Chapter 38
Cutaneous Manifestations of Gram-negative Infections
Saul N. Faust,
Diane Gbesemete,
Robert S. Heyderman,
Saul N. Faust
NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorDiane Gbesemete
NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorSaul N. Faust,
Diane Gbesemete,
Robert S. Heyderman,
Saul N. Faust
NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorDiane Gbesemete
NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
Search for more papers by this authorBook Editor(s):Peter Hoeger,
Veronica Kinsler,
Albert Yan,
John Harper,
Arnold Oranje,
Christine Bodemer,
Margarita Larralde,
David Luk, Vibhu Mendiratta,
Diana Purvis,
Peter Hoeger
Search for more papers by this authorVeronica Kinsler
Search for more papers by this authorAlbert Yan
Search for more papers by this authorJohn Harper
Search for more papers by this authorArnold Oranje
Search for more papers by this authorChristine Bodemer
Search for more papers by this authorMargarita Larralde
Search for more papers by this authorVibhu Mendiratta
Search for more papers by this authorDiana Purvis
Search for more papers by this authorFirst published: 20 November 2019
Summary
Gram-negative infections are a rare but potentially life-threatening cause of cutaneous lesions, often requiring urgent recognition and treatment. This chapter discusses the pathophysiology, clinical features and management of the most common Gram-negative infections.
Neisseria meningitidis is a common human nasopharyngeal commensal. In a minority of individuals it causes invasive, life-threatening disease. The cutaneous features are often recognizable at presentation and may cause significant morbidity.
Pseudomonas aeruginosa can cause both localized primary skin lesions and systemic infection with cutaneous manifestations. Pseudomonal skin infections are more commonly, but not exclusively, seen in immunocompromised individuals.
References
- Eykyn SJ, Gransden WR, Phillips I. The causative organisms of septicaemia and their epidemiology. J Antimicrob Chemother 1990; 25(suppl C): 41–58.
- Welch SB, Nadel S. Treatment of meningococcal infection. Arch Dis Child 2003; 88: 608–14.
- Jones D. Epidemiology of meningococcal disease in Europe and the USA. In: K Cartwright (ed.) Meningococcal Disease. Chichester: John Wiley, 1995: 71–114.
- Vieusseux G. Memoire sur la maladie qui a regne a Geneve au printemps de 1805. J Med Chir Pharm 1806: 163.
- Cartwright K. Introduction and historical aspects. In: K Cartwright (ed.) Meningococcal Disease. Chichester: John Wiley, 1995.
-
Herrick W. Extrameningeal meningococcal infections. Arch Intern Med 1919; 23: 409–18.
10.1001/archinte.1919.00090210003001 Google Scholar
- Yazdankhah SP, Caugant DA. Neisseria meningitidis: an overview of the carriage state. J Med Microbiol 2004; 53(Pt 9): 821–32.
- Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 2007; 369: 2196–210.
-
Apicella MA. Neisseria meningitidis. In: GL Mandell, JE Bennett, R Dolin (eds) Mandell, Douglas and Bennett's Principles and Practices of Infectious Diseases, 2, 7th edn. Philadelphia: Churchill Livingstone Elsevier, 2010: 2737–52.
10.1016/B978-0-443-06839-3.00211-3 Google Scholar
- Lingappa JR, Al-Rabeah AM, Hajjeh R et al. Serogroup W-135 meningococcal disease during the Hajj, 2000. Emerg Infect Dis 2003; 9: 665–71.
- Moura AS, Pablos-Méndez A, Layton M, Weiss D. Epidemiology of meningococcal disease, New York City, 1989-2000. Emerg Infect Dis 2003; 9: 355–61.
- Sridhar S, Greenwood B, Head C et al. Global incidence of serogroup B invasive meningococcal disease: a systematic review. Lancet Infect Dis 2015; 15: 1334–46.
- Maiden MC, Frosch M. Molecular techniques for the investigation of meningococcal disease epidemiology. Mol Biotechnol 2001; 18: 119–34.
- Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. Vaccine 2009; 27(suppl 2): B51–63.
- Christensen H, May M, Bowen L et al. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10: 853–61.
- Virji M, Alexandrescu C, Ferguson DJ et al. Variations in the expression of pili: the effect on adherence of Neisseria meningitidis to human epithelial and endothelial cells. Mol Microbiol 1992; 6: 1271–9.
- Virji M, Makepeace K, Ferguson DJ et al. Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis. Mol Microbiol 1992; 6: 2785–95.
- Lomholt H, Poulsen K, Caugant DA, Kilian M. Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases. Proc Natl Acad Sci U S A 1992; 89: 2120–4.
- Nassif X, Beretti JL, Lowy J et al. Roles of pilin and PilC in adhesion of Neisseria meningitidis to human epithelial and endothelial cells. Proc Natl Acad Sci U S A 1994; 91: 3769–73.
