Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon In Vitro Exposure to Daptomycin

Viridans group streptococci (VGS) are part of the normal flora that may cause bacteremia, often leading to endocarditis. We evaluated daptomycin against four clinical strains of VGS (MICs = 1 or 2 μg/ml) using an in vitro-simulated endocardial vegetation model, a simulated bacteremia model, and kill curves. Daptomycin exposure was simulated at 6 mg/kg of body weight and 8 mg/kg every 24 h for endocardial and bacteremia models. Total drug concentrations were used for analyses containing protein (albumin and pooled human serum), and free (unbound) drug concentrations (93% protein bound) were used for analyses not containing protein. Daptomycin MICs in the presence of protein were significantly higher than those in the absence of protein. Despite MICs below or at the susceptible breakpoint, all daptomycin regimens demonstrated limited kill in both pharmacodynamic models. A reduction of approximately 1 to 2 log₁₀ CFU was seen for all isolates and dosages except daptomycin at 6 mg/kg, which achieved a reduction of 2.7 log₁₀ CFU/g against one strain (Streptococcus gordonii 1649) in the endocardial model. Activity was similar in both pharmacodynamic models in the presence or absence of protein. Similar activity was noted in the kill curves over all multiples of the MIC. Regrowth by 24 h was seen even at 8× MIC. Postexposure daptomycin MICs for both pharmacodynamic models increased to >256 μg/ml for all isolates by 24 and 72 h. Despite susceptibility to daptomycin by standard MIC methods, these VGS developed high-level daptomycin resistance (HLDR) after a short duration following drug exposure not attributed to modification or inactivation of daptomycin. Further evaluation is warranted to determine the mechanism of resistance and clinical implications.     

Clinical Relevance of Efficacy Endpoints in OTC Headache Trials

Objective.— This analysis evaluates and ranks efficacy endpoints often used in headache trials concerning their clinical relevance in relation to the patient-related criterion “global assessment of overall efficacy” based on data gained in a large trial investigating different over-the-counter drugs in the treatment of headache. Background.— The original study showed a significant superiority of the fixed combination of acetylsalicylic acid+ paracetamol+caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. Methods.— For 1734 patients included in the efficacy analysis we investigated the correlation of patient's global efficacy assessment with the endpoints “time to 50% pain relief” (primary endpoint), “time to be pain-free,” pain intensity difference, sum of pain intensity difference, and extent of impairment of daily activities. Patients recorded pain intensity on a visual analog scale. Efficacy, tolerability, and extent of impairment of daily activity were assessed on verbal rating scales. A logistic regression, proportional odds model was adapted to the time to event data. Results.— The highest correlation with patient's global efficacy assessment was demonstrated for the primary endpoint time to 50% pain relief (r = 0.6727) and the sum of pain intensity difference (r = 0.7037). The frequency distribution of patient's global efficacy assessment depended primarily on the time to 50% pain relief and similarly, but to a somewhat lesser extent, on the reduction of pain intensity to 10 mm as assessed on the visual analog scale. More than 86% of the patients assessed efficacy as very good or good when their pain was reduced by 50% at least within 1 hour after drug intake. The patients accept a longer time span than 2 hours for reaching no pain to give a positive global evaluation of efficacy. Conclusions.— The time to 50% pain relief proved to be the best predictor for the global assessment of efficacy by the patient and is a useful endpoint for a univariate analysis.     

腹腔镜及开腹子宫肌瘤剔除术的疗效及安全性评价

目的探讨腹腔镜及开腹子宫肌瘤剔除术的疗效及安全性。方法选择2010～2011年在我院行子宫肌瘤手术的患者98例,根据手术方式的不同分为观察组(行腹腔镜手术)和对照组(行开腹子宫肌瘤剔除术),其中观察组50例,对照组48例,密切观察两组患者手术时间、术中出血量、肛门排气时间、留置导尿管时间、术后住院时间以及手术后并发症,如切口感染、皮下气肿、尿潴留等。结果观察组患者术中出血量、肛门排气时间、留置导尿管时间、术后住院时间均明显小于对照组,差异均有统计学意义(P<0.05)。观察组患者切口感染、尿潴留均明显小于对照组,差异均有统计学意义(P<0.05)。结论腹腔镜比开腹子宫肌瘤剔除术临床疗效更满意,且安全性好,成为临床治疗子宫肌瘤的首选方法之一。     

