Antibiotics and Therapeutic Agent Prescription in COVID-19 Management

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 (31 December 2021) | Viewed by 51860

Special Issue Editors


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Guest Editor
Infectious Diseases Department, Nord Franche-Comté Hospital, 90400 Trevenans, France
Interests: infectious diseases; COVID-19; clinical and diagnostic microbiology; pathogenic microorganism; antibiotic resistance; tickborne infections; lyme borreliosis; tuberculosis; AIDS and HIV infections; antiretroviral treatment

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Guest Editor
Infectious Diseases Department, Nord Franche-Comté Hospital, Montbeliard, France
Interests: infectious diseases; COVID-19; clinical and diagnostic microbiology; pathogenic microorganism; antibiotic resistance; zoonoses; lyme borreliosis

Special Issue Information

Dear Colleagues,

During the coronavirus disease 2019 (COVID-19) pandemic, only few therapeutic options have been approved for the treatment of COVID-19 with strong evidence. The spectrum of effective therapies to treat moderate-to-severe COVID-19 forms or prevent disease progression is growing and evolving rapidly. Several trials to assess the potential effectiveness of these therapeutics in hospitalized adults and outpatients, but also in specific populations such as children and pregnant women, are ongoing. However, some physicians and doctors still prescribe inappropriate treatment in COVID-19 patients. In Antibiotics, we present this Special Issue in view of the health emergency and the use of therapeutic agents with high uncertainty and potential for harm in order to improve treatment recommendations during COVID-19.

Dr. Souheil Zayet
Dr. Timothée Klopfenstein
Guest Editors

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Keywords

  • COVID-19
  • treatment
  • steroids
  • anti-interleukin-6
  • antibiotics
  • anticoagulants
  • immunoglobulin
  • antivirals
  • therapies
  • clinical trial
  • prescription
  • recommendations
  • diagnosis

Published Papers (11 papers)

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Editorial

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3 pages, 205 KiB  
Editorial
Antibiotics and Therapeutic Agent Prescription in COVID-19 Management
by Souheil Zayet and Timothée Klopfenstein
Antibiotics 2022, 11(4), 423; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11040423 - 22 Mar 2022
Cited by 2 | Viewed by 1663
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, only few therapeutic options have been approved for the treatment of COVID-19 with substantial evidence [...] Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)

