Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department’s Real-Life Experience
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- van Woensel, J.B.M. Viral Lower Respiratory Tract Infection in Infants and Young Children. BMJ 2003, 327, 36–40. [Google Scholar] [CrossRef] [PubMed]
- Katz, S.E.; Williams, D.J. Pediatric Community-Acquired Pneumonia in the United States. Infect. Dis. Clin. N. Am. 2018, 32, 47–63. [Google Scholar] [CrossRef] [PubMed]
- van de Maat, J.; van de Voort, E.; Mintegi, S.; Gervaix, A.; Nieboer, D.; Moll, H.; Oostenbrink, R.; Moll, H.A.; Oostenbrink, R.; van Veen, M.; et al. Antibiotic Prescription for Febrile Children in European Emergency Departments: A Cross-Sectional, Observational Study. Lancet Infect. Dis. 2019, 19, 382–391. [Google Scholar] [CrossRef] [PubMed]
- Keith, T.; Saxena, S.; Murray, J.; Sharland, M. Risk–Benefit Analysis of Restricting Antimicrobial Prescribing in Children: What Do We Really Know? Curr. Opin. Infect. Dis. 2010, 23, 242–248. [Google Scholar] [CrossRef] [PubMed]
- Cantarero-Arévalo, L.; Hallas, M.P.; Kaae, S. Parental Knowledge of Antibiotic Use in Children with Respiratory Infections: A Systematic Review. Int. J. Pharm. Pract. 2017, 25, 31–49. [Google Scholar] [CrossRef] [PubMed]
- Pichichero, M.E. Understanding Antibiotic Overuse for Respiratory Tract Infections in Children. Pediatrics 1999, 104, 1384–1388. [Google Scholar] [CrossRef]
- Florin, T.A.; Plint, A.C.; Zorc, J.J. Viral Bronchiolitis. Lancet 2017, 389, 211–224. [Google Scholar] [CrossRef]
- Little, P.; Francis, N.A.; Stuart, B.; O’Reilly, G.; Thompson, N.; Becque, T.; Hay, A.D.; Wang, K.; Sharland, M.; Harnden, A.; et al. Antibiotics for Lower Respiratory Tract Infection in Children Presenting in Primary Care in England (ARTIC PC): A Double-Blind, Randomised, Placebo-Controlled Trial. Lancet 2021, 398, 1417–1426. [Google Scholar] [CrossRef]
- Costelloe, C.; Metcalfe, C.; Lovering, A.; Mant, D.; Hay, A.D. Effect of Antibiotic Prescribing in Primary Care on Antimicrobial Resistance in Individual Patients: Systematic Review and Meta-Analysis. BMJ 2010, 340, c2096. [Google Scholar] [CrossRef]
- Gagliotti, C.; Buttazzi, R.; Ricchizzi, E.; Moro, M.L.; Ambretti, S.; Carretto, E.; Pedna, M.F.; Sarti, M.; Venturelli, C. Sorveglianza Dell’antibioticoresistenza e Uso Di Antibiotici Sistemici in Emilia-Romagna. Rapporto 2020; Regione Emilia-Romagna: Bologna, Italy, 2021. [Google Scholar]
- Gagliotti, C.; Buttazzi, R.; Ricchizzi, E.; Moro, M.L.; Ambretti, S.; Carretto, E.; Pedna, M.F.; Sarti, M.; Vecchi, E.; Venturelli, C. Sorveglianza Dell’antibioticoresistenza e Uso Di Antibiotici Sistemici in Emilia-Romagna. Rapporto 2021; Regione Emilia-Romagna: Bologna, Italy, 2022. [Google Scholar]
- Stanton, N.; Francis, N.A.; Butler, C.C. Reducing Uncertainty in Managing Respiratory Tract Infections in Primary Care. Br. J. Gen. Pract. 2010, 60, e466–e475. [Google Scholar] [CrossRef]