大剂量黄体酮治疗习惯性早期流产的疗效和安全性探讨

目的：比较不同剂量黄体酮对习惯性早期流产患者的临床效果。方法50例习惯性早期流产患者按照黄体酮用药剂量不同分为大剂量组和小剂量组各25例,所有患者连续治疗2个月后进行相关指标统计,并比较差异性。结果大剂量组体内血清HCG平均值为22199±208 IU/L,E2平均值1098±75 pmol/L,P平均值135±27 nmol/L,明显高于小剂量组统计结果（P〈0.05）,保胎治疗结束后,大剂量组保胎成功率为96%（24/25）,明显高于小剂量组（P〈0.05）。结论40mg剂量黄体酮在治疗习惯性早期流产方面具有较高的疗效和安全性。     

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and presence of myalgias or muscle complaints, was collected. Myalgias were noted in 3/49 (6.1%) patients receiving combination therapy compared with 5/171 (2.9%) of patients receiving daptomycin alone (P = 0.38). CPK elevations of >1,000 U/liter occurred in 5/49 (10.2%) patients receiving combination therapy compared to 9/171 (5.3%) patients receiving daptomycin alone (P = 0.32). Two of five patients experiencing CPK elevations of >1,000 U/liter in the combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (P = 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population.     

地洛他定治疗过敏性鼻炎的临床疗效和安全性评价

目的：比较地洛他定与氯雷他定治疗过敏性鼻炎的有效性和安全性。方法：入选过敏性鼻炎患者57例,其中研究组30例口服地洛他定（5mg/片）,每日1次,每次1片;对照组27例口服氯雷他定（10mg/片）,每日1次每次1片。两组疗程均为14d,观察两组疗效和不良反应。结果：研究组治疗有效率为96.7%,对照组治疗有效率为88.9%,两组间差异无统计学意义（P〉0.05）。所有患者在研究过程中均未出现严重不良事件,不良反应的发生率研究药和对照药分别为16.7%和11.1%,两者之间无显著性差异。结论：地洛他定片治疗过敏性鼻炎安全、有效。     

Evaluation of Endpoints for Antifungal Susceptibility Determinations with LY303366

We have previously reported poor correlation between the in vitro fungicidal activity of LY303366 and MIC results in RPMI medium based upon the manufacturer’s suggested susceptibility endpoint, lack of visual growth. Additionally, we have noted a significant trailing effect with LY303366 when MICs are determined in RPMI medium. These observations have led us to evaluate an alternative susceptibility endpoint for LY303366, an 80% reduction in growth compared with control (similar to that utilized for azoles). Two isolates each of Candida albicans, Candida glabrata, and Candida tropicalis were selected for testing. MICs were determined for LY303366 in RPMI 1640 medium buffered with morpholinepropanesulfonic acid. MICs were determined with suggested (MIC₁₀₀) and experimental (MIC₈₀) endpoints. The minimal fungicidal concentration (MFC) of LY303366 for each isolate was also determined. Time-kill curves were determined in RPMI medium with each isolate at concentrations of LY303366 ranging from 0.125 to 16× MIC₈₀ to assess the correlation between MIC₈₀ and fungicidal activity. Lastly, fungi exposed to LY303366 were examined via scanning electron microscope (SEM) for evidence of drug-induced ultrastructure change. MIC₈₀s for test isolates ranged from 0.015 to 0.12 μg/ml and were consistently three to five wells less than MIC₁₀₀s. Good correlation was observed between fungicidal activity, as assessed by kill curves, and the MIC₈₀. SEM data revealed significant ultrastructure changes induced by LY303366 even at sub-MIC₈₀s. Based on our results demonstrating better correlation between MIC₈₀ and fungicidal activity, i.e., time-kill curves and MFCs, we suggest that 80% reduction in visible growth be utilized as the endpoint for susceptibility determinations with LY303366 in RPMI medium.     

