Joshua Osowicki

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.

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.

Question 2: A pointed question: is a child at risk following a community-acquired needlestick injury?

You are asked to see a previously well 5-year-old boy who presented to the accident and emergency department. While playing in a public park he picked up a discarded 1 mL syringe with an attached 27-gauge needle and punctured the skin of his hand. His mother asks, “Will he catch AIDS? What should we do now?” In a child with a community-acquired needlestick injury (CA-NSI) (patient, intervention), what is the risk of blood-borne virus (BBV) transmission (outcome)? ### Introduction CA-NSI in children causes significant parental anxiety. The risk of HIV and hepatitis virus transmission following NSI in healthcare settings is well established. The risk of BBV transmission to a child from a CA-NSI is substantially less than from occupational exposure. Despite this, many clinical guidelines are based on occupational NSI. Medline was searched using the Ovid interface (1946 to present/no limits set) using MeSH subject headings: (*needlestick injuries/ or *needles/ or *syringes/) and (*blood-borne pathogens/ or (*hiv infections/ or *acquired immunodeficiency syndrome/ or *hiv seropositivity/) or (*hepatitis/ or *hepatitis, viral, human/ or *hepatitis b/ or *hepatitis c/) or (community.mp. or *community-acquired infections/ or *environmental exposure/)). No age limits were imposed for reported cases of BBV transmission from CA-NSI, on the basis that confirmed transmission at any age would support the theoretical possibility of transmission in children. Only papers addressing non-healthcare-related CA-NSI were included. Cross-sectional studies with no longitudinal follow-up and those reporting exclusively BBV transmission from injecting drug use were excluded. The search date was 11 May …

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.

Hospital-wide Rollout of Antimicrobial Stewardship: A Stepped-Wedge Randomized Trial

TO THE EDITOR—We commend Palmay et al on their large study of an antimicrobial stewardship program across 6 hospital departments, following its success in the intensive care unit (ICU) [1, 2]. Prospective audit and feedback is a wellvalidated stewardship intervention [3], and they measured a wide range of outcomes. While they showed reduced antimicrobial use in their target group, the authors highlight that there was no significant reduction in any key outcome measures when applied to all patients. We are concerned that the negative outcomes from this impressively resourced study could discourage efforts to institute stewardship programs in similar settings. The authors chose a stepped-wedged randomized design in response to a 2013 Cochrane review, which highlighted the lack of methodologically robust evidence in stewardship [4, 5]. Stepped-wedged trials are a form of crossover cluster randomized trial, a design identified as particularly susceptible to bias by the same review [4, 5]. Although randomization does control for allocation bias, the potential for bias at outcome assessment remains high; this is in contrast to the low risk of bias in, for example, interrupted time-series trials. The other methodological issue is the intervention itself. Patients receiving targeted antimicrobials on day 3 and day 10 of admission were selected for the intervention. These criteria would exclude many general medical and surgical patients who are likely to receive different antibiotics and be rapidly discharged. An intervention that targets all antibiotic usage on day 2 of admission would be more appropriate. Additionally, it is not clear whether the assessment of appropriateness of antibiotic therapy had the same criteria as in the ICU study and therefore whether this influenced the number of eligible patients. There are also issues with the choice of microbiological outcome measures. Clostridium difficile and resistant gramnegative pathogens are less clinically relevant outside the ICU, and, as acknowledged by the authors, the follow-up period was insufficient to detect changes. Potential shorter-term benefits including drug toxicity and catheter-related bloodstream infections were not measured. The acceptability of the intervention and reduction in days of therapy of targeted antimicrobials in eligible patients shows its efficacy in selected patient groups. However, it is not surprising that this benefit was not significant when applied to the whole study population. The stewardship team reviewed only 20% of all admitted patients; 47% of these had recommendations, of which 80% were accepted. Therefore, only 7.5% of admitted patients had a change in therapy resulting from the intervention. We appreciate that the extent of the intervention may have been limited by resource constraints. While reporting of negative results is important, we believe that the authors have potentially done their antimicrobial stewardship program a disservice through the inappropriate application of an ICU strategy to general wards. This study highlights the importance of tailoring antimicrobial stewardship interventions and outcomes to individual departments. Note

WHO/IVI global stakeholder consultation on group A Streptococcus vaccine development: Report from a meeting held on 12–13 December 2016

While progress towards a Group A Streptococcus (GAS) vaccine has been stalled by a combination of scientific, regulatory, and commercial barriers, the problem persists. The high and globally-distributed burden of disease attributable to GAS makes vaccination an imperative global public health goal. Advances across a range of scientific disciplines in understanding GAS diseases have made the goal a realistic one and focused attention on the need for coordinated global action. With a view to accelerating GAS vaccine development, the World Health Organization (WHO) and the International Vaccine Institute (IVI) convened a global stakeholder consultation on the 12th and 13th of December 2016, in Seoul, South Korea. Topics discussed included: (1) gaps in current knowledge of global GAS epidemiology, burden of disease, and molecular epidemiology; (2) contribution of pre-clinical models to candidate vaccine evaluation and new immunological assays to address GAS immunology knowledge gaps; (3) status and future of the GAS vaccine development pipeline; and (4) defining a pathway to licensure, policy recommendations and availability of a vaccine. The meeting determined to establish a GAS vaccine working group to coordinate preparation of a global vaccine values proposition, preferred product characteristics, and a technical research and development roadmap. A new global GAS vaccine consortium will drive strategic planning to anticipate requirements for licensure, prequalification, and policy recommendations.

Rheumatic fever: The rebound phenomenon returns: Rheumatic fever rebound phenomenon

Rheumatic fever: The rebound phenomenon returns Joshua Osowicki, Jeremy P Carr and Andrew C Steer Group A Streptococcus Research Group, Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Infectious Diseases Unit, Department of General Medicine, Royal Children’s Hospital Melbourne and Department of Paediatric Infection and Immunity, Monash Children’s Hospital, Melbourne, Victoria, Australia

Congenital Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis.

We present the case of a male infant with congenital tuberculosis in a nonendemic setting complicated by hemophagocytic lymphohistiocytosis, who was treated successfully with antituberculous therapy and corticosteroids. We review the pediatric literature concerning the unusual association of these 2 rare conditions.

International survey of paediatric infectious diseases consultants on the management of community-acquired pneumonia complicated by pleural empyema: Survey of antibiotics for empyema

Community‐acquired pneumonia (CAP) complicated by pleural empyema is an important paediatric problem. Antibiotic management decisions are made on the basis of little available data and without strong specific recommendations in guidelines.