Retrospective quantitative risk assessment of skin sensitization caused by an antimicrobial agent used in a consumer product: 2,3,5,6-Tetrachloro-4-(methylsulfonyl) pyridine.

BACKGROUND: Serious cases of allergic contact dermatitis (ACD) caused by exposure to 3,5,6-tetrachloro-4-(methylsulfonyl)pyridine (TCMSP; CAS no. 13108-52-6) used as an antimicrobial agent for desk mats have been reported in Japan. OBJECTIVE: A quantitative risk assessment (QRA) of TCMSP contained in desk mats was performed retrospectively. MATERIALS AND METHODS: A local lymph node assay (LLNA): BrdU-ELISA was conducted to determine a reliable EC1.6 value for TCMSP. The acceptable exposure level (AEL) for TCMSP was derived from the EC1.6 value by applying sensitization assessment factors (SAFs). The exposure level was estimated based on the assumption referring to the use conditions of thiabendazole in the same purpose. Then, the estimated exposure level was compared with the AEL to evaluate the skin sensitization risk. RESULTS: The AEL was calculated as 0.00458 µg/cm2 based on the EC1.6 value (0.011%, 2.75 µg/cm2 ) by applying a composite SAF of 600. The estimated TCMSP exposure level from the desk mat was 500 times greater than the AEL, indicating a serious skin sensitization risk. CONCLUSIONS: Assessments of skin sensitization potencies of chemicals to be used in consumer products are strongly recommended, and QRAs should be performed at the pre-marketing stage to avoid the skin sensitization risk in consumers.

Outpatient Versus Inpatient Intravenous Antimicrobial Therapy: A Population-Based Observational Cohort Study of Adverse Events and Costs.

BACKGROUND: Bacterial infections such as osteomyelitis and endocarditis routinely require several weeks of treatment with intravenous (IV) antimicrobials. Outpatient parenteral antimicrobial therapy (OPAT) programs allow patients to receive IV antimicrobials in an outpatient clinic or at home. The outcomes and costs of such treatments remain uncertain. METHODS: We conducted a retrospective observational cohort study over a 5-year study interval (1 June 2012 to 31 March 2018) using population-based linked administrative data from British Columbia, Canada. Patients receiving OPAT following a hospitalization for bacterial infection were matched based on infection type and implied duration of IV antimicrobials to patients receiving inpatient parenteral antimicrobial therapy (IPAT). Cumulative adverse events and direct healthcare costs were estimated over a 90-day outcome interval. RESULTS: In a matched cohort of 1842 patients, adverse events occurred in 35.6% of OPAT patients and 39.0% of IPAT patients (adjusted odds ratio, 1.04 [95% confidence interval {CI}, .83-1.30; P = .61). Relative to IPAT patients, OPAT patients were significantly more likely to experience hospital readmission (30.5% vs 23.0%) but significantly less likely to experience Clostridioides difficile diarrhea (1.2% vs 3.1%) or death (2.0% vs 8.8%). Estimated mean direct healthcare costs were $30 166 for OPAT patients and $50 038 for IPAT patients (cost ratio, 0.60; average cost savings with OPAT, $17 579 [95% CI, $14 131-$21 027]; P < .001). CONCLUSIONS: Outpatient IV antimicrobial therapy is associated with a similar overall prevalence of adverse events and with substantial cost savings relative to patients remaining in hospital to complete IV antimicrobials. These findings should inform efforts to expand OPAT use.

Assessment of Larval Toxicity and the Teratogenic Effect of Three Medicinal Plants Used in the Traditional Treatment of Urinary Tract Infections in Benin.

OBJECTIVE: Mangifera indica Linn, Bridelia ferruginea Benth, and Alstonia boonei De Wild are three plants commonly used in the traditional treatment of urinary tract infections in Benin. This study sets out to assess the cytotoxic and teratogenic effects of extracts of these plants on Artemia salina larvae and hen embryos. METHODS AND RESULTS: The aqueous and ethanolic extracts were obtained by maceration of the powders in solvents. Larval cytotoxicity was performed on Artemia salina larvae. The teratogenic effect of these plants was evaluated on chick embryos at 100 mg/kg and 300 mg/kg. The extracts were injected on the 7th and 14th days of incubation. The quality of the hatched chicks was evaluated by the Tona score followed by the hematological and the biochemical parameter assays. The extracts did not show cytotoxicity on the larvae. The eggs treated with plant extracts at 300 mg/kg significantly lowered the hatchability rate, except for the Mangifera indica Linn. The chicks obtained were all at the very good quality. Then, no significant variation was observed between hematological parameters except white blood cells. For the biochemical parameters, only ASAT showed some significant variations for a few extracts. It would be important to assess the genotoxicity of the plant extracts to determine more broader toxicity. These data justify the use of these medicinal plants in traditional Beninese medicine and constitute in fact a source of production of anti-infectious drugs.

