#Hydroxychloroquine and #azithromycin as a #treatment of #COVID19: results of an openlabel non-randomized clinical trial (Int J Antimicrob Agents., abstract)

[Source:  , full page: (LINK). Abstract, edited. Via Virology Blog, http://www.virology.ws/2020/03/19/hydroxychloroquine-reduces-viral-load-and-symptoms-in-covid-19-patients/ ]

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial

Philippe Gautret a,b$, Jean-Christophe Lagier a,c$, Philippe Parola a,b, Van Thuan Hoang a,b,d, Line Meddeb a, Morgane Mailhe a, Barbara Doudier a, Johan Courjon e,f,g, Valérie Giordanengo h, Vera Esteves Vieira a, Hervé Tissot Dupont a,c, Stéphane Honoré i,j, Philippe Colson a,c, Eric Chabrière a,c, Bernard La Scola a,c, Jean-Marc Rolain a,c, Philippe Brouqui a,c, Didier Raoult a,c*.

{a} IHU-Méditerranée Infection, Marseille, France. {b} Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France. {c} Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France. {d} Thai Binh University of Medicine and Pharmacy, Thai Binh, Viet Nam; {e} Infectiologie, Hôpital de l’Archet, Centre Hospitalier Universitaire de Nice, Nice, France; {f} Université Côte d’Azur, Nice, France; {g} U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Virulence Microbienne et Signalisation Inflammatoire, INSERM, Nice, France; {h} Department of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, 06200 Nice, France. {i} Service Pharmacie, Hôpital Timone, AP-HM, Marseille, France; {j} Laboratoire de Pharmacie Clinique, Aix Marseille Université, Marseille, France.

{$} equal work

{*} Corresponding author

Please cite this work as Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of  COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of  Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

Didier Raoult Didier.raoult@gmail.com

 

Abstract

Background

Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads.

Patients and methods

French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.

Results

Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.

Conclusion

Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Key words: 2019-nCoV; SARS-CoV-2; COVID-19; hydroxychloroquine; azithomycin; clinical trial

Keywords: SARS-CoV-2; COVID-19; Antivirals; Antibiotics; Azithromycin; Hydroxychloroquine.

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#Teicoplanin: An Alternative #Drug for the #Treatment of #Coronavirus #COVID19? (Int J Antimicrob Agents, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Antimicrob Agents, 105944 2020 Mar 13 [Online ahead of print]

Teicoplanin: An Alternative Drug for the Treatment of Coronavirus COVID-19?

Sophie Alexandra Baron 1, Christian Devaux 2, Philippe Colson 1, Didier Raoult 3, Jean-Marc Rolain 4

Affiliations: 1 Aix Marseille Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France. 2 Aix Marseille Univ, IRD, APHM, VITROME, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France. 3 Aix Marseille Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France; IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France. 4 Aix Marseille Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France; IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France. Electronic address: jean-marc.rolain@univ-amu.fr.

PMID: 32179150 DOI: 10.1016/j.ijantimicag.2020.105944

 

Abstract

In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency. Due to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococci infection, previously showed efficacy to inhibit the first stage of MERS-coronarivus viral cycle in human cells. This activity is conserved on the SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.

Keywords: COVID-19; Drug repurposing; SARS-CoV-2; Teicoplanin.

Copyright © 2020. Published by Elsevier B.V.

Conflict of interest statement – Declaration of Competing Interests The authors declare that they have no competing interests.

Keywords: COVID-19; SARS-CoV-2; Antivirals; Teicoplanin.

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#Critical #care #management of adults with community-acquired severe respiratory #viral #infection (Intensive Care Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Critical care management of adults with community-acquired severe respiratory viral infection.

Intensive Care Med. 2020 Feb 10;:

Authors: Arabi YM, Fowler R, Hayden FG

 

Abstract

With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17-53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.

PMID: 32040667 [PubMed – as supplied by publisher]

Keywords: Coronavirus; Influenza A; RSV; Antivirals; Antibiotics; COX-2-inhibitors; Statins.

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Association Between #Treatment with Oral Third-Generation #Cephalosporin #Antibiotics and #Mortality #Outcomes in #Ebola Virus Disease: A Multinational Retrospective Cohort Study (Trop Med Int Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Trop Med Int Health. 2020 Jan 7. doi: 10.1111/tmi.13369. [Epub ahead of print]

Association Between Treatment with Oral Third-Generation Cephalosporin Antibiotics and Mortality Outcomes in Ebola Virus Disease: A Multinational Retrospective Cohort Study.

Aluisio AR1, Perera SM2, Yam D3, Garbern S1, Peters JL4, Abel L4, Cho DK4, Woldemichael D2, Kennedy SB5, Massaquoi M5, Sahr F6, Liu T3, Levine AC1.

Author information: 1 Department of Emergency Medicine, Warren Alpert Medical School of Brown University, Providence, USA. 2 International Medical Corps, Washington, DC, USA. 3 Center for Statistical Sciences, Department of Biostatistics, Brown University School of Public Health, Providence, USA. 4 Warren Alpert Medical School of Brown University, Providence, USA. 5 Ministry of Health, Monrovia, Liberia. 6 College of Medicine and Allied Health Sciences, University of Sierra Leone, Sierra Leone, Freetown.

 

Abstract

OBJECTIVE:

To evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in Ebola Virus Disease (EVD).

METHODS:

This retrospective cohort studied EVD-infected patients admitted to five Ebola Treatment Units in Sierra Leone and Liberia during 2014-15. Empiric treatment with Cefixime 400 mg once daily for five days was the clinical protocol: however, due to resource variability, only a subset of patients received treatment. Data on sociodemographics, clinical characteristics, malaria status and Ebola viral loads were collected. The primary outcome was mortality compared between cases treated with Cefixime within 48 hours of admission to those not treated within 48 hours. Propensity scores were derived using clinical covariates. Mortality between treated and untreated cases was compared using propensity-matched conditional logistic regression and bootstrapped log-linear regression analyses to calculate an odds ratio (OR) and relative risk (RR), respectively, with associated 95% confidence intervals (CI).

RESULTS:

Of 424 cases analyzed, 360 (84.9%) met the Cefixime treatment definition. The mean age was 30.5 years and 40.3% were male. Median Cefixime treatment duration was 4 days (IQR: 3, 5). Among Cefixime-treated patients, mortality was 54.7% (95% CI: 49.6-59.8%), vs. 73.4% (95% CI: 61.5-82.7%) in untreated patients. In conditional logistic regression, mortality likelihood was significantly lower among cases receiving Cefixime (OR=0.48, 95% CI: 0.32-0.71; p=0.01). In the bootstrap analysis, a non-significant risk reduction was found with Cefixime treatment (RR=0.82, 95% CI: 0.64-1.16, p=0.11).

CONCLUSION:

Early oral Cefixime may be associated with reduced mortality in EVD and warrants further investigation.

© 2020 John Wiley & Sons Ltd.

KEYWORDS: Antibiotics; Cephalosporin; Cohort Study; Ebola Virus; Viral hemorrhagic fevers

PMID: 31912627 DOI: 10.1111/tmi.13369

Keywords: Antibiotics; Cephalosporins; Cefixime; Ebola.

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#NDM-β-Lactamase-5–Producing #Escherichia coli in Companion #Animals, #USA (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research Letter

New Delhi Metallo-β-Lactamase-5–Producing Escherichia coli in Companion Animals, United States

Stephen D. Cole, Laura Peak, Gregory H. Tyson, Renate Reimschuessel, Olgica Ceric, and Shelley C. Rankin

Author affiliations: University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA (S.D. Cole, S.C. Rankin); Louisiana State University, Baton Rouge, Louisiana USA (L. Peak); US Food and Drug Administration, Silver Spring, Maryland, USA (G.H. Tyson, R. Reimscheussel, O. Ceric)

 

Abstract

We report isolation of a New Delhi metallo-β-lactamase-5–producing carbapenem-resistant Escherichia coli sequence type 167 from companion animals in the United States. Reports of carbapenem-resistant Enterobacteriaceae in companion animals are rare. We describe a unique cluster of blaNDM-5–producing E. coli in a veterinary hospital.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; NDM1; USA.

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Novel Subclone of #Carbapenem-Resistant #Klebsiella pneumoniae Sequence Type 11 with Enhanced #Virulence and Transmissibility, #China (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research

Novel Subclone of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 with Enhanced Virulence and Transmissibility, China

Kai Zhou1, Tingting Xiao1, Sophia David1, Qin Wang, Yanzi Zhou, Lihua Guo, David Aanensen, Kathryn E. Holt, Nicholas R. Thomson, Hajo Grundmann2, Ping Shen2, and Yonghong Xiao2

Author affiliations: First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People’s Hospital); Shenzhen, China (K. Zhou); The Second Clinical Medical College of Jinan University, Shenzhen (K. Zhou); Zhejiang University, Hangzhou, China (T. Xiao, Q. Wang, Y. Zhou, L. Guo, P. Shen, Y. Xiao); Centre for Genomic Pathogen Surveillance, Cambridge, UK (S. David, D. Aanensen); University of Melbourne, Melbourne, Victoria, Australia (K.-E. Holt); London School of Hygiene and Tropical Medicine, London, UK (K.E. Holt, N.R. Thomson); Wellcome Trust Sanger Centre, Cambridge (N.R. Thomson); University of Freiburg, Freiburg, Germany (H. Grundmann).

 

Abstract

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; China.

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Low-temperature #laminar #flow #ward for the #treatment of #MDR #Acinetobacter baumannii #pneumonia (Eur J Clin Microbiol Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Eur J Clin Microbiol Infect Dis. 2020 Jan 2. doi: 10.1007/s10096-019-03790-x. [Epub ahead of print]

Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia.

Gong Z1,2, Li J, Luo H1,2, Zhan D2,3, Liu X1,2, Gao C1,2, Huang J1,2, Qian Y1,2, Song Y1,2, Quan W1,2, An S1,2, Tian Y1,2, Hu Z4, Sun J1,2, Yuan H5,6, Jiang R7,8.

Author information: 1 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China. 2 Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China. 3 Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China. 4 Department of clinical laboratories, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China. 5 Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China. hengjieyuan@163.com. 6 Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China. hengjieyuan@163.com. 7 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China. jiang116216@163.com. 8 Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China. jiang116216@163.com.

 

Abstract

This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level.

KEYWORDS: Acinetobacter baumannii; Pneumonia; Temperature; Treatment; Variation

PMID: 31898800 DOI: 10.1007/s10096-019-03790-x

Keywords: Antibiotics; Drugs Resistance; Acinetobacter baumannii; Nosocomial outbreaks; Pneumonia; Intensive care.

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