Diagnosis of bacterial infection in patients with COVID-19: is it a simple task? (literature review)

Diagnosing bacterial infection in patients with novel coronavirus infection (COVID-19) is not an easy task. Available data suggest that bacterial infection in patients with COVID-19 is rare and occurs in less than 10% of cases. At the same time, data of individual studies and systematic reviews indicate that more than 70% of patients with COVID-19 receive mainly empirical antimicrobial therapy with broad-spectrum antibiotics often before the diagnosis of COVID-19 has been verified. Therefore, this widespread empirical use of antibiotics is not supported by data on the need for their use. The article discusses the literature data on the significance of commonly accepted methods for diagnosing bacterial infection, with an emphasis on laboratory presence / absence tests. In everyday practice, the likelihood of bacterial coinfection in patients with COVID-19 is assessed by clinical presentation of the disease and the results of standard laboratory tests and imaging methods. However, when viral respiratory infection develops, this approach does not always allow to diagnose bacterial coinfection with sufficient significance. This issue may be handled by available modern test systems, the use of a combination of signs or additional laboratory criteria (for example, procalcitonin), and the analysis of the overall clinical presentation by the doctor using knowledge about patient risk groups.

Epidemiological Impact on Use of Antibiotics in Patients Hospitalized for COVID-19: A Retrospective Cohort Study in Italy.

The increased incidence of antimicrobial resistance during coronavirus disease 2019 (COVID-19) is a very important collateral damage of global concern. The cause is multifactorial and is particularly related to the high rates of antibiotic use in COVID-19 patients with a relatively low rate of secondary co-infection. To this end, we conducted a retrospective observational study of 1269 COVID-19 patients admitted during the years 2020, 2021 and 2022 in two Italian hospitals, with a focus on bacterial co-infections and antimicrobial therapy. Multivariate logistic regression was used to analyze the association between bacterial co-infection, antibiotic use and hospital death after adjustment for age and comorbidity. Bacterial co-infection was detected in 185 patients. The overall mortality rate was 25% (n = 317). Concomitant bacterial infections were associated with increased hospital mortality (ß = 1.002, p < 0.001). A total of 83.7% (n = 1062) of patients received antibiotic therapy, but only 14.6% of these patients had an obvious source of bacterial infection. There was a significantly higher rate of hospital mortality in patients who received antibiotics than in those who did not (χ2 = 6.22, p = 0.012). Appropriate prescribing and the rational use of antimicrobials according to the principles of antimicrobial stewardship can help prevent the emergence of antibiotic resistance.

COVID-19 pandemic and the quality of antibiotic use in primary care: an interrupted time-series study.

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain.

COVID-19 Vaccination is Associated with Reduced Outpatient Antibiotic Prescribing In Older Adults with Confirmed SARS-CoV-2: A Population Wide Cohort Study.

BACKGROUND: Antibiotics are frequently prescribed unnecessarily in outpatients with COVID-19. We sought to evaluate factors associated with antibiotic prescribing in those with SARS-CoV-2 infection. METHODS: We performed a population-wide cohort study of outpatients 66 years or older with PCR-confirmed SARS-CoV-2 from January 1st 2020 to December 31st 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1-week before (pre-diagnosis) and 1-week after (post-diagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary series COVID-19 vaccination, in univariate and multivariable analyses. RESULTS: We identified 13,529 eligible nursing home residents and 50,885 eligible community dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3,020 (22%) and 6,372 (13%) received at least one antibiotic prescription within 1 week of a SARS-CoV-2 positive result, respectively. Antibiotic prescribing in nursing home and community residents occurred at 15.0 and 10.5 prescriptions per 1000 person-days pre-diagnosis and 20.9 and 9.8 per 1000 person-days post-diagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted post-diagnosis IRRs of 0.7 (95%CI 0.4-1) and 0.3 (95%CI 0.3-0.4) respectively. CONCLUSIONS: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis, though was reduced in COVID-19 vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Innovations in Ambulatory Stewardship

Ambulatory antibiotic use accounts for most of the global consumption of antibiotics leading to selection pressure, multidrug resistance, and significant healthcare costs (https://www.cdc.gov/antibiotic-use/community/pdfs/16_268900-A_CoreElementsOutpatient_508.pdf) The Centers for Disease Control and Prevention established the Core Elements of outpatient antimicrobial stewardship in 2016 as a framework to develop, expand, and evaluate ambulatory stewardship programs, which must address overuse in multiple settings (e.g., urgent care centers, adult and pediatric outpatient practices, dental practices, and retail clinics). As such, we present examples of innovative yet adaptable outpatient stewardship initiatives encompassing a variety of settings. We also address patterns of ambulatory antibiotic prescribing and novel stewardship initiatives implemented during the novel coronavirus disease 2019 (COVID-19) pandemic. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

The state of current research on COVID-19 and antibiotic use: global implications for antimicrobial resistance.

BACKGROUND: During the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, the administration of antibiotics to patients was prevalent in numerous countries. Despite this, the rising threat of antimicrobial resistance (AMR) presents a significant public health concern. The escalation of AMR has been exacerbated by the ongoing COVID-19 pandemic. Against this backdrop, the primary aim of this study was to conduct a bibliometric and visual analysis of research pertaining to the use of antibiotics in COVID-19. METHODS: This study examined documents indexed in Scopus between 2020 and 2022. To visualize the trends and hotspots of research related to antibiotics and COVID-19, as well as collaborative networks, the researcher utilized version 1.6.18 of the VOSviewer software. Scopus data were analysed to extract information on the types of publications, annual research output, countries, institutions, funding agencies, journals, citations, and highly cited references. Microsoft Excel 2019 was used to process and organize the extracted data. RESULTS: This study analysed 1137 documents related to COVID-19 and antibiotics and found that the number of publications increased from 130 in 2020 to 527 in 2022. These publications included 777 (68.34%) articles and 205 (18.03%) reviews. The top five countries in terms of scientific production were the United States (n = 231; 20.32%), the United Kingdom (n = 156; 13.72%), China (n = 101; 8.88%), India (n = 100; 8.8%), and Italy (n = 63; 5.54%), and the leading institutions were Imperial College London (n = 21; 1.85%), University of Oxford (n = 20; 1.76%), and University College London (n = 15; 1.32%). The National Natural Science Foundation of China provided funding for the highest number of articles (n = 48; 4.22%), followed by the National Institutes of Health (n = 32; 2.81%). The most productive journals were Antibiotics (n = 90; 7.92%), Journal of Antimicrobial Chemotherapy (n = 30; 2.64%), and Infection Control and Hospital Epidemiology (n = 26; 2.29%). Finally, the research hotspots identified in this study were 'antimicrobial stewardship during the COVID-19 outbreak' and 'implications of the COVID-19 pandemic on the emergence of antimicrobial resistance.' CONCLUSIONS: This is the first bibliometric analysis of COVID-19-related research on antibiotics. Research was carried out in response to global requests to increase the fight against AMR and awareness of the issue. More restrictions on the use of antibiotics are urgently needed from policy makers and authorities, more so than in the current situation.

Prevalence and Predictors of Using Antibiotics without a Prescription in a Pediatric Population in the United States.

Non-prescription antibiotic use (using antibiotics without clinical guidance) increases the risk of the development of antibiotic resistance, adverse drug reactions, and other potential patient harm. Few studies have explored non-prescription use in children in the U.S. From January 2021 to April 2022, a diverse sample of caregivers of children under 18 years were surveyed in English and Spanish at two safety net clinics in Texas. We assessed the prevalence of antibiotic use in children in the previous 12 months, storage of antimicrobials, and intended use of non-prescription antibiotics (professed intention for future non-prescription antibiotic use). We also measured sociodemographic factors, types of antibiotics used, and symptoms that trigger non-prescription use. The response rate was 82%, and 17% were surveyed in Spanish. Of 322 participants surveyed, three Spanish-speaking caregivers reported giving non-prescription antibiotics to their child in the previous 12 months. Approximately 21% (n = 69) reported storing antimicrobials at home, specifically amoxicillin (n = 52), clindamycin (n = 10), cephalexin (n = 5), penicillin (n = 3), and trimethoprim/sulfamethoxazole (n = 3). Nearly 15% (n = 46) reported intention to give non-prescription antibiotics to their children. Younger caregiver age was associated with storage and intended use of non-prescription antibiotics. Our findings will guide the development of an educational intervention to decrease non-prescription antibiotic use.

