Staphylococcal pneumonia associated with Panton-Valentine leucocidin (PVL) toxin

Abstract

Panton-Valentine leukocidin (PVL) is a toxine which forms a pore-forming heptamer on neutrophil membrandes leading to neutrophil lysis. Invasive community-onset PVL producing staphylococcus aureus (S. aureus) induced diseases have emerged worldwide, but incidence vary and is strongly attributed to strain types and lineages. Unfortunately diagnostic microbiology laboratories do not routinely test for PVL. These strains have been reported to exceed in virulence hospital-acquired MRSA (methicillin-resistant S. aureus) causing sepsis, necrotizing fasciitis but in rare cases cause severe necrotizing pneumonia. PVL S. aureus necrotizing pneumonia requires early suspicion, particularly in young otherwise healthy individuals, when the clinical picture rapidly evolves, presenting with cavitary consolidation and bilateral infiltrates in the lung – which has been demonstrated within this article in a dramatic case – pleural effusion and hemoptysis. Prompt hospitalization and aggressive treatment with intravenous antimicrobial therapy is warranted to improve outcomes. However, in vitro findings suggest that some antibiotics binding to penicillin binding protein 1 may even increase bacterial PVL expression. In necrotizing pneumonia PVL S. aureus infection is prudent to antibiotic therapy at the highest safest dose at regular intervals to avoid a drop in concentration to sub-MIC. Decolonization and bioburden reduction are proven prophylactic methods also to prevent PVL S. aureus zoonotic cross infections.
This manuscript with case presentation gives an overview on important aspects of PVL S. aureus epidemiology, antimicrobial treatment options and decolonization strategies.

Zusammenfassung

Panton-Valentine Leukocidin (PVL) ist ein Toxin, das auf den Membranen von Neutrophilen ein porenbildendes Heptamer bildet und einen auf neutrophile Granulozyen lysierenden Effekt besitzt. Durch PVL-produzierende Staphylococcus aureus (S. aureus) ausgelöste Erkrankungen treten regional unterschiedlich auf. Die Differenz der Inzidenz hängt stark von den Stammtypen und -linien ab. Leider wird S. aureus in mikrobiologischen Laboren nicht routinemäßig auf PVL-produzierende Eigenschaften getestet. Die Virulenz PVL-produzierender S. aureus von im Krankenhaus erworbenen Infektionen lag über denen der MRSA (Methicillin-resistente S. aureus) und sie verursachen häufiger Sepsis, nekrotisierende Fasziitiden und in seltenen Fällen schwere nekrotisierende Pneumonien. Eine nekrotisierende Pneumonie, die durch PVL-produzierenden S. aureus verursacht wird, erfordert eine frühzeitige antimikrobielle Intervention. Dies betrifft insbesondere junge, ansonsten gesunde Personen, da sich sehr schnell kavitäre Einschmelzungen, Pleuraergüsse und bilaterale Infiltrate in der Lunge mit Hämoptysen entwickeln können, wie ein hier exemplarisch präsentierter Kasus eindrucksvoll demonstriert. In-vitro-Ergebnisse deuten allerdings darauf hin, dass einige Antibiotika, die an das Penicillin-bindende Protein 1 binden, die bakterielle PVL-Expression sogar noch steigern können, was die antimikrobiellen Therapieoptionen einschränkt. Bei einer nekrotisierenden Pneumonie mit PVL-produzierenden S. aureus ist eine Antibiotikatherapie mit der höchsten und sichersten Dosis in regelmäßigen Abständen erforderlich, um ein Absinken der Konzentration auf sub-MIC zu vermeiden. Dekolonisierung und Bioburden-Reduktion reduzieren das Erkrankungsrisiko einschließlich zoonotischer, PVL-produzierender S. aureus-Infektionen.
Diese Übersicht mit integrierter Falldarstellung stellt die Epidemiologie der PVL-produzierten S. aureus ausgelösten nekrotisierenden Pneumonie, deren antimikrobielle Behandlungsmöglichkeiten und Dekolonisierungsstrategien vor.

