers     Hybrid Journal   (Followers: 10, SJR: 0.529, h-index: 59)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 4, SJR: 0.743, h-index: 35)
Intl. Affairs     Hybrid Journal   (Followers: 51, SJR: 1.264, h-index: 53)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 27)
Intl. Health     Hybrid Journal   (Followers: 4, SJR: 0.835, h-index: 15)
Intl. Immunology     Hybrid Journal   (Followers: 3, SJR: 1.613, h-index: 111)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 32, SJR: 1.593, h-index: 69)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 59, SJR: 0.613, h-index: 19)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 128, SJR: 4.381, h-index: 145)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 3, SJR: 0.247, h-index: 8)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 28, SJR: 0.307, h-index: 15)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 8, SJR: 0.404, h-index: 18)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.457, h-index: 12)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 3, SJR: 1.69, h-index: 79)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 8, SJR: 0.906, h-index: 33)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 32, SJR: 0.231, h-index: 21)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 13, SJR: 0.833, h-index: 12)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.052, h-index: 42)
Intl. Political Sociology     Hybrid Journal   (Followers: 30, SJR: 1.339, h-index: 19)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 17, SJR: 0.539, h-index: 17)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 7, SJR: 0.998, h-index: 28)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 36, SJR: 2.184, h-index: 68)
Intl. Studies Review     Hybrid Journal   (Followers: 17, SJR: 0.783, h-index: 38)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 1, SJR: 0.155, h-index: 4)
ITNOW     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 4)
J. of African Economies     Hybrid Journal   (Followers: 15, SJR: 0.647, h-index: 30)
J. of American History     Hybrid Journal   (Followers: 39, SJR: 0.286, h-index: 34)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 13, SJR: 1.038, h-index: 60)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 17, SJR: 2.157, h-index: 149)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 3, SJR: 0.563, h-index: 43)
J. of Biochemistry     Hybrid Journal   (Followers: 43, SJR: 1.341, h-index: 96)
J. of Chromatographic Science     Hybrid Journal   (Followers: 16, SJR: 0.448, h-index: 42)
J. of Church and State     Hybrid Journal   (Followers: 11, SJR: 0.167, h-index: 11)
J. of Competition Law and Economics     Hybrid Journal   (Followers: 34, SJR: 0.442, h-index: 16)
J. of Complex Networks     Hybrid Journal   (Followers: 1, SJR: 1.165, h-index: 5)
J. of Conflict and Security Law     Hybrid Journal   (Followers: 12, SJR: 0.196, h-index: 15)
J. of Consumer Research     Full-text available via subscription   (Followers: 41, SJR: 4.896, h-index: 121)
J. of Crohn's and Colitis     Hybrid Journal   (Followers: 9, SJR: 1.543, h-index: 37)
J. of Cybersecurity     Hybrid Journal   (Followers: 3)
J. of Deaf Studies and Deaf Education     Hybrid Journal   (Followers: 8, SJR: 0.69, h-index: 36)
J. of Design History     Hybrid Journal   (Followers: 15, SJR: 0.166, h-index: 14)
J. of Economic Entomology     Full-text available via subscription   (Followers: 6, SJR: 0.894, h-index: 76)
J. of Economic Geography     Hybrid Journal   (Followers: 34, SJR: 2.909, h-index: 69)
J. of Environmental Law     Hybrid Journal   (Followers: 23, SJR: 0.457, h-index: 20)
J. of European Competition Law & Practice     Hybrid Journal   (Followers: 19)
J. of Experimental Botany     Hybrid Journal   (Followers: 14, SJR: 2.798, h-index: 163)
J. of Financial Econometrics     Hybrid Journal   (Followers: 21, SJR: 1.314, h-index: 27)
J. of Global Security Studies     Hybrid Journal   (Followers: 2)
J. of Heredity     Hybrid Journal   (Followers: 3, SJR: 1.024, h-index: 76)
J. of Hindu Studies     Hybrid Journal   (Followers: 7, SJR: 0.186, h-index: 3)
J. of Hip Preservation Surgery     Open Access  
J. of Human Rights Practice     Hybrid Journal   (Followers: 20, SJR: 0.399, h-index: 10)
J. of Infectious Diseases     Hybrid Journal   (Followers: 40, SJR: 4, h-index: 209)
J. of Insect Science     Open Access   (Followers: 9, SJR: 0.388, h-index: 31)

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Journal Cover Clinical Infectious Diseases
  [SJR: 4.742]   [H-I: 261]   [58 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1058-4838 - ISSN (Online) 1537-6591
   Published by Oxford University Press Homepage  [370 journals]
  • In the Literature
    • PubDate: 2017-06-15
      DOI: 10.1093/cid/cix400
  • News
    • Authors: Kaye D.
