Causative Agents Of Neonatal Sepsis Research Articles

Population pharmacokinetics of ciprofloxacin in newborns with early onset neonatal sepsis and suspected meningitis.

Neonatal Sepsis accounts for significant proportion of neonatal mortality globally. Ciprofloxacin can be used as an effective antimicrobial against common causative agents of neonatal sepsis. However, there is only limited information about its pharmacokinetic distribution in plasma and Cerebrospinal fluid (CSF) of neonates. Plasma and CSF samples were taken using a sparse sampling technique from neonates who received at least one dose of intravenous ciprofloxacin. Ciprofloxacin levels were analysed using high-performance liquid chromatography (HPLC). Population pharmacokinetic analysis was conducted using a non-linear mixed-effects modelling using Pumas® (Pharmaceutical Modelling and Simulation) package (Version 2.0). 53 neonates were enroled in the study of whom; 9 (17%) had meningitis. The median concentration of ciprofloxacin in CSF was 1.4 (0.94-2.06) ug/ml and plasma was 2.94 (1.8-5.0) ug/ml. A one-compartment model with first-order elimination fitted the data. Body weight was found to be a significant covariate on volume of distribution (Vd). Simulations based on the final model suggest that dose of 10 mg/kg, intravenous b.d may not be able to achieve the desirable indices. One compartment model with weight as a covariate explained the available data. Further studies with modified sampling strategy, larger sample size and variable dose levels are needed.

The effectiveness of empirical antibiotics treatment in neonatal sepsis: a retrospective study

Objective: This study aimed to investigate the effectiveness of empirical antibiotics in neonatal sepsis in Maternity and Children Hospital, Makkah, Saudi Arabia. Methods: This retrospective study was conducted among neonates at the neonatal intensive care unit (NICU) of the Maternity and Children Hospital between the period from November, 2021 to January, 2022. The collected data included demographics and clinical data of neonates, antibiotic administrated, and blood culture results, white blood cells count, and C-reactive protein (CRP) before and after antibiotic administration. Results: The data of 164 neonates were included with the mean age of 17.5±7.8 days. There was a male dominancy (51.8%), and 43.3% had normal body weight. Around 14.6% positive cultures were found with dominancy of Coagulase-negative (COG –ve) staphylococcus (4.9%). Empirical antibiotics revealed significant improvement in WBCs (P=0.002) and CRP (P=0.000). Conclusion: The most causative agents of neonatal sepsis were COG -ve Staphylococcus and E. Coil. Empirical therapy was effective in improving the laboratory markers associated with neonatal sepsis.

Bacteriological Profile and their Susceptibility Pattern in Neonatal Intensive Care Unit at Tertiary Care Hospital in Wah

Introduction: Neonatal sepsis is a clinical syndrome characterized by multiple symptoms and signs of infection during the first month of life. The objective of this study is to determine the frequency of commonly isolated bacteria from patients of neonatal sepsis and their susceptibility patterns in POF hospital at Wah.
 Methods: This cross-sectional study was carried out in POF Hospital Neonatal intensive care unit and Microbiology laboratory from January 2018 to December 2019. The blood samples of patients suspected with neonatal sepsis were processed as per standard methodology.
 Results: Out of ninety blood samples, fifty-one (56.7%) yielded the growth of Gram-negative rods and thirty-nine (43.3%) yielded Gram-positive cocci. Among Gram-positive bacteria, coagulase-negative staphylococci were the most common pathogen isolated from 53.8% cases followed by methicillin-resistant Staphylococcus aureus (15.3%). Among Gram-negative bacteria, Klebsiella pneumoniae (54.90%) was the most frequently identified bacteria followed by Serratia marcescens (27.45%). The Gram-positive cocci were the most susceptible to linezolid (100%) followed by vancomycin (87.2%). The Gram-negative rods depict remarkable resistance to ciprofloxacin (92.2%), gentamicin (100%), and meropenem (54.9%).
 Conclusions: The study concluded a predominance of Gram-negative bacteria as a causative agent of neonatal sepsis in our setup. The bacterial isolates are highly resistant to commonly prescribed oral as well as injectable antibiotics. Implementation of infection control policies is a dire need to combat the grave situation of increasing antibiotic resistance.

