Favipiravir for treating COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19. OBJECTIVES: To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023. SELECTION CRITERIA: We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.

Establishing an effective antimicrobial stewardship program at four secondary-care hospitals in India using a hub-and-spoke model.

Background: The high burden of antimicrobial resistance in India necessitates the urgent implementation of antimicrobial stewardship programs (ASPs) in all healthcare settings in India. Most ASPs are based at tertiary-care centers, with sparse data available regarding the effectiveness of an ASP in a low-resource primary/secondary-care setting. Methods: We adopted a hub-and-spoke model to implement ASPs in 4 low-resource, secondary-care healthcare settings. The study included 3 phases measuring antimicrobial consumption data. In the baseline phase, we measured days on antimicrobial therapy (DOTs) with no feedback provided. This was followed by the implementation of a customized intervention package. In the postintervention phase, prospective review and feedback were offered by a trained physician or ASP pharmacist, and days of therapy (DOT) were measured. Results: In the baseline phase, 1,459 patients from all 4 sites were enrolled; 1,233 patients were enrolled in the postintervention phase. Both groups had comparable baseline characteristics. The key outcome, DOT per 1,000 patient days, was 1,952.63 in the baseline phase and significantly lower in the post-intervention period, at 1,483.06 (P = .001). Usage of quinolone, macrolide, cephalosporin, clindamycin, and nitroimidazole significantly decreased in the postintervention phase. Also, the rate of antibiotic de-escalation was significantly higher in the postintervention phase than the baseline phase (44% vs 12.5%; P < .0001), which suggests a definite trend toward judicious use of antibiotics. In the postintervention phase, 79.9% of antibiotic use was justified. Overall, the recommendations given by the ASP team were fully followed in 946 cases (77.7%), partially followed in 59 cases (4.8%), and not followed in 137 cases (35.7%). No adverse events were noted. Conclusion: Our hub-and-spoke model of ASP was successful in implementing ASPs in secondary-care hospitals in India, which are urgently needed.

Evaluation of Remdesivir to the outcomes of hospitalized patients with COVID-19 infection in a tertiary-care hospital in southern India.

INTRODUCTION: Remdesivir was the only antiviral used in the treatment of COVID-19 in the first wave of the COVID-19 pandemic, following the adaptive COVID-19 treatment trial-1 interim analysis report. However, its use in moderate to critical hospitalized COVID-19 patients continues to be controversial. METHODOLOGY: In a cohort of 1,531 moderate to critical COVID-19 patients, we retrospectively performed a nested case-control study where 515 patients on Remdesivir were compared to 411 patients with no Remdesivir. Cases and controls were matched for age, sex and severity. The primary outcome was in-hospital mortality and secondary outcomes were duration of hospital stay, need for intensive care unit (ICU), progression to oxygen therapy, progression to non-invasive ventilation, progression to mechanical ventilation, and duration of ventilation. RESULTS: Mean age of the cohort was 57.05 + 13.5 years. 75.92% were males. Overall, in-hospital mortality was 22.46% (n = 208). There was no statistically significant difference in all-cause mortality among cases and controls (20.78% vs. 24.57%, p = 0.17). Progression to non-invasive ventilation was lower in the Remdesivir group (13.6% vs 23.7%, p < 0.001), however progression to mechanical ventilation was higher in the Remdesivir group (11.3% vs 2.7%, p value < 0.001*). In a subgroup analysis of critically ill patients, the use of Remdesivir lowered mortality (OR 0.32 95% CI: 0.13 - 0.75). CONCLUSIONS: Remdesivir did not decrease the in-hospital mortality in moderate to severe COVID-19 but decreased progression to non-invasive ventilation. Its mortality benefit in critically ill patients needs further evaluation. Remdesivir may be useful if given early in the treatment of patients with moderate COVID-19.

High rate of bacterial respiratory tract co-infections upon admission amongst moderate to severe COVID-19 patients.

