Exploring the infectious contribution to intussusception causality using the effects of COVID-19 lockdowns in Australia: An ecological study.

INTRODUCTION: Intussusception is the primary cause of acute bowel obstruction in infants. The majority of cases under 2 years of age are classed as idiopathic with viral infection implicated as one of the causes. COVID-19 public health measures led to significant decreases in communicable disease prevalence. During these times, reductions in intussusception frequency were reported - reductions greater than would be expected with our previous understanding of its infectious aetiology. METHODS: We conducted a retrospective, multi-state, ecological study over a twelve-year period. Monthly case numbers of ICD-10-AM K56.1 'Intussusception' coded admissions were acquired from state-wide admissions datasets from New South Wales (NSW), Victoria and Queensland, representing 77.62% of the eligible Australian population. These counts within differing jurisdictional lockdowns were compared to non-lockdown periods in order to investigate a correlation between intussusception frequency and lockdown periods. RESULTS: We found a negative association between intussusception frequency and lockdown periods in both eligible states. The largest reductions were seen in the under 2 year age groups with Victoria experiencing a 62.7% reduction (Rate ratio (RR) = 0.37, p < 0.0001) and NSW a 40.1% reduction (RR = 0.599, p = 0.006) during lockdown times. Controls for variations in lockdown restrictions between both regional and metropolitan areas also showed expected decreases. CONCLUSION: Our ecological study demonstrates significant decreases in the frequency of paediatric intussusception admissions during the COVID-19 lockdown periods. The unexpected magnitude of the reductions suggests that the true proportion of infectious disease-caused idiopathic intussusception is greatly underestimated.

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial.

BACKGROUND: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. METHODS: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. RESULTS: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. CONCLUSIONS: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. CLINICAL TRIALS REGISTRATION: NCT04126213.

WHAT IS THE CONTEXT?: Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. WHAT IS NEW?: In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11­15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. WHAT IS THE IMPACT?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers.

Live vaccines following intravenous immunoglobulin for Kawasaki disease: Are we vaccinating appropriately?

AIM: Australian and New Zealand guidelines recommend that live vaccines be postponed for 11 months after treatment of Kawasaki disease (KD) with intravenous immunoglobulin (IVIG). We aimed to describe patterns of live-vaccine administration after KD treatment, focusing on the measles-mumps-rubella/measles-mumps-rubella-varicella (MMR/MMRV) vaccines, and to compare real-world practice with current recommendations. METHODS: We combined data from inpatient Electronic Health Records and the Australian Immunisation Register for all children who received IVIG for the treatment of KD under the age of 5 years at two Australian tertiary children's hospitals over a 12-year period. Children who received IVIG <11 months before a scheduled MMR/MMRV were deemed 'at risk' of breaching the guidelines, and those whose subsequent vaccination occurred <11 months after the IVIG were deemed to have 'breached' the guidelines. RESULTS: Of those at risk, three-quarters (76%) breached the guidelines for their first MMR/MMRV. Findings were similar (50%-80%) for the second MMR/MMRV dose. CONCLUSIONS: The majority of Australian children treated for KD with IVIG may not be optimally protected by MMRV vaccination. Immunisation systems should address this avoidable risk.

Snotwatch: an ecological analysis of the relationship between febrile seizures and respiratory virus activity.

BACKGROUND: Febrile seizures are the commonest type of seizure in occurring in the first few years of life, mostly affecting children aged six months to five years old. While largely benign, the incidence of each febrile seizure increases the risk of recurrence, afebrile seizures and epilepsy. Viruses are the most frequent cause of febrile illnesses in which a febrile seizure occurs. Febrile seizure presentation patterns appear to follow a seasonal trend. AIMS: To identify patterns of febrile seizure incidence across different seasons with specific viral activity, and to establish a framework for analysing virus circulation data with common illnesses within a shared region and population. SETTING: Our study was a study of febrile seizure presentations in Victoria, Australia and respiratory virus detection. PARTICIPANTS: We obtained independent datasets of emergency department febrile seizure presentations at Monash Health and all respiratory multiplex PCR tests performed at Monash Health from January 2010-December 2019 to observe common trends in virus circulation and febrile seizure incidence. STUDY DESIGN: Trends were studied temporally through mixed effects Poisson regression analysis of the monthly incidence of febrile seizures and the rate of positive PCR tests. Peak viral seasons (95th centile incidence) were compared to median viral circulation (50th centile incidence) to calculate peak season risk ratios. RESULTS: We found a 1.75-2.06 annual risk ratio of febrile seizure incidence in June-September. Temporal analysis of our data showed this peak in febrile seizures was attributable to circulating viruses in this season, and virus modelling showed correlation with increased rates of positive Influenza A (1.48 peak season risk ratio), Influenza B (1.31 peak season risk ratio), Human metapneumovirus (1.19 peak season risk ratio) and Respiratory Syncytial Virus (1.53 peak season risk ratio) on PCR testing. CONCLUSION: Our ecological study statistically demonstrates the recognised winter peak in febrile seizure incidence and ascribes the seasonal relationship to several viral infections which affect the community, including a novel association with Human metapneumovirus.

