COVID-19 pneumonia and the appropriate use of antibiotics

Ginsburg, Amy Sarah; Klugman, Keith P.

doi:10.1016/s2214-109x(20)30444-7

Cited by 97 publications

(87 citation statements)

References 9 publications

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“…Earlier, 58% of COVID-19 patients in Wuhan were treated with antibiotics, suspecting that lung inflammation is mostly correlated with bacterial infections. Later, the WHO recommended using empiric antibiotics against the bacterial superinfections of COVID-19 patients (Ginsburg and Klugman, 2020), although we did not find any significant impact of antibiotics on reducing mortality rates of COVID-19 patients.…”

Section: Discussioncontrasting

confidence: 75%

Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis

et al. 2021

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Background: Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern.Objective and Methods: To estimate the efficacy and safety of COVID-19 therapeutics, we performed meta-analyses of the studies reporting clinical features and treatments of COVID-19 published from January 21 to September 6, 2020.Results: We included 136 studies that involved 102,345 COVID-19 patients. The most prevalent treatments were antibiotics (proportion: 0.59, 95% CI: [0.51, 0.67]) and antivirals (proportion: 0.52, 95% CI: [0.44, 0.60]). The combination of lopinavir/ritonavir and Arbidol was the most effective in treating COVID-19 (standardized mean difference (SMD) = 0.68, 95% CI: [0.15, 1.21]). The use of corticosteroids was associated with a small clinical improvement (SMD = −0.40, 95% CI: [−0.85, −0.23]), but with a higher risk of disease progression and death (mortality: RR = 9.26, 95% CI: [4.81, 17.80]; hospitalization length: RR = 1.54, 95% CI: [1.39, 1.72]; severe adverse events: RR = 2.65, 95% CI: [2.09, 3.37]). The use of hydroxychloroquine was associated with a higher risk of death (RR = 1.68, 95% CI: [1.18, 2.38]). The combination of lopinavir/ritonavir, ribavirin, and interferon-β (RR = 0.34, 95% CI: [0.22, 0.54]); hydroxychloroquine (RR = 0.58, 95% CI: [0.39, 0.58]); and lopinavir/ritonavir (RR = 0.72, 95% CI: [0.56, 0.91]) was associated with reduced hospitalization length. Hydrocortisone (RR = 0.05, 95% CI: [0.03, 0.10]) and remdesivir (RR = 0.74, 95% CI: [0.62, 0.90]) were associated with lower incidence of severe adverse events. Dexamethasone was not significant in reducing disease progression (RR = 0.45, 95% CI: [0.16, 1.25]) and mortality (RR = 0.90, 95% CI: [0.70, 1.16]). The estimated combination of corticosteroids with antivirals was associated with a better clinical improvement than antivirals alone (SMD = −1.09, 95% CI: [−1.64, −0.53]).Conclusion: Antivirals are safe and effective in COVID-19 treatment. Remdesivir cannot significantly reduce COVID-19 mortality and hospitalization length, while it is associated with a lower incidence of severe adverse events. Corticosteroids could increase COVID-19 severity, but it could be beneficial when combined with antivirals. Our data are potentially valuable for the clinical treatment and management of COVID-19 patients.

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Section: Discussioncontrasting

confidence: 75%

Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis

et al. 2021

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“…The selected 23 candidates for further investigation comprise anticancer, antimicrobial, and antiviral drugs (Figure 1D). Drugs from all three classes showed to lower the virus titre and to tune down the cytokine storm syndrome in the most severe cases of the disease (Ginsburg and Klugman, 2020). As expected, our approach identified antiviral drugs (against hepatitis C), which were already predicted as a COVID-19 treatment, or are currently in clinical trials against SARS-CoV-2 infection 1 (Jockusch et al, 2020;Mevada et al, 2020).…”

Section: Figuresupporting

confidence: 67%

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation

Serra

Fratello

Federico

et al. 2021

Preprint

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New affordable therapeutic protocols for COVID-19 are urgently needed despite the increasing number of effective vaccines and monoclonal antibodies. To this end, there is increasing attention towards computational methods for drug repositioning and de novo drug design. Here, we systematically integrated multiple data-driven computational approaches to perform virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the set of prioritized drugs, we selected a subset of representative candidates to test in human cells. Two compounds, 7-hydroxystaurosporine and bafetinib, showed synergistic antiviral effects in our in vitro experiments, and strongly inhibited viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, we extracted and prioritized the chemical substructures of the identified drugs, providing a chemical vocabulary that may help to design new effective drugs.

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“…In light of the new evidence from the RECOVERY trial, the widespread use in COVID-19 patients of macrolides in particular and antibiotics in general must be questioned. 26…”

Section: Discussionmentioning

confidence: 99%

Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Horby

Roddick

Spata

et al. 2020

Preprint

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SUMMARYBackgroundAzithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19.MethodsIn this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).FindingsBetween 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54).InterpretationIn patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).

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COVID-19 pneumonia and the appropriate use of antibiotics

Cited by 97 publications

References 9 publications

Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis

Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation

Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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