101例恶性梗阻性黄疸行经皮肝脏穿刺胆道引流术后胆道感染及抗感染治疗分析

目的 了解恶性梗阻性黄疸患者行经皮肝脏穿刺胆道引流术（PTCD）术后胆道感染的主要病原菌分布及药物敏感性特点,以及不同抗菌药物对主要病原菌的治疗效果,为临床合理使用抗菌药物提供依据。方法 对东方肝胆外科医院2013年9月至2014年10月收治的423例恶性梗阻性黄疸行PTCD治疗患者的临床资料进行回顾性调查,针对其中101例发生术后胆道感染的病例,分析细菌培养结果及耐药情况,评价抗菌药物治疗效果。结果 101例患者术后发生胆道感染,67例细菌培养结果阳性,共培养出细菌94株,其中G^-菌62株（65.96%）,G⁺菌32株（34.04%）,主要致病菌包括肺炎克雷伯杆菌、大肠杆菌、粪肠球菌和阴沟肠杆菌等。G^-菌中肺炎克雷伯杆菌和大肠杆菌的耐药率较高;G^-菌对亚胺培南、哌拉西林钠/他唑巴坦钠和阿米卡星耐药率较低;G⁺菌对达托霉素、万古霉素和利奈唑胺耐药率较低。我院PTCD术后感染治疗的总体有效率为88.1%,67例细菌培养结果为阳性的患者治疗有效率为97%。结论 我院PTCD术后胆道感染的抗菌治疗基本合理。建议医生积极行标本细菌培养,根据药敏结果选择敏感抗菌药物。针对主要分离菌中的G^-菌,头孢曲松耐药率高,治疗效果欠佳,建议医生减少头孢曲松的使用。对G⁺菌中的耐甲氧西林葡萄球菌（MRS）,可使用糖肽类抗菌药物。     

The effect of aspirin on antibiotic susceptibility

ABSTRACT

Introduction: Aspirin (acetylsalicylic acid, ASA) is often co-administered during the treatment of infections. Salicylic acid (SAL), the active metabolite of ASA, has significant effects on bacteria that might improve or (more likely) compromise the effectiveness of antibiotics.

Areas covered: In this review, we summarize the interactions between SAL and antibiotics, and describe the underlying mechanisms involved.

Expert opinion: In an era of rapidly increasing antibiotic resistance and lack of new antibiotic development, it is important to explore ways to optimize the effectiveness of antimicrobial treatment. This includes a better understanding of the interactions between commonly co-administered drugs. SAL might compromise the effectiveness of antibiotic treatment by inducing phenotypic resistance in bacteria. It can induce phenotypic resistance by up- or downregulating outer membrane proteins or efflux pumps, by upregulating antibiotic targets and by inducing enzymes with degrading activity. Moreover, SAL can increase the frequency of mutations leading to antibiotic resistance.     

To which extent can we decrease antibiotic duration in critically ill patients?

Introduction: Inadequate empirical antibiotic therapy is associated with higher mortality in critically ill patients with severe infections. Nevertheless, prolonged duration of antibiotic treatment is also potentially harmful. Development of new infections with more resistant pathogens is one of the arguments against the administration of prolonged courses of antibiotics.

Areas covered: We aim to describe the optimal duration of antimicrobial therapy in the most common infections affecting critically ill patients. A literature search was performed to identify all clinical trials, observational studies, meta-analysis, and reviews about this topic from PubMed.

Expert commentary: Diverse observational studies have reported a poor outcome in critically ill patients without a documented infection who receive prolonged antibiotic therapy. We summarize the available information about the optimal duration of antimicrobial therapy in critically ill patients with severe infections including community-acquired pneumonia, intra-abdominal infections, bacteremia, meningitis and urinary-tract infections as well as the clinical consequences of short antimicrobial courses in certain severe infections. The utility of procalcitonin to reduce the duration of antibiotics is also discussed. Finally, we give clear recommendations about the length of treatment for the most common infections in critically ill patients.     

