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.

Describing the Impact of Maternal Hyperimmune Globulin and Valacyclovir on the Outcomes of Cytomegalovirus Infection in Pregnancy: A Systematic Review.

Cytomegalovirus (CMV) is the leading infectious cause of congenital neurological disabilities. Valacyclovir and CMV hyperimmune globulin (HIG) may reduce vertical transmission and sequelae in neonates. A systematic review on valacyclovir and CMV HIG in preventing vertical transmission or reducing sequelae in neonates was conducted to 3 September 2021. Valacyclovir as a preventive strategy was supported by a well-conducted randomized controlled trial. Evidence supporting valacyclovir as a treatment strategy was limited to observational studies at moderate risk of bias. CMV HIG was not supported as a preventive strategy in 2 randomized controlled trials, which contrasted with observational studies. Evidence favoring CMV HIG as a treatment strategy was limited to observational studies at moderate risk of bias. The role of valacyclovir and CMV HIG in CMV infection in pregnancy is still being defined. Valacyclovir to prevent vertical transmission has the highest quality evidence in favor of use.

Antifungal use in children with acute leukaemia: state of current evidence and directions for future research.

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.

Consensus guidelines for the diagnosis and management of cryptococcosis and rare yeast infections in the haematology/oncology setting, 2021.

Cryptococcosis caused by the Cryptococcus neoformans-Cryptococcus gattii complex is an important opportunistic infection in people with immunodeficiency, including in the haematology/oncology setting. This may manifest clinically as cryptococcal meningitis or pulmonary cryptococcosis, or be detected incidentally by cryptococcal antigenemia, a positive sputum culture or radiological imaging. Non-Candida, non-Cryptococcus spp. rare yeast fungaemia are increasingly common in this population. These consensus guidelines aim to provide clinicians working in the Australian and New Zealand haematology/oncology setting with clear guiding principles and practical recommendations for the management of cryptococcosis, while also highlighting important and emerging rare yeast infections and their recommended management.

Antifungal prescribing in neonates: Using national point prevalence survey data from Australia.

We describe contemporary antifungal use in neonates, with point-prevalence survey data from the National Antimicrobial Prescribing Survey across Australian hospitals from 2014 to 2018. There were 247 antifungal prescriptions in 243 neonates in 20 hospitals, median age six days (range 0-27 days). In 219/247 prescriptions (89%) antifungals were prescribed as prophylaxis. Topical (oral) nystatin was the most frequently prescribed in 233/247 prescriptions (94%), followed by fluconazole 11/227 (4%), with substantial variation in dosing for both. Two of 243 neonates (0.8%) had invasive fungal infection. Nystatin use dominates current antifungal prescribing for Australian neonates, in contrast to other countries, and invasive fungal infection is rare. LAY SUMMARY: Novel nationwide surveillance found newborn infants in Australian hospitals commonly receive antifungal medications, mostly oral nystatin. This is given mainly to prevent rather than treat infection, which is rare. There is substantial unexplained variation in dosing of antifungal drugs nationally.

Improving quality and efficiency of care for advanced appendicitis in children.

BACKGROUND: Complicated appendicitis encompasses a spectrum of severity with heterogeneity in definition and substantial variation in care. Enhanced recovery after surgery or 'fast-track' protocols aim to reduce practice variation by standardizing care. These initiatives may improve quality and efficiency of care, preserve resources and expedite discharge. This study aims to evaluate the impact of a standardized Enhanced Recovery Pathway (ERP) on the post-operative recovery of children with a subset of complicated appendicitis termed 'advanced' appendicitis. METHODS: We defined advanced appendicitis as gangrenous or suppurative appendicitis without perforation, contained iatrogenic perforation, or localized purulent fluid. Children with operative findings reflecting these criteria were enrolled in the ERP protocol. Key protocol components include early upgrade of diet, avoidance of intravenous analgesia, abridged intravenous antibiotics, early ambulation and standardized discharge criteria. The study period was May 2018 to June 2019. A historical cohort was used as the comparator group. RESULTS: Outcomes for 44 children treated under the ERP were compared to 44 historical controls. There was a 20% reduction in median post-operative length of stay (1.80 vs. 2.24 days, p = 0.02). Intravenous analgesia was received by fewer patients (6.8% vs. 36.4%, p = 0.01) with significant reduction in antiemetic requirement (p = 0.03). No significant difference in 30-day complication rates was observed. CONCLUSION: Reduced post-operative length of stay and reduction in practice variation were achieved after implementation of a 'fast-track' protocol for children with advanced appendicitis. Additional benefits of this protocol include reduced provision of intravenous morphine analgesia, decreased resource use and cost savings.

