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Comparison of ampicillin plus gentamicin vs. penicillin plus gentamicin in empiric treatment of neonates at risk of early onset sepsis

Aim:  We aimed to compare the clinical efficacy of ampicillin (AMP) vs. penicillin (PEN) both combined with gentamicin in the empirical treatment of neonates at risk of early onset neonatal sepsis (EOS).

Risk factors associated with gut and nasopharyngeal colonization by common Gram-negative species and yeasts in neonatal intensive care units patients.

AIM To characterize dynamics of mucosal colonization of neonates by common aerobic Gram negative species and Candida spp. and to identify independent perinatal, neonatal, and environmental factors influencing the colonization process. STUDY DESIGN The nasopharyngeal (n=1145) and rectal (n=1242) swabs were collected on admission and thereafter twice a week in neonates with risk factors of early onset sepsis (n=276) admitted within the first 72 h of life. The association between colonization by different microbes and a total of 22 predefined risk factors was assessed using univariate and multiple logistic regression analyses. RESULTS Throughout the study about half of the patients had rectal (55.8%) or nasopharyngeal colonization (42.8%) with common Gram-negative microorganisms. Colonization dynamics and risk factors were in general similar for a given bacterial species in both mucosal sites; nonfermentative microbes more often found in nasopharyngeal swabs and Enterobacteriaceae in rectal swabs. All organisms except Escherichia coli were influenced by the duration of intensive care unit stay but other risk factors were species specific, perhaps reflecting their mode of acquisition. While colonization by E. coli and Candida albicans was associated with perinatal factors like term birth, vaginal delivery, and breast milk feeding; colonization by Klebsiella pneumoniae, Enteribacter cloacae, Acinetobacter spp. and non-albicans Candida spp. were mostly determined by hospital environment (treatment unit and period, artificial interventions and their duration) and gestation age ≤ 28 weeks. CONCLUSIONS The knowledge of risk factor profiles may permit the development of strategies to prevent heavy colonization and subsequent invasive disease in high risk infants.

Genetic relatedness of coagulase-negative Staphylococci from gastrointestinal tract and blood of preterm neonates with late-onset sepsis.

Background: Coagulase-negative staphylococci (CoNS) are the first colonizers of gastrointestinal tract (GIT) and the commonest cause of late-onset sepsis (LOS) in preterm neonates. Intravascular catheters are considered a major source of CoNS bacteremia. However, several cases of LOS remain without an identified source. To elucidate whether GIT could be a potential source of invasive strains, we aimed to assess the molecular similarity between CoNS from blood and GIT in preterm neonates with LOS. Methods: Altogether 22 blood and 53 GIT isolates collected from 22 neonates with LOS caused by CoNS (Staphylococcus haemolyticus in 13, Staphylococcus epidermidis in 7 and Staphylococcus hominis in 2 patients) were included. Rectal swabs were collected twice weekly from birth, but only isolates obtained before LOS were analyzed. S. epidermidis isolates were typed by multilocus variable number of tandem repeats analysis and multilocus sequence typing, S. haemolyticus by pulsed-field gel electrophoresis. Results: Eighteen of 22 neonates had the same CoNS species in GIT and bloodstream; all these isolates from them (altogether 18 blood and 28 GIT isolates) underwent typing. The genotypic similarity between bloodstream and ≥1 antecedent GIT isolates was observed in 13 of 18 patients—3 of 7 with S. epidermidis and 10 of 11 with S. haemolyticus infection. The concordant GIT isolates were collected 0–7 days before the positive blood culture. Conclusions: The similarity between CoNS from GIT and bloodstream indicates that preterm neonates harbour invasive strains in GIT before LOS. Whether there is a causal relationship between GIT colonization and LOS remains to be elucidated in further studies.

