RESUMO
The pharmacokinetic (PK)/pharmacodynamic (PD) approach has been widely used in clinical practice to optimize antimicrobial treatment. To promote the appropriate use of antimicrobial agents, it is important to consider certain factors, such as patient (e.g., age, physique, medical history, comorbidities, and organ dysfunction), site of infection (the target site where many causative bacteria are present), and microorganism (causative bacteria and susceptibility), and the dosing regimen should be selected based on the PK/PD approach. However, for renally excreted antibiotics, dosing regimens based on only renal function, such as creatinine clearance, are mainly used. Therefore, other factors such as patient pathological factors, antibiotic penetration of target sites, susceptibility of the causative bacteria to antibiotic, and clinical evaluation (efficacy and toxicity) should be considered simultaneously. These studies aimed to tailor the dosing of antimicrobial agents to individual patients by considering these factors. Multifaceted PK/PD evaluation may improve antimicrobial efficacy and safety, thereby contributing to the successful treatment of infectious diseases. Furthermore, improved treatment success rates may help manage the prevalence of antimicrobial-resistant bacteria, which is expected to become a significant problem in the future.
Assuntos
Medicina de Precisão , Humanos , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Farmacorresistência Bacteriana , Infecções Bacterianas/tratamento farmacológico , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/administração & dosagem , Bactérias/efeitos dos fármacos , Fatores EtáriosRESUMO
BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Humanos , Uganda/epidemiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Infecções Bacterianas/microbiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificaçãoRESUMO
Antibiotic resistance has emerged as a global threat, rendering the existing conventional treatment strategies ineffective. In view of this, antimicrobial peptides (AMPs) have proven to be potent alternative therapeutic interventions with a wide range of applications in clinical health. AMPs are small peptides produced naturally as a part of the innate immune responses against a broad range of bacterial, fungal and viral pathogens. AMPs present a myriad of advantages over traditional antibiotics, including their ability to target multiple sites, reduced susceptibility to resistance development, and high efficacy at low doses. These peptides have demonstrated notable potential in inhibiting microbes resistant to traditional antibiotics, including the notorious ESKAPE pathogens, recognized as the primary culprits behind nosocomial infections. AMPs, with their multifaceted benefits, emerge as promising candidates in the ongoing efforts to combat the escalating challenges posed by antibiotic resistance. This in-depth review provides a detailed discussion on AMPs, encompassing their classification, mechanism of action, and diverse clinical applications. Focus has been laid on combating newly emerging drug-resistant organisms, emphasizing the significance of AMPs in mitigating this pressing challenge. The review also illuminates potential future strategies that may be implemented to improve AMP efficacy, such as structural modifications and using AMPs in combination with antibiotics and matrix-inhibiting compounds.
Assuntos
Peptídeos Antimicrobianos , Bactérias , Humanos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Fungos/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Farmacorresistência Bacteriana , Peptídeos Catiônicos Antimicrobianos/farmacologia , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologiaRESUMO
This month, the United Nations (UN) General Assembly will convene its second High-Level Meeting on antimicrobial resistance, urging UN member states to take decisive action against this growing threat. The US Centers for Disease Control and Prevention (CDC) has released a list of the drug-resistant bacterial and fungal infections that pose the greatest concern to public health. Yet, despite increasing warnings from infectious disease experts, the public remains largely unaware of the true scale of the problem. In a world where antibiotics still protect us from bacterial infections, we are shielded from experiencing antimicrobial resistance as an immediate threat to our daily lives.
