We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The number of studies of controlled drug-release systems is growing constantly. Bionanocomposite materials which can be prepared from the combination of biopolymers with inorganic solids such as clay minerals offer interesting alternatives for use as drug-delivery systems. In the present study, new bionanocomposite drug-release systems were prepared from the intercalation of the antibiotic drug ciprofloxacin into montmorillonite using an ion-exchange reaction. In order to prepare more stable systems for oral ciprofloxacin release, this ciprofloxacin-clay intercalation compound was incorporated into i-carrageenan-gelatin biopolymer blend to produce bionanocomposite materials. Bionanocomposites of two distinct i-carrageenan and gelatin mass ratios were conformed as beads through an ionic gelification reaction with Ca2+ ions, and dried by freeze-drying where liquid nitrogen or conventional freezing was adopted in the freezing step. The resulting ciprofloxacin-clay hybrid was characterized by X-ray diffraction (XRD) analysis, Fourier-transform infrared (FTIR) spectroscopy, solid state 13C Nuclear Magnetic Resonance (NMR), thermal analysis, and scanning electron microscopy (SEM). The montmorillonite-ciprofloxacin hybrid incorporated into the bionanocomposite beads was evaluated by in vitro release studies which showed a significant difference in the release profiles in the aqueous medium used to simulate the gastrointestinal tract, depending on the blend composition and the freezing method employed in the preparation of the beads. The results point to bionanocomposite systems based on ciprofloxacin-clay hybrids and biopolymers that may be used as devices in the biomedical area.
To describe the characteristics and find out risk factors of COVID-19 patients infected with different categories of bacteria.
Design:
Case-control.
Methods:
We conducted a retrospective study including 129 COVID-19 patients admitted to a tertiary hospital between October 13, 2022 and December 31, 2022. Patients’ data were collected from the hospital information system. Patients were classified as having or not having confirmed secondary bacterial infections, or gram-positive and gram-negative bacterial infections for analysis. Categories and sources of isolated bacteria, characteristics of the patients, and the risk factors for developing secondary bacterial infections were analyzed.
Results:
Gram-negative bacteria accounted for the majority of secondary bacterial infections of the included patients. Critical type of COVID-19 (OR = 12.98, 95%CI 3.43∼49.18, p < 0.001), invasive therapy (OR = 9.96, 95%CI 3.01∼32.95, p < 0.001), and previous antibiotics use (OR = 17.23, 95%CI 1.38∼215.69, p = 0.027) were independent risk factors of secondary bacterial infections in COVID-19 patients. Ceftriaxone/cefotaxime use (OR = 15.45, 95%CI 2.72∼87.79, p = 0.002) was associated with gram-positive bacterial infections while age over 70 (OR = 3.30, 95%CI 1.06∼10.26, p = 0.039), invasive therapy (OR = 4.68, 95%CI 1.22∼17.93, p = 0.024), and carbapenems use (OR = 8.48, 95%CI 2.17∼33.15, p = 0.002) were associated with gram-negative bacterial infections.
Conclusions:
Critical patients with invasive therapy and previous antibiotics use should be cautious with secondary bacterial infections. Third-generation cephalosporins and carbapenems should be used carefully because both are risk factors for gram-positive or gram-negative bacterial infections.
To assess the safety and efficacy of a novel beta-lactam allergy assessment algorithm managed by an antimicrobial stewardship program (ASP) team.
Design:
Retrospective analysis.
Setting:
One quaternary referral teaching hospital and one tertiary care teaching hospital in a large western Pennsylvania health network.
Patients or participants:
Patients who received a beta-lactam challenge dose under the beta-lactam allergy assessment algorithm.
Interventions:
A beta-lactam allergy assessment protocol was designed and implemented by an ASP team. The protocol risk stratified patients’ reported allergies to identify patients appropriate for a challenge with a beta-lactam antibiotic. This retrospective analysis assessed the safety and efficacy of this protocol among patients receiving a challenge dose from November 2017 to July 2021.
Results:
Over a 45-month period, 119 total patients with either penicillin or cephalosporin allergies entered the protocol. Following a challenge dose, 106 (89.1%) patients were treated with a beta-lactam. Eleven patients had adverse reactions to a challenge dose, one of which required escalation of care to the intensive care unit. Of the patients with an unknown or low-risk reported allergy, 7/66 (10.6%) had an observed adverse reaction compared to 3/42 (7.1%) who had an observed reaction with a reported high-risk or anaphylactic allergy.
