Global antimicrobial resistance and antibiotic use in COVID-19 patients within health facilities: A systematic review and meta-analysis of aggregated participant data.

OBJECTIVES: The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study aimed to provide a comprehensive and up-to-date picture of global antimicrobial resistance (AMR) and antibiotic use in COVID-19 patients. METHODS: We conducted a systematic review to determine the prevalence of AMR and antibiotic usage among COVID-19 patients receiving treatment in healthcare facilities. Our search encompassed the PubMed, Web of Science, Embase, and Scopus databases, spanning studies published from December 2019 to May 2023. We utilized random-effects meta-analysis to assess the prevalence of multidrug-resistant organisms (MDROs) and antibiotic use in COVID-19 patients, aligning with both the WHO's priority list of MDROs and the AWaRe list of antibiotic products. Estimates were stratified by region, country, and country income. Meta-regression models were established to identify predictors of MDRO prevalence and antibiotic use in COVID-19 patients. The study protocol was registered with PROSPERO (CRD 42023449396). RESULTS: Among the 11,050 studies screened, 173 were included in the review, encompassing a total of 892,312 COVID-19 patients. MDROs were observed in 42.9% (95% CI 31.1-54.5%, I2 = 99.90%) of COVID-19 patients: 41.0% (95% CI 35.5-46.6%) for carbapenem-resistant organisms (CRO), 19.9% (95% CI 13.4-27.2%) for methicillin-resistant Staphylococcus aureus (MRSA), 24.9% (95% CI 16.7-34.1%) for extended-spectrum beta-lactamase-producing organisms (ESBL), and 22.9% (95% CI 13.0-34.5%) for vancomycin-resistant Enterococcus species (VRE), respectively. Overall, 76.2% (95% CI 69.5-82.9%, I2 = 99.99%) of COVID-19 patients were treated with antibiotics: 29.6% (95% CI 26.0-33.4%) with "Watch" antibiotics, 22.4% (95% CI 18.0-26.7%) with "Reserve" antibiotics, and 16.5% (95% CI 13.3-19.7%) with "Access" antibiotics. The MDRO prevalence and antibiotic use were significantly higher in low- and middle-income countries than in high-income countries, with the lowest proportion of antibiotic use (60.1% (95% CI 52.1-68.0%)) and MDRO prevalence (29.1% (95% CI 21.8-36.4%)) in North America, the highest MDRO prevalence in the Middle East and North Africa (63.9% (95% CI 46.6-81.2%)), and the highest proportion of antibiotic use in South Asia (92.7% (95% CI 90.4-95.0%)). The meta-regression identified antibiotic use and ICU admission as a significant predictor of higher prevalence of MDROs in COVID-19 patients. CONCLUSIONS: This systematic review offers a comprehensive and current assessment of MDRO prevalence and antibiotic use among COVID-19 patients in healthcare facilities. It underscores the formidable challenge facing global efforts to prevent and control AMR amidst the backdrop of the COVID-19 pandemic. These findings serve as a crucial warning to policymakers, highlighting the urgent need to enhance antimicrobial stewardship strategies to mitigate the risks associated with future pandemics.

Impacts of pharmacist-led multifaceted antimicrobial stewardship on antibiotic use and clinical outcomes in urology department of a tertiary hospital in Guangzhou, China: an interrupted time series study.

BACKGROUND: Limited research has explored the effectiveness of pharmacist-led antimicrobial stewardship programs (ASPs) in the urology department. OBJECTIVE: To evaluate the impact of pharmacist-led multifaceted ASPs on antibiotic use and clinical outcomes. METHODS: We conducted a prescription review of inpatients receiving one or more antibiotics in the urology department of a large teaching hospital in Guangzhou, China, from April 2019 to March 2023. The pharmacist-led multifaceted ASPs intervention included guidelines development, training, medication consultation, review of medical orders, indicator monitoring, and consultation. Our primary outcome was antibiotic consumption. The data was analysed using interrupted time series (ITS) analysis. RESULTS: Following the implementation of ASPs, we observed an immediate decrease in total antibiotic consumption (ß = -32.42 DDDs/100PD and -36.24 DOT/100PD, P < 0.001), Antibiotic use rate (ß = -7.87 %, P = 0.002), Second-generation cephalosporins (ß = -12.43 DDDs/100PD and -15.18 DOT/100PD, P < 0.001), Third-generation cephalosporins (ß = -5.13 DDDs/100PD, P = 0.001 and -6.16 DOT/100PD, P = 0.002), Fluoroquinolones (ß = -12.26 DDDs/100PD and -12.70 DOT/100PD, P < 0.001), and WHO Watch category antibiotics (ß = -32.07 DDDs/100PD and -34.96 DOT/100PD, P < 0.001). There were no differences observed in mortality rate before and after the intervention, and no significant short-term or long-term effects were found on length of hospital stay (LOS) using ITS. However, there was a significant short-term effect on average antibiotic cost (ß = -446.83 RMB, P = 0.004). CONCLUSION: The implementation of pharmacist-led multifaceted ASPs had positive impacts on reducing antimicrobial consumption without increasing LOS, antibiotic cost, or mortality rate.