Mechanisms of drug resistance in Mycoplasma pneumoniae

Mycoplasma pneumoniae is a pathogenic mycoplasma responsible for respiratory tract infections in humans, occurring worldwide in children and adults. This review briefly focuses on its antibiotic susceptibility profile and on the development of acquired resistance for this microorganism. The lack of a cell wall in mycoplasmas makes them intrinsically resistant to beta-lactams and to all antimicrobials which target the cell wall. Intrinsic resistance related to specific mycoplasma species concerns essentially the acrolide-lincosamide-streptogramin-ketolide (MLSK) antibiotic group. M. pneumoniae is susceptible to all MLSK antibiotics, except to lincomycin. Among the three antibiotic classes used for the treatment of mycoplasmal infections including tetracyclines, MLSK group, and fluoroquinolones, macrolides and related antibiotics are the drug of choice for respiratory infections caused by M. pneumoniae. Both target alterations and efflux mechanisms implicated in acquired antibiotic resistance have been described in mycoplasmas either by genetic mutation or transfer of new genes carried by transposons. At present, M. pneumoniae remains greatly susceptible to antibiotics, but as this mycoplasma is difficult to isolate, the number of clinical strains tested is limited and the occurrence of acquired resistance not well documented. However some strains having acquired resistance to MLSK have been decribed in vivo and erythromycin-resistant isolates are spreading now in Japan. To date, no clinical isolates resistant to fluoroquinolones or tetracyclines have been described in the literature, but some strains having acquired resistance to both classes have been selected in vitro. Molecular diagnosis of this acquired resistance has been related to target alterations, in ribosome for macrolides and tetracyclines, or in topoisomerase II genes for fluoroquinolones.     

我院2005～2008年院内感染病原微生物耐药情况分析

目的:了解我院院内感染的现状及病原微生物的耐药情况,为临床合理选择抗生素提供参考。方法:对2005～2008年我院院内各类标本病原微生物感染情况进行统计,并对院内感染病原微生物的药敏试验结果进行分析。结果:院内感染致病菌中革兰阴性菌与革兰阳性菌的比例约为2:1,且药敏试验结果显示院内感染均出现不同程度的耐药。结论:病原微生物耐药性的监测对院内感染治疗中抗生素的合理选择有着重要作用。     

Pseudomonas aeruginosa : résistance et options thérapeutiques à l’aube du deuxième millénaire

ObjectivesTo present to the clinician an overview of the pathologies caused by P. aeruginosa (clinical manifestations, antibiotic resistance, diagnostic, present and future therapeutic options) based on an analysis of the recent literature and on the opinions of specialists.Main PointsPseudomonas aeruginosa can cause a variety of nosocomial infections and can invade almost all anatomical sites (with a preference for the respiratory tract, especially in cystic fibrosis patients). Resistance is frequent and can be native (constitutive expression of β-lactamases and/or efflux pumps; low permeability of the outer membrane), but also acquired (genes coding for antibiotic-degrading enzymes, overexpression of efflux pumps, decreased permeability of porins, target mutations). These mechanisms often confer upon the organism a multiresistance phenotype, making susceptibility testing essential. The initial empiric treatment will most often be a combined therapy, based on local epidemiology (typically a β-lactam plus an aminoglycoside or a fluoroquinolone). This treatment will need to be readjusted as soon as possible based on susceptibility determinations, optimized use of the antibiotics selected, and clinical outcome. Colistin is useful when dealing with multiresistant isolates. Therapeutic innovations remain scarce.ConclusionsInfections caused by P. aeruginosa are potentially frightening. Treatment requires a correct diagnostic and rests upon a rational selection of antibiotics, the sue for which must be optimized on pharmacodynamic basis.     

Current research in empirical therapy for febrile neutropenia in cancer patients: what should be necessary and what is going on

Introduction: Fever is an important complication in neutropenic patients and standard of care calls for empirical broad-spectrum antibiotics, followed by ‘empirical' antifungal therapy in persisting fever. Emergence of infections due to resistant bacteria, especially Gram-negatives, and usefulness of empirical antifungal therapy represent the major concerns in this field.

