Vaccine value profile for Klebsiella pneumoniae.

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

A multifaceted approach to global health.

World Health Day underscores the scientific community's commitment to achieving health equity for all. It is paramount to eliminate bias in research that has traditionally focused on men, neglecting the specific needs of diverse populations. Innovative clinical trial designs are being developed with more inclusive enrollment. Ensuring equitable access to essential antibiotics, coupled with robust infection prevention and control measures, is vital to safeguarding public health. The pursuit of health equity extends beyond the realm of medicine. Investments in local food production and robust social safety nets are critical for mitigating the effects of climate change on access to healthy diets. Additionally, in times of polycrisis, prioritizing the unique needs of children and empowering community-led healthcare initiatives in conflict zones are essential steps. By taking these actions, we can move closer to realizing everyone's fundamental right to health.

Accelerating antibiotic access and stewardship: a new model to safeguard public health.

This Personal View discusses the challenges faced, especially by low-income and middle-income countries (LMICs), in responding to the growing burden of bacterial antimicrobial resistance. Many patients in LMICs lack access to effective and affordable treatments needed to successfully treat patients. Meanwhile, traditional antimicrobial stewardship models face implementation challenges due to financial, health system, and human resource constraints. These constraints call for a paradigm shift from traditional high-income country-style antimicrobial stewardship, which is often resource intensive and aimed at cost containment, to a broader concept of sustainable access. We suggest a model of context-adapted stewardship that continues to emphasise providing the right antibiotic, at the right time, for the right duration, and at an affordable price. Taking lessons from other disease areas, including tuberculosis, we identify interventions such as task shifting to various health-care workers and the implementation of a hub-and-spoke model to support appropriate use of antibiotics, to enable optimal access and maximisation of scarce resources.

Estimates of hospitalisations and deaths in patients with COVID-19 associated with undiagnosed diabetes during the first phase of the pandemic in eight low-income and middle-income countries: a modelling study.

Background: Patients with COVID-19 that had diagnosed chronic diseases - including diabetes - may experience higher rates of hospitalisation and mortality relative to the general population. However, the burden of undiagnosed co-morbidities during the pandemic has not been adequately studied. Methods: We developed a model to estimate the hospitalisation and mortality burden of patients with COVID-19 that had undiagnosed type 1 and type 2 diabetes (UD). The retrospective analytical modelling framework was informed by country-level demographic, epidemiological and COVID-19 data and parameters. Eight low-and middle-income countries (LMICs) were studied: Brazil, China, India, Indonesia, Mexico, Nigeria, Pakistan, and South Africa. The modelling period consisted of the first phase of the pandemic - starting from the date when a country identified its first COVID case to the date when the country reached 1% coverage with one dose of a COVID-19 vaccine. The end date ranged from Jan 20, 2021 for China to June 2, 2021 for Nigeria. Additionally, we estimated the change in burden under a scenario in which all individuals with UD had been diagnosed prior to the pandemic. Findings: Based on our modelling estimates, across the eight countries, 6.7 (95% uncertainty interval: 3.4-11.3) million COVID-19 hospitalised patients had UD of which 1.9 (0.9-3.4) million died. These represented 21.1% (13.4%-30.1%) of all COVID-19 hospitalisations and 30.5% (14.3%-55.5%) of all COVID-19 deaths in these countries. Based on modelling estimates, if these populations had been diagnosed for diabetes prior to the COVID-19 pandemic, 1.7% (-3.0% to 5.9%) of COVID-19 hospitalisations and 5.0% (-0.9% to 14.1%) of COVID-19 deaths could have been prevented, and 1.8 (-0.3 to 5.0) million quality-adjusted life years gained. Interpretation: Our findings suggest that undiagnosed diabetes contributed substantially to COVID-19 hospitalisations and deaths in many LMICs. Funding: This work was supported, in part, by the Bill & Melinda Gates Foundation [INV-029062] and FIND.

Antimicrobial resistance and the great divide: inequity in priorities and agendas between the Global North and the Global South threatens global mitigation of antimicrobial resistance.