Analysis of Changes in Antibiotic Use Patterns in Korean Hospitals during the COVID-19 Pandemic.

With the onset of the coronavirus disease 2019 (COVID-19) pandemic, changes in patient care and antibiotic use have occurred in hospitals. The data of the National Health Insurance System's claims of inpatients from all hospitals in Korea between January 2019 and December 2020 were obtained from the Health Insurance Review & Assessment Service and analyzed. The trend in the use of all antibacterial agents in both hospitals declined for the total number of COVID-19 patients at the bottom 10% and those in the top 10%. Specifically, a decreasing trend in the use of broad-spectrum antibacterial agents predominantly prescribed for community-acquired cases and narrow-spectrum beta-lactam agents were observed in both hospitals. In the aftermath of the COVID-19 pandemic, the total use of antibacterial agents has gradually decreased among patients with pneumonia and those with severe COVID-19. In contrast, its use has increased gradually among those with mild to moderate COVID-19. A decreasing trend in overall antibiotic use was observed during the COVID-19 pandemic, and an increasing trend in antibiotic use was observed in patients with mild to moderate COVID-19 in Korean hospitals.

Antibiotic use for respiratory tract infections among older adults living in long-term care facilities: a systematic review and meta-analysis.

BACKGROUND: Antibiotics are commonly prescribed for respiratory tract infections (RTIs) among older adults in long-term care facilities (LTCFs), and this contributes to the emergence of antimicrobial resistance. The objective of this study was to determine the antibiotic prescribing rate for RTIs among LTCF residents, and to analyse the antibiotic consumption patterns with the AwaRe monitoring tool, developed by the World Health Organization. METHODS: MEDLINE, EMBASE and CINAHL were searched from inception to March 2022. Original articles reporting antibiotic use for RTIs in LTCFs were included in this review. Study quality was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence Data. A random-effects meta-analysis was employed to calculate the pooled estimates. Subgroup analysis was conducted by type of RTI, country, and study start year. RESULTS: In total, 47 articles consisting of 50 studies were included. The antibiotic prescribing rate ranged from 21.5% to 100% (pooled estimate 69.8%, 95% confidence interval 55.2-82.6%). The antibiotic prescribing rate for lower respiratory tract infections (LRTIs) was higher than the rates for viral and general RTIs. Compared with Italy, France and the USA, the Netherlands had lower antibiotic use for LRTIs. A proportion of viral RTIs were treated with antibiotics, and all the antibiotics were from the Watch group. Use of antibiotics in the Access group was higher in the Netherlands, Norway, Switzerland and Slovenia compared with the USA and Australia. CONCLUSION: The antibiotic prescribing rate for RTIs in LTCFs was high, and AWaRe antibiotic use patterns varied by type of RTI and country. Improving antibiotic use may require coordination efforts.

Global antibiotic use during the COVID-19 pandemic: analysis of pharmaceutical sales data from 71 countries, 2020-2022.

