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The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis
Abstract
Background
Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat.
Methods
We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). 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.
Findings
We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR.
Interpretation
Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.
... Kasim Allel, 1,2,3 Anne Peters, 4 Luis Furuya-Kanamori, 5 Maria Spencer-Sandino, 4 Emma Pitchforth, 6 Laith Yakob, 7 Jose M Munita, 4,8 Eduardo A Undurraga 9,10 Original research ABSTRACT Introduction Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile. ...
... Kasim Allel, 1,2,3 Anne Peters, 4 Luis Furuya-Kanamori, 5 Maria Spencer-Sandino, 4 Emma Pitchforth, 6 Laith Yakob, 7 Jose M Munita, 4,8 Eduardo A Undurraga 9,10 Original research ABSTRACT Introduction Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile. ...
... Kasim Allel, 1,2,3 Anne Peters, 4 Luis Furuya-Kanamori, 5 Maria Spencer-Sandino, 4 Emma Pitchforth, 6 Laith Yakob, 7 Jose M Munita, 4,8 Eduardo A Undurraga 9,10 Original research ABSTRACT Introduction Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile. ...
Introduction
Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile.
Methods
We used a retrospective multicentre cohort study of BSI cases in three Chilean tertiary hospitals (2018–2022) to assess the impact of IEAT on 30-day and overall in-hospital mortality and quantify excess disease and economic burdens associated with IEAT. We determined the appropriateness of pathogen-antimicrobial pairings based on in vitro susceptibilities and pathogen-corresponding antibiotic treatment, allowing a 48-hour window after the initial blood culture. We addressed confounding using propensity scores and inverse probability weights (IPW). We used IPW-weighted logistic competing-risk survival models, including time-varying independent variables after blood tests as controls.
Results
Among 1323 BSI episodes, 432 (33%) received IEAT, with an average time to adequate therapy of 4.6 days. Compared with adequate treatment, IEAT was associated with 30-day and overall mortality risks that were 1.31 and 1.24 times higher, respectively. These risks were further inflated between twofold and fourfold when antibiotic-resistant bacteria (ARB) was included. Competing-risk models showed associations between IEAT and IEAT-ARB combinations with in-hospital mortality. Accounting for time-varying variables yielded similar results. The economic burden of IEAT resulted in an additional cost of ~US$9900 from premature mortality and 0.46 disability-adjusted life-years per patient with BSI.
Conclusion
Approximately one in three patients received IEAT, often associated with ARB. IEAT was linked to increased mortality risk and higher economic costs. Timely appropriate treatment, early pathogen detection and resistance profiling are likely to improve health and financial outcomes at the population level.
... [1][2][3][4][5][6] A recent study by Naghavi et al. estimated 1.14 million annual deaths attributable to ARB worldwide in 2021. 6 A substantial burden exists in the Americas, with an estimated annual toll of 141 thousand deaths attributed to ARB. 7 Among these, bloodstream infections (BSI) were responsible for a ...
... Last, we estimated the annual excess burden attributable to ARB BSI deaths in Chile, extrapolating our results to the national level using Monte Carlo simulations (n = 1000 repetitions from a random negative binomial distribution) and using mortality incidence attributed to ARB BSIs obtained from the most recent Global Burden of Disease (GBD) study estimates for the Americas. 7 We present upper and lower-bound uncertainty estimates following mortality incidences CIs. For details, refer to Supplementary Material S5 and S6. ...
... We found significant resistance, consistent with other findings in the region. 7 This study has some shortcomings. First, we used IPW methods, which may decrease the efficiency of our estimates and rely on observed variables. ...
Background
Antibiotic-resistant bloodstream infections (ARB BSI) cause an enormous disease and economic burden. We assessed the impact of ARB BSI caused by high- and critical-priority pathogens in hospitalised Chilean patients compared to BSI caused by susceptible bacteria.
Methods
We conducted a retrospective cohort study from 2018 to 2022 in three Chilean hospitals and measured the association of ARB BSI with in-hospital mortality, length of hospitalisation (LOS), and intensive care unit (ICU) admission. We focused on BSI caused by Acinetobacter baumannii, Enterobacterales, Staphylococcus aureus, Enterococcus species, and Pseudomonas aeruginosa. We addressed confounding using propensity scores, inverse probability weighting, and multivariate regressions. We stratified by community- and hospital-acquired BSI and assessed total hospital and productivity costs.
Findings
We studied 1218 adult patients experiencing 1349 BSI episodes, with 47.3% attributed to ARB. Predominant pathogens were Staphylococcus aureus (33% Methicillin-resistant ‘MRSA’), Enterobacterales (50% Carbapenem-resistant ‘CRE’), and Pseudomonas aeruginosa (65% Carbapenem-resistant ‘CRPA’). Approximately 80% of BSI were hospital-acquired. ARB was associated with extended LOS (incidence risk ratio IRR = 1.14, 95% CI = 1.05–1.24), increased ICU admissions (odds ratio OR = 1.25; 1.07–1.46), and higher mortality (OR = 1.42, 1.20–1.68) following index blood culture across all BSI episodes. In-hospital mortality risk, adjusted for time-varying and fixed confounders, was 1.35-fold higher (1.16–1.58) for ARB patients, with higher hazard ratios for hospital-acquired MRSA and CRE at 1.37 and 1.48, respectively. Using a societal perspective and a 5% discount rate, we estimated excess costs for ARB at 9.6 (5.0–16.4) million.
Interpretation
It is urgent to develop and implement interventions to reduce the burden of ARB BSIs, particularly from MRSA and CRE.
... The geographic differences, study population, and type of syndrome or presentation might explain the noticed differences. Furthermore, due to the cyclic spread of ESBL-PE in humans, livestock and environment, various factors including a lack of integrated tackling strategies (one health), low water, hygiene and sanitation coverage (WASH), poor facility-based infection prevention practices, poor AMR surveillance system, lack of robust diagnostic facilities, lack of trained workforce, inequalities on access to health-care, antibiotic misuse and weak regulatory mechanisms may determine the high prevalence of ESBL-PE in Africa [79][80][81][82]. ...
... In the WHO Africa region, it was reported that the limited supply chains posed repeated oral use of antimicrobials including Trimethoprim/sulfamethoxazole and amoxicillin-clavulanic acid, which might have triggered co-selection and spread of resistant bacterial strains; the co-selection might be further augmented through environmental agents, genetic linkage within plasmids and simultaneous regulation [85]. This may explain that K. pneumoniae and E.coli that are resistant to β-lactamase and or β-lactamase inhibitors were two of the four leading causes of AMR-related mortalities in Africa according to the cross-country analysis reports [82]. In addition to the above factors, transposition-related mutations, and the spread of β-lactamase genes through horizontal gene transfer might have contributed to the high rate ESBL-PE [86]. ...
Background
Worldwide, antimicrobial resistance (AMR) has grown to represent a serious threat to the diagnosis, management, and prevention of bacterial diseases. Due to their multidrug resistance attributes, the WHO has classified extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-PE)-associated infections as infections of critical significance, posing a serious risk to human health. Thus, the goal of this systematic review and meta-analysis was to assess the pooled prevalence of ESBL-PE and AMR among strains causing clinical infections in Africa.
Methods
In this systematic review and meta-analysis, two investigators independently made an electronic search in Google Scholar and PubMed databases using related keywords and corresponding “MeSH.” terms for the PubMed. The accessed studies were screened, assessed for eligibility, and critically evaluated as per the PRISMA guidelines. The prevalence and 95% confidence intervals (CI) for ESBL-PE in Africa were evaluated using a random-effects model of a meta-analysis. As a visual and statistical way assessment, the funnel plot and Egger's test were utilized to assess the risk of bias or publication bias, with a statistically significant level of bias being determined at p < 0.05.
Results
Twenty-six studies were included in the meta-analysis. Among the included studies done in Africa, the overall pooled proportion of ESBL-PE was reported to be 28% (95% CI 25–31%). ESBL-PE prevalence differed by region, the pooled estimates for East and North Africa were 29% (95% CI 20–38%) and 19% (95% CI 6–33%), respectively. The greatest sub-group analysis of pooled estimates among bacterial isolates was found in Klebsiella. pneumoniae, at 73% (95% CI 62–85%), while Proteus mirabilis had the lowest, at 40% (95% CI 1–81%).
Conclusions
In Africa, ESBL-PE is noticeably prevalent. The included studies demonstrated a significant variation in ESBL-PE resistance among the countries. This illustrates the necessity of actively monitoring antimicrobial resistance in Africa to develop interventions aimed at halting the spread of ESBL-PE.
... Asia Pacific (9.7%) and North America (10%). [2,3] The WHO adopted the Global Action Plan for AMR in 2015, and shortly thereafter SA developed the SA National Strategy Framework 2017 -2024, with goals to identify short-to medium-term interventions to preserve antibiotics, improve appropriate antibiotic use and prevent transmission of antibioticresistant organisms. In conjunction with this, a ministerial advisory committee (MAC) for AMR was formed in 2016 to advise the health minister on the appropriate approach to improve antimicrobial use. ...
... As with other LMICs, the greatest mortality from AMR is associated with K. pneumoniae infections. [3] In addition, the number of bloodstream infections caused by A. baumannii is increasing, and now ranks third after K. pneumoniae and S. aureus in the public sector, surpassing E. coli. [9] A. baumannii easily develops resistance to antimicrobials and has been linked to several outbreaks in SA, especially in the neonatal setting. ...
