Macrorestriction analysis of streptococcus agalactiae (group B Streptococcus) isolated from Malaysia

Streptococcus agalactiae or group B streptococci (GBS) often colonize the gastrointestinal and urogenital tracts of women, who may transmit these organisms to their offspring during the birth process. Using PFGE analysis, the genetic diversity of GBS was studied for strains isolated from pregnant women and their newborn infants in a teaching hospital. A total of 48 different PFGE profiles were obtained from 123 strains, with one profile (S1) appearing to be predominant among both groups studied, There was good overall correlation between the profiles obtained for strains from mother-infant pairs and for strains isolated from different body sites in the same individual. Occasional discrepancies seen in related body sites and among mother-infant pairs suggest concurrent carriage of different strains in the same individual as well as the possibility of an environmental source of organism for the neonate. The overall results demonstrated that many variants of GBS strains occur in Malaysia

Population Pharmacokinetics of Vancomycin in Premature Malaysian Neonates: Identification of Predictors for Dosing Determination▿

The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained using a population pharmacokinetic modeling approach. The predictive performance of the population model was evaluated by visual inspections of diagnostic plots and nonparametric bootstrapping with replacement. Dosing guidelines targeting a value of ≥400 for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) were explored using Monte Carlo simulation. Body size (weight), postmenstrual age, and small-for-gestational-age status are important factors explaining the between-subject variability of vancomycin pharmacokinetic parameter values for premature neonates. The typical population parameter estimates of clearance and distribution volume for a 1-kg premature appropriate-for-gestational-age neonate with a postmenstrual age of 30 weeks were 0.0426 liters/h and 0.523 liters, respectively. There was a 20% reduction in clearance for small-for-gestational-age infants compared to the level for the appropriate-for-gestational-age control. Dosage regimens based on a priori target response values were formulated. In conclusion, the pharmacokinetic parameter values for vancomycin in premature Malaysian neonates were estimated. Improved dosage regimens based on a priori target response values were formulated by incorporating body size, postmenstrual age, and small-for-gestational-age status, using Monte Carlo simulations with the model-estimated pharmacokinetic parameter values

Comparative study of IgA VH3 gene usage in healthy TST- and TST+ population exposed to tuberculosis : deep sequencing analysis

The acquired immune response against tuberculosis is commonly associated with T-cell responses with little known about the role of B cells or antibodies. There have been suggestions that B cells and humoral immunity can modulate the immune response to Mycobacterium tuberculosis. However, the mechanisms involving B-cell responses in M. tuberculosis are not fully understood, in particular the antibody gene preferences. We hypothesized that a preferential use of V genes can be seen associated with resistance to infection mainly in the IgA isotype, which is of prominent importance for infection by pathogens via the mucosal route. We studied healthy individuals with long-term exposure to tuberculosis, infected (TST(+)) and uninfected TST(−)) with M. tuberculosis. From a total of 22 V genes analysed, the TST(−) population preferred the V(H)3-23 and Vκ1 genes. The V(H)3-23 genes were subsequently subjected to 454 amplicon sequencing. The TST(−) population showed a higher frequency of the D3-10 segment compared with the D3-22 segment for the TST(+) population. The J segment usage pattern was similar for both populations with J4 segment being used the most. A preferential pairing of J4 segments to D3-3 was seen for the TST(−) population. The antibodyome difference between both populations suggests a preference for antibodies with V(H)3-23, D3-3, J(H)4 gene usage by the TST(−) population that could be associated with resistance to infection with M. tuberculosis

Major Articles Retinopathy of prematurity in extremely low birth weight infants in Malaysia

PURPOSE To identify differences in incidence, risk factors, and outcomes of retinopathy of prematurity (ROP) between 2 birth weight categories within a cohort of extremely low birth weight (ELBW) infants in Malaysia. METHODS This was a prospective study of infants in the Special Care Nursery at the University of Malaya Medical Centre between 2003 and 2005. Outcome measures were presence or absence of ROP, most severe stage of ROP observed, and whether laser treatment was performed. Risk factors for treatment were analyzed in this cohort of treated patients, who were further divided into groups of birth weight \751 g and birth weight 751-1,000 g. RESULTS The study protocol identified 70 qualifying ELBW infants. Of these, 41 (58.6%) developed ROP and 23 (32.9%) required laser treatment. Mean birth weight was 806.8 g (SD AE 142.5); mean gestation was 27.4 weeks (SD AE 2.2). Infants with birth weight \750 g were twice as likely to require treatment (OR 5 2, p 5 0.038). The risk factors for laser treatment by bivariate analysis were gestation \28 weeks (OR 5 1.8, p 5 0.001), duration of ventilation .1 week (OR 5 1.5, p 5 0.012), and intraventricular hemorrhage (OR 5 2.5, p 5 0.010). Zone 1 ROP was observed only in infants \751 g. CONCLUSIONS The incidence of ROP in ELBW infants in Malaysia is comparable to that seen in the ETROP and CRYO-ROP studies. Within this group, birth weight \750 g doubled the likelihood that treatment would be required. ( J AAPOS 2009;13:446-449) E xtremely low birth weight (ELBW) is defined as a birth weight of \1,000 g. 1 ELBW has been associated with major risk for perinatal mortality and morbidity, including an increased risk for retinopathy of prematurity (ROP). 5,9 However, there are no studies that look for meaningful divisions within the ELBW group. The aim of the present study was to analyze the incidence of ROP and risk factors for the development of ROP requiring laser treatment among 2 birth weight categories within a cohort of ELBW infants as well as differences between these categories in perinatal factors and number of examinations conducted. The basis of the categories for this study was based on the results of the CRYO-ROP study, 2 where ROP was detected in 90% of infants \751 g compared to 66% for those \1,251 g

Comparative cohorts of retinopathy of prematurity outcomes of differing oxygen saturation: real-world outcomes

Objective An ongoing third epidemic of retinopathy of prematurity (ROP) is contributed largely by developing nations. We describe a cohort of infants in a single neonatal unit where two limits of oxygen saturation were administered, to show real-world outcomes from trend in neonatology for higher oxygen to improve survival.Methods and analysis This retrospective, comparative study of prospectively collected data in an ROP screening programme included infants indicated by gestational age ≤32 weeks, birth weight <1501 g, ventilation for 7 days or requiring oxygen >1 month, who underwent dilated fundoscopic examination from age 4 weeks, every 2 weeks until full retinal vascularisation. Infants with ROP were examined weekly and treated where indicated. Data were divided into two epochs. Epoch 1 oxygen saturation targets were [88–92%], epoch 2 targets [90–95% (99%)] with allowance of increase to 20% for several hours after procedures. Outcome measures included development of ROP, treatment, mortality, sepsis and intraventricular haemorrhage.Results A total of 651 infants underwent examination between 2003 and 2016. The incidence of ROP in epoch 1 was 29.1% and epoch 2 was 29.3% (p=0.24). ROP progression doubled in epoch 2 (5 vs 11%, p=0.006), proportion of cases treated halved (14% vs 6%, p=0.0005), sepsis was halved (78.5% vs 41.2%, p<0.0001) and intraventricular haemorrhage doubled (20.2% vs 43.8%, p=0.0001) in epoch 2. Mortality was 4% and 0% in epochs 1 and 2, respectively.Conclusion Incidence of ROP did not differ, although ROP cases that worsened doubled with higher oxygen targets. ROP cases requiring treatment decreased, as did sepsis and mortality. Intraventricular haemorrhage cases doubled

Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial

BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O abstract 2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation. METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission. RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13). CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed

Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0

Objective: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0. Study design: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat. Results: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03). Conclusions: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed