key: cord-0936131-jnmhh3zs authors: Alshaikh, F.; Godman, B.; Kurdi, A.; Seaton, R. A.; Sindi, O. title: Prevalence of Bacterial Coinfection and Patterns of Antibiotics Prescribing in Patients with COVID-19: A Systematic review and Meta-Analysis date: 2022-03-04 journal: nan DOI: 10.1101/2022.03.02.22271779 sha: 60aeb15a50559550a5d7adfc2a7e0efaa841c777 doc_id: 936131 cord_uid: jnmhh3zs Background: Evidence around prevalence of bacterial coinfection and pattern of antibiotic use in COVID-19 is controversial although high prevalence rates of bacterial coinfection have been reported in previous similar global viral respiratory pandemics. Early data on the prevalence of antibiotic prescribing in COVID-19 indicates conflicting low and high prevalence of antibiotic prescribing which challenges antimicrobial stewardship programmes and increases risk of antimicrobial resistance (AMR). Aim: To determine current prevalence of bacterial coinfection and antibiotic prescribing in COVID-19 patients Data Source: OVID MEDLINE, OVID EMBASE, Cochrane and MedRxiv between January 2020 and June 2021. Study Eligibility: English language studies of laboratory-confirmed COVID-19 patients which reported (a) prevalence of bacterial coinfection and/or (b) prevalence of antibiotic prescribing with no restrictions to study designs or healthcare setting Participants: Adults (aged [≥] 18 years) with RT-PCR confirmed diagnosis of COVID-19, regardless of study setting. Methods: Systematic review and meta-analysis. Proportion (prevalence) data was pooled using random effects meta-analysis approach; and stratified based on region and study design. Results: A total of 1058 studies were screened, of which 22, hospital-based studies were eligible, compromising 76,176 of COVID-19 patients. Pooled estimates for the prevalence of bacterial co-infection and antibiotic use were 5.62% (95% CI 2.26 - 10.31) and 61.77% (CI 50.95 - 70.90), respectively. Sub-group analysis by region demonstrated that bacterial co-infection was more prevalent in North American studies (7.89%, 95% CI 3.30-14.18). Conclusion: Prevalence of bacterial coinfection in COVID-19 is low, yet prevalence of antibiotic prescribing is high, indicating the need for targeted COVID-19 antimicrobial stewardship initiatives to reduce the global threat of AMR. included terms related to "COVID-19", "Coinfections" and "Antibiotics" (Appendix 1). The 137 results of the search conducted were imported into Covidence online software for systematic 138 reviews, in which duplicate publications were removed. Reporting was based on the Preferred 139 Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for 140 systematic reviews. The study protocol was registered in the international register of 141 systematic reviews, PROSPERO, under the following ID: CRD42021261734 142 143 Study Selection 144 145 Two reviewers (FA and ON) independently screened tittles and abstracts and read full texts to 146 assess if they met the pre-set inclusion criteria, disputes were settled by third a reviewer 147 (AK). All English language articles, irrespective of their primary outcomes, reporting 148 bacterial coinfection rate and/or antibiotics use in, laboratory-confirmed (via Reverse 149 transcription polymerase chain reaction (RT-PCR)), COVID-19 human adult patients (≥ 18 150 years) in all healthcare settings were included (Outpatients and Inpatients). Studies in which 151 patients with suspected COVID-19, based on clinical symptoms and not laboratory confirmed 152 RT-PCR, were excluded. No restrictions to study design were applied. Case reports, case 153 notes, editorials, letters, systematic review, meta-analysis and qualitative studies were 154 excluded. Abstract only publications with no full text were also excluded. 155 156 Non-peer reviewed/ Pre-prints publications on MedRxiv were also included if the papers 157 contained relevant information regarding the topic of interest. 158 159 160 Data Extraction and quality assessment 161 162 Data was extracted into a standardised collection form that was created using COVID-19 patients. The following information, if reported, was also collected: bacterial 173 species isolated; the prevalence of most common bacteria; most common site of infection of 174 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 4, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 bacterial infection; clinical outcomes of co-infected patients; antibiotic class prescribed; 175 timing of antibiotic initiation in relation to COVID-19 onset and clinical outcomes of patients 176 prescribed antibiotics. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of 177 the observational studies included in the review [35] . 