Low Levels of Procalcitonin Are Related to Decreased Antibiotic Use in Children Hospitalized Due to Influenza
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Data Retrieval
2.3. Inclusion/Exclusion Criteria
2.4. Patients’ Characteristics
2.5. Laboratory Procedures
2.6. Study Groups
2.7. Study Endpoints
2.8. Treatment Success
2.9. Treatment Failure
2.10. Statistical Analysis
2.11. Ethics Committee
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Tokars, J.I.; Olsen, S.J.; Reed, C. Seasonal Incidence of Symptomatic Influenza in the United States. Clin. Infect. Dis. 2018, 66, 1511–1518. [Google Scholar] [CrossRef] [PubMed]
- Jayasundara, K.; Soobiah, C.; Thommes, E.; Tricco, A.C.; Chit, A. Natural attack rate of influenza in unvaccinated children and adults: A meta-regression analysis. BMC Infect. Dis. 2014, 14, 670. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Principi, N.; Esposito, S. Severe influenza in children: Incidence and risk factors. Expert. Rev. Anti Infect. Ther. 2016, 14, 961–968. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Li, Y.; O’Brien, K.L.; Madhi, S.A.; Widdowson, M.A.; Byass, P.; Omer, S.B.; Abbas, Q.; Ali, A.; Amu, A.; et al. Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: A systematic review and modelling study. Lancet Glob. Health 2020, 8, e497–e510. [Google Scholar] [CrossRef] [Green Version]
- Peltola, V.; Ziegler, T.; Ruuskanen, O. Influenza A and B virus infections in children Natural attack rate of influenza in unvaccinated children and adults: A meta-regression analysis. Clin. Infect. Dis. 2003, 36, 299–305. [Google Scholar] [CrossRef] [Green Version]
- McCullers, J.A. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat. Rev. Microbiol. 2014, 12, 252–262. [Google Scholar] [CrossRef]
- Klugman, K.P.; Chien, Y.W.; Madhi, S.A. Pneumococcal pneumonia and influenza: A deadly combination. Vaccine 2009, 27 (Suppl. S3), C9–C14. [Google Scholar] [CrossRef]
- Jain, S.; Kamimoto, L.; Bramley, A.M.; Schmitz, A.M.; Benoit, S.R.; Louie, J.; Sugerman, D.E.; Druckenmiller, J.K.; Ritger, K.A.; Chugh, R.; et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N. Engl. J. Med. 2009, 361, 1935–1944. [Google Scholar] [CrossRef] [Green Version]
- Muthuri, S.G.; Venkatesan, S.; Myles, P.R.; Leonardi-Bee, J.; Al Khuwaitir, T.S.; Al Mamun, A.; Anovadiya, A.P.; Azziz-Baumgartner, E.; Báez, C.; Bassetti, M.; et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: A meta-analysis of individual participant data. Lancet Respir. Med. 2014, 2, 395–404. [Google Scholar] [CrossRef] [Green Version]
- Lee, E.; Seo, J.H.; Kim, H.Y.; Na, S.; Kim, S.H.; Kwon, J.W.; Kim, B.J.; Hong, S.J. Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection. Korean J. Pediatr. 2011, 54, 329–334. [Google Scholar] [CrossRef] [Green Version]
- Kjærsgaard, M.; Leth, R.A.; Udupi, A.; Ank, N. Antibiotic stewardship based on education: Minor impact on knowledge, perception and attitude. Infect. Dis. 2019, 51, 753–763. [Google Scholar] [CrossRef] [PubMed]
- Assicot, M.; Gendrel, D.; Carsin, H.; Raymond, J.; Guilbaud, J.; Bohuon, C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993, 341, 515–518. [Google Scholar] [CrossRef]
- Dandona, P.; Nix, D.; Wilson, M.F.; Aljada, A.; Love, J.; Assicot, M.; Bohuon, C. Procalcitonin increase after endotoxin injection in normal subjects. J. Clin. Endocrinol. Metab. 1994, 79, 1605–1608. [Google Scholar] [CrossRef] [PubMed]
