Risks associated with antidepressants in patients with hypertension during pregnancy: a retrospective cohort study.

PURPOSE: In a cohort of pregnant women using antihypertensive drugs, we compared exposure to antidepressants versus no exposure and the possible association with birth weight, APGAR scores, NICU admission, and maternal admission to an obstetrical intensive care unit (OHC). It was hypothesized that pregnant women with hypertensive disorders using antidepressants are at greater risk of complications. METHODS: A retrospective cohort study in a general teaching hospital in Zwolle, in the Middle-Northern part of The Netherlands. Finally, 58 pregnancies in the exposed group and 273 pregnancies in the reference group met all inclusion and exclusion criteria. We compared the neonate's birthweight between the exposed to antidepressants group and the reference group as the primary outcome. Secondary outcomes were the APGAR score at 1 and 5 min and obstetric high care (OHC) admission of the mother and neonatal intensive care unit (NICU) admission of the child. RESULTS: We found no differences in birth weight in neonates of mothers with hypertensive disorders and whether or not to use antidepressants. Besides a possible higher risk of admission to an OHC in women with hypertension-complicated pregnancies using antidepressants, we found no other maternal or neonatal risks in this population. CONCLUSION: We found no additional maternal or neonatal risks of using antidepressants prescribed to women with hypertension disorders during pregnancy.

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial).

BACKGROUND: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. METHODS: The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18-24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. DISCUSSION: Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020.

Maternal and neonatal outcomes after benzodiazepine and benzodiazepine agonist exposure during pregnancy in women with mental disorders.

AIMS: To compare the gestational age of neonates in utero exposed to benzodiazepines (BDZs) with nonexposed controls. Secondary objectives were birth weight, presence of congenital malformations, APGAR score and the need for >3 months (prolonged) maternal psychiatric care. METHODS: A retrospective cohort study of women and neonates from 2013 to 2021 with univariate and multivariable analysis to study the associations between BDZ exposure and gestational age compared to nonexposed women with mental health problems. RESULTS: We found that BDZ exposure was not associated with a lower gestational age. We found that women in the exposed group had an increased risk of psychiatric care (adjusted odds ratio 2.58 [95% confidence interval 1.71-3.91], P < .001). CONCLUSION: We found that in utero BDZ exposure was not associated with a significantly lower gestational age of the neonates and was associated with prolonged psychiatric care of their mothers.

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND FINDINGS: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. CONCLUSIONS: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. TRIAL REGISTRATION: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.

The first fungi: mode of delivery determines early life fungal colonization in the intestine of preterm infants.

Aim: The role of intestinal fungi in human health and disease is becoming more evident. The mycobiota composition and diversity of preterm infants is affected by interactions with bacteria and clinical variables. In this study, we aimed to characterize the composition and the diversity of the preterm infant mycobiota and the effect of clinical variables on it in the first six postnatal weeks. Methods: Preterm infants (n = 50) and full-term infants (n = 6) admitted to Isala Women and Children's hospital (Zwolle, The Netherlands) who were born during 24-36 or 37-40 weeks of gestation, respectively, were included in this study. Feces were collected during the first six postnatal weeks (n = 109) and their mycobiota composition and diversity were characterized by ITS2 amplicon sequencing. Results: Composition analyses identified fungi and other eukaryotic kingdoms, of which Viridiplantae was most abundant. Of the fungal kingdom, Ascomycota and Basidiomycota were the first and second most prominent phyla in early life of all infants. Candida was the most abundant genus in the first six weeks of life and increased with gestational and postnatal age. Fungal phylogenetic diversity remained stable in the first six postnatal weeks. The individuality and the mode of delivery were identified as significant predictors for the variation in the mycobiota composition. Vaginally delivered infants were enriched in Candida spp., whereas infants delivered through emergency C-section were characterized by Malassezia spp. Conclusion: These results indicate that fungi and other eukaryotic kingdoms are detected in the intestine of preterm and full-term infants in the first six postnatal weeks. Similar to the microbiota, colonization of the preterm intestine with fungi is determined by clinical variables including individuality and mode of delivery.

Rotavirus Vaccine Safety and Effectiveness in Infants With High-Risk Medical Conditions.

