Single versus combined antibiotic therapy for gram-negative infections

OBJECTIVE: To evaluate the available clinical data regarding single versus combination antimicrobial therapy for treatment of gram-negative infections, focusing on the more recent data in predominantly nonneutropenic hosts. In vitro and in vivo data regarding various antimicrobial combinations are also discussed. DATA SOURCES: Clinical trials, review articles, and meta-analyses were identified from a MEDLINE search (1960-July 2003). Special attention was given to clinical outcome trials performed since 1989. Search terms included gram-negative infections, drug synergism, Pseudomonas aeruginosa, monotherapy, combination therapy, carbapenems, beta-lactams, cefepime, aminoglycosides, and fluoroquinolones. DATA SYNTHESIS: Although most of the studies were not randomized, double-blind, or controlled, the most recent literature indicates that monotherapy with agents that are active against isolated organisms, including P. aeruginosa, may be appropriate for most patients. Efficacy outcomes, including mortality, did not significantly differ in most studies comparing single and combination therapies. Some trials suggest that combination therapy may be preferred in neutropenic patients and those with pseudomonal infections. CONCLUSIONS: Hospitalized patients with gram-negative infections are often treated with combination antimicrobial agents; however, some of the recently available data, although limited, suggest that administration of monotherapy is a feasible alternative in certain patient populations.     

Practical considerations in the use of outpatient antimicrobial therapy for musculoskeletal infections

Successful treatment of many musculoskeletal infections often requires an extended course of outpatient antimicrobial therapy, much of which is administered parenterally outside the hospital under the guidance of an infectious disease specialist. Delivery of outpatient parenteral antimicrobial therapy (OPAT) may occur in physicians' offices, ambulatory infusion centers, or hospital clinics but most frequently is done in patients' homes, often by the patients themselves. In this article, we outline the essential elements of outpatient antimicrobial therapy for musculoskeletal infections with particular emphasis on OPAT, including patient selection and evaluation; antimicrobial administration, including the route, duration, and complications of central venous access; and clinical and laboratory monitoring of antimicrobial therapy. We believe that primary care physicians, orthopedists, and infectious disease specialists caring for patients with musculoskeletal infections should become familiar with the use of, indications for, and complications of OPAT.     

In vitro activities of antimicrobial agents against clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer.

We evaluated the in vitro activities of 21 different antimicrobial agents against nine clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer. The organisms were susceptible to most agents commonly used for the empiric therapy (aminoglycosides, ureidopenicillins, extended-spectrum cephalosporins, monobactams, and carbapenems) and prevention of infections (quinolones and trimethoprim-sulfamethoxazole) in this patient population.     

General principles of antimicrobial therapy.

Treatment with antimicrobial agents must be tailored to the individual patient, the site of infection, and the etiologic organism involved. Effectiveness, toxicity, and cost are the basic considerations in choosing a drug. Because initiation of therapy often cannot be delayed until microbiologic studies have been performed, empiric treatment should be sufficiently broad to cover the most likely pathogens, based on the site of infection and the type of host. Definitive therapy may differ from initial therapy and should be instituted as soon as specific laboratory and clinical data are available. Information about allergic reactions to drugs should be elicited; because of the numerous families of antimicrobial agents currently available, most infections in patients with drug allergies can be treated with adequate substitutes. Cautious conservatism is advocated in the use of new antimicrobial agents. The effects of new agents on the microbial ecology and the hospital environment should be considered.     

非结核分枝杆菌鉴定方法和病原谱分析

目的分析非结核分枝杆菌（NTM）鉴定方法和病原谱分布情况,为临床NTM的鉴定和病原谱分布提供依据和参考。 方法连续纳入2020年度安徽省胸科医院培养阳性的分枝杆菌培养物进行病原谱分析,采用MPB64抗原和PNB鉴别培养基对培养阳性菌株进行初步鉴定,熔解曲线法进行NTM分子生物学鉴定,并采用微孔板法进行药敏分析。 结果2 563株分枝杆菌培养阳性菌株,最终有207株鉴定为NTM,NTM的分离率为8.08%其中,117例为男性感染者,62.80%的感染者年龄超过60岁。排名前3位的菌种依次为胞内分枝杆菌（76.67%）、堪萨斯分枝杆菌（6.19%）、脓肿分枝杆菌（5.71%）。不同NTM对利奈唑胺、克拉霉素、莫西沙星和阿米卡星的敏感性较高,对多西环素、米诺环素、亚胺培南、磺胺甲唑的耐药率较高。 结论安徽省胸科医院NTM感染以男性和60岁以上感染者居多,胞内分枝杆菌为主要菌种,不同菌种的耐药率有所差异,应提升实验室检测NTM和耐药性的水平,为临床精准诊治NTM提供依据。     