Research

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13 pages, 5924 KiB  
Article
Does the Fetus Limit Antibiotic Treatment in Pregnant Patients with COVID-19?
by Tito Ramírez-Lozada, María Concepción Loranca-García, Claudia Erika Fuentes-Venado, Carmen Rodríguez-Cerdeira, Esther Ocharan-Hernández, Marvin A. Soriano-Ursúa, Eunice D. Farfán-García, Edwin Chávez-Gutiérrez, Xóchitl Ramírez-Magaña, Maura Robledo-Cayetano, Marco A. Loza-Mejía, Ivonne Areli Garcia Santa-Olalla, Oscar Uriel Torres-Paez, Rodolfo Pinto-Almazán and Erick Martínez-Herrera
Antibiotics 2022, 11(2), 252; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020252 - 16 Feb 2022
Cited by 4 | Viewed by 6006
Abstract
During pregnancy, there is a state of immune tolerance that predisposes them to viral infection, causing maternal-fetal vulnerability to the adverse effects of COVID-19. Bacterial coinfections significantly increase the mortality rate for COVID-19. However, it is known that all drugs, including antibiotics, will [...] Read more.
During pregnancy, there is a state of immune tolerance that predisposes them to viral infection, causing maternal-fetal vulnerability to the adverse effects of COVID-19. Bacterial coinfections significantly increase the mortality rate for COVID-19. However, it is known that all drugs, including antibiotics, will enter the fetal circulation in a variable degree despite the role of the placenta as a protective barrier and can cause teratogenesis or other malformations depending on the timing of exposure to the drug. Also, it is important to consider the impact of the indiscriminate use of antibiotics during pregnancy can alter both the maternal and fetal-neonatal microbiota, generating future repercussions in both. In the present study, the literature for treating bacterial coinfections in pregnant women with COVID-19 is reviewed. In turn, we present the findings in 50 pregnant women hospitalized diagnosed with SARS-CoV-2 without previous treatment with antibiotics; moreover, a bacteriological culture of sample types was performed. Seven pregnant women had coinfection with Staphylococcus haemolyticus, Staphylococcus epidermidis, Streptococcus agalactiae, Escherichia coli ESBL +, biotype 1 and 2, Acinetobacter jahnsonii, Enterococcus faecium, and Clostridium difficile. When performing the antibiogram, resistance to multiple drugs was found, such as macrolides, aminoglycosides, sulfa, dihydrofolate reductase inhibitors, beta-lactams, etc. The purpose of this study was to generate more scientific evidence on the better use of antibiotics in these patients. Because of this, it is important to perform an antibiogram to prevent abuse of empirical antibiotic treatment with antibiotics in pregnant women diagnosed with SARS-CoV-2. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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12 pages, 1202 KiB  
Article
Efficacy and Safety of Remdesivir in COVID-19 Positive Dialysis Patients
by Batool Butt, Tajamul Hussain, Mu’taman Jarrar, Kashaf Khalid, Waleed Albaker, Asma Ambreen and Yasir Waheed
Antibiotics 2022, 11(2), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020156 - 25 Jan 2022
Cited by 11 | Viewed by 3659
Abstract
(1) Background: Immune compromised hemodialysis patients are more likely to develop COVID-19 infections, which increase the risk of mortality. The benefits of Remdesivir, despite less literature support on its effectiveness in dialysis patients due to renal toxicity, can outweigh the risks if prescribed [...] Read more.
(1) Background: Immune compromised hemodialysis patients are more likely to develop COVID-19 infections, which increase the risk of mortality. The benefits of Remdesivir, despite less literature support on its effectiveness in dialysis patients due to renal toxicity, can outweigh the risks if prescribed early. The aim of this study was to evaluate the efficacy of Remdesivir on the 30-day in-hospital clinical outcome of hemodialysis population with COVID-19 infection and safety endpoints of adverse events. (2) Study design: A prospective quasi-experimental study design was used in the study. (3) Methods: The sample population consisted of 83 dialysis patients with COVID-19 who were administered Remdesivir at a dose of 100 mg before hemodialysis, as per hospital protocol. After the treatment with Remdesivir, we assessed the outcomes across two endpoints, namely primary (surviving vs. dying) as well as clinical and biochemical changes (ferritin, liver function test, C-reactive protein, oxygen requirements, and lactate dehydrogenase levels) and secondary (adverse effects, such as diarrhea, rise in ALT). In Kaplan–Meier analysis, the survival probabilities were compared between patients who received Remdesivir within 48 h of diagnosis and those who received it after 48 h. Cox regression analysis was employed to determine the predictors of outcome. (4) Results: Of the 83 patients, 91.5% survived and 8.4% died. Remdesivir administration did not reduce the death rate overall. Hospital stays were shorter (p = 0.03) and a nasopharyngeal swab for COVID-19 was negative earlier (p = 0.001) in survivors who had received Remdesivir within 48 h of diagnosis compared to those who had received Remdesivir after 48 h. The only variables linked to the 30-day mortality were serum CRP (p = 0.028) and TLC (p = 0.013). No major adverse consequences were observed with Remdesivir. (5) Conclusions: Remdesivir has the potential to shorten the recovery time for dialysis patients if taken within 48 h of onset of symptoms, without any adverse effects. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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7 pages, 231 KiB  