- Brendish NJ, Read RC. Neisseria meningitidis serogroup B bivalent factor H binding protein vaccine. Expert Rev Vaccines 2015; 14: 493–503.
- Frasch CE, Borrow R, Donnelly J. Bactericidal antibody is the immunologic surrogate of protection against meningococcal disease. Vaccine 2009; 27(suppl 2): 6.
- Stuart JM, Cartwright KA, Robinson PM, Noah ND. Effect of smoking on meningococcal carriage. Lancet 1989; 2: 723–5.
- Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. II. Development of natural immunity. J Exp Med 1969; 129: 1327–48.
- Blackwell CC, Weir DM, James VS et al. The Stonehouse study: secretor status and carriage of Neisseria species. Epidemiol Infect 1989; 102: 1–10.
- Moore PS, Hierholzer J, DeWitt W et al. Respiratory viruses and mycoplasma as cofactors for epidemic group A meningococcal meningitis. JAMA 1990; 264: 1271–5.
- Griffiss JM. Epidemic meningococcal disease: synthesis of a hypothetical immunoepidemiologic model. Rev Infect Dis 1982; 4: 159–72.
- Filice GA, Hayes PS, Counts GW et al. Risk of group A meningococcal disease: bacterial interference and cross-reactive bacteria among mucosal flora. J Clin Microbiol 1985; 22: 152–6.
- Harrison LH, Armstrong CW, Jenkins SR et al. A cluster of meningococcal disease on a school bus following epidemic influenza. Arch Intern Med 1991; 151: 1005–9.
- Flaegstad T, Gutteberg T, Kristiansen BE. Antibodies to meningococci in children with meningococcal disease. Scand J Infect Dis 1990; 22: 547–51.
- Brindle R, Simani P, Newnham R et al. No association between meningococcal disease and human immunodeficiency virus in adults in Nairobi, Kenya. Trans R Soc Trop Med Hyg 1991; 85: 651.
- Silber E, Sonnenberg P, Ho KC et al. Meningitis in a community with a high prevalence of tuberculosis and HIV infection. J Neurol Sci 1999; 162: 20–6.
- Greenwood BM. The epidemiology of acute bacterial meningitis in tropical Africa. In: JK Williams, J Burnie (eds) Bacterial Meningitis. London: Academic Press, 1987: 61–91.
- Peltola H. Burden of meningitis and other severe bacterial infections of children in Africa: implications for prevention. Clin Infect Dis 2001; 32: 64–75.
- Lewis R, Nathan N, Diarra L et al. Timely detection of meningococcal meningitis epidemics in Africa. Lancet 2001; 358: 287–93.
- Taha M-KK, Parent Du Chatelet I et al. Neisseria meningitidis serogroups W135 and A were equally prevalent among meningitis cases occurring at the end of the 2001 epidemics in Burkina Faso and Niger. J Clin Microbiol 2002; 40: 1083–4.
- Harrison LH, Pass MA, Mendelsohn AB et al. Invasive meningococcal disease in adolescents and young adults. JAMA 2001; 286: 694–9.
- Havens PL, Garland JS, Brook MM et al. Trends in mortality in children hospitalized with meningococcal infections, 1957 to 1987. Pediatr Infect Dis J 1989; 8: 8–11.
- Booy R, Habibi P, Nadel S et al. Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery. Arch Dis Child 2001; 85: 386–90.
- Nadel S. Prospects for eradication of meningococcal disease. Arch Dis Child 2012; 97: 993–8.
- Hill WR, Kinney TD. The cutaneous lesions in acute meningococcaemia: a clinical and pathologic study. JAMA 1947; 134: 513–18.
- Robboy SJ, Mihm MC, Colman RW, Minna JD. The skin in disseminated intravascular coagulation. Prospective analysis of thirty-six cases. Br J Dermatol 1973; 88: 221–9.
- Cahalane SF, Waters M. Fulminant meningococcal septicaemia. A hospital experience. Lancet 1975; 2: 120–1.
- Evans RW, Glick B, Kimball F, Bobell M. Fatal intravascular consumption coagulopathy in meningococcal sepsis. Am J Med 1969; 46: 910–8.
- McGehee WG, Rapaport SI, Hjort PF. Intravascular coagulation in fulminant meningococcemia. Ann Intern Med 1967; 67: 250–60.
- Ferguson JH, Chapman OD. Fulminating meningococcic infections and the so-called Waterhouse-Friderichsen syndrome. Am J Pathol 1948; 24: 763–95.
- Sotto MN, Langer B, Hoshino-Shimizu S, de Brito T. Pathogenesis of cutaneous lesions in acute meningococcemia in humans: light, immunofluorescent, and electron microscopic studies of skin biopsy specimens. J Infect Dis 1976; 133: 506–14.
- Waage A, Halstensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1987; 1: 355–7.
- Waage A, Brandtzaeg P, Halstensen A et al. The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med 1989; 169: 333–8.