178 179 180 Data Synthesis, sensitivity analysis and publication bias 181 182 The two primary outcomes were the prevalence of bacterial coinfection in patients and the prevalence of antibiotics use in COVID-19 patients. Further sub-group 184 analysis was conducted based on studies' region/continent and design. Proportion 185 (prevalence) outcome data across all studies were pooled using a random effect meta-analysis 186 with Freeman and Tukey method [36] . Results were presented using forest plots, to 187 demonstrate the studies' effect size, and 95% confidence intervals (CI). Heterogeneity was 188 assessed using I 2 statistic. A value below 40% was considered to be low heterogeneity, 30 -189 60% was considered to be moderate heterogeneity, 50-90% was substantial, and 75-100% is 190 considerable heterogeneity [37] . Publication bias was assessed through Funnel plots followed 191 by Egger's asymmetry test [38] . All analyses were carried out using STATA/BE 17.0 for 192 Windows (64-bit x 86-64) using the Metaprop command package. 193 194 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint Retrospective cohort studies accounted for the majority of the studies involved (n = 18, 81%), 209 whilst prospective cohort studies accounted for the remaining (n=4, 18%). Of the 22 studies 210 included, 3 (13%) studies were pre-prints [55, 56, 58] , whilst the remaining (n=19, 86%) were 211 peer-reviewed. A total of 13 (59%) studies were conducted in multicentre settings, whilst the 212 remainder (n=9, 40%) were conducted in single centre settings. All of the studies included 213 were conducted in hospital settings, whether it be in a normal, isolation or an intensive care 214 ward. Twenty one out of the 22 studies have been classified as a "Good" rating during the 215 quality assessment process. 216 217 Geographical distribution 218 219 The majority of the studies included in the review took place in the United States of America 220 (USA) (n=10, 45%), followed by the United Kingdom ( value of 99.69%, indicating considerable heterogeneity (Figure 2) . Of all the 20 studies (90%) reporting on bacterial coinfection, the most commonly reported 246 bacterial organism was S. aureus (n=8, 40%), followed by E.coli (n=3, 15%). The most 247 common source of bacterial coinfection was respiratory (n=10, 50%), followed by blood 248 (n=2, 10%) and urine (n=2, 10%). 249 250 251 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The prevalence of bacterial coinfection was highest in North America (7.89%, 95% CI 3.30-258 14.18), followed by Asia (5.3%, 95% CI 4.03 -6.73), with Europe having the lowest 259 prevalence (3.57%, 95% CI 1.72 -6) (Figure 3) . Heterogeneity was considerable in both 260 North America and Europe, I 2 = 98.89% and 96.75% respectively. Studies in Asia had low 261 heterogeneity with an I 2 value of 0%. 262 263 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) 10.92) (Figure 4) . Heterogeneity was considerable in both retrospective and prospective, I 2 = 271 98.88% and 98.62% (Appendix Fig. A) respectively. 272 273 274 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) (Figure 6) . Heterogeneity 297 was considerable across all with studies in Europe being the most heterogeneous (I 2 = 298 99.91%), followed by Asia (I 2 = 99.18%) (Appendix Fig. B) , followed by North America (I 2 299 = 97.28%). 300 301 302 303 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) (Figure 7) . Heterogeneity was considerable in both Retrospective and 312 Prospective cohort studies, with I 2 value of 99.72% and 97.82%, respectively. 313 314 315 316 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 4, 2022. ; https://doi.org/10.1101/2022.03.02.22271779 doi: medRxiv preprint 317 318 Figure 7 . Antibiotic use by study design 319 320 Bias assessment 321 322 As detected by the funnel plots generated (Figure 8) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 4, 2022. Urinary tract infections (UTIs) were the most prevalent source of bacterial coinfection (57%) 359 as reported by Neto et al [45] . The authors attributed the high UTI rate to the lack of a fixed 360 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 4, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 defining clinical characteristics of bacterial coinfection and to high risk factors for UTIs 361 amongst the study population, e.g. elderly hospitalised female patients and diabetic patients. 362 High bacterial coinfection prevalence rates (16%) were reported by Puznik et al [39] , the 363 second largest study included in this review, when compared to the low prevalence rates 364 reported by Russell et al [49] (0.65%), the largest study in the review. This may be due to a 365 number of factors. These include the frequency of microbiological investigations, in which, 366 investigation rates were higher in the study of Puznik et al. Interpretation of microbiological 367 results in which gram-negative bacteria in sputum samples of non-ventilated patients were 368 taken which may have over-estimated significance of bacterial coinfection [39] . 