两性霉素B脂质体联合氟康唑治疗早产儿真菌性中枢感染研究

目的 探讨两性霉素B脂质体联合氟康唑治疗早产儿真菌感染的疗效及安全性.方法 收集2009.10 - 2011.5收治的中枢神经系统真菌感染早产儿7例,均应用两性霉素B脂质体联合氟康唑治疗,总疗程8 ～ 12周,监测治疗过程中患儿临床症状、体征及相关的血清学、脑脊液及影像学检查指标.结果 两性霉素B脂质体联合氟康唑足量长疗程治疗使早产儿真菌感染得到良好控制,除1例放弃治疗外,余6例症状明显改善,血培养均转阴,中枢神经系统病灶较前明显改善.治疗过程中未发现较严重的药物不良反应.结论 两性霉素B脂质体联合氟康唑治疗早产儿真菌性中枢感染有效且相对安全.     

Urinary tract infections and diurnal incontinence in girls

To evaluate a possible relationship between urinary tract infections (UTI) and diurnal incontinence (DIC), we studied 251 girls aged 4 years or more who were referred with a history of recurrent UTI and/or DIC. During follow up (mean 35 months), 110 girls (44%) had both UTI and DIC, 50 (20%) only infections, and 41 (16%) only DIC whereas 50 (20%) had neither infection nor DIC. In 110 girls with infections occurring with intervals of at least 6 and 12 months, DIC was definitively initiated by infection on 32 (19%) occasions. Most girls were continent before the infection occurred. When the girls remained free of infection for 6 or 12 months respectively, the frequency of DIC remained unchanged. In conclusion, no support for the concept of DIC leading to UTI was obtained, whereas the reverse was found in some cases and suggested in others.Abbreviations UTI urinary tract infection(s) - DIC diurnal incontinence     

实体瘤患儿行自体外周血干细胞移植治疗中真菌感染情况

目的通过对31例实体瘤患儿行自体外周血干细胞移植(auto-PBSCT)治疗中真菌感染的情况进行分析,总结其临床特点、诊断与治疗经验。方法回顾性分析2006年5月-2009年12月本院儿科收治的31例实体瘤患儿行auto-PBSCT治疗过程中防治真菌感染的过程。结果 1.Ⅳ期进展期神经母细胞瘤患儿2例行自体外周血干细胞移植过程中经微生物学检查明确并肺部真菌感染,其中1例并脑、肝真菌感染;2例患儿血培养均为近平滑假丝酵母菌;4例患儿行肺部CT检查,表现为密度增高、渗出炎症阴影;1例进展期神经母细胞瘤患儿明确真菌感染后应用氟康唑、两性霉素B脂质体、伏立康唑静脉滴注抗真菌治疗有效,体温正常,度过骨髓抑制期,原发病获得部分缓解;1例进展期神经母细胞瘤患儿因存在颅内、骨骼、脊髓、肺、肝多发转移肿瘤,于自体外周血造血干细胞移植9 d后骨髓抑制期死亡。2.部分缓解期Ⅳ期神经母细胞瘤1例及进展期肝母细胞瘤1例患儿表现为发热、咳嗽、抽搐,怀疑侵袭性真菌感染,给予氟康唑、两性霉素B、伏立康唑治疗后好转度过骨髓抑制期,原发病获得部分缓解。3.余27例实体瘤患儿auto-PBSCT治疗中应用氟康唑预防真菌感染,临床未发生侵袭性真菌感染,1例进展期Ⅳ期神经母细胞瘤患儿因有多脏器转移,且有原发心脏损害,大剂量化疗后骨髓抑制期免疫耐受差,导致多脏器衰竭死亡。余26例实体瘤患儿顺利度过骨髓抑制期,病情获得缓解。结论实体瘤患儿auto-PBSCT治疗中易并真菌感染,需结合病史、血培养、G试验及CT、MRI等影像学检查做出诊断,经验性应用氟康唑、伏立康唑、两性霉素B等可防治真菌感染,原发病严重未缓解者预后差。     

Successful treatment of bilateral renal fungal balls with liposomal amphotericin B and fluconazole in an extremely low birth weight infant