流感疫苗的安全性及免疫效果研究

为探讨防感灵（流感疫苗）的安全性和免疫效果，于１９９６年对６０岁以上的老人、１８～４０岁成人、３～６岁儿童各５０人进行全程接种。接种后进行连续三天全身和局部反应观察并用血凝抑制试验作免疫前后抗体测定。结果接种后反应轻微，未见异常反应，仅１人出现发热，５人出现局部疼痛，副反应率为４．０％，出现的副反应在接种后２４小时均自动消失。接种后流感ＨＩ抗体阳转率:Ｈ３Ｎ２为８７．７％；Ｈ１Ｎ１为８８．４％，Ｂ型为８１．６％。免疫后三周ＨＩ抗体平均滴度ＧＭＴ分别为:Ｈ３Ｎ２１∶７１．０９，Ｈ１Ｎ１１∶１０２．６１，Ｂ型１∶３０．５７。本研究结果表明防感灵具有安全性高、免疫效果良好的特点，值得推广使用。     

Efficacy Profiles of Daptomycin for Treatment of Invasive and Noninvasive Pulmonary Infections with Streptococcus pneumoniae

Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ∼70% or ∼60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.The Gram-positive bacterium Streptococcus pneumoniae is the most prevalent pathogen in community-acquired pneumonia (CAP). CAP is known to frequently progress to invasive pneumococcal disease, thereby causing significant morbidity and mortality worldwide. In developed countries, death from pneumococcal disease occurs primarily among elderly individuals, in whom bacteremic pneumonia is associated with case-fatality rates of 10 to 20% and in whom pneumococcal bacteremia is associated with a case-fatality rate of up to 60% (33). As such, S. pneumoniae causes more deaths from invasive infections than any other bacterium and is the fifth leading cause of death worldwide (12). The worldwide increase in the rates of resistance of S. pneumoniae to frequently used antibiotics such as beta-lactams and macrolides and the rapid global spread of multidrug-resistant clones require both the development of novel immunization strategies and the search for novel antibiotic substances that are active against S. pneumoniae strains resistant to other antimicrobial drugs (1, 9, 24). The clinical situation with S. pneumoniae is further complicated by the fact that pathogenicity profiles vary considerably between and among different serotypes of S. pneumoniae. For example, serotypes 19 and 23 of S. pneumoniae are considered less virulent in humans and mice, whereas serotypes 2 and 4 frequently cause invasive pneumococcal disease and multiorgan failure (MOF) (14). It is just the progression from local infection to sepsis and MOF that contributes to the unacceptably high mortality rates in intensive care units. In view of the distinct pathogenicity profiles of S. pneumoniae serotypes and strains that result in different clinical courses, novel antibiotic substances with the potential to cure infections with S. pneumoniae need to be rigorously validated in experimental model systems specifically representing the major clinical phenotypes of pneumococcal lung infections, i.e., localized pneumococcal pneumonia or invasive pneumococcal disease.Daptomycin is a novel, transmembrane pore-forming 13-amino-acid compound that is produced by Streptomyces roseosporus (21). It belongs to the group of cyclic lipopeptides (for a review, see reference 25), which have particular efficacy against Gram-positive bacterial pathogens, whereas Gram-negative bacterial pathogens are not affected, probably due to their outer membrane (28). Daptomycin inserts into the bacterial cell membrane in a calcium-dependent manner and causes oligomerization of the daptomycin peptide into transmembrane pores, thereby triggering membrane leakage, the release of intracellular ions, and rapid cell death (28, 29). Daptomycin has potent bactericidal activity against a wide range of Gram-positive bacteria and antibiotic-resistant Gram-positive pathogens, such as vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate S. aureus, and penicillin-resistant Streptococcus pneumoniae, for which there are few therapeutic alternatives (4, 27, 30). Importantly, the spontaneous bacterial acquisition of daptomycin resistance has rarely been observed (11, 27, 31). Until now, daptomycin has been approved for use for the treatment of complicated skin and soft tissue or skin structure infections caused by Gram-positive bacteria and for the treatment of endocarditis and staphylococcal sepsis (10). However, in a mouse model of S. pneumoniae or MRSA pneumonia, daptomycin failed to significantly purge bacterial loads at 24 h after infection, although the findings of time-response and survival studies were not reported (26). In contrast, daptomycin was found to be effective in a rat model of hematogenous pneumonia caused by S. aureus (26). Of note, in a phase III clinical trial for the treatment of patients with community-acquired pneumonia, daptomycin (applied at a dose of 4 mg/kg of body weight) failed to achieve superiority over ceftriaxone (efficacies, 79 and 87%, respectively) (23). Thus, the currently available experimental and clinical data for mice and humans suggest that daptomycin has little efficacy against Gram-positive bacterial infections of the lung, possibly due to interactions of the compound with pulmonary surfactant components (26), and is therefore currently not recommended for use for the monotherapy of pneumonia.To the best of our knowledge, no detailed experimental data are available from investigations of the efficacy of daptomycin in defined mouse models of S. pneumoniae-induced lung infections either causing pneumonia in the absence of sepsis or causing fatal invasive pneumococcal disease. Therefore, in the current study, we made use of self-glowing, bioluminescent strains of S. pneumoniae with different virulence profiles to determine the efficacy of daptomycin compared to that of ceftriaxone in two models: a model of pneumococcal pneumonia caused by a less virulent serotype 19 S. pneumoniae strain and a model of septic pneumococcal disease caused by a highly invasive serotype 2 S. pneumoniae strain.     

