Healthcare-worker-associated outbreak of Panton-Valentine-leukocidin-producing meticillin-sensitive Staphylococcus aureus in a large neonatal unit in London: successful targeted suppression therapy following failure of mass suppression therapy.

BACKGROUND: Staphylococcus aureus is a leading cause of healthcare-associated infection, and outbreaks have been associated with neonatal units and colonization of healthcare workers. AIM: To describe an outbreak of Panton-Valentine-leukocidin-producing meticillin-sensitive Staphylococcus aureus (PVL-MSSA) in a neonatal intensive care unit. METHODS: Multi-disciplinary outbreak control investigation. RESULTS: Over a period of 16 months, seven neonates were identified as positive for PVL-MSSA. Isolates were identified in blood cultures (two patients), nasopharyngeal aspirate (one patient) and rectal screening swabs (four patients). Epidemiological and whole-genome sequencing data suggested a long-term carrier as the most likely source. Despite two rounds of mass suppression therapy of staff, using chlorhexidine initially followed by octenidine-based regimens, positive patients continued to be identified. Staff screening subsequently identified one healthcare worker colonized with the outbreak strain of PVL-MSSA who underwent enhanced screening and further suppression therapy. No further cases have been identified to date. Compliance with mass suppression therapy was >95% and a post-administration staff satisfaction survey showed that the majority of staff agreed with the steps taken, with low rates of adverse reactions. CONCLUSION: S. aureus outbreaks are commonly associated with colonization of healthcare workers, and are challenging to manage within environments such as neonatal units. This study highlights the utility of whole-genome sequencing in identifying and mapping an outbreak. It is recommended that targeted staff screening should be considered early in similar outbreaks. In this setting, mass suppression therapy was not an effective strategy despite a high level of staff engagement and compliance.

Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage.

AIMS: To investigate the relation between cerebral blood flow on the first day of postnatal life and the severity of any subsequent germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH). METHODS: Cerebral blood flow was measured in 24 babies during the first 24 hours of life using near infrared spectroscopy. Repeated cerebral ultrasound examination was performed to define the maximum extent of GMH-IVH. Infants were classified as: normal scan, minor periventricular haemorrhage (haemorrhage that resolved), or severe GMH-IVH (haemorrhage distending the ventricles, that progressed to either post haemorrhagic dilatation or porencephalic cyst formation). RESULTS: Cerebral blood flow was significantly lower in the infants with GMH-IVH (median 7.0 ml/100 g/min) than those without haemorrhage (median 12.2 ml/100 g/min), despite no difference in carbon dioxide tension and a higher mean arterial blood pressure. On subgroup analysis, those infants with severe GMH-IVH had the lowest cerebral blood flow. CONCLUSION: A low cerebral blood flow on the first day of life is associated with the subsequent development of severe intraventricular haemorrhage.

Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain.

The use of near-infrared spectroscopy to measure noninvasively changes in the redox state of cerebral cytochrome oxidase in vivo is controversial. We therefore tested these measurements using a multiwavelength detector in the neonatal pig brain. Exchange transfusion with perfluorocarbons revealed that the spectrum of cytochrome oxidase in the near-infrared was identical in the neonatal pig, the adult rat, and in the purified enzyme. Under normoxic conditions, the neonatal pig brain contained 15 micromol/L deoxyhemoglobin, 29 micromol/L oxyhemoglobin, and 1.2 micromol/L oxidized cytochrome oxidase. The mitochondrial inhibitor cyanide was used to determine whether redox changes in cytochrome oxidase could be detected in the presence of the larger cerebral hemoglobin concentration. Addition of cyanide induced full reduction of cytochrome oxidase in both blooded and bloodless animals. In the blooded animals, subsequent anoxia caused large changes in hemoglobin oxygenation and concentration but did not affect the cytochrome oxidase near-infrared signal. Simultaneous blood oxygenation level-dependent magnetic resonance imaging measurements showed a good correlation with near-infrared measurements of deoxyhemoglobin concentration. Possible interference in the near-infrared measurements from light scattering changes was discounted by simultaneous measurements of the optical pathlength using the cerebral water absorbance as a standard chromophore. We conclude that, under these conditions, near-infrared spectroscopy can accurately measure changes in the cerebral cytochrome oxidase redox state.

Cerebral blood flow is independent of mean arterial blood pressure in preterm infants undergoing intensive care.

