Bacterial Etiology and Risk Factors Associated with Cellulitis and Purulent Skin Abscesses in Military Trainees

Ryan C Johnson, Michael W Ellis, Carey D Schlett, Eugene V Millar, Patrick T LaBreck, Deepika Mor, Emad M Elassal, Jeffrey B Lanier, Cassie L Redden, Tianyuan Cui, Nimfa Teneza-Mora, Danett K Bishop, Eric R Hall, Kimberly A Bishop-Lilly, D Scott Merrell, Ryan C Johnson, Michael W Ellis, Carey D Schlett, Eugene V Millar, Patrick T LaBreck, Deepika Mor, Emad M Elassal, Jeffrey B Lanier, Cassie L Redden, Tianyuan Cui, Nimfa Teneza-Mora, Danett K Bishop, Eric R Hall, Kimberly A Bishop-Lilly, D Scott Merrell

Abstract

Military trainees are at high risk for skin and soft-tissue infections (SSTIs). Although Staphylococcus aureus is associated with purulent SSTI, it is unclear to what degree this pathogen causes nonpurulent cellulitis. To inform effective prevention strategies and to provide novel insights into SSTI pathogenesis, we aimed to determine the etiology of SSTI in this population. We conducted a prospective observational study in US Army Infantry trainees with SSTI (cutaneous abscesses and cellulitis) from July 2012 through December 2014. We used standard microbiology, serology, and high-throughput sequencing to determine the etiology of SSTI. Furthermore, we compared purported risk factors as well as anatomic site colonization for S. aureus. Among 201 SSTI cases evaluated for SSTI risk factors, cellulitis was associated with lower extremity blisters (P = 0.01) and abscess was associated with methicillin-resistant S. aureus (MRSA) colonization (P<0.001). Among the 22 tested cellulitis cases that were part of the microbiome analysis, only 1 leading edge aspirate was culturable (Coagulase-negative Staphylococcus). Microbiome evaluation of aspirate specimens demonstrated that Rhodanobacter terrae was the most abundant species (66.8% average abundance), while abscesses were dominated by S. aureus (92.9% average abundance). Although abscesses and cellulitis share the spectrum of clinical SSTI, the bacterial etiologies as determined by current technology appear distinct. Furthermore, the presence of atypical bacteria within cellulitis aspirates may indicate novel mechanisms of cellulitis pathogenesis.

Clinical trials registration: NCT01105767.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
Microbial composition within purulent abscesses (A and C) and cellulitis (B and D) samples. The microbiomes were characterized at the bacterial phylum level (A and B) as well as genus (g) and species (s) levels (C and D). Each column corresponds to a single SSTI microbiome.

