Tuberculosis in Poland in 2020.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2020 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2020, data from Statistics Poland on deaths from tuberculosis in 2019, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2020 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2020, 3,388 TB cases were reported in Poland. The incidence rate was 8.8 cases per 100,000 with large variability between voivodeships from 5.5 to 13.3 per 100,000. A decrease in the incidence was found in 15 voivodeships, the most significant in Slaskie voivodship (63.9%). The number of all pulmonary tuberculosis cases was 3,237 i.e. 8.4 per 100,000. Pulmonary cases represented 95.5% of all TB cases. In 2020, 151 extrapulmonary TB cases were notified (4.5% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,573 cases (79.5% of all pulmonary TB cases, the incidence rate 6.7 per 100,000). The number of smear-positive pulmonary TB cases was 1,771 i.e. 4.6 per 100,000 (54.7% of all pulmonary TB cases). In 2020, there were 38 cases (15 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.6% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with increasing age from 0.7 per 100,000 among children (0-14 years) to 15.0 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 12.1 per 100,000. There were 39 cases in children up to 14 years of age (1.2% of the total) and 49 cases in adolescents between 15 and 19 years of age - rates 0.7 and 2.7 per 100,000 respectively. In 2020, there were 2,506 cases of tuberculosis in men and 882 in women. The TB incidence in men - 13.5 per 100,000 was 3.0 times higher than among women - 4.5. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 50-54 years - 26.8 vs. 4.1 and in age group 55 to 59 years - 28.7 vs. 4.8. In 2020, there were 116 patients of foreign origin among all cases of tuberculosis in Poland (3.4%). In 2019, TB was the cause of death for 456 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: TB incidence in Poland in 2020 was 36.7% lower than in 2019. Such significant declines in the incidence have not been observed in the last two decades. As in previous years, there were differences in incidence rates between voivodeships with an unexpectedly sharp decrease in incidence in Silesia (Slaskie voivodeship). The percentage of tuberculosis cases with bacteriological confirmation exceeded 78%, more than in EU/EEA countries (67.3%). The percentage of MDR-TB cases was still lower than the average in EU/EEA countries (1.6% vs. 3.8%). The highest incidence rates were found in Poland in the older age groups (EU/EEAaged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.2%, less than the average in EU/EEA countries (3.8%). The incidence of tuberculosis in men was three times higher than in women in Poland, and six times higher in patients aged 50 to 59. The impact of migration on the TB pattern in Poland has not yet become significant in 2020. The percentage of foreigners among TB patients was 3.4% (33% in EU/EEA countries).

Role of non-coding RNAs in tuberculosis and their potential for clinical applications.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of mortality due to infectious diseases, only surpassed in 2020 by COVID-19. Despite the development in diagnostics, therapeutics, and evaluation of new vaccines for TB, this infectious disease remains uncontrollable due to the emergence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) TB, among other factors. The development in transcriptomics (RNomics) has enabled the study of gene expression in TB. It is considered that non-coding RNAs (ncRNAs) from host [microRNAs (miRNAs)] and Mtb [small RNAs (sRNAs)] are important elements in TB pathogenesis, immune resistance, and susceptibility. Many studies have shown the importance of host miRNAs in regulating immune response against Mtb via in vitro and in vivo mice models. The bacterial sRNAs play a major role in survival, adaptation, and virulence. Here, we review the characterization and function of host and bacteria ncRNAs in TB and their potential use in clinical applications as diagnostic, prognostic, and therapeutic biomarkers.

Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study.

OBJECTIVES: Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. METHODS: TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). RESULTS: Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. CONCLUSIONS: A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.

Current therapeutic delivery approaches using nanocarriers for the treatment of tuberculosis disease.

