The impact of the COVID-19 pandemic on antibiotic consumption and prevalence of pathogens in primary and secondary healthcare settings in Northern Ireland.

AIM: To evaluate the impact of the COVID-19 pandemic on the patterns of antimicrobial use and the incidence of pathogens in primary and secondary healthcare settings in Northern Ireland. METHODS: Data were collected on antibiotic use and Gram-positive and Gram-negative pathogens from primary and secondary healthcare settings in Northern Ireland for the period before (January 2015-March 2020) and during (April 2020-December 2021) the pandemic. Time series intervention analysis methods were utilized. RESULTS: In the hospital setting, the mean total hospital antibiotic consumption during the pandemic was 1864.5 defined daily doses (DDDs) per 1000 occupied-bed days (OBD), showing no significant change from pre-pandemic (P = .7365). During the pandemic, the use of second-generation cephalosporins, third-generation cephalosporins, co-amoxiclav and levofloxacin increased, there was a decrease in the percentage use of the hospital Access group (P = .0083) and an increase in the percentage use of Watch group (P = .0040), and the number of hospital Klebsiella oxytoca and methicillin-susceptible Staphylococcus aureus cases increased. In primary care, the mean total antibiotic consumption during the COVID-19 pandemic was 20.53 DDDs per 1000 inhabitants per day (DID), compared to 25.56 DID before the COVID-19 pandemic (P = .0071). During the pandemic, there was a decrease in the use of several antibiotic classes, an increase in the percentage use of the Reserve group (P = .0032) and an increase in the number of community-onset Pseudomonas aeruginosa cases. CONCLUSION: This study provides details of both changes in antibiotic consumption and the prevalence of infections in hospitals and primary care before and during the COVID-19 pandemic that emphasize the importance of antimicrobial stewardship in pandemic situations.

Risk Factors Associated with Mortality in COVID-19 Hospitalized Patients: Data from the Middle East.

This study aimed to assess the risk factors for COVID-19 mortality among hospitalized patients in Jordan. All COVID-19 patients admitted to a tertiary hospital in Jordan from September 20, 2020, to August 8, 2021, were included in this study. Demographics, clinical characteristics, comorbidities, and laboratory results were extracted from the patients' electronic records. Multivariable logistic and machine learning (ML) methods were used to study variable importance. Out of 1,613 COVID-19 patients, 1,004 (62.2%) were discharged from the hospital (survived), while 609 (37.8%) died. Patients who were of elderly age (>65 years) (OR, 2.01; 95% CI, 1.28-3.16), current smokers (OR, 1.61; 95%CI, 1.17-2.23), and had severe or critical illness at admission ((OR, 1.56; 95%CI, 1.05-2.32) (OR, 2.94; 95%CI, 2.02-4.27); respectively), were at higher risk of mortality. Comorbidities including chronic kidney disease (OR, 2.90; 95% CI, 1.90-4.43), deep venous thrombosis (OR, 2.62; 95% CI, 1.08-6.35), malignancy (OR, 2.22; 95% CI, 1.46-3.38), diabetes (OR, 1.31; 95% CI, 1.04-1.65), and heart failure (OR, 1.51; 95% CI, 1.02-2.23) were significantly associated with increased risk of mortality. Laboratory abnormalities associated with mortality included hypernatremia (OR, 11.37; 95% CI, 4.33-29.81), elevated aspartate aminotransferase (OR, 1.81; 95% CI, 1.42-2.31), hypoalbuminemia (OR, 1.75; 95% CI, 1.37-2.25), and low platelets level (OR, 1.43; 95% CI, 1.05-1.95). Several demographic, clinical, and laboratory risk factors for COVID-19 mortality were identified. This study is the first to examine the risk factors associated with mortality using ML methods in the Middle East. This will contribute to a better understanding of the impact of the disease and improve the outcome of the pandemic worldwide.

Identification of thresholds in relationships between specific antibiotic use and carbapenem-resistant Acinetobacter baumannii (CRAb) incidence rates in hospitalized patients in Jordan.