OBJECTIVE: Preterm infants are often presumed to have a pressure passive cerebral circulation implying that a low mean arterial blood pressure (MABP) results in reduced cerebral perfusion. The aim of this study was to determine whether cerebral blood flow (CBF) was compromised in preterm infants whose MABP fell below 30 mm Hg (4 kPa). METHODS: Thirty preterm infants undergoing intensive care were studied within the first 24 hours of life. CBF was measured using near infrared spectroscopy. The infants were analyzed in two groups on the basis of their MABP at the time of study: group 1 had a MABP below 30 mm Hg and group 2 more than 30 mm Hg. CBF in the two groups was compared. RESULTS: There was no significant difference in the mean CBF between the two groups. In group 1 the median MABP was 27.2 mm Hg (range, 23.7-29.9 mm Hg) and CBF was 13.9 (standard deviation, +/-6.9) mL . 100 g-1 . min-1. In group 2 the median MABP was 35.3 mm Hg (range, 30.1-39.3 mm Hg) and CBF was 12.3 (standard deviation, +/-6.4) mL . 100 g-1 . min-1. Mortality and incidence of cranial ultrasound scan abnormalities were also not significantly different. CONCLUSION: These results indicate that preterm infants undergoing intensive care are able to maintain adequate cerebral perfusion at a MABP in the range of 23.7 to 39.3 mm Hg.

Cerebral blood flow increases over the first three days of life in extremely preterm neonates.

AIM: To measure changes in cerebral haemodynamics over the first three days of life in very preterm infants with normal brains. METHODS: Eleven mechanically ventilated infants (median gestational age 26 weeks) without evidence of major abnormalities on cranial ultrasound examination were studied. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured using near infrared spectroscopy at least twice over the first three days of life. RESULTS: Cerebral blood flow increased significantly with time (p = 0.02; stepwise linear regression) and this was independent of mean arterial blood pressure, PaCO2, and haematocrit. CONCLUSION: This change is likely to represent a normal adaptive response of the cerebral circulation to postnatal life.

Mild hypothermia after severe transient hypoxia-ischemia reduces the delayed rise in cerebral lactate in the newborn piglet.

This study tested the hypothesis that mild hypothermia after severe transient hypoxia-ischemia reduces the subsequent delayed rise in cerebral lactate peak-area ratios as determined by proton (1H) magnetic resonance spectroscopy (MRS) in the newborn piglet. Nine piglets aged < 24 h underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine]/[inorganic phosphate] had fallen close to zero and [nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] was below about a third of baseline. On resuscitation rectal and tympanic temperatures were lowered to 35 degrees C for 12 h after which normothermia (38.5 degrees C) was resumed. 1H MRS data collected over 48 or 64 h after resuscitation were compared with concurrently established data from 12 piglets similarly subjected to transient cerebral hypoxia-ischemia, but maintained normothermic, and six sham-operated controls. The severity of the primary insult (judged from the time integral of depletion of [NTP]/[EPP]) was similar in the hypothermic and normothermic groups. The maximum lactate/N-acetylaspartate ratio observed between 24 and 48 h after resuscitation in the hypothermic group was 0.10 (0.05-0.97), median (interquartile range), which was significantly lower than that observed in the normothermic group, 1.28 (0.97-2.14), and not significantly different from that observed in the control group, 0.08 (0.06-0.11). Similar results were obtained for lactate/choline and lactate/total creatine. We conclude that mild hypothermia after a severe acute cerebral hypoxic-ischemic insult reduces the delayed elevation in lactate peak-area ratios, thus reflecting reduced lactate accumulation.

Magnesium sulfate after transient hypoxia-ischemia fails to prevent delayed cerebral energy failure in the newborn piglet.

Severely birth-asphyxiated human infants develop delayed ("secondary") cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that i.v. magnesium sulfate (MgSO4) after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Twelve piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine (PCr)]/[inorganic phosphate (Pi)], as determined by phosphorus magnetic resonance spectroscopy, had fallen virtually to zero, and nucleotide triphosphate (NTP) had fallen below a third of baseline. The piglets were randomized to receive, blind, either: 1) three i.v. infusions of 12.5% MgSO4 heptahydrate solution: 400 mg.kg-1 MgSO4.7H2O starting 1 h after resuscitation, and 200 mg.kg-1 12 and 24 h later (n = 6); or 2) three infusions of placebo, 0.9% NaCl (n = 6). Phosphorus and proton spectroscopy were continued until 48 h after resuscitation, and values were compared between the two groups. Mean plasma magnesium levels, 1 h after each of the three doses of MgSO4, were 2.1, 2.0, and 1.9 mmol.L-1, respectively. The severity of the primary insult, determined by the time-integral of depletion of cerebral [NTP]/[exchangeable phosphate pool (EPP)], was similar in the MgSO4-treated and placebo groups. After resuscitation, there was no difference in the progression or severity of delayed energy failure between the two groups, as judged by cerebral [PCr]/[Pi], [NTP]/[EPP], or lactate/creatine and N-acetylaspartate/creatine peak-area ratios. We conclude that MgSO4 did not decrease the severity of delayed cerebral energy failure.