Feasibility and acceptability of targeted salivary cytomegalovirus screening through universal newborn hearing screening.

AIM: This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated. METHODS: The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019-March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive ('refer') result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of 'referred' infants whose parents completed the salivary CMV screening test ≤21 days of life. Acceptability was measured through parent survey. RESULTS: Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken ≤21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32. CONCLUSIONS: Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic.

Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. RESULTS: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

SCN1A Variants in vaccine-related febrile seizures: A prospective study.

OBJECTIVE: Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe developmental and epileptic encephalopathy Dravet syndrome. Following vaccination, febrile seizures may raise the specter of poor outcome and inappropriately implicate vaccination as the cause. We aimed to determine the prevalence of SCN1A variants in children having their first febrile seizure either proximal to vaccination or unrelated to vaccination compared to controls. METHODS: We performed SCN1A sequencing, blind to clinical category, in a prospective cohort of children presenting with their first febrile seizure as vaccine proximate (n = 69) or as non-vaccine proximate (n = 75), and children with no history of seizures (n = 90) recruited in Australian pediatric hospitals. RESULTS: We detected 2 pathogenic variants in vaccine-proximate cases (p.R568X and p.W932R), both of whom developed Dravet syndrome, and 1 in a non-vaccine-proximate case (p.V947L) who had febrile seizures plus from 9 months. All had generalized tonic-clonic seizures lasting >15 minutes. We also found enrichment of a reported risk allele, rs6432860-T, in children with febrile seizures compared to controls (odds ratio = 1.91, 95% confidence interval = 1.31-2.81). INTERPRETATION: Pathogenic SCN1A variants may be identified in infants with vaccine-proximate febrile seizures. As early diagnosis of Dravet syndrome is essential for optimal management and outcome, SCN1A sequencing in infants with prolonged febrile seizures, proximate to vaccination, should become routine. ANN NEUROL 2020;87:281-288.

Influenza Epidemiology, Vaccine Coverage and Vaccine Effectiveness in Children Admitted to Sentinel Australian Hospitals in 2017: Results from the PAEDS-FluCAN Collaboration.

BACKGROUND: In 2017, Australia experienced record influenza notifications. Two surveillance programs combined to summarize the epidemiology of hospitalized influenza in children and report on vaccine effectiveness (VE) in the context of a limited nationally funded vaccination program. METHODS: Subjects were prospectively recruited (April-October 2017). Case patients were children aged ≤16 years admitted to 11 hospitals with an acute respiratory illness and laboratory-confirmed influenza. Controls were hospitalized with acute respiratory illness and tested negative for influenza. VE estimates were calculated using the test-negative design. RESULTS: A total of 1268 children were hospitalized with influenza: 31.5% were <2 years old, 8.3% were indigenous, and 45.1% had comorbid conditions predisposing to severe influenza. Influenza B was detected in 34.1% with influenza A/H1N1 and A/H3N2 detected in 47.2% and 52.8% of subtyped influenza A specimens. The median length of stay was 3 days (interquartile range, 1-5), 14.5% were admitted to the intensive care unit, and 15.9% received oseltamivir. Four in-hospital deaths occurred (0.3%): one was considered influenza associated. Only 17.1% of test-negative-controls were vaccinated. The VE of inactivated quadrivalent influenza vaccine for preventing hospitalized influenza was estimated at 30.3% (95% confidence interval, 2.6%-50.2%). CONCLUSIONS: Significant influenza-associated morbidity was observed in 2017 in Australia. Most hospitalized children had no comorbid conditions. Vaccine coverage and antiviral use was inadequate. Influenza vaccine was protective in 2017, yet VE was lower than previous seasons. Multiple Australian states have introduced funded preschool vaccination programs in 2018. Additional efforts to promote vaccination and monitor effectiveness are required.

Positive predictive value of ICD-10 codes to detect anaphylaxis due to vaccination: A validation study.