At the age of 8 weeks, an extremely low birth weight infant (gestational age 26 0/7 weeks, birth weight 740 g) had non-obstructing bilateral renal fungal balls. Urine cultures had repeatedly grown Candida albicans. Combination therapy with liposomal amphotericin B intravenously and fluconazole orally was administered for 6 weeks. Monotherapy with fluconazole was then continued until complete resolution of the renal fungal balls. Conclusion Combination therapy with liposomal amphotericin B and fluconazole was successful in eliminating non-obstructing bilateral renal fungal balls and obviated the need for surgical intervention. Received: 10 December 1999 and in revised form: 18 February and 12 March 2000 Accepted: 24 March 2000     

Cryptococcal meningitis in a child with hyperimmunoglobulin E syndrome

A 13-year-old boy with hyperimmunoglobulin E (hyper-IgE) syndrome presented with headache, blurred vision, photophtobia and bilateral papilledema due to cryptococcal meningitis. Treatment with amphotericin B, and S-fluorocytosine for several weeks and repeated lumbar punctures did not reduce the intracranial pressure, and a myeloperitoneal shunt was performed. The child was maintained on fluconazole for an additional six months. Patients with hyper-IgE syndrome are at increased risk of opportunistic fungal infections such as cryptococcal meningitis.     

Frequency of urinary tract infection in pediatric liver transplantation candidates

An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty-six children (9 girls, 17 boys; mean age, 7.66 +/- 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilson's disease in one, and alpha-1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 +/- 3.49 yr, which was significantly lower than in those without UTI (9.75 +/- 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60%) patients with UTI. VCUG demonstrated vesicoureteral reflux in two patients. In conclusion, symptomatic UTI is common in children with cirrhosis. It occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease. In febrile children with chronic liver disease, UTI should be considered in the differential diagnosis.     

儿童泌尿系统感染诊治进展

泌尿系统感染(UTI)是儿科最常见的细菌感染性疾病之一,约30%的婴幼儿在初次感染6~12个月反复发作。而在有泌尿系统发育畸形的儿童中,约30%的患儿以UTI为首发表现,故UTI可能是潜在肾脏结构异常的前哨事件。婴幼儿UTI常并膀胱输尿管反流等先天性尿路畸形,对于反复感染的高危患儿,易出现肾脏损害及肾瘢痕,进而导致终末期肾病。因此,早期识别、及时治疗和合理管理对改善预后十分重要。现总结近年来国内外相关文献,以期为儿童UTI的诊治提供临床参考。     

Targeted fluconazole prophylaxis for high-risk very low birth weight infants

Antifungal prophylaxis is increasingly used in very low birth weight (VLBW) infants who are at risk for severe fungal infections. Our objective was to assess the effectiveness of targeted fluconazole prophylaxis for high-risk VLBW infants. A retrospective cohort study with historical controls was performed. During the period 2007-2008, all high-risk VLBW infants (birth weight, ≤1,000?g; gestational age, ≤28?weeks; seven antimicrobial therapy or additional risk factors present) received fluconazole prophylaxis until risk factors were not present. Treated infants were compared to a gestational age- and birth weight-matched untreated cohort. Statistical analyses used univariate and multivariate analyses. The main outcome variable was a breakthrough fungal bloodstream infection (BSI). The prophylaxis cohort of 130 VLBW infants was compared to 319 control infants. The rate of fungal infections was significantly lower in the fluconazole prophylaxis group (1 of 130 vs. 19 of 319, p?=?0.016); however, they did not differ in mortality (16.2 vs. 15?%, p?=?0.77) or complications of prematurity. Fluconazole prophylaxis was associated with a significant decrease in candidal BSI (odds ratio, 0.05; 95?% confidence interval, 0.005-0.523). Selective vs. nonselective prophylaxis reduced the number of infants treated from 247 to 130. Conclusion Targeted fluconazole prophylaxis in VLBW infants is effective in preventing fungal infections without increasing the risk of BSI among low-risk infants.     

Strategies for the prevention of neonatal candidiasis

Invasive fungal infections represent the third-leading cause of late-onset sepsis in very-low-birth-weight infants (VLBWI) and have a high rate of infection-associated mortality. The infants at high risk for fungal sepsis are VLBWI with presence of additional risk factors that contribute to increased colonization and concentration of fungal organisms. Colonization with Candida spp. in neonates is secondary to either maternal vertical transmission or nosocomial acquisition in the nursery. Multiple sites may become colonized and a direct correlation between fungal colonization and subsequent progression to invasive candidemia was determined. Randomized, single and multiple-center, placebo-controlled trials found intravenous fluconazole prophylaxis to be effective in decreasing fungal colonization and sepsis for at-risk preterm infants <1500 g birth weight. The prophylactic use of fluconazole was found to be safe with no significant development of fungal resistance. Fluconazole prophylaxis administered to preterm neonates with birth weight <1000 g and/or 27 weeks' gestation or less has the potential of reducing and potentially eliminating invasive fungal infections and Candida-related mortality.     