Antibiotic resistance is a global threat, with a disproportionate burden of mortality in low- and middle-income countries. It is increasing in both the public and private healthcare sectors within South Africa, especially in Gram-negative organisms, and is associated with increased use of World Health Organization watch and reserve antibiotics. There is a need for improved access to new antibiotics to treat infections caused by drug-resistant organisms in order to limit side-effects and improve patient outcomes of currently available antibiotics. We propose the responsible introduction of these new antibiotics with both administrative and clinical oversight in order to preserve the longevity of these precious antibiotics.
... Whilst the need for unified global action is clear, these geo-spatial disparities highlight the necessity for efforts to be regionalized. With over two in five infectionrelated deaths associated with AMR in the Americas in 2019 (Aguilar et al., 2023), the need for analysis of the Latin American context is urgent. ...
... Self-reported engagement with the NAP appears to be related to individual countries' efforts to tackle AMR. A recent study showed an inverse relationship between progress towards a NAP and AMR mortality rates in the Americas, with the countries that had the lowest mortality rates also showing greater progress in their AMR NAPs (Aguilar et al., 2023). ...
In 2015, the World Health Assembly adopted a global action plan (GAP) on antimicrobial resistance (AMR). Member states were encouraged to develop their own national action plans (NAPs) in alignment with the GAP. To-date, in systematic assessments of NAPs, the Latin American specific context has not been previously analysed. Here we examined 11 Latin American NAPs published between 2015 and 2021 using content analysis. We focused on two approaches: 1) alignment between the strategic objectives and actions defined in the GAP, and those outlined in the NAPs via a content indicator; and 2) assessment of the NAPs via a governance framework covering ‘policy design’, ‘implementation tools’, and ‘monitoring and evaluation’ areas. We observed a high alignment with the strategic objectives of the GAP; however, the opposite was observed for the corresponding actions. Our results showed that the governance aspects contained within coordination and participation domains were addressed by every Latin American NAP, whereas monitoring and assessment areas, as well as incorporating the environment, would need more attention in subsequent NAPs. Given that AMR is a global health threat and collective efforts across regions are necessary to combat it, our findings can benefit Member states by highlighting how to strengthen their AMR strategies in Latin America, while also supporting global policy formulation.
... Lower respiratory, bloodstream, and intra-abdominal infections dominated, underscoring the critical role of resistance in worsening infection outcomes. Effective interventions are needed to mitigate the public health impact of AMR [46]. ...
... Increasing AMR is a global issue, with risks shared by all countries. However, AMR is particularly problematic in Ethiopia, which has the 170 th highest age-standardized mortality rate resulting from AMR (per 100,000 people), among the ranking of 204 countries assessed, e.g., > 150 deaths per 100 000 population attributable to AMR in 2019 (Sartorius et al. 2024). In general, high rates of AMR are common in places with inadequate sanitation, poor water quality, greater industrial pollution, poor governance, and limited universal healthcare (Collignon et al. 2018, Graham et al. 2019b). ...
... Extensive misuse of antibiotics contributes to increasing AMR, potentially reversing decades of medical accomplishments (3,4). In 2021, it was estimated globally, there were 1.14 million deaths due to AMR, with 1 in 5 deaths occurring in children under 5 years of age, with the highest rates of AMR in low-and middle-income countries (LMICs) (5,6). This is set to rise to 8.22 million deaths by 2050 alongside considerable morbidity, combined with an annual economic loss of approximately $US1 trillion unless addressed (6)(7)(8). ...
Introduction
Surveillance of antibiotic use is crucial for identifying targets for antibiotic stewardship programs (ASPs), particularly in pediatric populations within countries like Pakistan, where antimicrobial resistance (AMR) is escalating. This point prevalence survey (PPS) seeks to assess the patterns of antibiotic use in pediatric patients across Punjab, Pakistan, employing the WHO AWaRe classification to pinpoint targets for intervention and encourage rational antibiotic usage.
Methods
A PPS was conducted across 23 pediatric wards of 14 hospitals in the Punjab Province of Pakistan using the standardized Global-PPS methodology developed by the University of Antwerp. The study included all pediatric inpatients receiving antibiotics at the time of the survey, categorizing antibiotic prescriptions according to the WHO Anatomical Therapeutic Chemical classification and the AWaRe classification system.
Results
Out of 498 pediatric patients, 409 were receiving antibiotics, representing an antibiotic use prevalence of 82.1%. A substantial majority (72.1%) of the prescribed antibiotics fell under the WHO's Watch category, with 25.7% in the Access category and 2.2% in the Reserve group. The predominant diagnoses were respiratory infections, notably pneumonia (32.4%). The most commonly used antibiotics were ceftriaxone (37.2%) and Vancomycin (13.5%). Only 2% of antibiotic uses were supported by culture sensitivity reports, highlighting a reliance on empirical therapy.
Conclusion
The high prevalence of antibiotic use, particularly from the Watch category, and low adherence to culture-based prescriptions underscore the critical need for robust antibiotic stewardship programs in Pakistan. Strengthening these programs could help mitigate AMR and optimize antibiotic use, aligning with global health objectives.
... Gram-negative infections, caused by bacteria, such as Klebsiella pneumonia (Kpn), Escherichia coli (Eeo), and Acinetobacter baumannii (Aba), are becoming increasingly common and pose a serious threat to life by causing severe infections [1]. In addition, these bacteria are increasingly becoming resistant to drugs worldwide. ...
Objective: To assess the efficacy and safety of cefiderocol (CFDC) in the treatment of Gram-negative bacteria (GNB) infections. Methods: Relevant studies were collected from PubMed, Web of Science, Cochrane, and Embase databases, from inception to 15 October 2023. The search formula was as follow: “cefiderocol”, “S-649266”, “Gram-Negative Bacteria”, “Gram Negative Bacteria”, “Klebsiella pneumoniae”, “Hyalococcus pneumoniae”, and “Bacterium pneumoniae proposal”. Stata 15.0 software was employed to pool data with risk ratios (RRs) and 95% confidence intervals (CIs). Data were pooled using a random- or a fixed-effects model. Results: After a comprehensive study selection, 11 studies (5 RCTs and 7 observational studies) were retrieved that compared the efficacy of CFDC with other regimens, e.g., imipenem/cilastatin. The clinical response (RR = 1.00, 95% CI 0.94–1.08, I2 = 0%) and microbiological response (RR = 0.95 95% CI = 0.80-1.14, I2 = 68.7%) of CFDC were comparable to the control group. No significant differences were observed in mortality and adverse events. Furthermore, subgroup analyses showed that CFDC enhanced microbiological eradication in the follow-up group (RR = 1.25, 95% CI 1.05-1.49) and patients with complicated urinary tract infections (cUTI) (RR = 1.32, 95% CI 1.11- 1.57). Conclusions: CFDC is a novel iron-carrying cephalosporin with the potential to effectively combat Gram-negative bacterial infections. Additional large and high-quality RCTs are required to further confirm the safety of CFDC.
... For instance, the problem of Antimicrobial Resistance (AMR), which results in bacteria developing mechanisms to counter the effects of antibiotics, is a current worldwide health concern [3]. Conventional antibiotics exert their action on bacterial cells and are commonly ineffective because bacteria develop a resistance mechanism, including enzyme secretion that degrades the antibiotics or forms a biofilm layer as shown in Fig. 1 [4]. ...
Molecular Communication (MC) utilizes chemical molecules to transmit information, introducing innovative strategies for pharmaceutical interventions and enhanced immune system monitoring. This paper explores Molecular communication based approach to disrupt Quorum Sensing (QS) pathways to bolster immune defenses against antimicrobial-resistant bacteria. Quorum Sensing enables bacteria to coordinate critical behaviors, including virulence and antibiotic resistance, by exchanging chemical signals, known as autoinducers. By interfering with this bacterial communication, we can disrupt the synchronization of activities that promote infection and resistance. The study focuses on RNAIII inhibiting peptide (RIP), which blocks the production of critical transcripts, RNAII and RNAIII, within the Accessory Gene Regulator (AGR) system, thereby weakening bacterial virulence and enhancing host immune responses. The synergistic effects of combining QS inhibitors like RIP with traditional antimicrobial treatments reduce the need for highdose antibiotics, offering a potential solution to antibiotic resistance. This molecular communication-based approach presents a promising path to improved treatment efficacy and more robust immune responses against bacterial infections by targeting bacterial communication.
... The rise in microbial resistance due to excessive and inappropriate use of antimicrobials has resulted in 141,000 deaths in 2019 [1]. This threat compromises the effectiveness of current antimicrobials, including food preservatives [2]. ...
The increasing concern over microbial resistance to conventional antimicrobial agents used in food preservation has led to growing interest in plant-derived antimicrobial peptides (AMPs) as alternative solutions. In this study, the antimicrobial mechanisms of chia seed-derived peptides YACLKVK, KLKKNL, KLLKKYL, and KKLLKI were investigated against Staphylococcus aureus (SA) and Escherichia coli (EC). Fluorometric assays and scanning electron microscopy (SEM) demonstrated that the peptides disrupt bacterial membranes, with propidium iodide (PI) uptake reaching 72.34% in SA, calcein release of 98.27%, and N-phenyl-1-naphthylamine (NPN) uptake of 84.35% in EC. Increased membrane permeabilization was observed at concentrations above 5 mg/mL. SEM results further confirmed significant morphological changes, supporting the observed membrane damage. Additionally, the peptides showed intracellular activity by altering EC DNA mobility, suggesting a secondary antimicrobial mechanism through DNA interaction. These results indicate that the peptides are promising antimicrobials with potential mechanisms beyond membrane disruption, highlighting the need for further research to comprehensively understand their antimicrobial mechanisms.