Article
The Predictive Value of Cell Blood Count Parameters to Diagnose Pulmonary Embolism in Patients with SARS-CoV-2 Infection: A Case Control Study
by Alessio Strazzulla, Sarra Abroug Ben Halima, Ibrahim Chouchane, Marwa Rezek, Marcella Pinto Stiebler, Sarra Hamrouni, Mohammad Maalaoui, Nouha Ghriss, Renaud Guedec-Ghelfi, Cyrus Moini, Mehran Monchi and Nabil Belfeki
Antibiotics 2022, 11(1), 60; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11010060 - 04 Jan 2022
Cited by 9 | Viewed by 1499
Abstract
Introduction: Acute pulmonary embolism (aPE) is frequently associated with coronavirus infectious disease-2019 (COVID-19) with an incidence of more than 16%. Among the new promising biomarkers of aPE, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) showed correlations with aPE prognosis. The aim of [...] Read more.
Introduction: Acute pulmonary embolism (aPE) is frequently associated with coronavirus infectious disease-2019 (COVID-19) with an incidence of more than 16%. Among the new promising biomarkers of aPE, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) showed correlations with aPE prognosis. The aim of this study was to conduct an exploratory analysis to check the possible role of cell blood count (CBC) parameters as diagnostic and prognostic biomarkers of aPE in COVID-19 patients. Materials and Methods: A case control study was conducted. Two populations were compared: (i) patients hospitalised from 31 January 2020 to 30 June 2021 with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection and aPE confirmed at angio computed tomography (aCT) or pulmonary scintigraphy (COVID-19 aPE group); (ii) patients hospitalised from 31 January 2017 to 30 June 2021 without SARS-CoV-2 infection whose suspicion of aPE was excluded by aCT or pulmonary scintigraphy (no-aPE group). Results: Overall, 184 patients were included in the study, 83 in COVID-19 aPE group and 101 in no-aPE group. At the univariate analysis, COVID-19 patients with aPE had higher NLR, PLR, neutrophil and lymphocyte counts than patients without aPE (p < 0.05). No significant difference was found in mean platelet volume and platelet counts. No difference in mortality rate was detected. At the multivariate analysis, neutrophil and lymphocyte counts were both associated with diagnostic of aPE while no CBC parameters were associated with mortality at day#7. Conclusions: Neutrophiland lymphocyte counts could be predictors of the early detection of aPE in COVID-19 patients. The value of CBC indices as biomarkers of aPE in daily clinical practice needs to be investigated in further studies. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
11 pages, 614 KiB  
Article
Comparison of Low-Versus High-Dose Steroids in the Clinical Outcome of Hospitalized COVID-19 Patients
by Zubia Jamil, Fahad N. Almajhdi, Samreen Khalid, Muhammad Asghar, Jamal Ahmed and Yasir Waheed
Antibiotics 2021, 10(12), 1510; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10121510 - 09 Dec 2021
Cited by 8 | Viewed by 2723
Abstract
(1) Objectives: Patients with COVID-19 infection have been given various formulations and dosages of steroids over the last year and a half. This study aims to compare the effects of different formulations and doses of steroids on the 30 day in-hospital clinical outcome [...] Read more.
(1) Objectives: Patients with COVID-19 infection have been given various formulations and dosages of steroids over the last year and a half. This study aims to compare the effects of different formulations and doses of steroids on the 30 day in-hospital clinical outcome of patients with severe COVID-19 infection. (2) Material and Methods: An analysis of a retrospective cohort was carried out on patients with severe COVID-19 infection in a high-dependency unit (HDU) between February and July 2021. In total, 557 patients were included in this study. Patients who did not receive steroids (124) were excluded. Patients were divided into three groups based on dosages of steroids (Dexamethasone = 6 mg/day, Dexamethasone > 6 mg/day, and Methylprednisolone = 500 mg/day), given for 10 days. First, clinical outcome was evaluated on the 10th day of steroid administration in relation to mode of oxygen delivery. Then, Kaplan–Meier analysis was employed to determine 30 day in-hospital survival in relation to the use of steroid. (3) Results: Three groups were statistically equal according to biochemical characteristics. After 10 days of Methylprednisolone = 500 mg/day vs. Dexamethasone = 6 mg/day, 10.9% vs. 6.2% of patients required invasive ventilation (p = 0.01). The 30 day in-hospital mortality was lowest, 3%, in individuals receiving Dexamethasone = 6 mg/day, compared to 3.9% in individuals receiving Dexamethasone > 6 mg/day and 9.9% in individuals receiving Methylprednisolone = 500 mg/day, respectively. The median elapsed time was longer than 28 days between admission and outcome for Dexamethasone = 6 mg/day, compared to 18 days for Dexamethasone > 6 mg/day and 17 days for Methylprednisolone = 500 mg/day (p = < 0.0001). Dexamethasone = 6 mg/day was found to be a positive predictor of clinical outcome in COVID-19 patients on regression analysis. (4) Conclusions: Low-dose Dexamethasone (6 mg/day) is more effective than high-dose Dexamethasone and Methylprednisolone in improving the survival outcome of severe COVID-19 cases. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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13 pages, 1649 KiB  