Efficacy and safety of itraconazole use in infants

Background

Itraconazole has been used to treat fungal infections, in particular invasive fungal infections in infants or neonates in many countries.

Data sources

Literature search was conducted through Ovid EMBASE, PubMed, ISI Web of Science, CNKI and Google scholarship using the following key words: “pediatric” or “infant” or “neonate” and “fungal infection” in combination with “itraconazole”. Based on the literature and our clinical experience, we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy.

Results

Of 45 articles on the use of itraconazole in infancy, 13 are related to superficial fungal infections including tinea capitis, sporotrichosis, mucosal fungal infections and opportunistic infections. The other 32 articles are related to systemic fungal infections including candidiasis, aspergillosis, histoplasmosis, zygomycosis, trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila.

Conclusion

Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants. With a good compliance, it is cost-effective in treating infantile fungal infections. The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.

     

Neonatal urinary tract infections: Analysis of the patients and recurrences

BACKGROUND: Early diagnosis and proper treatment, including long-term follow up, are very important for neonatal urinary tract infections (UTI). METHODS: The present study reports the analysis and long-term follow-up results of 71 newborns treated for UTI. RESULTS: Forty-one per cent of patients were preterm babies. Suspected sepsis and hyperbilirubinemia were the main presenting features. Community-acquired and nasocomial UTI accounted for 63% and 37% of cases, respectively. The leading causative agents were Escherichia coli for community-acquired UTI and Klebsiella pneumoniae for nasocomial UTI. The urosepsis rate was 5%. Abnormal ultrasonography findings were present in 23% and vesicoureteral reflux was present in 15% of babies. A total of 23% of patients showed renal photopenic areas on dimercaptosuccinic acid scan. The recurrence rate was 28% occurring between 1.5 and 12 months, in particular in the first 6 months. Most of the recurrences developed in patients with no predisposing abnormalities. CONCLUSION: Pediatric nephrologic follow-up of babies experiencing UTI in the neonatal period is very important to identify the predisposing congenital abnormalities and scarred kidneys, to diagnose and to treat the recurrences earlier.     

Infections in children undergoing allogeneic bone marrow transplantation in India

We studied the clinical profile of infections among 221 pediatric patients who underwent 230 allogeneic transplants between 1986 and June 2004. All patients developed febrile neutropenia. There were 283 documented infections, which included bacterial (36.9%), viral (45.7%), fungal (11.1%) and other infections (6.3%) including tuberculosis. Bacterial and fungal infections were more common in the first 30 days following BMT, while viral infections were more common >30 days after BMT. Bacterial pathogens were predominantly gram-negative organisms (72.7%), when compared with gram-positive organisms (27.3%). Common gram-negative organisms included NFGNB, Pseudomonas, Escherichia coli and Klebsiella while coagulase negative Staphylococci was the main gram-positive organism. Bacteremia (61.2%) was the main source positive cultures and was mainly because of gram-negative organisms (81%), predominantly NFGNB and Pseudomonas. Exactly 103/221(43.7%) transplants had 128 documented viral infections commonly because of Cytomegalovirus, Herpes group of viruses and transfusion related hepatitis. Thirty of 221 (13.5%) of transplants had 30 documented fungal infections with the majority being because of aspergillus (90%). Tuberculosis was seen in 1.7% of transplants while catheter infections were seen in 21 patients (9.1%). Infection related mortality was seen in 12% predominantly because of CMV or fungal infections. A sub group analysis (pre-1998 vs. post-1998) revealed higher incidences of gram-negative infections, bacteremia and bacterial infection related mortality in the pre-1998 era when compared with the recent times. The profile and mortality of infections in this series from India is not significantly different from reports from the West.     