... L'antibiorésistance entraîne environ 700 000 décès chaque année, un chiffre qui pourrait atteindre 10 millions d'ici 2050 si aucune action n'est entreprise, d'après un rapport d'un groupe de chercheurs des Nations Unies travaillant sur la résistance aux antimicrobiens. Ce nombre dépassera celui des décès annuels dus au cancer dans le monde [15,16] . ...
Introduction. Urinary tract infection in women is very common. The aim of this study is to analyze, in light of guidelines, the diagnostic and therapeutic approach of general practitioners in the Setif region regarding this condition. Methods. This is a descriptive cross-sectional study of practices, conducted anonymously. The survey was based on a pre-established questionnaire with 80 GPs. The questionnaire comprised two essential components: diagnostic approach and therapeutic modalities. Results. The diagnosis of uncomplicated acute cystitis is based on clinical examination plus urine dipstick test according to 28 GPs (35%), while 39 (45%) only prescribe treatment based on urine dipstick results. For first-line treatment, 35 (45%) GPs prescribe a first generation cephalosporin, and 10 (13%) did not provide any response. Short-duration treatment (4-7 days) is prescribed by 44 (55%) GPs, while 30 (38%) did not respond to this question. Among pregnant women, 68 (85%) conduct urine culture for diagnosis, and 71 (88%) provide treatment based on these results, while 34 (43%) did not respond to the question of first-line treatment. Conclusion. Although some practices align with international standards, deficiencies persist. It is crucial to improve awareness and training of practitioners to ensure optimal management of this common condition, while also contributing to the fight against antibiotic resistance, often overlooked in our country.
... Additionally, the impact of ABR on morbidity and mortality is substantial. A study published in the Lancet estimates that bacterial antibiotic resistance was responsible for approximately 1.27 million deaths globally in 2019 (Aguilar et al., 2023). Antibiotic-resistant infections are associated with longer hospital stays, increased risk of complications, and higher mortality rates compared to infections caused by susceptible bacteria (Peters et al., 2019). ...
Antibiotic resistance (ABR) is a major global health threat that puts decades of medical progress at risk. Bacteria develop resistance through various means, including modifying their targets, deactivating drugs, and utilizing efflux pump systems. The main driving forces behind ABR are excessive antibiotic use in healthcare and agriculture, environmental contamination, and gaps in the drug development process. The use of advanced detection technologies, such as next-generation sequencing (NGS), clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics, and metagenomics, has greatly improved the identification of resistant pathogens. The consequences of ABR on public health are significant, increased mortality rates, the endangerment of modern medical procedures, and resulting in higher healthcare expenses. It has been expected that ABR could potentially drive up to 24 million individuals into extreme poverty by 2030. Mitigation strategies focus on antibiotic stewardship, regulatory measures, research incentives, and raising public awareness. Furthermore, future research directions involve exploring the potential of CRISPR-Cas9 (CRISPR-associated protein 9), nanotechnology, and big data analytics as new antibiotic solutions. This review explores antibiotic resistance, including mechanisms, recent trends, drivers, and technological advancements in detection. It also evaluates the implications for public health and presents strategies for mitigating resistance. The review emphasizes the significance of future directions and research needs, stressing the necessity for sustained and collaborative efforts to tackle this issue.
... It is estimated that by 2050, almost 10 million deaths will be caused by anti-microbial resistant (AMR) bacteria, making AMR a bigger global killer than cancer [18]. Africa is disproportionately affected by the rise in AMR due to insufficient environmental health practices, poor household and healthcare infrastructure, and misuse and overuse of antibiotics, which all contribute to the transmission of AMR pathogens and a concomitant higher risk of mortality from common infections that are now resistant to standard treatments [19,20]. ...
Inadequate waste management and poor sanitation practices in Low- and Middle-Income Countries (LMICs) leads to waste accumulation in urban and peri-urban residential areas. This increases human exposure to hazardous waste, including plastics, which can harbour pathogenic bacteria. Although lab-based studies demonstrate how plastic pollution can increase the persistence and dissemination of dangerous pathogens, empirical data on pathogen association with plastic in real-world settings are limited. We conducted a year-long spatiotemporal sampling survey in a densely populated informal settlement in Malawi, quantifying enteric bacterial pathogens including ESBL-producing E. coli, Klebsiella pneumoniae, Salmonella spp., Shigella spp., and Vibrio cholerae. Culture-based screening and molecular approaches were used to quantify the presence of each pathogen, together with the distribution and frequency of resistance to antibiotics. Our data indicate that these pathogens commonly associate with urban waste materials. Elevated levels of these pathogens precede typical infection outbreaks, suggesting that urban waste piles may be an important source of community transmission. Notably, many pathogens displayed increased levels of AMR, including against several ‘last resort’ antibiotics. These findings highlight urban waste piles as potential hotspots for the dissemination of infectious diseases and AMR and underscores the need for urgent waste management interventions to mitigate public health risks.
... Antimicrobial resistance (AMR) is expected to cause significant clinical losses, severe economic consequences, and the loss of 10 million lives annually by 2050, according to the highly cited review on antimicrobial resistance. 1 According to a recent systematic investigation, AMR bacteria were responsible for 4.95 million deaths in 2019, and 1.27 million of them were directly related to AMR. 2 Based on the results of the Global Burden of Disease, Injuries, and Risk Factors (GBD) research, AMR was reported as the third most common cause of death after ischemic heart disease and stroke. 3 The stages of the process of bacterial resistance to antibiotics include; (i) genetic mutations in bacteria; (ii) overuse of broad-spectrum antibiotics; and (iii) bacteria form a biofilm which functions as a protector so that the bacteria are resistant to antibacterials. ...
Red ginger rhizome (Zingiber officinale var. Rubrum) and avocado leaves (Persea americana Mill.) are empirically known as one of the medicinal plants used in Taro Village, Gianyar Regency, Bali which have great potential in treating infectious diseases caused by antibiotic resistance, such as MRSA. This study aims to analyze the phytoconstituents and anti-MRSA potential contained in red ginger rhizome and avocado leaves extracts by assessing their inhibitory effects on three proteins related to MRSA resistance and virulence (PBAP2a, transglycosylase, and glycosyltransferase). Phytoconstituents of avocado leaf and red ginger extracts were analyzed using GC-MS. Molecular docking was performed in silico to determine the similarity properties of predicted drugs, bioactivity, toxicity, identification of active sites and validation of protein structures, and docking simulations were performed between compounds found in the extract and their target proteins. Phytoconstituent analysis revealed that avocado leaves and red ginger extracts as a whole have 43 types of compounds and 10 bioactive compounds each with beneficial drug-like properties. The compound 6,11-hexadecadien-1-ol from avocado leaves extracts was predicted to have hepatotoxic properties. There were at least 3 compounds, namely beta-bisabolene from avocado leaves extract, zingiberenol and gamma-curcumene from red ginger rhizome extract, showing the lowest binding affinity for the target protein. Red ginger rhizome and avocado leaves extracts showed valuable potential as anti-MRSA agents through the mechanism of inhibition of three resistance-related proteins, as predicted by in silico analysis.
... Although significant decreases were observed in H. influenzae co-infections, the rates of other pathogens did not change significantly during the pandemic, revealing the differential effects of the COVID-19 pandemic. The AMR of S. aureus exacerbates global health risks, leading to increased mortality, prolonged hospital stays, and higher healthcare costs 4,25,26 . Our study revealed high resistance among pediatric CAP patient-derived S. aureus strains to penicillins, first-generation macrolides, and lincosamides. ...
The COVID-19 pandemic has significantly transformed the infection spectrum of various pathogens. This study aimed to evaluate the impact of the COVID-19 pandemic on Staphylococcus aureus (S. aureus) infections among pediatric patients with community acquired pneumonia (CAP). We retrospectively reviewed pediatric CAP admissions before (from 2018 to 2019) and during (from 2020 to 2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) profiles of S. aureus isolates were examined to assess the pandemic’s effect. As a result, a total of 399 pediatric CAP patients with S. aureus infections were included. The positivity rate, gender, and age distribution of patients were similar across both periods. There was a marked reduction in respiratory co-infections with Haemophilus influenzae (H. influenzae) during the COVID-19 pandemic, compared to 2019. Additionally, there were significant changes in the resistance profiles of S. aureus isolates to various antibiotics. Resistance to oxacillin and tetracycline increased, whereas resistance to penicillin, gentamicin, and quinolones decreased. Notably, resistance to erythromycin significantly decreased in methicillin-resistant S. aureus (MRSA) strains. The number of S. aureus isolates, the proportion of viral co-infections, and the number of resistant strains typically peaked seasonally, primarily in the first or fourth quarters of 2018, 2019, and 2021. However, shifts in these patterns were noted in the first quarter of 2020 and the fourth quarter of 2022. These findings reveal that the COVID-19 pandemic has significantly altered the infection dynamics of S. aureus among pediatric CAP patients, as evidenced by changes in respiratory co-infections, AMR patterns, and seasonal trends.
... Antimicrobial resistance (AMR), resulting from the horizontal spread of resistance genes mediated by chromosomal mutations or mobile elements such as plasmids, has become one of the most remarkable public health challenges worldwide since the 1970s [1]. One Health surveillance for antimicrobial resistance has been promoted by the scientific community and by international organizations for more than a decade. ...