[Retrocession, a risk area in care pathway]. / Les rétrocessions, une zone à risque dans le parcours des patients.

OBJECTIVES: Medication errors are common at transitions points in care pathway. The pharmacist can secure patient care in "retrocession" (dispensing specific drugs by hospital pharmacy to outpatient) due to his prescription analysis (both regulatory and pharmacotherapeutic). The "retrocession" is a risk area in care pathway. The objective of this study is to evaluate iatrogenic and economic risks in "retrocession" dispense by identifying pharmaceutical interventions. MATERIAL AND METHODS: This is a prospective monocentric study performed during 8months in university hospital. All the prescriptions have been analyzed and divided into 3 categories: "first prescription" (a new prescription for a new treatment or a new patient), continued therapy with new prescription and prescription renewal. Therapeutic optimizations and regulatory pharmaceutical interventions performed have been systematically recorded. RESULTS: Among 7166 prescriptions analyzed, 161 pharmaceutical interventions (2.2%) are done. The highest rate of therapeutic optimizations and regulatory pharmaceutical interventions concern the "first prescription" category (9.3%). The most involved drugs in medication errors on a "first prescription" are cancer drugs (36%) and anti-infectives (24%). CONCLUSION: The first dispensation in "retrocession" is the riskiest step, especially with pharmacotherapeutic intervention. Thanks to pharmacist counseling sessions, especially in oncology, this risk is better controlled. This study demonstrates the interest of developing pharmacist counseling sessions for the treatment's introduction regardless of therapeutic class.

In vitro assessment of the antimicrobial efficacy of chitosan nanoparticles against major fish pathogens and their cytotoxicity to fish cell lines.

Nanotechnology is an emerging avenue employed in disease prevention and treatment. This study evaluated the antimicrobial efficacy of chitosan nanoparticles (CSNPs) against major bacterial and oomycete fish pathogens in comparison with chitosan suspension. Initially, the minimum inhibitory concentrations (MIC, MIC90 ) were determined and the per cent inhibition of bacterial growth was calculated. Subsequently, the minimum bactericidal concentrations (MBCs) were determined. The time-dependent disruptions of CSNP-treated pathogens were observed via transmission electron microscopy (TEM), and the effect of CSNPs on the viability of two fish cell lines was assessed. No antimicrobial effect was observed with chitosan, while CSNPs (105 nm) exhibited a dose-dependent and species-specific antimicrobial properties. They were bactericidal against seven bacterial isolates recording MBC values from 1 to 7 mg/ml, bacteriostatic against four further isolates recording MIC values from 0.125 to 5 mg/ml and fungistatic against oomycetes recording MIC90 values of 3 and 4 mg/ml. TEM micrographs showed the attachment of CSNPs to the pathogenic cell membranes disrupting their integrity. No significant cytotoxicity was observed using 1 mg/ml CSNPs, while low dose-dependent cytotoxicity was elicited by the higher doses. Therefore, it is anticipated that CSNPs are able to compete and reduce using antibiotics in aquaculture.

Tackling antimicrobial resistance in Bangladesh: A scoping review of policy and practice in human, animal and environment sectors.