369 370 The analyses conducted around bacterial coinfection in COVID-19 patients suggests that 371 bacterial coinfection prevalence rates are lower than seen in previous viral pandemics. During 372 the 2009 swine flu pandemic, up to 55% of mortalities were as a result of bacterial 373 pneumonia 46 . Previous pandemics have also reported that S. pneumoniae, β -hemolytic 374 streptococci, H. influenzae, and S. aureus were the most commonly identified bacterial co-375 pathogens [13] . In this review, S. aureus has been the most identified bacterial co-pathogen. 376 377 This review also identified very high antibiotic use in COVID-19 patients, which is consistent 378 with previous reviews including those of Langford et al (2021) [33] , which reported a 379 prevalence of 74.6% (95% CI 68.3-80.0%). Differences between the results seen in this 380 review and the review of Langford et al may be attributed to the fact that the latter review 381 also included case series with ≥ 10 patients. This can potentially be attributed to the time 382 period of the pandemic in which the studies were conducted. There was scarceness of cohort 383 studies in the review of Langford et al (2021) [33] , which is different to our study. This review 384 also included a wider selection of nations in addition to a larger number of patients. 385 386 The increase in antibiotic use observed during this pandemic might have impacted and 387 setback antimicrobial stewardship (AMS) efforts globally, especially in regions where AMS 388 programmes are just starting as seen in Africa with previous knowledge and resource issues 389 [61] [62] [63] . This is starting to change in Africa with a growing number of AMS activities to 390 address identified concerns [64] [65] [66] . However, remarkably, in certain regions globally, 391 specifically in Europe, there was a decline in antibiotic use overall in 2020, despite high 392 antibiotic use in COVID-19 positive patients. This can potentially be attributed to a number 393 of factors including social distancing measures and reduction in medical activities [67] [68] [69] . 394 Nonetheless, inappropriate use of antibiotics during COVID-19 is a potential driver of the 395 silent AMR pandemic [24, 70] . However, with current changes observed in global human 396 behaviour, relating to personal hygiene, and increased interest in infection control since the 397 emergence of this pandemic, we should see a rise in AMS activities globally [71] . 398 399 Sub-group analysis based on the key regions demonstrated that the prevalence of reported 400 bacterial coinfection was higher in North America followed by Asia and Europe at 7.89%, 401 5.30% and 3.57%, respectively. Antibiotic use was also higher in North America (68.84%), 402 followed by Europe (60%) and Asia (40.81%). Our hypothesis suggests that the reason for 403 higher prevalence of bacterial coinfection and antibiotic use in North America is due to the 404 presence of larger number of studies and patients from the region in this review, in addition 405 to possibly higher rates of microbiology investigation and over interpretation of microbiology 406 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 4, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 results. Nevertheless, studies from Asia are reporting high use of antibiotics including the 407 study of Hassan et al, which reported extremely high use of antibiotics (92%) in COVID-19 408 patients [72] , however, this study was not included in our meta-analysis as it has not met our 409 inclusion criteria. We are also aware of more recent studies in Asia reporting high rates since 410 our analysis [22, 73] . 411 412 In this review, investigating regional distribution of co-infection and antibiotic use was key. 413 Its significance is directly correlated to the fact that antimicrobial use varies considerably 414 across regions, albeit some convergence [74] . It is quite apparent that high antibiotic 415 consumption is common in low-and middle-income countries (LMICs) in contrast to high-416 income countries (HICs) [74] . In addition, AMR rates vary considerably across countries and 417 regions, with high AMR rates quite evident in regions such as South Asia and Sub-Sahara 418 Africa, therefore, it was practical, in this review, to breakdown antibiotic usage rates by 419 region [75, 76] . 