- Ivanovska, V.; Hek, K.; Mantel Teeuwisse, A.K.; Leufkens, H.G.M.; Nielen, M.M.J.; van Dijk, L. Antibiotic Prescribing for Children in Primary Care and Adherence to Treatment Guidelines. J. Antimicrob. Chemother. 2016, 71, 1707–1714. [Google Scholar] [CrossRef] [PubMed]
- National Institute for Health and Care Excellence (NICE). Bronchiolitis in Children: Diagnosis and Management; NICE: London, UK, 2021. [Google Scholar]
- Bradley, J.S.; Byington, C.L.; Shah, S.S.; Alverson, B.; Carter, E.R.; Harrison, C.; Kaplan, S.L.; Mace, S.E.; McCracken, G.H.; Moore, M.R.; et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin. Infect. Dis. 2011, 53, e25–e76. [Google Scholar] [CrossRef] [PubMed]
- Rudan, I. Epidemiology and Etiology of Childhood Pneumonia. Bull. World Health Organ. 2008, 86, 408–416. [Google Scholar] [CrossRef] [PubMed]
- Harris, M.; Clark, J.; Coote, N.; Fletcher, P.; Harnden, A.; McKean, M.; Thomson, A.; On behalf of the British Thoracic Society Standards of Care Committee. British Thoracic Society Guidelines for the Management of Community Acquired Pneumonia in Children: Update 2011. Thorax 2011, 66, ii1–ii23. [Google Scholar] [CrossRef]
- Gotta, V.; Baumann, P.; Ritz, N.; Fuchs, A.; Baer, G.; Bonhoeffer, J.M.; Heininger, U.; Szinnai, G.; Bonhoeffer, J.; for the ProPAED Study Group. Drivers of Antibiotic Prescribing in Children and Adolescents with Febrile Lower Respiratory Tract Infections. PLoS ONE 2017, 12, e0185197. [Google Scholar] [CrossRef]
- Moro, M.L.; Marchi, M.; Gagliotti, C.; Di Mario, S.; Resi, D.; the “Progetto Bambini a Antibiotici [ProBA]” Regional Group. Why Do Paediatricians Prescribe Antibiotics? Results of an Italian Regional Project. BMC Pediatr. 2009, 9, 69. [Google Scholar] [CrossRef]
- Iacchini, S.; Pezzotti, P.; Caramia, A.; Del Grosso, M.; Camilli, R.; Errico, G.; Giufrè, M.; Pantosti, A.; Maraglino, F.; Palamara, A.T.; et al. AR-ISS: Sorveglianza Nazionale dell’Antibiotico-Resistenza. Dati 2021; Rapporti ISS Sorveglianza RIS-1/2022; Istituto Superiore di Sanità: Roma, Italy, 2022. [Google Scholar]
- Handy, L.K.; Bryan, M.; Gerber, J.S.; Zaoutis, T.; Feemster, K.A. Variability in Antibiotic Prescribing for Community-Acquired Pneumonia. Pediatrics 2017, 139, e20162331. [Google Scholar] [CrossRef]
- Prat, C.; Domínguez, J.; Rodrigo, C.; Gimenez, M.; Azuara, M.; Jiménez, O.; Gali, N.; Ausina, V. Procalcitonin, C-Reactive Protein and Leukocyte Count in Children with Lower Respiratory Tract Infection. Pediatr. Infect. Dis. J. 2003, 22, 963–967. [Google Scholar] [CrossRef]
- Peltola, V.; Mertsola, J.; Ruuskanen, O. Comparison of Total White Blood Cell Count and Serum C-Reactive Protein Levels in Confirmed Bacterial and Viral Infections. J. Pediatr. 2006, 149, 721–724. [Google Scholar] [CrossRef]
- World Health Organization. Revised WHO Classification and Treatment of Pneumonia in Children at Health Facilities: Evidence Summaries; World Health Organization: Geneva, Switzerland, 2014; ISBN 978-92-4-150781-3. [Google Scholar]
- Jehan, F.; Nisar, I.; Kerai, S.; Brown, N.; Ambler, G.; Zaidi, A.K.M. Should Fast Breathing Pneumonia Cases Be Treated with Antibiotics? The Scientific Rationale for Revisiting Management in Low and Middle Income Countries. Int. J. Infect. Dis. 2019, 85, 64–66. [Google Scholar] [CrossRef]
