Penicillin Allergy De-labeling Results in Significant Changes in Outpatient Antibiotic Prescribing Patterns.

Unverified penicillin allergies are common but most patients with a penicillin allergy label can safely use penicillin antibiotics. Penicillin allergy labels are associated with poor clinical outcomes and overuse of second-line antibiotics. There is increasing focus on penicillin allergy "de-labeling" as a tool to improve antibiotic prescribing and antimicrobial stewardship. The effect of outpatient penicillin allergy de-labeling on long-term antibiotic use is uncertain. We performed a retrospective pre- and post- study of antibiotic dispensing patterns, from an electronic dispensing data repository, in patients undergoing penicillin allergy assessment at Auckland City Hospital, New Zealand. Over a mean follow-up of 4.55 years, 215/304 (70.7%) of de-labeled patients were dispensed a penicillin antibiotic. Rates of penicillin antibiotic dispensing were 0.24 (0.18-0.30) penicillin courses per year before de-labeling and 0.80 (0.67-0.93) following de-labeling with a reduction in total antibiotic use from 2.30 (2.06-2.54) to 1.79 (1.59-1.99) antibiotic courses per year. In de-labeled patients, the proportion of antibiotic courses that were penicillin antibiotics increased from 12.81 to 39.62%. Rates of macrolide, cephalosporin, trimethoprim/co-trimoxazole, fluoroquinolone, "other" non-penicillin antibiotic use, and broad-spectrum antibiotic use were all lower following de-labeling. Further, antibiotic costs were lower following de-labeling. In this study, penicillin allergy de-labeling was associated with significant changes in antibiotic dispensing patterns.

Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years.

BACKGROUND: In a two-centre randomized placebo-controlled trial of Lactobacillus rhamnosus HN001 (HN001) (6 × 109 colony-forming units [cfu]) or Bifidobacterium lactis HN019 (HN019) (9 × 109 cfu) taken daily from 35-week gestation to 6 months' post-partum in mothers while breastfeeding and from birth to age 2 years in infants, we showed that HN001 significantly protected against eczema development at 2, 4 and 6 years and atopic sensitization at 6 years. There was no effect of HN019. We report here the findings for 11 year outcomes. METHODS: At age 11 years, eczema was defined as previously using the UK Working Party's Diagnostic Criteria. Asthma, wheeze, hay fever and rhinitis were defined based on the International Study of Asthma and Allergies in Childhood (ISAAC) questions. Atopic sensitization was defined as one or more positive responses (mean wheal diameter ≥3 mm) to a panel of food and aeroallergens. Analysis was intention-to-treat using hazard ratios to assess probiotic effects on the 11-year lifetime prevalence and relative risks for point or 12-month prevalence at 11 years. RESULTS: Early childhood HN001 supplementation was associated with significant reductions in the 12-month prevalence of eczema at age 11 years (relative risk [RR] = 0.46, 95% CI 0.25-0.86, P = 0.015) and hay fever (RR = 0.73, 95% CI 0.53-1.00, P = 0.047). For the lifetime prevalence, HN001 was associated with a significant reduction in atopic sensitization (hazard ratio [HR] = 0.71, 95% CI 0.51-1.00, P = 0.048), eczema (HR = 0.58, 95% CI 0.41-0.82, P = 0.002) and wheeze (HR = 0.76, 95% CI 0.57-0.99, P = 0.046). HN019 had no significant effect on these outcomes. CONCLUSION: This is the first early probiotic intervention to show positive outcomes for at least the first decade of life across the spectrum of allergic disease.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

BACKGROUND: In a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35 weeks of gestation until 6 months post-partum if breastfeeding and their child from birth to age 2 years halved the risk of eczema during the first 2 years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented. METHODS: In this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6 × 109 colony-forming units) was taken daily by mothers from 14-16 weeks of gestation till 6 months post-partum if breastfeeding, but was not given directly to the child. Women were recruited from the same study population as the first study, where they or their partner had a history of treated asthma, eczema or hay fever. RESULTS: Women were randomized to HN001 (N = 212) or placebo (N = 211). Maternal-only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD ≥ 10, wheeze or atopic sensitization in the infant by 12 months. This contrasts with the mother and child intervention study, where HN001 was associated with reductions in eczema (hazard ratio (HR): 0.39, 95% CI 0.19-0.79, P = .009) and SCORAD (HR = 0.61, 95% 0.37-1.02). However, differences in the HN001 effect between studies were not significant. HN001 could not be detected in breastmilk from supplemented mothers, and breastmilk TGF-ß/IgA profiles were unchanged. CONCLUSION: Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

Paediatric food-induced anaphylaxis hospital presentations in New Zealand.

