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Lancet (London, England) Feb 2022Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths,...
BACKGROUND
Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.
METHODS
We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level.
FINDINGS
On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62-6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911-1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9-35·3), and lowest in Australasia, at 6·5 deaths (4·3-9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000-1 270 000) deaths attributable to AMR and 3·57 million (2·62-4·78) deaths associated with AMR in 2019. One pathogen-drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000-100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.
INTERPRETATION
To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen-drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat.
FUNDING
Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Global Burden of Disease; Global Health; Humans; Models, Statistical
PubMed: 35065702
DOI: 10.1016/S0140-6736(21)02724-0 -
International Journal of Environmental... Sep 2022One of the public health issues faced worldwide is antibiotic resistance (AR). During the novel coronavirus (COVID-19) pandemic, AR has increased. Since some studies... (Review)
Review
One of the public health issues faced worldwide is antibiotic resistance (AR). During the novel coronavirus (COVID-19) pandemic, AR has increased. Since some studies have stated AR has increased during the COVID-19 pandemic, and others have stated otherwise, this study aimed to explore this impact. Seven databases-PubMed, MEDLINE, EMBASE, Scopus, Cochrane, Web of Science, and CINAHL-were searched using related keywords to identify studies relevant to AR during COVID-19 published from December 2019 to May 2022, according to PRISMA guidelines. Twenty-three studies were included in this review, and the evidence showed that AR has increased during the COVID-19 pandemic. The most commonly reported resistant Gram-negative bacteria was , followed by , , and . and were highly resistant to tested antibiotics compared with and . Moreover, showed high resistance to colistin. Commonly reported Gram-positive bacteria were and . The resistance of to ampicillin, erythromycin, and Ciprofloxacin was high. Self-antibiotic medication, empirical antibiotic administration, and antibiotics prescribed by general practitioners were the risk factors of high levels of AR during COVID-19. Antibiotics' prescription should be strictly implemented, relying on the Antimicrobial Stewardship Program (ASP) and guidelines from the World Health Organization (WHO) or Ministry of Health (MOH).
Topics: Ampicillin; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Erythromycin; Escherichia coli; Humans; Microbial Sensitivity Tests; Pandemics; Pseudomonas aeruginosa; COVID-19 Drug Treatment
PubMed: 36231256
DOI: 10.3390/ijerph191911931 -
Clinical Microbiology and Infection :... Mar 2023COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.
OBJECTIVE
We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings.
DATA SOURCE
A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022.
STUDY ELIGIBILITY
Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted.
METHODS
Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed.
RESULTS
Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40).
CONCLUSION
The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; COVID-19; Carbapenems
PubMed: 36509377
DOI: 10.1016/j.cmi.2022.12.006 -
Medicina (Kaunas, Lithuania) Dec 2018The use of antibiotic prophylaxis in extraction and implant dentistry is still controversial, with varying opinions regarding their necessity. The overuse of... (Review)
Review
The use of antibiotic prophylaxis in extraction and implant dentistry is still controversial, with varying opinions regarding their necessity. The overuse of antibiotics has led to widespread antimicrobial resistance and the emergence of multi drug resistant strains of bacteria. The main aim of this work was to determine whether there is a genuine need for antibiotic prophylaxis in two common dental procedures; dental implants and tooth extractions. Electronic searches were conducted across databases such as Cochrane Register of Controlled Trials, the UK National Health Service, Centre for reviews, Science Direct, PubMed and the British Dental Journal to identify clinical trials of either dental implants or tooth extractions, whereby the independent variable was systemic prophylactic antibiotics used as part of treatment in order to prevent postoperative complications such as implant failure or infection. Primary outcomes of interest were implant failure, and postoperative infections which include systemic bacteraemia and localised infections. The secondary outcome of interest was adverse events due to antibiotics. The Critical Appraisal Skills Programme tool was used to assess the risk of bias, extract outcomes of interest and to identify studies for inclusion in the meta-analysis. Seven randomised clinical trials (RCTs) were included in the final review comprising = 1368 patients requiring either tooth extraction(s) or dental implant(s). No statistically significant evidence was found to support the routine use of prophylactic antibiotics in reducing the risk of implant failure ( = 0.09, RR 0.43; 95% CI 0.16⁻1.14) or post-operative complications ( = 0.47, RR: 0.74; 95% CI 0.34⁻1.65) under normal conditions. Approximately 33 patients undergoing dental implant surgery need to receive antibiotics in order to prevent one implant failure from occurring. There is little conclusive evidence to suggest the routine use of antibiotic prophylaxis for third molar extractive surgery in healthy young adults. There was no statistical evidence for adverse events experienced for antibiotics vs. placebo. Based on our analysis, even if financially feasible, clinicians must carefully consider the appropriate use of antibiotics in dental implants and extraction procedures due to the risk of allergic reactions and the development of microbial drug resistance.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Databases, Factual; Dental Implants; Drug Resistance, Multiple, Bacterial; Endocarditis; Female; Humans; Hypersensitivity; Male; Middle Aged; Randomized Controlled Trials as Topic; Surgical Wound Infection; Tooth Extraction; Young Adult
PubMed: 30513764
DOI: 10.3390/medicina54060095 -
Gastroenterology Nov 2018In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure.