      PubDate: 2017-04-19
      DOI: 10.1093/cid/cix377
  • Evidence of Archaeal Methanogens in Brain Abscess
    • Authors: Drancourt M; Nkamga V, Lakhe N, et al.
      First page: 1
      Abstract: Background.Methanogens are antibiotic-resistant anaerobic archaea that escape routine detection in clinical microbiology. We hypothesized that methanogens are part of the anaerobic community that cause brain abscess.Methods.Methanogens were investigated in 1 index sample using specific polymerase chain reaction (PCR) sequencing and culture. The pathogenesis of a methanogen isolate was assessed in a mouse model. Archaea-specific quantitative (q) PCR and metagenomics were used to detect specific archaeal sequences in brain abscess samples and controls.Results.In 1 index sample, routine culture found Porphyromonas endodontalis and Streptococcus intermedius, and specific culture found Methanobrevibacter oralis susceptible to metronidazole and fusidic acid. Archaea-targeted PCR sequencing and metagenomics confirmed M. oralis along with 14 bacteria, including S. intermedius. Archaea-specific qPCR yielded archaea in 8/18 brain abscess specimens and 1/27 controls (P < .003), and metagenomics yielded archaea, mostly methanogens, in 28/32 brain abscess samples, and no archaea in 71 negative controls (P < 10–6). Infection of mice brains yielded no mortality in 14 controls and death in 17/22 M. oralis-inoculated mice (P < 10–6), 32/95 S. intermedius-inoculated mice (P < 10–6), and 75/104 mice inoculated with M. oralis mixed with S. intermedius (P < 10–6) 7 days post-inoculation.Conclusion.Methanogens belong to the anaerobic community responsible for brain abscess, and M. oralis may participate in the pathogenicity of this deadly infection. In mice, a synergy of M. oralis and S. intermedius was observed. Antibiotic treatment of brain abscess should contain anti-archaeal compounds such as imidazole derivatives in most cases.
      PubDate: 2017-04-01
      DOI: 10.1093/cid/cix286
  • Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in
           Patients Coinfected With Human Immunodeficiency Virus Type 1: An
           Open-Label, Phase 3 Study
    • Authors: Wyles D; Bräu N, Kottilil S, et al.
      First page: 6
      Abstract: Background.A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1.Methods.This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis. All patients received sofosbuvir-velpatasvir once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Efficacy and safety were assessed in all patients receiving at least 1 dose of treatment.Results.Of 106 patients, 91 (86%) were men, 48 (45%) were black, and 19 (18%) had cirrhosis. SVR12 was achieved by 101 of 106 (95% [95% confidence interval {CI}, 89%–99%]) patients: 74 of 78 (95% [95% CI, 87%–99%]) with genotype 1; all 11 (100% [95% CI, 72%–100%]) with genotype 2; 11 of 12 (92% [95% CI, 62%–100%]) with genotype 3; and all 5 (100% [95% CI, 48%–100%]) with genotype 4. All 19 patients with cirrhosis had SVR12. Two patients relapsed, 2 were lost to follow-up, and 1 withdrew consent. Two discontinued treatment due to adverse events and 2 had serious adverse events. The most common adverse events were fatigue (25%), headache (13%), upper respiratory tract infection (8%), and arthralgia (8%).Conclusions.Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1.Clinical Trials Registration.NCT02480712.
      PubDate: 2017-03-29
      DOI: 10.1093/cid/cix260
  • Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With
           Hepatitis C Virus Genotype 3 Infection: An Open-Label Study
    • Authors: Feld JJ; Ramji A, Shafran SD, et al.
      First page: 13
      Abstract: Background.Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection.Methods.We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance.Results.Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%–94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%).Conclusions.In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis.Clinical Trials Registration.NCT02413593.
      PubDate: 2017-05-23
      DOI: 10.1093/cid/cix289
  • Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis
           Treated With an Intensified Antituberculosis Regimen
    • Authors: Heemskerk A; Nguyen M, Dang H, et al.