The association between ambient temperature and antimicrobial resistance of Klebsiella pneumoniae in China: a difference-in-differences analysis.

Introduction: Antimicrobial resistance (AMR) of Klebsiella pneumoniae (K. pneumoniae) poses a significant global public health threat and is responsible for a high prevalence of infections and mortality. However, knowledge about how ambient temperature influences the AMR of K. pneumoniae is limited in the context of global warming. Methods: AMR data of 31 Chinese provinces was collected from the China Antimicrobial Resistance Surveillance System (CARSS) between 2014 and 2020. Socioeconomic and meteorological data were collected from the China Statistical Yearbook during the same period. A modified difference-in-differences (DID) approach was applied to estimate the association between ambient temperature and third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) and carbapenem-resistant K. pneumoniae (CRKP). Furthermore, moderating effects of socioeconomic factors were also evaluated. Results: Every 1°C increase in annual average temperature was associated with a 4.7% (relative risk (RR):1.047, 95% confidence intervals (CI): 1.031-1.082) increase in the detection rate of 3GCRKP, and a 10.7% (RR:1.107, 95% CI: 1.011-1.211) increase in the detection rate of CRKP. The relationships between ambient temperature and 3GCRKP and CRKP were found to be moderated by socioeconomic status (GDP per capita, income per capita, and consumption per capita; the interaction p-values <0.05), where higher economic status was found to strengthen the effects of temperature on the detection rate of 3GCRKP and weaken the effects on the detection rate of CRKP. Discussion: Ambient temperature was found to be positively associated with AMR of K. pneumoniae, and this association was moderated by socioeconomic status. Policymakers should consider the impact of global warming and high temperatures on the spread of 3GCRKP and CRKP when developing strategies for the containment of AMR.

Estimating the effect of increasing ambient temperature on antimicrobial resistance in China: A nationwide ecological study with the difference-in-differences approach.

Antimicrobial resistance (AMR) and the possible consequences of rising ambient temperatures brought on by global warming have been extensively discussed. However, the epidemiological evidence on the effects of temperature on AMR is rare and little is known about the role of socioeconomic inequities. This ecological study obtained 31 provinces AMR data of Escherichia Coli (E. coli) from the China Antimicrobial Resistance Surveillance System (CARSS) over the period from 2014 to 2020, which were linked to the meteorological and socioeconomic data published in the China Statistical Yearbook. Modified difference-in-differences (DID) analyses were performed to estimate the effect of ambient temperature on AMR of E. coli to third-generation cephalosporins (ceftriaxone and cefotaxime), carbapenems, and quinolones, adjusting for variations in meteorological and socioeconomic factors. We estimated that every 1 °C increase in average ambient temperature was associated with 2.71 % (95 % confidence interval [CI]: 1.20-4.24), 32.92 % (95 % CI: 15.62-52.81), and 1.81 % (95 % CI: 0.47-3.16) increase in the prevalence of E. coli resistance to third-generation cephalosporins (ceftriaxone and cefotaxime), carbapenems and quinolones, respectively. The link was more profound in the regions with lower temperature and a median level of average humidity, and the regions with lower income, lower expenditure (in economics), lower health resources, and lower hospital admissions. Neither the replacement of the temperature variable nor the alternative approaches for confounding adjustment changed the positive association between ambient temperature and AMR. In general, there exists a positive association between ambient temperature and AMR, although the strength of such an association varies by socioeconomic and health services factors. The association is possibly nonlinear, especially for E. coli resistance to third-generation cephalosporins. The findings suggest that AMR control programs should explicitly incorporate weather patterns to increase their effectiveness.

Epidemiological Characteristics and Antimicrobial Resistance Changes of Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii under the COVID-19 Outbreak: An Interrupted Time Series Analysis in a Large Teaching Hospital.

BACKGROUND: To investigate the epidemiological characteristics and resistance changes of carbapenem-resistant organisms (CROs) under the COVID-19 outbreak to provide evidence for precise prevention and control measures against hospital-acquired infections during the pandemic. METHODS: The distribution characteristics of CROs (i.e., carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii) were analyzed by collecting the results of the antibiotic susceptibility tests of diagnostic isolates from all patients. Using interrupted time series analysis, we applied Poisson and linear segmented regression models to evaluate the effects of COVID-19 on the numbers and drug resistance of CROs. We also conducted a stratified analysis using the Cochran-Mantel-Haenszel test. RESULTS: The resistance rate of carbapenem-resistant Acinetobacter baumannii (CRAB) was 38.73% higher after the COVID-19 outbreak compared with before (p < 0.05). In addition, the long-term effect indicated that the prevalence of CRAB had a decreasing trend (p < 0.05). However, the overall resistance rate of Klebsiella pneumoniae did not significantly change after the COVID-19 outbreak. Stratified analysis revealed that the carbapenem-resistant Klebsiella pneumoniae (CRKP) rate increased in females (OR = 1.98, p < 0.05), those over 65 years old (OR = 1.49, p < 0.05), those with sputum samples (OR = 1.40, p < 0.05), and those in the neurology group (OR = 2.14, p < 0.05). CONCLUSION: The COVID-19 pandemic has affected the change in nosocomial infections and resistance rates in CROs, highlighting the need for hospitals to closely monitor CROs, especially in high-risk populations and clinical departments. It is possible that lower adherence to infection control in crowded wards and staffing shortages may have contributed to this trend during the COVID-19 pandemic, which warrants further research.