AIM: Globally, rates of paediatric food-induced anaphylaxis (FIA) are increasing. Little data is available regarding the epidemiology of FIA among New Zealand (NZ) children. This study investigated the incidence of paediatric (0-14 years) FIA hospital presentations in NZ over a 10-year period. METHODS: Ministry of Health public hospital discharge data from 2006 to 2015 were analysed using FIA-related International Classification of Diseases codes (T78.0 - anaphylactic shock due to adverse food reaction and T78.2 - anaphylactic shock unspecified and free text qualifier) to identify acute hospital presentations. RESULTS: The overall annualised FIA hospital presentation rate was 16.2 per 100 000 children. Subgroup analysis indicated a significantly higher rate in males (19.1/100 000) than in females (13.1/100 000), and among children aged less than 2 years of age (50.5/100 000) compared with older children. Rates among Asian and Pacific children were higher than Maori and NZ European children. In 67.7% of cases, a single specific allergen was suggested by the information provided; among these cases, nuts (48%), specifically peanuts (26%), were the most commonly reported allergen, followed by cow's milk (21%). Time trend analysis showed a 2.8-fold increase in the overall annualised rate for the 10-year period. CONCLUSION: These findings are consistent with other international studies indicating increasing rates of FIA in children. These data will provide information for a review of NZ paediatric allergy services to ensure current international standards with regard to the equitable delivery of timely, appropriate and accessible care are being met. Reasons for differences by gender, age and ethnicity require further investigation.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

BACKGROUND: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. METHODS/DESIGN: The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. DISCUSSION: The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.

Adult food-induced anaphylaxis hospital presentations in New Zealand.

BACKGROUND: Food allergy including anaphylaxis is an increasing clinical problem in many countries. Little information is available regarding prevalence, causative foods and time trends in the New Zealand adult population. OBJECTIVE: This cross-sectional study investigated the incidence of hospital presentation with food-induced anaphylaxis in New Zealand among adults and adolescents over a 10-year period. METHODS: Ministry of Health hospital discharge data from 2002 to 2011 were analysed using food allergy and anaphylaxis-related International Classification of Diseases (ICD) codes to identify acute hospital presentations. RESULTS: There was an average annualised rate of hospital food-induced anaphylaxis presentations of 4.8 per 100 000 adults (aged ≥15 years) for the period reviewed. Subgroup analyses revealed significant differences by gender, age group and ethnicity, notably higher rates in females, younger adults (15-34 years) and Pacific Island populations. Seafood was the most common food allergen group, followed by nuts. Time trend analysis revealed a 1.7-fold increase in the 10-year period, mainly attributable to an increase in rates in the Pacific Island population. CONCLUSIONS: These data confirm food-induced anaphylaxis as an increasing problem in New Zealand and show significant differences in incidence of hospital presentation in different ethnic populations. Future research will be required to understand and address disparities in the incidence of these conditions.

Differential effects of two probiotics on the risks of eczema and atopy associated with single nucleotide polymorphisms to Toll-like receptors.

BACKGROUND: There is strong evidence to support a genetic predisposition to eczema and more recently studies have suggested that probiotics might be used to prevent eczema by modifying the expression of putative allergy-associated genes. The aim of this present study was to investigate whether two probiotics, Lactobacillus rhamnosus HN001 (HN001) and Bifidobacterium animalis subsp. lactis HN019 (HN019), can modify the known genetic predisposition to eczema conferred by genetic variation in the Toll-like receptor (TLR) genes in a high-risk infant population. METHODS: We selected 54 SNPs in the Toll-like receptor genes. These SNPs were analysed in 331 children of sole European ancestry as part of a double-blind, randomized, placebo-controlled trial examining the effects of HN001 and HN019 supplementation on eczema development and atopic sensitization. RESULTS: The data showed that 26 TLR SNPs interacted with HN001 resulting in a significantly reduced risk of eczema, 18 for eczema severity as defined by SCORAD ≥ 10 and 20 for atopic sensitization compared to placebo. There were only two SNPs that interacted with HN019 resulting in a reduced risk of eczema, eczema severity or atopy. CONCLUSIONS: This is the first study to show that the negative impact of specific TLR genotypes may be positively affected by probiotic supplementation. HN001 exhibits a much stronger effect than HN019 in this respect.