Antimicrobial stewardship capacity and manpower needs in the Asia Pacific.

OBJECTIVES: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. METHODS: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. RESULTS: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. CONCLUSION: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.

Antibiotic prescribing in neonatal sepsis: an Australian nationwide survey.

OBJECTIVE: To evaluate quality and variation in antibiotic prescribing for neonatal sepsis. DESIGN: We analysed prescribing in hospitalised neonates using the National Antimicrobial Prescribing Survey in Australian neonates from 1 January 2014 to 31 December 2018. SETTING: Data from antibiotic point prevalence surveys performed in hospitals, ranging from rural hospitals to tertiary paediatric and maternity hospitals within Australia. PATIENTS: Admitted neonates <28 days of age from participating hospitals. MAIN OUTCOME MEASURES: Variation and appropriateness in prescribing for neonatal sepsis and variation in dosing for gentamicin and benzylpenicillin across hospitals. RESULTS: A total of 415 prescriptions among 214 neonates from 39 different hospitals were included. The majority of prescriptions (342, 82.4%) were for neonates <7 days of age. The most commonly prescribed antibiotics were gentamicin and benzylpenicillin, with 323 (77.8%) prescriptions. Dosing variability was substantial, with doses ranging from 2 to 8 mg/kg for gentamicin (median 5 mg/kg, IQR 4-5) and from 45 to 72 mg/kg for benzylpenicillin (median 60 mg/kg, IQR 50-60), although only 13 (3.2%) and 19 (4.6%) prescriptions were locally assessed as inappropriate or non-compliant with guidelines, respectively. At time of audit, 22% of antibiotics had been given for more than 48 hours and 9% more than 72 hours, although microbiologically confirmed infection was documented in only nine (4.2%) neonates. CONCLUSIONS: Prescribing for neonatal sepsis was dominated by use of benzylpenicillin and gentamicin with substantial variation in dosing. A small minority had culture-confirmed infection. Efforts to standardise antibiotic dosing and duration for suspected neonatal sepsis are recommended.

Systematic Review of Kingella kingae Musculoskeletal Infection in Children: Epidemiology, Impact and Management Strategies.

Kingella kingae, a pathogen often responsible for musculoskeletal infections in children is the most common cause of septic arthritis and osteomyelitis in children 6 to 36 months of age. The aim of this study was to perform a systematic review of previous studies to determine the proportion of K. kingae in bacteriologically proven musculoskeletal infections among the pediatric population. A secondary objective was to describe the diagnostic strategies and outcome of patients with musculoskeletal infections caused by K. kingae. A systematic review was conducted to identify publications that report on musculoskeletal infections caused by K. kingae in the pediatric population (patients 0 to <18 years old with microbiologic culture and/or polymerase chain reaction (PCR) confirmation of K. kingae and a description of the musculoskeletal infection involved). Of 144 studies included in this review, we sought to determine the proportion of K. kingae pediatric musculoskeletal infections. A total of 711 (30.8%) out of 2308 pediatric cases with culture and/or PCR proven musculoskeletal infections had K. kingae successfully identified from twenty-nine studies. Of the 1070 patients who were aged less than 48 months, K. kingae was the organism identified in 47.6% of infections. We found the average age from the collated studies to be 17.73 months. Of 520 pediatric musculoskeletal patients in which K. kingae infections were identified and where the studies reported the sites of infection, a large proportion of cases (65%) were joint infections. This was followed by 18.4% osteoarticular infection (concomitant bone and joint involvement), with isolated bone and spine at 11.9% and 3.5%, respectively. Twenty-one papers reported clinical and laboratory findings in children with confirmed K. kingae infection. The median temperature reported at admission was 37.9°C and mean was 38.2°C. Fourteen studies reported on impact and treatment, with the majority of children experiencing good clinical outcome and function following antibiotic treatment with no serious orthopaedic sequelae.

Does screening for congenital cytomegalovirus at birth improve longer term hearing outcomes?

Currently, the diagnosis of congenital cytomegalovirus (cCMV) infection in most highly resourced countries is based on clinical suspicion alone. This means only a small proportion of cCMV infections are diagnosed. Identification, through either universal or targeted screening of asymptomatic newborns with cCMV, who would previously have gone undiagnosed, would allow for potential early treatment with antiviral therapy, ongoing audiological surveillance and early intervention if sensorineural hearing loss (SNHL) is identified. This paper systematically reviews published papers examining the potential benefits of targeted and universal screening for newborn infants with cCMV. We found that the treatment of these infants with antiviral therapy remains controversial, and clinical trials are currently underway to provide further answers. The potential benefit of earlier identification and intervention (eg, amplification and speech therapy) of children at risk of later-onset SNHL identified through universal screening is, however, clearer.