- Brandtzaeg P, Kierulf P, Gaustad P et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis 1989; 159: 195–204.
- Brandtzaeg P, Sandset PM, Joø GB et al. The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. Thromb Res 1989; 55: 459–70.
- Girardin E, Grau GE, Dayer JM et al. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N Engl J Med 1988; 319: 397–400.
- Pathan N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child 2003; 88: 601–7.
- Gedde-Dahl TW, Bjark P, Høiby EA et al. Severity of meningococcal disease: assessment by factors and scores and implications for patient management. Rev Infect Dis 1990; 12: 973–92.
- Faust SN, Heyderman RS, Levin M. Disseminated intravascular coagulation and purpura fulminans secondary to infection. Baillieres Best Pract Res Clin Haematol 2000; 13: 179–97.
- Gimbrone M. Vascular endothelium: nature's blood container. In: M Gimbrone (ed.) Endothelium in Haemostasis and Thrombosis. Edinburgh: Churchill Livingstone, 1986: 1–12.
- Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001; 29(7 Suppl): 7.
- Faust SN, Levin M, Harrison OB et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med 2001; 345: 408–16.
- Proceedings of the Third Margaux Conference on Critical Illness: The Endothelium - an Underrecognized Organ in Critical Illness? Sedona, Arizona, USA. November 14-18, 2001. Crit Care Med 2002;30(5 suppl): S179–348.
- Heyderman RS, Klein NJ, Shennan GI, Levin M. Deficiency of prostacyclin production in meningococcal shock. Arch Dis Child 1991; 66: 1296–9.
- Heyderman RS, Klein NJ, Shennan GI, Levin M. Reduction of the anticoagulant activity of glycosaminoglycans on the surface of the vascular endothelium by endotoxin and neutrophils: evaluation by an amidolytic assay. Thromb Res 1992; 67: 677–85.
- Osterud B, Flaegstad T. Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis. Thromb Haemost 1983; 49: 5–7.
- Eling M, Stephens AC, Oragui EE et al. Tissue factor pathway inhibitor (TFPI) levels in the plasma and urine of children with meningococcal disease. Thromb Haemost 2001; 85: 240–4.
- Fourrier F, Lestavel P, Chopin C et al. Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates. Intensive Care Med 1990; 16: 121–4.
- Hesselvik JF, Malm J, Dahlbäck B, Blombäck M. Protein C, protein S and C4b-binding protein in severe infection and septic shock. Thromb Haemost 1991; 65: 126–9.
- Brandtzaeg P, Joø GB, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. Thromb Res 1990; 57: 271–8.
- Powars D, Larsen R, Johnson J et al. Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 1993; 17: 254–61.
- Hermans PW, Hibberd ML, Booy R et al. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group. Lancet 1999; 354: 556–60.
- Westendorp RG, Hottenga JJ, Slagboom PE. Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock. Lancet 1999; 354: 561–3.
- Kirchhofer D, Sakariassen KS, Clozel M, et al. Relationship between tissue factor expression and deposition of fibrin, platelets, and leukocytes on cultured endothelial cells under venous blood flow conditions. Blood 1993; 81: 2050–8.
- Zimmerman GA, Prescott SM, McIntyre TM. Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol Today 1992; 13: 93–100.
- Wachtfogel YT, Abrams W, Kucich U et al. Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation. J Clin Invest 1988; 81: 1310–6.
- Bone RC. Modulators of coagulation. A critical appraisal of their role in sepsis. Arch Intern Med 1992; 152: 1381–9.
- Dixon GL, Heyderman RS, Kotovicz K et al. Endothelial adhesion molecule expression and its inhibition by recombinant bactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidis. Infect Immun 1999; 67: 5626–33.
- Harrison OB, Robertson BD, Faust SN et al. Analysis of pathogen-host cell interactions in purpura fulminans: expression of capsule, type IV pili, and PorA by Neisseria meningitidis in vivo. Infect Immun 2002; 70: 5193–201.
- Klein NJ, Ison CA, Peakman M et al. The influence of capsulation and lipooligosaccharide structure on neutrophil adhesion molecule expression and endothelial injury by Neisseria meningitidis. J Infect Dis 1996; 173: 172–9.
- Dunn KL, Virji M, Moxon ER. Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili. Microb Pathog 1995; 18: 81–96.
- Heyderman RS, Klein NJ, Daramola OA et al. Induction of human endothelial tissue factor expression by Neisseria meningitidis: the influence of bacterial killing and adherence to the endothelium. Microb Pathog 1997; 22: 265–74.
- Join-Lambert O, Lecuyer H, Miller F et al. Meningococcal interaction to microvasculature triggers the tissular lesions of purpura fulminans. J Infect Dis 2013; 208: 1590–7.
- Lecuyer H, Borgel D, Nassif X, Coureuil M. Pathogenesis of meningococcal purpura fulminans. Pathog Dis 2017; 75(3).
