Lm

Bundy, Alan; Wallen, Lincoln

doi:10.1007/978-3-642-96868-6_125

Cited by 3 publications

(6 citation statements)

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“…Meningitis is characterized by an overwhelming cytokine response and immune cell influx to the site of infection (29). Meningitis is a particularly complex disease and results in a neonatal mortality rate as high as 40% (29,30).…”

Section: Introductionmentioning

confidence: 99%

Identification of zinc-dependent mechanisms used by Group B Streptococcus to overcome calprotectin-mediated stress

Burcham

Breton

Radin

et al. 2020

Preprint

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Nutritional immunity is an elegant host mechanism used to starve invading pathogens of necessary nutrient metals. Calprotectin, a metal binding protein, is produced abundantly by neutrophils and is found in high concentrations within inflammatory sites during infection. Group B Streptococcus (GBS) colonizes the gastrointestinal and female reproductive tracts and is commonly associated with severe invasive infections in newborns such as pneumonia, sepsis, and meningitis. Though GBS infections induce robust neutrophil recruitment and inflammation, the dynamics of GBS and calprotectin interactions remain unknown. Here we demonstrate that disease and colonizing isolate strains exhibit susceptibility to metal starvation by calprotectin. We constructed a mariner transposon (Krmit) mutant library in GBS and identified 258 genes that contribute to surviving calprotectin stress. Nearly 20% of all underrepresented mutants following treatment with calprotectin, are predicted metal transporters, including known zinc systems. As calprotectin binds zinc with picomolar affinity, we investigated the contribution of GBS zinc uptake to overcoming calprotectin-imposed starvation. Quantitative RT-PCR revealed a significant upregulation of genes encoding zinc-binding proteins, adcA, adcAII, and lmb, following calprotectin exposure, while growth in calprotectin revealed a significant defect for a global zinc acquisition mutant (ΔadcAΔadcAIIΔlmb) compared to the GBS WT strain. Further, mice challenged with the ΔadcAΔadcAIIΔlmb mutant exhibited decreased mortality and significantly reduced bacterial burden in the brain compared to mice infected with WT GBS; this difference was abrogated in calprotectin knockout mice. Collectively, these data suggest that GBS zinc transport machinery are important for combatting zinc-chelation by calprotectin and establishing invasive disease.ImportanceGBS asymptomatically colonizes the female reproductive tract but is a common causative agent of meningitis. GBS meningitis is characterized by extensive infiltration of neutrophils, carrying high concentrations of calprotectin, a metal chelator. To persist within inflammatory sites and cause invasive disease, GBS must circumvent host starvation attempts. Here, we identified global requirements for GBS survival during calprotectin challenge, including known and putative systems involved in metal ion transport. We characterized the role of zinc import in tolerating calprotectin stress in vitro, and in a mouse model of infection. We observed that a global zinc-uptake mutant was less virulent compared to the parental GBS strain and found calprotectin knockout mice to be equally susceptible to infection by WT and mutant strains. These findings suggest that calprotectin production at the site of infection results in a zinc-limited environment and reveals the importance of GBS metal homeostasis to invasive disease.

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Section: Introductionmentioning

confidence: 99%

Identification of zinc-dependent mechanisms used by Group B Streptococcus to overcome calprotectin-mediated stress

Burcham

Breton

Radin

et al. 2020

Preprint

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“…In developing countries, the reported mortality rates are even higher, reaching 40%–58%. 10 Despite advances in perinatal and neonatal critical care medicine, the outcome of this condition remains poor, with a 20%–60% rate of adverse outcomes among survivors. Neonates are particularly vulnerable to bacterial infections due to perinatal exposure, incomplete vaccination and relative immune immaturity.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and Outcomes of Neonatal Meningitis: Results of the Turkish Neo-Meningitis Nationwide Study