      First page: 20
      Abstract: Background.Drug-resistant tuberculous meningitis (TBM) is difficult to diagnose and treat. Mortality is high and optimal treatment is unknown. We compared clinical outcomes of drug-resistant and -susceptible TBM treated with either standard or intensified antituberculosis treatment.Methods.We analyzed the influence of Mycobacterium tuberculosis drug resistance on the outcomes of patients with TBM enrolled into a randomized controlled trial comparing a standard, 9-month antituberculosis regimen (containing rifampicin 10 mg/kg/day) with an intensified regimen with higher-dose rifampicin (15 mg/kg/day) and levofloxacin (20 mg/kg/day) for the first 8 weeks. The primary endpoint of the trial was 9-month survival. In this subgroup analysis, resistance categories were predefined as multidrug resistant (MDR), isoniazid resistant, rifampicin susceptible (INH-R), and susceptible to rifampicin and isoniazid (INH-S + RIF-S). Outcome by resistance categories and response to intensified treatment were compared and estimated by Cox regression.Results.Of 817 randomized patients, 322 had a known drug resistance profile. INH-R was found in 86 (26.7%) patients, MDR in 15 (4.7%) patients, rifampicin monoresistance in 1 patient (0.3%), and INH-S + RIF-S in 220 (68.3%) patients. Multivariable regression showed that MDR (hazard ratio [HR], 5.91 [95% confidence interval {CI}, 3.00–11.6]), P < .001), was an independent predictor of death. INH-R had a significant association with the combined outcome of new neurological events or death (HR, 1.58 [95% CI, 1.11–2.23]). Adjusted Cox regression, corrected for treatment adjustments, showed that intensified treatment was significantly associated with improved survival (HR, 0.34 [95% CI, .15–.76], P = .01) in INH-R TBM.Conclusions.Early intensified treatment improved survival in patients with INH-R TBM. Targeted regimens for drug-resistant TBM should be further explored.Clinical Trials Registration.ISRCTN61649292.
      PubDate: 2017-05-04
      DOI: 10.1093/cid/cix230
  • Risk of Acute Coronary Heart Disease After Sepsis Hospitalization in the
           REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
    • Authors: Wang HE; Moore JX, Donnelly JP, et al.
      First page: 29
      Abstract: Background.Sepsis is associated with long-term health consequences. We sought to determine the long-term risks of acute and fatal coronary heart disease (CHD) events after sepsis hospitalizations among community-dwelling adults.Methods.We analyzed data from 30329 participants in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Sepsis events included hospitalizations for a serious infection with ≥2 systemic inflammatory response syndrome criteria. Acute CHD events included myocardial infarctions (MIs; nonfatal and fatal) and acute CHD deaths. Fatal CHD included deaths ≤28 days of an acute MI and acute CHD deaths. We age- and time-matched each sepsis participant with 5 nonsepsis participants. We assessed the associations between sepsis hospitalizations and future acute and fatal CHD events using Cox regression, Gray’s model, and competing risks analysis, adjusting for comorbidities.Results.The matched cohort contained 1070 sepsis and 5350 nonsepsis participants. Risk of acute CHD was higher for sepsis than nonsepsis controls after adjusting for sex, race, education, income, region, tobacco use, and select chronic medical conditions (0–1 year adjusted hazard ratio [HR], 4.38 [95% confidence interval (CI), 2.03–9.45]; 1–4 years, 1.78 [1.09–2.88]; and 4+ years, 1.18 [0.52–2.67]). Risk of fatal CHD was similarly higher for sepsis than nonsepsis individuals (0–1 year adjusted HR, 3.12 [95% CI, 1.35–7.23]; 1–4 years, 3.29 [1.89–5.74]; and 4+ years HR, 1.15 [0.34–3.94]).Conclusions.The long-term risks of acute and fatal CHD are elevated after sepsis hospitalization. Management of acute CHD risk may be important for individuals surviving a sepsis event.
      PubDate: 2017-03-23
      DOI: 10.1093/cid/cix248
  • Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in
           Patients Recently Treated with Azithromycin
    • Authors: Wind CM; de Vries E, Schim van der Loeff MF, et al.
      First page: 37
      Abstract: Background.Increasing azithromycin usage and resistance in Neisseria gonorrhoeae threatens current dual treatment. Because antimicrobial exposure influences resistance, we analyzed the association between azithromycin exposure and decreased susceptibility of N. gonorrhoeae.Methods.We included N. gonorrhoeae isolates of patients who visited the Amsterdam STI Clinic between 1999 and 2013 (t0), with another clinic visit in the previous 60 days (t–1). Exposure was defined as the prescription of azithromycin at t–1. Using multivariable linear regression, we assessed the association between exposure and azithromycin minimum inhibitory concentration (MIC). Whole genome sequencing (WGS) was performed to produce a phylogeny and identify multilocus sequence types (MLST), N. gonorrhoeae multiantigen sequence types (NG-MAST), and molecular markers of azithromycin resistance.Results.We included 323 isolates; 212 were unexposed to azithromycin, 14 were exposed ≤30 days, and 97 were exposed between 31 and 60 days before isolation. Mean azithromycin MIC was 0.28 mg/L (range, <0.016–24 mg/L). Linear regression adjusted for age, ethnicity, infection site, and calendar year showed a significant association between azithromycin exposure ≤30 days and MIC (β, 1.00; 95% confidence interval, 0.44–1.56; P = .002). WGS was performed on 31 isolates: 14 unexposed, 14 exposed to azithromycin ≤30 days before isolation, and 3 t–1 isolates. Exposure to azithromycin was significantly associated with A39T or G45D mtrR mutations (P = .046) but not with MLST or NG-MAST types.Conclusions.The results suggest that frequent azithromycin use in populations at high risk of contracting N. gonorrhoeae induces an increase in MIC and may result in resistance.
