45. Clinical characteristics and outcomes of PVL-producing Staphylococcus aureus sepsis in children
Main Article Content
Abstract
Panton-Valentine leukocidin (PVL), a major virulence factor secreted by Staphylococcus aureus, is associated with severe clinical manifestations, underscoring the gravity of the situation. However, the role of PVL in Staphylococcus aureus sepsis remains unclear. We conducted a descriptive case series study on 187 children with Staphylococcus aureus bloodstream infection at the Vietnam National Children’s Hospital from 2022 to 2025, aiming to evaluate the association between PVL presence and clinical presentation, laboratory findings, and treatment outcomes. Of 187 cases, 87% were methicillin-resistant S. aureus (MRSA), and 36.4 % were multidrug-resistant S. aureus strain All isolates were fully susceptible to vancomycin. PVL gene-carrying strains accounted for 71.1%. PVL-positive S. aureus strains were associated with osteoarticular infections (osteomyelitis, septic arthritis). Notably, there was no significant difference in treatment outcomes between PVL-positive and PVL-negative S. aureus bloodstream infections in children, highlighting the need for further research in this area.
Article Details
Keywords
PVL, Staphylococcus aureus, Sepsis, Children
References
1. Inagaki K, Lucar J, Blackshear C, et al. Methicillin-susceptible and Methicillin-resistant Staphylococcus aureus Bacteremia: Nationwide Estimates of 30-Day Readmission, In-hospital Mortality, Length of Stay, and Cost in the United States. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019; 69(12): 2112-2118. doi:10.1093/cid/ciz123.
2. Kaneko J, Kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes. Biosci Biotechnol Biochem. 2004; 68(5): 981-1003. doi:10.1271/bbb.68.981.
3. Panton PN, Valentine FCO. Staphylococcal Toxin. The Lancet. 1932; 219(5662): 506-508. doi:10.1016/S0140-6736(01)24468-7.
4. Vandenesch F, Naimi T, Enright MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis. 2003; 9(8): 978-984. doi:10.3201/eid0908.030089.
5. Shallcross LJ, Fragaszy E, Johnson AM, et al. The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis. Lancet Infect Dis. 2013; 13(1): 43-54. doi:10.1016/S1473-3099(12)70238-4.
6. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2005; 6(1): 2-8. doi:10.1097/01.PCC.0000149131.72248.E6.
7. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3): 268-281. doi:10.1111/j.1469-0691.2011.03570.x.
8. Campbell AJ, Mowlaboccus S, Coombs GW, et al. Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia. J Glob Antimicrob Resist. 2022; 29: 197-206. doi:10.1016/j.jgar.2022.03.012.
9. Qu MD, Kausar H, Smith S, et al. Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: A case-control study. PLoS ONE. 2022; 17(3): e0265476. doi:10.1371/journal.pone.0265476.
10. Gijón M, Bellusci M, Petraitiene B, et al. Factors associated with severity in invasive community-acquired Staphylococcus aureus infections in children: a prospective European multicentre study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2016; 22(7): 643.e1-6. doi:10.1016/j.cmi.2016.04.004.
11. Bocchini CE, Hulten KG, Mason EO Jr, et al. Panton-Valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children. Pediatrics. 2006; 117(2): 433-440. doi:10.1542/peds.2005-0566.
12. Dohin B, Gillet Y, Kohler R, et al. Pediatric bone and joint infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus. Pediatr Infect Dis J. 2007; 26(11): 1042-1048. doi:10.1097/INF.0b013e318133a85e.
13. Gillet Y, Issartel B, Vanhems P, et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet Lond Engl. 2002; 359(9308): 753-759. doi:10.1016/S0140-6736(02)07877-7.
14. Murray RJ, Robinson JO, White JN, et al. Community-acquired pneumonia due to pandemic A(H1N1)2009 influenzavirus and methicillin resistant Staphylococcus aureus co-infection. PloS One. 2010; 5(1): e8705. doi:10.1371/journal.pone.0008705.
15. Correa-Jiménez O, Pinzón-Redondo H, Reyes N. High frequency of Panton-Valentine leukocidin in Staphylococcus aureus causing pediatric infections in the city of Cartagena-Colombia. J Infect Public Health. 2016 Jul-Aug; 9(4): 415-20. doi: 10.1016/j.jiph.2015.10.017.
16. Gillet Y, Dumitrescu O, Tristan A, et al. Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal diseases. Int J Antimicrob Agents. 2011; 38(6): 457-464. doi:10.1016/j.ijantimicag.2011.05.003.
17. Saeed K, Gould I, Esposito S, et al. Panton-Valentine leukocidin-positive Staphylococcus aureus: a position statement from the International Society of Chemotherapy. Int J Antimicrob Agents. 2018; 51(1): 16-25. doi:10.1016/j.ijantimicag.2017.11.002.
18. Lewis D, Campbell R, Cookson B, et al. Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections (PVL-SA) in England. Health Prot Agency Lond UK. Published online 2008.
19. Yamaki J, Lee M, Shriner KA, Wong-Beringer A. Can clinical and molecular epidemiologic parameters guide empiric treatment with vancomycin for methicillin-resistant Staphylococcus aureus infections? Diagn Microbiol Infect Dis. 2011; 70(1): 124-130. doi:10.1016/j.diagmicrobio.2010.12.003.
20. Wehrhahn MC, Robinson JO, Pearson JC, et al. Clinical and laboratory features of invasive community-onset methicillin-resistant Staphylococcus aureus infection: a prospective case-control study. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2010; 29(8): 1025-1033. doi:10.1007/s10096-010-0973-4.