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Antibacterianos , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Centers for Disease Control and Prevention, U.S. , Micoses/tratamento farmacológico , Micoses/microbiologia , Nações Unidas , Estados UnidosRESUMO
The widespread spread of bacterial antimicrobial resistance (AMR) and multidrug-resistant bacteria poses a significant threat to global public health. Traditional methods for detecting bacterial AMR are simple, reproducible, and intuitive, requiring long time incubation and high labor intensity. To quickly identify and detect bacterial AMR is urgent for clinical treatment to reduce mortality rate, and many new methods and technologies were required to be developed. This review summarizes the current phenotypic and genotypic detection methods for bacterial AMR. Phenotypic detection methods mainly include antimicrobial susceptibility tests, while genotypic detection methods have higher sensitivity and specificity and can detect known or even unknown drug resistance genes. However, most of the current tests are either genotypic or phenotypic and rarely combined. Combining the advantages of phenotypic and genotypic methods, combined with the joint application of multiple rapid detection methods may be the trend for future AMR testing. Driven by rapid diagnostic technology, big data analysis, and artificial intelligence, detection methods of bacterial AMR are expected to constantly develop and innovate. Adopting rational detection methods and scientific data analysis can better address the challenges of bacterial AMR and ensure human health and social well-being.
Assuntos
Antibacterianos , Bactérias , Farmacorresistência Bacteriana , Genótipo , Testes de Sensibilidade Microbiana , Saúde Única , Fenótipo , Humanos , Antibacterianos/farmacologia , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana/genética , Infecções Bacterianas/microbiologia , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
PURPOSE: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. PATIENTS AND METHODS: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. RESULTS: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. CONCLUSION: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.
Assuntos
Antibacterianos , Bile , Doenças Biliares , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Doenças Biliares/microbiologia , Doenças Biliares/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Adulto , Bile/microbiologia , Antibacterianos/uso terapêutico , Fatores de Risco , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológico , Prevalência , Adulto JovemRESUMO
Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.
Assuntos
Infecções Bacterianas , COVID-19 , Coinfecção , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , Coinfecção/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/mortalidade , Antibacterianos/uso terapêutico , Farmacorresistência BacterianaRESUMO
Owing to the unique quantum size effect and surface effect, gold-based nanomaterials (GNMs) are promising for pathogen detection and broad-spectrum antimicrobial activity. This review summarizes recent research on GNMs as sensors for detecting pathogens and as tools for their elimination. Firstly, the need for pathogen detection is briefly introduced with an overview of the physicochemical properties of gold nanomaterials. And then strategies for the application of GNMs in pathogen detection are discussed. Colorimetric, fluorescence, surface-enhanced Raman scattering (SERS) techniques, dark-field microscopy detection and electrochemical methods can enable efficient, sensitive, and specific pathogen detection. The third section describes the antimicrobial applications of GNMs. They can be used for antimicrobial agent delivery and photothermal conversion and can act synergistically with photosensitizers to achieve the precise killing of pathogens. In addition, GNMs are promising for integrated pathogen detection and treatment; for example, combinations of colorimetric or SERS detection with photothermal sterilization have been demonstrated. Finally, future outlooks for the applications of GNMs in pathogen detection and treatment are summarized.
Assuntos
Bactérias , Ouro , Nanopartículas Metálicas , Ouro/química , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Humanos , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Colorimetria/métodos , Nanoestruturas/química , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , AnimaisRESUMO
This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4-20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p < 0.05). The findings suggest re-evaluating the necessity of antibiotics in COVID-19 cases based on clinical assessments, focusing on the presence of bacterial infections rather than empirical treatment. Further research is necessary to more accurately identify patients with bacterial co-infections who would benefit from antibiotic treatment.
