Identifying Foods That Optimize Intake of Key Micronutrients During Pregnancy.

BACKGROUND: Most pregnant women in the United States are at risk of inadequate intake of vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids from foods alone. Very few United States dietary supplements provide sufficient doses of all 6 nutrients without inducing excess intake. OBJECTIVE: We aimed to identify energy-efficient foods that provide sufficient doses of these nutrients and could be consumed in lieu of dietary supplements to achieve the recommended intake in pregnancy. METHODS: In a previous analysis of 2,450 pregnant women, we calculated the range of additional intake needed to shift 90% of participants to intake above the estimated average requirement and keep 90% below the tolerable upper level for these 6 nutrients. Here, we identified foods and beverages from the 2019 to 2020 Food and Nutrient Database for Dietary Studies that provide target levels of these nutrients without exceeding the additional energy intake recommended for pregnancy beginning in the second trimester (340 kilocalories). RESULTS: We identified 2358 candidate foods meeting the target intake range for at least one nutrient. No candidate foods provided target amounts of all 6 nutrients. Seaweed (raw or cooked without fat) provided sufficient vitamin A, folate, calcium, iron, and omega-3s (5 of 6 nutrients) but would require an intake of >5 cups/d. Twenty-one other foods/beverages (mainly fish, vegetables, and beverages) provided target amounts of 4 of the 6 nutrients. Few foods met targets for vitamin D (n = 54) or iron (n = 93). CONCLUSIONS: Results highlight the difficulty in meeting nutritional requirements from diet alone and imply that dietary supplements are likely necessary to meet vitamin D and iron targets in pregnancy, as well as omega-3 fatty acid targets for individuals who do not consume fish products. Other foods could be added in limited amounts to help meet intake targets without exceeding caloric recommendations or nutrient safety limits.

Phylogenetically diverse Bradyrhizobium genospecies nodulate Bambara groundnut (Vigna subterranea L. Verdc) and soybean (Glycine max L. Merril) in the northern savanna zones of Ghana.

A total of 102 bacterial strains isolated from nodules of three Bambara groundnut and one soybean cultivars grown in nineteen soil samples collected from northern Ghana were characterized using multilocus gene sequence analysis. Based on a concatenated sequence analysis (glnII-rpoB-recA-gyrB-atpD-dnaK), 54 representative strains were distributed in 12 distinct lineages, many of which were placed mainly in the Bradyrhizobium japonicum and Bradyrhizobium elkanii supergroups. Twenty-four of the 54 representative strains belonged to seven putative novel species, while 30 were conspecific with four recognized Bradyrhizobium species. The nodA phylogeny placed all the representative strains in the cosmopolitan nodA clade III. The strains were further separated in seven nodA subclusters with reference strains mainly of African origin. The nifH phylogeny was somewhat congruent with the nodA phylogeny, but both symbiotic genes were mostly incongruent with the core housekeeping gene phylogeny indicating that the strains acquired their symbiotic genes horizontally from distantly related Bradyrhizobium species. Using redundancy analysis, the distribution of genospecies was found to be influenced by the edaphic factors of the respective sampling sites. In general, these results mainly underscore the high genetic diversity of Bambara groundnut-nodulating bradyrhizobia in Ghanaian soils and suggest a possible vast resource of adapted inoculant strains.

Push button replication: Is impact evaluation evidence for international development verifiable?

OBJECTIVE: Empirical research that cannot be reproduced using the original dataset and software code (replication files) creates a credibility challenge, as it means those published findings are not verifiable. This study reports the results of a research audit exercise, known as the push button replication project, that tested a sample of studies that use similar empirical methods but span a variety of academic fields. METHODS: We developed and piloted a detailed protocol for conducting push button replication and determining the level of comparability of these replication findings to original findings. We drew a sample of articles from the ten journals that published the most impact evaluations from low- and middle-income countries from 2010 through 2012. This set includes health, economics, and development journals. We then selected all articles in these journals published in 2014 that meet the same inclusion criteria and implemented the protocol on the sample. RESULTS: Of the 109 articles in our sample, only 27 are push button replicable, meaning the provided code run on the provided dataset produces comparable findings for the key results in the published article. The authors of 59 of the articles refused to provide replication files. Thirty of these 59 articles were published in journals that had replication file requirements in 2014, meaning these articles are non-compliant with their journal requirements. For the remaining 23 of the 109 articles, we confirmed that three had proprietary data, we received incomplete replication files for 15, and we found minor differences in the replication results for five. CONCLUSION: The findings presented here reveal that many economics, development, and public health researchers are a long way from adopting the norm of open research. Journals do not appear to be playing a strong role in ensuring the availability of replication files.

