Evaluation of Clinical, Laboratory, and Radiologic Parameters Affecting Antibiotic Use and Associated Cost in RSV-Positive Children with Acute Lower Respiratory Tract Infections

Evaluation of Clinical, Laboratory, and Radiologic Parameters Affecting Antibiotic Use and Associated Cost in RSV-Positive Children with Acute Lower Respiratory Tract Infections | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 18 August 2025 V1 Latest version Share on Evaluation of Clinical, Laboratory, and Radiologic Parameters Affecting Antibiotic Use and Associated Cost in RSV-Positive Children with Acute Lower Respiratory Tract Infections Authors : Burcu Büşra Acar 0000-0003-2223-0336 [email protected] , Elif Böncüoğlu 0000-0002-3521-0484 , Şahika Şahinkaya , Elif Kıymet , Nuri Bayram , and İlker Devrim Authors Info & Affiliations https://doi.org/10.22541/au.175554197.73635806/v1 164 views 108 downloads Contents Abstract Introduction Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background & objectives: Acute lower respiratory tract infections (LRTIs) are a major cause of morbidity and mortality in children under five years of age. Respiratory syncytial virus (RSV) is the leading viral pathogen in infants, yet empirical antibiotics are often prescribed due to difficulty distinguishing bacterial from viral infections. This study aimed to determine clinical, laboratory, and radiologic parameters influencing antibiotic continuation and to evaluate associated costs in RSV-positive infants. Methods: We retrospectively reviewed records of 209 hospitalized infants aged 1–24 months with RSV infection confirmed by multiplex polymerase chain reaction (mPCR) at a tertiary pediatric hospital between April 2017 and April 2021. Patients with co-infections or other exclusion criteria were omitted. Data on demographics, comorbidities, clinical features, laboratory and radiologic findings, treatments, and costs were analyzed. Multivariate logistic regression identified independent predictors of antibiotic continuation. Results: Overall, 69.4% of patients received antibiotics; intravenous β-lactams were most common. Prolonged antibiotic administration showed a significant relationship with elevated C-reactive protein (CRP) values both at the time of admission and at peak measurement (p = 0.003 and p = 0.001, respectively), as well as with the presence of alveolar infiltrates on chest radiographs (p = 0.016). Patients in whom antibiotics were continued had notably longer median hospital stays, extended antibiotic treatment durations, and higher treatment-related costs (all p < 0.01). Conclusions: Antibiotic continuation in RSV-positive infants was primarily driven by elevated CRP and radiologic findings, highlighting the need for evidence-based prescribing to reduce unnecessary antibiotic use and associated costs. Incorporating rapid molecular diagnostics into routine care may improve decision-making and support antimicrobial stewardship. Introduction Lower respiratory tract infections (LRTIs) remain a significant contributor to illness and death among children under five worldwide. Particularly in those younger than two years, these conditions often present as bronchiolitis or pneumonia, which are clinically challenging to differentiate. Consequently, the designation acute lower respiratory tract infection is commonly applied for this patient group [1,2] . Although viruses are the predominant cause of LRTIs, Respiratory Syncytial Virus (RSV) stands out as the most frequent pathogen in children under two and is among the primary causes of hospitalization during infancy [3,4] . RSV cases occur most often in the autumn and winter months and are typically treated symptomatically [5] . Nevertheless, because RSV manifestations can resemble bacterial LRTIs, clinicians frequently initiate empirical antibiotic therapy, especially when distinguishing between the two is uncertain. [6,7] . While multiplex polymerase chain reaction (mPCR) testing can help differentiate bacterial from viral etiologies, the decision to initiate or continue antibiotics before obtaining results often depends on clinical presentation, specific laboratory indicators such as CRP, and radiologic imaging, though the relative influence of these factors remains under discussion. It is also well known that RSV infection can be more severe in children with underlying health issues. In a detailed review by Yılmaz et al., risk factors such as prematurity, chronic lung disease, congenital heart anomalies, and neurological disorders were highlighted as contributors to more severe RSV courses, warranting closer monitoring and prophylactic measures. [14] . This research set out to examine the influence of RSV confirmation via mPCR on antibiotic usage in pediatric patients, with a particular focus on the contributions of comorbidities, laboratory parameters, and radiologic findings Materials and Methods Between April 2017 and April 2021, medical records of 209 children hospitalized in the Pediatric Emergency Unit, neonatal wards, and the Pediatric Infectious Diseases Department of ***** Hospital of Health and Surgery were retrospectively reviewed in a descriptive and comparative manner. The research adhered to the ethical standards outlined in the Declaration of Helsinki and received approval from the Clinical Research Ethics Committee of the University of Health Sciences, ***** Pediatric Diseases and Surgery Training and Research Hospital (Protocol No. 634; Decision No. 2021/17-03; approved on November 4, 2021). Eligible participants were children aged 1–24 months with a confirmed diagnosis of RSV infection identified through multiplex PCR, based on information from hospital files and laboratory systems. Only cases in which RSV was the single pathogen detected were considered. Exclusion criteria comprised co-infections, positive results in blood or urine cultures, hospitalization in the neonatal unit (0–28 days of age), age exceeding 24 months, need for intensive care, or discharge prior to completion of therapy. Information for the analysis was retrieved from the hospital’s electronic medical records, encompassing patient demographics, personal and familial medical backgrounds, presenting complaints, physical examination results, laboratory data (including CRP levels, total leukocyte counts, and culture results), imaging findings, as well as details regarding antibiotic use (type, route, treatment duration, and related expenses). Data on inhalation therapies such as salbutamol and adrenaline were also documented. The primary endpoint was to identify clinical, laboratory, and imaging variables linked to the persistence of antibiotic treatment in infants testing positive for RSV. Secondary endpoints included total hospital stay, length of antibiotic therapy, and per-patient direct antibiotic expenditure. Due to the retrospective study design, neither adverse events nor antibiotic-related complications were monitored or recorded. RSV subtypes A/B and other respiratory pathogens were detected with the Fast Track Diagnostics Respiratory Pathogens 21 Plus assay (Luxembourg). Viral nucleic acids were extracted using the EZ1 Virus Mini Kit v2.0, followed by amplification on the Rotor-Gene Q system. These procedural details were provided to highlight diagnostic accuracy. For economic evaluation, antibiotic and hospitalization costs were calculated using a micro-costing approach, drawing from hospital billing submissions to the *****. Costs initially expressed in Turkish Lira (TRY) were converted to US Dollars (USD) at an average exchange rate of 1 USD = 7.7784 TRY, reflecting the period from April 2020 to April 2022. Statistical analysis Categorical data were evaluated using either the Chi-square test or Fisher’s exact test, as appropriate. For continuous data, analyses were carried out with the Mann–Whitney U test or suitable parametric methods, based on whether the variables showed a normal distribution. These continuous measures included laboratory results (such as CRP levels and total leukocyte counts), total hospitalization time, antibiotic treatment duration, and associated costs. To determine factors independently linked to the continuation of antibiotic therapy, multivariable logistic regression was applied, adjusting for possible confounders. Subgroup comparisons or interaction testing were not performed. The dataset contained very few missing values, which were addressed by excluding incomplete cases. Given the retrospective nature of the study, utilizing fully completed hospital records, loss to follow-up did not occur. No sensitivity analyses were undertaken. Results with a p-value below 0.05 were considered statistically significant. Results 1,209 patients with RSV-positive acute lower respiratory tract infection were identified. Following the application of exclusion criteria—including co-infections, positive blood or urine cultures, admission to the neonatal intensive care unit within the first 28 days of life, age above 24 months, need for intensive care, or discharge prior to treatment completion—209 patients met the inclusion requirements and were analyzed. Participants were divided into two principal categories according to antibiotic use following RSV detection: Group A – No antibiotic therapy or appropriate discontinuation of antibiotics ( n=64 ): • No antibiotic administered at any stage ( n=9 ) • Antibiotic therapy initiated but discontinued during follow-up ( n=55 ), including: – Discontinuation based on mPCR results ( n=47 ) – Discontinuation for other reasons ( n=8 ) Group B – Inappropriate continuation of antibiotics ( n=145 ). Given the retrospective nature of the research and the reliance on complete medical records, there were no cases lost to follow-up. Patient numbers are presented at the beginning of the Results section, and the study flow is illustrated in Figure 1. Tables 1, 2, and 3 present an overview of the demographic and clinical characteristics. Wheezing was observed significantly more often in Group A (p = 0.011), while other presenting symptoms showed no statistically significant differences between the groups. Details of the chest radiograph results are provided in Table 2. Alveolar infiltrates were significantly more prevalent among Group B patients (p = 0.016), whereas normal radiographic findings occurred more frequently in Group A. The distribution and frequency of inhaled treatments are also provided in Table 2. Use of adrenaline was significantly greater in Group B (p = 0.031). Overall, 69.4% (n = 145) of the cohort received antibiotic therapy, with intravenous beta-lactams being the most commonly administered agents. Group A comprised 64 patients (30.6%) who either never received antibiotics or had them discontinued. Although macrolide, aminoglycoside, and oseltamivir use was somewhat higher in Group B, the differences did not reach statistical significance. Laboratory parameters, including CRP and leukocyte counts, are detailed in Table 4. Group B exhibited markedly higher CRP levels than Group A (p 0.05) Data regarding hospitalization length, total antibiotic days, and treatment costs are presented in Table 4. All three measures were significantly greater in Group B (All comparisons yielded p-values below 0.05.). Table 5 displays the results of the multivariable logistic regression, highlighting variables independently linked to the continuation of antibiotic treatment.In the final model, both the presence of alveolar infiltrates and elevated CRP levels retained statistical significance. Discussion In Turkey, antibiotic prescription rates for pediatric infections remain substantially higher than those in Organisation for Economic Co-operation and Development (OECD) countries (8) . In this retrospective review involving 209 children with RSV-confirmed LRTI, a considerable proportion ultimately did not require antimicrobial therapy. Despite this, decisions about initiating or continuing antibiotics were frequently influenced by CRP measurements and chest radiography interpretations. In contrast to prior findings by Afzal et al., who demonstrated that viral PCR testing improves diagnostic accuracy and reduces unnecessary antibiotic use, our findings suggest that such molecular confirmation does not always translate into reduced antibiotic prescription in routine clinical practice (13) . Peak CRP concentrations were notably greater in Group B, indicating that this marker likely had a decisive impact on prescribing behavior. This finding is consistent with the study conducted by Trischler et al., which also reported that elevated CRP levels increased the likelihood of antibiotic administration (9). Similarly, Rebnord et al. also reported that elevated CRP levels were associated with increased antibiotic prescriptions in children with respiratory symptoms (10) . Children showing alveolar infiltrates on chest radiographs were more frequently prescribed or maintained on antibiotics. This pattern may reflect a clinical tendency to associate these radiographic changes despite their possible occurrence in viral disease with bacterial pneumonia (11) . In our multivariate logistic regression analysis, the presence of alveolar infiltration was shown to increase the likelihood of antibiotic therapy by 0.52-fold (p=0.044). Group comparisons revealed that neither wheezing nor adrenaline administration served as meaningful predictors for antibiotic initiation, implying that these variables, in isolation, are insufficient for guiding treatment decisions. In our study, 47.4% of patients had underlying comorbidities. This high proportion demonstrates that RSV infection affects not only healthy children but also those with pre-existing health conditions. Yılmaz et al. emphasized that RSV may present with a more severe clinical course in children with comorbidities and that these groups should be prioritized for prophylaxis (14) . The elevated baseline vulnerability of such patients could contribute to the inclination toward empirical antibiotic coverage. These observations highlight the importance of tailoring guideline-based approaches specifically for at-risk pediatric subgroups. The rate and duration of parenteral antibiotic use were significantly higher in this study. This trend suggests a conservative approach in the face of clinical uncertainty. However, existing guidelines report that oral antibiotics may be sufficient for mild to moderate pneumonia cases (6,12) . This observation highlights the necessity of re-evaluating current treatment strategies in the context of evidence-based practices. Conclusion This study demonstrated that decisions regarding antibiotic use in RSV-related acute LRTI were largely shaped by measurable clinical indicators, particularly CRP elevation and radiographic detection of alveolar infiltrates. Strikingly, even when RSV was confirmed as the sole etiologic agent through molecular testing, nearly 70% of cases continued to receive antibiotic therapy inappropriately. This suggests that non-specific laboratory and imaging findings although not definitive for bacterial disease continue to exert a disproportionate influence on prescribing behavior, reflecting a gap between guideline recommendations and daily practice. Our results further emphasize the potential role of rapid molecular diagnostic tools, such as multiplex PCR (mPCR), in guiding more rational treatment strategies and curbing unnecessary antibiotic administration. Since RSV infections may manifest more severely in children with underlying comorbidities, and non-guideline antibiotic prescribing appears more prevalent in this subgroup, a more cautious, evidence-based approach is warranted. Addressing antimicrobial resistance in this context requires not only incorporating molecular diagnostics into routine pediatric workflows but also delivering targeted education for clinicians to reduce reliance on non-specific inflammatory or radiographic markers when viral etiology is confirmed. Ultimately, these measures could assist pediatricians in minimizing empirical antibiotic use in infants with RSV infection, aligning clinical care more closely with established stewardship principles. Limitations This study has several limitations. First, its retrospective and single-center design may have introduced selection bias, as the findings may not be fully generalizable to all pediatric populations with RSV infection. Second, data were extracted from medical records, which may be subject to information bias due to incomplete or inaccurate documentation. Third, potential confounding factors, such as differences in clinicians’ prescribing behaviors or institutional protocols, could not be fully controlled. In addition, radiologic findings were interpreted in the context of clinical judgment, which may be prone to observer bias. Finally, the exclusion of patients with co-infections may limit the applicability of results to more complex clinical scenarios. Key Messages Despite confirmed viral etiology, empirical antibiotic use in RSV-related LRTIs remains frequent, primarily driven by CRP and radiographic findings, with notable cost impact. Funding: The present study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The research was conducted using institutional resources provided by hospital. 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Yilmaz D, Tasar S, Tuz AE, Eroz NA, Oncel EK, Aksay AK, Yilmaz N. Overview of Pediatric Respiratory Syncytial Virus (RSV) infections: has risk perception for RSV changed in children with comorbid conditions? Eur J Clin Microbiol Infect Dis. 2025;44(2):333-342. doi: 10.1007/s10096-024-05003-6. Supplementary Material File (figures.docx) Download 31.91 KB File (table 1 comparison of demographic characteristics 2.docx) Download 29.07 KB Information & Authors Information Version history V1 Version 1 18 August 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords antibiotic use cost analysis lower respiratory tract infection multiplex pcr respiratory syncytial virus Authors Affiliations Burcu Büşra Acar 0000-0003-2223-0336 [email protected] Ege Universitesi View all articles by this author Elif Böncüoğlu 0000-0002-3521-0484 Izmir Demokrasi Universitesi View all articles by this author Şahika Şahinkaya TC Saglik Bakanligi SBU Dr Behcet Uz Cocuk Hastaliklari Ve Cerrahisi Egitim Ve Arastirma Hastanesi View all articles by this author Elif Kıymet Bakircay Universitesi View all articles by this author Nuri Bayram TC Saglik Bakanligi SBU Dr Behcet Uz Cocuk Hastaliklari Ve Cerrahisi Egitim Ve Arastirma Hastanesi View all articles by this author İlker Devrim TC Saglik Bakanligi SBU Dr Behcet Uz Cocuk Hastaliklari Ve Cerrahisi Egitim Ve Arastirma Hastanesi View all articles by this author Metrics & Citations Metrics Article Usage 164 views 108 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Burcu Büşra Acar, Elif Böncüoğlu, Şahika Şahinkaya, et al. 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