OBJECTIVES: Rotavirus vaccination has 87% to 100% effectiveness against severe rotavirus acute gastroenteritis (AGE) in healthy infants in high-income countries. Little is known whether infants with medical risk conditions (MRCs) are equally protected and if the vaccine is equally well tolerated. We conducted a quasi-experimental prospective multicenter before-after cohort study to assess the vaccine effectiveness (VE) and safety profile of the human rotavirus vaccine (HRV) among MRC infants that required prolonged or frequent postnatal care. METHODS: The Netherlands has no national rotavirus immunization program, but HRV was implemented in routine care for MRC infants in 13 Dutch hospitals. Participants in the before and after cohort, HRV unvaccinated and vaccinated, respectively, were followed for occurrence of (rotavirus) AGE. VE of at least 1 dose was estimated by using time-to-event analysis for severe rotavirus AGE. Vaccine-related serious adverse event (AEs) after HRV were retrieved systematically from medical charts. Solicited AEs after vaccinations were prospectively collected and compared between vaccination time points with or without HRV. RESULTS: In total, 1482 high-risk infants with MRC were enrolled, including 631 in the before and 851 in the after cohorts; 1302 infants were premature (88.3%), 447 were small for gestational age (30.2%), and 251 had at least 1 congenital disorder (17.0%). VE against severe rotavirus AGE was 30% (95% confidence interval [CI]: -36% to 65%). Overall, the observed number of rotavirus hospitalizations was low and not significantly different between the cohorts (2 and 2, respectively). The rate of vaccine-related serious AE was 0.24 per 100 vaccine doses. The adjusted risk ratio for any AE after HRV vaccination compared with other routine vaccinations was 1.09 (95% CI: 1.05 to 1.12) for concomitant administration and 0.91 (95% CI: 0.81 to 0.99) for single HRV administration. Gastrointestinal AEs were 10% more frequent after HRV. CONCLUSIONS: In contrast to previous findings among healthy term infants, in routine use, HRV offered limited protection to vulnerable medical risk infants. HRV is generally well tolerated in this group in single administration, but when coadministered with routine vaccines, it is associated with higher risk of (mostly gastrointestinal) AE. Our study highlights the importance of studying vaccine performance in subgroups of medically vulnerable infants.

From Mum to Bum: An Observational Study Protocol to Follow Digestion of Human Milk Oligosaccharides and Glycoproteins from Mother to Preterm Infant.

The nutritional requirements of preterm infants are challenging to meet in neonatal care, yet crucial for their growth, development and health. Aberrant maturation of the gastrointestinal tract and the microbiota could affect the digestion of human milk and its nutritional value considerably. Therefore, the main objective of the proposed research is to investigate how the intestinal microbiota of preterm and full-term infants differ in their ability to extract energy and nutrients from oligosaccharides and glycoproteins in human milk. This pilot study will be an observational, single-center study performed at the Neonatal Intensive Care Unit at Isala Women and Children's Hospital (Zwolle, The Netherlands). A cohort of thirty mother-infant pairs (preterm ≤30 weeks of gestation, n = 15; full-term 37-42 weeks of gestation, n = 15) will be followed during the first six postnatal weeks with follow-up at three- and six-months postnatal age. We will collect human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants. A combination of 16S rRNA amplicon sequencing, proteomics, peptidomics, carbohydrate analysis and calorimetric measurements will be performed. The role of the microbiota in infant growth and development is often overlooked yet offers opportunities to advance neonatal care. The 'From Mum to Bum' study is the first study in which the effect of a preterm gut microbiota composition on its metabolic capacity and subsequent infant growth and development is investigated. By collecting human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants at each timepoint, we can follow digestion of human milk from the breast of the mother throughout the gastrointestinal tract of the infant, or 'From Mum to Bum'.

[Rotavirus infections in neonates: not as innocent as expected]. / Rotavirusinfectie bij een neonaat: niet zo onschuldig als verwacht.

BACKGROUND: Rotavirus is a common cause of gastroenteritis in children. It is much less known that rotavirus infections can lead to encephalitis with convulsions in neonates. CASE DESCRIPTION: A premature boy (36 weeks + 5 days) developed neonatal convulsions 17 days post-partum. His sister had symptoms of gastroenteritis. Cerebral MRIs showed extensive white matter abnormalities in diffusion-weighted images and, a few weeks later, cystic white matter abnormalities. There were no gastrointestinal phenomena or pleocytosis in the cerebrospinal fluid. Rotavirus was detected in the stools, using molecular diagnostics (PCR). CONCLUSION: Rotavirus infection at a neonatal age can have serious consequences. Due to the absence of gastrointestinal phenomena, pleocytosis and demonstrability of rotavirus in faeces and not in CSF, this clinical picture has long remained undiagnosed. Instructions on hand hygiene during the post-partum period contributes to the prevention of rotavirus infection in neonates. Herd immunity through rotavirus vaccination for all neonates could lead to significant risk reduction.

Gram-negative Late-onset Sepsis in Extremely Low Birth Weight Infants Is Emerging in The Netherlands Despite Quality Improvement Programs and Antibiotic Stewardship!