Keywords

staphylococcus aureus - panton-valentine leucocidin toxin - PVL - pneumonia

Schlüsselwörter

Staphylokokkus aureus - Panton-Valentine Leucocidin Toxin - PVL - Pneumonie

Publication History

Received: 24 April 2025

Accepted after revision: 22 July 2025

Article published online:
12 August 2025

• References

• 1 Tong SYC, Davis JS, Eichenberger E. et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015; 28: 603-661
• 2 Morgan MS. Diagnosis and treatment of Panton-Valentine leukocidin (PVL)-associated staphylococcal pneumonia. Int J Antimicrob Agents 2007; 30: 289-296
• 3 Price JR, Cole K, Bexley A. et al. Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing. Lancet Infect Dis 2017; 17: 207-214
• 4 Denis O, Deplano A, De Beenhouwer H. et al. Polyclonal emergence and importation of community-acquired methicillin-resistant Staphylococcus aureus strains harbouring Panton-Valentine leucocidin genes in Belgium. J Antimicrob Chemother 2005; 56: 1103-1106
• 5 Hayward A, Knott F, Petersen I. et al. Increasing hospitalizations and general practice prescriptions for community-onset staphylococcal disease, England. Emerg Infect Dis 2008; 14: 720-726
• 6 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: 753-759
• 7 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: 16-25
• 8 Krutikov M, Rahman A, Tiberi S. Necrotizing pneumonia (aetiology, clinical features and management). Curr Opin Pulm Med 2019; 25: 225-232
• 9 Tsai Y-F, Ku Y-H. Necrotizing pneumonia: a rare complication of pneumonia requiring special consideration. Curr Opin Pulm Med 2012; 18: 246-252
• 10 Chou D-W, Wu S-L, Lee C-T. Intensive care unit-acquired complicated necrotizing pneumonia caused by Enterobacter cloacae: A case report. Intractable Rare Dis Res 2018; 7: 283-286
• 11 Alkhalifa W, Ali BA, AlDandan H. et al. Rhodococcus equi bacteremia with necrotizing pneumonia and brain abscess in a newly diagnosed HIV patient in Saudi Arabia: A case report and review of literature. Heliyon 2023; 9: e21953
• 12 Schiavo DN, Bauer PR, Iyer VN. et al. Fatal fulminant necrotizing pneumonia: a case report. J Med Case Reports 2014; 8: 37
• 13 Demir T, Coplu N, Bayrak H. et al. Panton-Valentine leucocidin gene carriage among Staphylococcus aureus strains recovered from skin and soft tissue infections in Turkey. J Antimicrob Chemother 2012; 67: 837-840
• 14 Hewagama S, Spelman T, Woolley M. et al. The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl) in Central Australia, 2006–2010. BMC Infect Dis 2016; 16: 382
• 15 Takadama S, Nakaminami H, Sato A. et al. Dissemination of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus USA300 clone in multiple hospitals in Tokyo, Japan. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 2018; 24: 1211.e1-1211.e7
• 16 Asiimwe BB, Baldan R, Trovato A. et al. Molecular epidemiology of Panton-Valentine Leukocidin-positive community-acquired methicillin resistant Staphylococcus aureus isolates in pastoral communities of rural south western Uganda. BMC Infect Dis 2017; 17: 24
• 17 Robinson DA, Kearns AM, Holmes A. et al. Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet Lond Engl 2005; 365: 1256-1258
• 18 Pantelides NM, Gopal Rao G, Charlett A. et al. Preadmission screening of adults highlights previously unrecognized carriage of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus in London: a cause for concern?. J Clin Microbiol 2012; 50: 3168-3171
• 19 Waldenburger S, Vogel U, Goebeler M. et al. Community-acquired skin infections caused by Staphylococcus aureus: What is the role of the Panton-Valentine leukocidin toxin?. J Dtsch Dermatol Ges J Ger Soc Dermatol JDDG 2014; 12: 59-66
• 20 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: 43-54
• 21 Shahini Shams Abadi M, Nikokar I, Hoseini Alfatemi SM. et al. Epidemiology of Panton-Valentine Leukocidin harbouring Staphylococcus aureus in cutaneous infections from Iran: a systematic review and meta-analysis. Infez Med 2017; 25: 217-223
• 22 Sharma-Kuinkel BK, Ahn SH, Rude TH. et al. Presence of genes encoding panton-valentine leukocidin is not the primary determinant of outcome in patients with hospital-acquired pneumonia due to Staphylococcus aureus. J Clin Microbiol 2012; 50: 848-856
• 23 Genestier A-L, Michallet M-C, Prévost G. et al. Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils. J Clin Invest 2005; 115: 3117-3127
• 24 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: 981-1003
• 25 Lina G, Piémont Y, Godail-Gamot F. et al. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis Off Publ Infect Dis Soc Am 1999; 29: 1128-1132
• 26 Diep BA, Chan L, Tattevin P. et al. Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury. Proc Natl Acad Sci U S A 2010; 107: 5587-5592
• 27 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: 978-984