      PubDate: 2017-03-24
      DOI: 10.1093/cid/cix249
  • Comparing the Efficacy of Drug Regimens for Pulmonary Tuberculosis:
           Meta-analysis of Endpoints in Early-Phase Clinical Trials
    • Authors: Bonnett LJ; Ken-Dror G, Koh GW, et al.
      First page: 46
      Abstract: Background.A systematic review of early clinical outcomes in tuberculosis was undertaken to determine ranking of efficacy of drugs and combinations, define variability of these measures on different endpoints, and to establish the relationships between them. Methods.Studies were identified by searching PubMed, Medline, Embase, LILACS (Latin American and Caribbean Health Sciences Literature), and reference lists of included studies. Outcomes were early bactericidal activity results over 2, 7, and 14 days, and the proportion of patients with negative culture at 8 weeks.Results.One hundred thirty-three trials reporting phase 2A (early bactericidal activity) and phase 2B (culture conversion at 2 months) outcomes were identified. Only 9 drug combinations were assessed on >1 phase 2A endpoint and only 3 were assessed in both phase 2A and 2B trials. Conclusions.The existing evidence base supporting phase 2 methodology in tuberculosis is highly incomplete. In future, a broader range of drugs and combinations should be more consistently studied across a greater range of phase 2 endpoints.
      PubDate: 2017-04-10
      DOI: 10.1093/cid/cix247
  • Setting Tuberculosis Regimen Development on a Firm Foundation
    • Authors: Phillips P.
      First page: 55
      Abstract: tuberculosisdrug developmentclinical trialsEBA.
      PubDate: 2017-04-10
      DOI: 10.1093/cid/cix250
  • Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus
           Infection in Solid Organ Transplant Recipients
    • Authors: Fisher CE; Knudsen JL, Lease ED, et al.
      First page: 57
      Abstract: Background.Ganciclovir-resistant (ganR) cytomegalovirus (CMV) is an emerging and important problem in solid organ transplant (SOT) recipients. Only through direct comparison of ganR- and ganciclovir-sensitive (ganS) CMV infection can risk factors and outcomes attributable specifically to ganciclovir resistance appropriately be determined.Methods.We performed a retrospective, case-control (1:3) study of SOT recipients with genotypically confirmed ganR-CMV (n = 37) and ganS-CMV infection (n = 109), matched by donor/recipient CMV serostatus, year and organ transplanted, and clinical manifestation. We used χ2 (categorical) and Mann-Whitney (continuous) tests to determine predisposing factors and morbidity attributable to resistance, and Kaplan-Meier plots to analyze survival differences.Results.The rate of ganR-CMV was 1% (37/3467) overall and 4.1% (32/777) among CMV donor-positive, recipient-negative patients, and was stable over the study period. GanR-CMV was associated with increased prior exposure to ganciclovir (median, 153 vs 91 days, P < .001). Eighteen percent (3/17) of lung transplant recipients with ganR-CMV had received <6 weeks of prior ganciclovir (current guideline-recommended resistance testing threshold), and all non-lung recipients had received ≥90 days (median, 160 [range, 90–284 days]) prior to diagnosis of ganR-CMV. GanR-CMV was associated with higher mortality (11% vs 1%, P = .004), fewer days alive and nonhospitalized (73 vs 81, P = .039), and decreased renal function (42% vs 19%, P = .008) by 3 months after diagnosis.Conclusions.GanR-CMV is associated with longer prior antiviral duration and higher attributable morbidity and mortality than ganS-CMV. Upcoming revised CMV guidelines should incorporate organ transplant–specific thresholds of prior drug exposure to guide rational ganR-CMV testing in SOT recipients. Improved strategies for prevention and treatment of ganR-CMV are warranted.
