"Getting to Zero": preventing invasive Candida infections and eliminating infection-related mortality and morbidity in extremely preterm infants

Prevention of invasive Candida infections (ICI) is an achievable goal for every NICU and supported by A-1 evidence. Due to the incidence of ICI, high infection-associated mortality and neurodevelopmental impairment, antifungal prophylaxis should be targeted to infants <1000 g or ≤ 27 weeks gestation. There is A-1 evidence for both fluconazole and nystatin prophylaxis for the prevention of ICI. Evidence currently would favour fluconazole prophylaxis in high-risk preterm infants since intravenous fluconazole prophylaxis has greater efficacy compared to enteral nystatin prophylaxis, efficacy in the most immature patients in whom mortality is the highest, requires less dosing, and can be given to infants with gastrointestinal disease or haemodynamic instability. All NICUs caring for extremely preterm infants should use antifungal prophylaxis. Even in NICUs with low rates of ICI, antifungal prophylaxis is crucial to improving survival and neurodevelopmental outcomes for this vulnerable population. For infants 1000-1500 g if there is concern for ICI in the NICU, either drug could be chosen for prophylaxis. Fluconazole prophylaxis administered at 3 mg/kg twice a week, while intravenous access is required, appears to be the safest and most effective schedule in preventing ICI while attenuating the emergence of fungal resistance. Invasive Candida infections are one group of infections we can prevent.     

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.     

Twice‐weekly fluconazole prophylaxis in premature infants: Association with cholestasis

Background: Fluconazole prophylaxis is effective in preventing invasive candidiasis in extremely low‐birthweight (ELBW) infants. The authors previously reported an increased incidence of cholestasis with fluconazole prophylaxis in ELBW infants, which led to fluconazole prophylaxis being changed to a less frequent dosing (LFD) schedule of twice a week at their institution. The purpose of the present study was therefore to evaluate the effectiveness and safety of LFD fluconazole prophylaxis in preventing invasive candidiasis in ELBW infants. Methods: ELBW infants who received the LFD regimen of fluconazole (twice a week for up to 6 weeks) were compared with infants who received the frequent dosing (FD) schedule (every 72 h for first 2 weeks, every 48 h for next 2 weeks and every 24 h for the final 2 weeks). The two groups were compared for baseline demographics, risk factors for candidiasis, the rate of invasive fungal infection and the incidence and severity of cholestasis. Results: There was no significant difference in the incidence of invasive candidiasis in infants who received the LFD (2/104, 2%) compared to FD (0/140, 0%; P= 0.4) fluconazole prophylaxis. The severity of cholestasis was lower and a trend towards decreased incidence of cholestasis was observed on the LFD schedule. Conclusion: The LFD regimen of fluconazole prophylaxis is effective in preventing invasive fungal infection in ELBW infants. The severity of cholestasis was decreased with the LFD schedule.     

Predictors of trough serum gentamicin concentrations in neonates

Neonates admitted to an intensive care nursery frequently receive gentamicin sulfate therapy. This study was undertaken to determine predictors of an elevated (greater than or equal to 2 mg/L) trough serum concentration of gentamicin sulfate (undesirable because of potential toxic effects). A total of 140 infants with birth weight of 496 to 4545 g and gestational age of 23 to 42 weeks who received gentamicin in the first days of life were studied prospectively. The trough serum concentration of gentamicin was not significantly affected by concurrent use of dopamine hydrochloride, indomethacin, furosemide, or umbilical artery catheters. Of 11 infants weighing between 1000 and 1500 g on an 18-hour dosing interval, 55% had trough serum gentamicin concentration of 2 mg/L or more. Use of the recommended 24-hour dosing interval for infants weighing less than 1000 g and an 18-hour schedule for preterm infants weighing more than 1000 g resulted in a significant number of elevated trough serum gentamicin concentrations in the latter. A dosing interval of 24 hours for infants less than 1500 g and 18 hours in infants between 1500 and 3250 g is suggested.     

Antifungal prophylaxis for the prevention of neonatal candidiasis?