BACKGROUND: Antibiotic resistance is a major threat to public health worldwide. The relationship between the intensity of antibiotic use and resistance might not be linear, suggesting that there might be a threshold of antibiotic use, beyond which resistance would be triggered. OBJECTIVES: To identify thresholds in antibiotic use, below which specific antibiotic classes have no significant measurable impact on the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb), but above which their use correlates with an increase in the incidence of CRAb. METHODS: The study took place at a tertiary teaching hospital in Jordan. The study was ecological in nature and was carried out retrospectively over the period January 2014 to December 2019. The outcome time series for this study was CRAb cases. The primary explanatory variables were monthly use of antibiotics and the use of alcohol-based hand rub (ABHR). Non-linear time-series methods were used to identify thresholds in antibiotic use. RESULTS: Non-linear time-series analysis determined a threshold in third-generation cephalosporin and carbapenem use, where the maximum use of third-generation cephalosporins and carbapenems should not exceed 8 DDD/100 occupied bed days (OBD) and 10 DDD/100 OBD, respectively. ABHR had a significant reducing effect on CRAb cases even at lower usage quantities (0.92 L/100 OBD) and had the most significant effect when ABHR exceeded 3.4 L/100 OBD. CONCLUSIONS: The identification of thresholds, utilizing non-linear time-series methods, can provide a valuable tool to inform hospital antibiotic policies through identifying quantitative targets that balance access to effective therapies with control of resistance. Further studies are needed to validate the identified thresholds, through being prospectively adopted as a target for antimicrobial stewardship programmes, and then to evaluate the impact on reducing CRAb incidence.

Impact of an antimicrobial stewardship programme on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistant Acinetobacter baumannii (CRAb) in hospitals in Jordan.

OBJECTIVES: To evaluate the impact of an antimicrobial stewardship programme (ASP) on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistant Acinetobacter baumannii (CRAb) in hospitalized patients. METHODS: The study was a retrospective, ecological assessment in a tertiary teaching hospital over 6 years (January 2014 to December 2019). The intervention involved the implementation of an ASP in February 2018, which remains in effect today. This ASP consists of several components, including education, antibiotic guidelines, antibiotic restriction policy with prior approval, audit of compliance to the restriction policy and feedback. Restricted antibiotics were imipenem/cilastatin, ertapenem, meropenem, vancomycin, teicoplanin, tigecycline, colistin, amikacin, piperacillin/tazobactam, levofloxacin and ciprofloxacin. The intervention was evaluated by time-series methods. RESULTS: Statistically significant decreases in the level of antibiotic use, after the introduction of the ASP, were observed for the following antibiotics: imipenem/cilastatin (P = 0.0008), all carbapenems (P = 0.0001), vancomycin (P = 0.0006), colistin (P = 0.0016) and third-generation cephalosporins (P = 0.0004). A statistically significant decrease in the slope, after the introduction of the ASP, for ertapenem (P = 0.0044) and ciprofloxacin (P = 0.0117) was observed. For piperacillin/tazobactam, there was a significant increasing trend (P = 0.0208) before the introduction of the ASP. However, this increased trend was halted post-introduction of the ASP (P = 0.4574). The introduction of the ASP was associated with a significant impact on reducing the levels of CRAb (P = 0.0237). CONCLUSIONS: The introduced antimicrobial stewardship interventions contributed to a reduction in the use of several broad-spectrum antibiotics, reversed the trends of increasing use of other antibiotics and were associated with a significant reduction in CRAb.

A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking.

OBJECTIVES: To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. METHODS: The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed-days and per 100 bed-days/age-adjusted comorbidity score. RESULTS: Results showed that antibiotic use had significant positive relationships with the sum of age-adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. CONCLUSIONS: The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects.

Antimicrobial consumption in an acute NHS Trust during the COVID-19 pandemic: intervention time series analysis.