Incidence and Antibiogram of Acinetobacter Causing Neonatal Sepsis Among Hospitalised Patients

Background: Acinetobacter species are typical nosocomial pathogens causinginfections and high mortality, almost exclusively in compromised hospitalizedpatients. Multidrug-resistant Acinetobacter spp. blood infection in the neonatalintensive care unit patients create a great problem in hospital settings. The studywas done to detect prevalence of acinetobacter spp. as the causative agent ofneonatal sepsis with its antibiogram
 Materials and methods: A total of 100 clinically suspected neonatal sepsis caseswas enrolled in the study. Bacteriological profile and antibiotic sensitivity pattern ofacinetobacter spp. were done accordingly.
 Results: Among the 100 suspected neonatal sepsis cases, 28% were culture positiveand 72% were culture negative. Klebsiella species was the predominant isolatedbacteria which was 53.58% followed by Acinetobacter spp. (14.28%) E. coli(10.72%)Pseudomonas spp. (7.14%) S. aureus (7.14%) & Candida (7.14%). Acinetobacter spp.showed 100% resistant to ampicillin, ciprofloxacin, gentamycin, amikacin,ceftazidime, cefotaxime & cefepime, 75% resistant to meropenem & 50% sensitiveto levofloxacin.
 Conclusion: It is essential to conduct periodic bacteriological profile along withroutine antimicrobial sensitivity testing time to time for effective management ofneonatal sepsis.
 Chatt Maa Shi Hosp Med Coll J; Vol.19 (1); January 2020; Page 20-23

Epidemiology of neonatal sepsis caused by multidrug resistant pathogens in a neonatal intensive care unit level 3.

Aim Steady progress in intensive treatment worldwide has increased the survival of immature neonates, but with multiple invasive procedures, which have increased the risk of infection, thus the bacterial resistance to antibiotics. The aim of this study was to analyse the epidemiology of multidrug resistance pathogens as causative agents of neonatal sepsis in the neonatal intensive care unit. Methods A retrospective cohort study conducted at the Intensive care unit of the Paediatric Clinic of Tuzla over a three-year period (2016-2018) analysed epidemiology of neonatal sepsis caused by multidrug resistance pathogens. Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results Of the total of 921 treated neonates, multidrug resistance (MDR) pathogens among causative agents of neonatal sepsis were found in 22 neonates (2.38%) with no gender difference. Prematurity and low birth weight were confirmed as the most significant risk factors. From the maternal risk factors a significant difference was found in the first birth and in vitro fertilization. Clinically, MDR sepsis manifested frequently as late onset sepsis, with longer hospital stay and higher mortality. The findings of leukopenia, thrombocytopenia and coagulation disorders were significant. Gram negative bacteria were frequently isolated, in particular Acinetobacter, which showed the greatest resistance to antibiotics. Conclusion Neonatal MDR sepsis is a threat to life, it complicates the treatment, increases costs and mortality. Outcomes can be improved by preventive strategies, earlier and more accurate diagnosis and rational use of antibiotics.

Bacterial Causative Agents of Neonatal Sepsis and Their Antibiotic Susceptibility in Neonatal Intensive Care Units (NICUs) and Neonatal Wards in Iran: A Systematic Review

Context: Sepsis is one of the most common causes of neonatal mortality, especially in developing countries. The purpose of this study was to systematically review the bacterial causative agents of neonatal sepsis and their antibiotic susceptibility in Iran. Material and Methods: We searched all previously published papers to gather related information on Iranian neonatal sepsis in international and national databases (in both Persian and English) from 2006 to 2018. The standard STROBE checklist was used for quality assessment. The data were analyzed by statistical methods with a random-effects model using Stata 14 software. Results: A total of 89,472 neonates with sepsis (presented in 17 studies) were included in this systematic review. The mortality rate of neonates was 28.0%. The proportions of neonatal sepsis caused by Gram-negative and Gram-positive bacteria were 66.0% and 33.0%, respectively. The most common bacteria causing neonatal sepsis were Klebsiella pneumoniae and Pseudomonas aeruginosa (Gram-negative) and coagulase-negative staphylococci and Staphylococcus aureus (Gram-positive). Conclusions: Gram-negative bacteria are the most common causes of neonatal sepsis in Iran. Imipenem is the most effective antibiotic against Gram-negative bacilli and vancomycin against Gram-positive cocci causing neonatal sepsis in Iran.