Tuberculosis is a major health issue globally and a leading cause of death due to the infective microorganism Mycobacterium tuberculosis. Treatment of drug resistance tuberculosis requires longer treatment with multiple daily doses of drugs. Unfortunately, these drugs are often associated with poor patient compliance. In this situation, a need has been felt for the less toxic, shorter, and more effective treatment of the infected tuberculosis patients. Current research to develop novel anti-tubercular drugs shows hope for better management of the disease. Research on drug targeting and precise delivery of the old anti-tubercular drugs with the help of nanotechnology is promising for effective treatment. This review has discussed the status currently available treatments for tuberculosis patients infected with Mycobacterium alone or in comorbid conditions like diabetes, HIV and cancer. This review also highlighted the challenges in the current treatment and research on the novel anti-tubercular drugs to prevent multi-drug-resistant tuberculosis. It presents the research highlights on the targeted delivery of anti-tubercular drugs using different nanocarriers for preventing multi-drug resistant tuberculosis. Report has shown the importance and development of the research on nanocarriers mediated anti-tubercular delivery of the drugs to overcome the current challenges in tuberculosis treatment.

Tuberculosis infection prevention and control in rural Papua New Guinea: an evaluation using the infection prevention and control assessment framework.

BACKGROUND: Papua New Guinea (PNG) is one of the 14 countries categorised as having a triple burden of tuberculosis (TB), multidrug-resistant TB (MDR TB), and TB-human immunodeficiency virus (HIV) co-infections. TB infection prevention and control (TB-IPC) guidelines were introduced in 2011 by the National Health Department of PNG. This study assesses the implementation of this policy in a sample of district hospitals in two regions of PNG. METHODS: The implementation of TB-IPC policy was assessed using a survey method based on the World Health Organization (WHO) IPC assessment framework (IPCAF) to implement the WHO's IPC core components. The study included facility assessment at ten district hospitals and validation observations of TB-IPC practices. RESULTS: Overall, implementation of IPC and TB-IPC guidelines was inadequate in participating facilities. Though 80% of facilities had an IPC program, many needed more clearly defined IPC objectives, budget allocation, and yearly work plans. In addition, they did not include senior facility managers in the IPC committee. 80% (n = 8 of 10) of hospitals had no IPC training and education; 90% had no IPC committee to support the IPC team; 70% had no surveillance protocols to monitor infections, and only 20% used multimodal strategies for IPC activities. Similarly, 70% of facilities had a TB-IPC program without a proper budget and did not include facility managers in the TB-IPC team; 80% indicated that patient flow poses a risk of TB transmission; 70% had poor ventilation systems; 90% had inadequate isolation rooms; and though 80% have personal protective equipment available, frequent shortages were reported. CONCLUSIONS: The WHO-recommended TB-IPC policy is not effectively implemented in most of the participating district hospitals. Improvements in implementing and disseminating TB-IPC guidelines, monitoring TB-IPC practices, and systematic healthcare worker training are essential to improve TB-IPC guidelines' operationalisation in health settings to reduce TB prevalence in PNG.

Retaining Patients with Drug-Resistant Tuberculosis on Treatment During the COVID-19 Pandemic - Dharavi, Mumbai, India, 2020-2022.

Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum†; historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies.

Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa.

BACKGROUND: Updated World Health Organization (WHO) treatment guidelines prioritize all-oral drug-resistant tuberculosis (DR-TB) regimens. Several poorly tolerated drugs, such as amikacin and para-aminosalicylic acid (PAS), remain treatment options for DR-TB in WHO-recommended longer regimens as Group C drugs. Incomplete treatment with anti-TB drugs increases the risk of treatment failure, relapse, and death. We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. METHODS: We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. RESULTS: Among 242 patients, 131 (54%) were male, 97 (40%) were living with HIV, 175 (72%) received second-line treatment prior to first hospitalization, and 191 (79%) died during the study period. At initial hospitalization, 134 (55%) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]) without resistance to ofloxacin or amikacin, and 102 (42%) had resistance to ofloxacin and/or amikacin. Most patients (129 [53%]) had multiple hospitalizations and DST changes occurred in 146 (60%) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18%), capreomycin (18%), PAS (17%) and kanamycin (16%) than other DR-TB drugs (P<0.001), including ethionamide (8%), moxifloxacin (7%), terizidone (7%), ethambutol (7%), and pyrazinamide (6%). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56-1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51-0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. CONCLUSION: We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.

Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets.

Mycobacterium tuberculosis (M. tb), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host's immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) M. tb strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB-the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years-reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the M. tb pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in M. tb.

Progress on diagnosis and treatment of drug-resistant tuberculosis in line with World Health Organization recommendations in six priority countries in the Western Pacific Region.

Background: Diagnosis and treatment of drug-resistant tuberculosis (DR-TB) have radically changed in accordance with recommendations from the World Health Organization (WHO) in the past decade, allowing rapid and simple diagnosis and shorter treatment duration with new and repurposed drugs. Methods: A descriptive analysis of the status and progress of DR-TB diagnosis and treatment in six priority countries in the Western Pacific Region was conducted using information from interviews with countries and the WHO TB database. Results: Over the past decade, the use of Xpert MTB/RIF has increased in the six priority countries, in parallel with implementation of national policies and algorithms to use Xpert MTB/RIF as an initial diagnostic test for TB and detection of rifampicin resistance. This has resulted in increases in the number of people diagnosed with multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB). Shorter treatment regimens with new and repurposed drugs have also been adopted for MDR/RR-TB cases, alongside a decentralized model of care, leading to improved treatment outcomes. Discussion: The Western Pacific Region has achieved considerable progress in the diagnosis and treatment of DR-TB, in line with the evolving WHO recommendations in the past decade. The continued commitment of Member States is needed to address remaining challenges, such as the impact of the coronavirus disease pandemic, suboptimal management and health system issues.

Challenges of diabetes in elderly TB patients.

Diabetes mellitus (DM) and tuberculosis (TB) are worldwide health burdens post-COVID-19. TB is the second-leading cause of death by a single infectious microbe. There is much evidence around the world about the responsibility of TB-DM co-morbidity. Both TB and DM prevalence is high in low- and middle-income countries. Especially the elderly with diabetes are more prone to TB infection due to compromised immune systems. Diabetic patients are three times as likely to develop tuberculosis as non-diabetic patients. DM interferes with the status of TB and leads to undesirable outcomes in the treatment of TB. This may later lead to the development of multidrug-resistant tuberculosis (MDR-TB). The coexistence of TB and DM leads to a high mortality rate and therefore becomes an enormous challenge for the medical field. This viewpoint includes the most current information about TB and DM, disease complications, treatment strategies, challenges to be faced in disease management and the importance of TB-DM bidirectional screening in older adults, which helps in early detection and better treatment programme.

Exploring the Impact of the COVID-19 Pandemic on Tuberculosis Care and Prevention.

The COVID-19 pandemic has set back the global tuberculosis (TB) response by several years. In 2020, access to TB prevention and care declined sharply, with TB notifications dropping by 18% compared to 2019. Declines were more pronounced in children, with a 24% drop in 0-14 year-olds and a 28% drop in 0-4 year-olds. As a result, in 2020 the number of deaths due to TB increased to 1.5 million across all ages, reversing a decade-long declining trend. Progress toward the UN High Level Meeting targets for 2022 is at risk, including the targets related to children for TB and drug-resistant TB treatments, and TB preventive therapy. Nonetheless, ending TB by 2030 as envisaged in the Sustainable Development Goals (SDGs) is still possible, but requires increased investments in accelerated case detection, subclinical TB, preventive therapy and an effective vaccine. Investing in TB could prepare the world better for fighting a future airborne pandemic.

