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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 -
European Review For Medical and... Apr 2019Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years,...
Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years, with relapses and failures. The optimal type, route of administration, and duration of antibiotic treatment remain controversial, and the emergence of multi-drug resistant organisms poses major therapeutic challenges. Identification of the causative agent and subsequent targeted antibiotic treatment has a major impact on patients' outcome. In this review, we summarize which intravenous and oral antibiotics are the best options available for the treatment of chronic osteomyelitis, according to specific aetiologies.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Chronic Disease; Humans; Osteomyelitis
PubMed: 30977893
DOI: 10.26355/eurrev_201904_17500 -
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 -
Clinical Journal of the American... Dec 2016Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this study was to determine the risk of AKI attributable to intravenous vancomycin.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We conducted a systematic review of randomized, controlled trials and cohort studies that compared patients treated with intravenous vancomycin with a control group of patients given a comparator nonglycopeptide antibiotic and in which kidney function or kidney injury outcomes were reported. PubMed and Cochrane Library were searched from 1990 to September of 2015. Two reviewers extracted data and assessed study risk of bias, and one reviewer adjudicated the assessments. A meta-analysis was conducted on seven randomized, controlled trials (total of 4033 patients).
RESULTS
Moderate quality evidence suggested that vancomycin treatment is associated with a higher risk of AKI, with a relative risk of 2.45 (95% confidence interval, 1.69 to 3.55). The risk of kidney injury was similar in patients treated for skin and soft tissue infections compared with those treated for nosocomial pneumonia and other complicated infections. There was an uncertain risk of reporting bias, because kidney function was not a prespecified outcome in any of the trials. The preponderance of evidence was judged to be indirect, because the majority of studies compared vancomycin specifically with linezolid.
CONCLUSIONS
Our findings suggest that there is a measurable risk of AKI associated with vancomycin, but the strength of the evidence is moderate. A randomized, controlled trial designed to study kidney function as an outcome would be needed to draw unequivocal conclusions.
Topics: Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Humans; Linezolid; Risk Factors; Vancomycin
PubMed: 27895134
DOI: 10.2215/CJN.05920616 -
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 -
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 :... Apr 2021Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
BACKGROUND
Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
OBJECTIVES
Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection.
SOURCES
We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals.
CONTENT
Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression.
IMPLICATIONS
We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions.
Topics: Algorithms; Anti-Bacterial Agents; Humans; Nocardia; Nocardia Infections
PubMed: 33418019
DOI: 10.1016/j.cmi.2020.12.019 -
Heart (British Cardiac Society) Jun 2017The use of antibiotic prophylaxis (AP) for prevention of infective endocarditis (IE) is controversial. In recent years, guidelines to cardiologists and dentists have... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The use of antibiotic prophylaxis (AP) for prevention of infective endocarditis (IE) is controversial. In recent years, guidelines to cardiologists and dentists have advised restriction of AP to high-risk groups (in Europe and the USA) or against its use at all (in the UK). The objective of this systematic review was to appraise the evidence for use of AP for prevention of bacteraemia or IE in patients undergoing dental procedures.
METHODS
We conducted electronic searches in Medline, Embase, Cochrane Library and ISI Web of Science. We assessed the methodological characteristics of included studies using the Strengthening the Reporting of Observational Studies in Epidemiology criteria for observational studies and the Cochrane Risk of Bias Tool for trials. Two reviewers independently determined the eligibility of studies, assessed the methodology of included studies and extracted the data.
RESULTS
We identified 178 eligible studies, of which 36 were included in the review. This included 10 time-trend studies, 5 observational studies and 21 trials. All trials identified used bacteraemia as an endpoint rather than IE. One time-trend study suggests that total AP restriction may be associated with a rising incidence of IE, while data on the consequences of relative AP restriction are conflicting. Meta-analysis of trials indicates that AP is effective in reducing the incidence of bacteraemia (risk ratio 0.53, 95% CI 0.49 to 0.57, p<0.01), but case-control studies suggest this may not translate to a statistically significant protective effect against IE in patients at low risk of disease.
CONCLUSIONS
The evidence base for the use of AP is limited, heterogeneous and the methodological quality of many studies is poor. Postprocedural bacteraemia is not a good surrogate endpoint for IE. Given the logistical challenges of a randomised trial, high-quality case-control studies would help to evaluate the role of dental procedures in causing IE and the efficacy of AP in its prevention.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Endocarditis; Humans
PubMed: 28213367
DOI: 10.1136/heartjnl-2015-309102 -
Gut Microbes 2021Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying... (Meta-Analysis)
Meta-Analysis
Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying mechanisms are thought related to dysbiosis of the gut microbiome. We conducted a systematic review of the association between antibiotics and disruption of the pediatric gut microbiome. Searches used MEDLINE, EMBASE and Web of Science. Eligible studies: association between antibiotics and gut microbiome dysbiosis; children 0-18 years; molecular techniques of assessment; outcomes of microbiome richness, diversity or composition. Quality assessed by Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Meta-analysis where possible. A total of 4,668 publications identified: 12 in final analysis (5 randomized controlled trials (RCTs), 5 cohort studies, 2 cross-sectional studies). Microbiome richness was measured in 3 studies, species diversity in 6, and species composition in 10. Quality of evidence was good or fair. 5 studies found a significant reduction in diversity and 3 a significant reduction in richness. Macrolide exposure was associated with reduced richness for twice as long as penicillin. Significant reductions were seen in (5 studies) and (2 studies), and significant increases in Proteobacteria such as (4 studies). A meta-analysis of RCTs of the effect of macrolide (azithromycin) exposure on the gut microbiome found a significant reduction in alpha-diversity (Shannon index: mean difference -0.86 (95% CI -1.59, -0.13). Antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be taken into account when prescribing antibiotics for children.: CRD42018094188.
Topics: Anti-Bacterial Agents; Bacteria; Child; Child, Preschool; Dysbiosis; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn
PubMed: 33651651
DOI: 10.1080/19490976.2020.1870402 -
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