Impact of empiric antibiotic regimen on bowel colonization in neonates with suspected early onset sepsis

The purpose of this study was to compare the impact of ampicillin and penicillin used for empiric treatment of early onset sepsis (EOS) on initial gut colonization by aerobic and facultative anaerobic microorganisms. A cluster-randomized, two-center, switch-over study was conducted in two paediatric intensive care units in Estonia and included 276 neonates. Rectal swabs were collected twice a week until discharge or day 60. Colonizing microbes were identified on species level and tested for ampicillin resistance (AR). The number of patients colonized with Gram negative microorganisms and Candida spp was similar in both treatment arms but ampicillin resulted in longer colonization duration (CD) of K. pneumonia (p = 0.012), AR Serratia spp (p = 0.012) and Candida spp (p = 0.02) and penicillin in that of AR Acinetobacter spp (p = 0.001). As for Gram positive microorganisms penicillin treatment was associated with a greater number of colonized patients and higher CD of Enterococcus spp and S. aureus but lower ones of S. haemolyticus and S. hominis. Influence of ampicillin and penicillin on initial gut colonization is somewhat different but these differences are of low clinical relevance and should not be a limiting step when choosing between these two antibiotics for the empiric treatment of EOS.

The development of gut microbiota in critically ill extremely low birth weight infants assessed with 16S rRNA gene based sequencing

Objective: An increasing number of studies that are using high-throughput molecular methods are rapidly extending our knowledge of gut microbial colonization in preterm infants whose immaturity and requirement for extensive treatment may result in altered colonization process. We aimed to describe the profile of gut microbiota in 50 extremely low birth weight (<1200 g) critically ill infants at three different time points during the first two months of life by using 16S rRNA gene specific sequencing. Patients and Methods: Stool samples were collected at the age of one week, one month and two months. Bacterial community profiling was done using universal amplification of 16S rRNA gene and 454 pyrosequencing. Results: The diversity of gut microbiota in preterm neonates in the first week of life was low but increased significantly over two months. The gut microbiota was dominated by facultative anaerobic bacteria (Staphylococcus spp. and Enterobacteriaceae) and lacked colonization with bacteria known to provide resistance against pathogens (Bacteroides, Bifidobacterium, and Lactobacillus) throughout the study. Colonization of Escherichia coli and uncultured Veillionella was positively correlated with maturity. Infants born to mothers with chorioamnionitis had significantly higher bacterial diversity than those without. Conclusions: High prevalence and abundance of potentially pathogenic Enterobacteriaceae and Staphylococcaceae with low prevalence and abundance of colonization resistance providing taxa bifidobacteria, Bacteroides and lactobacilli may lead to high infection risk via microbial translocation from the gut. Additionally, our data suggest that maternal chorioamnionitis may have an effect on the diversity of infants’ gut microbiota; however, the mechanisms involved remain to be elucidated.

Clinical parameters predicting failure of empirical antibacterial therapy in early onset neonatal sepsis, identified by classification and regression tree analysis

BackgroundAbout 10-20% of neonates with suspected or proven early onset sepsis (EOS) fail on the empiric antibiotic regimen of ampicillin or penicillin and gentamicin. We aimed to identify clinical and laboratory markers associated with empiric antibiotic treatment failure in neonates with suspected EOS.MethodsMaternal and early neonatal characteristics predicting failure of empiric antibiotic treatment were identified by univariate logistic regression analysis from a prospective database of 283 neonates admitted to neonatal intensive care unit within 72 hours of life and requiring antibiotic therapy with penicillin or ampicillin and gentamicin. Variables, identified as significant by univariate analysis, were entered into stepwise multiple logistic regression (MLR) analysis and classification and regression tree (CRT) analysis to develop a decision algorithm for clinical application. In order to ensure the earliest possible timing separate analysis for 24 and 72 hours of age was performed.ResultsAt 24 hours of age neonates with hypoglycaemia ≤ 2.55 mmol/L together with CRP values > 1.35 mg/L or those with BW ≤ 678 g had more than 30% likelihood of treatment failure. In normoglycaemic neonates with higher BW the best predictors of treatment failure at 24 hours were GA ≤ 27 weeks and among those, with higher GA, WBC ≤ 8.25 × 109 L-1 together with platelet count ≤ 143 × 109 L-1. The algorithm allowed capture of 75% of treatment failure cases with a specificity of 89%. By 72 hours of age minimum platelet count ≤ 94.5 × 109 L-1 with need for vasoactive treatment or leukopaenia ≤ 3.5 × 109 L-1 or leukocytosis > 39.8 × 109 L-1 or blood glucose ≤ 1.65 mmol/L allowed capture of 81% of treatment failure cases with the specificity of 88%. The performance of MLR and CRT models was similar, except for higher specificity of the CRT at 72 h, compared to MLR analysis.ConclusionThere is an identifiable group of neonates with high risk of EOS, likely to fail on conventional antibiotic therapy.