Impact of COVID-19 on selected essential public health services – lessons learned from a retrospective record review in the Free State, South Africa (preprint)

Background In an attempt to discern lessons to improve future pandemic responses, this study measured the effects of the COVID-19 pandemic on essential public health services (EPHSs) related to primary health care (PHC) and outpatient department (OPD) utilisation, antiretroviral treatment (ART) commencement, drug-susceptible tuberculosis (DS-TB) confirmation and treatment commencement, and Bacillus Calmette-Guérin (BCG) coverage, in the Free State province of South Africa during January 2019 to March 2021. Methods A pre-post study design comparing EPHS performance between 2019 and 2020/21 was employed. Routinely collected data were analysed. An interrupted time series analysis was used to measure changes in service use and outcomes from January 2019 to March 2021. Median changes were compared using Wilcoxon sign ranked tests. A 5% statistical significance level was considered Results Over the study period, the median values for the annual number of PHC visits was 1.8, 55.3% for unreferred OPD visits, 69.4% for ART commencement, 95.1% and 18.7% for DS-TB confirmation and treatment commencement respectively, and 93.7% for BCG coverage. While BCG coverage increased by 5.85% (p=0.0101), declines were observed in PHC utilisation (10.53%; p=0.0010), unreferred OPD visits (12.05%; p=0.0006), ART commencement (9.53%; p=0.0174), and DS-TB confirmation (5.24%; p≥0.050) and treatment commencement (3.80%; p≥0.050). Given the importance of PHC in addressing a new pandemic, along with the existing HIV and TB epidemics – as well as the entire quadruple burden of disease – in South Africa, the finding that the PHC utilisation rate statistically significantly decreased in the Free State post-COVID-19 commencement is particularly concerning. Conclusions The lessons learned from this retrospective review attest to a measure of resilience in EPHS delivery in the Free State in as far as a significant hike in BCG vaccination over the study period, 2019-2020/21 was observed. As evidenced by a declines in PHC service utilisation, the decreased numbers of new patients commencing ART and lower confirmed DS-TB case and DS-TB treatment commencement rates, we also learned that EPHS delivery in the province was fragile.

Coping with drug resistant tuberculosis alongside COVID-19 and other stressors in Zimbabwe: a qualitative study. (preprint)

Background Households in low-resource settings are more vulnerable to events which adversely affect their livelihoods, including shocks such as the death of a family member, inflation, droughts and more recently COVID-19. Drug Resistant Tuberculosis (DR-TB) is also another shock that inflicts physical, psychological and socioeconomic burden on individuals and households. We describe experiences and coping strategies among people affected by DR-TB and their households in Zimbabwe during the COVID-19 pandemic, 2020 to 2021. Methods We conducted 16 in-depth interviews with adults who had just completed or were completing DR-TB treatment. Interview themes included health seeking behaviour, impact of DR-TB on livelihoods and coping strategies adopted during treatment. We analysed data using thematic analysis. Results Health seeking from providers outside the public sector, extra-pulmonary TB and health system factors resulted in delayed DR-TB diagnosis and treatment and increased financial drain on households. DR-TB reduced productive capacity and narrowed job opportunities leading to income loss that continued even after completion of treatment. Household livelihood was further adversely affected by lockdowns due to COVID-19, outbreaks of bird flu and cattle disease. Stockouts of DR-TB medicines, common during COVID-19, exacerbated loss of productive time and transport costs as medication had to be accessed from other clinics that were further away. Reversible coping strategies included: reducing number of meals; relocating in search of caregivers and/or family support; spending savings; negotiating with school authorities to keep children in school. Some households had to adopt irreversible coping strategies such as selling productive assets and withdrawing children from school. Conclusion DR-TB combined with COVID-19 and other stressors pushed households into deeper poverty, and vulnerability. Multi-sectoral approaches that combine health systems, psychosocial and economic interventions are crucial to mitigate diagnostic delays and suffering, and meaningfully support people with DR-TB and their households to compensate the loss of livelihoods during and post DR-TB treatment.

Tuberculosis in the Russian Federation: Prognosis and Epidemiological Models in a Situation After the COVID-19 Pandemic.

