Setting occupational exposure limits for antimicrobial agents: A case study based on a quaternary ammonium compound-based disinfectant.

Antimicrobial agents have become an essential tool in controlling the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and guidelines on their use have been issued by various public health agencies. Through its Emerging Viral Pathogen Guidance for Antimicrobial Pesticides, the US Environmental Protection Agency has approved numerous surface disinfectant products for use against SARS-CoV-2. Despite their widespread use and range of associated health hazards, the majority of active ingredients in antimicrobial products, such as surface disinfectants, lack established occupational exposure limits (OELs) to assist occupational health professionals in characterizing risks from exposures to these chemicals. Based on established approaches from various organizations, a framework for deriving OELs specific to antimicrobial agents was developed that relies on a weight-of-evidence evaluation of the available data. This framework involves (1) a screening-level toxicological assessment based on a review of the existing literature and recommendations, (2) identification of the critical adverse effect(s) and dose-response relationship(s), (3) identification of alternative health-based exposure limits (HBELs), (4) derivation of potential OELs based on identified points of departure and uncertainty factors and/or modification of existing alternative HBELs, and (5) selection of an appropriate OEL. To demonstrate the use of this framework, a case study is described for selection of an OEL for a disinfectant product containing quaternary ammonium compounds (quats). Three potential OELs were derived for this product based on irritation toxicity data, developmental and reproductive toxicity (DART) data, and modification of an existing HBEL. The final selected OEL for the quats-containing product was 0.1 mg/m3, derived from modification of an existing HBEL. This value represented the lowest resulting value of the three approaches, and thus, was considered protective of irritation and potential DART.

Government policy interventions to reduce human antimicrobial use: A systematic review and evidence map.

BACKGROUND: Growing political attention to antimicrobial resistance (AMR) offers a rare opportunity for achieving meaningful action. Many governments have developed national AMR action plans, but most have not yet implemented policy interventions to reduce antimicrobial overuse. A systematic evidence map can support governments in making evidence-informed decisions about implementing programs to reduce AMR, by identifying, describing, and assessing the full range of evaluated government policy options to reduce antimicrobial use in humans. METHODS AND FINDINGS: Seven databases were searched from inception to January 28, 2019, (MEDLINE, CINAHL, EMBASE, PAIS Index, Cochrane Central Register of Controlled Trials, Web of Science, and PubMed). We identified studies that (1) clearly described a government policy intervention aimed at reducing human antimicrobial use, and (2) applied a quantitative design to measure the impact. We found 69 unique evaluations of government policy interventions carried out across 4 of the 6 WHO regions. These evaluations included randomized controlled trials (n = 4), non-randomized controlled trials (n = 3), controlled before-and-after designs (n = 7), interrupted time series designs (n = 25), uncontrolled before-and-after designs (n = 18), descriptive designs (n = 10), and cohort designs (n = 2). From these we identified 17 unique policy options for governments to reduce the human use of antimicrobials. Many studies evaluated public awareness campaigns (n = 17) and antimicrobial guidelines (n = 13); however, others offered different policy options such as professional regulation, restricted reimbursement, pay for performance, and prescription requirements. Identifying these policies can inform the development of future policies and evaluations in different contexts and health systems. Limitations of our study include the possible omission of unpublished initiatives, and that policies not evaluated with respect to antimicrobial use have not been captured in this review. CONCLUSIONS: To our knowledge this is the first study to provide policy makers with synthesized evidence on specific government policy interventions addressing AMR. In the future, governments should ensure that AMR policy interventions are evaluated using rigorous study designs and that study results are published. PROTOCOL REGISTRATION: PROSPERO CRD42017067514.

Comparison of knowledge to antimicrobial stewardship institution policies targeting Staphylococcus aureus bacteremia and candidemia between medical doctors and pharmacists in an academic teaching hospital in Japan.

