Selective decontamination of the digestive tract: effect of cessation of routine application at an ICU

Background: Selective decontamination of the digestive tract (SDD) with non-absorbable antibiotics was extensively used at intensive care units (ICU) in Europe to prevent nosocomial infections in critically ill patients. After three recent meta-analyses in which it was demonstrated that SDD did not influence hospital stay and mortality in these patients several ICU's decided to stop the routine use of SDD. Objective: To examine the effects of the cessation of SDD on nosocomial infections, mortality and hospital stay at an ICU in post-operative patients.Design: Retro-and prospective follow-up.Patients: Post-operative patients with mechanical ventilation (MV) for 5 days at an ICU were included. The retrospective group (SDD group) comprised of 138 patients (mean age 66, range 10–91; 78% male) and the prospective group (non-SDD group) of 142 patients (mean age 67, range 18–85; 65% male). The SDD regime consisted of colistin, tobramycin and amphotericin B. Cessation of the SDD was accompanied by a shortening of the routine intravenous cefuroxime prophylaxis.Results: There was a nonsignificant increase from an average 21 to 23 days ICU stay in the non-SDD group when compared with the SDD group (p>0.05). Of the 280 patients 97 (35%) died on the ICU. The risk of death was lower in the non-SDD group (adjusted hazard ratio 0.7 with 95% CI 0.5–1.1). There was a trend towards an increase in infections as a cause of death in the non-SDD group (38% of the ceased patients versus 20% in the SDD group) (p>0.05). The incidence of respiratory tract infection (per 1000 person days) was 80 (95% CI 48–113) in the non-SDD group versus 19 (95% CI 8–22) in the SDD group (adjusted hazard ratio 4.5 (95% CI 2.9–7.1)). Conclusion: The cessation of the routine application of SDD in post-operative patients mechanically ventilated for 5 days or more did nod adversely affect survival nor increased length of stay at the ICU. There may have been a shift to infections as a cause of death after cessation of SDD.     

Predictors of in-hospital mortality for bloodstream infections caused by Enterobacter species or Citrobacter freundii

STUDY OBJECTIVE: To identify predictors of in-hospital mortality among patients with bacteremia caused by Enterobacter cloacae, Enterobacter aerogenes, or Citrobacter freundii. DESIGN: Retrospective cohort study. SETTING: 1300-bed tertiary academic medical center. PATIENTS: One hundred twenty-four patients who had bloodstream infections caused by E. cloacae (3), E. aerogenes (71), or C. freundii (50) between 1998 and 2004. MEASUREMENTS AND MAIN RESULTS: Data from patients with bloodstream infections caused by Enterobacter sp or C. freundii were retrospectively segregated according to hospital survival (98 survivors, 26 nonsurvivors). Multiple patient characteristics and processes of care were evaluated to identify factors contributing to in-hospital mortality. Multiple logistic regression was performed based on univariate comparisons to determine independent risk factors for in-hospital mortality. Among the 124 cases of bacteremia, the crude in-hospital mortality rate was 21% (26 cases). Univariate analysis revealed that survivors were more likely to receive an aminoglycoside as part of their empiric antimicrobial regimen (40% [39/98]) compared with nonsurvivors (19% [5/26], p=0.05). Other factors related to antimicrobial therapy including choice and number of agents used did not differ between survivors and nonsurvivors (p>0.05). Vasopressor use (31% [30/98] vs 62% [16/26]), care in an intensive care unit (19% [19/98] vs 54% [14/26]), and acute renal failure (13% [13/98] vs 31% [8/26]) occurred more frequently in nonsurvivors (p<0.05). Multiple logistic regression identified resistance to second- or third-generation cephalosporins (adjusted odds ratio [OR] 5.16, 95% confidence interval [CI] 2.66-10.0, p=0.013), trimethoprim-sulfamethoxazole resistance (adjusted OR 5.44, 95% CI 2.53-11.7, p=0.027), and mechanical ventilation (adjusted OR 12.2, 95% CI 5.99-24.5, p<0.001) as independent determinants of mortality. CONCLUSION: Among patients with Enterobacter sp or C. freundii bloodstream infections, those with trimethoprim-sulfamethoxazole-resistant or second or third-generation cephalosporin-resistant strains or those who required mechanical ventilation had an increased risk of mortality.     

Voriconazole: in the treatment of invasive aspergillosis

Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged > or =12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for > or =7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for > or=14 days). At the investigators' discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (approximately 30% of patients) and skin rashes (6%). Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.     