Anaphylaxis is more common with rocuronium and succinylcholine than with atracurium.

BACKGROUND: Intraoperative anaphylaxis is a rare but serious occurrence, often triggered by neuromuscular-blocking drugs (NMBDs). Previous reports suggest that the rates of anaphylaxis may be greater for rocuronium than for other NMBDs, but imprecise surrogate metrics for new patient exposures to NMBDs complicate interpretation. METHODS: This was a retrospective, observational cohort study of intraoperative anaphylaxis to NMBDs at two hospitals between 2006 and 2012. Expert anesthetic and immunologist collaborators investigated all referred cases of intraoperative anaphylaxis where NMBDs were administered and identified those where a NMBD was considered responsible. New patient exposures for each NMBD were extracted from electronic anesthetic records compiled during the same period. Anaphylaxis rates were calculated for each NMBD using diagnosed anaphylaxis cases as the numerator and the number of new patient exposures as the denominator. RESULTS: Twenty-one patients were diagnosed with anaphylaxis to an NMBD. The incidence of anaphylaxis was 1 in 22,451 new patient exposures for atracurium, 1 in 2,080 for succinylcholine, and 1 in 2,499 for rocuronium (P < 0.001). CONCLUSIONS: In Auckland, the rate of anaphylaxis to succinylcholine and rocuronium is approximately 10-fold higher than to atracurium. Previous estimates of NMBD anaphylaxis rates are potentially confounded by inaccurate proxies of new patient exposures. This is the first study to report anaphylaxis rates using a hard denominator of new patient exposures obtained directly from anesthetic records.

Late-onset bolus intravenous beta-lactam antibiotic adverse reaction: short-lived symptoms during drug administration and associated laboratory abnormalities.

BACKGROUND: In the 1970s, there were 2 reports of a late-onset adverse reaction during bolus infusions of benzyl penicillin, characterized by short-lived symptoms, most commonly abdominal pain. The mechanism is not known. We set out to further characterize this reaction. METHODS: We conducted a prospective observational study of all adult patients receiving bolus intravenous (IV) beta-lactam antibiotics under the care of our Outpatient IV Antibiotic Service from 1 August 2007 to 31 January 2010, focusing on those who developed infusion-related symptoms. RESULTS: During the 30-month study, 11 of the 163 patients (7%) treated with bolus IV beta-lactam antibiotics developed a late-onset infusion-related adverse reaction. Six of 30 patients (20%) treated with benzyl penicillin developed this adverse reaction compared to 5 of 133 (4%) treated with any other beta-lactam antibiotic (p = 0.006). The median duration of beta-lactam antibiotic before reaction onset was 25 days. Abdominal pain occurred in 9 patients (82%), fever in 3 (27%), and rash in 5 (45%). Seven patients (64%) developed a combination of thrombocytopenia, neutropenia, and/or lymphopenia and 6 (55%), elevated liver enzymes. CONCLUSIONS: This adverse reaction, occurring late during prolonged IV bolus beta-lactam treatment, is most often characterized by short-lived abdominal pain occurring at the time of infusion and is more common in patients receiving benzyl penicillin. It is frequently associated with cytopenias and elevated liver enzymes. It may have both immunological and non-immunological mechanisms.

A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clearly established, although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years. OBJECTIVE: To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years. METHODS: Double-blind, randomized placebo-controlled trial of infants at risk of allergic disease. Pregnant women were randomized to take Lactobacillus rhamnosus HN001 (L rhamnosus), Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding, and their infants were randomized to receive the same treatment from birth to 2 years (n = 474). The infant's cumulative prevalence of eczema and point prevalence of atopy, using skin prick tests to common allergens, was assessed at 2 years. RESULTS: Infants receiving L rhamnosus had a significantly (P = .01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30-0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58-1.41). There was no significant effect of L rhamnosus (HR, 0.74; 95% CI, 0.46-1.18) or B animalis subsp lactis (HR, 0.82; 95% CI, 0.52-1.28) on atopy. L rhamnosus (71.5%) was more likely than B animalis subsp lactis (22.6%) to be present in the feces at 3 months, although detection rates were similar by 24 months. CONCLUSION: We found that supplementation with L rhamnosus, but not B animalis subsp lactis, substantially reduced the cumulative prevalence of eczema, but not atopy, by 2 years. Understanding how Lactobacilli act to prevent eczema requires further investigation.

