注射用甲磺酸加替沙星疑致血糖异常49例临床病例调查分析

目的:对我院2006年1月至9月各科室应用注射用甲磺酸加替沙星的患者113例进行监测,对患者中49例加替沙星疑致血糖异常的临床特点及药品安全评价,临床应用合理性情况进行调研分析。方法:回顾性分析2006年1月至9月我院发生的49例加替沙星疑致血糖异常的临床资料。结果:应用注射用甲磺酸加替沙星49例发生治疗相关血糖异常,用药后1d～23d血糖值异常,均有明显波动,最高达51.67mmol/L,其中3例出现低血糖,46例均为高血糖。结论:糖尿病患者和非糖尿病患者均有可能发生加替沙星治疗相关的血糖异常的危险,老年人、肝肾功能障碍者慎用。     

加替沙星和左氧氟沙星注射液对血糖影响的回顾性队列研究

目的:调查加替沙星注射液对血糖的影响,并与左氧氟沙星注射液比较。方法:采用回顾性队列研究,收集我院2005年9月至2006年8月,使用加替沙星注射液或左氧氟沙星注射液治疗感染性疾病的住院患者300例,分为2组:加替沙星组150例(糖尿病患者35例,非糖尿病患者115例),给予加替沙星400mg/d静脉滴注;左氧氟沙星组150例(糖尿病患者38例,非糖尿病患者112例),给予左氧氟沙星200～500mg/d静脉滴注。分析2组患者血糖的变化。结果:加替沙星组发生血糖异常6例(发生率为4.0%),左氧氟沙星组发生血糖异常1例(发生率0.7%),2组相比差异有统计学意义(P=0.044)。加替沙星组糖尿病患者中血糖升高2例(5.71%),血糖降低1例(2.86%),兼有血糖降低和升高者2例(5.71%);非糖尿病患者中血糖升高1例(0.87%)。左氧氟沙星组38例糖尿病患者中兼有血糖降低和升高者1例(2.6%)。结论:加替沙星引起血糖异常的发生率高于左氧氟沙星。对应用加替沙星的患者,尤其是糖尿病患者应加强血糖监测。     

加替沙星致糖代谢紊乱文献分析

目的了解加替沙星致糖代谢紊乱的情况，预防血糖紊乱的发生。方法采用文献计量学方法，对国内外公开报道的17例加替沙星致糖代谢紊乱病例进行总结性分析。结果加替沙星引起血糖异常升高5例，最高值达38．50mmol／L，血糖异常下降12例，最低值为1．22mmol／L；17例患者中，糖尿病4例，超过60岁12例，16例在停药及相应治疗后均恢复正常，1例死亡。结论加替沙星对糖尿病患者和非糖尿痛患者均可导致糖代谢紊乱，表现为血糖异常升高或降低，老年患者应慎用加替沙星；临床医生应密切监测患者血糖变化，降低不良反应发生率，保障患者的安全。     

氟喹诺酮类药物引起血糖异常71例文献分析

目的：探讨氟喹诺酮类药物引起血糖异常的特点,为临床安全用药提供参考。方法：通过数据库搜索2000年1月-2010年1月氟喹诺酮类药物引起血糖异常的相关文献。结果：引起血糖异常涉及7种氟喹诺酮类药物,共71例;60岁以上老年人多见,有44例（61．97％）;低血糖多见,一般出现在首次用药后1～3d,高血糖通常发生在首次用药3d后;引起血糖异常的氟喹诺酮类药物以加替沙星居多,有46例（64．78％）。结论：氟喹诺酮类药物引起血糖异常与多种因素有关。医务人员应重视氟喹诺酮类药物引起血糖异常的现象,在用药时应加强对患者的血糖监测,确保用药安全。     

加替沙星对住院患者血糖影响的随访研究

目的：研究加替沙星对住院患者血糖的影响，为临床安全应用该药提供科学依据。方法：2007年5月至10月期间接受加替沙星或左氧氟沙星治疗的475例来自13所医院的住院患者纳入随访研究。其中加替沙星组230例，左氧氟沙星组245例。患者的给药剂量均为400mg／d，静脉滴注，用药时间为7d。给药前、给药后第4天及停药后测定患者的血糖水平。结果：停药后高血糖和血糖升高的发生率，加替沙星组高于左氧氟沙星组（分别为13．91％对6．53％和18．70％对9．80％），差异有统计学意义（P〈0．01）。停药后血糖降低的发生率，左氧氟沙星组高于加替沙星组（36．73％对22．17％），差异有统计学意义（P〈0．01）。加替沙星组停药后高血糖、血糖升高及降低的发生率，糖尿病患者分别为12．90％、17．74％及22．58％，非糖尿病患者分别为14．29％、19．05％和24．40％，差异无统计学意义（均P〉0．05）。结论：加替沙星可致血糖升高或降低，因此临床使用时应予以注意，并应作血糖水平测定。     