Staphylococcus aureus bacteremia (SAB) and candidemia have significant impacts on mortality. Both have important implications for antimicrobial stewardship programs (ASPs). However, there are limited data regarding who should be educated and what components should be considered for the ASPs. Hence, we investigated the possibility of the key elements for implications of SAB and candidemia managements for ASPs. We conducted a cross-sectional study on the knowledge of antimicrobial stewardship institution policies targeting SAB and candidemia for all medical doctors (MDs) and pharmacists to using an E-learning system. To compare the differences in proportions of appropriate knowledge between junior residents and other MDs, and all MDs and pharmacists, we performed bivariate analyses using Fisher's exact test and χ2 test with odds ratios (ORs) with 95% confidence intervals (CIs). In total, all 395 MDs (71 junior residents, 137 senior residents and fellows, and 187 attending doctors) and all 63 pharmacists including 4 antimicrobial stewardship teams pharmacists responded to survey. MDs other than junior residents responded significantly inappropriately to the questions on the candidemia than junior residents (OR = 0.6, 95% CI: 0.4-1.0). Pharmacists had a significantly lower proportion of appropriate knowledge to the candidemia than MDs (OR = 0.4, 95% CI: 0.2-0.8). The major pitfall was failure to consult an ophthalmologist (82.5%). Next step, we will conduct educational intervention about institution policies, and evaluate whether to improve the knowledges and practices by pre-post test and chart review.

Comparison of Anti-Microbial Effects of Low-Level Laser Irradiation and Microwave Diathermy on Gram-Positive and Gram-Negative Bacteria in an In Vitro Model.

Background and Objectives: The aim of this study was to compare the effects of low-level laser therapy and continuous microwave diathermy on the growth of Gram-negative and Gram-positive bacteria and to establish their efficacy as an alternative therapeutic modality. MATERIALS AND METHODS: Laser fluence of 13 Joules (J)/cm2, 18 J/cm2 and 30 J/cm2 were used against several bacterial strains. Microwave dosages of 25, 50 and 100 watts (W) were used, respectively. RESULTS: A significant difference between the three groups was observed using repeated analysis of variance (RANOVA) (F value: 0.74, and p value: 0.001). The Greenhouse-Geisser correction (GG) revealed significant results for laser irradiation alone. However, effect size calculation showed effects with microwave diathermy as well as laser fluence. CONCLUSIONS: Low-level laser therapy appears to be an effective modality of treatment when compared with continuous microwave diathermy on the Gram-negative and the Gram-positive bacterial strains tested. Microwave diathermy revealed large and medium effects on the bacterial cell counts with dominant effects on Gram-negative strains.

Influence of Morbid Obesity on the Clinical Pharmacokinetics of Various Anti-Infective Drugs: Reappraisal Using Recent Case Studies-Issues, Dosing Implications, and Considerations.

Owing to availability of scanty pharmacokinetic data, dosing decisions in morbid obesity is increasingly challenging in the field of anti-infective drugs. However, in recent years data are emerging that describe the pharmacokinetics of anti-infective drugs in morbidly obese subjects. The objectives of the present work were: (1) to collate the recent reports pertaining to the pharmacokinetics in morbidly obese subjects for several anti-infective drugs and provide an overview of the pharmacokinetic data along with the applicable pharmacodynamics and/or clinical outcome; (2) to perform regression analysis on limited dataset for a few drugs to verify the existence of relationships between Cmax/Ctrough versus steady-state volume of distribution (Vss)/clearance to enable data prediction in morbid obesity subjects; (3) to provide a general discussion on issues and dosing implications. The key findings of this review were: (a) drugs such as vancomycin, ethambutol, and fluconazole, where the VSS is substantially greater in morbidly obese patients, need a dosing strategy with the appropriate body mass descriptors; (b) other drugs such as moxifloxacin, linezolid, doripenem, meropenem, voriconazole, oseltamivir, tigecycline, levofloxacin may not ordinarily need dosing adjustments;

The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults.