Fungal infections in solid organ transplantation

Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following transplantation are relatively common due to the transplant recipients overall immunosuppressed status. The incidence of invasive mycoses following solid organ transplant ranges from 5 to 42% depending on the organ transplanted. These mycoses are associated with high overall mortality rates. Candida and Aspergillus spp. produce most of these infections. This article will review the risk factors, clinical presentation and treatment of invasive fungal infections in solid organ transplant patients, and evaluate the role of prophylactic therapy in this group of patients.     

Caspofungin as primary antifungal prophylaxis in stem cell transplant recipients

STUDY OBJECTIVES: To assess the effectiveness and tolerability of caspofungin as primary prophylaxis against invasive fungal infections in stem cell transplant recipients who are poor candidates for triazole or lipid amphotericin B prophylaxis due to renal or hepatic dysfunction, and to determine whether any patient characteristics are independently associated with an increased risk of breakthrough invasive fungal infection during caspofungin prophylaxis. DESIGN: Retrospective medical record review. SETTING: Tertiary care comprehensive cancer center. PATIENTS: One hundred twenty-three adult stem cell transplant recipients who received caspofungin 35-50 mg/day for up to 100 days after transplantation as primary antifungal prophylaxis between January 1, 2002, and June 30, 2005. MEASUREMENTS AND MAIN RESULTS: Data were collected on host and transplant characteristics such as transplant type, neutropenia, graft-versus-host disease (GVHD), and corticosteroid use, as well as evidence of breakthrough invasive fungal infections. Of the 123 patients, 117 (95.1%) were allogeneic recipients, and the median time to engraftment was 12 days (range 6-26 days). Fifty (40.7%) of the patients developed GVHD of grade 2 or greater and received corticosteroids for more than 21 days. Median duration of caspofungin prophylaxis was 73 days (range 10-100 days). Nine patients (7.3%) developed breakthrough invasive fungal infections (two cases of mixed Aspergillus species and one each of Aspergillus terreus, Rhizopus, Exserohilum, an unspecified mold, Cryptococcus, Candida glabrata, and Candida tropicalis). Median time to invasive fungal infection development was 65 days (range 12-88 days). Only one case occurred during the neutropenic period before engraftment. Multivariate analysis showed that Pseudomonas coinfection (p=0.04) and infliximab therapy (p=0.02) were associated with breakthrough invasive fungal infections in patients receiving caspofungin. By day 100, there were five (4.1%) deaths, two of which were directly attributable to invasive fungal infections. No caspofungin-related adverse events were reported. CONCLUSION: Caspofungin seems to be an effective and well-tolerated option for primary antifungal prophylaxis in the highly immunosuppressed stem cell transplant patient population.     

Fungal infections in solid organ transplantation

Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following transplantation are relatively common due to the transplant recipients overall immunosuppressed status. The incidence of invasive mycoses following solid organ transplant ranges from 5 to 42% depending on the organ transplanted. These mycoses are associated with high overall mortality rates. Candida and Aspergillus spp. produce most of these infections. This article will review the risk factors, clinical presentation and treatment of invasive fungal infections in solid organ transplant patients, and evaluate the role of prophylactic therapy in this group of patients.     

Daptomycin versus vancomycin for complicated skin and skin structure infections: clinical and economic outcomes

STUDY OBJECTIVE: To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections. DESIGN: Prospective, open-label study. SETTING: Level 1 trauma center in Detroit, Michigan. PATIENTS: Fifty-three adult patients with complicated skin and skin structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. INTERVENTION: Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5-20 microg/ml. MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). CONCLUSIONS: Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for complicated skin and skin structure infections.     

The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients

A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.     

Caspofungin for the treatment of fungal infections: a systematic review of randomized controlled trials

During the last decade, owing to the low effectiveness and high toxicity of older antifungals, new antifungal agents have been released to the market for the treatment of patients with fungal infections. Several randomized controlled trials (RCTs) have been designed to evaluate the effectiveness of caspofungin in comparison with other antifungal agents. This review was conducted to examine further the role of caspofungin in the treatment of patients with fungal, mainly Candida, infections. Two reviewers independently performed the literature search, study selection and data extraction from relevant RCTs. A total of six RCTs comparing caspofungin with amphotericin B (deoxycholate in four and liposomal in one RCT) or fluconazole (in one RCT), which studied a total of 1974 patients, were included in our review. Success of the applied treatment in the clinically evaluable patients was achieved in 496/943 (52.6%) of the caspofungin-treated patients and in 381/852 (44.7%) of the amphotericin B- and lipid amphotericin B-treated patients. Discontinuation due to drug toxicity was significantly less common in patients receiving caspofungin than amphotericin B (odds ratio (OR) 0.25, 95% confidence interval (CI) 0.07-0.85, random effects model). Development of nephrotoxicity, hypokalaemia and fever also occurred significantly less often with caspofungin than amphotericin B (OR 0.23, 95% CI 0.14-0.36, fixed effects model; OR 0.3, 95% CI 0.12-0.76, random effects model; and OR 0.26, 95% CI 0.08-0.79, random effects model, respectively). No difference in mortality was noted. Caspofungin was associated with better clinical outcomes (higher cure and fewer adverse effects) than amphotericin B in the treatment of patients with fungal infections.     