- Tsou, P.Y.; Rafael, J.; Ma, Y.K.; Wang, Y.H.; Raj, S.; Encalada, S.; Deanehan, J.K. Diagnostic accuracy of procalcitonin for bacterial pneumonia in children—A systematic review and meta-analysis. Infect. Dis. 2020, 52, 683–697. [Google Scholar] [CrossRef] [PubMed]
- Tujula, B.; Hämäläinen, S.; Kokki, H.; Pulkki, K.; Kokki, M. Review of clinical practice guidelines on the use of procalcitonin in infections. Infect. Dis. 2020, 52, 227–234. [Google Scholar] [CrossRef]
- Li, Z.; He, L.; Li, S.; He, W.; Zha, C.; Ou, W.; Hou, Q.; Wang, W.; Sun, X.; Liang, H. Combination of procalcitonin and C-reactive protein levels in the early diagnosis of bacterial co-infections in children with H1N1 influenza. Influenza Other. Respir. Viruses 2019, 13, 184–190. [Google Scholar] [CrossRef] [Green Version]
- Rodríguez, A.H.; Avilés-Jurado, F.X.; Díaz, E.; Schuetz, P.; Trefler, S.I.; Solé-Violán, J.; Cordero, L.; Vidaur, L.; Estella, Á.; Pozo Laderas, J.C.; et al. Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis. J. Infect. 2016, 72, 143–151. [Google Scholar] [CrossRef]
- Ahn, S.; Kim, W.Y.; Kim, S.H.; Hong, S.; Lim, C.M.; Koh, Y.; Lim, K.S.; Kim, W. Role of procalcitonin and C-reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza Other Respir. Viruses 2011, 5, 398–403. [Google Scholar] [CrossRef] [Green Version]
- Guervilly, C.; Coisel, Y.; Botelho-Nevers, E.; Dizier, S.; Castanier, M.; Lepaul-Ercole, R.; Brissy, O.; Roch, A.; Forel, J.M.; Papazian, L. Significance of high levels of procalcitonin in patients with influenza A (H1N1) pneumonia. J. Infect. 2010, 61, 355–358. [Google Scholar] [CrossRef]
- Cuquemelle, E.; Soulis, F.; Villers, D.; Roche-Campo, F.; Ara Somohano, C.; Fartoukh, M.; Kouatchet, A.; Mourvillier, B.; Dellamonica, J.; Picard, W.; et al. Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med. 2011, 37, 796–800. [Google Scholar] [CrossRef]
- Ingram, P.R.; Inglis, T.; Moxon, D.; Speers, D. Procalcitonin and C-reactive protein in severe 2009 H1N1 influenza infection. Intensive Care Med. 2010, 36, 528–532. [Google Scholar] [CrossRef] [PubMed]
- Stockmann, C.; Ampofo, K.; Killpack, J.; Williams, D.J.; Edwards, K.M.; Grijalva, C.G.; Arnold, S.R.; McCullers, J.A.; Anderson, E.J.; Wunderink, R.G.; et al. Procalcitonin Accurately Identifies Hospitalized Children with Low Risk of Bacterial Community-Acquired Pneumonia. J. Pediatric. Infect. Dis. Soc. 2018, 7, 46–53. [Google Scholar] [CrossRef] [PubMed]
- Wu, M.H.; Lin, C.C.; Huang, S.L.; Shih, H.M.; Wang, C.C.; Lee, C.C.; Wu, J.Y. Can procalcitonin tests aid in identifying bacterial infections associated with influenza pneumonia? A systematic review and meta-analysis. Influenza Other Respir. Viruses 2013, 7, 349–355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piacentini, E.; Sánchez, B.; Arauzo, V.; Calbo, E.; Cuchi, E.; Nava, J.M. Procalcitonin levels are lower in intensive care unit patients with H1N1 influenza A virus pneumonia than in those with community-acquired bacterial pneumonia. A pilot study. J. Crit. Care 2011, 26, 201–205. [Google Scholar] [CrossRef] [PubMed]
- Hammond, N.E.; Corley, A.; Fraser, J.F. The utility of procalcitonin in diagnosis of H1N1 influenza in intensive care patients. Anaesth. Intensive Care 2011, 39, 238–241. [Google Scholar] [CrossRef] [Green Version]
