Andrew J. Daley

Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term.

OBJECTIVES To test the hypothesis that the impact of postnatal sepsis/necrotizing enterocolitis (NEC) on neurodevelopment may be mediated by white matter abnormality (WMA), which can be demonstrated with magnetic resonance imaging (MRI). STUDY DESIGN A prospective cohort of 192 unselected preterm infants (gestational age <30 weeks), who were evaluated for sepsis and NEC, underwent imaging at term-equivalent age and neurodevelopmental outcome at 2 years corrected age with the Bayley Scales of Infant Development. RESULTS Sixty-eight preterm (35%) infants had 100 episodes of confirmed sepsis, and 9 (5%) infants had confirmed NEC. Coagulase-negative staphylococci accounted for 73% (73/100) of the episodes of confirmed sepsis. Infants with sepsis/NEC had significantly more WMA on MRI at term compared with infants in the no-sepsis/NEC group. They also had poorer psychomotor development that persisted after adjusting for potential confounders but which became nonsignificant after adjusting for WMA. CONCLUSIONS Preterm infants with sepsis/NEC are at greater risk of motor impairment at 2 years, which appears to be mediated by WMA. These findings may assist in defining a neuroprotective target in preterm infants with sepsis/NEC.

Ten-year study on the effect of intrapartum antibiotic prophylaxis on early onset group B streptococcal and Escherichia coli neonatal sepsis in Australasia.

Background: Intrapartum antibiotics have reduced the incidence of neonatal early onset (EO) group B streptococcal (GBS) disease. Some surveillance data suggest that this success may be at the cost of increasing rates of non-GBS infection, especially in premature neonates. Objective: To examine rates of EOGBS infection and EO Escherichia coli neonatal sepsis in Australasia. Methodology: Analysis of trends in EO (<48 h age) GBS and E. coli sepsis from longitudinal prospective surveillance data collected from representative tertiary obstetric hospitals in each state of Australia and selected centers in New Zealand during a 10-year period from 1992 through 2001. Statistical analysis used Poisson regression. Results: 206 GBS and 96 E. coli cases occurred in 298,319 live births during the study period. The EOGBS sepsis rate fell from a peak of 1.43/1000 live births in 1993 to 0.25/1000 in 2001 (P < 0.001). The overall EO E. coli sepsis rate was 0.32/1000. In babies with birth weight <1500 g, it was 6.20/1000. There was an overall trend to decreasing EO E. coli sepsis (P = 0.07), and there was no significant change in E. coli sepsis in babies <1500 g (P = 0.60). Sixty-nine percent of E. coli cases occurred in the <1500 g cohort; the case fatality rate in this group was 50%. The overall case fatality rate from E. coli sepsis was 36%, and this rate remained stable during the study period (P = 0.47). Conclusions: The increasing use of intrapartum antibiotics produced a steady decline in EOGBS disease in Australasia. There was also a trend to decreasing EO E. coli sepsis in all babies, and the rate in very low birth weight infants remained stable.

Comparison of various antimicrobial agents as catheter lock solutions: preference for ethanol in eradication of coagulase-negative staphylococcal biofilms

Coagulase-negative staphylococci (CoNS) are the main causative agents of bacteraemia in infants managed in neonatal intensive care units (NICUs). Intraluminal colonization of long-term central venous catheters by these bacteria and subsequent biofilm formation are the prerequisites of the bloodstream infections acquired in NICUs. The catheter lock technique has been used to treat catheter colonization; however, the optimum choice of antimicrobial agents and their corresponding concentrations and exposure times have not been determined. The effectiveness of catheter lock solutions (CLSs) was assessed by determining the minimal biofilm eradication concentration of antimicrobial agents against CoNS biofilms. Five conventional antibiotics (oxacillin, gentamicin, vancomycin, ciprofloxacin and rifampicin) alone or in combination, as well as ethanol, were evaluated. Ethanol was found to be superior to all of these conventional antibiotics when used as a CLS. A time-kill study and confocal laser scanning microscopy revealed that exposure to 40 % ethanol for 1 h was sufficient to kill CoNS biofilm cells. To our knowledge, this is the first in vitro study to provide solid evidence to support the rationale of using ethanol at low concentrations for a short time as a CLS, instead of using conventional antibiotics at high concentrations for a long period to treat catheter-related bloodstream infections.