- Melican K, Michea Veloso P, Martin T et al. Adhesion of Neisseria meningitidis to dermal vessels leads to local vascular damage and purpura in a humanized mouse model. PLoS Pathog 2013; 9: e1003139.
- Weatherall DJ, Bell JI, Clegg JB et al. Genetic factors as determinants of infectious disease transmission in human communities. Phil Trans R Soc Lond B1988; 321: 327 Pathogenesis of meningococcal purpura fulminans 48.
- Hibberd ML, Sumiya M, Summerfield JA et al. Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet 1999; 353: 1049 Pathogenesis of meningococcal purpura fulminans 53.
- Westendorp RG, Langermans JA, Huizinga TW et al. Genetic influence on cytokine production in meningococcal disease. Lancet 1997; 349: 1912–13.
- Bredius RG, Derkx BH, Fijen CA et al. Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children. J Infect Dis 1994; 170: 848–53.
- Bertina RM. Factor V Leiden and other coagulation factor mutations affecting thrombotic risk. Clin Chem 1997; 43: 1678–83.
- Kondaveeti S, Hibberd ML, Booy R et al. Effect of the Factor V Leiden mutation on the severity of meningococcal disease. Pediatr Infect Dis J 1999; 18: 893–6.
- Kornelisse RF, Hazelzet JA, Savelkoul HF et al. The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock. J Infect Dis 1996; 173: 1148–56.
- Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD. Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 1990; 323: 1651–7.
- Marzouk O, Thomson AP, Sills JA et al. Features and outcome in meningococcal disease presenting with maculopapular rash. Arch Dis Child 1991; 66: 485–7.
- Pollard AJ, Britto J, Nadel S et al. Emergency management of meningococcal disease. Arch Dis Child 1999; 80: 290–6.
- Kingston ME, Mackey D. Skin clues in the diagnosis of life-threatening infections. Rev Infect Dis 1986; 8: 1–11.
- Toews WH, Bass JW. Skin manifestations of meningococcal infection; an immediate indicator of prognosis. Am J Dis Child 1974; 127: 173–6.
- Stiehm ER, Damrosch DS. Factors in the prognosis of meningococcal infection. Review of 63 cases with emphasis on recognition and management of the severely ill patient. J Pediatr 1966; 68: 457–67.
- Brandtzaeg P, Dahle JS, Høiby EA. The occurrence and features of hemorrhagic skin lesions in 115 cases of systemic meningococcal disease. NIPH Ann 1983; 6: 183.
- Cartwright KA, Jones DM. ACP Broadsheet 121: June 1989. Investigation of meningococcal disease. J Clin Pathol 1989; 42: 634–9.
- Nadel S. Lumbar puncture should not be performed in meningococcal disease. Arch Dis Child 2001; 84: 375.
- van Deuren M, van Dijke BJ, Koopman RJ et al. Rapid diagnosis of acute meningococcal infections by needle aspiration or biopsy of skin lesions. Br Med J (Clin Res Ed) 1993; 306: 1229–32.
- Periappuram M, Taylor MR, Keane CT. Rapid detection of meningococci from petechiae in acute meningococcal infection. J Infect 1995; 31: 201–3.
- Netter A, Sakabuer M. The presence of meningococci in the purpuric elements of meningococcal infection. Br J Child Dis 1917(14): 101–4.
-
Tompkins V. The diagnostic value of smears from purpuric lesions of the skin in meningococcal disease. JAMA 1943( 123): 31–2.
10.1001/jama.1943.82840360001008 Google Scholar
- McLean S, Caffey J. Endemic meningococcus bacteremia in early life: the diagnostic value of smears from purpuric lesions. Am J Dis Child 1931( 42): 1053–74.
- Kaplan SL. Antigen detection in cerebrospinal fluid—pros and cons. Am J Med 1983; 75: 109–18.
- Cuevas LE, Hart CA, Mughogho G. Latex particle agglutination tests as an adjunct to the diagnosis of bacterial meningitis: a study from Malawi. Ann Trop Med Parasitol 1989; 83: 375–9.
- Newcombe J, Cartwright K, Palmer WH, McFadden J. PCR of peripheral blood for diagnosis of meningococcal disease. J Clin Microbiol 1996; 34: 1637–40.
- Kotilainen P, Jalava J, Meurman O et al. Diagnosis of meningococcal meningitis by broad-range bacterial PCR with cerebrospinal fluid. J Clin Microbiol 1998; 36: 2205–9.
- Booy R, Kroll JS. Bacterial meningitis and meningococcal infection. Curr Opin Pediatr 1998; 10: 13–8.
- Hackett SJ, Carrol ED, Guiver M et al. Improved case confirmation in meningococcal disease with whole blood Taqman PCR. Arch Dis Child 2002; 86: 449–52.
- Botha P. Penicillin-resistant Neisseria meningitidis in southern Africa. Lancet 1988; 1: 54.