Oncel,

Cizmeci,

Karadag-Oncel

et al. 2023

Pediatric Infectious Disease Journal

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Objective: To investigate the incidence and etiology of neonatal meningitis and to assess the associated risk factors, complications and outcomes in a nationwide multicenter retrospective descriptive study. Method: Twenty-seven centers from 7 geographical regions participated in the study. Newborns with a positive cerebrospinal fluid culture and/or cerebrospinal fluid polymerase chain reaction were included in the study. Demographic characteristics, clinical, laboratory and neuroimaging findings and mortality characteristics were analyzed. Results: A total of 634 confirmed cases of neonatal meningitis were included in the final analysis. The incidence was 2.51 per 1000 intensive care unit hospitalizations and mortality was observed in 149 (23.5%). Gram-positive bacteria were the predominant pathogens (54.5%), with coagulase-negative Staphylococci accounting for 45.3% of the cases, followed by gram-negative organisms (37.3%). Viral and fungal organisms were isolated in 3.2% and 1.7% of the infants, respectively. Gram-negative culture growth was more common in infants who died (51% vs. 34.6%; P < 0.001). In the multivariable model, the odds of mortality was higher in those with respiratory distress requiring invasive ventilatory support [odds ratio (OR): 10.3; 95% confidence interval (CI): 4.9–21.7; P < 0.01], hypotension requiring inotropes (OR: 4.4; 95% CI: 2.7–7.1; P < 0.001), low birth weight status (OR: 2.5; 95% CI: 1.4–4.6; P = 0.002), lack of exposure to antenatal steroids (OR: 2.4; 95% CI: 1.3–4.4; P = 0.005) and the presence of concomitant sepsis (OR: 1.9; 95% CI: 1.1–3.2; P = 0.017). Conclusions: In this nationwide study, neonatal meningitis was found to be associated with high mortality. Coagulase-negative Staphylococci was the most common causative microorganism followed by gram-negative bacteria. Severe clinical presentation with invasive mechanical ventilation and inotrope requirement, as well as concomitant sepsis, low birth weight status and lack of exposure to antenatal steroids, were found to be independent risk factors for mortality.

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“…Since late-onset BM is usually due to organisms acquired from the environment or caregivers, it is advisable to strengthen the infection control and prevention practices in the hospital environment. 9 , 13 …”

Section: Discussionmentioning

confidence: 99%

“…According to the results of our study, there was a high antimicrobial-resistant rate of neonate CSF bacterial isolates among Cephalosporin 90% (18/20), Cotrimoxazole 89% (8/9), Penicillin 77.3% (17/22), and Aminoglycosides 54.5% (12/22). The antibiotic choices for NBM, including ampicillin, gentamicin, or cefuroxime, 13 are also becoming ineffective. Our paper reported a higher resistance to β-lactam (around 77%) and Aminoglycoside (54.5%) antibiotics than a review paper in the sub-Saharan African countries, with 68% and 27% of bacterial isolates from neonates were resistant to β-lactam and aminoglycoside antibiotics, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Etiology of Neonatal Bacterial Meningitis and Their Antibiotic Susceptibility Pattern at the University of Gondar Comprehensive Specialized Hospital, Ethiopia: A Seven-Year Retrospective Study

Biset

Benti

Molla

et al. 2021

IDR

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Background: Meningitis, which is mostly caused by infectious agents, occurs more commonly during the first month of life. Bacterial meningitis is an important source of mortality and morbidity, especially in neonates of resource-limited countries. We aimed to determine the prevalence and etiological agents of bacterial meningitis and their antibiotic susceptibility pattern in neonates at the University of Gondar Comprehensive Specialized Hospital. Methods: We collected retrospective data from bacteriological results of cerebrospinal fluid of meningitis suspected neonates from 2013 to 2019. Sample collection, culture preparation, bacterial identification, and susceptibility testing were performed using standard microbiological techniques. We extracted data on socio-demographic characteristics and culture and antibiotic susceptibility testing results. We inputted the data using Epi-info version 7 and exported it to SPSS version 20 for analysis. Results: In this study, 1101 cerebrospinal fluid samples, 595 (54%) male and 506 (46%) female neonates, were cultured to look for meningitis-causing bacteria. Of 1101 cerebrospinal fluid, 19 (1.73%) were culture positive for meningitis-causing bacteria. The common etiological agents were Klebsiella pneumoniae 36.8% (7), non-lactose-fermenter Gramnegative rods 21% (4), and Group B streptococcus 15.8% (3). The overall resistance rate among cephalosporin, cotrimoxazole, penicillin, and aminoglycosides classes were 90%, 88.9%, 77.3%, and 54.54%, respectively. Of all isolates, 58% (11) were multidrugresistant, including all the non-lactose-fermenter Gram-negative rods and 71.4% of the Klebsiella pneumonia isolates. Conclusion:The prevalence of neonatal bacterial meningitis was 1.73%. Klebsiella pneumonia and other Gram-negative rods, with a high multidrug-resistant rate, were the leading cause of neonatal bacterial meningitis. Further studies are needed to explore the source of infection, incidence, and risk factors of neonatal bacterial meningitis.

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Lm

Cited by 3 publications

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Identification of zinc-dependent mechanisms used by Group B Streptococcus to overcome calprotectin-mediated stress

Identification of zinc-dependent mechanisms used by Group B Streptococcus to overcome calprotectin-mediated stress

Epidemiology and Outcomes of Neonatal Meningitis: Results of the Turkish Neo-Meningitis Nationwide Study

Etiology of Neonatal Bacterial Meningitis and Their Antibiotic Susceptibility Pattern at the University of Gondar Comprehensive Specialized Hospital, Ethiopia: A Seven-Year Retrospective Study

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