PURPOSE: To validate the use of selected International Classification of Disease Codes 10th revision (ICD-10) to predict (positive predictive value) anaphylaxis due to vaccination using emergency department (ED) data. METHODS: We conducted a retrospective study using ED encounter data from a large tertiary-care teaching hospital, Monash Medical Centre, Melbourne, Australia. We searched all ED encounters potentially due to anaphylaxis after vaccination, between 1 January 2010 and 31 December 2018, using ICD-10-CM codes T80.5, T80.6, T88.1, T88.6, and T78.2. Health records of potential cases were examined to determine if they met the Brighton Collaboration (BC) criteria for anaphylaxis. We calculated the PPV to evaluate the accuracy of the selected ICD-10-CM codes in predicting anaphylaxis due to vaccination. RESULTS: Of the 69 health records identified and reviewed, 29 (42.2%) met the criteria for anaphylaxis regardless of the cause, and 24.6% (17/69) of records were confirmed as anaphylaxis triggered by vaccination (low positive predictive value). However, of the 23 records identified using ICD-10-CM code T80.5, 22 were classified as anaphylaxis cases regardless of the cause, and 12 were anaphylaxis due to vaccination cases giving PPV of 95.7% and 52.2%, respectively. CONCLUSIONS: Given that there is no specific ICD-10-CM code for anaphylaxis due to vaccination, ICD-10-CM code T80.5 may be suitable to monitor anaphylaxis due to vaccination in the ED setting. The current study was conducted at a single centre and needs to be confirmed by future multicentre studies.

Invasive group A Streptococcus disease in Australian children: 2016 to 2018 - a descriptive cohort study.

OBJECTIVES: Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children. METHODS: IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated. RESULTS: A total of 181 patients were identified, with most (115, 63.5%) <5 years old. The mean annual minimum incidence rate was 1.6 (95% confidence interval: 1.1-2.3) per 100,000 children across the study period. An epidemiological correlation with the seasonal burden of influenza was noted. Contact prophylaxis was not consistently offered. Of 96 patients with emm-typing results available, 72.9% showed emm-1, -4 or - 12. CONCLUSIONS: Robust surveillance systems and cohesive patient management guidelines are needed. Making iGAS disease nationally notifiable would help facilitate this. Influenza vaccination may contribute to reducing seasonal increases in iGAS incidence. The burden of disease emphasises the need for ongoing progress in GAS vaccine development.

Antimicrobial prescribing for children in primary care.

AIM: To describe the patterns of antimicrobial prescribing in general practice for children aged ≤18 years. METHODS: This is a review of routinely collected patient data extracted from computerised medical records from 39 general practices in eastern metropolitan Melbourne over a 5-year period, 2010-2014. MAIN OUTCOME MEASURES: Proportion of paediatric consultations resulting in antibiotic prescription, type and frequency of antibiotics prescribed, antibiotic prescribing stratified by age, reason for indication and inter-practice variation. RESULTS: There were 744 883 consultations for 89 983 individual paediatric patients and 85 913 prescriptions for antibiotics during the study period. Of these antibiotic prescriptions, 75 410 were associated with a consultation, and 10 503 (12.2% of all prescriptions) had no associated consultation in the data. On average, one in five individual children was prescribed an antibiotic each year. The most commonly prescribed antibiotics were cephalexin, amoxycillin/clavulanate, cefaclor, phenoxymethylpenicillin and roxithromycin. Less than 3% of all prescriptions were for amoxycillin. Prescribing of cefaclor and roxithromycin decreased, although cefaclor remained the third most common antibiotic choice for general practitioners. Peaks in prescribing were noted over winter months. Reason for prescription was not recorded for 82% of prescriptions. The frequency of antibiotic prescription per consultation varied substantially (2.1-19.7%) between general practitioner clinics. Overall, antibiotic prescribing decreased by 2.3% over the 5-year period. CONCLUSIONS: This study provides a focused examination of antibiotic prescribing practices for children in Australian general practice. More information is required to better understand specific prescribing practices in children, including the low frequency of amoxycillin prescription and ongoing prescription of cefaclor.

A study comparing the practice of Australian maternity care providers in relation to maternal immunisation.