BACKGROUND: Antimicrobial resistance (AMR) has become an emerging issue in the developing countries as well as in Bangladesh. AMR is aggravated by irrational use of antimicrobials in a largely unregulated pluralistic health system. This review presents a 'snap shot' of the current situation including existing policies and practices to address AMR, and the challenges and barriers associated with their implementation. METHODS: A systematic approach was adopted for identifying, screening, and selecting relevant literature on AMR situation in Bangladesh. We used Google Scholar, Pubmed, and Biomed Central databases for searching peer-reviewed literature in human, animal and environment sectors during January 2010-August 2019, and Google for grey materials from the institutional and journal websites. Two members of the study team independently reviewed these documents for inclusion in the analysis. We used a 'mixed studies review' method for synthesizing evidences from different studies. RESULT: Of the final 47 articles, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Nineteen articles on human health dealt with prescribing and/or use of antimicrobials, five on self-medication, two on non-compliance of dosage, and 10 on the sensitivity and resistance patterns of antibiotics. Four papers focused on the use of antimicrobials in food animals and seven on environmental contamination. Findings reveal widespread availability of antimicrobials without prescription in the country including rise in its irrational use across sectors and consequent contamination of environment and spread of resistance. The development and transmission of AMR is deep-rooted in various supply and demand side factors. Implementation of existing policies and strategies remains a challenge due to poor awareness, inadequate resources and absence of national surveillance. CONCLUSION: AMR is a multi-dimensional problem involving different sectors, disciplines and stakeholders requiring a One Health comprehensive approach for containment.

Indicators of the hospital use of antimicrobial agents based on consumption.

OBJECTIVE: To identify indicators of hospital use of antimicrobials from the  benchmark analysis of consumption data between hospitals at the same level  through the collective judgement of a group of experts. METHOD: A committee formed by members of the Spanish Societies of Hospital Pharmacy and Infectious Diseases and Clinical Microbiology prepared a proposal of indicators which was submitted to  consensus by a panel of 21 experts on infectious diseases, microbiology and  antimicrobial therapy, through a modified Delphi method. The panel  underwent two rounds of scores by e-mail. Participants assigned a score  from 1 (completely disagree) to 9 (completely agree) to the relevance of  each indicator in four dimensions: scientific evidence, efficacy and safety,  ecological impact and cost. Scores were processed according to the RAND- UCLA method. An indicator was considered to be relevant if at least one  dimension other than cost obtained a median score equal to or higher than 7 without disagreement among the panel. RESULTS: The committee submitted an initial proposal of 14 indicators. After the first round of panel scores, one indicator was ruled out and two  were  modified for moving on to the second round. Finally, 13 indicators  were considered relevant. CONCLUSIONS: Determining indicators of the hospital use of antimicrobial agents based on consumption can allow the antimicrobial  stewardship programs to detect any potential problems with the use of  antimicrobial agents, and to help guide their efforts in order to implement actions of improvement, as well as to assess the impact of the  measures implemented.

Objetivo: Identificar unos indicadores del uso hospitalario de  antimicrobianos a partir del análisis comparativo de los datos de consumo  entre hospitales del mismo nivel por medio del juicio colectivo de un grupo  de expertos.Método: Un comité formado por miembros de la Sociedad Española de Farmacia Hospitalaria y de la Sociedad Española de Enfermedades  Infecciosas y Microbiología Clínica preparó una propuesta de indicadores que  fue sometida a consenso por un panel de 21 expertos en enfermedades infecciosas, microbiología y terapéutica antimicrobiana  mediante un método Delphi modificado. El panel se sometió a dos rondas de  puntuaciones por correo electrónico. Los participantes puntuaron de 1  (completamente en desacuerdo) a 9 (completamente de acuerdo) la  relevancia de cada indicador en cuatro dimensiones: evidencia científica,  eficacia y seguridad, repercusión ecológica y coste. Las puntuaciones fueron  procesadas según el método UCLA-RAND. Un indicador fue juzgado como relevante si al menos una dimensión distinta al coste obtenía una  mediana de puntuación igual o superior a 7 sin haber desacuerdo entre el  panel.Resultados: El comité planteó una propuesta inicial de 14 indicadores. Tras  la primera ronda de puntuaciones del panel, un indicador fue desestimado y  dos fueron modificados para el paso a la segunda ronda. Finalmente, 13  indicadores fueron considerados relevantes.Conclusiones: El establecimiento de indicadores del uso hospitalario de  antimicrobianos basados en el consumo puede permitir a los programas de  optimización de antimicrobianos detectar cuáles son los problemas potenciales de uso de los antimicrobianos, y ayudar a orientar sus esfuerzos para emprender acciones de mejora, así como para valorar el impacto de las medidas efectuadas.

Clinical and economic impact of the taurolidine lock on home parenteral nutrition.