BACKGROUND: Randomized controlled trials suggest that prophylactic administration of antifungal agents reduce the rate of colonization and invasive Candida infection in a subgroup of high-risk very low birth weight (VLBW) neonates. The extent of antifungal prophylaxis use in the United Kingdom and Ireland is unknown. METHODS: A postal questionnaire was administered to neonatologists practicing in the United Kingdom and Ireland caring for VLBW infants. Information was requested on the prophylactic agents used, dosing schedules and duration of therapy. The rationale for reported practices was also ascertained. RESULTS: The response rate was 55% (125/228). Antifungal prophylaxis use was reported by 66 (53%) respondents. First-line agents utilized included oral nystatin (53%) and intravenous fluconazole (41%). The most frequent indications for antifungal prophylaxis included antibiotic administration in 45 (68%) and decreased birth weight in 33 (50%) respondents. The majority of respondents who did not use antifungal prophylaxis felt that the perceived rate of invasive fungal disease within their unit was not high enough to justify its use. CONCLUSIONS: A small majority of clinicians caring for VLBW neonates routinely use antifungal prophylaxis. This reflects the wide variation in the incidence of invasive disease, lack of guidelines supporting a role for prophylaxis and concerns related to emergence of resistant strains.     

Ureaplasma urealyticum and its association with chronic lung disease in Asian neonates

OBJECTIVE: The aim of the present prospective cohort study was to evaluate the relationship between lower respiratory tract colonization with Ureaplasma urealyticum and development of chronic lung disease (CLD) in a high-risk neonatal population. METHODS: Prospective cohort study of preterm infants with a birthweight < 1,500 g needing mechanical ventilation within 24 h of birth in a tertiary care neonatal unit. Endotracheal aspirates from these infants were cultured within 24 h for U. urealyticum and the rate of colonization was determined. The primary outcome measure was the incidence of CLD at 28 days of life. RESULTS: Of the 41 infants studied, 10 (24%) infants were colonized with U. urealyticum. The colonization rate was higher in babies < 1,000 g compared with babies weighing 1,000-1,500 g (P = 0.04). There was no significant difference between the colonized and non-colonized groups with regard to the antenatal use of steroids, maternal prolonged rupture of membranes, gestational age, birthweight, sex, respiratory distress syndrome, use of surfactant, patent ductus arteriosus and gastrooesophageal reflux. Of the 37 survivors, 20 (54%) developed CLD; eight infants (88.5%) in the colonized group developed CLD compared with 12 infants (42.8%) in the non-colonized group (P = 0.01). CONCLUSIONS: Neonates colonized with U. urealyticum were twice as likely to have CLD than non-colonized babies (relative risk 2.01; 95% confidence interval 1.27-3.37). These data suggest a significant association between colonization with U. urealyticum and CLD in infants weighing < 1,500 g.     

Urinary tract infection in very low birth weight preterm infants

BACKGROUND: The prevalence of urinary tract infection (UTI) in preterm neonates ranges between 4 and 25%. The need for a radiologic investigation has not yet been established in very low birth weight premature newborns (<1500 g birth weight). PATIENTS AND METHODS: For an 11-year period (1990 to 2001), medical records of 62 very low birth weight premature infants admitted to a Level III neonatal intensive care unit and who developed UTI were reviewed retrospectively. Results of renal ultrasound and voiding cystourethrograms were compared between extremely low birth weight infants (birth weight, <1000 g) (Group A, Patient 34) and premature infants with birth weight between 1001 and 1500 g (Group B, Patient 28). RESULTS: UTI was more common in Group A (12.2%) than in Group B (5.7%) infants. Renal ultrasound detected mild renal pelvic dilatation (unilateral or bilateral) in 9 infants in Group A (26%) and in 1 infant in Group B (3.5%). Voiding cystourethrograms were performed in 26 of 34 (76%) infants in Group A and in 17 of the 28 (61%) premature infants in Group B. Vesicourethral reflux (VUR) was observed in 6 infants, 2 in group A (7.7%) and 4 in Group B (23%). CONCLUSIONS: We found that the rate of VUR was lower in very low birth weight premature newborns than that reported in the medical literature among term newborns who developed UTI. VUR was less frequent in extremely low birth weight infants who developed UTI than in infants weighing 1001 to 1500 g.     