BACKGROUND: Women's decisions regarding vaccination during pregnancy are heavily influenced by maternity care provider (MCP) recommendations. Understanding why MCPs may not recommend vaccination is central to improving vaccination rates. AIMS: To examine the knowledge, attitudes and practice of Australian MCPs to maternal vaccination. METHODS: We surveyed obstetricians, midwives and general practitioners (GPs) between September and November 2016. Providers were asked about their knowledge and current practice, and about their perceived roles in discussing and administering maternal vaccinations. RESULTS: Eight hundred and seventy surveys were completed. Each MCP group believed they had the primary responsibility for discussing vaccinations but all groups perceived GPs as primarily responsible for administering vaccines. More midwives had concerns about safety (21/129, 16%) than obstetricians (9/359, 3%) and GPs (7/326, 2%) (P < 0.001). Overall, 83% of MCPs recommended diphtheria-tetanus-acellular pertussis vaccination (dTpa) and 78% inactivated influenza vaccination (IIV) according to guidelines, with no differences between groups. Overall 77% provided dTpa onsite (GPs 99%, midwives 70%, obstetricians 60%, P < 0.001) and 71% provided IIV (GPs 99%, midwives 48%, obstetricians 54%, P < 0.001). Factors associated with recommending vaccination in accordance with guidelines and providing vaccination onsite were similar across groups: personal history of vaccination, confidence in vaccine knowledge, and awareness of recommendations for and belief in the safety of maternal dTpa. CONCLUSIONS: Among MCPs, the rates of recommending and providing maternal vaccination were higher than previously reported. Further improvements might be expected with increased awareness of guidelines, further education around vaccine safety, and by changing perceptions of the role of obstetricians and midwives in providing maternal vaccinations.

Seroresponses and safety of 13-valent pneumococcal conjugate vaccination in kidney transplant recipients.

BACKGROUND: Conjugated pneumococcal vaccine is recommended for kidney transplant recipients, however, their immunogenicity and potential to trigger allograft rejection though generation of de novo anti-human leukocyte antigen antibodies has not been well studied. METHODS: Clinically stable kidney transplant recipients participated in a prospective cohort study and received a single dose of 13-valent conjugate pneumococcal vaccine. Anti-pneumococcal IgG was measured for the 13 vaccine serotypes pre and post vaccination and functional anti-pneumococcal IgG for 4 serotypes post vaccination. Anti-human leukocyte antigen antibodies antibodies were measured before and after vaccination. Kidney transplant recipients were followed clinically for 12 months for episodes of allograft rejection or invasive pneumococcal disease. RESULTS: Forty-five kidney transplant recipients participated. Median days between pre and post vaccination serology was 27 (range 21-59). Post vaccination, there was a median 1.1 to 1.7-fold increase in anti-pneumococcal IgG antibody concentrations for all 13 serotypes. Kidney transplant recipients displayed a functional antibody titer ≥1:8 for a median of 3 of the 4 serotypes. Post vaccination, there were no de novo anti-human leukocyte antigen antibodies, no episodes of biopsy proven rejection or invasive pneumococcal disease. CONCLUSION: A single dose of 13-valent conjugate pneumococcal vaccine elicits increased titers and breadth of functional anti-pneumococcal antibodies in kidney transplant recipients without stimulating rejection or donor-specific antibodies.

Respiratory virus detection and co-infection in children and adults in a large Australian hospital in 2009-2015.

AIM: This hospital network-based retrospective observational study aimed to describe the prevalence and seasonality of paediatric and adult viral respiratory pathogens and their rates of co-infections, following the introduction of a rapid multiplex molecular diagnostic assay. METHODS: All nasopharyngeal samples tested in patients presenting to Monash Health, Melbourne, Australia, from August 2009 to July 2015 by means of multiplex tandem polymerase chain reaction using the Respiratory Pathogen 12Plex kit (AusDiagnostics) were included in the analysis. RESULTS: There were 28 729 patient samples analysed after duplicate samples were excluded. Positive results were twice as likely in paediatrics, 7573/11 491 (65.9%), compared to adults, 5410/17 238 (31.4%). Co-infection was more frequent in paediatrics, 1642/7573 (21.7% of positives), compared to adults 299/5410 (5.5%). Adenovirus had a high prevalence as a co-infection, 639/990 (64.5%), in paediatrics. Testing frequency increased by 179% in the paediatric group and by 949% for adults over the 6 years of observation. CONCLUSIONS: This study demonstrated a significant difference in the positive detection rate of pathogens and co-infections between the population groups. Adenovirus had a surprisingly high prevalence as a co-infection, especially in paediatric patients. Over the study period, rapid uptake of the test was observed, especially in adults. This raises concerns about how we can ensure that testing remains rational and is able to be provided in a cost-effective manner in the future.

A quality improvement initiative to reduce central line infection in neonates using checklists.