替硝唑合剂治疗牙体牙髓病临床疗效及安全性评价

目的分析并观察替硝唑合剂与甲醛甲酚或CP进行暂封治疗牙体牙髓病的临床疗效进行比较,并对用药的安全性做出合理评价。方法选取来本校附属医院口腔科就诊的牙体牙髓病患者104例,随机分为两组,观察组52例、对照组52例,对照组牙髓病患者采取甲醛甲酚或CP进行暂封,采取根管充填剂或干髓剂作为填塞剂,进行永久性充填;观察组牙髓病患者则采取替硝唑合剂联合甲醛甲酚或CP进行暂封进行治疗,采取根管充填剂作为填塞剂,进行永久性充填。治疗7d一疗程结束后,观察两组的治疗有效率及患者的临床症状改善等情况。结果 7d一个疗程结束后,分析上述104例患者的恢复情况,观察组患者临床症状的改善情况较对照组显著好转,两组的治疗总有效率相比,差异具有统计学意义(P0.05)。结论采取替硝唑合剂局部根管内给药,对牙体牙髓病的治疗效果较好。应用替硝唑合剂以后,患者的临床症状恢复较快,痛苦减少,应在临床工作中进行推广应用。     

Efficacy of Daptomycin against Bacillus anthracis in a Murine Model of Anthrax Spore Inhalation

