- Research article
- Open Access
Antibiotic utilization in hospitalized children under 2 years of age with influenza or respiratory syncytial virus infection – a comparative, retrospective analysis
BMC Infectious Diseases volume 20, Article number: 606 (2020)
Infections due to Respiratory Syncytial Virus (RSV) and Influenza virus (FLU) are leading causes of hospitalization in young children. Yet, there is little data on factors associated with antibiotic use in these patients.
We conducted a retrospective, single-center study of all patients below 2 years of age hospitalized between 2014 and 2018. We compared children with RSV infection to children with FLU infection analyzing clinical characteristics and factors contributing to an increased rate of antimicrobial utilization.
RSV infection was diagnosed in 476/573 (83.1%), FLU in 95/573 (16.6%), and RSV-FLU-co-infection in 2/573 (0.3%) patients. Median age was lower for RSV compared to FLU (4 vs. 12 months; p < 0.0001). Children with RSV had longer hospitalization (5 vs. 4 days; p = 0.0023) and needed oxygen more frequently (314/476 vs. 23/95; p < 0.0001) than FLU patients. There was no significant difference in the overall antibiotic utilization between RSV and FLU patients (136/476 vs. 21/95; p = 0.2107). Logistic regression analyses revealed that septic appearance on admission (odds ratio [OR] 8.95, 95% confidence interval [CI] 1.5–54.1), acute otitis media (OR 4.5, 95% CI 2.1–9.4), a longer oxygen therapy (OR 1.40; 95% CI 1.13–1.74) and a higher C-reactive protein (CRP) (OR 1.7, 95% CI 1.5–2.0) were significantly associated with antibiotic use in both groups, but not age or pneumonia.
In our cohort, the rate of antibiotic utilization was comparable between RSV and FLU patients, while for both groups distinct clinical presentation and a high CRP value were associated with higher antibiotic use.
Respiratory tract infections (RTI) are the most common diagnoses in children, especially below the age of 2 years . They substantially contribute to morbidity and mortality worldwide . Furthermore, RTI are associated with large societal impacts , including a high health-economic burden , caused by a high hospitalization rate among the very young, causing frequent parental absence from work . Moreover, antimicrobial consumption is heavily driven by RTI  due to the clinical challenge of distinguishing between viral and bacterial etiologies and the lack of a reliable diagnostic reference standard [7, 8]. Antimicrobial stewardship (AMS) programs are increasingly implemented  to counteract this antibiotic overuse which is strongly associated with the upsurge in antimicrobial resistance ,
The respiratory syncytial virus (RSV) and the Influenza virus (FLU) account for the majority of RTI in infants leading to hospitalization [11, 12]. With the advent of novel point-of-care tests based on nucleic acid amplification, diagnostic accuracy and turnaround time of results have dramatically increased over the past years, both for RSV and FLU [13, 14]. Yet, there is only limited data indicating the potential clinical benefit of rapid viral testing as a tool of AMS in the hospital setting . The overall quality of evidence was generally regarded low, making only for a “weak recommendation” in the latest Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America for implementing an AMS program .
In a recent systematic review with meta-analysis, including both diagnostic accuracy studies and clinical impact studies, no firm conclusion could be made on the clinical impact of viral testing on antibiotic use due to the heterogeneity of the included studies , of which only two had included children.
Little is known about the factors that influence antibiotic prescription in patients with a positive RSV or FLU test. We sought to analyze the rate of antibiotic use in RSV and FLU patients and associated clinical and laboratory factors.
Study setting and design
This retrospective, single-center analysis was conducted at the University Children’s Hospital Mannheim, Medical Faculty Mannheim of the Heidelberg University, Germany. The local ethics committee approved of the study (2018-832R-MA). All patients below 2 years of age hospitalized for RSV or FLU infection between the April 2014 and April 2018 were included, thereby covering 4 complete epidemic seasons. Patients were identified by a hospital database search for the corresponding ICD-10 codes (J12.1, J21.0, J20.5, B97.4; J09-J11.-) as the primary diagnosis and, to avoid selection bias, also as secondary diagnosis. RSV or FLU infection were each defined as a positive result from a nasopharyngeal swab either in a rapid point-of-care test (Sofia® Influenza A + B Fluorescent Immunoassay and Sofia® RSV Fluorescent Immunoassay; Quidel, San Diego, California, USA) or in a multiplex PCR (Biofire® Filmarray® Respiratory Panel, Biomérieux, Marcy-l’Étoile, France), which comprises adenovirus; coronaviruses 229E, HKU1, OC43, and NL63; human metapneumovirus; human rhinovirus/enterovirus; influenza A (including substrains) and B; parainfluenza viruses 1 to 4; RSV; Bordetella pertussis; Chlamydophila pneumoniae; and Mycoplasma pneumoniae.
