Valganciclovir Dosing According to Body Surface Area and Renal Function in Pediatric Solid Organ Transplant Recipients

Oral valganciclovir is effective prophylaxis for cytomegalovirus (CMV) disease in adults receiving solid organ transplantation (SOT). However, data in pediatrics are limited. This study evaluated the pharmacokinetics and safety of valganciclovir oral solution or tablets in 63 pediatric SOT recipients at risk of CMV disease, including 17 recipients ≤2 years old. Patients received up to 100 days' valganciclovir prophylaxis; dosage was calculated using the algorithm: dose (mg) = 7 × body surface area × creatinine clearance (Schwartz method; CrCLS). Ganciclovir pharmacokinetics were described using a population pharmacokinetic approach. Safety endpoints were measured up to week 26. Mean estimated ganciclovir exposures showed no clear relationship to either body size or renal function, indicating that the dosing algorithm adequately accounted for both these variables. Mean ganciclovir exposures, across age groups and organ recipient groups were: kidney 51.8 ± 11.9 μg * h/mL; liver 61.7 ± 29.5 μg * h/mL; heart 58.0 ± 21.8 μg * h/mL. Treatment was well tolerated, with a safety profile similar to that in adults. Seven serious treatment-related adverse events (AEs) occurred in five patients. Two patients had CMV viremia during treatment but none experienced CMV disease. In conclusion, a valganciclovir-dosing algorithm that adjusted for body surface area and renal function provides ganciclovir exposures similar to those established as safe and effective in adults     

Prevention of haemophilic synovitis: prophylaxis

Summary.  It has been proven that early prophylactic therapy can prevent bleeding and arthropathy. Numerous retrospective non-randomized cohort studies have demonstrated that prophylaxis, if started early in life, is associated with a considerable reduction of the mean number of joint bleeds and the rate of joint deterioration. It is quite extraordinary that despite the considerable evidence base it has been considered necessary by investigators to pursue the ideal of the controlled randomized trial and expose children to the risk of cerebral bleed. This questionable ethical approach is driven by the reluctance of the 'willingness to pay' but it is important that patients are not subjected to unnecessary investigation at either the behest of the Cochrane Database or those who control the financing of haemophilia care.     

Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy

Objective: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. Methods: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. Results: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml ·  min⁻¹ at week 26 to 180 ml · min⁻¹ at week 36. In 7 of 25 women, CL/F increased >20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol · l⁻¹. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. Conclusion: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml · min⁻¹ (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml · min⁻¹ in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas. Received: 3 July 1996 / Accepted in revised form: 5 November 1996     

利多卡因对兔内毒素性急性肺损伤的预防作用

目的　研究利多卡因对兔内毒素性急性肺损伤的预防作用。方法　雄性健康新西兰兔 2 4只 ,分 3组 :空白组 (S -S ,输注生理盐水 ) ,内毒素组 (L -S ,输注内毒素后输注生理盐水 ) ,预防组 (Ld2 -L ,输注内毒素前 10min输注利多卡因负荷量 2mg·kg- 1 ,然后 2mg·kg- 1 ·h- 1 ) ,控制呼吸 ,吸氧浓度 95 % ,输注内毒素后 6h杀兔。观察氧合指数 (PaO2 FiO2 )、肺动态顺应性 (Cdyn)、支气管肺泡灌洗液 (BALF)白蛋白含量、肺湿 干重比值、肺组织超氧化物歧化酶 (SOD)、丙二醛 (MDA)和髓过氧化物酶 (MPO)以及肺形态学变化。结果　内毒素组PaO2 FiO2 、Cdyn 和肺组织SOD活性明显下降 ;BALF白蛋白含量、肺湿 干重比值和肺组织MDA和MPO含量明显上升 ;肺泡结构严重毁坏 ,肺泡间隔增宽 ,大量炎症细胞浸润。利多卡因预防可明显减轻这些变化。结论　利多卡因对兔内毒素性急性肺损伤有明显的预防作用     

Response to a hepatitis B polypeptide vaccine in micelle form in a young adult population

Polypeptide micelles with relative molecular weights of 25,000 (p25) and 30,000 (gp30) daltons were prepared from native 22-nm hepatitis B surface antigen (HBsAg) particles. This p25/gp30 complex was alum-adsorbed, and three dosage levels (20 micrograms, 4 micrograms, and 0.8 micrograms) were administered at 0, 1, and 6 months to 51 human volunteers. Local and systemic reactions were clinically insignificant, and all vaccinees seroconverted, regardless of dose. As anticipated, antibody responses diminished as the dosage was reduced. Seroconversion rates and geometric mean antibody levels for the 20 micrograms dosage group were significantly better than those observed with a commercial vaccine and were comparable to those achieved after immunization with 40 micrograms of the intact 22-nm particles used to prepare the polypeptides. By 2 weeks, an anti-HBs response was elicited in 80% of the group receiving 20 micrograms of the polypeptide vaccine. This rapid response to immunization may be particularly beneficial for postexposure prophylaxis where the early development of immunity is advantageous.     

抗生素不同用药方案预防乳癌手术部位感染的成本效果分析

目的探讨抗生素不同用药方案对乳癌术后手术部位感染的预防效果和成本的影响。方法506例乳腺癌改良根治手术患者随机分为观察组(n=253)和对照组(n=253)。观察组术前半小时静脉滴注头孢曲松2.0g;对照组术后3d每天静脉滴注头孢曲松2.0g。观察和记录术后患者手术部位感染情况并计算感染有关的医疗成本。结果术后感染发生率观察组和对照组分别为1.19%(3/252)和1.58%(4/253),其中手术部位感染共6例(1.19%),观察组和对照组各3例(1.19%),差异无统计学意义(P>0.05);对照组呼吸道感染1例。预防和治疗术后感染的直接医疗费用观察组为(163±78)元,对照组为(388±134)元,差异有统计学意义(P<0.05)。结论成本-效果分析表明,术前单次头孢曲松在预防手术部位感染方面与对照组等效,且医疗费用显著降低,具有更高的性价比。     

Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein

Phenotypically, ganciclovir-resistant human cytomegalovirus strains could be selected by aciclovir as effectively as by ganciclovir in vitro. Three clinical human cytomegalovirus isolates with different sensitivities against ganciclovir, aciclovir, foscarnet, and cidofovir, but without any mutation in the viral UL97 protein known to confer ganciclovir resistance, were propagated each in duplicate in the presence of ganciclovir or aciclovir. After drug selection, all 12 strains were less susceptible to ganciclovir (increase of 50% focus reduction dose between 2.1- and 31.5-fold) but were still sensitive to foscarnet and cidofovir; 7/12 exhibited a ganciclovir-resistant phenotype with a 50% focus reduction dose >30 microM, and in 6 out of these typical mutations in the UL97 coding region could be found by genotyping. All four strains selected from one isolate carried the identical UL97 mutation at amino acid position 460 (methionine to valine). The decreased sensitivity to ganciclovir and aciclovir in the other strains could neither be attributed to known UL97 mutations nor to mutations in the viral polymerase (UL54), which have been reported to induce resistance.     

Group B Streptococcal infection in neonates and colonization in pregnant women: An epidemiological retrospective analysis

Background

Group B Streptococcus (GBS) infection is one of the major causes of neonatal morbidity and mortality. Universal GBS screening with intrapartum antibiotic prophylaxis (IAP) in pregnant women were initiated in 2012 in Taiwan. This study aimed to analyze the most recent maternal GBS colonization rate and the changes in neonatal GBS infection rate from 2011 to 2016.

Perioperative Cefamandolprophylaxe bei aortocoronaren Bypass-Operationen Serumkonzentrationsverlauf während der extrakorporalen Zirkulation

Zusammenfassung Eine perioperative antibiotische Kurzprophylaxe mit 2 g Cefamandol intravenös bei Narkoseeinleitung wurde bei 12 Patienten während coronarchirurgischer Eingriffe unter Verwendung der Herz-Lungen-Maschine durchgeführt. Bei Beginn der extrakorporalen Zirkulation (= EKZ) kam es infolge Hämodilution zu einem Absinken der Serumkonzentrationen von 110,96 ± 40,29 mcg/ml auf 70,89 ± 34,65 g/ml innerhalb von 10 min. Im weiteren Verlauf der EKZ war der Abfall der Serumspiegel gleich schnell wie davor und danach. Nach 240 min fanden sich noch Serumspiegel von 16,80 ± 9,32 g/ml. Als Ursache für das Versagen einer antibiotischen Prophylaxe kommt bei einer Operationsdauer von mehr als 4 h das Absinken der Serumspiegel unter die minimale Hemmkonzentration der entsprechenden Keime in Frage.

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Perioperative cefamandole prophylaxis in aortocoronary bypass operations: Course of serum concentration during extracorporeal circulation

Summary Antibiotic prophylaxis with 2 g Cefamandole at induction of anaesthesia was performed in 12 male patients undergoing aortocoronary bypass surgery. Caused by hemodilution, there was a marked decrease of serum concentration at the beginning of extracorporeal circulation, from 110.96 ± 40.29 mcg/ml to 70.89 ± 34.65 mcg/ml within 10 min. During extracorporeal circulation, elimination was as fast as before and after perfusion. 240 min after application, mean serum concentrations of 16.80 ± 9.32 mcg/ml were measured. Failure of antibiotic prophylaxis in operations exceeding 4 h might be due to unadaequate antibiotic concentrations, beyond the minimal inhibitory concentration for the pathogens, reported to cause infections after cardiac operations.