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Introduces the physical action of antibiotics and antiseptics including penetration through biofilms, persister cells, surface activity, physical sterilization and antibiofilm molecules.
The prenatal and early-life periods pose a crucial neurodevelopmental window whereby disruptions to the intestinal microbiota and the developing brain may have adverse impacts. As antibiotics affect the human intestinal microbiome, it follows that early-life antibiotic exposure may be associated with later-life psychiatric or neurocognitive outcomes.
Aims
To explore the association between early-life (in utero and early childhood (age 0–2 years)) antibiotic exposure and the subsequent risk of psychiatric and neurocognitive outcomes.
Method
A search was conducted using Medline, PsychINFO and Excerpta Medica databases on 20 November 2023. Risk of bias was assessed using the Newcastle-Ottawa scale, and certainty was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) certainty assessment.
Results
Thirty studies were included (n = 7 047 853 participants). Associations were observed between in utero antibiotic exposure and later development of autism spectrum disorder (ASD) (odds ratio 1.09, 95% CI: 1.02–1.16) and attention-deficit hyperactivity disorder (ADHD) (odds ratio 1.19, 95% CI: 1.11–1.27) and early-childhood exposure and later development of ASD (odds ratio 1.19, 95% CI: 1.01–1.40), ADHD (odds ratio 1.33, 95% CI: 1.20–1.48) and major depressive disorder (MDD) (odds ratio 1.29, 95% CI: 1.04–1.60). However, studies that used sibling control groups showed no significant association between early-life exposure and ASD or ADHD. No studies in MDD used sibling controls. Using the GRADE certainty assessment, all meta-analyses but one were rated very low certainty, largely owing to methodological and statistical heterogeneity.
Conclusions
While there was weak evidence for associations between antibiotic use in early-life and later neurodevelopmental outcomes, these were attenuated in sibling-controlled subgroup analyses. Thus, associations may be explained by genetic and familial confounding, and studies failing to utilise sibling-control groups must be interpreted with caution. PROSPERO ID: CRD42022304128
Antimicrobial resistance (AMR) has become a worldwide growing concern over the past decades. Thus, encouraging manufacturers to develop new antibiotics is needed. We hypothesised that transparency on the regulatory appraisals of antibiotics would provide an incentive to pharmaceutical development. We thus aimed at reporting the French health technology assessment (HTA) opinions and reimbursement decision on antibiotics to those German (G-BA) and English (NICE) HTA bodies.
A qualitative analysis of the Transparency Committee of the French National Authority for Health (TC-HAS) opinions regarding antibiotics assessment between 2016 and 2020 was performed. Decisions of reimbursement by TC-HAS were compared to those from G-BA and NICE when available. TC-HAS recognized a clinical benefit (CB) for 15/15 evaluated indications, a clinical added value for 9/15, and a public health interest for 8/15. Among the valued antibiotics by HAS, 5 were recommended for restricted use as a “reserve” to protect against the risk of resistance emergence. A comparison of HTA opinions was possible across HTA for only 8 antibiotics. The G-BA granted a reserve status for 4 drugs and NICE a reserve with restricted use for 5 antibiotics. Three of these antibiotics were positioned similarly by the English, German, and French HTA bodies. This qualitative analysis of HTA opinions between different European HTA bodies shows a consistent reimbursement decision of antibiotics against MDR bacteria and tuberculosis besides the differences in the applied assessment methods. This work also shows how HTA bodies could recognize a clinical added value in a context of the emergence of antibiotic resistance.
The gut microbiome is widely recognized for its significant contribution to maintaining human health across all life stages, from infancy to adulthood and beyond. This perspective article focuses on the impacts of well-supported microbiome research on global caesarean delivery rates, breastfeeding practices, and antimicrobial use. The article also explores the impact of dietary choices, particularly those involving ultra-processed foods, on the gut microbiota and their potential contribution to conditions like obesity, metabolic syndrome, and inflammatory diseases. This perspective aims to emphasize the need for updated guidelines and policy interventions to address the increasing global trends of caesarean deliveries, reduced breastfeeding, overuse of antibiotics, and consumption of highly processed foods to counter their adverse effects on gut health.