METHODS
We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs.
RESULTS
We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001).
CONCLUSIONS
Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
Topics: Adolescent; Adult; Aged; Child; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Prevalence; World Health Organization; Young Adult
PubMed: 29990487
DOI: 10.1053/j.gastro.2018.07.007 -
Emerging Infectious Diseases Jul 2020A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate... (Meta-Analysis)
Meta-Analysis
A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate the effect of macrolide resistance on the manifestations and clinical judgment during M. pneumoniae infections. We found no difference in clinical severity between MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections. However, in the pooled data, patients infected with MRMP had a longer febrile period (1.71 days), length of hospital stay (1.61 day), antibiotic drug courses (2.93 days), and defervescence time after macrolide treatment (2.04 days) compared with patients infected with MSMP. The risk of fever lasting for >48 hours after macrolide treatment was also significantly increased (OR 21.24), and an increased proportion of patients was changed to second-line treatment (OR 4.42). Our findings indicate diagnostic and therapeutic challenges after the emergence of MRMP. More precise diagnostic tools and clearly defined treatment should be appraised in the future.
Topics: Anti-Bacterial Agents; Asia; Child; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Macrolides; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 32568052
DOI: 10.3201/eid2607.200017 -
Frontiers in Cellular and Infection... 2023Bacterial biofilms are complex microbial communities encased in extracellular polymeric substances. Their formation is a multi-step process. Biofilms are a significant... (Review)
Review
Bacterial biofilms are complex microbial communities encased in extracellular polymeric substances. Their formation is a multi-step process. Biofilms are a significant problem in treating bacterial infections and are one of the main reasons for the persistence of infections. They can exhibit increased resistance to classical antibiotics and cause disease through device-related and non-device (tissue) -associated infections, posing a severe threat to global health issues. Therefore, early detection and search for new and alternative treatments are essential for treating and suppressing biofilm-associated infections. In this paper, we systematically reviewed the formation of bacterial biofilms, associated infections, detection methods, and potential treatment strategies, aiming to provide researchers with the latest progress in the detection and treatment of bacterial biofilms.
Topics: Humans; Biofilms; Bacteria; Bacterial Infections; Extracellular Polymeric Substance Matrix; Anti-Bacterial Agents
PubMed: 37091673
DOI: 10.3389/fcimb.2023.1137947 -
Journal of Global Antimicrobial... Mar 2020Staphylococcus aureus is one of the most common pathogens causing nosocomial and community-acquired infections associated with high morbidity and mortality. Mupirocin... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Staphylococcus aureus is one of the most common pathogens causing nosocomial and community-acquired infections associated with high morbidity and mortality. Mupirocin has been increasingly used for treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections. The aim of this study was to determine the prevalence of mupirocin-resistant S. aureus (MuRSA), mupirocin-resistant MRSA (MuRMRSA), high-level MuRSA (HLMuRSA) and high-level MuRMRSA (HLMuRMRSA) worldwide.
METHODS
Online databases including Medline, Embase and Web of Science were searched (2000-2018) to identify studies addressing the prevalence of MuRSA, MuRMRSA, HLMuRSA and HLMuRMRSA. STATA v. software was used to interpret the data.
RESULTS
Of the 2243 records identified from the databases, 30 and 63 studies fulfilled the eligibility criteria for MuRSA and MuRMRSA, respectively. Finally, 27 and 60 studies were included separately for HLMuRSA and HLMuRMRSA, respectively. The analyses revealed pooled and averaged prevalences of MuRSA, MuRMRSA, HLMuRSA and HLMuRMRSA of 7.6% [95% confidence interval (CI) 6.2-9.0%], 13.8% (95% CI 12.0-15.6%), 8.5% (95% CI 6.3-10.7%) and 8.1% (95% CI 6.8-9.4%), respectively.