Areas covered: Clinical trials registered in 5 international databases were referred for randomized clinical trials (RCTs) of empirical antibacterial therapy or empirical antifungal therapy in neutropenic cancer patients. The majority of RCTs compared antibiotics without major differences in the spectrum of activity, especially in the wake of the present epidemiology with an increase of infections and mortality due to resistant Gram-negatives; oral therapy and home care were analyzed in 3 RCTs. As regards empirical antifungal therapy, 1 ongoing study is comparing ‘standard' empirical treatment vs diagnostic-driven approach.

Expert opinion: In an era of increasing antibiotic resistance the comparison of different strategies more than that of different drugs will probably represent the future in studies in this field. The next future will tell us if a diagnostic-driven approach is safe for fungal infections, or if we should continue to treat them only on the basis of the persistence of febrile neutropenia.     

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (beta-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.     

Therapies on the horizon for Clostridium difficile infections

Introduction: Clostridium difficile infections are a leading cause of healthcare facility outbreaks of gastrointestinal illness that may have serious complications and a high rate of recurrent disease. Despite the availability of standard antibiotic treatments, data from national surveillance programs indicate that the incidence of this disease continues to increase, placing a heavy burden on healthcare systems. New emerging strategies are being tested to replace or augment these standard antibiotics.

Areas covered: Thirty-two current investigational agents focusing on different strategies for both prevention and treatment of C. difficile infections are reviewed. Data was gathered from a literature search of public databases for published trials from 1999-November 13, 2015 and from the author’s compendium of knowledge. Agents reviewed included 13 antibiotics, two antibiotic inactivators, seven bacteria or yeasts acting to enhance the normal microbiome, seven immunizing agents and three toxin binders. Of the 32 investigational treatments reviewed, 8 (25%) showed significant efficacy in phase II or III clinical trials and are actively being developed as new therapies for C. difficile infections.

Expert opinion: A number of potential treatments have floundered during their development process, while others have shown promising results. The strongest efficacy has been in the areas of newer antibiotics, probiotics, monoclonal antibodies and vaccines. By targeting the pathogenic pathway of C. difficile infections, multiple strategies for prevention and treatment have been developed.     

尿路感染者病原体检测及耐药性分析

目的探讨尿路感染的病原茼分布及耐药情况，指导临床合理用药。方法对医院2006年1月～2007年12月间住院及门诊尿路感染患者尿培养分离出的391株病原菌进行鉴定和药物敏感性分析。结果391株尿路感染的菌株中以革兰阴性菌为主，其中以大肠埃希菌最常见，其次为肺炎克雷伯菌、铜绿假单胞菌；革兰阳性菌中以肠球菌属为主；真菌感染的数量明显增加；细菌对各种抗菌药物有不同程度的耐药率，表现为多重耐药。结论尿路感染常见病原菌耐药严重，临床应根据药物敏感性试验结果有针对性地筛选敏感药物进行治疗。     

Novel prevention strategies for bacterial infections in cirrhosis

Introduction: Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is mostly based on the use of orally administered poorly absorbed antibiotics such as norfloxacin (selective intestinal decontamination). However, antibiotic prophylaxis leads to antibiotic resistance, limiting therapy and increasing morbidity and mortality. Prevention of bacterial infections in cirrhosis should therefore move away from antibiotics.

Areas Covered: This review focuses on various potentially novel methods to prevent infections in cirrhosis focusing on non-antibiotic strategies. The use of probiotics, nonselective intestinal decontamination with rifaximin, prokinetics and beta-blockers or fecal microbiota transplant as means of targeting altered gut microbiota, bile acids and FXR agonists are all potential alternatives to selective intestinal decontamination. Prokinetics and beta-blockers can improve intestinal motility, while bile acids and FXR agonists help by improving the intestinal barrier. Finally, granulocyte colony stimulating factor (G-CSF) and statins are emerging therapeutic strategies that may improve immune dysfunction in cirrhosis.

Expert Opinion: Evidence for these strategies has been restricted to animal studies and proof-of concept studies but we expect this to change in coming years.     

