Combination effects of cephalexin and gentamicin on Edwardsiella tarda and Streptococcus iniae

The objective of this study was to determine the in vitro activity of cephalexin-gentamicin combination by a microbroth chequerboard technique against clinical isolates of Edwardsiella tarda and Streptococcus iniae. Gentamicin was shown more susceptible than cephalexin against both bacteria. The effect of cephalexin-gentamicin combination against both bacteria represented additive interaction. The combination even showed synergic interaction (22%) against E. tarda, with a FIC index of <0.5 as a borderline. No antagonism for cephalexin-gentamicin combination was observed for any bacterial strain.     

对乙酰氨基酚过量致新生儿肝功能异常

1例28d男性新生儿因喘憋2d、发热1d由家人喂服对乙酰氨基酚颗粒半包（约0．125g）,半天后患儿病情加重,体温38．1℃,心率273次／min,呼吸437次／min。呈点头样呼吸,口唇发绀,三凹征（＋）,双肺可闻及明显干湿哕音,腹部膨隆,肝肋下6cm。实验室检查：丙氨酸转氨酶（ALT）979U／L,天冬氨酸转氨酶（AST）1661U／L,碱性磷酸酶（ALP）469U／L,谷氨酰转肽酶（γ-GT）158U／L,谷氨酰脱氢酶（GLDH）294U／L,乳酸脱氢酶（LDH）2989U／L,α-羟丁酸脱氢酶（α-HBDH）1141U／L。诊断为新生儿肺炎并心力衰竭、急性肝损伤。给予抗炎、抗病毒、保肝降酶等治疗。7d后复查：AIJT72U／L,AST32U／L,ALP244U／L,γ—GT128U／L,GLDH31U／L,LDH262U／L。     

Ceftazidime in the treatment of meningitis caused by multiresistant Serratia marcescens]

A patient of subarachnoid hemorrhage was treated with spinal CSF drainage. Serratia marcescens meningitis occurred because of the spinal CSF drainage. The organism was multiresistant and refractory to antibiotics including piperacillin, imipenem, gentamicin and cephaloridine. It was sensitive to ceftazidime (CAZ). Treatment with CAZ resulted in clinical improvement associated with rapid clearing of the organism from CSF. CAZ serum level was high enough and CAZ penetration into the CSF was satisfactory. According to the evaluation of CAZ concentrations in serum and CSF, two regimens of treatment were recommended. One is an administration of CAZ 1 g x 4 times/day. Another is a combination with CAZ administration 2 g x 2 times/day and followed by 1 g x 4 times/day. The results suggest that CAZ is an extremely effective antibiotic for meningitis caused by CAZ-susceptible bacteria.     

结核性脑膜炎患者抗结核治疗致药物性肝炎临床分析

目的：探讨结核性脑膜炎患者抗结核治疗致药物性肝炎的发病规律及临床特点。方法：分析本院119例结核性脑膜炎患者的规则抗结核治疗,住院＋门诊随访观察至疗程24周的临床资料。结果：119例结核性脑膜炎患者在抗结核治疗24周期间有39例出现药物性肝炎,发生率为32．8％,其中32例发生在强化期（16周内）,经加强护肝、调整抗结核方案等个体化治疗,药物性肝炎治愈率94．9％,结核性脑膜炎治疗有效率90.3％。结论：重视结核性脑膜炎抗结核治疗过程中出现的药物性肝损害,早期制定个体化用药对策,即能使肝功能恢复正常,又使抗结核治疗有效。     

Case of meningitis caused by group B Streptococcus treated with high dose of meropenem

We reported a case of meningitis caused by group B Streptococcus treated with high dose of meropenem (MEPM). A 67-year-old male was suffering from lumbago, fever up, vomiting and convulsion. He had received tumor resection of spinal cord at 40 years old. At the first consultation to our hospital, he had felt strong neck stiffness with Glasgow Coma Scale 5 (El, V1, M3), and his body temperature was 37.0 degrees C. His laboratory findings were as follows; white blood cell count 14600/microL, C-reactive protein 4.39mg/dL, and marked elevation of the cell count in the cerebrospinal fluid. We had administered high dose of meropenem, 6 g/day, and also vancomycin (VCM) on therapeutic drug monitoring. Since his clinical symptoms and laboratory findings had not shown adequate response after 4 days later, we had changed VCM to linezolid 1200 mg/day, and had also continued MEPM, which had resulted in prompt resolution of the clinical symptoms and laboratory findings. Microbiological examination for cerebrospinal fluid has yielded a growth of serotype III group B Streptococcus (Streptococcus agalactiae). Since there have been few data on 6 g/day MEPM against meningitis in spite of recommendation in several guidelines, further studies would be necessary including pharmacokinetic-pharmacodynamic analysis.     