- Berrón S, Vázquez JA. Increase in moderate penicillin resistance and serogroup C in meningococcal strains isolated in Spain. Is there any relationship? Clin Infect Dis 1994; 18: 161–5.
- Angyo IA, Okpeh ES. Changing patterns of antibiotic sensitivity and resistance during an outbreak of meningococcal infection in Jos, Nigeria. J Trop Pediatr 1998; 44: 263–5.
- Jones DM, Sutcliffe EM. Meningococci with reduced susceptibility to penicillin. Lancet 1990; 335: 863–4.
- Blondeau JM, Ashton FE, Isaacson M et al. Neisseria meningitidis with decreased susceptibility to penicillin in Saskatchewan, Canada. J Clin Microbiol 1995; 33: 1784–6.
- Jackson LA, Tenover FC, Baker C et al. Prevalence of Neisseria meningitidis relatively resistant to penicillin in the United States, 1991. Meningococcal Disease Study Group. J Infect Dis 1994; 169: 438–41.
- Oppenheim BA. Antibiotic resistance in Neisseria meningitidis. Clin Infect Dis 1997; 24(suppl 1): 101.
- Temime L, Boëlle PY, Courvalin P, Guillemot D. Bacterial resistance to penicillin G by decreased affinity of penicillin-binding proteins: a mathematical model. Emerg Infect Dis 2003; 9: 411–17.
- Mastrantonio P, Stefanelli P, Fazio C et al. Serotype distribution, antibiotic susceptibility, and genetic relatedness of Neisseria meningitidis strains recently isolated in Italy. Clin Infect Dis 2003; 36: 422–8.
- Tapsall JW, Shultz T, Limnios E et al. Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999. Pathology 2001; 33: 359–61.
- Richter SS, Gordon KA, Rhomberg PR et al. Neisseria meningitidis with decreased susceptibility to penicillin: report from the SENTRY antimicrobial surveillance program, North America, 1998-99. Diagn Microbiol Infect Dis 2001; 41: 83–8.
- de Jonge E, Levi M, Stoutenbeek CP, van Deventer SJ. Current drug treatment strategies for disseminated intravascular coagulation. Drugs 1998; 55: 767–77.
- Balk R, Emerson T, Fourrier F et al. Therapeutic use of antithrombin concentrate in sepsis. Semin Thromb Hemost. 1998; 24: 183–94.
- Giudici D, Baudo F, Palareti G et al. Antithrombin replacement in patients with sepsis and septic shock. Haematologica 1999; 84: 452–60.
- Emerson TE. Antithrombin III replacement in animal models of acquired antithrombin III deficiency. Blood Coagul Fibrinolysis 1994; 5(suppl 1): S37–45.
- Taylor FB, Emerson TE, Jordan R et al. Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock 1988; 26: 227–35.
- Rivard GE, David M, Farrell C, Schwarz HP. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr 1995; 126: 646–52.
- Lundsgaard-Hansen P, Doran JE, Rubli E et al. Purified fibronectin administration to patients with severe abdominal infections. A controlled clinical trial. Ann Surg 1985; 202: 745–59.
- White B, Livingstone W, Murphy C et al. An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood 2000; 96: 3719–24.
- Taylor FB, Chang A, Ruf W et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127–34.
- Angelini GD, Cooper GJ, Lamarra M, Bryan AJ. Unorthodox use of aprotinin to control life-threatening bleeding after cardiopulmonary bypass. Lancet 1990; 335: 799–800.
- Creasey AA, Reinhart K. Tissue factor pathway inhibitor activity in severe sepsis. Crit Care Med 2001; 29(7 suppl): 9.
- Zenz W, Muntean W, Gallistl S et al. Recombinant tissue plasminogen activator treatment in two infants with fulminant meningococcemia. Pediatrics 1995; 96: 144–8.
- Colman RW, Robboy SJ, Minna JD. Disseminated intravascular coagulation (DIC): an approach. Am J Med 1972; 52: 679–89.
- Corrigan JJ, Ray WL, May N. Changes in the blood coagulation system associated with septicemia. N Engl J Med 1968; 279: 851–6.
- Gérard P, Moriau M, Bachy A et al. Meningococcal purpura: report of 19 patients treated with heparin. J Pediatr 1973; 82: 780–6.
- Ockelford P. Heparin 1986. Indications and effective use. Drugs 1986; 31: 81–92.
- Warren BL, Eid A, Singer P et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286: 1869–78.
- Derkx B, Wittes J, McCloskey R. Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal Septic Shock Trial Study Group. Clin Infect Dis 1999; 28: 770–7.
- Levin M, Quint PA, Goldstein B et al. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 2000; 356: 961–7.
- Bone RC, Fisher CJ, Clemmer TP et al. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987; 317: 653–8.
- Jafari HS, McCracken GH. Sepsis and septic shock: a review for clinicians. Pediatr Infect Dis J 1992; 11: 739–48.