Group B Streptococcus detection in pregnant women: comparison of qPCR assay, culture, and the Xpert GBS rapid test

BackgroundGroup B Streptococcus (GBS) is one of the most important causative agents of neonatal sepsis. As administration of prophylactic antibiotics during labor can prevent GBS infection, routine screening for this bacterium in prenatal care before the onset of labor is recommended. However, many women present in labor without having undergone such testing during antenatal care, and the turnaround time of detection methods is insufficient for results to be obtained before delivery.MethodsVaginal and anorectal specimens were collected from 270 pregnant women. Each sample was tested by Xpert GBS, qPCR, and culture for GBS detection.ResultsThe overall prevalence of maternal GBS colonization was 30.7% according to Xpert GBS, 51.1% according to qPCR, and 14.3% according to cultures. Considering the qPCR method as the reference, the Xpert GBS had a sensitivity of 53% and specificity of 93%. Positive Xpert GBS results were correlated to marital status (married or cohabitating) and with prematurity as a cause of neonatal hospitalization. Positive cultures were related with ischemic–hypoxic encephalopathy requiring therapeutic hypothermia.ConclusionsCombined enrichment/qPCR and the Xpert GBS rapid test found a high prevalence of GBS colonization. The Xpert GBS technique gives faster results and could be useful for evaluating mothers who present without antenatal GBS screening results and are at risk of preterm labor, thus allowing institution of prophylactic antibiotic therapy.

High prevalence of group B streptococcus ST17 hypervirulent clone among non-pregnant patients from a Hungarian venereology clinic

BackgroundAlthough Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed.MethodsNinety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR.ResultsThe serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene.21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele.ConclusionsThe presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections.This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.

Common Pathogens Associated with Neonatal Sepsis and Their Antibiotic Resistance Pattern in Sohag University Hospital

Introduction: Neonatal sepsis is defined as a clinical syndrome in an infant 28 days of life or younger, manifested by systemic signs of infection and isolation of a bacterial pathogen from the bloodstream[EmanShehab El-Din et al, 2015]. Positive blood culture and sensitivity of the isolate is the best guide to antimicrobial therapy and once started should be modified according to the culture sensitivity reports[Aggarwalet al, 2001]. Aim of the work: To determine clinical and microbiological pattern of neonatal sepsis in Sohag university hospital with special focus on causative pathogens and their response to used antimicrobials. Patient and methods: Our study conducted over a period of 18 months between October 2015 and April 2017 at Sohag university hospital and included 75 neonates with suspected sepsis and positive blood culture using Egyptian neonatal network (EGNN) guidelines, subjected to full clinical examination, septic screen(CBC, ESR and CRP) and blood culture and sensitivity tests. Results: All studied neonates presented with late onset sepsis with higher incidence in infants born via CS especially with low and very low birth weight.The incidence of neonatal sepsis was predominantly due gram negative bacteria mainly Klepseillapneumonae followed by staphylococcus haemolyticusandstaphylococcus epidermidis. Klebseilla isolates showed high sensitivity for aminoglycosides and quinolones antibiotics with resistance to penicillin's group, Staphylococcus isolates showed resistance to penicillin's and aminoglycosides while sensitive to quinolones and nitrofurantions. E.coli and Pseudomonas species showed moderate sensitivity to 3rd generation cephalosporins, aminoglycosides, quinolones and nitrofurantoins with resistance to classic penicillin's. Conclusion: In our study gram negative bacteria mainly Klepseillapneumonae was the most causative agent of neonatal sepsis. Most isolated organisms showed resistance to classic penicillins.Klepseillapneumonaeshowed high sensitivity for aminoglycosides and quinolones, Staphylococcus isolates showed high sensitivity to quinolones and nitrofurantions while E.coli and Pseudomonas species showed moderate sensitivity to 3rd generation cephalosporins, aminoglycosides, quinolones and nitrofurantoins.

