Management of antimicrobial use in the intensive care unit

Critically ill patients admitted to the intensive care unit (ICU) are frequently treated with antimicrobials. The appropriate and judicious use of antimicrobial treatment in the ICU setting is a constant clinical challenge for healthcare staff due to the appearance and spread of new multiresistant pathogens and the need to update knowledge of factors involved in the selection of multiresistance and in the patient's clinical response. In order to optimize the efficacy of empirical antibacterial treatments and to reduce the selection of multiresistant pathogens, different strategies have been advocated, including de-escalation therapy and pre-emptive therapy as well as measurement of pharmacokinetic and pharmacodynamic (pK/pD) parameters for proper dosing adjustment. Although the theoretical arguments of all these strategies are very attractive, evidence of their effectiveness is scarce. The identification of the concentration-dependent and time-dependent activity pattern of antimicrobials allow the classification of drugs into three groups, each group with its own pK/pD characteristics, which are the basis for the identification of new forms of administration of antimicrobials to optimize their efficacy (single dose, loading dose, continuous infusion) and to decrease toxicity. The appearance of new multiresistant pathogens, such as imipenem-resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii, carbapenem-resistant Gram-negative bacteria harbouring carbapenemases, and vancomycin-resistant Enterococcus spp., has determined the use of new antibacterials, the reintroduction of other drugs that have been removed in the past due to toxicity or the use of combinations with in vitro synergy. Finally, pharmacoeconomic aspects should be considered for the choice of appropriate antimicrobials in the care of critically ill patients.     

Drug use in a surgical intensive care unit

A retrospective review of drug usage in 180 patients admitted to a surgical intensive care unit was conducted. The average stay was three days and the total and daily number of drugs averaged 7.6 and 5.6, respectively. The most common drug class used was antibiotics, with cefazolin being the most commonly used antibiotic. Other commonly used drugs include analgesics, diuretics, H2-antagonists, vasoactive drugs and inotropes, antacids, and antiarrhythmics. This study indicates that patients admitted to a surgical intensive care unit are exposed to a variety of potent drugs, often given in combination over a short time period. Although further studies are needed to delineate specific aspects of drug use and patient characteristics, this study suggests that there is a need for close monitoring of drug therapy in these patients with special attention to reduction of drug costs.     

Research on medication use in the neonatal intensive care unit

Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.

Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.

Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research.     

Management of Candida infections in the adult intensive care unit

The epidemiology of Candida infection in intensive care units (ICUs) and the management strategies for such infections in non-neutropenic intensive care patients are discussed in this review. Candida species are one of the leading causes of nosocomial bloodstream infections and a significant cause of morbidity in patients admitted to the ICU. Prophylactic, pre-emptive and empiric treatment strategies for Candida infections have been explored in ICU patients. Routine prophylaxis should not be administered to the whole population of ICU patients, because the concerns about the selection of azole-resistant Candida strains or the induction of resistance are justified. Treatment of fungal infections is now possible with newer antifungal agents, including newer azoles (e.g., voriconazole, posaconazole) and echinocandins (e.g., micafungin, anidulafungin). However, there is a critical need for improvement in diagnosis of invasive Candida infection in order to provide clinicians the opportunity to intervene earlier in the diseases course.     

瑞芬太尼用于危重病人的镇痛与镇静

瑞芬太尼是一种由酯酶代谢的强效μ阿片样受体激动剂,起效快、消除快,代谢不依赖于器官功能,用于外科重症监护室中气管插管机械通气病人或重症病人,能提供充分的镇痛并在此基础上保持病人镇静状态,减少麻醉性镇静药的使用,缩短呼吸机维持时间,促进拔管。本文综述危重病人中瑞芬太尼的药动学特点,及其在外科重症监护室的应用。     

Management of systemic candidal infections in the intensive care unit.

