Survey of Pediatric Status Epilepticus Treatment Practices and Adherence to Management Guidelines (Pedi-SPECTRUM e-Survey).

Aim: Survey of treatment practices and adherence to pediatric status epilepticus (PSE) management guidelines in India. Methods: This eSurvey was conducted over 35 days (15th October to 20th November 2023) and included questions related to hospital setting; antiseizure medications (ASMs); ancillary treatment; facilities available; etiology; and adherence to PSE management guidelines. Results: A total of 170 respondents participated, majority of them were working in tertiary level hospitals (94.1%) as pediatric intensivists (56.5%) and pediatricians (19.4%), and were in clinical practice for 2-10 years (46.5%). Majority use intravenous (IV) midazolam and levetiracetam as first- and second-line ASMs (67.1 and 51.2%, respectively). In cases with refractory status epilepticus (RSE), the most commonly used ASM is midazolam infusion (92.4%). For super-refractory status epilepticus (SRSE), the commonly used third-line ASMs include midazolam infusion (34.1%), thiopentone infusion (26.5%), high dose phenobarbitone (18.2%), and ketamine infusion (15.3%). Overall, in cases with SRSE, 44.7% respondents use ketamine infusion, 42.5% use add-on oral topiramate, and 34.7% use high-dose phenobarbitone (1-3 mg/kg/hour) infusion. Most respondents targeted both clinical and EEG seizure control (48.8%). Ancillary treatment used for SRSE included IV pyridoxine (57.1%), methylprednisolone (45.3%), IVIG (42.4%), ketogenic diet (40.6%), and second-line immunomodulation (33.5%). Most common causes were febrile SE, viral encephalitis, and febrile illness-related epilepsy syndrome (60.6%, 52.4%, and 37.1%, respectively). Facilities available included pediatric intensive care units (PICU) (97.1%), mechanical ventilation (98.2%), pediatric neurologist (68.8%), MRI brain (86.5%), EEG (69.4%), and viral PCR (58.2%). The compliance with guidelines for timing of initiation of ASM ranged from 63.5 to 88.8%. Conclusion: Intravenous midazolam bolus/es, levetiracetam, and midazolam infusion are commonly used first-, second-, and third-line ASMs, respectively. There were wide variations in use of ASMs for RSE and SRSE, ancillary treatment, and compliance to PSE management guidelines. How to cite this article: Suthar R, Angurana SK, Nallasamy K, Bansal A, Muralidharan J. Survey of Pediatric Status Epilepticus Treatment Practices and Adherence to Management Guidelines (Pedi-SPECTRUM e-Survey). Indian J Crit Care Med 2024;28(5):504-510.

Clinical course and molecular characterization of human Bocavirus associated with acute lower respiratory tract infections in tertiary care hospital of north India.

Respiratory samples from 139 hospitalized children were screened for the Human Bocavirus (HBoV) genome. Positive samples were sequenced for partial VP1/VP2 gene followed by molecular and phylogenetic analyses. HBoV positivity was noted in 7.2% (10/139) patients. All HBoV positive children presented with fever followed by cough and respiratory distress (90%; 9/10). Three children developed multisystemic viral illness with one fatality. Eight children required intensive care management and mechanical ventilation required for 5 children. Nucleotide percent identity of partial VP1/VP2 gene of HBoV study strains were ranging from 97.52% to 99.67%. Non-synonymous amino acid mutations in VP1 protein revealed T591S (n=8) and Y517S (n=1) mutations in comparison to HBoVSt1 strain where N475S (n=8) and S591T (n=2) mutations in comparison to HBoVSt2 strain. One study strain showed A556P, H556P, I561S and M562R non-synonymous mutations. All the study strains belong to HBoV1 type. Seven HBoV strains belong to same lineage and three belong to another lineage. For evolutionary dynamics, GTR+I substitution model with uncorrelated relaxed lognormal clock and Bayesian Skyline tree prior showed 9.0 x 10-4 [95% HPD interval: 3.1 x10-6, 2.1 x 10-3] nucleotide substitutions/site/year. The clinical suspicion and virological screening is necessary for identification HBoV in children.

Pattern of Fluid Overload and its Impact on Mortality Among Mechanically Ventilated Children: Secondary Analysis of the ReLiSCh Trial.

