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.

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.

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.

Effects of Antibiotic Cycling Policy on Incidence of Healthcare-Associated MRSA and Clostridioides difficile Infection in Secondary Healthcare Settings.

This quasi-experimental study investigated the effect of an antibiotic cycling policy based on time-series analysis of epidemiologic data, which identified antimicrobial drugs and time periods for restriction. Cyclical restrictions of amoxicillin/clavulanic acid, piperacillin/tazobactam, and clarithromycin were undertaken over a 2-year period in the intervention hospital. We used segmented regression analysis to compare the effect on the incidence of healthcare-associated Clostridioides difficile infection (HA-CDI), healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA), and new extended-spectrum ß-lactamase (ESBL) isolates and on changes in resistance patterns of the HA-MRSA and ESBL organisms between the intervention and control hospitals. HA-CDI incidence did not change. HA-MRSA incidence increased significantly in the intervention hospital. The resistance of new ESBL isolates to amoxicillin/clavulanic acid and piperacillin/tazobactam decreased significantly in the intervention hospital; however, resistance to piperacillin/tazobactam increased after a return to the standard policy. The results question the value of antibiotic cycling to antibiotic stewardship.

Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. METHODS: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.

Impact of Multidisciplinary Team Escalating Approach on Antibiotic Stewardship in the United Arab Emirates.

Antimicrobial stewardship programs (ASP) are an essential strategy to combat antimicrobial resistance. This study aimed to measure the impact of an ASP multidisciplinary team (MDT) escalating intervention on improvement of clinical, microbiological, and other measured outcomes in hospitalised adult patients from medical, intensive care, and burns units. The escalating intervention reviewed the patients' cases in the intervention group through the clinical pharmacists in the wards and escalated complex cases to ID clinical pharmacist and ID physicians when needed, while only special cases required direct infectious disease (ID) physicians review. Both non-intervention and intervention groups were each followed up for six months. The study involved a total of 3000 patients, with 1340 (45%) representing the intervention group who received a total of 5669 interventions. In the intervention group, a significant reduction in length of hospital stay (p < 0.01), readmission (p < 0.01), and mortality rates (p < 0.01) was observed. Antibiotic use of the WHO AWaRe Reserve group decreased in the intervention group (relative rate change = 0.88). Intravenous to oral antibiotic ratio in the medical ward decreased from 4.8 to 4.1. The presented ASP MDT intervention, utilizing an escalating approach, successfully improved several clinical and other measured outcomes, demonstrating the significant contribution of clinical pharmacists atimproving antibiotic use and informing antimicrobial stewardship.

Author Correction: A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance.

Balancing access to antibiotics with the control of antibiotic resistance is a global public health priority. At present, antibiotic stewardship is informed by a 'use it and lose it' principle, in which antibiotic use by the population is linearly related to resistance rates. However, theoretical and mathematical models suggest that use-resistance relationships are nonlinear. One explanation for this is that resistance genes are commonly associated with 'fitness costs' that impair the replication or transmissibility of the pathogen. Therefore, resistant genes and pathogens may only gain a survival advantage where antibiotic selection pressures exceed critical thresholds. These thresholds may provide quantitative targets for stewardship-optimizing the control of resistance while avoiding over-restriction of antibiotics. Here, we evaluated the generalizability of a nonlinear time-series analysis approach for identifying thresholds using historical prescribing and microbiological data from five populations in Europe. We identified minimum thresholds in temporal relationships between the use of selected antibiotics and incidence rates of carbapenem-resistant Acinetobacter baumannii (Hungary), extended-spectrum ß-lactamase-producing Escherichia coli (Spain), cefepime-resistant E. coli (Spain), gentamicin-resistant Pseudomonas aeruginosa (France) and methicillin-resistant Staphylococcus aureus (Northern Ireland) in different epidemiological phases. Using routinely generated data, our approach can identify context-specific quantitative targets for rationalizing population antibiotic use and controlling resistance. Prospective intervention studies that restrict antibiotic consumption are needed to validate these thresholds.

Reduction in the incidence of hospital-acquired MRSA following the introduction of a chlorine dioxide 275†ppm based disinfecting agent in a district general hospital.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile are major nosocomial pathogens whose control relies on effective antimicrobial stewardship and infection control practices. This study evaluates the impact of a chlorine dioxide-based disinfectant (275 ppm) on the incidence of hospital-acquired (HA) MRSA and HA-Clostridium difficile infection (CDI) in a district general hospital. METHODS: This study was carried out from November 2009 to September 2013. From November 2009 to October 2011 sodium dichloroisocyanurate was used for routine environmental disinfection. In November 2011, this was changed to a chlorine dioxide 275 ppm based disinfectant. This product was introduced into the hospital in a phased manner with intensive training on its use provided to all nursing, nursing auxiliary and hotel services staff. The effect of this change on the incidence of HA-MRSA and HA-CDI was assessed using segmented regression analysis of interrupted time series. In addition, the potential cost savings as a result of this intervention were assessed. RESULTS: The HA-MRSA trend from November 2009 to October 2011 significantly increased (p=0.006). Following the introduction of the chlorine dioxide-based disinfectant there was significant decrease in the HA-MRSA trend, with the monthly incidence being reduced by 0.003 cases/100 bed days (p=0.001), equating to an average of four cases per month after 12 months of use This resulted in an annual potential cost saving of £276 000. No significant effect on the incidence of HA-CDI was observed (coefficient -0.03; p=0.873). CONCLUSION: This study highlights the importance of effective environmental inanimate surface decontamination in controlling the spread of MRSA and the potential cost savings that can be achieved through decreasing HA-MRSA rates.