The use of whole body diffusion-weighted post-mortem magnetic resonance imaging in timing of perinatal deaths.

OBJECTIVES: Diffusion-weighted MRI provides information regarding body water movement following death, which may be an imaging marker of post-mortem interval (time since death; PMI) or maceration (degree of tissue degradation during intra-uterine retention) in perinatal deaths. Our aim was to evaluate the relationship between maceration, PMI and body organ apparent diffusion coefficient (ADC) values in a cohort of subjects across a wide gestational range. MATERIALS: Whole body post-mortem MRI with diffusion-weighted imaging (DWI) sequences were performed at 1.5 T, with b values of 0, 500 and 1000 mm2/s. Mean ADC values were calculated from regions of interest (ROIs) placed in the lungs, myocardium, spleen, renal cortex, liver and psoas muscle by two independent readers. Multivariable regression analysis was performed against PMI, gestational age, post-mortem weight, maceration score and gender. RESULTS: Eighty perinatal deaths were imaged with mean gestational age of 32 weeks (18-41 weeks), of which 49 (61.3%) were male. The mean PMI was 8 days (1-18 days). Maceration scores were statistically significant predictive factors for ADC values in all included body organs except the lungs, but PMI was not a predictor for ADC values in any body organ. In the absence of maceration (n = 14), PMI was not statistically associated with ADC values in any of the body areas. The ratio of agreement in the majority of body areas was close to 1 (range between 0.95 and 1.10). CONCLUSION: Maceration, not PMI, is significantly associated with ADC values in perinatal deaths. Further research is needed to understand organ-specific changes in the post-mortem period.

Multifaceted intervention to optimize antibiotic use for intra-abdominal infections.

OBJECTIVES: Implementing evidence-based practice guidelines is challenging. We used a multifaceted, continuous educational approach to disseminate an up-to-date internal guideline adapted from published guidelines for management of intra-abdominal infections (IAI). PATIENTS AND METHODS: The intervention consisted of continuing educational sessions, internal guideline pocket cards and posters with collaboration among all key stakeholders starting in December 2010. We emphasized risk stratification and the use of ceftriaxone/metronidazole for treatment of low-risk IAI, and discouraged the use of fluoroquinolones due to the high local resistance rates. We then compared patients with IAI before the intervention (April-November 2010) to those after implementation of the guideline (April-November 2011) in a surgical unit at a tertiary care teaching hospital in Hamilton, Ontario, Canada. Antibiotic use was measured in in-hospital days of antibiotic therapy (DOT) per 1000 patient days (PD). RESULTS: 152 and 145 patients with IAI were included in the pre- and post-intervention periods, respectively. There was a significant reduction in the proportion of patients who received ciprofloxacin therapy from 74% to 34% (OR 0.18, 95% CI 0.11-0.31) and in DOT/1000 PD from 221 to 74 (OR 0.3, 95% CI 0.2-0.3). Also, a reduction in the DOT/1000 PD for piperacillin/tazobactam was seen (from 116 to 67; OR 0.6, 95% CI 0.5-0.7). There was an increase in the use of ceftriaxone from 1.3% to 53% of patients (OR 85, 95% CI 20-515) and from 6 to 92 DOT/1000 PD (OR 17, 95% CI 10-25). This change in practice was sustained over >2 years since the end of the active intervention, as shown in the unit-wide antimicrobial utilization data. CONCLUSIONS: A multifaceted intervention aimed at all key stakeholders resulted in a high adherence to evidence-based treatment guidelines for IAI and has initiated a sustained culture change in prescribing of antibiotics.

Management and outcomes in patients with Staphylococcus aureus bacteremia after implementation of mandatory infectious diseases consult: a before/after study.