Background
A novel plasmid-mediated resistance–nodulation–division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the post-antibiotic era, including the “last-resort” antibiotic tigecycline.
Results
In this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance. Galleria mellonella and mouse infection models in vivo further revealed that harmaline is a promising candidate to reverse tigecycline resistance. Inspiringly, harmaline works synergistically with tigecycline by undermining tmexCD1-toprJ1-mediated multidrug resistance efflux pump function via interactions with TMexCD1-TOprJ1 active residues and dissipation of the proton motive force (PMF), and triggers a vicious cycle of disrupting cell membrane integrity and metabolic homeostasis imbalance.
Conclusion
These results reveal the potential of harmaline as a novel tigecycline adjuvant to combat hypervirulent K. pneumoniae infections.
... Problems arising from antimicrobial resistance affect both the developing and developed nations posing great risks to public health [3]. Worldwide, the centre for disease control estimated that 4.95 million people lost their lives due to antimicrobial resistance related infections in 2019 [4]. To curb this menace, metal nanoparticles such as copper, zinc and silver are increasingly being utilized as antimicrobial agents as they have been shown to possess good inhibitory activity [5][6][7]. ...
Biological synthesis of metal nanoparticles has caught the interest of scientists due to the environment friendly synthesis approach which yields metallic nanoparticles with antimicrobial potency. In the present study silver nanoparticles were produced using a green method with the assistance of Fusarium sp. fungal cell filtrate and their antimicrobial potency was explored. The silver nanoparticles depicted a surface plasma resonance of 434 nm when run in the Ultra Violet–Visible Spectrophotometer. The functional group present in the nanoparticles were investigated using an Attenuated Total Reflectance-Fourier Transform Infrared where –OH, C–H, amide I and amide II functional groups were notable. The morphology and crystallinity of the produced silver nanoparticles was investigated with the help of a Scanning Electron Microscope and X-ray Diffraction. The X-ray diffraction results revealed that the nanoparticles were crystalline in nature with a face centred cubic structure and a crystallite size of 38.5 nm. The Scanning Electron Microscope revealed that the nanoparticles were spherical with sizes ranging between 3 to 43 nm. Antimicrobial studies of the synthesised silver nanoparticles were conducted at different concentrations (1 mM, 10 mM, 20 mM and 100 mM) against disease causing microorganisms Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, the results showed that at a concentration of 1 mM there was no inhibition but as the concentration was increased to 20 mM and 100 mM, there was a notable inhibition with the maximum inhibition zone being 17 ± 0.6 mm.
... Furthermore, an estimated 4.95 million deaths were associated with bacterial AMR (Murray et al., 2022). Specifically, it was reported that 569,000 deaths (with a 95% UI of 406,000-771,000) were linked to bacterial AMR, and an additional 141,000 deaths (ranging from 99,900 to 196,000) were attributable to bacterial AMR within the 35 countries situated in the WHO Region of the Americas during the same year (Aguilar et al., 2023). It is worth noting that mortality related to antibiotic resistance has now escalated to become the third most prominent cause of death on a global scale (Murray et al., 2022). ...
Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites in patients. This includes Staphylococcus aureus bacteremia (SaB), which exhibits a severe infection frequently associated with significant mortality rate of approximately 25%. In the absence of better alternative therapies, antibiotics is still the main approach for treating infections. However, excessive use of antibiotics has, in turn, led to an increase in antimicrobial resistance. Hence, it is imperative that new strategies are developed to control drug-resistant S. aureus infections. Bacteriophages are viruses with the ability to infect bacteria. Bacteriophages, were used to treat bacterial infections before the advent of antibiotics, but were subsequently replaced by antibiotics due to limited theoretical understanding and inefficient preparation processes at the time. Recently, phages have attracted the attention of many researchers again because of the serious problem of antibiotic resistance. This article provides a comprehensive overview of phage biology, animal models, diverse clinical case treatments, and clinical trials in the context of drug-resistant S. aureus phage therapy. It also assesses the strengths and limitations of phage therapy and outlines the future prospects and research directions. This review is expected to offer valuable insights for researchers engaged in phage-based treatments for drug-resistant S. aureus infections.
... Resistance to antibiotics, drugs used to kill or slow the growth of bacteria and other microorganisms, is known as antibiotic resistance [43]. It's common practice to use antibiotics to treat a wide range of bacterial illnesses. ...
The postoperative burden remains significant due to the possibility of prolonged hospitalization, escalated healthcare costs, and patient distress caused by postorthopedic surgical site infections (SSIs). Orthopedic surgery is likewise faced with a significant challenge posed by these conditions. A positive association has been observed between the presence of postorthopedic SSIs and heightened susceptibility to adverse health outcomes, along with elevated rates of morbidity and mortality. Systemic antibiotic prophylaxis (SAP) reduces the risk of acquiring an SSI. Closed fractures, open fractures, arthroplasty, and percutaneous fixation each possess distinct attributes that impact the data and antimicrobial therapy. When implementing SAP, it is crucial to strike a delicate equilibrium between maintaining effective antibiotic stewardship protocols and preventing the occurrence of SSIs. This practice effectively prevents both the incidence of negative consequences and the emergence of antibiotic resistance. The objective of this study was to examine the existing literature on the use of surgical antibiotic prophylaxis in orthopedic surgery and explore the potential consequences associated with the inappropriate administration of antibiotics.
Background Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) impose the greatest burden among critical bacterial pathogens. Evidence for sex differences among antibiotic resistant bacterial infections is increasing but a focus on policy implications is needed. We assessed impact of CRE/MRSA on excess length of hospital stay, intensive care unit admission, and mortality by sex from a retrospective cohort study (n = 873) of patients in three Chilean hospitals, 2018-2021.
Background: Plant essential oils have been identified as potential alternatives or additions to topical antimicrobial formulations. Cinnamon Essential Oil (CEO), offers potential as an alternative to topical antimicrobials, addressing the threat of antimicrobial resistance. Excessive use of antibiotics drives resistance, necessitating safe and effective treatments. CEO's active components, cinnamaldehyde, and eugenol, exhibit strong antimicrobial properties. Objectives: This study focuses on the formulation design and antibacterial activity of topical microemulgels containing different variants of Ceylon and Cassia Cinnamon oils. It examines how the microemulgel formulation enhances the skin's absorption and delivery of active ingredients, leading to improved efficacy. Method: The particle size, Polydispersibility Index (PDI), and Minimum Inhibitory Concentration (MIC) of both variants of cinnamon oil microemulgels were investigated. Additionally, in-vitro permeation and in vivo, acute skin irritation studies were conducted on the microemulgels. Results: The study revealed that S.aureus and P.aeruginosa showed increased susceptibility to microemulgels containing Ceylon cinnamon oil (Cinnamomum zeylanicum) and Cassia cinnamon oil (Cinnamomum cassia), suggesting the efficacy of cinnamon oil as an antimicrobial agent. Conclusion: The findings carry wider significance for pushing forward research and innovation in topical drug delivery through essential oils. This effort aims to rejuvenate the efficacy of antibiotics and foster the creation of novel therapeutic methods for prevalent, minor skin infections.
Background/Objectives: Plant-derived compounds are increasingly valued in drug discovery for their therapeutic potential. This study aims to examine the antimicrobial, antioxidant, and anticancer properties of kombucha beverages fermented with Gardenia jasminoides (GJ) and various types of Camellia sinensis teas: matcha green tea (MGT), organic green tea (OGT), and decaffeinated green tea (DGT). Methods: Two experimental designs were employed: (1) using black tea as a base substrate, infusing the four teas post-fermentation over 0–14 days, and (2) directly fermenting tea–herb combinations over 0–21 days. Antioxidant activity was assessed via the DPPH assay. Microbial dynamics were analyzed through total mesophilic bacteria and Lactobacillus counts. Antimicrobial potential was evaluated against E. coli, S. aureus, and S. enteritidis over 24 h. Cytotoxicity assays were conducted on Caco-2 and U251 cell lines to assess anticancer effects, with pH-adjusted controls used to differentiate bioactivity from acidity. Results: In the first experiment, GJ kombucha displayed the highest antioxidant potential (IC50: 14.04 µg/mL), followed by MGT (IC50: 32.85 µg/mL) and OGT (IC50: 98.21 µg/mL). In the second setup, unfermented GJ kombucha initially showed high antioxidant activity (IC50: 12.94 µg/mL), improving during fermentation to reach an IC50 of 18.26 µg/mL by day 21. Microbial analysis indicated moderate increases in total mesophilic bacteria and Lactobacillus in GJ kombucha after 14 days, while MGT, OGT, and DGT exhibited higher increments. GJ kombucha consistently demonstrated the highest antimicrobial activity against E. coli, S. aureus, and S. enteritidis, with significant inhibitory effects observed by 24 h. Cytotoxicity assays showed that GJ kombucha reduced Caco-2 cell viability to 20% at 800 µg/mL after 14 days, while U251 cells maintained 50% viability at the same concentration. Conclusions: This study highlights the antimicrobial, antioxidant, and anticancer potential of GJ kombucha, with fermentation enhancing bioactive metabolite production. Optimizing fermentation conditions, identifying specific bioactive compounds, expanding cytotoxicity testing, and exploring broader therapeutic applications of kombucha could maximize its health benefits and establish it as a natural antimicrobial and anticancer agent.
Background
Gram-negative bloodstream infections are associated with significant morbidity and mortality in children. Increasing antimicrobial resistance (AMR) is reported globally, yet efforts to track pediatric AMR at a national level over time are lacking.