OBJECTIVES: To assess the pattern of fluid overload (FO) and its impact on mortality among mechanically ventilated children. METHODS: In this secondary analysis of an open-label randomized controlled trial (ReLiSCh trial, October 2020-September 2021), hemodynamically stable mechanically ventilated children (n = 100) admitted to a tertiary level pediatric intensive care unit (PICU) in North India were enrolled. The primary outcome was pattern of FO (FO% >10% and cumulative FO% from day 1-7); and secondary outcomes were pattern of FO among survivors and non-survivors, and prescription practices of maintenance fluid. RESULTS: The median (IQR) age was 3.5 (0.85-7.5) y and 57% were males. Common diagnoses were pneumonia (27%), scrub typhus (14%), Landry-Guillain-Barré syndrome (9%), dengue (8%), central nervous system infections (7%) and staphylococcal sepsis (6%). Common organ dysfunction included acute respiratory distress syndrome (ARDS) (41%), shock (38%), and acute kidney injury (AKI) (9%). The duration PICU stay was 11 (7-17) d and mortality was 12%. The FO% >10% was noted in 19% children; and there was significant increase in cumulative FO% from day 1-7 [1.2 (0.2-2.6)% to 8.5 (1.7-14.3)%, (p = 0.000)]. Among non-survivors, higher proportion had FO% >10% (66.7% vs. 12.5%, p 0.0001); and trend towards higher cumulative FO% on first seven days. From day 1-7, the percentage of maintenance fluid received increased from 60 (50-71)% to 70 (60-77)% (p = 0.691). CONCLUSIONS: One-fifth of mechanically ventilated children had FO% >10% and there was significant increase in cumulative FO% from day 1-7. Non-survivors had significantly higher degree of FO.

Three-Point Ultrasonography for Confirmation of Endotracheal Tube Position in Children (TRUCE Study).

OBJECTIVES: To investigate the diagnostic accuracy of three-point ultrasonography for confirmation of endotracheal tube (ETT) position among children undergoing endotracheal intubation (ETI) with chest radiograph as reference standard. METHODS: This prospective observational study was conducted from January 2021 through December 2021 (12 mo) in the pediatric emergency room (PER) and pediatric intensive care unit (PICU), Division of Pediatric Critical Care, Advanced Pediatrics Centre (APC), Post-Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Children aged 3 mo to 12 y, undergoing ETI in PER or PICU were included. Three-point ultrasonography (suprasternal notch and bilateral anterior chest) was done following ETI for confirmation of correct ETT position. Chest radiograph was used as a reference standard. Interobserver agreement between two investigators (IG and SKA) (kappa statistic) was determined for three-point ultrasonography to confirm the correct ETT position. RESULTS: One hundred fifty-five children with median (IQR) age of 4.5 (1-7) y were enrolled; 60% (n = 94) were males. On neck ultrasound, bilaminar sign was present in 100% of children. On lung ultrasound, bilateral and unilateral pleural sliding were present in 97.4% and 2.6% children, respectively. Three-point ultrasonography identified the correct position of ETT in 97.4% children as compared to 83.2% on chest radiograph. Sensitivity of three-point ultrasonography to identify the correct position of ETT was 98%. The interobserver agreement between two examiners was 96.8% (kappa of 0.53, p = 0.000). CONCLUSIONS: Three-point ultrasonography is an effective, sensitive, safe, and reproducible bedside method for identification of correct placement of ETT in children admitted to PER and PICU.

Recurrent Guillain-Barré Syndrome: Clinical Profile and Outcome.

OBJECTIVES: To compare clinical, neurological, treatment and outcome of recurrent Guillian-Barré Syndrome (GBS) with non-recurrent GBS. Also, to compare different episodes of recurrent GBS. METHODS: The patient's case records were retrieved retrospectively from the electronic database and case record files. Clinical profile, nerve conduction study, treatment, and outcome details of children with a diagnosis of GBS admitted in Pediatric Intensive Care Unit (PICU) from 2010 to March 2022 were screened. Recurrent GBS cases, as defined by the National Institute of Neurological and Communicative Diseases and Strokes (NINCDS) criteria, were analysed separately. The comparison was made between the first episode of recurrent GBS with non-recurrent GBS, and predictors of recurrence were identified. A comparison of course and outcome was also done between different episodes of GBS in recurrent cases. RESULTS: Recurrent GBS was observed in 11 (4.7%) out of 234 cases during the study period. The presence of respiratory (p 0.015) and gastrointestinal illness (p 0.007) as preceding illnesses were associated with recurrence. No difference was noted between the first episode of recurrent GBS and non-recurrent GBS. The first and second episodes of GBS in 11 recurrent cases were similar in course and outcome. CONCLUSIONS: Recurrent GBS is underreported but a known entity. No difference was seen between the two episodes of recurrent GBS. However, more data is required to find the features of recurrent GBS so that limited PICU resources can be used judiciously and intervention planned accordingly.