381例加替沙星不良反应分析

目的：探讨加替沙星对肝功能及血糖的影响，为临床安全使用加替沙星提供依据。方法：分析我院381例住院期间使用过加替沙星的患者血糖及肝肾功能前后变化。结果：用药前后血糖值完整者110例，静滴加替沙星后血糖上升46例，其中17例用药前血糖值正常，用药后升高至异常范围；用药后血糖下降者64例，其中15例用药前血糖值正常，用药后在正常的基础上下降，其中43例〉60岁（67．2％）。静滴加替沙星后，肝、肾功能异常的总人数中大部分都是用药前肝、肾功能原本有异常的患者。结论：血糖异常、合并使用影响血糖的药物的患者，老年人以及肝、肾功能不全患者应慎用此药，如需用药，应调整剂量，密切监测血糖及相关实验室指标。     

299例药源性血糖异常分析

目的探讨药源性血糖异常的特点和规律,促进临床合理用药。方法检索1998～2008年中国医院数字图书馆CNKI期刊知识库收载的中英文医药卫生期刊,对其报道的药源性血糖异常个案进行统计与分析。结果引起血糖异常的药物种类前3位是：激素及其相关药物118例（39．46％）、抗微生物药物71例（23．74％）、抗肿瘤药物30例（10．03％）;而位居前3位的药品分别是：格列本脲52例（17．39％）、加替沙星49例（16．39％）左旋门冬酰胺酶26例（8．70％）。激素及其相关用药118例,（39．46％）、抗微生物药物71例（23．74％）、抗肿瘤药30例（10．03）;位居前3位的药品分别是格列本脲52例（17．39％）、加替沙星49例（16．39％）、左旋门冬酰胺酶26例（8．70％）。结论应严格用药指征,重视药物引起血糖异常的现象,加强对患者血糖监测,以减少药源性血糖异常的发生,确保用药安全。     

加替沙星相关血糖异常临床病例分析

目的:了解加替沙星对住院患者血糖水平的影响。方法:通过计算机管理系统进行回顾性研究,对2005年6月1日至2006年6月1日732例应用加替沙星患者及32例应用红霉素患者的血糖数据进行分析与比较,并采用排除法结合病例分析对加替沙星致血糖异常的因果关系与危险因素进行评估。结果:加替沙星引起血糖异常35例,其中高血糖27例(3.69%),低血糖8例(1.09%)。此外,35例中,非糖尿病患者为24例(68.57%),老年患者(>60岁)为27例(77.14%)。所有患者在停药及相应治疗后均恢复正常。32例应用红霉素患者未出现血糖异常。结论:加替沙星可引起血糖异常,尤其是老年患者。临床医师应了解该不良反应的风险,对使用加替沙星的患者进行血糖监测以保障患者安全。     

不合理用药——禁忌证用药

新修订的加替沙星说明书已明确,该药禁用于糖尿病患者。国家药品不良反应监测中心收到的病例资料报告显示,修改说明书后,仍不断有关于糖尿病患者使用加替沙星并发生血糖异常不良反应的报告。     

加替沙星致高血糖2例

2例患者静脉滴注加替沙星引发高血糖。第1例为81岁男性,因慢性阻塞性肺疾病急性加重,给予加替沙星0.4g 5%葡萄糖注射液250ml静脉滴注,1次/d。3d后患者出现烦躁、多尿、口渴、疲劳,血糖由用药前6.01mmol/L升至28.84mmol/L。立即停用加替沙星,给予12U胰岛素静脉滴注,2d后血糖恢复到5.2mmol/L。第2例为61岁男性梗阻性胆管炎、胆汁淤积性肝硬化患者,给予加替沙星0.4g 5%葡萄糖注射液250ml静脉滴注,1次/d,谷胱甘肽1.2g 葡萄糖氯化钠注射液250ml静脉滴注,1次/d,消炎利胆片6片,3次/d。治疗后第4天,血糖由用药前的5.60mmol/L升为13.81mmol/L。遂停用加替沙星,改为克林霉素静脉滴注。3d后血糖降至5.84mmol/L。     

