Restriction Of Antibiotic Use Research Articles

Lowbury Lecture 2021: tales of the unexpected in antibiotic resistance

Since the 1990s few new antibiotics have become available; during the same period the appearance and spread of bacteria no longer susceptible to first- and second-line antibiotics has accelerated; indeed some bacterial infections have become untreatable with existing antibiotics. Control of antibiotic resistance is multifactorial, and includes restrictive antibiotic use and good infection control. This lecture addresses three aspects of antibiotic resistance, with reference to the Netherlands, that illustrate the complexity of antibiotic resistance epidemiology. Initially selective decontamination of the digestive tract (SDD) was not adopted in the Netherlands because of concern about antibiotic resistance. However, three trials showed that SDD regimens, including four days of systemic cephalosporins, gave better clinical outcomes with no effect on antibiotic-resistant bacteria. Many predictions have been made about the impact of infections with antibiotic-resistant bacteria on human health. However, the situation is complex, because the risk factors for infection with multidrug-resistant bacteria are also risk factors for poor clinical outcome. A study in eight Dutch hospitals estimated the mortality attributable to antibiotic resistance as close to zero. Concern about the emergence of resistance in Staphylococcus aureus has limited the universal use of mupirocin to prevent surgical site infections. However, the risk may have been overstated, and universal decolonization with mupirocin and chlorhexidine has now become standard of care in patients undergoing cardiothoracic or orthopaedic surgery in many Dutch hospitals. Prophylactic antibiotics can improve patient outcomes with acceptable risks of promoting resistance.

A Study on Prescribing Pattern, Indications and Rationality of Restricted Antibiotic Use in a Tertiary Care Hospital

Background: Antibiotic stewardship aims to optimise restricted antibiotic use and thereby prevent the emergence of antibiotic resistance and improve treatment outcome. Resistance to conventional antimicrobial’s is a major reason why restricted antibiotics are prescribed. Aim: To assess the prescribing pattern of restricted antibiotics, the indications for which restricted antibiotics were prescribed, the drug related problems associated and the sensitivity pattern of the isolated organisms. Results: Out of 340 patients included in the study, majority of patients was in the age group of 58-67(60.06 ±14.90) in both genders. There was a male (64.12%) dominance observed in the study populace and the minimum and maximum age observed was 18 and 93 years respectively. Most commonly prescribed antibiotic was Piperacillin tazobactum (31%) followed by Linezolid (16.06%). Empirically the most prescribed antibiotic was Piperacillin tazobactum (27.37%) while in definitive therapy it was Cefepime tazobactum (10.63%). The most common indication for which restricted antibiotics prescribed were for respiratory tract infection (n=116), followed by infection prophylaxis (n=114). Mean days of restricted antibiotic therapy was found to be 8.85 days ± 8.11. The maximum duration of antibiotic treatment was 62 days and minimum was 1 day. In 47% of cases IV to oral conversion was possible. When analysed retrospectively, in majority of the patients the duration of restricted antibiotic treatment was inappropriate (69.71%) while the inappropriateness in frequency and dose were 7.05% and 3.23% respectively. The total number of cultures collected were 292 in that 120 cultures were urine and found growth in 50.83%, followed by 84 cultures in sputum which accounted for 67.85% growth. The most common organism isolated was Klebsiella pneumoniae 39.73% cases followed by Pseudomonas aeruginosa 17.46% and Acinetobacter baumannii15.41. There was clinical cure in 91.47% of cases. Conclusion: When analysed retrospectively majority of the restricted antibiotics showed inappropriateness. This higher amount of inappropriateness could have been avoided to a certain extent, by the timely interventions of a clinical pharmacist. By implementing an effective antimicrobial stewardship program we could improve the rational use of restricted antibiotics and thereby prevent the future resistance and improve clinical outcome.