Paradigm shift of respiratory viruses causing lower respiratory tract infection in children during COVID-19 pandemic in India.

INTRODUCTION: Acute lower respiratory tract infections (ALRTIs) are the commonest cause of mortality in children mostly attributed to respiratory viruses. During the coronavirus disease 2019 (COVID-19) pandemic, the dynamics and transmission of infections changed worldwide due to widespread public health measures. This study aimed to understand the pattern of respiratory viruses associated with ALRTIs in children pre and during COVID-19 pandemic in India. METHODOLOGY: Respiratory samples were collected from ALRTI patients during pre-pandemic period (October 2019 to February 2020; n = 166), Delta (July 2021 to December 2021; n = 78) and Omicron wave (January 2022 to July 2022; n = 111). Samples were screened for Influenza (Inf) A pdmH1N1, InfA H3N2, InfB, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human bocavirus (hBoV), human rhinovirus (hRV), and parainfluenza virus (PIV-2 and PIV-3) by nucleic acid amplification techniques (NAATs). RESULTS: Significantly higher proportion of children with ALRTIs had virus/es isolated during pre-pandemic period than during mid-pandemic period [78.9% (131/166) vs. 52.9% (100/189); p < 0.001). RSV positivity was significantly higher (51.2%) in pre-pandemic period than 10.3% and 0.9% during the Delta and Omicron waves respectively. No significant difference in positivity rate of Inf A pdmH1N1, Inf A H3N2 and Inf B was seen. The increase in positivity of hRV (39.2% vs 42.3% vs 56.8%) and hBOV (1.2% vs 5.1% vs 9%) was documented in pre-pandemic, delta wave and omicron wave respectively. CONCLUSIONS: The COVID-19 pandemic significantly impacted the frequency and pattern of respiratory viruses among hospitalized children with ALRTIs in India.

Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Severe dengue associated with Staphylococcus aureus sepsis in pediatric patients: a case series.

BACKGROUND: Staphylococcus aureus co-infection is seldom reported in children with severe dengue. METHODOLOGY: In this retrospective study, we reported five children with severe dengue and S. aureus co-infection admitted to pediatric intensive care unit (PICU) during July-December 2021. RESULTS: All children had prolonged fever, persistence of bilateral pleural effusion beyond the critical phase, thrombocytopenia and raised inflammatory markers [C-reactive protein (CRP) and procalcitonin]. S. aureus was isolated from pleural fluid (n = 2, 40%), blood (n = 2, 40%) and endotracheal aspirate (n = 1, 20%). Four children (80%) grew methicillin-sensitive S. aureus, while 1 (20%) had methicillin-resistant S. aureus. Two children (40%) had septic thromboemboli in skin, and 1 (20%) had limb cellulitis. One child required anterior thoracotomy, pericardiectomy and bilateral pleural decortication, while all other children required intercostal chest tube drainage. All children required prolonged targeted antibiotics, invasive mechanical ventilation and had prolong stay in PICU and all of them survived. CONCLUSION: In children with severe dengue, persistence of fever, persistence of pleural effusion beyond critical phase and raised CRP and procalcitonin should raise suspicion of bacterial/S. aureus co-infection.

Status Dystonicus in Children: A Cross-Sectional Study and Review of Literature.

