Archive for November, 2019

Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide.

Open Forum Infect Dis. October 4, 2019 V.6 N.10

Schafer JJ1, Sassa KN1, O’Connor JR1, Shimada A2, Keith SW2, DeSimone JA3.

Abstract

BACKGROUND:

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with human immunodeficiency virus (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown.

METHODS:

This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥1 year with 2 consecutive HIV ribonucleic acid values <200 copies/mL before a TAF switch were included. Body weight, BMI, cholesterol, and ASCVD risk score were collected for the year before and after the switch. Pre- and postswitch values were compared with the Wilcoxon signed-rank test. Changes in BMI and ASCVD scores were modeled using generalized estimating equations regression.

RESULTS:

One hundred ten patients were included. In unadjusted analyses, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD risk score in the year after switching from TDF to TAF (each P ≤ .01). In regression models, switching from TDF to TAF was associated with a 0.45 kg/m2 increase in BMI (95% confidence interval [CI], 0.14-0.76) and a 13% increase in ASCVD risk score (95% CI, 4%-23%).

CONCLUSIONS:

We observed significant BMI and ASCVD score increases in PWH 1 year after switching from TDF to TAF. The mechanism of changes is unclear and requires additional study.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786703/pdf/ofz414.pdf

November 26, 2019 at 7:19 am

Tailoring Antimicrobial Susceptibility Testing to Individual Species of Coagulase-Negative Staphylococci: Next Up, Staphylococcus epidermidis

Journal of Clinical Microbiology December 2019 V.57 N.12

Accurate detection of methicillin resistance among staphylococci is vital for patient care. Methicillin resistance is most commonly mediated by acquisition of the mecA gene, which encodes an altered penicillin binding protein, PBP2a.

Application of phenotypic methods to detect mecA-mediated beta-lactam resistance in staphylococci is becoming more complex as species-specific differences are identified among coagulase-negative staphylococci (CoNS).

Previously, interpretative criteria and antimicrobial susceptibility testing (AST) methods specific to the CoNS group were used to evaluate Staphylococcus epidermidis.

A manuscript by S. N. Naccache, K. Callan, C.-A. D. Burnham, M. A. Wallace, et al. (J Clin Microbiol 57:e00961-19, 2019, https://doi.org/10.1128/JCM.00961-19) details experiments revealing that S. epidermidis, the most common clinically isolated CoNS, requires tailored use of previously described methods and interpretive criteria to reliably identify the presence of mecAmediated methicillin resistance.

FULL TEXT

https://jcm.asm.org/content/57/12/e01391-19.abstract?etoc

PDF

https://jcm.asm.org/content/jcm/57/12/e01391-19.full.pdf

 

 

November 23, 2019 at 10:30 am

Perspective – Eastern Equine Encephalitis Virus — Another Emergent Arbovirus in the United States

NEJM November 21, 219 V.381 P.1989-1992

David M. Morens, M.D., Gregory K. Folkers, M.S., M.P.H., and Anthony S. Fauci, M.D.

Humans have always lived in intimate association with arthropods that transmit pathogens between humans or from animals to humans. About 700,000 deaths due to vectorborne diseases occur globally each year, according to World Health Organization estimates. In the summer and fall of 2019, nine U.S. states have reported 36 human cases (14 of them fatal) of one of the deadliest of these diseases: eastern equine encephalitis (EEE), an arthropod-borne viral (arboviral) disease transmitted by mosquitoes. In recent years, the Americas have witnessed a steady stream of other emerging or reemerging arboviruses, such as dengue, West Nile, chikungunya, Zika, and Powassan, as well as increasing numbers of travel-related cases of various other arboviral infections. This year’s EEE outbreaks may thus be a harbinger of a new era of arboviral emergences……

FULL TEXT

https://www.nejm.org/doi/full/10.1056/NEJMp1914328?query=TOC

PDF

https://www.nejm.org/doi/pdf/10.1056/NEJMp1914328?articleTools=true

November 21, 2019 at 8:06 am

Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents

NEJM November 21, 219 V.381 P.2009-2019

Shibadas Biswal, M.D., Humberto Reynales, M.D., Ph.D., Xavier Saez-Llorens, M.D., Pio Lopez, M.D., Charissa Borja-Tabora, M.D., Pope Kosalaraksa, M.D., Chukiat Sirivichayakul, M.D., Veerachai Watanaveeradej, M.D., Luis Rivera, M.D., Felix Espinoza, M.D., LakKumar Fernando, M.D., Reynaldo Dietze, M.D., et al., for the TIDES Study Group*

BACKGROUND

Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019.

METHODS

We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype.

RESULTS

Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively).

CONCLUSIONS

TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927. opens in new tab.)