Measurement of cranial optical path length as a function of age using phase resolved near infrared spectroscopy.

Near infrared spectroscopy (NIRS) has been used to measure concentration changes of cerebral hemoglobin and cytochrome in neonates, children, and adults, to study cerebral oxygenation and hemodynamics. To derive quantitative concentration changes from measurements of light attenuation, the optical path length must be known. This is obtained by multiplying the source/ detector separation by a laboratory measured differential path length factor (DPF) which accounts for the increased distance traveled by light due to scattering. DPF has been measured by time of flight techniques on small populations of adults and postmortem infants. The values for adults are greater than those for newborns, and it is not clear how to interpolate the present data for studies on children. Recent developments in instrumentation using phase resolved spectroscopy techniques have produced a bedside unit which can measure optical path length on any subject. We have developed an intensity modulated optical spectrometer which measures path length at four wavelengths. Two hundred and eighty three subjects from 1 d of age to 50 y were studied. Measurements were made at a fixed frequency of 200 MHz and a source detector separation of 4.5 cm. Results suggest a slowly varying age dependence of DPF, following the relation DPF690 = 5.38 + 0.049A0.877, DPF744 = 5.11 + 0.106A0.723, DPF807 = 4.99 + 0.067A0.814, and DPF832 = 4.67 + 0.062A0.819, where DPF690 is the DPF measured at 690 nm and A is age is expressed in years from full term. There was a wide scatter of values, however, implying that ideally DPF should be measured at the time of each study.

Nitric oxide avoids the need for a second course of ECMO in congenital diaphragmatic hernia.

Inhaled nitric oxide was effectively used to avoid the need for a second course of extracorporeal membrane oxygenation (ECMO) in a neonate with a congenital diaphragmatic hernia and recurrent pulmonary hypertension following ECMO.

Role of ECMO in the treatment of respiratory syncytial virus bronchiolitis: a collaborative report.

AIM: To report the collaborative experience of extracorporeal membrane oxygenation (ECMO) in the treatment of respiratory syncytial virus (RSV) bronchiolitis between April 1989 and January 1995. METHODS: The medical records of patients with confirmed RSV bronchiolitis referred to three centres (Leicester, Glasgow, and Great Ormond Street) were reviewed. RESULTS: Twenty four infants were identified. Seventeen had been born prematurely (gestational range 23-40 weeks, median 30 weeks). Thirteen infants had been mechanically ventilated after birth and seven of these had evidence of bronchopulmonary dysplasia (BPD). The age of onset of RSV infection varied from three to 64 weeks (mean 17.4 weeks, median 12 weeks). Ventilation before ECMO ranged from one to 16 days and oxygenation indices at the time of referral ranged from 21-73 (mean 39). Ribavirin was used in eight of the 24 patients. Sixteen patients received venoarterial and eight veno-venous ECMO. ECMO hours ranged from 32-647 (median 196 hours). One infant died (survival rate 96%). Cranial ultrasound abnormalities were detected in three patients. However, at follow up only one of the 23 survivors had evidence of developmental delay. CONCLUSION: A group of paediatric patients in whom ECMO can be of benefit has been identified. The use of ECMO should be considered when other means of support prove unsuccessful.

Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy.

We have used an intensity modulated optical spectrometer, which measures the phase shift across tissue experienced by intensity modulated near-infrared light, to determine the absolute optical pathlength through tissue. The instrument is portable and takes only 5 s to record pathlength at four wavelengths (690 nm, 744 nm, 807 nm and 832 nm). The absolute pathlength divided by the known spacing between the light source and detector on the skin is the differential pathlength factor (DPF) which previous studies have shown is approximately constant for spacings greater than 2.5 cm. DPF results are presented for measurements on 100 adults and 35 newborn infants to determine the statistical variation on the DPF. All measurements were made at a frequency of 200 MHz with source-detector spacings of > 4 cm. Results at 807 nm show a DPF of 4.16(+/- 18.8%) for adult arm, 5.51(+/- 18%) for adult leg, 6.26(+/- 14.1%) for adult head and 4.99(+/- 9%) for the head of a newborn infant. A wavelength dependence was obtained for DPF on all tissues and a difference in DPF between male and female was observed for both the adult arm and leg. The results can be used to improve the quantitation of chromophore concentration changes in adults and newborn infants.