Background: Despite bacterial coinfection rates of less than 10%, antibiotics are prescribed to an estimated 75% of patients with COVID-19, potentially exacerbating antimicrobial resistance. We estimated the associations of COVID-19 cases and vaccinations with global antibiotic sales during the first two years of the COVID-19 pandemic. Methods: We obtained monthly data on broad-spectrum antibiotic sales volumes (cephalosporins, penicillins, macrolides, and tetracyclines) in 71 countries during March 2020-May 2022 from the IQVIA MIDAS® database. These data were combined with country-month-level COVID-19 case and vaccination data from Our World in Data. We used least squares (pooled) and fixed-effects panel data regression models, accounting for country characteristics, to estimate the associations between antibiotic sales volumes and COVID-19 cases and vaccinations per 1000 people. Findings: Sales of all four antibiotics fell sharply during April and May 2020, followed by a gradual rise to near pre-pandemic levels through May 2022. In fixed-effects regression models, a 10% increase in monthly COVID-19 cases was associated with 0.2%-0.3% higher sales of cephalosporins, 0.2%-0.3% higher sales of penicillins, 0.4%-0.6% higher sales of macrolides, and 0.3% higher sales of all four antibiotics combined per 1000 people. Across continents, a 10% increase in monthly COVID-19 cases was associated with 0.8%, 1.3%, and 1.5% higher macrolides sales in Europe, North America, and Africa respectively. Sales of other antibiotics across continent were also positively associated with COVID-19 cases, although the estimated associations were smaller in magnitude. No consistent associations were observed between antibiotic sales and COVID-19 vaccinations. Results from pooled regression analysis were similar to those from the fixed-effects models. Interpretation: Antibiotic sales were positively associated with COVID-19 cases globally during 2020-2022. Our findings underline that antibiotic stewardship in the context of COVID-19 remains essential. Funding: Bill & Melinda Gates Foundation.

First publication of endemic channels as part of a pediatric Antimicrobial Stewardship Program: when to turn on the alarms? Recommendations of a pediatric ASP program.

BACKGROUND: Pediatric Antimicrobial Stewardship Programs (ASP) consider DOT a fundamental measure to quantify the impact of ASP. Novel strategies have been described, but no endemic channels (EC) have been reported to compare antibiotic use within historical patterns. This report describes the process of constructing an EC and analyzing its interpretation. METHODS: This was a descriptive study of the construction, implementation, and analysis of EC. The median and quartile method, as well as the geometric mean (GM) and confidence interval (CI) methods using DOT for the last 4 years were used. ECs have also been elaborated on in critical services (PICU). RESULTS: GM and CI method seem to be more sensitive in identifying changes in antimicrobial use. Ceftriaxone increased its use starting in December 2021, reaching the warning zone in March 2022 in relation to increased cases of bacterial and complicated pneumonia. Piperacillin-tazobactam showed an important increase in PICU during the first 8 months of 2021, reaching the alert zone until August 2021; thereafter, its use decreased, and this variation was related to a modification in the presentation of complicated appendicitis during the COVID 19 pandemic restrictions. The use of ampicillin-sulbactam has increased since January 2022 because of a change in local guidelines regarding its use in appendicitis and peritonitis. The changes identified in each EC allowed ASP to take different conducts. CONCLUSION: EC allowed us to construct a new tool to measure ASP impact, internal comparison of antibiotic use facilitated taking timely interventions. EC could be useful for all pediatric and adult ASP.

Impact of the COVID-19 Outbreak on the Antibiotic Use Patterns among a Rural Community Population in Eastern China.

There are growing concerns that the coronavirus disease of 2019 (COVID-19) pandemic may change antibiotic use patterns and accelerate antibiotic resistance, but evidence from the community level is lacking. This study aims to estimate the impact of the COVID-19 outbreak on the antibiotic use patterns among a community population in Eastern China. A self-administered medicine diary was used to collect information on antibiotic use from July 2019 to June 2021 among a rural community in Eastern China. We analyzed the changes in antibiotic use patterns over five months from August to December 2019 and the corresponding months in 2020. The risk of antibiotic use and its changes were measured with the incidence rate (IR) and relative risk (RR). In total, 1111 participants were eligible for the final analysis (440 in 2019 and 671 in 2020). After the COVID-19 outbreak, antibiotic use increased by 137% (5.43 per 100 person months in the 2019 vs. 12.89 per 100 person months in the 2020), and after the adjustment of covariates, the adjusted RR was 1.72 (95% CI: 1.10~2.34). It was higher among those who were women (RR = 2.62), aged 35-59 years old (RR = 2.72), non-farmers (RR = 2.75), had less than six years of education (RR = 2.61), had an annual household income over CNY 100,000 (USD 14,940) (RR = 2.60), and had no history of chronic diseases (RR = 2.61) (all p < 0.05). The proportion of cephalosporins consumed increased from 54.29% in 2019 to 64.92% in 2020 (p = 0.011). Among those aged 35 years and older, the proportion of antibiotics obtained from medical facilities increased, while the proportion obtained from retail pharmacies, homes, and other sources decreased (all p < 0.05). The COVID-19 outbreak changed antibiotic use patterns in this study population (Eastern China) significantly. More efforts to monitor and enhance antibiotic stewardship activities at the community level are needed in future.