- Rambaud-Althaus, C.; Althaus, F.; Genton, B.; D’Acremont, V. Clinical Features for Diagnosis of Pneumonia in Children Younger than 5 Years: A Systematic Review and Meta-Analysis. Lancet Infect. Dis. 2015, 15, 439–450. [Google Scholar] [CrossRef]
- Ginsburg, A.S.; Mvalo, T.; Nkwopara, E.; McCollum, E.D.; Ndamala, C.B.; Schmicker, R.; Phiri, A.; Lufesi, N.; Izadnegahdar, R.; May, S. Placebo vs Amoxicillin for Nonsevere Fast-Breathing Pneumonia in Malawian Children Aged 2 to 59 Months: A Double-Blind, Randomized Clinical Noninferiority Trial. JAMA Pediatr. 2019, 173, 21. [Google Scholar] [CrossRef] [PubMed]
- Farida, H.; Triasih, R.; Lokida, D.; Mardian, Y.; Salim, G.; Wulan, W.N.; Butar-butar, D.P.; Sari, R.A.; Budiman, A.; Hayuningsih, C.; et al. Epidemiologic, Clinical, and Serum Markers May Improve Discrimination between Bacterial and Viral Etiologies of Childhood Pneumonia. Front. Med. 2023, 10, 1140100. [Google Scholar] [CrossRef] [PubMed]
- Bhuiyan, M.U.; Blyth, C.C.; West, R.; Lang, J.; Rahman, T.; Granland, C.; De Gier, C.; Borland, M.L.; Thornton, R.B.; Kirkham, L.-A.S.; et al. Combination of Clinical Symptoms and Blood Biomarkers Can Improve Discrimination between Bacterial or Viral Community-Acquired Pneumonia in Children. BMC Pulm. Med. 2019, 19, 71. [Google Scholar] [CrossRef] [PubMed]
- Grammatico-Guillon, L.; Shea, K.; Jafarzadeh, S.R.; Camelo, I.; Maakaroun-Vermesse, Z.; Figueira, M.; Adams, W.G.; Pelton, S. Antibiotic Prescribing in Outpatient Children: A Cohort From a Clinical Data Warehouse. Clin. Pediatr. 2019, 58, 681–690. [Google Scholar] [CrossRef]
Variables | Total Population | LRTI n = 368 | CAP n = 216 | p | Patients Discharged Home n = 416 | Patients Hospitalized n = 168 | p |
---|---|---|---|---|---|---|---|
Females—n (%) | 274 (46.9) | 174 (47.5) | 100 (46.5) | n.s. | 220 (47.1) | 54 (46.2) | n.s. |
Blood test performed—n (%) | 147 (25.2) | 86 (23.5) | 61 (28.4) | n.s. | 96 (20.6) | 51 (43.6) | <0.001 |
CRP > 3 mg/dL—n (%) | 52 (8.9) | 26 (7) | 26 (12) | n.s. | 18 (4.3) | 34 (20.2) | n.s. |
CRP (DS) [mg/dL] | 4.7 (6.6) | 3.2 (3.9) | 6.8 (8.8) | 0.004 | 3.3 (4.3) | 5.2 (7.3) | 0.026 |
CXR performed—n (%) | 329 (56.6) | 154 (42.1) | 175 (81.4) | <0.001 | 267 (57.2) | 64 (54.7) | n.s. |
Consolidations at CXR—n (%) | 113 (34.3) | 8 (5.2) | 105 (60.0) | <0.001 | 86 (32.2) | 28 (43.8) | n.s |
Mean age (SD) [months] | 39.4 (35.7) | 33.8 (32.9) | 49.0 (38.3) | <0.001 | 42.5 (35.0) | 27.2 (35.9) | <0.001 |
Mean weight (SD) [Kg] | 15.6 (9.9) | 14.1 (8.6) | 17.7 (11.4) | <0.001 | 16.5 (9.9) | 12.1 (9.7) | <0.001 |
Mean duration of fever (SD) [days] | 3.1 (2.6) | 2.9 (2.6) | 3.4 (2.5) | 0.012 | 3.0 (2.3) | 3.3 (3.5) | n.s. |
Mean body temperature (SD) [°C] | 37.8 (1) | 37.8 (1) | 38.9 (1.1) | 0.039 | 37.8 (1.1) | 37.9 (1.1) | n.s. |
Mean heart rate (SD) [bpm] | 143.2 (22.9) | 143.8 (23.0) | 142.3 (23.0) | n.s. | 140.4 (22.2) | 154.5 (22.8) | <0.001 |