Background: Status dystonicus is a life-threatening, underrecognized movement disorder emergency. We aimed to ascertain the etiology, clinical presentation, complications, and outcomes of status dystonicus in children and reviewed the literature for similar studies. Methods: Records of all children aged <14 years admitted to a single center with status dystonicus between 2014 and 2018 were reviewed. Results: Twenty-four children (75% male) were identified with status dystonicus. The annual incidence rate was 0.05 per 1000 new admissions <12 years of age. The mean age at presentation was 6.3 ± 3.6 years. Median duration of hospital stay was 10.5 days (interquartile range 5-21.7). The severity of dystonia at presentation was grade 3 (n = 9; 37.5%) and 4 (n = 9; 37.5%). The most common triggering factor was intercurrent illness/infection (n = 18; 75%). The most common underlying etiologies were cerebral palsy (n = 8; 33.3%), complicated tubercular meningitis (n = 3; 12.5%), and mitochondrial disorders (n = 3; 12.5%). Basal ganglia involvement was seen in 15 cases (62.5%). Respiratory and/or bulbar compromise (n = 20; 83.3%) and rhabdomyolysis (n = 15; 62.5%) were most commonly seen. Oral trihexyphenidyl (96%) followed by oral or intravenous diazepam (71%), oral baclofen (67%), and midazolam infusion (54%) were the most common drugs used. Clonidine was used in 33% cases, without any significant side effects. Three children died owing to refractory status dystonicus and its complications; the mortality rate was 12.5%. Conclusion Status dystonicus is a neurologic emergency in children with severe dystonia, with significant complications and a high mortality rate. Static and acquired disorders are more common than heredo-familial causes. Identification and treatment of infection in children is important as the majority of cases are triggered by an intercurrent infection.

Cerebral Phaeohyphomycosis: Subacute Meningoencephalitic Presentation in a Child.

Cerebral phaeohyphomycosis is a rare but serious fungal infection of the central nervous system caused by dematiaceous septate fungi characterized by the presence of melanin-like pigment within the cell wall that is a pale brown to black. It is associated with poor prognosis despite aggressive treatment. We report a previously well 3-year boy with cerebral phaeohyphomycosis who had subacute meningoencephalitic presentation with refractory raised intracranial pressure and had fatal outcomes. The diagnosis was confirmed by histopathological examination of brain tissue obtained by brain biopsy.

Updated Management Protocol for Multisystem Inflammatory Syndrome in Children (MIS-C).

The multisystem inflammatory syndrome in children (MIS-C) is a post-viral immunological or hyper-inflammatory complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection commonly seen in older children, who commonly present with fever, multi-systemic involvement including myocardial dysfunction and shock, and hyper-inflammation. The treatment of MIS-C is adapted from the treatment of other immunological or hyper-inflammatory conditions and these treatment protocols are not uniform across the globe, and more so, in India. We propose a uniform management protocol for MIS-C based on our experience of treating MIS-C cases, available evidence till now, and recent guidelines. The aims are to identify children with MIS-C with high sensitivity, recognize other infections or inflammatory processes, stratify treatment based on severity, and manage hyper-inflammatory syndrome.

Acute neurological complications during acute lymphoblastic leukemia therapy: A single-center experience over 10 years.

BACKGROUND: Acute neurological complications occur in 3.6-11% of children treated for acute lymphoblastic leukemia (ALL). This analysis aimed to evaluate the profile of acute neuro-toxicity and its etiology in children with ALL. METHODS: A retrospective case analysis of central nervous system events in children treated for ALL at our center was performed. Details of events were retrieved from the case records (January 2006-December 2015) and analyzed. RESULTS: Ninety (9.5%) neurological events occurred in 923 patients treated for ALL. Phase of therapy were: induction (38), consolidation (5), interim maintenance (5), intensification (15) and maintenance (27). Seizures and neurological deficits were the presenting features in 64 and 40 children, respectively. Events included : neuro-infections in 18, posterior reversible encephalopathy syndrome (PRES) in 7, epilepsy in 6, intracranial bleed in 5, systemic infection with neurological complication in 4, hydrocephalus and aseptic meningitis in 3 each, methotrexate encephalopathy and metabolic seizures in 2 children each. Seizures and status epilepticus of unknown etiology and neurological deficits of unknown etiology was observed in 26 and 13 children, respectively. Seizures occurred mainly in induction (12) and intensification phase (9). Status epilepticus transpired in maintenance phase in 9/14 patients. Induction phase was complicated by PRES in 7, intracranial bleed in 5 and cerebral sinus venous thrombosis in 1 patient. Neuroimaging was done in 86% of events. There were 18 (20.6%) deaths: neuro-infections (8), status epilepticus (6), systemic infection (2), bleed (1), and unexplained encephalopathy (demyelination)(1). At last follow-up, 53 patients were well and 7 children persist to have a neurological disability. CONCLUSION: Ten percent of children on treatment for ALL suffered an acute neuro-toxicity. Morbidity and high-incidence of neuroinfections are major concerns.