Chart review included present and past medical history, family history, preexisting antibiotic therapy, clinical findings, results of laboratory, microbiological and radiological investigations, data on therapy, need for oxygen, intensive care, and length of stay. Clinical appearance was defined as documented as the physical examination upon admission, including “well”, “ill”, and “septic” appearance. The clinical syndrome was defined according to the discharge diagnosis and/or the documented clinical symptoms on admission, as either upper respiratory tract infection (URTI), bronchitis/bronchiolitis, pneumonia, or fever of unknown origin (FUO).
Case numbers were compared between the seasons to check for imbalances.
We compared children with RSV infection to children with FLU infection. Especially, clinical characteristics and factors contributing to an increased rate of antimicrobial utilization were analysed of RSV and FLU infected children. Furthermore, we defined subgroups of children within each group and compared those treated with antibiotics (RSV+AB+; FLU+AB+) to those who were not treated with antibiotics (RSV+AB-; FLU+AB-), respectively. Antibiotic utilization was defined as any given dose during the hospital stay. We assessed antibiotic therapy in terms of substance and length of therapy.
Statistical analyses were performed in SAS (Statistical Analysis System, North Carolina, USA). Mann-Whitney U test was used for group comparison between RSV and FLU. For multiple comparisons, Kruskal-Wallis test and one-way analysis of variance were applied. Logistic regressions were performed to assess potential risk factors for antibiotic utilization.
Overall, 573 children were eligible for analysis, with a median age of 5 months (IQR 2–11) and a male predominance of 325/573 (56.7%). Of the 573 children, 476 were identified as having RSV infection (83.1%), and 95 as having FLU infection (16.6%), while in two patients, RSV-FLU co-infection was detected (0.3%). RSV patients were significantly younger than FLU patients (4 vs. 12 months; p < 0.0001) (Table 1), while 19.5% of RSV patients were 28 days of age or younger and 47.7% 3 months of age or younger. The majority of RSV patients presented during the months January and February (32.4 and 25.4%), while FLU patients were predominantly diagnosed in February and March (43.2 and 25.3%) (Fig. 1).
We assessed the seasonal variability (Fig. 1). Numbers were comparable between the seasons except for one season each with a higher burden of RSV (2016/2017) and FLU (2017/2018).
Baseline risk factors
We assessed patients with respect to a positive past medical history with focus on prematurity, congenital heart disease, congenital diaphragmatic hernia, trisomy 21, and recurrent episodes of bronchitis, but could not find any significant differences, although prematurity and recurrent bronchitis were slightly more common in RSV (4.4 and 4.8%, respectively) than in FLU patients (2.1 and 3.1%, respectively), both missing statistical significance. Furthermore, similar sick contacts were observed for 38.9% of RSV and for 45.3% of FLU patients (statistically not significant).
Clinical presentation, treatment and outcome of RSV and FLU patients
Both patient groups presented with similar durations of illness, but a significant number of FLU patients had received antibiotics before presenting to the hospital (14.7% vs. 6.7%; p = 0.0188). The clinical syndrome diagnosed upon admission was lower respiratory tract infection (49.6%) or pneumonia (50.2%) for most of the RSV patients (compared to 6.3% und 22.1% for FLU patients, respectively; both p < 0.0001), while in FLU patients, upper respiratory tract infections (49.5%) and FUO (22.1%) accounted for the majority of clinical manifestations (compared to 0.2 and 0% for RSV patients, respectively; both p < 0.0001). In association with this, fever, and also febrile convulsions were significantly more often found in FLU patients (Table 1). Acute otitis media was significantly more often diagnosed among FLU patients (p < 0.0001).
RSV patients needed significantly more often oxygen therapy (66% vs. 24.2%; p < 0.0001) and salbutamol (68.3% vs. 27.1%; p < 0.0001) than FLU patients, and had longer hospital stays (5 vs. 4 days; p = 0.0023), while there were no statistically significant differences concerning the need for intensive care and antibiotic therapy. One FLU patient died due to severe pneumonia with suspected bacterial co-infection, leading to respiratory failure.
Laboratory, microbiological and radiological findings in RSV and FLU patients
No significant differences were found between both groups concerning C-reactive protein (CRP) and white blood cell counts (WBC). Chest radiographs were performed slightly more often in RSV patients (28.4% vs. 19.8%; not significant), while infiltrates were slightly more frequently diagnosed among FLU patients (72.2% vs. 53.3%; not significant).
