Safety and efficacy of linezolid in 16 infants and children in Japan

Linezolid, an oxazolidinone antibiotic, exhibits a broad spectrum of activity against Gram-positive bacteria. It has been licensed for adult use in Japan since 2006 for MRSA infections, and has also been used off-label for pediatric patients. At our university hospital, a total of 16 infants and children (including one non-Japanese Asian) were administered linezolid owing to infection with multidrug-resistant Gram-positive bacteria, after consent had been provided. All patients had severe underlying diseases or indications for surgery. Eighty-eight percent of the causal microorganisms were methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus and all were sensitive to linezolid. Linezolid was administered because the antecedent anti-MRSA medications were ineffective or contraindicated, or intravenous-to-oral switch therapy was requested owing to cardiac or orthopedic surgical-site infections. The median duration of administration was 13 days (range 3-31 days). The overall efficacy was 91 % (10/11) in those for whom efficacy could be evaluated. Only two patients (both teen-aged) encountered linezolid-related adverse effects (13 %, 2/16). One patient showed elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), requiring that administration be withdrawn, but enzyme levels returned to normal after the patient had been switched to vancomycin. The other patient showed transiently decreased platelet counts. Linezolid is considered generally safe and effective for children in Japan, especially for those who cannot use other anti-MRSA medications or those who require oral antibiotics for infections with multidrug-resistant Gram-positive bacteria.     

Impact of ontogeny on linezolid disposition in neonates and infants

The impact of age on linezolid disposition during the first few months of life has not been previously investigated. We characterized linezolid pharmacokinetics after a single, 10.0-mg/kg intravenous dose in 42 infants stratified as follows: group 1 (n = 9), gestational age <34 weeks and postnatal age <8 days; group 2 (n = 7), gestational age <34 weeks and postnatal age 8 days to 12 weeks; group 3 (n = 11), gestational age >or=34 weeks and postnatal age <8 days; and group 4 (n = 15), gestational age >or=34 weeks and postnatal age 8 days to 12 weeks. Linezolid was quantitated by a validated HPLC-triple-quadrupole mass spectrometer method from repeated blood samples (n = 7, 0.3 mL each) obtained over a 12-hour period. Pharmacokinetic parameters were determined by standard model-dependent techniques. The values (mean +/- SD) for total body clearance (CL) (0.25 +/- 0.12 L x h(-1) x kg(-1)), apparent volume of distribution (VD(ss)) (0.75 +/- 0.19 L/kg), and elimination half-life (t(1/2)) (2.8 +/- 2.1 hours) from the entire study cohort were similar to values reported previously for children and adolescents. Examination of the linezolid pharmacokinetics as a function of age revealed that CL increased rapidly during the first week of life and as a function of postnatal age. Age stratification revealed lower values for CL in those infants aged less than 8 days (group 1, 0.12 +/- 0.06 L x h(-1) x kg(-1); group 3, 0.23 +/- 0.12 L x h(-1) x kg(-1)) as compared with those aged 8 days to 12 weeks (group 2, 0.31 +/- 0.07 L x h(-1) x kg(-1); group 4, 0.31 +/- 0.10 L x h(-1) x kg(-1)). In contrast to the results for CL, gestational age served to be the most useful predictor of VD(ss). Evaluation of the pharmacokinetic data would appear to support the use of linezolid dosing regimens currently approved for infants and young children in neonates with postnatal age greater than 7 days.     

Relationship between cytopenia and gestational age in infants and neonates treated with linezolid therapy

BackgroundLinezolid has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants. Major adverse events associated with linezolid treatment is cytopenia. However, there were few reports about the relationship between cytopenia and gestational age. Primary objective of this study was to compare the relationship between cytopenia in infants and neonates treated with linezolid therapy and gestational age.MethodsIn total, 44 patients were divided into two groups depend on their gestational age [<180 days; low gestational age group (20 patients); >180 days group; high gestational age group (24 patients)]. All patients treated with linezolid from April 2014 to March 2018 at NICU or GCU of Aichi Medical University Hospital. Investigation items were as follows; sex, age, weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, concomitant medications, hematologic abnormalities during linezolid treatment.ResultsThe incidence of overall cytopenia in low gestational age group was significantly higher than high gestational age group (65.0 % vs. 25.0 %; p < 0.05). Of note, the incidence of thrombocytopenia in low gestational age group showed significantly higher than high gestational age group (45.0% vs. 8.3%, p < 0.05). Then, the proportion of patients occurred thrombocytopenia who received linezolid 10 mg/kg every 8 h were higher than 10 mg/kg every 12 h in both groups.ConclusionIn cases linezolid is administered three times a day should be more carefully of thrombocytopenia in patients with gestational days less than 180 days.     

小儿阑尾炎的腹腔镜阑尾切除术115例临床体会

目的 探讨小儿阑尾炎的腹腔镜阑尾切除术的应用及技巧.方法 分析 2003年2月～2008年9月115例小儿阑尾炎患者采用腹腔镜阑尾切除术治疗的临床资料.结果 115例均成功完成手术.满意恢复出院.结论 腹腔镜阑尾切除术是目前小儿阑尾炎治疗的一种较好术式选择,在应用熟练及掌握技巧基础上,提倡用于小儿阑尾炎.     

利奈唑胺治疗儿童社区获得性金黄色葡萄球菌肺炎的临床疗效分析

目的 分析儿童社区获得性金葡菌肺炎应用利奈唑胺治疗的临床疗效.方法 选择2008年1月1日-2009年3月1日在青岛大学医学院附属医院儿科及青岛市儿童医院诊断并住院治疗的社区获得性金葡菌肺炎患儿22例为研究对象,通过对住院天数、体温变化、肺部影像学改变以及实验室指标的变化进行分析,判断其临床效果.结果 患儿的体温开始下降时间为(1.8±0.4) d,体温恢复正常的时间为(2.7±1.7) d,住院时间为(13.0± 2.3) d,外周血白细胞(WBC)、C反应蛋白(CRP)和红细胞沉降率(ESR)恢复正常的时间分别为(8.29±2.81) d、(13.29±2.77) d和(13.14±3.72) d,总有效率100%,不良反应发生率4.6%.结论 利奈唑胺治疗儿童社区获得性金葡菌肺炎效果可靠.     

Clinical and pharmacokinetic evaluation of moxalactam in infants and children

Moxalactam, a new beta-lactam antibiotic was evaluated in the treatment of 21 pediatric patients including 16 with clinical and radiological evidence of pneumonia and 5 with urinary tract infection (UTI). Clinical and radiological resolution of pneumonia occurred in all. Bacteriological efficacy in pneumonia, however, was assessed in only 1 patient whose blood culture grew H. influenzae type b. In patients with UTI, the therapy was successful, bacteriologically as well as clinically. The only side effects observed were mild transient elevation of SGOT and alkaline phosphatase in 6 cases. The peak and trough levels of the drug were manyfold higher than the known minimum inhibitory concentrations of common pathogens. The mean t1/2 projected of 95 and 124 min with intravenous and intramuscular route, respectively, were similar to those reported in adults.     

Clinical and pharmacokinetic evaluation of parenteral moxalactam in infants and children.

Thirty-four infants and children ranging in age from 2.5 to 180 months (mean, 40 months) were treated with parenteral moxalactam (150 mg/kg per day) for suspected or proved bacterial infections outside the central nervous system. Six patients infected with Haemophilus influenzae b, nine infected with Staphylococcus aureus, three infected with Streptococcus pneumoniae, one infected with Streptococcus pyogenes, one infected with Enterobacter aerogenes, one infected with Fusobacterium nucleotum, and one infected with Staphylococcus epidermidis, microaerophilic streptococcus, and Propionibacterium sp. were clinically and bacteriologically cured. One patient with polymicrobial pansinusitis did not respond to moxalactam. No patients developed meningitis. All of the isolates tested were inhibited by less than or equal to 5 micrograms of moxalactam per ml, except for one Staphylococcus epidermidis isolate which was resistant to greater than 20 micrograms/ml. Five patients had transient neutropenia which resolved after the drug was discontinued. The mean peak serum level was 106 micrograms/ml at 15 min after a 50-mg/kg dose. The mean elimination half-life was 91.2 min. These data indicate that this dosage of moxalactam is a safe and effective treatment for bacterial infections outside the central nervous system.     

Current status of parenteral feeding with fat emulsions. Clinical experience in children

Total parenteral nutrition with lipid emulsions is considered to be a standard regimen in Europe treating pediatric diseases since more than 10 years. Due to the high energy requirements during childhood only by administration of fat emulsions the adequate input of energy can be guaranteed. It should be emphasized that i.v. administration of lipid emulsion must be performed continuously (by means of a bypass or with mixed solutions) in a dosage up to 2 g/kg/day. In order to control the function of fat elimination from the vessel system the daily estimation of serum triglycerides, which should not exceed values higher than 150-200 mg/dl during the infusion regime is highly recommended. Parenteral nutrition with fat should be performed according to strict indications; contraindications against administration of fat are severe shock, severe coagulation disturbances and rare forms of lipid disorders (with inability to metabolize fats, such as the inborn Apolipoprotein-C-II-deficiency). Observing all rules including strict sterile cautions, parenteral nutrition with fat serves as a valuable well-experienced tool treating pediatric patients. Beside the known problems with the catheter no problems should be expected.     

Hematologic effects of linezolid: summary of clinical experience

Linezolid has been associated with reversible myelosuppression. Clinical trial data were evaluated for anemia, thrombocytopenia, and neutropenia. Thrombocytopenia and a slight increased risk for anemia were evident at > or =2 weeks of linezolid treatment. Hematologic abnormalities were consistent with mild, reversible, duration-dependent myelosuppression. Appropriate monitoring is warranted with linezolid use.     