Article
Presumed Urinary Tract Infection in Patients Admitted with COVID-19: Are We Treating Too Much?
by Johan Van Laethem, Stephanie C. M. Wuyts, Jan Pierreux, Lucie Seyler, Gil Verschelden, Thibault Depondt, Annelies Meuwissen, Patrick Lacor, Denis Piérard and Sabine D. Allard
Antibiotics 2021, 10(12), 1493; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10121493 - 06 Dec 2021
Cited by 6 | Viewed by 3201
Abstract
Despite the low rates of bacterial co-/superinfections in COVID-19 patients, antimicrobial drug use has been liberal since the start of the COVID-19 pandemic. Due to the low specificity of markers of bacterial co-/superinfection in the COVID-19 setting, overdiagnosis and antimicrobial overprescription have become [...] Read more.
Despite the low rates of bacterial co-/superinfections in COVID-19 patients, antimicrobial drug use has been liberal since the start of the COVID-19 pandemic. Due to the low specificity of markers of bacterial co-/superinfection in the COVID-19 setting, overdiagnosis and antimicrobial overprescription have become widespread. A quantitative and qualitative evaluation of urinary tract infection (UTI) diagnoses and antimicrobial drug prescriptions for UTI diagnoses was performed in patients admitted to the COVID-19 ward of a university hospital between 17 March and 2 November 2020. A team of infectious disease specialists performed an appropriateness evaluation for every diagnosis of UTI and every antimicrobial drug prescription covering a UTI. A driver analysis was performed to identify factors increasing the odds of UTI (over)diagnosis. A total of 622 patients were included. UTI was present in 13% of included admissions, and in 12%, antimicrobials were initiated for a UTI diagnosis (0.71 daily defined doses (DDDs)/admission; 22% were scored as ‘appropriate’). An evaluation of UTI diagnoses by ID specialists revealed that of the 79 UTI diagnoses, 61% were classified as probable overdiagnosis related to the COVID-19 hospitalization. The following factors were associated with UTI overdiagnosis: physicians who are unfamiliar working in an internal medicine ward, urinary incontinence, mechanical ventilation and female sex. Antimicrobial stewardship teams should focus on diagnostic stewardship of UTIs, as UTI overdiagnosis seems to be highly prevalent in admitted COVID-19 patients. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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12 pages, 972 KiB  
Article
Beneficial Effects of Anticoagulants on the Clinical Outcomes of COVID-19 Patients
by Zubia Jamil, Azmat Ali Khan, Samreen Khalid, Muhammad Asghar, Khalid Muhammad and Yasir Waheed
Antibiotics 2021, 10(11), 1394; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10111394 - 13 Nov 2021
Cited by 8 | Viewed by 2048
Abstract
(1) Background: Severe coronavirus disease can be complicated by a hypercoagulable state in conjunction with sepsis, increasing the risk of venous thromboembolism. This study aimed to observe the effect of anticoagulants on 30-day high-dependency unit (HDU) outcomes of moderate to severe coronavirus disease [...] Read more.
(1) Background: Severe coronavirus disease can be complicated by a hypercoagulable state in conjunction with sepsis, increasing the risk of venous thromboembolism. This study aimed to observe the effect of anticoagulants on 30-day high-dependency unit (HDU) outcomes of moderate to severe coronavirus disease 2019 (COVID-19) patients of a tertiary care hospital at Rawalpindi, Pakistan. (2) Methods: A retrospective propensity-based case–control study was carried out to examine COVID-19 patients admitted to the HDU. Patient groups who did and did not receive anticoagulants were labeled as “anticoagulant” and “non-anticoagulant”, respectively. Case–control matching (1:1) was performed via propensity scores (calculated by a regression model). Kaplan–Meier and logrank analyses were used to study survival probability. Single predictors of outcomes were determined by Cox regression analysis. (3) Results: The anticoagulant group had elevated D-dimers, advanced age, more comorbidities and a higher frequency of severe disease compared to the non-anticoagulant group (p < 0.05). Therefore, 47 cases and 47 matched controls were selected based on their propensity scores. The primary endpoint was outcome (survived vs. died). The 30-day in-HDU mortality was 25.5% for cases and 61.7% for controls (p = 0.0004). The median time from admission to death was 16 days for the case group and 7 days for the control group (p < 0.0001). The 30-day mortality was 19.1% for the enoxaparin group and 16.4% for the heparin group (p > 0.05). Enoxaparin (therapeutic and prophylactic doses) and heparin (prophylactic dose) were found to be independent factors affecting the outcomes of these patients (p < 0.001). (4) Conclusions: Anticoagulants play a beneficial role in reducing mortality among COVID-19 patients. Both anticoagulant formulations, enoxaparin (therapeutic and prophylactic doses) and heparin (prophylactic dose), were associated with improving survival among these patients. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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11 pages, 2016 KiB  