Symbiotic N2 Fixation and Grain Yield of Endangered Kersting's Groundnut Landraces in Response to Soil and Plant Associated Bradyrhizobium Inoculation to Promote Ecological Resource-Use Efficiency.

Kersting's groundnut (Macrotyloma geocarpum Harms) is a neglected, endangered food and medicinal legume in Africa. Efforts to harness the benefits of the legume-rhizobia symbiosis have focused on few major legumes to the neglect of underutilized ones such as Kersting's groundnut. This study assessed plant growth, N-fixed and grain yield of five Kersting's groundnut landraces in response to inoculation with Bradyrhizobium strain CB756 at two locations in the Northern Region of Ghana. The transferability of cowpea-derived Simple Sequence Repeat (SSR) markers to Kersting's groundnut was also assessed. The symbiotic results revealed significant variation in nodulation, shoot biomass, δ15N, percent N derived from fixation, amount of N-fixed and soil N uptake. The cross-taxa SSR primers revealed monomorphic bands with sizes within the expected range in all the Kersting's groundnut landraces. The results of the aligned nucleotide sequences revealed marked genetic variability among the landraces. Kersting's groundnut was found to be a low N2-fixer, with 28-45% of its N derived from fixation at Nyankpala and 15-29% at Savelugu. Nitrogen contribution was 28-50 kg N-fixed·ha-1 at Nyankpala, and 12-32 kg N-fixed·ha-1 at Savelugu. Uninoculated plants of the Kersting's groundnut landraces Puffeun, Dowie, Sigiri and Boli, respectively, contributed 22, 16, 13, and 15 kg N-fixed·ha-1 from symbiosis at Savelugu as opposed to 89, 82, 69, and 89 kg N·ha-1 from soil. Landrace Puffeun was highly compatible with the introduced strain CB756 if based on δ15N and %Ndfa values, while Dowie, Funsi and Boli showed greater compatibility with native rhizobia in Ghanaian soils. The unimproved Kersting's groundnut in association with soil microsymbionts could produce grain yield of 1,137-1,556 kg ha-1 at Nyankpala, and 921-1,192 kg ha-1 at Savelugu. These findings suggest the need for further work to improve the efficiency of the Kersting's groundnut-rhizobia symbiosis for increased grain yield and resource-use efficiency in cropping systems.

Bacteria related to Bradyrhizobium yuanmingense from Ghana are effective groundnut micro-symbionts.

The identification of locally-adapted rhizobia for effective inoculation of grain legumes in Africa's semiarid regions is strategic for developing and optimizing cheap nitrogen fixation technologies for smallholder farmers. This study was aimed at selecting and characterising effective native rhizobia, from Ghanaian soils for groundnut (Arachis hypogaea L.) inoculation. From surface-disinfected root nodules of cowpea and groundnut plants grown on farmers' fields, 150 bacterial isolates were obtained, 30 of which were eventually found to nodulate groundnut plants. After testing the symbiotic potential of these isolates on groundnut on sterilized substrate, seven of them, designated as KNUST 1001-1007, were evaluated in an open field pot experiment using 15N-labelled soil. Although 15N dilution analyses did not indicate differences among treatments in the proportion of nitrogen (N) derived from the atmosphere (%Ndfa), all seven strains increased total N derived from N2 fixation by inoculated groundnut plants as compared to the non-inoculated control. Inoculation with KNUST 1002 led to total N accumulation as high as that of the groundnut reference strain 32H1. Genetic characterisation of the isolates by sequence analysis of 16S rRNA gene, 16S - 23S rRNA intergenic transcribed spacer (ITS) region and nodC gene revealed that isolates KNUST 1003 and 1007 were related to Rhizobium tropici, a common bean symbiont. The other five isolates, including KNUST 1002 belonged to the Bradyrhizobium genus, being closely related to Bradyrhizobium yuanmingense. Therefore, this study revealed novel native Ghanaian rhizobia with potential for the development of groundnut inoculants.