21. Darboe S, Dobreniecki S, Jarju S, et al. Prevalence of Panton-Valentine Leukocidin (PVL) and Antimicrobial Resistance in Community-Acquired Clinical Staphylococcus aureus in an Urban Gambian Hospital: A 11-Year Period Retrospective Pilot Study. Front Cell Infect Microbiol. 2019; 9: 170. doi:10.3389/fcimb.2019.00170.
22. McGuire E, Neill C, Collin SM, et al. Is Panton-Valentine leucocidin (PVL) toxin associated with poor clinical outcomes in patients with community-acquired Staphylococcus aureus bacteraemia? J Med Microbiol. 2023; 72(4). doi:10.1099/jmm.0.001683.
2. Kaneko J, Kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes. Biosci Biotechnol Biochem. 2004; 68(5): 981-1003. doi:10.1271/bbb.68.981.
3. Panton PN, Valentine FCO. Staphylococcal Toxin. The Lancet. 1932; 219(5662): 506-508. doi:10.1016/S0140-6736(01)24468-7.
4. Vandenesch F, Naimi T, Enright MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis. 2003; 9(8): 978-984. doi:10.3201/eid0908.030089.
5. Shallcross LJ, Fragaszy E, Johnson AM, et al. The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis. Lancet Infect Dis. 2013; 13(1): 43-54. doi:10.1016/S1473-3099(12)70238-4.
6. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2005; 6(1): 2-8. doi:10.1097/01.PCC.0000149131.72248.E6.
7. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3): 268-281. doi:10.1111/j.1469-0691.2011.03570.x.
8. Campbell AJ, Mowlaboccus S, Coombs GW, et al. Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia. J Glob Antimicrob Resist. 2022; 29: 197-206. doi:10.1016/j.jgar.2022.03.012.
9. Qu MD, Kausar H, Smith S, et al. Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: A case-control study. PLoS ONE. 2022; 17(3): e0265476. doi:10.1371/journal.pone.0265476.
10. Gijón M, Bellusci M, Petraitiene B, et al. Factors associated with severity in invasive community-acquired Staphylococcus aureus infections in children: a prospective European multicentre study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2016; 22(7): 643.e1-6. doi:10.1016/j.cmi.2016.04.004.
11. Bocchini CE, Hulten KG, Mason EO Jr, et al. Panton-Valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children. Pediatrics. 2006; 117(2): 433-440. doi:10.1542/peds.2005-0566.
12. Dohin B, Gillet Y, Kohler R, et al. Pediatric bone and joint infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus. Pediatr Infect Dis J. 2007; 26(11): 1042-1048. doi:10.1097/INF.0b013e318133a85e.
13. Gillet Y, Issartel B, Vanhems P, et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet Lond Engl. 2002; 359(9308): 753-759. doi:10.1016/S0140-6736(02)07877-7.
14. Murray RJ, Robinson JO, White JN, et al. Community-acquired pneumonia due to pandemic A(H1N1)2009 influenzavirus and methicillin resistant Staphylococcus aureus co-infection. PloS One. 2010; 5(1): e8705. doi:10.1371/journal.pone.0008705.
15. Correa-Jiménez O, Pinzón-Redondo H, Reyes N. High frequency of Panton-Valentine leukocidin in Staphylococcus aureus causing pediatric infections in the city of Cartagena-Colombia. J Infect Public Health. 2016 Jul-Aug; 9(4): 415-20. doi: 10.1016/j.jiph.2015.10.017.
16. Gillet Y, Dumitrescu O, Tristan A, et al. Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal diseases. Int J Antimicrob Agents. 2011; 38(6): 457-464. doi:10.1016/j.ijantimicag.2011.05.003.
17. Saeed K, Gould I, Esposito S, et al. Panton-Valentine leukocidin-positive Staphylococcus aureus: a position statement from the International Society of Chemotherapy. Int J Antimicrob Agents. 2018; 51(1): 16-25. doi:10.1016/j.ijantimicag.2017.11.002.
18. Lewis D, Campbell R, Cookson B, et al. Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections (PVL-SA) in England. Health Prot Agency Lond UK. Published online 2008.
19. Yamaki J, Lee M, Shriner KA, Wong-Beringer A. Can clinical and molecular epidemiologic parameters guide empiric treatment with vancomycin for methicillin-resistant Staphylococcus aureus infections? Diagn Microbiol Infect Dis. 2011; 70(1): 124-130. doi:10.1016/j.diagmicrobio.2010.12.003.
20. Wehrhahn MC, Robinson JO, Pearson JC, et al. Clinical and laboratory features of invasive community-onset methicillin-resistant Staphylococcus aureus infection: a prospective case-control study. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2010; 29(8): 1025-1033. doi:10.1007/s10096-010-0973-4.
21. Darboe S, Dobreniecki S, Jarju S, et al. Prevalence of Panton-Valentine Leukocidin (PVL) and Antimicrobial Resistance in Community-Acquired Clinical Staphylococcus aureus in an Urban Gambian Hospital: A 11-Year Period Retrospective Pilot Study. Front Cell Infect Microbiol. 2019; 9: 170. doi:10.3389/fcimb.2019.00170.
22. McGuire E, Neill C, Collin SM, et al. Is Panton-Valentine leucocidin (PVL) toxin associated with poor clinical outcomes in patients with community-acquired Staphylococcus aureus bacteraemia? J Med Microbiol. 2023; 72(4). doi:10.1099/jmm.0.001683.