Kinetics of Targeted Phage Rescue in a Mouse Model of Systemic Escherichia coli K1.

Escherichia (E.) coli K1 strains remain common causative agents of neonatal sepsis and meningitis. We have isolated a lytic bacteriophage (ΦIK1) against E. coli strain IHE3034 and tested its specificity in vitro, as well as distribution and protective efficacy in vivo. The phage was shown to be specific to the K1 capsular polysaccharide. In the lethal murine model, a high level of protection was afforded by the phage with strict kinetics. A single dose of 1 x 108 phage particles administered 10 and 60 minutes following the bacterial challenge elicited 100 % and 95 % survival, respectively. No mice could be rescued if phage administration occurred 3 hours postinfection. Tissue distribution surveys in the surviving mice revealed that the spleen was the primary organ in which accumulation of active ΦIK1 phages could be detected two weeks after phage administration. These results suggest that bacteriophages have potential as therapeutic agents in the control of systemic infections.

Comparison of microbial pattern in early and late onset neonatal sepsis in referral center Haji Adam Malik hospital Medan Indonesia

Neonatal sepsis contributes a significant rate of infants mortality and morbidity. The pathogens are diverse from region to another and change time to time even in the same place. To analyze the microbial pattern in early and late onset neonatal sepsis andthe pattern of antibiotic resistance of the causative microbes at one of referral center hospital in Indonesia, Haji Adam Malik Hospital, a cross-sectional descriptive study was conducted on neonates with sepsis diagnosis proven with positive blood culture within one year period (2015-2016). Among 626 neonates admitted to perinatology unit, the total of 154 neonates was proven to have neonatal sepsis with positive blood culture with the incidence rate 24.6%. Seventy-nine (51.3%) neonates were diagnosed with early onset sepsis while 75 (48,7%) neonates had late-onset sepsis. Klebsiella pneumonia was the most commonly isolated organism in both early and late onset sepsis, encompassing 19.5% of cases. Periodic surveillance of the causative agents of neonatal sepsis is needed to implement the rational, empirical choice of antibiotic prescription while waiting for blood culture result to come out.

853: The cost effectiveness of multiple GBS screening intervals

Group B streptococcus (GBS) is the leading causative agent of neonatal sepsis in the United States. As such, the CDC recommends a single GBS screening in the form of rectovaginal culture at 35-37 weeks gestation to determine use of maternal intrapartum antibiotic prophylaxis (IAP) to prevent perinatal transmission. However, prediction of perinatal transmission is complicated by the conversion of some women to GBS-positive status prior to delivery, despite a negative initial test result. This study set out to evaluate the use of repeat screening at varying weekly intervals as a cost-effective strategy to decrease rates of GBS transmission to neonates and subsequent outcomes. A decision-analytic model was created using TreeAgePro and probabilities, costs, and utilities derived from the literature. The screening strategies compared included: the usual care of no repeat screening; one additional test at 39, 40, or 41 weeks gestation; every other week testing beginning at 38 weeks; or weekly testing beginning at 37 weeks. This model was then applied to a theoretical cohort of 1,800,000 women based on the estimated number of nulliparous, term-births annually in the United States. The cost-effectiveness threshold was set at $100,000 per quality-adjusted life year (QALY). Univariate sensitivity analyses were performed to evaluate the robustness of the results. In our model, at baseline assumptions of antepartum culture sensitivity of 97% when compared to intrapartum culture, a single repeat screen at 41 weeks was the cost-effective strategy. This persisted to culture sensitivity as low as 94.6% and culture cost ranging from $14 to $44. When compared to no retesting, a single retest at 41 weeks yielded 1.1 fewer neonatal deaths at a cost of $2.7 million. However, weekly testing resulted in 5 fewer neonatal deaths at a cost of $120 million when compared to no repeat testing (Table 1). Repeat antepartum GBS screening at 41 weeks compared to usual care is a cost-effective strategy. Rescreening at 41 weeks appears to be cost effective at a variety of hypothetical culture sensitivities and costs. Repeat antepartum screening should be considered in the management of women with initial GBS negative screening.