Daptomycin demonstrated in vitro (MIC₉₀, 4 μg/ml) and in vivo activities against Bacillus anthracis. Twice-daily treatment with a dose of 50 mg/kg of body weight was begun 24 h after challenge and continued for 14 or 21 days; results were compared to those for controls treated with phosphate-buffered saline or ciprofloxacin. Day 43 survival rates were 6/10 mice for the 14-day and 9/10 mice for the 21-day treatment groups, compared to survival with ciprofloxacin: 8/10 and 9/10 mice, respectively. Culture results from tissues removed at the termination of the experiment were negative.Anthrax, the causative agent for which is Bacillus anthracis, is primarily a disease of animals. In humans, B. anthracis can produce a fatal disease if spores are inhaled or ingested (11). Of even greater concern is the potential use of this organism as a biological weapon, as demonstrated in the recent bioterrorist-related outbreak (4, 5, 20). Even though antibiotic treatments exist for infections by this organism, the possibility of emerging natural resistance and “engineered” resistance remains of great concern (15). For example, penicillin has long been the treatment of choice for anthrax, yet numerous reports of β-lactamase-producing strains and reports of treatment failures have appeared in the literature (1, 9, 13, 17). There have been more recent reports of resistance to other potential anthrax-therapeutic antibiotics (2, 6, 21). With the added concern of possible engineered resistance in a biological-threat-agent setting, it becomes important to assess and expand the spectrum of antibiotics available for treatment.Daptomycin is a cyclic lipopeptide antibiotic with demonstrated bactericidal activity against many Gram-positive bacteria (22). Its unique mode of action, inserting into and disrupting the bacterial membrane (24), makes it an appealing alternate therapeutic for B. anthracis infection if mechanisms resistant to existing treatments are encountered. The 30 B. anthracis strains used in this study were from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) collection and included the Ames strain. The remaining strains were isolates from human or animal infections throughout the world and represent the eight genotypes identified by Keim et al. (16).MICs were determined by the microdilution method in 96-well plates based on current Clinical and Laboratory Standards Institute (CLSI) methods (7). Antibiotics were quality controlled with Staphylococcus aureus ATCC 29213 according to the CLSI (8). The daptomycin values (Fig. ​(Fig.1)1) were as follows: range, 0.5 to 4 μg/ml; MIC₅₀, 2 μg/ml; and MIC₉₀, 4 μg/ml. A level of 4 μg/ml is well within achievable levels in serum after animal dosing and indicated that daptomycin should be further evaluated in the anthrax inhalation model (14). Animal research was conducted in compliance with the Animal Welfare Act and other U.S. statutes and regulations governing the use of animals and adhered to the principles stated in the Guide for the Care and Use of Laboratory Animals (19). USAMRIID is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International.Open in a separate windowFIG. 1.Daptomycin susceptibility distribution for B. anthracis (n = 30). Susceptibilities were determined by broth microdilution according to CLSI document M7-A7 and M100-S18 guidelines (7, 8).For the antibiotic efficacy studies, female BALB/c mice (6 to 8 weeks old) were challenged by aerosol with between 75 and 100 times the established 50% lethal dose (LD₅₀) (3.4 × 10⁴ CFU/whole body) of the Ames strain spore preparation as previously described (14). Antibiotic treatment was initiated 24 h after challenge. Treatments were as follows (10 mice/group): ciprofloxacin administered intraperitoneally (i.p.) at 30 mg/kg of body weight twice a day (BID) for 14 and 21 days, daptomycin administered subcutaneously (s.c.) at 50 mg/kg BID for 14 and 21 days, and i.p. administered phosphate-buffered saline (PBS) BID (control). Daptomycin dosing information was based on data in a previous study (18). Animals were observed and deaths recorded (Fig. ​(Fig.2).2). Surviving mice from each group were euthanized at day 43 postchallenge. Tissue bacterial burdens were determined as follows. Lungs, spleens, and the mediastinum region were aseptically removed, weighed, and homogenized in 1 ml of sterile water. Homogenates were serially diluted 1:10 in water, and 100-μl aliquots were plated on blood agar plates (BAP) to enumerate any B. anthracis spores present. Homogenates were also heat shocked for 15 min at 65°C, serially diluted, and plated as described above to determine B. anthracis spore burdens.Open in a separate windowFIG. 2.Proportional survival from daptomycin (DAPT) or ciprofloxacin (CIP) treatment in the postexposure prophylaxis model of inhalation anthrax. All treatments began at 24 h postchallenge. Control animals received PBS i.p. Mice received ciprofloxacin i.p. at 30 mg/kg or daptomycin at 50 mg/kg s.c. twice daily for 14 or 21 days. The results of 14- and 21-day ciprofloxacin and 14- and 21-day daptomycin treatments were not significantly different (14 days, P > 0.3; 21 days, P > 0.9). Survival values with daptomycin for 14 days (P = 0.0037) and 21 days (P = 0.0004) were significantly different from the control value.Ciprofloxacin has proven in vitro activity against B. anthracis and has demonstrated efficacy in mice, primates, and humans (3, 12, 14). The data summarized in Table ​Table11 indicate that 21 days of treatment with daptomycin yields results equivalent to those with ciprofloxacin and may be sufficient to achieve a cure. This was further supported by our inability to culture organisms from the tissues of most of the surviving animals 43 days postchallenge. The deaths observed in the 14-day treatment groups are very similar to what has been observed for ciprofloxacin and other antibiotics in this animal model. This is believed to be due to the residual lung spore burden, which is still sufficient to support an infection once antibiotic pressure is removed (14). The deaths after the 14-day treatment along with the lung spore load data verify the need for extended antibiotic courses to ensure near-100% cure rates. These data closely match those observed in the nonhuman primate model (12).