A Clinico-Microbiological Study of Β-Lactamase Producing Klebsiella Pneumoniae Among Neonates From Neonatal Intensive Care Unit At Tertiary Care Hospital, Ujjain

Abstract: Infection caused by drug resistance Klebsiella pneumoniae is very common now days in community as well as nosocomial environment. K.pneumoniae is second most common pathogen in neonatal septicemia. Our aim to detect drug resistance K.pneumoniae by production of β-lactamase enzymes such as extended spectrum β-lactamase (ESBL), AmpC β-lactamase, metalo β-lactamase (MBL) and carbapenemase in neonatal septicemia. A total 13 isolates of K.pneumoniae detected from neonates admitted in tertiary care centre during study period from February 2015 to July 2016. We analyzed risk factors in K. pneumoniae infection among neonates on the basis of prolong rupture of membrane, preterm birth, onset of septicemia etc. Antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion methods. β-lactamase enzymes includes, Extended spectrum β-lactamase(ESBL), AmpC β-lactamase, metalo β-lactamase (MBL)and carbapenemase were detected by phenotypic methods using standard guidelines. Distribution of MDR, XDR and PDR detected according to antimicrobial resistance pattern as per guideline. Among 13 K.pneumoniae isolate, antimicrobial resistance profile was studied. Isolates were 100% resistant to third generation cephalosporin and least resistant to imipenem 54%. MDR K.pneumoniae were 23 %, XDR were 77% and no PDR isolated. ESBL production seen in 23.1%, AmpC in 7.7 %, MBL in 00 % and Carbapenemase in 46.1 %. The study indicates that drug resistance higher in NICU of our institute. It requires strict implementation of infection control guidelines in NICU by safe hygiene practices, restricted use of broad spectrum antibiotics as empirical therapy and also formulation of uniform antibiotic policy for such patients based on the current trend of antibiotic resistance.

Longitudinal Analysis of Gut Bacteriome, Mycobiome, Virome and Metabolome in Allogeneic Stem Cell Transplantation Reveals Susceptibility for Acute Graft-Versus-Host Disease

The intestinal microbiome directly effects outcomes in patients undergoing allogeneic stem cell transplantation (ASCT) (Peled et al., N Engl J Med, 2020). Recent developments in microbiome research allow us to look beyond bacterial communities at the composition of the intestinal mycobiome and virome. However, only few studies have addressed these fungal (Zhang et al., Nat Commun, 2021; Legoff et al., Nat Med, 2017) and viral communities (Van Der Velden et al., Biol Blood Marrow Transplant, 2013) in the ASCT setting.Loss of bacterial diversity and domination of single taxa was linked to increased incidence of graft-versus-host-disease (aGvHD) and mortality. However, the functional consequences of intestinal dysbiosis remain poorly understood. Recently, microbial-derived metabolites such as short-chain fatty acids (SCFAs), indoles and secondary bile acids (BA) have been proposed to explain how microbiota exert effects on epithelial and immune responses and shown to protect from GVHD in animal models.To assemble a complete picture of the phylogenetic and metabolic changes which occur as patients undergo ASCT we designed a multiomics approach and identified patterns in bacteriome, mycobiome, virome and metabolome dynamics in relation to clinical factors and GvHD.353 stool samples from 80 patients undergoing ASCT were obtained at two different transplantation centers (Munich and Regensburg) at defined timepoints before and after transplantation. Changes in metabolite composition were evaluated via mass spectrometry using a targeted metabolomic profiling approach, accompanied by bacterial 16S rDNA-, fungal 18S-ITS- and deep virome sequencing. Results were linked among each other and with clinical metadata such as GvHD, response to steroids, antimicrobial therapy and mortality.Longitudinal profiling of ASCT patients revealed a significant loss of bacterial, fungal and viral diversity following ASCT. At both centers, the effect was most pronounced in the early post-transplant period. Patients that developed GI-GVHD had the lowest diversity scores (Panel 1). GVHD patient samples were dominated by Enteroccocus and Candida, and loss of Caudovirales species, indicative of deep dysbiosis effecting all intestinal communities.ASCT had a strong impact on microbiome function and their ability to produce metabolites. We assayed each sample for production of metabolites with reported protective effects: SCFAs (acetate, butyrate and propionate), indoles (indole-3-carboxylaldehyde, ICA) and BAs (deoxycholic and lithocholic acid). When admitted to the transplantation unit (timepoint “conditioning”) most patients had rich metabolite expression profiles. In the early post-transplant period, metabolite levels became progressively more depleted. GVHD patients displayed a nearly complete loss of metabolites (Panel 2a). Importantly, levels of the metabolite ICA at early timepoints could predict the occurrence of GVHD, leading us to consider prophylactic administration in future studies.We performed beta diversity analysis to identify clinical factors that had the highest impact on microbial communities. As expected, we noted that administration of broad-spectrum antibiotics had a profound impact of bacteria, fungi and viruses; but also had a significant negative effect on metabolites levels.Lastly, we report on a case of successful treatment of severe GI-GVHD with fecal microbiota transplant. Response to treatment was characterized by the recipient adopting the FMT donor's rich metabolite expression profile (Panel 2b) .To our knowledge, this is the first multicenter study that combines bacteriome, mycobiome, virome and metabolome analyses a longitudinal fashion in matched patient cohorts. Our results are consistent with previous findings that there are major alterations in gut microbiome and metabolite composition after ASCT. We expand upon those findings by characterizing the time course of phylogenetic alterations and their functional consequences. Those alterations play an important role in GvHD pathogenesis and might serve as potential biomarkers to identify patients at high risk for developing lethal GvHD early on. Our results highlight two strategies for targeted microbiome-based interventions: (1) preventing loss of microbial communities by restrictive use of antibiotics and (2) prophylactic administration of metabolite cocktails. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Re-thinking treatment strategies for febrile neutropenia in paediatric oncology population: the perspective from a developing country