Selective digestive tract decontamination in critically ill patients

INTRODUCTION: Selective decontamination of the digestive tract (SDD) has been proposed to prevent endogenous and exogenous infections and to reduce mortality in critically ill patients. Although the efficacy of SDD has been confirmed by randomized controlled trials (RCTs) and systematic reviews, SDD has been the subject of intense controversy, based mainly on an insufficient evidence of efficacy and on concerns about resistance. AREAS COVERED: This article reviews the philosophy, the current evidence on the efficacy of SDD and the issue of emergence of resistance. All SDD RCTs were searched using Embase and Medline, with no restriction of language, gender or age. Personal archives were also explored, including abstracts from major scientific meetings; references in papers and published meta-analyses on SDD were crosschecked. Up-to-date evidence of the impact of SDD on carriage, infections and mortality is presented, and the efficacy of SDD in selected patient groups was investigated, along with the problem of the emergence of resistance. EXPERT OPINION: SDD significantly reduces the number of infections of the lower respiratory tract and bloodstream, multiple organ failure and mortality. It also controls resistance, particularly when the full protocol of parenteral and enteral antimicrobials is used.     

慢性阻塞性肺疾病继发真菌感染临床分析

目的探讨分析慢性阻塞性肺疾病（COPD）继发真菌感染。方法本次研究选择的对象共302例,均为本院2010年5月～2012年5月收治的COPD患者,继发真菌感染40例,回顾相关资料。结果本组共302例COPD患者中,继发真菌感染40例,占13．2％（40／302）,真菌感染的40例患者中,死亡者占15％（6／40）：非真菌感染262例患者中,死亡者占4．6％（12／262）,真菌感染组死亡率显著高于非真菌感染组（P〈0．05）。痰标本均取自气管深部,以白色念珠菌为主,共26例,占65％（26／40）;其次为克柔念珠菌占12．5％（5／40）;曲霉菌占5％（2／40）;光滑念珠菌占2．5％（1／40）;热带念珠菌占2．5％（1／40）;其他5例。结论慢性阻塞性肺疾病继发真菌感染受危险因素的影响,临床需采取有效措施明确诊断,避免医源性危险因素产生的影响,积极给予抗真菌药物．以缓解病情,降低死亡率,改善患者生存质量。     

Comparison of patient outcomes with bivalirudin versus unfractionated heparin in percutaneous coronary intervention

OBJECTIVE: To compare clinical outcomes and glycoprotein IIb-IIIa inhibitor use in patients undergoing percutaneous coronary intervention (PCI) who received bivalirudin or unfractionated heparin (UFH) in a real-world setting. DESIGN: Retrospective cohort analysis. SETTING: University-affiliated medical center. PATIENTS: One thousand seventy-five adult patients who underwent PCI and received either bivalirudin (539 patients) or UFH (536 patients) from April 1, 2003-April 1, 2004. MEASUREMENT AND MAIN RESULTS: Patient data on demographics, comorbidities, laboratory values, and reports of radiologic examinations, cardiac catheterizations, and discharge summaries were obtained. Outcomes evaluated included rates of in-hospital mortality, myocardial infarction, revascularization, and length of stay (LOS), as well as Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) and Thrombosis in Myocardial Infarction (TIMI) bleeding categorization. Bivalirudin use was associated with a significant reduction in TIMI major (5.0% vs 9.7%, p=0.003), REPLACE-2 major (5.4% vs 12.9%, p<0.001), and TIMI minor (1.7% vs 6%, p<0.001) bleeding complications compared with UFH use. Significantly fewer patients in the bivalirudin group received glycoprotein IIb-IIIa inhibitors (27.3% vs 62.7%, p<0.001). Patients receiving bivalirudin had significantly fewer myocardial infarctions after catheterization (10.7% [40/375] vs 18.0% [51/284], p=0.007). No differences were noted in mortality and revascularization rates between groups. A shortened LOS was observed in the bivalirudin group. CONCLUSIONS: This real-world analysis that included high-risk patients provides further evidence that bivalirudin is an attractive alternative to UFH because of a decrease in bleeding events without compromising efficacy.     

