Ayala Maayan-Metzger

Methicillin-resistant Staphylococcus aureus in Neonatal Intensive Care Unit

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.

Invasive pediatric Kingella kingae infections: a nationwide collaborative study.

Background: Kingella kingae is a gram-negative coccobacillus, increasingly recognized as an invasive pediatric pathogen. To date, only few small series of invasive K. kingae infections have been published, mostly from single medical centers. A nationwide multicenter study was performed to investigate the epidemiologic, clinical, and laboratory features of children with culture-proven K. kingae infections. Methods: Clinical microbiology laboratories serving all 22 medical centers in Israel were contacted in a search for children aged 0 to 18 years from whom K. kingae was isolated from a normally sterile site, dating from as far back as possible until December 31, 2007. Medical records of identified patients were reviewed using uniform case definitions. Results: A total of 322 episodes of infection were identified in 321 children, of which 96% occurred before the age of 36 months. The annual incidence in children aged <4 years was 9.4 per 100,000. Infections showed a seasonal nadir between February and April. Skeletal system infections occurred in 169 (52.6%) children and included septic arthritis, osteomyelitis, and tenosynovitis. Occult bacteremia occurred in 140 children (43.6%), endocarditis in 8 (2.5%), and pneumonia in 4 (1.2%). With the exception of endocarditis cases, patients usually appeared only mildly ill. About one-quarter of children had a body temperature <38°C, 57.1% had a blood white blood cell count <15,000/mm3, 22.0% had normal C-reactive protein values, and 31.8% had nonelevated erythrocyte sedimentation rate. Conclusions: K. kingae infections usually occur in otherwise healthy children aged 6 to 36 months, mainly causing skeletal system infections and bacteremia, and occasionally endocarditis and pneumonia. Clinical presentation is usually mild, except for endocarditis, necessitating a high index of suspicion.

Necrotizing Enterocolitis in Full-Term Infants: Case-Control Study and Review of the Literature

OBJECTIVE: To examine the increasing number of full-term infants at our hospital exhibiting necrotizing enterocolitis (NEC) in order to characterize these cases and to discover common risk factors.METHODS: Medical charts were reviewed for all full-term infants (gestational age > 36 weeks) that were born in our institution during a 5-year period (from January 1, 1998 to December 31, 2002) and that developed definite NEC. Data regarding the rate of Cesarean section (CS) in our institution over the study period and five years prior to the study was also recorded.RESULTS: During the 5 years of the study, 14 full-term infants were found to have NEC. The incidence of NEC in full-term infants increased from 0.16 to 0.71 per 1000 live births in the 5-year period. Mean birth weight was 2829 g. All the NEC infants except one were delivered by CS, and all of them were fed either with a mixture of breast milk and formula or entirely by formula. Seven of the infants (50%) had no major known risk factors predisposing them for NEC. Mean age of disease onset was very early (4.1 days) in most of the infants (12 infants), and the colon was the main NEC site. The short-term outcome was favorable in all but one case, which required explorative laparotomy for intestinal perforation. The number of infants born by CS has been steadily increasing, and was almost three times greater during the study period in comparison to the preceding years.CONCLUSIONS: The etiology of NEC in the full-term population seems to differ from the etiology for the preterm group in its intestinal location and in the timing of its onset. The increase in the rate of CS over the years might be related to the concurrent increase in NEC, and this relationship should be further investigated.

Hypoglycemia rates in the first days of life among term infants born to diabetic mothers.

Objectives: To discover the risk factors for developing hypoglycemia in newborns born to diabetic mothers and to characterize the rates of glucose concentrations in the first two days of life. Methods: Retrospective recordings of medical charts of 576 healthy term infants of diabetic mothers during an 18-month period. We determined the following pre-feeding glucose concentrations: ‘normoglycemia’ (≥47 mg/dl = 2.6 mmol/l), ‘mild hypoglycemia’ (40–46 mg/dl = 2.2– 2.5 mmol/l), ‘moderate hypoglycemia’ (30–39 mg/dl = 1.7–2.1 mmol/l) and ‘severe hypoglycemia’ (<30 mg/dl = 1.7 mmol/l). Results: Glucose concentrations below ‘normoglycemia’ and ‘severe hypoglycemia’ were observed in 280 (48.6%) and 23 (4%) of the infants, respectively. The main risk factors for developing glucose concentrations below ‘normoglycemia’ in the first day of life were large size for gestational age and maternal insulin-dependent diabetes mellitus. ‘Severe hypoglycemia’ was more common among infants born to mothers who needed insulin (either type A2 or insulin-dependent diabetes mellitus). Infants born to mothers with insulin-dependent diabetes mellitus were less mature, heavier, large for their gestational age and exhibited more ‘severe and moderate hypoglycemia’ in the first day of life as compared to infants born to diabetes type A1 and A2 mothers. In addition, infants who were large for gestational age tended to have more ‘moderate hypoglycemia’ when born to diabetes type A1 mothers compared to small and appropriate-for-gestational-age infants. Thirty infants (5%) still had hypoglycemia on the second day of life. This subgroup of infants did not differ with regard to maternal-type diabetes. Conclusions: Infants born to diabetic mothers tend to have a high rate of hypoglycemia on the first day of life when a relatively high cut-off point (≥47 mg/dl = 2.6 mmol/l) is used. Infants born large for gestational age as well as those born to mothers with juvenile diabetes mellitus are at higher risk and should be closely monitored.