黏液型铜绿假单胞菌感染实验鉴定和病例回顾分析

目的 探讨黏液型铜绿假单胞菌的临床分布特点及对常用抗菌药物敏感度。方法 对医院2013年分离的53株非重复性黏液型铜绿假单胞菌感染病例进行回顾性分析,通过查阅病历获得患者一般资料、疾病情况、抗生素使用等信息,并对菌株进行药敏分析。结果 所有菌株均分离自痰标本,患者以老年人为主,平均年龄66.7±9.1岁。50例患者有呼吸道感染的慢性病史; 所有患者住院期间均使用了2种或2种以上抗菌药物,联合使用过大环内酯类的仅11例。53株菌对临床常用的抗菌药物均表现了较高的体外敏感性,除替卡西林/克拉维酸(64.2%)、头孢吡肟(60.4%)以外,其它药物敏感率均高于70%。结论 黏液型铜绿假单胞菌的易感人群为老年有呼吸道感染慢性病史的患者,体外培养对抗菌药物敏感性较高,临床上多采用联合抗菌药物治疗,大环内酯类药物使用率较低。     

Evaluation and management of patients with pulmonary nontuberculous mycobacterial infections

Nontuberculous mycobacteria (NTM) are emerging pathogens increasingly associated with chronic pulmonary disease. NTM are environmental saprophytes found in soil, dust and water and, unlike Mycobacterium tuberculosis, NTM are not transmitted from person to person. Pulmonary disease caused by NTM is a particular problem in older people without underlying immune compromise. The diagnosis of NTM pulmonary disease usually requires either multiple respiratory cultures that grow NTM or heavy growth of NTM from a single bronchoscopy or lung-biopsy specimen. High resolution computed tomography is the most useful radiographic study for diagnosis and to determine the extent of disease. Treatment includes multiple medications with activity against the particular NTM species, as single-drug therapy is likely to select for resistant organisms. Data demonstrating the effectiveness of specific drug regimens for NTM pulmonary disease are limited. Clarithromycin and azithromycin form the backbone of most treatment regimens because these drugs are active against many NTM species. Drug tolerability and cost are the major barriers to successful treatment of NTM pulmonary disease. Adjunctive therapies, including mucus clearance techniques and appetite stimulants, are unproven but may be of value in management of NTM pulmonary disease. Multicenter, randomized trials of macrolide-based therapies are sorely needed to determine the safest and most effective treatments for NTM pulmonary disease.     

Complications and risks in hematopoietic stem cell transplant patients.

Hematopoietic stem cell transplantation is a recognized treatment for hematological diseases such as leukemia and lymphoma, certain solid organ tumors, and a limited number of immunologic disorders. The major risks associated with this procedure are infections and development of graft-vs-host disease. Bacterial or viral agents are the most common cause of infections, but fungal and protozoan organisms may also be isolated. Bacterial infections occur most frequently in the first 30 days after transplant, whereas the onset of viral infections usually occurs later during the first three months posttransplant. Studies have demonstrated that there are a variety of predisposing factors that influence the type of infection a patient develops. These include underlying disease, type of chemotherapy regimen, type of antimicrobial and antiviral regimen, presence of graft-vs-host disease, and period of severe neutropenia posttransplant. Of these, the period of neutropenia appears to be the most significant. Graft-vs-host disease is seen in those patients who have received allogeneic hematopoietic stem cell transplants. New antimicrobial and antiviral agents and manipulation of the hematopoietic stem cell transplant to select specific cell types for infusion have provided some methods to prevent or decrease the number and severity of infections or to prevent/control graft-vs-host disease.     

The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.     

General principles of antimicrobial therapy

Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.     

Antibiotic therapy for severe infections in infants and children.

In infants and children, the absorption, distribution, metabolism, and excretion of drugs may differ considerably in comparison with these factors in adults; consequently, differences exist in therapeutic efficacy and toxicity of various antibiotic agents. Because of known toxicity, certain drugs--such as chloramphenicol in high doses, the sulfonamides, and tetracycline--should not be used in neonates. Antibiotic therapy should be modified in neonates because of biologic immaturity of organs important for the termination of drug action. Because of poor conjugation, inactivation, or excretion, the serum concentrations of many antibiotics may be higher and more prolonged in neonates than in older infants; thus, lower doses and longer intervals between administration may be necessary. In this article, we suggest dosages of antimicrobial agents for severe infections in children, older infants, and neonates. Included in the discussion are the cephalosporins, especially the third-generation cephalosporins that have assumed an important role in empiric treatment of bacterial meningitis in pediatric patients because of their ability to penetrate the central nervous system and their effectiveness against beta-lactamase-positive and negative strains of Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis, and many gram-negative bacteria in the Enterobacteriaceae group. In patients with congenital or acquired immunodeficiencies, antifungal, antiviral, or anti-Pneumocystis agents are often added to the antimicrobial regimen for severe infections. We review the agents available for such treatment in children, the drugs used for childhood tuberculosis, and certain new antibiotics (aztreonam, ticarcillin-clavulanate, ciprofloxacin, and imipenem-cilastatin) that have proved useful in select cases but whose precise role in pediatric practice will necessitate additional clinical experience.     