Routine use of fluconazole prophylaxis in a neonatal intensive care unit does not select natively fluconazole-resistant Candida subspecies

BACKGROUND: We have previously demonstrated efficacy against fungal colonization and infection of fluconazole prophylaxis that was routinely administered since 2001 in our ICU for preterm infants <1500 g at birth (VLBW). With prolonged use, concerns exist for the emergence of acquired fungal resistance and of Candida subspecies that are natively fluconazole-resistant (NFR), mostly Candida glabrata and Candida krusei. METHODS: We evaluated retrospectively all clinical and surveillance fungal isolates obtained from VLBW infants in our NICU during a 10-year period (1997-2006). Each fungal isolate was speciated, infants colonized or infected with NFR-Candida spp were identified and the incidence rates of colonization and infection by these fungal species were calculated. A comparison was made of the 6-year (2001-2006) prophylaxis period with the 4-year (1997-2000) preprophylaxis period. RESULTS: Overall, colonization by NFR-Candida spp ranged between 2.8% and 6.6% of VLBW infants yearly admitted, without any increasing trend during the study period. There were 18 of 434 (4.1%) neonates colonized by these species. Five episodes of systemic fungal infections caused by NFR-Candida spp occurred (incidence rate, 1.1%). No significant differences were detected when compared with the preprophylaxis period, when 11 of 295 infants (3.7%) were colonized by NFR-Candida spp and 4 episodes of infection occurred (1.4%) (P = 0.84 and 0.76, respectively). CONCLUSIONS: Fluconazole prophylaxis administered to VLBW neonates in 4- to 6-week courses after birth does not lead to the emergence of natively fluconazole-resistant Candida spp.     

Candida infections in premature infants weighing less than 1,500 g. Mucocutaneous colonization and incidence of systemic infections]

BACKGROUND: An increasing incidence of systemic candidiasis has been reported in low birth weight infants requiring intensive care. We have retrospectively analyzed mucocutaneous Candida-colonization and infection rate in 422 preterm infants with a birthweight < 1,500 g. METHODS: All infants were treated at the NICU, University of G?ttingen, from 1/1985-5/1991. 359 neonates (85%) were on mechanical ventilation, no prophylactic antimycotic regimen was applied. Mucocutaneous swabs and cultures from various anatomic sites were regularly obtained from all infants. RESULTS: 37/422 preterm infants (8.8%) had mucocutaneous colonization with candida, none of our patients developed systemic candidiasis. In 7 mechanically ventilated patients (1.9%) Candida albicans or Candida tropicalis was repeatedly detected in the bronchial secretions; 1 patient who had invasive Candida-pneumonia was effectively treated with 5-Fluocytosin and Fluconazol. 4/352 (1.1%) central silastic catheters were colonized with Candida albicans; none of these patients required specific treatment. CONCLUSION: The low rate of mucocutaneous Candida-colonization and invasive infection found in our patients may be explained--at least in part--by epidemiological and obstetrical factor as well as by the procedures of the neonatal management.     

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.     

Neonatal liver abscesses due to Candida infection effectively treated with caspofungin

Candidiasis is relatively frequent in neonatal and pediatric intensive care units (ICUs), particularly in preterm infants less than 28 weeks of gestational age. Neonatal candidiasis shows high mortality and is often associated to poor neurodevelopmental prognosis in survivor patients. Amphotericin B and fluconazole are the first choice drugs for the treatment of neonatal candidiasis. Caspofungin is an alternative antifungal agent, which is recommended for invasive candidiasis in adults, but has been poorly experienced in neonates and infants as far as now. We report the first two infants with Candida liver abscesses treated with caspofungin. In the first infant bloodstream and liver lesions were cleared by combination therapy with fluconazole, liposomal amphotericin and caspofungin, while in the second one by caspofungin alone.
Conclusion: Our observations confirm the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal drugs. More extensive data are recommended in order to asses a specific neonatal schedule.     

肺表面活性物质对不同胎龄早产儿肺透明膜病的预防作用

目的 分析不同胎龄早产儿应用肺表面活性物质(PS)预防新生儿肺透明膜病(HMD)的临床疗效及安全性,探讨应用PS预防HMD的最佳时机.方法 2000年9月至2006年9月3所医院NICU收治胎龄＜35周的早产儿911例,其中预防性应用PS 146例(预防组),未预防性应用PS 765例(非预防组).比较两组间不同胎龄早产儿的HMD患病率、7d内病死率、机械通气时间、总吸氧时间、住院时间及主要并发症的发生情况.结果 预防组HMD患病率较非预防组降低了28.1%(P＜0.05).预防组中胎龄＜30周、30周和31周早产儿HMD患病率较非预防组分别降低了43.2%、58.4%、50.9%(P＜0.05).预防组7d内病死率(6.2%)较非预防组(18.2%)明显降低(P＜0.05);其胎龄＜30周、30周和31周早产儿7d内病死率分别减低了23.0%、26.0%、17.6%(P＜0.05).预防组机械通气时间、总吸氧时间均较非预防组明显降低(P＜0.05);但住院时间差异无显著性(P＞0.05).预防组肺出血、呼吸机相关性肺炎、气漏的发生率均低于非预防组(P＜0.05).结论 预防性应用PS可减少HMD患病率,降低早产儿的病死率,缩短机械通气和总吸氧时间,减少肺出血、呼吸机相关性肺炎、气漏的发生率.胎龄≤31周的早产儿预防性应用PS效果更为显著. 18.2%)明显降低(P＜0.05);其胎龄＜30周、30周和31周早产儿7d内病死率分别减低了23.0%、26.O%、17.6%(P＜0.05).预防组机械通气时间、总吸氧时间均较非预防组明显降低(P＜0.05);但住院时间差异无显著性(P＞0.05).预防组肺出血、呼吸机相关性肺炎、气漏的发生率均低于非预防组(P＜0.05).结论 预防性应用PS可减少HMD患病率,降低 产儿的病死率,缩短机械通气和总吸氧时间,减少肺出血、呼吸机相关性肺炎、气漏的发生率.胎龄≤31周的早产儿预防性应用PS效果更为显著. 18.2%)明显降低(P＜0.05);其胎龄＜30周、30周和31周早产儿7d内病死率分别减低了23.0%、26.O%、17.6%(P＜0.05).预防组机械通气时间、总吸氧时间均较非预防组明显降低(P＜0.05);但住院时间差异无显     

氟康唑预防极低出生体重儿侵袭性真菌感染疗效和安全性的Meta分析

目的 系统评价使用氟康唑预防极低出生体重儿（VLBWI）侵袭性真菌感染的疗效和安全性,为临床更好地预防性使用氟康唑提供依据。方法 计算机检索PubMed、Embase、Cochrane图书馆、万方数据库、中国科技期刊数据库（维普）和中国知网,纳入VLBWI预防性使用氟康唑的随机对照试验（RCT）研究。采用Review Manager 5.3统计软件对符合纳入标准的临床研究进行Meta分析。结果 共纳入12篇RCT研究,合计1 679例VLBWI。Meta分析结果显示：试验组（使用氟康唑）侵袭性真菌感染的发生率显著低于安慰剂对照组（RR=0.44,95% CI：0.27~0.71,P < 0.001）;真菌定植率低于对照组（RR=0.31,95% CI：0.24~0.40,P < 0.001）;住院期间病死率低于对照组（RR=0.74,95% CI：0.58~0.94,P=0.01）。使用不同预防剂量氟康唑的两组侵袭性真菌感染发生率和真菌定植率比较差异均无统计学意义（P > 0.05）;耐药情况及并发症发生率在试验组和对照组组间比较差异均无统计学意义（P > 0.05）。结论 氟康唑预防VLBWI侵袭性真菌感染有效且相对安全。小剂量给药可取得类似预防效果。     

Strategies for prevention of nosocomial sepsis in the neonatal intensive care unit

PURPOSE OF REVIEW: Infants hospitalized in the neonatal intensive care unit, particularly preterm infants, have very high rates of nosocomial sepsis (also referred to as late onset sepsis or healthcare-associated sepsis). Today's preventive strategies for nosocomial sepsis focus on augmenting the immunologic and functional immaturities of premature infants and ameliorating the risks of extrinsic factors by the use of prophylactic antibiotics and best clinical practices. RECENT FINDINGS: Topical emollients improved neonatal skin condition, but were associated with an increased risk of nosocomial bacterial sepsis and coagulase negative staphylococcal infections, and thus should not be used in extremely-low-birth-weight infants. Single-center studies have shown that probiotics containing anaerobic bacteria may reduce the rate of necrotizing enterocolitis, the severity of necrotizing enterocolitis, and/or bacterial sepsis. Single-center studies have shown that prophylactic fluconazole reduces the rates of invasive candidiasis and/or colonization of extremely-low-birth-weight infants. Quality improvement projects to improve adherence to appropriate hand hygiene and best practices for central venous catheter insertion and maintenance can reduce rates of nosocomial sepsis. SUMMARY: The safety and efficacy of probiotics and prophylactic fluconazole require large multicenter trials. Quality improvement initiatives, however, can be performed now and can reduce the rates of nosocomial sepsis in the neonatal intensive care unit.     