Assuntos
Antibacterianos , Tratamento Farmacológico da COVID-19 , COVID-19 , Humanos , Turquia/epidemiologia , Masculino , Antibacterianos/uso terapêutico , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , COVID-19/mortalidade , COVID-19/epidemiologia , Coinfecção/tratamento farmacológico , SARS-CoV-2/isolamento & purificação , Adulto , Infecções Bacterianas/tratamento farmacológico , Resultado do Tratamento , Unidades de Terapia Intensiva/estatística & dados numéricosRESUMO
BACKGROUND: Understanding the aetiological organisms causing maternal infections is crucial to inform antibiotic treatment guidelines, but such data are scarce from Sub-Saharan Africa (SSA). We performed this systematic review and meta-analysis to address this gap. METHODS: Microbiologically confirmed maternal infection data were collected from PubMed, Embase, and African Journals online databases. The search strategy combined terms related to bacterial infection, pregnancy, postnatal period, observational studies, SSA. Exclusion criteria included colonization, asymptomatic infection, and screening studies. Pooled proportions for bacterial isolates and antimicrobial resistance (AMR) were calculated. Quality and completeness of reporting were assessed using the Newcastle-Ottawa and STROBE checklists. FINDINGS: We included 14 papers comprising data from 2,575 women from four sources (blood, urine, surgical wound and endocervical). Mixed-growth was commonly reported at 17% (95% CI: 12%-23%), E. coli from 11%(CI:10%-12%), S. aureus from 5%(CI: 5%-6%), Klebsiella spp. at 5%(CI: 4%- 5%) and Streptococcus spp. at 2%(CI: 1%-2%). We observed intra-sample and inter-sample heterogeneity between 88-92% in all meta-analyses. AMR rates were between 19% -77%, the highest with first-line beta-lactam antibiotics. Convenience sampling, and limited reporting of laboratory techniques were areas of concern. INTERPRETATION: We provide a comprehensive summary of microbial aetiology of maternal infections in SSA and demonstrate the paucity of data available for this region. We flag the need to review the current local and international empirical treatment guidelines for maternal bacterial infections in SSA because there is high prevalence of AMR among common causative bacteria. FUNDING: This research was supported by the NIHR-Professorship/NIHR300808 and the Wellcome-Strategic-award /206545/Z/17/Z. TRIAL REGISTRATION: Prospero ID CRD42021238515.
Assuntos
Antibacterianos , Infecções Bacterianas , Farmacorresistência Bacteriana , Complicações Infecciosas na Gravidez , Humanos , África Subsaariana/epidemiologia , Feminino , Gravidez , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificaçãoRESUMO
BACKGROUND: Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts. METHODS: We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; 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 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 attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level. FINDINGS: In 2021, we estimated 4·71 million (95% UI 4·23-5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00-1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000-372 000] and 57 200 attributable deaths [34 100-80 300] in 1990, to 550 000 associated deaths [500 000-600 000] and 130 000 attributable deaths [113 000-146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000-834 000) in 1990, to 1·03 million associated deaths (909 000-1·16 million) in 2021, and from 127 000 attributable deaths (82 100-171 000) in 1990, to 216 000 (168 000-264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56-2·26) deaths attributable to AMR and 8·22 million (6·85-9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2-69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5-89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (-6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8-102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08-13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths. INTERPRETATION: This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050. FUNDING: UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust.
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Antibacterianos , Infecções Bacterianas , Farmacorresistência Bacteriana , Previsões , Saúde Global , Humanos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/mortalidade , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Anos de Vida Ajustados por Deficiência/tendências , Idoso , Lactente , Pré-Escolar , Criança , Pessoa de Meia-Idade , Adulto , Adolescente , Masculino , FemininoRESUMO
