Celia Cooper

The Antibiotic Resistance and Prescribing in European Children Project: A Neonatal and Pediatric Antimicrobial Web-based Point Prevalence Survey in 73 Hospitals Worldwide

Background: The neonatal and pediatric antimicrobial point prevalence survey (PPS) of the Antibiotic Resistance and Prescribing in European Children project (http://www.arpecproject.eu/) aims to standardize a method for surveillance of antimicrobial use in children and neonates admitted to the hospital within Europe. This article describes the audit criteria used and reports overall country-specific proportions of antimicrobial use. An analytical review presents methodologies on antimicrobial use. Methods: A 1-day PPS on antimicrobial use in hospitalized children was organized in September 2011, using a previously validated and standardized method. The survey included all inpatient pediatric and neonatal beds and identified all children receiving an antimicrobial treatment on the day of survey. Mandatory data were age, gender, (birth) weight, underlying diagnosis, antimicrobial agent, dose and indication for treatment. Data were entered through a web-based system for data-entry and reporting, based on the WebPPS program developed for the European Surveillance of Antimicrobial Consumption project. Results: There were 2760 and 1565 pediatric versus 1154 and 589 neonatal inpatients reported among 50 European (n = 14 countries) and 23 non-European hospitals (n = 9 countries), respectively. Overall, antibiotic pediatric and neonatal use was significantly higher in non-European (43.8%; 95% confidence interval [CI]: 41.3–46.3% and 39.4%; 95% CI: 35.5–43.4%) compared with that in European hospitals (35.4; 95% CI: 33.6–37.2% and 21.8%; 95% CI: 19.4–24.2%). Proportions of antibiotic use were highest in hematology/oncology wards (61.3%; 95% CI: 56.2–66.4%) and pediatric intensive care units (55.8%; 95% CI: 50.3–61.3%). Conclusions: An Antibiotic Resistance and Prescribing in European Children standardized web-based method for a 1-day PPS was successfully developed and conducted in 73 hospitals worldwide. It offers a simple, feasible and sustainable way of data collection that can be used globally.

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy, 2014

Antifungal agents may be associated with significant toxicity or drug interactions leading to sub‐therapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy. These risks may be minimised by clinical assessment, laboratory monitoring, avoidance of particular drug combinations and dose modification. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre‐hydration and electrolyte supplementation may also be required. Therapeutic drug monitoring (TDM) of antifungal agents is warranted, especially where non‐compliance, non‐linear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Recommended indications for voriconazole and posaconazole TDM in the clinical management of haematology patients are provided. With emerging knowledge regarding the impact of pharmacogenomics upon metabolism of azole agents (particularly voriconazole), potential applications of pharmacogenomic evaluation to clinical practice are proposed.

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.

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 Māori 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; Māori 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.

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.

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.

Successful treatment of disseminated mucormycosis in a neutropenic patient with T-cell acute lymphoblastic leukaemia

Mucormycosis is a rare angioinvasive fungal infection, more commonly seen in immunosuppressed patients, with reported mortality rates of 95% in disseminated disease. We present a case report of a patient with T-cell acute lymphoblastic leukaemia who developed disseminated infection with mucormycosis (involving the pancreas, left occipital lobe, right lower lobe of lung, appendix and right kidney) after having completed induction and consolidation chemotherapy. Growth of Lichtheimia corymbifera was initially isolated following a right pleural tap with fungal elements identified repeatedly on subsequent pathology specimens. Following radical surgical debridement and concurrent treatment with combination antifungal therapy, the patient survived. This case demonstrates that aggressive multisite surgical de-bulking of disseminated fungal foci, in conjunction with combination antifungal therapy and reversal of immunosuppression, can result in survival despite the grave prognosis associated with disseminated mucormycosis.

The impact of an infectious diseases consultation on antimicrobial prescribing.

Hagerstown, MD XXX The Impact of an Infectious Diseases Consultation on Antimicrobial Prescribing for severe mastitis and breast abscess. The infant was started on clindamycin and gentamicin. She became febrile to 100.5°F and was transferred to our institution for further evaluation and management. On examination, the child was afebrile and nontoxic appearing. She was tachypneic but comfortable with no signs of respiratory distress. A 4 cm × 2 cm firm, nonmobile mass overlying the right lateral 9th and 10th ribs extending to the back was noted. The mass appeared to be tender to palpation but had no associated erythema or crepitus. Notably, auscultation of the lungs revealed decreased breath sounds over the right middle and lower lobes. Laboratory data at the time of transfer revealed a white blood cell count of 27,310/μL with 39% segmented neutrophils and 9% bands. Platelets were elevated at 770,000/μL. Chest radiograph demonstrated a right lower lobe chest mass with associated medial right 10th rib destruction. A noncontrast chest computed tomography showed a large loculated fluid density in the right hemithorax abutting and inseparable from the pleura, with adjacent osteolytic changes in the posterior right 10th rib and soft tissue thickening of the posterior chest wall. The neonate was admitted for further management and started on empiric antimicrobial therapy with clindamycin, gentamicin and ampicillin. Gentamicin was discontinued in the first 12 hours of admission in favor of cefotaxime. A contrast computed tomography of the chest mass was performed in consideration of potential surgical intervention. This study demonstrated a large, peripherally enhancing fluid collection centered within the right hemithorax consistent with empyema necessitatis. Extension and abscess formation in the posterolateral right chest wall was seen accompanied by osseous involvement of the posterolateral right 9th, 10th and 11th ribs. The patient underwent fluoroscopy-guided percutaneous drainage with pigtail catheter placement, resulting in the removal of 20 mL of purulent fluid. Gram stain of the fluid demonstrated many white blood cells and many Gram-positive cocci in clusters, and cultures grew MRSA. At that time, it was relayed to the medical team that the patient’s mother had undergone incision and drainage of a breast abscess at the outlying hospital with cultures also demonstrating MRSA. Ampicillin and cefotaxime were discontinued, and clindamycin was continued pending susceptibility testing. Culture results confirmed clindamycin-susceptible MRSA. The infant remained stable in the postoperative period. A repeat chest radiograph on the day of catheter removal revealed considerable improvement in aeration of the right lung. After receiving a total of 4 weeks of intravenous clindamycin, the patient was discharged home on oral clindamycin to complete an additional 4 weeks of therapy. DNA fragment analysis via pulsed-field gel electrophoresis was performed on both the mother’s and the patient’s isolates. The strain was confirmed as USA300, and the isolates from mother and infant were identical by this analysis. Telephone follow up with the family after treatment completion revealed that the patient was growing well and thriving, without any untoward side effects from prolonged antimicrobial therapy. Despite the relatively widespread incidence of invasive infection secondary to CA-MRSA, there are only 3 reported cases of CA-MRSA associated empyema necessitatis documented in the pediatric literature and none involving neonates. None of these prior cases identified breast-feeding or maternal breast abscess as potential routes of acquisition. The diagnosis of empyema necessitatis requires tomographic imaging to visualize the pathognomonic changes of a pleural effusion connected to the chest wall mass. Treatment of this condition requires a combination of antimicrobial therapy targeted at the most likely causative agent(s) in conjunction with prompt surgical drainage. The optimal duration of antibiotic therapy for empyema necessitatis and associated osteomyelitis in a patient who has undergone surgical drainage is not established. We recommended a total of 8 weeks therapy given the age of the patient and the invasive nature of the infection, including contiguous osteomyelitis.

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

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.

Disseminated mucormycosis in a paediatric patient: Lichtheimia 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.