Methods
The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia. EUCAST 2022 was used for MIC interpretation and the AMR package in R for data analysis.
Results
Over a nine-year period, there were 3,145 bloodstream infections with 3,266 gram-negative isolates reported in hospitalized children aged <18 years; 21.0% were from neonates. The median length of stay was 9 days, and 30-day all-cause mortality was 5.2%. A greater odds of death was observed in those with a multi-drug resistant organism (aOR: 2.1, 95%CI: 1.3, 3.3, p: 0.001).
Escherichia coli (44.5%) and Klebsiella pneumoniae complex (12.6%) were the two most frequently reported organisms. Overall resistance in Enterobacterales to gentamicin/tobramycin was 11.6%, to ceftazidime/ceftriaxone was 12.9%, and 13.2% to ciprofloxacin. Resistance increased over time.
Of 201 Pseudomonas aeruginosa isolates reported, 19.7% were resistant to piperacillin-tazobactam, 13.1% resistant to cefepime/ceftazidime and 9.8% to ciprofloxacin. Of 108 Acinetobacter spp. isolates, one was resistant to meropenem, and two were resistant to ciprofloxacin. Resistance did not increase over time.
Conclusion
AMR in gram-negative organisms causing bloodstream infections in Australian children is increasing which should be considered when updating guidelines and empiric treatment regimens. Ongoing pediatric-specific national surveillance with pediatric reporting must remain a priority to strengthen antimicrobial stewardship and infection control programs.
The rising concern over microbial resistance and the potential impact on human health of conventional antimicrobial agents commonly utilized in food preservation has led to the research of plant antimicrobial peptides (AMPs) and their mechanisms of action. Therefore, study investigated the antimicrobial mechanisms of peptides YACLKVK, KLKKNL, KLLKKYL, and KLLKI, derived from a chia seed peptide fraction, against Staphylococcus aureus (SA) and Escherichia coli (EC). The analysis incorporated fluorometric assays and scanning electron microscopy (SEM) to determine membrane permeabilization and bacterial cell morphological changes. The peptides disrupt bacterial membranes, as shown by a propidium iodide (PI) uptake of 72.34 ± 1.87% in SA, calcein release of 98.27 ± 0.93%, and N-Phenyl-1-naphthylamine (NPN) uptake of 84.35 ± 3.03%, in EC. At concentrations above 5 mg/mL, an increased effect on membrane permeabilization was observed. SEM results indicated marked morphological alterations, thus supporting fluorometric findings of cell membrane damage. Furthermore, changes in electrophoretic mobility of EC DNA indicated peptide-DNA interactions, suggesting a supplementary antimicrobial effect through intracellular target engagement beyond membrane disruption. These results highlighted the peptides as promising novel antimicrobial agents with the capability to disrupt bacterial cell membranes and potentially target DNA. The need for further exploration of the peptides' intracellular actions and comprehensive antimicrobial mechanisms is emphasized.
This paper explores the integration of IoT devices, data analytics, and education techniques to enhance pediatric dental health outcomes. By leveraging real-time data collection, analysis, and personalized interventions, IoT can empower both caregivers and children to adopt proactive dental hygiene practices. This comprehensive approach not only improves oral health but also establishes lifelong habits for overall wellness. Pediatric dental health is a vital but often overlooked component of overall well-being. Despite its significance, it frequently lacks the attention it deserves. Integrating Internet of Things (IoT) technologies into pediatric dental care presents an opportunity for substantial improvement in early prevention and education strategies. This comprehensive approach not only enhances oral health but also establishes lifelong habits conducive to overall wellness. Pediatric dental health is a crucial determinant of overall well-being, yet it frequently remains overshadowed by other health priorities. Addressing pediatric dental health requires proactive measures, including early prevention and education strategies. The integration of Internet of Things (IoT) technologies presents a promising avenue to revolutionize pediatric dental care and enhance health outcomes. This paper delves into the potential of IoT devices, data analytics, and education techniques in improving pediatric dental health. By harnessing real-time data collection, analysis, and personalized interventions, IoT empowers caregivers and children to adopt proactive dental hygiene practices. This holistic approach not only enhances oral health but also fosters the development of lifelong habits conducive to overall wellness. Through a comprehensive examination of IoT integration, this paper underscores the transformative impact it can have on pediatric dental health, emphasizing the importance of prioritizing innovative approaches to address this critical aspect of childhood well-being.
Antibiotic resistance is an urgent public health threat: an estimated 2 out of every 5 infection deaths are associated with antibiotic resistant bacteria. Current actions to reduce this threat include requiring prescriptions for antibiotic use, antibiotic stewardship programs, educational programs targeting patients and healthcare providers, and limiting antibiotic use in agriculture, aquaculture, and animal husbandry. Early warning of the emergence and spread of antibiotic resistant bacteria would aid these efforts. The SARS-CoV-2 pandemic demonstrated the value of wastewater surveillance as an early warning system for viral spread and detection of the emergence of new viral strains. In this commentary we explore whether monitoring wastewater for antibiotic resistant genes and/or bacteria resistant to antibiotics might provide similarly useful information for public health action. Using carbapenem resistance as an example, we highlight technical challenges associated with using wastewater to quantify temporal/spatial trends in antibiotic resistant bacteria (ARBs) and antibiotic resistant genes (ARGs) and compare with clinical information. We also comment on using wastewater to track foodborne outbreaks. We conclude with our assessment that beyond source tracking the value added of screening wastewater for ARBs and ARGs for direct public health action is relatively low with current technologies compared to surveillance methods already in place.
This paper examines the importance of integrating pediatric oral health into primary care as a strategic approach to addressing these disparities and improving oral health outcomes for all children in the United States. It explores the current state of pediatric oral health, highlighting existing disparities and barriers to access to care. It discusses the potential benefits of integration, including increased access to care, early intervention, improved continuity of care, and enhanced patient outcomes. It reviews successful integration models and strategies for overcoming challenges. By prioritizing pediatric oral health within primary care and implementing evidence-based integration strategies by examining the prevailing landscape of pediatric oral health, including extant disparities and access barriers, it underscores the urgency of holistic intervention. It elucidates the multifaceted advantages of integration, encompassing augmented access to care, timely intervention, bolstered continuity of care, and amplified patient outcomes. These models underscore the potency of collective action, fostering seamless communication, fortified care coordination, and bespoke oral health services catering to diverse pediatric needs. Moreover, it delves into the intricacies of overcoming entrenched challenges, including reimbursement intricacies, workforce scarcities, and resource limitations. By foregrounding pediatric oral health within the primary care milieu and propelling evidence-based integration strategies, transformative strides toward eradicating oral diseases in children are envisaged. It posits that by cultivating a paradigm wherein pediatric oral health is seamlessly interwoven into primary care, a future characterized by equitable oral health outcomes and universal well-being beckons.
Introduction
Limited information on costs and the cost-effectiveness of hospital interventions to reduce antibiotic resistance (ABR) hinder efficient resource allocation.
Methods
We conducted a systematic literature review for studies evaluating the costs and cost-effectiveness of pharmaceutical and non-pharmaceutical interventions aimed at reducing, monitoring and controlling ABR in patients. Articles published until 12 December 2023 were explored using EconLit, EMBASE and PubMed. We focused on critical or high-priority bacteria, as defined by the WHO, and intervention costs and incremental cost-effectiveness ratio (ICER). Following Preferred Reporting Items for Systematic review and Meta-Analysis guidelines, we extracted unit costs, ICERs and essential study information including country, intervention, bacteria-drug combination, discount rates, type of model and outcomes. Costs were reported in 2022 US dollars (1 per patient, contrasting with generally higher pharmaceutical intervention costs. Several studies found that linezolid-based treatments for methicillin-resistant Staphylococcus aureus were cost-effective compared with vancomycin (ICER up to 1160/QALY or 1206 and $1115 per life-year saved in Europe and the USA). Comparisons were hindered by within-study differences.
Conclusion
Robust information on ABR interventions is critical for efficient resource allocation. We highlight cost-effective strategies for mitigating ABR in hospitals, emphasising substantial knowledge gaps, especially in low-income and middle-income countries. Our study serves as a resource for guiding future cost-effectiveness study design and analyses.
PROSPERO registration number CRD42020341827 and CRD42022340064
Citation: Ablakimova, N.; Smagulova, G.A.; Rachina, S.; Mussina, A.Z.; Zare, A.; Mussin, N.M.; Kaliyev, A.A.; Shirazi, R.; Tanideh, N.; Tamadon, A.
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.
Background:
Patient-level surveillance of antimicrobial use (AMU) in Canadian hospitals empowers the reduction of inappropriate AMU and was piloted in 2017 among 14 hospitals in Canada. We aimed to describe AMU on the basis of patient-level data in Canadian hospitals in 2018 in terms of antimicrobial prescribing prevalence and proportions, antimicrobial indications, and agent selection in medical, surgical and intensive care wards.
Methods:
Canadian adult, pediatric and neonatal hospitals were invited to participate in the standardized web-based cross-sectional Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) conducted in 2018. An identified site administrator assigned all wards admitting inpatients to specific surveyors. A physician, pharmacist or nurse with infectious disease training performed the survey. The primary outcomes were point prevalence rates for AMU over the study period regarding prescriptions, indications and agent selection in medical, surgical and intensive care wards. The secondary outcomes were AMU for resistant organisms and practice appropriateness evaluated on the basis of quality indicators. Antimicrobial consumption is presented in terms of prevalence and proportions.
Results:
Forty-seven of 118 (39.8%) hospitals participated in the survey; 9 hospitals were primary care centres, 15 were secondary care centres and 23 were tertiary or specialized care centres. Of 13 272 patients included, 33.5% (n = 4447) received a total of 6525 antimicrobials. Overall, 74.1% (4832/6525) of antimicrobials were for therapeutic use, 12.6% (n = 825) were for medical prophylaxis, 8.9% (n = 578) were for surgical prophylaxis, 2.2% (n = 143) were for other use and 2.3% (n = 147) were for unidentified reasons. A diagnosis or indication was documented in the patient's file at the initiation for 87.3% (n = 5699) of antimicrobials; 62.9% (n = 4106) of antimicrobials had a stop or review date; and 72.0% (n = 4697) of prescriptions were guided by local guidelines.
Interpretation:
Overall, three-quarters of AMU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.
Background:
Antimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption.
Methods:
In this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years.
Findings:
We analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3 (95% uncertainty interval 13·2-15·6) defined daily doses (DDD) per 1000 population per day in 2018 (40·2 [37·2-43·7] billion DDD), an increase of 46% from 9·8 (9·2-10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8-5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia.
Interpretation:
To our knowledge, this is the first study that incorporates antibiotic usage and consumption data and uses geostatistical modelling techniques to estimate antibiotic consumption for 204 countries from 2000 to 2018. Our analysis identifies both high rates of antibiotic consumption and a lack of access to antibiotics, providing a benchmark for future interventions.
Funding:
Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill & Melinda Gates Foundation.
Abstract
Background: Frequently used fluoroquinolones have been subject to increasing safety concerns and regulatory alerts. This study characterized ambulatory fluoroquinolone utilization in the United States and evaluated the impact of 2016 Food and Drug Administration (FDA) safety advisories on its use.
Methods: We used IQVIA's National Disease and Therapeutic Index to quantify adult outpatient fluoroquinolone use ("treatment visits"). Descriptive statistics and segmented regression were used to report trends and quantify the varied use before and after FDA's 2016 alerts.
Results: Between 2015 to 2019, fluoroquinolone use decreased by 26.7% (18.7 million treatment visits in 2015 to 13.7 million treatment visits in 2019). Annual use declined by 44%, 24%, and 24% for respiratory, urogenital, and gastrointestinal conditions, respectively; and by 66% among providers ≤44 years old vs negligible decline among those ≥65 years old. Before 2016 FDA advisories, there were approximately 4.8 million fluoroquinolone treatment visits/quarter, which had a statistically significant immediate drop by 641035 visits (95% confidence interval [CI], -937368 to -344702; P=.000) after FDA's 2016 advisories. A statistically significant difference of approximately 45000 visits/quarter (95% CI, -85956 to -3122; P=.036) was observed after the advisories.
Conclusions: Large reductions in ambulatory fluoroquinolone use in the United States have coincided with increasing evidence of safety concerns and FDA advisories. However, fluoroquinolone use varies significantly based on patient and provider characteristics, suggesting heterogeneous effects of emerging risks on clinical practice.
Keywords: antibiotic stewardship; black-box warnings; fluoroquinolones; segmented regression; trends
Background: The impact of United States (US) Food and Drug Administration (FDA) safety warnings on outpatient fluoroquinolone use is unclear.
Methods: Annual changes in outpatient ciprofloxacin, levofloxacin and moxifloxacin prescription fills (IQVIA National Prescription Audit databases) were assessed using a regression model. Monthly fills during baseline (August 2014–April 2016), first (May 2016–June 2018), and second FDA warning periods (July 2018–February 2020) were compared by interrupted time series analysis.
Results: From 2015 through 2019, total fluoroquinolone fills decreased from 35,616,786 (111.1/1000 persons) to 21,100,050 (64.3/1000 persons) annually (10.8% annually ( P =0.001)). Ciprofloxacin, levofloxacin, and moxifloxacin fills decreased annually by 10.4% ( P =0.001), 11.2% ( P <0.001), and 17.7% ( P =0.008), respectively. During the baseline period, there was no significant change in monthly fluoroquinolone fills. In May 2016 and during the first warning period, monthly fluoroquinolone fills decreased significantly ( P -values<0.001); the trend of decreased fills was significantly greater than that of the baseline period ( P =0.02). There was no change in fluoroquinolone fills in July 2018. Monthly fills decreased significantly throughout the second warning period ( P <0.001), but the trend did not differ from that of the first warning period. Trends for ciprofloxacin, the most commonly prescribed fluoroquinolone, were similar to those for the class. Fills of prescriptions by infectious diseases specialists ( P <0.005) and nurse practitioners ( P =0.04) significantly increased during the study.
Conclusions: US outpatient fluoroquinolone prescription fills significantly decreased from August 2014-February 2020, most strongly in association with May 2016 FDA warnings. FDA safety warnings are useful tools for leveraging outpatient antimicrobial stewardship.
Background
Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) emerged in the 1990s as a global community pathogen primarily involved in skin and soft tissue infections (SSTIs) and pneumonia. To date, the CG-MRSA SSTI burden in Latin America (LA) has not been assessed.
Objective
The main objective of this study was to report the rate and genotypes of community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) causing community-onset skin and soft tissue infections (CO-SSTIs) in LA over the last two decades. In addition, this research determined relevant data related to SSTIs due to CG-MRSA, including risk factors, other invasive diseases, and mortality.
Data sources
Relevant literature was searched and extracted from five major databases: Embase, PubMed, LILACS, SciELO, and Web of Science.
Methods
A systematic review was performed, and a narrative review was constructed.
Results
An analysis of 11 studies identified epidemiological data across LA, with Argentina presenting the highest percentage of SSTIs caused by CG-MRSA (88%). Other countries had rates of CG-MRSA infection ranging from 0 to 51%. Brazil had one of the lowest rates of CG-MRSA SSTI (4.5–25%). In Argentina, being younger than 50 years of age and having purulent lesions were predictive factors for CG-MRSA CO-SSTIs. In addition, the predominant genetic lineages in LA belonged to sequence types 8, 30, and 5 (ST8, ST30, and ST5).
Conclusion
There are significant regional differences in the rates of CG-MRSA causing CO-SSTIs. It is not possible to conclude whether or not CG-MRSA CO-SSTIs resulted in more severe SSTI presentations or in a higher mortality rate.
Background:
Treatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of appropriate initial antibiotic therapy (AIAT) and inappropriate initial antibiotic therapy (IIAT) in P. aeruginosa infections, and the literature on risk factors for acquisition of resistant P. aeruginosa among hospitalized adult patients in LATAM.
Methods:
MEDLINE, EMBASE, Cochrane, and LILAC were searched between 2000 and August 2019. Abstracts and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when studies were sufficiently similar.
Results:
The screening of 165 citations identified through literature search yielded 98 full-text articles that were retrieved and assessed for eligibility, and 19 articles conducted in Brazil (14 articles), Colombia (4 articles), and Cuba (1 article) met the inclusion criteria. Of 19 eligible articles, six articles (840 subjects) examined AIAT compared to IIAT in P. aeruginosa infections; 17 articles (3203 total subjects) examined risk factors for acquisition of resistant P. aeruginosa; and four articles evaluated both. Four of 19 articles were rated low risk of bias and the remaining were deemed unclear or high risk of bias. In meta-analysis, AIAT was associated with lower mortality for P. aeruginosa infections (unadjusted summary OR 0.48, 95% CI 0.28-0.81; I2 = 59%), compared to IIAT and the association with mortality persisted in subgroup meta-analysis by low risk of bias (3 articles; unadjusted summary OR 0.46, 95% CI 0.28-0.81; I2 = 0%). No meta-analysis was performed for studies evaluating risk factors for acquisition of resistant P. aeruginosa as they were not sufficiently similar. Significant risk factors for acquisition of resistant P. aeruginosa included: prior use of antibiotics (11 articles), stay in the intensive care unit (ICU) (3 articles), and comorbidity score (3 articles). Outcomes were graded to be of low strength of evidence owing to unclear or high risk of bias and imprecise estimates.
Conclusion:
Our study highlights the association of AIAT with lower mortality and prior use of antibiotics significantly predicts acquiring resistant P. aeruginosa infections. This review reinforces the need for rigorous and structured antimicrobial stewardship programs in the LATAM region.
Background:
Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.
Methods:
We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.
Findings:
In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.
Interpretation:
Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.
Funding:
The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.
The surveillance of antimicrobial-resistant isolates has proven to be one of the most valuable tools to understand the global rise of multidrug-resistant bacterial pathogens. We report the first insights into the current situation in the Caribbean, where a pilot project to monitor antimicrobial resistance (AMR) through phenotypic resistance measurements combined with whole-genome sequencing was set up in collaboration with the Caribbean Public Health Agency (CARPHA). Our first study focused on Klebsiella pneumoniae, a highly relevant organism amongst the Gram-negative opportunistic pathogens worldwide causing hospital- and community-acquired infections. Our results show that not only carbapenem resistance, but also hypervirulent strains, are circulating in patients in the Caribbean. Our current data does not allow us to infer their prevalence in the population. We argue for the urgent need to further support AMR surveillance and stewardship in this almost uncharted territory, which can make a significant impact on the reduction of antimicrobial usage. This article contains data hosted by Microreact (https://microreact.org).