Fast-track surgery for uncomplicated appendicitis in children: a matched case-control study.

BACKGROUND: Standardized post-operative protocols reduce variation and enhance efficiency in patient care. Patients may benefit from these initiatives by improved quality of care. This matched case-control study investigates the effect of a multidisciplinary criteria-led discharge protocol for uncomplicated appendicitis in children. METHODS: Key protocol components included limiting post-operative antibiotics to two intravenous doses, avoidance of intravenous opioid analgesia, prompt resumption of diet, active encouragement of early ambulation and nursing staff autonomy to discharge patients that met assigned criteria. The study period was from August 2015 to February 2016. Outcomes were compared with a historical control group matched for operative approach. RESULTS: Outcomes for 83 patients enrolled to our protocol were compared with those of 83 controls. There was a 29.2% reduction in median post-operative length of stay in our protocol-based care group (19.6 versus 27.7 h; P < 0.001). The rate of discharges within 24 h improved from 12 to 42%. There was no significant difference in complication rate (4.8 versus 7.2%; P = 0.51). Mean oral morphine dose equivalent per kilogram requirement was less than half (46%) that of control group patients (P < 0.001). Mean number of ondansetron doses was also significantly lower. Projected annual direct cost savings following protocol implementation was AUD$77 057. CONCLUSION: Implementation of a criteria-led discharge protocol at our hospital decreased length of stay, reduced variation in care, preserved existing low morbidity, incurred substantial cost savings, and safely rationalized opioid and antiemetic medication. These protocols are inexpensive and offer tangible benefits that are accessible to all health care settings.

Epidemiology and Mortality of Staphylococcus aureus Bacteremia in Australian and New Zealand Children.

IMPORTANCE: Staphylococcus aureus bacteremia (SAB) in children causes significant morbidity and mortality, but the epidemiology in children is not well characterized. OBJECTIVE: To describe the epidemiology of SAB in children and adolescents younger than 18 years from Australia and New Zealand. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study, using data from the Australian New Zealand Cooperative on Outcomes in Staphylococcal Sepsis cohort for 1153 children with SAB from birth to less than 18 years in pediatric and general hospitals across Australia and New Zealand, collected between January 1, 2007, and December 31, 2012. Multivariate analysis was performed to identify risk factors for mortality. Incidence calculations were calculated separately for Australasian children younger than 15 years using postcode population denominator data from Australian and New Zealand census data. MAIN OUTCOMES AND MEASURES: Demographic data, hospital length of stay, principal diagnosis, place of SAB onset (community or hospital), antibiotic susceptibility and principal antibiotic treatment, and 7- and 30-day mortality. RESULTS: Of the 1153 children with SAB, complete outcome data were available for 1073 children (93.1%); of these, males accounted for 684 episodes (63.7%) of SAB. The median age was 57 months (interquartile range, 2 months to 12 years). The annual incidence of SAB for Australian children was 8.3 per 100 000 population and was higher in indigenous children (incident rate ratio, 3.0 [95% CI, 2.4-3.7]), and the incidence for New Zealand children was 14.4 per 100 000 population and was higher in Maori children (incident rate ratio, 5.4 [95% CI, 4.1-7.0]). Community-onset SAB occurred in 761 cases (70.9%), and 142 cases (13.2%) of the infections were methicillin-resistant S aureus (MRSA). Bone or joint infection was most common with 348 cases (32.4%), and endocarditis was uncommon with 30 cases (2.8%). Seven- and 30-day mortality rates were 2.6% (n = 28) and 4.7% (n = 50), respectively. Risk factors for mortality were age younger than 1 year; Maori or Pacific ethnicity; endocarditis, pneumonia, or sepsis; and receiving no treatment or treatment with vancomycin. Mortality was 14.0% (6 of 43) in children with methicillin-susceptible S aureus (MSSA) treated with vancomycin compared with 2.6% (22 of 851) in children treated with alternative agents (OR, 6.1 [95% CI, 1.9-16.7]). MRSA infection was associated with increased length of stay but not mortality. CONCLUSIONS AND RELEVANCE: In this large cohort study of the epidemiology of SAB in children, death was uncommon, but the incidence was higher for infants and varied by treatment, ethnicity, and clinical presentation. This study provides important information on the epidemiology of SAB in children and risk factors for mortality.

Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines.

Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research.

Lactobacillus Sepsis following a Laparotomy in a Preterm Infant: A Note of Caution.