BACKGROUND: Infectious disease (ID) consultations have been shown to increase adherence to guidelines and decrease mortality for patients with Staphylococcus aureus bacteremia (SAB). Here, we assessed the impact of a mandatory ID consultation policy for SAB. METHODS: We retrospectively reviewed all consecutive adult patients with SAB at two tertiary care teaching hospitals in Hamilton, ON, Canada. Mandatory ID consults for SAB were implemented on January 1(st) 2012. We compared SAB cases in 2011 (control group) with those in 2012 (intervention group). Outcomes included adherence to the Infectious Diseases Society of America guidelines and patient outcomes. RESULTS: We reviewed 128 SAB cases in 2011 and 124 in 2012. The majority of S. aureus were methicillin-susceptible (97/128, 75.8 % in 2011 and 100/124, 80.6 % in 2012). ID involvement increased significantly from 93/128 (72.7 %) in 2011, to 103/124 (83.1 %) in 2012 (odds ratio [OR] 1.9, 95 % confidence interval [CI] 1.1-3.3, p = 0.047). There was also a significant decrease in the median time to ID involvement from 2 days to 1 (p = 0.001). In patients who survived the minimum treatment course (greater than 13 days), there was a significant improvement in adherence to IDSA guidelines in 2012 (65/102, 63.7 % vs. 77/96, 80.2 %; OR 2.3, 95 % CI 1.2-4.4, p = 0.01). Mortality and SAB relapse rates were similar in both groups. CONCLUSIONS: Creating an automated ID consultation for SAB led to an increase in involvement of ID, a significant decrease in time to ID involvement, and better adherence to IDSA guidelines. The study was not sufficiently powered to detect significant changes in mortality and SAB relapse rates.

Self-disinfecting sink drains reduce the Pseudomonas aeruginosa bioburden in a neonatal intensive care unit.

AIM: Water in sink drains is a known source of gram-negative bacteria. We aimed to evaluate the impact of self-disinfecting sink drains on the emission of aerosolised bacteria and on Pseudomonas aeruginosa acquisition among neonates. METHODS: Aerosol bacterial growth and patient Pseudomonas aeruginosa acquisition rates were measured at baseline (Phase One), for 13 months after sinks were relocated or redesigned during refurbishment (Phase Two) and for 13 months after introducing self-disinfecting sink drains (Phase Three). RESULTS: Cultures were positive for bacterial growth in 56%, 24% and 13% of the tested aerosols in Phases One, Two and Three, respectively. Comparing Phases Two and Three produced an odds ratio (OR) of 0.47, with a 95% confidence interval (CI) of 0.22-0.99 (p = 0.047), for all bacteria and an OR of 0.31 and CI of 0.12-0.79 (p = 0.013) for Pseudomonas aeruginosa. Rates of Pseudomonas aeruginosa positive clinical cultures were 0.34, 0.27 and 0.13 per 1000 patient days during the respective phases, with a significant increase of time to the next positive clinical culture in Phase Three. CONCLUSION: Self-disinfecting sink drains were superior to sink replacements in preventing emissions from aerosols pathogens and may reduce hospital-acquired infections. The bioburden reduction should be confirmed in a larger multicentre trial.

A brief report of West Nile Virus neuroinvasive disease in the summer of 2012 in Hamilton, Ontario.

West Nile neuroinvasive disease is a severe infectious disease that is associated with a high mortality rate, especially in immunocompromised hosts. Physicians who are aware of its clinical presentations may be able to order diagnostic tests more appropriately and avoid inappropriate treatment. In the present series, the cases of seven patients admitted to Hamilton Health Sciences (Hamilton, Ontario) in the summer of 2012 with a diagnosis of West Nile neuroinvasive disease were retrospectively reviewed based on available medical records. According to the clinical and laboratory criteria published by the Centers for Disease Control and Prevention, five cases were diagnosed as encephalitis, one case as meningitis and one case as meningomyelitis. Patients were managed supportively. Forty-three percent (three of seven) presented with rash, 71% (five of seven) did not report headache despite exhibiting neurological symptoms, 43% (three of seven) did not have fever on presentation and 37.5% of cerebrospinal fluid samples exhibited a neutrophil predominance. The mortality rate in the present series was 14.3% (one of seven), and 57.1% (four of seven) of the patients had residual symptoms on discharge and at follow-up.

La maladie neuro-invasive du Nil occidental est une grave maladie infectieuse associée à un taux de mortalité élevé, notamment chez les hôtes immunodéprimés. Les médecins qui en connaissent les présentations cliniques peuvent demander des tests diagnostiques plus pertinents et éviter un traitement inutile. Dans la présente série, le cas de sept patients hospitalisés au Hamilton Health Sciences de Hamilton, en Ontario, pendant l'été 2012 en raison d'un diagnostic de maladie neuro-invasive du Nil occidental a fait l'objet d'une analyse rétrospective d'après les dossiers médicaux disponibles. Selon les critères cliniques et de laboratoire publiés par les Centers for Disease Control and Prevention, cinq cas ont été diagnostiqués comme une encéphalite, un cas comme une méningite et un cas comme une méningomyélite. Les patients ont reçu une prise en charge de soutien. Quarante-trois pour cent d'entre eux (trois sur sept) ont eu une éruption, 71 % (cinq sur sept) n'ont pas déclaré de céphalée malgré les symptômes neurologiques, 43 % (trois sur sept) ne faisaient pas de fièvre à la présentation et 28 % (deux sur sept) avaient une prédominance de neutrophiles dans les prélèvements de liquide céphalorachidien. Le taux de mortalité observé s'élevait à 14,3 % (un cas sur sept), et 57,1 % des patients (quatre sur sept) présentaient des symptômes résiduels au congé et au suivi.