BACKGROUND: Late-onset sepsis (LOS) is still an important cause of morbidity and mortality in premature infants. Indwelling devices and lower birth weight (BW) are the most important risk factors. Quality improvement programmes are implemented to reduce incidence of LOS. An increasing number of extremely low BW infants (ELBWs) (≤1000 g) are treated in the Netherlands, including infants with gestational age (GA) 24 weeks since Dutch law changed in 2010. We evaluated the incidence and causative microorganisms of LOS in ELBWs over an 8-year period in 2 Dutch neonatal intensive care units (NICUs). METHODS: The first LOS episodes of all ELBWs admitted to the NICU of the Wilhelmina Children's Hospital Utrecht and the Isala Hospital Zwolle were included retrospectively from January 2008 to December 2015. LOS was defined as clinical signs of sepsis >72 hours postpartum, combined with a positive blood culture and C-reactive protein of ≥10 mg/L. RESULTS: Two hundred fifty-five out of 923 ELBWs (27.6%) had an episode of LOS, and no decrease in incidence was seen over the years. ELBWs with LOS had lower GA and BW. The percentage of Gram-negative organisms increased from 0% in 2008 to 27% in 2015, mainly in infants with GA <26 weeks. The number of invasive fungal infections decreased to zero. CONCLUSIONS: No significant decrease in incidence of LOS in ELBWs was seen, despite the introduction of quality improvement programmes and attention to antibiotic stewardship. Furthermore, an increase in Gram-negative LOS was observed, with an overrepresentation among the growing proportion of the NICU population at the lowest GA and weight. Prevention, including high compliance to hand hygiene policies, may be an impactful intervention.

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

BACKGROUND: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. METHODS/DESIGN: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. DISCUSSION: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. TRIAL REGISTRATION: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Discordant Transient Extreme Hyperleukocytosis in Dichorionic Diamniotic Twins: The Role of the Sex?

Although a leukemoid reaction is a well-recognized phenomenon in the neonatal intensive care unit, transient extreme hyperleukocytosis in premature infants is rare. The exact mechanism is still unclear and several hypotheses are documented in the literature. In this case report, we describe 2 dichorionic diamniotic premature twins, of whom the 2 girls had extreme hyperleukocytosis, whereas their siblings did not, emphasizing the potentially important role of the sex in this phenomena.

Reduced expression of PBP-2A by neonatal mecA-positive coagulase-negative staphylococci (CoNS) blood isolates: ß-lactams are useful first-line agents for the treatment of neonatal CoNS sepsis, restricting the use of vancomycin.

OBJECTIVES: Vancomycin use for neonatal coagulase-negative staphylococci (CoNS) sepsis is based on a high CoNS carriage rate of mecA, encoding penicillin-binding protein (PBP)-2a, with low affinity for, and associated with resistance to, ß-lactam antibiotics. The relationship between mecA gene carriage, phenotypic expression of the gene by PBP-2a production and in vitro resistance to the ß-lactam antibiotics oxacillin, cefazolin and amoxicillin/clavulanate was determined for 85 CoNS blood isolates randomly obtained from our collection of isolates from neonates with CoNS sepsis. METHODS: The relationship between mecA gene carriage, phenotypic expression of the gene by PBP-2a production and in vitro resistance to the ß-lactam antibiotics oxacillin, cefazolin and amoxicillin/clavulanate was determined for randomly obtained CoNS blood isolates from our collection of isolates from neonates with CoNS sepsis. The mecA gene was detected using multiplex PCR, and PBP-2a expression was determined using a latex agglutination (LA) test (Oxoid). ß-Lactam susceptibility was determined using the Phoenix automated system and, in addition, by Etest with interpretation of MIC values according to the reference MIC breakpoints adopted from the CLSI guidelines M100-S20, Infobase™. RESULTS: Among 85 CoNS blood isolates, 73 (86%) were mecA positive and 12 (14%) were mecA negative. None of the mecA-negative isolates expressed PBP-2a and all were ß-lactam susceptible. All mecA-positive CoNS isolates were oxacillin resistant, although most oxacillin MICs were not very high, ranging from 2 to 8 mg/L for the majority of isolates. Only 8/73 (11%) mecA-positive CoNS isolates had oxacillin MICs ≥32 mg/L (range 32 to >256 mg/L). mecA-positive CoNS blood isolates, although fully resistant to oxacillin, were almost universally susceptible to cefazolin and amoxicillin/clavulanate, which was associated with a low expression rate of PBP-2a. CONCLUSIONS: ß-Lactam antibiotics are useful for the treatment of neonatal CoNS sepsis, reserving vancomycin for selected cases.

Shortening the antibiotic course for the treatment of neonatal coagulase-negative staphylococcal sepsis: fine with three days?