BackgroundThis study was conducted to evaluate the microbiological profile of bacterial isolates in febrile neutropenia in a pediatric oncology unit, thereby, reviewing the use of restricted antibiotics and need for aggressive medical treatment accordingly.MethodsA prospective observational study was conducted in a paediatric haemat-oncology division of a tertiary care teaching hospital in southern India from September 2014 to August 2016. One hundred and thirty children with febrile neutropenia were enrolled in the study. Blood cultures were performed using automated system. Cultures from other sites were obtained if needed, based on the clinical profile. Standard antibiotic susceptibility testing was done. Statistical analysis was done using SPSS.ResultsOne hundred and thirty children were enrolled for the study. Two hundred and fifty episodes of febrile neutropenia were studied. Three hundred and eighty four cultures were sent and 92 (24%) cultures were positive. There were 48 (52.2%) Gram negative isolates followed by 33 (35.8%) Gram positive isolates, six (6.5%) fungal isolates and five (5.5%) poly-microbial cultures. Lactose fermenting Gram negative bacilli (20 isolates, 31.5%) were the most frequently isolated in the Gram negative group, with Escherichia coli being the most common organism (19 isolates, 20.6%). Amongst the Gram positive coagulase negative staphylococcus was the most common (twenty seven isolates, 29%). Escherichia coli and Non lactose fermenting gram negative bacteria (NFGNB) had only 36, 25% sensitivity to ceftazidime, respectively. Most Gram negative bacilli were found to have better sensitivity to amikacin (mean: 57%). There was a higher prevalence of extended spectrum beta lactamase producing organisms. Pan drug resistance, Extreme drug resistance and Multi drug resistance was found in three, twenty and thirteen Gram negative isolates respectively.Escherichia coli and Klebsiella were often drug resistant. Significantly higher mortality was associated with Gram negative isolates (eight deaths out of the thirteen deaths, 61.5%).ConclusionsOur results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each region. Given that significant mortality is attributed to drug resistant Gram negative bacilli, early initiation of appropriate antibiotics to cover for drug resistance is required while formulating empirical antibiotic policies for febrile neutropenia in the oncology units in the developing world.

Relationship of organic farming and human health

In the last decade, the assembly and ingestion of organic food have exaggerated steady worldwide, despite the lower productivity of organic crops. Such foods run byorganic standards of manufacture, management, dispensation, and marketing. Most notably, the employment of artificial fertilizers, pesticides, and genetic modification isn’t allowed. One major reason for the exaggerated demand is that the perception that organic food is a lot of environmentally friendly and on the mend than conservatively made food. Shoppers of organic food tend to possess healthier dietary patterns overall. Medicine studies purpose to the negative effects of bound pesticides on children’s psychological feature development at current levels of exposure. Such risks will be decreased with organic food, particularly throughout maternity and in infancy, and by introducing non-pesticidal plant protection in typical agriculture. There are units few familiar integrative variations between organic and traditional crops. Maybe most significantly, there are indications that organic crops have lower metal content than typical crops because of variations in fertilizer usage and soil organic matter, a difficulty that’s extremely relevant to human health. Organic milk, and possibly additionally meat, contains a higher content of omega-3 fatty acid fatty acids compared to traditional product, however this is often unlikely to be nutritionally vital in lightweight of alternative dietary sources. The current use of antibiotics in typical animal production may be a key driver of antibiotic resistance. The hindrance of disease and a lot of restrictive use of antibiotics, as practiced in organic production, may minimize this risk, with probably tidy edges for public health. This review summarizes the scientific proof for integrative variations and health edges of organic compared with conventionally made food.