Risk factors and treatment strategies for systemic candidal infections in the intensive care unit (ICU) are discussed. The past two decades have seen a dramatic increase in the frequency of infections caused by Candida species. Risk factors associated with candidemia include treatment with multiple antimicrobials for extended periods, presence of central venous catheters, total parenteral nutrition, colonization by Candida species, abdominal surgery, prolonged stay in the ICU, and compromised immune status. Since the 1960s, conventional amphotericin B has been the primary treatment option for fungal infections. Although effective, amphotericin B has extensive toxicity. Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease nephrotoxicity and improve drug delivery. Practitioners have also been offered alternatives by the introduction of less toxic azole antifungals, such as ketoconazole, fluconazole, and itraconazole; however, their widespread use has resulted in other problems, such as the selection of resistant isolates. There is controversy concerning fluconazole's effectiveness. In the treatment of systemic candidal infections, especially in critically ill patients. Clinical trials do not support the prophylactic or empirical use of fluconazole in the ICU. Treating patients who have no microbiological evidence of infection provides no therapeutic benefit and shifts the fungal flora to noncandidal strains that are more resistant to fluconazole. Patients in ICUs are often susceptible to systemic candidal infection. Preemptive therapy with fluconazole may reduce mortality in high-risk patients. Fluconazole and amphotericin B appear equally effective in treating established systemic candidal infections.     

Enoxaparin use in the neonatal intensive care unit: experience over 8 years

STUDY OBJECTIVE: To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU). DESIGN: Retrospective chart review. SETTING: Level III NICU in a Canadian academic center. PATIENTS: All neonates treated with enoxaparin while in the NICU between January 1, 1998, and June 1, 2006. MEASUREMENTS AND MAIN RESULTS: Data abstracted included patient demographics, diagnosis of thrombosis and its progression, enoxaparin dosages with corresponding antifactor Xa levels, and adverse events. Sixteen neonates (four term, 12 preterm) were treated with enoxaparin at a mean +/- SD initial subcutaneous dose of 1.41 +/- 0.15 mg/kg every 12 hours. The target therapeutic range (antifactor Xa level 0.5-1.0 U/ml) was achieved by 12 infants at a mean +/- SD dose of 1.92 +/- 0.43 mg/kg every 12 hours, after a mean of 5.6 days (range 1-15 days). Preterm infants required a higher dose (per kilogram) compared with term infants to maintain therapeutic antifactor Xa levels (mean +/- SD 1.94 +/- 0.39 vs 1.65 +/- 0.14 mg/kg every 12 hrs, p<0.001). Enoxaparin doses were more strongly correlated to antifactor Xa levels in term infants (r(2)=0.51, p<0.001) compared with preterm infants (r(2)=0.20, p<0.001). Ten (71%) of 14 thromboembolic events resolved, either partially or completely, at a mean of 39 days (range 8-61 days) of enoxaparin therapy. Nine infants (56%) experienced minor local adverse effects at the site of the indwelling subcutaneous catheter (induration, bruises, hematomas, or leakage). Systemic adverse events that were possibly related to enoxaparin therapy included osteopenia (one infant), scleral hemorrhage (one), and minor gastrointestinal tract bleeding (three) found in gastric feeding tubes. No adverse effects were associated with antifactor Xa levels greater than 1.0 U/ml. CONCLUSION: Enoxaparin may be effective in the treatment of neonatal thrombosis. An initial dosage of 1.5 mg/kg every 12 hours is likely inadequate to obtain therapeutic antifactor Xa levels rapidly and differs for term and preterm neonates. Therapeutic levels in preterm infants may be more variable, and the pharmacokinetics of this drug in preterm infants requires further evaluation. Future studies in neonates should prospectively evaluate a higher starting dose of enoxaparin to document effectiveness, acceptance, compliance with treatment guidelines, and adverse effects.     

重症监护病房中革兰阴性菌耐药机制及抗菌药物应用对策

革兰阴性菌(G^-菌)主要耐药机制有以下三方面：使药物失活、阻止药物到达作用靶、药物作用靶位改变。G菌感染用药对策包括：尽量减少抗生素不适当应用，尽早应用有针对性的敏感抗生素。本通过分析重症监护病房中G菌耐药机制及抗菌药物应用对策，为临床合理用药提供参考。     

Spotlight on remifentanil: its analgesic and sedative use in the intensive care unit

Remifentanil (Ultivatrade), a 4-anilidopiperidine derivative of fentanyl, is an ultra-short-acting micro-opioid receptor agonist indicated to provide analgesia and sedation in mechanically ventilated intensive care unit (ICU) patients. Analgesia-based sedation with remifentanil is a useful option for mechanically ventilated patients in the ICU setting. Its unique properties (e.g. organ-independent metabolism, lack of accumulation, rapid offset of action) set it apart from other opioid agents. Remifentanil is at least as effective as comparator opioids such as fentanyl, morphine and sufentanil in providing pain relief and sedation in mechanically ventilated ICU patients. Moreover, it allows fast and predictable extubation, as well as being associated with a shorter duration of mechanical ventilation and quicker ICU discharge than comparators in some studies. In addition, remifentanil is generally well tolerated in this patient population. Thus, remifentanil is a welcome addition to the currently available pharmacological agents employed in the management of mechanically ventilated ICU patients.     