Polymicrobial brain abscesses: A complex condition with diagnostic and therapeutic challenges.

Brain abscesses (BA) are focal parenchymal infections that remain life-threatening conditions. Polymicrobial BAs (PBAs) are complex coinfections of bacteria or bacterial and nonbacterial pathogens such as fungi or parasites, with diagnostic and therapeutic challenges. In this article, we comprehensively review the prevalence, pathogenesis, clinical manifestations, and microbiological, histopathological, and radiological features of PBAs, as well as treatment and prognosis. While PBAs and monomicrobial BAs have some similarities such as nonspecific clinical presentations, PBAs are more complex in their pathogenesis, pathological, and imaging presentations. The diagnostic challenges of PBAs include nonspecific imaging features at early stages and difficulties in identification of some pathogens by routine techniques without the use of molecular analysis. Imaging of late-stage PBAs demonstrates increased heterogeneity within lesions, which corresponds to variable histopathological features depending on the dominant pathogen-induced changes in different areas. This heterogeneity is particularly marked in cases of coinfections with nonbacterial pathogens such as Toxoplasma gondii. Therapeutic challenges in the management of PBAs include initial medical therapy for possibly underrecognized coinfections prior to identification of multiple pathogens and subsequent broad-spectrum antimicrobial therapy to eradicate identified pathogens. PBAs deserve more awareness to facilitate prompt and appropriate treatment.

Implementing a 4% EDTA Central Catheter Locking Solution as a Quality Improvement Project in a Large Canadian Hospital.

Oncology and critical care patients often require central vascular access devices (CVADs), which can make them prone to central line-associated bloodstream infections (CLABSIs) and thrombotic occlusions. According to the literature, CLABSIs are rampant and increased by 63% during the COVID-19 pandemic, highlighting the need for innovative interventions. Four percent ethylenediaminetetraacetic acid (4% EDTA) is an antimicrobial locking solution that reduces CLABSIs, thrombotic occlusions, and biofilm. This retrospective pre-post quality improvement project determined if 4% EDTA could improve patient safety by decreasing CLABSIs and central catheter occlusions. This was implemented in all adult cancer and critical care units at a regional cancer hospital and center. Before implementing 4% EDTA, there were 36 CLABSI cases in 16 months (27 annualized). After implementation, there were 6 cases in 6 months (12 annualized), showing a statistically significant decrease of 59% in CLABSIs per 1000 catheter days. However, there was no significant difference in occlusions (alteplase use). Eighty-eight percent of patients had either a positive or neutral outlook, while most nurses reported needing 4% EDTA to be available in prefilled syringes. The pandemic and nursing shortages may have influenced the results; hence, randomized controlled trials are needed to establish a causal relationship between 4% EDTA and CLABSIs and occlusions.

Retrospective Review of the Clinical Outcomes of Surgically Managed Patients with Intracranial Abscesses: A Single-Center Review.

