Single dose mezlocillin versus three dose cefuroxime plus metronidazole for the prophylaxis of wound infection after large bowel surgery

A prospective, randomized, controlled trial was conducted in 116 consecutive patients undergoing colorectal surgery to compare single dose prophylaxis with mezlocillin to cefuroxime plus metronidazole in three doses. Patients were randomized to receive either a single dose of iv mezlocillin (5.0 g) or three doses of iv cefuroxime plus metronidazole at 8-hourly intervals. The first dose was given on the operating table. The overall wound infection rate in the mezlocillin treated patients (n = 54) was 30% and in the patients treated with cefuroxime plus metronidazole (n = 56) 25%. This difference is not statistically significant. When trivial wound infections were disregarded the wound infection rates were 11% and 16% respectively, which again was not statistically significant.     

A comparison of teicoplanin versus cephradine plus metronidazole in the prophylaxis of post-operative infection in vascular surgery

A total of 272 patients were enrolled into this prospective, unblinded, randomized comparison of single-dose teicoplanin vs three doses of cephradine plus metronidazole as prophylaxis for vascular surgery at St James's and Seacroft Hospitals, Leeds, UK. In all, 71.3% of patients (194/272) were enrolled at St James's University Hospital. Patients received either a single dose of teicoplanin, 6 mg/kg i.v., or cephradine, 1 g i.v. with metronidazole, 1 g rectally, at induction of anaesthesia followed by two further 1 g doses of cephradine and metronidazole 8 and 16 hours later. There were 136 patients in each treatment group. The most common operations were femoropopliteal grafts (96) and aortic aneurysm repairs (47). In the 'intention-to-treat' analysis, primary wound infections were seen in 4.4% of patients (6/136) receiving teicoplanin and 5.9% of patients (8/136) receiving cephradine plus metronidazole (95% CI -6.7%, +3.8%). Other disturbances to wound healing occurred in 23 patients (11 in the teicoplanin and 12 in the cephradine plus metronidazole group). Secondary respiratory tract infections occurred in 17 patients (8 receiving teicoplanin and 9 receiving cephradine plus metronidazole). In the evaluable patients analysis, primary wound infections occurred in 3.5% of patients (4/114) receiving teicoplanin and 5.1% of patients (6/117) receiving cephradine plus metronidazole. Staphylococcus aureus and Proteus sp. were the most common pathogens in primary wound infections. Despite the absence of Gram-negative cover in the teicoplanin group, Gram-negative infections occurred more often in the cephradine plus metronidazole group. Surgery of the lower extremities carried the highest risk of post-operative infection. Rates of infection were significantly higher at Seacroft Hospital (P = 0.001), and significantly higher for cephradine plus metronidazole between the two hospitals (P = 0.0008). Adverse events occurred in 40 patients receiving teicoplanin (29.4%) and 39 patients receiving cephradine plus metronidazole (28.7%). In 19 patients receiving teicoplanin (14%) and 15 receiving cephradine plus metronidazole (11%) these events were considered to be related to the study drugs. The most often reported events were infections, cardiac events and vascular phenomena (haematoma or emboli). Marked changes in haematological parameters and liver function tests were noted seven days after operation in patients in each treatment group, but these resolved quickly as the effects of the operation subsided. ESR remained elevated in both groups at the six-month follow-up assessment. It is concluded from this two-centre study that a single dose of teicoplanin shows similar efficacy to a three-dose regimen of cephradine plus metronidazole as prophylaxis for wound infection in vascular surgery. Both regimens were well tolerated, and there was an equal incidence of adverse events in the two regimens, which reflected the poor general health status of this elderly study population.     

A prospective randomized trial to compare triple dose mezlocillin with triple dose cefuroxime plus metronidazole as prophylaxis in colorectal surgery

The results of a prospective randomized clinical trial to compare three dose regimens of mezlocillin with cefuroxime plus metronidazole for prophylaxis in emergency and elective colorectal surgery are reported. Severe wound infection occurred in five patients (10%) receiving mezlocillin and in four patients (7%) receiving cefuroxime and metronidazole. There were two episodes of septicaemia, each in the mezlocillin group. The total number of surgically related infections was less with cefuroxime plus metronidazole (n = 10) compared with mezlocillin (n = 17), but this was not statistically significant (P greater than 0.1).     

