Tannette G. Krediet

Variation in antibiotic use in neonatal intensive care units in the Netherlands

OBJECTIVESnTo examine the variation in quantity and classes of antibiotics used in all 10 tertiary care neonatal intensive care units (NICUs) in the Netherlands during 2005.nnnMETHODSnWe collected data from all tertiary care NICUs in the Netherlands on clinical and demographic characteristics and the type and quantity of systemic antibiotic use [expressed as defined daily doses (DDD)/100 admissions] in 2005. Antibiotics were ranked by volume of DDDs, and those antibiotics which accounted for 90% of the total volume of use [drug utilization (DU) 90%] were noted.nnnRESULTSnAntibiotic consumption ranged from 130 to 360 DDD/100 admissions. In total, 9-24 different antibiotics were used, of which 3-10 were in the DU90% segment.nnnCONCLUSIONSnBy comparing antibiotic use in Dutch NICUs we found a considerable variation in the number of different antibiotics used and in the total amount of antibiotic use. Further exploration of the opportunities to reach consensus in antibiotic policy, and to increase attention to antibiotic stewardship, is recommended.

In-line filters in central venous catheters in a neonatal intensive care unit

Abstract Nosocomial sepsis remains an important cause of morbidity in neonatal intensive care units. Central venous catheters (CVCs) and parenteral nutrition (TPN) are major risk factors. In-line filters in the intravenous (IV) administration sets prevent the infusion of particles, which may reduce infectious complications. We randomized infants to in-line filter (for clear fluids and lipid emulsions) or no filter placement. Sepsis, nursing time and costs were assessed. IV sets without filters were changed every 24 h, IV-sets with filters every 96 h. Of 442 infants with a CVC, 228 were randomized to filter placement, 214 to no filter. No differences were found in clinical characteristics, CVC-use, and catheter days. Nosocomial sepsis occurred in 37 (16.2%) infants with filters, in 35 (16.3%) in the group without filter (NS). Nursing time to change the IV-administration sets was 4 min shorter in the filter-group (P<0.05). Costs of materials used were comparable. In conclusion, the incidence of sepsis when using filters was not reduced but the nursing time for changing the intravenous sets was reduced without a difference in costs.

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.

Severe neonatal group A streptococcal disease

Abstract Since the mid-1980s, an increase in incidence of invasive disease caused by group A streptoccoci has been noted amongst adults and children; however, neonatal disease is still rare. Between 1979 and 1998, seven neonates with severe group A streptoccocal disease were admitted to our neonatal intensive care unit. The clinical presentation, treatment and outcome are described. In three cases of early-onset disease vertical transmission was documented.nConclusion Because the incidence of group A streptococcal disease in the general population seems to have increased over the last two decades, we should be aware of the possibility and particularly the severity of group A streptococcal disease in the neonatal period.

Oxidative Stress and Proinflammatory Cytokine Levels are Increased in Premature Neonates of Preeclamptic Mothers with HELLP Syndrome

Background: Respiratory distress syndrome (RDS) incidence is increased in infants of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes. Objectives: We hypothesize that end-tidal carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are higher in infants of preeclamptic mothers with HELLP syndrome than in those of preeclamptic mothers without HELLP syndrome. Methods: Prospective study of 36 infants of preeclamptic mothers (GA <32 weeks) admitted to the Neonatal Intensive Care Unit. ETCOc was measured at 0–12, 48–72 and 168 h postnatally using the CO-Stat™ End-Tidal Breath Analyzer. Simultaneously, blood was sampled for MDA, IL-8 and IL-6. Results: At 0–12 h, ETCOc, MDA and IL-8 values (median[range]) were significantly higher in HELLP infants than in infants from preeclamptic mothers without HELLP (ETCOc 2.2 [1.5–3.9] vs. 1.8 [0.5–2.9] ppm; MDA 2.3 [1.3–4.1] vs. 1.5 [0.4–3.1] µmol/l; IL-8 145 [24–606] vs. 62 [26–397] pg/ml; all p <0.05). MDA remained significantly higher during the first 168 h of life (2.3 [0.8–5.8] vs. 1.1 [0.8–3.7] µmol/l, p = 0.02). Conclusion: Oxidative stress and proinflammatory cytokine levels are increased in infants of preeclamptic mothers with HELLP syndrome. These processes may cause inactivation of surfactant explaining the increased RDS incidence in these infants.

