A multicentre, retrospective audit of fosfomycin use for urinary tract infections in Australian children and adolescents.

BACKGROUND: Urinary tract infections (UTIs) due to MDR organisms are increasingly common. The lack of paediatric data on efficacious antibiotics makes UTI treatment particularly challenging. Data on the efficacy of fosfomycin use for UTI in children are variable. METHODS: We conducted a retrospective audit of children aged 0-18 years who were treated with fosfomycin for UTI at seven tertiary paediatric hospitals in Australia over a 7 year period, from 2014 to 2020. RESULTS: Ninety-one children with a median age of 5 years (range 2 months to 18 years) received oral fosfomycin for UTI. The majority (57/91, 63%) had one or more comorbidity, with the most common being renal tract anomalies (24/91, 26%). Fifty-nine (65%) had febrile UTI, 14/91 (15%) had pyelonephritis and 1/91 (1%) was bacteraemic. A majority (80/91, 88%) of urinary cultures had an ESBL-producing Gram-negative pathogen isolated. Fosfomycin susceptibility was evident in all 80 isolates tested. For uncomplicated UTI, the most common dose in children aged <1, 1-12 and >12 years was 1, 2 and 3 g, respectively. For complicated UTI, doses of 2 and 3 g were most common. The median duration of fosfomycin administration was 5 days (range 1-82). Clinical cure was achieved in 84/90 (93%); the six with treatment failure had underlying comorbidities. Overall, 2/91 (2%) children experienced drug-related adverse effects comprising gastrointestinal symptoms in both, which resolved after treatment discontinuation. CONCLUSIONS: Fosfomycin is well tolerated and associated with favourable treatment outcomes in children with UTI. Further research on the optimal dosing strategy is required.

Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme.

OBJECTIVE: Serogroup W and Y invasive meningococcal disease increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) invasive meningococcal disease, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, the vaccine coverage in the eligible school cohorts aged 14 to 19 years was 84%. We assessed the impact of the MenACWY vaccination programme on meningococcal carriage. METHODS: An observational study of culture-defined oropharyngeal meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme in UK school students, aged 15 to 19 years, using two cross-sectional studies: 2014 to 2015 "UKMenCar4" and 2018 "Be on the TEAM" (ISRCTN75858406). RESULTS: A total of 10 625 participants preimplementation and 13 438 postimplementation were included. Carriage of genogroups C, W, and Y (combined) decreased from 2.03 to 0.71% (OR 0.34 [95% CI 0.27-0.44], p < 0.001). Carriage of genogroup B meningococci did not change (1.26% vs 1.23% [95% CI 0.77-1.22], p = 0.80) and genogroup C remained rare (n = 7/10 625 vs 17/13 438, p = 0.135). The proportion of serogroup positive isolates (i.e. those expressing capsule) decreased for genogroup W by 53.8% (95% CI -5.0 - 79.8, p = 0.016) and for genogroup Y by 30.1% (95% CI 8.946·3, p = 0.0025). DISCUSSION: The UK MenACWY vaccination programme reduced carriage acquisition of genogroup and serogroup Y and W meningococci and sustained low levels of genogroup C carriage. These data support the use of quadrivalent MenACWY conjugate vaccine for indirect (herd) protection.

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.