For 19 patients, a multiplex PCR on a nasopharyngeal swab was available (14 RSV patients, 5 FLU patients). Among the 14 patients with RSV infection for whom a multiplex PCR was available, adenovirus was concomitantly detected in two patients and coronavirus and Bordetella pertussis in one patient, each. In FLU patients, adenovirus and human metapneumovirus were detected in one patient, each. Blood cultures were ordered in 165 patients with RSV, of whom 9 were positive, all of which were deemed contaminants (5 coagulase negative staphylococci; 1 co-detection of Staphylococcus epidermidis, Streptococcus mitis, and Streptococcus peroris; 1 co-detection of Micrococcus luteus and Pseudomonas stutzeri; 1 Micrococcus luteus; 1 Rothia dentocariosa). For FLU patients, blood cultures were ordered in 54, with 3 positive cultures, all regarded as contamination (2 Staphylococcus hominis; 1 Corynebacterium afermentans).
Antibiotics were prescribed in 136/476 (28.6%) of RSV patients and 21/95 (22.1%) of FLU patients (p = 0.2107). A monotherapy was used in 77/136 (56.6%) in RSV patients and 15/21 (71.4%) of FLU patients (p = 0.2395), while the remaining fractions were prescribed a combination therapy. For RSV patients, the most frequently ordered therapies were aminopenicillin monotherapy in 44/136 (32.4%), ampicillin + flucloxacillin combination therapy in 41/136 (30.1%), and ampicillin + gentamicin combination therapy in 17/136 (12.5%). For FLU patients, ampicillin/sulbactam was prescribed in 7/21 (33.3%), followed by an aminopenicillin monotherapy in 4/21 (19.0%) and ampicillin + flucloxacillin combination therapy in 4/21 (19.0%). The distribution of prescribed antibiotics is depicted in Fig. 2. The median length of antibiotic therapy was 5.5 days for RSV patients (IQR 4–7) and 6 days for FLU patients (IQR 4–8) (p = 0.3680).
Subgroup comparison – RSV patients
We compared RSV patients who received antibiotics (RSV+AB+) during the hospital stay to those without antibiotics (RSV+AB-). Children who were RSV+AB+ were significantly older than RSV+AB- (6 vs. 3 months; p = 0.0025) (Table 2). Furthermore, they presented significantly more often with fever (91.2% vs. 60.6%; p < 0.0001), a septic appearance (48.5% vs. 30%; p = 0.0002), pneumonia (76.8% vs. 39.1%; p < 0.0001), acute otitis media (26.5% vs. 10%; p < 0.0001), and a higher CRP on admission (26.9 mg/L vs. 4.3 mg/L; p < 0.0001). During the hospital stay, RSV + AB+ children had significantly higher rates of chest radiographies (60.3% vs. 15.6%; p < 0.0001), blood cultures obtained (52.2% vs. 27.6%; p < 0.0001), oxygen therapy (80.1% vs. 60%; p < 0.0001), intensive care stays (9.6% vs. 0.9%; p < 0.0001), and longer hospital stays in total (6 days vs. 5 days; p < 0.0001).
Subgroup comparison – FLU patients
For FLU patients, a significant difference upon clinical presentation was a higher rate of pneumonia (52.4% vs. 13.5%; p = 0.0005) and acute otitis media (57.1% vs. 28.4%; p = 0.0199) among children receiving antibiotics (FLU+AB+) compared to children without antibiotics (FLU+AB-) (Table 2). Apart from that, FLU+AB+ children had significantly higher CRP on admission (23.1 mg/L vs. 4.9 mg/L; p < 0.0001) and peak CRP (54.9 mg/L vs. 9.4 mg/L; p < 0.0001) in the course of disease; a higher rate of chest radiography performed (52.4% vs. 9.5%; p < 0.0001), higher need for oxygen therapy (57.1% vs. 14.9%; p = 0.0002), and a longer hospital stay (6 days vs. 5 days; p = 0.0003).
Risk factors for antibiotic use
We performed a multivariate logistic regression to identify risk factors associated with antibiotic utilization among both RSV and FLU. The best model fit for antibiotic use at any time point was achieved for the following factors (c-index 0.916) (Table 3): otitis media (odds ratio 8.33; 95% confidence interval 3.58–19.37), peak CRP (OR 1.77; 95% CI 1.54–2.04), and the length of oxygen therapy (OR 1.40; 95% CI 1.13–1.74). Septic appearance (OR 4.882; 95% CI 0.866–27.505; p = 0.0723) was statistically not significant.