This chapter discusses the extent to which standard economic efficiency analysis can be applied to the economics of reducing ill health caused by environmental factors. This type of analysis is relevant when production functions can be applied to public health environmental situations such as those involving the public supply of safe water and sanitation. On the other hand, different analytical approaches are required to assess more holistically the social economic efficiency of public policies to control most environmentally related diseases. Concrete theoretical evidence about the analytical significance of the presence of externalities is backed up with examples. These cases include cadmium poisoning, drinking water contaminations, issues involved in the control of COVID-19, and the willingness of individuals to vaccinate against infectious diseases. In addition, particular attention is paid to problems involved in determining the social economic efficiency of the amount and use of methods of controlling environmentally related diseases when their effectiveness declines with use.
Inappropriate antibiotic use is a key driver of antibiotic resistance and one that can be mitigated through stewardship. A better understanding of current prescribing practices is needed to develop successful stewardship efforts. This study aims to identify factors that are associated with human cases of enteric illness receiving an antibiotic prescription. Cases of laboratory-confirmed enteric illness reported to the FoodNet Canada surveillance system between 2015 and 2019 were the subjects of this study. Laboratory data were combined with self-reported data collected from an enhanced case questionnaire that included demographic data, illness duration and symptoms, and antibiotic prescribing. The data were used to build univariable logistic regression models and a multivariable logistic regression model to explore what factors were associated with a case receiving an antibiotic prescription. The final multivariable model identified several factors as being significantly associated with cases being prescribed an antibiotic. Some of the identified associations indicate that current antibiotic prescribing practices include a substantial level of inappropriate use. This study provides evidence that antibiotic stewardship initiatives targeting infectious diarrhoea are needed to optimize antibiotic use and combat the rise of antibiotic resistance.
Blastocystis sp. is a prevalent protistan parasite found globally in the gastrointestinal tract of humans and various animals. This review aims to elucidate the advancements in research on axenic isolation techniques for Blastocystis sp. and their diverse applications. Axenic isolation, involving the culture and isolation of Blastocystis sp. free from any other organisms, necessitates the application of specific media and a series of axenic treatment methods. These methods encompass antibiotic treatment, monoclonal culture, differential centrifugation, density gradient separation, micromanipulation and the combined use of culture media. Critical factors influencing axenic isolation effectiveness include medium composition, culture temperature, medium characteristics, antibiotic type and dosage and the subtype (ST) of Blastocystis sp. Applications of axenic isolation encompass exploring pathogenicity, karyotype and ST analysis, immunoassay, characterization of surface chemical structure and lipid composition and understanding drug treatment effects. This review serves as a valuable reference for clinicians and scientists in selecting appropriate axenic isolation methods.
Meningitis is inflammation of the meningeal membranes of the brain and spinal cord. Encephalitis is inflammation of the brain parenchyma with or without inflammation of the meninges. Cerebral perfusion is a function of arterial pressure and intracranial pressure (i.e., cerebral perfusion pressure = mean arterial pressure – intracranial pressure). Hypoperfusion results from cerebral edema and increased intracranial pressure (ICP). Meningitis is a life-threatening condition with up to 30% mortality and high risk of long-term neurological complications.
The differential diagnosis for meningitis and encephalitis includes subarachnoid hemorrhage, cerebral venous thrombosis, metabolic/toxic encephalopathy and other infections not involving the central nervous system (CNS).
Severe crush injury can result in sequelae such as significant bony fractures, rhabdomyolysis, extremity compartment syndrome or crush syndrome. Crush syndrome comprises the systemic manifestations that arise as a result of a crush injury followed by reperfusion. From the rupture of muscle cells, substances such as myoglobin, potassium, phosphorus and creatinine phosphokinase are released into the bloodstream. The patient can subsequently develop hyperkalemia, hypocalcemia, hypovolemia, shock, compartment syndrome, lactic acidosis or renal failure from traumatic rhabdomyolysis (seen in up to 40% of patients with crush injury).
Community-acquired pneumonia (CAP) is a pneumonia that is not acquired in a hospital but, as the name suggests, is acquired elsewhere. Usual pathogens include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Chlamydophila pneumoniae, Legionella pneumophila and Moraxella catarrhalis.
Healthcare-associated pneumonia (HCAP) is no longer recognized as a clinical entity by the 2019 ATS/IDSA Guidelines on the Management of Community-Acquired Pneumonia. HCAP designation did not uniformly predict drug-resistant organisms, so management is driven on an individual basis.
Infective endocarditis (IE) is a microbial infection of the endothelial layer of the heart, the valves or both. The mitral valve is most commonly affected, except in patients with intravenous drug use (IVDU), where the tricuspid valve is more commonly affected. Risk factors include age, chronic hemodialysis, poor dentition, valvulopathy, immunocompromised status, diabetes, IVDU, prosthetic valve and implanted cardiac devices. More than 50% of cases of IE occur in patients older than 60 years.