重症监护病房耐碳青霉烯类肺炎克雷伯菌的耐药基因型及系统进化分析

目的 通过分析某三甲医院重症监护病房（ICU）的耐碳青霉烯类肺炎克雷伯菌（CRKP）的耐药基因及系统进化关系,为耐药菌防控的管理提供参考依据。方法 收集安徽医科大学第二附属医院2018年3―7月ICU住院病人分离的19株CRKP,使用VITEK-2 Compact系统进行细菌鉴定及药敏试验,应用Illumina Hiseq 2500平台进行全基因组测序（WGS）,应用MLST软件测定ST型,应用Kaptive软件检测荚膜型,应用Staramr软件筛查菌株的耐药基因,应用Ridom SeqSphere+软件进行cgMLST分型及最小生成树（MST）的构建,并应用CSI Phylogeny 1.4软件及FigTree v1.4.4软件构建最大似然树（MLT）,以分析其系统进化关系。结果 19株CRKP除了对替加环素敏感,对其他常用抗菌药物均呈现耐药,19株CRKP均携带blaKPC-2耐药基因,均属于ST11-KL64型,MST图中以AY7007、AY7003为中心聚集为一簇,cgMLST分型均为CT1774型,MLT图显示分为四组克隆型,组内亲缘性关系相近。结论 该院ICU分离的CRKP...     

人文关怀护理在重症监护室中的应用

目的探讨人文关怀护理在重症监护室中的应用效果。方法选择80例重症患者分为两组,各40例,观察组采用人文关怀护理,对照组采用常规护理,比较两组的护理满意度、焦虑和抑郁评分。结果观察组护理态度、护理质量、护理管理及护理技术满意度显著高于对照组,焦虑和抑郁评分显著低于对照组．差异有统计学意义（P〈0.05）。结论重症监护室内进行人文关怀护理能提高患者的治疗信心,改善其焦虑和抑郁．对促进护患关系有积极的作用。     

重症监护室临终关怀研究进展

近年来临终关怀在中国已有较大发展,随着重症医学的发展趋势,重症监护室(ICU)终末期患者将成为临终关怀的一大特殊群体而越来越受到人们的关注。目前,国内外就ICU临终关怀进行了多方面研究,但在具体实践中却困难重重。为推动开展ICU优质的临终关怀服务,满足终末期患者生理、心理及社会多方面的需求,给予合理的临终关怀措施,提高临终生命质量,使之能够无痛苦、安宁、舒适地走完人生的最后旅程,该文就ICU临终关怀的必要性、护理措施及影响因素进行综述。     

Assessing antibacterial pharmacoeconomics in the intensive care unit

Intensive care units (ICUs) represent areas of high use of antibacterials and other pharmacy goods and services. Many institutions view their ICUs as a target for drug-use surveillance and cost-containment programmes. Economic assessment of antibacterial interventions in the ICU should include all direct costs and patient outcomes. Nonetheless, many of these institutions focus their efforts at reducing antibacterial costs without considering the consequences of these actions. It is possible that devoting more resources to antibacterials can have an overall positive economic impact if more appropriate antibacterial use reduces length of stay, decreases bacterial resistance or lowers frequency of adverse complications. Two consequences of antibacterial use which can result in substantial economic burdens to institutions are drug-induced complications (toxicities and adverse events) and the development of antibacterial-resistant organisms. These events are logical targets for performing pharmacoeconomic studies to evaluate appropriate and inappropriate antibacterial use. Either of these problems can increase length of stay, which is the single most important variable influencing the overall cost of patient care. The primary goal of patient care is to hasten patients' clinical improvement. This will result in decreased antibacterial acquisition costs, decreased lengths of ICU and hospital stays, and ultimately decreased consumption of hospital resources. These can be accomplished by using strategies to guide antibacterial use in order to reduce failures, adverse events, toxicity and antimicrobial resistance.