Coalescence of co-infection and antimicrobial resistance with SARS-CoV-2 infection: The blues of post-COVID-19 world

In viral respiratory infections, bacterial co-pathogens are widely known to co-infect, and they significantly increase the morbidity and mortality rate. During the influenza season, the advent of 2019-nCoV (novel coronavirus) has led to the widespread use of oral and intravenous antibiotics and inhibitors of neuraminidase enzyme. Owing to causes such as extended intubation, the ubiquitous use of intrusive catheters, and compromised host immunity, coronavirus disease (COVID-19) patients are at heightened risk of secondary bacterial and fungal infections, leading to the difficulty in their treatment. Apart from the pandemic, the primary risk is a likely surge in multidrug resistance. In this work, we evaluated the coalescence of present co-infection alongside the COVID-19 and post-pandemic antimicrobial resistance due to high ongoing drug use for the treatment of COVID-19. We found that while there is currently limited evidence of bacterial infections in COVID-19, available proof supports the restricted use of antibiotics from an antibiotic stewardship viewpoint, primarily upon entry. Paramount attempts should be made to collect sputum and blood culture samples as well as pneumococcal urinary antigen monitoring in order to endorse stringent antibiotic usage. For antimicrobial stewardship, inflammatory markers like procalcitonin have been added, but such biomarkers are typically upraised in COVID-19. Antimicrobials cannot be completely removed in wastewater treatment plants (WWTPs) and once they enter the water environment, possesses a great risk of inducing resistance to drugs in microbes. Hence, their prescription and administrations should be regulated and alternate solutions such as vaccines, preventive measures and personal hygiene should be given top priority. It is imperative to establish an antimicrobial strategy discrete to COVID-19, as this pandemic has caused an outbreak of numerous other associated diseases and has the potential to drive microbial resistance. Coordinated plans are essential for this at the citizen, health-care and policy levels.

Animal Production With Restrictive Use of Antibiotics to Contain Antimicrobial Resistance in Sweden-A Qualitative Study.

Antibacterial resistance (ABR), is a growing global threat to human and animal health. Efforts to contain ABR are urgently needed. This qualitative interview study explored perceptions of work to contain ABR among stakeholders in food animal production in Sweden, with focus on broiler production. Semi-structured interviews were carried out with a strategic sample of 13 stakeholders in different parts of production, from professionals at policy level, veterinary authorities, to poultry farmers and poultry veterinarians. Conventional inductive content analysis was used for data analysis. A latent theme, “Working in unison,” emerged, based on the consistency expressed by the informants when they discussed ABR, use of antibiotics, and animal health management. This theme was built on four domains representing the content of the interviews: Knowledge and engagement; Cooperation; Animal health concept; and Development in balance with economic prerequisites. According to the informants, ABR has not been an isolated issue in Sweden but has been included in a tradition of animal health and welfare, and actions have been driven by the industry or by government regulations. Veterinarians described how they worked closely with farmers. Farmers felt involved in the development of animal health management methods. The One Health concept was well-known among stakeholders at national level but not at farm level. Close cooperation between stakeholders seems to facilitate development of animal production with low use of antibiotics.

Enabling appropriate use of antibiotics: review of European Union procedures of harmonising product information, 2007 to 2020.

IntroductionAntimicrobial resistance (AMR) is one of the most important challenges in modern clinical practice. The European regulatory network has a strategy to support prevention of AMR by applying specific referral procedures.AimThe aim of this study was to evaluate post-authorisation changes made in the product information of key antibiotics that underwent referral procedures between 2007 and 2020.MethodIn a comprehensive analysis of the changes made for antibiotics, we extracted information on changes from the European Commission community register of medicinal products and the European Medicines Agency’s database for antibiotics that went through referrals. Changes made in the specific sections of the summary of product characteristics of each referral procedure were scrutinised.ResultsWe identified 15 antibiotics from seven classes of antibiotics during the study period. The outcome of all referrals included the restriction of antibiotic use. Therapeutic indications were revised for all antibiotics, with septicaemia and gonorrhoea most common diseases removed. Posology and/or method of administration was updated for all; the majority of referrals included adjustment of dosage for specific populations. Information on contraindication (most regarding hypersensitivity) and information on warnings was amended for all referrals.ConclusionOur findings highlight the importance of the regulatory actions. The changes made in the product information aim to ensure appropriate use. Ongoing harmonisation activities are likely to lead to further refinements and restrictions on individual antibiotics in support of rational use. However, further research is required to examine the impact of post-referral label changes on the clinical practice.