OBJECTIVE: This study analyzed patient, radiologic, and clinical factors associated with operative brain abscesses and patients' functional outcomes. METHODS: A retrospective analysis was conducted of neurosurgical cases of brain abscesses from 2009 to 2019 at a Canadian center. Functional outcome was recorded as Modified Rankin Scale score and Extended Glasgow Outcome Scale score. Multivariate analysis was conducted to identify relevant prognostic factors. RESULTS: We identified 139 patients managed surgically for brain abscesses. Resection alone was performed in 64% of patients, whereas 26.6% underwent aspiration alone. Most were adults (93.2%) and male (68.3%). Immunocompromise risk factors included diabetes (24.5%), cancer (23.7%), and immunosuppressive therapy (11.5%). Likely sources were postoperative (17.3%), systemic spread (16.5%), and poor dentition (12.9%). Microorganisms cultured from abscess samples were mixed growth (28%), Streptococcus anginosus (24.5%), and Staphylococcus aureus (7.9%). Disposition was home (42.4%) or repatriation to a home hospital (50.4%). By Extended Glasgow Outcome Scale, 25.2% had an unfavorable outcome including a mortality of 11.5%. Factors on multivariate analysis associated with poor outcome included diabetes (odds ratio, 2.8; 95% confidence interval [CI], 1.2-5.0) and ventricular rupture (odds ratio, 5.0; 95% CI, 1.7-13.5; hazard ratio, 12; 95% CI, 3.9-37.0). Supratentorial superficial eloquently located abscess was also associated with poor outcome (hazard ratio, 5.5; 95% CI, 1.8-16.7). Outcomes were similar with surgical excision and aspiration. CONCLUSIONS: Ventricular rupture and diabetes are significant risk factors for poor outcomes in intraparenchymal brain abscesses. No clear difference in outcomes was found between surgical excision or aspiration in our retrospective cohort.

Prevalence and predictors of urethral chlamydia and gonorrhea infection in male inmates in an Ontario correctional facility.

OBJECTIVES: To determine the prevalence of urethral chlamydia and gonorrhea in males in a correctional facility in Ontario, Canada, and to explore risk factors for infection. METHODS: Between June and December, 2009, 500 adult males who had been newly admitted at a correctional facility in southern Ontario completed a survey of risk factors and provided a urine sample for testing. Those who tested positive were treated and their names were provided to the local public health unit for follow-up including contact tracing. Prevalence and 95% confidence intervals were calculated for infection with chlamydia and gonorrhea, respectively, and a multivariable model was used to look at risk factors for infection. RESULTS: The study population reported high levels of sexual risk behaviours and drug use. The overall chlamydia prevalence was 2.9% (95% CI 1.6-4.8) and the overall gonorrhea prevalence was 0.6% (95% CI 0.1-1.8). Rates were particularly high for chlamydia in younger males, at 16% (95% CI 4.5-36) in 18-19 year olds and 3.7% (95% CI 1.0-9.3) in 20-24 year olds, and for gonorrhea in males aged 20-24 at 1.9% (95% CI 0.2-6.6). A multivariable logistic regression model revealed that though not statistically significant, younger age was associated with infection. CONCLUSION: The relatively high prevalence of chlamydia and gonorrhea found in this study suggests that primary and secondary prevention programs should be instituted for males in correctional facilities, in particular among younger inmates. Further research is required to ensure internal and external generalizability of these results, as well as to determine the cost-effectiveness of potential interventions.

Purposeful microbiology comment added to urine cultures with Staphylococcus aureus increases orders for follow-up blood cultures.

INTRODUCTION: Patients with Staphylococcus aureus bacteriuria (SABU) often have underlying invasive disease, including S. aureus bacteremia (SAB). It has been proposed that most patients with SABU should have a blood culture done to rule out SAB. A preliminary audit suggested that our local hospitals had a low rate of follow-up blood culture orders for patients with SABU. In response to this, our microbiology laboratory changed the comment appended to urine cultures with growth of S. aureus to make a more assertive link between SABU and SAB and to recommend follow-up blood cultures. AIM: We designed a retrospective quasi-experimental study to see if the change in microbiology comment wording had an effect on clinician behaviour. We hypothesized that this simple comment change to make a more assertive link between SABU and SAB would lead to an increase in follow-up blood culture orders. METHODOLOGY: We used microbiology records to identify adult patients with urine cultures positive for Staphylococcus aureus at three acute-care hospitals in Hamilton, Ontario, Canada, for 1 year pre- and post-intervention. We recorded urine and blood culture results, timing, patient demographics, and in-hospital mortality. RESULTS: A total of 243 adult patients with urine cultures with S. aureus were identified for inclusion. The primary outcome was met, as there was a significant increase in blood culture orders between the pre-intervention and post-intervention groups (66.9 % vs 80.4 %). This difference was mainly driven by an increase for emergency department and urgent care patients (30.6 % vs 63.6 %). The inpatient group had a high baseline rate of blood culture orders that did not change significantly (80.0 % vs 84.7 %). There was no significant change in detection of SAB (23.5 % vs 32.7 %) or inpatient mortality (18.0 % vs 24.7 %). CONCLUSION: Our study shows that a simple, purposeful comment appended to urine cultures with S. aureus leads to a significant increase in follow-up blood culture orders.