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

Maize-grain legume intercropping for enhanced resource use efficiency and crop productivity in the Guinea savanna of northern Ghana.

Smallholder farmers in the Guinea savanna practise cereal-legume intercropping to mitigate risks of crop failure in mono-cropping. The productivity of cereal-legume intercrops could be influenced by the spatial arrangement of the intercrops and the soil fertility status. Knowledge on the effect of soil fertility status on intercrop productivity is generally lacking in the Guinea savanna despite the wide variability in soil fertility status in farmers' fields, and the productivity of within-row spatial arrangement of intercrops relative to the distinct-row systems under on-farm conditions has not been studied in the region. We studied effects of maize-legume spatial intercropping patterns and soil fertility status on resource use efficiency, crop productivity and economic profitability under on-farm conditions in the Guinea savanna. Treatments consisted of maize-legume intercropped within-row, 1 row of maize alternated with one row of legume, 2 rows of maize alternated with 2 rows of legume, a sole maize crop and a sole legume crop. These were assessed in the southern Guinea savanna (SGS) and the northern Guinea savanna (NGS) of northern Ghana for two seasons using three fields differing in soil fertility in each agro-ecological zone. Each treatment received 25 kg P and 30 kg K ha-1 at sowing, while maize received 25 kg (intercrop) or 50 kg (sole) N ha-1 at 3 and 6 weeks after sowing. The experiment was conducted in a randomised complete block design with each block of treatments replicated four times per fertility level at each site. Better soil conditions and rainfall in the SGS resulted in 48, 38 and 9% more maize, soybean and groundnut grain yield, respectively produced than in the NGS, while 11% more cowpea grain yield was produced in the NGS. Sole crops of maize and legumes produced significantly more grain yield per unit area than the respective intercrops of maize and legumes. Land equivalent ratios (LERs) of all intercrop patterns were greater than unity indicating more efficient and productive use of environmental resources by intercrops. Sole legumes intercepted more radiation than sole maize, while the interception by intercrops was in between that of sole legumes and sole maize. The intercrop however converted the intercepted radiation more efficiently into grain yield than the sole crops. Economic returns were greater for intercrops than for either sole crop. The within-row intercrop pattern was the most productive and lucrative system. Larger grain yields in the SGS and in fertile fields led to greater economic returns. However, intercropping systems in poorly fertile fields and in the NGS recorded greater LERs (1.16-1.81) compared with fertile fields (1.07-1.54) and with the SGS. This suggests that intercropping is more beneficial in less fertile fields and in more marginal environments such as the NGS. Cowpea and groundnut performed better than soybean when intercropped with maize, though the larger absolute grain yields of soybean resulted in larger net benefits.

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing.

OBJECTIVE: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. STUDY DESIGN: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. RESULTS: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). CONCLUSION: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

Intestinal fatty-acid binding protein and metronidazole response in premature infants.

OBJECTIVES: In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. STUDY DESIGN: We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. RESULTS: Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p = 0.006). CONCLUSION: While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants.

Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents.

Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pediatric age groups. A population PK analysis was performed in NONMEM using samples collected in an opportunistic study from children receiving i.v. clindamycin per standard of care. The final model was used to optimize pediatric dosing to match adult exposure proven effective against CA-MRSA. A total of 194 plasma PK samples collected from 125 children were included in the analysis. A one-compartment model described the data well. The final model included body weight and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (l/h) = 13.7 × (weight/70)(0.75) × (PMA(3.1)/(43.6(3.1) + PMA(3.1))); V (l) = 61.8 × (weight/70). Maturation reached 50% of adult CL values at ~44 weeks PMA. Our findings support age-based dosing.

Risk of necrotizing enterocolitis in very-low-birth-weight infants with isolated atrial and ventricular septal defects.