Identifying Antibiotic Use Targets for the Management of Antibiotic Resistance Using an Extended-Spectrum ß-Lactamase-Producing Escherichia coli Case: A Threshold Logistic Modeling Approach.

The aim of this study was to develop a logistic modeling concept to improve understanding of the relationship between antibiotic use thresholds and the incidence of resistant pathogens. A combined approach of nonlinear modeling and logistic regression, named threshold logistic, was used to identify thresholds and risk scores in hospital-level antibiotic use associated with hospital-level incidence rates of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli). Threshold logistic models identified thresholds for fluoroquinolones (61.1 DDD/1000 occupied bed days (OBD)) and third-generation cephalosporins (9.2 DDD/1000 OBD) to control hospital ESBL-producing E. coli incidence. The 60th percentile of ESBL-producing E. coli was determined as the cutoff for defining high incidence rates. Threshold logistic analysis showed that for every one-unit increase in fluoroquinolones and third-generation cephalosporins above 61.1 and 9.2 DDD/1000 OBD levels, the average odds of the ESBL-producing E. coli incidence rate being ≥60th percentile of historical levels increased by 4.5% and 12%, respectively. Threshold logistic models estimated the risk scores of exceeding the 60th percentile of a historical ESBL-producing E. coli incidence rate. Threshold logistic models can help hospitals in defining critical levels of antibiotic use and resistant pathogen incidence and provide targets for antibiotic consumption and a near real-time performance monitoring feedback system.

Comparison of antibiotic use in the COVID-19 pandemic with the pre-pandemic period in a university hospital.

Introduction: The appropriate use of antibiotics is an important strategy in slowing the development of antimicrobial resistance. This study aimed to evaluate antibiotic consumption and antibiotic use during the coronavirus disease 2019 (COVID-19) pre-pandemic period and pandemic period. Methods: Antibiotic consumption was evaluated with the antibiotic consumption index (ACI). Results: Antibiotics with the largest increase in ACI value during the pandemic period compared to the previous year increased from 0.4 to 1.8 DDI/100 bed days in moxifloxacin. Teicoplanin, linezolid, and clindamycin were not affected in terms of consumption. Conclusions: It was observed that the use of many intravenous antibiotics in our hospital increased during the pandemic period.

Socio-cultural determinants of antibiotic resistance: a qualitative study of Greeks' attitudes, perceptions and values.

BACKGROUND: Antibiotic resistance is a complex phenomenon heavily influenced by social, cultural, behavioural, and economic factors that lead to the misuse, overuse and abuse of antibiotics. Recent research has highlighted the role that norms and values can play for behaviours that contribute to resistance development, and for addressing such behaviours. Despite comparatively high antibiotic consumption in Greece, both at the community and healthcare level, Greeks have been shown to be relatively aware of the connection between antibiotic overuse and antibiotic resistance. This suggests that Greeks' non-judicious use cannot simply be explained by lack of awareness but may relate to other factors specific to Greek society. The present study aimed to explore attitudes, perceived norms, and values in relation to antibiotics, in order to improve understanding of socio-cultural determinants of antibiotic resistance in Greece. METHODS: Data were collected through online focus group discussions in 2021. Twenty Greeks were recruited through purposive sampling, aiming for as heterogeneous groups as possible regarding gender (12 women, 8 men), age (range 21-55, mean 33), and education level. Interview transcripts were analysed inductively using thematic content analysis. RESULTS: Participants considered antibiotic overconsumption as a consolidated habit influenced by ease of access, social expectations and, more generally, cultural practices. While critical of such norms and practices, participants opposed stewardship measures that would prioritize the societal interest in maintaining antibiotic effectiveness over individual needs. Participants considered responsibility for antibiotic resistance to be shared by the whole society, but the role of government actors and health professionals as well as of food producers was emphasized. Notably, scepticism about the prospect of effectively managing antibiotic resistance in Greece was commonly expressed. CONCLUSIONS: The study makes explicit attitudes, perceived norms and values that, besides limited awareness, may contribute to non-judicious antibiotic use in Greece. These socio-cultural determinants of antibiotic resistance warrant further research and should be considered when designing measures aimed to mitigate this problem.