Objective: To determine the impact of the COVID-19 pandemic on antimicrobial consumption and trends of therapeutic drugs for COVID-19 treatments, including corticosteroids, remdesivir and monoclonal antibodies (tocilizumab) from April 2017 to September 2022 in a secondary care NHS Trust in England. Methods: A retrospective intervention time series analysis was conducted for April 2017 to September 2022 at the Mid Yorkshire Teaching NHS Trust. Data were retrieved from the pharmacy dispensing system as defined daily doses (DDDs) monthly and reported per 1000 occupied bed days (OBDs). Antimicrobial consumption and COVID-19 treatment options were measured. DDDs were calculated according to the classification of antimicrobials for systemic use (J01) and for other drugs classification. Trends for antimicrobial consumption and other therapeutic drugs for treating COVID-19 were also determined in each wave in England. Results: During the pandemic: total antibiotic consumption decreased from 826.4 to 728.2 DDDs per 1000 OBDs (P = 0.0067); piperacillin/tazobactam use increased (P < 0.0001) and ciprofloxacin use decreased (P < 0.0001); there were no changes in Access, Watch, Reserve antibiotic use, and the proportion of antifungal consumption was consistent throughout the study. The use of total antibiotics (P = 0.024), levofloxacin (P = 0.0007), piperacillin/tazobactam (P = 0.0015) and co-amoxiclav (P = 0.0198) increased during wave one. Consumption of COVID-19 treatment drugs was highest during wave two, with 624.3 DDDs per 1000 OBDs for dexamethasone (P = 0.4441), 6.8 DDDs per 1000 OBDs for remdesivir (P < 0.0001) and 35.01 DDDs per 1000 OBDs for tocilizumab (P = 0.2544). Discussion: This study determined the consumption of antimicrobials trends before and during the pandemic. The individual wave antimicrobial consumption indicates maximum consumption in the first wave, advocating for antimicrobial stewardship and preparedness for future pandemics.

Identification of antibiotic consumption targets for the management of Clostridioides difficile infection in hospitals- a threshold logistic modelling approach.

BACKGROUND: This study aims to demonstrate the utility of a threshold logistic approach to identifying thresholds for specific antibiotic use associated with Clostridioides difficile infection (CDI) in an English teaching hospital. METHODS: 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-onset, healthcare-associated (HOHA) CDI cases. RESULTS: Using a threshold logistic regression approach, an incidence greater than 0.2645 cases/1000 occupied bed-days (OBD; 85th percentile) was determined as the cutoff rate to define a critical (high) incidence rate of HOHA CDI. Fluoroquinolones and piperacillin-tazobactam were found to have thresholds at 84.8 and 54 defined daily doses (DDD)/1000 OBD, respectively. Analysis of data allowed calculating risk scores for HOHA CDI incidence rates exceeding the 85th percentile, i.e. entering critical incidence level. The threshold-logistic model also facilitated performing 'what-if scenarios' on future values of fluoroquinolones and piperacillin-tazobactam use to understand how HOHA CDI incidence rates may be affected. CONCLUSION: Using threshold logistic analysis, critical incidence levels and antibiotic use targets to control HOHA CDI were determined. Threshold logistic models can be used to inform and enhance the effective design and implementation of antimicrobial stewardship programs.

Exploring thresholds and interaction effects among antibiotic usage, covariates, and their effect on antibiotic resistance using an extended-spectrum ß-Lactamase-producing Klebsiella pneumoniae case.

BACKGROUND: This study was aimed to explore thresholds with interaction effects among antibiotic usage, covariates (alcohol-based hand rub (ABHR)), and their effect on extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-producing K. pneumoniae) in hospitalized patients. METHODS: Multivariate Adaptive Regression Spline models were used. These considered second-order interactions among antibiotic use and ABHR in addition to potential thresholds that further improve explained variance in the ESBL-producing K. pneumoniae response. The study involved collecting monthly hospital-level data for January 2017-December 2021. RESULTS: Analysis of the main effects showed that third-generation cephalosporins above 2.00 DDD/100 occupied bed days (OBD) generally increased ESBL-producing K. pneumoniae incidence (cases/100 OBD). Levels of ABHR above 6.61 L/100 OBD were shown to generally decrease ESBL-producing K. pneumoniae incidence. Second-order interactions revealed that when third-generation cephalosporin use was greater than 3.71 DDD/100 OBD, and ABHR was greater than 6.6 L/100 OBD (same as main effect threshold), ABHR partially lost effectiveness in its ability to reduce ESBL-producing K. pneumoniae incidence. This demonstrates the importance of not exceeding the identified thresholds of 3.71 DDD/100 OBD for third-generation cephalosporin use. CONCLUSION: The main-effect thresholds in third-generation cephalosporins and ABHR, and the identified interaction between third-generation cephalosporins and ABHR can inform effective hospital antimicrobial stewardship.

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.

A Threshold Logistic Modelling Approach for Identifying Thresholds between Antibiotic Use and Methicillin-Resistant Staphylococcus aureus Incidence Rates in Hospitals.

The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also aimed to assess the impact of exceeding those thresholds that resulted in increased MRSA rates. The study was undertaken in a 700-bed hospital in England between January 2015 and December 2021 (84 monthly observations). By employing the threshold logistic modelling approach, we: (i) determined the cut-off percentile value of MRSA incidence that defines a critical level of MRSA; (ii) identified thresholds for fluoroquinolone and co-amoxiclav use that would accelerate MRSA incidence rates and increase the probability of reaching critical incidence levels; (iii) enabled a better understanding of the effect of antibiotic use on the probability of reaching a critical level of resistant pathogen incidence; (iv) developed a near real-time performance monitoring feedback system; (v) provided risk scores and alert signals for antibiotic use, with the ability to inform hospital policies, and control MRSA incidence; and (vi) provided recommendations and an example for the management of pathogen incidence in hospitals. Threshold logistic models can help hospitals determine quantitative targets for antibiotic usage and can also inform effective antimicrobial stewardship to control resistance in hospitals. Studies should work toward implementing and evaluating the proposed approach prospectively, with the aim of determining the best counter-measures to mitigate the risk of increased resistant pathogen incidence in hospitals.

Predictors of invasive mechanical ventilation in hospitalized COVID-19 patients: a retrospective study from Jordan.

OBJECTIVES: To identify early indicators for invasive mechanical ventilation utilization among COVID-19 patients. METHODS: This retrospective study evaluated COVID-19 patients who were admitted to hospital from 20 September 2020, to 8 August 2021. Multivariable logistic regression and machine learning (ML) methods were employed to assess variable significance. RESULTS: Among 1,613 confirmed COVID-19 patients, 365 patients (22.6%) received invasive mechanical ventilation (IMV). Factors associated with IMV included older age >65 years (OR,1.46; 95%CI, 1.13-1.89), current smoking status (OR, 1.71; 95%CI, 1.22-2.41), critical disease at admission (OR, 1.97; 95%CI, 1.28-3.03), and chronic kidney disease (OR, 2.07; 95%CI, 1.37-3.13). Laboratory abnormalities that were associated with increased risk for IMV included high leukocyte count (OR, 2.19; 95%CI, 1.68-2.87), low albumin (OR, 1.76; 95%CI, 1.33-2.34) and high AST (OR, 1.71; 95%CI, 1.31-2.22). CONCLUSION: Our study suggests that there are several factors associated with the increased need for IMV among COVID-19 patients. These findings will help in early identification of patients at high risk for IMV and reallocation of hospital resources toward patients who need them the most to improve their outcomes.

Identifying Targets for Antibiotic Use for the Management of Carbapenem-Resistant Acinetobacter baumannii (CRAb) in Hospitals-A Multi-Centre Nonlinear Time-Series Study.

Solutions are needed to inform antimicrobial stewardship (AMS) regarding balancing the access to effective antimicrobials with the need to control antimicrobial resistance. Theoretical and mathematical models suggest a non-linear relationship between antibiotic use and resistance, indicating the existence of thresholds of antibiotic use beyond which resistance would be triggered. It is anticipated that thresholds may vary across populations depending on host, environment, and organism factors. Further research is needed to evaluate thresholds in antibiotic use for a specific pathogen across different settings. The objective of this study is to identify thresholds of population antibiotic use associated with the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb) across six hospital sites in Oman. The study was an ecological, multi-centre evaluation that involved collecting historical antibiotic use and CRAb incidence over the period from January 2015 to December 2019. By using non-linear time-series analysis, we identified different thresholds in the use of third-generation cephalosporins, piperacillin-tazobactam, aminoglycoside, and fluoroquinolones across participating hospitals. The identification of different thresholds emphasises the need for tailored analysis based on modelling data from each hospital. The determined thresholds can be used to set targets for each hospital AMS, providing a balance between access to these antibiotics versus controlling CRAb incidence.

Exploration of the Experience of Care Home Managers of COVID-19 Vaccination Programme Implementation and Uptake by Residents and Staff in Care Homes in Northern Ireland.