Article
Efficacy of Ceftazidime and Cefepime in the Management of COVID-19 Patients: Single Center Report from Egypt
by Ragaey A. Eid, Marwa O. Elgendy, Ahmed O. El-Gendy, Sara O. Elgendy, Lassaad Belbahri, Ahmed M. Sayed and Mostafa E. Rateb
Antibiotics 2021, 10(11), 1278; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10111278 - 20 Oct 2021
Cited by 20 | Viewed by 6648
Abstract
The purpose of this study was to explore the value of using cefepime and ceftazidime in treating patients with COVID-19. A total of 370 (162 males) patients, with RT-PCR-confirmed cases of COVID-19, were included in the study. Out of them, 260 patients were [...] Read more.
The purpose of this study was to explore the value of using cefepime and ceftazidime in treating patients with COVID-19. A total of 370 (162 males) patients, with RT-PCR-confirmed cases of COVID-19, were included in the study. Out of them, 260 patients were treated with cefepime or ceftazidime, with the addition of steroids to the treatment. Patients were divided into three groups: Group 1: patients treated with cefepime (124 patients); Group 2: patients treated with ceftazidime (136 patients); Group 3 (control group): patients treated according to the WHO guidelines and the Egyptian COVID-19 management protocol (110 patients)/ Each group was classified into three age groups: 18–30, 31–60, and >60 years. The dose of either cefepime or ceftazidime was 1000 mg twice daily for five days. Eight milligrams of dexamethasone were used as the steroidal drug. Careful follow-ups for the patients were carried out. In vitro and in silico Mpro enzyme assays were performed to investigate the antiviral potential of both antibiotics. The mean recovery time for Group 1 was 12 days, for Group 2 was 13 days, and for Group 3 (control) was 19 days. No deaths were recorded, and all patients were recovered without any complications. For Group 1, the recovery time was 10, 12, and 16 days for the age groups 18–30, 30–60, and >60 years, respectively. For Group 2, the recovery time was 11, 13, and 15 days for the age groups 18–30, 30–60, and >60 years, respectively. For Group 3 (control), the recovery time was 15, 16, and 17 days for the age groups 18–30, 30–60, and >60 years, respectively. Both ceftazidime and cefepime showed very good inhibitory activity towards SARS CoV-2′s Mpro, with IC50 values of 1.81 µM and 8.53 µM, respectively. In conclusion, ceftazidime and cefepime are efficient for the management of moderate and severe cases of COVID-19 due to their potential anti-SARS CoV-2 activity and low side effects, and, hence, the currently used complex multidrug treatment protocol can be replaced by the simpler one proposed in this study. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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14 pages, 1312 KiB  
Article
Challenges in Steroid and Anticoagulant Therapy in Severe COVID-19 Pneumonia: A Prospective Study
by Alaa Thabet Hassan, Alaa E. Abd Elmoniem, Marwa Mahmoud Abdelrady, Mona Embarek Mohamed, Mohamed A. Mokhtar, Abdelhalim A. Elsherif, Ghada Mohamed Saied and Soheir M. Kasem
Antibiotics 2021, 10(10), 1214; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10101214 - 06 Oct 2021
Cited by 6 | Viewed by 1858
Abstract
Background: As COVID-19 has neither a standard treatment protocol nor guidelines, there are many treatment protocols for anti-inflammatory corticosteroids and anti-coagulations for severe COVID-19 pneumonia patients. This study aimed to assess the most suitable modality in this high-risk group. Methods: A prospective, experimental [...] Read more.
Background: As COVID-19 has neither a standard treatment protocol nor guidelines, there are many treatment protocols for anti-inflammatory corticosteroids and anti-coagulations for severe COVID-19 pneumonia patients. This study aimed to assess the most suitable modality in this high-risk group. Methods: A prospective, experimental study design was adopted that included 123 severe COVID-19 pneumonia patients admitted at Assiut University Hospital. Patients were divided into three groups according to a combined corticosteroid and anticoagulants therapy protocol. Group A included 32 patients, group B included 45 patients, and group C included 46 patients. Assessment of cases was conducted according to the treatment type and duration, weaning duration from oxygen therapy, length of hospital and ICU stay, and complications during