BACKGROUND & AIMS: Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to provide a review of the literature and specific, updated recommendations for eradication therapy in adults. METHODS: A systematic literature search identified studies on H pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized, and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. RESULTS: Because of increasing failure of therapy, the consensus group strongly recommends that all H pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant nonbismuth quadruple therapy (proton pump inhibitor [PPI] + amoxicillin + metronidazole + clarithromycin [PAMC]) and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline [PBMT]). PPI triple therapy (PPI + clarithromycin + either amoxicillin or metronidazole) is restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin). Rifabutin regimens should be restricted to patients who have failed to respond to at least 3 prior options. CONCLUSIONS: Optimal treatment of H pylori infection requires careful attention to local antibiotic resistance and eradication patterns. The quadruple therapies PAMC or PBMT should play a more prominent role in eradication of H pylori infection, and all treatments should be given for 14 days.

Paramedical staffs knowledge and attitudes towards antimicrobial resistance in Dire Dawa, Ethiopia: a cross sectional study.

BACKGROUND: The continuing emergence, development and spread of pathogenic organisms that are resistant to antimicrobials are a cause of increasing concern. The control of antimicrobial resistance requires knowledge of factors causing antimicrobial resistance, good attitudes towards the intervention strategies as well as changes in antibiotic prescribing behavior of health workers. Hence, this study was aimed to assess paramedical staffs' knowledge and attitudes towards antimicrobial resistance and their antibiotics prescription practices in Dire Dawa, Ethiopia. METHODS: A cross-sectional survey was conducted among paramedical staffs working in hospitals and health centers. A total of 218 paramedical staffs were participated and a self-administered questionnaire was used to collect data. Data was analyzed using SPSS version 20. Chi square/Fisher's exact tests were used for comparison of data and a p value of less than 0.05 was considered statistically significant. RESULTS: Out of the total, 137 (62.8%) of paramedical staffs had good knowledge on the factors causing antimicrobial resistance. The most common causes of antimicrobial resistance reported were patients' poor adherence (96.5%), self prescription (95%), and empiric choice of antibiotics (94.5%). In general, more than 80% of the respondents had positive attitudes towards the antimicrobials resistance intervention strategies. Relatively less proportion of participants recognized that antimicrobial resistance as a problem in their local institutions. The most perceived driving forces for unnecessary antibiotics prescriptions were treatment failure (67.7%) and patient push (53.3%). The majority, 76.9% of the prescribers mentioned that standard treatment guidelines were available in their institutions though only 15.7% of them reported referring the guidelines on the daily basis. Among the prescribers, 85.8% never attended formal trainings on antibiotics prescriptions. CONCLUSIONS: As this study generated important information on knowledge and attitudes of paramedical staffs about antimicrobial resistance, it identified areas of misconceptions and specific groups to be targeted for educational interventions regarding antimicrobial resistance. It is, therefore, suggested that a well-planned, organized and structured training programs should be undertaken to improve the appropriate use of antibiotics.

Network meta-analysis of studies included in the Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis.

AIM: The recent ADA-commissioned Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis has provided the most exhaustive library of clinical trials on scaling and root planing (SRP) with or without adjuncts. This network meta-analysis (NMA) compared the adjuncts against each other. MATERIALS AND METHODS: A star-shaped NMA was performed based on 36 indirect comparisons of clinical attachment-level (CAL) gains among nine adjuncts in 74 studies from the Clinical Practice Guideline. RESULTS: All pairwise differences were accompanied by wide confidence intervals, and none of the adjuncts were statistically significantly superior to another. Local doxycycline hyclate and photodynamic therapy with a diode laser had the highest probabilities for ranking first and second, respectively. Publication bias was evident, with fewer than expected studies with small effects. The lack of these studies inflated the treatment effects by an estimated by 20%. CONCLUSIONS: Adjuncts improve CAL gain by about a third of a mm over 6-12 months compared with SRP alone, but no significant differences were found among the adjuncts. The patient-perceived benefit of this gain is unclear because CAL is a physical measure made by the clinician and not a patient-oriented outcome. Publication bias inflated the observed treatment effects.

Substandard/counterfeit antimicrobial drugs.

Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue.

Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050?

Marlieke de Kraker and colleagues reflect on the need for better global estimates for the burden of antimicrobial resistance.