Too much of a good thing, is it bad? Adrenaline on trial.

Adrenaline is vital in the treatment of severe allergic reactions (anaphylaxis), however it is often underutilised or inappropriately administered. Adrenaline treatment is not without risk and most adverse reactions to adrenaline occur when it is given in overdose or as an intravenous bolus. We report a case of myocardial injury and hypotension following inappropriate administration of adrenaline.

Occupational respiratory health of New Zealand horse trainers.

OBJECTIVES: To confirm that working with horses is an occupational respiratory hazard and observed associations are not attributable to confounding. METHODS: A postal survey of the respiratory health of 659 horse trainers and a comparison group of 506 vegetable growers was conducted. Data were analysed using logistic regression. RESULTS: Relative to vegetable growers, horse trainers reported higher rates of chronic bronchitis [odds ratio (OR) = 6.8, 95% confidence interval (CI): 2.2-21.4] and organic dust toxic syndrome/farmers' lung (ODTS/FL) (OR = 3.5, 95% CI: 1.8-6.8). Grinding oats, spreading hay, and using powdered feed supplements were associated with increased respiratory symptoms among trainers. Associations between symptoms and working with horses increased for full-time workers. CONCLUSIONS: This study found evidence that working with horses is a risk factor for ODTS/FL and bronchitis. The associations did not appear to be explained by bias, including confounding. However, the possibility of confounding cannot be entirely ruled out, and confirmatory studies are needed. Future studies should consider inorganic dust exposures.

Endotoxin exposure, wheezing, and rash in infancy in a New Zealand birth cohort.

BACKGROUND: Wheezing in infancy is common and is associated with small lungs, viral respiratory tract infection, and environmental tobacco smoke exposure. Recently, increased levels of endotoxin in the domestic environment have also been associated with infant wheezing, particularly among infants with a family history of atopic disease. OBJECTIVE: To explore associations between exposure to endotoxin at 3 months of age and reported symptoms of wheezing, rhinitis, itchy scaly rash, and atopy at 15 months in a birth cohort of 881 New Zealand children. METHODS: Using standardized methods, a 1-m(2) site from the bedroom floors of the 3-month-old infants was sampled and analyzed for endotoxin. RESULTS: Wheezing was significantly associated with higher endotoxin levels (odds ratio [OR], 1.54; 95% CI, 1.03-2.30), particularly among infants with a parental history of allergic disease (OR, 1.67; 95% CI, 1.07-2.60). Higher endotoxin concentrations were also strongly associated with recurrent itchy rashes (OR, 1.87; 95% CI, 1.14-3.05), particularly among infants who were atopic (OR, 4.64; 95% CI, 1.56-13.77) or had a parental history of allergic disease (OR, 2.10; 95% CI, 1.22-3.61). CONCLUSION: Domestic endotoxin was associated with reported airway and skin symptoms in this large group of New Zealand infants. The role of endotoxin in the development of respiratory and skin disease in infancy deserves further study. CLINICAL IMPLICATIONS: Reducing domestic endotoxin exposure might reduce infant wheezing and atopic dermatitis, but the long-term benefits of this remain unclear.

Anaphylaxis management: the essential role of adrenaline (epinephrine) auto-injectors. Should PHARMAC fund them in New Zealand?

Anaphylaxis is an important life-threatening medical emergency. There is extensive evidence supporting the early use of intramuscular adrenaline for first medical responders and for self-initiated treatment, in at-risk individuals. Major patient groups identified as at ongoing risk are children and adults with severe food allergy, patients with venom allergy who have not been desensitised, and those with idiopathic anaphylaxis. Individual anaphylactic events are largely unpredictable. The most effective and safe route of administration for adrenaline is intramuscular, but it is difficult for patients and carers to achieve accurate and timely self-administration using an ampoule, needle, and syringe. The adrenaline auto-injector device which is available in New Zealand (the EpiPen) is not funded by PHARMAC, and thus only available to patients and families who are able to afford the purchase cost. It is difficult to understand the continued unwillingness of PHARMAC to fund an adrenaline auto-injector device to at-risk individuals, given the large body of information supporting its efficacy and use. The Australian model, where authorisation from a relevant specialist is required, could be used.