INTRODUCTION: catheter-related bloodstream infections (CRBSI) are one of the most serious concerns in patients on home parenteral nutrition (HPN) which involve high morbidity and cost for the healthcare system. In the last years, taurolidine lock has proven to be beneficial in the prevention of CRBSI; however, the evidence of its efficiency is limited. OBJECTIVE: to determine if taurolidine lock is a cost-effective intervention in patients on HPN. MATERIALS AND METHODS: retrospective study in patients on HPN with taurolidine lock. We compared the CRBSI rate and cost of its complications before and during taurolidine lock. RESULTS: thirteen patients, six (46%) males and seven (54%) females, with a mean age of 61.08 (SD = 14.18) years received taurolidine lock. The total days of catheterization pre and per-taurolidine were 12,186 and 5,293, respectively. The underlying disease was benign in five patients (38.5%) and malignant in eight (61.5%). The CRBSI rate pre vs per-taurolidine was 3.12 vs 0.76 episodes per 1,000 catheter days (p = 0.0058). When the indication was a high CRBSI rate, this was 9.72 vs 0.39 (p < 0.001) in pre and per-taurolidine period respectively. No differences have been observed in the occlusion rates. None of the patients reported any adverse effects. The total cost of CRBSI in the pre-taurolidine period was 151,264.14 euros vs 24,331.19 euros in the per-taurolidine period. CONCLUSIONS: our study shows that taurolidine lock is a cost-effective intervention in patients on HPN with high risk of CRBSI.

Evaluation of Renal Function Estimation Formulas Specific to Dynamic Renal Function for Drug Dosing in Critically Ill Patients.

OBJECTIVES: The study compared estimated creatinine clearance (eCrCl) between the Cockcroft-Gault (CG) equation and the Jelliffe, Chiou, and Brater equations designed for estimation in dynamic renal function and resulting antimicrobial dosing concordance of five antimicrobials (cefepime, meropenem, piperacillin/tazobactam, vancomycin, and fluconazole) commonly used in the intensive care unit (ICU). METHODS: Electronic medical records were used to identify the target patient population. Analysis of variance tests with repeated measures were performed to compare eCrCl. Bowker's tests of symmetry were applied to compare the dosing regimen discordance between CG and candidate equations. RESULTS: From January 1, 2008 through December 31, 2012, we identified 387 patients with acute kidney injury (AKI), among whom 62% (n = 240) were older adults (65 years and older) and 46% (n = 178) were obese (body mass index ≥30). In the declining phase of renal function, eCrCl means were different between the CG and Brater equations (32.0 vs 26.1 mL/min, P < 0.001). The dosing regimen discordance rates (CG vs candidate equations) in declining renal function varied from 19.3% to 25% and were statistically significant for cefepime and meropenem (P < 0.001) based on Food and Drug Administration recommendations for dose adjustment. In the improving phase, eCrCl means were different (P < 0.001) between CG (43.0 mL/min) and candidate formulas (Brater 47.9, Chiou 31.7, and Jelliffe 55.3 mL/min). The dosing regimen discordance rates (CG vs candidate equations) in the improving phase varied from 8.3% to 39% and were statistically significant for all 5 antimicrobials (P < 0.001). CONCLUSIONS: Differences in eCrCl between CG and candidate formulas were observed in surgical ICU patients with acute kidney injury. Discordant dosing recommendations may affect antimicrobial regimens in ICU patients with dynamic renal function.

Prevalence of Contact Allergens in Personal Care Products for Babies and Children.

BACKGROUND: Personal care products marketed for babies and children are often regarded as "safe" or "gentle." However, little is known about the prevalence of contact allergens in these types of products. OBJECTIVE: This study assessed the prevalence of important sensitizers in personal care products marketed for babies and children. A secondary objective of this study was to determine whether a product's cost correlates with content of sensitizing ingredients. METHODS: The ingredient lists of 533 unique personal care products were analyzed for presence of fragrance, betaines, propylene glycol, methylchloroisothiazolinone, methylisothiazolinone, formaldehyde, lanolin, and neomycin. Price per ounce was determined for each product as well. CONCLUSIONS: Most personal care products for babies and children contain 1 or more sensitizers. Products containing more sensitizers tend to cost less than those without any sensitizing ingredients.

Infectious risk of biological drugs vs. traditional systemic treatments in moderate-to-severe psoriasis: a cohort analysis in the French insurance database.

