Mediastinal Nontuberculous Mycobacterial Infection in Children: A Multidisciplinary Approach.

BACKGROUND: Mediastinal infections due to nontuberculous mycobacteria remain an exceedingly rare entity. Most cases in the published literature do not include pediatric patients. Due to their clinical infrequency, poor response to antimicrobial therapy and often precarious anatomical location, the optimal management of these lesions can be challenging. METHODS: Retrospective medical record review of 4 pediatric cases of mediastinal nontuberculous mycobacteria infection was undertaken. Each child presented with nonspecific respiratory symptoms, including significant acute airway obstruction and required a range of investigations to confirm the diagnosis. Nonresponsiveness to conservative measures and antimycobacterial therapy ultimately resulted in surgical intervention to obtain clinical improvement. RESULTS: All 4 children had extensive evaluation and multidisciplinary involvement in otolaryngology, respiratory medicine, pediatric surgery, infectious diseases and cardiothoracic surgery. They all eventually had their disease debulked via thoracotomy in addition to prolonged antimycobacterial therapy, with successful clinical outcomes. CONCLUSIONS: Mediastinal nontuberculous mycobacteria infections in the pediatric population are rare and diagnostically challenging. A high clinical suspicion should be maintained, and multidisciplinary input sought. Targeted surgery with adjuvant medical therapy can reduce disease burden with minimal long-term morbidity.

Postnatal Cytomegalovirus Infection: Is it Important? A 10-Year Retrospective Case-control Study of Characteristics and Outcomes in Very Preterm and Very Low Birth Weight Infants.

BACKGROUND: To determine the characteristics and outcomes of postnatal cytomegalovirus (pCMV) infection in preterm infants in a neonatal intensive care unit (NICU). METHODS: A retrospective, matched case-control study in a tertiary NICU. Infants born between January 2009 and December 2019, <32 weeks' gestational age (GA) and/or birth weight (BW) <1500 g with pCMV infection were matched 1:1 with cytomegalovirus-(CMV)-negative infants by year of admission, gender, GA and BW. Primary outcome was death ≤36 weeks' postmenstrual age or bronchopulmonary dysplasia (BPD). Secondary outcomes were length of ventilation (LOV), length of stay (LOS) and neurodevelopmental impairment (NDI) at corrected age 1 and 2 years. RESULTS: Forty-eight pCMV-positive infants (median GA 25.3 weeks, BW 695 g, age 58 days) were identified from 1659 infants (incidence 2.9%). The most common symptoms of pCMV infection were abdominal distension (43.8%), sepsis-like syndrome (29.2%), thrombocytopenia (60.5%) and conjugated hyperbilirubinemia (60.9%). Compared with controls, there were no significant differences in the composite outcome of death or BPD (56.3% vs. 37.5%; P = 0.1) or NDI at 1 and 2 years (51.9% vs. 44%; P = 0.8; 71.4% vs. 50%; P = 0.4). pCMV-positive infants had a significantly longer median LOV (23.5 vs. 12 days)* and LOS (140 vs. 110.5 days)*. Eleven (22.9%) infants received antivirals. Ten improved and 1 died. Two untreated infants died (1 from pCMV infection). CONCLUSIONS: Clinically identifiable pCMV infections are significant and associated with increased respiratory support and prolonged hospital stay in vulnerable infants. pCMV screening and preventive measures against transmission merit consideration.*P < 0.05.

Adherence to surgical antibiotic prophylaxis guidelines in children: A cohort study.

AIMS: Surgical antimicrobial prophylaxis (SAP) is an important measure to reduce post-operative infections. Guidelines exist, but their efficacy and performance in children is poorly understood compared with adults. To review adherence to SAP guidelines, this study assesses risk factors for non-adherence and rate of early post-surgical infections. METHODS: A retrospective cohort study of paediatric surgical cases (0-<18 years) at a tertiary children's hospital was performed. Patient characteristics, surgical factors and antimicrobial details were evaluated against hospital guidelines for overall adherence and domains of: antimicrobial choice, dose, re-dosing, timing and duration. Multiple regression analysis was used to determine risk factors for non-adherence. Hospital records were reviewed for post-operative infections at 7 and 30 days. RESULTS: Among 326 cases, overall guideline adherence was 39.6% but varied by domain and surgical subspecialty. Incorrect wound classification was associated with overall non-adherence on multivariate regression (odds ratio (OR): 2.59; P < 0.001). Incorrect antimicrobial choice was more likely in children with penicillin hypersensitivity (OR 138.34, P = 0.004) and incorrect dosing more likely in adolescent patients (OR 4.33; P = 0.004). Presence of invasive devices was associated with prolonged duration of antimicrobials (OR 2.92, P = 0.016). Only two post-operative infections were documented by 30 days, but data were insufficient to exclude mild infections managed in the community. CONCLUSIONS: SAP was suboptimal in children, with areas for improvement including better guidance on wound classification, allergy management and care for adolescent patients. Documented infections were rare, but mild infections were unable to be excluded due to limited post-discharge information.

Management and prevention of cytomegalovirus infection in paediatric hematopoietic stem cell transplant (HSCT) recipients: A binational survey.

CMV infection is an important cause of morbidity and mortality among HSCT recipients. Optimal strategies for prevention and management of CMV disease following haematopoietic stem cell transplantation remain uncertain. We conducted an online survey of Australasian paediatric allogeneic HSCT centres on management and prevention of CMV disease in this patient group. We asked for one response from a representative of the HSCT team and one from a representative of the ID team at each centre. All Australasian paediatric HSCT centres responded to our survey. Management of CMV in pre-transplant setting was consistent between centres. All centres used a pre-emptive strategy to prevent CMV disease, guided by quantitative CMV PCR. In the post-transplant post engraftment setting, all centres recommended using ganciclovir (5mg/kg/dose twice daily) as a first-line therapy for CMV reactivation or disease, with treatment duration of 14 days, provided declining CMV quantitative PCR. There was substantial variability of practice between centres in post-transplant management of CMV reactivation, especially during the pre-engraftment phase. Similarly, there was lack of uniformity in indication, dosing and duration of maintenance therapy. Divergence was noted between responses from HSCT and ID physicians within centres. This study identifies areas of uniformity and others of great variability in prevention and management strategies for CMV in paediatric HSCT. Data on CMV infection and management in HSCT patients should be routinely collected as part of prospective trials to inform guidelines and improve prevention and treatment of this important complication.

Neonatal Cytomegalovirus Palatal Ulceration and Bocavirus Pneumonitis Associated With a Defect of Lymphocyte Cytotoxicity Caused by Mutations in UNC13D.

Single gene defects that impair lymphocyte cytotoxicity can predispose to severe viral infection that normally remains subclinical. The classic severe presentation is hemophagocytic lymphohistiocytosis. Here, we report the case of a neonate who presented with cytomegalovirus palatal ulceration and bocavirus pneumonitis secondary to impaired cytotoxicity caused by biallelic mutations in the UNC13D gene.

Cryptococcal infections in children: retrospective study and review from Australia.

Aim: Cryptococcosis causes significant morbidity and mortality worldwide, but pediatric data are limited. Methods: A retrospective literature review of Australian pediatric cryptococcosis and additional 10-year audit of cases from a large pediatric network. Results: 22 cases of cryptococcosis in children were identified via literature review: median age was 13.5 years (IQR 7.8-16 years), 18/22 (82%) had meningitis or central nervous system infection. Where outcome was reported, 11/18 (61%) died. Of six audit cases identified from 2008 to 2017, 5 (83%) had C. gattii disease and survived. One child with acute lymphoblastic leukemia and C. neoformans infection died. For survivors, persisting respiratory or neurological sequelae were reported in 4/6 cases (67%). Conclusion: Cryptococcosis is uncommon in Australian children, but is associated with substantial morbidity.

Screening and Primary Care Access for Newly Arrived Paediatric Refugees in Regional Australia: A 5 year Cross-sectional Analysis (2007-12).

Aim: This study aimed to determine the prevalence of health conditions in newly arrived refugee children and access to timely heath screening. Methods: Cross-sectional data from screening of refugee children in regional Australia (2007-12) were analysed for health conditions and timeliness of primary care access. The health of 376 newly arrived refugee children (0-15 years) was assessed. Refugee children came from African (45%), Southeast Asian (29%) and Eastern Mediterranean (10%) regions. Access to primary care screening was present in 367 children (97% of arrivals). Completion of all recommended screening tests was 72%. Of 188 children with arrival and screening dates recorded, 88% were screened within 1 month and 96% within 6 months of arrival. Timely access of remaining children could not be assessed. Conclusion: Primary care was highly accessible to almost all newly arrived refugee children. Health screening was timely in those children with complete medical records.

A Pilot Study of a Computerized Decision Support System to Detect Invasive Fungal Infection in Pediatric Hematology/Oncology Patients.

OBJECTIVE: Computerized decision support systems (CDSSs) can provide indication-specific antimicrobial recommendations and approvals as part of hospital antimicrobial stewardship (AMS) programs. The aim of this study was to assess the performance of a CDSS for surveillance of invasive fungal infections (IFIs) in an inpatient hematology/oncology cohort. METHODS: Between November 1, 2012, and October 31, 2013, pediatric hematology/oncology inpatients diagnosed with an IFI were identified through an audit of the CDSS and confirmed by medical record review. The results were compared to hospital diagnostic-related group (DRG) coding for IFI throughout the same period. RESULTS: A total of 83 patients were prescribed systemic antifungals according to the CDSS for the 12-month period. The CDSS correctly identified 19 patients with IFI on medical record review, compared with 10 patients identified by DRG coding, of whom 9 were confirmed to have IFI on medical record review. CONCLUSIONS: CDSS was superior to diagnostic coding in detecting IFI in an inpatient pediatric hematology/oncology cohort. The functionality of CDSS lends itself to inpatient infectious diseases surveillance but depends on prescriber adherence.

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.

Congenital cytomegalovirus--time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification.

OBJECTIVES: To report on the burden of disease in Australian infants with congenital cytomegalovirus (cCMV) infection in the era of neonatal hearing screening and improved diagnostic techniques. DESIGN, SETTING AND PARTICIPANTS: National data were collected from across Australia via the Australian Paediatric Surveillance Unit (APSU) with monthly reporting by > 1000 clinicians between January 1999 and February 2009. For each reported case, data on investigations and epidemiological and clinical features were analysed. Detailed clinical reviews were performed on 42 infants in two Sydney tertiary paediatric infectious diseases clinics. RESULTS: There were 195 infants with cCMV identified, including 126 definite and 69 probable cases. Of these, 175 (90%) were symptomatic and only 15 were treated with antiviral agents. Identification was delayed beyond 60 days of age in 30 cases (15%). During the period of study, neonatal hearing screening was introduced for most Australian infants. Detection of hearing loss increased from 19% of cCMV cases in 1999-2003 to 31% in 2004-2009. Of 42 infants whose cases were reviewed in detail, 33 (79%) had symptomatic disease. DNA detection of CMV, using polymerase chain reaction testing of newborn screening cards, was useful in retrospective identification, and was strongly correlated with the presence of clinical sequelae (15/18; 83%). CONCLUSIONS: Congenital CMV is underdiagnosed, infrequently treated, and often manifests as isolated hearing loss. Delayed diagnoses both before and after the introduction of neonatal hearing screening represent missed treatment and management opportunities and are likely to lead to poorer, life-long outcomes for these children. Retrospective analysis of newborn screening cards for CMV should be undertaken for infants with sensorineural hearing loss, to identify unrecognised cCMV.

Once-daily gentamicin in infants and children: a prospective cohort study evaluating safety and the role of therapeutic drug monitoring in minimizing toxicity.

BACKGROUND: The clinical evidence base for ototoxicity and nephrotoxicity outcomes with once-daily dosing (ODD) of gentamicin in children is suboptimal. Therapeutic drug monitoring (TDM) in once-daily gentamicin regimens is variable and its role in predicting or preventing clinical toxicity is unclear. We aimed to assess the safety of ODD of gentamicin and the usefulness of TDM in a pediatric cohort. METHODS: Children with suspected sepsis were prospectively enrolled to receive ODD of gentamicin at 7 mg/kg/day. Hearing and renal function were objectively assessed at baseline, during therapy, and after therapy. TDM was performed using an interval-adjusted graphical method (Hartford nomogram). RESULTS: A total of 79 children (median age: 5.6 years; range: 1 month-16 years) received 106 episodes of therapy. In all, 61% of these episodes were for febrile neutropenia. Evaluation was complete in 88% for ototoxicity and 92% for nephrotoxicity. Two patients (1.88%, 95% confidence interval: 0.10%-7.13%) experienced permanent hearing loss. One patient (0.94%, 95% confidence interval: <0.10%-5.73%) experienced transient nephrotoxicity. No abnormal serum gentamicin values were detected, even in those experiencing toxicity. Children experiencing toxicity were undergoing treatment for malignancies and had received nephrotoxic or ototoxic medicines before gentamicin. CONCLUSIONS: In this pediatric cohort receiving ODD of gentamicin, nephrotoxicity was uncommon and reversible, but irreversible ototoxicity occurred more frequently. TDM using a nomogram neither predicted nor prevented toxicity, which was only observed in those with risk factors.

Nontuberculous mycobacterial infection in children: a prospective national study.

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

Pertussis prevention and treatment: a call for wider access to azithromycin.

Azithromycin is recommended as the first-line antibiotic for the prophylaxis and treatment of pertussis, a common vaccine-preventable communicable disease. Azithromycin is better tolerated than other macrolide antibiotics. Access to azithromycin is limited, as the product information and the Pharmaceutical Benefits Scheme do not include azithromycin for pertussis. Issues regarding access to azithromycin are highlighted in a case report of pertussis exposure in a tertiary paediatric hospital.