A comparison between imipenem and metronidazole prophylaxis against sepsis following appendicectomy

A single preoperative dose of imipenem/cilastatin was compared with metronidazole for the prevention of infectious sequelae following emergency appendicectomy. Patients with established sepsis received in addition 72 h of either intravenous imipenem or ampicillin, gentamicin and metronidazole postoperatively. Two hundred and sixty-eight patients were studied. Wound infection rate in low-risk patients was 9% for metronidazole and 8% for imipenem. When sepsis was already established intraperitoneally the wound infection rate was 24% for the triple therapy regimen and 8% for imipenem. There was no statistically significant difference between the infection rates in the two groups of treatment whatever the state of the appendix, but there was a trend in favour of imipenem in those patients with a perforated appendix.     

Incidence of surgical site infections and accompanying risk factors in Vietnamese orthopaedic patients

A cohort study of surgical site infections (SSIs) was conducted in 582 orthopaedic surgical patients at Cho Ray Hospital, a reference hospital in Ho Chi Minh City, Vietnam, in order to determine the incidence and analyse risk factors for SSIs in this population. The SSI incidence rate was 12.5% (73 of 582); 3.6% incisional SSIs, 6.8% deep incisional SSIs and 2.1% organ/space SSIs. The incidence increased from 2% in clean wounds to 44.6% in dirty wounds, or 1.3% in patients with a National Nosocomial Infections Surveillance (NNIS) risk index of 0 to 75% in patients with an NNIS risk ratio of 3. In multi-variate analysis, having a dirty wound [odds ratio (OR) 8.7; 95% confidence intervals (CI) 4.6--16.4], American Society of Anesthesiologists' score >2 (OR 3.9; 95%CI 1.8-8.8), procedures with external fixation (OR 2.9; 95%CI 1.4-5.9), emergency surgery with motor-vehicle-related trauma (OR 2.1; 95%CI 1.2-3.9), or duration of procedure >2h (OR 2.1; 95%CI 1.1-4.2) were independent risk factors for SSI. Lack of appropriate prophylaxis was of borderline significance (OR 3.2; 95%CI 0.9-11.1, P=0.06). Among 76 patients with SSIs, 22 patients were discovered during postdischarge follow-up. These late SSIs had age as an additional risk factor (OR 2.8; 95%CI 1.1-7.2). Our data show that SSIs were frequent and differed widely by wound class. The NNIS risk index was predictive of SSI for this population. With a high number of motor vehicle accidents in Vietnam, the majority of orthopaedic operations are trauma related. Emergency surgery for injuries sustained in these accidents, and procedures with external fixation were especially prone to infections.     

Adverse impact of surgical site infections in English hospitals

Between October 1997 and June 2001, 140 English hospitals participating in the surveillance of surgical site infection (SSI) with the Nosocomial Infection National Surveillance Service (NINSS) reported 2832 SSIs following 67 410 surgical procedures in nine defined categories of surgery. Limb amputation had the highest incidence of SSI with 14.3 SSIs per 100 operations. For all categories of surgery, except knee prosthesis (P=0.128), there was a linear increase in the incidence of SSI when the American National Nosocomial Infections Surveillance risk index increased. Superficial incisional SSI was more common than deep incisional and organ/space SSI, and accounted for more than half of all SSIs for all categories of surgery. The postoperative length of stay (LOS) was longer for patients with SSI, and when adjusted for other factors influencing LOS, the extra LOS due to SSI ranged from 3.3 days for abdominal hysterectomy to 21.0 days for limb amputation, and was at least nine days for the other categories. The additional cost attributable to SSI ranged from pound959 for abdominal hysterectomy to pound6103 for limb amputation. Deep incisional and organ/space SSI combined incurred a greater extra LOS and cost than superficial incisional SSI for all categories of surgery, except limb amputation. The crude mortality rate was higher for patients with SSI for all categories of surgery but, after controlling for confounding, only patients with SSI following hip prosthesis had a mortality rate that was significantly higher than those without SSI [odds ratio (OR)=1.8, P=0.002]. However, the adjusted mortality rate for patients with deep incisional and organ/space SSI compared with those without SSI was significantly higher for vascular surgery (OR=6.8, P<0.001), hip prosthesis (OR=2.5, P=0.005) and large bowel surgery (OR=1.8, P=0.04). This study shows that the adverse impact of SSI differs greatly for different categories of surgery, and highlights the importance of measuring the impact for defined categories rather than for all SSIs and all surgical procedures.     

