Improvement of adherence to hand hygiene practice using a multimodal intervention program in a neonatal intensive care.

Nosocomial infections are serious complications among preterm infants admitted to neonatal intensive care units (NICU). Hand hygiene is one of the most effective measures to prevent these infections. This study, performed in a tertiary level NICU, highlights the importance of a multimodal intervention program for adherence to hand hygiene. The compliance with hand hygiene among health care workers of the NICU increased significantly from 23% in the baseline assessment to 50% in the second assessment and the incidence of sepsis decreased from 13.4% to 11.3% after implementation of an intervention program.

Severe neonatal parechovirus infection and similarity with enterovirus infection.

BACKGROUND: Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae. Less is known about severe neonatal infection caused by the parechoviruses (PeV) of which type 1 (PeV1) and type 2 (PeV2) were previously known as echovirus 22 and echovirus 23. They belong to the same family of Picornaviridae as the EV. Of the PeV, so far only PeV3 has been associated in 2 recent reports with severe neonatal infection including involvement of central nervous system. METHODS: We compared the clinical signs, diagnosis, laboratory data, cerebral imaging, and neurodevelopmental outcome of 11 neonates with PeV infection with 21 infants with EV infection treated in our hospital between 1994 and 2006. The diagnosis of EV infection or PeV infection was confirmed by a positive EV and/or PeV real time-polymerase chain reaction on blood, cerebrospinal fluid, (CSF) or stool or a viral culture of stool, nasopharyngeal swab, and/or CSF. RESULTS: The 32 infants presented with sepsis-like illness and the most frequent signs were: fever, seizures, irritability, rash, and feeding problems. All patients received antibiotic treatment. Eleven of 21 infants infected with EV and 7 of 11 infants infected with PeV were full-term. Differentiation between the infants infected with EV and PeV on the basis of fever, irritability, rash, and seizures was not possible. Myocarditis was exclusively seen in 4 patients infected by EV. Eight of 11 patients with a PeV infection had meningoencephalitis of whom only 1 infant developed pleocytosis in the CSF. Serum C-reactive protein and CSF protein values were significantly higher in infants with EV infection than in those with PeV infection. Cerebral imaging of all infants with EV or PeV cerebral infection showed mild to severe white matter abnormalities. In 1 infant with EV infection and 3 infants with PeV infection, neurodevelopmental delay occurred. Mortality and long-term sequelae were mainly associated with myocarditis in the infants who were infected with EV (4 of 21). CONCLUSIONS: It is not possible to distinguish neonatal PeV from EV infection on the basis of clinical signs. Neonates with PeV or EV infection present with sepsis-like illness and the most frequent signs are fever, seizures, irritability, rash, and feeding problems.

Clinical and epidemiologic characteristics of viral infections in a neonatal intensive care unit during a 12-year period.

BACKGROUND: The incidence of viral infections in patients treated in the neonatal intensive care unit (NICU) is not well-known. We summarized the data of all patients with laboratory-confirmed viral infections admitted at the NICU of our hospital during the period of 1992-2003. OBJECTIVES: To determine the incidence of viral infections among infants hospitalized in a NICU, the associated clinical manifestations and their outcome. METHODS: Retrospective analysis of epidemiologic, virologic and clinical data from infants with proven viral infection. The diagnosis viral infection was confirmed by positive viral culture and/or polymerase chain reaction from clinical samples. RESULTS: Viral infection was confirmed in 51 of 5396 infants (1%) admitted to the NICU; 20 (39%) had an enterovirus and parechovirus (EV/PEV) infection, 15 (29%) a respiratory syncytial virus (RSV) infection, 5 (10%) a rotavirus infection, 3 (6%) a cytomegalovirus (CMV) infection, 2 (4%) an adenovirus infection, 2 (4%) a parainfluenza virus infection, 2 (4%) a herpes simplex virus infection, 1 (2%) a rhinovirus infection and 1 (2%) a rubella virus infection. Three of the infants presented at birth with symptomatic rubella virus, CMV or herpes simplex virus infection. RSV infection developed mostly in hospitalized infants (60%), and 93% of infections occurred during the winter (November-March). The clinical presentations of EV/PEV disease were sepsis-like illness, prolonged seizures in term infants and gastrointestinal disease in preterm infants. RSV, parainfluenza virus, rhinovirus and CMV caused respiratory disease, predominantly in preterm infants. Gastrointestinal disease was seen only in preterm infants with adenovirus, rotavirus or EV/PEV infection. Mortality and serious sequelae were high in patients infected with EV/PEV (10 and 15%, respectively). CONCLUSIONS: The incidence of viral infection in the NICU was 1%. Enteroviral infections were the most frequently diagnosed infections, occurred often in term infants born at home and presented with sepsis-like illness or seizures. Preterm infants hospitalized from birth mainly developed gastrointestinal disease caused by rotavirus and adenovirus infection or respiratory disease caused by RSV, parainfluenza and CMV infection. Enteroviruses were responsible for the highest mortality and development of serious sequelae.

