key: cord-0725166-tzq7ohld authors: Mazumder, Payal; Kalamdhad, Ajay; Chaminda, GG Tushara; Kumar, Manish title: Coalescence of co-infection and antimicrobial resistance with SARS-CoV-2 infection: the blues of post-COVID-19 world date: 2021-02-21 journal: nan DOI: 10.1016/j.cscee.2021.100093 sha: 1afd745ab9c14df37222ee352153e262ba61f272 doc_id: 725166 cord_uid: tzq7ohld In viral respiratory infections, bacterial co-pathogens are widely known to co-infect, and they significantly increase the morbidity and mortality rate. During the influenza season, the advent of 2019-nCoV (novel coronavirus) has led to the widespread use of oral and intravenous antibiotics and inhibitors of neuraminidase enzyme. Owing to causes such as extended intubation, the ubiquitous use of intrusive catheters, and compromised host immunity, coronavirus disease (COVID-19) patients are at heightened risk of secondary bacterial and fungal infections, leading to the difficulty in their treatment. Apart from the pandemic, the primary risk is a likely surge in multidrug resistance. In this work, we evaluated the coalescence of present co-infection alongside the COVID-19 and post-pandemic antimicrobial resistance due to high ongoing drug use for the treatment of COVID-19. We found that while there is currently limited evidence of bacterial infections in COVID-19, available proof supports the restricted use of antibiotics from an antibiotic stewardship viewpoint, primarily upon entry. Paramount attempts should be made to collect sputum and blood culture samples as well as pneumococcal urinary antigen monitoring in order to endorse stringent antibiotic usage. For antimicrobial stewardship, inflammatory markers like procalcitonin have been added, but such biomarkers are typically upraised in COVID-19. Antimicrobials cannot be completely removed in wastewater treatment plants (WWTPs) and once they enter the water environment, possesses great risk of inducing resistance to drugs in microbes. Hence, their prescription and administrations should be regulated and alternate solutions such as vaccines, preventive measures and personal hygiene should be given top priority. It is imperative to establish an antimicrobial strategy discrete to COVID-19, as this pandemic has caused outbreak of numerous other associated diseases and has the potential to drive microbial resistance. Coordinated plans are essential for this at the citizen, health-care and policy levels. Reviewer #3: This is case study that Coalescence of co----infection and antimicrobial resistance with SARS infection and antimicrobial resistance with SARS infection and antimicrobial resistance with SARS infection and antimicrobial resistance with SARS----CoV CoV CoV CoV----2 2 convention is particularly prevailing [1] . In viral respiratory tract infections like influenza, bacterial co-pathogens are widely recognized, requiring prompt diagnosis and antibacterial treatment [2] [3] [4] . The prevalence, occurrence and characteristics of bacterial infection in patients with severe acute coronavirus 2 respiratory syndrome (SARS-CoV-2) is off the beaten track and has been established as a major information deficit [5, 6] . Several guidelines promote the use of first-hand antibiotics for acute COVID-19 patients, extrapolating questions about elevated impermanence in patients with bacterial superinfection throughout influenza pandemics [7, 8] . This hypothesis, however, raises concerns about antibiotic usage and ensuing bacterial resistance-related damage. Basic conditions and risk factors for bacterial and fungal infections, such as chronic respiratory diseases, corticosteroid treatment, immunoinflammatory reaction (cytokine storm) and intubation / mechanical ventilation, are shared by COVID-19 hospitalized patients in intensive care units (ICUs). In 50% of COVID-19 deaths, secondary infections were detected. Bacterial and fungal secondary infections or coinfections are also a likely cause impacting the mortality of COVID-19 patients who are seriously ill [9] . The new COVID-19 pandemic will definitely change the landscape of antimicrobial resistance (AMR), as many hospitalized COVID-19 patients are medicated with broad-spectrum antibiotics with uncertain effectiveness [10] [11] [12] [13] [14] [15] [16] [17] [18] . Redundant doses of antibiotics upon hospitalization can raise the individual risk of severe hospital-acquired pneumonia (HAP) and J o u r n a l P r e -p r o o f other adverse events, as COVID-19 patients also require respiratory assistance and extended hospitalization [19, 20] . The prevalence of use of antibiotics (94-100%) was much greater inhospital care than the recorded occurrence of secondary infection (10-15%) [21] . The average fraction of COVID-19 patients with bacterial co-infection was found to be 6.9% [22] . encountered 30% bacterial infection in seriously ill patients [25, 26] and 12% in non-ICU hospitalized patients [27] . The most frequently known bacterial co-pathogens were identified to be Streptococcus pneumoniae and Staphylococcus aureus [25, 27] . The ubiquity of secondary infection in SARS-CoV-2 infected patients is not well known. Present wastewater treatment technology cannot provide complete removal of antibacterial biocides. These compounds will then aggregate in various environmental compartments, affecting the functioning of autochthonous microbes. Consequently, the occurrence of antimicrobials in the environment can promote the prevalence of AMR [28, 29, 30] . Considering the above said