Optimising operational use of artesunate-mefloquine: a randomised comparison of four treatment regimens

A randomised trial was conducted in adults and children (> 1 year old) with acute falciparum malaria in Western Myanmar to compare the operational effectiveness of 4 different artesunate-mefloquine combinations. All regimens were well tolerated. During 42 days follow-up polymerase chain reaction genotyping-confirmed recrudescence occurred in 11 of 187 (5.9%) patients who received observed single low-dose mefloquine (15 mg/kg) and artesunate (4 mg/kg), 7 of 192 (3.6%) patients following observed single high-dose mefloquine (25 mg/kg) and artesunate (4 mg/kg), 7 of 180 (3.9%) patients following observed artesunate 4 mg/kg on day 0 plus self-administered mefloquine 15 mg/kg on day 1 and 10 mg/kg on day 2 with artesunate 4 mg/kg/day on day 1 and 2, and none of 177 patients who received this 3 d regimen under direct observation (P = 0.01). Compared with 3 d treatment regimens, single dose treatments were followed by significantly more P vivax infections during the 42 d follow-up (P = 0.009). Post treatment anaemia (haemoglobin < 10 g/dL) was reduced by the 3 d regimens. Gametocyte appearance was low with all 4 regimens. Single dose observed mefloquine-artesunate regimens were very effective, but the 3 d artesunate-mefloquine regimen is the best treatment for acute falciparum malaria in Western Myanmar. Active measures to ensure absorption and improve adherence will be necessary to realise this advantage operationally.     

Surgical-site infection following spinal fusion: a case-control study in a children's hospital.

OBJECTIVES: To determine the rates of surgical-site infections (SSIs) after spinal surgery and to identify the risk factors associated with infection. DESIGN: SSIs had been identified by active prospective surveillance. A case-control study to identify risk factors was performed retrospectively. SETTING: University-associated, tertiary-care pediatric hospital. PATIENTS: All patients who underwent spinal surgery between 1994 and 1998. Cases were all patients who developed an SSI after spinal surgery. Controls were patients who did not develop an SSI, matched with the cases for the presence or absence of myelodysplasia and for the surgery date closest to that of the case. RESULTS: There were 10 infections following 125 posterior spinal fusions, 4 infections after 50 combined anterior-posterior fusions, and none after 95 other operations. The infection rate was higher in patients with myelodysplasia (32 per 100 operations) than in other patients (3.4 per 100 operations; relative risk = 9.45; P < .001). Gram-negative organisms were more common in early infections and Staphylococcus aureus in later infections. Most infections occurred in fusion involving sacral vertebrae (odds ratio [OR] = 12.0; P = .019). Antibiotic prophylaxis was more frequently suboptimal in cases than in controls (OR = 5.5; P = .034). Five patients required removal of instrumentation and 4 others required surgical debridement. CONCLUSIONS: Patients with myelodysplasia are at a higher risk for SSIs after spinal fusion. Optimal antibiotic prophylaxis may reduce the risk of infection, especially in high-risk patients such as those with myelodysplasia or those undergoing fusion involving the sacral area.     