Selective digestive tract decontamination in critically ill patients

Introduction: Selective decontamination of the digestive tract (SDD) has been proposed to prevent endogenous and exogenous infections and to reduce mortality in critically ill patients. Although the efficacy of SDD has been confirmed by randomized controlled trials (RCTs) and systematic reviews, SDD has been the subject of intense controversy, based mainly on an insufficient evidence of efficacy and on concerns about resistance.

Areas covered: This article reviews the philosophy, the current evidence on the efficacy of SDD and the issue of emergence of resistance. All SDD RCTs were searched using Embase and Medline, with no restriction of language, gender or age. Personal archives were also explored, including abstracts from major scientific meetings; references in papers and published meta-analyses on SDD were crosschecked. Up-to-date evidence of the impact of SDD on carriage, infections and mortality is presented, and the efficacy of SDD in selected patient groups was investigated, along with the problem of the emergence of resistance.

Expert opinion: SDD significantly reduces the number of infections of the lower respiratory tract and bloodstream, multiple organ failure and mortality. It also controls resistance, particularly when the full protocol of parenteral and enteral antimicrobials is used.     

Posaconazole

Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit (primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase II study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for >or=1 year.     

Micafungin

Micafungin, an echinocandin antifungal agent with a novel mechanism of action, inhibits beta-(1,3)-D-glucan synthase interfering with fungal cell wall synthesis. It shows excellent antifungal activity against a broad range of Candida spp., including azole-resistant strains, and Aspergillus spp. in in vitro and animal studies. In HIV-positive patients, intravenous micafungin 50-150 mg/day dose-dependently eradicated endoscopically confirmed oesophageal candidiasis, with micafungin 100 and 150 mg/day being more effective than micafungin 50 mg/day and as effective as fluconazole 200 mg/day in a double-blind trial. In nonblind trials, micafungin (monotherapy or combination therapy) was effective against invasive aspergillosis, candidiasis and candidaemia in paediatric and adult patients with newly diagnosed or refractory infections. Micafungin 50 mg/day provided significantly better antifungal prophylaxis than fluconazole 400 mg/day in 882 haematopoietic stem cell transplant recipients in a randomised, double-blind trial. Respective overall success rates were 80% and 73.5%. Micafungin is generally well tolerated. Adverse events were not dose- or infusion-related with micafungin 12.5-900 mg/day; no histamine-like reactions occurred. Micafungin was as well tolerated as fluconazole, with numerically fewer micafungin recipients discontinuing treatment (4.2% vs 7.2%).     

Posaconazole : a review of its use in the prophylaxis of invasive fungal infections

Posaconazole is a second-generation triazole antifungal agent with a broad spectrum of activity that includes Aspergillus spp., Candida spp. and the Zygomycetes. In the US, posaconazole oral suspension administered three times daily is indicated for prophylaxis against invasive Aspergillus and Candida infections in patients aged > or =13 years who are at high risk of developing these infections because of immunosuppression, such as haematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or those with haematological malignancies with prolonged neutropenia as a result of chemotherapy. EU-approved prophylactic indications for posaconazole are similar to those in the US.Posaconazole provided effective prophylaxis against invasive fungal infections and was generally well tolerated in two large, well designed trials in HSCT recipients with GVHD, or patients receiving induction-remission chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) that was expected to result in prolonged neutropenia. It offers coverage of clinically relevant pathogens and is potentially associated with fewer drug-drug interactions than other licensed triazole antifungal agents. Its usefulness in some patients may be limited by the lack of an intravenous formulation, although one is currently being developed. As with other antifungal agents, concerns remain regarding the potential emergence of resistance to broad-spectrum antifungal prophylaxis with posaconazole. Despite this, posaconazole is a valuable emerging option for use as prophylaxis against invasive fungal infections in immunocompromized patients who are at high risk of developing these infections.     

The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment?

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.     

老年危重患者深部真菌感染临床调查

目的　了解老年危重患者深部真菌感染的感染率与相关病死率 ,并分析感染相关危险因素。方法　采用回顾性调查研究的方法对 1999年 6月～ 2 0 0 1年 5月华山医院老年科 ICU的患者进行调查。结果　在调查的 2 4 7名患者中 ,有 32名患者发生深部真菌感染 ,感染率为 12 .96 % ;其中 ,18人死亡 ,相关病死率为 5 6 .2 5 % ,高于平均水平。最常见感染部位为肺部 (2 8例 ,87.5 % )。念珠菌是最常见的感染菌种 ,尤其是白念珠菌 (31株 ,72 .0 9% )。在单因素分析中 ,入住 ICU时间 (P=0 .0 0 0 )、使用广谱抗生素种类数 (P=0 .0 18)、合并严重细菌感染 (P=0 .0 0 0 )、具有 COPD基础 (P=0 .0 14 )、气管插管 (P=0 .0 11)为发生深部真菌感染的危险因素 ;L ogistic多因素回归分析显示合并严重细菌感染及使用广谱抗生素为老年科 ICU深部真菌感染的独立危险因素。结论　老年科 ICU深部真菌感染发生率较高 ,预后差 ,应采取有效措施 ,控制各类危险因素 ,切实降低其发病率。     