CONCLUSION
Overall, these results show a global increase in the prevalence of HLMuRSA and HLMuRMRSA among clinical S. aureus isolates over time. However, there was only a significant increase in the prevalence of MuRMRSA compared with the other categories, especially MuRSA. Since mupirocin remains the most effective antibiotic for MSSA and MRSA decolonisation both in patients and healthcare personnel, a reduction of its effectiveness presents a risk for invasive infection. Monitoring of mupirocin resistance development remains critical.
Topics: Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mupirocin; Population Surveillance; Prevalence; Staphylococcal Infections
PubMed: 31442624
DOI: 10.1016/j.jgar.2019.07.032 -
The Lancet. Infectious Diseases Mar 2016Topical and oral antibiotics are routinely used to treat acne. However, antibiotic resistance is increasing, with many countries reporting that more than 50% of... (Review)
Review
Topical and oral antibiotics are routinely used to treat acne. However, antibiotic resistance is increasing, with many countries reporting that more than 50% of Propionibacterium acnes strains are resistant to topical macrolides, making them less effective. We reviewed the current scientific literature to enable proposal of recommendations for antibiotic use in acne treatment. References were identified through PubMed searches for articles published from January, 1954, to March 7, 2015, using four multiword searches. Ideally, benzoyl peroxide in combination with a topical retinoid should be used instead of a topical antibiotic to minimise the impact of resistance. Oral antibiotics still have a role in the treatment of moderate-to-severe acne, but only with a topical retinoid, benzoyl peroxide, or their combination, and ideally for no longer than 3 months. To limit resistance, it is recommended that benzoyl peroxide should always be added when long-term oral antibiotic use is deemed necessary. The benefit-to-risk ratio of long-term antibiotic use should be carefully considered and, in particular, use alone avoided where possible. There is a need to treat acne with effective alternatives to antibiotics to reduce the likelihood of resistance.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Benzoyl Peroxide; Drug Resistance, Bacterial; Humans; Propionibacterium acnes; Retinoids
PubMed: 26852728
DOI: 10.1016/S1473-3099(15)00527-7 -
JAMA Network Open Jul 2022The proportion of macrolide-resistant Mycoplasma pneumoniae (MRMP) infections has changed, and it differs according to geographical region. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The proportion of macrolide-resistant Mycoplasma pneumoniae (MRMP) infections has changed, and it differs according to geographical region.
OBJECTIVE
To analyze the global patterns, including the temporal trends, regional variations, and variant types, in the proportion of MRMP infections in this systematic review and meta-anaysis.
DATA SOURCES
PubMed, Cochrane Library, and Embase databases were searched for observational studies from inception to September 10, 2021.
STUDY SELECTION
Observational studies reporting the proportion of MRMP infections were screened independently by 2 authors. The presence of MRMP infection was defined as any case of M pneumoniae infection positive for any variants associated with macrolide resistance identified using respiratory samples.
DATA EXTRACTION AND SYNTHESIS
Data were extracted independently and in duplicate by 2 reviewers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was used. Random-effects meta-analyses were used to estimate the proportion of MRMP infections.
MAIN OUTCOMES AND MEASURES
The global patterns in the proportion of MRMP infections were estimated, and the temporal trends and variant types of MRMP infection with regional differences were investigated.
RESULTS
This study included 153 studies from 150 articles (27 408 samples in 26 countries) in the meta-analysis. The global patterns in the proportion of MRMP infections showed an increasing trend with regional differences. The proportion of MRMP infections was highest in the Western Pacific regions (53.4%; 95% CI, 47.4%-60.3%), followed by the South East Asian region (9.8%; 95% CI, 0.8%-100%), the region of the Americas (8.4%; 95% CI, 6.1%-11.6%), and the European region (5.1%; 95% CI, 3.3%-8.0%). The most commonly identified variant of MRMP infection was A2063G (96.8%; 95% CI, 95.8%-97.7%), followed by A2064G (4.8%; 95% CI, 3.5%-6.7%). The proportion of MRMP infections was the highest in studies including only children (37.0%; 95% CI, 29.8%-46.1%), followed by those including only adults (15.9%; 95% CI, 6.4%-39.7%) and those including both children and adults (16.7%; 95% CI, 10.1%-27.6%).
CONCLUSIONS AND RELEVANCE
This study provides global trends in the proportion of MRMP infections and suggests that strategies to prevent the spread of MRMP infection and to treat MRMP infections are needed to decrease disease burden.
Topics: Adult; Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Humans; Macrolides; Microbial Sensitivity Tests; Pneumonia, Mycoplasma; United States
PubMed: 35816304
DOI: 10.1001/jamanetworkopen.2022.20949