- Paiva, M.B.; Botoni, F.A.; Teixeira, A.L., Jr.; Miranda, A.S.; Oliveira, C.R.; Abrahão Jde, O.; Faria, G.M.; Nobre, V. The behavior and diagnostic utility of procalcitonin and five other inflammatory molecules in critically ill patients with respiratory distress and suspected 2009 influenza a H1N1 infection. Clinics 2012, 67, 327–334. [Google Scholar] [CrossRef]
- Pfister, R.; Kochanek, M.; Leygeber, T.; Brun-Buisson, C.; Cuquemelle, E.; Machado, M.B.; Piacentini, E.; Hammond, N.E.; Ingram, P.R.; Michels, G. Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: A prospective cohort study, systematic review and individual patient data meta-analysis. Crit. Care 2014, 18, R44. [Google Scholar] [CrossRef] [Green Version]
- Lipsett, S.C.; Hall, M.; Ambroggio, L.; Desai, S.; Shah, S.S.; Brogan, T.V.; Hersh, A.L.; Williams, D.J.; Grijalva, C.G.; Gerber, J.S.; et al. Predictors of Bacteremia in Children Hospitalized with Community-Acquired Pneumonia. Hosp. Pediatr. 2019, 9, 770–778. [Google Scholar] [CrossRef]
- Neuman, M.I.; Hall, M.; Lipsett, S.C.; Hersh, A.L.; Williams, D.J.; Gerber, J.S.; Brogan, T.V.; Blaschke, A.J.; Grijalva, C.G.; Parikh, K.; et al. Utility of Blood Culture among Children Hospitalized with Community-Acquired Pneumonia. Pediatrics 2017, 140, e20171013. [Google Scholar] [CrossRef] [Green Version]
- Andrews, A.L.; Simpson, A.N.; Heine, D.; Teufel, R.J., 2nd. A Cost-Effectiveness Analysis of Obtaining Blood Cultures in Children Hospitalized for Community-Acquired Pneumonia. J. Pediatr. 2015, 167, 1280–1286. [Google Scholar] [CrossRef]
- Heine, D.; Cochran, C.; Moore, M.; Titus, M.O.; Andrews, A.L. The prevalence of bacteremia in pediatric patients with community-acquired pneumonia: Guidelines to reduce the frequency of obtaining blood cultures. Hosp. Pediatr. 2013, 3, 92–96. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klein, E.Y.; Monteforte, B.; Gupta, A.; Jiang, W.; May, L.; Hsieh, Y.H.; Dugas, A. The frequency of influenza and bacterial coinfection: A systematic review and meta-analysis. Influenza Other Respir. Viruses 2016, 10, 394–403. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bender, J.M.; Ampofo, K.; Gesteland, P.; Sheng, X.; Korgenski, K.; Raines, B.; Daly, J.A.; Valentine, K.; Srivastava, R.; Pavia, A.T.; et al. Influenza virus infection in infants less than three months of age. Pediatr. Infect. Dis. J. 2010, 29, 6–9. [Google Scholar] [CrossRef] [PubMed]
- Mermond, S.; Berlioz-Arthaud, A.; Estivals, M.; Baumann, F.; Levenes, H.; Martin, P.M. Aetiology of community-acquired pneumonia in hospitalized adult patients in New Caledonia. Trop. Med. Int. Health 2010, 15, 1517–1524. [Google Scholar] [CrossRef] [Green Version]
- Kotula, J.J., 3rd; Moore, W.S., 2nd; Chopra, A.; Cies, J.J. Association of Procalcitonin Value and Bacterial Coinfections in Pediatric Patients with Viral Lower Respiratory Tract Infections Admitted to the Pediatric Intensive Care Unit. J. Pediatr. Pharmacol. Ther. 2018, 23, 466–472. [Google Scholar] [CrossRef]
- Esposito, S.; Tagliabue, C.; Picciolli, I.; Semino, M.; Sabatini, C.; Consolo, S.; Bosis, S.; Pinzani, R.; Principi, N. Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia. Respir. Med. 2011, 105, 1939–1945. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leng, Y.; Chen, C.; Zhang, Y.; Luo, C.; Liu, B. Ability of serum procalcitonin to distinguish focus of infection and pathogen types in patients with bloodstream infection. Ann. Transl. Med. 2019, 7, 135. [Google Scholar] [CrossRef]