AIM: Because of the COVID-19 pandemic, many support programs for tuberculosis (TB) patients have been discontinued and TB mass screening activities decreased worldwide, resulting in a decrease in new case detection and an increase in TB deaths (WHO, WHO global lists of high burden countries for TB, multidrug/rifampicin-resistant TB (MDR/RR-TB) and TB/HIV, 2021-2025, 2021). The study aimed to assess changes in epidemiological indicators of tuberculosis in the Russian Federation and to simulate these indicators in the post-COVID-19 period. MATERIALS AND METHODS: The main epidemiological indicators of tuberculosis were analyzed with the use of government statistical data for the period from 2009 to 2021. Further mathematical modeling of epidemiological indicators for the coming years was carried out, taking into account the TB screening by chest X-ray. Statistical analysis was carried out using the software environment R (v.3.5.1) for statistical computing and the commercial software Statistical Package for the Social Sciences (SPSS Statistics for Windows, version 24.0, IBM Corp., 2016). Time series forecasting was performed using the programming language for statistical calculations R, version 4.1.2 and the bsts package, version 0.9.8. STUDY RESULTS: The study has found that the mean regression coefficient of a single predictor differs in the model for TB incidence and mortality (0.0098 and 0.0002, respectively). Forecast of overall incidence, the incidence of children and the forecast for mortality using the basic scenario (screening 75-78%) for the period from 2022 to 2026 was characterized by a mean decrease rate of 23.1%, 15.6% and 6.0% per year, respectively. A conservative scenario (screening 47-63%) of overall incidence indicates that the incidence of children and the forecast for mortality will continue to decrease with a mean decrease rate of 23.2%, 15.6% and 6.0% per year, respectively. Comparable data were obtained from the forecast of overall incidence, the incidence of children and the forecast for mortality using the optimistic scenario (screening 82-89%) with a mean decrease rate of 22.9%, 15.4% and 6.0% per year, respectively. CONCLUSIONS: It has been proven that the significance of screening with chest X-ray as a predictor of mortality is minimal. However, TB screening at least 60% of the population (chest X-ray in adults and immunological tests in children) have provided relationship between the TB screening rate and TB mortality rate (TB mortality rate increases with an increase in the population coverage and, conversely, decreases with a decrease in the population coverage).

Association of SARS-CoV-2 status and antimicrobial-resistant bacteria with inadequate empiric therapy in hospitalized patients: a US multicenter cohort evaluation (July 2019 - October 2021) (preprint)

Background: Antibiotic usage and antimicrobial resistance (AMR) patterns changed during the COVID-19 pandemic. Inadequate empiric antibiotic therapy (IET) is a significant public health problem and contributes to AMR. We evaluated factors associated with IET before and during the COVID-19 pandemic to determine the impact of the pandemic on antibiotic management. Methods: This multicenter, retrospective cohort analysis included hospitalized US adults who had a positive bacterial culture (specified gram-positive or gram-negative bacteria) from July 2019 to October 2021 in the BD Insights Research Database. IET was defined as antibacterial therapy within 48 hours that was not active against the pathogen. AMR results were based on facility reports. Multivariate analysis was used to identify risk factors associated with IET in patients with any positive bacterial culture and AMR-positive cultures, including multidrug-resistant (MDR) pathogens. Results:Of 278,344 eligible patients in 269 hospitals, 56,733 (20.4%) received IET; rates were higher in patients with AMR-positive (n=93,252) or MDR-positive (n=39,000) cultures (34.9% and 45.0%, respectively). Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients had significantly higher rates of IET (25.9%) compared with SARS-CoV-2-negative (20.3%) or not tested (19.7%) patients overall and in the AMR and MDR subgroups. Patients with AMR- or MDR-positive cultures had more days of therapy and longer lengths of stay. In multivariate analyses, AMR, MDR, SARS-CoV-2-positive status, respiratory source, and prior admissions were identified as key IET risk factors. Conclusions: IET remained a persistent problem during the COVID-19 pandemic and occurred at higher rates in patients with AMR/MDR bacteria or a co-SARS-CoV-2 infection.