Central line–associated bloodstream infections in the pediatric intensive care and hemato-oncology unit: a prospective observational study from Western India

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Abstract Introduction: Central line–associated bloodstream infections (CLABSI) are serious patient safety hazards in pediatric intensive care. Children from hemato-oncology have prolonged line duration yet may incur different infection risks and resistance patterns versus general PICU patients. Thus, the aim of the study was to compare central line utilization, incidence of CLABSI, risk factors and antimicrobial resistance between PICU and hemato-oncology patients, and to identify targets for quality improvement in a resource-limited setting. Methods A prospective observational study in a tertiary PICU in India over 24 months. All children aged 1 month–18 years requiring central venous access were enrolled. We recorded insertion practices, line duration, and CLABSI incidence using standard definitions. Antimicrobial isolates and resistance profiles were compared between the PICU and hemato-oncology subgroups. Results Among 1,931 central line days in 69 children, there were 13 CLABSI episodes. Hemato-oncology patients had longer line durations but lower CLABSI incidence (5.08/1,000 line days) vs general PICU patients (10.87/1,000 line days). Gram-negative bacteria predominated across both groups; PICU isolates showed higher resistance to cephalosporins and carbapenems. Conclusion Infection risk in PICU is shaped not only by line duration but also by insertion urgency, patient acuity, and antimicrobial exposure. Structured bundles, safe insertion/maintenance practices, and stewardship programs are recommended to improve patient safety in pediatric critical care in LMICs.
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Children from hemato-oncology have prolonged line duration yet may incur different infection risks and resistance patterns versus general PICU patients. Thus, the aim of the study was to compare central line utilization, incidence of CLABSI, risk factors and antimicrobial resistance between PICU and hemato-oncology patients, and to identify targets for quality improvement in a resource-limited setting. Methods A prospective observational study in a tertiary PICU in India over 24 months. All children aged 1 month–18 years requiring central venous access were enrolled. We recorded insertion practices, line duration, and CLABSI incidence using standard definitions. Antimicrobial isolates and resistance profiles were compared between the PICU and hemato-oncology subgroups. Results Among 1,931 central line days in 69 children, there were 13 CLABSI episodes. Hemato-oncology patients had longer line durations but lower CLABSI incidence (5.08/1,000 line days) vs general PICU patients (10.87/1,000 line days). Gram-negative bacteria predominated across both groups; PICU isolates showed higher resistance to cephalosporins and carbapenems. Conclusion Infection risk in PICU is shaped not only by line duration but also by insertion urgency, patient acuity, and antimicrobial exposure. Structured bundles, safe insertion/maintenance practices, and stewardship programs are recommended to improve patient safety in pediatric critical care in LMICs. Central Line-Associated Bloodstream Infections Catheter-Related Infections Intensive Care Units Oncology Antimicrobial Resistance Risk Factors Microbial Sensitivity Tests Gram-Negative Bacterial Infections Observational study Quality improvement Figures Figure 1 Figure 2 Figure 3 Key Message CLABSI remains a significant safety challenge in our PICU, particularly among patients undergoing urgent line insertions. Hemato‑oncology patients had longer line use but lower CLABSI rates, suggesting possible protective practices worth adapting across PICU. High prevalence of gram‑negative organisms with major resistance highlights the urgent need for local antimicrobial stewardship. Quality improvement interventions — central line bundles, staff training, standardized insertion/maintenance protocols — are essential to reduce CLABSI in resource‑limited pediatric settings. Introduction: Central venous catheters (CVCs) are essential in pediatric intensive care units (PICUs) for administration of fluids, parenteral nutrition, antibiotics, inotropes, chemotherapy, and hemodynamic monitoring. Despite their benefits, central lines are associated with a wide range of complications including infection, thrombosis, and mechanical problems, which may contribute to increased morbidity, mortality, and healthcare costs. 1 Among these, central line-associated bloodstream infections (CLABSI) remain one of the most significant. CLABSI is defined as per Center for Disease Control (CDC) guidelines as an identified eligible blood stream organism (a laboratory confirmed bloodstream infection (LCBI), not secondary to an infection at another body site) in a patient with an eligible central line (placed for more than two consecutive calendar days) present on the day of event of LCBI. 1 The CDC via the National Healthcare Safety network (NHSN), has implemented a robust reporting system for CLABSI, wherein it was observed that CLABSI rates have reduced from 7.9 per 1000 central line days in 1992–1999, to 0.8 per 1000 central line days in 2013, and has remained < 1 per 1000 central line days from the 2016–2022, in PICUs across the USA. 2–3 In India, the Indian Council of Medical Research (ICMR) also provides annual CLABSI data and reports the total bloodstream infection (BSI) rate in the PICU as 3.74 per 1000 patient days. CLABSI rates in the pediatric population, as reported by certain Indian studies, are variable ranging from between 5 to 15 per 1000 central line days. 4 – 7 The most common organisms associated with CLABSI include gram-negative bacilli such as Klebsiella, Pseudomonas, Acinetobacter , and Proteus , along with gram-positive species like Staphylococcus epidermidis and fungal pathogens such as Candida albicans . 4 – 5 , 8 Antimicrobial resistance is an increasing concern, particularly in Indian studies, with gram-negative bacilli frequently resistant to quinolones, third- and fourth-generation cephalosporins, and carbapenems. 4 – 5 Therefore, ongoing surveillance of microbiological patterns and antimicrobial resistance is essential to guide empirical therapy and infection prevention strategies in PICUs. Several risk factors for CLABSI have been described, including deficiencies in hand hygiene, barrier precautions, skin antisepsis, or central line maintenance; patient-related factors such as malignancy, frequent transfusions, prior CLABSI, and need for parenteral nutrition; and equipment-related factors such as multi-lumen catheters or non-sterile hubs. 9 – 13 Bundle-based checklists have been shown to reduce risk, but adherence remains variable, especially in resource-limited settings. CLABSI is one of the major contributors to healthcare-associated infections (HAIs) in pediatric inpatient settings, leading to prolonged hospitalisation, higher costs, and increased morbidity and mortality. 14 – 20 Hence, studies describing central line use, incidence of CLABSI, associated risk factors, and microbiological trends are vital for improving patient outcomes and ensuring safety, particularly in low- and middle-income country (LMIC) settings. Children with underlying hemato-oncological conditions often represent a unique subgroup of PICU patients, as they frequently require prolonged central venous access and have distinct risk profiles. Differences in risk factors and usage patterns between PICU patients in general and those with hemato-oncological conditions highlight the need for targeted research. The present study therefore describes central line practices and outcomes in a tertiary PICU, with a specific focus on CLABSI, while also comparing findings with a hemato-oncology subgroup whose structured care might provide insights into safer practices applicable to PICU. Objectives: Primary Objective: To describe the patterns, indications, and outcomes of central line use in the Pediatric Intensive Care Unit (PICU) of a tertiary care hospital Secondary Objectives: To determine the incidence and microbiological profile of central line-associated bloodstream infections (CLABSI) in the PICU Materials and Methods: Study design: This was a prospective observational study conducted in the pediatric intensive care unit (PICU) of a tertiary care teaching hospital in Western India over a 24-month period. Children with underlying hemato-oncological conditions admitted to the PICU formed a predefined subgroup for analysis. Approval was obtained from the Institutional Ethics Committee (BVDUMC/IEC/36 dated 11/08/2022), and informed written consent was obtained from parents or guardians; assent was taken from older children as applicable. Participants: We included all pediatric patients (1 month–18 years) admitted to the PICU who required central venous catheterization for any indication. Central venous catheters (CVCs) included peripherally inserted central catheters (PICC), internal jugular, subclavian, and femoral catheters. Patients with hemato-oncological diagnoses admitted to the PICU were analyzed and compared with the PICU group. Data Collection: For each patient, demographic details, comorbidities, initial clinical and laboratory parameters, central line type and indication, associated devices (endotracheal tube, urinary catheter), antimicrobial use and sensitivity patterns, blood product and chemotherapy administration, length of hospitalization, and outcomes were recorded. Positive culture reports were considered if differential growth between the central and peripheral cultures was observed, at least 48 hours after insertion of the central line, when CLABSI was suspected clinically. Central Line Devices and Maintenance: In the PICU, a double-lumen radio-opaque polyurethane CVC was routinely used, while PICC lines consisted of single-lumen biostable polyurethane catheters with StatLock™ stabilization devices. For every insertion, a CLABSI bundle checklist was followed, including strict hand hygiene, maximal barrier precautions, and skin antisepsis. Reinsertion was considered a new episode, and the checklist was reapplied. Daily checklist adherence was monitored during PICU stay. All insertions were performed by trained personnel, and staff underwent periodic reinforcement sessions on central line insertion and maintenance protocols. Children discharged from the PICU with PICC lines (e.g., those with underlying hemato-oncological conditions) were followed up weekly in the hospital for dressing changes and review of any new symptoms (fever, local site changes, systemic instability). Suspected CLABSI prompted paired blood cultures (central and peripheral) and further work-up. Definitions and Microbiological Methods: CLABSI was defined according to CDC–NHSN criteria. 1 When CLABSI was suspected, blood culture samples were collected simultaneously from central and peripheral sites, at least 48 hours after insertion. Pediatric blood culture bottles (BD BACTEC™ Peds Plus™/Fenriched Soybean-Casein Digest broth with CO2) were used. Standard ICMR guidelines for asepsis and sample volume were followed. 21 Positive cultures were subjected to gram staining, species identification by the VITEK system, and antimicrobial susceptibility testing using Kirby-Bauer disc diffusion. Minimum inhibitory concentrations (MICs) were reported as per standard guidelines. ​​Statistical Analysis: Data were analyzed using SPSS version 29. Descriptive statistics (mean, standard deviation, frequency) were used for baseline characteristics. Normality was assessed with the Shapiro–Wilk test and histograms. Continuous variables were compared using the independent samples t-test or Mann–Whitney U test, as appropriate; categorical variables were compared using the Chi-square or Fisher’s exact test. Univariate logistic regression identified risk factors associated with CLABSI. A p-value < 0.05 was considered statistically significant. Device Utilization and CLABSI Rates: Device utilization ratio (DUR) and CLABSI incidence were calculated as: DUR = Number of central line days Number of patient days CLABSI incidence rate = Number of CLABSIs x 1000 Number of central line days Results: Patient Characteristics: A total of 69 children, with 1931 central line days, were consecutively enrolled in the study upon admission to the PICU. Demographics, diagnoses, duration of hospitalization, and outcomes are summarized in Table 1 . Overall, females accounted for 55.1% of the study population. The mean ± SD age in the PICU cohort was 4.13 ± 5.46 years. Children with underlying hemato-oncological diagnoses admitted to the PICU were older on average (8.06 ± 5.06 years, p < 0.05). Table 1 Characteristics of the population of children admitted to the pediatric intensive care unit (PICU) versus the hemato-oncological (HO) unit Total [n (%)] PICU [n (%)] HO [n (%)] p-value Number of patients 69 (100%) 46 (66.67%) 23 (33.34%) - Mean age ± Standard deviation (SD) in years 5.44 ± 5.61 4.13 ± 5.46 8.06 ± 5.06 0.005 Sex : Male 31 (44.93%) 18 (39.13%) 13 (56.52%) - Female 38 (55.07%) 28 (60.87%) 10 (43.48%) - Diagnosis* : Medical 40 (57.97%) - - - Surgical 14 (20.29%) - - - Oncological 21 (30.43%) - - - Total duration of hospital stay in days 26.34 ± 20.02 24.84 ± 20.32 29.34 ± 19.50 0.382 Outcomes : Discharged 56 (81.16%) 37 (80.44%) 19 (82.61%) - Death 10 (14.49%) 6 (13.04%) 4 (17.39%) - Discharged on request 2 (2.90%) 2 (4.35%) 0 - Discharged against medical advice 1 (1.45%) 1(2.17%) 0 - *Note: An overlap of the diagnosis; medical surgical and oncological, was noted in the study population in certain patients and hence were counted in both diagnostic categories Purely medical diagnoses were the most common in the PICU, including neurological (20.8%), respiratory (19%), gastrointestinal (7.9%), and cardiac (4.7%) illnesses, while others had multisystem involvement. Among the subgroup of children with hemato-oncological conditions, hematological malignancies (65.2%) predominated, mainly pre-B cell acute lymphoblastic leukemia, followed by acute myelocytic leukemia and T-cell acute lymphoblastic leukemia. Lymphomas (13.4%) and bone and soft tissue cancers (21.8%) were also represented. The mean duration of hospital stay was 24.84 ± 20.32 days for the overall PICU population. Outcomes were favorable, with 85.5% of patients discharged successfully (Table 1 ). Central Line Characteristics and Utilization: Device characteristics are detailed in Table 2 . The device utilization ratio (DUR) for the PICU cohort was calculated, and within this group, children with underlying hemato-oncological diagnoses had longer central line durations. This difference was largely due to the predominant use of PICC lines for chemotherapy in hemato-oncological patients, which were maintained for extended periods. The mean ± SD of central line days was 12.0 ± 3.68 in the general PICU population compared with 59.95 ± 40.99 in the hemato-oncology subgroup (p < 0.001). Table 2 Device characteristics of central lines in children admitted to the pediatric intensive care unit (PICU) versus the hemato-oncological (HO) unit Type of central line Total;[n = 69](%) PICU; [n = 46](%) HO; [n = 23](%) p-value PICC line 19 (23.54%) 0 19 (82.60%) - Jugular (including reinsertions) 39 (56.52%) 32 (69.56%) 7 (30.43%) - Subclavian 14 (20.23%) 12 (26.09%) 2 ( 8.69%) - Femoral 7 (10.14%) 6 (13.04%) 1 (4.34%) - Device Utilization Ratio (DUR) 1.06 0.45 2.04 - Mean + SD of DUR 1.46 ± 2.22 0.59 ± 0.24 3.18 ± 3.25 < 0.001 Median IQR of DUR [Q1,Q3] 0.75 [0.50,1.39] 0.57 [0.43, 0.77] 2.3 [1.39, 3.64] < 0.001 Total number of central line (CL) days 1931 ( 100%) 552 (28.59%) 1379 (71.41%) - Mean number ± Standard deviation of CL days 27.98 ± 33 12 ± 3.68 59.95 ± 40.99 < 0.001 Median IQR of CL days [Q1,Q3] 15 [8,32] 10 [7,16] 49 [32,95] < 0.001 CLABSI (total number) 13 (18.84%) 6 (13.04%) 7 (30.43%) - CLABSI incidence/ 1000 CL days 6.73 per 1000 CL days 10.87 per 1000 CL days 5.08 per 1000 CL days - The most common indication for central line insertion was ionotropic support and administration of multiple intravenous drugs, accounting for nearly half of all cases (46%). Chemotherapy represented the next most frequent indication (32%), predominantly in children with underlying hemato-oncological conditions. Other reasons included difficult peripheral IV access (15%), prolonged antibiotic therapy (6%), and less commonly perioperative support for surgery (3%). CLABSI Incidence: A total of 13 CLABSI episodes were identified during the study period. The overall CLABSI incidence in the PICU cohort is presented in Table 2 . Although line duration was longer among hemato-oncological patients, their CLABSI incidence was lower than that observed in other PICU patients with shorter-duration central lines. This finding suggests potentially protective practices in the HO unit. Microbiological Profile and Antimicrobial Resistance: Gram-negative organisms accounted for 76.9% (n = 10) of isolates. Six of these were from patients with hemato-oncological conditions. Gram-positive organisms were isolated in 15.4% (n = 2), one each from a child with and without hemato-oncological disease. Fungal infection was identified in one PICU patient (7.7%). The species distribution is illustrated in Fig. 1 . Antimicrobial resistance patterns are depicted in Figs. 2 and 3 . Risk Factors Associated with CLABSI: Central line–related and non-central line–related risk factors were analyzed (Table 3 ). Elevated odds ratios (OR) were observed for PICC line (OR 2.193), femoral line (OR 2.2), and central line duration longer than two weeks (OR 3.333). Among non-central line factors, use of more than two antibiotics (OR 3.636) and blood product administration (OR 2.833) were associated with higher odds of CLABSI. However, none of these reached statistical significance. Table 3 Risk factors associated with CLABSI among children admitted to the pediatric intensive care unit (PICU) versus the hemato-oncological (HO) unit Risk factor Odds Ratio (OR) 95% Confidence interval P value Central line related risk factors: PICC line 2.193 0.600–8.021 0.235 Femoral line 2.2 0.361–13.370 0.392 Jugular line 1.052 0.163–6.776 0.957 Subclavian line 0.770 0.143–4.138 0.761 Central Line duration more than 2 weeks 3.333 0.816–13.602 0.093 Non central line related risk factors : Mechanically ventilated 0.793 0.225–2.797 0.791 ANC more than 500 0.181 0.010–3.151 0.241 Inotropic support 0.739 0.199–2.744 0.652 More than two antibiotics 3.636 0.729–18.131 0.115 Chemotherapy 1.535 0.400–5.883 0.531 Blood product usage 2.833 0.597–13.437 0.190 Antifungal therapy 1.136 0.320–4.028 0.843 Discussion: CLABSI is increasingly recognized not only as an infectious complication but also as a sentinel patient safety event. Our findings add to the quality improvement literature from resource-limited PICUs. It also highlights the practical challenges of central line care in critically ill children and provides comparative insights between pediatric intensive care and hemato-oncology patients. The inclusion of a hemato-oncology comparator group was deliberate: by contrasting these populations, we aimed not only to measure incidence but also to identify transferable quality and safety practices. Central lines were most often required for ionotropic support and multiple drug infusions in the PICU, whereas chemotherapy was the dominant indication among hemato-oncology patients. These differences influenced line duration and utilization ratios: oncology patients had longer line dwell times but a lower CLABSI incidence, while PICU patients, despite shorter line use, experienced higher infection rates. This contrast underscores the importance of tailoring infection prevention strategies to patient profile and clinical environment. Maintaining sterility in the PICU posed challenges not typically encountered in oncology wards. Urgent line placements during resuscitation limited adherence to full aseptic precautions. Frequent manipulations for blood sampling, medication delivery, and concurrent invasive devices increased contamination risk. In addition, variable staff experience and the rotation of trainees made consistent compliance with bundle protocols difficult, despite daily checklist use. These findings highlight the critical role of ongoing staff training, supervision, and reinforcement of line care protocols in the intensive care setting. The lower CLABSI rates in hemato-oncology, despite prolonged line exposure, suggest that elective insertions, specialized nursing, and structured protocols may have contributed. These practices could inform quality improvement initiatives in our PICU. The microbiological profile revealed a predominance of gram-negative organisms, consistent with national surveillance data and prior Indian studies. 1 – 3 In our PICU, these pathogens demonstrated substantial resistance to cephalosporins and carbapenems, though colistin retained activity. By contrast, the oncology subgroup, while also dominated by gram-negative organisms, demonstrated lower rates of resistance and fewer fungal infections. This likely reflects differences in antimicrobial exposure, patient acuity, and care environment. Pediatric HO unit data from India remain sparse 4 – 5 ; however, emerging reports from newly established hemato-oncology services in the country highlight practical challenges in line maintenance and the potential role of alternative devices such as midlines. 22 Studies from both Indian and international oncology cohorts have shown that structured bundle approaches can reduce device-associated infections, 23 and that CLABSI epidemiology in ambulatory pediatric oncology varies significantly depending on risk profiles and care practices. 24 – 25 Together, these findings reinforce the importance of tailored infection-prevention strategies in the hemato-oncology setting. Risk factors such as prolonged central line duration, femoral insertion, PICC use, exposure to multiple antibiotics, and blood product administration were associated with increased odds of CLABSI, though statistical significance was not reached. These trends align with prior studies, including Karagiannidou et al., who reported risk factors like multiple CVCs, mechanical ventilation, and severe neutropenia, 26 and Woods-Hill et al., who identified hematological and immunological conditions, malignancies, and prolonged CVC use as significant predictors. 10 Other studies have highlighted the contribution of steroid use, blood product exposure, and parenteral nutrition. 11 – 13 Pediatric oncology patients are particularly vulnerable due to underlying immunosuppression, with increased risk in patients with acute myeloid leukemia and high-risk acute lymphoblastic leukemia subgroups. 9 , 27 – 28 National data from the Antimicrobial Resistance Research and Surveillance Network (AMRSN) and the ICMR in 2022 reported a high prevalence of gram-negative organisms (70.9%), compared to gram-positive species (16.9%) and fungi (12.2%) across ICUs. 21 A New Delhi study showed a similar predominance of gram-negative isolates (72.6%), 15 while Singhal et al. reported higher gram-positive prevalence (79%) and yeast species (13%). 4 Indian studies have also documented substantial resistance to carbapenems and cephalosporins among gram-negative bacteria. 5 Globally, resistance patterns vary: in the United States, staphylococcal species show high methicillin resistance 29 , with Klebsiella pneumoniae and Candida parapsilosis among frequent PICU pathogens. 30 Italy has reported Enterobacteriaceae and Staphylococcus aureus as leading pathogens, 31 Brazil documented Klebsiella pneumoniae dominance, 32 and Poland described Pseudomonas aeruginosa and Staphylococcus epidermidis as common, along with frequent Candida isolates. 33 Middle Eastern countries have highlighted Candida parapsilosis and extended-spectrum beta-lactamase (ESBL)–producing gram-negative pathogens. 34 In Egypt, Klebsiella species showed low sensitivity to carbapenems, 16 while Oman reported high resistance among gram-positive organisms and high case fatality rates for gram-negative infections. 20 Taken together, our study underscores that central line management in the PICU requires heightened vigilance and adaptation to high-acuity care, whereas hemato-oncology patients, though immunocompromised, may benefit from standardized protocols and relatively stable clinical settings. Integrating routine surveillance, optimizing antimicrobial stewardship, and strengthening team-based accountability can help bridge these differences. Implications for Practice and Quality Improvement The findings of this study reinforce that CLABSI prevention is not only dependent on adherence to bundle components but also on the broader context of care. In the PICU, where central lines are frequently inserted under urgent conditions and handled by multiple providers, sustaining sterility requires regular staff training, real-time supervision, and process audits. In contrast, oncology patients benefit from structured protocols and predictable line use, suggesting that lessons from hemato-oncology care can be adapted to the intensive care environment. Implementing targeted surveillance, optimizing antimicrobial stewardship, and strengthening team-based accountability can further reduce infection rates and improve outcomes in resource-limited settings. 35 Conclusion: In our unit, we observed that while hemato‑oncology patients had central lines for longer durations, their lower incidence of CLABSI compared to general PICU patients indicates that care practices, not just exposure, influence outcomes. The high resistance among gram‑negative pathogens emphasizes that prevention must go hand in hand with antimicrobial stewardship. Moving forward, we plan to adopt and monitor strict central line insertion and maintenance bundles, enhance staff training, and strengthen surveillance as part of our ongoing quality improvement efforts. These changes are likely to improve patient safety in pediatric intensive care in settings like ours. Learning from hemato-oncology practices may help strengthen central line safety in PICUs, especially in resource-limited settings. Limitations: This study has several limitations. It was conducted in a single tertiary care center with a modest sample size, which may restrict generalizability. Illness severity scoring systems such as PRISM III or PIM3 were not applied, limiting adjustment for baseline risk. Long-term outcomes of patients with CLABSI, including readmissions, chronic morbidity, and healthcare costs, were not evaluated. While device utilization ratio (DUR) was used to compare trends within this cohort, its broader applicability across different settings requires further validation. In addition, the comparative performance of PICC lines and CVCs in pediatrics remains underexplored, warranting further studies in larger, multicenter cohorts. Abbreviations CLABSI – Central Line-Associated Bloodstream Infection PICU – Pediatric Intensive Care Unit HO – Hemato-Oncology PICC – Peripherally Inserted Central Catheter CL – Central Line DUR – Device Utilization Ratio CDC – Centers for Disease Control and Prevention LCBI – Laboratory Confirmed Bloodstream Infection NHSN – National Healthcare Safety Network ICMR – Indian Council of Medical Research BSI – Bloodstream Infection CVC – Central Venous Catheter HAIs – Hospital Acquired Infections MIC – Minimum Inhibitory Concentration SD – Standard Deviation IQR – Interquartile Range OR – Odds Ratio ANC – Absolute Neutrophil Count TMP-SMX – Trimethoprim-Sulfamethoxazole Declarations Disclaimers: None Ethics approval and consent to participate: Ethical approval for this study was obtained on 11/08/2022 from the Institutional Ethics Committee of Bharati Vidyapeeth Deemed to be University Medical college, approval number: BVDUMC / IEC / 36. Written informed consent was obtained from the parents or legal guardians of all participants prior to enrolment in the study. Additionally assent was obtained from children wherever appropriate. Consent for publication: An informed consent has been taken as mentioned above. No details, images or videos are included in the manuscript. Availability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Source(s) of support in the form of grants/ funding, equipment, drugs, or all of these: None Registration number, in case of a registered clinical trial: Not applicable Conflicts of interest of each author: None. The authors declare that they have no competing interests Funding : None Manuscript has been read and approved by all the authors, requirements for authorship have been met, and each author believes that the manuscript represents honest work. Author contributions: Acknowledgements: The Department of Pediatrics at Bharati Vidyapeeth Medical College, Hospital and Research Centre, Pune. References Centers for Disease Control and Prevention. Bloodstream infection event (Central Line-Associated bloodstream infection and non-central line associated bloodstream infection). Device-associated Module. 2024;4(2):1–20. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf Pronovost PJ, Cleeman JI, Wright D, Srinivasan A. Fifteen years after To Err is Human: a success story to learn from. BMJ Qual Saf. 2016;25(6):396–9. 10.1136/bmjqs-2015-004720 . Prestel C, Fike L, Patel P, Dudeck M, Edwards J, Sinkowitz-Cochran R, et al. A review of pediatric central line-associated bloodstream infections reported to the National Healthcare Safety Network: United States, 2016–2022. J Pediatr Infect Dis Soc. 2023;12(9):519–21. 10.1093/jpids/piad057 . Singhal T, Shah S, Thakkar P, Naik R. The incidence, aetiology and antimicrobial susceptibility of central line-associated bloodstream infections in intensive care unit patients at a private tertiary care hospital in Mumbai, India. Indian J Med Microbiol. 2019;37(4):521–6. 10.4103/ijmm.IJMM_19_19 . Tomar S, Lodha R, Das B, Sood S, Kapil A. Central line-associated bloodstream infections (CLABSI): microbiology and antimicrobial resistance pattern of isolates from the pediatric ICU of a tertiary care Indian hospital. Clin Epidemiol Glob Health. 2015;3(Suppl 1):S16–9. 10.1016/j.cegh.2015.09.001 . Sellamuthu R, Nair S, Chandrasekar J, Kesavan S, Shivam V. Risk factors of central line-associated bloodstream infection (CLABSI): a prospective study from a paediatric intensive care unit in South India. Cureus. 2023;15(8):e43789. 10.7759/cureus.43789 . Kannan A, Pratyusha K, Thakur R, Sahoo MR, Jindal A. Infections in critically ill children. Indian J Pediatr. 2023;90(3):289–97. 10.1007/s12098-022-04390-3 . Scarselli A, Smarrazzo A, De Sanctis F, Ravà L, Carletti M, Ciofi Degli Atti M, et al. The burden of central line-associated bloodstream infections in children with medical complexity. J Vasc Access. 2023;24(2):198–204. 10.1177/11297298221144784 . National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. National guidelines for infection prevention and control in healthcare facilities. 2020. Available from: https://ncdc.mohfw.gov.in/wp-content/uploads/2024/03/83538105781625557301.pdf Woods-Hill CZ, Srinivasan L, Schriver E, Haj-Hassan T, Bezpalko O, Sammons JS. Novel risk factors for central-line associated bloodstream infections in critically ill children. Infect Control Hosp Epidemiol. 2020;41(1):67–72. 10.1017/ice.2019.274 . Ares G, Hunter CJ. Central venous access in children: indications, devices, and risks. Curr Opin Pediatr. 2017;29(3):340–6. 10.1097/MOP.0000000000000492 . İşgüder R, Devrim İ, Ceylan G, Kara A, Gülfidan G, Ağin H. Risk factors for recurrent central line-associated bloodstream infections in a pediatric intensive care unit. Turk J Med Sci. 2017;47(4):1128–36. 10.3906/sag-1608-59 . Wylie MC, Graham DA, Potter-Bynoe G, Kleinman ME, Randolph AG, Costello JM, et al. Risk factors for central line–associated bloodstream infection in pediatric intensive care units. Infect Control Hosp Epidemiol. 2010;31(10):1049–56. 10.1086/656596 . Diekema DJ, Beekmann SE, Chapin KC, Morel KA, Munson E, Doern GV. Epidemiology and outcome of nosocomial and community-onset bloodstream infection. J Clin Microbiol. 2003;41(8):3655–60. 10.1128/JCM.41.8.3655-3660.2003 . Centers for Disease Control and Prevention. Vital signs: central line-associated bloodstream infections—United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep. 2011;60(8):243–8. Abdelmoneim H, Ibrahim H, Ahmed A, Mohammed K. Incidence of Central Line-Associated Blood Steam Infection in Pediatric Intensive Care Unit (PICU). Egypt J Hosp Med. 2020;78(1):136–41. 10.21608/ejhm.2020.68483 . Ziegler MJ, Pellegrini DC, Safdar N. Attributable mortality of central line-associated bloodstream infection: systematic review and meta-analysis. Infection. 2015;43(1):29–36. 10.1007/s15010-014-0701-2 . Nowak JE, Brilli RJ, Lake MR, Sparling KW, Butcher J, Schulte M, et al. Reducing catheter-associated bloodstream infections in the pediatric intensive care unit: business case for quality improvement. Pediatr Crit Care Med. 2010;11(5):579–87. 10.1097/PCC.0b013e3181ce75d3 . Rosenthal VD. Central line–associated bloodstream infections in limited-resource countries: a review of the literature. Clin Infect Dis. 2009;49(12):1899–907. 10.1086/648439 . Lutwick L, Al-Maani AS, Mehtar S, Memish Z, Rosenthal VD, Dramowski A, et al. Managing and preventing vascular catheter infections: a position paper of the International Society for Infectious Diseases. Int J Infect Dis. 2019;84:22–9. 10.1016/j.ijid.2019.03.025 . Indian Council of Medical Research, Bhargava B, Tandon N. Standard operating procedures: bacteriology antimicrobial resistance surveillance and research network. 2nd ed. Indian Council of Medical Research. 2019. Available from: https://main.icmr.nic.in/sites/default/files/guidelines/Bacteriology_SOP_2nd_Ed_2019.pdf Kundavaram R, Abraham AR, Chaudhary NK, Tadepalli K, Malik S. Safety and utility of various intravenous access devices in a newly established pediatric hematology oncology unit in Central India: is midline an acceptable option? Future Health. 2023;1:35–40. 10.1016/j.fh.2023.11.001 . Prakash SS, Rajshekar D, Cherian A, Sastry AS. Care bundle approach to reduce device-associated infections in a tertiary care teaching hospital, South India. J Lab Physicians. 2017;9(4):273–8. 10.4103/JLP.JLP_100_17 . Rinke ML, Milstone AM, Chen AR, Mirski K, Bundy DG, Colantuoni E, et al. Ambulatory pediatric oncology CLABSIs: epidemiology and risk factors. Pediatr Blood Cancer. 2013;60(11):1882–9. 10.1002/pbc.24627 . Özalp Gerçeker G, Yardımcı F, Aydınok Y. Central line–associated bloodstream infections in children with hematologic and oncologic diseases: first prevalence results from a university hospital. J Pediatr Oncol Nurs. 2019;36(5):327–36. 10.1177/1043454219856705 . Karagiannidou S, Zaoutis T, Maniadakis N, Papaevangelou V, Kourlaba G. Attributable length of stay and cost for pediatric and neonatal central line-associated bloodstream infections in Greece. J Pediatr. 2021;232:253–e2612. 10.1016/j.jpeds.2021.01.023 . Ahluwalia J, Kataria K, Kumar S, Bhalla AK, Bains HS. Effect of central line bundle implementation on central line-associated bloodstream infection rates in a tertiary care hospital. Indian J Crit Care Med. 2018;22(9):633–6. 10.5005/jp-journals-10071-22936 . Miller MR, Griswold M, Harris JM, Yenokyan G, Huskins WC, Moss M, et al. Decreasing PICU catheter-associated bloodstream infections: NACHRI’s quality transformation efforts. Pediatrics. 2010;125(2):206–13. 10.1542/peds.2009-1382 . Ezhumalai G, Manoharan M, Rameshkumar K, Chandramohan M, Suresh S. Impact of central line bundle implementation on incidence of central line-associated bloodstream infection in a tertiary care hospital. Indian J Crit Care Med. 2018;22(11):781–6. 10.5005/jp-journals-10071-23029 . Haddadin Y, Annamaraju P, Regunath H. Central line associated blood stream infections. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430891/ Kim JY, Jung MJ, Kim MJ, Jung JY. Effectiveness of central line bundles in reducing central line-associated bloodstream infections in neonatal and pediatric ICU: a systematic review and meta-analysis. Int J Environ Res Public Health. 2021;18(22):11998. 10.3390/ijerph182211998 . Bala I, Mishra P, Pawar M, Kapoor PM, Vohra V, Agarwal J, et al. ISCCM guidelines for the prevention of hospital-acquired infections in intensive care unit. Indian J Crit Care Med. 2023;27(3):203–28. 10.5005/jp-journals-10071-24393 . Maki DG, Kluger DM, Crnich CJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc. 2006;81(9):1159–1171. 10.4065/81.9.1159 Kaplan R, Aucoin J, Brewer C, Jensen D, Adams G, Schwartz M, et al. Impact of a quality improvement bundle on central line maintenance and CLABSI rates in pediatric oncology patients. Pediatr Qual Saf. 2022;7(5):e591. 10.1097/pq9.0000000000000591 . Schulman J, Stricof R, Stevens TP, Horgan M, Gase K, Holzman IR, et al. Statewide NICU central-line–associated bloodstream infection rates decline after bundles and checklists. Pediatrics. 2011;127(3):436–44. 10.1542/peds.2010-1722 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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00:23:00","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":134499,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7851349/v1/2125f50bdd4e75d4c23bcecc.html"},{"id":97744592,"identity":"7dfb9cce-674c-475b-a55d-2a55dee295be","added_by":"auto","created_at":"2025-12-09 00:22:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":210161,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eDistribution of microbiological organism between the pediatric intensive care unit (PICU) versus the hemato-oncology (HO) unit\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e","description":"","filename":"Figure1BMC300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-7851349/v1/6f5b34b86288c37e02aa6504.png"},{"id":97744591,"identity":"a4636467-7369-4d18-98c1-665859f95eba","added_by":"auto","created_at":"2025-12-09 00:22:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":354956,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eAntimicrobial resistance patterns of various microbiological species isolated from central and peripheral lines in the pediatric intensive care unit (PICU)\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNote: Only one fungal organism, Candida parapsilosis was isolated, which was pan sensitive.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(antifungals tested: fluconazole, micafungin, voriconazole, caspofungin and amphotericin B). TMP - SMX - Trimethoprim - sulfamethoxazole\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2BMC300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-7851349/v1/252352acce64b54c149cfadf.png"},{"id":97896881,"identity":"e67b7775-110d-4c82-aaff-ff43eb547848","added_by":"auto","created_at":"2025-12-10 15:37:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":312230,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eAntimicrobial resistance patterns of various microbiological species isolated from central and peripheral lines in the hemato-oncology (HO) unit\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNote: No fungal organisms were isolated in the HO unit. TMP - SMX - Trimethoprim - sulfamethoxazole\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3BMC300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-7851349/v1/1729c95ea2c86d908876f65d.png"},{"id":99790158,"identity":"49058343-e76b-4a77-9a91-98d4f5efc642","added_by":"auto","created_at":"2026-01-08 12:56:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2382010,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7851349/v1/0b5e818d-40da-42c9-82d2-dcf0e65ed8dd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Central line–associated bloodstream infections in the pediatric intensive care and hemato-oncology unit: a prospective observational study from Western India","fulltext":[{"header":"Key Message","content":"\u003cul\u003e\n\u003cli\u003eCLABSI remains a significant safety challenge in our PICU, particularly among patients undergoing urgent line insertions.\u003c/li\u003e\n\u003cli\u003eHemato‑oncology patients had longer line use but lower CLABSI rates, suggesting possible protective practices worth adapting across PICU.\u003c/li\u003e\n\u003cli\u003eHigh prevalence of gram‑negative organisms with major resistance highlights the urgent need for local antimicrobial stewardship.\u003c/li\u003e\n\u003cli\u003eQuality improvement interventions \u0026mdash; central line bundles, staff training, standardized insertion/maintenance protocols \u0026mdash; are essential to reduce CLABSI in resource‑limited pediatric settings.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction:","content":"\u003cp\u003eCentral venous catheters (CVCs) are essential in pediatric intensive care units (PICUs) for administration of fluids, parenteral nutrition, antibiotics, inotropes, chemotherapy, and hemodynamic monitoring. Despite their benefits, central lines are associated with a wide range of complications including infection, thrombosis, and mechanical problems, which may contribute to increased morbidity, mortality, and healthcare costs.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Among these, central line-associated bloodstream infections (CLABSI) remain one of the most significant.\u003c/p\u003e\u003cp\u003eCLABSI is defined as per Center for Disease Control (CDC) guidelines as an identified eligible blood stream organism (a laboratory confirmed bloodstream infection (LCBI), not secondary to an infection at another body site) in a patient with an eligible central line (placed for more than two consecutive calendar days) present on the day of event of LCBI.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The CDC via the National Healthcare Safety network (NHSN), has implemented a robust reporting system for CLABSI, wherein it was observed that CLABSI rates have reduced from 7.9 per 1000 central line days in 1992\u0026ndash;1999, to 0.8 per 1000 central line days in 2013, and has remained\u0026thinsp;\u0026lt;\u0026thinsp;1 per 1000 central line days from the 2016\u0026ndash;2022, in PICUs across the USA. \u003csup\u003e2\u0026ndash;3\u003c/sup\u003e In India, the Indian Council of Medical Research (ICMR) also provides annual CLABSI data and reports the total bloodstream infection (BSI) rate in the PICU as 3.74 per 1000 patient days. CLABSI rates in the pediatric population, as reported by certain Indian studies, are variable ranging from between 5 to 15 per 1000 central line days.\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe most common organisms associated with CLABSI include gram-negative bacilli such as \u003cem\u003eKlebsiella, Pseudomonas, Acinetobacter\u003c/em\u003e, and \u003cem\u003eProteus\u003c/em\u003e, along with gram-positive species like \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e and fungal pathogens such as \u003cem\u003eCandida albicans\u003c/em\u003e.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Antimicrobial resistance is an increasing concern, particularly in Indian studies, with gram-negative bacilli frequently resistant to quinolones, third- and fourth-generation cephalosporins, and carbapenems.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Therefore, ongoing surveillance of microbiological patterns and antimicrobial resistance is essential to guide empirical therapy and infection prevention strategies in PICUs.\u003c/p\u003e\u003cp\u003eSeveral risk factors for CLABSI have been described, including deficiencies in hand hygiene, barrier precautions, skin antisepsis, or central line maintenance; patient-related factors such as malignancy, frequent transfusions, prior CLABSI, and need for parenteral nutrition; and equipment-related factors such as multi-lumen catheters or non-sterile hubs.\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Bundle-based checklists have been shown to reduce risk, but adherence remains variable, especially in resource-limited settings.\u003c/p\u003e\u003cp\u003eCLABSI is one of the major contributors to healthcare-associated infections (HAIs) in pediatric inpatient settings, leading to prolonged hospitalisation, higher costs, and increased morbidity and mortality.\u003csup\u003e\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Hence, studies describing central line use, incidence of CLABSI, associated risk factors, and microbiological trends are vital for improving patient outcomes and ensuring safety, particularly in low- and middle-income country (LMIC) settings.\u003c/p\u003e\u003cp\u003eChildren with underlying hemato-oncological conditions often represent a unique subgroup of PICU patients, as they frequently require prolonged central venous access and have distinct risk profiles. Differences in risk factors and usage patterns between PICU patients in general and those with hemato-oncological conditions highlight the need for targeted research. The present study therefore describes central line practices and outcomes in a tertiary PICU, with a specific focus on CLABSI, while also comparing findings with a hemato-oncology subgroup whose structured care might provide insights into safer practices applicable to PICU.\u003c/p\u003e"},{"header":"Objectives:","content":"\u003cp\u003ePrimary Objective:\u003c/p\u003e\u003cp\u003eTo describe the patterns, indications, and outcomes of central line use in the Pediatric Intensive Care Unit (PICU) of a tertiary care hospital\u003c/p\u003e\u003cp\u003eSecondary Objectives:\u003c/p\u003e\u003cp\u003eTo determine the incidence and microbiological profile of central line-associated bloodstream infections (CLABSI) in the PICU\u003c/p\u003e"},{"header":"Materials and Methods:","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStudy design:\u003c/h2\u003e\u003cp\u003eThis was a prospective observational study conducted in the pediatric intensive care unit (PICU) of a tertiary care teaching hospital in Western India over a 24-month period. Children with underlying hemato-oncological conditions admitted to the PICU formed a predefined subgroup for analysis. Approval was obtained from the Institutional Ethics Committee (BVDUMC/IEC/36 dated 11/08/2022), and informed written consent was obtained from parents or guardians; assent was taken from older children as applicable.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants:\u003c/h3\u003e\n\u003cp\u003eWe included all pediatric patients (1 month\u0026ndash;18 years) admitted to the PICU who required central venous catheterization for any indication. Central venous catheters (CVCs) included peripherally inserted central catheters (PICC), internal jugular, subclavian, and femoral catheters. Patients with hemato-oncological diagnoses admitted to the PICU were analyzed and compared with the PICU group.\u003c/p\u003e\n\u003ch3\u003eData Collection:\u003c/h3\u003e\n\u003cp\u003eFor each patient, demographic details, comorbidities, initial clinical and laboratory parameters, central line type and indication, associated devices (endotracheal tube, urinary catheter), antimicrobial use and sensitivity patterns, blood product and chemotherapy administration, length of hospitalization, and outcomes were recorded.\u003c/p\u003e\u003cp\u003ePositive culture reports were considered if differential growth between the central and peripheral cultures was observed, at least 48 hours after insertion of the central line, when CLABSI was suspected clinically.\u003c/p\u003e\n\u003ch3\u003eCentral Line Devices and Maintenance:\u003c/h3\u003e\n\u003cp\u003eIn the PICU, a double-lumen radio-opaque polyurethane CVC was routinely used, while PICC lines consisted of single-lumen biostable polyurethane catheters with StatLock\u0026trade; stabilization devices. For every insertion, a CLABSI bundle checklist was followed, including strict hand hygiene, maximal barrier precautions, and skin antisepsis. Reinsertion was considered a new episode, and the checklist was reapplied. Daily checklist adherence was monitored during PICU stay. All insertions were performed by trained personnel, and staff underwent periodic reinforcement sessions on central line insertion and maintenance protocols.\u003c/p\u003e\u003cp\u003eChildren discharged from the PICU with PICC lines (e.g., those with underlying hemato-oncological conditions) were followed up weekly in the hospital for dressing changes and review of any new symptoms (fever, local site changes, systemic instability). Suspected CLABSI prompted paired blood cultures (central and peripheral) and further work-up.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eDefinitions and Microbiological Methods:\u003c/h2\u003e\u003cp\u003eCLABSI was defined according to CDC\u0026ndash;NHSN criteria.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e When CLABSI was suspected, blood culture samples were collected simultaneously from central and peripheral sites, at least 48 hours after insertion. Pediatric blood culture bottles (BD BACTEC\u0026trade; Peds Plus\u0026trade;/Fenriched Soybean-Casein Digest broth with CO2) were used. Standard ICMR guidelines for asepsis and sample volume were followed.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Positive cultures were subjected to gram staining, species identification by the VITEK system, and antimicrobial susceptibility testing using Kirby-Bauer disc diffusion. Minimum inhibitory concentrations (MICs) were reported as per standard guidelines.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003e​​Statistical Analysis:\u003c/h3\u003e\n\u003cp\u003eData were analyzed using SPSS version 29. Descriptive statistics (mean, standard deviation, frequency) were used for baseline characteristics. Normality was assessed with the Shapiro\u0026ndash;Wilk test and histograms. Continuous variables were compared using the independent samples t-test or Mann\u0026ndash;Whitney U test, as appropriate; categorical variables were compared using the Chi-square or Fisher\u0026rsquo;s exact test. Univariate logistic regression identified risk factors associated with CLABSI. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003ch3\u003eDevice Utilization and CLABSI Rates:\u003c/h3\u003e\n\u003cp\u003eDevice utilization ratio (DUR) and CLABSI incidence were calculated as:\u003c/p\u003e\u003cp\u003eDUR\u0026thinsp;=\u0026thinsp;Number of central line days\u003c/p\u003e\u003cp\u003eNumber of patient days\u003c/p\u003e\u003cp\u003eCLABSI incidence rate\u0026thinsp;=\u0026thinsp;Number of CLABSIs x 1000\u003c/p\u003e\u003cp\u003eNumber of central line days\u003c/p\u003e"},{"header":"Results:","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePatient Characteristics:\u003c/h2\u003e\u003cp\u003eA total of 69 children, with 1931 central line days, were consecutively enrolled in the study upon admission to the PICU. Demographics, diagnoses, duration of hospitalization, and outcomes are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Overall, females accounted for 55.1% of the study population. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD age in the PICU cohort was 4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;5.46 years. Children with underlying hemato-oncological diagnoses admitted to the PICU were older on average (8.06\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of the population of children admitted to the pediatric intensive care unit (PICU) versus the hemato-oncological (HO) unit\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal [n (%)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePICU [n (%)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHO [n (%)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of patients\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e69 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (66.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 (33.34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean age\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard deviation (SD) in years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.44\u0026thinsp;\u0026plusmn;\u0026thinsp;5.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;5.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.06\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (44.93%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (39.13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (56.52%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38 (55.07%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (60.87%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (43.48%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiagnosis*\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedical\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 (57.97%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgical\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (20.29%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOncological\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (30.43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal duration of hospital stay in days\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.34\u0026thinsp;\u0026plusmn;\u0026thinsp;20.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.84\u0026thinsp;\u0026plusmn;\u0026thinsp;20.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29.34\u0026thinsp;\u0026plusmn;\u0026thinsp;19.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.382\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDischarged\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (81.16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (80.44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (82.61%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDeath\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (14.49%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (13.04%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (17.39%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDischarged on request\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2.90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (4.35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDischarged against medical advice\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.45%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(2.17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e*Note: An overlap of the diagnosis; medical surgical and oncological, was noted in the study population in certain patients and hence were counted in both diagnostic categories\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePurely medical diagnoses were the most common in the PICU, including neurological (20.8%), respiratory (19%), gastrointestinal (7.9%), and cardiac (4.7%) illnesses, while others had multisystem involvement. Among the subgroup of children with hemato-oncological conditions, hematological malignancies (65.2%) predominated, mainly pre-B cell acute lymphoblastic leukemia, followed by acute myelocytic leukemia and T-cell acute lymphoblastic leukemia. Lymphomas (13.4%) and bone and soft tissue cancers (21.8%) were also represented.\u003c/p\u003e\u003cp\u003eThe mean duration of hospital stay was 24.84\u0026thinsp;\u0026plusmn;\u0026thinsp;20.32 days for the overall PICU population. Outcomes were favorable, with 85.5% of patients discharged successfully (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eCentral Line Characteristics and Utilization:\u003c/h2\u003e\u003cp\u003eDevice characteristics are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The device utilization ratio (DUR) for the PICU cohort was calculated, and within this group, children with underlying hemato-oncological diagnoses had longer central line durations. This difference was largely due to the predominant use of PICC lines for chemotherapy in hemato-oncological patients, which were maintained for extended periods. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of central line days was 12.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.68 in the general PICU population compared with 59.95\u0026thinsp;\u0026plusmn;\u0026thinsp;40.99 in the hemato-oncology subgroup (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDevice characteristics of central lines in children admitted to the pediatric intensive care unit (PICU) versus the hemato-oncological (HO) unit\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eType of central line\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal;[n\u0026thinsp;=\u0026thinsp;69](%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePICU; [n\u0026thinsp;=\u0026thinsp;46](%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHO; [n\u0026thinsp;=\u0026thinsp;23](%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePICC line\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (23.54%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (82.60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eJugular\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(including reinsertions)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (56.52%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (69.56%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (30.43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSubclavian\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (20.23%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (26.09%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 ( 8.69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemoral\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (10.14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (13.04%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (4.34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDevice Utilization Ratio (DUR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean\u0026thinsp;+\u0026thinsp;SD of DUR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.46 \u0026plusmn; 2.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.59 \u0026plusmn; 0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.18 \u0026plusmn; 3.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedian IQR of DUR [Q1,Q3]\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.75 [0.50,1.39]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.57 [0.43, 0.77]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.3 [1.39, 3.64]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal number of central line (CL) days\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1931 ( 100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e552 (28.59%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1379 (71.41%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean number\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard deviation\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eof CL days\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27.98\u0026thinsp;\u0026plusmn;\u0026thinsp;33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;3.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59.95\u0026thinsp;\u0026plusmn;\u0026thinsp;40.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedian IQR of CL days [Q1,Q3]\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 [8,32]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 [7,16]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e49 [32,95]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLABSI (total number)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (18.84%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (13.04%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (30.43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLABSI incidence/ 1000 CL days\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.73 per 1000 CL days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.87 per 1000 CL days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.08 per 1000 CL days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe most common indication for central line insertion was ionotropic support and administration of multiple intravenous drugs, accounting for nearly half of all cases (46%). Chemotherapy represented the next most frequent indication (32%), predominantly in children with underlying hemato-oncological conditions. Other reasons included difficult peripheral IV access (15%), prolonged antibiotic therapy (6%), and less commonly perioperative support for surgery (3%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eCLABSI Incidence:\u003c/h2\u003e\u003cp\u003eA total of 13 CLABSI episodes were identified during the study period. The overall CLABSI incidence in the PICU cohort is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Although line duration was longer among hemato-oncological patients, their CLABSI incidence was lower than that observed in other PICU patients with shorter-duration central lines. This finding suggests potentially protective practices in the HO unit.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eMicrobiological Profile and Antimicrobial Resistance:\u003c/h2\u003e\u003cp\u003eGram-negative organisms accounted for 76.9% (n\u0026thinsp;=\u0026thinsp;10) of isolates. Six of these were from patients with hemato-oncological conditions. Gram-positive organisms were isolated in 15.4% (n\u0026thinsp;=\u0026thinsp;2), one each from a child with and without hemato-oncological disease. Fungal infection was identified in one PICU patient (7.7%). The species distribution is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Antimicrobial resistance patterns are depicted in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eRisk Factors Associated with CLABSI:\u003c/h2\u003e\u003cp\u003eCentral line\u0026ndash;related and non-central line\u0026ndash;related risk factors were analyzed (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Elevated odds ratios (OR) were observed for PICC line (OR 2.193), femoral line (OR 2.2), and central line duration longer than two weeks (OR 3.333). Among non-central line factors, use of more than two antibiotics (OR 3.636) and blood product administration (OR 2.833) were associated with higher odds of CLABSI. However, none of these reached statistical significance.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRisk factors associated with CLABSI among children admitted to the pediatric intensive care unit (PICU) versus the hemato-oncological (HO) unit\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRisk factor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOdds Ratio (OR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% Confidence interval\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eCentral line related risk factors:\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePICC line\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.193\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.600\u0026ndash;8.021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.235\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemoral line\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.361\u0026ndash;13.370\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.392\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eJugular line\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.052\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.163\u0026ndash;6.776\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.957\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSubclavian line\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.770\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.143\u0026ndash;4.138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.761\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCentral Line duration more than 2 weeks\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.333\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.816\u0026ndash;13.602\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.093\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNon central line related risk factors\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMechanically ventilated\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.793\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.225\u0026ndash;2.797\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.791\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eANC more than 500\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.181\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.010\u0026ndash;3.151\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.241\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInotropic support\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.739\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.199\u0026ndash;2.744\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.652\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMore than two antibiotics\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.636\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.729\u0026ndash;18.131\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.535\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.400\u0026ndash;5.883\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.531\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBlood product usage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.833\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.597\u0026ndash;13.437\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.190\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAntifungal therapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.320\u0026ndash;4.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.843\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion:","content":"\u003cp\u003eCLABSI is increasingly recognized not only as an infectious complication but also as a sentinel patient safety event. Our findings add to the quality improvement literature from resource-limited PICUs. It also highlights the practical challenges of central line care in critically ill children and provides comparative insights between pediatric intensive care and hemato-oncology patients. The inclusion of a hemato-oncology comparator group was deliberate: by contrasting these populations, we aimed not only to measure incidence but also to identify transferable quality and safety practices.\u003c/p\u003e\u003cp\u003eCentral lines were most often required for ionotropic support and multiple drug infusions in the PICU, whereas chemotherapy was the dominant indication among hemato-oncology patients. These differences influenced line duration and utilization ratios: oncology patients had longer line dwell times but a lower CLABSI incidence, while PICU patients, despite shorter line use, experienced higher infection rates. This contrast underscores the importance of tailoring infection prevention strategies to patient profile and clinical environment.\u003c/p\u003e\u003cp\u003eMaintaining sterility in the PICU posed challenges not typically encountered in oncology wards. Urgent line placements during resuscitation limited adherence to full aseptic precautions. Frequent manipulations for blood sampling, medication delivery, and concurrent invasive devices increased contamination risk. In addition, variable staff experience and the rotation of trainees made consistent compliance with bundle protocols difficult, despite daily checklist use. These findings highlight the critical role of ongoing staff training, supervision, and reinforcement of line care protocols in the intensive care setting. The lower CLABSI rates in hemato-oncology, despite prolonged line exposure, suggest that elective insertions, specialized nursing, and structured protocols may have contributed. These practices could inform quality improvement initiatives in our PICU.\u003c/p\u003e\u003cp\u003eThe microbiological profile revealed a predominance of gram-negative organisms, consistent with national surveillance data and prior Indian studies.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e In our PICU, these pathogens demonstrated substantial resistance to cephalosporins and carbapenems, though colistin retained activity. By contrast, the oncology subgroup, while also dominated by gram-negative organisms, demonstrated lower rates of resistance and fewer fungal infections. This likely reflects differences in antimicrobial exposure, patient acuity, and care environment. Pediatric HO unit data from India remain sparse\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e ; however, emerging reports from newly established hemato-oncology services in the country highlight practical challenges in line maintenance and the potential role of alternative devices such as midlines.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Studies from both Indian and international oncology cohorts have shown that structured bundle approaches can reduce device-associated infections,\u003csup\u003e23\u003c/sup\u003e and that CLABSI epidemiology in ambulatory pediatric oncology varies significantly depending on risk profiles and care practices.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e–\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Together, these findings reinforce the importance of tailored infection-prevention strategies in the hemato-oncology setting.\u003c/p\u003e\u003cp\u003eRisk factors such as prolonged central line duration, femoral insertion, PICC use, exposure to multiple antibiotics, and blood product administration were associated with increased odds of CLABSI, though statistical significance was not reached. These trends align with prior studies, including Karagiannidou et al., who reported risk factors like multiple CVCs, mechanical ventilation, and severe neutropenia,\u003csup\u003e26\u003c/sup\u003e and Woods-Hill et al., who identified hematological and immunological conditions, malignancies, and prolonged CVC use as significant predictors.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Other studies have highlighted the contribution of steroid use, blood product exposure, and parenteral nutrition.\u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Pediatric oncology patients are particularly vulnerable due to underlying immunosuppression, with increased risk in patients with acute myeloid leukemia and high-risk acute lymphoblastic leukemia subgroups.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e–\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNational data from the Antimicrobial Resistance Research and Surveillance Network (AMRSN) and the ICMR in 2022 reported a high prevalence of gram-negative organisms (70.9%), compared to gram-positive species (16.9%) and fungi (12.2%) across ICUs.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e A New Delhi study showed a similar predominance of gram-negative isolates (72.6%),\u003csup\u003e15\u003c/sup\u003e while Singhal et al. reported higher gram-positive prevalence (79%) and yeast species (13%).\u003csup\u003e4\u003c/sup\u003e Indian studies have also documented substantial resistance to carbapenems and cephalosporins among gram-negative bacteria.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Globally, resistance patterns vary: in the United States, staphylococcal species show high methicillin resistance\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, with Klebsiella pneumoniae and Candida parapsilosis among frequent PICU pathogens.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Italy has reported Enterobacteriaceae and Staphylococcus aureus as leading pathogens,\u003csup\u003e31\u003c/sup\u003e Brazil documented Klebsiella pneumoniae dominance,\u003csup\u003e32\u003c/sup\u003e and Poland described Pseudomonas aeruginosa and Staphylococcus epidermidis as common, along with frequent Candida isolates.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e Middle Eastern countries have highlighted Candida parapsilosis and extended-spectrum beta-lactamase (ESBL)–producing gram-negative pathogens.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e In Egypt, Klebsiella species showed low sensitivity to carbapenems,\u003csup\u003e16\u003c/sup\u003e while Oman reported high resistance among gram-positive organisms and high case fatality rates for gram-negative infections. \u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTaken together, our study underscores that central line management in the PICU requires heightened vigilance and adaptation to high-acuity care, whereas hemato-oncology patients, though immunocompromised, may benefit from standardized protocols and relatively stable clinical settings. Integrating routine surveillance, optimizing antimicrobial stewardship, and strengthening team-based accountability can help bridge these differences.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eImplications for Practice and Quality Improvement\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThe findings of this study reinforce that CLABSI prevention is not only dependent on adherence to bundle components but also on the broader context of care. In the PICU, where central lines are frequently inserted under urgent conditions and handled by multiple providers, sustaining sterility requires regular staff training, real-time supervision, and process audits. In contrast, oncology patients benefit from structured protocols and predictable line use, suggesting that lessons from hemato-oncology care can be adapted to the intensive care environment. Implementing targeted surveillance, optimizing antimicrobial stewardship, and strengthening team-based accountability can further reduce infection rates and improve outcomes in resource-limited settings.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Conclusion:","content":"\u003cp\u003eIn our unit, we observed that while hemato‑oncology patients had central lines for longer durations, their lower incidence of CLABSI compared to general PICU patients indicates that care practices, not just exposure, influence outcomes. The high resistance among gram‑negative pathogens emphasizes that prevention must go hand in hand with antimicrobial stewardship. Moving forward, we plan to adopt and monitor strict central line insertion and maintenance bundles, enhance staff training, and strengthen surveillance as part of our ongoing quality improvement efforts. These changes are likely to improve patient safety in pediatric intensive care in settings like ours. Learning from hemato-oncology practices may help strengthen central line safety in PICUs, especially in resource-limited settings.\u003c/p\u003e"},{"header":"Limitations:","content":"\u003cp\u003eThis study has several limitations. It was conducted in a single tertiary care center with a modest sample size, which may restrict generalizability. Illness severity scoring systems such as PRISM III or PIM3 were not applied, limiting adjustment for baseline risk. Long-term outcomes of patients with CLABSI, including readmissions, chronic morbidity, and healthcare costs, were not evaluated. While device utilization ratio (DUR) was used to compare trends within this cohort, its broader applicability across different settings requires further validation. In addition, the comparative performance of PICC lines and CVCs in pediatrics remains underexplored, warranting further studies in larger, multicenter cohorts.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul\u003e\n \u003cli\u003eCLABSI – Central Line-Associated Bloodstream Infection\u003c/li\u003e\n \u003cli\u003ePICU – Pediatric Intensive Care Unit\u003c/li\u003e\n \u003cli\u003eHO – Hemato-Oncology\u003c/li\u003e\n \u003cli\u003ePICC – Peripherally Inserted Central Catheter\u003c/li\u003e\n \u003cli\u003eCL – Central Line\u003c/li\u003e\n \u003cli\u003eDUR – Device Utilization Ratio\u003c/li\u003e\n \u003cli\u003eCDC – Centers for Disease Control and Prevention\u003c/li\u003e\n \u003cli\u003eLCBI – Laboratory Confirmed Bloodstream Infection\u003c/li\u003e\n \u003cli\u003eNHSN – National Healthcare Safety Network\u003c/li\u003e\n \u003cli\u003eICMR – Indian Council of Medical Research\u003c/li\u003e\n \u003cli\u003eBSI – Bloodstream Infection\u003c/li\u003e\n \u003cli\u003eCVC – Central Venous Catheter\u003c/li\u003e\n \u003cli\u003eHAIs – Hospital Acquired Infections\u003c/li\u003e\n \u003cli\u003eMIC – Minimum Inhibitory Concentration\u003c/li\u003e\n \u003cli\u003eSD – Standard Deviation\u003c/li\u003e\n \u003cli\u003eIQR – Interquartile Range\u003c/li\u003e\n \u003cli\u003eOR – Odds Ratio\u003c/li\u003e\n \u003cli\u003eANC – Absolute Neutrophil Count\u003c/li\u003e\n \u003cli\u003eTMP-SMX – Trimethoprim-Sulfamethoxazole\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclaimers:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate: Ethical approval for this study was obtained on 11/08/2022 from the Institutional Ethics Committee of Bharati Vidyapeeth Deemed to be University Medical college, approval number: BVDUMC / \u0026nbsp;IEC / 36. Written informed consent was obtained from the parents or legal guardians of all participants prior to enrolment in the study. Additionally assent was obtained from children wherever appropriate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eAn informed consent has been taken as mentioned above. No details, images or videos are included in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource(s) of support in the form of grants/ funding, equipment, drugs, or all of these:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegistration number, in case of a registered clinical trial:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest of each author:\u003c/strong\u003e None. The authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003eManuscript has been read and approved by all the authors, requirements for authorship have been met, and each author believes that the manuscript represents honest work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"603\" height=\"139\" 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\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e The Department of Pediatrics at Bharati Vidyapeeth Medical College, Hospital and Research Centre, Pune.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCenters for Disease Control and Prevention. Bloodstream infection event (Central Line-Associated bloodstream infection and non-central line associated bloodstream infection). Device-associated Module. 2024;4(2):1\u0026ndash;20. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePronovost PJ, Cleeman JI, Wright D, Srinivasan A. Fifteen years after To Err is Human: a success story to learn from. BMJ Qual Saf. 2016;25(6):396\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmjqs-2015-004720\u003c/span\u003e\u003cspan address=\"10.1136/bmjqs-2015-004720\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrestel C, Fike L, Patel P, Dudeck M, Edwards J, Sinkowitz-Cochran R, et al. A review of pediatric central line-associated bloodstream infections reported to the National Healthcare Safety Network: United States, 2016\u0026ndash;2022. J Pediatr Infect Dis Soc. 2023;12(9):519\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/jpids/piad057\u003c/span\u003e\u003cspan address=\"10.1093/jpids/piad057\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSinghal T, Shah S, Thakkar P, Naik R. The incidence, aetiology and antimicrobial susceptibility of central line-associated bloodstream infections in intensive care unit patients at a private tertiary care hospital in Mumbai, India. Indian J Med Microbiol. 2019;37(4):521\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/ijmm.IJMM_19_19\u003c/span\u003e\u003cspan address=\"10.4103/ijmm.IJMM_19_19\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTomar S, Lodha R, Das B, Sood S, Kapil A. Central line-associated bloodstream infections (CLABSI): microbiology and antimicrobial resistance pattern of isolates from the pediatric ICU of a tertiary care Indian hospital. Clin Epidemiol Glob Health. 2015;3(Suppl 1):S16\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cegh.2015.09.001\u003c/span\u003e\u003cspan address=\"10.1016/j.cegh.2015.09.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSellamuthu R, Nair S, Chandrasekar J, Kesavan S, Shivam V. Risk factors of central line-associated bloodstream infection (CLABSI): a prospective study from a paediatric intensive care unit in South India. Cureus. 2023;15(8):e43789. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.43789\u003c/span\u003e\u003cspan address=\"10.7759/cureus.43789\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKannan A, Pratyusha K, Thakur R, Sahoo MR, Jindal A. Infections in critically ill children. Indian J Pediatr. 2023;90(3):289\u0026ndash;97. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12098-022-04390-3\u003c/span\u003e\u003cspan address=\"10.1007/s12098-022-04390-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eScarselli A, Smarrazzo A, De Sanctis F, Rav\u0026agrave; L, Carletti M, Ciofi Degli Atti M, et al. The burden of central line-associated bloodstream infections in children with medical complexity. J Vasc Access. 2023;24(2):198\u0026ndash;204. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/11297298221144784\u003c/span\u003e\u003cspan address=\"10.1177/11297298221144784\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNational Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. National guidelines for infection prevention and control in healthcare facilities. 2020. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ncdc.mohfw.gov.in/wp-content/uploads/2024/03/83538105781625557301.pdf\u003c/span\u003e\u003cspan address=\"https://ncdc.mohfw.gov.in/wp-content/uploads/2024/03/83538105781625557301.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWoods-Hill CZ, Srinivasan L, Schriver E, Haj-Hassan T, Bezpalko O, Sammons JS. Novel risk factors for central-line associated bloodstream infections in critically ill children. Infect Control Hosp Epidemiol. 2020;41(1):67\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/ice.2019.274\u003c/span\u003e\u003cspan address=\"10.1017/ice.2019.274\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAres G, Hunter CJ. Central venous access in children: indications, devices, and risks. Curr Opin Pediatr. 2017;29(3):340\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MOP.0000000000000492\u003c/span\u003e\u003cspan address=\"10.1097/MOP.0000000000000492\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eİşg\u0026uuml;der R, Devrim İ, Ceylan G, Kara A, G\u0026uuml;lfidan G, Ağin H. Risk factors for recurrent central line-associated bloodstream infections in a pediatric intensive care unit. Turk J Med Sci. 2017;47(4):1128\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3906/sag-1608-59\u003c/span\u003e\u003cspan address=\"10.3906/sag-1608-59\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWylie MC, Graham DA, Potter-Bynoe G, Kleinman ME, Randolph AG, Costello JM, et al. Risk factors for central line\u0026ndash;associated bloodstream infection in pediatric intensive care units. Infect Control Hosp Epidemiol. 2010;31(10):1049\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1086/656596\u003c/span\u003e\u003cspan address=\"10.1086/656596\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDiekema DJ, Beekmann SE, Chapin KC, Morel KA, Munson E, Doern GV. Epidemiology and outcome of nosocomial and community-onset bloodstream infection. J Clin Microbiol. 2003;41(8):3655\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1128/JCM.41.8.3655-3660.2003\u003c/span\u003e\u003cspan address=\"10.1128/JCM.41.8.3655-3660.2003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCenters for Disease Control and Prevention. Vital signs: central line-associated bloodstream infections\u0026mdash;United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep. 2011;60(8):243\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbdelmoneim H, Ibrahim H, Ahmed A, Mohammed K. Incidence of Central Line-Associated Blood Steam Infection in Pediatric Intensive Care Unit (PICU). Egypt J Hosp Med. 2020;78(1):136\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21608/ejhm.2020.68483\u003c/span\u003e\u003cspan address=\"10.21608/ejhm.2020.68483\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZiegler MJ, Pellegrini DC, Safdar N. Attributable mortality of central line-associated bloodstream infection: systematic review and meta-analysis. Infection. 2015;43(1):29\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s15010-014-0701-2\u003c/span\u003e\u003cspan address=\"10.1007/s15010-014-0701-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNowak JE, Brilli RJ, Lake MR, Sparling KW, Butcher J, Schulte M, et al. Reducing catheter-associated bloodstream infections in the pediatric intensive care unit: business case for quality improvement. Pediatr Crit Care Med. 2010;11(5):579\u0026ndash;87. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PCC.0b013e3181ce75d3\u003c/span\u003e\u003cspan address=\"10.1097/PCC.0b013e3181ce75d3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRosenthal VD. Central line\u0026ndash;associated bloodstream infections in limited-resource countries: a review of the literature. Clin Infect Dis. 2009;49(12):1899\u0026ndash;907. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1086/648439\u003c/span\u003e\u003cspan address=\"10.1086/648439\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLutwick L, Al-Maani AS, Mehtar S, Memish Z, Rosenthal VD, Dramowski A, et al. Managing and preventing vascular catheter infections: a position paper of the International Society for Infectious Diseases. Int J Infect Dis. 2019;84:22\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijid.2019.03.025\u003c/span\u003e\u003cspan address=\"10.1016/j.ijid.2019.03.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIndian Council of Medical Research, Bhargava B, Tandon N. Standard operating procedures: bacteriology antimicrobial resistance surveillance and research network. 2nd ed. Indian Council of Medical Research. 2019. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://main.icmr.nic.in/sites/default/files/guidelines/Bacteriology_SOP_2nd_Ed_2019.pdf\u003c/span\u003e\u003cspan address=\"https://main.icmr.nic.in/sites/default/files/guidelines/Bacteriology_SOP_2nd_Ed_2019.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKundavaram R, Abraham AR, Chaudhary NK, Tadepalli K, Malik S. Safety and utility of various intravenous access devices in a newly established pediatric hematology oncology unit in Central India: is midline an acceptable option? Future Health. 2023;1:35\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.fh.2023.11.001\u003c/span\u003e\u003cspan address=\"10.1016/j.fh.2023.11.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrakash SS, Rajshekar D, Cherian A, Sastry AS. Care bundle approach to reduce device-associated infections in a tertiary care teaching hospital, South India. J Lab Physicians. 2017;9(4):273\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/JLP.JLP_100_17\u003c/span\u003e\u003cspan address=\"10.4103/JLP.JLP_100_17\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRinke ML, Milstone AM, Chen AR, Mirski K, Bundy DG, Colantuoni E, et al. Ambulatory pediatric oncology CLABSIs: epidemiology and risk factors. Pediatr Blood Cancer. 2013;60(11):1882\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/pbc.24627\u003c/span\u003e\u003cspan address=\"10.1002/pbc.24627\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e\u0026Ouml;zalp Ger\u0026ccedil;eker G, Yardımcı F, Aydınok Y. Central line\u0026ndash;associated bloodstream infections in children with hematologic and oncologic diseases: first prevalence results from a university hospital. J Pediatr Oncol Nurs. 2019;36(5):327\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1043454219856705\u003c/span\u003e\u003cspan address=\"10.1177/1043454219856705\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaragiannidou S, Zaoutis T, Maniadakis N, Papaevangelou V, Kourlaba G. Attributable length of stay and cost for pediatric and neonatal central line-associated bloodstream infections in Greece. J Pediatr. 2021;232:253\u0026ndash;e2612. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpeds.2021.01.023\u003c/span\u003e\u003cspan address=\"10.1016/j.jpeds.2021.01.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhluwalia J, Kataria K, Kumar S, Bhalla AK, Bains HS. Effect of central line bundle implementation on central line-associated bloodstream infection rates in a tertiary care hospital. Indian J Crit Care Med. 2018;22(9):633\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5005/jp-journals-10071-22936\u003c/span\u003e\u003cspan address=\"10.5005/jp-journals-10071-22936\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiller MR, Griswold M, Harris JM, Yenokyan G, Huskins WC, Moss M, et al. Decreasing PICU catheter-associated bloodstream infections: NACHRI\u0026rsquo;s quality transformation efforts. Pediatrics. 2010;125(2):206\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.2009-1382\u003c/span\u003e\u003cspan address=\"10.1542/peds.2009-1382\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEzhumalai G, Manoharan M, Rameshkumar K, Chandramohan M, Suresh S. Impact of central line bundle implementation on incidence of central line-associated bloodstream infection in a tertiary care hospital. Indian J Crit Care Med. 2018;22(11):781\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5005/jp-journals-10071-23029\u003c/span\u003e\u003cspan address=\"10.5005/jp-journals-10071-23029\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHaddadin Y, Annamaraju P, Regunath H. Central line associated blood stream infections. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK430891/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK430891/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim JY, Jung MJ, Kim MJ, Jung JY. Effectiveness of central line bundles in reducing central line-associated bloodstream infections in neonatal and pediatric ICU: a systematic review and meta-analysis. Int J Environ Res Public Health. 2021;18(22):11998. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijerph182211998\u003c/span\u003e\u003cspan address=\"10.3390/ijerph182211998\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBala I, Mishra P, Pawar M, Kapoor PM, Vohra V, Agarwal J, et al. ISCCM guidelines for the prevention of hospital-acquired infections in intensive care unit. Indian J Crit Care Med. 2023;27(3):203\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5005/jp-journals-10071-24393\u003c/span\u003e\u003cspan address=\"10.5005/jp-journals-10071-24393\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaki DG, Kluger DM, Crnich CJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc. 2006;81(9):1159\u0026ndash;1171. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4065/81.9.1159\u003c/span\u003e\u003cspan address=\"10.4065/81.9.1159\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaplan R, Aucoin J, Brewer C, Jensen D, Adams G, Schwartz M, et al. Impact of a quality improvement bundle on central line maintenance and CLABSI rates in pediatric oncology patients. Pediatr Qual Saf. 2022;7(5):e591. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/pq9.0000000000000591\u003c/span\u003e\u003cspan address=\"10.1097/pq9.0000000000000591\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchulman J, Stricof R, Stevens TP, Horgan M, Gase K, Holzman IR, et al. Statewide NICU central-line\u0026ndash;associated bloodstream infection rates decline after bundles and checklists. Pediatrics. 2011;127(3):436\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.2010-1722\u003c/span\u003e\u003cspan address=\"10.1542/peds.2010-1722\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Central Line-Associated Bloodstream Infections, Catheter-Related Infections, Intensive Care Units, Oncology, Antimicrobial Resistance, Risk Factors, Microbial Sensitivity Tests, Gram-Negative Bacterial Infections, Observational study, Quality improvement","lastPublishedDoi":"10.21203/rs.3.rs-7851349/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7851349/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\u003cp\u003eCentral line\u0026ndash;associated bloodstream infections (CLABSI) are serious patient safety hazards in pediatric intensive care. Children from hemato-oncology have prolonged line duration yet may incur different infection risks and resistance patterns versus general PICU patients. Thus, the aim of the study was to compare central line utilization, incidence of CLABSI, risk factors and antimicrobial resistance between PICU and hemato-oncology patients, and to identify targets for quality improvement in a resource-limited setting.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA prospective observational study in a tertiary PICU in India over 24 months. All children aged 1 month\u0026ndash;18 years requiring central venous access were enrolled. We recorded insertion practices, line duration, and CLABSI incidence using standard definitions. Antimicrobial isolates and resistance profiles were compared between the PICU and hemato-oncology subgroups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 1,931 central line days in 69 children, there were 13 CLABSI episodes. Hemato-oncology patients had longer line durations but lower CLABSI incidence (5.08/1,000 line days) vs general PICU patients (10.87/1,000 line days). Gram-negative bacteria predominated across both groups; PICU isolates showed higher resistance to cephalosporins and carbapenems.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eInfection risk in PICU is shaped not only by line duration but also by insertion urgency, patient acuity, and antimicrobial exposure. Structured bundles, safe insertion/maintenance practices, and stewardship programs are recommended to improve patient safety in pediatric critical care in LMICs.\u003c/p\u003e","manuscriptTitle":"Central line–associated bloodstream infections in the pediatric intensive care and hemato-oncology unit: a prospective observational study from Western India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-09 00:22:55","doi":"10.21203/rs.3.rs-7851349/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f000211b-0ba5-4bbf-a361-3e3944422c1d","owner":[],"postedDate":"December 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T06:25:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-09 00:22:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7851349","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7851349","identity":"rs-7851349","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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