氟康唑预防极低出生体重儿真菌感染有效性和安全性的Meta分析

目的 对NICU高危极低出生体重儿预防性应用氟康唑的有效性及安全性的研究进行Meta分析,为更好地预防性使用氟康唑提供依据.方法 制定原始文献的纳入标准及检索策略,检索Cochrane图书馆临床对照试验数据库、PubMed、EMBASE、Ovid全文数据库、近3年有关新生儿感染和抗生素应用的国际儿科会议、中国生物医学文献光盘数据库、中国期刊全文数据库和中国维普数据库中的文献,收集有关对极低出生体重儿预防性应用氟康唑的随机对照临床研究,剔除不符合要求的文献,应用RevMan4.2软件进行Meta分析,采用异质性检验(齐性检验),然后统计合并效应量(加权合并,计算效应尺度及95%CI),得出合并后的RR值及其95%CI.结果 共5篇文献符合纳入标准进入Meta分析.数据合并分析结果显示,预防性应用氟康唑可以明显降低极低出生体重儿的真菌定植率,从48%降低到11%,RR值(95%CI)为0.32(0.23 to 0.44),P<0.000 01;明显降低真菌感染率,从15%降低到6%,RR值(95%CI)为0.44(0.29 to 0.65),P<0.0001;病死率差异性无统计学意义,RR值(95%CI)为0.68(0.43 to 1.07),P=0.09;预防性使用氟康唑没有增加对极低出生体重儿的肝脏和胆红素等不良反应,对念珠菌的最低抑菌浓度也没有影响,但对是否增加氟康唑耐药菌的发生率结论不同.结论 对NICU中高危的极低出生体重儿预防性使用氟康唑可以明显降低真菌的定植率和感染率,但有可能增加氟康唑耐药菌株的发生.不同的NICU是否采用氟康唑预防用药,需要仔细评估,要根据不同NICU的真菌感染率制定不同的预防政策,需要定期随访真菌的感染率,动态观察氟康唑耐药菌株的发生率,随时对预防政策进行调整.     

Uropathogens of various childhood populations and their antibiotic susceptibility

To define the uropathogens of various childhood populations and their antibiotic susceptibility, 646 episodes of urinary tract infections (UTI) were studied. Of the community-acquired UTI 78% were caused by Escherichia coli and 12% by Klebsiella whereas only 65% of hospital-acquired UTI were caused by E. coli (P less than 0.01), and other pathogens, including Pseudomonas, were more common. In children with UTI who did not have an underlying disorder, most infections were caused by E. coli and Klebsiella species. Children with urinary malformations or urinary catheters or those who developed UTI while receiving antibiotic prophylaxis had fewer E. coli infections and more infections caused by other pathogens, including Pseudomonas (P less than 0.01). Children receiving antibiotic prophylaxis had also significantly more Enterococcus and Acinetobacter infections (P less than 0.001), and children with urinary catheters had more Enterobacter infections (P less than 0.05). Isolates of these risk groups showed increased resistance to antibiotics. Only 30-53% were susceptible to trimethoprim-sulfamethoxazole, which is usually recommended for UTI; 19 to 25% and 27 to 66% were susceptible to ampicillin and cephalothin, respectively. In contrast uropathogens of immunocompromised children did not differ significantly from those of children with no underlying disturbances, nor did they show distinct antibiotic susceptibility patterns.     

Prophylactic cefdinir for pediatric cases of complicated urinary tract infection

Background: This study evaluated the effect of prophylactic cefdinir (3 mg/kg given once daily) for the prevention of recurrent and complicated urinary tract infections (UTI) in pediatric patients. Methods: The study included 14 infants who were observed for at least 6 months following the first signs of infection (eight boys, six girls; mean age at admission [±SD]: 6.2 [±7.4] months). Twelve patients had vesico‐ureteric reflux (grade I, two; grade II, three; grade III, six; grade IV, one), and two patients had ureteropelvic junction stenosis. Results: No patients discontinued medication due to diarrhea or other adverse drug reactions. The patients had a 6‐month recurrence‐free rate of 93% (13/14); only one patient had recurrent UTI. The mean urinary cefdinir concentration was 16.3 [±11.7]µg/mL; there was considerable variability among individual measurements, even though the samples were collected at similar intervals after drug intake (mean 18.00 [±2.63] h after dose). However, the lowest measured urinary cefdinir concentration (1.16 µg/mL) was sufficient to eradicate Escherichia coli, one of the most significant causes of UTI. Fecal cultures, obtained at monthly clinic visits during the observation period, indicated that the patients' E. coli strains were very sensitive to cefdinir. No patients were infected with Pseudomonas aeruginosa or other non‐fermenting Gram‐negative bacilli or fungi. Conclusions: These results show that cefdinir given 3 mg/kg once daily is very effective and safe for preventing recurrent complicated UTI in infants.     

