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Antibacterial Therapy in Adults with COVID-19

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 29672

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Prof. Dr. Sabine Danielle Allard

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Guest Editor

Department of Internal Medicine and Infectious Diseases, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel, 1090 Brussels, Belgium
Interests: HIV immunology; SARS-CoV-2 immunology; mRNA vaccines; antimicrobial stewardship; COVID-19

Dr. Johan Van Laethem

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Guest Editor

Department of Internal Medicine and Infectious Diseases, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel, 1090 Brussels, Belgium
Interests: antimicrobial stewardship; multi-drug resistant infections; antibiotics; diagnostic stewardship

Special Issue Information

Dear Colleagues,

Since the emergence of the Coronavirus-19 infectious disease (COVID-19) pandemic, a rising number of reports have underlined the risk of increasing antimicrobial resistance due to antibiotic overuse in COVID-19 patients. In addition, many physicians and pharmacists involved in antimicrobial stewardship have had to shift their activities to the containment of the COVID-19 crisis. In contrast to this observed overconsumption of antibiotics, very few bacterial superinfections have been documented in COVID-19 patients, especially in patients admitted outside the intensive care unit and in the first days of admission. However, identification of bacterial co-/superinfections in COVID-19 patients is difficult, as inflammatory and radiological markers of bacterial infection lack specificity in this setting. Furthermore, studies regarding the effect of immune suppression, including the use of corticosteroids and anti-interleukins, and the effect of potential immunomodulatory properties of certain antibiotics on the occurrence of bacterial co-/superinfection are needed.

This Special Issue of Antibiotics seeks the submission of manuscripts aiming to increase our knowledge regarding (more or less specific) markers associated with bacterial co-/superinfection in COVID-19 patients, quantitative and qualitative data regarding antibiotic prescriptions in COVID-19 patients, potential beneficial effects of antibiotic use in certain COVID-19 subgroups, detrimental effects associated with antibiotic overuse in COVID-19 patients, and evidence-based guidelines which could facilitate the decision process when antibiotic prescriptions are considered.

Prof. Dr. Sabine Danielle Allard
Dr. Johan Van Laethem
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

antibiotics
antimicrobial stewardship
Sars-CoV-2
COVID 19
antimicrobial resistance
bacterial co-infection
bacterial superinfection

Published Papers (10 papers)

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Research

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13 pages, 3189 KiB

Open AccessArticle

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France

by Paul Laffont-Lozes, Didier Laureillard, Paul Loubet, Robin Stephan, Myriam Chiaruzzi, Edouard Clemmer, Aurelie Martin, Claire Roger, Laurent Muller, Pierre-Géraud Claret, Radjiv Goulabchand, Clarisse Roux, Jean-Philippe Lavigne, Albert Sotto and Romaric Larcher

Antibiotics 2023, 12(1), 88; https://doi.org/10.3390/antibiotics12010088 - 04 Jan 2023

Cited by 2 | Viewed by 1673

Abstract

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/− tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02–1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11–1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07–6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14–0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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10 pages, 1518 KiB

Open AccessArticle

Mid-Regional Pro-Adrenomedullin as a Prognostic Factor for Severe COVID-19 ARDS

by Etienne de Montmollin, Katell Peoc’h, Mehdi Marzouk, Stéphane Ruckly, Paul-Henri Wicky, Juliette Patrier, Pierre Jaquet, Romain Sonneville, Lila Bouadma and Jean-François Timsit

Antibiotics 2022, 11(9), 1166; https://doi.org/10.3390/antibiotics11091166 - 29 Aug 2022

Cited by 7 | Viewed by 1937

Abstract

Mid-regional proadrenomedullin (MR-proADM) protects against endothelial permeability and has been associated with prognosis in bacterial sepsis. As endothelial dysfunction is central in the pathophysiology of severe SARS-CoV-2 infection, we sought to evaluate MR-proADM both as a prognostic biomarker and as a marker of bacterial superinfection. Consecutive patients admitted to the ICU for severe SARS-CoV-2 pneumonia were prospectively included and serum was bio-banked on days 1, 3, and 7. MR-proADM levels were measured blindly from clinical outcomes in batches at the end of follow-up. Among the 135 patients included between April 2020 and May 2021, 46 (34.1%) had died at day 60. MR-proADM levels on days 1, 3, and 7 were significantly higher in day-60 non-survivors. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve (0.744, p < 0.001) of day-1 MR-proADM compared favorably with the AUC ROC curve of day-1 procalcitonin (0.691, p < 0.001). Serial MR-proADM measurements on days 3 and 7 may add prognostic information. After adjusting for CRP, LDH, and lymphocyte values, day-1 MR-proADM remained significantly associated with day-60 mortality. MR-proADM concentrations were significantly higher in patients with respiratory superinfections (on days 3 and 7) and bloodstream infections (on days 1, 3, and 7) than in patients without infection. Our results suggest that MR-proADM is a good predictor of outcome in severe SARS-CoV-2 infection and could be a useful tool to assess bacterial superinfection in COVID-19 patients. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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11 pages, 1057 KiB