Comparison of community-acquired methicillin-resistant Staphylococcus aureus bacteremia to other staphylococcal species in a neonatal intensive care unit

Hospital acquired infections including staphylococcal species are common in neonatal intensive care units. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was recently observed in our unit. The clinical and laboratory characteristics of all neonates with Staphylococcus aureus bacteremia during an 11-year period were retrospectively reviewed. Three groups of patients were compared: 1. Patients with CA-MRSA defined as MRSA-resistant only to β-lactams, but sensitive to all other antibiotic groups and carried SCCmec IV. 2. Patients with multi-drug-resistant (MDR)-MRSA and 3. Patients with MSSA (methicillin-sensitive S. aureus). Forty-three neonates with documented S. aureus bacteremia were included. Of these 41 were preterm babies. Eleven infants had CA-MRSA, 20 had MDR-MRSA and 12 had MSSA bacteremia, the Panton-Valentine-Leukocidine gene (pvl-gene) was not present in any of these strains. Risk factors, clinical manifestations and laboratory tests were similar in all three groups studied. Although neonates infected with CA-MRSA were more premature and had more related diseases, the mortality rate was similar in all groups (9.1% in the CA-MRSA group). Skin infections, osteomyelitis or pneumatocele were not observed more frequently in the CA-MRSA group. We did not find significant differences in risk factors or outcomes in neonates in the three groups. One possible explanation for this observation is that the CA-MRSA outbreak strain did not contain the pvl-gene, which has been suggested to be a significant virulence factor.

Early Treated Hypotension and Outcome in Very Low Birth Weight Infants

Background: Early hypotension is a common problem among preterm infants. Studies have shown conflicting data regarding the definition of hypotension, the way to treat it and the correlation to outcome. Objectives: To investigate the risk factors for developing hypotension and its relations to short- and long-term outcomes. Methods: Medical charts of all surviving very low birth weight infants were retrospectively reviewed during a 4-year period. The data of infants suffering from early hypotension and needed treatment were compared with those of a control group with ‘normal’ blood pressure. In addition, medical charts were reviewed for neurodevelopment outcome. Results: The study and control groups comprised 109 infants each. The mean blood pressures were 24.1 ± 3.2 and 30.3 ± 4.3 mm Hg in the study and control groups (p < 0.0001). No significant perinatal variables were found to predict hypotension. Bronchopulmonary dysplasia and retinopathy of prematurity were related to treated hypotension. Logistic regression analysis found that neonatal treated hypotension was related to periventricular leukomalacia, with an odds ratio of 2.61 (95% CI 1.0–7.12), p = 0.049. Intraventricular hemorrhages grades 2–4 were found to be related to lower mean blood pressure, with an odds ratio of 1.3 (95% CI 1.12–1.51), p < 0.01. Major long-term neurological disability was found by regression analysis to be related to periventricular leukomalacia and treated hypotension, with odds ratios of 63.1 (95% CI 13.3–299, p < 0.001) and 5.4 (95% CI 1.29–22.7, p = 0.01). Conclusions: This study supports the hypothesis that early provision of antihypotensive therapy is related to intraventricular hemorrhage, periventricular leukomalacia and major neurodevelopment impairment.

Clot formation of neonates tested by thromboelastography correlates with gestational age

Evaluation of clot formation in neonates is troublesome. Our aim was to investigate cord blood clot formation of pre-term versus full-term infants and adults, using rotating thromboelastogram (ROTEM), Pentafarm, Munich, Germany). ROTEM was investigated in cord blood of 184 full-term and 47 pre-term infants. Measurements of the clotting time (CT), clot formation time (CFT) and maximal clot firmness (MCF) were obtained in order to asses reference values for this age group, and compare between full-term and pre-term neonates and compared to adult controls. For each infant demographic information and data regarding pregnancy and delivery were gathered. Infants were prospectively followed until discharge. CT and CFT were significantly shorter among pre-term and term infants as compared to adults [median CT: 185, 194, 293 seconds respectively, p pound0.001, CFT: 80, 76, 103 seconds respectively, p pound0.001). MCF was lower in pre-term and term as compared to adults (p pound0.001) with significantly lower values in pre-term as compared to full-term neonates (p=0.004). Clotting time and MCF correlated with gestational age (R=0.132, p=0.045, R= 0.259, p<0.001, respectively). No association was found between any ROTEM values and the occurrence of post-natal complications in infants of our study group. This is the first study assessing clot formation by ROTEM in pre-term infants. Clot formation parameters of term and premature infants correlated with gestational age. The predictive value of clot formation tests in neonates deserves further attention.