鲍曼不动杆菌生物膜与耐药性的研究进展

鲍曼不动杆菌为革兰阴性杆菌,是导致医院感染的常见条件致病菌之一。由于其易产生耐药性及植入性医疗操作的增加,鲍曼不动杆菌生物膜导致的院内感染成为临床医师的极大挑战。因此,了解鲍曼不动杆菌的耐药机制具有重要的意义,分析其生物膜对耐药性的影响及其机制有助于开发新的联合治疗方案。此文从细菌生物膜的角度归纳鲍曼不动杆菌的耐药机制研究进展,讨论鲍曼不动杆菌生物膜的形成过程、调节因素以及对耐药性的影响,概述了亚致死剂量抗生素对鲍曼不动杆菌耐药形成的影响,为针对鲍曼不动杆菌生物膜所致感染制定适宜的治疗方案和防控耐药菌株传播提供参考。     

Programmed cell death in human pathogenic fungi – a possible therapeutic target

ABSTRACT

Introduction: Diseases caused by pathogenic fungi are increasing because of antibiotic overuse, the rise of immunosuppressive therapies, and climate change. The limited variety of antimycotics and the rapid adaptation of pathogenic fungi to antifungal agents serve to exacerbate this issue. Unfortunately, about 1.6 million people are killed by fungal infections annually.

Areas covered: The discovery of the small antimicrobial proteins produced by microorganisms, animals, humans, and plants will hopefully overcome challenges in the treatment of fungal infections. These small proteins are highly stable and any resistance to them rarely evolves; therefore, they are potentially good candidates for the treatment and prevention of infections caused by pathogenic fungi. Some of these proteins target the programmed cell death machinery of pathogenic fungi; this is potentially a novel approach in antimycotic therapies. In this review, we highlight the elements of apoptosis in human pathogenic fungi and related model organisms and discuss the possible therapeutic potential of the apoptosis-inducing, small, antifungal proteins.

Expert opinion: Small antimicrobial proteins may establish a new class of antimycotics in the future. The rarity of resistance and their synergistic effects with other frequently used antifungal agents may help pave the way for their use in the clinic.     

Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply “precision medicine” to antimicrobial chemotherapy?

Introduction: For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae.

Areas covered: We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered ‘old’ antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the contemporary clinical experience treating CRE infections with antibiotic combination therapy. Finally, we discuss ceftazidime/avibactam and imipenem/relebactam, containig a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration.

Expert opinion: Defining the molecular mechanisms of resistance and applying insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches should be the new paradigm in treating infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta-lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic.     

Multidrug resistance in Helicobacter pylori: current state and future directions

ABSTRACT

Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported.

Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined.

Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23–36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.     

Current strategies for the treatment of complicated intraabdominal infections

Introduction: Complicated intraabdominal infections (cIAIs) are a common cause of infection-related morbidity and mortality in hospitalized patients and present many challenges unique from other serious infections. cIAIs are generally polymicrobial in nature; however, controversy exists around the pathogenicity of some of the frequently identified microorganisms. Increasing antibiotic resistance among commonly isolated bacteria poses further challenges for clinicians managing patients with cIAIs.

Areas covered: This article highlights the microbiology and recent trends in antibiotic resistance most relevant to cIAIs, provides recommendations for treatment using currently available antimicrobials and introduces antibiotics in development with potential roles in managing cIAIs.

Expert opinion: Successful treatment of cIAI requires a combination of timely source control and thorough assessment of patient characteristics to guide selection of an appropriate empiric antimicrobial regimen. Specific considerations that should be made when choosing antibiotics include the origin of infection, presence of risk factors for potentially resistant pathogens and severity of disease. While it is encouraging that agents in development may prove helpful in the treatment of cIAIs with resistant pathogens, further identification of novel antibiotics is needed to address this growing concern. In addition, adherence to the principles of antimicrobial stewardship is needed if current antimicrobial resources are to be preserved for the treatment of cIAIs.     

口腔感染及其并发症的药物防治策略

口腔感染最常见为草绿色链球菌、厌氧菌单独或混合感染,心瓣膜疾病、免疫损害及人工关节置入患者接受口腔手术后,若发生感染,则危害更大。该文回顾性分析了近年来有关口腔感染的药物敏感性研究,牙源性感染、非牙源性感染、口腔术后局灶性感染等的临床防治进展,以及肝、肾功能损害患者和孕妇等特殊患者的用药情况。