Antibiotic Use and Bacterial Infection in COVID-19 Patients in the Second Phase of the SARS-CoV-2 Pandemic: A Scoping Review.

This scoping review aimed to explore the prevalence and patterns of global antibiotic use and bacterial infection in COVID-19 patients from studies published between June 2020 and March 2021. This review was reported in line with the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews, and the protocol is registered with the Open Science Framework. Compared with our previously-published review of the period (December 2019-June 2020), the antibiotic prescribing rate for COVID-19 patients (June 2020-March 2021) was found to have declined overall (82.3% vs. 39.7%), for mild and moderate patients (75.1% vs. 15.5%), and for severe and critical patients (75.3% vs. 48.3%). The seven most frequently prescribed antibiotics in COVID-19 patients were all on the "Watch" list of the WHO AWaRe antibiotics classification. The overall reported bacterial infection rate in COVID-19 patients was 10.5%, and the most frequently reported resistant pathogen in COVID-19 patients was Staphylococcus aureus, followed by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. There is an urgent need to establish comprehensive and consistent guidelines to assist clinicians in selecting appropriate antibiotics for COVID-19 patients when needed. The resistance data on the most frequently used antibiotics for COVID-19 patients for certain resistant pathogens should be closely monitored.

Disproportionate reduction in respiratory vs. non-respiratory outpatient clinic visits and antibiotic use in children during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic led to improved hygiene and reduced social encounters. Near elimination of the activity of respiratory syncytial virus and influenza viruses were observed, worldwide. Therefore, we assessed the rates of pediatric outpatient clinic visits and medications prescribed at those visits during the coronavirus disease 2019 (COVID-19) pandemic and pre-COVID-19 period (2016-2019). METHODS: Monthly and annual incidence rates for respiratory and non-respiratory diagnoses and dispensed prescription rates were calculated. Acute gastroenteritis (AGE) visits were analyzed separately since the mode of transmission is influenced by hygiene and social distancing. RESULTS: Overall, 5,588,702 visits were recorded. Respiratory and AGE visits declined by 49.9% and 47.3% comparing the COVID-19 and pre-COVID-19 periods. The respective rate reductions for urinary tract infections, trauma, and skin and soft tissue infections were 18.2%, 19.9%, and 21.8%. Epilepsy visits increased by 8.2%. Overall visits rates declined by 21.6%. Dispensed prescription rates of antibiotics and non-antibiotics respiratory medications declined by 49.3% and 44.4%, respectively. The respective declines for non-respiratory antibiotics and non-antibiotics were 15.1% and 0.2%. Clinic visits and prescription rates reductions were highest in April-May, following the first lockdown in Israel. CONCLUSIONS: COVID-19 pandemic resulted in a substantial reduction in respiratory outpatient clinic visits and dispensed respiratory drugs, with only a mild reduction seen for non-respiratory visits. These trends were probably driven by COVID-19 mitigation measures and by the profound disruption to non-SARS COV-2 respiratory virus activity.

Antibiotic (Mis)Use in COVID-19 Patients before and after Admission to a Tertiary Hospital in Serbia.

Antimicrobial resistance (AMR) is a global concern, and antibiotic use has risen throughout the COVID-19 pandemic. Up to 75% of COVID-19 patients are treated with antibiotics despite little evidence for their use. A retrospective study from 6 March 2020 (the start of the pandemic in Serbia) to 31 December 2021 was conducted at the Clinic for Infectious and Tropical Diseases, University Clinical Centre of Serbia. In total, 523 patients with a microbiological diagnosis of COVID-19 were included. Patient data were analysed, including antibiotic use before and after admission. Pre-admission use of antibiotics for COVID-19 treatment was documented in more than half of patients (58.1%), of which a third (34.1%) used more than one antibiotic. Macrolides, cephalosporins, and fluoroquinolones were mainly used, most frequently among patients aged between 31-45 years (75.2%). Prior antibiotic use was associated with a longer duration of illness at admission (8.8 vs. 5.7, p < 0.001), oxygen therapy upon admission (27.6% vs. 16.0%, p = 0.002), and a lower vaccination rate (60.7% vs. 50.7%, p = 0.04). When hospitalised, 72.1% of patients received antibiotics, primarily cephalosporins (71.9%). Significant efforts are needed to reduce antibiotic use in the community and improve prescribing rates by healthcare professionals.

