Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucro...Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.展开更多
The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The thera...The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.展开更多
Our previous study suggested that the production of superantigens and heat-shock protein 60 by small intestinal bacteria might play a role in Kawasaki disease (KD). We demonstrated that they were all resistant to comm...Our previous study suggested that the production of superantigens and heat-shock protein 60 by small intestinal bacteria might play a role in Kawasaki disease (KD). We demonstrated that they were all resistant to commonly used antibiotics, except for sulamethoxazole trimethoprim (SMX-TMP). We used SMX-TMP for 7 cases of KD that were unresponsive to intravenous immunoglobulin (IVIG) and studied the antipyretic potency of this treatment. In 6 out of the 7 cases, we demonstrated that antipyretic potency was observed without side effects within 2 days of the initial administration. Antimicrobial therapy using SMX-TMP might represent a novel strategy for cases of KD that are unresponsive to IVIG.展开更多
This paper explores one of the underappreciated reasons for lack of efficacy in certain cases of antimicrobial therapy, namely the occurrence of a non-genetic resistance to antimicrobial drugs due to a metabolic quies...This paper explores one of the underappreciated reasons for lack of efficacy in certain cases of antimicrobial therapy, namely the occurrence of a non-genetic resistance to antimicrobial drugs due to a metabolic quiescence of microorganisms. T</span><span style="font-family:Verdana;">his review has centered on those microorganisms of particular importance in obstetrics and gynecology and accordingly has reviewed the nature and extent of the persister phenotype in relation to infectious agents affecting women’s health. We show how the quiescent persister microbial phenotype represents the next significant issue that could compromise successful antibiotic therapy. A brief history of antimicrobial therapy is provided as context for the problem posed by the persister phenotype. This review has been focused on the current literature having relevance for physicians concerned with women’s health. The study of this phenotype has led to increasing understanding of the molecular mechanisms for this state which also provides ideas for rational development of drug candidates to interdict these organisms in human disease and explores the possibility of developing specifically targeted molecules to address persisters, research on screening botanicals, existing drugs and chemicals to discover novel approaches to the clinical consequence of microbial persisters. Of interest in this review, is the return to naturally occurring botanical substances, first to be used as anti</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">infectives, now being considered as possible agents to address persister microorganisms. Overall this paper aims to provide information tailored especially to the obstetrics and gynecology specialists.展开更多
Helicobacter pylori(H. pylori) antimicrobial resistance is an urgent, global issue. In2017, the World Health Organization designated clarithromycin-resistant H.pylori as a high priority bacterium for antibiotic resear...Helicobacter pylori(H. pylori) antimicrobial resistance is an urgent, global issue. In2017, the World Health Organization designated clarithromycin-resistant H.pylori as a high priority bacterium for antibiotic research and development. In addition to clarithromycin, resistance to metronidazole and fluoroquinolones has also increased worldwide. Recent international guidelines for management of H.pylori infection recommend bismuth or non-bismuth quadruple therapy for 14 d as a first-line treatment for H. pylori in areas of high clarithromycin and/or metronidazole resistance. Although these treatment regimens provide acceptable H. pylori eradication rates, the regimens used should not contribute to future resistance of H. pylori to antimicrobials. Moreover, these regimens can promote resistance, due to prolonged therapy with multiple antibiotics. A new strategy that can eradicate H. pylori as well as reduce the antibiotics used is required to prevent future antimicrobial resistance in H. pylori. Dual-therapy with vonoprazan and amoxicillin could be a breakthrough for H. pylori eradication in an era of growing antimicrobial resistance. This regimen may provide a satisfactory eradication rate of H. pylori and also minimize antimicrobial resistance due to single antibiotic use and the strong inhibitory effect of vonoprazan on gastric acid secretion.展开更多
Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative stra...Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G^(+)) and Gram-negative (G^(–)) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G^(–) bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.展开更多
The management of Helicobacter pylori(H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issu...The management of Helicobacter pylori(H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available cultureor molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.展开更多
To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance.METHODSA total of 1034 patients infected by Helic...To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance.METHODSA total of 1034 patients infected by Helicobacter pylori (H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire.RESULTSIntention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate.CONCLUSIONAntimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.展开更多
The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on t...The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on time to optimization of antimicrobial therapy in hospitalized patients with gram-negative bacteremia. Time to antibiotic optimization was compared in patients with gram-negative bacilli isolated from blood cultures obtained from March-May 2011 （pre-RAIDS） versus March-May 2013 （post-RAIDS）. The results show that patients in the pre-RAIDS study group had a significantly longer time to antibiotic optimization when compared to the post-RAIDS group （median （IQR）, 27.6 （10.8-75.8） h vs. 3.1 （0.8-34.3） h, p = 0.03）. The RAIDS protocol resulted in quicker time to antibiotic de-escalation （pre- vs. post-RAIDS; median （IQR）, 27.6 （10.8-134.5） h vs. 4.3 （1.4-32.6） h, p = 0.03）. There were no differences in clinical outcomes such as clinical cure, microbiological cure, and 30-day mortality between pre-RAIDS and post-RAIDS study groups. Patients in the post-RAIDS arm were more likely to receive appropriate empiric and definitive treatment. Implementation of the RAIDS protocol, which was an ASP （antimicrobial stewardship program） initiative, resulted in quicker time to antibiotic de-escalation and overall treatment optimization. RAIDS reduced the unnecessary use of broad-spectrum antimicrobial in this study population.展开更多
目的比较抗菌光动力疗法(aPDT)与全身抗菌药物辅助治疗牙周炎的疗效。方法搜索Embase、PubMed、Web of Science、Cochrane Library、中国知网、万方数据库、维普数据库共7个数据库,搜索时间从建库至2023年11月止,被搜索文献的语言类型...目的比较抗菌光动力疗法(aPDT)与全身抗菌药物辅助治疗牙周炎的疗效。方法搜索Embase、PubMed、Web of Science、Cochrane Library、中国知网、万方数据库、维普数据库共7个数据库,搜索时间从建库至2023年11月止,被搜索文献的语言类型为中文或英文。根据纳入排除标准筛选文献。用Cochrane工具进行文献质量评价。用RevMan 5.4软件和Stata 14.0软件对被纳入的文献进行Meta分析和发表偏倚检测。结果共有8篇文献被纳入。Meta分析结果表明,治疗后3个月时,当光敏剂(PS)为亚甲基蓝(MB)时,龈下刮治和根面平整术(SRP)+aPDT对探诊深度(PD)的改善效果优于SRP+全身抗菌药物;治疗后3个月时,当PS为吩噻嗪氯时,SRP+全身抗菌药物对PD的改善效果优于SRP+aPDT(P<0.05)。治疗后3个月,SRP+aPDT/SRP+全身抗菌药物对临床附着水平(CAL)、探诊出血(BOP)的改善效果均无明显区别(P>0.05);治疗后6个月,SRP+aPDT/SRP+全身抗菌药物对PD、CAL、BOP的改善效果均无明显区别(P>0.05)。与基线期相比,治疗后3个月时,SRP+aPDT使PD、CAL、BOP分别改善了(0.80±0.19)mm、(0.94±0.29)mm、19.74%±1.91%(P<0.05);而SRP+全身抗菌药物使PD、CAL、BOP分别改善了(1.02±0.27)mm、(0.95±0.25)mm、19.39%±11.83%(P<0.05)。治疗后6个月,SRP+aPDT使PD、CAL、BOP分别改善了(1.37±0.47)mm、(1.29±0.52)mm、28.97%±2.43%(P<0.05);而SRP+全身抗菌药物使PD、CAL、BOP分别改善了(1.55±0.53)mm、(1.34±0.49)mm、29.34%±10.47%(P<0.05)。结论SRP+MB-aPDT对PD的改善效果优于SRP+全身抗菌药物;SRP+全身抗菌药物对PD的改善效果优于SRP+吩噻嗪氯-aPDT,MB-aPDT或许能成为全身抗菌药物辅助治疗牙周炎的替代方法。牙周炎类型、2型糖尿病、吸烟、aPDT次数、全身抗菌药物的种类及其治疗时间等因素对于SRP+aPDT/SRP+全身抗菌药物的治疗效果影响相当。展开更多
文摘Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.
文摘The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.
文摘Our previous study suggested that the production of superantigens and heat-shock protein 60 by small intestinal bacteria might play a role in Kawasaki disease (KD). We demonstrated that they were all resistant to commonly used antibiotics, except for sulamethoxazole trimethoprim (SMX-TMP). We used SMX-TMP for 7 cases of KD that were unresponsive to intravenous immunoglobulin (IVIG) and studied the antipyretic potency of this treatment. In 6 out of the 7 cases, we demonstrated that antipyretic potency was observed without side effects within 2 days of the initial administration. Antimicrobial therapy using SMX-TMP might represent a novel strategy for cases of KD that are unresponsive to IVIG.