FULL TEXT

https://www.nejm.org/doi/full/10.1056/NEJMoa1903869?query=TOC

PDF

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1903869?articleTools=true

November 21, 2019 at 8:05 am

2019-11 Hospital-Acquired Infections in New York State, 2018 –  N York State Department of Health 24 Pags

Contents

Introduction ………………………………………………………………………………………………………… 3

Surgical Site Infections (SSIs)………………………………………………………………………………………………. 4

Catheter-Associated Infections ………………………………………………………………………………………………………… 5

Laboratory-identified (LabID) infections………………………………………………………………………………………. 6

Clostridioides difficile Infections (CDI)……………………………………………………………………………………………….. 7

Carbapenem-resistant Enterobacteriaceae (CRE) Infections………………………………………………………………………………………. 8

Methicillin-resistant Staphylococcus aureus (MRSA) Infections………………………………………………………………………………………. 9

Hospital Performance …………………………………………………………………………………………………………10

Role of the State Health Department…………………………………………………………………………………….23

What Patients Can do to Prevent Infections………………………………………………………………………………………..24

PDF

https://www.health.ny.gov/statistics/facilities/hospital/hospital_acquired_infections/2018/docs/hospital_acquired_infection_p1.pdf

November 20, 2019 at 7:11 am

– INFECTONEWS CUMPLE 14 AÑOS –

Gracias a todos los colegas y amigos por comentarios, sugerencias y aportes.

Saludos cordiales y buenos deseos …

 

 – INFECTONEWS TODAY (NOV 19/2019) IS 14 YEARS OLD –

 Thanks to all colleagues and friends for comments, suggestions and contributions.

Best regards and good wishes …

Jorge Omar Calabrese – Tres Aroyos, prov Buenos Aires, Argentina

joc156@yahoo.com.ar

November 18, 2019 at 7:27 pm

Omadacycline as a promising new agent for the treatment of infections with Mycobacterium abscessus.

Omadacycline: A Potential New Treatment for Mycobacterium abscessus

SOURCE

J Antimicrob Chemother. October 1, 2019 V.74 N.10 P.2930-2933.

Bax HI1,2, de Vogel CP2, Mouton JW2, de Steenwinkel JEM2.

Author information

1 Department of Internal Medicine, Division of Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands.

2 Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Abstract

BACKGROUND:

Despite intensive treatment regimens, the outcome of Mycobacterium abscessus infections is extremely poor and thus novel treatment regimens are needed. Although tigecycline seems to be one of the best options currently available, its long-term use is hampered by severe toxic side effects as well as the need for intravenous administration and the relatively high concentrations required for efficacy.

OBJECTIVES:

To assess the in vitro activity of omadacycline against M. abscessus and compare it with the activity of tigecycline.

METHODS:

The concentration- and time-dependent killing capacities of omadacycline and tigecycline against M. abscessus subspecies abscessus were determined using a time-kill kinetics assay. Time-kill curves as well as concentration-effect curves were generated.

RESULTS:

Time-kill curves showed strong concentration-dependent antimicrobial activity for both omadacycline and tigecycline. Omadacycline showed inhibition of mycobacterial growth at 4 mg/L and mycobacterial killing at concentrations ≥16 mg/L. Tigecycline showed mycobacterial killing at concentrations ≥4 mg/L, achieving elimination at concentrations ≥16 mg/L. The concentration-effect curves after 7 days of exposure showed stasis, 1 log mycobacterial killing and 2 log mycobacterial killing at 3.3, 4.0 and 4.8 mg/L for omadacycline and 2.2, 2.7 and 3.4 mg/L for tigecycline, respectively.

CONCLUSIONS:

The results of this in vitro study on omadacycline activity, together with its favourable (pharmacokinetic) properties, suggest that omadacycline is a potential new agent for the treatment of M. abscessus infections

FULL TEXT

https://academic.oup.com/jac/article/74/10/2930/5522506

PDF (CLIC en PDF)

November 18, 2019 at 7:07 pm

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens.

Measles Virus Infection Negatively Affects Host Immune Status

New evidence shows that measles infection decreases the breadth and titers of preexisting antibodies to a wide variety of pathogens

SOURCE

Science. November 1, 2019 V.366 N.6465 P.599-606.

Mina MJ1,2,3, Kula T4,2, Leng Y4, Li M2, de Vries RD5, Knip M6,7, Siljander H6,7, Rewers M8, Choy DF9, Wilson MS9, Larman HB10, Nelson AN11, Griffin DE11, de Swart RL5, Elledge SJ1,2,12.