Epidemiology of Acute Gastroenteritis Caused by Rotavirus among Children Less than Five Years Old Admitted in Hospital, in North India.

OBJECTIVES: To report the data of burden of rotaviral acute gastroenteritis in under-five children from two states post-introduction of the vaccine. METHODS: Children under 5 y of age hospitalized with diarrhea from the states of Haryana and Himachal Pradesh in north India were recruited in the study. Commercially available ELISA kits were used for testing rotavirus in the collected stool samples. Genotyping of the positive samples was done by reverse-transcription polymerase chain reaction. RESULTS: Out of 345 samples collected, 69 (20%) were found to be positive for rotavirus by ELISA. Genotyping was done and G3P[8] (31.3%), G1P[8] (13.4%), G2P[4] (13.4%) were found to be prevalent strains. Mixed strains were also found in 19.4% stool samples. CONCLUSIONS: The study highlighted the high burden of rotavirus associated diarrhea in north Indian states. The data is helpful for evaluating the impact of vaccine on the severity of acute gastroenteritis and the changing strains after the introduction of rotavirus vaccine in the Universal Immunization Program.

Epidemiology of Hospitalized Intussusception Cases from Northern States in India.

OBJECTIVE: To describe epidemiology of intussusception post-introduction of the rotavirus vaccine. METHODS: Hospital-based active surveillance system was set up in three tertiary care hospitals in Chandigarh and Haryana, India, to enroll children <2 y of age admitted with intussusception as per Brighton Collaboration Level-I criteria. The clinical characteristics, treatment modalities, seasonal trends, and outcome of the illness episodes were described. RESULTS: A total of 224 cases were reported. Majority were males (71%) and infants (69.5%). Number of intussusception was more in summer season. Location of intussusception was ileo-colic in 85% of the cases. Nearly 54% cases were treated conservatively and 46% needed surgical intervention. CONCLUSION: Surveillance data provided the epidemiological description of intussusception cases post-introduction of the rotavirus vaccine in northern India. This data could be used to assess the impact of vaccine and safety with a special focus on intussusception.

Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality.

OBJECTIVE: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. DESIGN: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Pediatric intensive care unit of a tertiary level teaching hospital in India. PATIENTS: Fifty children with severe sepsis aged 3 months to 12 years. MATERIAL AND METHODS: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor ß1 [TGF-ß1]) cytokines. PRIMARY OUTCOME: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). SECONDARY OUTCOMES: To compare cytokine levels among survivors and nonsurvivors. RESULTS: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-ß1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = -0.257, P = .09) and TGF-ß (ρ = -0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. CONCLUSION: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.

Antimicrobial Stewardship Programs in Resource Constrained Environments: Understanding and Addressing the Need of the Systems.

World Health Organization (WHO) has identified antimicrobial resistance as one of the top 10 threats to public health. The agency has formulated a global action plan to tackle antimicrobial resistance by reducing incidence of infectious diseases, increasing knowledge and awareness and promoting rational use of antimicrobials amongst other measures. While the core elements of successful antimicrobial stewardship (AMS) programs are much publicized, there application in resource limited settings is fraught with several challenges. The key limiting factors include lack of clear political commitment, inadequate funding, overcrowded healthcare systems, lax legal and regulatory frameworks, non-uniform access to diagnostics, absence of electronic health record systems, limited knowledge and awareness especially with existence of multiple systems of medicines, issues with access to quality assured medicines, in-house pharmacies, and shortage of trained manpower. Since these implementation-impeding issues may differ considerably from those experienced in developed economies, intervention efforts in low- and middle-income countries (LMICs) need to address the context and focus on the root causes prevailing locally. In this article, we review the evidence highlighting the magnitude of these challenges and suggest feasible models with effective application. We also share the evidence from our center where we have contextualized the core elements to resource constrained settings. These domains include delivering prospective audit and feedback, prescriber education, development of evidence-based and implementable guidelines, and optimization of surgical antibiotic prophylaxis. However, there is a tremendous need for scaling up, extending outreach and honing these models while at the same time, addressing the existing strategic challenges that curtail the full potential of global antimicrobial stewardship.