Transferability of cefpirome to cerebrospinal fluid of rabbits with meningitis caused by Staphylococcus aureus

The transferability of cefpirome (HR810, CPR) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 362 +/- 6.63 micrograms/ml at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 60 minutes after administration, and the mean maximum concentration was 14.6 +/- 2.85 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows, Cmax (CSF/serum): 4.04%; AUC (CSF/serum): 5.14% between 15 and 60 minutes, 8.12% between 15 and 120 minutes and 10.4% between 15 and 180 minutes; T 1/2 for CPR in CSF: 154 minutes; T 1/2 (CSF/serum): 3.96. In comparison to those of other beta-lactam antibiotics which were obtained in the same way, the transferability of CPR was intermediate, but the peak CSF level was high, and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for this drug.     

Transferability of cefodizime to cerebrospinal fluid of rabbits with meningitis caused by Staphylococcus aureus

The transferability of cefodizime (THR-221, CDZM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean blood concentration was 195 +/- 18.3 micrograms/ml using phosphate buffer solution (PBS) standard and 474 +/- 22.0 micrograms/ml using rabbit serum standard, respectively, at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF vs. PBS standard was maximum at 60 minutes after administration, and the mean maximum concentration was 8.74 +/- 2.16 micrograms/ml. Pharmacokinetic parameters calculated from those values were as follows, respectively, for PBS standard and rabbit serum standard; Cmax (CSF/serum): 4.48% and 1.84%. AUC (CSF/serum): 6.15% and 2.02% between 15 and 60 minutes, 10.6% and 3.00% between 15 and 120 minutes and 13.4% and 3.48% between 15 and 180 minutes. T 1/2 for CDZM in CSF: 141 minutes in both cases. T 1/2 (CSF/serum): 3.27 and 2.11. Concentrations in CSF determined using an high performance liquid chromatography method in another rabbits were similar to those determined using the bioassay vs. rabbit serum standard. The bioassayed concentration of this drug (AUC (CSF/serum] vs. PBS standard ranked 9th among 23 other beta-lactam antibiotics tested. That is, the drug distributed favorably as compared to other antibiotics, and it may be worthwhile of running clinical trials on this drug in meningitis when antimicrobial potential against main pathogens of meningitis are considered.     

去甲万古霉素在耐青霉素肺炎链球菌引起的兔脑膜炎中的治疗评价

目的静脉注射不同剂量的去甲万古霉素,了解其在耐青霉素肺炎链球菌引起的兔脑膜炎模型中的脑脊液透过率;比较不同剂量药物的杀菌效果;同时研究去甲万古霉素与磷霉素联合用药在体内、体外是否具有协同作用。方法脑膜炎模型的建立参照Dacey和Sande的方法并做了改进;抗生素浓度的测定采用微生物效价测定法;体外联合药敏实验采用棋盘设定微量肉汤稀释法。以8h内的平均杀菌率评估体内联合用药。结果在兔脑膜炎模型中,去甲万古霉素的脑脊液透过率为19.6%;40mg/kg去甲万古霉素单次静脉注射(0h)平均杀菌率为(-0.93±0.26)△lgCFU/(ml·h);20mg/kg去甲万古霉素两次静脉注射(0,4h)平均杀菌率为(-0.57±0.45)△lgCFU/(ml·h)。体外联合药敏实验表明磷霉素与去甲万古霉素联合应用表现为相加作用占25%,无关作用占75%,无协同或拮抗作用。体内三种不同剂量的磷霉素与去甲万古霉素联合应用,三组的平均杀菌率分别为(-0.45±0.21)△lgCFU/(ml·h)、(-0.46±0.25)△lgCFU/(ml·h)、(-0.42±0.28)△lgCFU/(ml·h),三者之间无明显差别。结论在耐青霉素肺炎链球菌致脑膜炎的兔模型中,去甲万古霉素的脑脊液透过率与万古霉素相似,但同等剂量条件下,去甲万古霉素的杀菌效果明显好于万古霉素。磷霉素不适于单独治疗耐青霉素肺炎链球菌所致脑膜炎,体外及体内实验证实磷霉素与去甲万古霉素联合应用分别表现为无关作用和拮抗作用。     

Transferability of meropenem to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus]

The transferability of meropenem (MEPM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 93.1 +/- 13.5 micrograms/ml at 15 minutes after intravenous administration of MEPM at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 15 minutes after administration at 4.42 +/- 2.24 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows: Cmax (CSF/serum) 4.75%, AUC (CSF/serum) 10.4% between 15 and 60 minutes, 13.9% between 15 and 120 minutes and 15.7% between 15 and 180 minutes, T 1/2 for MEPM in CSF: 50.9 minutes, T 1/2 (CSF/serum): 2.19. In comparison to those of imipenem which were obtained in the same way, the transferability of MEPM was similar and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worth-while of running clinical trials for this drug.     