Open AccessArticle

Diagnostic Accuracy of Procalcitonin upon Emergency Department Admission during SARS-CoV-2 Pandemic

by Stefano Malinverni, Silvia Lazzaroni, Maïa Nuňez, Thierry Preseau, Frédéric Cotton, Delphine Martiny, Fatima Bouazza, Vincent Collot, Deborah Konopnicki, Stéphane Alard and Magali Bartiaux

Antibiotics 2022, 11(9), 1141; https://doi.org/10.3390/antibiotics11091141 - 23 Aug 2022

Cited by 2 | Viewed by 1330

Abstract

Introduction: Procalcitonin is a marker for bacterial diseases and has been used to guide antibiotic prescription. Procalcitonin accuracy, measured at admission, in patients with community-acquired pneumonia (CAP), is unknown in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Objectives: To evaluate the diagnostic accuracy of procalcitonin to assess the need for antibiotic treatment in patients with CAP presenting to the emergency department during the SARS-CoV-2 pandemic. Methods: We performed a real-world diagnostic retrospective accuracy study of procalcitonin in patients admitted to the emergency department. Measures of diagnostic accuracy were calculated based on procalcitonin results compared to the reference standard of combined microbiological and radiological analysis. Sensitivity, specificity, positive and negative predictive values, and area under (AUC) the receiver-operating characteristic (ROC) curve were calculated in two analyses: first assessing procalcitonin ability to differentiate microbiologically proven bacteria from viral CAP and then clinically diagnosed bacterial CAP from viral CAP. Results: When using a procalcitonin threshold of 0.5 ng/mL to identify bacterial etiology within patients with CAP, we observed sensitivity and specificity of 50% and 64.1%, and 43% and 82.6%, respectively, in the two analyses. The positive and negative predictive values of a procalcitonin threshold of 0.5 ng/mL to identify patients for whom antibiotics should be advised were 46.4% and 79.7%, and 48.9% and 79% in the two analyses, respectively. The AUC for the two analyses was 0.60 (95% confidence interval [CI] 0.52–0.68) and 0.62 (95% CI, 0.55–0.69). Conclusions: Procalcitonin measured upon admission during the SARS-CoV-2 pandemic should not guide antibiotic treatment in patients with CAP. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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12 pages, 263 KiB

Open AccessArticle

Co-Administration of Remdesivir and Azithromycin May Protect against Intensive Care Unit Admission in COVID-19 Pneumonia Requiring Hospitalization: A Real-Life Observational Study

by Andrea Ticinesi, Domenico Tuttolomondo, Antonio Nouvenne, Alberto Parise, Nicoletta Cerundolo, Beatrice Prati, Ilaria Zanichelli, Angela Guerra, Nicola Gaibazzi and Tiziana Meschi

Antibiotics 2022, 11(7), 941; https://doi.org/10.3390/antibiotics11070941 - 14 Jul 2022

Cited by 5 | Viewed by 1643

Abstract

The benefits of remdesivir treatment, with or without co-administration of antibiotics such as azithromycin, are uncertain in COVID-19 pneumonia. The aim of this retrospective single-center study was to assess the effects of remdesivir, with or without azithromycin, on hospital mortality, intensive care unit (ICU) admission, and need of non-invasive ventilation. The clinical records of the COVID-19 patients hospitalized in an Italian ward in March 2021 were analyzed, and data on comorbidities and clinical, radiological, and laboratory presentation of the disease were collected. Among 394 participants (234 M), 173 received remdesivir (43.9%), including 81 with azithromycin (20.5%). Remdesivir recipients were younger, with less comorbidities, and had better PaO₂/FiO₂ and clinical outcomes, including reduced mortality, but the differences were not independent of covariates. Rates of ICU transferal were 17%, 9%, and 1% in the no remdesivir, remdesivir without azithromycin, and remdesivir/azithromycin groups, respectively. In a stepwise multivariate logistic regression model, remdesivir/azithromycin co-treatment was independently associated with reduced ICU admission (vs remdesivir alone, OR 0.081, 95% CI 0.008–0.789, p = 0.031; vs no remdesivir, OR 0.060, 95% CI 0.007–0.508, p = 0.010). These data suggest that the therapeutical effect of remdesivir in COVID-19 pneumonia may be potentiated by azithromycin. The association between the two drugs should be further investigated. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