泊沙康唑预防侵袭性真菌感染疗效及安全性的Meta分析

目的系统评价泊沙康唑预防侵袭性真菌感染的疗效及安全性。方法检索PubMed、Web of Science、Embase、Cochrane Library、Clinicaltrials.gov、中国知网期刊全文数据库、维普中文科技期刊数据库、万方数据库及中国生物医学文献数据库,截止时间2019年9月20日,收集所有关于泊沙康唑与其他抗真菌药预防侵袭性真菌感染疗效及安全性的对比研究,采用RevMan 5.2软件进行Meta分析。结果共纳入符合标准的文献13篇。Meta分析结果显示,泊沙康唑预防疗效优于氟康唑(RR=0.41,95%CI:0.27~0.62,P<0.0001)和伊曲康唑(RR=0.21,95%CI:0.09~0.54,P=0.001),但与伏立康唑(RR=0.34,95%CI:0.05~2.11,P=0.24)、两性霉素B脂质复合物(RR=0.30,95%CI:0.01~7.02,P=0.46)及米卡芬净(RR=0.44,95%CI:0.19~1.02,P=0.06)预防疗效相当。泊沙康唑全因死亡率(RR=0.80,95%CI:0.66~0.97,P=0.02)和证实或很可能是侵袭性真菌感染引起的死亡率(RR=0.35,95%CI:0.18~0.67,P=0.002]均低于其他抗真菌药,且未增加不良反应的发生率,甚至比伏立康唑(RR=0.36,95%CI:0.20~0.67,P=0.001)的不良反应发生率更低。结论泊沙康唑预防侵袭性真菌感染具有良好的疗效和安全性,能降低患者的全因死亡率和侵袭性真菌感染相关死亡率。     

Clinical pharmacy services, hospital pharmacy staffing, and medication errors in United States hospitals

The direct relationships and associations among clinical pharmacy services, pharmacist staffing, and medication errors in United States hospitals were evaluated. A database was constructed from the 1992 National Clinical Pharmacy Services database. Both simple and multiple regression analyses were employed to determine relationships and associations. A total of 429,827 medication errors were evaluated from 1081 hospitals (study population). Medication errors occurred in 5.22% of patients admitted to these hospitals each year. Hospitals experienced a medication error every 22.04 hours (every 19.13 admissions). These findings suggest that at minimum, 90,895 patients annually were harmed by medication errors in our nation's general medical-surgical hospitals. Factors associated with increased medication errors/occupied bed/year were drug-use evaluation (slope = 0.0023476, p=0.006), increased staffing of hospital pharmacy administrators/occupied bed (slope = 29.1972932, p<0.001), and increased staffing of dispensing pharmacists/occupied bed (slope = 19.3784148, p<0.001). Factors associated with decreased medication errors/occupied bed/year were presence of a drug information service (slope = -0.1279301, p<0.001), pharmacist-provided adverse drug reaction management (slope = -0.3409332, p<0.001), pharmacist-provided drug protocol management (slope = -0.3981472, p=0.013), pharmacist participation on medical rounds (slope = -0.6974303, p<0.001), pharmacist-provided admission histories (slope = -1.6021493, p<0.001), and increased staffing of clinical pharmacists/occupied bed (slope = -9.5483813, p<0.001). As staffing increased for clinical pharmacists/occupied bed from the 10th percentile to the 90th percentile, medication errors decreased from 700.98 +/- 601.42 to 245.09 +/- 197.38/hospital/year, a decrease of 286%. Specific increases or decreases in yearly medication errors associated with these clinical pharmacy services in the 1081 study hospitals were drug-use evaluation (21,372 more medication errors), drug information services (26,738 fewer medication errors), adverse drug reaction management (44,803 fewer medication errors), drug protocol management (90,019 fewer medication errors), medical round participation (42,859 fewer medication errors), and medication admission histories (17,638 fewer medication errors). Overall, clinical pharmacy services and hospital pharmacy staffing variables were associated with medication error rates. The results of this study should help hospitals reduce the number of medication errors that occur each year.