      PubDate: 2017-03-29
      DOI: 10.1093/cid/cix259
  • Comparing Child-Pugh, MELD, and FIB-4 to Predict Clinical Outcomes in
           Hepatitis C Virus-Infected Persons: Results From ERCHIVES
    • Authors: Butt AA; Ren Y, Lo Re V, III, et al.
      First page: 64
      Abstract: Background.Identifying hepatitis C virus (HCV)-positive persons at high risk of early complications can help prioritize treatment decisions. We conducted this study to compare Child-Turcotte-Pugh (CP), MELD, and FIB-4 scores for predicting clinical outcomes and to identify those at low risk of complications.Methods.Within electronically retrieved cohort of HCV-infected veterans, we identified HCV-positive persons and excluded those with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), prevalent hepatic decompensation (HD), hepatocellular carcinoma (HCC), and those treated for HCV. We calculated incidence rates for HD, HCC, and all-cause mortality at 1, 3, and 5 years after HCV diagnosis. Using receiver operating characteristic (ROC) curves, we determined the optimal cut-off values for each score for these outcomes.Results.Among 21 116 persons evaluated, 89.7% were CP Class-A, 79.9% had MELD<9, and 43.4% had FIB-4<1.45. AUROC for HD at 1, 3, and 5 years was higher for FIB-4 (0.84–0.86) compared with MELD (0.70–0.76) (P < .001). AUROC for HCC at 1, 3, and 5 years was 0.81–0.82 for FIB-4 but 0.61–0.68 for CP and MELD scores. (P < .001) AUROC for all-cause mortality at 3 and 5 years was 0.65–0.68. The optimal cut-off scores to identify persons at low risk of complications were as follows: CP <5; MELD <8; FIB-4 <3 for HD and HCC, and <2 for all-cause mortality, below which <1.5% developed HD and HCC and ≤2.5% died at 3 years.Conclusions.FIB-4 score is a better predictor of HD and HCC in HCV-positive persons. A score of <3 is associated with a low risk of HD and HCC 1 and 3 years after HCV diagnosis.
      PubDate: 2017-03-22
      DOI: 10.1093/cid/cix224
  • Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates
           With Innate Immune Activation and Dysfunction of Monocytes
    • Authors: Janssen S; Schutz C, Ward A, et al.
      First page: 73
      Abstract: Background.Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population.Methods.This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalized HIV-infected tuberculosis patients with CD4 counts <350 cells/µL were included; tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without active tuberculosis were recruited as controls. Whole blood was stimulated with Escherichia coli derived lipopolysaccharide, heat-killed Streptococcus pneumoniae, and Mycobacterium tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex), were assessed for associations with 12-week mortality using Cox proportional hazard models. Second, we investigated associations of these immune markers with tuberculosis mycobacteremia.Results.Sixty patients were included (median CD4 count 53 cells/µL (interquartile range [IQR], 22–132); 16 (27%) died after a median of 12 (IQR, 0–24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony-stimulating factor 3), and antiinflammatory markers (increased interleukin-1 receptor antagonist and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis.Conclusions.Twelve-week mortality was associated with greater pro- and antiinflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis.
      PubDate: 2017-03-24
      DOI: 10.1093/cid/cix254
  • Disability Among Middle-Aged and Older Persons With Human Immunodeficiency
           Virus Infection
    • Authors: Johs NA; Wu K, Tassiopoulos K, et al.
      First page: 83
      Abstract: Background.Older human immunodeficiency virus (HIV)-infected adults may experience higher rates of frailty and disability than the general population. Improved understanding of the prevalence, risk factors, and types of impairment can better inform providers and the healthcare system.Methods.HIV-infected participants within the AIDS Clinical Trials Group A5322 HAILO study self-reported disability by the Lawton-Brody Instrumental Activities of Daily Living (IADL) Questionnaire. Frailty was measured by 4-m walk time, grip strength, self-reported weight loss, exhaustion, and low activity. Logistic regression models identified characteristics associated with any IADL impairment. Agreement between IADL impairment and frailty was assessed using the weighted kappa statistic.Results.Of 1015 participants, the median age was 51 years, 15% were aged ≥60 years, 19% were female, 29% black, and 20% Hispanic. At least 1 IADL impairment was reported in 18% of participants, most commonly with housekeeping (48%) and transportation (36%) and least commonly with medication management (5%). In multivariable models, greater disability was significantly associated with neurocognitive impairment, lower education, Medicare/Medicaid insurance (vs private/other coverage), smoking, and low physical activity. Although a greater proportion of frail participants had IADL impairment (52%) compared to non-frail (11%) persons, agreement was poor (weighted kappa <0.18, 95% confidence interval, 0.13, 0.23).Conclusion.IADL disability occurs frequently among middle-aged and older HIV-infected adults on effective antiretroviral therapy. Potentially modifiable risk factors (smoking, physical activity) provide targets for interventions to maintain independent living. Systematic recognition of persons at greater risk for disability can facilitate connection to resources that may help preserve independence.