- Margaretten W, McAdams AJ. An appraisal of fulminant meningococcemia with reference to the Shartzman phenomenon. Am J Med 1958; 25: 868–76.
- Annane D, Sébille V, Charpentier C et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862–71.
- Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699–709.
- Nadel S, Goldstein B, Williams MD et al. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007; 369: 836–43.
- Martí-Carvajal AJ, Solà I, Gluud C et al. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. Cochrane Database Syst Rev 2012; 12.
- de Kleijn ED, de Groot R, Hack CE et al. Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: a randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med 2003; 31: 1839–47.
- Rintala E, Kauppila M, Seppälä OP et al. Protein C substitution in sepsis-associated purpura fulminans. Crit Care Med 2000; 28: 2373–8.
- Bernard G, Artigas A, Dellinger P et al. Clinical expert round table discussion (session 3) at the Margaux Conference on Critical Illness: the role of activated protein C in severe sepsis. Crit Care Med 2001; 29(7 suppl): 7.
- W Zenz, B Zöhrer, SN Faust et al. (eds). Use of tissue plasminogen activator (t-PA) in children with fulminant meningococcaemia. Royal College of Paediatrics and Child Health Annual Meetings; 2001; York, UK. London: Royal College of Paediatrics and Child Health.
- Nectoux E, Mezel A, Raux S et al. Meningococcal purpura fulminans in children: I. Initial orthopedic management. J Child Orthop 2010; 4: 401–7.
- Davies MS, Nadel S, Habibi P et al. The orthopaedic management of peripheral ischaemia in meningococcal septicaemia in children. J Bone Joint Surg Br 2000; 82: 383–6.
- Monsell F. The skeletal consequences of meningococcal septicaemia. Arch Dis Child 2012; 97: 539–44.
- Herrera R, Hobar PC, Ginsburg CM. Surgical intervention for the complications of meningococcal-induced purpura fulminans. Pediatr Infect Dis J 1994; 13: 734–7.
- Hudson DA, Goddard EA, Millar KN. The management of skin infarction after meningococcal septicaemia in children. Br J Plast Surg 1993; 46: 243–6.
- Harris NJ, Gosh M. Skin and extremity loss in meningococcal septicaemia treated in a burn unit. Burns 1994; 20: 471–2.
- Arévalo JM, Lorente JA, Fonseca R. Surgical treatment of extensive skin necrosis secondary to purpura fulminans in a patient with meningococcal sepsis. Burns 1998; 24: 272–4.
- Huang DB, Price M, Pokorny J et al. Reconstructive surgery in children after meningococcal purpura fulminans. J Pediatr Surg 1999; 34: 595–601.
- Boeckx WD, Nanhekhan L, Vos GD et al. Minimizing limb amputations in meningococcal sepsis by early microsurgical arteriolysis. J Pediatr Surg 2009; 44: 1625–30.
- Nectoux E, Mezel A, Raux S et al. Meningococcal purpura fulminans in children. II: Late orthopedic sequelae management. J Child Orthop 2010; 4: 409–16.
- Buysse CM, Oranje AP, Zuidema E et al. Long-term skin scarring and orthopaedic sequelae in survivors of meningococcal septic shock. Arch Dis Child 2009; 94: 381–6.
- Allport T, Read L, Nadel S, Levin M. Critical illness and amputation in meningococcal septicemia: is life worth saving? Pediatrics 2008; 122: 629–32.
- Buysse CM, Raat H, Hazelzet JA et al. Surviving meningococcal septic shock: health consequences and quality of life in children and their parents up to 2 years after pediatric intensive care unit discharge. Crit Care Med 2008; 36: 596–602.
- Whittle HC, Abdullahi MT, Fakunle FA et al. Allergic complications of meningococcal disease. I. Clinical aspects. Br Med J 1973; 2: 733–7.
- Edwards MS, Baker CJ. Complications and sequelae of meningococcal infections in children. J Pediatr 1981; 99: 540–5.
- Greenwood BM, Whittle HC, Bryceson AD. Allergic complications of meningococcal disease. II. Immunological investigations. Br Med J 1973; 2: 737–40.
- Benoit FL. Chronic meningococcemia. Case report and review of the literature. Am J Med 1963; 35: 103–12.
- Leibel RL, Fangman JJ, Ostrovsky MC. Chronic meningococcemia in childhood. Case report and review of the literature. Am J Dis Child 1974; 127: 94–8.
- Nielsen HE, Koch C, Mansa B et al. Complement and immunoglobulin studies in 15 cases of chronic meningococcemia: properdin deficiency and hypoimmunoglobulinemia. Scand J Infect Dis 1990; 22: 31–6.
- Prins JM, Lauw FN, Derkx BH et al. Endotoxin release and cytokine production in acute and chronic meningococcaemia. Clin Exp Immunol 1998; 114: 215–9.
