Reasonable Selection of Antibiotics for Respiratory Infection
余凤姣, 陶晓南
华中科技大学同济医学院附属协和医院呼吸与危重症医学科,武汉 430022
YU Fengjiao,, TAO Xiaonan,
Department of Respiratory and Critical Care Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
The irrational use of drugs in China is still serious. Moreover, the abuse of antibiotics is a prominent problem, and the usage of antibiotics is far exceeding the standard established by WHO, which is no more than 40 DDD (daily drug dose, DDD) per 100 people per day. Respiratory infection is one of the common clinical diseases and one of major complications. The use of antibiotics is essential for respiratory diseases. In order to promote the safe, effective and economical use of antibiotics and to avoid bacterial resistance, it is very important to standardize the anti-infective treatment for respiratory infections and systemic infections. This article summarizes the selection strategies and experience of the "six appropriate" use of antibiotics in respiratory infections for reference.
Key words:
Antibiotics
;
Respiratory infection
;
Rational drug use
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Abstract The distinction between bacterial and viral causes of infections of the respiratory tract is a major but important clinical challenge. We investigated the diagnostic performance of human neutrophil lipocalin (HNL) in respiratory tract infections compared to those of C-reactive protein (CRP) and procalcitonin (PCT). Patients were recruited from the emergency department and from a primary care unit ( n = 162). The clinical diagnosis with regard to bacterial or viral cause of infection was complemented with objective microbiological/serological testing. HNL was measured in whole blood after preactivation with the neutrophil activator formyl-methionine-leucine-phenylalanine (fMLP) (B-HNL), and CRP and PCT were measured in plasma. Head-to-head comparisons of the three biomarkers showed that B-HNL was a superior diagnostic means to distinguish between causes of infections, with areas under the concentration-time curve (AUCs) of receiver operating characteristic (ROC) analysis for HNL of 0.91 (95% confidence interval [CI], 0.83 to 0.96) and 0.92 (95% CI, 0.82 to 0.97) for all respiratory infections and for upper respiratory infections, respectively, compared to 0.72 (95% CI, 0.63 to 0.80) and 0.68 (95% CI, 0.56 to 0.79) for CRP, respectively ( P = 0.001). In relation to major clinical symptoms of respiratory tract infections (cough, sore throat, stuffy nose, and signs of sinusitis), AUCs varied between 0.88 and 0.93 in those patients with likely etiology (i.e., etiology is likely determined) of infection, compared to 0.63 and 0.71 for CRP, respectively, and nonsignificant AUCs for PCT. The diagnostic performance of B-HNL is superior to that of plasma CRP (P-CRP) and plasma PCT (P-PCT) in respiratory tract infections, and the activity specifically reflects bacterial challenge in the body. The rapid and accurate analysis of HNL by point-of-care technologies should be a major advancement in the diagnosis and management of respiratory infections with respect to antibiotic treatment. Copyright 2017 Venge et al.
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Abstract It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews. The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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Since its approval, fluoroquinolones have become one of the most prescribed antibacterial agents. Because of its widespread use, serious concerns about the emergence of resistance in , spp, and entrobacteriaceae, has arisen, especially because of between fluoroquinolones. Huge efforts has been done to identify pharmacokinetic (PK) parameters like maximum serum concentration (Cmax), area under the curve of serum concentrations (AUC) and pharmacodynamic (PD) parameters like the minimum inhibitory concentration () or the mutant prevention concentration (), to optimize the use of the new fluoroquinolones, especially against these difficult to treat microorganisms. The new fluoroquinolones commercially available in Spain, and , have significant differences in their PK (Cmax, half-life, volume of distribution, etc), PD (, ,) and in their PK/PD parameters (AUC/; AUC/) that allow clinicians to establish clear preference for the utilization of one of them. Proper use of these new fluoroquinolones according to these PK/PD parameters will result in better management of with a reduction in the emergence of resistance. Based on data reviewed in this paper use, with best PK/PD characteristics, should be preferred over . Should be used, alternative dosing strategies would be recommended to avoid selection of resistant variants.
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Monte Carlo simulations allow prediction and comparison of concentration–time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT>MIC, 40%fT>MICand 100%fT>MIC. For the target of 40%fT>MIC, all 0.5-h infusion regimens achieved optimal exposures (CFR65≥6590%) againstEscherichia coliandStaphylococcus aureus, with nearly optimal exposure againstKlebsiella pneumoniae(CFR65≥6589.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception ofPseudomonas aeruginosaandAcinetobacterspp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT>MICtarget, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT>MICand 100%fT>MICwere achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary.
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A pharmacokinetic/pharmacodynamic (PK/PD) analysis is important in antibiotic chemotherapy. Basically, the in vivo efficacy of antibiotics that exert concentration-dependent effects can be predicted using conventional PK/PD indices such as the ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC) and/or the ratio of the maximum plasma concentration to MIC (Cmax/MIC), whereas that of antibiotics with time-dependent effects can be determined using the period of time for which the drug concentration exceeds the MIC (time above MIC [TAM]). However, an optimal PK/PD index remains to be established for some antibiotics. Thus, a PK/PD model which describes the PK profile and effect of an antibiotic was developed, and the results obtained from this model were interpreted to form a PK/PD index map to assess the optimal PK/PD index for the antibiotic. The findings from the map were generally consistent with clinical outcomes even for the antibiotics which proved to be exceptions to the conventional classification. For example, AUC/MIC was an optimal index for azithromycin despite its time-dependent bactericidal activity, and Cmax/MIC was a poor index for arbekacin despite its concentration-dependent profile. Thus, the map would be useful for selecting the appropriate PK/PD index for an antibiotic.
Treatment for tuberculosis (TB) using the standard oral antibiotic regimen is effective but inefficient, requiring high drug dosing and lengthy treatment times. Three concurrent first-line antibiotics recommended by the World Health Organization (WHO) guidelines are pyrazinamide, rifampicin and isoniazid. Combining these antibiotics in a novel formulation for dry powder inhalation (DPI) may facilitate rapid and efficient resolution of local and systemic infection. However, spray-dried individually, these antibiotics were found to be physically unstable. A solution of the three antibiotics, at the WHO-recommended ratio, was spray-dried. The collected powder was assessed by a series of in vitro methods to investigate aerosol performance, particle physico-chemical characteristics and dissolution profile. Particles obtained were spherical with a surface composed primarily of rifampicin, as identified by TOF-SIMS. A mass median aerodynamic diameter of 3.5 0.1 and fine particle fraction (<5) of 45 3% indicated excellent aerosol performance. The combination powder was differentiated by the presence of rifampicin dihydrate and the delta polymorph of pyrazinamide. Quantitative analysis indicated individual particles contained the three antibiotics at the expected proportions (400:150:75 w/w). This excipient-free triple antibiotic DPI formulation could be used as a significant enhanced treatment for TB.
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Purpose The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to...
A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study
Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of america and the american thoracic society
A proposal of a pharmacokinetic/pharmacodynamic (PK/PD) index map for selecting an optimal PK/PD index from conventional indices (AUC/MIC, Cmax/MIC, and TAM) for antibiotics
, 陶晓南