14 pages, 898 KiB

Open AccessArticle

Safety and Efficacy of Ivermectin for the Prevention and Treatment of COVID-19: A Double-Blinded Randomized Placebo-Controlled Study

by Nasikarn Angkasekwinai, Pinyo Rattanaumpawan, Methee Chayakulkeeree, Pakpoom Phoompoung, Pornpan Koomanachai, Sorawit Chantarasut, Walaiporn Wangchinda, Varalak Srinonprasert and Visanu Thamlikitkul

Antibiotics 2022, 11(6), 796; https://doi.org/10.3390/antibiotics11060796 - 12 Jun 2022

Cited by 4 | Viewed by 9096

Abstract

The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 are still controversial topics. From August to November 2021, we conducted a double-blinded, randomized controlled trial at Siriraj Hospital, Thailand. Eligible participants were adults ≥ 18 years with suspected COVID-19 who underwent a SARS-CoV-2 RT-PCR test. After enrollment, the participants were randomized to receive either ivermectin (400–600 µg/kg/d) or placebo once daily for 3 days. Among 983 participants, 536 (54.5%) with a negative RT-PCR result were enrolled in the prevention study, and 447 (45.5%) with a positive RT-PCR result were enrolled in the treatment study. In the prevention study, the incidence of COVID-19 on Day 14 was similar between the ivermectin and the placebo group (4.7% vs. 5.2%; p = 0.844; Δ = −0.4%; 95% CI; −4.3–3.5%). In the treatment study, there was no significant difference between the ivermectin and placebo group for any Day 14 treatment outcome: proportion with oxygen desaturation (2.7% vs. 1.9%; p = 0.75), change in WHO score from baseline (1 [−5, 1] vs. 1 [−5, 1]; p = 0.50), and symptom resolution (76% vs. 82.2%; p = 0.13). The ivermectin group had a significantly higher proportion of transient blurred vision (5.6% vs. 0.6%; p < 0.001). Our study failed to demonstrate the efficacy of a 3-day once daily of ivermectin for the prevention and treatment of COVID-19. The given regimen of ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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15 pages, 611 KiB

Open AccessArticle

A Retrospective, Monocentric Study Comparing Co and Secondary Infections in Critically Ill COVID-19 and Influenza Patients

by Diane Marcoux, Isabelle Etienne, Alain Van Muylem, Elisa Gouvea Bogossian, Nicolas Yin, Fabio Silvio Taccone and Maya Hites

Antibiotics 2022, 11(6), 704; https://doi.org/10.3390/antibiotics11060704 - 24 May 2022

Cited by 2 | Viewed by 1660

Abstract

Few data are available on infectious complications in critically ill patients with different viral infections. We performed a retrospective monocentric study including all of the patients admitted to the intensive care unit (ICU) with confirmed COVID-19 (as of 13 March 2020) or Influenza A and/or B infections (as of 1 January 2015) until 20 April 2020. Coinfection and secondary infections (occurring within and after 48 h from admission, respectively) were recorded. Fifty-seven COVID-19 and 55 Influenza patients were included. Co-infections were documented in 13/57 (23%) COVID-19 patients vs. 40/55 (73%) Influenza patients (p < 0.001), most of them being respiratory (9/13, 69% vs. 35/40, 88%; p = 0.13) and of bacterial origin (12/13, 92% vs. 29/40, 73%; p = 0.25). Invasive aspergillosis infections were observed only in Influenza patients (8/55, 15%). The COVID-19 and Influenza patients presented 1 (0–4) vs. 0 (0–4) secondary infections (p = 0.022), with comparable sites being affected (lungs: 35/61, 57% vs. 13/31, 42%; p = 0.16) and causative pathogens occurring (Gram-negative bacteria: 51/61, 84% vs. 23/31, 74%; p > 0.99). The COVID-19 patients had longer ICU lengths of stay (15 (–65) vs. 5 (1–89) days; p = 0.001), yet the two groups had comparable mortality rates (20/57, 35% vs. 23/55, 41%; p = 0.46). We report fewer co-infections but more secondary infections in the ICU COVID-19 patients compared to the Influenza patients. Most of the infectious complications were respiratory and of bacterial origin. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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11 pages, 472 KiB