• 28 Osterlund A, Kahlmeter G, Bieber L. et al. Intrafamilial spread of highly virulent staphylococcus aureus strains carrying the gene for Panton-Valentine leukocidin. Scand J Infect Dis 2002; 34: 763-764
• 29 Balis E, Diacaki C, Tselioti P. et al. Community-acquired pneumonia and bacteremia due to methicillin-resistant Staphylococcus aureus carrying Panton-Valentine-leukocidin gene in Greece: two case reports and literature review. J Chemother Florence Italy 2007; 19: 703-708
• 30 CDC. Strategies to Prevent Hospital-onset Staphylococcus aureus Bloodstream Infections in Acute Care Facilities. EmStaphylococcus Aureusem. 2024 Accessed April 02, 2025 at: https://www.cdc.gov/staphylococcus-aureus/hcp/prevent-in-acute-care-facilities/index.html
• 31 Health Protection Agency. Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections (PVL-SA) in England. London: UK Government; 2008
• 32 Klein JL, Petrovic Z, Treacher D. et al. Severe community-acquired pneumonia caused by Panton-Valentine leukocidin-positive Staphylococcus aureus: first reported case in the United Kingdom. Intensive Care Med 2003; 29: 1399
• 33 Vardakas KZ, Matthaiou DK, Falagas ME. Incidence, characteristics and outcomes of patients with severe community acquired-MRSA pneumonia. Eur Respir J 2009; 34: 1148-1158
• 34 Haque NZ, Arshad S, Peyrani P. et al. Analysis of pathogen and host factors related to clinical outcomes in patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2012; 50: 1640-1644
• 35 Gillet Y, Vanhems P, Lina G. et al. Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin. Clin Infect Dis Off Publ Infect Dis Soc Am 2007; 45: 315-321
• 36 Gillet Y, Tristan A, Rasigade J-P. et al. Prognostic factors of severe community-acquired staphylococcal pneumonia in France. Eur Respir J 2021; 58: 2004445
• 37 Dumitrescu O, Badiou C, Bes M. et al. Effect of antibiotics, alone and in combination, on Panton-Valentine leukocidin production by a Staphylococcus aureus reference strain. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 2008; 14: 384-388
• 38 Dumitrescu O, Choudhury P, Boisset S. et al. Beta-lactams interfering with PBP1 induce Panton-Valentine leukocidin expression by triggering sarA and rot global regulators of Staphylococcus aureus. Antimicrob Agents Chemother 2011; 55: 3261-3271
• 39 Gillet Y, Dumitrescu O, Tristan A. et al. Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal diseases. Int J Antimicrob Agents 2011; 38: 457-464
• 40 Wargo KA, Eiland EH. Appropriate antimicrobial therapy for community-acquired methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis Off Publ Infect Dis Soc Am 2005; 40: 1376-1378 author reply 1378–1379
• 41 Micek ST, Dunne M, Kollef MH. Pleuropulmonary complications of Panton-Valentine leukocidin-positive community-acquired methicillin-resistant Staphylococcus aureus: importance of treatment with antimicrobials inhibiting exotoxin production. Chest 2005; 128: 2732-2738
• 42 British Thoracic Society. Annotated BTS CAP guideline summary of recommendations (2015). BTS Guidelines for the Management of Community Acquired Pneumonia in Adults: update 2009. Accessed April 02, 2025 at: https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults/
• 43 Liu C, Bayer A, Cosgrove SE. et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis Off Publ Infect Dis Soc Am 2011; 52: e18-55
• 44 Ewig S, Kolditz M, Pletz M. et al. Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie – Update 2021. Pneumologie 2021; 75: 665-729
• 45 Gauduchon V, Cozon G, Vandenesch F. et al. Neutralization of Staphylococcus aureus Panton Valentine leukocidin by intravenous immunoglobulin in vitro. J Infect Dis 2004; 189: 346-353
• 46 Gillissen A. Stellenwert von Kortikosteroiden bei der ambulant erworbenen Pneumonie. Pneumo News 2024; 16: 42-45
• 47 Chaudhuri D, Nei AM, Rochwerg B. et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med 2024; 52: e219-e233
• 48 Schweigert M, Dubecz A, Beron M. et al. Surgical therapy for necrotizing pneumonia and lung gangrene. Thorac Cardiovasc Surg 2013; 61: 636-641
• 49 von Eiff C, Becker K, Machka K. et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med 2001; 344: 11-16
• 50 Sharara SL, Maragakis LL, Cosgrove SE. Decolonization of Staphylococcus aureus. Infect Dis Clin North Am 2021; 35: 107-133
• 51 Botelho-Nevers E, Gagnaire J, Verhoeven PO. et al. Decolonization of Staphylococcus aureus carriage. Med Mal Infect 2017; 47: 305-310
• 52 Botelho-Nevers E, Gagnaire J, Verhoeven PO. et al. Decolonization of Staphylococcus aureus carriage. Med Mal Infect 2017; 47: 305-310
• 53 Dahal M, Schwan WR. Management of methicillin-resistant Staphylococcus aureus mediated ventilator-associated pneumonia. Curr Trends Microbiol 2018; 12: 95-107