reasoning, we put an effort first to understand the possibilities of other microbial co-infections alongside of COVID-19; and then evaluate the rational of multidrug prescriptions for the treatment of COVID-19 to finally assess the threat of antimicrobial resistance scenario in the post-COVID-19 era. We wish to contribute raising awareness so that the pre-problem measures can be subsequently taken via an antibiotic stewardship perspective. Acinetobacter baumannii and Klebsiella pneumoniae were isolated from the respiratory tract from one COVID-19 patient in China [46] . A few other studies include 1 positive report of PCR for Mycoplasma pneumonia, 0 positive for Legionella [47] . One from the two reports for secondary infection published on bacterial pathogens [48, 49] . Again, in another study from China, among 3 gram-negative species, 1 out of 29 (3%) A. baumannii and 2 out of 29 (7%) Enterobacter cloacae were reported [50] . Table 1 Presently, no antiviral medication is available to cure SARS-Cov-2 infection; and it will also take a couple of years to produce one and achieve clearance for it [51] . fumigatus along with IPA was reported in a 56-year-old COVID-19 patient admitted in ICU [71] . The existence of Aspergillus is a prognostic sign of severity or is only related to degenerating patient's health is still, possibly leading to death remains uncertain. Carbapenemase-producing Enterobacterales (CPE)-E. coli has been observed in COVID-19 patients. Rectal swabs screenings patients were conducted and analyzed with the help of multiplex PCR as well as by culturing on selective chromogenic media [72] . that may contribute to resistance in these viruses to antiviral drugs [28] . As antibiotics are anticipated to have a marginal advantage as pragmatic therapy in COVID-19 treatment and results in auxiliary pernicious effects viz., toxicity, adverse events, antibiotic resistance, and Clostridioides difficile sepsis, it is advisable for clinicians to advocate them aptly [75] [76] [77] [78] . Increasing the statistics of presumptuous stratagems linked with the prescription of antibiotics, immunomodulatory drugs such as steroidal anti-inflammatory drugs and overpopulated in clinics can contribute to an increase in nosocomial diseases. Simultaneously, there could be a chance of worsening of the Healthcare-Associated Diseases J o u r n a l P r e -p r o o f due to the sensitivity of the patient's microbiota to these stimuli, through the emergence and distribution of resistance aspects and further virulent strains. In manually ventilated COVID- The prevalence of telemedicine to control antimicrobial stewardship has previously demonstrated an improved selection of antibiotics and decline in resistance [84] . It is important to collect microbiological data, primarily to classify formerly identified or evolving pathogens linked to secondary co-infections in patients with SARS [85] . Epidemiological investigations with AMR surveillance systems that endorse the generation of the standard datasets on the efficacy of antimicrobial intercession in COVID-19 patients, particularly in acute stage patients in ICUs, should be sustained [86] . Measures taken by people would also be quintessential in sustaining the pandemic and mitigating its effect on our routine lives. Appropriate use of personal hygiene devices like personal protection equipment (PPE) kits, masks, adequate handwashing and maintaining physical distancing should be continued to be safe from getting infected and prepared for future waves [87] . The continuation of J o u r n a l P r e -p r o o f antimicrobial treatment and duration of hospital stay of COVID-19 patients can be shortened substantially with stewardship measures. Antimicrobial governance initiatives should actively involve and train medical practitioners and pharmacists to reduce mishandling of antibiotics during the COVID-19 pandemic [88, 89] . The recommendations made in this study and their efficient inclusions in the formation of applicable policies and the preparation of concrete instructions/guidelines will be crucial to ensure our battle against AMR continues and the quest to conquer it consummates. 6. 6. 6. We conclude that the overall proportion of secondary infection has been poor among patients with COVID-19, but the prescription of antimicrobials is soaring. There is inadequate proof to encourage the extensive usage of empirical antibiotics, particularly in those COVID- [52] Ledford, H., Cyranoski, d., Van Noorden, R. The UK has approved a COVID vaccinehere's what scientists now want to know. Nature article (2020) . https://www.icpcovid.com/sites/default/files/2020-12/Ep%2092%202B%20The%20UK%20has%20approved%20a%20COVID%20vaccine%20%E2 %80%94%20here%E2%80%99s%20what%20scientists%20now%20want%20to%20know.pdf Environmental side effects of the injudicious use of antimicrobials in the era of COVID-19 Rate and influence of respiratory virus coinfection on pandemic (H1N1) influenza disease The frequency of influenza and bacterial coinfection: a systematic review and metaanalysis Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States COVID-19: don't neglect antimicrobial stewardship principles! Co-infections: potentially lethal and unexplored in COVID-19 World Health Organization. Clinical management of COVID-19 interim guidance Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical Characteristics of Coronavirus Disease 2019 in China Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan: A Retrospective Observational