Author information

1 Division of Genetics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA. selledge@genetics.med.harvard.edu  mmina@hsph.harvard.edu

2 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

3 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

4 Division of Genetics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA.

5 Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, 3015 CN, Rotterdam, Netherlands.

6 Children’s Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland.

7 Research Program for Clinical and Molecular Metabolism, University of Helsinki, 00014 Helsinki, Finland.

8 Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Denver, CO 80045, USA.

9 Genentech Inc., South San Francisco, CA 94080, USA.

10 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

11 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

12Program in Virology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.

FULL TEXT

https://science.sciencemag.org/content/366/6465/599.long

PDF

https://science.sciencemag.org/content/sci/366/6465/599.full.pdf

November 18, 2019 at 7:04 pm

Cefiderocol, a Siderophore Cephalosporin for Gram-Negative Bacterial Infections: Pharmacokinetics and Safety in Subjects With Renal Impairment.

J Clin Pharmacol. May 2017 V.57 N.5 P.584-591. doi: 10.1002/jcph.841. Epub 2016 Nov 22.

Katsube T1, Echols R2, Arjona Ferreira JC2, Krenz HK2, Berg JK3, Galloway C4.

Author information

1 Shionogi & Co, Ltd, Osaka, Japan.

2 Shionogi Inc, Florham Park, NJ, USA.

3 DaVita Clinical Research, Minneapolis, MN, USA.

4 DaVita Clinical Research, Lakewood, CO, USA.

Abstract

Cefiderocol, a new injectable siderophore cephalosporin antibiotic, has promising in vitro and in vivo activity against Gram-negative bacteria including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Cefiderocol is mainly renally eliminated. The pharmacokinetics and safety of cefiderocol in subjects with renal impairment were assessed following a single 1000-mg intravenous 1-hour infusion of cefiderocol. Subjects with mild, moderate, or severe renal impairment and end-stage renal disease (ESRD) requiring hemodialysis were compared with demographically (age, body mass index, and sex) matched healthy subjects with normal renal function. The effect of hemodialysis on the clearance of cefiderocol was also assessed. Total drug clearance from plasma (CL) and terminal half-life (t1/2 ) correlated with renal function. Ratios (90% confidence intervals) of area under the plasma concentration-time curve from 0 to infinity (AUC) in mild, moderate, severe, and ESRD groups compared to those with normal renal function were 1.0 (0.8-1.3), 1.5 (1.2-1.9), 2.5 (2.0-3.3), and 4.1 (3.3-5.2), respectively. Maximum plasma concentration (Cmax ) was similar between renal-impairment groups and the normal-renal-function group. Approximately 60% of cefiderocol was removed by hemodialysis for 3 to 4 hours. The plasma-protein-unbound fraction was similar between various renal function groups. The incidence of adverse events did not appear to have any correlation with the degree of renal impairment. Single 1000-mg intravenous doses of cefiderocol were generally well tolerated in subjects with impaired renal function except for 1 subject who discontinued due to urticaria. In conclusion, renal impairment impacted AUC, CL, and t1/2 without affecting Cmax . Cefiderocol was significantly removed by intermittent hemodialysis.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412848/pdf/JCPH-57-584.pdf

November 16, 2019 at 10:10 am

Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa.

Antimicrob Agents Chemother. November 21, 2016 V.60 N.12 P. 7396-7401. Print 2016 Dec.

Ito A1, Nishikawa T2, Matsumoto S2, Yoshizawa H2, Sato T2, Nakamura R2, Tsuji M2, Yamano Y2.

Author information

1 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan akinobu.ito@shionogi.co.jp.

2 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.

Abstract

Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin conjugated with a catechol moiety at the third-position side chain. The in vitro activity of cefiderocol against Pseudomonas aeruginosa was enhanced under iron-depleted conditions, whereas that of ceftazidime was not affected. The monitoring of [thiazole-14C]cefiderocol revealed the increased intracellular accumulation of cefiderocol in P. aeruginosa cells incubated under iron-depleted conditions compared with those incubated under iron-sufficient conditions. Cefiderocol was shown to have potent chelating activity with ferric iron, and extracellular iron was efficiently transported into P. aeruginosa cells in the presence of cefiderocol as well as siderophores, while enhanced transport of extracellular ferric iron was not observed when one of the hydroxyl groups of the catechol moiety of cefiderocol was replaced with a methoxy group. We conclude that cefiderocol forms a chelating complex with iron, which is actively transported into P. aeruginosa cells via iron transporters, resulting in potent antibacterial activity of cefiderocol against P. aeruginosa.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119021/pdf/zac7396.pdf

November 16, 2019 at 10:09 am

Older Posts


Calendar

November 2019
M T W T F S S
 123
45678910
11121314151617
18192021222324
252627282930  

Posts by Month

Posts by Category