Study of Antimicrobial Utilization and Cost of Therapy in Medicine Intensive Care Unit of a Tertiary Care Hospital in Eastern India.

IntroductionHigh utilization of antimicrobial agent (AMA) and inappropriate usage in an intensive care unit (ICU) intensifies resistant organism, morbidity, mortality, and treatment cost. Prescription audit and active feedback are a proven method to check the irrational prescription. To analyze and compare the utilization of drugs, the World Health Organization (WHO) proposed daily defined dose (DDD)/100 patient days and days of therapy (DOT)/100 patient days to measure utilization of AMAs. Data of AMAs utilization are required for planning an antibiotic policy and for follow-up of intervention strategies.Materials and methodsA prospective observational study was conducted for 1 year from July 2018 to June 2019 and the data obtained from ICU of a tertiary care hospital. The demographic data, the disease data, and the utilization of different classes of AMAs [WHO–Anatomical Therapeutic Chemical (ATC) classification] as well as their cost were recorded. Total number of patient days, DDD, DDD/100 patient days, and DOT/100 patient days were calculated as proposed by the WHO. Statistical analysis was performed using statistical software SPSS version 25.0. The descriptive analysis was performed using summary statistics median [interquartile range (IQR)].ResultsA total 939 patients were included, out of them 332 (35.4%) were female. The median age of the total patients was 58 (45–70). The median length of stay in ICU was 3 days. Mortality rate during our study period was 38.6%. The highly utilized AMAs in our study was ceftriaxone (36.95 DDD/100 patient days) followed by piperacillin/tazobactam (31.57), meropenem (26.4), doxycycline (21.53), and polymyxin B (21.38). The association between APACHE II and SOFA score with use of restricted antibiotics found to be statistical significant (p value 0.018 and 0.000, respectively). The cost of antibiotics per patient and patient days were $449.97 and $93.77, respectively, while median value of total cost was $2,343.26.ConclusionCeftriaxone was the highest utilized AMA. The risk of receiving restricted antibiotics intensified with increasing prevalence of multidrug resistance bacteria and associated comorbidities. High treatment cost is responsible for higher utilization of restricted antibiotics in ICU.How to cite this articlePatra SK, Mishra SB, Rath A, Samal S, Iqbal SN. Study of Antimicrobial Utilization and Cost of Therapy in Medicine Intensive Care Unit of a Tertiary Care Hospital in Eastern India. Indian J Crit Care Med 2020;24(10):938–942.

Recommendations for antibacterial therapy in adults with COVID-19 – an evidence based guideline

ScopeThe Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). MethodsWe performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions addressed by the guideline and RecommendationsWe assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.

The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study.

Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for low-risk penicillin allergies in hospitalized inpatients. Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days). Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51 [95% confidence interval {CI}, 5.39-20.48]), improved appropriate antibiotic prescribing (adjusted OR, 2.13 [95% CI, 1.45-3.13]), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 [95% CI, .27-.54]). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 [95% CI, 5.09-23.31]) and β-lactam/β-lactamase inhibitors (OR, 6.68 [95% CI, 3.94-11.35]) and a reduction in restricted antibiotic use (OR, 0.52 [95% CI, .36-.74]) and inappropriate prescriptions (relative risk ratio, 0.43 [95% CI, .26-.72]) in the delabeled group compared with the group who retained their allergy label. This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.

Restrictive antibiotic use in children hospitalized for pneumonia: A retrospective inpatient study

IntroductionReducing antibiotic use is a global priority, but the extent to which antibiotic prescriptions can be reduced in children hospitalized for community-acquired pneumonia is unknown. This study aimed to analyse the prescribing experience from a facility with a long-standing practice of restrictive antibiotic use. MethodsWe conducted a retrospective analysis of children from birth to 18 years, hospitalized for pneumonia at an integrative medicine hospital in Germany. Antibiotic prescription rate and clinical outcomes were analyzed. The Moreno Bacterial Pneumonia Score, a composite laboratory, clinical and radiologic score, was applied to estimate the proportion of viral and bacterial pneumonia. Results252 pneumonia episodes were included, with 172 categorized as probably viral and 80 as bacterial pneumonia. Antibiotic prescription rate was 32 % overall, 26 % for presumed viral and 51 % for presumed bacterial pneumonia. Children with probable bacterial pneumonia who were managed with antibiotics had higher CRP values than those managed without antibiotics (p < 0.001). 13 % of bacterial pneumonia episodes initially managed without antibiotics received antibiotics after hospital day 2. Hospitalization duration was longer for bacterial pneumonia episodes managed with antibiotics than those managed without (7.0 versus 4.9 days, p = 0.003). ConclusionsThe observed antibiotic prescription rate of 32 % was much lower than rates reported in the literature - 88–98 %. Children were safely managed with a restrictive antibiotic prescription strategy when physicians judged this to be appropriate. Our findings suggest that a delayed prescription strategy for childhood pneumonia deserves further study. Trial registrationthe study was registered at clinicaltrials.org, NCT03256474.

