Cause Of Neonatal Sepsis Research Articles

Bacteriological Profile of Neonatal Sepsis in a Tertiary Hospital in Bangladesh

Objectives: To evaluate the common pathogens associated with neonatal sepsis in a tertiary care hospital in Bangladesh and their antibiotic susceptibility pattern. Materials and Method: This prospective study was done at Special Care Baby Unit (SCABU) BIRDEM Hospital from January to December 2008. Neonates whose blood culture yielded growth of bacteria were included in this study. Results: Sepsis was associated with Low Birth Weight and common organism isolated was Klebsiella and Enterobacter Ampicillin, Genatamicin and third generation cephalosporin were almost resistance to all organisms. Conclusion: Bacterial profile is not the same as western countries, Gram-negative bacteria and in particular Klebsiella and enterobacter species are the leading causes of neonatal sepsis and resistance to ampicillin, gentamicin and third generation cephalosporin DOI: http://dx.doi.org/10.3329/jbcps.v30i2.11406 J Bangladesh Coll Phys Surg 2012; 30: 66-70

Recurrent Late-Onset Group B Streptococcus Sepsis in a Preterm Infant Acquired by Expressed Breastmilk Transmission: A Case Report

Group B Streptococcus is a known cause of neonatal sepsis, being more common in the early period by maternal genital tract transmission and less so in the late neonatal period, ascribed to intestinal colonization or horizontal transmission. Although breastmilk transmission of Group B Streptococcus has rarely been reported in the past, most cases are of patients nursed on the mother's breast and less commonly in expressed breastmilk-fed infants. This case describes a preterm infant (born at a gestational age of 24 weeks 6 days) in the neonatal intensive care unit who acquired recurrent late-onset sepsis with Group B Streptococcus with the mother's expressed breastmilk culture growing the same organism that was later matched to the infant's isolate. The mother had presented with features of mastitis only during the second episode of sepsis and was then treated with oral antibiotics. The infant was fed on formula feeds after the second incidence and remained healthy, being discharged on a regular follow-up plan at 39 weeks corrected gestational age.

Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. Despite aggressive campaigns using antenatal prophylactic antibiotic therapy, infections continue. Developing an effective maternal vaccine is a public health priority. Antibody (Ab) to the capsular polysaccharide (CPS) is considered the dominant “protective” immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic carbohydrate structures, and cells. The results showed marked differences in the fine specificity among these mAbs to a single carbohydrate structure. Cross-reactions with synthetic GD3 and GT3 carbohydrates, representing structures found on surfaces of neural and developing cells, were demonstrated using carbohydrate array technology. The anti-CPSIII mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we serendipitously demonstrated cross-reactions of some anti-CPSIII mAbs with antigens, likely carbohydrates, found on human leukocytes. These studies suggest caution in the development of a maternal vaccine to prevent infection by this important human pathogen.

Variation in Reported Neonatal Group B Streptococcal Disease Incidence in Developing Countries

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis in developed countries. Its burden in the developing world is less clear. Studies reporting neonatal GBS disease incidence from developing countries were identified from 5 literature databases. Studies were assessed with respect to case finding and culture methods. Only 20 studies were identified. The GBS incidence ranged 0-3.06 per 1000 live births with variation within and between geographic regions. All but 1 study identified GBS cases within a hospital setting, despite the potential for births in the community. Possible case under-ascertainment was only discussed in 2 studies. A higher GBS incidence was reported when using automated culture methods. Prospective, population-based surveillance is urgently needed in developing countries to provide an accurate assessment of the neonatal GBS disease burden. This will be crucial for the design of interventions, including novel vaccines, and the understanding of their potential to impact mortality from neonatal sepsis.

L-Ficolin and Capsular Polysaccharide-Specific IgG in Cord Serum Contribute Synergistically to Opsonophagocytic Killing of Serotype III and V Group B Streptococci

Group B streptococci (GBS; Streptococcus agalactiae) are the most common cause of neonatal sepsis and meningitis. Serotype-specific IgG antibody is known to protect neonates against GBS infections by promoting opsonophagocytosis. The L-ficolin-mediated lectin pathway of the complement is also a potential mechanism for opsonization of GBS, because L-ficolin activates the complement after binding to serotype Ib, III, V, VI, and VIII GBS. In the present study, we investigated how L-ficolin and serotype-specific IgG in cord sera contribute to opsonophagocytic killing of GBS. Neither L-ficolin nor serotype-specific IgG concentrations correlated with C3b deposition on serotype Ib and VI GBS, suggesting L-ficolin- and serotype-specific IgG-independent mechanisms of complement activation. The percentage of serotype VIII GBS killed was high regardless of the concentration of L-ficolin and IgG. In contrast, L-ficolin and serotype-specific IgG can each initiate C3b deposition on serotype III and V GBS and promote phagocytosis by polymorphonuclear leukocytes, but L-ficolin and serotype-specific IgG together promote opsonophagocytic killing to a greater extent than does either alone in vitro. This synergy was observed when serotype III-specific IgG concentrations were between 1 and 6 μg/ml and when serotype V-specific IgG concentrations were between 2 and 5 μg/ml. Concentrations of serotype III-specific IgG in cord blood above 7 μg/ml are considered protective for neonates colonized with GBS, but most neonates with IgG levels of less than 7 μg/ml do not develop GBS infections. The data presented here suggest that L-ficolin enhances opsonophagocytosis of serotype III and V GBS when serotype-specific IgG alone is suboptimal for protection.

Group B streptococcal carriage, serotype distribution and antibiotic susceptibilities in pregnant women at the time of delivery in a refugee population on the Thai-Myanmar border

BackgroundGroup B Streptococcus (GBS) is the leading cause of neonatal sepsis in the developed world. Little is known about its epidemiology in the developing world, where the majority of deaths from neonatal infections occur. Maternal carriage of GBS is a prerequisite for the development of early onset GBS neonatal sepsis but there is a paucity of carriage data published from the developing world, in particular South East Asia.MethodsWe undertook a cross sectional study over a 13 month period in a remote South East Asian setting on the Thai-Myanmar border. During labour, 549 mothers had a combined vaginal rectal swab taken for GBS culture. All swabs underwent both conventional culture as well as PCR for GBS detection. Cultured GBS isolates were serotyped by latex agglutination, those that were negative or had a weak positive reaction and those that were PCR positive but culture negative were additionally tested using multiplex PCR based on the detection of GBS capsular polysaccharide genes.ResultsThe GBS carriage rate was 12.0% (95% CI: 9.4-15.0), with 8.6% positive by both culture and PCR and an additional 3.5% positive by PCR alone. Serotypes, Ia, Ib, II, III, IV, V, VI and VII were identified, with II the predominant serotype. All GBS isolates were susceptible to penicillin, ceftriaxone and vancomycin and 43/47 (91.5%) were susceptible to erythromycin and clindamycin.ConclusionsGBS carriage is not uncommon in pregnant women living on the Thai-Myanmar border with a large range of serotypes represented.

Global Burden of Infant Group B Streptococcal Disease

Since the 1970s, group B streptococcus (GBS) has been a major cause of neonatal sepsis in high-income countries, but information from low- and

Group B Streptococcal Disease in Korean Neonates

【Group B streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in developed countries. This article reviews the neonatal invasive GBS disease, maternal GBS colonization, and prevention strategies in the context of recent epidemiological changes in Korea. Although Korean neonates had been supposed to have low incidence of invasive GBS disease, GBS has been recently reported to be the most common cause of invasive neonatal infection after 1990s. Among Korean pregnant women, GBS carriage rate in the vagina and rectum has been reported to be much lower than that in Western countries. However, it has increased in recent studies. For decision making about preventive strategy for neonatal GBS disease in Korea, further studies are required in terms of the incidence of neonatal GBS infection and serotype distribution. In addition, studies about maternal carriage rate and serotype distribution have to be continued.】

Isolation And Identification Of Bacteria Associated With Neonatal Septiceamia At The Specialist Hospital, Bauchi.

A prospective study of neonatal septicemia undertaken at the specialist hospital Bauchi between January - March 2008 in which 101 samples were collected and analyzed. Bacterial growth was observed in 51 of the blood samples representing 50.5%. Six genera of organisms were identified as possible causes of neonatal sepsis. Staphylococcus aureus was isolated in 39.2% of the sample as the highest isolated while Pseudomonas aerogenosawas isolated in 3.9% of the samples as least isolate. A distribution of the organism according to age group indicated that 47.1% organisms were isolated during the early onset sepsis (0 - 7 days) with Escherichia coli having highest incidenceof 33.3%, 52.9% organisms were isolated during the late onset sepsis (8 - 28 days) with S. aureushaving high incidenceof 51.9%. A total of 45.1% of the organisms were isolatedin males while 54.9% organisms were isolated in females. The study indicates the neonatal septicemia is major causesof neonatal morbidity and mortality at the Specialist Hospital Bauchi Key Word: neonatal sepsis mobility

Characterization of Group B Streptococcus Isolated from Women in Saitama City, Japan

Streptococcus agalactiae (group B streptococcus; GBS) is a common cause of neonatal sepsis and meningitis. Intrapartum antibiotic prophylaxis is effective in reducing neonatal GBS disease. Penicillin is recommended for intrapartum antibiotic prophylaxis; however, other antibiotics are administered to pregnant women with penicillin allergy. Serotyping and antibiotic susceptibility testing were performed on 376 GBS isolates collected from vaginal swabs in Saitama City. Of the 376 isolates, 328 (87.2%) were obtained from obstetrics and gynecology clinics. Although approximately 80% of the isolates (299/376) were from women of reproductive age (age, 15-49 years), no definite information on their pregnancy status was obtained. The most frequent serotype was V (19.1%) followed by Ib (18.6%), III (16.2%), VI (14.9%), and Ia (14.6%). None of the isolates were resistant to penicillins and cephalosporins. Isolates that were resistant to erythromycin (12.8%), clindamycin (9.0%), ofloxacin (19.4%), levofloxacin (18.4%), and tetracycline (46.5%) were detected. There was a high prevalence of resistance to erythromycin (39.3%) and clindamycin (27.9%) in serotype III. In addition, almost all serotype Ib isolates were resistant to ofloxacin and levofloxacin (both, 91.4%). Pulsed-field gel electrophoresis analysis on certain GBS isolates (serotype Ib, III, and V) indicated that there was genetic diversity among the resistant isolates obtained from a limited area of Japan. In conclusion, present intrapartum antibiotic prophylaxis with penicillins would be effective in Japan; however, performing susceptibility testing before administering other antibiotics is important in order to ensure activity against the relevant isolate.

Possible Solution to the Problem of Nonhemolytic Group B Streptococcus on Granada Medium

Group B Streptococcus (GBS) is an important cause of neonatal sepsis. Screening for maternal GBS colonization is generally advised at 35 to 37 weeks of gestation. For laboratory detection of GBS, one of the methods recommended by the CDC ([2][1]) is culturing of a vulvorectal swab on Granada medium

Prevention of neonatal group B streptococcus disease in the 21st century

There have been significant reductions in early-onset neonatal group B streptococcus (GBS) disease following implementation of maternal intrapartum antibiotic prophylaxis (IAP) policies. Nevertheless, GBS remains a leading cause of neonatal sepsis in Australia and New Zealand resulting in considerable morbidity and mortality, particularly among preterm infants. In the United States, the universal screening-based approach for identifying women for IAP results in apparently lower rates of early-onset neonatal GBS infection than risk-based assessment. In addition, IAP has altered the profile of newborn infants who develop early-onset disease. Many affected infants lack the typical intrapartum risk factors for GBS infection, are born to mothers with a negative GBS screen or represent missed opportunities for prevention. Clinicians should remain alert for signs of sepsis in any newborn infant. We provide an update of GBS preventative management strategies in the perinatal period taking into account recent United States, Australian and New Zealand guidelines.

Genetic Differences Between Invasive and Noninvasive Neonatal Group B Streptococcal Isolates

Streptococcus agalactiae, also known as group B streptococcus (GBS), is the most common cause of neonatal sepsis and meningitis. To improve our understanding of the pathogenesis of neonatal GBS sepsis, better knowledge of clonal relatedness and diversity among invasive and noninvasive GBS isolates is critical. In a Germany-based study, invasive neonatal GBS isolates were compared with noninvasive isolates from neonates in whom sepsis was suspected, but whose blood cultures were sterile. The comparison was conducted by means of pulsed-field gel electrophoresis and surface protein gene profiling. In addition, multilocus sequence typing was performed on invasive and noninvasive isolates of the most frequent invasive serotype III. Pulsed-field gel electrophoresis analysis of noninvasive GBS showed a remarkably more diverse fingerprinting pattern than that of invasive isolates. In contrast to invasive strains, noninvasive isolates did not show any clustering. Surface protein gene profiling also showed significantly different distribution patterns between the 2 panels of isolates. Multilocus sequence typing of invasive and noninvasive serotype III isolates revealed the same clonal complexes, but displayed different sequence types (ST); ST-17 was most common (68.6%) among invasive strains, whereas ST-389 (clonal complex-19) was predominant among noninvasive strains (47.8%). Our results illustrate a large molecular diversity among neonatal noninvasive GBS strains. Invasive strains, however, represent only a small proportion of the noninvasive GBS population. These findings suggest a selection process that prefers more virulent strains during invasion.

Transmission probabilities and durations of immunity for three pathogenic group B Streptococcus serotypes

Group B Streptococcus (GBS) remains a major cause of neonatal sepsis and is an emerging cause of invasive bacterial infections. The 9 known serotypes vary in virulence, and there is little cross-immunity. Key parameters for planning an effective vaccination strategy, such as average length of immunity and transmission probabilities by serotype, are unknown. We simulated GBS spread in a population using a computational model with parameters derived from studies of GBS sexual transmission in a college dormitory. Here we provide estimates of the duration of immunity relative to the transmission probabilities for the 3 GBS serotypes most associated with invasive disease: Ia, III, and V. We also place upper limits on the durations of immunity for serotype Ia (570 days), III (1125 days) and V (260 days). Better transmission estimates are required to establish the epidemiological parameters of GBS infection and determine the best vaccination strategies to prevent GBS disease.

C-reactive protein and interleukin-6 responses for differentiating fungal and bacterial aetiology in late-onset neonatal sepsis

Fungal infections are increasingly frequent causes of neonatal sepsis (NS). This study examined the predictive value of the combined evaluation of the C-reactive protein (CRP) and interleukin-6 (IL-6) responses for differentiating fungal and bacterial aetiologies in patients with NS. From January to September 2007, neonates who were diagnosed with NS and had their CRP and IL-6 levels measured were selected. Based on their blood culture results, the neonates were divided into two groups: group of fungal sepsis (FS) and group of bacterial sepsis (BS). FS included 14 Candida albicans and one non-albicans Candida isolates and BS included five Klebsiella pneumoniae, three Pseudomonas aeruginosa, three Enterococcus faecalis, two coagulase-negative Staphylococcus species, one Enterococcus faecium and one Acinetobacter species. Significant differences were observed in the CRP (FS vs. BS: 28.10 ± 11.03 vs. 11.39 ± 2.94 mg l(-1), P = 0.026) and IL-6 (FS vs. BS: 38.60 ± 24.24 vs. 392.82 ± 102.46 ng l(-1), P = 0.000) levels between groups. The combined evaluation of the CRP and IL-6 responses better predicted the causative micro-organism in NS.

Streptococcus pneumoniae sepsis in the newborn

Streptococcus pneumoniae (SP) is an uncommon cause of neonatal sepsis. To report on the spectrum of morbidity associated with SP infections in the neonatal period. A case series of SP infection in the neonatal period was studied. Maternal and neonatal outcomes were noted. Four cases of neonatal SP infection are reported, one of which was due to a strain with reduced susceptibility to penicillin. All four cases had very early onset of severe clinical disease with bacteremia and pneumonia. In one case a retrospective diagnosis of meningitis was made as well. Maternal illness was a feature in one of these infants. Although less common now than in the pre-antibiotic era, Streptococcus pneumoniae remains a rare but important cause of neonatal sepsis and can mimic early onset Group B streptococcal sepsis. It is unclear whether current infant or adult pneumococcal immunisation programs might influence its incidence in the neonatal period. The potential for strains with reduced susceptibility to β-lactam antibiotics to cause neonatal infection needs to be considered in relevant settings.

Early- and Late-Onset Group B Streptococcal Infections: Overview and Case Studies

Infants that are admitted and cared for in the neonatal intensive care unit are at risk for sepsis. Group B Streptococcus (GBS) is the most common cause of neonatal sepsis and meningitis. Group B Streptococcus is classified into early- and late-onset sepsis. With early onset, infants develop symptoms within 7 days of birth. With late onset, they develop symptoms between 7 days and 3 months of life. Prompt identification and treatment of suspected septic infants are crucial. Infants who develop early- or late-onset GBS sepsis are at risk for sequelae ranging from normal physiologic outcome to devastating long-term conditions and even death. Despite advances in medical management of pregnant women being screened for GBS, infants are still becoming infected with GBS and suffering those consequences. Current research is looking at developing a vaccination that would be given to childbearing women to prevent the spread of GBS sepsis. Although there is research being done in this area, it is of utmost importance that clinicians are vigilant in prompt assessment and treatment of infants suspected of having sepsis.

Use of rifampin in persistent coagulase negative staphylococcal bacteremia in neonates

BackgroundCoagulase negative staphylococci (CoNS) are the most common cause of neonatal sepsis in the Neonatal Intensive Care Unit (NICU). A minority of neonates does not respond to vancomycin therapy and develops persistent bacteremia, which may be treated with rifampin. We evaluated the use of rifampin in persistent CoNS bacteremia.MethodsRetrospective study of 137 neonates with CoNS bacteremia during admission to a tertiary NICU between July 2006 and July 2009. Main outcome measures were total duration of bacteremia and the adequacy of vancomycin and rifampin therapy.Results137/1696 (8.0%) neonates developed a CoNS bacteremia. Eighteen were treated with rifampin because of persistent bacteremia (3 positive blood cultures at least 48 hours apart with clinical symptoms) or (a serious suspicion of) an intravascular thrombus. Duration of bacteremia prior to rifampin therapy (8.0 ± 3.6 days) was positively correlated (p < 0.001) to the total duration of bacteremia (10.3 ± 3.7 days). After starting rifampin therapy C-reactive protein (CRP) levels of all neonates declined and blood cultures became sterile after 2.3 ± 1.6 days. Vancomycin levels were not consistently measured in all neonates, resulting in late detection of subtherapeutic trough levels.ConclusionRifampin may be effective in the treatment of persistent CoNS infections in neonates. Outcome may be improved by adequate monitoring of vancomycin trough levels.

Enhanced Expression of lmb Gene Encoding Laminin-Binding Protein in Streptococcus agalactiae Strains Harboring IS1548 in scpB-lmb Intergenic Region

Group B streptococcus (GBS) is the main cause of neonatal sepsis and meningitis. Bacterial surface proteins play a major role in GBS binding to and invasion of different host surfaces. The scpB and lmb genes, coding for fibronectin-binding and laminin-binding surface proteins, are present in almost all human GBS isolates. The scpB-lmb intergenic region is a hot spot for integration of two mobile genetic elements (MGEs): the insertion element IS1548 or the group II intron GBSi1. We studied the structure of scpB-lmb intergenic region in 111 GBS isolates belonging to the intraspecies major clonal complexes (CCs). IS1548 was mostly found (72.2%) in CC19 serotype III strains recovered more specifically (92.3%) from neonatal meningitis. GBSi1 was principally found (70.6%) in CC17 strains, mostly (94.4%) of serotype III, but also (15.7%) in CC19 strains, mostly (87.5%) of serotype II. No MGE was found in most strains of the other CCs (76.0%), notably CC23, CC10 and CC1. Twenty-six strains representing these three genetic configurations were selected to investigate the transcription and expression levels of scpB and lmb genes. Quantitative RT-PCR showed that lmb transcripts were 5.0- to 9.6-fold higher in the group of strains with IS1548 than in the other two groups of strains (P<0.001). Accordingly, the binding ability to laminin was 3.8- to 6.6-fold higher in these strains (P≤0.001). Moreover, Lmb amount expressed on the cell surface was 2.4- to 2.7-fold greater in these strains (P<0.001). By contrast, scpB transcript levels and fibronectin binding ability were similar in the three groups of strains. Deletion of the IS1548 sequence between scpB and lmb genes in a CC19 serotype III GBS strain substantially reduced the transcription of lmb gene (13.5-fold), the binding ability to laminin (6.2-fold), and the expression of Lmb protein (5.0-fold). These data highlight the importance of MGEs in bacterial virulence and demonstrate the up-regulation of lmb gene by IS1548; the increased lmb gene expression observed in CC19 serotype III strains with IS1548 may play a role in their ability to cause neonatal meningitis and endocarditis.

Acquisition of extended-spectrum β-lactamase producing Escherichia coli strains in male and female infants admitted to a neonatal intensive care unit: molecular epidemiology and analysis of risk factors

Extended-spectrum beta-lactamases (ESBLs) are bacterial enzymes that confer resistance to advanced generation cephalosporins and can lead to therapeutic failures. There has been no analysis of factors associated with the risk of acquisition of ESBLs in neonates in an intensive care unit from northern India. The CTX-M ESBL enzymes impart resistance against advanced generation cephalosporins (e.g. cefotaxime) and CTX-M variants have become the most prevalent ESBLs worldwide. The CTX-M-15 enzyme in particular is increasingly being reported from Escherichia coli isolates from northern India together with TEM-1. Moreover, E. coli is the most common cause of neonatal sepsis. Accordingly, this study aimed to: (i) characterize the mode of transmission of bla(CTX-M) and bla(TEM) among ESBL-producing E. coli strains isolated from patients admitted to a neonatal intensive care unit (NICU), and (ii) identify factors associated with the acquisition of the said strains in male and female neonates. A total of 97 ESBL-producers was identified among 266 E. coli strains isolated from 238 neonates. The isolates were screened for bla(CTX-M), bla(TEM), armA, rmtA and rmtB, the last three genes being responsible for aminoglycoside resistance. PCR amplified bla(CTX-M) genes were cloned and sequenced. Five bla(CTX-M-15), two rmtB, two bla(TEM-1) and thirteen class1 integrons were detected. All the bla(CTX-M-15) positive isolates, except one, were clonally related. Both univariate and multivariate analyses of factors for the acquisition of the said strains were performed with respect to the sex of the neonates. 'Length of stay in the NICU' was found to be the single independent factor associated with ESBL acquisition. In conclusion, our data suggest that male neonates who are colonized or infected by ESBL-producing E. coli have a longer stay in the NICU compared to their female counterparts. This prolonged stay may be due to male neonates becoming colonized/infected earlier than their female counterparts. Plasmid-mediated-conjugal transfer was found to be the mechanism of transfer of the bla(CTX-M-15) resistance marker in the described setting.