Clinical assessment of cardiac performance in infants and children following cardiac surgery

Objective To compare clinical assessment of cardiac performance with an invasive method of haemodynamic monitoring.Design and setting Prospective observational study in a 16-bed tertiary paediatric intensive care unit.Patients and participants Infants and children undergoing cardiopulmonary bypass and surgical repair of congenital heart lesions.Interventions Based on physical examination and routinely available haemodynamic monitoring in the paediatric intensive care unit, medical and nursing staff assessed cardiac index, systemic vascular resistance index and volume status. Clinical assessment was compared with cardiac index, systemic vascular resistance index and global end diastolic volume index, obtained by femoral artery thermodilution.Measurements and results A total of 76 clinical estimations of the three parameters were made in 16 infants and children undergoing biventricular repair of congenital heart lesions. Agreement was poor between clinical and invasive methods of determining all three studied parameters of cardiac performance. Cardiac index was significantly underestimated clinically; mean difference was 0.71 l min^–1 m^–2 (95% range of agreement ±2.7). Clinical estimates of systemic vascular resistance (weighted =0.15) and volume status (weighted =0.04) showed poor levels of agreement with measured values and were overestimated clinically. There was one complication related to a femoral arterial catheter and one device failure.Conclusions Routine clinical assessment of parameters of cardiac performance agreed poorly with invasive determinations of these indices. Management decisions based on inaccurate clinical assessments may be detrimental to patients. Invasive haemodynamic monitoring using femoral artery thermodilution warrants cautious further evaluation as there is little agreement with clinical assessment which is presently standard accepted care in this patient population.     

Initial experience with fenoldopam in children

Fenoldopam is a direct-acting vasodilator that acts at the postsynaptic dopamine 1 receptors in renal, coronary, cerebral, and splanchnic vasculature resulting in arterial dilation and a lowering of the mean arterial pressure (MAP). Preliminary evidence suggests its efficacy in the treatment of hypertensive urgencies and emergencies in adults. We present four children in whom fenoldopam was used to control MAP in various clinical scenarios, including hypertensive emergencies and urgencies, intraoperative reduction of MAP for controlled hypotension, and control of MAP during extracorporeal membrane oxygenation. The possible applications of fenoldopam and suggested dosing regimens in children are reviewed.     

Clinical uses and controversies of neuromuscular blocking agents in infants and children.

OBJECTIVE: To review the pharmacology of neuromuscular blocking drugs (NMBDs), their use in critically ill or injured infants and children, and the relevance of developmental changes in neuromuscular transmission. DATA SOURCES: Computerized search of the medical literature. STUDY SELECTION: Studies specifically examining the following were reviewed: a) the developmental changes in neuromuscular transmission; b) the pharmacokinetics and pharmacodynamics of all clinically available NMBDs in neonates, infants, children, and adults; and c) clinical experience with NMBDs in the critical care setting. Particular attention was directed toward studies in the pediatric population. DATA SYNTHESIS: Neuromuscular transmission undergoes maturational changes during the first 2 months of life. Alterations in body composition and organ function affect the pharmacokinetics and pharmacodynamics of the NMBDs throughout active growth and development. Numerous NMBDs have been developed during the last two decades with unique pharmacologic profiles and potential clinical advantages. The NMBDs are routinely used in critically ill or injured patients of all ages. This widespread use is associated with rare but significant clinical complications, such as prolonged weakness. CONCLUSIONS: Significant gaps in our knowledge of the pharmacokinetics and pharmacodynamics of NMBDs in infants and children continue to exist. Alterations in electrolyte balance and organ-specific drug metabolism may contribute to complications with the use of NMBDs in the critical care arena.     

小儿急性阑尾炎CT联合B超检查的临床意义

目的探讨CT和B超检查诊断小儿急性阑尾炎的临床意义。方法回顾性分析53例小儿急性阑尾炎的临床、CT和B超特征。结果CT与B超共同诊断为单纯性阑尾炎17例、化脓性阑尾炎13例、坏疽性阑尾炎10例、阑尾周围脓肿13例；急性阑尾炎的CT直接征象为阑尾肿大增粗（直径〉6mm）、壁增厚和阑尾石，间接征象有阑尾．盲肠周围脂肪内条索影等；B超征象为阑尾肿胀增粗（直径〉6mm），壁增厚≥2mm，浆膜层毛糙，回声增强，黏膜毛糙，回声中断或阑尾内积液、积脓或粪石。结论CT和B超两者结合对急性阑尾炎的诊断特别是对临床表现不典型的阑尾炎具有很高准确率。     

Pneumonia in infants and children

The diagnosis of pneumonia in infants and children is commonly made despite the lack of a definitive test or screening procedure to aid the clinician. Treatment decisions are usually based upon the knowledge of the most likely causative pathogens important in the individual patient's age group. Morbidity due to pneumonia is, in most cases, mild, so that most children can be managed at home.