Local audit of empiric antibiotic therapy in bacteremia: A retrospective cohort study.

BACKGROUND: It is unclear if a local audit would be useful in providing guidance on how to improve local practice of empiric antibiotic therapy. We performed an audit of antibiotic therapy in bacteremia to evaluate the proportion and risk factors for inadequate empiric antibiotic coverage. METHODS: This retrospective cohort study included patients with positive blood cultures across 3 hospitals in Hamilton, Ontario, Canada during October of 2019. Antibiotic therapy was considered empiric if it was administered within 24 hours after blood culture collection. Adequate coverage was defined as when the isolate from blood culture was tested to be susceptible to the empiric antibiotic. A multivariable logistic regression model was used to predict inadequate empiric coverage. Diagnostic accuracy of a clinical pathway based on patient risk factors was compared to clinician's decision in predicting which bacteria to empirically cover. RESULTS: Of 201 bacteremia cases, empiric coverage was inadequate in 56 (27.9%) cases. Risk factors for inadequate empiric coverage included unknown source at initiation of antibiotic therapy (adjusted odds ratio (aOR) of 2.76 95% CI 1.27-6.01, P = 0.010) and prior antibiotic therapy within 90 days (aOR of 2.46 95% CI 1.30-4.74, P = 0.006). A clinical pathway that considered community-associated infection as low risk for Pseudomonas was better at ruling out Pseudomonas bacteremia with a negative likelihood ratio of 0.17 (95% CI 0.03-1.10) compared to clinician's decision with negative likelihood ratio of 0.34 (95% CI 0.10-1.22). CONCLUSIONS: An audit of antibiotic therapy in bacteremia is feasible and may provide useful feedback on how to locally improve empiric antibiotic therapy.

Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial.

Importance: Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required. Objective: To determine whether 5 days of high-dose amoxicillin for CAP was associated with noninferior rates of clinical cure compared with 10 days of high-dose amoxicillin. Design, Setting, and Participants: The SAFER (Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections) study was a 2-center, parallel-group, noninferiority randomized clinical trial consisting of a single-center pilot study from December 1, 2012, to March 31, 2014, and the follow-up main study from August 1, 2016, to December 31, 2019 at the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. Research staff, participants, and outcome assessors were blinded to treatment allocation. Eligible children were aged 6 months to 10 years and had fever within 48 hours, respiratory symptoms, chest radiography findings consistent with pneumonia as per the emergency department physician, and a primary diagnosis of pneumonia. Children were excluded if they required hospitalization, had comorbidities that would predispose them to severe disease and/or pneumonia of unusual origin, or had previous ß-lactam antibiotic therapy. Data were analyzed from March 1 to July 8, 2020. Interventions: Five days of high-dose amoxicillin therapy followed by 5 days of placebo (intervention group) vs 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin (control group). Main Outcomes and Measures: Clinical cure at 14 to 21 days. Results: Among the 281 participants, the median age was 2.6 (interquartile range, 1.6-4.9) years (160 boys [57.7%] of 279 with sex listed). Clinical cure was observed in 101 of 114 children (88.6%) in the intervention group and in 99 of 109 (90.8%) in the control group in per-protocol analysis (risk difference, -0.016; 97.5% confidence limit, -0.087). Clinical cure at 14 to 21 days was observed in 108 of 126 (85.7%) in the intervention group and in 106 of 126 (84.1%) in the control group in the intention-to-treat analysis (risk difference, 0.023; 97.5% confidence limit, -0.061). Conclusions and Relevance: Short-course antibiotic therapy appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should consider recommending 5 days of amoxicillin for pediatric pneumonia management in accordance with antimicrobial stewardship principles. Trial Registration: ClinicalTrials.gov Identifier: NCT02380352.

Screening for and decolonization of Staphylococcus aureus carriers before total joint replacement is associated with lower S aureus prosthetic joint infection rates.