OBJECTIVE: Necrotizing enterocolitis (NEC) is associated with a significant morbidity and mortality in premature infants. We sought to identify the frequency of NEC in very-low-birth-weight infants with isolated ventricular septal defects (VSDs) or atrial septal defects (ASDs) using a large multicenter database. STUDY DESIGN: We identified a cohort of infants with birth weight <1500 g cared for in 312 neonatal intensive care units (NICUs) managed by the Pediatrix Medical Group between 1997 and 2010. We examined the association between the presence of an ASD or a VSD with development of NEC using logistic regression to control for small-for-gestational age status, antenatal steroid use, antenatal antibiotic use, gestational age, sex, race, Apgar score at 5 min and method of delivery. RESULT: Of the 98 523 infants who met inclusion criteria, 1904 (1.9%) had an ASD, 1943 (2.0%) had a VSD and 146 (0.1%) had both. The incidence of NEC was 6.2% in infants without septal defects, 9.3% in those with an ASD, 7.8% in those with a VSD, and 10.3% in infants with both an ASD and a VSD. Compared with infants without septal defects, the adjusted odds ratios for developing NEC for each group-ASD alone, VSD alone and ASD with VSD-were 1.26 (95% confidence interval 1.07 to 1.49), 1.27 (1.07 to 1.51) and 1.79 (1.03 to 3.12), respectively. CONCLUSION: The presence of an ASD or a VSD was associated with NEC in this cohort of premature infants.

Urinary tract infection concordance with positive blood and cerebrospinal fluid cultures in the neonatal intensive care unit.

OBJECTIVE: Urinary tract infections (UTI) are common in the neonatal intensive care unit (NICU). Blood, urine and cerebrospinal fluid (CSF) cultures are frequently obtained to evaluate for infection. We sought to determine the concordance between positive urine cultures and blood or CSF cultures. STUDY DESIGN: Infants <121 days of age with a UTI admitted to 322 NICUs managed by the Pediatrix Medical Group from 1997 to 2010 were identified. UTIs were defined by isolation of a single pathogenic organism in a urine sample obtained by catheterization or suprapubic tap. The UTI was concordant if the same organism was identified in the blood or CSF within 3 days of the urine culture. RESULT: Of 5681 infants with a urine culture, 984 had 1162 UTIs. In total, 976 UTIs (84%) had a blood culture collected within 3 days, and 127 (13%) were concordant. Of the 1162 UTIs, 77 (7%) had a CSF culture collected within 3 days, and 2 (3%) were concordant. CONCLUSION: Collection of a urine culture in infants evaluated for late-onset sepsis is important. Concordance was observed in 13% of blood cultures and 3% of CSF cultures. These findings may be related to the initiation of empirical antimicrobial therapy before evaluation for disseminated infection or poor blood culture sensitivity.

Fluconazole pharmacokinetics and safety in premature infants.

Invasive candidiasis (IC) in the premature infant population is a common infection that results in substantial morbidity and mortality. For these patients, fluconazole is among the first line therapies to treat and prevent IC, and yet few prospective studies investigating its pharmacokinetics (PK) and safety have been performed in this vulnerable population. We review five phase I studies examining the PK of fluconazole in premature infants, which demonstrate markedly differing kinetics compared to adults. Based on these data, a treatment dose of 12 mg/kg/day, with the potential need of a loading dose of 25 mg/kg to achieve rapid steady state concentrations, achieves surrogate pharmacodynamic targets. Additionally, fluconazole appears to be safe to use in this population, with only minimal reversible hepatobiliary effects.

Neonatal fungal infections: when to treat?

Candida infections are a major cause of morbidity and mortality in neonatal intensive care units. Mortality following Candida bloodstream infections is as high as 40%, and neurodevelopmental impairment is common among survivors. Because invasive fungal infections are common and extremely difficult to diagnose, empirical treatment with antifungal therapy should be considered in high-risk, low-birth-weight infants who fail to quickly respond to empirical antibacterial treatment. Risk factors to consider when deciding to administer empirical antifungal therapy include: prior exposure to third-generation cephalosporins, extreme prematurity, and presence of central venous catheters.

Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units.