The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by biological drugs (BD) and a group treated by traditional systemic treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi-Pyrénées area (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between 'exposed' patients treated with BD (adalimumab, etanercept, infliximab, or ustekinumab) and 'unexposed' patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine). We realized a survival analysis on the first infectious event, defined as an anti-infective drug delivery or a hospital diagnosis of infection. We selected 101 'exposed' and 788 'unexposed' patients. In our multivariate Cox model, 'exposure' did not seem to decrease the time frame of the first infectious event compared with 'nonexposure' (HR = 0.94, P = 0.62). Among all treatment, the safest seemed to be ustekinumab while the least safe was etanercept. We found factors statistically associated with the risk of infection: gender (female vs. male), economic deprivation, chronic hepatitis B or C, history of cancer, at least one infectious event, and the number of different drugs during the 6-month period before the study. We did not find any difference of infective risk between the BD and the TST. This result enhances the recent PSONET registries conclusions.

Application of in Vitro T Cell Assay Using Human Leukocyte Antigen-Typed Healthy Donors for the Assessment of Drug Immunogenicity.

It is unclear whether priming of naïve T cells to drugs is detectable in healthy human donors expressing different human leukocyte antigen (HLA) alleles. Thus, we examined T cell priming with drugs associated with HLA risk alleles and control compounds in 14 HLA-typed donors. Nitroso sulfamethoxazole and piperacillin activated T cells from all donors, whereas responses to carbamazepine and oxypurinol were only seen in donors expressing HLA-B*15:02 and HLA-B*58:01, respectively. Weak flucloxacillin-specific T cell responses were detected in donors expressing HLA-B*57:01 and HLA-B*58:01. These data show that the priming of T cells with certain drugs is skewed toward donors expressing specific HLA alleles.

Medicinal foods and beverages among Maasai agro-pastoralists in northern Tanzania.

ETHNOPHARMACOLOGICAL RELEVANCE: Pastoralist Maasai populations of east Africa use several different wild plants as dietary and medicinal additives in beverages (soups and teas), yet little is known about how the plants used and the rationales for use compare and contrast across different Maasai beverages, including how gender specific dietary and health concerns structure patterns of intake. AIM OF THE STUDY: We investigated three Maasai beverages: almajani (tea or herbal infusion); motorí (traditional soup); and okiti (psychoactive herbal tea). In order to build knowledge about the cultural functions of these Maasai food-medicines and their incidence of use we also investigated use rationales and self-reported frequencies of use. We conclude by examining gender differences and the possible pharmacological antimicrobial activity of the most frequently used plants. MATERIALS AND METHODS: Research was conducted in 2015, with a population of semi-nomadic agropastoralist Maasai residing in northern Tanzania. Data were collected using key informant interviews, plant collections, n = 32 structured surveys, and n = 40 freelist interviews followed by a literature review to determine the known antimicrobial activity of the most used plants. RESULTS: We identified 20 plants that Maasai add to soup, 11 in tea, and 11 in the psychoactive tea, for a total of 24 herbal additives. Seven plant species were used in all three Maasai beverages, and these clustered with 10 common ailments. Based on self-reports, women use the beverages less frequently and in smaller amounts than men. There were also several gender differences in the plants that Maasai add to motorí and their associated use rationales. CONCLUSIONS: There are several intersections concerning the plant species used and their associated rationales for use in almajani, motori, and okiti. Moving outward, Maasai beverages and their additives increasingly involve gender specific concerns. Female use of food-medicines, relative to men, is structured by concerns over pregnancy, birth, and lactation. The frequent consumption of herbal additives, many of which contain antimicrobial compounds, potentially helps modulate infections, but could have other unintentional effects as well.