The best model fit for antibiotic use on admission (c-index 0.896) (Table 4) was achieved for otitis media (OR 4.5, 95% CI 2.1–9.4), CRP on admission (OR 1.7, 95% CI 1.5–2.0), and septic appearance (OR 8.95, 95% CI 1.5–54.1). Pneumonia as a potential risk factor (OR 3.629, 95% CI 0.902–14.602) missed statistical significance.
In this large retrospective four-season-analysis we present data on more than 570 children below the age of 2 years with RSV or FLU infection, demonstrating a high antibiotic use in a substantial proportion of children.
Recent systematic reviews with meta-analyses had shown that viral testing, including FLU and RSV, does not affect antibiotic prescription rates [17, 18], indicating that other factors pertaining to the decision-making of physicians need to be addressed by AMS measures.
Although RSV patients were significantly younger in our cohort, this apparently did not contribute to a higher rate of antibiotic utilization, as RSV children with antibiotics were significantly older than RSV children that did not receive antibiotics. Instead, driving factors for a potential antibiotic overuse were a high CRP, the presence of acute otitis media, septic appearance and the length of oxygen therapy.
FLU patients presented significantly more often with fever, febrile convulsions, acute otitis media, and upper respiratory tract infection or fever of unknown origin, while RSV patients presented significantly more often with a lower oxygen saturation, septic appearance, and lower respiratory tract infection or pneumonia.
We found higher rates of blood cultures obtained from FLU patients than from RSV patients, which in large part can be explained by the higher rate of febrile children in the FLU cohort, while chest radiographies were more frequently performed among those who received antibiotics within both groups. Interestingly, we found rates of chest infiltrates comparable between treated and non-treated patient groups. One possible explanation is that performing a chest radiograph serves as a surrogate for disease severity and hence influences the decision to prescribe antibiotics. In previous studies, it was hypothesized that less specific radiologic findings may have pushed physicians towards antibiotic treatment, even in the absence of infiltrates . Still, it is generally advised against routinely performing chest radiographs in children who present with typical clinical findings of viral bronchiolitis, of which the majority is caused by RSV .
Male children were more predominant in both RSV and FLU cohorts, which had been reported similarly in previous studies , yet without convincing explanations so far . Of note, the rate of antibiotic use before admission was 2.2 times higher among FLU patients, while during hospitalization, more RSV patients received antibiotics.
The antibiotic utilization in 28.6% of RSV and 22.1% of FLU patients respectively is lower than in comparable cohorts published in the recent past [23, 24], which may reflect a stronger reluctance to use antibiotics in children with point-of-care test confirmed viral infections at our hospital.
Complex medical comorbidities, such as chronic lung disease due to prematurity and congenital heart disease, are known risk factors for hospitalization due to RSV infection [25, 26]. In our cohort, we did not find any difference in these comorbidities between RSV and FLU patients.
The strengths of our study are the study size, allowing for robust statistical analyses, the long inclusion period, accounting for fluctuations of virus seasonality, and the consistency in standard of care during the inclusion period, thereby avoiding unwanted biasing effects.
Certain limitations of the study also merit critical appraisal. First, we obtained data retrospectively, bringing about the usual constraints and biases inherent to the nature of retrospective analyses. As such, we could not assess the effect of vaccination coverage, especially pertaining to influenza, on the study outcomes since these data were not systematically obtained. In Germany, currently no general recommendation for FLU vaccination for children exists, but only for those with chronic medical conditions. Secondly, no reference method was applied with regard to the correctness of antibiotic utilization. The correct judgement whether an antibiotic is warranted or not is hindered by the lack of a reference standard. Several methods exist to account for this, e.g. a panel of expert referees, blinded to each other, reviewing each case and adjudicating on the “correct” etiology, i.e. bacterial, viral, bacterial-viral co-infection, or unknown, as applied in other studies [21, 27]. Third, our cohort lacked an additional systematic viral testing beyond RSV and Influenza for all patients, making it impossible to judge whether other viruses, such as adenovirus, may have played a causative role, especially in cases with higher CRP . Other viruses, albeit rarer, such as the human metapneumovirus, can be equally or even more associated with antibiotic overuse in children, as described by Schreiner and colleagues . An extensive pathogen testing in conjunction with a control group of healthy children may have helped to better appraise the role of other viruses or bacteria, since some microorganisms can be found abundantly also in healthy controls , and the co-presence of some pathogens have been reported to correlate with disease severity . Of note, O’Grady and colleagues had found that more than half of children with an acute respiratory infection had a viral-bacterial “co-detection” in nasal swabs, the bacterium in most cases being Haemophilus influenzae . In another study in children with lower respiratory tract infections , the most common detected potentially pathogenic colonizers were Haemophilus influenzae (32.1%), Moraxella catharralis (26.7%), Staphylococcus aureus (17.7%) and Streptococcus pneumoniae (16.7%). Nevertheless, detection of bacterial colonizers may not help in the decision to initiate antibiotic therapy. Instead, there is evidence that the utilization of viral point-of-care diagnostics may prevent the usage of antibiotics [33, 34]. Overall, this fits well into the concept of diagnostic as well as antibiotic stewardship. Fourth, our cohort had a low case fatality rate, which reduces comparability to cohorts from other backgrounds, e.g. from low- and middle-income countries, where mortality may be higher . Finally, the low baseline rate of antibiotic utilization may limit the generalizability of our results to other settings where the culture of prescribing antibiotics especially in infants and young children below the age of 2 years may differ  due to a lack of AMS or other reasons.
In light of the imperfection of both clinical features  and laboratory parameters such as CRP [37, 38], novel diagnostics measures are needed to better distinguish between viral and bacterial infections and thereby help reducing unwarranted antibiotic therapy. New host-protein based assays, e.g. combining CRP with Myxovirus resistance protein A , but also combinations of CRP and tumor-necrosis-factor related apoptosis inducing ligand and interferon-gamma induced protein 10, have shown very convincing results in studies [21, 40,41,42], with high diagnostic accuracy and a potential to dampen unnecessary antibiotic use. Transcriptomic signatures have also shown to be very accurate in establishing the true etiology [43, 44], and although cost issues and turnaround times steadily improve , practical feasibility and implementation into the clinical workflow are persisting challenges still to be taken.
In summary, we show that clinical appearance on admission, the presence of otitis media, but also a high CRP and the length of oxygen therapy are the main factors associated with antibiotic use in our cohort of in children below the age of 2 years with RSV or FLU infection. It remains to be proven in prospective studies if AMS interventions aiming at viral testing, e.g. as multiplex PCR, in conjunction with more precise biomarkers or combinations thereof can help to effectively reduce antibiotic treatment in children with RSV infection and Influenza.
Availability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
Fever of unknown origin
Polymerase chain reaction
Respiratory syncytial virus
Respiratory tract infection
Upper respiratory tract infection
White blood cell count
Ozkaya-Parlakay A, Gulhan B, Bedir-Demirdag T, Kanik-Yuksek S. Viral etiology of bronchiolitis among pediatric patients. Pediatr Infect Dis J. 2019;38(9):e233. https://doi.org/10.1097/inf.0000000000002382 Epub 2019/08/14. PubMed PMID: 31408060.
GBD 2017 Lower Respiratory Infections Collaborators. Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2020;20(1):60–79. https://doi.org/10.1016/s1473-3099(19)30410-4 Epub 2019/11/05. PubMed PMID: 31678026.
Hodgson D, Atkins KE, Baguelin M, Panovska-Griffiths J, Thorrington D, van Hoek AJ, et al. Estimates for quality of life loss due to Respiratory Syncytial Virus. Influenza Other Respir Viruses. 2020;14(1):19–27. https://doi.org/10.1111/irv.12686 Epub 2019/10/19. PubMed PMID: 31625688; PubMed Central PMCID: PMCPMC6928035.
Chirikov VV, Simoes EAF, Kuznik A, Kwon Y, Botteman M. Economic Burden Trajectories in Commercially Insured US Infants with Respiratory Syncytial Virus. J Infect Dis. 2019. https://doi.org/10.1093/infdis/jiz160 Epub 2019/04/16. PubMed PMID: 30982895.
Scholz S, Damm O, Schneider U, Ultsch B, Wichmann O, Greiner W. Epidemiology and cost of seasonal influenza in Germany - a claims data analysis. BMC Public Health. 2019;19(1):1090. https://doi.org/10.1186/s12889-019-7458-x Epub 2019/08/15. PubMed PMID: 31409319; PubMed Central PMCID: PMCPMC6693205.
Kronman MP, Zhou C, Mangione-Smith R. Bacterial prevalence and antimicrobial prescribing trends for acute respiratory tract infections. Pediatrics. 2014;134(4):e956–65. https://doi.org/10.1542/peds.2014-0605 Epub 2014/09/17. PubMed PMID: 25225144.
Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D. Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review. Lancet. 2010;375(9717):834–45. https://doi.org/10.1016/s0140-6736(09)62000-6 Epub 2010/02/06. PubMed PMID: 20132979.
Craig JC, Williams GJ, Jones M, Codarini M, Macaskill P, Hayen A, et al. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses. BMJ. 2010;340:c1594. https://doi.org/10.1136/bmj.c1594 Epub 2010/04/22. PubMed PMID: 20406860; PubMed Central PMCID: PMCPMC2857748.
Kronman MP, Banerjee R, Duchon J, Gerber JS, Green MD, Hersh AL, et al. Expanding existing antimicrobial stewardship programs in pediatrics: what comes next. J Pediatric Infect Dis Soc. 2018;7(3):241–8. https://doi.org/10.1093/jpids/pix104 Epub 2017/12/22. PubMed PMID: 29267871.
Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM Jr, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315(17):1864–73. https://doi.org/10.1001/jama.2016.4151 Epub 2016/05/04. PubMed PMID: 27139059.
The Pneumonia Etiology Research for Child Health (PERCH) Study Group. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet. 2019;394(10200):757–79. https://doi.org/10.1016/s0140-6736(19)30721-4 Epub 2019/07/02. PubMed PMID: 31257127; PubMed Central PMCID: PMCPMC6727070.
Arriola CS, Kim L, Langley G, Anderson EJ, Openo K, Martin AM, et al. Estimated burden of community-onset respiratory syncytial virus-associated hospitalizations among children aged <2 years in the United States, 2014-15. J Pediatric Infect Dis Soc. 2019. https://doi.org/10.1093/jpids/piz087 Epub 2019/12/24. PubMed PMID: 31868913.
Azar MM, Landry ML. Detection of Influenza A and B Viruses and Respiratory Syncytial Virus by Use of Clinical Laboratory Improvement Amendments of 1988 (CLIA)-Waived Point-of-Care Assays: a Paradigm Shift to Molecular Tests. J Clin Microbiol. 2018;56(7). https://doi.org/10.1128/jcm.00367-18 Epub 2018/04/27. PubMed PMID: 29695519; PubMed Central PMCID: PMCPMC6018333.
Kitt E, Drew RJ, Cunney R, Beekmann SE, Polgreen P, Butler K, et al. Diagnosis and Management of Pediatric Influenza in the era of rapid diagnostics. J Pediatric Infect Dis Soc. 2020;9(1):51–5. https://doi.org/10.1093/jpids/piy118 Epub 2018/11/27. PubMed PMID: 30476135.
Bonner AB, Monroe KW, Talley LI, Klasner AE, Kimberlin DW. Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. Pediatrics. 2003;112(2):363–7 Epub 2003/08/05. PubMed PMID: 12897288.
Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–77. https://doi.org/10.1093/cid/ciw118 Epub 2016/04/16. PubMed PMID: 27080992; PubMed Central PMCID: PMCPMC5006285.
Vos LM, Bruning AHL, Reitsma JB, Schuurman R, Riezebos-Brilman A, Hoepelman AIM, et al. Rapid molecular tests for influenza, respiratory syncytial virus, and other respiratory viruses: a systematic review of diagnostic accuracy and clinical impact studies. Clin Infect Dis. 2019;69(7):1243–53. https://doi.org/10.1093/cid/ciz056 Epub 2019/01/29. PubMed PMID: 30689772.
Lee JJ, Verbakel JY, Goyder CR, Ananthakumar T, Tan PS, Turner PJ, et al. The Clinical Utility of Point-of-Care Tests for Influenza in Ambulatory Care: A Systematic Review and Meta-analysis. Clin Infect Dis. 2019;69(1):24–33. https://doi.org/10.1093/cid/ciy837 Epub 2018/10/05. PubMed PMID: 30285232; PubMed Central PMCID: PMCPMC6579962.
Ecochard-Dugelay E, Beliah M, Boisson C, Perreaux F, de Laveaucoupet J, Labrune P, et al. Impact of chest radiography for children with lower respiratory tract infection: a propensity score approach. PLoS One. 2014;9(5):e96189. https://doi.org/10.1371/journal.pone.0096189 Epub 2014/05/03. PubMed PMID: 24788944; PubMed Central PMCID: PMCPMC4008561.
Carande EJ, Galiza EP, Nickless A, Pollard AJ, Drysdale SB. Viral bronchiolitis management in hospitals in the UK. J Clin Virol. 2018;104:29–33. https://doi.org/10.1016/j.jcv.2018.04.010 Epub 2018/04/29. PubMed PMID: 29704736.
van Houten CB, de Groot JAH, Klein A, Srugo I, Chistyakov I, de Waal W, et al. A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study. Lancet Infect Dis. 2017;17(4):431–40. https://doi.org/10.1016/s1473-3099(16)30519-9 Epub 2016/12/26. PubMed PMID: 28012942.
Ben-Shmuel A, Sheiner E, Wainstock T, Landau D, Vaknin F, Walfisch A. The association between gender and pediatric respiratory morbidity. Pediatr Pulmonol. 2018;53(9):1225–30. https://doi.org/10.1002/ppul.24083 Epub 2018/06/27. PubMed PMID: 29943901.
van Houten CB, Naaktgeboren C, Buiteman BJM, van der Lee M, Klein A, Srugo I, et al. Antibiotic overuse in children with respiratory syncytial virus lower respiratory tract infection. Pediatr Infect Dis J. 2018;37(11):1077–81. https://doi.org/10.1097/inf.0000000000001981 Epub 2018/03/31. PubMed PMID: 29601448.
van Houten CB, Cohen A, Engelhard D, Hays JP, Karlsson R, Moore E, et al. Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment). Eur J Clin Microbiol Infect Dis. 2019;38(3):505–14. https://doi.org/10.1007/s10096-018-03454-2 Epub 2019/02/02. PubMed PMID: 30707378; PubMed Central PMCID: PMCPMC6394715.
Lim A, Butt ML, Dix J, Elliott L, Paes B. Respiratory syncytial virus (RSV) infection in children with medical complexity. Eur J Clin Microbiol Infect Dis. 2019;38(1):171–6. https://doi.org/10.1007/s10096-018-3409-1 Epub 2018/10/31. PubMed PMID: 30374685.
Resch B, Puchas C, Resch E, Urlesberger B. Epidemiology of respiratory syncytial virus-related hospitalizations and the influence of viral Coinfections in southern Austria in a 7-year period. Pediatr Infect Dis J. 2020;39(1):12–6. https://doi.org/10.1097/inf.0000000000002494 Epub 2019/10/28. PubMed PMID: 31651808.
van Houten CB, Naaktgeboren CA, Ashkenazi-Hoffnung L, Ashkenazi S, Avis W, Chistyakov I, et al. Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases. J Clin Epidemiol. 2019;112:20–7. https://doi.org/10.1016/j.jclinepi.2019.03.010 Epub 2019/04/02. PubMed PMID: 30930247.
Franz A, Adams O, Willems R, Bonzel L, Neuhausen N, Schweizer-Krantz S, et al. Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection. J Clin Virol. 2010;48(4):239–45. https://doi.org/10.1016/j.jcv.2010.05.007 Epub 2010/07/22. PubMed PMID: 20646956.
Schreiner D, Groendahl B, Puppe W, Off HNT, Poplawska K, Knuf M, et al. High antibiotic prescription rates in hospitalized children with human metapneumovirus infection in comparison to RSV infection emphasize the value of point-of-care diagnostics. Infection. 2019;47(2):201–7. https://doi.org/10.1007/s15010-018-1194-5 Epub 2018/08/23. PubMed PMID: 30132249.
Thorburn K, Harigopal S, Reddy V, Taylor N, van Saene HK. High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis. Thorax. 2006;61(7):611–5. https://doi.org/10.1136/thx.2005.048397 Epub 2006/03/16. PubMed PMID: 16537670; PubMed Central PMCID: PMCPMC2104657 competing interests with regard to the contents of this manuscript.
O'Grady KF, Grimwood K, Sloots TP, Whiley DM, Acworth JP, Phillips N, et al. Prevalence, codetection and seasonal distribution of upper airway viruses and bacteria in children with acute respiratory illnesses with cough as a symptom. Clin Microbiol Infect. 2016;22(6):527–34. https://doi.org/10.1016/j.cmi.2016.02.004 Epub 2016/02/27. PubMed PMID: 26916343; PubMed Central PMCID: PMCPMC7128568.
Tenenbaum T, Franz A, Neuhausen N, Willems R, Brade J, Schweitzer-Krantz S, et al. Clinical characteristics of children with lower respiratory tract infections are dependent on the carriage of specific pathogens in the nasopharynx. Eur J Clin Microbiol Infect Dis. 2012;31(11):3173–82. https://doi.org/10.1007/s10096-012-1682-y Epub 2012/08/02. PubMed PMID: 22850740.
Schneider JE, Boehme C, Borisch B, Dittrich S. Application of a simple point-of-care test to reduce UK healthcare costs and adverse events in outpatient acute respiratory infections. J Med Econ. 2020;23(7):673–82. https://doi.org/10.1080/13696998.2020.1736872 Epub 2020/04/08. PubMed PMID: 32259465.
Cantais A, Mory O, Plat A, Bourmaud A, Giraud A, Costille M, et al. Impact of bedside diagnosis of influenza in the paediatric emergency ward. Clin Microbiol Infect. 2019;25(7):898–903. https://doi.org/10.1016/j.cmi.2018.11.019 Epub 2018/12/07. PubMed PMID: 30502486.
Scheltema NM, Gentile A, Lucion F, Nokes DJ, Munywoki PK, Madhi SA, et al. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series. Lancet Glob Health. 2017;5(10):e984–e91. https://doi.org/10.1016/s2214-109x(17)30344-3 Epub 2017/09/16. PubMed PMID: 28911764; PubMed Central PMCID: PMCPMC5599304.
van de Maat J, van de Voort E, Mintegi S, Gervaix A, Nieboer D, Moll H, et al. Antibiotic prescription for febrile children in European emergency departments: a cross-sectional, observational study. Lancet Infect Dis. 2019;19(4):382–91. https://doi.org/10.1016/s1473-3099(18)30672-8 Epub 2019/03/05. PubMed PMID: 30827808.
Van den Bruel A, Thompson MJ, Haj-Hassan T, Stevens R, Moll H, Lakhanpaul M, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ. 2011;342:d3082. https://doi.org/10.1136/bmj.d3082 Epub 2011/06/10. PubMed PMID: 21653621.
Brown JVE, Meader N, Wright K, Cleminson J, McGuire W. Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020. https://doi.org/10.1001/jamapediatrics.2019.5669 Epub 2020/02/06. PubMed PMID: 32011640.
Self WH, Rosen J, Sharp SC, Filbin MR, Hou PC, Parekh AD, et al. Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections. J Clin Med. 2017;6(10). https://doi.org/10.3390/jcm6100094 Epub 2017/10/11. PubMed PMID: 28991170; PubMed Central PMCID: PMCPMC5664009.
Oved K, Cohen A, Boico O, Navon R, Friedman T, Etshtein L, et al. A novel host-proteome signature for distinguishing between acute bacterial and viral infections. PLoS One. 2015;10(3):e0120012. https://doi.org/10.1371/journal.pone.0120012 Epub 2015/03/19. PubMed PMID: 25785720; PubMed Central PMCID: PMCPMC4364938.
Srugo I, Klein A, Stein M, Golan-Shany O, Kerem N, Chistyakov I, et al. Validation of a Novel Assay to Distinguish Bacterial and Viral Infections. Pediatrics. 2017;140(4). https://doi.org/10.1542/peds.2016-3453 Epub 2017/09/15. PubMed PMID: 28904072.
Ashkenazi-Hoffnung L, Oved K, Navon R, Friedman T, Boico O, Paz M, et al. A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study. Eur J Clin Microbiol Infect Dis. 2018;37(7):1361–71. https://doi.org/10.1007/s10096-018-3261-3 Epub 2018/04/28. PubMed PMID: 29700762; PubMed Central PMCID: PMCPMC6015097.
Mahajan P, Kuppermann N, Mejias A, Suarez N, Chaussabel D, Casper TC, et al. Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger. JAMA. 2016;316(8):846–57. https://doi.org/10.1001/jama.2016.9207 Epub 2016/08/24. PubMed PMID: 27552618; PubMed Central PMCID: PMCPMC5122927.
Herberg JA, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, et al. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children. JAMA. 2016;316(8):835–45. https://doi.org/10.1001/jama.2016.11236 Epub 2016/08/24. PubMed PMID: 27552617; PubMed Central PMCID: PMCPMC5997174.
Gomez-Carballa A, Cebey-Lopez M, Pardo-Seco J, Barral-Arca R, Rivero-Calle I, Pischedda S, et al. A qPCR expression assay of IFI44L gene differentiates viral from bacterial infections in febrile children. Sci Rep. 2019;9(1):11780. https://doi.org/10.1038/s41598-019-48162-9 Epub 2019/08/15. PubMed PMID: 31409879; PubMed Central PMCID: PMCPMC6692396.
We thank Sylvia Büttner for technical assistance.
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not applicable. Open access funding provided by Projekt DEAL.
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This study was approved by the ethics committee of the Medical Faculty Mannheim, Heidelberg University (2018-832R-MA). The need for informed consents was waived due to the retrospective nature of the study.
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The authors declare that they have no competing interests.
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Papan, C., Willersinn, M., Weiß, C. et al. Antibiotic utilization in hospitalized children under 2 years of age with influenza or respiratory syncytial virus infection – a comparative, retrospective analysis. BMC Infect Dis 20, 606 (2020). https://doi.org/10.1186/s12879-020-05336-5
- Influenza virus
- Respiratory syncytial virus
- Antimicrobial stewardship