Randomized controlled trial of standard versus double dose cotrimoxazole for childhood pneumonia in Pakistan

OBJECTIVE: Increasing concern over bacterial resistance to cotrimoxazole, which is recommended by WHO as a first-line drug for treating non-severe pneumonia, led to the suggestion that this might not be optimal therapy. However, changing to alternative antimicrobial agents, such as amoxicillin, is costly. We compared the clinical efficacy of twice-daily cotrimoxazole in standard versus double dosage for treating non-severe pneumonia in children. METHODS: A randomized controlled multicentre trial was implemented in seven hospital outpatient departments and two community health programmes. A total of 1143 children aged 2-59 months with non-severe pneumonia were randomly allocated to receive 4 mg trimethoprim plus 20 mg sulfamethoxazole/kg of body weight or 8 mg trimethoprim plus 40 mg sulfamethoxazole/kg of body weight orally twice-daily for 5 days Treatment failure occurred when a child required a change of therapy, died or was lost to follow-up. Children required a change of therapy if their condition worsened (they developed chest indrawing or danger signs) or if at 48 hours after enrollment, their clinical condition was the same (defined as having a respiratory rate that was 5 breaths/minute higher or lower than at the time of enrollment). FINDINGS: The results of 1134 children were analysed: 578 were assigned to the standard dose of cotrimoxazole and 556 to the double dose. Treatment failed in 112 children (19.4%) in the standard group and 118 (21.2%) in the double-dose group (relative risk 1.10; 95% confidence interval = 0.87-1.37). Using multivariate analysis we found that treatment was more likely to fail in children who were not given the medicine correctly (P = 0.001), in those younger than 12 months (P = 0.004), those who had used antibiotics previously (P = 0.002), those whose respiratory rate was > or =20 breaths/minute above the age-specific cut-off point (P = 0.006), and those from urban areas (P = 0.042). CONCLUSION: Both standard and double strength cotrimoxazole were equally effective in treating non-severe pneumonia. Close follow-up of patients is essential to prevent worsening of disease. Definitions of clinical failure need to be more specific. Surveillance in both rural and urban areas is essential in the development of treatment policies that are based on clinical outcomes.     

Rates of surgical-site infection: an international comparison.

OBJECTIVES: To quantify the occurrence of surgical-site infections (SSIs) in an Italian region and to estimate the proportion of potentially avoidable infections through benchmarking comparison. DESIGN: Prospective study during 1 month based on a convenience sample of surgical patients admitted to 31 public hospitals. All of the patients undergoing an intervention included among the 44 operative procedures of the National Nosocomial Infections Surveillance (NNIS) System were enrolled. Ninety-five percent of the patients were actively observed after discharge for up to 30 days for all of the operations and for up to 1 year for operations involving implantation. RESULTS: Among the 6,167 operative procedures studied, 290 infections were recorded (4.7 per 100 procedures), 206 (71%) of which were SSIs (3.3 per 100 procedures; 95% confidence interval, 2.9-3.9). One hundred thirty-five SSIs (65.5%) were superficial infections, 53 (25.7%) were deep infections, and 12 (5.8%) were organ-space infections; in 6 cases (2.9%), the type of SSI was not recorded. The frequency of SSIs observed in this study was significantly higher for several procedures than that expected when the NNIS System rates (standardized infection ratio [SIR] ranging from 1.77 to 6.42) or the Hungarian rates (SIR ranging from 1.28 to 3.04) were applied to the study population. CONCLUSIONS: The high intensity of postdischarge surveillance can in part explain the differences observed. To allow for meaningful benchmarking comparison, in addition to intrinsic patient risk, data on the intensity of postdischarge surveillance should be included in published reports.     

减低剂量及标准剂量硼替佐米联合疗法对不同类型多发性骨髓瘤的近期疗效对比

目的 探讨减低剂量及标准剂量硼替佐米联合阿霉素、地塞米松治疗不同类型多发性骨髓瘤（MM）的近期疗效及安全性.方法 对52例初诊、复发及难治MM患者给予硼替佐米1.3 mg/m2（标准剂量组,26例）或1.0～1.1 mg/m2（减低剂量组,26例）,第1,4,8,11天快速静脉注射,阿霉素10 mg/m2,第1～4天静脉注射,地塞米松40mg/d,第1～4天静脉滴注,治疗1～6个疗程.比较两组患者的疗效和不良反应.结果 标准剂量组治疗总反应率为80.8％（21/26）,与减低剂量组的88.5％（23/26）比较差异无统计学意义（P=0.739）;两组白细胞、血小板减少发生率比较差异均无统计学意义[23.1％（6/26）比15.4％（4/26）,P=0.281;11.5％（3/26）比7.7％（2/26）,P=0.620];标准剂量组与减低剂量组比较,由硼替佐米诱导的Ⅲ～Ⅳ级周围神经病[15.4％（4/26）比3.8％（1/26）,P=0.038）]、带状疱疹[26.9％（7/26）比7.7％（2/26）,P=0.029]、乏力[38.5％（10/26）比15.4％（4/26）,P=0.045]及腹胀发生率[19.2％（5/26）比3.8％（1/26）,P=0.028]前者均高于后者,差异有统计学意义.结论 减低剂量联合疗法治疗初诊和复发、难治MM患者的疗效反应与标准剂量类似,但患者对减低剂量联合方案具有更好的耐受性.     