Significance
Antibiotic resistance, driven by antibiotic consumption, is a growing global health threat. Our report on antibiotic use in 76 countries over 16 years provides an up-to-date comprehensive assessment of global trends in antibiotic consumption. We find that the antibiotic consumption rate in low- and middle-income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries. However, inequities in drug access persist, as many LMICs continue to be burdened with high rates of infectious disease-related mortality and low rates of antibiotic consumption. Our findings emphasize the need for global surveillance of antibiotic consumption to support policies to reduce antibiotic consumption and resistance while providing access to these lifesaving drugs.
Since the first clinical isolate of methicillin-resistant Staphylococcus aureus was described in 1961, this pathogen has established itself as a leading cause of health care-associated infections. More recently, MRSA has become a relatively common cause of infection among persons without typical health care-associated risk factors and is now the most common cause of community-onset purulent skin and soft-tissue infections in many regions of the USA. The appearance of “community-associated” MRSA is not due to the expansion of health care-associated MRSA into the community but rather the result of the independent emergence of a novel clone of MRSA. There are some encouraging data to suggest that the incidence of MRSA infection, particularly invasive infections, is decreasing in the USA, but this pathogen remains a common cause of infection associated with substantial morbidity and mortality. Thus, there is ongoing need for effective and safe prevention, diagnosis, and treatment strategies.
Drug-resistant bacterial infections pose a serious and growing public health threat globally. In this review, we describe the role of the National Antimicrobial Resistance Monitoring System (NARMS) in providing data that help address the resistance problem and show how such a program can have broad positive impacts on public health. NARMS was formed two decades ago to help assess the consequences to human health arising from the use of antimicrobial drugs in food animal production in the United States. A collaboration among the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the United States Department of Agriculture, and state and local health departments, NARMS uses an integrated "One Health" approach to monitor antimicrobial resistance in enteric bacteria from humans, retail meat, and food animals. NARMS has adapted to changing needs and threats by expanding surveillance catchment areas, examining new isolate sources, adding bacteria, adjusting sampling schemes, and modifying antimicrobial agents tested. NARMS data are not only essential for ensuring that antimicrobial drugs approved for food animals are used in ways that are safe for human health but they also help address broader food safety priorities. NARMS surveillance, applied research studies, and outbreak isolate testing provide data on the emergence of drug-resistant enteric bacteria; genetic mechanisms underlying resistance; movement of bacterial populations among humans, food, and food animals; and sources and outcomes of resistant and susceptible infections. These data can be used to guide and evaluate the impact of science-based policies, regulatory actions, antimicrobial stewardship initiatives, and other public health efforts aimed at preserving drug effectiveness, improving patient outcomes, and preventing infections. Many improvements have been made to NARMS over time and the program will continue to adapt to address emerging resistance threats, changes in clinical diagnostic practices, and new technologies, such as whole genome sequencing.
Objective:
To provide information on the prevalence and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and the distinction between community-associated MRSA and health care-associated MRSA.
Quality of evidence:
The MEDLINE and EMBASE databases were searched from 2005 to 2016. Epidemiologic studies were summarized and the relevant treatment literature was based on level I evidence.
Main message:
The incidence of community-associated MRSA infection is rising. Certain populations, including indigenous Canadians and homeless populations, are particularly affected. Community-associated MRSA can be distinguished from health care-associated MRSA based on genetic, epidemiologic, or microbiological profiles. It retains susceptibility to some oral agents including trimethoprim-sulfamethoxazole, clindamycin, and tetracyclines. Community-associated MRSA typically presents as purulent skin and soft tissue infection, but invasive infection occurs and can lead to severe, complicated disease. Treatment choices and the need for empiric MRSA coverage are influenced by the type and severity of infection.
Conclusion:
Community-associated MRSA is a common cause of skin and soft tissue infections and might be common in populations where overcrowding and limited access to clean water exist.
Background
The in vitro activity of tigecycline and comparator agents was evaluated against Gram-positive and Gram-negative isolates collected in Latin American centers between 2004 and 2015 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) global surveillance study.
Methods
Minimum inhibitory concentrations (MICs) were determined using the broth microdilution methodology according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Antimicrobial susceptibility was determined using CLSI breakpoints, except for tigecycline for which the US Food and Drugs Administration breakpoints were used.
Results
A total of 48.3% (2202/4563) of Staphylococcus aureus isolates were methicillin-resistant S. aureus (MRSA). All MRSA isolates were susceptible to linezolid and vancomycin, and 99.9% (2199/2202) were susceptible to tigecycline. Among Streptococcus pneumoniae isolates, 13.8% (198/1436) were penicillin-resistant; all were susceptible to linezolid and vancomycin, and 98.0% (194/198) were susceptible to tigecycline. Susceptibility was >99.0% for linezolid and tigecycline against Enterococcus faecium and Enterococcus faecalis isolates. A total of 40.8% (235/576) E. faecium and 1.6% (33/2004) E. faecalis isolates were vancomycin-resistant. Among the Enterobacteriaceae, 36.3% (1465/4032) of Klebsiella pneumoniae isolates, 16.4% (67/409) of Klebsiella oxytoca isolates and 25.4% (1246/4912) of Escherichia coli isolates were extended-spectrum β-lactamase (ESBL) producers. Of the ESBL-producing K. pneumoniae and E. coli isolates, susceptibility was highest to tigecycline [93.4% (1369/1465) and 99.8% (1244/1246), respectively] and meropenem [86.9% (1103/1270) and 97.0% (1070/1103), respectively]. A total of 26.7% (966/3613) of Pseudomonas aeruginosa isolates were multidrug-resistant (MDR). Among all P. aeruginosa isolates, susceptibility was highest to amikacin [72.8% (2632/3613)]. A total of 70.3% (1654/2354) of Acinetobacter baumannii isolates were MDR, and susceptibility was highest to minocycline [88.3% (2079/2354) for all isolates, 86.2% (1426/1654) for MDR isolates]. Tigecycline had the lowest MIC90 (2 mg/L) among A. baumannii isolates, including MDR isolates.
Conclusions
This study of isolates from Latin America shows that linezolid, vancomycin and tigecycline continue to be active in vitro against important Gram-positive organisms such as MRSA, and that susceptibility rates to meropenem and tigecycline against members of the Enterobacteriaceae, including ESBL-producers, were high. However, we report that Latin America has high rates of MRSA, MDR A. baumannii and ESBL-producing Enterobacteriaceae which require continued monitoring.
Electronic supplementary material
The online version of this article (doi:10.1186/s12941-017-0222-0) contains supplementary material, which is available to authorized users.
Introduction
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is of growing concern globally. The risk for transmission of antimicrobial resistant organisms across several continents to the Caribbean is a real one given its tourism industry. After a cluster of cases of CRKP were detected, several studies detailed in this report were initiated to better characterize the problem.
Methods
A hospital-wide point prevalence study and active surveillance were performed at Queen Elizabeth Hospital (QEH) in Barbados in 2013 to assess the prevalence of CRKP infection/colonization. Following this, a 1-year longitudinal study measured the prevalence of CRKP isolates in the hospital and across all healthcare facilities in the country.
Results
In 2013, eleven viable isolates of CRKP from cluster of cases were sent for molecular epidemiology studies. When sequenced, they were found to be the ST-258 clone. Identification of a cluster of cases of CRKP ST-258/512 clones indicated person-to-person transmission. In September 2013, the hospital-wide point prevalence study revealed 18% of patients (53/299) at the hospital were either colonized or infected with CRKP. The infection to colonization ratio was 1:7. Patients who were infected/colonized vs. non-colonized were older (64.7 vs. 48.7 years, p<0.0001), were hospitalized longer (42.5 days vs. 27 days, p = 0.0042), were more likely to have an invasive device (66% vs. 32%, p<0.0001), especially urinary catheters (55% vs. 24%, p<0.0001), and were more likely to have used antimicrobials within the prior 14 days (91% vs. 46%, p<0.0001). Specific antimicrobials, including fluoroquinolones and piperacillin-tazobactam, were significantly associated with infection/colonization. In 2014, the 12-month period prevalence of CRKP in Barbados was 49.6 per 100,000 population and of blood stream infections was 3.2 per 100,000 population.
Conclusions
This point prevalence study identified patients at-risk of acquisition of CRKP and allowed QEH to implement interventions aimed at decreasing the prevalence of CRKP. Organization of a National and regional Infection Prevention and Control Committee in 2014 aimed to strengthen antimicrobial resistance surveillance programs across the English-speaking Caribbean were established.
Marlieke de Kraker and colleagues reflect on the need for better global estimates for the burden of antimicrobial resistance.
Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website.
Antimicrobial resistance is a global public health challenge, which has accelerated by the overuse of antibiotics worldwide. Increased antimicrobial resistance is the cause of severe infections, complications, longer hospital stays and increased mortality. Overprescribing of antibiotics is associated with an increased risk of adverse effects, more frequent re-attendance and increased medicalization of self-limiting conditions. Antibiotic overprescribing is a particular problem in primary care, where viruses cause most infections. About 90% of all antibiotic prescriptions are issued by general practitioners, and respiratory tract infections are the leading reason for prescribing. Multifaceted interventions to reduce overuse of antibiotics have been found to be effective and better than single initiatives. Interventions should encompass the enforcement of the policy of prohibiting the over-the-counter sale of antibiotics, the use of antimicrobial stewardship programmes, the active participation of clinicians in audits, the utilization of valid rapid point-of-care tests, the promotion of delayed antibiotic prescribing strategies, the enhancement of communication skills with patients with the aid of information brochures and the performance of more pragmatic studies in primary care with outcomes that are of clinicians' interest, such as complications and clinical outcomes.