Mean respiratory rate (SD) [breaths per min] | 39.9 (14.5) | 41.9 (14.6) | 35.8 (13.4) | <0.001 | 38.2 (13.8) | 45.2 (15.1) | <0.001 |
Mean SpO2 (SD) [%] | 96.6 (4.4) | 96.8 (2.5) | 96.3 (6.4) | n.s. | 96.9 (2.1) | 95.1 (8.9) | 0.025 |
Mean WBC count (SD) [/mmc] | 15.0 (7.8) | 14.0 (6.7) | 16.3 (8.9) | n.s. | 13.9 (7.3) | 13.9 (6.9) | n.s. |
Mean neutrophil count (SD) [%] | 63.4 (18.1) | 59.22 (19.4) | 68.7 (14.7) | <0.001 | 62.9 (17.3) | 62.6 (71.6) | n.s. |
Total Population n = 584 | LRTI n = 368 | CAP n = 216 | p | Patients Discharged Home n = 416 | Patients Hospitalized n = 168 | p | |
---|---|---|---|---|---|---|---|
Antibiotic prescription—n (%) | |||||||
Overall | 495 (84.8) | 285 (77.4) | 210 (97.2) | <0.001 | 365 (87.7) | 130 (77.4) | <0.001 |
<2 years | 190 (38.4) | 130 (45.6) | 60 (28.6) | 118 (32.4) | 72 (55.4) | ||
2–5 years | 197 (39.8) | 109 (38.3) | 88 (41.9) | 160 (43.8) | 37 (28.4) | ||
>5 years | 108 (21.8) | 46 (16.1) | 62 (29.5) | 87 (23.8) | 21 (16.2) | ||
NO antibiotic prescription in PED | 86 | 81 | 5 | 50 | 36 | ||
Continued an already prescribed therapy | 104 | 55 | 49 | 90 | 14 | ||
Amoxicillin | |||||||
N (%) | 116 | 90 | 26 | 92 | 24 | ||
Median daily dose (IQR) [mg/kg/day] | 75 (63–82) | 74 (59–80) | 82 (75–95) | <0.001 | 75 (63–82) | 75 (68–81) | n.s. |
Median administration/day (IQR) | 3 (3–3) | 3 (3–3) | 3 (3–3) | n.s. | 3 (3–3) | 3 (3–3) | n.s. |
Median length of therapy (IQR) | 7 (7–7) | 7 (7–7) | 7 (7–8) | n.s. | 7 (7–7) | 7 (5–7) | <0.001 |
Amoxicillin -clavulanic acid | |||||||
N (%) | 147 | 81 | 66 | 135 | 12 | ||
Median daily dose (IQR) [mg/kg/day] | 78 (74–92) | 80 (74–88) | 78 (738–94) | n.s. | 78 (74–92) | 84 (77–93) | n.s. |
Median administration/day (IQR) | 3 (3–3) | 3 (3–3) | 3 (3–3) | n.s. | 3 (3–3) | 3 (3–3) | n.s. |
Median length of therapy (IQR) | 7 (7–8) | 7 (7–8) | 7 (7–8) | 0.021 | 7 (7–8) | 6.5 (5.3–8) | 0.030 |
Oral cephalosporin | |||||||
N (%) | 23 | 19 | 4 | 20 | 3 | ||
Median daily dose (IQR) [mg/kg/day] | 8 (8–8) | 8 (8–8) | 8 (8–10) | n.s. | 8 (8–9) | 8 (7–8) | n.s. |
Median administration/day (IQR) | 2 (2–2) | 2 (2–2) | 2 (2–2) | n.s. | 2 (2–2) | 2 (2–2) | n.s. |
Median length of therapy (IQR) | 7 (7–8) | 7 (7–8) | 7 (7–7.8) | n.s. | 7 (7–8) | 7 (6–7) | n.s. |
Parenteral cephalosporin | |||||||
N (%) | 68 | 6 | 62 | 56 | 12 | ||
Median daily dose (IQR) [mg/kg/day] | 57.5 (48–67) | 52.5 (44–81) | 59 (48–67) | n.s. | 55 (45–65) | 68 (64–77) | 0.004 |
Median administration/day (IQR) | 1 (1–1) | 1 (1–1.3) | 1 (1–1) | n.s. | 1 (1–1) | 1 (1–1) | n.s. |
Median length of therapy (IQR) | 5 (3–6) | 3 (1.8–5.5) | 5 (3–6) | n.s. | 5 (3–6.8) | 5 (2.3–5) | n.s. |
Clarithromycin | |||||||
N (%) | 53 | 41 | 12 | 44 | 9 | ||
Median daily dose (IQR) [mg/kg/day] | 16 (15–19) | 17 (15–19) | 16 (15–18) | n.s. | 16 (15–19) | 16 (16–19) | n.s. |
Median administration/day (IQR) | 2 (2–2) | 2 (2–2) | 2 (2–2) | n.s. | 2 (2–2) | 2 (2–2) | n.s. |
Median length of therapy (IQR) | 7 (7–10) | 7 (7–10) | 7 (7–10) | n.s. | 7.5 (7–10) | 7 (4–8.5) | 0.043 |
Azithromycin | |||||||
N (%) | 11 | 9 | 2 | 9 | 2 | ||