Study Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study, The Lancet Clinical characteristics 368 of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China Clinical Features of 69 Cases with Coronavirus Disease Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia Clinical Practice Guidelines by the Infectious Diseases Society of America and the Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis Bacterial and fungal co-infection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing Macrolides in critically ill patients with Middle East Respiratory Syndrome Critically ill patients with 2009 influenza A(H1N1) infection in Canada Critical care services and 2009 H1N1 influenza in Australia and New Zealand The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza A(H1N1)pdm09 Potential Emergence of Antiviral-Resistant Pandemic Viruses via Environmental Drug Exposure of Animal Reservoirs. Environmental Science and Technology Antibiotic Discovery: Where Have We Come from, Where Do We Go? Sustainable Discovery and Development of Antibiotics -Is a Nonprofit Approach the Future? COVID-19 pathophysiology: a review COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Making Waves Perspectives of Modelling and Monitoring of SARS-CoV-2 in Aquatic Environment for COVID-19 Pandemic Bacterial and fungal colonization of the respiratory tract in COVID-19 patients should not be neglected The first 29 COVID-19-patients in a clinic: early experiences from a Dutch hospital The first 100 COVID-19 patients admitted to the Elisabeth-Tweesteden Hospital COVID-19 in the Emergency Department of Bernhoven hospital Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical features of patients infected with 2019 novel coronavirus in Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a de-scriptive study Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable incidence of atypical bacteria coinfection based on diagnostic assays Bacterial and viral infections associated with influenza Co-infections in people with COVID-19: a systematic review and meta-analysis Emerging Co-Pathogens: New Delhi Metallo-beta-lactamase producing Enterobacterales Infections in New York City COVID-19 Patients Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study The first 100 COVID-19 patients admitted to the Elisabeth-Tweesteden Hospital Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical features of patients infected with 2019 novel coronavirus in Clinical Features of 69 Cases with Coronavirus Disease Clinical features of patients infected with 2019 novel coronavirus in Wuhan India's vaccine roll-out faces key obstacles Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus fusion Unique synergistic antiviral effects of Shufeng Jiedu Capsule and oseltamivir in influenza A viral-induced acute exacerbation of chronic obstructive pulmonary disease The Chinese prescription lianhua qingwen capsule exerts antiinfluenza activity through the inhibition of viral propagation and impacts immune function New insights into the antiviral effects of chloroquine Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model A systematic review of therapeutic agents for the treatment of the Middle East respiratory syndrome coronavirus (MERSCoV) Comparative effectiveness of combined favipiravir and oseltamivir therapy versus oseltamivir monotherapy in critically ill patients with influenza virus infection The novel coronavirus Disease-2019 (COVID-19): Mechanism of action, detection and recent therapeutic strategies Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review Current Status of COVID-19 Therapies and Drug Repositioning Applications. iScience 23, 101303 Biomedical application, drug delivery and metabolic pathway of antiviral nanotherapeutics for combating viral pandemic: A review Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19 COVID-19 associated pulmonary aspergillosis Recovery of a triazole-resistant Aspergillus fumigatus in respiratory specimen of COVID-19 patient in ICU -A case report on behalf of the SARS-CoV-2 Hospital Foch study group. 2020. Carbapenemase-producing Enterobacterales outbreak: Another dark side of COVID-19 Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Update on Therapeutic Options The lurking scourge of multidrug resistant Candida auris in times of COVID-19 pandemic COVID-19: don't neglect antimicrobial stewardship principles! COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital Association of adverse events with antibiotic use in hospitalized patients Early administered antibiotics do not impact mortality in critically ill patients with COVID-19 Hazardous mismatch between pulmonary pathogens and antibiotic treatments in COVID-19 patients COVID-19 rapid guideline: managing suspected or confirmed pneumonia in adults in the community Clinical management of COVID-19 COVID-19) treatment guidelines. National Institutes of Health Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment Antibiotic prescribing during pediatric direct-to-consumer telemedicine visits Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Could the COVID-19 pandemic aggravate antimicrobial resistance? Antimicrobial stewardship programme: a vital resource for hospitals during the global outbreak of coronavirus disease 2019 (COVID-19) COVID-19 and Influenza Co-Infection: Report of Three Cases A case series of coinfection with SARS-CoV-2 and influenza virus in Louisiana J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:J o u r n a l P r e -p r o o f