This study aimed to determine the excess length of stay, extra expenditures, and attributable mortality to healthcare-associated S. aureus bloodstream infection (BSI) at a teaching hospital in central Brazil. The study design was a matched (1:1) case-control. Cases were defined as patients > 13 years old, with a healthcare-associated S. aureus BSI. Controls included patients without an S. aureus BSI, who were matched to cases by gender, age (± 7 years), morbidity, and underlying disease. Data were collected from medical records and from the Brazilian National Hospital Information System (Sistema de Informações Hospitalares do Sistema Único de Saúde - SIH/SUS). A Wilcoxon rank sum test was performed to compare length of stay and costs between cases and controls. Differences in mortality between cases and controls were compared using McNemar's tests. The Mantel-Haenzel stratified analysis was performed to compare invasive device utilization. Data analyses were conducted using Epi Info 6.0 and Statistical Package for Social Sciences (SPSS 13.0). 84 case-control pairs matched by gender, age, admission period, morbidity, and underlying disease were analyzed. The mean lengths of hospital stay were 48.3 and 16.2 days for cases and controls, respectively (p
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is resistant to almost all antimicrobial agents, and CRKP infections are associated with substantial morbidity and mortality.
To describe an outbreak of CRKP in Puerto Rico, determine risk factors for CRKP acquisition, and detail the successful measures taken to control the outbreak.
Two case-control studies.
A 328-bed tertiary care teaching hospital.
Twenty-six CRKP case patients identified during the outbreak period of February through September 2008, 26 randomly selected uninfected control patients, and 26 randomly selected control patients with carbapenem-susceptible K. pneumoniae (CSKP) hospitalized during the same period.
We performed active case finding, including retrospective review of the hospital's microbiology database and prospective perirectal surveillance culture sampling in high-risk units. Case patients were compared with each control group while controlling for time at risk. We sequenced the bla(KPC) gene with polymerase chain reaction for 7 outbreak isolates and subtyped these isolates with pulsed-field gel electrophoresis.
In matched, multivariable analysis, the presence of wounds (hazard ratio, 19.0 [95% confidence interval {CI}, 2.5-142.0]) was associated with CRKP compared with no K. pneumoniae. Transfer between units (adjusted odds ratio [OR], 7.5 [95% CI, 1.8-31.1]), surgery (adjusted OR, 4.0 [95% CI, 1.0-15.7]), and wounds (adjusted OR, 4.9 [95% CI, 1.1-21.8]) were independent risk factors for CRKP compared to CSKP. A novel K. pneumoniae carbapenemase variant (KPC-8) was present in 5 isolates. Implementation of active surveillance for CRKP colonization and cohorting of CRKP patients rapidly controlled the outbreak.
Enhanced surveillance for CRKP colonization and intensified infection control measures that include limiting the physical distribution of patients can reduce CRKP transmission during an outbreak.
Objectives
. To determine the prevalence of ESBL non-CRE (carbapenem-resistant Enterobacterales) phenotype isolates among clinical isolates of Escherichia coli and Klebsiella pneumoniae collected in 2018-2019 for the SMART global surveillance program and to review trends in prevalence over 5 years (2015-2019).
Methods
. MICs were determined by CLSI reference broth microdilution. ESBL non-CRE phenotypes were defined as nonsusceptible to ceftriaxone (MIC ≥2 µg/ml) and susceptible to ertapenem (MIC ≤0.5 µg/ml).
Results
. In 2018-2019, ESBL non-CRE phenotypes among E. coli were more common in respiratory tract infection isolates than other infection sources across all global regions; for K. pneumoniae there was wide variation by geographic region in the specimen source most frequently associated with this phenotype. In most regions, ESBL non-CRE phenotype isolates were found more frequently in samples of patients in ICUs than from non-ICU patients and from patients with length of hospital stay at the time of specimen collection of ≥48 hours than stays <48 hours. ESBL non-CRE phenotypes exceeded 50% of isolates for E. coli from India, Thailand, Vietnam, China, Russia, Mexico, Kenya, and Kuwait and for K. pneumoniae from Lithuania and Kuwait. ESBL non-CRE phenotype E. coli increased significantly (p<0.05) in Asia (excluding China), Australia/New Zealand, and Latin America from 2015-2019 while ESBL non-CRE phenotype K. pneumoniae increased significantly in Latin America, United States, and Canada.
Conclusion
. There was marked variability in ESBL rates across countries, over time, and by sample source and ward type. Trending data from 2015-2019 showed ESBL rates are increasing in many regions worldwide.
The Food and Drug Administration warned against fluoroquinolone use for conditions with effective alternative agents. An estimated 5.1% of adult ambulatory fluoroquinolone prescriptions were for conditions that did not require antibiotics, and 19.9% were for conditions where fluoroquinolones are not recommended first-line therapy. Unnecessary fluoroquinolone use should be reduced.
Introduction: Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. infections are major causes of morbidity and mortality, especially due to the emergence and spread of β-lactamases. Carbapenemases, which are β-lactamases with the capacity to hydrolyze or inactivate carbapenems, have become a serious concern as they have the largest hydrolytic spectrum and therefore limit the utility of most β-lactam antibiotics. Areas covered: Here, we present an update of the current status of carbapenemases in Latin America and the Caribbean. Expert commentary: The increased frequency of reports on carbapenemases in Latin America and the Caribbean shows that they have successfully spread and have even become endemic in some countries. Countries such as Brazil, Colombia, Argentina, and Mexico account for the majority of these reports. Early suspicion and detection along with implementation of antimicrobial stewardship programs in all healthcare settings are crucial for the control and prevention of carbapenemase-producing bacteria.
Bacterial organisms (n = 13,494) were consecutively collected in 2011-2014 from 21 Latin American medical centres (11 nations). Antimicrobial susceptibility was determined by broth microdilution at a central laboratory. Tigecycline was very active against Gram-positive organisms, with MIC50/90 values of 0.06/0.06 µg/mL for Staphylococcus aureus (n = 2878), 0.06/0.12 µg/mL for coagulase-negative staphylococci (n = 880), 0.06/0.06 µg/mL for enterococci (n = 708) and ≤0.03/≤0.03-0.06 µg/mL for streptococci (n = 1352). All Gram-positive species exhibited 100.0% susceptibility (FDA and/or EUCAST criteria), except for Streptococcus pneumoniae (99.8% susceptible). The S. aureus oxacillin resistance rate varied from 28.0% (Brazil) to 55.0% (Argentina), and the overall vancomycin resistance rate was 15.5% (Enterococcus faecium, 50.3%; and Enterococcus faecalis, 2.3%). The E. faecium vancomycin resistance rate varied from a low (26.3%) in Argentina to a high (71.7%) in Brazil. Against Enterobacteriaceae (n = 4543), tigecycline MIC50/90 values were 0.25/1 µg/mL; 98.3% and 94.2% of strains were considered susceptible according to FDA and EUCAST breakpoints, respectively. Overall, 37.7% and 57.3% of Escherichia coli and Klebsiella pneumoniae exhibited the CLSI ESBL screening phenotype. The highest CLSI ESBL screening phenotype rates among E. coli and Klebsiella spp. strains were observed for isolates collected from Mexico (69.9%) and Chile (69.9%), respectively. Occurrence of carbapenem-resistant Enterobacteriaceae was substantially higher in Brazil (9.0%) and Argentina (6.3%) compared with Chile and Mexico (0.4-0.7%). Tigecycline was also active against Acinetobacter spp. (MIC50/90, 1/2 µg/mL; 92.3/72.1% inhibited at ≤2/≤1 µg/mL) and Stenotrophomonas maltophilia (MIC50/90, 0.5/2 µg/mL; 91.5/83.0% inhibited at ≤2/≤1 µg/mL).
Department of Maternal and Child Nursing and Public Health
- E J S Prates
Department of Maternal and Child Nursing and Public Health (E J S
Prates BS), Federal University of Minas Gerais, Belo Horizonte, Brazil;
Chia, Colombia; (E Roilides MD); International Nosocomial Infection Control Consortium (V D Rosenthal MD), Independent Consultant
- K E Rudd Md
Unisabana Center for Translational Science (L F Reyes PhD), Universidad de La Sabana, Chia, Colombia; Critical Care Department (L F
Reyes PhD), Clinica Universidad De La Sabana, Chia, Colombia; (E
Roilides MD); International Nosocomial Infection Control Consortium
(V D Rosenthal MD), Independent Consultant, Buenos Aires,
Argentina; Department of Critical Care Medicine (K E Rudd MD),
University of Pittsburgh, Pittsburgh, PA, USA; National Heart, Lung,
and Blood Institute (A Seylani BS), National Institute of Health, Rockville, MD, USA; Department of Pathology, Lenox Hill Hospital (S Sham
MBBS), Northwell Health, New York, NY, USA; Department of Medicine (Prof J Sifuentes-Osornio MD), National Institute of Nutrition,
Tlalpan, Mexico; Department of Pulmonary and Critical Care Medicine
(H Singh MD), Medical College of Wisconsin, Milwaukee, WI, USA;
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Department of Clinical Pharmacy and Outcomes Sciences (I Yunusa
PhD), University of South Carolina, Columbia, SC, USA; Addictology
Department (Prof M S Zastrozhin PhD), Russian Medical Academy of
Continuous Professional Education, Moscow, Russia; Mahidol Oxford
Tropical Medicine Research Unit (C Dolecek PhD), Mahidol University,
Bangkok, Thailand.
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