- Cunha, B.A.; Syed, U.; Strollo, S. Swine influenza (H1N1) pneumonia: Elevated serum procalcitonin levels not due to superimposed bacterial pneumonia. Int. J. Antimicrob. Agents 2010, 35, 515–516. [Google Scholar] [CrossRef]
- Terpos, E.; Ntanasis-Stathopoulos, I.; Elalamy, I.; Kastritis, E.; Sergentanis, T.N.; Politou, M.; Psaltopoulou, T.; Gerotziafas, G.; Dimopoulos, M.A. Hematological findings and complications of COVID-19. Am. J. Hematol. 2020, 95, 834–847. [Google Scholar] [CrossRef] [Green Version]
- Liu, F.; Li, L.; Xu, M.; Wu, J.; Luo, D.; Zhu, Y.; Li, B.; Song, X.; Zhou, X. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J. Clin. Virol. 2020, 127, 104370. [Google Scholar] [CrossRef]
- Hu, R.; Han, C.; Pei, S.; Yin, M.; Chen, X. Procalcitonin levels in COVID-19 patients. Int. J. Antimicrob. Agents 2020, 56, 106051. [Google Scholar] [CrossRef] [PubMed]
- Baer, G.; Baumann, P.; Buettcher, M.; Heininger, U.; Berthet, G.; Schäfer, J.; Bucher, H.C.; Trachsel, D.; Schneider, J.; Gambon, M.; et al. Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (ProPAED): A randomized controlled trial. PLoS ONE 2013, 8, e68419. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Florin, T.A.; Ambroggio, L.; Brokamp, C.; Zhang, Y.; Rattan, M.; Crotty, E.; Belsky, M.A.; Krueger, S.; Epperson, T.N.T.; Kachelmeyer, A.; et al. Biomarkers and Disease Severity in Children with Community-Acquired Pneumonia. Pediatrics 2020, 145, e20193728. [Google Scholar] [CrossRef] [PubMed]
No-PAT (n = 291) | PAT (n = 80) | ||||||
---|---|---|---|---|---|---|---|
median | LQ | UQ | median | LQ | UQ | p | |
Age (months) | 33.0 | 11.0 | 64.0 | 35.5 | 19.0 | 61.0 | 0.117 |
Duration of signs/symptoms (days) | 2.0 | 1.0 | 4.0 | 4.5 | 2.0 | 6.0 | 0.000 |
Duration of fever (days) | 2.0 | 1.0 | 4.0 | 4.0 | 2.0 | 6.0 | 0.000 |
Length of stay (days) | 5.0 | 4.0 | 7.0 | 6.0 | 5.0 | 7.0 | 0.013 |
Breath rate (per minute) | 25.0 | 22.0 | 32.0 | 25.5 | 20.0 | 30.0 | 0.969 |
Heart rate (per minute) | 110.0 | 100.0 | 126.0 | 115.0 | 100.0 | 120.0 | 0.990 |
CRP (mg/L) | 5.42 | 1.54 | 14.34 | 6.72 | 2.05 | 20.72 | 0.325 |
PCT (ng/mL) | 0.18 | 0.10 | 0.37 | 0.15 | 0.10 | 0.32 | 0.337 |
WBC (*10^3/µL) | 7.72 | 5.35 | 10.86 | 7.41 | 4.77 | 11.85 | 0.731 |
ANC (*10^3/µL) | 3.56 | 2.09 | 6.32 | 3.41 | 2.15 | 5.47 | 0.577 |
Antibiotic frequency (%) | 28.9 | 61.3 | 0.000 * |
Antibiotic Treatment (n = 84) | Without Antibiotic (n = 207) | ||||||
---|---|---|---|---|---|---|---|
median | LQ | UQ | median | LQ | UQ | p | |
Age (months) | 17.50 | 8.00 | 42.5 | 39.00 | 13.00 | 69.00 | 0.000 |
Duration of signs/symptoms (days) | 3.00 | 1.00 | 5.00 | 2.00 | 1.00 | 4.00 | 0.08 |
Duration of fever (days) | 2.00 | 1.00 | 4.00 | 1.00 | 1.00 | 4.00 | 0.29 |
Length of stay (days) | 7.00 | 6.00 | 11.00 | 5.00 | 3.00 | 6.00 | 0.000 |
Breath rate (per minute) | 29 | 24 | 40 | 24 | 21 | 30 | 0.000 |
Heart rate (per minute) | 120 | 100 | 132 | 108 | 95 | 120 | 0.001 |
CRP (mg/L) | 10.77 | 3.69 | 37.75 | 4.21 | 1.27 | 11.13 | 0.000 |
PCT (ng/mL) | 0.3 | 0.13 | 1.15 | 0.17 | 0.10 | 0.29 | 0.000 |
WBC (*10^3/µL) | 9.27 | 5.47 | 14.05 | 7.26 | 5.35 | 9.82 | 0.003 |