Median daily dose (IQR) [mg/kg/day] | 10 (10–10) | 10 (10–11) | 10 (10–10) | n.s. | 10 (10–10) | 12 (11–12) | n.s. |
Median administration/day (IQR) | 1 (1–1) | 1 (1–1) | 1 (1–1) | n.s. | 1 (1–1) | 1 (1–1) | 0.036 |
Median length of therapy (IQR) | 5 (3–5) | 5 (3–5) | 5 (5–5) | n.s. | 5 (3–5) | 3 (3–3.5) | n.s. |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
OR | CI 95% | p | OR | CI 95% | p | |
Female | 0.212 | 0.877–1.806 | n.s. | |||
Age groups (ref < 2 years) | ||||||
2–5 years | 0.325 | 0.213–0.496 | <0.001 | 0.369 | 0.199–0.684 | 0.002 |
>5 years | 0.347 | 0.206–0.585 | <0.001 | 0.394 | 0.164–0.948 | 0.038 |
Body temperature > 38.5 °C | 1.350 | 0.912–1.996 | n.s. | |||
Heart rate > 160 bpm | 3.194 | 2.156–4.730 | <0.001 | 2.388 | 1.365–4.179 | 0.002 |
Respiratory rate > 60 breaths per minute | 3.583 | 1.819–7.058 | <0.001 | 1.912 | 0.906–4.043 | n.s. |
SpO2 < 92% | 7.416 | 3.213–17.116 | <0.001 | 3.119 | 1.050–9.266 | 0.041 |
N% > 75 | 1.916 | 0.918–3.999 | n.s. | |||
CRP > 3 mg/dl | 1.549 | 0.765–3.134 | n.s. | |||
Diagnosis of LRTI | 1.042 | 0.718–1.511 | n.s. | |||
>3 days of fever | 0.862 | 0.601–1.238 | n.s. |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
OR | CI 95% | p | OR | CI 95% | p | |
Female | 1.025 | 0.648–1.620 | n.s. | |||
Age groups (ref < 2 years) | ||||||
2–5 years | 2.814 | 1.642–4.822 | <0.001 | 1.914 | 0.902–4.061 | n.s. |
>5 years | 4.050 | 1.863–8.806 | <0.001 | 3.115 | 0.828–11.721 | n.s. |
Body temperature > 38.5 °C | 1.421 | 0.823–2.452 | n.s. | |||
Heart rate > 160 bpm | 0.514 | 0.317–0.831 | 0.007 | 0.941 | 0.469–1.888 | n.s. |
Respiratory rate > 60 breaths per minute | 0.039 | 0.222–0.963 | 0.039 | 0.651 | 0.286–1.485 | n.s. |
SpO2 < 92% | 0.838 | 0.311–2.260 | n.s. | |||
N% > 75 | 5.542 | 0.688–44.672 | n.s. | |||
CRP > 3 mg/dL | 7.747 | 0.977–61.402 | n.s. | |||
Diagnosis of LRTI | 0.084 | 0.033–0.210 | <0.001 | 0.069 | 0.016–0.297 | <0.001 |
>3 days of fever | 4.267 | 2.460–7.401 | <0.001 | 3.633 | 1.752–7.533 | <0.001 |
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Pierantoni, L.; Lasala, V.; Dondi, A.; Cifaldi, M.; Corsini, I.; Lanari, M.; Zama, D. Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department’s Real-Life Experience. Life 2023, 13, 1922. https://doi.org/10.3390/life13091922
Pierantoni L, Lasala V, Dondi A, Cifaldi M, Corsini I, Lanari M, Zama D. Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department’s Real-Life Experience. Life. 2023; 13(9):1922. https://doi.org/10.3390/life13091922
Chicago/Turabian StylePierantoni, Luca, Valentina Lasala, Arianna Dondi, Marina Cifaldi, Ilaria Corsini, Marcello Lanari, and Daniele Zama. 2023. "Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department’s Real-Life Experience" Life 13, no. 9: 1922. https://doi.org/10.3390/life13091922
APA StylePierantoni, L., Lasala, V., Dondi, A., Cifaldi, M., Corsini, I., Lanari, M., & Zama, D. (2023). Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department’s Real-Life Experience. Life, 13(9), 1922. https://doi.org/10.3390/life13091922