Secondary Bacterial Infection and Clinical Characteristics in Patients With COVID-19 Admitted to Two Intensive Care Units of an Academic Hospital in Iran During the First Wave of the Pandemic.

Data on the prevalence of bacterial co-infections and secondary infection among adults with COVID-19 admitted to the intensive care unit (ICU) are rare. We aimed to determine the frequency of secondary bacterial infection, antibiotic use, and clinical characteristics in patients admitted to the ICU with severe SARS-CoV-2 pneumonia. This was a retrospective cohort study of adults with severe COVID-19 admitted to two ICUs from March 6 to September 7, 2020 in an academic medical center in Isfahan, Iran. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed and also typical pattern of CT scan was used for the diagnosis of COVID-19. Data collection included the age, gender, main symptoms, history of underlying disease, demographics, hospital stay, outcomes, and antibiotic regimen of the patient. Antimicrobial susceptibility testing was carried out according to the CLSI guidelines. During the study period, 553 patients were referred to the both ICUs for COVID-19 with severe pneumonia. Secondary bacterial infection was detected in 65 (11.9%) patients. The median age was 69.4 (range 21-95) years; 42 (63.6%) were men. Notably, 100% (n = 65) of the patients with superinfection were prescribed empirical antibiotics before first positive culture, predominantly meropenem (86.2%) with a median duration of 12 (range 2-32) days and levofloxacin (73.8%) with a median duration of nine (range 2-24) days. Most prevalent causative agents for secondary bacterial infection were Klebsiella pneumoniae (n = 44) and Acinetobacter baumannii (n = 33). Most patients with secondary bacterial infection showed extensive drug-resistance. The mortality among patients who acquired superinfections was 83% against an overall mortality of 38.1% in total admitted COVID-19 patients. We found a high prevalence of carbapenem-resistant Gram-negative bacilli in COVID-19 patients admitted to our ICUs, with a high proportion of K. pneumoniae followed by A. baumannii. These findings emphasize the importance of implementation of strict infection control measures and highlight the role of antimicrobial stewardship during a pandemic.

The burden of Clostridioides difficile infection in COVID-19 patients: A systematic review and meta-analysis.

OBJECTIVES: The main aim of this systematic review and meta-analysis was to assess the proportion of confirmed COVID-19 patients with Clostridioides difficile infection (CDI) and to describe risk factors and outcome of these patients. METHODS: MEDLINE and Cochrane Central Register of Controlled Trials databases were searched up to July 15, 2021. We included studies reporting data on CDI occurring in patients with a confirmed diagnosis of COVID-19. We pooled proportion of CDI patients using a random effects model (DerSimonian-Laird method) stabilising the variances using the Freeman-Tukey double arcsine transformation. RESULTS: Thirteen studies were included in the systematic review. All the studies retrospectively collected data between February 2020 and February 2021. The reported CDI incidence rates ranged from 1.4 to 4.4 CDI cases per 10,000 patient-days. Seven studies reported data on the number of COVID-19 patients who developed CDI and the total number of COVID-19 patients in the study period and were included in the meta-analysis, comprising 23,697 COVID-19 patients. The overall pooled proportion of COVID-19 patients who had CDI was 1% [95% confidence interval: 1-2]. Among studies reporting CDI occurrence in patients with and without COVID-19, the majority of them reported reduced or unchanged CDI rates compared to pre-COVID period. CONCLUSIONS: CDI is a relevant issue for COVID-19 patients. Adherence to infection prevention and control measures and to the antimicrobial stewardship principles is crucial even during the COVID-19 pandemic.