Conclusions:
Our implemented protocol was safe and effective, with over 90% of patients tolerating the challenge without incident and many going on to receive indicated beta-lactam therapy. This protocol may serve as a framework for other inpatient ASP teams to implement a low-barrier allergy assessment led by ASP teams.
Antagonism among bacteria is widespread and plays an important role in structuring communities. Inhibitory compounds can confer competitive advantage, but energetic trade-offs can result in non-transitive (i.e. ‘rock-paper-scissors’) interactions, ultimately allowing co-existence and community stability. Competition in sedimentary habitats is especially keen given high densities and attachment to inorganic particles. Because measuring trade-offs between bacterial species is challenging, much of our understanding of competitive interactions is based on theoretical modelling and simplified in vitro experiments. Our objectives were to determine (1) if interference competition occurs in microcosms mimicking in situ conditions; (2) whether the presence of sediment influences antagonistic interactions; and (3) if more complex assemblages alleviate or synergize interactions. Four sedimentary isolates, including antibiotic-producing, resistant and susceptible strains were incubated in porewater microcosms in 1-, 2- and 3-species combinations, both with and without natural sediments. Microcosms were sampled over 72 h to generate growth curves using quantitative PCR. Multiple growth attributes (growth rate, maximum density, lag time) were used to assess effects of treatment (species combinations) and environment (sediment vs porewater alone). Antimicrobial producers were more effective at inhibiting target species in microcosms that included sediment, in agreement with theory. We observed growth inhibition by antimicrobial-producing bacteria in both 2- and 3-species microcosms. However, the expected protection of sensitive bacterial strains by resistant strains was observed in only one (of four) 3-species combinations, thus the ‘rock-paper-scissors’ prediction was not fully supported. These results reinforce the notion that interspecies interactions are context-dependent, reliant on environmental conditions and the species involved.
Infusion of an internal teat sealant into the mammary gland of the dairy cow at drying off has been claimed to reduce the incidence of clinical mastitis over many months in the subsequent lactation, despite the absence of any ingredient of the sealant remaining for that long. However, these claims have been poorly substantiated, often by lack of identification on when the infection occurred in the period from calving to disease, if the infection was present at post calving sampling and if the pathogen causing the disease was that causing an earlier infection. Moreover, no hypothesis on how any effect on clinical mastitis might occur has been advanced in any of the publications claiming the effect. That the effect might occur is only reported in a minority of publications, and the possibility that this is relatively specific to Gram-negative pathogens is reviewed.
A 45-year-old presents for a preoperative visit. She reports regular menses that have become increasingly heavy in the past year and have not improved with hormonal management. Three weeks ago, she received a transfusion in the emergency department where imaging was notable for uterine fibroids. She received counseling on treatment options and desires hysterectomy. Her history is remarkable for two full-term vaginal deliveries. She has no history of abnormal cervical cytology or sexually transmitted diseases. Her past medical history is significant for exercise-induced asthma and surgical history for tonsillectomy. She is currently taking combined oral contraceptives, multivitamins, iron, and calcium with vitamin D. She is a non-smoker, does not drink alcohol, and is sexually active with one female partner. She reports a penicillin allergy characterized by the development of hives during prior treatment for a urinary tract infection 10 years ago.
To assess the effect of individual compared to clinic-level feedback on guideline-concordant care for 3 acute respiratory tract infections (ARTIs) among family medicine clinicians caring for pediatric patients.
Design:
Cluster randomized controlled trial with a 22-month baseline, 26-month intervention period, and 12-month postintervention period.
Setting and participants:
In total, 26 family medicine practices (39 clinics) caring for pediatric patients in Virginia, North Carolina, and South Carolina were selected based upon performance on guideline-concordance for 3 ARTIs, stratified by practice size. These were randomly allocated to a control group (17 clinics in 13 practices) or to an intervention group (22 clinics in 13 practices).
Interventions:
All clinicians received an education session and baseline then monthly clinic-level rates for guideline-concordant antibiotic prescribing for ARTIs: upper respiratory tract infection (URI), acute bacterial sinusitis (ABS), and acute otitis media (AOM). For the intervention group only, individual clinician performance was provided.
Results:
Both intervention and control groups demonstrated improvement from baseline, but the intervention group had significantly greater improvement compared with the control group: URI (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.37–1.92; P < 0.01); ABS (OR, 1.45; 95% CI, 1.11–1.88; P < 0.01); and AOM (OR, 1.59; 95% CI, 1.24–2.03; P < 0.01). The intervention group also showed significantly greater reduction in broad-spectrum antibiotic prescribing percentage (BSAP%): odds ratio 0.80, 95% CI 0.74-0.87, P < 0.01. During the postintervention year, gains were maintained in the intervention group for each ARTI and for URI and AOM in the control group.