Open AccessArticle

Antimicrobial Use in Hospitalised Patients with COVID-19: An International Multicentre Point-Prevalence Study

by Lea Papst, Roberto Luzzati, Biljana Carević, Carlo Tascini, Nina Gorišek Miksić, Vera Vlahović Palčevski, Zorana M. Djordjevic, Omar Simonetti, Emanuela Sozio, Milica Lukić, Goran Stevanović, Davor Petek and Bojana Beović

Antibiotics 2022, 11(2), 176; https://doi.org/10.3390/antibiotics11020176 - 28 Jan 2022

Cited by 9 | Viewed by 2642

Abstract

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9–85.6%) on the day of the study. Differences between hospitals were statistically significant (χ² (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4–100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the “Watch” group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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12 pages, 1086 KiB

Open AccessReview

Azithromycin through the Lens of the COVID-19 Treatment

by Georgia G. Kournoutou and George Dinos

Antibiotics 2022, 11(8), 1063; https://doi.org/10.3390/antibiotics11081063 - 05 Aug 2022

Cited by 12 | Viewed by 5356

Abstract

Azithromycin has become famous in the last two years, not for its main antimicrobial effect, but for its potential use as a therapeutic agent for COVID-19 infection. Initially, there were some promising results that supported its use, but it has become clear that scientific results are insufficient to support such a positive assessment. In this review we will present all the literature data concerning the activity of azithromycin as an antimicrobial, an anti-inflammatory, or an antivirus agent. Our aim is to conclude whether its selection should remain as a valuable antivirus agent or if its use simply has an indirect therapeutic contribution due to its antimicrobial and/or immunomodulatory activity, and therefore, if its further use for COVID-19 treatment should be interrupted. This halt will prevent further antibiotic resistance expansion and will keep azithromycin as a valuable anti-infective therapeutic agent. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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11 pages, 2387 KiB

Open AccessSystematic Review

Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Anti-Microbial Resistance

by Shahana Seher Malik and Sunil Mundra

Antibiotics 2023, 12(1), 45; https://doi.org/10.3390/antibiotics12010045 - 28 Dec 2022

Cited by 29 | Viewed by 2392

Abstract

The emergence of COVID-19 infection led to the indiscriminate use of antimicrobials without knowing their efficacy in treating the disease. The gratuitous use of antibiotics for COVID-19 treatment raises concerns about the emergence of antimicrobial resistance (AMR). In this systematic review, we performed a thorough systematic search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of scientific databases (Scopus, Web of Science, and PubMed) to identify studies where antibiotics were prescribed to treat COVID-19 (December 2019 to December 2021). Of 970 identified studies, 130 were included in our analyses. Almost 78% of COVID-19 patients have been prescribed an antibiotic. Cephalosporins were the most prescribed (30.1% of patients) antibiotics, followed by azithromycin (26% of patients). Antibiotics were prescribed for COVID-19 patients regardless of reported severity; the overall rate of antibiotic use was similar when comparing patients with a severe or critical illness (77.4%) and patients with mild or moderate illness (76.8%). Secondary infections were mentioned in only 11 studies. We conclude that concerns related to COVID-19 and the lack of treatment strategy led to the overuse of antibiotics without proper clinical rationale. Based on our findings, we propose that antimicrobial stewardship should be retained as a priority while treating viral pandemics. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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7 pages, 713 KiB

Open AccessPerspective

Beyond Guidelines and Reports on Bacterial Co-/Superinfections in the Context of COVID-19: Why Uniformity Matters

by Johan Van Laethem, Denis Piérard and Sabine D. Allard

Antibiotics 2022, 11(10), 1446; https://doi.org/10.3390/antibiotics11101446 - 20 Oct 2022

Cited by 1 | Viewed by 1225

Abstract

Background: In the period following the declaration of the COVID-19 pandemic, more evidence became available on the epidemiology of bacterial co-/superinfections (bCSs) in hospitalized COVID-19 patients. Various European therapeutic guidelines were published, including guidance on rational antibiotic use. Methods: In this letter to the editor, we provide an overview of the largest meta-analyses or prospective studies reporting on bCS rates in COVID-19 patients and discuss why the reader should interpret the results of those reports with care. Moreover, we compare different national and international COVID-19 therapeutic guidelines from countries of the European Union. Specific attention is paid to guidance dedicated to rational antibiotic use. Results: We found a significant heterogeneity in studies reporting on the epidemiology of bCSs in COVID-19 patients. Moreover, European national and international guidelines differ strongly from each other, especially with regard to the content and extent of antibiotic guidance in hospitalized COVID-19 patients. Conclusion: A standardized way of reporting on bCSs and uniform European guidelines on rational antibiotic use in COVID-19 patients are crucial for antimicrobial stewardship teams to halt unnecessary antibiotic use in the COVID-19 setting. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

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