BACKGROUND: Prosthetic joint infections (PJI) can be devastating postoperative complications after total joint replacement (TJR). The role of decolonization of Staphylococcus aureus carriers prior to surgery still remains unclear, and the most recent guidelines do not state a formal recommendation for such strategy. Our purpose was to seek further evidence supporting preoperative screening and S aureus decolonization in patients undergoing TJR. METHODS: This was a quasiexperimental quality improvement study comparing a 5-year baseline of deep and organ-space PJIs (2005- 2010) to a 1-year intervention period (May 2015 to July 2016). The intervention consisted of nasal and throat screening for S aureus preoperatively and decolonization of carriers over 5 days prior to surgery. RESULTS: Prior to the intervention, we identified 42 deep and/or organ-space PJIs in 8,505 patients undergoing TJR (0.5%). S aureus was the causal microorganism in 28 of 42 (66.6%) cases. During the intervention, 22.5% (424 of 1,883) of patients were S aureus carriers. The PJI rate was similar overall (0.4%, 7 of 1,883; odds ratio, 0.75; 95% confidence interval, 0.34-1.67; P = .58), but there was a significant reduction in S aureus PJI to only 1 case during the intervention (odds ratio, 0.15; 95% confidence interval, 0.004-0.94; P = .039). CONCLUSIONS: Active screening for S aureus and decolonization of carriers prior to TJR was associated with a reduction in PJI due to S aureus, but no changes in overall PJI rates were observed.

Review of high dose vancomycin in the treatment of Clostridioides difficile infection.

BACKGROUND: Guidelines recommend oral vancomycin as first-line therapy for Clostridioides difficile infection. Guideline recommendations vary regarding dosing of vancomycin. Our aim was to summarize the current evidence on the efficacy and adverse effects of high dose oral and vancomycin retention enema (>500 mg/day) for the treatment of C. difficile infection. METHODS: We searched clinical studies and major guidelines in the English language using MEDLINE, the Cochrane Library and Embase from 1985 until 15 April 2020. RESULTS: No evidence supports the use of high dose oral vancomycin in the treatment of severe C. difficile infection. Weak evidence from observational studies supports the use of high dose oral vancomycin in addition to intravenous metronidazole and high dose vancomycin retention enema in fulminant C. difficile infection. Vancomycin retention enema can be used in severe C. difficile infection when oral administration is not possible, or in conditions when the oral formulation cannot reach the colon such as Hartman's pouch, ileostomies, or colon diversions. CONCLUSIONS: The dosing schedules for oral vancomycin and vancomycin enemas are not clearly defined due to widely varying results in clinical studies. Large, comparative multicenter trials are urgently needed to define the role of high dose vancomycin in C. difficile infection.

Compliance with personal precautions against exposure to bloodborne pathogens among laboratory workers: a Canadian survey .

A survey was conducted in laboratories across Canada to determine rates of compliance with recommended safety precautions against exposure to bloodborne pathogens and the rationale for current behaviors. Laboratory workers reported high rates of exposure to bodily fluids and poor rates of compliance with personal protective behaviors. This national study has identified several deficiencies and strategies for improvement.

Short-course antimicrobial therapy for paediatric respiratory infections (SAFER): study protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is commonly diagnosed in children. The Infectious Disease Society of America guidelines recommend 10 days of high-dose amoxicillin for the treatment of non-severe CAP but 5-day "short course" therapy may be just as effective. Randomized trials in adults have already demonstrated non-inferiority of 5-day short-course treatment for adults hospitalized with severe CAP and for adults with mild CAP treated as outpatients. Minimizing exposure to antimicrobials is desirable to avoid harms including diarrhoea, rashes, severe allergic reactions, increased circulating antimicrobial resistance, and microbiome disruption. METHODS: The objective of this multicentre, randomized, non-inferiority, controlled trial is to investigate whether 5 days of high-dose amoxicillin is associated with lower rates of clinical cure 14-21 days later as compared to 10 days of high-dose amoxicillin, the reference standard. Recruitment and enrolment will occur in the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. All children in the study will receive 5 days of amoxicillin after which point they will receive either 5 days of a different formulation of amoxicillin or a placebo. Assuming a clinical failure rate of 5% in the reference arm, a non-inferiority margin of 7.5%, one-sided alpha set at 0.025 and power of 0.80, 270 participants will be required. Participants from a previous feasibility study (n = 60) will be rolled over into the current study. We will be performing multiplex respiratory virus molecular testing, quantification of nasopharyngeal pneumococcal genomic loads, salivary inflammatory marker testing, and faecal microbiome profiling on participants. DISCUSSION: This is a pragmatic study seeking to provide high-quality evidence for front-line physicians evaluating children presenting with mild CAP in North American emergency departments in the post-13-valent pneumococcal, conjugate vaccine era. High-quality evidence supporting the non-inferiority of short-course therapy for non-severe paediatric CAP should be generated prior to making changes to established guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02380352 . Registered on 2 March 2015.