Conclusions:
Monthly individual peer feedback is superior to clinic-level only feedback in family medicine clinics for 3 pediatric ARTIs and for BSAP% reduction.
Trial registration:
ClinicalTrials.gov identifier: NCT04588376, Improving Antibiotic Prescribing for Pediatric Respiratory Infection by Family Physicians with Peer Comparison.
The aim was to determine the association between healthcare workers’ (HCWs) country of birth and their knowledge of appropriate use of antibiotics, and whether the association changed after an educational intervention.
Background:
Older residents in nursing homes have been recognized to receive excessively antibiotic treatments. HCWs often represent an important link between the older resident and the general practitioner prescribing the antibiotics, thus their knowledge of appropriate use of antibiotics is important.
Methods:
This study was conducted as a prospective pre-post study. Totally, 312 HCWs from 7 nursing homes in Denmark were included. For statistical analyses, χ2 test and a linear mixed regression model were applied.
Findings:
Native HCWs were more likely to have a higher percentage of correct responses to single statements related to knowledge of appropriate use of antibiotics. Native HCWs had a significantly higher knowledge-of-antibiotic score compared to foreign HCWs (−7.53, P < 0.01). This association remained significant after adjusting for relevant covariates (−5.64, P < 0.01). Native HCWs’ mean change in knowledge-of-antibiotic score after the intervention did not differ from the foreign HCWs’ mean change in knowledge-of-antibiotic score.
Conclusion:
Our findings indicate that HCWs born outside Denmark reveal a lower knowledge-of-antibiotic score than HCWs born in Denmark despite comparable educational backgrounds. All participants increased their knowledge from baseline to follow-up. Our findings also indicate that an educational seminar cannot equalize the difference in knowledge between native and foreign HCWs. Studies with larger sample size and a more detailed measurement of cultural identity should investigate this association further.
Two issues relate to prescribing for the surgical patient: managing their previous medication during the metabolically stressful and starved perioperative period, and prescribing drugs required as a consequence of surgery. The author considers both issues, with particular attention paid to perioperative anticoagulation, fluids and analgesia, and prophylaxis.
Choice of antibiotic should be dictated by spectrum of activity, tissue penetration, potency and cost, and local patterns of infection. While advising prescribers to check with their local microbiologist or use their smartphone formulary app, the author describes the most common infectious disease presentations, and the first- and second-line antibiotic therapy based on national guidelines.
Antibiotics are designed to affect gut microbiota and subsequently gut homeostasis. However, limited information exists about short- and long-term effects of early antibiotic intervention (EAI) on gut homeostasis (especially for the small intestine) of pigs following antibiotic withdrawal. We investigated the impact of EAI on specific bacterial communities, microbial metabolites and mucosal immune parameters in the small intestine of later-growth-stage pigs fed with diets differing in CP levels. Eighteen litters of piglets were fed creep feed with or without antibiotics from day 7 to day 42. At day 42, pigs within each group were offered a normal- or low-CP diet. Five pigs per group were slaughtered at days 77 and 120. At day 77, EAI increased Enterobacteriaceae counts in the jejunum and ileum and decreased Bifidobacterium counts in the jejunum and ileum (P < 0.05). Moreover, tryptamine, putrescine, secretory immunoglobulin (Ig) A and IgG concentrations in the ileum and interleukin-10 (IL-10) mRNA and protein levels in the jejunum and ileum were decreased in pigs with EAI (P < 0.05). At day 120, EAI only suppressed Clostridium cluster XIVa counts in the jejunum and ileum (P < 0.05). These results suggest that EAI has a short-term effect on specific bacterial communities, amino acid decarboxylation and mucosal immune parameters in the small intestine (particularly in the ileum). At days 77 and 120, feeding a low-CP diet affected Bifidobacterium, Clostridium cluster IV, Clostridium cluster XIVa and Enterobacteriaceae counts in the jejunum or ileum (P < 0.05). Moreover, feeding a low-CP diet increased the concentrations of Igs in the jejunum and decreased pro-inflammatory cytokines levels in the jejunum and ileum (P < 0.05). At day 120, feeding a low-CP diet increased short-chain fatty acid concentrations, reduced ammonia and spermidine concentrations and up-regulated genes related to barrier function in the jejunum and ileum (P < 0.05). These results suggest that feeding a low-CP diet changes specific bacterial communities and intestinal metabolite concentrations and modifies mucosal immune parameters. These findings contribute to our understanding on the duration of the impact of EAI on gut homeostasis and may provide basis data for nutritional modification in young pigs after antibiotic treatment.