Neonatal group B streptococcal infection: incidence and strategies for prevention in Europe.

We sent a questionnaire to all members of the European Society for Paediatric Infectious Diseases and to all delegates of the European Association of Perinatal Medicine to determine existing policies for prevention of neonatal group B streptococcal (GBS) infection in Europe. The incidence of GBS colonization in pregnant women and of neonatal GBS infection varies. Policies for prevention of GBS infection are not well-developed.

Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents.

BACKGROUND: In an era with increased maternal antibiotic use, patterns in early- and late-onset sepsis and antibiotic susceptibility may have changed. OBJECTIVES: To identify longitudinal trends in causative microorganisms for neonatal sepsis and analyze antibiotic susceptibility of all blood isolates of infants with sepsis. METHODS: Early- and late-onset sepsis cases from 29 years (1978-2006) were studied retrospectively, in five clusters of 5 years (period I-V) and one cluster of 4 years (period VI), including antibiotic susceptibility profiles of blood isolates during the years 1999-2006. RESULTS: The incidence of early-onset sepsis decreased (p < 0.01) from 4% during period I (1978-1982) to 1.2% during period VI (2003-2006). 78% of the infants with group B streptococcal (GBS) sepsis were premature during period I, compared to 47% during period VI (p < 0.05). The incidence of early-onset Gram-negative infections remained low during all periods. The incidence of late-onset sepsis, predominantly caused by coagulase-negative staphylococci (CONS) and Staphylococcus aureus, increased since period III from 7.1 to 13.9% in period VI (p < 0.01). Infections due to fungi or yeasts were rare (incidence <0.3%). The majority of CONS blood isolates were oxacillin-resistant, but vancomycin-susceptible. 95% of CONS blood isolates were susceptible for first-generation cephalosporins. Amoxicillin/clavulanic acid-resistant Escherichia coli were infrequent causes of infection. CONCLUSIONS: The incidence of early-onset sepsis mainly caused by GBS decreased. In contrast, the incidence of late-onset sepsis, predominantly caused by CONS, increased significantly. The incidence of fungal and yeast infections remained low. The majority of CONS blood isolates were susceptible for first-generation cephalosporins.

Neonatal phrenic nerve injury due to traumatic delivery.

AIMS: To describe the clinical course of infants recovering spontaneously from diaphragmatic paralysis due to perinatal phrenic nerve injury as well as those that underwent plication of the diaphragm. METHODS: Between 1990 and 2006, 14 newborns admitted to the Neonatal Intensive Care Unit (NICU) of the Wilhelmina Children's Hospital in Utrecht, The Netherlands, were diagnosed with diaphragmatic paralysis due to obstetric phrenic nerve injury. The clinical and follow-up data were studied retrospectively. RESULTS: Four infants recovered spontaneously and could be weaned from mechanical ventilation within nine days without further treatment. Plication of the diaphragm was performed in 10 infants because of failure to wean from ventilatory support or serious persistent respiratory distress. Time between birth and plication ranged from 10 to 51 days, with a median of 19 days. Satisfactory respiratory outcome was achieved in 86% of the cases. CONCLUSIONS: The minority of infants suffering from diaphragmatic paralysis due to perinatal phrenic nerve injury recovers spontaneously. Infants who fail to wean from ventilatory support and undergo early plication have a quick recovery and can be extubated successfully within a few days.

Removal of percutaneously inserted central venous catheters in neonates is associated with the occurrence of sepsis.

BACKGROUND: Clinical signs of sepsis are frequently observed after removal of a percutaneously inserted central venous catheter (PCVC) in neonates admitted at our Neonatal Intensive Care Unit (NICU). To substantiate this finding and to evaluate the effect of antibiotics administered at the time of removal of a PCVC, we conducted a retrospective study among all infants with a PCVC, admitted at our NICU during 2002 and 2005. METHODS: Clinical data, infectious complications and use of antibiotics were studied retrospectively. RESULTS: A PCVC was inserted in 345 infants. Sepsis occurred in 90/345 (26%) infants, in 50/90 (56%) during indwelling PCVC and in 40/90 (44%) after removal of the PCVC. Of the latter 40 sepsis episodes, 24 (60%) occurred within 5 days after removal of a PCVC with a clustering of 21 cases of sepsis within 72 h after the removal. The remaining 16 episodes occurred after 7 days. Administration of antibiotics during removal of the PCVC significantly reduced the incidence of sepsis: 22/213 (10.3%) cases of sepsis occurred when no antibiotics were administered versus 2/132 (1.5%) cases of sepsis when antibiotics were administered (p = 0.002). CONCLUSION: Our study suggests that peripherally inserted central venous catheters are associated with sepsis not only during the indwelling period of the catheter, but also after removal. Administration of antibiotics targeted at the time of removal of the catheter significantly reduced the incidence of sepsis. Future prospective studies are warranted to confirm this observation.