文摘This paper explores one of the underappreciated reasons for lack of efficacy in certain cases of antimicrobial therapy, namely the occurrence of a non-genetic resistance to antimicrobial drugs due to a metabolic quiescence of microorganisms. T</span><span style="font-family:Verdana;">his review has centered on those microorganisms of particular importance in obstetrics and gynecology and accordingly has reviewed the nature and extent of the persister phenotype in relation to infectious agents affecting women’s health. We show how the quiescent persister microbial phenotype represents the next significant issue that could compromise successful antibiotic therapy. A brief history of antimicrobial therapy is provided as context for the problem posed by the persister phenotype. This review has been focused on the current literature having relevance for physicians concerned with women’s health. The study of this phenotype has led to increasing understanding of the molecular mechanisms for this state which also provides ideas for rational development of drug candidates to interdict these organisms in human disease and explores the possibility of developing specifically targeted molecules to address persisters, research on screening botanicals, existing drugs and chemicals to discover novel approaches to the clinical consequence of microbial persisters. Of interest in this review, is the return to naturally occurring botanical substances, first to be used as anti</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">infectives, now being considered as possible agents to address persister microorganisms. Overall this paper aims to provide information tailored especially to the obstetrics and gynecology specialists.
文摘Helicobacter pylori(H. pylori) antimicrobial resistance is an urgent, global issue. In2017, the World Health Organization designated clarithromycin-resistant H.pylori as a high priority bacterium for antibiotic research and development. In addition to clarithromycin, resistance to metronidazole and fluoroquinolones has also increased worldwide. Recent international guidelines for management of H.pylori infection recommend bismuth or non-bismuth quadruple therapy for 14 d as a first-line treatment for H. pylori in areas of high clarithromycin and/or metronidazole resistance. Although these treatment regimens provide acceptable H. pylori eradication rates, the regimens used should not contribute to future resistance of H. pylori to antimicrobials. Moreover, these regimens can promote resistance, due to prolonged therapy with multiple antibiotics. A new strategy that can eradicate H. pylori as well as reduce the antibiotics used is required to prevent future antimicrobial resistance in H. pylori. Dual-therapy with vonoprazan and amoxicillin could be a breakthrough for H. pylori eradication in an era of growing antimicrobial resistance. This regimen may provide a satisfactory eradication rate of H. pylori and also minimize antimicrobial resistance due to single antibiotic use and the strong inhibitory effect of vonoprazan on gastric acid secretion.
基金The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China(grant Nos.82272067,81971678,22107123,and M-0696)Natural Science Foundation of Hunan Province(grant Nos.2022JJ80052,2022JJ40656,20231120077,China)+1 种基金Scientific Research Fund of Hunan Provincial Education Department(22B0009,China)the Central South University Innovation-Driven Research Program(2023CXQD004,China).
文摘Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G^(+)) and Gram-negative (G^(–)) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G^(–) bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.
文摘The management of Helicobacter pylori(H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available cultureor molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.
文摘To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance.METHODSA total of 1034 patients infected by Helicobacter pylori (H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire.RESULTSIntention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate.CONCLUSIONAntimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.
文摘The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on time to optimization of antimicrobial therapy in hospitalized patients with gram-negative bacteremia. Time to antibiotic optimization was compared in patients with gram-negative bacilli isolated from blood cultures obtained from March-May 2011 （pre-RAIDS） versus March-May 2013 （post-RAIDS）. The results show that patients in the pre-RAIDS study group had a significantly longer time to antibiotic optimization when compared to the post-RAIDS group （median （IQR）, 27.6 （10.8-75.8） h vs. 3.1 （0.8-34.3） h, p = 0.03）. The RAIDS protocol resulted in quicker time to antibiotic de-escalation （pre- vs. post-RAIDS; median （IQR）, 27.6 （10.8-134.5） h vs. 4.3 （1.4-32.6） h, p = 0.03）. There were no differences in clinical outcomes such as clinical cure, microbiological cure, and 30-day mortality between pre-RAIDS and post-RAIDS study groups. Patients in the post-RAIDS arm were more likely to receive appropriate empiric and definitive treatment. Implementation of the RAIDS protocol, which was an ASP （antimicrobial stewardship program） initiative, resulted in quicker time to antibiotic de-escalation and overall treatment optimization. RAIDS reduced the unnecessary use of broad-spectrum antimicrobial in this study population.