Evaluating hospital performance in antibiotic stewardship to guide action at national and local levels in a lower-middle income setting

ABSTRACT Background Inappropriate use of antibiotics can lead to the development of resistant pathogens. Ensuring proper use of these important drugs in all healthcare facilities is essential. Unfortunately, however, very little is known about how antibiotics are used in LMIC clinical settings, nor to what degree antibiotic stewardship programmes are in place and effective. Objective We aimed to record all Antibiotic Stewardship policies and structures in place in 16 Kenyan hospitals. We also wanted to examine the context of antibiotic-related practices in these hospitals. Methods We generated a set of questions intended to assess the knowledge and application of antibiotic stewardship policies and practices in Kenya. Using a set of 17 indicators grouped into four categories, we surveyed 16 public hospitals across the country. Additionally, we conducted 31semi-structured interviews with frontline healthcare workers and hospital managers to explore the context of, and reasons for, the results. Results Only one hospital had a resourced ABS policy in place. In all other hospitals, our survey teams commonly identified structures, resources and processes that in some way demonstrated partial or full control of antibiotic usage. This was verified by the qualitative interviews that identified common underlying issues. Most positively, we find evidence discipline-specific clinical guidelines have been well accepted and have conditioned and restricted antibiotic use. Conclusion Only one hospital had an official ABS programme, but many facilities had existing structures and resources that could be used to improve antibiotic use. Thus, ABS Strategies should be built upon existing practices with national ABS policies taking maximum advantage of existing structures to manage the supply and prescription of antimicrobials. We conclude that ABS interventions that build on established responsibilities, methods and practices would be more efficient than interventions that presume a need to establish new ABS apparatus.

Enteral lactoferrin does not reduce late-onset infection in very preterm infants.

Late-onset sepsis is a major cause of morbidity and mortality in neonates, but predominantly in preterm infants. In survivors, it can prolong length of hospital stay, worsen long-term neurodevelopmental outcomes and increase the associated social burden of disease.1 Lactoferrin, a mammalian iron-binding whey glycoprotein with important bacteriostatic and anti-inflammatory properties, plays a role in promoting growth of probiotic bacteria in the gut.2 A recent Cochrane review suggested reductions in both sepsis and necrotizing enterocolitis with oral lactoferrin supplementation.3 Many of these studies enrolled small numbers and had limitations in study design and implementation. The ELFIN randomised, placebo-controlled trial is the largest trial of this intervention. A major strength lies in the large number (>2000) of participating babies with more than 99% of outcome data being available. Important consideration was given to limit bias for the study; randomisation was successful in balancing baseline demographic and prognostic characteristics. Measures were put in place to define the spectrum of late-onset infection in order to reduce potential sources of bias. This is in contrast to most previous studies, in which only culture-proven late-onset sepsis was used as a marker.4 This does not necessarily completely rule out bias. The primary outcome used encompasses both microbiologically confirmed and clinically suspected late-onset infection, from trial entry until hospital discharge. Although these results were confirmed, using pre-defined criteria, by masked central end-point review committees, clinically suspected late-onset infection remains a subjective outcome. As it accounts for more than 40% of the cases in this study, this might be considered a confounding factor. Based on the GRADE system (grading of recommendation, assessment, development and evaluation), due to the relative imprecision of the primary outcome and inconsistency of the main result, lactoferrin is not recommended as a routine intervention to prevent late-onset sepsis in very preterm infants. Although other trials of lactoferrin are ongoing (Mooselmokadem trial; NCT01821989, estimated n = 180), NEOLACTO (NCT01525316, n = 414) and LIFT (ACTRN12611000247976, target sample size of 1500), it would be difficult to anticipate that these would bring about a change in the grade of recommendation, unless a substantial positive effect were seen in the largest of these trials. Although the risk of adverse outcomes in more mature preterm infants is generally lower, the effect size, favouring lactoferrin, was larger in this study in infants born at 30 or more weeks of gestation. Although not statistically significant, this finding may be clinically relevant. Lactoferrin promotes growth of probiotic bacteria, so this finding begs the question of whether this effect could be related to lower rates of exclusive breastmilk feeding and more restricted use of broad-spectrum antibiotics in larger infants. Evidently, there is still a need for novel research into the use of alternative interventions as adjuvants in preventing late-onset sepsis, and reducing mortality and morbidity in the very preterm population. Is there, for example, a need for further large scale studies to look at the effectiveness of using lactoferrin in combination with probiotic therapy or other interventions designed to decrease infection risk?5 https://ebneo.org/2019/11/enteral-lactoferrin-late-onset-infection/ None.