BACKGROUND: The incidence of coagulase-negative staphylococcal (CoNS) sepsis is high in neonatal intensive care units (NICUs) and treatment significantly adds to the antibiotic pressure, increasing the threat of resistance. Because infants recover within 24-48 h, blood cultures are negative within 48 h and CRP normalizes within 72 h, we reduced anti-CoNS treatment from 7 to 3 days in infants with uncomplicated CoNS sepsis. OBJECTIVES: The aim of the study was to evaluate the effect of short (3 days) treatment duration for CoNS sepsis. METHODS: All infants with CoNS sepsis from January 2006 to September 2010 were evaluated. Before 2008 the duration of anti-CoNS treatment was 7 days, but in 2008 it was reduced to 3 days, provided that infants recovered within 48 h, CRP value decreased, thrombocytes were normal and central venous catheters were either not present or removed. Clinical results of treatment for 3 days were compared with 7 days of treatment. RESULTS: There were 142 infants with CoNS sepsis who were eligible for 3 days of antimicrobial treatment duration, 62 (44%) from the period 2006-2008 were treated over 7 days (Group 1) and 80 (56%) from the period 2008-2010 were treated over 3 days (Group 2). Clinical characteristics were not different between the groups. All infants recovered within 48 h and CoNS sepsis did not relapse. CONCLUSIONS: Antibiotic treatment for CoNS sepsis may be shortened to 3 days when clinical improvement is rapid and central lines are not present. Prospective randomized studies are needed to confirm the results of this single-center study. Future studies may reveal the effects on the development of antimicrobial resistance.

A seven-year survey of management of coagulase-negative staphylococcal sepsis in the neonatal intensive care unit: vancomycin may not be necessary as empiric therapy.

BACKGROUND: The typical empiric therapy for coagulase-negative staphylococcal (CONS) sepsis includes vancomycin. In our neonatal intensive care unit, we have consistently avoided the use of vancomycin to treat CONS sepsis, except for specific cases, and have used instead cefazolin as empiric agent. OBJECTIVES: The clinical outcome of infants with CONS sepsis was evaluated in relation to the susceptibility of CONS blood isolates to cefazolin over a period of 7 years. METHODS: Clinical characteristics, symptoms of sepsis and antibiotic use were studied retrospectively. Susceptibility of CONS blood isolates to cefazolin was determined by E-test. RESULTS: Of 163 infants with proven CONS sepsis, 121/140 (86%) infants with a cefazolin-susceptible (minimum inhibition concentration (MIC) ≤8 mg/l) and 21/23 (91%) with a cefazolin-resistant (MIC ≥32 mg/l) blood isolate were treated with cefazolin. 21 (13%) infants were switched to vancomycin, in only 3 of them CONS had become resistant to cefazolin. The majority (81%) of the infants with a good response to cefazolin had the indwelling central venous catheter removed, in contrast to only 22% of the infants with cefazolin treatment failure. Median cefazolin MIC values were 0.75-2 mg/l during the study period. CONCLUSIONS: The great majority of infants with CONS sepsis was successfully treated with cefazolin. The use of vancomycin could be restricted to specific cases. Despite the consistent use of cefazolin in neonatal CONS sepsis over an extended period of time, cefazolin MIC values remained low and in the susceptible range. Removal of the central venous catheter in infants with clinical symptoms of sepsis is an important therapeutic measure.

Prevention of neonatal late-onset sepsis associated with the removal of percutaneously inserted central venous catheters in preterm infants.

OBJECTIVES: Indwelling central venous catheters are the most important risk factors for the development of sepsis attributable to coagulase-negative staphylococci among preterm infants admitted to neonatal intensive care units. In addition, removal of a central venous catheter also may cause coagulase-negative staphylococci sepsis, which may be prevented by the short-term administration of an anti-staphylococcal agent during the procedure of removal. The administration of a specific anti-staphylococcal agent (cefazolin) was evaluated for the prevention of central venous catheter removal-associated coagulase-negative staphylococci sepsis. DESIGN: A prospective, open, randomized, controlled intervention study. SETTING: Twenty-eight-bed neonatal intensive care unit at a tertiary care children's hospital. PATIENTS: Eighty-eight preterm infants (gestational age <37 wks) admitted to the neonatal intensive care unit with indwelling percutaneously inserted central venous catheters. INTERVENTION: From April 2007 to January 2010, infants were randomized to receive two doses of cefazolin during removal of the percutaneously inserted central venous catheter (intervention group, n = 44) or no antimicrobial agent (control group, n = 44). Percutaneously inserted central venous catheter removal-associated sepsis was defined as sepsis occurring <48 hrs after removal of the percutaneously inserted central venous catheter. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics and central venous catheter duration did not show differences between both groups. Five infants (11%) of the control group developed coagulase-negative staphylococci sepsis <48 hrs after removal of the percutaneously inserted central venous catheter compared to none (0%) in the intervention group (p = .021). CONCLUSIONS: Two doses of the anti-staphylococcal agent cefazolin during the procedure of removal of a percutaneously inserted central venous catheter were effective in the prevention of coagulase-negative staphylococci sepsis. It is recommended to include this regimen in the guidelines on management of central venous catheters in very-low-birth-weight infants.

Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy.

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.