Agnieszka Kordek

Early detection of an early onset infection in the neonate based on measurements of procalcitonin and C-reactive protein concentrations in cord blood

Abstract Background: The aim of this study was to test the diagnostic model of combining procalcitonin (PCT) and C-reactive protein (CRP) levels in the cord blood and routinely used biochemical parameters and clinical data in the prediction of early onset neonatal infection. Methods: PCT and CRP concentrations were measured in cord blood of neonates with infection (group A, n=46) and compared with uninfected neonates (group B, n=240). Inclusion criteria for group A were based on obstetric history, clinical data and results of laboratory tests. Logistic regression was applied. The receiver operating characteristic (ROC) curves were constructed for PCT, CRP and the diagnostic model. Results: There was a highly significant (p<0.000001) difference in PCT and CRP concentrations between both groups. The cut-off point for PCT in cord blood was 1.22 ng/mL [sensitivity % (SE%) 80.43, specificity % (SP%) 71.67, positive predictive value % (PPV%) 35.24, negative predictive value % (NPV%) 95.03], and 1.0 mg/L for CRP (SE% 73.91, SP% 77.92, PPV% 39.08, NPV% 93.97). In total, seven variables were included in the model (concentrations of PCT and CRP in cord blood, tocolysis, nutritional status of the newborn, Apgar score, neutrophil ratio and red blood cell count in neonatal venous blood), which proved to offer the highest sensitivity (91.3%; 95% CI: 83–99) and specificity (90%; 95% CI: 86–94) for the detection of early onset neonatal infection. The likelihood ratio for the model was high at 9.13, with PPV% 63.64 (95% CI: 52–75), NPV% 98.18 (95% CI: 96–100) and calculated area under the curve at 0.973. Conclusions: The diagnostic model based on seven clinical and laboratory parameters, using the concentration of PCT and CRP measurements in the cord blood, could be a useful tool for the prediction of early onset neonatal infection. Clin Chem Lab Med 2008;46:1143–8.

Necrotising Enterocolitis in Preterm Infants: Epidemiology and Antibiotic Consumption in the Polish Neonatology Network Neonatal Intensive Care Units in 2009

The aim of this study was to describe the epidemiology of necrotising enterocolitis (NEC), antibiotic consumption and the usefulness of microbiological tests in very low birth weight (VLBW) Polish newborns. Methods Prospective surveillance was performed in the year 2009 by local infection control teams. The study covered 910 infants hospitalized in six Polish neonatal intensive care units. Two kinds of indicators were used for the description of antibiotic usage: the duration of treatment (days of treatment, DOTs) and the defined daily dose (DDD). Results NEC incidence was 8.7% and fatality rate was 19%. Chorioamnionitis, late gestational age and low birth weight were identified as risk factors for NEC. Catheterization, mechanical ventilation and other selected procedures were used considerably longer in newborns with NEC than in the remaining neonates. Total usage of antibiotics reached 2.9 DDDs or 1.437 days; the average use of drugs per case of NEC amounted to 0.47 DDD or 23.2 DOTs. The level of antibiotic usage was analysed with correlation to microbiological tests performed and it was non-significantly greater in the group of children with NEC in whom the tests were performed. Conclusions A high risk of developing NEC is closely associated with VLBW and with inflammation of the amnion during labour. We observed no relationship between the consumption of antibiotics in neonates with NEC and positive results of microbiological testing indicating sepsis accompanying NEC or gut colonization with pathogens.

Late-onset bloodstream infections of Very-Low-Birth-Weight infants: data from the Polish Neonatology Surveillance Network in 2009–2011

BackgroundLate-Onset Bloodstream Infections (LO-BSI) continue to be one of the most important complications associated with hospitalization of infants born with very low birth weight (VLBW). The aims of this study were to assess the epidemiology of LO-BSI together with the risk factors and the distribution of causative pathogens at six Polish neonatal intensive care units that participated in the Polish Neonatology Surveillance Network from January 1, 2009 to December 31, 2011.MethodsThe surveillance covered 1,695 infants whose birth weights were <1501 grams (VLBW) in whom LO-BSI was diagnosed >72 hours after delivery. Case LO-BSI patients were defined according to NeoKISS.ResultsFour hundred twenty seven episodes of LO-BSI were diagnosed with a frequency of 25.3% and an incidence density of 6.7/1000 patient-days (pds). Results of our multivariate analysis demonstrated that surgical procedures and lower gestational age were significantly associated with the risk of LO-BSI. Intravascular catheters were used in infants with LO-BSI significantly more frequently and/or for longer duration: Central venous cathters (CVC) (OR 1.29) and Peripheral venous catheters (PVC) (OR 2.8), as well as, the total duration of total parenteral nutrition (13 vs. 29 days; OR 1.81). Occurrence of LO-BSI was significantly associated with increased the length of mechanical ventilation (MV) (OR 2.65) or the continuous positive airway pressure (CPAP) (OR 2.51), as well as, the duration of antibiotic use (OR 2.98). The occurrence of more than one infection was observed frequently (OR 9.2) with VLBW with LO-BSI. Microorganisms isolated in infants with LO-BSI were dominated by Gram-positive cocci, and predominantly by coagulase-negative staphylococci (62.5%).ConclusionsIndependent risk factor for LO-BSI in VLBV infants are: low gestational age and requirement for surgery. The incidence rates of LO-BSI especially CVC-BSI were higher in the Polish NICUs surveillance than those of other national networks, similar to the central- and peripheral utilization ratio.

Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

Cytochrome P450 monooxygenases catalyze the metabolism of approximately 40-60% of widely used drugs with a A6986G CYP3A5 polymorphism determining expresser (A6986, *1) and reduced- expresser (*3) variants with modified drug metabolism activity. In this report, the allele frequency of CYP3A5 *1 and *3 (A6986 or G6986, respectively) was analyzed by the PCR-RFLP technique in a cohort of 200 Polish newborns from the West Pomeranian region. Of the studied group, 1% (n = 2/200) proved homozygous for the CYP3A5*1 allele, 89% (n = 178/200) for the *3 allele, and 10% (n = 20/200) were heterozygous for *1/*3. Similar frequencies were found in other Caucasian European populations. This study provides basic genetic data related to the metabolism of drugs, with a narrow therapeutic window in a Polish population.

Enterobacteriaceae infections of very low birth weight infants in Polish neonatal intensive care units: resistance and cross-transmission.

Background: The aims of our study were analysis of the occurrence of infections by members of the Enterobacteriaceae family in 6 Polish neonatal intensive care units in 2009, their drug resistance, the epidemiology of extended-spectrum &bgr;-lactamase (ESBL)-producing strains and the possibility of using modern tools of microbiology diagnosis in infection control, especially for the reduction of antimicrobial resistance. Methods: A prospective surveillance covered 910 newborns. Case patients were defined as neonates with very low birth weight who had clinical signs of septicemia, pneumonia or necrotizing enterocolitis. Early-onset infection was defined as infection diagnosed within 3 days after delivery. Results: The incidence of Enterobacteriaceae infections was 2.6/1000 patient-days. The risk of Enterobacteriaceae pneumonia increased with the length of hospitalization (P = 0.0356). The most common pathogen was Escherichia coli (12.4% of all strains, in early-onset infection 18.5%) and Klebsiella spp. (9.1% of all). The ESBL phenotype was found in 37% of isolates, of which 89.3% were producing CTX-M-type, 70.2% TEM-type and 8.5% SHV-type. Epidemic clones were detected in the 2 studied neonatal intensive care units: 6 of the 9 ESBL-positive Enterobacter cloacae and 16 of the 18 ESBL-positive Klebsiella pneumoniae strains were classified into 1 epidemic clone, which showed resistance to penicillin without inhibitors, amoxycillin/clavulanic acid, cephalosporins, aztreoname, aminoglycosides and trimethoprim/sulfamethoxazole. Conclusions: Enterobacteriaceae bacilli are a significant problem in neonatal intensive care units, especially in early-onset infection and for long hospitalized very low birth weight infants. The observed high drug resistance was in large part related to the dominance of epidemic strains as a result of horizontal transmission. The best way to reduce drug resistance would be adequate procedures of isolation and hand hygiene.

Maternal venous procalcitonin levels do not correlate with umbilical cord blood and venous blood concentrations in the neonate.

Abstract Background: To compare procalcitonin (PCT) concentrations between maternal blood and levels in umbilical cord or venous blood of neonates who were born with or without infection. Methods: Forty-six women with singleton pregnancies, complicated by premature rupture of membranes, preterm delivery and/or chorioamnionitis, were enrolled in this study. The study group comprised 15 patients and their infected newborns. The control group consisted of 31 women and their healthy newborns. We compared PCT concentrations between maternal, umbilical cord and neonatal serum, in both study and control groups. Additionally, PCT levels were compared between the corresponding compartments. Results: PCT concentrations in the umbilical cord and venous blood in infected newborns, but not in non-infected neonates, were significantly higher than maternal serum PCT levels. PCT concentrations of mothers who delivered infected newborns were comparable to those in the controls. However, PCT concentrations in the umbilical cord and in the venous blood of the infected newborns were higher than in healthy newborns. Conclusion: Measurement of maternal PCT concentration during labor does not contribute to early prediction of infection in the neonate. However, umbilical cord PCT concentrations, as well as its neonatal venous levels on the second day of life, seem to be related to intrauterine infection, and may be a useful tool in the diagnosis of early neonatal infection.