      PubDate: 2017-03-27
      DOI: 10.1093/cid/cix253
  • Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015
    • Authors: Bazan JA; Turner A, Kirkcaldy RD, et al.
      First page: 92
      Abstract: Background.Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae.Methods.In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015.Results.Seventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24–38) and had a median of 2 sex partners in the last 3 months (IQR = 1–3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52).Conclusions.Between January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission.
      PubDate: 2017-05-08
      DOI: 10.1093/cid/cix215
  • Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for
           Treatment of Methicillin-Susceptible Staphylococcus aureus Infections
           Complicated by Bacteremia: A Nationwide Cohort Study
    • Authors: McDanel JS; Roghmann M, Perencevich EN, et al.
      First page: 100
      Abstract: Background.To treat patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections, β-lactams are recommended for definitive therapy; however, the comparative effectiveness of individual β-lactams is unknown. This study compared definitive therapy with cefazolin vs nafcillin or oxacillin among patients with MSSA infections complicated by bacteremia.Methods.This retrospective study included patients admitted to 119 Veterans Affairs hospitals from 2003 to 2010. Patients were included if they had a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin. Cox proportional hazards regression and ordinal logistic regression were used to identify associations between antibiotic therapy and mortality or recurrence. A recurrent infection was defined as a MSSA blood culture between 45 and 365 days after the first MSSA blood culture.Results.Of 3167 patients, 1163 (37%) patients received definitive therapy with cefazolin. Patients who received cefazolin had a 37% reduction in 30-day mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], .51–.78) and a 23% reduction in 90-day mortality (HR, 0.77; 95% CI, .66–.90) compared with patients receiving nafcillin or oxacillin, after controlling for other factors. The odds of recurrence (odds ratio, 1.13; 95% CI, .94–1.36) were similar among patients who received cefazolin compared with patients who received nafcillin or oxacillin, after controlling for other factors.Conclusions.In this large, multicenter study, patients who received cefazolin had a lower risk of mortality and similar odds of recurrent infections compared with nafcillin or oxacillin for MSSA infections complicated by bacteremia. Physicians might consider definitive therapy with cefazolin for these infections.
      PubDate: 2017-03-31
      DOI: 10.1093/cid/cix287
  • Definitive Treatment for Methicillin-Susceptible Staphylococcus aureus
           Bacteremia: Data Versus a Definitive Answer'
    • Authors: Karchmer AW.
      First page: 107
      Abstract: S. aureus bacteremiacefazolinantistaphylococcal penicillins.
      PubDate: 2017-03-31
      DOI: 10.1093/cid/cix288
  • Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant
           Pseudomonas aeruginosa Infections: Clinical Effectiveness and Evolution of
    • Authors: Haidar G; Philips NJ, Shields RK, et al.
      First page: 110
      Abstract: Background.Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited.Methods.We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates.Results.Median age was 58 years; 9 patients (43%) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants.Conclusions.In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam’s place in the armamentarium.
      PubDate: 2017-02-25
      DOI: 10.1093/cid/cix182
  • Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated
           Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome:
           A Prospective Observational Study
    • Authors: Walker NF; Wilkinson KA, Meintjes G, et al.
      First page: 121
      Abstract: Background.Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB.Methods.We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)–infected and –uninfected TB patients and controls, and a prospective cohort study of HIV-1–infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation.Results.MMP activity differed between HIV-1–infected and –uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1–infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1–uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis–antigen driven. Mycobacterium tuberculosis–induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro.Conclusions.MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1–infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS.
      PubDate: 2017-05-05
      DOI: 10.1093/cid/cix231
  • Clinical, Serological, and Virological Analysis of 572 Chikungunya
           Patients From 2010 to 2013 in India
    • Authors: Jain J; Nayak K, Tanwar N, et al.