ANC (*10^3/µL) | 4.24 | 2.05 | 8.44 | 3.52 | 2.09 | 5.42 | 0.067 |
Endpoint | ||||||||
---|---|---|---|---|---|---|---|---|
Antibiotic use (No-PAT group) | AUC of 0.658 (95%CI: 0.581 to 0.734, p < 0.01) | |||||||
Cut-off | Sensitivity | 95%CI | Specificity | 95%CI | PPV | 95%CI | NPV | 95%CI |
0.4 ng/mL * | 46.43% | 35.47% to 57.65% | 85.51% | 79.96% to 90.00% | 56.52% | 46.49% to 66.04% | 79.73% | 76.18% to 82.87% |
0.25 ng/mL | 58.33% | 47.06% to 69.00% | 68.60% | 61.80% to 74.86% | 42.98% | 36.51% to 49.70% | 80.23% | 75.61% to 84.15% |
0.5 ng/mL | 36.90% | 26.63% to 48.13% | 88.41% | 83.24% to 92.43% | 56.36% | 44.70% to 67.36% | 77.54% | 74.43% to 80.38% |
1 ng/mL | 26.19% | 17.20% to 36.93% | 95.65% | 91.91% to 97.99% | 70.97% | 54.01% to 83.57% | 76.15% | 73.70% to 78.45% |
Antibiotic continuation (PAT group) | 0.713 (95%CI: 0.6–0.83, p < 0.01) | |||||||
Cut-off | Sensitivity | 95%CI | Specificity | 95%CI | PPV | 95%CI | NPV | 95%CI |
0.23 ng/mL * | 54.55% | 38.85% to 69.61% | 88.89% | 70.84% to 97.65% | 88.89% | 72.69% to 96.01% | 54.55% | 45.82% to 63.00% |
0.25 ng/mL | 52.27% | 36.69% to 67.54% | 88.89% | 70.84% to 97.65% | 88.46% | 71.77% to 95.85% | 53.33% | 44.94% to 61.55% |
0.5 ng/mL | 27.27% | 14.96% to 42.79% | 96.30% | 81.03% to 99.91% | 92.31% | 62.29% to 98.87% | 44.83% | 40.06% to 49.70% |
1 ng/mL | 18.18% | 8.19% to 32.71% | 100.00% | 87.23% to 100.00% | 100% | 42.86% | 39.48% to 46.30% | |
LRTI | AUC = 0.60 (95%CI: 0.53 to 0.66, p < 0.01) | |||||||
0.27 ng/mL * | 49.21% | 40.19% to 58.26% | 72.24% | 66.19% to 77.76% | 47.69% | 41.07% to 54.40% | 73.44% | 69.61% to 76.96% |
Radiologically confirmed pneumonia | AUC 0.626 (95%CI: 0.56 to 0.7, p < 0.01) | |||||||
0.27 ng/mL * | 55.43% | 44.70% to 65.81% | 71.68% | 66.01% to 76.89% | 39.23% | 33.20% to 45.61% | 82.99% | 79.33% to 86.11% |
Antibiotic Implementation (No-PAT) | Odds Reduction of Antibiotic Treatment | ||||||
---|---|---|---|---|---|---|---|
Cut-off | OR | 95%CI | p | % | 95%CI | ||
0.25 | 0.33 | 0.19 | 0.57 | 0.000 | 67 | 43 | 81 |
0.5 | 0.22 | 0.12 | 0.42 | 0.000 | 78 | 58 | 88 |
1 | 0.12 | 0.05 | 0.28 | 0.000 | 88 | 72 | 95 |
Antibiotic continuation (PAT) | Odds reduction of antibiotic treatment | ||||||
Cut-off | OR | 95%CI | p | % | 95%CI | ||
0.25 | 0.09 | 0.02 | 0.44 | 0.003 | 91 | 56 | 98 |
0.5 | 0.12 | 0.01 | 0.98 | 0.048 | 88 | 2 | 99 |
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Wrotek, A.; Wrotek, O.; Jackowska, T. Low Levels of Procalcitonin Are Related to Decreased Antibiotic Use in Children Hospitalized Due to Influenza. Diagnostics 2022, 12, 1148. https://doi.org/10.3390/diagnostics12051148
Wrotek A, Wrotek O, Jackowska T. Low Levels of Procalcitonin Are Related to Decreased Antibiotic Use in Children Hospitalized Due to Influenza. Diagnostics. 2022; 12(5):1148. https://doi.org/10.3390/diagnostics12051148
Chicago/Turabian StyleWrotek, August, Oliwia Wrotek, and Teresa Jackowska. 2022. "Low Levels of Procalcitonin Are Related to Decreased Antibiotic Use in Children Hospitalized Due to Influenza" Diagnostics 12, no. 5: 1148. https://doi.org/10.3390/diagnostics12051148
APA StyleWrotek, A., Wrotek, O., & Jackowska, T. (2022). Low Levels of Procalcitonin Are Related to Decreased Antibiotic Use in Children Hospitalized Due to Influenza. Diagnostics, 12(5), 1148. https://doi.org/10.3390/diagnostics12051148