Practice of Perioperative Rational Use of Antibacterial Drugs Based on Drug Pathway

[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.

Mass drug administration of antibacterials: weighing the evidence regarding benefits and risks

Background: Mass drug administration(MDA)is a strategy to improve health at the population level through widespread delivery of medicine in a community.We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials,focusing predominantly on azithromycin as it has the greatest evidence base.Main body: High-quality evidence from randomized controlled trials(RCTs)indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma.In addition,RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline.This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin,with the greatest effect observed in children<1 year of age.In addition,observational data suggest that infections such as skin and soft tissue infections,rheumatic heart disease,acute respiratory illness,diarrheal illness,and malaria may all be treated by azithromycin and thus incidentally impacted by MDA-azithromycin.However,the mechanism by which MDA-azithromycin reduces childhood mortality remains unclear.Verbal autopsies performed in MDA-azithromycin childhood mortality studies have produced conflicting data and are underpowered to answer this question.In addition to benefits,there are several important risks associated with MDA-azithromycin.Direct adverse effects potentially resulting from MDA-azithromycin include gastrointestinal side effects,idiopathic hypertrophic pyloric stenosis,cardiovascular side effects,and increase in chronic diseases such as asthma and obesity.Antibacterial resistance is also a risk associated with MDA-azithromycin and has been reported for both gram-positive and enteric organisms.Further,there is the risk for cross-resistance with other antibacterial agents,especially clindamycin.Conclusions: Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma,yaws,and mortality in children<5 years of age in certain under-resourced settings.However,there are significant potential risks that need to be considered when deciding how,when,and where to implement these programs.Robust systems to monitor benefits as well as adverse effects and antibacterial resistance are warranted in communities where MDA-azithromycin programs are implemented.

Evaluation of ceftriaxone dosing regimens based on PK/PD models and Monte Carlo simulations

In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball software combining PK and PD parameters with 10000 simulation runs to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)for the seven clinically common dosing regimens of ceftriaxone(1 g qd,1.5 g qd,1 g bid,2 g qd,1 g tid,1.5 g bid,and 2 g bid).A%fT≥50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR≥90%or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy,i.e.the clinically optimal regimen.All eight pathogenic bacteria had a CFR>90%when the dosing regimen was 2 g bid and 1 g tid,seven pathogenic bacteria had a CFR>90%when the dosing regimen was 1 g bid and 1.5 g bid,except for Pseudomonas aeruginosa,and all pathogenic bacteria had a CFR<90%when the dosing regimen was 1 g qd and 1.5 g qd.The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections,and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.

KL-0153, a novel inhibitor of Pseudomonas aeruginosa MexAB-OprM efflux pump

Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.

A review of global initiatives to fight antibiotic resistance and recent antibiotics' discovery

Data from across the world have shown an overall decline in the antibiotic pipeline and continually rising resistance to all first-line and last-resort antibiotics. The gaps in our knowledge of existing prevalence and mechanisms of antibiotic resistance(ABR) are all too well known. Several decades of antibiotic abuse in humans, animals, and agricultural practices have created health emergency situations and huge socio-economic impact. This paper discusses key findings of the studies conducted by several national and international collaborative organizations on the current state of affairs in ABR.Alongside, a brief overview of the antibacterial agents' discovery in recent years approved by the US FDA is discussed.