To limit the catastrophic effects of the increasing bacterial resistance to antimicrobials on health, food, environmental, and geopolitical security, and ensure that no country or region is left behind, a coordinated global approach is required. In this Viewpoint, we argue that the diverging resource availabilities, needs, and priorities of the Global North and the Global South in terms of the actions required to mitigate the antimicrobial resistance pandemic are a direct threat to success. We argue that evidence suggests a need to prioritise and support infection prevention interventions (ie, clean water and safe sanitation, increased vaccine coverage, and enhanced infection prevention measures for food production in the Global South contrary to the focus on research and development of new antibiotics in the Global North) and to recalibrate global funding resources to address this need. We call on global leaders to redress the current response, which threatens mitigation of the antimicrobial resistance pandemic.

The Tokyo 2020 and Beijing 2022 Olympic Games held during the COVID-19 pandemic: planning, outcomes, and lessons learnt.

The COVID-19 pandemic profoundly affected all mass gatherings for sporting and religious events, causing cancellation, postponement, or downsizing. On March 24, 2020, the Japanese Government, the Tokyo Organising Committee of the Olympic and Paralympic Games, and the International Olympic Committee decided to postpone the Tokyo 2020 Olympic and Paralympic Games until the summer of 2021. With the emergence of SARS-CoV-2, the potential creation of a superspreading event that would overwhelm the Tokyo health system was perceived as a risk. Even with a delayed start date, an extensive scale of resources, planning, risk assessment, communication, and SARS-CoV-2 testing were required for the Games to be held during the COVID-19 pandemic. The effectiveness of various mitigation and control measures, including the availability of vaccines and the expansion of effective testing options, allowed event organisers and the Japanese Government to successfully host the rescheduled 2020 Tokyo Olympic Games from July 23 to Aug 8, 2021 with robust safety plans in place. In February and March, 2022, Beijing hosted the 2022 Winter Olympic Games as scheduled, built on the lessons learnt from the Tokyo Games, and developed specific COVID-19 countermeasure plans in the context of China's national framework for the plan called Zero COVID. Results from the testing programmes at both the Tokyo and Beijing Games show that the measures put in place were effective at preventing the spread of COVID-19 within the Games, and ensured that neither event became a COVID-19-spreading event. The extensive experience from the Tokyo and Beijing Olympic Games highlights that it is possible to organise mass gatherings during a pandemic, provided that appropriate risk assessment, risk mitigation, and risk communication arrangements are in place, leaving legacies for future mass gatherings, public health, epidemic preparedness, and wider pandemic response.

Understanding the value of biobank attributes to researchers using a conjoint experiment.

Biobanks are important in biomedical and public health research, and future healthcare research relies on their strength and capacity. However, there are financial challenges related to the operation of commercial biobanks and concerns around the commercialization of biobanks. Non-commercial biobanks depend on grant funding to operate and could be valuable to researchers if they can enable access to quality specimens at lower costs. The objective of this study is to estimate the value of specific biobank attributes. We used a rating-based conjoint experiment approach to study how researchers valued handling fee, access, quality, characterization, breadth of consent, access to key endemics, and time taken to fulfil requests. We found that researchers placed the greatest relative importance on the quality of specimens (26%), followed by the characterization of specimens (21%). Researchers with prior experience purchasing biological samples also valued access to key endemic in-country sites (11.6%) and low handling fees (5.5%) in biobanks.

Response to antimicrobial resistance in South-East Asia Region.

Antimicrobial resistance (AMR) inflicts significant mortality, morbidity and economic loss in the 11 countries in the WHO South-East Asia Region (SEAR). With technical assistance and advocacy from WHO, all countries have developed their respective National Action Plans on AMR that are aligned with the Global Action Plan. Historically, the WHO Regional Office has been proactive in advocacy at the highest political level. The past decade has seen an enhancement of the country's capacity to combat AMR through national efforts catalyzed and supported through several WHO initiatives at all levels-global, regional and country levels. Several countries including Bangladesh, India, Indonesia, Nepal, Sri Lanka and Thailand have observed a worrying trend of increasing drug resistance, despite heightened awareness and actions. Recent AMR data generated by the countries are indicative of fragmented progress. Lack of technical capacity, financial resources, weak regulatory apparatus, slow behavioural changes at all levels of the antimicrobial stewardship landscape and the COVID-19 pandemic have prevented the effective application of several interventions to minimize the impact of AMR.