420 421 In terms of study design, sub-group analysis has demonstrated that retrospective studies had 422 higher prevalence of bacterial coinfection than prospective ones at 5.92% vs 3.97% 423 respectively. Whilst, on the other hand, antibiotic use was higher in prospective than 424 retrospective studies, 77.83% vs 56.02%, respectively. The main hypothesis that might 425 explain these variations in prevalence from the main meta-analyses is the study design itself. 426 Prospective studies had well-defined processes to determine bacterial coinfection in COVID-427 19 patients, such as pre-defined clinical characteristics that prompt microbiological 428 sampling [49] ; hence likely lower bacterial coinfection rates but higher justifiable antibiotic 429 use. 430 431 Despite having 10 out of 22 studies included in this review published in 2021, all the studies 432 included have been conducted mainly in the first few months of the pandemic (February and 433 April 2020) with the exception of one study conducted in June 2020 [60] . The results from this 434 review demonstrates that there is insufficient evidence supporting considerable empiric 435 antibiotic prescribing in COVID-19 patients due to a low prevalence of bacterial coinfection. 436 Nonetheless, antibiotics use was high mirroring the findings in other reviews. As the 437 pandemic evolves, and new COVID-19 specific therapeutics come into clinical practice, it 438 will be important to assess their impact on antibiotic use. The early phase of the pandemic 439 from which most of the published studies to date relate has been characterised by a lack of 440 specific COVID-19 therapies and it may be as treatment options become available, and the 441 understanding of the low prevalence of bacterial co-infection becomes more established, that 442 there will be less reliance or defaulting to antibiotic prescribing. We will be following this up 443 in future studies. 444 445 Strengths and Limitations 446 447 We believe the key strengths of this review included a comprehensive search strategy 448 spanning several databases, including both pre-prints and peer-reviewed studies, resulting in 449 22 studies being included, representing over 76,000 patients. 450 451 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) In addition 3 (13%) of the 22 studies included in this review were non-peer reviewed, which 474 might raise concerns regarding their quality [55, 56, 58] . However, one of these studies is now 475 published, so it is unlikely to be of low quality [58] . The remaining two, despite not being 476 published, have still attained a "good" quality rating using the NOS, in addition, both studies 477 weighted in the forest plot were small, and therefore unlikely to affect the overall results 478 479 Future reviews and studies should aim at diversifying study regions, and to include or 480 conduct studies that are more up to date. Studies should also include data on the 481 appropriateness of antibiotic therapy, diagnostic tests and measures used to determine the 482 infection. However, despite these limitations, we believe the findings give good guidance 483 regarding the need to improve the rationality of antibiotic prescribing in patients with 484 COVID-19 to reduce the occurrence of AMR within facilities. 485 486 Conclusion 487 488 This study demonstrates that the prevalence of bacterial coinfection amongst COVID-19 489 patients was low, 5.62%, nevertheless, antibiotics use amongst COVID-19 patients was high 490 (61.77%). The findings of this study encourage a more rational approach to antibiotics 491 prescribing in COVID-19 patients, an approach based on laboratory-confirmed diagnosis of 492 coinfection, rather than clinical, advocating for more antimicrobial stewardship (AMS). We 493 know that antimicrobial stewardship programmes have been successfully instigated across 494 countries including LMICs, and we will be looking to build on this. 495 496 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 4, 2022. ; https://doi.org/10.1101/2022.03.02.22271779 doi: medRxiv preprint Funding 498 The authors declare that no funds, grants, or other support were received during the 499 preparation of this manuscript 500 501 Competing Interests 502 The authors have no relevant financial or non-financial interests to disclose 503 504 Author Contributions 505 Data collection and analysis were performed by Faisal Alshaikh, Oula Sindi and Amanj 506 Kurdi. The first draft of the manuscript was written by Faisal Alshaikh and all authors 507 commented on previous versions of the manuscript. All authors read and approved the final 508 manuscript 509 510 Data Availability 511 All data generated or analysed during this study are included in this published article 512 513 Ethics approval 514 Not applicable 515 516 Consent to participate 517 Not applicable 518 519 Consent to publish 520 