BACKGROUND: Very-low-birth-weight (VLBW, <1500 g birth weight) infants are at high risk for both early- and late-onset sepsis. Prior studies have observed a predominance of Gram-negative organisms as a cause of early-onset sepsis and Gram-positive organisms as a cause of late-onset sepsis. These reports are limited to large, academic neonatal intensive care units (NICUs) and may not reflect findings in other units. The purpose of this study was to determine the risk factors for sepsis, the causative organisms, and mortality following infection in a large and diverse sample of NICUs. METHODS: We analysed the results of all cultures obtained from VLBW infants admitted to 313 NICUs from 1997 to 2010. RESULTS: Over 108,000 VLBW infants were admitted during the study period. Early-onset sepsis occurred in 1032 infants, and late-onset sepsis occurred in 12,204 infants. Gram-negative organisms were the most commonly isolated pathogens in early-onset sepsis, and Gram-positive organisms were most commonly isolated in late-onset sepsis. Early- and late-onset sepsis were associated with increased risk of death controlling for other confounders (odds ratio 1.45 [95% confidence interval [CI] 1.21,1.73], and OR 1.30 [95%CI 1.21, 1.40], respectively). CONCLUSIONS: This is the largest report of sepsis in VLBW infants to date. Incidence for early-onset sepsis and late-onset sepsis has changed little over this 14-year period, and overall mortality in VLBW infants with early- and late-onset sepsis is higher than in infants with negative cultures.

Sepsis in young infants with congenital heart disease.

BACKGROUND: We sought to describe the incidence, pathogen distribution, and mortality associated with blood culture-proven sepsis in young infants with congenital heart disease (CHD) admitted to a neonatal intensive care unit (NICU). METHODS: Cohort study of all blood cultures obtained from infants with CHD between 4 and 120 days of age cared for in 250 NICUs managed by the Pediatrix Medical Group in the United States between 1996 and 2007. RESULTS: Of 11,638 infants with CHD, 656 (6%) had 821 episodes of sepsis: a cumulative incidence of 71/1000 admissions. Gram-positive organisms were the most common cause (64%), and coagulase-negative Staphylococcus and Staphylococcus aureus were the most frequently isolated species. On multivariable regression, infants with sepsis were more likely to die compared to infants with sterile blood cultures (odds ratio [OR] = 1.53 [95% confidence interval: 1.09, 2.13]). Infants with Gram-negative bacteraemia and candidaemia were more likely to die than infants with sterile blood cultures (OR = 2.01 [1.20, 3.37], and OR = 3.18 [1.60, 6.34], respectively). CONCLUSION: Infants with CHD have a high incidence of culture-proven sepsis, especially with staphylococcal organisms. Gram-negative bacteraemia and candidaemia are strongly associated with increased mortality in this group of young infants.

Evaluation of a digital microfluidic real-time PCR platform to detect DNA of Candida albicans in blood.

Species of Candida frequently cause life-threatening infections in neonates, transplant and intensive care unit (ICU) patients, and others with compromised host defenses. The successful management of systemic candidiasis depends upon early, rapid diagnosis. Blood cultures are the standard diagnostic method, but identification requires days and less than half of the patients are positive. These limitations may be eliminated by using real-time polymerase chain reaction (PCR) to detect Candida DNA in the blood specimens of patients at risk. Here, we optimized a PCR protocol to detect 5-10 yeasts in low volumes of simulated and clinical specimens. We also used a mouse model of systemic candidiasis and determined that candidemia is optimally detectable during the first few days after infection. However, PCR tests are often costly, labor-intensive, and inconvenient for routine use. To address these obstacles, we evaluated the innovative microfluidic real-time PCR platform (Advanced Liquid Logic, Inc.), which has the potential for full automation and rapid turnaround. Eleven and nine of 16 specimens from individual patients with culture-proven candidemia tested positive for C. albicans DNA by conventional and microfluidic real-time PCR, respectively, for a combined sensitivity of 94%. The microfluidic platform offers a significant technical advance in the detection of microbial DNA in clinical specimens.

Safety and pharmacokinetics of multiple-dose anidulafungin in infants and neonates.

Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5 mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration-time curve (range) was 75 (30-109) µg·h/ml and 98 (55-278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug-related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5 mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight-based dosing and in adult patients receiving 100 mg/day.