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Objective: To compare procalcitonin and C-reactive protein in the detection of neonatal sepsis keeping blood culture as gold standard. Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit, Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, from Jul to Dec 2018. Methodology: Neonates up to 28 days of age with the suspicion of sepsis were selected. All the patients with congenital malformation were excluded. Two bed-sided tests i.e., procalcitonin and C-reactive protein was performed using standardized laboratory methods. The diagnostic strength of both tests was compared. Results: A total of 154 neonates were enrolled in this study. Male neonates were dominant in this study 95 (61.7%). The mean age of patients was 6.1 ± 3.8 days. C reactive protein had a sensitivity and specificity of 50.9% and 28.7% respectively. While procalcitonin was found to have a comparatively high sensitivity and specificity 73.6% and 38.6% respectively. On blood culture test; klebsiella pneumoniae, pseudomonas, staphylococcus aureus were found out to be the most common pathogens. Conclusion: Procalcitonin has a better sensitivity and specificity than C reactive protein in the diagnosis of early neonatal sepsis.

Background\udNeonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs.\udMethods\udThe Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality.\udFindings\udBetween Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69–234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04–74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37–2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life.\udInterpretation\udFindings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs.\udFunding\udBill & Melinda Gates Foundation.

We report the case of a 12 days old baby boy who presented with swelling and bluish discoloration on his left hip at Pakistan Institute of Medical Sciences in November 2018. Ultrasound (USS) was useful in making the diagnosis of a neonatal psoas abscess. He was treated with extraperitoneal drainage and with systemic antibiotics. The clinical presentation and diagnosis, treatment of this rare condition and brief literature review is given in this case report. Key Words: Abscess, Iliopsoas, Neonate, Staphylococcus aureus, Extraperitoneal Drainage. Continuous....

Background: Neonatal sepsis is the third most common reason of neonatal mortality in Pakistan. Blood culture, the gold standard test for diagnosis of neonatal sepsis, is time consuming. Therefore, rapid diagnostic tests with good specificity and sensitivity is needed for accurate and early diagnosis of this condition. The objective of this study was to determine the diagnostic value of abnormal (≥ 0.2) immature-to-total-neutrophil ratio in neonatal sepsis.Material and Methods: This cross-sectional study was carried out on 288 neonates, aged 0-28 days, admitted with suspected sepsis. Detailed history of the neonates was recorded including gender, age, birth weight, maternal age, gestational age and clinical features. Blood culture and Peripheral blood films were done in each case. Differential leucocyte counts, total Polymorphoneutrophil count (PMN), immature neutrophil count, mature neutrophil count and calculation of I/T ratio was carried out in the Pathology Department of PIMS, Islamabad. The study outcome was divided into three groups on the basis of positive or negative blood culture and I/T ratio as normal, probable sepsis and proven sepsis group. Data was analyzed by SPSS version 21.0. Diagnostic value of I/T ratio was determined in NS by calculating values of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) by considering the blood culture as the gold standard test of NS.Results: The mean age and weight of the neonates at the time of admission was 1.1 (± 0.6) days and 2.51 (± 0.40) kg, respectively. About 60% of the neonates were males and 118(41%) neonates had I/T ratio of ≥ 0.2. On the basis of positive or negative blood culture and I/T ratio, 82 (28.5%) neonates were diagnosed as proven sepsis, 43 (14.9%) neonates had probable sepsis and remaining 163 (56.6%) neonates were declared as normal. Out of 82 neonates with positive blood cultures, 75 (91.5%) had I/T ratio ≥ 0.2, while 7 (8.5%) had I/T ratio ≤ 0.2. The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of abnormal I/T ratio to diagnose neonatal sepsis was 91%, 79%, 64%, 96% and 83%, respectively.Conclusions: Due to substantially high diagnostic accuracy of I/T ratio ≥ 0.2, we recommend it as a useful, rapid and cost-effective tool in accurate diagnosis of neonatal sepsis.

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs., Genomic and clinical analysis of 916 bacterial isolates from neonates with sepsis in seven low- and middle-income countries (the BARNARDS study) reveals that the main species present were antimicrobial-resistant Klebsiella, Escherichia coli and Enterobacter.

