Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

BACKGROUND: Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. OBJECTIVE: Describe the characteristics of UTI, including HRC, in VLBW infants. METHODS: We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. RESULTS: Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. CONCLUSIONS: UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

"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.

B-type natriuretic peptide concentrations to guide treatment of patent ductus arteriosus.

OBJECTIVE: To determine whether b-type natriuretic peptide (BNP) concentrations can guide treatment of patent ductus arteriosus (PDA) to reduce the number of indomethacin doses without increasing morbidity. DESIGN: Prospective, randomised, controlled trial. SETTING: Single-centre referral neonatal intensive care unit. PATIENTS: Infants with echocardiographic diagnosis of PDA. Infants with congenital heart disease or renal insufficiency were excluded. INTERVENTIONS: BNP measurement and echocardiography were performed in all subjects before and after indomethacin treatment. The investigational group had BNP concentrations measured 12 and 24 h after the first dose (before the 2nd and 3rd doses of indomethacin). Indomethacin dosing was withheld in the BNP-guided group if the 12 or 24 h BNP concentrations were found to be <100 pg/ml. MAIN OUTCOME MEASURES: Number of doses of indomethacin given during the primary course of treatment (three doses every 12 h). RESULTS: Sixty patients were randomly assigned to control (n = 30) and BNP-guided (n = 30) treatment groups. There was no difference between the groups with respect to gestational age (26(+3) vs 25(+5) weeks, respectively), Apgar scores, delivery method, gender or indomethacin prophylaxis. Median baseline and 48 h BNP concentrations did not differ between the groups (0 h: 500 vs 542 pg/ml; 48 h: 85 vs 126 pg/ml; control and BNP-guided groups, respectively). During primary indomethacin treatment, the BNP-guided group received fewer doses of indomethacin than controls (70 vs 88 doses, p<0.05). The rate of PDA ligation, intestinal perforation and chronic lung disease did not differ between groups. CONCLUSIONS: BNP-guided treatment reduced the number of primary indomethacin doses. There was no increase in PDA persistence or associated morbidity.

Population pharmacokinetics of fluconazole in young infants.

Fluconazole is being increasingly used to prevent and treat invasive candidiasis in neonates, yet dosing is largely empirical due to the lack of adequate pharmacokinetic (PK) data. We performed a multicenter population PK study of fluconazole in 23- to 40-week-gestation infants less than 120 days of age. We developed a population PK model using nonlinear mixed effect modeling (NONMEM) with the NONMEM algorithm. Covariate effects were predefined and evaluated based on estimation precision and clinical significance. We studied fluconazole PK in 55 infants who at enrollment had a median (range) weight of 1.02 (0.440 to 7.125) kg, a gestational age at birth (BGA) of 26 (23 to 40) weeks, and a postnatal age (PNA) of 2.3 (0.14 to 12.6) weeks. The final data set contained 357 samples; 217/357 (61%) were collected prospectively at prespecified time intervals, and 140/357 (39%) were scavenged from discarded clinical specimens. Fluconazole population PK was best described by a one-compartment model with covariates normalized to median values. The population mean clearance (CL) can be derived for this population by the equation CL (liter/h) equals 0.015 . (weight/1)(0.75) . (BGA/26)(1.739) . (PNA/2)(0.237) . serum creatinine (SCRT)(-4.896) (when SCRT is >1.0 mg/dl), and using a volume of distribution (V) (liter) of 1.024 . (weight/1). The relative standard error around the fixed effects point estimates ranged from 3 to 24%. CL doubles between birth and 28 days of age from 0.008 to 0.016 and from 0.010 to 0.022 liter/kg/h for typical 24- and 32-week-gestation infants, respectively. This population PK model of fluconazole discriminated the impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in young infants will require adjustment for BGA and PNA to achieve targeted systemic drug exposures.

Fungal infections in neonates: update on prevention and treatment.

Neonates with gastrointestinal diseases and extremely preterm infants are at highest risk for developing invasive fungal infections. Candida species are commensal organisms that colonize skin and mucosal surfaces as well as adhere to catheter surfaces. Due to the immature immune system of neonates including compromise of the developing barrier defenses of the skin or mucosal membranes, Candida can invade into the bloodstream and disseminate, often making these infections difficult to eradicate. Treatment of bloodstream infections uniquely involves both starting antifungal therapy and removing central venous catheters. Liposomal amphotericin formulations and echinochandins are currently being studied in neonates. Prevention for high risk patients is now feasible with fluconazole prophylaxis.

Amatoxin poisoning in northern California, 1982-1983.

Twenty-two patients who ate mushrooms containing hepatotoxic amatoxins were treated during the fall and winter seasons of 1982 and 1983. All patients were treated with intensive supportive care and repeated oral doses of activated charcoal. In two patients fulminant hepatic failure developed and they died. One patient in whom encephalopathy developed had an orthotopic liver transplant and survived. Liver biopsy specimens obtained from five patients during the acute illness showed centrilobular hemorrhagic necrosis. The hepatic histopathology in a biopsy specimen from a 5-year-old boy eight weeks after mushrooms were eaten showed bands of fibrosis and islands of hepatocytes suggestive of early cirrhosis. Radioimmunoassay for amanitins, done on the serum from all patients, detected the toxins in only three, probably because most of the specimens were obtained 24 hours or more after the ingestion. This series, with a mortality rate of 9%, illustrates the outcome in patients who receive intensive supportive care and provides a background on which success of specific treatments should be judged.

[Spinal mechanisms of motor disinhibition following barbamyl administration]. / O spinal'nykh mekhanizmakh dvigatel'nogo rastormazhivaniia pri vvedenii barbamila

Prior to and following an intravenous introduction of 250 mg of barbamil by the stimulation of the EMG method the authors studied the H-reflex and M-response of the soleus and gastronemius muscles. The use of singular electric stimula of an increasing intensity as well as multiple repetitions of singular stimula of equal intensity of depicted the following. Barbamil decreases the threshold and increases the amplitude of H-reflexes, and does not influence the M-response. When using pair stimula, barbamil shortens the period of absolute nonexcitation and the second phase of depression in the cycle of restituted H-reflexes to the second stimula in the pair. On this basis the author comes to the conclusion that the action of this preparation on the segmental apparatus of the spinal cord is expressed in an inhibition of gamma-impulsation, a blocking of inhibitive interneurons and an easier reflex excitation of alpha-motoneurons. The report deals with a discussion of these mechanisms for the effect of a prolonged disinhibition.