Coupled models of genomic surveillance and evolving pandemics with applications for timely public health interventions.

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population.

Modeling of malaria vaccine effectiveness on disease burden and drug resistance in 42 African countries.

BACKGROUND: The emergence of antimalarial drug resistance poses a major threat to effective malaria treatment and control. This study aims to inform policymakers and vaccine developers on the potential of an effective malaria vaccine in reducing drug-resistant infections. METHODS: A compartmental model estimating cases, drug-resistant cases, and deaths averted from 2021 to 2030 with a vaccine against Plasmodium falciparum infection administered yearly to 1-year-olds in 42 African countries. Three vaccine efficacy (VE) scenarios and one scenario of rapidly increasing drug resistance are modeled. RESULTS: When VE is constant at 40% for 4 years and then drops to 0%, 235.7 (Uncertainty Interval [UI] 187.8-305.9) cases per 1000 children, 0.6 (UI 0.4-1.0) resistant cases per 1000, and 0.6 (UI 0.5-0.9) deaths per 1000 are averted. When VE begins at 80% and drops 20 percentage points each year, 313.9 (UI 249.8-406.6) cases per 1000, 0.9 (UI 0.6-1.3) resistant cases per 1000, and 0.9 (UI 0.6-1.2) deaths per 1000 are averted. When VE remains 40% for 10 years, 384.7 (UI 311.7-496.5) cases per 1000, 1.0 (0.7-1.6) resistant cases per 1000, and 1.1 (UI 0.8-1.5) deaths per 1000 are averted. Assuming an effective vaccine and an increase in current levels of drug resistance to 80% by 2030, 10.4 (UI 7.3-15.8) resistant cases per 1000 children are averted. CONCLUSIONS: Widespread deployment of a malaria vaccine could substantially reduce health burden in Africa. Maintaining VE longer may be more impactful than a higher initial VE that falls rapidly.

Malaria can become resistant to the drugs used to treat it, posing a major threat to malaria treatment and control. An effective vaccine has the potential to reduce both resistant infections and antimalarial drug use. However, how successfully a vaccine can protect against infection (vaccine efficacy) and the impact of increasing drug resistance remain unclear. Using a mathematical model, we estimate the impact of malaria vaccination in 42 African countries over a 10-year period in multiple scenarios with differing vaccine efficacy and drug resistance. Our model suggests that a moderately effective vaccine with sustained protection over a long period could avert more resistant infections and deaths than a vaccine that is highly protective initially but lowers in efficacy over time. Nevertheless, implementation of an effective malaria vaccine should be accelerated to mitigate the health and economic burden of drug resistance.

Global patterns and correlates in the emergence of antimicrobial resistance in humans.

Antimicrobial resistance (AMR) is a critical global health threat, and drivers of the emergence of novel strains of antibiotic-resistant bacteria in humans are poorly understood at the global scale. We examined correlates of AMR emergence in humans using global data on the origins of novel strains of AMR bacteria from 2006 to 2017, human and livestock antibiotic use, country economic activity and reporting bias indicators. We found that AMR emergence is positively correlated with antibiotic consumption in humans. However, the relationship between AMR emergence and antibiotic consumption in livestock is modified by gross domestic product (GDP), with only higher GDP countries showing a slight positive association, a finding that differs from previous studies on the drivers of AMR prevalence. We also found that human travel may play a role in AMR emergence, likely driving the spread of novel AMR strains into countries where they are subsequently detected for the first time. Finally, we used our model to generate a country-level map of the global distribution of predicted AMR emergence risk, and compared these findings against reported AMR emergence to identify gaps in surveillance that can be used to direct prevention and intervention policies.