Not applicable 521 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 4, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Early transmission dynamics in 524 of novel coronavirus-infected pneumonia Characteristics of and important lessons from the coronavirus 527 disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the 528 Chinese Center for Disease Control and Prevention WHO discontinues hydroxychloroquine and lopinavir/ritonavir 532 treatment arms for COVID-19. World Heal Organ News Release Effect of 534 hydroxychloroquine in hospitalized patients with COVID-19: preliminary results from a 535 multi-centre, randomized Dexamethasone in hospitalized patients with Covid-19 Chloroquine and hydroxychloroquine for the prevention or treatment of COVID-19 in Africa: 540 caution for inappropriate off-label use in healthcare settings. The American journal of 541 tropical medicine and hygiene Rapid 543 assessment of the potential paucity and price increases for suggested medicines and 544 protection equipment for COVID-19 across developing countries with a particular focus on 545 Africa and the implications Co-infections in people with COVID-19: a 547 systematic review and meta-analysis Secondary bacterial infections associated with 549 influenza pandemics. Frontiers in microbiology Bacterial pneumonia and pandemic 551 influenza planning. Emerging infectious diseases Community-acquired respiratory coinfection in critically ill patients 554 with pandemic 2009 influenza A (H1N1) virus Predominant role of bacterial pneumonia as 556 a cause of death in pandemic influenza: implications for pandemic influenza preparedness. 557 The Journal of infectious diseases Bacterial and viral infections associated with 559 influenza. Influenza and other respiratory viruses Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East 562 respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. The Lancet 563 infectious diseases Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable 566 incidence of atypical bacteria coinfection based on diagnostic assays. Canadian respiratory 567 journal 569 Critically ill patients with the Middle East respiratory syndrome: a multicenter retrospective 570 cohort study Antimicrobial consumption among 66 acute care hospitals in Catalonia: impact of the 573 COVID-19 pandemic Antimicrobial consumption 575 among hospitalized patients with COVID-19 in Pakistan. SN comprehensive clinical 576 medicine Antibiotic Prescribing Patterns at COVID-19 Dedicated Wards in Bangladesh: Findings from 579 a Single Center Study. Infection Prevention in Practice Clinical course and risk factors for 581 mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. 582 The lancet Management 584 of children admitted to hospitals across Bangladesh with suspected or confirmed COVID-19 585 and the implications for the future: a nationwide cross-sectional study Hygiene: microbial strategies to reduce pathogens and drug resistance in 588 clinical settings The COVID-19 pandemic: a threat to antimicrobial resistance containment How covid-19 is accelerating the threat of antimicrobial resistance Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-596 resistant bacteria in the EU and the European Economic Area in 2015: a population-level 597 modelling analysis. The Lancet infectious diseases The cost of antimicrobial resistance Strategies to improve antimicrobial utilization with a special focus on developing countries. 602 Life Clinical and economic impact of antibiotic 604 resistance in developing countries: a systematic review and meta-analysis Bacterial Co-Infections in Coronavirus Disease 607 2019 Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid 610 review and meta-analysis. Clinical Microbiology and Infection Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other 613 pathogens: A systematic review and meta-analysis Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clinical 616 Microbiology and Infection The Newcastle-Ottawa Scale (NOS) for assessing the quality of 621 nonrandomised studies in meta-analyses 2021 [Available from: The Newcastle-Ottawa Scale 622 (NOS) for assessing the quality of nonrandomised studies in meta-analyses Transformations related to the angular and the square root. 624 The Annals of Mathematical Statistics Random-effects model for meta-analysis of clinical trials: 626 an update The performance of tests of publication bias and other 628 sample size effects in systematic reviews of diagnostic test accuracy was assessed A multicenter 631 analysis of the clinical microbiology and antimicrobial usage in hospitalized patients in the 632 US with or without COVID-19 An 634 observational cohort study of bacterial co-infection and implications for empirical antibiotic 635 