The majority of cases are due to Gram-positive cocci such as Staphylococcus and Streptococcus species. In patients with negative blood cultures and no recent antibiotic use, the organisms are often the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella). Approximately 50% of patients require surgical management.
For the clinical applications of this chapter, necrotizing soft tissue infections (NSTIs) will refer to infection of deep subcutaneous tissues and adjacent fascia.
Mortality is estimated to be around 20–50% in observational literature with variation by infection site and specific organism.
Paucity of early physical examination findings can lead to a delay in diagnosis, as classic superficial findings do not manifest until later in the disease course.
Infection leads to toxin production, cytokine activation and microthrombosis, which all contribute to ischemia, impaired antibiotic delivery and rapid progression.
Early surgical intervention decreases morbidity and mortality.
NSTIs can be classified based on microbial etiology, with polymicrobial etiology being the most common. Type I necrotizing fasciitis is polymicrobial in origin. Type II is monomicrobial, often caused by group A Streptococcus (typically, S. pyogenes). Staphylococcal NSTIs are increasing in prevalence due to community-associated methicillin-resistant S. aureus.
Exotoxin release by clostridia, staphylococci and streptococci can enhance cytokine release and promote an inflammatory cascade, which can lead to death if untreated.
NSTIs are more common in patients with comorbidities including diabetes mellitus, chronic alcoholism, chronic renal failure, HIV, liver failure (which is classically associated with Vibrio vulnificus) and other immunosuppressed states.
Critical illness should be viewed as a continuum from prehospital development of disease, through emergency department (ED) presentation to intensive care unit (ICU) admission to post-ICU care and ultimately to hospital discharge. Over two million patients are admitted to ICUs from EDs each year in the US. Critical care visits increased by 80% between 2006 and 2014. More than 50% of ICU admissions remain in the ED in excess of 6 hours. ICU patients who remain in the ED have been shown to have worse outcomes.
This Research Communication investigates how well U.S. dairy farmers understand the voting behaviour and willingness to pay of consumers for products with production traits relevant to animal health, welfare and biotechnology. Accurately understanding consumer behaviour is key to making sound production decisions and reducing risks. Comparing survey data with the literature shows that U.S. dairy farmers correctly assess consumer attitudes and behaviour over animal welfare practices like pain-controlled dehorning but could improve knowledge of attitudes towards antibiotic use and novel biotechnologies like gene editing.
To assess the proportion of inpatients who received guideline-concordant antibiotics for community-acquired bacterial pneumonia (CABP) in special populations of the All of Us database.
Background:
CABP contributes significantly to healthcare burden worldwide. The American Thoracic Society and Infectious Disease Society of America jointly published guidelines for the treatment of CABP. Guideline-concordant antibiotics for CABP are associated with better patient and cost outcomes.
Methods:
This was a retrospective cohort study of patients with pneumonia (n = 1608; SNOMED 233604007) from 10/1/2018 to 1/01/22 in the All of Us database. Cases were excluded for treatment setting other than inpatient, prior (within 90 days) pneumonia, receipt of intravenous antibiotics, respiratory isolation of methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, and/or other non-community-acquired types of pneumonia. Patients were grouped based on patient age, sex, race, and ethnicity. The proportion of patients on guideline-concordant therapy was compared within groups using chi-square statistics. Significant associations were assessed using multivariate logistic regression models.
Results:
A total of 1608 cases were included, and 45% of these patients received guideline-concordant antibiotics. Non-Hispanic White (NHW) patients vs. Black patients were associated with a 36% higher likelihood for receiving guideline-concordant antibiotics (adjusted OR, 1.36; 95% CI 1.02–1.81), whereas NHW vs. Hispanic patients were associated with a 34% lower likelihood for receiving guideline-concordant antibiotics (aOR 0.66; 0.48–0.91).
Conclusion:
Black patients with CABP in the All of Us database were less likely to receive guideline-concordant antibiotics, and Hispanic patients were more likely to receive guideline-concordant antibiotics, than NHW patients.
While great emergencies are fortunately rare and certainly devastating, the upside is that they are often accelerators of progress. Wars, pandemics, and emergencies have been catalysts for medical innovation out of necessity - a desperate attempt to compensate for the circumstances. They bend the trajectory of discovery in new directions and increase the rate at which certain medical discoveries are made. Chapter 16 is thus about how wars, outbreaks, and other emergencies influence the rate and direction of medical progress. It explores how both World Wars, the pandemic of 1918, and COVID-19 have altered the trajectory of discovery.
When companies working in the pharmaceutical sector choose to develop new products, they have a certain set of choices. They can decide not to develop anything new, they can choose to make incremental improvements to existing products or choose to create something entirely new. In the short term, firms are also under pressure by shareholders to provide value, which may discourage longer-term investments. This may lead to an affinity for incremental discoveries and pursuits that are more likely to succeed in the short-term, such as me-too drugs. Chapter 11 explores how financial considerations influence the rate and direction of drug development, using antibiotics as a primary case example. Additionally, the chapter explores why there is missing novelty in drug development and how we might stimulate more breakthroughs in the future.
During your obstetric call duty in a tertiary hospital center, you receive a telephone call from a colleague on call duty at a community hospital center where a 34-year-old G3P2 presented with uterine contractions at 27 weeks’ gestation.
The ‘livestock revolution’ has seen the lives and livelihoods of peri-urban peoples increasingly intertwine with pigs and poultry across Africa in response to a rising demand for meat protein. This ‘revolution’ heralds the potential to address both poverty and nutritional needs. However, the intensification of farming has sparked concern, including for antibiotic misuse and its consequences for antimicrobial resistance (AMR). These changes reflect a micro-biopolitical conundrum where the agendas of microbes, farmers, publics, authorities and transnational agencies are in tension. To understand this requires close attention to the practices, principles and potentials held between these actors. Ethnographic research took place in a peri-urban district, Wakiso, in Uganda between May 2018 and March 2021. This included a medicine survey at 115 small- and medium-scale pig and poultry farms, 18 weeks of participant observation at six farms, 34 in-depth interviews with farmers and others in the local livestock sector, four group discussions with 38 farmers and 7 veterinary officers, and analysis of archival, media and policy documents. Wide-scale adoption of quick farming was found, an entrepreneurial phenomenon that sees Ugandans raising ‘exotic’ livestock with imported methods and measures for production, including antibiotics for immediate therapy, prevention of infections and to promote production and protection of livelihoods. This assemblage – a promissory assemblage of the peri-urban – reinforced precarity against which antibiotics formed a potential layer of protection. The paper argues that to address antibiotic use as a driver of AMR is to address precarity as a driver of antibiotic use. Reduced reliance on antibiotics required a level of biosecurity and economies of scale in purchasing insurance that appeared affordable only by larger-scale commercial producers. This study illustrates the risks – to finances, development and health – of expanding an entrepreneurial model of protein production in populations vulnerable to climate, infection and market dynamics.
Broiler chickens are among the main livestock sectors worldwide. With individual treatments being inapplicable, contrary to many other animal species, the need for antimicrobial use (AMU) is relatively high. AMU in animals is known to drive the emergence and spread of antimicrobial resistance (AMR). High farm biosecurity is a cornerstone for animal health and welfare, as well as food safety, as it protects animals from the introduction and spread of pathogens and therefore the need for AMU. The goal of this study was to identify the main biosecurity practices associated with AMU in broiler farms and to develop a statistical model that produces customised recommendations as to which biosecurity measures could be implemented on a farm to reduce its AMU, including a cost-effectiveness analysis of the recommended measures. AMU and biosecurity data were obtained cross-sectionally in 2014 from 181 broiler farms across nine European countries (Belgium, Bulgaria, Denmark, France, Germany, Italy, the Netherlands, Poland and Spain). Using mixed-effects random forest analysis (Mix-RF), recursive feature elimination was implemented to determine the biosecurity measures that best predicted AMU at the farm level. Subsequently, an algorithm was developed to generate AMU reduction scenarios based on the implementation of these measures. In the final Mix-RF model, 21 factors were present: 10 about internal biosecurity, 8 about external biosecurity and 3 about farm size and productivity, with the latter showing the largest (Gini) importance. Other AMU predictors, in order of importance, were the number of depopulation steps, compliance with a vaccination protocol for non-officially controlled diseases, and requiring visitors to check in before entering the farm. K-means clustering on the proximity matrix of the final Mix-RF model revealed that several measures interacted with each other, indicating that high AMU levels can arise for various reasons depending on the situation. The algorithm utilised the AMU predictive power of biosecurity measures while accounting also for their interactions, representing a first step toward aiding the decision-making process of veterinarians and farmers who are in need of implementing on-farm biosecurity measures to reduce their AMU.