The Coronavirus 2019 (COVID-19) pandemic disproportionately affected people living and working in care homes. This study aimed to explore the experience of care home managers on the implementation and uptake of the COVID-19 vaccination programme by residents and staff in care homes in Northern Ireland. An exploratory mixed methods approach was used, i.e., semi-structured interviews to design the cross-sectional survey and content analysis of statements using open ended questions. Care home managers were approached and sixty-seven valid quantitative and forty-nine descriptive responses were analysed. The study identified eight themes which described factors that motivated residents (family visits and relationship with managers and staff), and staff vaccine uptake (return to normal life at work and trust in care home managers). The identified themes also confirmed that vaccine uptake is negatively influenced by perceived side effects. The findings indicated that social media can promote or decelerate the uptake of vaccine despite the accessibility to a successful vaccination programme. The study highlights the important role of managers in handling the challenges through building trust and establishing relationships with staff and residents. The findings identified challenges to the uptake of the COVID-19 vaccine by staff and residents that can inform the implementation of future vaccination programmes.

Mexico's precursor chemical controls: emergence of less potent types of methamphetamine in the United States.

BACKGROUND: This study examines whether Mexico's controls on ephedrine and pseudoephedrine, the two precursor chemicals that yield the most potent form of methamphetamine, d-methamphetamine, impacted the prevalence/availability of less potent types of methamphetamine in the United States-types associated with the alternative precursor chemical P2P. METHOD: Using ARIMA-intervention time series analysis of monthly drug exhibits (a prevalence/availability indicator) from the System to Retrieve Information from Drug Evidence (STRIDE), we tested whether Mexico's controls, which began in 2005, were associated with growth/decline in d-methamphetamine and growth/decline in P2P-associated, less potent l-methamphetamine, racemic methamphetamine (a 50:50 ratio of d- and l-isomers), and mixed isomer methamphetamine (an unequal ratio of d- and l-isomers). Heroin, cocaine and marijuana exhibits were used for quasi-control (01/2000-04/2011). RESULTS: Mixed-isomer exhibits constituted about 4% of the methamphetamine exhibits before Mexico's controls, then rose sharply in association with them and remained elevated, constituting about 37% of methamphetamine exhibits in 2010. d-Methamphetamine exhibits dropped sharply; l-methamphetamine and racemic methamphetamine exhibits had small rises. d-Methamphetamine exhibits partially recovered in the US West, but little recovery occurred in the US Central/South. Quasi-control series were generally unaffected. CONCLUSION: The US methamphetamine market changed. Widespread emergence of less potent methamphetamine occurred in conjunction with Mexico's controls. And prevalence/availability of the most potent type of the drug, d-methamphetamine, declined, a partial recovery in the West notwithstanding. Granting that lower potency drugs typically engender less dependence and attendant problems, these findings suggest that, following Mexico's controls, the potential harm of a sizeable amount of the US methamphetamine supply decreased.

Changing over-the-counter ephedrine and pseudoephedrine products to prescription only: impacts on methamphetamine clandestine laboratory seizures.

BACKGROUND: Clandestine laboratory operators commonly extract ephedrine and pseudoephedrine-precursor chemicals used to synthesize methamphetamine-from over-the-counter cold/allergy/sinus products. To prevent this activity, two states, Oregon in 07/2006 and Mississippi in 07/2010, implemented regulations classifying ephedrine and pseudoephedrine as Schedule III substances, making products containing them available by prescription only. Using simple pre-regulation versus post-regulation comparisons, reports claim that the regulations have substantially reduced clandestine laboratory seizures (an indicator of laboratory prevalence) in both states, motivating efforts to implement similar regulation nationally. This study uses ARIMA-intervention time-series analysis to more rigorously evaluate the regulations' impacts on laboratory seizures. METHODS: Monthly counts of methamphetamine clandestine laboratory seizures were extracted from the Clandestine Laboratory Seizure System (2000-early 2011) for Oregon, Mississippi and selected nearby states (for quasi-control). FINDINGS: Seizures in Oregon and nearby western states largely bottomed out months before Oregon's regulation, and changed little thereafter. No significant impact for Oregon's regulation was found. Mississippi and nearby states generally had elevated seizures before Mississippi's regulation. Mississippi experienced a regulation-associated drop of 28.9 seizures (50.2%) in the series level (p<0.01), while nearby states exhibited no comparable decline. CONCLUSIONS: Oregon's regulation encountered a floor effect, making any sizable impact infeasible. Mississippi, however, realized a substantial impact, suggesting that laboratories, if sufficiently extant, can be meaningfully impacted by prescription precursor regulation. It follows that national prescription precursor regulation would have little impact in western states with low indicated laboratory prevalence, but may be of significant use in regions facing higher indicated prevalence.