Early Discontinuation of Antibiotics in Patients Admitted With Clinically Suspected Serious Infection but Negative Cultures: Retrospective Cohort Study of Practice Patterns and Outcomes at 111†US Hospitals.

Background: The optimal duration for antibiotics in patients hospitalized with culture-negative serious infection (CNSI) is unknown. We compared outcomes in patients with CNSI treated with 3 or 4 vs ≥5 days of antibiotics. Methods: CNSI was identified among adults admitted to 111 US hospitals between 2009 and 2014 via electronic health record data, defined as suspected serious infection (blood cultures drawn and ≥3 days of antibiotics) and negative culture- and nonculture-based tests for infection. Patients treated with antibiotics on their last hospital day and patients with diagnosis codes for sepsis-mimicking conditions were excluded. Among patients without fevers/hypothermia or vasopressors by day 3, we calculated odds ratios for in-hospital mortality or discharge to hospice associated with 3 or 4 vs ≥5 days of antibiotics, adjusting for confounders. Results: Antibiotics were discontinued in 3 or 4 days in 1862 (9%) of 20 714 patients with CNSI. Early discontinuation was not associated with higher mortality odds overall (adjusted odds ratio [aOR], 1.27; 95% CI, .98-1.65), in patients presenting with (1.39; .88-2.22) and without sepsis (1.17; .81-1.69), and in those with pulmonary (1.23; .65-2.34) and nonpulmonary CNSI (1.30; .99-1.72). Early discontinuation appeared detrimental with propensity score weighting (aOR, 1.36; 95% CI, 1.03-1.80) and when retaining patients with sepsis mimics (1.38; 1.16-1.65), but it was protective (0.48; .37-.64]) when retaining patients who received antibiotics on their last hospital day. Conclusions: Early discontinuation of antibiotics in CNSI was not associated with significant harm in our primary analysis, but different conclusions based on alternative analytic decisions, as well as risk of residual confounding, indicate that randomized controlled trials are needed.

Attributed causes of excess mortality during the COVID-19 pandemic in a south Indian city.

Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India-an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27-33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0-13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.

Global incidence in hospital-associated infections resistant to antibiotics: An analysis of point prevalence surveys from 99 countries.

BACKGROUND: Hospital-associated infections (HAIs) are an important cause of morbidity and mortality around the world. Many HAIs are caused by drug-resistant bacterial pathogens, but there are major gaps in our understanding of the number of hospital-associated drug-resistant infections (HARIs) worldwide. As such, we estimated trends in prevalence of HARIs caused by high priority pathogens (Escherichia coli, Acinetobacter spp., Klebsiella spp., Staphylococcus aureus, Enterobacter spp., and Pseudomonas spp.) in 195 countries. METHODS AND FINDINGS: Resistance prevalence estimates were extracted from 474-point prevalence surveys (PPS) from 99 countries published between 2010 and 2020 coupled with country-level estimates of hospitalization rates and length of stay. Prevalence estimates were transformed in yearly incidence of HARIs per year by country and income group. We estimate the global number of HARIs per year to be 136 million (95% credible interval (CI) 26 to 246 million) per year, with the highest burden in China (52 million, 95% CI 10 to 95 million), Pakistan (10 million, 95% CI 2 to 18 million), and India (9 million, 95% CI 3 to 15 million). Among income groups, middle-income countries bore the highest burden of HARIs per year (119 million, 95% CI 23 to 215 million). Our analysis was constrained by the limited number of PPS for HARIs, lack of community-associated data on antibiotic-resistant infections, and our population level analysis. CONCLUSIONS: In this study, we observe, in the absence of systematic surveillance systems for HARIs, a baseline overview of their rates. Our yearly estimates highlight the global threat of HARIs and may help define strategies to tackle resistance in hospital settings.

Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis.

BACKGROUND: Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. METHODS AND FINDINGS: We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. CONCLUSIONS: A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

Global antimicrobial-resistance drivers: an ecological country-level study at the human-animal interface.