Neonatal hypothyroidism caused by maternal nicotine exposure is reversed by higher T3 transfer by milk after nicotine withdraw

Maternal nicotine exposure leads to neonatal hypothyroidism that can be returned to euthyroidism after nicotine withdrawal. Here, we examined the transfer of iodine through milk, deiodinase activities (D1 and D2), and serum T3, T4 and TSH in rat offspring after maternal exposure to nicotine. One day after birth, a minipump was implanted to dams releasing nicotine (NIC), 6 mg/kg/day for 13 days or vehicle saline. Animals were killed at the day 15 and 21 of lactation. At day 15, NIC-treated dams showed decreased T4 and mammary 2 h-radioiodine uptake (RAIU) and increase of TSH, thyroid 2 h-RAIU, liver D1 and mammary D2. At the cessation of NIC-exposure, pups displayed decreased T3, T4 and thyroid 2 h-RAIU and increased TSH. At weaning (21-postnatal day), NIC-treated dams recovered their T4 and TSH, but increased deiodinase level in the liver and mammary gland. Milk T3 content in NIC-treated dams was higher at both day 15 and 21, and thyroid function was recovered at the day 21. Thus, thyroid function was affected by nicotine in both mothers and pups, suggesting a primary hypothyroidism. After nicotine withdrawal, pups recovered thyroid function probably due to the increased lactational transfer of T3 in relation with increased mammary gland deiodinase activities.     

Neonatal death and lung injury in rats caused by intrauterine exposure to O,O,S-trimethylphosphorothioate

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is an impurity present in a number of widely used organophosphorus insecticides and has been recognized as a potent lung toxicant. OOS-TMP was given p.o. to pregnant rats on gestation day (G) 20 at 0.5, 2.5, 10 and 40 mg/kg. Control dams or pair-fed dams (pair-fed to 40 mg/kg) received 2 ml/kg corn oil. Neonates from treated dams died within 72 h after delivery in a dose-related manner: 100% at 40 mg/kg, 86% at 10 mg/kg, 15% at 2.5 mg/kg, 1% at 0.5 mg/kg, with 3% in controls and 2% in neonates from pair-fed dams. Neonates from treated (40 or 10 mg/kg) and control dams were cross-fostered. The cross-fostering did not affect mortality of neonates from either dosed dams or from control dams. Disposition of OOS-TMP was studied by using [³H]-OOS-TMP at 0.5, 2.5 and 10 mg/kg. Concentrations of OOS-TMP equivalent in fetal lung were about one half of those in mothers at all doses. In another set of experiments, dams (five dams for each dose) were dosed on G 20 with OOS-TMP p.o. at 0, 0.5, 2.5, 10, and 40 mg/kg or pair-fed (pair-fed to 40 mg/kg) and the fetuses were delivered by cesarean section (C-section) on G 23. In neonates from dams dosed with 10 and 40 mg/kg, cyanosis occurred within 4 h after C-section. Histopathological examination revealed dose-related proliferation of type II pneumocytes in dams and proliferation of interstitial cells and delayed septal/capillary development in neonates. However, we could not detect these changes in control fetuses or in fetuses from pair-fed dams. Even at 0.5 mg/kg we found changes in pulmonary morphology in dams and neonates. In other organs such as, liver, brain, spleen, adrenal gland and kidney, we could not detect any morphological changes at 40 mg/kg in either dams or neonates. Thus it was concluded that OOS-TMP caused lung injury in neonates by intrauterine exposure and elicited a lethal response in the neonates.     

Therapy of porphyria cutanea tarda

Porphyria cutanea tarda (PCT) is the most common type of porphyria. There is an association of PCT with haemochromatosis, diabetes mellitus and hepatitis C infection. The basis of treatment of PCT consists of three elements: avoidance of triggering factors, iron depletion and porphyrin elimination. Alcohol and certain systemic medical drugs, such as oestrogens (or tuberculostatics), should be considered as triggering factors, and as far as possible, avoided. Other triggering factors, such as chronic haemodialysis in renal insufficiency, need a different approach. The hallmark in iron depletion is phlebotomy. Porphyrin elimination is achieved using low-dose chloroquin therapy. The treatment is safe and effective but has its limits in cases with haemochromatosis (HFE) gene mutations. Here iron depletion needs additional phlebotomy. In patients with chronic haemodialysis-associated PCT, chloroquine is ineffective. Erythropoietin, desferroxamine and small-volume phlebotomy have been employed to control the disease. Childhood PCT is very rare. No controlled studies are available, but published experience suggests that body weight-adapted chloroquine therapy or small volume phlebotomy might be useful.