therapy in patients presenting with COVID-19 to hospitals in North West London Antibiotic 638 prescribing patterns for coronavirus disease 2019 (COVID-19) in two emergency 639 departments with rapid procalcitonin Bacterial and fungal 642 coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a 643 UK secondary-care setting Bacterial 645 and viral co-infections in patients with severe SARS-CoV-2 pneumonia admitted to a French 646 ICU Bacterial co-infections and antibiotic prescribing practice in adults with COVID-19: 649 experience from a single hospital cluster. Therapeutic Advances in Infectious Disease Bacterial infections and patterns of antibiotic use in patients with COVID 19 Characteristics of 655 COVID 19 patients with bacterial coinfection admitted to the hospital from the emergency 656 department in a large regional healthcare system Clinical and etiological analysis 659 of co infections and secondary infections in COVID 19 patients: An observational study. 660 The Clinical Respiratory Journal Co-662 infection in critically ill patients with COVID-19: an observational cohort study from 663 Co-665 infections, secondary infections, and antimicrobial usage in hospitalised patients with 666 COVID-19 from the ISARIC WHO CCP-UK study: a prospective, multicentre cohort study Community-acquired 669 coinfection in coronavirus disease 2019: A retrospective observational experience. Clinical 670 Infectious Diseases Empiric 672 antibacterial therapy and community-onset bacterial coinfection in patients hospitalized with 673 coronavirus disease 2019 (COVID-19): a multi-hospital cohort study. Clinical Infectious 674 Diseases Evaluation of superinfection, 676 antimicrobial usage, and airway microbiome with metagenomic sequencing in COVID-19 677 patients: A cohort study in Shanghai Few bacterial co-infections but frequent empiric antibiotic use in the early phase of 681 hospitalized patients with COVID-19: results from a multicentre retrospective cohort study in 682 The Netherlands Incidence of co-infections and superinfections in hospitalized patients 685 with COVID-19: a retrospective cohort study 688 Investigation of subsequent and co-infections associated with SARS-CoV-2 (COVID-19) in 689 hospitalized patients Limited role for 691 antibiotics in COVID-19: scarce evidence of bacterial coinfection. Available at SSRN 692 3622388 694 Prevalence of co-infection at the time of hospital admission in COVID-19 patients, a 695 multicenter study. Open forum infectious diseases Rate of Antibiotic 697 Use and Associated Risk Factors in COVID-19 Hospitalized Patients. medRxiv. 2020 Rates of 699 bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort 700 study in light of antibiotic stewardship The clinical impact of bacterial co-infection among moderate, severe and critically 704 ill COVID-19 patients in the second referral hospital in Surabaya Status of 706 antimicrobial stewardship programmes in Nigerian tertiary healthcare facilities: findings and 707 implications Antimicrobial stewardship knowledge and perception among physicians and pharmacists at 710 leading tertiary teaching hospitals in Zambia: implications for future policy and practice Antibiotic stewardship in low-and middle-income countries: the same but different? Clinical 714 microbiology and infection Supporting 716 antimicrobial stewardship in Ghana: Evaluation of the impact of training on knowledge and 717 attitudes of healthcare professionals in two hospitals. JAC-antimicrobial resistance Antibiotic Prescribing Patterns in Ghana, Uganda, Zambia and Tanzania Hospitals: Results 721 from the Global Point Prevalence Survey (G-PPS) on Antimicrobial Use and Stewardship 722 Interventions Implemented Implementation of 724 antimicrobial stewardship programmes in African countries: a systematic literature review. 725 Journal of global antimicrobial resistance English surveillance programme for antimicrobial utilisation and 728 resistance (ESPAUR) Report for 2020 to 2021 Pilot study 732 on the current management of children with COVID-19 in hospitals in Bangladesh; findings 733 and implications COVID-19: don't neglect 735 antimicrobial stewardship principles! Clinical Microbiology and Infection Use of 737 Antimicrobials among Suspected COVID-19 Patients at Selected Hospitals, Bangladesh: 738 Findings from the First Wave of COVID-19 Pandemic Current 740 management of children with COVID-19 in hospitals in India; pilot study and findings. 741 Advances in Human Biology Global 743 increase and geographic convergence in antibiotic consumption between Global 746 burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022 A global analysis of 748 antimicrobial resistance and its drivers COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies