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1.
BMC Infect Dis ; 20(1): 682, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942989

RESUMO

BACKGROUND: Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU. METHODS: This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012-2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains. RESULTS: Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone. CONCLUSIONS: Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.


Assuntos
Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/prevenção & controle , Controle de Infecções/métodos , Surtos de Doenças/prevenção & controle , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , França , Humanos , Higiene , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Estudos Retrospectivos , Sequenciamento Completo do Genoma
2.
PLoS One ; 15(8): e0237085, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776958

RESUMO

BACKGROUND: Sepsis is the third most common cause of death among neonates, with about 225,000 newborns dying every year globally. Data concerning the microbial etiology of neonatal sepsis and antimicrobial resistance profiles of its causative agents are necessary to inform targeted and effective treatment and prevention strategies. OBJECTIVE: To determine the proportion of newborns with symptoms and signs of sepsis who had a positive blood culture, its bacterial etiology, the antimicrobial resistance patterns as well as the factors associated with culture-positivity and case fatality at Mulago national referral hospital in Uganda. METHODS: We conducted a cross-sectional study among 359 neonates with symptoms and signs of sepsis who presented to the pediatric emergency care unit of Mulago national referral hospital from mid-January to end of December 2018. We performed blood culture and antimicrobial susceptibility testing, and conducted polymerase chain reaction to identify methicillin-resistant Staphylococcus aureus (MRSA) isolates. We used multivariable logistic regression to estimate the association between potential risk factors and culture-positive neonatal sepsis. FINDINGS: Of the 359 neonates recruited, 46 (12.8%; 95% CI 9.5%, 16.7%) had a positive blood culture. The predominant isolated bacteria were Staphylococcus aureus in 29 (63.0%), Escherichia coli in seven (15.2%), and Klebsiella pneumoniae in five (10.9%). Of the 46 pathogens, 73.9% were resistant to ampicillin, 23.9% to gentamicin and 8.7% to ceftriaxone. We isolated MRSA from the blood specimens of 19 (5.3%) of the 359 neonates, while 3 (0.8%) grew extended spectrum beta lactamase producers. The case fatality risk among neonates with neonatal sepsis was 9.5% (95% CI: 6.6%, 13.0%). Cesarean section delivery was strongly associated with culture-positive sepsis (adjusted odds ratio 3.45, 95% CI: 1.2, 10.1). CONCLUSION: One in eight neonates with clinical signs of sepsis grew a likely causative bacterial pathogen. S. aureus was the main pathogen isolated and a third of these isolates were MRSA. A significant proportion of the isolated bacterial pathogens were resistant to the first and second line antibiotics used for the treatment of neonatal sepsis. There is need to revisit the current treatment guidelines for neonatal sepsis.


Assuntos
Sepse Neonatal/epidemiologia , Infecções Estafilocócicas/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Recém-Nascido , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Sepse Neonatal/etiologia , Sepse Neonatal/microbiologia , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Uganda
3.
PLoS One ; 15(6): e0235391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603368

RESUMO

BACKGROUND: Neonatal septicemia is a life threatening medical emergency that requires timely detection of pathogens with urgent rational antibiotics therapy. METHODS: A cross-sectional study was conducted between March 2017 to September 2018 among 317 septicemia suspected neonates at neonatal intensive care unit, Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, North Ethiopia. A 3 mL of blood was collected from each participant. Identification of bacterial species was done using the standard microbiological techniques. Antibiotic sensitivity test was done using disk diffusion method. Data were entered and analyzed using computer software SPSS version 22. Bivariate and multivariate regression analysis was applied to determine the association between variables. RESULTS: Of the 317 (190 male and 127 female) neonates, 116 (36.6%) were found to be with culture proven septicemia. Klebsiella species were the predominant etiologic agents. Length of hospital stay (AOR (adjusted odds ratio) = 3.65 (2.17-6.13), p < 0.001) and low birth weight (AOR = 1.64 (1.13-2.78), p = 0.04) were the factors associated with neonatalsepticemia. Most isolates showeda frightening drug resistance rate to the commonly used antimicrobial drugs. K. pneumoniae, E. coli, Enterobacter and Citrobacter species were 57% to100% resistant to ceftazidime, ceftriaxone, gentamycin, amoxacillin-clavulunic acid and ampicillin. All, 9 (100%) isolates of S. aureus were resistant to oxacilline, ampicillin,erythromycin and gentamycin. Furthermore, 55.6% S. aureus isolates were Methicillin Resistant Staphylococcus aureus. CONCLUSION: Neonaltal septicemia is found to be significantly high in the present study. As most of the isolates are potentially related to hospital acquired infections, prevention and control policy should have to be more strengthening in the neonatal intensive care unit.


Assuntos
Antibacterianos/uso terapêutico , Bactérias , Sepse Neonatal , Ampicilina/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Citrobacter/efeitos dos fármacos , Citrobacter/isolamento & purificação , Estudos Transversais , Farmacorresistência Bacteriana , Enterobacter/efeitos dos fármacos , Enterobacter/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Etiópia , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Klebsiella/efeitos dos fármacos , Klebsiella/isolamento & purificação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/microbiologia , Oxacilina/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
4.
PLoS One ; 15(6): e0235002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574197

RESUMO

Streptococcus agalactiae or Group B Streptococcus (GBS) is a leading cause of sepsis in neonates. As a preventative measure prophylactic antibiotic administration is common in pregnant women colonised with GBS, but antibiotic-resistance and adverse effects on neonatal microbiomes may result. Use of bacteriophages (phages) is one option for targeted therapy. To this end, four phages (LF1 -LF4) were isolated from wastewater. They displayed lytic activity in vitro against S. agalactiae isolates collected from pregnant women and neonates, with 190/246 isolates (77.2%) and 10/10 (100%) isolates susceptible to at least one phage, respectively. Phage genomes ranged from 32,205-44,768 bp and all phages were members of the Siphoviridae family. High nucleotide identity (99.9%) was observed between LF1 and LF4, which were closely related to a putative prophage of S. agalactiae. The genome organisation of LF2 differed, and it showed similarity to a different S. agalactiae prophage, while LF3 was more closely related to a Streptococcus pyogenes phage. Lysogenic gene presence (integrase, repressor and regulatory modules), was suggestive of temperate phages. In a therapeutic context, temperate phages are not ideal candidates, however, the broad host range activity of these phages observed on clinical isolates in vitro is promising for future therapeutic approaches including bioengineered phage or lysin applications.


Assuntos
Sepse Neonatal/terapia , Terapia por Fagos , Siphoviridae/genética , Fagos de Streptococcus/genética , Streptococcus agalactiae/virologia , DNA Viral/isolamento & purificação , Feminino , Genômica , Especificidade de Hospedeiro/genética , Humanos , Recém-Nascido , Lisogenia , Sepse Neonatal/microbiologia , Filogenia , Gravidez , Siphoviridae/isolamento & purificação , Fagos de Streptococcus/isolamento & purificação , Streptococcus agalactiae/isolamento & purificação , Streptococcus pyogenes/virologia
5.
Nat Microbiol ; 5(5): 735-745, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32341568

RESUMO

The multidrug-resistant Staphylococcus capitis NRCS-A clone is responsible for sepsis in preterm infants in neonatal intensive care units (NICUs) worldwide. Here, to retrace the spread of this clone and to identify drivers of its specific success, we investigated a representative collection of 250 S. capitis isolates from adults and newborns. Bayesian analyses confirmed the spread of the NRCS-A clone and enabled us to date its emergence in the late 1960s and its expansion during the 1980s, coinciding with the establishment of NICUs and the increasing use of vancomycin in these units, respectively. This dynamic was accompanied by the acquisition of mutations in antimicrobial resistance- and bacteriocin-encoding genes. Furthermore, combined statistical tools and a genome-wide association study convergently point to vancomycin resistance as a major driver of NRCS-A success. We also identified another S. capitis subclade (alpha clade) that emerged independently, showing parallel evolution towards NICU specialization and non-susceptibility to vancomycin, indicating convergent evolution in NICU-associated pathogens. These findings illustrate how the broad use of antibiotics can repeatedly lead initially commensal drug-susceptible bacteria to evolve into multidrug-resistant clones that are able to successfully spread worldwide and become pathogenic for highly vulnerable patients.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Sepse Neonatal/microbiologia , Staphylococcus capitis/efeitos dos fármacos , Staphylococcus capitis/genética , Adulto , Teorema de Bayes , França , Genes Bacterianos/genética , Genoma Bacteriano , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Testes de Sensibilidade Microbiana , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Recombinação Genética , Infecções Estafilocócicas/microbiologia , Staphylococcus capitis/isolamento & purificação , Staphylococcus capitis/patogenicidade , Vancomicina/uso terapêutico
6.
PLoS One ; 15(4): e0231239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294121

RESUMO

BACKGROUND: Chorioamnionitis has been linked to spontaneous preterm labor and complications such as neonatal sepsis. We hypothesized that microbial cell-free (cf) DNA would be detectable in maternal plasma in patients with chorioamnionitis and could be the basis for a non-invasive method to detect fetal exposure to microorganisms. OBJECTIVE: The purpose of this study was to determine whether next generation sequencing could detect microbial cfDNA in maternal plasma in patients with chorioamnionitis. STUDY DESIGN: Maternal plasma (n = 94) and umbilical cord plasma (n = 120) were collected during delivery at gestational age 28-41 weeks. cfDNA was extracted and sequenced. Umbilical cord plasma samples with evidence of contamination were excluded. The prevalence of microorganisms previously implicated in choriomanionitis, neonatal sepsis and intra-amniotic infections, as described in the literature, were examined to determine if there was enrichment of these microorganisms in this cohort. Specific microbial cfDNA associated with chorioamnionitis was first detected in umbilical cord plasma and confirmed in the matched maternal plasma samples (n = 77 matched pairs) among 14 cases of histologically confirmed chorioamnionitis and one case of clinical chorioamnionitis; 63 paired samples were used as controls. A correlation of rank of a given microorganism across maternal plasma and matched umbilical cord plasma was used to assess whether signals found in umbilical cord plasma were also present in maternal plasma. RESULTS: Microbial DNA sequences associated with clinical and/or histological chorioamnionitis were enriched in maternal plasma in cases with suspected chorioamnionitis when compared to controls (12/14 microorganisms, p = 0.02). Analysis of the microbial cfDNA in umbilical cord plasma among the 1,251 microorganisms detectable with this assay identified Streptococcus mitis, Ureaplasma spp., and Mycoplasma spp. in cases of suspected chorioamnionitis. This assay also detected cfDNA from Lactobacillus spp. in controls. Comparison between maternal plasma and umbilical cord plasma confirmed these signatures were also present in maternal plasma. Unbiased analysis of microorganisms with significantly correlated signal between matched maternal plasma and umbilical cord plasma identified the above listed 3 microorganisms, all of which have previously been implicated in patients with chorioamnionitis (Mycoplasma hominis p = 0.0001; Ureaplasma parvum p = 0.002; Streptococcus mitis p = 0.007). These data show that the pathogen signal relevant for chorioamnionitis can be identified in both maternal and umbilical cord plasma. CONCLUSION: This is the first report showing the detection of relevant microbial cell-free cfDNA in maternal plasma and umbilical cord plasma in patients with clinical and/or histological chorioamnionitis. These results may lead to the development of a specific assay to detect perinatal infections for targeted therapy to reduce early neonatal sepsis complications.


Assuntos
Ácidos Nucleicos Livres/sangue , Corioamnionite/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Cordão Umbilical/microbiologia , Adulto , Corioamnionite/microbiologia , Estudos de Coortes , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Sangue Fetal/microbiologia , Idade Gestacional , Humanos , Recém-Nascido , Mycoplasma/genética , Mycoplasma/patogenicidade , Sepse Neonatal/sangue , Sepse Neonatal/diagnóstico , Sepse Neonatal/microbiologia , Gravidez , Streptococcus mitis/genética , Streptococcus mitis/patogenicidade , Cordão Umbilical/patologia , Ureaplasma/genética , Ureaplasma/patogenicidade , Adulto Jovem
8.
Proc Natl Acad Sci U S A ; 117(14): 7941-7949, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32179676

RESUMO

Late-onset sepsis (LOS) is a highly consequential complication of preterm birth and is defined by a positive blood culture obtained after 72 h of age. The causative bacteria can be found in patients' intestinal tracts days before dissemination, and cohort studies suggest reduced LOS risk in breastfed preterm infants through unknown mechanisms. Reduced concentrations of epidermal growth factor (EGF) of maternal origin within the intestinal tract of mice correlated to the translocation of a gut-resident human pathogen Escherichia coli, which spreads systemically and caused a rapid, fatal disease in pups. Translocation of Escherichia coli was associated with the formation of colonic goblet cell-associated antigen passages (GAPs), which translocate enteric bacteria across the intestinal epithelium. Thus, maternally derived EGF, and potentially other EGFR ligands, prevents dissemination of a gut-resident pathogen by inhibiting goblet cell-mediated bacterial translocation. Through manipulation of maternally derived EGF and alteration of the earliest gut defenses, we have developed an animal model of pathogen dissemination which recapitulates gut-origin neonatal LOS.


Assuntos
Translocação Bacteriana/imunologia , Receptores ErbB/metabolismo , Infecções por Escherichia coli/imunologia , Escherichia coli/imunologia , Microbioma Gastrointestinal/imunologia , Leite Humano/imunologia , Sepse Neonatal/imunologia , Animais , Animais Recém-Nascidos , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Aleitamento Materno , Colo/metabolismo , Colo/microbiologia , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Transgênicos , Leite Humano/metabolismo , Sepse Neonatal/metabolismo , Sepse Neonatal/microbiologia , Transdução de Sinais/imunologia , Fatores de Tempo
9.
PLoS One ; 15(2): e0227823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32012172

RESUMO

Staphylococcus epidermidis has emerged as the leading agent causing neonatal late-onset sepsis in preterm neonates; although the severity of the episodes caused by this species is often underestimated, it might exert relevant short- and long-term detrimental effects on neonatal outcomes. In this context, the objective of this study was to characterize a collection of S. epidermidis strains obtained from meconium and feces of preterm infants, and to assess the potential role of the enteral feeding tubes as potential reservoirs for this microorganism. A total of 26 preterm infants were enrolled in the study. Meconium and fecal samples were collected weekly during their first month of life (n = 92). Feeding samples were collected after their pass through the enteral feeding tubes (n = 84). S. epidermidis was present in the fecal samples of all the infants in, at least, one sampling time at concentrations ranging from 6.5 to 7.8 log10 CFU/g. Initially, 344 isolates were obtained and pulsed-field gel electrophoresis (PFGE) profiling allowed the reduction of the collection to 101 strains. Among them, multilocus sequence typing (MLST) profiling showed the presence of 32 different sequence types (ST). Globally, most of the STs to hospital-adapted high-risk clones and belonged to clonal complexes (CC) associated to the hospital environment, such as CC2. The virulence gene most commonly detected among the strains was altE. High resistance rates to macrolides and aminoglycosides were detected and 64% of the strains harboured the mecA gene, which was codified in SCCmec types. Our results indicates the existence of a complex and genetically diverse S. epidermidis population in the NICU environment. A better knowledge of S. epidermidis strains may help to devise strategies to avoid their conversion from symbiont to pathobiont microorganisms in the NICUs.


Assuntos
Epidemiologia Molecular , Sepse Neonatal/genética , Infecções Estafilocócicas/genética , Staphylococcus epidermidis/genética , Antibacterianos/uso terapêutico , Eletroforese em Gel de Campo Pulsado , Nutrição Enteral/efeitos adversos , Fezes/microbiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Testes de Sensibilidade Microbiana , Sepse Neonatal/microbiologia , Sepse Neonatal/patologia , Sepse Neonatal/prevenção & controle , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus epidermidis/patogenicidade
10.
JAMA Netw Open ; 3(2): e1921124, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32049298

RESUMO

Importance: High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens. Objective: To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries. Design, Setting, and Participants: A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019. Exposures: The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted. Main Outcomes and Measures: Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level. Results: Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from -15.9% in China to -52.9% in Indonesia. Conclusions and Relevance: This study's findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Sepse Neonatal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ásia/epidemiologia , Bactérias/efeitos dos fármacos , Tomada de Decisão Clínica , Árvores de Decisões , Quimioterapia Combinada , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Humanos , Incidência , Recém-Nascido , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico
12.
BMC Infect Dis ; 20(1): 151, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070296

RESUMO

BACKGROUND: Early diagnosis of neonatal sepsis is essential to prevent severe complications and avoid unnecessary use of antibiotics. The mortality of neonatal sepsis is over 18%in many countries. This study aimed to develop a predictive model for the diagnosis of bacterial late-onset neonatal sepsis. METHODS: A case-control study was conducted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand. Data were derived from the medical records of 52 sepsis cases and 156 non-sepsis controls. Only proven bacterial neonatal sepsis cases were included in the sepsis group. The non-sepsis group consisted of neonates without any infection. Potential predictors consisted of risk factors, clinical conditions, laboratory data, and treatment modalities. The model was developed based on multiple logistic regression analysis. RESULTS: The incidence of late proven neonatal sepsis was 1.46%. The model had 6 significant variables: poor feeding, abnormal heart rate (outside the range 100-180 x/min), abnormal temperature (outside the range 36o-37.9 °C), abnormal oxygen saturation, abnormal leucocytes (according to Manroe's criteria by age), and abnormal pH (outside the range 7.27-7.45). The area below the Receiver Operating Characteristics (ROC) curve was 95.5%. The score had a sensitivity of 88.5% and specificity of 90.4%. CONCLUSION: A predictive model and a scoring system were developed for proven bacterial late-onset neonatal sepsis. This simpler tool is expected to somewhat replace microbiological culture, especially in resource-limited settings.


Assuntos
Sepse Neonatal/diagnóstico , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Humanos , Incidência , Recém-Nascido , Masculino , Modelos Biológicos , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Centros de Atenção Terciária/estatística & dados numéricos , Tailândia/epidemiologia
13.
PLoS One ; 15(1): e0227570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978069

RESUMO

BACKGROUND: Neonatal sepsis is accounted for 30-50% of annual neonatal deaths in developing countries. We performed a systematic review and meta-analysis study to evaluate the national prevalence and identification of the etiological pathogens of neonatal sepsis in Iran. METHODS: A comprehensive literature search was done on the national and international databases for studies published between 2000 and 2019. The DerSimonian and Laird random-effects model was used to calculate pooled prevalence estimates, with 95% confidence intervals (CIs). Subgroup analyses and meta-regressions regarding the gender, type of sepsis and time during were also performed. Data were extracted, analyzed, and presented according to PRISMA guideline. RESULTS: Of 944 publications identified, 22 studies containing 14,683 neonates met the eligibility criteria. The pooled national prevalence of sepsis in Iran was 15.98% (95%CI, 11.96-20.46%; 1,367/14,683). Prevalence rate in boys (20.42%; 95%CI, 9.03-34.8%) was slightly higher than girls (18.5%; 95%CI, 7.4-32.8). A decreasing trend in prevalence of neonatal sepsis was found in recent years, although not statistically significant (c = -0.005; P value = 0.4). The most prevalent causative bacterial pathogens were Enterobacter spp. (23.04%), followed by Klebsiella pneumoniae (17.54%), coagulase-negative Staphylococci (14.06%), Escherichia coli (13.92%), Pseudomonas aeruginosa (12.67%), and Staphylococcus aureus (11.48%). CONCLUSION: Our findings showed a high prevalence of neonatal sepsis in suspected neonates, suggesting the need to implement preventive measures, routine assessment, and close monitoring of neonates. Also, Enterobacter spp. and Klebsiella pneumoniae were identified as the principal bacterial pathogens responsible for neonatal septicemia in Iran.


Assuntos
Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Humanos , Recém-Nascido , Irã (Geográfico)/epidemiologia , Prevalência
14.
PLoS One ; 15(1): e0226817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978082

RESUMO

BACKGROUND: A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. METHODS: Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. RESULTS: Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. CONCLUSION: Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Candida/isolamento & purificação , Candidíase/diagnóstico , Sepse Neonatal/microbiologia , RNA Ribossômico 16S/genética , Idade de Início , Bactérias/genética , Candida/genética , DNA Ribossômico/genética , Diagnóstico Precoce , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Enterococcus/genética , Enterococcus/isolamento & purificação , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Reação em Cadeia da Polimerase Multiplex , Mycoplasma/genética , Mycoplasma/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Streptococcus/genética , Streptococcus/isolamento & purificação , Ureaplasma/genética , Ureaplasma/isolamento & purificação
15.
Indian J Pediatr ; 87(2): 122-124, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900849

RESUMO

Sepsis is one of the major causes of neonatal deaths in India and worldwide. Pathogens encountered in neonatal sepsis vary worldwide; reports from developing countries more commonly show Gram negative organisms, most common being Acinetobacter spp., Klebsiella spp. and Escherichia coli. Recent studies show that the incidence of antimicrobial resistance, to third generation cephalosporins and carbapenems, has been on a rise. Because of widespread antimicrobial resistance, 'Higher' or 'Reserve' antibiotics are increasingly being used as first/second line antibiotics. In the past decade, there has been a resurgence in the use of colistin as a result of Extended-spectrum ß-lactamase (ESBL)- producing Enterobacteriaceae and carbapenem resistant Enterobacteriaceae (CRE), which retain susceptibility only to colistin. The increasing burden of drug resistant Gram negative organisms, particularly Acinetobacter spp., Klebsiella spp., and E. coli might pose a formidable threat in coming years.


Assuntos
Antibacterianos/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/microbiologia , Hemocultura/métodos , Carbapenêmicos/uso terapêutico , Colistina/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Escherichia coli/efeitos dos fármacos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Índia , Klebsiella/efeitos dos fármacos , Sepse Neonatal/diagnóstico , beta-Lactamases
16.
Clin Microbiol Infect ; 26(4): 463-469, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31336200

RESUMO

OBJECTIVES: The objective of this study was to assess the prevalence of maternal recto-vaginal extended-spectrum ß-lactamase producing Enterobacteriacea (ESBL-E) colonization, identify risk factors for maternal and neonatal ESBL-E colonization, and subsequent impact on neonatal mortality. METHODS: A prospective, cross-sectional study was conducted at the University of Abuja Teaching Hospital from April 2016 to May 2017. Maternal-neonatal pairs were screened for ESBL-E exposure at time of delivery. Neonatal mortality was assessed at 28 days. RESULTS: A total of 1161 singleton deliveries were evaluated. In total, 9.7% (113/1161) of mothers and 4.3% (50/1161) of infants had ESBL-E-positive cultures at delivery. Maternal antibiotic exposure was associated with ESBL-E recto-vaginal colonization (18.6% (21/113) vs. 8.4% (88/1048), p < 0.001)). Maternal ESBL-E colonization (adjusted odds ratio (AOR) 14.85; 95% CI 7.83-28.15) and vaginal delivery (AOR 6.35; 95% CI 2.63-17.1) were identified as a risk factor for positive ESBL-E neonatal surface cultures. Neonatal positive ESBL-E surface cultures were a risk factor for neonatal mortality (stillbirths included, AOR 4.84; 95% CI 1.44-16.31). The finding that maternal ESBL-E recto-vaginal colonization appeared protective in regards to neonatal mortality (AOR 0.22; 95% CI .06-0.75) requires further evaluation. CONCLUSIONS: Maternal ESBL-E recto-vaginal colonization is an independent risk factor for neonatal ESBL-E colonization and neonates with positive ESBL-E surface cultures were identified as having increased risk of neonatal mortality.


Assuntos
Portador Sadio/microbiologia , Infecções por Enterobacteriaceae/transmissão , Enterobacteriaceae/fisiologia , Mães , Reto/microbiologia , Vagina/microbiologia , Adulto , Portador Sadio/epidemiologia , Portador Sadio/transmissão , Estudos Transversais , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Sepse Neonatal/etiologia , Sepse Neonatal/microbiologia , Nigéria/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , beta-Lactamases
17.
Am J Perinatol ; 37(7): 689-694, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31087314

RESUMO

OBJECTIVE: Multidrug-resistant gram-negative bacilli (MDR-GNB) have emerged globally as a serious threat and with a high case fatality rate (CFR). STUDY DESIGN: We performed a case-control study in a Thai neonatal intensive care unit to identify the risk factors for 30-day CFR of GNB sepsis between 1991 and 2017. The CFR was analyzed by Cox's proportional hazards model. RESULTS: For 27 years, the percentage of MDR-GNB from GNB sepsis was 66% (169/257). The medians (interquartile ranges) of gestational age and birth weight of the neonates with GNB sepsis were 33 (29-38) weeks and 1,817 (1,100-2,800) grams, respectively. The 30-day CFRs of the neonates with MDR-GNB and non-MDR-GNB sepsis were 33% (56/169) and 20% (18/88), respectively, (hazard ratio [HR] = 1.74; 95% confidence interval [CI]: 1.03-2.97; p = 0.04). Using Cox's proportional hazards model, nonsurvivors in GNB sepsis were more likely to have septic shock (adjusted HR [aHR] = 6.67; 95% CI: 3.28-13.57; p < 0.001) or no microbiological cure (aHR = 10.65; 95% CI: 4.98-22.76; p < 0.001) than survivors. CONCLUSION: Neonates suspected of sepsis with septic shock need broad-spectrum empirical antimicrobial therapy until the second successive negative culture, especially in high MDR areas.


Assuntos
Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/mortalidade , Sepse Neonatal/mortalidade , Análise de Variância , Peso ao Nascer , Estudos de Casos e Controles , Farmacorresistência Bacteriana Múltipla , Feminino , Idade Gestacional , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/microbiologia , Fatores de Risco , Análise de Sobrevida
18.
Eur J Clin Microbiol Infect Dis ; 39(3): 583-591, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31773363

RESUMO

Neonatal sepsis is a great challenge for clinicians and infection control practitioners, especially in facilities with limited resources. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly increasing and carriages a major threat to neonates. We aimed to examine phenotypes causing neonatal late onset sepsis (NLOS) in comparison with neonatal early onset sepsis (NEOS) with further investigations of genotypes, and genetic relatedness of CRKP in neonatal late-onset sepsis. Our study included 88 neonates diagnosed with sepsis: 58 with (NLOS) and 30 with (NEOS) from November 2015 to April 2016, at neonatal intensive care unit (NICU) of Cairo University Hospital. K. pneumoniae was the most common encountered pathogen in the NLOS group (37.9%) with a mean sepsis score of 6.39 when compared to the NEOS group (p < 0.05). In Klebsiella group, C-reactive protein and interleukin-6 levels were significantly high (p ˂ 0.001) and 56.5% of the isolates were meropenem resistant. The most prevalent carbapenemase gene was OXA-48 which was identified in 14/23 (60.8%) followed by NDM-1 which was identified in 12/23 (52.2%) as detected by multiplex PCR. Coexistence of both carbapenemases was found in 52.2% (12/23). The blaKPC, blaIMP, and blaVIM genes were not harbored in the isolates. By investigating the genetic relatedness of CRKP by pulsed-field gel electrophoresis, 23 isolates of K. pneumoniae revealed various pulsed-field gel electrophoresis (PFGE) patterns, demonstrating that the isolates were non-clonal. Awareness of the existing phenotypes and genotypes is important for proper treatment and infection control practices.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Variação Genética , Unidades de Terapia Intensiva Neonatal , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Enterobacteriáceas Resistentes a Carbapenêmicos/classificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Estudos Transversais , Egito/epidemiologia , Humanos , Recém-Nascido , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/classificação , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Prognóstico , Vigilância em Saúde Pública , Resultado do Tratamento
19.
Am J Perinatol ; 37(5): 497-502, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30900217

RESUMO

OBJECTIVE: This study aimed to evaluate soluble cluster of differentiation 14 subtype (sCD14-ST), also named presepsin, as an early marker for the diagnosis of culture-proven early-onset sepsis (EOS) in neonates and to assess its relation to disease severity and mortality. STUDY DESIGN: Out of 60 neonates with risk factors of EOS, 31 neonates were diagnosed as having culture-proven EOS. They were compared with 20 nonseptic controls. We obtained blood samples on day 1 of life for sCD14-ST measurement and sepsis screening. Blood samples were repeated on day 3 in EOS neonates. RESULTS: sCD14-ST was significantly higher in EOS neonates than controls (p < 0.001). Neonates who later developed septic shock had significantly higher day 1 sCD14-ST level than those who did not (p < 0.001). Furthermore, neonates who died had significantly higher day 1 sCD14-ST than survivors (p < 0.001). On day 3, there was a significant decline in sCD14-ST levels than initial levels among survivors. There was a significant positive correlation between day 1 sCD14-ST level and Tollner's sepsis severity score. CONCLUSION: sCD14-ST could be used as a powerful diagnostic and prognostic marker of EOS. Its quantitative measurement at birth could be a good predictor of sepsis severity and mortality.


Assuntos
Receptores de Lipopolissacarídeos/sangue , Sepse Neonatal/diagnóstico , Fragmentos de Peptídeos/sangue , Técnicas Bacteriológicas , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Recém-Nascido , Masculino , Sepse Neonatal/sangue , Sepse Neonatal/microbiologia , Sepse Neonatal/mortalidade , Estudos Prospectivos , Curva ROC , Choque Séptico/etiologia
20.
Rev Chilena Infectol ; 36(4): 433-441, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-31859766

RESUMO

BACKGROUND: Infections caused by extended-spectrum beta-lactamases enterobacteria (ESBL-EP) have implications for neonatal morbidity and mortality. AIM: To describe the prevalence of ESBL-EP in neonatal sepsis and associated factors. METHODS: A prospective cohort study was conducted from August 2016 to August 2017; newborn babies (NB) hospitalized in the Hospital Civil de Guadalajara "Dr. Juan I. Menchaca" were included. The ESBL-EP were investigated by double-disk synergy test and its association with clinical and demographic characteristics of the NB. RESULTS: A total of 1,501 hospitalized NB were studied, with an average gestational age of 36.3 weeks. They were diagnosed 196 neonatal sepsis events, the most frequent etiologies were enterobacteria (45.5%). Resistance to ampicilin was found in 88.8% and to broad spectrum cephalosporins in more than 42% of the strains; 22.9% of them were ESBL phenotype. Apgar ≤ 7 at five minutes of life (OR 4.6; 95% CI 1.47-14.6) and gestational age < 37 weeks (OR 5.4; 95% CI 1.04-27.) increase the risk. CONCLUSION: In enterobacteria that cause neonatal sepsis, 22.9% were EP-ESBL; infection was more likely in patients with Apgar ≤ 7 at five minutes of age and in preterm infants.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Sepse Neonatal/microbiologia , beta-Lactamases/biossíntese , Adolescente , Adulto , Criança , Enterobacteriaceae/classificação , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
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