Use of antimicrobials for food-producing animals is a major public concern due to the risk of antimicrobial resistance. Although dairy production has a relatively low usage of antimicrobials, the potential for further reduction should be explored. The objective of the study was to estimate the current differences in antimicrobial use in Danish organic and conventional dairy herds and to describe the differences between them. Based on data from three different sources, 2604 herds (306 organic and 2298 conventional) were identified for the study. These herds had been either organic or conventional for the entire period from 2015 to 2018. Antimicrobial use was calculated as the treatment incidence in Animal Daily Doses (ADDs)/100 animals/day for three age groups: adult cattle, young stock and calves. For adult cattle, the ratio of median treatment incidence between conventional and organic production ranged from 2.8 : 1 to 3.4 : 1, depending on the specific year. For cows, 25% of the organic herds had a higher treatment incidence than the 25% of conventional herds with the lowest treatment incidence. Antimicrobial use for young stock was low and at a similar level in both the organic and conventional production systems. For calves, the median treatment incidence was 1.2 times higher in conventional herds and 1.6 times higher for the 75th percentile. Analyses of treatment incidence in adult cattle showed an overall decrease from 2015 to 2018 in both organic and conventional herds. The decrease was greater for the conventional herds (0.12 ADD/100 animals/day) compared to the organic herds (0.04 ADD/100 animals/day) over the 4-year period. In addition, herd size was an important risk factor for treatment incidence in conventional herds, increasing by 0.07 ADD/100 animals/day per 100 cows, whereas herd size had a minor influence on the treatment incidence in organic herds. The results of this study demonstrate the large variation in antimicrobial use within both organic and conventional herds, suggesting that further reduction is possible. Furthermore, herd size appears to be a risk factor in conventional herds but not in organic herds – an aspect that should be studied in more detail.
Introduction: Acute pharyngitis is a common emergency department (ED) presentation. The Centor (Modified/McIsaac) score uses five criteria (age, tonsillar exudates, swollen tender anterior cervical nodes, absence of a cough, and history of fever) to predict Group A Streptococcus (GAS) infection. The recommendation is patients with a Centor score of 0-1 should not undergo testing and should not be given antibiotics, patients with a score of 2-3 may warrant throat cultures, and for patients with a score ≥ 4, empiric antibiotics may be appropriate. Associated pain is often first managed with acetaminophen or non-steroidal anti-inflammatory drugs, however recent evidence suggests a short course of low-to-moderate dose corticosteroids as adjunctive therapy may reduce inflammation and provide pain relief. The objective of this study was to describe the ED management of acute pharyngitis for adult patients presenting to an academic ED over a two-year study period. Methods: This was a retrospective chart review of all adult (> 17 years) patients presenting to Mount Sinai Hospital ED with a discharge diagnosis of acute pharyngitis (ICD-10 code J02.9) from January 1st 2016 to December 31st 2018. Trained research personnel reviewed medical records and extracted data using a computerized, data abstraction form. Results: Of the 638 patients included in the study, 286 (44.8%) had a Centor score of 0-1, 328 (51.4%) had a score of 2-3, and 24 (3.8%) had a score of ≥ 4. Of those with a Centor score of 0-1, 83 (29.0%) had a throat culture, 88 (30.8%) were prescribed antibiotics, 15 (5.2%) were positive for GAS and 74 (25.9%) were given corticosteroids in the ED or at discharge. Of those with a Centor score of 2-3, 156 (47.6%) had a throat culture, 220 (67.1%) were prescribed antibiotics, 44 (13.4%) were positive for GAS, and 145 (44.2%) were given corticosteroids. Of those with a Centor score ≥ 4, 14 (58.3%) had a throat culture, 18 (75.0%) were prescribed antibiotics, 7 (29.2%) were positive for GAS and 12 (50.0%) were given corticosteroids. Conclusion: As predicted, a higher Centor score was associated with higher risk of GAS infection, increased antibiotic prescribing and use of corticosteroids. Many patients with low Centor scores were prescribed antibiotics and also had throat cultures. Further work is required to understand clinical decision making for the management of acute pharyngitis.