Gut colonization by aerobic microorganisms is associated with route and type of nutrition in premature neonates

We hypothesized that the beneficial effects of early enteral compared with parenteral feeding are related to the increased variety of aerobic microorganisms that colonize the gut. Our aim was to describe the relationship, first, between the type of feeding and mucosal colonization and, second, between the type of feeding and the development of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm neonates. In total, 159 neonates aged 72 hours or less with risk factors for early-onset sepsis were recruited to a prospective 2-center study. Rectal swabs were collected on admission and twice per week thereafter. The feeding regimen was recorded for the first 7 days and categorized into total parenteral nutrition (TPN) and 2 regimens of enteral nutrition, that is, breast milk containing regimen (BMCR), for which breast milk constituted at least 11% of the enteral diet, or formula. Herein, 70 neonates received formula, 48 received BMCR, and 41 received TPN; 69 cases of LOS and 15 cases of NEC were observed in 50 neonates. A multiple logistic regression analysis indicated that formula and BMCR were associated with 4- to 5-fold increases in colonization by Gram-negative bacteria (odds ratio [OR], 4.52; 1.87-10.95, and OR, 4.95; 1.90-12.87, respectively) and 5 to 9 times higher odds of colonization by Gram-positive microorganisms (OR, 5.75; 1.89-16.72, and OR, 8.61; 2.52-29.36, respectively) compared with TPN. The only difference between BMCR and the other feeding groups was the higher colonization with Staphylococcus haemolyticus in the latter (formula-OR, 6.24; 1.73-22.50; TPN-OR, 2.75; 1.08-6.97). Compared with BMCR, TPN was associated with an increased odds of LOS (OR, 3.04; 1.02-9.07) and an increased odds of death (19.75; 3.64-107.12) compared with formula. Although early enteral feeding is associated with a higher odds of colonization with opportunistic microorganisms, it should be preferred over TPN whenever feasible, due to the favorable effect on the prevention of LOS.

Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units.

Late‐onset sepsis (LOS) in preterm neonates is increasingly reported to be associated with gut‐colonizing Staphylococcus epidermidis. We aimed to describe the molecular epidemiology of S. epidermidis colonizing the gut of neonates hospitalized in two neonatal intensive care units. S. epidermidis from rectal swabs were typed by multilocus variable‐number tandem‐repeat analysis (MLVA), randomly chosen isolates of predominant MLVA types additionally by multilocus sequence typing. Antimicrobial susceptibility, the presence of icaA, IS256, arginine catabolic mobile element (ACME), agr type, and SCCmec type were determined. Of 276 neonates (38.4%), 106 were colonized with S. epidermidis, yielding a total of 139 isolates (62 in one unit and 77 in another unit). Of the 55 MLVA types identified, the five predominant detected in both units corresponded to sequence type (ST) 2, ST5, and ST59 or its single locus variant ST81 and formed three major MLVA clonal complexes accounting for 74.8% of all isolates. Overall, the prevalence of mecA, icaA, IS256, and ACME was 91.4%, 28.1%, 64%, and 77%, respectively. Of the mecA‐positive isolates (n = 127), 43.9% carried SCCmec type IV. Of eight episodes of LOS, four were caused by ST2 and two by ST5. Preventing gut colonization with nosocomial epidemic S. epidermidis in hospitalized neonates could contribute to the prevention of LOS.

Ampicillin versus penicillin in the empiric therapy of extremely low-birthweight neonates at risk of early onset sepsis

Background:  There are no comparative data on the impact of different empiric antibiotic regimens on early bowel colonization as well as on clinical efficacy in extremely low‐birthweight (ELBW) neonates at risk of early onset sepsis (EOS).