Early onset neonatal meningitis in Australia and New Zealand, 1992–2002

Objectives: To study the epidemiology of early onset neonatal bacterial meningitis (EONBM) in Australasia. Design: Prospective surveillance study, 1992–2002, in 20 neonatal units in Australia and New Zealand. EONBM was defined as meningitis occurring within 48 hours of delivery. Results: There were 852 babies with early onset sepsis, of whom 78 (9.2%) had EONBM. The incidence of early onset group B streptococcal meningitis fell significantly from a peak of 0.24/1000 live births in 1993 to 0.03/1000 in 2002 (p trend  =  0.002). There was no significant change over time in the incidence of Escherichia coli meningitis. The rate of EONBM in very low birthweight babies was 1.09/1000 compared with the rate in all infants of 0.11/1000. The overall rate of EONBM was 0.41/1000 in 1992 and 0.06 in 2001, but this trend was not significant (p trend  =  0.07). Case-fatality rates for EONBM did not change significantly with time. Birth weight <1500 g (odds ratio (OR) 7.2 (95% confidence interval (CI) 4.8 to 10.9)) and Gram negative bacillary meningitis (OR 3.3 (95% CI 2.2 to 4.9)) were significant risk factors for mortality. Sixty two percent of the 129 babies who died from early onset sepsis or suspected sepsis did not have a lumbar puncture performed. Conclusion: The incidence of early onset group B streptococcal meningitis has fallen, probably because of maternal intrapartum antibiotic prophylaxis, without a corresponding change in E coli meningitis. Gram negative bacillary meningitis still carries a worse prognosis than meningitis with a Gram positive organism.

Guidelines for the prevention of sepsis in asplenic and hyposplenic patients

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has a mortality of up to 50%. The spectrum of causative organisms is evolving as are recommended preventive strategies, which include education, prophylactic and standby antibiotics, preventive immunizations, optimal antimalarial advice when visiting endemic countries and early management of animal bites. However, there is evidence that adherence to these strategies is poor. Consensus‐updated guidelines have been developed to help Australian and New Zealand clinicians and patients in the prevention of sepsis in asplenic and hyposplenic patients.

Antibiotic susceptibility of coagulase-negative staphylococci isolated from very low birth weight babies: comprehensive comparisons of bacteria at different stages of biofilm formation.

BackgroundCoagulase-negative staphylococci are major causes of bloodstream infections in very low birth weight babies cared for in Neonatal Intensive Care Units. The virulence of these bacteria is mainly due to their ability to form biofilms on indwelling medical devices. Biofilm-related infections often fail to respond to antibiotic chemotherapy guided by conventional antibiotic susceptibility tests.MethodsCoagulase-negative staphylococcal blood culture isolates were grown in different phases relevant to biofilm formation: planktonic cells at mid-log phase, planktonic cells at stationary phase, adherent monolayers and mature biofilms and their susceptibilities to conventional antibiotics were assessed. The effects of oxacillin, gentamicin, and vancomycin on preformed biofilms, at the highest achievable serum concentrations were examined. Epifluorescence microscopy and confocal laser scanning microscopy in combination with bacterial viability staining and polysaccharide staining were used to confirm the stimulatory effects of antibiotics on biofilms.ResultsMost coagulase-negative staphylococcal clinical isolates were resistant to penicillin G (100%), gentamicin (83.3%) and oxacillin (91.7%) and susceptible to vancomycin (100%), ciprofloxacin (100%), and rifampicin (79.2%). Bacteria grown as adherent monolayers showed similar susceptibilities to their planktonic counterparts at mid-log phase. Isolates in a biofilm growth mode were more resistant to antibiotics than both planktonic cultures at mid-log phase and adherent monolayers; however they were equally resistant or less resistant than planktonic cells at stationary phase. Moreover, for some cell-wall active antibiotics, concentrations higher than conventional MICs were required to prevent the establishment of planktonic cultures from biofilms. Finally, the biofilm-growth of two S. capitis isolates could be enhanced by oxacillin at the highest achievable serum concentration.ConclusionWe conclude that the resistance of coagulase-negative staphylococci to multiple antibiotics initially remain similar when the bacteria shift from a planktonic growth mode into an early attached mode, then increase significantly as the adherent mode further develops. Furthermore, preformed biofilms of some CoNS are enhanced by oxacillin in a dose-dependent manner.

Antibiotic-resistant Gram-negative bacteremia in pediatric oncology patients--risk factors and outcomes.

Background: Infection with antibiotic-resistant (AR) Gram-negative (GN) bacteria is associated with increased morbidity and mortality. The aim of this study was to determine risk factors and outcomes associated with GN bacteremia with acquired resistance to antibiotics used in the empiric treatment of febrile neutropenia in pediatric oncology patients at our institution. Methods: All episodes of GN bacteremia in oncology patients at the Royal Children’s Hospital Melbourne, from 2003 to 2010 were retrospectively reviewed. Information regarding age, diagnosis, phase of treatment, inpatient status, previous AR GN infection, treatment with inotropes or ventilatory support, admission to intensive care unit, and hospital and intensive care unit length of stay were obtained from electronic records. Results: A total of 280 episodes of GN bacteremia in 210 patients were identified. Of these, 42 episodes in 35 patients were caused by an AR GN organism. Factors independently associated with AR GN bacteremia were high-intensity chemotherapy (odds ratio 3.7, 95% confidence interval: 1.2–11.4), hospital-acquired bacteremia (odds ratio 4.3, 95% confidence interval: 2.0–9.6) and isolation of AR GN bacteria from any site within the preceding 12 months (odds ratio 9.9, 95% confidence interval: 3.8–25.5). Episodes of AR GN bacteremia were associated with longer median hospital length of stay (23.5 days versus 14.0 days; P = 0.0007), longer median intensive care unit length of stay (3.8 days versus 1.6 days; P = 0.02) and a higher rate of invasive ventilation (15% versus 5.2%; P = 0.03). No significant difference in infection-related or all-cause mortality between the 2 groups was identified. Conclusions: In pediatric oncology patients, AR GN bacteremia is associated with an increased rate of adverse outcomes and is more likely in patients who have received high-intensity chemotherapy, have been in hospital beyond 48 hours and who have had previous AR GN infection or colonization.