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. Interpretation Our data raise questions about the empirical use of combined ampicillin–gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. Funding The Bill & Melinda Gates Foundation.

Bartter syndrome is an autosomal recessive disorder caused by gene mutations that involve hypokalaemia, hypochloraemia and metabolic alkalosis along with raised serum renin, hyperaldosteronism and normal blood pressure. We report two cases of neonatal Bartter syndrome. Case 1 was a product of non-consanguineous marriage and mother had unexplained polyhydramnios in pregnancy while case 2 was a product of consanguineous marriage. Both cases were diagnosed based on hypokalaemia, hypochloraemia and metabolic alkalosis along with elevated serum renin and aldosterone levels. Case 1 positively responded to indomethacin while case 2 had Protein C and S deficiency and sepsis as coexisting diseases and thus could not be given indomethacin and expired. Regular antenatal visits can help in diagnosis of the syndrome particularly if unexplained poly hydramniosis investigated .

To compare the need of mechanical ventilation between LISA (less invasive surfactant administration) method and conventional INSURE method (INtubation SURfactant administration and Extubation) in spontaneously breathing preterm infants with respiratory distress syndrome (RDS).An experimental study.Department of Neonatology, PIMS, Islamabad, from April to December 2017.A total of 100 preterm infants34 weeks gestation, on nasal CPAP requiring fraction of inspire oxygen (FiO2)0.4, with respiratory distress syndrome (RDS) were included in the study and divided randomly into two groups, 50 each.There were 28 (56%) males in LISA and 31 (62%) in the INSURE group. Median birth weight was 1300 grams (IQR 600) in LISA, while 1400 grams (IQR 400) in INSURE infants. C-section rate was 52% (n=26) and 48% (n=24) in LISA and INSURE, respectively. Pre-natal steroids were given to 38 patients (76%) in LISA and 30 patients (60%) in INSURE group. LISA patients had significantly less need of mechanical ventilation with p-value0.05 {30% (n=15) vs. 60% (n=30)}. The median duration of mechanical ventilation was 40 hours (IQR 75) and 71 hours (IQR 62) in LISA and INSURE, respectively. Similarly, median FiO2 reduction was 30 (IQR 30) in LISA group and it was 25 (IQR 10) in INSURE group, with p-value0.05. There was no significant difference in mortality, hospital stay and complications.LISA technique was safe, non-invasive approach of surfactant administration, with reduced need of mechanical ventilation rate and duration.

Phosphorylation of the ribosomal S6 subunit is tightly correlated with enhanced translation initiation of a subset of mRNAs that encodes components of the protein synthesis machinery, which is an important early event that controls mammalian cell growth and proliferation. The recently identified S6 kinase 2 (S6K2), together with its homologue S6K1, is likely responsible for the mitogen-stimulated phosphorylation of S6. Like S6K1, the activation of S6K2 requires signaling from both the phosphatidylinositol 3-kinase and the mammalian target of rapamycin (mTOR). Here we report the investigation of the mechanisms of S6K2 regulation by mTOR. We demonstrate that similar to S6K1 the serum activation of S6K2 in cells is dependent on mTOR kinase activity, amino acid sufficiency, and phosphatidic acid. Previously we have shown that mTOR is a cytoplasmic-nuclear shuttling protein. As a predominantly nuclear protein, S6K2 activation was facilitated by enhanced mTOR nuclear import with the tagging of an exogenous nuclear localization signal and diminished by enhanced mTOR nuclear export with the tagging of a nuclear export sequence. However, further increase of mTOR nuclear import by the tagging of four copies of nuclear localization signal resulted in its decreased ability to activate S6K2, suggesting that mTOR nuclear export may also be an integral part of the activation process. Consistently, the nuclear export inhibitor leptomycin B inhibited S6K2 activation. Taken together, our observations suggest a novel regulatory mechanism in which an optimal cytoplasmic-nuclear distribution or shuttling rate for mTOR is required for maximal activation of the nuclear S6K2.