A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone

STUDY OBJECTIVES: To compare rates of blood glucose abnormalities in hospitalized patients receiving fluoroquinolones or ceftriaxone, and to describe the characteristics of patients who develop blood glucose abnormalities while receiving these agents. DESIGN: Retrospective chart review. SETTING: Two community-based hospitals in the Houston, Texas, region. PATIENTS: Seventeen thousand one hundred eight patients who received fluoroquinolones or ceftriaxone; of those, 101 received levofloxacin, gatifloxacin, or ceftriaxone and also had serum glucose concentrations above 200 or below 50 mg/dl within 72 hours of receiving the drug. MEASUREMENTS AND MAIN RESULTS: Baseline demographics of patients with glucose abnormalities while receiving gatifloxacin, levofloxacin, or ceftriaxone were similar. Mean +/- SD patient age, weight, and estimated creatinine clearance were 67 +/- 17 years, 79 +/- 21 kg, and 52 +/- 32 ml/minute, respectively. Dysglycemia rates relative to treatment were as follows: gatifloxacin 76 (1.01%) of 7540 patients, levofloxacin 11 (0.93%) of 1179, ceftriaxone 14 (0.18%) of 7844, ciprofloxacin 0 (0%) of 545, and any fluoroquinolone 87 (0.94%) of 9264. Dysglycemia was more likely to occur in patients receiving any fluoroquinolone than in those receiving ceftriaxone (relative risk [RR] 3.32, 95% confidence interval (CI) 2.31-4.78, p < 0.05). The rate of dysglycemia did not differ with gatifloxacin and levofloxacin (RR 1.07, 95% CI 0.62-1.86, p = 0.8). Of the 101 patients with dysglycemias, hypoglycemia occurred in nine (9%) and hyperglycemia in 92 (91%). In a multivariate analysis of patients receiving fluoroquinolones, only concomitant sulfonylurea therapy was identified as an independent risk factor for development of hypoglycemia compared with patients who experienced hyperglycemia. CONCLUSION: In the 17,108 patients receiving a fluoroquinolone or ceftriaxone, the rate of dysglycemia was greater in those receiving levofloxacin or gatifloxacin than in those receiving ceftriaxone. However, no difference was noted in the rate of glucose abnormalities with levofloxacin versus gatifloxacin. Clinicians should be aware of dysglycemic events that may occur in patients receiving fluoroquinolones, especially in those with diabetes mellitus or those receiving sulfonylureas.     

Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy

Severe and resistant hypoglycemia occurred in two patients with diabetes mellitus who were receiving concomitant gatifloxacin and glyburide. An 84-year-old woman treated with glyburide for type 2 diabetes mellitus experienced, for the first time, a severe episode of hypoglycemia after 2 days of gatifloxacin 400 mg/day for nonproductive cough. Her blood glucose level on hospital admission was 28 mg/dl. Gatifloxacin and glyburide were discontinued, and the patient was treated with intravenous dextrose infused over 36 hours. Glyburide was restarted before her discharge, with no recurrence of hypoglycemia. A 79-year-old man with type 2 diabetes mellitus treated with glyburide was prescribed gatifloxacin 400 mg/day for pneumonia. After 1 day of therapy, the patient was admitted to the emergency department in a coma. His blood glucose level was 18 mg/dl. Despite discontinuation of gatifloxacin and oral hypoglycemic therapy, hypoglycemia was reversed only after administration of multiple boluses of intravenous dextrose, followed by intravenous dextrose infused over 48 hours. On hospital day 7, gliclazide and levofloxacin were started; the patient experienced no recurrence of hypoglycemia and was discharged on day 10. Several cases of severe and resistant hypoglycemia associated with gatifloxacin therapy have been reported in the recent literature. Although the exact mechanism is not fully understood, it may be linked to a gatifloxacin-induced closing of the adenosine 5'-triphosphate-sensitive potassium channels in the pancreatic beta cells, leading to insulin secretion. The onset of hypoglycemia in relation to the start of gatifloxacin suggests that the drug precipitated this adverse event. Patients receiving oral hypoglycemic agents are at greater risk of experiencing gatifloxacin-induced hypoglycemia than patients not receiving these agents. Clinicians should be aware of this potentially life-threatening adverse event and monitor blood glucose levels in all patients receiving concomitant oral hypoglycemic agents and gatifloxacin.     

Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study

STUDY OBJECTIVES: To compare the incidence of hypoglycemic events in patients exposed to gatifloxacin or levofloxacin, and to measure the odds of experiencing a hypoglycemic event after receiving gatifloxacin versus levofloxacin while adjusting for confounders. DESIGN: Nested case-control study within a historical cohort. SETTING: A tertiary care, 730-bed, teaching hospital in central Illinois. PATIENTS: Seven thousand two hundred eighty-seven hospitalized patients who received gatifloxacin or levofloxacin therapy. MEASUREMENTS AND MAIN RESULTS: A total of 113 patients (case patients) had blood glucose levels below 51 mg/dl; 113 control patients, matched for age and sex, had no hypoglycemia. Matched conditional logistic regression models adjusted the odds of having hypoglycemia for significant covariates. The 12-month incidence of hypoglycemia was 11/1000 patients after levofloxacin administration and 21/1000 patients after gatifloxacin (absolute risk increase 10/1000 patients, 95% confidence interval [CI] 4-16/1000). Renal failure, sepsis syndrome, and concomitant hypoglycemic drug therapy significantly predicted hypoglycemia. After adjustment for significant predictors, the odds of having hypoglycemia were 2.81 (95% CI 1.02-7.70) times higher after gatifloxacin than levofloxacin therapy. CONCLUSION: Among inpatients, the incidence of hypoglycemic events is greater after treatment with gatifloxacin than levofloxacin. The odds of experiencing hypoglycemic events are greater with gatifloxacin even after adjusting for other hypoglycemia risk factors, such as concomitant hypoglycemic drugs, renal failure, and sepsis syndrome.     

Identification of adverse drug reactions in geriatric inpatients using a computerised drug database

INTRODUCTION AND OBJECTIVE: Geriatric patients with multiple comorbidities are at high risk of experiencing an adverse drug reaction (ADR) during hospitalisation. The aim of the study was to compare the rate of ADRs as predicted by a computerised pharmacological database to the actual rate determined by direct observation in a sample of geriatric patients. STUDY DESIGN: During a 4-month period, geriatric patients were monitored using prospective observation. Patients were intensively screened for ADRs by a pharmacoepidemiological team (PET), consisting of two pharmacists and a physician. Actual ADRs detected by the PET were compared with those predicted by a computerised drug database. Furthermore, the set of actual ADRs, which resulted from drug-drug interactions (DDIs), were contrasted with potential DDIs signalled by the database. The main outcome measures were the incidence of actual ADRs. For the detection rate of the database we focused on frequent ADRs (>1% according to product information and database) and all DDIs indicated automatically by the database. RESULTS: 163 patients (121 female), mean age 79.8 +/- 7.1 years (range 60-98), were included in the study which was conducted on a geriatric rehabilitation hospital ward. The mean duration of hospitalisation was 24.3 +/- 8.4 days. Elderly patients received an average of 14.0 drugs (range 2-35) during their hospital stay.Of all patients, 60.7% experienced at least one ADR. The PET detected a total of 153 ADRs, with a mean of 0.9 ADRs per patient (range 0-5). The computerised drug database predicted an average of 309 potential ADRs for each patient; however, only 21 ADRs per patient were of high frequency. In 48% of ADR-positive patients (defined by PET) at least one of these frequent ADRs occurred.DDIs were detected by the PET in 14.7% of patients. Our database indicated a mean of 12 potential DDIs per patient. In 14 out of 24 DDI-positive patients, at least one signal indicated a real DDI. The database sensitivity was consequently 58.3%. CONCLUSION: In geriatric patients the incidence of ADRs is high. Computerised drug databases are a useful tool for detecting and avoiding ADRs. Our software, however, also produced a large number of signals that did not relate to actual ADRs found by the PET. The sheer number of these 'false' signals shows the need for refinement and optimisation of databases for daily clinical use.     

Effects of gatifloxacin and levofloxacin on rates of hypoglycemia and hyperglycemia among elderly hospitalized patients

STUDY OBJECTIVES: To compare rates of hypoglycemia and hyperglycemia among elderly hospitalized patients with normal blood glucose concentrations at baseline who were receiving either gatifloxacin or levofloxacin, and to determine if appropriateness of their doses, according to their package inserts, was associated with hypoglycemia or hyperglycemia. DESIGN: Retrospective cohort study. SETTING: Integrated Veterans Administration (VA) health care system. PATIENTS: Nine hundred thirty-seven elderly (>or= 65 yrs) patients with documented blood glucose levels of 65-140 mg/dl before receiving a fluoroquinolone. MEASUREMENTS AND MAIN RESULTS: Between January 2003 and April 2004, 405 patients receiving levofloxacin met study criteria. In April 2004, gatifloxacin was substituted for levofloxacin on the formulary of this VA system. Thus, between April 2004 and December 2004, 532 patients received gatifloxacin. All blood glucose concentrations during hospitalization that were measured during fluoroquinolone therapy or within 72 hours of completion of therapy were reviewed. Demographic characteristics, comorbidities, insulin and oral hypoglycemic therapies, disease severity, blood glucose levels, and outcomes were recorded and compared between groups. The two groups were similar at baseline for all characteristics examined except previous hospitalization. In the logistic regression, gatifloxacin was independently associated with both hypoglycemia (adjusted odds ratio [AOR] 2.5, 95% confidence interval [CI] 1.2-5.7, p=0.04) and hyperglycemia (AOR 2.4, 95% CI 1.5-3.6, p<0.001). Improper dosage adjustment based on renal function was not associated with higher rates of hypoglycemia and hyperglycemia for either drug. Of the 532 patients receiving gatifloxacin, 465 (87.4%) received appropriate doses, yet gatifloxacin was associated with higher rates of hypoglycemia and hyperglycemia compared with patients receiving levofloxacin. CONCLUSIONS: Higher rates of both hypoglycemia and hyperglycemia were noted among elderly hospitalized patients who received gatifloxacin compared with those receiving levofloxacin, irrespective of dosing.     

Anti-infectives-induced adverse drug reactions in hospitalized patients

OBJECTIVES: To assess the rate and seriousness of adverse drug reactions (ADRs) attributable to anti-infective agents in hospitalized patients; to estimate the likelihood of experiencing anti-infectives-induced ADRs at different length of drug usage in the hospital; to compare different classes of anti-infectives in inducing ADRs; to determine the impact of age and sex on anti-infectives-induced ADRs. DESIGN: Prospective cohort study. PARTICIPANTS: Patients admitted to the infectious diseases department at a university teaching hospital, on Sunday to Wednesday, over a 9 months period, who received at least one anti-infective agent were eligible to enter the study. MAIN OUTCOME MEASURES: Any suspected noxious and untoward medical events, including laboratory tests abnormalities following anti-infective therapy. METHODS: All patients admitted have received at least one anti-infective drug. Anti-infective agents induced ADRs were detected by interviewing patients and daily chart review. The seriousness, causality, and type of reactions were classified based on World Health Organization (WHO) definitions. Chi-square analysis was performed to assess the influence of sex and age on occurring ADRs. Both Kaplan-Meier and life table method were used to estimate the time to occur the ADR in anti-infective users. To compare the estimated risk of ADRs induced by different classes of anti-infectives, odds ratios were estimated. In all classes of anti-infectives, the odds ratio of each class was estimated with regard to anti-tuberculosis agents, which had the highest prevalence of ADRs. RESULTS: During the study period, 460 patients were entered the study. During the same period, 38 ADRs were recognized of which 20 (42%) were serious. The most recognized ADRs were suspected to be induced by anti-tuberculosis agents (29.8%). However in comparing with anti-tuberculosis agents, anti-fungal agents were associated with the highest ADR rate (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.41-1.256) whereas cephalosporines were associated with the lowest rate, (OR, 0.1; 95%CI, 0.04-0.26). The survival analysis shows that the likelihood of experiencing an ADR was increased at first 14 days of drug therapy. Also Chi-square analysis shows that greater risk of anti-infectives-induced ADRs was observed in women. CONCLUSION: The rate of ADRs induced by anti-infective agents in this study was 8.2%. This is higher than a standard (5%) which has been reported in other studies. This study also shows that some of the classes of anti-infective agents like anti-fungals need more attention.     

加替沙星不良反应的中文文献分析

目的：分析加替沙星不良反应发生规律及特点,为临床用药提供参考。方法：对国内近5年内应用加替沙星出现的不良反应报道进行整理、归纳和分析。结果：加替沙星不良反应类型有13种,其中以过敏反应最为常见,严重者出现过敏性休克。不良反应的发生与性别年龄无关,反应在30min内发生者有18例（占54.55%）,都为首次用药发生,提示不良反应以首用即发型和速发型为主。结论：临床医师、药师及生产企业应重视加替沙星的不良反应,临床上用药前应权衡使用。     

我院690例药品不良反应报告分析

目的：对我院药品不良反应（ADR）报告进行分析,探讨ADR发生的特征,挖掘预警信号,为临床安全用药提供参考。方法：对我院收集到的690例ADR有效报告,按患者年龄、性别、给药途径、ADR程度、药品类型、ADR涉及器官或系统及临床表现等进行分类统计与分析。结果：60岁以上个案占38.4%,ADR发生频率与年龄有一定的相关性,但无性别差异;涉及药品12类351种,主要为抗感染药（占25.07%）和中成药（占14.53%）,引起严重ADR的药物主要为抗感染药和抗肿瘤药;静脉给药方式是引发ADR的重要给药途径（占56.5%）;30.29%ADR临床表现为皮肤及其附件损害。结论：应进一步加强对抗感染药、中成药及抗肿瘤药的安全性监测,指导临床合理用药,减少ADR的重复发生。