BACKGROUND: Antimicrobial resistance (AMR) is a pressing, holistic, and multisectoral challenge facing contemporary global health. In this study we assessed the associations between socioeconomic, anthropogenic, and environmental indicators and country-level rates of AMR in humans and food-producing animals. METHODS: In this modelling study, we obtained data on Carbapenem-resistant Acinetobacter baumanii and Pseudomonas aeruginosa, third generation cephalosporins-resistant Escherichia coli and Klebsiella pneumoniae, oxacillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium AMR in humans and food-producing animals from publicly available sources, including WHO, World Bank, and Center for Disease Dynamics Economics and Policy. AMR in food-producing animals presented a combined prevalence of AMR exposure in cattle, pigs, and chickens. We used multivariable ß regression models to determine the adjusted association between human and food-producing animal AMR rates and an array of ecological country-level indicators. Human AMR rates were classified according to the WHO priority pathogens list and antibiotic-bacterium pairs. FINDINGS: Significant associations were identified between animal antimicrobial consumption and AMR in food-producing animals (OR 1·05 [95% CI 1·01-1·10]; p=0·013), and between human antimicrobial consumption and AMR specifically in WHO critical priority (1·06 [1·00-1·12]; p=0·035) and high priority (1·22 [1·09-1·37]; p<0·0001) pathogens. Bidirectional associations were also found: animal antibiotic consumption was positively linked with resistance in critical priority human pathogens (1·07 [1·01-1·13]; p=0·020) and human antibiotic consumption was positively linked with animal AMR (1·05 [1·01-1·09]; p=0·010). Carbapenem-resistant Acinetobacter baumanii, third generation cephalosporins-resistant Escherichia coli, and oxacillin-resistant Staphylococcus aureus all had significant associations with animal antibiotic consumption. Analyses also suggested significant roles of socioeconomics, including governance on AMR rates in humans and animals. INTERPRETATION: Reduced rates of antibiotic consumption alone will not be sufficient to combat the rising worldwide prevalence of AMR. Control methods should focus on poverty reduction and aim to prevent AMR transmission across different One Health domains while accounting for domain-specific risk factors. The levelling up of livestock surveillance systems to better match those reporting on human AMR, and, strengthening all surveillance efforts, particularly in low-income and middle-income countries, are pressing priorities. FUNDING: None.

COVID-19 and Outpatient Antibiotic Prescriptions in the United States: A County-Level Analysis.

Background: Declines in outpatient antibiotic prescribing were reported during the beginning of the coronavirus disease 2019 (COVID-19) pandemic in the United States; however, the overall impact of COVID-19 cases on antibiotic prescribing remains unclear. Methods: This was an ecological study using random-effects panel regression of monthly reported COVID-19 county case and antibiotic prescription data, controlling for seasonality, urbanicity, health care access, nonpharmaceutical interventions (NPIs), and sociodemographic factors. Results: Antibiotic prescribing fell 26.8% in 2020 compared with prior years. Each 1% increase in county-level monthly COVID-19 cases was associated with a 0.009% (95% CI, 0.007% to 0.012%; P < .01) increase in prescriptions per 100 000 population dispensed to all ages and a 0.012% (95% CI, -0.017% to -0.008%; P < .01) decrease in prescriptions per 100 000 children. Counties with schools open for in-person instruction were associated with a 0.044% (95% CI, 0.024% to 0.065%; P < .01) increase in prescriptions per 100 000 children compared with counties that closed schools. Internal movement restrictions and requiring facemasks were also associated with lower prescribing among children. Conclusions: The positive association of COVID-19 cases with prescribing for all ages and the negative association for children indicate that increases in prescribing occurred primarily among adults. The rarity of bacterial coinfection in COVID-19 patients suggests that a fraction of these prescriptions may have been inappropriate. Facemasks and school closures were correlated with reductions in prescribing among children, possibly due to the prevention of other upper respiratory infections. The strongest predictors of prescribing were prior years' prescribing trends, suggesting the possibility that behavioral norms are an important driver of prescribing practices.