Effects of social norm feedback on antibiotic prescribing and its characteristics in behaviour change techniques: a mixed-methods systematic review.

Low-cost and low-barrier antibiotic stewardship strategies are urgently needed to deal with the widespread problem of antibiotic resistance. Social norm feedback could be a promising strategy. In this mixed-methods systematic review (PROSPERO: CRD42022361039), we aimed to identify the key behaviour change techniques used in social norm feedback for antibiotic stewardship and assess their effectiveness in reducing antibiotic prescribing. We searched PubMed, Embase, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2000, and Jan 20, 2022. 3547 studies were screened, of which 23 studies reporting the effects of social norm feedback interventions on antibiotic prescribing met the inclusion criteria. 19 behaviour change techniques were tested in the included studies. The meta-analyses showed that social norm feedback is an effective strategy for reducing antibiotic prescribing, with an overall rate difference of 4% (p<0·0001). The behaviour change technique with the highest effective ratio (ER=13) was information about health consequences, followed by instruction on how to perform the behaviour (ER=9) and adding objects to the environment (ER=9). Social norm feedback is a promising strategy to reduce antibiotic prescribing, and can be incorporated into the clinical decision-making support system.

Association between antibiotic resistance and increasing ambient temperature in China: An ecological study with nationwide panel data.

Background: Antibiotic resistance leads to longer hospital stays, higher medical costs, and increased mortality. However, research into the relationship between climate change and antibiotic resistance remains inconclusive. This study aims to address the gap in the literature by exploring the association of antibiotic resistance with regional ambient temperature and its changes over time. Methods: Data were obtained from the China Antimicrobial Surveillance Network (CHINET), monitoring the prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB), Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) in 28 provinces/regions over the period from 2005 to 2019. Log-linear regression models were established to determine the association between ambient temperature and antibiotic resistance after adjustment for variations in socioeconomic, health service, and environmental factors. Findings: A 1 °C increase in average ambient temperature was associated with 1.14-fold increase (95%-CI [1.07-1.23]) in CRKP prevalence and 1.06-fold increase (95%-CI [1.03-1.08]) in CRPA prevalence. There was an accumulative effect of year-by-year changes in ambient temperature, with the four-year sum showing the greatest effect on antibiotic resistance. Higher prevalence of antibiotic resistance was also associated with higher antibiotic consumption, lower density of health facilities, higher density of hospital beds and higher level of corruption. Interpretation: Higher prevalence of antibiotic resistance is associated with increased regional ambient temperature. The development of antibiotic resistance under rising ambient temperature differs across various strains of bacteria. Funding: The National Key R&D Program of China (grant number: 2018YFA0606200), National Natural Science Foundation of China (grant number: 72074234), Fundamental Scientific Research Funds for Central Universities, P.R. China (grant number: 22qntd4201), China Medical Board (grant number: CMB-OC-19-337).

Application of the Artificial Intelligence Algorithm Model for Screening of Inborn Errors of Metabolism.

Inborn errors of metabolism (IEMs) are strongly related to abnormal growth and development in newborns and can even result in death. In total, 94,648 newborns were enrolled for expanded newborn screening using tandem mass spectrometry (MS/MS) from 2016 to 2020 at the Neonatal Disease Screening Center of the Maternal and Child Health Hospital in Shaoyang City, China. A total of 23 confirmed cases were detected in our study with an incidence rate of 1:4,115. A total of 10 types of IEM were identified, and the most common IEMs were phenylalanine hydroxylase deficiency (PAHD; 1:15,775) and primary carnitine deficiency (PCD; 1:18,930). Mutations in phenylalanine hydroxylase (PAH) and SLC22A5 were the leading causes of IEMs. To evaluate the application effect of artificial intelligence (AI) in newborn screening, we used AI to retrospectively analyze the screening results and found that the false-positive rate could be decreased by more than 24.9% after using AI. Meanwhile, a missed case with neonatal intrahepatic cholestasis citrin deficiency (NICCD) was found, the infant had a normal citrulline level (31 µmol/L; cutoff value of 6-32 µmol/L), indicating that citrulline may not be the best biomarker of intrahepatic cholestasis citrin deficiency. Our results indicated that the use of AI in newborn screening could improve efficiency significantly. Hence, we propose a novel strategy that combines expanded neonatal IEM screening with AI to reduce the occurrence of false positives and false negatives.