A methodology based on multiple criteria decision analysis for combining antibiotics in empirical therapy.

The current situation of critical progression in resistance to more effective antibiotics has forced the reuse of old highly toxic antibiotics and, for several reasons, the extension of the indications of combined antibiotic therapy as alternative options to broad spectrum empirical mono-therapy. A key aspect for selecting an appropriate and adequate antimicrobial therapy is that prescription must be based on local epidemiology and knowledge since many aspects, such as prevalence of microorganisms and effectiveness of antimicrobials, change from hospitals, or even areas and services within a single hospital. Therefore, the selection of combinations of antibiotics requires the application of a methodology that provides objectivity, completeness and reproducibility to the analysis of the detailed microbiological, epidemiological, pharmacological information on which to base a rational and reasoned choice. We proposed a methodology for decision making that uses a multiple criteria decision analysis (MCDA) to support the clinician in the selection of an efficient combined empiric therapy. The MCDA includes a multi-objective constrained optimization model whose criteria are the maximum efficacy of therapy, maximum activity, the minimum activity overlapping, the minimum use of restricted antibiotics, the minimum toxicity of antibiotics and the activity against the most prevalent and virulent bacteria. The decision process can be defined in 4 steps: (1) selection of clinical situation of interest, (2) definition of local optimization criteria, (3) definition of constraints for reducing combinations, (4) manual sorting of solutions according to patient's clinical conditions, and (5) selection of a combination. In order to show the application of the methodology to a clinical case, we carried out experiments with antibiotic susceptibility tests in blood samples taken during a five years period at a university hospital. The validation of the results consists of a manual review of the combinations and experiments carried out by an expert physician that has explained the most relevant solutions proposed according to current clinical knowledge and their use. We show that with the decision process proposed, the physician is able to select the best combined therapy according to different criteria such as maximum efficacy, activity and minimum toxicity. A method for the recommendation of combined antibiotic therapy developed on the basis of a multi-objective optimization model may assist the physicians in the search for alternatives to the use of broad-spectrum antibiotics or restricted antibiotics for empirical therapy. The decision proposed can be easily reproduced for any local epidemiology and any different clinical settings.

Early initiation of broad-spectrum antibiotics in premature infants

Neonatal sepsis remains one of the main reasons for mortality among premature infants, and the early initiation of empirical broad-spectrum antibiotics could increase the risk of complications, including late-onset sepsis. This study aimed to investigate the complications related to the use of empirical broad-spectrum antibiotics in the first week of life. A retrospective study of 365 neonates with gestational age ≤32 weeks and birth weight <1500 g who survived and had no confirmed sepsis in the first week of life from July 2015 to June 2018 was performed in a large tertiary Neonatal Intensive Care Unit. The primary outcome of this study was the incidence of a composite outcome consisting of late-onset sepsis, necrotizing enterocolitis, and mortality. The secondary outcomes were the incidences of late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and infant mortality. Of the 365 premature infants, 75 (20.5%) received broad-spectrum antibiotics. Multivariate regression analysis revealed that administration of broad-spectrum antibiotics in infants was independently associated with adverse outcomes. The composite outcome (late-onset sepsis, necrotizing enterocolitis, and death) had an odds ratio of 3.03 with 95% confidence interval of 1.41-6.49. Administration of empirical broad-spectrum antibiotics in the first week of life is associated with severe adverse outcomes. Thus, the restricted use of broad-spectrum antibiotics in the first week of life is recommended.

Ethnoveterinary knowledge of farmers in bilingual regions of Switzerland – is there potential to extend veterinary options to reduce antimicrobial use?