Probiotics for preterm infants have been shown to reduce the incidence of necrotising enterocolitis and all-cause mortality in a recent meta-analysis. It has been argued, however, that some of these results may not be applicable to specific subgroups, e.g. infants with a birth weight of <1,000 g. The specific role of probiotics in improving health outcomes in preterm and term infants following intestinal surgery is not well defined. We report a case of a premature infant diagnosed with late-onset sepsis due to Lactobacillus rhamnosus following a laparotomy. We review pertinent published cases. This case highlights the importance of considering preterm infants as being at a higher risk of systemic probiotic infection following intestinal surgery.

Australia-wide Point Prevalence Survey of Antimicrobial Prescribing in Neonatal Units: How Much and How Good?

BACKGROUND: There is increasing recognition of the threat to neonatal patients from antibiotic resistance. There are limited data on antimicrobial prescribing practices for hospitalized neonates. We aimed to describe antimicrobial use in hospitalized Australian neonatal patients, and to determine its appropriateness. METHODS: Multicentre single-day hospital-wide point prevalence survey in 2012, in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. The appropriateness of antimicrobial prescriptions was also assessed. All patients admitted at 8 am on the survey day, in 6 neonatal units in tertiary children's hospitals across 5 states, were included in an analysis of the quantity and quality of all antimicrobial prescriptions. RESULTS: The point prevalence survey included 6 neonatal units and 236 patients. Of 109 patients (46%) receiving at least 1 antimicrobial, 66 (61%) were being treated for infection, with sepsis the most common indication. There were 216 antimicrobial prescriptions, 134 (62%) for treatment of infection and 82 (38%) for prophylaxis, mostly oral nystatin. Only 15 prescriptions were for targeted as opposed to empirical treatment. Penicillin and gentamicin were the most commonly prescribed antibiotics, with vancomycin third most common. Half of all treated patients were receiving combination antimicrobial therapy. There was marked variation in vancomycin and gentamicin dosing. Overall, few prescriptions (4%) were deemed inappropriate. CONCLUSION: This is the first Australia-wide point prevalence survey of neonatal antimicrobial prescribing in tertiary children's hospitals. The findings highlight positive practices and potential targets for quality improvement.

Corrigendum to 'Disseminated mucormycosis in a paediatric patient: Lictheimia corymbifera successfully treated with combination antifungal therapy' [Medical Mycology Case Reports (2014) 18-21].

[This corrects the article DOI: 10.1016/j.mmcr.2014.08.002.].

Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital.

OBJECTIVES: To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use. DESIGN: Multicentre single-day hospital-wide point prevalence survey, conducted in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. SETTING: Eight children's hospitals across five Australian states, surveyed during late spring and early summer 2012. PATIENTS: Children and adolescents who were inpatients at 8 am on the day of the survey. MAIN OUTCOME MEASURES: Quantity and quality of antimicrobial prescribing. RESULTS: Of 1373 patients, 631 (46%) were prescribed at least one antimicrobial agent, 198 (31%) of whom were < 1 year old. The highest antimicrobial prescribing rates were in haematology and oncology wards (76% [95/125]) and paediatric intensive care units (55% [44/80]). Of 1174 antimicrobial prescriptions, 550 (47%) were for community-acquired infections, 175 (15%) were for hospital-acquired infections and 437 (37%) were for prophylaxis. Empirical treatment accounted for 72% of antimicrobial prescriptions for community-acquired infections and 58% for hospital-acquired infections (395 and 102 prescriptions, respectively). A total of 915 prescriptions (78%) were for antibacterials; antifungals and antivirals were predominantly used for prophylaxis. The most commonly prescribed antibacterials were narrow-spectrum penicillins (18% [164 prescriptions]), ß-lactam-ß-lactamase inhibitor combinations (15% [136]) and aminoglycosides (14% [128]). Overall, 957 prescriptions (82%) were deemed appropriate, but this varied between hospitals (range, 66% [74/112]) to 95% [165/174]) and specialties (range, 65% [122/187] to 94% [204/217]). Among surgical patients, 65 of 187 antimicrobial prescriptions (35%) were deemed inappropriate, and a common reason for this was excessive prophylaxis duration. CONCLUSION: A point prevalence survey is a useful cross-sectional method for quantifying antimicrobial use in paediatric populations. The value is significantly augmented by adding assessment of prescribing quality.

Disseminated mucormycosis in a paediatric patient: Lichthemia corymbifera successfully treated with combination antifungal therapy.

Mucormycosis is a severe fungal infection that largely affects immunocompromised individuals. It carries a high morbidity and mortality rate and is characterised by extensive angioinvasion and necrosis of host tissue. This case report details success in treating disseminated mucormycosis in a paediatric patient with an underlying haematological malignancy. Treatment included institution of combination antifungal therapy with liposomal amphotericin B and caspofungin, aggressive surgical debridement of infected tissue and reversal of underlying immunosuppression.