BACKGROUND: The role of bacterial and viral co-infection in the current COVID-19 pandemic remains elusive. The aim of this study was to describe the rates and features of co-infection on admission of COVID-19 patients, based on molecular and routine laboratory methods. METHODS: A retrospective study of COVID-19 and non-COVID-19 patients undergoing Biofire®, FilmArray® Pneumonia Panel, bioMérieux, and routine cultures during the first 3 days from admission, between June 2019 and March 2021. RESULTS: FilmArray tests were performed in 115 COVID-19 and in 61 non-COVID-19 patients. Most (>99%) COVID-19 patients had moderate-critical illness, 37% required mechanical ventilation. Sputa and endotracheal aspirates were the main samples analyzed. Positive FilmArray tests were found in 60% (70/116) of the tests amongst COVID-19 patients and 62.5% (40/64) amongst non-COVID-19 patients. All 70 cases were positive for bacterial targets, while one concomitant virus (Rhinovirus/Enterovirus) and one Legionella spp. were detected. The most common bacterial targets were Haemophilus influenzae (36%), Staphylococcus aureus (23%), Streptococcus pneumoniae (10%) and Enterobacter cloacae (10%). Correlation between FilmArray and cultures was found in 81% and 44% of negative and positive FA tests, respectively. Positive FilmArray results typically (81%) triggered the administration of antibiotic therapy and negative results resulted in antimicrobials to be withheld in 56% of cases and stopped in 8%. Bacterial cultures of COVID-19 patients were positive in 30/88 (34%) of cases. CONCLUSIONS: Bacterial co-infection is common amongst moderate-critical COVID-19 patients on admission while viral and atypical bacteria were exceedingly rare. Positive FilmArray results could trigger potentially unnecessary antibiotic treatment.KEY POINTWe found high rates of on-admission bacterial co-infection amongst hospitalized moderate to severe COVID-19 patients. Molecular tests (Biofire, FilmArray) and routine microbiological tests revealed 60% and 34% bacterial co-infection, respectively, while viral and fungal co-infections were rare.

High Rates of Bacterial Pulmonary Co-Infections and Superinfections Identified by Multiplex PCR among Critically Ill COVID-19 Patients.

BACKGROUND: The role of bacterial co-infection and superinfection among critically ill COVID-19 patients remains unclear. The aim of this study was to assess the rates and characteristics of pulmonary infections, and associated outcomes of ventilated patients in our facility. METHODS: This was a retrospective study of ventilated COVID-19 patients between March 2020 and March 2021 that underwent BioFire®, FilmArray® Pneumonia Panel, testing. Community-acquired pneumonia (CAP) was defined when identified during the first 72 h of hospitalization, and ventilator-associated pneumonia (VAP) when later. RESULTS: 148 FilmArray tests were obtained from 93 patients. With FilmArray, 17% of patients had CAP (16/93) and 68% had VAP (64/93). Patients with VAP were older than those with CAP or those with no infection (68.5 vs. 57-59 years), had longer length of stay and higher mortality (51% vs. 10%). The most commonly identified FilmArray target organisms were H. influenzae, S. pneumoniae, M. catarrhalis and E. cloacae for CAP and P. aeruginosa and S. aureus for VAP. FilmArray tests had high negative predictive values (99.6%) and lower positive predictive values (~60%). CONCLUSIONS: We found high rates of both CAP and VAP among the critically ill, caused by the typical and expected organisms for both conditions. VAP diagnosis was associated with poor patient outcomes.

Epidemiological, clinical and laboratory features of acute Q fever in a cohort of hospitalized patients in a regional hospital, Israel, 2012-2018.

INTRODUCTION: Acute Q fever is endemic in Israel, yet the clinical and laboratory picture is poorly defined. METHODS: A retrospective study reviewing the medical records of acute Q fever patients, conducted in a single hospital in the Sharon district, Israel. Serum samples from suspected cases were preliminary tested by a qualitative enzyme immunoassay (EIA). Confirmatory testing at the reference laboratory used an indirect immunofluorescence assay (IFA). Positive cases were defined as fever with at least one other symptom and accepted laboratory criteria such as a single-phase II immunoglobulin G (IgG) antibody titer ≥1:200. Cases not fulfilling these criteria and in which acute Q fever was excluded, served as a control group. RESULTS: Between January 2012 and May 2018, 484 patients tested positive. After confirmatory testing, 65 (13.4%) were positive for acute Q fever (with requisite clinical picture), 171 (35.3%) were definitely not infected, the remaining 248 were excluded because of past/chronic/undetermined infection. The average age was 58 years and 66% were males. Most resided in urban areas with rare animal exposure. Pneumonia was seen in 57% of cases and a combination with headache/hepatitis was highly suggestive of acute Q fever diagnosis. Syncope/presyncope, fall and arthritis were more common in acute Q fever cases. Laboratory indexes were similar to the control group, except for erythrocyte sedimentation rate (ESR) which was more common and higher in the study group. CONCLUSION: Acute Q fever in the Sharon district could be better diagnosed by using a syndromic approach in combination with improved rapid diagnostic testing.

Impact of an antimicrobial stewardship intervention in India: Evaluation of post-prescription review and feedback as a method of promoting optimal antimicrobial use in the intensive care units of a tertiary-care hospital.