Ethnopharmacological relevanceIn the pre-antibiotic era, a broad spectrum of medicinal plants was used to treat livestock. This knowledge was neglected in European veterinary medicine for decades but kept alive by farmers. Emergence of multidrug resistant bacterial strains requires a severely restricted use of antibiotics in veterinary medicine. We conducted a survey on the ethnoveterinary knowledge of farmers in the bilingual (French and German speaking) Western region of Switzerland, namely the cantons of Fribourg, Neuchâtel and Jura, and in the French speaking part of the canton of Bern.Aim of the studyTo find out whether differences exist in plants used by farmers in French speaking and bilingual regions of Switzerland as compared to our earlier studies conducted in Switzerland. Additional focus was on plants that are used in diseases which commonly are treated with antimicrobials, on plants used in skin afflictions, and on plants used in animal species such as horses, for which the range of veterinary medicinal products is limited.Material and methodsWe conducted in 2015 semistructured interviews with 62 dialog partners, mainly cattle keeping farmers but also 18 horse keeping farmers. Of these, 41 were native French (FNS) and 21 native German speakers (GNS). Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected.ResultsA total of 345 homemade remedies were reported, of which 240 contained only one plant species (Homemade Single Species Herbal Remedy Reports; HSHR). A total of 289 use reports (UR) were mentioned for the 240 HSHR, and they comprised 77 plant species belonging to 41 botanical families. Of these, 35 plant species were solely reported from FNS, 20 from GNS, and 22 from both. Taking into account earlier ethnoveterinary studies conducted in Switzerland only 10 (FNS) and 6 (GNS) plant species connected with 7% of FNS and GNS UR respectively were “unique” to the respective language group.The majority of the UR (219) was for treatment of cattle, while 38 UR were intended to treat horses. The most UR were for treatment of gastrointestinal and skin diseases. The most frequently mentioned plants were Linum usitatissimum L., Coffea L., Matricaria chamomilla L., Camellia sinensis (L.) Kuntze, and Quercus robur L. for gastrointestinal diseases, and Calendula officinalis L., Hypericum perforatum L. and Sanicula europaea L. for skin afflictions.ConclusionNo clear differences were found between the medicinal plants used by French native speakers and German native speakers. Several of the reported plants seem to be justified to widen the spectrum of veterinary therapeutic options in gastrointestinal and dermatological disorders in cattle and horses, and to reduce, at least to a certain degree, the need for antibiotic treatments. Our findings may help to strengthen the role of medicinal plants in veterinary research and practice, and to consider them as a further measure in official strategies for lowering the use of antibiotics.

Comparison of different approaches to antibiotic restriction in food-producing animals: stratified results from a systematic review and meta-analysis

BackgroundWe have previously reported, in a systematic review of 181 studies, that restriction of antibiotic use in food-producing animals is associated with a reduction in antibiotic-resistant bacterial isolates. While informative,...

Endocarditis: An Ever Increasing Problem in Cardiac Surgery.

Endocarditis remains one of the most threatening diagnoses in cardiac surgery and is still increasing. Particularly, device-related as well as prosthetic endocarditis appears to be on the rise. Early mortality and periprocedural complications are high jeopardizing the success of surgical efforts. We looked at the development of the numbers and the distribution of endocarditis in an all-comer analysis. From 2003 to 2017, 752 patients with endocarditis were transferred to our cardiosurgical institution (mean age 65 ± 13 years; mean logistic EuroSCORE 28.01%; males 74.33%). A total of 89.49% of them were surgically treated; 30.01% redo cases thereof; and 9.17% had been operated previously for acute endocarditis. While the total number of cardiosurgical procedures remained relatively stable throughout the years, 20 patients were admitted in 2003 and 79 in 2017 yielding more than fourfold increase (p < 0.001). Early mortality of all patients was 25.1%. Septic emboli occurred in 23.7% and 43.8% cerebral emboli thereof. A significant increase of aortic, mitral, and tricuspid valves involvement was observed (p < 0.001). An increase of device-related endocarditis was also noted (p < 0.001). Endocarditis remains a serious problem with high early mortality and morbidity. The vast increase of electrophysiological device implantations has resulted in an increase of tricuspid valve involvement. Liberalization of endocarditis prophylaxis, that is, more restrictive use of antibiotics in 2007 may have at least partially contributed to an increase of the individual risk to suffer from acute endocarditis. A renaissance of a stricter endocarditis-prophylaxis may thus be considered.