This introduction outlines the scope of the book titled “Challenges in Tackling Antimicrobial Resistance: Economic and Policy Responses”, and then summarises the main messages of each chapter which focus on the following big questions around AMR policy. What is the evidence on the rise of AMR and its health and economic impact? How can it be most effectively addressed in the community and in hospitals? What role is played by antimicrobial use in the food and livestock sector and what can be done about it? How can the discovery of new antibiotics be reinvigorated to replace those rendered ineffective by resistance?What needs to be done to develop new diagnostic tests so that infections can be speedily identified or ruled out and unnecessary antibiotic use avoided? Can more use be made of vaccines to tackle AMR? How have civil society movements contributed to policy development in the fight against AMR? What does the international community need to do in terms of global collective action to tackle AMR?
Vaccination is one of the most effective measures to reduce antimicrobial resistance in both human and animal pathogens. There are multiple pathways by which vaccines may act to reduce resistance: theycan prevent infections by focal pathogens, reducing the need to use antibiotics; they can selectively protect against resistant subtypes of a pathogen; they can reduce infections by other pathogen species which are routinely treated with antibiotics (not necessarily appropriately) thus reducingbystander selection;and they could selectively reduce transmission in settings such as hospitals which may have higher proportions of resistant strains. Because vaccines are highly specific to their targeted pathogens, they are much less likely to induce resistance compared to antibiotics. Hence they can be delivered to large populations as a preventive measure to reduce transmission. The impact of vaccination on resistance has been demonstrated for vaccines against Streptococcus pneumoniae, Haemophilus influenzae type b and influenza. Current and pipeline vaccines against pathogens such as Vibrio cholerae, Escherichia coli, Salmonella typhi, RSV, diarrhoeal viruses and nosocomial bacteria may also have potential to reduce resistance. Economic evaluations of vaccines need to be expanded to capture their benefits in reducing resistance, in order to incentivize development and introduction of the right vaccines. Accurately doing so will require health systems, epidemiological and economic research.
Antimicrobial resistance (AMR) has profound consequences for the treatment of infections. By limiting treatment options, it often makes it necessary to resort to antibiotics with a broader spectrum of action some of which are potentially less effective or safe than narrow-spectrum antibiotics. This limitation in our ability to treat infections effectively has an impact on health care budgets but also broader and potentially disastrous consequences on a variety of economic sectors. This chapter provides an overview of the health and economic burden of AMR. It first presents the current state of knowledge on the epidemiology of AMR and discusses the main analytical challenges in determining the current and long-term effects of resistance on populations in terms of morbidity, mortality, and length of hospital stay. In addition, a summary of the current literature on the economic impact of AMR is provided along with a detailed discussion of the characteristics and limitations of existing economic models. Finally, it identifies the main knowledge gaps and suggests avenues for future research and approaches to address them.
Antibiotics are widely used in food animal production to treat disease outbreaks, to prevent disease and, in some countries, to improve feed efficiency and enhance animal growth. Due to this complexity, the availability of reliable data on antibiotic use in livestock production is limited, but improving, especially for OECD countries. The highlight intensive animal production systems tend to use more antibiotics than the extensive systems. Over recent decades the adoption of improved biosecurity measures, animal husbandry practices and better farm management have contributed to a reduction in the use of antibiotics in many countries. All pathways of transmission of resistant pathogens between animals, humans and the environment (and vice versa) are not well understood, and this remains a major challenge for researchers and policymakers. With the growing public awareness of the risks associated with AMR, there is increased interest in developing alternative interventions to antibiotics in animal production. While estimating the economic costs and benefits of antibiotic use in production can be reduced without any adverse impact of farmers’ income, animal health and welfare.
An effective global AMR response will require diagnostics that are affordable and accessible, can be used at the point-of-care (POC), and can rapidly determine antimicrobial susceptibility or detect resistance. These tests are urgently needed to guide patient management, reduce inappropriate use of antibiotics and improve patient outcomes. POC tests with resistance detection and data transmission capabilities will be useful for AMR surveillance to monitor AMR trends and detect emergence of novel resistance in real time to enable timely optimisation of AMR strategies. Connected diagnostics have the potential to improve the efficiency of health care systems by simplifying patient pathways, guiding appropriate use of drugs and other resources and improving patient outcomes. POC tests are also useful in reducing the cost of R&D for new antibiotics. To ensure innovation in diagnostics development and deployment, a sound business case needs to be made to quantify the risk of not having diagnostics to improve the specificity of syndromic management. Financing mechanisms to incentivize diagnostic innovation, de-risk R&D and to finance the deployment of novel diagnostic solutions for AMR within different health systems are urgently needed.