Central line associated blood stream infections (CLABSI) are the most common complication of central catheters in neonates. These infections increase length of hospital stay, hospital costs and impact on mortality and morbidities. We performed a quasi-experimental study, over 24 months, utilising a pre-post design to determine the impact checklists had on central line infections. We introduced checklists for insertion, daily maintenance and procedural access based on the existing clinical guideline. Infections and compliance were monitored and reported back to the unit each month. We utilised the interrupted time series analysis to evaluate the impact of introduction of the checklists. Over the 24 months, 318 infants were included with a total of 509 central lines inserted. In the post intervention phase, definite CLABSI rates declined by 41%, from 13.8 definite CLABSIs per 1000 central-line days to 7.8 definite CLABSIs per 1000 central-line days. There was significant change in the mean levels in the post intervention phase (coefficient crude -0.01015; 95% CI -0.01980-0.00051, p value 0.039). Checklist compliance for insertion was 70%, and daily maintenance compliance overall mean was 66%. CONCLUSION: Our quality improvement initiative using checklists, supported with education and feedback, significantly reduced CLABSI in our neonatal unit. What is Known: • Central line associated blood stream infection (CLABSI) continue to cause mortality and morbidity in the neonatal population. • Bundles of intervention use quality improvement methodology to reduce CLABSI and checklists can assist with the introduction of these. What is New: • Checklists assist with reducing central line infection. • To ensure the success of checklists, robust education, leadership and continuous feedback are vital.

Empiric antibiotic regimens for neonatal sepsis in Australian and New Zealand neonatal intensive care units.

AIM: Neonatal sepsis remains an important cause of morbidity and mortality, and requires prompt empiric treatment. However, only a minority of babies who receive antibiotics for suspected sepsis have an infection. Antimicrobial exposure in infancy has important short- and long-term consequences. There is no consensus regarding empirical antimicrobial regimens. METHODS: The study included a survey of empiric antimicrobial regimens in all tertiary neonatal intensive care units in Australia and New Zealand in 2013-2014. RESULTS: All 27 units responded. For early-onset sepsis, all units used a combination of gentamicin with either penicillin or ampicillin. For late-onset sepsis, the frequency of units using empiric vancomycin (41%) versus empiric flucloxacillin (48%) was similar. Gestational age or the presence of a central venous catheter had little influence on using vancomycin instead of flucloxacillin. For late-onset sepsis with meningitis there was marked variation in antimicrobial combinations, with 15 different regimens described. A total of 93% used a cefotaxime-based regimen, either as monotherapy (22%) or combined with a second (22%) or third (48%) agent. For suspected necrotising enterocolitis, 89% used an aminoglycoside, metronidazole and a penicillin. Historical outbreaks of multi-resistant organisms exerted long-term influence over regimen choice. CONCLUSIONS: There was limited use of broad-spectrum agents such as carbapenems or third-generation cephalosporins. In this region with low methicillin-resistant Staphylococcus aureus prevalence, empiric vancomycin use was common, selected for activity against coagulase-negative staphylococci. Empiric vancomycin is rarely necessary because coagulase-negative staphylococci are often contaminants and sepsis is rarely fulminant, occurring almost exclusively in extremely low birthweight infants. Implementation of appropriate, local antimicrobial policies is crucial to minimise antimicrobial exposure in this vulnerable population and halt the development of antimicrobial resistance.

Allergic adverse events following 2015 seasonal influenza vaccine, Victoria, Australia.

Australia was alerted to a possible increase in allergy-related adverse events following immunisation (AEFI) with 2015 seasonal trivalent influenza vaccines (TIV) by the Victorian state vaccine safety service, SAEFVIC. We describe SAEFVIC's initial investigation and upon conclusion of the 2015 influenza vaccination programme, to define the signal event and implications for vaccine programmes. Allergy-related AEFI were defined as anaphylaxis, angioedema, urticaria or generalised allergic reaction. Investigations compared 2015 TIV AEFI reports to previous years as proportions and reporting risk (RR) per 100,000, stratified by influenza vaccine brand. The initial investigation showed an increased proportion of allergy-related AEFI compared with 2014 (25% vs 12%), predominantly in adults, with insufficient clinical severity to alter the programme risk-benefit. While overall TIV AEFI RR in 2015 was similar to previous years (RR: 1.07, 95% confidence interval (CI): 0.88-1.29), we identified a near-doubling RR for allergy-related AEFI in 2015 (RR: 1.78, 95% CI: 1.14-- 2.80) from 2011 to 2014 with no difference by vaccine brand or severity increase identified. This increase in generalised allergy-related AEFI, across all used vaccine brands, supports evidence of variable reactogenicity arising from influenza vaccine strain variations. This investigation underlines the importance of effective seasonal influenza vaccine pharmacovigilance.