TABLE 1.

Study results^a

Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty

The prevalence of Staphylococcus aureus causing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.     

重组人尿激酶原治疗急性心肌梗死的有效性及安全性评价

目的：观察国产重组人尿激酶原（Pro—uk）溶栓治疗急性心肌梗死（AMI）的有效性及安全性。方法：将68例发病6h内的AMI患者随机分为Pro—uk组（n=43）和尿激酶（UK）组（n=25）。其中Pro—uk 50mg组22例、Pro-uk 60mg组21例。观察主要疗效及安全性指标。结果：在溶栓后90min进行冠状动脉造影，Pro—uk组总的梗死相关动脉再通率（TIMI2级＋TIMI3级）为76．7％，明显高于UK组52．2％（P〈0．05），其中Pro—uk50mg为77．3％（17／22），60mg为76．2％（16／21）。Pro—uk组轻度出血并发症显著低于UK组（P〈0．05）；两组均无颅内出血等严重并发症发生。早期心脏事件发生率以及不良反应发生率两组差异均无统计学意义。结论：AMI时应用Pro—uk50-60mg进行静脉溶栓成功率高，使用安全，副作用低。     

刺络放血治疗慢性荨麻疹效果与安全性的系统评价

目的系统评价刺络放血治疗慢性荨麻疹的效果与安全性。方法计算机综合检索PubMed、MEDLINE、中国生物医学文献数据库(CBM)、中国学术期刊全文数据库(CNKI)、万方(WanFang)、维普(VIP)和读秀学术搜索(DuXiu)等数据库,检索时限均从建库至2019年11月,查找刺络放血疗法治疗慢性荨麻疹的随机对照试验(RCTs)。研究者按照纳入与排除标准进行文献筛选、数据提取和质量评价后,使用RevMan 5.3软件对最终获得的数据进行Meta分析。结果纳入11个RCTs,共886例慢性荨麻疹患者,随访过程中脱落4例,最终纳入882例患者。Meta分析结果显示,刺络放血疗法治疗慢性荨麻疹的总有效率优于其他疗法[RR=1.18,95%CI(1.10,1.28),Z=4.44,(P<0.00001)];痊愈率[RR=1.74,95%CI(1.47,2.06),Z=6.50(P<0.00001)],复发率[RR=0.35,95%CI(0.25,0.49),Z=6.16(P<0.00001)]也均优于常规疗法,且较少产生不良反应。结论本系统评价结果显示,与常规抗组胺药及其他中医疗法相比,刺络放血疗法具有更高的治愈率、有效率及较低的复发率。但由于纳入文献数据质量偏低,存在一定的偏倚风险,因此,需要更多高质量随机对照试验对其疗效优势做进一步的验证。     

阿奇霉素序贯疗法治疗小儿支原体肺炎的效果观察及安全性评价

目的探讨阿奇霉素序贯疗法治疗小儿支原体肺炎的临床疗效及安全性。方法选取70例支原体肺炎患儿,随机分为观察组和对照组。观察组给予阿奇霉素序贯疗法,对照组给以红霉素治疗,比较两组患儿临床疗效、临床症状消失时间和不良反应发生情况。结果观察组患儿临床疗效有效率显著高于对照组,退烧时间、咳嗽消失时间、啰音消失时间及X线阴影消失时间较对照组显著缩短,且不良反应发生率显著低于对照组,差异具有统计学意义(P<0.05)。结论阿奇霉素序贯疗法治疗小儿支原体肺炎临床疗效高,缩短临床症状消失时间,降低不良反应发生率,安全可靠,是治疗小儿支原体肺炎的理想方法。     

Considerations and Evaluation of Early-Onset Colorectal Cancer

Worldwide there has been an alarming increase in the incidence of early-onset colorectal cancer (eoCRC). This prompted the United States Preventive Services Task Force to lower the age of colorectal cancer screening to 45 years for average-risk individuals. Nurse practitioners have an important role in implementing these evidence-based guidelines, understanding the risk factors for eoCRC, identifying concerning signs and symptoms of eoCRC, and providing thorough evaluations. Although more research is needed to understand eoCRC, nurse practitioners can use current knowledge to make meaningful impacts on the communities they serve.