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

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.

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.

Treatment of symptomatic congenital cytomegalovirus infection with valganciclovir.

Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. Some congenitally infected infants will develop sequelae later in life, especially sensorineural hearing loss (SNHL) and mental retardation. There is no generally accepted antiviral therapy for the treatment of symptomatic congenital CMV infections yet. We present a neonate with symptomatic congenital CMV infection, who was treated with intravenous (iv) ganciclovir (GCV) during 18 days and subsequently with oral valganciclovir (VGCV) for 5.5 months, in an attempt to prevent development of SNHL. GCV was given intravenously 10 mg/kg/day in two doses and VGCV doses ranged from 280-850 mg/m2 bidaily (bid). Our experience shows that it is not possible to give a fixed dosing regime for VGCV in neonates and that continuous adaptation of dose is necessary to achieve stable target levels of GCV and to keep the viral load in urine at undetectable level. At 18 months of age no hearing deterioration has occurred. While the current findings are encouraging, the limitations of a single case report with a relatively short follow-up emphasizes the need for further prospective randomized studies to evaluate pharmacokinetics, efficacy and safety of VGCV therapy in neonates with congenital CMV infection.

Staphylococcal scalded skin syndrome in two very low birth weight infants.

Two premature infants with very low birth weight were diagnosed with staphylococcal scalded skin syndrome (SSSS) during hospitalization in the neonatal intensive care unit. This syndrome which is rare in premature infants, is characterized by blistering and superficial desquamation of the skin and is caused by two epidermolytic toxins (ETA and ETB) produced by Staphylococcus aureus. Staphylococcal scalded skin syndrome usually occurs in young children probably because of inefficient clearance of the epidermolytic toxins from the bloodstream, which causes dysfunction of cell adhesion in the superficial epidermis. Early diagnosis and early treatment with parenterally administered beta-lactamase resistant penicillins are important to prevent life threatening complications of this syndrome.

Molecular epidemiology of coagulase-negative staphylococci causing sepsis in a neonatal intensive care unit over an 11-year period.

Coagulase-negative staphylococci (CoNS) are the major causative microorganisms in neonatal nosocomial sepsis. Previous studies have shown that CoNS sepsis in the neonatal intensive care unit (NICU) is caused by predominant molecular types that are widely distributed among both neonates and staff. Some of these molecular types may persist in the NICU for years. The purpose of the present study was to determine the dynamic behavior of CoNS strains causing sepsis over a prolonged period of time by determining the molecular types of all blood isolates from septicemic infants over a period of 11 years (1991 to 2001). The results show that neonatal CoNS sepsis is increasingly caused by a few predominant molecular clusters. The most striking finding was that in recent years one molecular cluster emerged as the predominant cause of neonatal CoNS sepsis, responsible for no less than 31% (20 of 65) of blood isolates in 2001. Antibiotic resistance, particularly beta-lactam resistance, is probably an important selective force considering the high mecA gene carriage of CoNS blood isolates (70 to 92%). We conclude that neonatal CoNS sepsis is increasingly caused by a limited number of predominant molecular CoNS types and that antibiotic resistance is probably a major selective force.

Epidemiology of neonatal group B streptococcal disease in The Netherlands 1997-98.

Group B streptococcal (GBS) infection is still an important cause of morbidity and mortality in newborn infants. In The Netherlands, there are no published data on the incidence of neonatal GBS infection. We collected data of all infants with GBS disease during the first 3 months of life, as reported to the Dutch Paediatric Surveillance Unit (DPSU) during a period of 2 years (1997-98). Neonates with early-onset GBS disease (both sepsis and probable sepsis) were included for further analysis. The level of completeness of the DPSU data was determined by capture-recapture techniques. The incidence of early-onset GBS disease in The Netherlands in 1997-98, as calculated from the DPSU data, was 0.9 per 1000 live births. After correction for under-reporting, the incidence was estimated to be 1.9 per 1000 live births. The case fatality rate of early-onset GBS disease was only 5%. Despite the decrease in the mortality rate during the last decades, it remains a serious condition with potential irreversible brain damage. Therefore, formal guidelines for the prevention of neonatal early-onset GBS disease in The Netherlands were introduced in 1999. The data collected in this study may serve as baseline data for evaluation of the effect of these guidelines.