OBJECTIVE: Antimicrobial stewardship programs (ASPs) are effective in developed countries. In this study, we assessed the effectiveness of an infectious disease (ID) physician-driven post-prescription review and feedback as an ASP strategy in India, a low middle-income country (LMIC). DESIGN AND SETTING: This prospective cohort study was carried out for 18 months in 2 intensive care units of a tertiary-care hospital, consisting of 3 phases: baseline, intervention, and follow up. Each phase spanned 6 months. PARTICIPANTS: Patients aged ≥15 years receiving 48 hours of study antibiotics were recruited for the study. METHODS: During the intervention phase, an ID physician reviewed the included cases and gave alternate recommendations if the antibiotic use was inappropriate. Acceptance of the recommendations was measured after 48 hours. The primary outcome of the study was days of therapy (DOT) per 1,000 study patient days (PD). RESULTS: Overall, 401 patients were recruited in the baseline phase, 381 patients were recruited in the intervention phase, and 379 patients were recruited in the follow-up phase. Antimicrobial use decreased from 831.5 during the baseline phase to 717 DOT per 1,000 PD in the intervention phase (P < .0001). The effect was sustained in the follow-up phase (713.6 DOT per 1,000 PD). De-escalation according to culture susceptibility improved significantly in the intervention phase versus the baseline phase (42.7% vs 23.6%; P < .0001). Overall, 73.3% of antibiotic prescriptions were inappropriate. Recommendations by the ID team were accepted in 60.7% of the cases. CONCLUSION: The ID physician-driven implementation of an ASP was successful in reducing antibiotic utilization in an acute-care setting in India.

Patterns of Adverse Drug Reaction in the Medical Wards of a Teaching Hospital: A Prospective Observational Cohort Study.

INTRODUCTION: According to the World Health Organization (WHO) definition, an Adverse Drug Reaction (ADR) is a response to a drug that is noxious and unintended and occurs at doses normally used in humans for the prophylaxis, diagnosis, and treatment of disease. The risk factors of ADR are multi-factorial and include poly-pharmacy, age, gender, race, genetics and inter-current disease. PATIENTS AND METHODS: This was a hospital based, prospective, observational cohort study undertaken in a tertiary care hospital in south India to assess the different patterns of adverse drug reaction in medical wards over 6 months. The severity of ADR was assessed using Hartwig Siegel scale and causality by Naranjo and WHO UMC Scale. Preventability was assessed using Schumock and Thornton scale and other parameters such as incidence, onset, duration, management and outcome were also assessed. Risk factors were assessed by bi-variate logistic regression analysis and length of hospital stay by T test. RESULTS: The incidence of ADR was 10.42% in medicine wards. The causality of ADR done by Naranjo scale showed that most of the ADRs were probable (7.38%). Anti-tubercular agents were the leading cause of ADR. Duration of hospitalization was significantly longer (7.18 ± 2.64 vs. 5.06 ± 2.13 days) in patients with ADR (Odds ratio 1.38, 95% Confidence interval 1.26 to 1.51). 7.28% of ADRs were moderately severe. Seriousness criteria assessment showed that 0.33% were serious reactions. Most of the ADRs were definitely preventable. Most of the ADRs were managed by discontinuing the suspected drug. The present study showed female gender predominance over males for ADRs and no relationship with age. CONCLUSION: Adverse drug reactions impose significant burden on hospitals through prolonging patient stay and by increasing admission rates. The occurrence of ADR in this study was higher when compared to that reported in previous studies. This study highlights the importance of ADR reporting among ADR reporting among health care professionals in hospital.

Quantifying the distribution of nanodiamonds in pre-Younger Dryas to recent age deposits along Bull Creek, Oklahoma panhandle, USA.

High levels of nanodiamonds (nds) have been used to support the transformative hypothesis that an extraterrestrial (ET) event (comet explosion) triggered Younger Dryas changes in temperature, flora and fauna assemblages, and human adaptations [Firestone RB, et al. (2007) Proc Natl Acad Sci USA 104(41):16016-16021]. We evaluate this hypothesis by establishing the distribution of nds within the Bull Creek drainage of the Beaver River basin in the Oklahoma panhandle. The earlier report of an abundance spike of nds in the Bull Creek I Younger Dryas boundary soil is confirmed, although no pure cubic diamonds were identified. The lack of hexagonal nds suggests Bull Creek I is not near any impact site. Potential hexagonal nds at Bull Creek were found to be more consistent with graphene/graphane. An additional nd spike is found in deposits of late Holocene through the modern age, indicating nds are not unique to the Younger Dryas boundary. Nd distributions do not correlate with depositional environment, pedogenesis, climate perturbations, periods of surface stability, or cultural activity.