Low prevalence of hearing impairment among very low birthweight infants as detected by universal neonatal hearing screening

Objectives: To (a) study the prevalence of hearing impairment in a cohort of very low birthweight (VLBW) infants and (b) evaluate the effectiveness of transient evoked otoacoustic emissions (TEOAE) as a first stage in-hospital hearing screening tool in this population. Study design: The study group was a cohort of 346 VLBW infants born in 1998–2000 at The Sheba Medical Center. The prevalence of hearing impairment in the study group was compared with that of all other newborn infants participating in a universal newborn hearing screening programme during the same period. To evaluate the effectiveness of TEOAE, a control group of 1205 healthy newborns who had no known risk factors for hearing impairment was selected. The results and follow up of hearing screening for these infants were examined retrospectively. Results: Only one VLBW infant (0.3%) was diagnosed with bilateral sensory-neural hearing loss. In addition, nine infants (2.7%) were diagnosed with conductive hearing loss. Bronchopulmonary dysplasia and low Apgar score were the most significant factors for predicting the occurrence of conductive hearing loss. The percentage of VLBW infants who successfully passed the in-hospital TEOAE screening was 87.2, compared with 92.2% in the full term control group. No false negative cases were detected on follow up. Conclusions: The study shows a low incidence of sensory-neural hearing loss in a cohort of VLBW infants and a relatively high incidence of conductive hearing loss. TEOAE screening was found to be an effective first stage in-hospital hearing screening tool in this population.

Liver enzyme abnormalities in Gram-negative bacteremia of premature infants

Background. Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to Gram‐negative bacteria are not known. Patients and methods. Charts of all preterm infants who had positive blood cultures for either Gram‐negative bacteria or coagulase‐negative staphylococci were reviewed. Neonates with Gram‐negative bacteremia (n = 54) were compared with neonates with coagulase‐negative staphylococcal bacteremia (n = 31). In addition infants with Gram‐negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with Gram‐negative bacteremia and normal liver enzymes (n = 29). Results. Liver enzyme abnormalities accompanied 46.3% (25 of 54) of Gram‐negative bacteremia and 12.9% (4 of 31) of episodes of coagulase‐negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with Gram‐negative bacteremia than in those with coagulase‐negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with Gram‐negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with Gram‐negative bacteremia and normal liver enzymes (7.3 ± 6.3 days vs. 4.0 ± 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. Conclusions. Gram‐negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all Gram‐negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Transmission of Staphylococcus aureus from mothers to newborns.

Background: The study objective was to define the risk factors and the route of Staphylococcus aureus transmission between mother and newborn. Methods: Women at late pregnancy were screened for nasal and vaginal S. aureus colonization. Newborns were screened for nasal, auricular, umbilical, and rectal colonization at birth and before discharge. Carrier mothers and their newborns were rescreened at 1 month. Pulse-field gel electrophoresis was used to assess strain genetic relatedness. Results: Of the 208 women screened, 34% were colonized with S. aureus. Overall, by 72–100 hours after birth, the cumulative incidence of S. aureus acquisition was 42.6/100 newborns of carrier mothers versus 7.4/100 newborns of noncarrier mothers (adjusted risk ratio = 5.7; 95% confidence interval [CI], 2.3–13.9). The risk to acquire a maternal strain was significantly higher than nonmaternal strain (adjusted risk ratio = 1.5; 95% CI, 1.3–1.9); Newborns to carrier mothers were also at a risk to acquire nonmaternal S. aureus strains compared with newborns to noncarrier mothers (adjusted risk ratio = 2.9; 95% CI, 1.6–5.4). The cumulative incidence of S. aureus acquisition was similar among newborns delivered by cesarean versus vaginal delivery (24.5 vs. 23.0/100 cases). At 1-month follow-up, the cumulative incidence of S. aureus acquisition reached 69.7/100 newborns of carrier mothers. Genetically identical strains were isolated in 32/40 (80%) mother-newborn pairs, among these, the source of the newborn strain was a maternal nasal strain in 29/32 (90%). Conclusions: Newborns of carrier mothers are at risk to acquire S. aureus colonization. Most newborns of carrier mothers are colonized within the first month of life. Horizontal transmission from the mother is probably the major source for S. aureus carriage in newborns.