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

OBJECTIVESnVancomycin 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, β-lactam antibiotics. The relationship between mecA gene carriage, phenotypic expression of the gene by PBP-2a production and in vitro resistance to the β-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.nnnMETHODSnThe relationship between mecA gene carriage, phenotypic expression of the gene by PBP-2a production and in vitro resistance to the β-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). β-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™.nnnRESULTSnAmong 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 β-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.nnnCONCLUSIONSnβ-Lactam antibiotics are useful for the treatment of neonatal CoNS sepsis, reserving vancomycin for selected cases.

Unmyelinated White Matter Loss in the Preterm Brain Is Associated with Early Increased Levels of End-Tidal Carbon Monoxide

Objective Increased levels of end-tidal carbon monoxide (ETCOc) in preterm infants during the first day of life are associated with oxidative stress, inflammatory processes and adverse neurodevelopmental outcome at 2 years of age. Therefore, we hypothesized that early ETCOc levels may also be associated with impaired growth of unmyelinated cerebral white matter. Methods From a cohort of 156 extremely and very preterm infants in which ETCOc was determined within 24 h after birth, in 36 infants 3D-MRI was performed at term-equivalent age to assess cerebral tissue volumes of important brain regions. Results Linear regression analysis between cerebral ventricular volume, unmyelinated white matter/total brain volume-, and cortical grey matter/total brain volume-ratio and ETCOc showed a positive, negative and positive correlation, respectively. Multivariable analyses showed that solely ETCOc was positively related to cerebral ventricular volume and cortical grey matter/total brain volume ratio, and that solely ETCOc was inversely related to the unmyelinated white matter/total brain volume ratio, suggesting that increased levels of ETCOc, associated with oxidative stress and inflammation, were related with impaired growth of unmyelinated white matter. Conclusion Increased values of ETCOc, measured within the first 24 hours of life may be indicative of oxidative stress and inflammation in the immediate perinatal period, resulting in impaired growth of the vulnerable unmyelinated white matter of the preterm brain.

1394 Clinical Outcome of Neonatal Conssepsis with a Vancomycin-Sparing Regimen: Favourable Results with Cefazolin as First Choice Agent

Background and aims: The typical empiric antimicrobial treatment protocol for neonatal coagulase-negative staphylococci (CONS) sepsis includes vancomycin. However, the protocol in our NICU prescribes cefazolin to cover CONS. The susceptibility of CONS blood isolates to cefazolin and clinical outcome of infants with CONS sepsis was studied during 2000-2006. 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: 163/185 infants with proven CONS sepsis were treated with cefazolin. Median MIC value of cefazolin was 0.75-2 (range 0.01-256) µg/ml and 77-96% of all isolates was susceptible to cefazolin (MIC ≤8 µg/ml) during 2000-2006. In 121/140 (86%) infants with cefazolin-susceptible and 21/23 cases (91%) with cefazolin-resistant CONS isolate cefazolin was clinically efficacious. 12/17 second blood cultures in 19 non-responders yielded CONS with unchanged MIC. In 78% of good responders and 22% of non-responders a central venous catheter was removed at onset of sepsis. Nonresponders were switched to vancomycin. Conclusions: Majority of CONS isolates remained susceptible to cefazolin over a period of 7 years. Cefazolin is clinically efficacious in >85% of cases and can be recommended as first choice agent for therapy of CONS sepsis. Removal of a central venous catheter may be the most important therapeutic measure.

NO CEREBRAL WHITE MATTER DAMAGE DUE TO CONS SEPSIS IN PRETERM INFANTS DETERMINED BY APPARANT DIFUSSION COEFFICIENT (ADC) ON MRI

Background and aims: Neonatal sepsis may cause cerebral white matter (WM) damage in preterm infants, compromising outcome. Coagulase-negative staphylococcal (CONS) sepsis is a frequent cause of morbidity in preterm infants, however generally not developing into a fulminant disease. To determine the impact of CONS sepsis on cerebral WM, the ADC of 3 WM regions was measured using diffusion-weighted MRI (DW-MRI) performed at term-equivalent age. Methods: Cerebral DW-MRI was performed routinely in 81 preterm infants (GA< 31 weeks). Four infants with cerebral white matter damage due to venous infarction or hydrocephalus, before CONS sepsis occurred in 1, were excluded. The ADC of frontal, parietal and occipital WM was calculated in 31 infants with CONS sepsis and 50 infants without sepsis. Results: ADC values in parietal WM were significantly lower as compared to frontal or occipital WM in both groups (p< 0.001), indicating developmental differences (table 1). No differences were found in ADC values of infants with or without CONS sepsis in all 3 regions of cerebral WM. Conclusions: CONS sepsis in preterm infants is not associated with cerebral white matter damage as determined by ADCs in cerebral MRI at termequivalent age.