      First page: 133
      Abstract: Background.Chikungunya fever (CHIK) is a major public health concern in India. Characterized by acute fever with joint pain and swelling, most patients recover from this self-limiting illness in 7–10 days, with cessation of joint pain post-acute episode. However, in some patients, joint pain persists, lasting for months or even years. The precise correlates to the chronic phase of this debilitating illness and/or this remarkable heterogeneity in disease manifestation are poorly understood.Methods.We evaluated 572 chikungunya patients from India who were recruited on the basis of positive real-time polymerase chain reaction and/or CHIK virus immunoglobulin (IgM) after receiving consent. Arthralgic conditions were monitored using visual analog score (VAS) 12 weeks after onset of fever in 130 patients. Initial viral load, IgG, and initial neutralization response were assayed and correlated with clinical and VAS information in 40 patients.Results.Our extensive screening revealed that patients with higher initial viral loads during the acute phase of illness had poor prognosis at the post-acute phase with more restricted joint movement and higher VAS. Additionally, patients who showed early seroconversion to neutralizing IgG responses had better prognosis, as many of these patients did not manifest restricted joint movements at the post-acute phase.Conclusions.Our study sheds light on chikungunya disease with respect to disease progression and assesses clinical, virological, and serological parameters of chikungunya disease severity. Importantly, it reveals that initial high viral load and neutralizing IgG response may function in a seemingly contrasting manner to negatively or positively dictate disease outcome.
      PubDate: 2017-04-01
      DOI: 10.1093/cid/cix283
  • Progress in the Fight Against Multidrug-Resistant Bacteria 2005–2016:
           Modern Noninferiority Trial Designs Enable Antibiotic Development in
           Advance of Epidemic Bacterial Resistance
    • Authors: Rex JH; Talbot GH, Goldberger MJ, et al.
      First page: 141
      Abstract: From a public health perspective, new antibacterial agents should be evaluated and approved for use before widespread resistance to existing agents emerges. However, for multidrug-resistant pathogens, demonstration of superior efficacy of a new agent over a current standard-of-care agent is routinely feasible only when epidemic spread of these dangerous organisms has already occurred. One solution to enable proactive drug development is to evaluate new antibiotics with improved in vitro activity against MDR pathogens using recently updated guidelines for active control, noninferiority trials of selected severe infections caused by more susceptible pathogens. Such trials are feasible because they enroll patients with infections due to pathogens with a “usual drug resistance” phenotype that will be responsive to widely registered standard-of-care comparator antibiotics. Such anticipatory drug development has constructively reshaped the antibiotic pipeline and offers the best chance of making safe and efficacious antibiotics available to the public ahead of epidemic resistance.
      PubDate: 2017-05-18
      DOI: 10.1093/cid/cix246
  • Intercountry Transfer of Triazole-Resistant Aspergillus fumigatus on Plant
    • Authors: Dunne K; Hagen F, Pomeroy N, et al.
      First page: 147
      Abstract: We investigated whether plants imported to Ireland from the Netherlands might harbor triazole-resistant Aspergillus fumigatus. Samples of plant bulbs were positive for triazole-resistant A. fumigatus with CYP51A mutations. We hypothesize that this represents a route for intercountry transfer of an emerging resistance mechanism in a major opportunistic mold pathogen.
      PubDate: 2017-03-29
      DOI: 10.1093/cid/cix257
  • Infectivity of Post-Kala-azar Dermal Leishmaniasis Patients to Sand Flies:
           Revisiting a Proof of Concept in the Context of the Kala-azar Elimination
           Program in the Indian Subcontinent
    • Authors: Molina R; Ghosh D, Carrillo E, et al.
      First page: 150
      Abstract: We compared xenodiagnosis with quantitative polymerase chain reaction in skin biopsies from 3 patients with maculopapular or nodular post–kala-azar dermal leishmaniasis (PKDL). All patients infected sand flies. Parasite loads in skin varied from 1428 to 63 058 parasites per microgram. PKDL detection and treatment are important missing components of the kala-azar elimination program.
      PubDate: 2017-05-18
      DOI: 10.1093/cid/cix245
  • A Randomized Controlled Trial of a Behavioral Weight Loss Program for
           Human Immunodeficiency Virus–Infected Patients
    • Authors: Becofsky K; Wing EJ, McCaffery J, et al.
      First page: 154
      Abstract: Obesity compounds the negative health effects of human immunodeficiency virus (HIV) infection. We conducted the first randomized trial of behavioral weight loss for HIV-infected patients (n = 40). Participants randomized to an Internet behavioral weight loss program had greater 12-week weight loss (mean, 4.4 ± 5.4 kg vs 1.0 ± 3.3 kg; P = .02) and improvements in quality of life than controls.Clinical Trials Registration.NCT02421406.
      PubDate: 2017-03-23
      DOI: 10.1093/cid/cix238
  • Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections
           Caused by Carbapenem-Resistant Pseudomonas aeruginosa
    • Authors: Munita JM; Aitken SL, Miller WR, et al.
      First page: 158
      Abstract: A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.