Pharmacokinetics of chlormadinone acetate following single and multiple oral dosing of chlormadinone acetate (2 mg) and ethinylestradiol (0.03 mg) and elimination and clearance of a single dose of radiolabeled chlormadinone acetate

BACKGROUND: Published data on pharmacokinetic parameters for chlormadinone acetate (CMA) are in part contradictory, especially with regard to terminal half-life (t(1/2,z)). MATERIALS AND METHODS: Single and multiple doses of CMA (2 mg) and ethinylestradiol (EE; 0.03 mg) were administered to healthy female volunteers for six menstrual cycles. Plasma concentrations of CMA and EE were determined by gas chromatography-mass spectrometry. Single-dose and steady-state pharmacokinetic parameters were calculated. In a separate study, healthy female volunteers were given a single 2-mg dose of radiolabeled CMA. Concentrations of radioactivity in fecal and urine samples were determined via liquid scintillation. Excretion of total radioactivity was calculated as percentage of administered dose. RESULTS: Eighteen women completed the repeated-dose study. Peak plasma concentrations for CMA and EE were reached within 1 and 2 h after taking the study drug. Peak plasma concentrations of CMA were approximately 1600 pg/mL after single-dose administration and 2000 pg/mL after multiple dosing. CMA and EE showed linear pharmacokinetics throughout six cycles, with constant trough values of approximately 400-500 pg/mL for CMA and 20-40 pg/mL for EE. Mass balance factors were 1.2-1.4 for CMA and 1.6-1.7 for EE, and accumulation factors were 1.7-2 for CMA and 1.7-1.8 for EE. Mean t(1/2,z) of CMA was approximately 25 h after single dosing and 36-39 h at steady state. In the excretion balance study, mean dose of CMA recovered was 87.3+/-6.4%, with urinary and fecal excretion accounting for 45% and 42%, respectively. CONCLUSIONS: The pharmacokinetics of CMA and EE is linear after multiple dosing and remains stable during long-term administration, once steady state is reached. The t(1/2,z) of CMA was 36-39 h after multiple dosing, which is considerably shorter than the 80 h often quoted in the literature.     

对苯二甲酸的毒代动力学研究

通过研究对苯二甲酸 (TPA)在大鼠的毒代动力学 ,为制定生物接触限值 (BEI)提供依据。选清洁级 SD大鼠 8只 ,一次性灌胃染毒 10 0 mg/ kg BW TPA后 ,采用反相高效液相色谱法测定尿 TPA浓度 ,用3P97计算毒代动力学参数。结果显示 ,TPA在体内的毒代动力学行为符合一级吸收二室模型 ,吸收速率常数 ka为 0 .5 1/ h,吸收相半衰期 t1 /2 ka=0 .488h,分布相半衰期 t1 /2 d为 2 .44 6 h,达峰时间 tpeak为 2 .16 h,消除速率常数 K u为 0 .143/ h,消除相半衰期 t1 /2β为 31.5 5 1h,TPA经尿排泄累积量为 10 .0 0 mg,2 4h内约 5 0 %的 TPA由尿排泄 ,48h内约 5 2 % ,72 h内约 5 3%以上的 TPA由尿排泄。结论 :TPA在体内吸收快、消除快 ,主要以原形由尿排泄 ,提示职业人群的工后尿 TPA可作为接触性生物标志物。     

Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae)

The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.     