- Visakorpi R. Ciprofloxacin in meningococcal carriers. Scand J Infect Dis Suppl 1989; 60: 108–11.
- Pollard AJ, Begg N. Meningococcal disease and healthcare workers. Br Med J (Clin Res Ed) 1999; 319: 1147–8.
- Control of meningococcal disease: guidance for consultants in communicable disease control. PHLS Meningococcal Infections Working Group and Public Health Medicine Environmental Group. Commun Dis Rep CDR Rev 1995; 5: 95.
- Forum HPAMaH. Guidance for public health management of meningococcal disease in the UK 2018 [Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/322008/Guidance_for_management_of_meningococcal_disease_pdf.pdf.
- Frasch CE. Meningococcal vaccine: past, present and future. In: K Cartwright (ed.) Meningococcal Disease. Chichester: John Wiley, 1995: 246–83.
- Shinefield HR, Black S. Postlicensure surveillance for Haemophilus influenzae type b invasive disease after use of Haemophilus influenzae type b oligosaccharide CRM197 conjugate vaccine in a large defined United States population: a four-year eight-month follow-up. Pediatr Infect Dis J 1995; 14: 978–81.
- Hargreaves RM, Slack MP, Howard AJ et al. Changing patterns of invasive Haemophilus influenzae disease in England and Wales after introduction of the Hib vaccination programme. Br Med J (Clin Res Ed) 1996; 312: 160–1.
- Bose A, Coen P, Tully J et al. Effectiveness of meningococcal C conjugate vaccine in teenagers in England. Lancet 2003; 361: 675–6.
- Lakshman R, Jones I, Walker D et al. Safety of a new conjugate meningococcal C vaccine in infants. Arch Dis Child 2001; 85: 391–7.
- Salleras L, Domínguez A, Cardeñosa N. Impact of mass vaccination with polysaccharide conjugate vaccine against serogroup C meningococcal disease in Spain. Vaccine 2003; 21: 725–8.
- Ramsay ME, Andrews N, Kaczmarski EB, Miller E. Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England. Lancet 2001; 357: 195–6.
- Ramsay ME, Andrews NJ, Trotter CL et al. Herd immunity from meningococcal serogroup C conjugate vaccination in England: database analysis. Br Med J (Clin Res Ed) 2003; 326: 365–6.
- Pollard AJ, Perrett KP, Beverley PC. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat Rev Immunol 2009; 9: 213–20.
- Silvestre JF, Betlloch MI. Cutaneous manifestations due to Pseudomonas infection. Int J Dermatol 1999; 38: 419–31.
- Logan LK, Gandra S, Mandal S et al. Multidrug- and carbapenem-resistant Pseudomonas aeruginosa in children, United States, 1999-2012. J Pediatric Infect Dis Soc 2017; 6: 352–9.
- Wu DC, Chan WW, Metelitsa AI et al. Pseudomonas skin infection: clinical features, epidemiology, and management. Am J Clin Dermatol 2011; 12: 157–69.
- Goering R, Dockrell H, Zuckerman M et al. Mims' Medical Microbiology, 5th edn. Edinburgh: Elsevier Saunders, 2012.
- Diekema DJ, Pfaller MA, Jones RN et al. Survey of bloodstream infections due to gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997. Clin Infect Dis 1999; 29: 595–607.
- Bucior I, Pielage JF, Engel JN. Pseudomonas aeruginosa pili and flagella mediate distinct binding and signaling events at the apical and basolateral surface of airway epithelium. PLoS Pathog 2012; 8: e1002616.
- Korpi F, Hashemi FB, Irajian G et al. Flagellin and pilin immunization against multi-drug resistant Pseudomonas aeruginosa protects mice in the burn wound sepsis model. Immunol Lett 2016; 176: 8–17.
- Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol 2009; 11: 1034–43.
- Wilkins M, Hall-Stoodley L, Allan RN, Faust SN. New approaches to the treatment of biofilm-related infections. J Infect 2014; 69 (suppl 1): 52.
-
Pier GB, Ramphal R. Pseudomonas aeruginosa. In: GL Mandell, JE Bennett, R Dolin (eds) Mandell, Douglas and Bennett's Principles and Practices of Infectious Diseases, 2, 7th edn. Philadelphia: Churchill Livingstone Elselvier, 2010: 2835–60.
10.1016/B978-0-443-06839-3.00219-8 Google Scholar
- Sampedro I, Parales RE, Krell T, Hill JE. Pseudomonas chemotaxis. FEMS Microbiol Rev 2015; 39: 17–46.
- Andonova M, Urumova V. Immune surveillance mechanisms of the skin against the stealth infection strategy of Pseudomonas aeruginosa-review. Comp Immunol Microbiol Infect Dis 2013; 36: 433–48.
- Stieritz DD, Holder IA. Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: description of a burned mouse model. J Infect Dis 1975; 131: 688–91.
- Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, 2013. Available at: https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
- Høiby N, Bjarnsholt T, Givskov M et al. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 2010; 35: 322–32.
- Rubinstein E, Ostfeld E, Ben-Zaray S, Schiby G. Necrotizing external otitis. Pediatrics 1980; 66: 618–20.
- Chiller K, Selkin BA, Murakawa GJ. Skin microflora and bacterial infections of the skin. J Investig Dermatol Symp Proc 2001; 6: 170–4.
- Saegeman V, Van Meensel B. Aeromonas associated with swimming pool folliculitis. Pediatr Infect Dis J 2016; 35: 118–19.
- Julià Manresa M, Vicente Villa A, Gené Giralt A, González-Enseñat MA. Aeromonas hydrophila folliculitis associated with an inflatable swimming pool: mimicking Pseudomonas aeruginosa infection. Pediatr Dermatol 2009; 26: 601–3.
- Stewart D, Benitz W, Newbo CO. Umbilical cord care in the newborn infant. Pediatrics 2016; 138(3).
- Mull CC, Scarfone RJ, Conway D. Ecthyma gangrenosum as a manifestation of Pseudomonas sepsis in a previously healthy child. Ann Emerg Med 2000; 36: 383–7.
- Pandit AM, Siddaramappa B, Choudhary SV, Manjunathswamy BS. Ecthyma gangrenosum in a new born child. Indian J Dermatol Venereol Leprol 2003; 69: 52–3.
- Whitecar JP Jr, Luna M, Bodey GP. Pseudomonas bacteremia in patients with malignant diseases. Am J Med Sci 1970; 60: 216–23.
- Vaiman M, Lazarovitch T, Heller L, Lotan G. Ecthyma gangrenosum and ecthyma-like lesions: review article. Eur J Clin Microbiol Infect Dis 2015; 34: 633–9.
- Cohen N, Capua T, Bilavsky E et al. Ecthyma gangrenosum skin lesions in previously healthy children. Acta Paediatr 2015; 104: 8.
- Ghanaiem H, Engelhard D. A healthy 2-year-old child with a round black skin lesion. J Pediatr 2013; 163: 1225–50.
- Church D, Elsayed S, Reid O et al. Burn wound infections. Clin Microbiol Rev 2006; 19: 403–34.
- Altoparlak U, Erol S, Akcay MN et al. The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns 2004; 30: 660–4.
- Barajas-Nava LA, López-Alcalde J, Roqué i Figuls M et al. Antibiotic prophylaxis for preventing burn wound infection. Cochrane Database Syst Rev 2013(6).
- Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis 2007; 44: 705–10.
- Kobayashi L, Konstantinidis A, Shackelford S et al. Necrotizing soft tissue infections: delayed surgical treatment is associated with increased number of surgical debridements and morbidity. J Trauma 2011; 71: 1400–5.
- Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis: current concepts and review of the literature. J Am Coll Surg 2009; 208: 279–88.
- Zhao G-JJ, Hong G-LL, Liu J-QQ et al. Septic shock due to community-acquired Pseudomonas aeruginosa necrotizing fasciitis: A case report and literature review. Exp Ther Med 2014; 7: 1545–8.
- Totapally BR. Epidemiology and outcomes of hospitalized children with necrotizing soft tissue infections. Pediatr Infect Dis J 2017; 36: 641–4.
- Mikaeloff Y, Kezouh A, Suissa S. Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease. Br J Clin Pharmacol 2008; 65: 203–9.
- Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg 2014; 101: 25.
- Wong CH, Khin LW, Heng KS et al. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med 2004; 32: 1535–41.
- Leichtle SW, Tung L, Khan M et al. The role of radiologic evaluation in necrotizing soft tissue infections. J Trauma Acute Care Surg 2016; 81: 921–4.
- Wong C-HH, Chang H-CC, Pasupathy S et al. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am 2003; 85-A: 1454–60.
- Stulberg DL, Penrod MA, Blatny RA. Common bacterial skin infections. Am Fam Physician 2002; 66: 119–24.
- Lehrhoff S, Yost J, Robinson M et al. Serratia marcescens folliculitis and concomitant acne vulgaris. Dermatol Online J 2012; 18: 19.
- Leyden JJ, Marples RR, Mills OH Jr, Kligman AM. Gram-negative folliculitis—a complication of antibiotic therapy in acne vulgaris. Br J Dermatol 1973; 88: 533–8.
- Neubert U, Jansen T, Plewig G. Bacteriologic and immunologic aspects of gram-negative folliculitis: a study of 46 patients. Int J Dermatol 1999; 38: 270–4.
- Boni R, Nehrhoff B. Treatment of gram-negative folliculitis in patients with acne. Am J Clin Dermatol 2003; 4: 273–6.
- British National Formulary for Children. London: BMJ Group and Pharmaceutical Press and RCPCH Publications, 2010.