INTRODUCTION: The greater predisposition to infections, as well as the possibility of a worse response to treatment, can lead to the excessive use of antimicrobials among cancer patients. C-reactive protein (CRP) has gained prominence as a tool for monitoring therapeutic responses and reducing the duration of antibiotic therapy; however, few studies have analyzed this protein in cancer patient populations. We hypothesize that cancer patients with a good response to antibiotic therapy show a faster decline in serum CRP levels, which would allow us to identify candidates for short-course treatments. OBJECTIVE: To evaluate the behavior of serum CRP levels among adult cancer patients using antibiotic therapy, and its association with the duration of this treatment, therapeutic response, and clinical recurrence. METHODS: This work consisted of a retrospective study with cancer patients admitted to a university hospital between September 2018 and December 2019. Adults (age ≥ 18 years) who underwent at least one course of antibiotic therapy were included. CRP behavior over the first 7 days of treatment was classified as: i) good response: when the CRP value on the fifth day of therapy reached 50% or less of the peak value detected in the first 48 h of treatment, and ii) poor response: Maintenance, within the same interval, of a CRP value > 50% of the peak value in the first 48 h. The duration of antibiotic therapy was categorized as up to seven full days or more. Outcomes were assessed by events that occurred during the 30 days of hospitalization or until hospital discharge. PRIMARY OUTCOME: Clinical recurrence of the index infection. SECONDARY OUTCOMES: i) Death from any cause; ii) microbiological recurrence; iii) therapeutic response; iv) colitis associated with Clostridioides difficile; and v) isolation of multi-resistant bacteria, whether in clinical or surveillance samples. RESULTS: The final analysis consisted of 212 patients, with a median age (IQ) of 59.2 (48 - 67) years old and a predominance of females (65%), who were hypertensive (35%), smokers (21%), and diabetics (17.8%). There was no difference in clinical recurrence between the two groups (8.1% vs. 12.2%; p = 0.364), with a lower 30-day mortality in the good CRP response group (32.2% vs. 14.5%; p = 0.002). Despite the tendency towards a lower occurrence of other secondary outcomes in the good response group, these differences were not statistically significant. In the poor CRP response group, outcomes like clinical recurrence, mortality, and therapeutic response were significantly worse, regardless of the duration of antibiotic treatment. CONCLUSION: In this study, cancer patients with a good CRP response during antibiotic therapy presented lower mortality and a higher proportion of satisfactory therapeutic responses. CRP can be a useful tool when combined with other clinical information in optimizing the duration of antimicrobial treatment in a hospitalized cancer population.
Assuntos
Antibacterianos , Infecções Bacterianas , Proteína C-Reativa , Neoplasias , Humanos , Proteína C-Reativa/análise , Masculino , Feminino , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Estudos Retrospectivos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Pessoa de Meia-Idade , Idoso , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/mortalidade , Infecções Bacterianas/sangue , Prognóstico , Adulto , Resultado do TratamentoRESUMO
INTRODUCTION: Within the context of the coronavirus disease 2019 (COVID-19) pandemic, this study investigated the multifaceted challenges of bacterial infections in cancer patients with COVID-19. It focuses on clinical predictors, resistance patterns, and microbiological characteristics. METHODOLOGY: Over 18 months, 112 adult cancer patients with coronavirus infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) were enrolled. Bloodstream and respiratory samples were evaluated for bacterial infection using the Phoenix automation system for definitive species identification. In vitro susceptibility testing followed the Clinical Laboratory Standards Institute (CLSI) M100-Ed30 guidelines. RESULTS: Bacterial infections affected 25.0% of patients, encompassing bacteremia (21.4%) and respiratory tract infections (8.0%). Multivariable analysis identified hypertension, age < 60, and critical COVID-19 as significant predictors for bacterial infections (p-values = 0.024, 0.029, and 0.039, respectively). Most patients received antimicrobial therapy (93.8%), including last-resort carbapenems (52.7%) and colistin (8.9%). Thirty-three bacterial isolates were identified, with secondary infections doubling co-infection rates. Escherichia coli, Klebsiella species, and Staphylococcus aureus were the most common co-infecting species, while Klebsiella, Acinetobacter, and Pseudomonas species were more frequently associated with secondary infections. Alarmingly, 84.8% of isolates displayed high resistance patterns. All isolated S. aureus species were methicillin-resistant, and 62.5% of Gram-negative bacteria were exclusively sensitive to colistin. CONCLUSIONS: The dominance of highly transmissible hospital-acquired bacterial species, with increased resistance and extensive antibiotic use in COVID-19 patients, necessitates strict infection control and antimicrobial stewardship. Developing customized antimicrobial strategies for cancer patients with COVID-19 is crucial to managing bacterial infections effectively and improving patient outcomes.
Assuntos
Antibacterianos , Infecções Bacterianas , COVID-19 , Coinfecção , Neoplasias , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Masculino , Coinfecção/microbiologia , Coinfecção/epidemiologia , Coinfecção/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias/complicações , Feminino , Idoso , Infecções Bacterianas/microbiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , SARS-CoV-2 , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Idoso de 80 Anos ou mais , Infecções Respiratórias/microbiologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificaçãoRESUMO
BACKGROUND: In addition to antibiotic resistance, persistence is another cause of treatment failure in bacterial infections, representing a significant public health concern. Due to a lack of adequate data on clinical isolates, this study was initiated to investigate persistence in clinical isolates in Burkina Faso. METHODS: Eighty (80) clinical isolates, including 32 Pseudomonas aeruginosa, 41 Staphylococcus aureus, and 7 Salmonella sp. obtained from clinical laboratories in Burkina Faso, were analyzed to assess their susceptibility to ciprofloxacin and gentamicin, as well as to determine the presence of persistence genes. The effects of ciprofloxacin and gentamicin on persister formation were evaluated by conducting colony counts at 1, 3, 5, 7, and 20 h after exposing the bacteria to high concentrations of these antibiotics. RESULTS: Results showed high sensitivity to both antibiotics (72.5% for ciprofloxacin and 82.5% for gentamicin). Persister formation occurred in Staphylococcus aureus with gentamicin and in Salmonella sp. with ciprofloxacin, while Pseudomonas aeruginosa did not form persisters. The mazF gene was found in 28.13% of P. aeruginosa and 2.44% of S. aureus isolates, and the hipA gene in 28.57% of Salmonella sp. None of the relE1 or relE2 genes were detected. CONCLUSIONS: The study revealed high sensitivity in clinical bacterial isolates to ciprofloxacin and gentamicin. Staphylococcus aureus and Salmonella sp. showed persister formation under antibiotic stress, with low frequencies of the studied persistence genes. These findings enhance understanding of clinical bacterial behavior and inform strategies against antibiotic-resistant infections.
Assuntos
Antibacterianos , Ciprofloxacina , Gentamicinas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Staphylococcus aureus , Burkina Faso , Humanos , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Gentamicinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Salmonella/efeitos dos fármacos , Salmonella/genética , Salmonella/isolamento & purificação , Farmacorresistência Bacteriana/genética , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológicoRESUMO
Multi-resistant bacteria such as Escherichia coli and Klebsiella pneumoniae are a growing threat worldwide. The spread of Carbapenemase-producing strains is particularly worrying. New antibiotics and combination therapies offer treatment options, but the development of resistant pathogens remains a major challenge.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Humanos , Antibacterianos/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologiaRESUMO
Antibiotic resistance in bacterial pathogens is a major threat to global health, exacerbated by the misuse of antibiotics. In hospital practice, results of bacterial cultures and antibiograms can take several days. Meanwhile, prescribing an empirical antimicrobial treatment is challenging, as clinicians must balance the antibiotic spectrum against the expected probability of susceptibility. We present here a proof of concept study of a machine learning-based system that predicts the probability of antimicrobial susceptibility and explains the contribution of the different cofactors in hospitalized patients, at four different stages prior to the antibiogram (sampling, direct examination, positive culture, and species identification), using only historical bacterial ecology data that can be easily collected from any laboratory information system (LIS) without GDPR restrictions once the data have been anonymised. A comparative analysis of different state-of-the-art machine learning and probabilistic methods was performed using 44,026 instances over 7 years from the Hôpital Européen Marseille, France. Our results show that multilayer dense neural networks and Bayesian models are suitable for early prediction of antibiotic susceptibility, with AUROCs reaching 0.88 at the positive culture stage and 0.92 at the species identification stage, and even 0.82 and 0.92, respectively, for the least frequent situations. Perspectives and potential clinical applications of the system are discussed.
Assuntos
Antibacterianos , Bactérias , Aprendizado de Máquina , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Teorema de Bayes , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Estudo de Prova de Conceito , Hospitalização , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , França/epidemiologia , Redes Neurais de ComputaçãoRESUMO
This article discusses the recent regulatory restrictions on the use of fluoroquinolones and their impact on treating orthopaedic infections. We focus on the balance between the benefits and risks of fluoroquinolones in scenarios involving severe infections where alternative antibiotics may be less effective. The discussion includes a summary of recent evidence on adverse effects and the implications for clinical practice.