Epidemiology, antibiotic consumption and molecular characterisation of Staphylococcus aureus infections – data from the Polish Neonatology Surveillance Network, 2009–2012

BackgroundOur aim was to determine and characterize S. aureus (SA) isolated from infections in newborns for antibiotic resistance, virulence factors, genotypes, epidemiology and antibiotic consumption.MethodsProspective surveillance of infections was conducted. Data about antibiotic treatment were analyzed. Antimicrobial susceptibility was assessed. PCR amplification was used to detect resistance and virulence genes. Typing methods such as PFGE, spa-typing and SCCmec were used.ResultsSA was found to be associated with 6.5% of infections. Methicillin-Resistant Staphylococcus aureus accounted for 32.8% of SA-infections. An incidence of MRSA-infections was 1.1/1000 newborns. MRSA-infections were diagnosed significantly earlier than MSSA-infections in these newborns (14th day vs. 23rd day (p = 0.0194)). MRSA-infections increased the risk of newborn’s death. Antibiotic consumption in both group was similar, but a high level of glycopeptides-usage for MSSA infections was observed.In the MRSA group, more strains were resistant to erythromycin, clindamycin, gentamicin and amikacin than in the MSSA group. Hla gene was present in 93.9% of strains, and seg and sei in 65.3% of strains, respectively. One dominant clone was found among the 14 MRSA isolates. Fifteen strains belonging to SCCmec type IV were spa-t015 and one strain belonging to SCCmec type V was spa-t011.ConclusionsResults obtained in the study point at specific epidemiological situation in Polish NICU (more detailed studies are recommended).High usage of glycopeptides in the MSSA infections treatment indicates the necessity of antimicrobial stewardship improvement and introducing molecular screening for early identification of infections.

Molecular Studies of an Impetigo Bullosa Epidemic in Full-Term Infants

Background: Carriers ofStaphylococcus aureus strains can be the source of epidemic infection for patients. Objectives: A molecular epidemiological analysis of an impetigo bullosa outbreak in a neonatal ward was performed in order to determine a potential source of the infection and possible routes of subsequent spreading of the epidemic strain. Methods: The genetic relatedness of S. aureus strains isolated from 6 neonates with epidermal lesions and from 21 staff members was verified by the pulsed field gel electrophoresis (PFGE) method. Additionally, detection of eta and etb genes of S. aureus strains using PCR was performed. Results: None of the infected newborns’ mothers was a carrier. Seven strains, 6 isolated from the newborns and 1 taken from a midwife, showed the same restriction pattern, i.e. type A. In the other 20 health care workers colonized with S. aureus, 3 genetic types could be distinguished, i.e. B (2), C (7) and D (2), as well as 9 strains with unique PFGE patterns. The eta gene detected in 7 strains belonged to the genetic type A; there was no etb gene in any of the 27 S. aureus isolates. Conclusions: The presence of the same genetic type A of S. aureus in the infected newborns is a factor which indicates that the impetigo bullosa was a hospital infection. A probable source of the infection was a midwife who was colonized with the same S. aureus type. She was present at the birth of the first infected newborn. Today, molecular methods are essential for prompt recognition of an epidemic and implementation of appropriate infection control strategies.

Infections and risk-adjusted length of stay and hospital mortality in Polish Neonatology Intensive Care Units

BACKGROUND The objectives of this study were to analyze the impact of infections on prolonging hospital stay with consideration of underlying risk factors and determining the mortality rates and its association with infections. METHODS An electronic database developed from a continuous prospective targeted infection surveillance program was used in the study. Data were collected from 2009 to 2012 in five Polish tertiary academic neonatal intensive care units (NICUs). The length of stay (LOS) of 2,003 very low birth weight (VLBW) neonates was calculated as the sum of the number of days since birth until death or until reaching a weight of 1,800g. RESULTS The median LOS for neonates with infections was twice as high as for neonates without infection. LOS was significantly affected by the overall general condition of the neonate, as expressed by both gestational age and birth weight as well as by the Clinical Risk Index for Babies (CRIB) score; another independent factor was presence of at least one infection. Risk of in-hospital mortality was significantly increased by male sex and vaginal birth and was lower among breastfed neonates. Deaths were significantly more frequent in neonates without infection. CONCLUSIONS The general condition of VLBW infants statistically increase both their risk of mortality and LOS; this is in contrast to the presence of infection, which significantly prolonged LOS only.

Possible counter effect in newborns of 1936A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10.

Objective:Cyclic adenosine monophosphate/protein kinase A (PKA) is important in embryonic development. The human AKAP10 gene is polymorphic: 1936A>G results in changes to a PKA-binding domain and increased targeting to mitochondria. Previous studies found G1936 as ‘deleterious’ in adults, and this study investigates whether this holds true in preterm birth.Study Design:Study group consisted of 80 preterm newborns (PTNs) born before the 38th gestation week. Control group consisted of 123 full-term healthy newborns born after the 37th gestation week with uncomplicated pregnancies. Genomic DNA was extracted from umbilical blood and AKAP10 genotypes were identified by PCR/restriction enzyme.Result:Significant differences in frequencies of 1936A>G genotypes/alleles between both groups were found. PTNs had increased frequency (55%) of AA homozygotes (odds ratio, AA versus AG+GG: 2.63 (95% confidence interval: 1.33 to 5.20), P=0.006) after adjustments: mothers with previous PTNs, smoking, first pregnancy, first delivery and Cesarean section.Conclusion:Results suggest G1936 is preventative factor against preterm birth, in contrast with previously asserted negative effects in adults.