2018年度某三甲综合医院常见多重耐药菌的科室分布特点及耐药性分析

目的分析陆军军医大学第二附属医院2018年度多重耐药菌(MDRO)的临床分布及其对常用抗菌药物的耐药性,为医院感染的防控及临床合理利用抗菌药物提供依据。方法采用回顾性分析方法,抽取该院2018年1-12月的5368例住院患者送检标本中多重耐药菌检测情况和细菌药敏试验数据,统计分析多重耐药菌的临床分布特点及其耐药情况。结果2018年度本院共检出多重耐药菌848株,检出菌株量排前5位的分别是鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、大肠埃希菌;多重耐药菌在痰液标本中的检出率为最高,其次为血液标本、伤口标本和尿标本;检测出的耐甲氧西林金黄色葡萄球菌(MRSA)对糖肽类、硝基呋喃类、恶唑酮类抗菌药物极其敏感,对于氨基糖苷类和喹诺酮类抗菌药物的敏感率≥75%,而对于青霉素类、大环内酯类和林可霉素类抗菌药物的耐药率极高;耐碳青霉烯类大肠埃希菌对碳青霉烯类抗菌药物耐药率极低,而对青霉素类、头孢菌素类、氨基糖苷类、氟喹诺酮类抗菌药物均显示出较高的耐药率耐碳青酶烯类铜绿假单胞菌(CR-PAE)对多黏菌素B极为敏感,对氨基糖苷类的阿米卡星与喹诺酮类的环丙沙星耐药率相对较低,对β-内酰胺酶类、头孢菌素类、碳青霉烯类等抗菌药物的耐药率较高,而对于β-内酰胺类与酶抑制剂复合物的耐药率较低。结论医院多重耐药菌感染日益严重,应该加强对多重耐药菌株的监控,根据送检药敏结果合理选用抗菌药物治疗,加强医护人员多重耐药菌预防控制知识和手卫生培训,严格落实消毒隔离措施,从而有效预防和控制多重耐药菌的感染和暴发。     

Usefulness and problems of the urinary tract infection criteria for evaluating drug efficacy for complicated urinary tract infections

We aimed to reveal the usefulness of and problematic points with the Criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (draft fourth edition) proposed by the UTI Subcommittee of the Clinical Evaluation Guidelines Committee, Japan Society of Chemotherapy, for evaluating antimicrobial agents for complicated urinary tract infections. We conducted a multicenter trial involving 159 patients with complicated urinary tract infections without indwelling urinary catheters. The antimicrobial agents used were cefcapene pivoxil and levofloxacin. "Early evaluation" took place the day after completion of 7 days of therapy; "late evaluation" took place 5-9 days after the end of treatment, and "follow-up evaluation" was done 4-6 weeks after treatment. In the early evaluation, overall clinical efficacy was judged as excellent in 52.9% of the patients, moderate in 26.1%, and poor in 21.0%, and the bacteriological response was judged as "eradicated" for 86.4% of the 198 bacterial strains isolated. Of 96 patients included in the "late evaluation" category in accordance with the draft fourth edition, the clinical outcome was judged as "cured" in 68.4% and the microbiological outcome was judged as "eradicated" in 59.4%. These rates may be low, because 25 patients in whom clinical efficacy was evaluated as "poor" at the end of treatment were separately classified as "failed" at the late evaluation. Of the 49 patients with an excellent clinical response at the end of treatment, symptoms were exacerbated in 18 at the follow-up evaluation. Overall, the draft fourth edition, with some modifications of the third edition criteria, such as the addition of a follow-up evaluation 7 days after the cessation of drug administration, has the potential to play a role in the international standards for evaluating antimicrobial drug efficacy for complicated urinary tract infections.     