Global analysis of strategies to tackle antimicrobial resistance.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health issue driven by inappropriate use of antimicrobials resulting in decreased efficacy on the background of an extremely limited pipeline for new antibiotics. We sought to analyse the effectiveness of key policies and strategies in tackling AMR globally and identify gaps in these. METHOD: The scope, magnitude, history and drivers of AMR were reviewed using supporting evidence. Our methodology included a literature review and semi-structured survey, whilst the analyses process was guided by an adapted health policy analyses framework. RESULTS: Six key policies of global, UK and Nigerian origin were identified along with supporting literature. Seven respondents from key organisations were identified and interviewed. Their responses were analysed using framework analyses principles. CONCLUSIONS: Antimicrobial resistance is driven by several factors, ranging from poverty to poor implementation of inadequate policies. The UK AMR strategy is the most comprehensive with room for improvement. Nigeria lacks a specific AMR policy, but has other policies which address health system drivers of AMR. Similarly, the UK's surveillance system is extensive with recent findings corresponding to global findings. Nigeria's surveillance system is focused on detecting and tackling epidemics as indicated by its recent success with Ebola, but there is room for improvement and it could be expanded to cover AMR. Global policies do not add much value to the UK strategy and provide little guidance on how low-income countries, for example Nigeria can fill current gaps in surveillance and policies as key drivers are not fully addressed.

Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters.

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.

Antimicrobial Stewardship in Inpatient Settings in the Asia Pacific Region: A Systematic Review and Meta-analysis.

BACKGROUND: An antimicrobial stewardship program (ASP) is one of the core elements needed to optimize antimicrobial use. Although collaboration at the national level to address the importance of ASPs and antimicrobial resistance has occurred in the Asia Pacific region, hospital-level ASP implementation in this region has not been comprehensively evaluated. METHODS: We conducted a systematic review and meta-analysis to assess the efficacy of ASPs in inpatient settings in the Asia Pacific region from January 2005 through March 2016. The impact of ASPs on various outcomes, including patient clinical outcomes, antimicrobial prescription outcomes, microbiological outcomes, and expenditure were assessed. RESULTS: Forty-six studies were included for a systematic review and meta-analysis. The pooled risk ratio for mortality from ASP before-after trials and 2-group comparative studies were 1.03 (95% confidence interval [CI], .88-1.19) and 0.69 (95% CI, .56-.86), respectively. The pooled effect size for change in overall antimicrobial and carbapenem consumption (% difference) was -9.74% (95% CI, -18.93% to -.99%) and -10.56% (95% CI, -19.99% to -3.03%), respectively. Trends toward decreases in the incidence of multidrug-resistant organisms and antimicrobial expenditure (range, 9.7%-58.1% reduction in cost in the intervention period/arm) were also observed. CONCLUSIONS: ASPs in inpatient settings in the Asia Pacific region appear to be safe and effective to reduce antimicrobial consumption and improve outcomes. However, given the significant variations in assessing the efficacy of ASPs, high-quality studies using standardized surveillance methodology for antimicrobial consumption and similar metrics for outcome measurement are needed to further promote antimicrobial stewardship in this region.

An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of a Guideline for the Management of Antimicrobial/Warfarin Interactions in the Inpatient Setting and Across Transition of Care.

BACKGROUND: Drug-drug interactions (DDIs) with warfarin and antimicrobial agents are a common cause of international normalized ratio (INR) instability, which can affect the risk for bleeding and thrombotic events. OBJECTIVE: The purpose of this study was to assess the impact of a comprehensive guideline for the management of warfarin-antimicrobial DDIs across transitions of care. The guideline emphasizes improving identification of significant antimicrobial-warfarin DDIs during hospitalization, empirical warfarin dose modification based on DDI and baseline INR, patient education, documentation of the DDI, communication with outpatient providers regarding the DDI and anticipated antimicrobial stop date, and warfarin dose adjustment on discontinuation of antimicrobial. METHODS: This retrospective, single-center, quasiexperimental, pre-post study compared end points 3 months before and after guideline implementation. The primary outcome was time within therapeutic range (TTR). RESULTS: The study included 78 preguideline and 31 postguideline patients; baseline characteristics were similar between groups. Implementation of the guideline resulted in greater in-hospital TTR (72% vs 50%, P = 0.04) and improved TTR across transition of care (70% vs 46%, P = 0.01). Documentation of DDI in the pharmacy anticoagulation discharge summary significantly improved in the postguideline group (40% vs 14%, P = 0.02) and numerically improved within the daily pharmacy progress notes (94% vs 82%, P = 0.13). The implementation of the guideline was associated with a nonsignificant, numerical reduction in bleeding events compared with the preguideline group (0 vs 4 events, P = 0.11). CONCLUSION: This single-center approach to optimize the comprehensive management of significant antimicrobial-warfarin DDIs resulted in improved communication with outpatient providers and improved INR TTR.