A study of transfer factor for opportunistic infections in cancer patients

Although supportive care during therapy of patients with malignancies has improved, infection remains the major cause of death in these patients. The problem of ?opportunistic”? infections is becoming more apparent as better antibiotics are found. The control of these infections depends in part on mechanisms of cell-mediated immunity. It has been demonstrated that delayed-type hypersensitivity can be transferred from one person to another. Therefore, we used transfer factor in the treatment of 15 patients, most with leukemia, who had fungal, viral, or mycobacterial infections that were not responding to conventional therapy. Seven of ten evaluable patients had therapeutic control of their infections while receiving transfer factor. Transfer factor appears to have contributed to these clinical improvements and is a modality of treatment that deserves further investigation.     

Effects of cessation of a policy of neonatal fluconazole prophylaxis on fungal resurgence

Fluconazole has been used as prophylaxis against systemic fungal infections in preterm neonates. We conducted a study to determine whether cessation of a policy of prophylactic fluconazole results in a resurgence of fungal infections in a unit. Neonates born in the 3 epoches: A 36-month pre-Fluconazole prophylaxis epoch (Group 1), a 21-month Fluconazole prophylaxis epoch (Group 2) and a 39-month post Fluconazole prophylaxis epoch (Group 3) were compared for incidence and onset of fungal sepsis and resistance patterns. There was a decline in the incidence of fungal sepsis from Group 1 to Group 2, and it remained stable from Group 2 to Group 3. There was no significant difference in resistance to Fluconazole and to any of the azoles in Groups 1, 2 and 3 respectively.     

Cartilage-hair hypoplasia associated with IgG2 deficiency

We report on a 1 year old boy with cartilage-hair hypoplasia (CHH). He suffered from recurrent upper respiratory infections and short-limbed dwarfism. As with most patients with CHH, he had impaired cellular immunity as determined by lymphocyte reactivity. In addition, he had a selective IgG2 deficiency. This combination of immunodeficiencies has not previously been reported for patients with CHH. His recurrent upper respiratory infections were likely to be associated with cellular immunodeficiency and IgG2 deficiency.     

Chronic granulomatous disease presenting with disseminated intracranial aspergillosis

We describe an 8-year-old boy who presented with multiple unresectable aspergillus brain abscesses as the initial presentation of X-linked chronic granulomatous disease (CGD). He failed initial therapy with amphotericin B, but was subsequently salvaged with voriconazole. CGD should be considered in the differential diagnosis for all children presenting with invasive fungal infections, particularly, those involving the central nervous system (CNS). Whereas, optimal pharmacologic therapy is still unknown for CNS aspergillosis, voriconazole may have an advantage due to its ability to cross the blood brain barrier and excellent oral absorption and bioavailability.     

Bilateral megaureters in the Adriamycin rat model

Congenital obstructive uropathy is associated with significant morbidity and mortality in the human neonate. The pathophysiology of congenital obstructive uropathy is poorly understood. There are very few experimental models of prenatal obstruction of the urinary tract, except in the fetal lamb or inbred rats. Prenatal exposure to Adriamycin in a rat model leads to a spectrum of malformations including urinary tract anomalies. We hypothesized that Adriamycin administration during a particular time frame could yield a high incidence of urinary tract anomalies and therefore designed this study to investigate the rates of urinary tract anomalies at different windows of Adriamycin injection in rat embryos. Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats at different times from days 6 to 10 of gestation. Control animals were given saline. Embryos recovered on gestational day 21 by cesarean section were examined for urinary tract anomalies, and malformations were noted. Sections were then processed for paraffin embedding, sectioned at 5 m, and stained with hematoxylin and eosin for histological examination. Anomalies of the urinary tract occurred maximally following Adriamycin administration on days 7, 8, and 9 of gestation (91.6%) compared with 16% of controls. The most common urinary tract anomaly in the Adriamycin group was bilateral megaureters with a hypoplastic bladder (81%). Other anomalies included unilateral or bilateral ureterohydronephrosis with a normal-sized bladder, duplex kidney, and unilateral or bilateral renal agenesis. In conclusion, the critical embryologic window for the development of bilateral megaureters with a small bladder in the Adriamycin rat model occurs following Adriamycin administration on gestational days 7–9. This simple experimental model of bilateral megaureter may allow further research into the pathophysiology of this condition.