Varicella and the pregnant woman: Prevention and management

Infection with varicella zoster virus (VZV) is often considered a childhood ‘right of passage’; however, primary infection occurring in women of child‐bearing age can have significant adverse consequences both for the mother and for her fetus. During the first trimester, primary VZV infection may result in stillbirth or a baby born with the stigmata of the congenital varicella syndrome, while infection in the peripartum period can result in neonatal varicella, which carries a significant mortality rate despite appropriate antiviral therapy. Varicella in pregnant women can progress to pneumonitis and other severe sequelae that may also compromise the viability of the fetus. Exposure to VZV most commonly occurs in the community or from children in the household, but occasionally, exposure may occur in the hospital environment. Determining a womans serostatus prior to pregnancy is advised, as effective vaccines are now available and should be administered to non‐pregnant seronegative women of child‐bearing age. Clinical practice guidelines for management of a pregnant woman exposed to VZV are presented.

Nontuberculous Mycobacterial Infection in Children A Prospective National Study

Background: The epidemiology and management of nontuberculous mycobacterial (NTM) infection in Australian children is unknown. Methods: From July 2004 to June 2007, clinicians identified children with NTM infection as part of a nationwide active surveillance network. Following notification, detailed data were collected. Results: From 192 reports, data were received on 153 cases (response rate: 79.7%). Of these, 102 met inclusion criteria. The median age was 2.9 years. Predisposing conditions were infrequent and included chronic respiratory disease (n = 12) and immunosuppression (n = 6). Lymphadenitis was the most frequent presentation (n = 68) with pulmonary and disseminated disease infrequent (n = 14 and 3, respectively). NTM was isolated in 68 cases with Mycobacterium avium-intracellulare complex most frequently isolated (33/68; 48.5%). Surgery was performed in 78 cases and 42 children were treated with antimycobacterial therapy. Twenty-five subjects received surgery and antimycobacterial therapy. Follow-up data were available for 77 children with recurrence observed in 18 cases. Complete excision was associated with a higher rate of treatment success when compared with all other therapies (OR: 9.48 [95% CI: 2.00–44.97], P = 0.001). Mycobacterium lentiflavum infection accounted for 4.4% of culture confirmed cases and had a lower rate of treatment success than other species (0% vs. 78.2%; P = 0.016). Conclusions: The incidence of NTM infection in Australian children is 0.84 of 100,000 (95% CI: 0.68–1.02). Infection occurs most often in young children without predisposing conditions. Despite therapy, there was recurrence in 23.4% of cases.

Reducing hospital-acquired infections and improving the rational use of antibiotics in a developing country: an effectiveness study

Background Prevention of hospital-acquired infections (HAI) is central to providing safe and high quality healthcare. Transmission of infection between patients by health workers, and the irrational use of antibiotics have been identified as preventable aetiological factors for HAIs. Few studies have addressed this in developing countries. Aims To implement a multifaceted infection control and antibiotic stewardship programme and evaluate its effectiveness on HAIs and antibiotic use. Methods A before-and-after study was conducted over 27 months in a teaching hospital in Indonesia. All children admitted to the paediatric intensive care unit and paediatric wards were observed daily. Assessment of HAIs was made based on the criteria from the Centers for Disease Control and Prevention. The multifaceted intervention consisted of a hand hygiene campaign, antibiotic stewardship (using the WHO Pocket Book of Hospital Care for Children guidelines as standards of antibiotic prescribing for community-acquired infections), and other elementary infection control practices. Data were collected using an identical method in the preintervention and postintervention periods. Results We observed a major reduction in HAIs, from 22.6% (277/1227 patients) in the preintervention period to 8.6% (123/1419 patients) in the postintervention period (relative risk (RR) (95% CI) 0.38 (0.31 to 0.46)). Inappropriate antibiotic use declined from 43% (336 of 780 patients who were prescribed antibiotics) to 20.6% (182 of 882 patients) (RR 0.46 (0.40 to 0.55)). Hand hygiene compliance increased from 18.9% (319/1690) to 62.9% (1125/1789) (RR 3.33 (2.99 to 3.70)). In-hospital mortality decreased from 10.4% (127/1227) to 8% (114/1419) (RR 0.78 (0.61 to 0.97)). Conclusions Multifaceted infection control interventions are effective in reducing HAI rates, improving the rational use of antibiotics, increasing hand hygiene compliance, and may reduce mortality in hospitalised children in developing countries.