Index of Suspicion in the Nursery

Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital. Two days after birth, twin B continues to have glucose …

A Soluble Form of the Pilus Protein FimA Targets the VDAC-Hexokinase Complex at Mitochondria to Suppress Host Cell Apoptosis

Inhibition of apoptotic response of host cells during an early phase of infection is a strategy used by many enteroinvasive bacterial pathogens to enhance their survival. Here, we report the identification of a soluble form of the pilus protein FimA from the culture supernatants of E. coli K1, Salmonella, and Shigella that can potently inhibit Bax-mediated release of cytochrome c from isolated mitochondria. Similar to the infected cells, HCT116 cells stably expressing FimA display a delay in the integration of Bax into outer mitochondrial membrane induced by apoptotic stimuli. FimA targets to mitochondria through binding to VDAC1, which is a prerequisite step for E. coli K1 to render the short-term blockade of apoptotic death in the host cells. Interestingly, FimA strengthens the VDAC1-hexokinase interaction and prevents dissociation of hexokinase from VDAC1 triggered by apoptotic stimuli. Together, these data thus reveal a paradigm of antiapoptosis mechanism undertaken by the enteroinvasive bacteria.

Is thrombocytopenia suggestive of organism‐specific response in neonatal sepsis?

It is controversial whether thrombocytopenia is suggestive of one (or more) causative agents of neonatal sepsis: a low platelet count has been related in turn to Gram-positive, Gram-negative or fungal sepsis. A retrospective, cohort study on 514 very low-birthweight (VLBW) neonates admitted over a 9 year period to a large tertiary neonatal intensive care unit (NICU) in Italy was carried out. Through database search, data on platelet counts, sepsis, clinical course, and microbiological culture were collected and analyzed. Statistical analysis was performed to look for significant association between thrombocytopenia and sepsis caused by different (Gram-positive, Gram-negative or fungal) organisms. Sepsis diagnosed on microbiological criteria occurred in 197 of 514 VLBW neonates (38.3%), and thrombocytopenia (at least one finding of platelet count <80,000/mm(3)) was detected in 34 (17.2%) of the 197 septic infants. Thrombocytopenia occurred in 10 of 51 neonates with fungal sepsis (19.6%), and in 24 of 146 with bacterial sepsis (16.4%; P = 0.37). The difference was not significant when clustering for sepsis caused by Gram-positive (nine thrombocytopenic of 51 with Gram-positive sepsis, 17.6%; P = 0.40) and Gram-negative organisms (15/95, 15.7%; P = 0.22), or when considering only coagulase-negative Staphylococcus sepsis (6/37, 16.2%; P = 0.25). In contrast with previous reports, thrombocytopenia might not be an organism-specific marker of sepsis. Caution should be maintained in relating a low platelet count to any infectious agent (or group of agents) in preterm VLBW neonates.

Evaluation of a real-time fluorescent PCR assay for rapid detection of Group B Streptococci in neonatal blood

Streptococcus agalactiae (Group B Streptococcus: GBS) is the major causative agent of neonatal sepsis. Neonates at risk for GBS infections are empirically administered broad-spectrum antibiotics for at least 48 h pending blood culture results. A rapid assay to expedite detection of GBS would facilitate initiation of specific antibiotic therapy. Conversely, expeditious proof of absence of infection will avoid unnecessary antibiotic use. Using the LightCycler™, we evaluated a hybridization probe polymerase chain reaction (PCR) assay to detect GBS-specific cfb gene target DNA sequence in blood specimens. Both sensitivity and specificity of the real-time PCR assay was 100%. The assay demonstrated 100% specificity when tested against 26 non-GBS bacteria. This method is capable of detecting as few as ∼100 copies or 10 pg of GBS genomic DNA. This real-time PCR method is rapid, sensitive, and specific for the detection of GBS in neonatal blood samples and holds great promise in its utility in the diagnostic laboratory.