Efficacy of artesunate plus chloroquine for the treatment of uncomplicated malaria in children in Burkina Faso: a double-blind, randomized, controlled trial

Chloroquine (CQ)-resistant Plasmodium falciparum is compromising malaria control in Africa. Combining artesunate (AS) with standard antimalarial drugs increases cure rates and may delay drug resistance. We compared the safety and efficacy of CQ alone and CQ combined with AS (CQ-AS) for treating uncomplicated P. falciparum malaria in Burkina Faso between August 1999 and August 2000. Chloroquine (25 mg/kg over 3 d) combined with AS or placebo (4 mg/kg/d for 3 d) was administered to 300 children aged 6 to 59 months in a randomized, double-blind study. Follow-up extended over 28 d. No adverse drug reactions were recorded. By day 14, parasites were cleared in 120/147 (81.6%) CQ AS-treated children compared with 53/143 (37.1%) CQ-treated children (odds ratio [OR] = 7.55, 95% CI 4.27-13.43, P < 0.001). Corresponding rates for day 28 were 71/145 (49.0%) vs. 27/142 (19.0%) (OR= 4.09, 95% CI 2.33-7.21, P < 0.001). Children who received CQ-AS had significantly faster parasite and fever clearance. Despite the beneficial effects of adding AS, the high failure rate at day 28 of CQ-AS precludes its use as the first-line regimen for treating CQ-resistant P. falciparum in Burkina Faso.     

Rates of surgical site infection after hip replacement as a hospital performance indicator: analysis of data from the English mandatory surveillance system

OBJECTIVE: To describe rates of surgical site infection (SSI) after hip replacement and to use these data to provide a simple mechanism for identifying poorly performing hospitals that takes into account variations in sample size. DESIGN: Prospective surveillance study. SETTING: A total of 125 acute care hospitals in England that participated in mandatory SSI surveillance from April 1, 2004 through March 31, 2005. PATIENTS: Patients who underwent total hip replacement (THR) or hip hemiarthroplasty (HH). METHODS: A standard data set was collected for all eligible operations at participating hospitals for a minimum of 3 months annually. Defined methods were used to identify SSIs that occurred during the inpatient stay. Data were checked for quality and accuracy, and funnel plots were constructed by plotting the incidence of SSI against the number of operations. RESULTS: Data were collected on 16,765 THRs and 5,395 HHs. The cumulative SSI incidence rates were 1.26% for THR and 4.06% for HH; the incidence densities were 1.38 SSIs per 1,000 postoperative inpatient days for THR and 2.3 SSIs per 1,000 postoperative inpatient days for HH. The risk of infection associated with revision surgery was significantly higher than that associated with primary surgery (2.7% [95% confidence interval, 2.0%-3.5%] vs. 1.1% [95% confidence interval, 1.0%-1.2%]; P=.003). Rates varied considerably among hospitals. Nineteen hospitals had rates above the 90th percentile. However, the use of funnel plots to adjust for the precision of estimated SSI rates identified 7 hospitals that warranted further investigation, including 2 with crude rates below the 90th percentile. CONCLUSIONS: Funnel plots of rates of SSI after hip replacement provide a valuable method of presenting hospital performance data, clearly identifying hospitals with unusually high or low rates while adjusting for the precision of the estimated rate. This information can be used to target and support local interventions to reduce the risk of infection.     

甲硝唑经口腔吸收在大鼠体内的代谢动力学

目的　证实甲硝唑可经口腔吸收进入体内 ,了解其在体内的吸收和排泄情况 ,为含甲硝唑口腔卫生用品的安全性评价提供依据。方法　采用 SD大鼠 ,经结扎食管 30 min后口腔给予含 8%甲硝唑的牙膏 1mg/g(体重 ) ,于给药后0 .5、1、1.5、2、2 .5、3、4.5 h取血 ,应用高效液相色谱法测定血中甲硝唑含量 ,并进行药代动力学分析。结果　口腔给药后 ,0 .5 h血清中即可测得甲硝唑 6 .88μg/ml,说明甲硝唑可经口腔粘膜吸收。血清药 -时曲线拟合表明符合一级吸收一室模型 :C=10 .1419(e- 0 .43 3 7t- e- 1 0 .2 571 t) ,处理后的各项药代动力学参数为 :A=10 .144 9μg/ml;Ke=0 .4337h;Ka=10 .2 5 71h;L ag time=0 .3770 h;t1 / 2 (ka) =0 .0 6 76 h;t1 / 2 (ke) =1.5 984h;T(peak) =0 .32 2 0 h;C(max) =8.44 96 μg/ml;AUC=2 2 .40 43μg/(ml·h) ;CL/F(S) =1.42 93mg/(kg· h) ;V/F(C) =3.2 936 (mg/kg)。结论　甲硝唑可经口腔粘膜吸收进入血液。鉴于甲硝唑的遗传毒性作用 ,建议禁止或限制将甲硝唑加入口腔卫生用品中 ,以免人们长期接触产生不良后果。     

Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole

The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.     

Randomized, controlled, double-blind trial with ivermectin on Loa loa microfilaraemia: efficacy of a low dose (approximately 25 microg/kg) versus current standard dose (150 microg/kg)

Neurological serious adverse events (SAEs) following ivermectin treatment may occur in individuals harbouring high Loa loa microfilarial densities and are of major concern in the context of mass ivermectin distributions organized in Africa for onchocerciasis and lymphatic filariasis control. As those SAEs are induced by the rapid and massive microfilaricidal effect of a standard dose of ivermectin (150 microg/kg), we performed a randomized, controlled, double-blind trial to determine whether ivermectin given as: (a) a single low dose of 1.5mg (i.e. 25 microg/kg for a 60 kg person); or (b) two doses of 1.5mg given at a 2 week interval leads to a more progressive decrease in Loa microfilarial loads compared with the standard dosage. A low dose of ivermectin brought about a significantly smaller decrease in Loa microfilaraemia than the standard dose. However, this decrease was not sufficiently different from that obtained after the standard dose to be acceptable to public health programmes, which require a wide safety margin. A second low dose of ivermectin given 15 days after the first dose did not lead to a further decrease in Loa microfilaraemia. Lastly, the variability in the response observed in the group treated with 25 microg/kg suggests that even lower doses would have no effect on a significant number of patients. Ivermectin given at a low dose (相似文献   

重症患者不同负荷剂量替考拉宁早期谷浓度的监测

目的了解给予不同负荷剂量替考拉宁的重症感染患者治疗3 d后的血清药物谷浓度(Cmin)及目标Cmin达标情况,旨在探讨理想的负荷剂量。方法选取2016年2月1日—2017年2月28日入住某院重症医学科重症感染患者,按不同药物负荷剂量(替考拉宁标准剂量6 mg/kg;高剂量10 mg/kg)和不同尿肌酐清除率(Ccr:以50 mL/min为标准线)水平分为4个亚组:标准剂量正常肌酐清除率组(G_(SD1)组)、标准剂量低肌酐清除率组(G_(SD2)组)、高剂量正常肌酐清除率组(G_(HD1)组)、高剂量低肌酐清除率组(G_(HD2)组),比较替考拉宁血清Cmin、目标Cmin达标情况以及不良反应情况。结果共入选患者49例,标准剂量组17例,其第4 d用药前Cmin为(5.98±2.67)mg/L;高剂量组32例,Cmin为(9.05±4.25)mg/L;高剂量组Cmin高于标准剂量组,差异有统计学意义(t=3.10,P=0.003)。G_(SD1)、G_(SD2)、G_(HD1)、G_(HD2)组Cmin分别为(5.78±2.72)、(6.34±2.78)、(8.21±3.77)、(12.07±4.81)mg/L,4组间Cmin比较,差异有统计学意义(F=4.766,P=0.006),G_(HD2)组高于G_(HD1)组、G_(SD2)组和G_(SD1)组;Cmin达标率分别为9.09%(1/11)、16.67%(1/6)、28.00%(7/25)、71.43%(5/7),差异有统计学意义(χ~2=8.766,P=0.033)。各组治疗期间均未发现明显药物相关性皮疹、肝肾功能损害。结论不论患者Ccr正常与否,给予标准负荷剂量的替考拉宁早期均不能达到目标Cmin;低Ccr者给予高负荷剂量替考拉宁早期可达目标Cmin;而正常Ccr者,则需进一步提高负荷剂量。