非发酵菌致危重患者获得性肺部感染118例分析

目的　探讨我院ICU内危重患者非发酵菌致肺部感染的临床特征和对常用抗生素的敏感性。方法　对 118例ICU内危重患者非发酵菌所致的肺部感染的临床资料和细菌学药敏试验做回顾性分析。结果　 118例患者细菌培养提示主要非发酵菌为铜绿假单胞菌 70株 ,鲍曼氏不动杆菌 5 6株 ,脑膜脓毒金黄杆菌 5 2株 ,嗜麦芽假单胞菌 4 6株 ,88%为混合感染 ,细菌耐药性高 ,头孢哌酮 /舒巴坦、哌拉西林 /他唑巴坦为相对敏感抗生素。结论　非发酵菌致肺部感染多发生于有各种基础病、免疫低下、长期使用抗生素的老龄患者 ,细菌耐药性高 ,治疗应选用加酶抑制剂抗菌药物     

Antibiotics--past, present, and future

The drug therapy for diseases other than those caused by microbial agents involves treating the host. In infectious diseases therapy, the goal is to rid the host of the pathogen. Hence, drug therapy is aimed at the pathogen. Because a second living agent is involved in the triangle, drug therapy is affected by the pathogen's nature, its tissue specificity, and, most importantly, the changes it undergoes to survive. The history of antimicrobial therapy has clearly demonstrated that the drugs that are used to treat infections are also responsible for making them more difficult to treat in future. The only way to keep antimicrobial agents useful is to use them appropriately and judiciously.     

Immunotherapy for primary immunodeficiency diseases

The 2 most commonly encountered primary immunodeficiency syndromes in adult practice are antibody deficiency disorders and hereditary angioedema.Immunologic therapy for these disorders has significantly improved patient management. Therapy with immunoglobulin leads to improvement in overall quality of life. With increasing survival rates and decreasing levels of life-threatening infections in patients with primary antibody deficiencies, disease complications are more commonly encountered. Treatment of these complications with monoclonal antibody therapy seems promising and is likely to increase in the future. More recently,several additional agents have become available, including novel drugs targeted at different elements of the disease process.     

Antituberculous agents. Isoniazid, rifampin, streptomycin, ethambutol, and pyrazinamide

Effective antituberculous drugs have radically improved the prognosis of the patient with active tuberculosis. Surgical therapy is rarely needed, and sanitoriums have largely vanished. Triple-drug therapy may be indicated initially for cavitary pulmonary disease, meningitis, miliary disease, and moderate to severe renal disease. Short-course therapy twice or three times weekly with isoniazid and rifampin may be used in cavitary pulmonary disease and probably in these other serious infections as well. Isoniazid alone is adequate for prophylaxis. The major cause of therapeutic failure is noncompliance of the patient in taking the medication regularly. The second major cause of treatment failure is resistance of tubercle bacilli to the antimicrobial agents used. When treatment failure is apparent, careful reassessment by physicians experienced in the treatment of tuberculosis is indicated. A single drug should never be added to a failing regimen.     

Nontuberculous mycobacterial infections in cancer patients in a medical center in Taiwan, 2005-2008

Data on the nontuberculous mycobacterial (NTM) species that cause infection and the characteristics of disease caused by these pathogens in cancer patients are limited, so we perform this study to investigate the species distribution of NTM isolates from various clinical specimens and to elucidate the epidemiologic trends in NTM isolates and diseases among cancer patients. From 2005 through 2008, cancer patients with NTM infections as defined by the American Thoracic Society/Infectious Diseases Society of America criteria were identified at the National Taiwan University Hospital. The medical records of all patients were reviewed. During the study period, a total of 219 cancer patients with NTM infections were identified. Among them, 133 (60.7%) patients were older than 65 years, most of whom were men. Lung cancer was the most common type of cancer, followed by hematologic cancer and gastrointestinal tract cancer. Pulmonary NTM infection was the most common type of infection in 205 (93.6%) patients, followed by skin and soft tissue infections (n = 7, 3.2%), disseminated infections (n = 4, 1.8%), and genitourinary tract infection (n = 3, 1.4%). Disseminated infections occurred exclusively in patients with hematologic cancer. Mycobacterium avium complex (MAC) caused the majority of pulmonary NTM infections in cancer patients; in contrast, M. abscessus was the most common causative pathogen of extrapulmonary NTM diseases, followed by MAC. In conclusion, physicians need to be aware of the possibility of co-existing pulmonary NTM infection in patients with lung cancer. In addition, disseminated NTM infection should be considered in patients with hematologic cancer.     

Antimicrobial agents in urinary tract infections

Urinary tract infections are commonly encountered in clinical practice and are usually readily treatable. Although many antimicrobial agents that have been available for some time remain effective in the eradication of bacteriuria, the recent introduction of the fluoroquinolone norfloxacin represents an important addition to the therapeutic armamentarium. The efficacy of single-dose therapy with antimicrobial agents such as trimethoprim-sulfamethoxazole or amoxicillin has been shown to be similar to that with conventional (7- to 10-day) treatment in women with uncomplicated lower urinary tract infections. The long-term administration of agents such as trimethoprim-sulfamethoxazole or nitrofurantoin in low doses is usually effective for suppression or prophylaxis of recurrent bacteriuria.