treatment. Three months follow-up after discharge was performed. Results: the three patient groups showed significant differences regarding the 3-month outcome, whereas Group C showed the highest cure rate, lowest lung fibrosis, and lowest mortality rate over the other two groups. The in-hospital outcome, the development of pulmonary embolism, bleeding, hematoma, acute kidney disease, and myocardial infarction showed a significant difference between groups (p values < 0.05). Mortality predictors among severe COVID-19 patients by multivariable Cox hazard regression included treatment modality, history of comorbid diseases, increased C reactive protein, high neutrophil-lymphocyte ratio, and shorter ICU and hospital stay. Conclusion: the use of combined methylprednisolone and therapeutic Enoxaparin, according to a flexible protocol for COVID-19 patients with severe pneumonia, had two benefits; the prevention of disease complications and improved clinical outcome. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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7 pages, 2545 KiB  
Perspective
Oral Nirmatrelvir/Ritonavir Therapy for COVID-19: The Dawn in the Dark?
by Yuan-Pin Hung, Jen-Chieh Lee, Chun-Wei Chiu, Ching-Chi Lee, Pei-Jane Tsai, I-Lin Hsu and Wen-Chien Ko
Antibiotics 2022, 11(2), 220; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020220 - 09 Feb 2022
Cited by 66 | Viewed by 11876
Abstract
Nirmatrelvir/ritonavir (Paxlovid™) is an effective and safe antiviral drug that inhibits the main protease (Mpro), 3CL protease, of SARS-CoV-2. A reduction in COVID-19-related hospitalization or death was observed in patients treated with nirmatrelvir/ritonavir within five days of symptom onset. Moreover, good [...] Read more.
Nirmatrelvir/ritonavir (Paxlovid™) is an effective and safe antiviral drug that inhibits the main protease (Mpro), 3CL protease, of SARS-CoV-2. A reduction in COVID-19-related hospitalization or death was observed in patients treated with nirmatrelvir/ritonavir within five days of symptom onset. Moreover, good oral availability enables the usage of nirmatrelvir/ritonavir, not only in hospitalized patients, but also among outpatients. Nirmatrelvir (PF-07321332) has been demonstrated to stop the spread of COVID-19 in animal models. Despite frequent mutations in the viral genomes of SARS-CoV-2, nirmatrelvir shows an effective antiviral effect against recent coronavirus mutants. Despite the promising antiviral effect of nirmatrelvir, there are several unresolved concerns. First, the final results of large-scale clinical trials for early therapy of mild cases of COVID-19 are not yet published. Second, the effectiveness of nirmatrelvir against upcoming variants in the coming years requires close monitoring. Considering the promising preliminary results of the EPIC-HR trial, nirmatrelvir/ritonavir in conjunction with vaccines and non-pharmacological interventions, may represent the dawn in the dark of the COVID-19 pandemic. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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8 pages, 1967 KiB  
Perspective
Molnupiravir—A Novel Oral Anti-SARS-CoV-2 Agent
by Ching-Chi Lee, Chih-Chia Hsieh and Wen-Chien Ko
Antibiotics 2021, 10(11), 1294; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10111294 - 23 Oct 2021
Cited by 57 | Viewed by 9312
Abstract
Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly resulted in a global pandemic with approximately 4 million deaths. Effective oral antiviral agents are urgently needed to treat coronavirus disease-2019 (COVID-19), block SARS-CoV-2 transmission, and prevent progression to severe illness. [...] Read more.
Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly resulted in a global pandemic with approximately 4 million deaths. Effective oral antiviral agents are urgently needed to treat coronavirus disease-2019 (COVID-19), block SARS-CoV-2 transmission, and prevent progression to severe illness. Molnupiravir (formerly EIDD-2801), a prodrug of beta-d-N4-hydroxycytidine (EIDD-1931) and an inhibitor of RNA-dependent RNA polymerase, possesses significant activity against SARS-CoV-2. Its prophylactic efficacy has been evidenced in a ferret model. Two phase-I trials (NCT04392219 and NCT04746183) have demonstrated that oral molnupiravir is safe and well-tolerated at therapeutic doses. After five-days of oral molnupiravir therapy, satisfactory efficacies, assessed by eliminating nasopharyngeal virus in patients with early and mild COVID-19, were disclosed in two phase-II trials (NCT04405739 and NCT 04405570). Two phase-II/III trials, NCT04575597 and NCT04575584, with estimated enrollments of 1850 and 304 cases, respectively, are ongoing. The NCT04575597 recently released that molnupiravir significantly reduced the risk of hospitalization or death in adults experiencing mild or moderate COVID-19. To benefit individual and public health, clinical applications of molnupiravir to promptly treat COVID-19 patients and prevent SARS-CoV-2 transmission may be expected. Full article
(This article belongs to the Special Issue Antibiotics and Therapeutic Agent Prescription in COVID-19 Management)
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