The pharmacokinetics and safety of micafungin, a novel echinocandin, in premature infants

BACKGROUND:: Candidal fungal infection rates in neonates are increasing and are a significant cause of mortality, especially in low birth weight infants. Micafungin is an echinocandin that works by inhibiting 1,3-beta-D-glucan synthase, an enzyme responsible for fungal cell wall synthesis. The objective of this study was to determine the safety and pharmacokinetics of micafungin in premature infants. METHODS:: This was a phase I, single-dose, multicenter, open-label, sequential-dose trial of intravenous micafungin investigating 3 doses (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg) in 18 premature infants weighing >1000 g (n = 6 in each dosage group). A further 5 infants (500-1000 g) were enrolled in the 0.75 mg/kg dosage group only. RESULTS:: The mean +/- standard deviation gestational age in the >1000 g dosage group was 26.4 +/- 2.4 weeks and, on entry, patients had one or more of a variety of underlying conditions, including sepsis, pneumonia and other infections caused by Candida or other species. Micafungin pharmacokinetics in preterm infants appears linear. However, premature infants >1000 g on average displayed a shorter half-life (8 hours) and a more rapid rate of clearance (approximately 39 mL/h per kg) compared with published data in older children and adults. All doses of micafungin were well tolerated and no serious drug-related adverse events were observed. CONCLUSIONS:: Single doses of micafungin, ranging up to 3.0 mg/kg, appear well tolerated in premature infants weighing >1000 g. The drug's elimination half-life and total plasma clearance in preterm infants appear dissimilar to published values for these parameters in older children and adults. The reason(s) for this apparent difference remain to be investigated.     

Managing "healthy" late preterm infants

Background:  Late preterm infants are often managed in nursery rooms despite the risks associated with prematurity. The objective of this study was to determine the risks facing late preterm infants admitted to nursery rooms and to establish a management strategy.
Methods:  A total of 210 late preterm infants and 2648 mature infants were assessed. Infants born at 35 and 36 weeks' gestation weighing ≥2000 grams admitted to a nursery room and not requiring medical intervention at birth were of particular interest. The admission rates to the neonatal intensive care unit were evaluated according to the chart review.
Results:  Infants born at 35 and 36 weeks' gestation weighing ≥2000 grams had significantly higher admission rates than term infants at birth (Cochran–Mantel–Haenszel test, P < 0.001; common risk ratio, 4.27; 95% confidence interval, 2.41–7.55) and after birth ( P < 0.001; common risk ratio, 3.57; 95% confidence interval, 2.40–5.33). More than 80% of admissions from the nursery room to the neonatal intensive care unit after birth were due to apnea or hypoglycemia in neonates born at 35 and 36 weeks' gestation. The admission rates due to apnea increased with decreasing gestational age. The admission rates due to hypoglycemia with no cause other than prematurity accounted for 24.3% of admissions for those born at 35 weeks' gestation and 14.1% of admissions for those born at 36 weeks' gestation; hypoglycemia due to other causes accounted for fewer admissions.
Conclusion:  The management strategy for late preterm infants should be individualized, based on apnea and hypoglycemia. The respiratory state of late preterm infants should be monitored for at least 2 days, and they should be screened for hypoglycemia on postnatal day 0.     

Risk factors for Candida species colonization of neonatal intensive care unit patients.

BACKGROUND: Candida spp. are increasingly important pathogens in neonatal intensive care units (NICU). Prior colonization is a major risk factor for candidemia, but few studies have focused on risk factors for colonization, particularly in NICU patients. METHODS: A prospective, multicenter cohort study was performed in six NICUs to determine risk factors for Candida colonization. Infant gastrointestinal tracts were cultured on admission and weekly until NICU discharge and health care worker hands were cultured monthly for Candida spp. RESULTS: The prevalence of Candida spp. colonization was 23% (486 of 2157 infants); 299 (14%), 151 (7%) and 74 (3%) were colonized with Candida albicans, Candida parapsilosis and other Candida spp., respectively. Multiple logistic regression analysis adjusting for length of stay, birth weight < or = 1000 g and gestational age < 32 weeks revealed that use of third generation cephalosporins was associated with either C. albicans (155 incident cases) or C. parapsilosis (104 incident cases) colonization. Use of central venous catheters or intravenous lipids were risk factors for C. albicans, whereas delivery by cesarean section was protective. Use of H2 blockers was an independent risk factor for C. parapsilosis. Of 2989 cultures from health care workers' hands, 150 (5%) were positive for C. albicans and 575 (19%) for C. parapsilosis, but carriage rates did not correlate with NICU site-specific rates for infant colonization. CONCLUSIONS: We speculate that NICU patients acquire Candida spp., particularly C. parapsilosis, from the hands of health care workers. H2 blockers, third generation cephalosporins and delayed enteral feedings alter gastrointestinal tract ecology, thereby facilitating colonization.     

早产儿医院感染败血症的临床特点与病原学分析

目的调查分析早产儿医院感染败血症的临床特点、病原菌分布及药敏情况。方法回顾性分析我院新生儿科2007年1月至2011年12月发生医院感染败血症的早产儿病例。结果研究期间共出院早产儿5660例,排除染色体异常和住院时间小于5天的病例,纳入分析5392例,发生医院感染败血症81例,发生率1.5%,共治愈60例,治愈率74.1%。发病时表现多种多样,最常见的实验室指标异常是C反应蛋白（CRP）升高。病原菌以革兰阴性菌最多见（57.6%）,真菌占第二位（30.3%）。其中,革兰阴性杆菌以肺炎克雷伯菌为主,对大部分β内酰胺类抗生素耐药;革兰阳性菌以表皮葡萄球菌为主,大多对青霉素耐药,对万古霉素敏感;真菌感染均为念珠菌,对氟康唑、两性霉素B均敏感。结论早产儿医院感染败血症临床表现各异,CRP升高是较敏感的指标。致病菌主要为革兰阴性菌和真菌,革兰阴性菌对大部分β-内酰胺类抗生素耐药。     

Prolonged indomethacin treatment in preterm infants with symptomatic patent ductus arteriosus: efficacy,drug level monitoring,and patient selection

Indomethacin treatment for 1 week monitored by drug level determinations was evaluated in 32 preterm infants with symptomatic patent ductus arteriousus (sPDA). Inter- and intra-individual indomethacin dispositions varied considerably with the need for marked dosage adjustments to maintain the drug level within the proposed therapeutic range. The overall success rate of this prolonged treatment was 63%. There were no significant differences between the groups of responders (n=20), relapsers (n=5) and non-responders (n=7) with respect to postnatal age, sex, total indomethacin dose, and indomethacin serum concentrations. The responders, however, had significantly higher birth weights. Eighty-five percent of infants weighing more than 1000g (n=20) were treated successfully. Only four of these children experienced adverse reactions. The benefit-to-risk ratio was lowest in the group of infants weighing 1000 g or less (n=12) with a success rate of only 25% and, potentially, severe adverse reactions in ten infants. In conclusion, prolonged indomethacin treatment is an alternative to conventional short-term treatment and appears to be particularly efficacious and safe in infants weighing more than 1000 g. In infants weighing 1000 g or less and suffering from severe pulmonary diseases, this treatment cannot generally be recommended. The advantage of on-line drug level monitoring during indomethacin treatment deserves further investigation.     

Patterns of fungal colonization in preterm infants weighing less than 1000 grams at birth

BACKGROUND: Colonization with Candida spp. is an important risk factor for systemic infection in very low birth weight (VLBW; <1500 g) and extremely low birth weight (ELBW, <1000 g) infants. ELBW infants are at a higher risk than VLBW infants for fungal sepsis and its associated mortality, but few studies have examined fungal colonization exclusively in ELBW infants. METHODS: Fungal colonization data were analyzed retrospectively in 50 high risk ELBW infants. Weekly surveillance fungal cultures of the skin, gastrointestinal tract, respiratory tract and umbilicus had been performed from birth through the first 6 weeks of life. Colonization was analyzed for time of initial colonization, site, species and spread of Candida from one site to another. RESULTS: Candida was isolated from surveillance cultures in 31 of 50 (62%) infants. Colonization was inversely proportional to gestational age. Initial week of both the fungal colonization of the skin [1 (0-6) week, median (range)] and gastrointestinal tract [2 (0-6)] preceded colonization of the respiratory tract [3 (1-6)] (P = 0.0001). Among infants colonized by only 1 of the species, colonization at 2 or more sites occurred similarly with Candida albicans (77%) and Candida parapsilosis (85%), whereas colonization at 3 or more sites occurred more frequently with C. albicans (69%) compared with C. parapsilosis (23%) (P = 0.047). CONCLUSIONS: Fungal colonization occurs on the skin and gastrointestinal tract before the respiratory tract. In addition, C. albicans is more likely than C. parapsilosis to colonize multiple sites.