      PubDate: 2017-03-14
      DOI: 10.1093/cid/cix014
  • Risk in the “Red Zone”: Outcomes for Children Admitted to Ebola
           Holding Units in Sierra Leone Without Ebola Virus Disease
    • Authors: Fitzgerald FF; Wing KK, Naveed AA, et al.
      First page: 162
      Abstract: We collected data on 1054 children admitted to Ebola Holding Units in Sierra Leone and describe outcomes of 697/1054 children testing negative for Ebola virus disease (EVD) and accompanying caregivers. Case-fatality was 9%; 3/630 (0.5%) children discharged testing negative were readmitted EVD-positive. Nosocomial EVD transmission risk may be lower than feared.
      PubDate: 2017-03-20
      DOI: 10.1093/cid/cix223
  • Impact of an Integrated Antibiotic Allergy Testing Program on
           Antimicrobial Stewardship: A Multicenter Evaluation
    • Authors: Trubiano JA; Thursky KA, Stewardson AJ, et al.
      First page: 166
      Abstract: Background.Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels [AALs]) and their impact on antibiotic prescribing, incorporation of antibiotic allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing.Methods.AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre–AAT-AMS) and 3 months following testing (post–AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were “de-labeled” of their AAL, spectrum of antibiotic courses pre– and post–AAT-AMS, and antibiotic appropriateness (using standard definitions).Results.From the 118 antibiotic allergy–tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients—56% (55/98) with all AALs removed. Post-AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio [aOR], 2.81, 95% confidence interval [CI], 1.45–5.42), as was narrow-spectrum β-lactams (aOR, 3.54; 95% CI, 1.98–6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00–30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI, .09–.29), after adjusting for indication, Charlson comorbidity index, and care setting.Conclusions.An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs.
      PubDate: 2017-05-18
      DOI: 10.1093/cid/cix244
  • A Transmissible Rash of Palms and Soles in a 58-Year-Old Man
    • First page: 175
      Abstract: (See pages 176–7 for the Answer to the Photo Quiz.)
      PubDate: 2017-06-15
      DOI: 10.1093/cid/cix255
  • A Transmissible Rash of Palms and Soles in a 58-Year-Old Man
    • Authors: Guery R; Aguilar C, Schuffenecker I, et al.
      First page: 176
      Abstract: (See page 175 for the Photo Quiz.)
      PubDate: 2017-06-15
      DOI: 10.1093/cid/cix256
  • Should We Revisit the Nephrotoxic Potential of Piperacillin-Tazobactam as
    • Authors: Manian FA.
      First page: 178
      Abstract: To the Editor—Navalkele et al should be commended for their study of the comparative risk of acute kidney injury (AKI) in patients who receive vancomycin combined with either piperacillin–tazobactam (VPT) or cefepime [1]. The authors’ findings of significantly higher risk of AKI in the VPT group supports much of the existing literature in implicating VPT as a potentially nephrotoxic drug combination [2]. Although the exact mechanism underlying VPT-associated nephrotoxicity remains unclear, an additive nephrotoxic effect of vancomycin (eg, acute tubular necrosis) and that of piperacillin (eg, acute interstitial nephritis [AIN]) is often posited [2, 3].
      PubDate: 2017-04-13
      DOI: 10.1093/cid/cix321
  • Reply to Manian
    • Authors: Pogue JM; Navalkele B, Kaye KS.
      First page: 178
      Abstract: To the Editor—
      PubDate: 2017-04-13
      DOI: 10.1093/cid/cix322
  • The Need for Outcome Studies Prior to Large-Scale Implementation of
           Screening for Anal Cancer
    • Authors: Allan-Blitz L; Klausner JD.
      First page: 179
      Abstract: To the Editor—We read with great interest the article by Gaisa et al [1] in which the authors documented the increased rates of anal high-grade squamous intraepithelial lesions among human immunodeficiency virus–infected women. While we recognize the impact that cervical cancer screening has had on disease prevention, we are concerned that the conclusions drawn by Gaisa et al may perpetuate the false notion that anal cancer screening is supported by evidence of reduced morbidity and mortality.
      PubDate: 2017-04-13
      DOI: 10.1093/cid/cix328
  • Reply to Allan-Blitz and Klausner
    • Authors: Gaisa M; Sigel K, Aberg J, et al.
      First page: 180
      Abstract: To the Editor—We read with interest the letter by Allan-Blitz and Klausner [1] regarding our recently published article in Clinical Infectious Diseases [2]. In our study we found high rates of anal high-grade squamous intraepithelial lesions (HSILs) in women with human immunodeficiency virus (HIV) infection, including those who did not meet criteria for screening according to existing guidelines.
      PubDate: 2017-04-13
      DOI: 10.1093/cid/cix330
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