References

    1. Edelsberg J, Taneja C, Zervos M, Haque N, Moore C, Reyes K, et al. Trends in US hospital admissions for skin and soft tissue infections. Emerging infectious diseases. 2009. September;15(9):1516–8. Pubmed Central PMCID: 2819854. 10.3201/eid1509.081228
    1. Hersh AL, Chambers HF, Maselli JH, Gonzales R. National trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. Archives of internal medicine. 2008. July 28;168(14):1585–91. 10.1001/archinte.168.14.1585
    1. Pallin DJ, Egan DJ, Pelletier AJ, Espinola JA, Hooper DC, Camargo CA Jr. Increased US emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, during the emergence of community-associated methicillin-resistant Staphylococcus aureus. Annals of emergency medicine. 2008. March;51(3):291–8. 10.1016/j.annemergmed.2007.12.004
    1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2014. July 15;59(2):e10–52. 10.1093/cid/ciu444
    1. Zinderman CE, Conner B, Malakooti MA, LaMar JE, Armstrong A, Bohnker BK. Community-acquired methicillin-resistant Staphylococcus aureus among military recruits. Emerging infectious diseases. 2004. May;10(5):941–4. Pubmed Central PMCID: 3323224. 10.3201/eid1005.030604
    1. Campbell KM, Vaughn AF, Russell KL, Smith B, Jimenez DL, Barrozo CP, et al. Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. Journal of clinical microbiology. 2004. September;42(9):4050–3. Pubmed Central PMCID: 516279. 10.1128/JCM.42.9.4050-4053.2004
    1. Stryjewski ME, Chambers HF. Skin and soft-tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2008. June 1;46 Suppl 5:S368–77. 10.1086/533593
    1. Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. The New England journal of medicine. 2006. August 17;355(7):666–74. 10.1056/NEJMoa055356
    1. Rajan S. Skin and soft-tissue infections: classifying and treating a spectrum. Cleveland Clinic journal of medicine. 2012. January;79(1):57–66. 10.3949/ccjm.79a.11044
    1. Tognetti L, Martinelli C, Berti S, Hercogova J, Lotti T, Leoncini F, et al. Bacterial skin and soft tissue infections: review of the epidemiology, microbiology, aetiopathogenesis and treatment: a collaboration between dermatologists and infectivologists. Journal of the European Academy of Dermatology and Venereology: JEADV. 2012. August;26(8):931–41. 10.1111/j.1468-3083.2011.04416.x
    1. Gunderson CG. Cellulitis: definition, etiology, and clinical features. The American journal of medicine. 2011. December;124(12):1113–22. 10.1016/j.amjmed.2011.06.028
    1. Swartz MN. Clinical practice. Cellulitis. The New England journal of medicine. 2004. February 26;350(9):904–12. 10.1056/NEJMcp031807
    1. Duvanel T, Auckenthaler R, Rohner P, Harms M, Saurat JH. Quantitative cultures of biopsy specimens from cutaneous cellulitis. Archives of internal medicine. 1989. February;149(2):293–6. .
    1. Perl B, Gottehrer NP, Raveh D, Schlesinger Y, Rudensky B, Yinnon AM. Cost-effectiveness of blood cultures for adult patients with cellulitis. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 1999. December;29(6):1483–8. 10.1086/313525
    1. Newell PM, Norden CW. Value of needle aspiration in bacteriologic diagnosis of cellulitis in adults. Journal of clinical microbiology. 1988. March;26(3):401–4. . Pubmed Central PMCID: 266301.
    1. Hook EW 3rd, Hooton TM, Horton CA, Coyle MB, Ramsey PG, Turck M. Microbiologic evaluation of cutaneous cellulitis in adults. Archives of internal medicine. 1986. February;146(2):295–7. .
    1. Patel Wylie F, Kaplan SL, Mason EO, Allen CH. Needle aspiration for the etiologic diagnosis of children with cellulitis in the era of community-acquired methicillin-resistant Staphylococcus aureus. Clinical pediatrics. 2011. June;50(6):503–7. 10.1177/0009922810394652
    1. Johnson RC, Ellis MW, Lanier JB, Schlett CD, Cui T, Merrell DS. Correlation between nasal microbiome composition and remote purulent skin and soft tissue infections. Infection and immunity. 2015. February;83(2):802–11. Pubmed Central PMCID: 4294227. 10.1128/IAI.02664-14
    1. Ellis MW, Griffith ME, Dooley DP, McLean JC, Jorgensen JH, Patterson JE, et al. Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains in soldiers: a cluster randomized controlled trial. Antimicrobial agents and chemotherapy. 2007. October;51(10):3591–8. Pubmed Central PMCID: 2043273. 10.1128/AAC.01086-06
    1. Ellis MW, Griffith ME, Jorgensen JH, Hospenthal DR, Mende K, Patterson JE. Presence and molecular epidemiology of virulence factors in methicillin-resistant Staphylococcus aureus strains colonizing and infecting soldiers. Journal of clinical microbiology. 2009. April;47(4):940–5. Pubmed Central PMCID: 2668321. 10.1128/JCM.02352-08
    1. Ellis MW, Schlett CD, Millar EV, Wilkins KJ, Crawford KB, Morrison-Rodriguez SM, et al. Hygiene strategies to prevent methicillin-resistant Staphylococcus aureus skin and soft tissue infections: a cluster-randomized controlled trial among high-risk military trainees. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2014. June;58(11):1540–8. Pubmed Central PMCID: 4017895. 10.1093/cid/ciu166
    1. Turner S, Pryer KM, Miao VP, Palmer JD. Investigating deep phylogenetic relationships among cyanobacteria and plastids by small subunit rRNA sequence analysis. The Journal of eukaryotic microbiology. 1999. Jul-Aug;46(4):327–38. .
    1. Wang Y, Qian PY. Conservative fragments in bacterial 16S rRNA genes and primer design for 16S ribosomal DNA amplicons in metagenomic studies. PloS one. 2009;4(10):e7401 Pubmed Central PMCID: 2754607. 10.1371/journal.pone.0007401
    1. Ellis MW, Johnson RC, Crawford K, Lanier JB, Merrell DS. Molecular characterization of a catalase-negative methicillin-susceptible Staphylococcus aureus subsp. aureus strain collected from a patient with cutaneous abscess. Journal of clinical microbiology. 2014. January;52(1):344–6. Pubmed Central PMCID: 3911441. 10.1128/JCM.02455-13
    1. Cole JR, Wang Q, Cardenas E, Fish J, Chai B, Farris RJ, et al. The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic acids research. 2009. January;37(Database issue):D141–5. Pubmed Central PMCID: 2686447. 10.1093/nar/gkn879
    1. Elliott D, Kufera JA, Myers RA. The microbiology of necrotizing soft tissue infections. American journal of surgery. 2000. May;179(5):361–6. .
    1. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Annals of surgery. 1995. May;221(5):558–63; discussion 63–5. . Pubmed Central PMCID: 1234638.
    1. Dall L, Peterson S, Simmons T, Dall A. Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy. Cutis. 2005. March;75(3):177–80. .
    1. Bergkvist PI, Sjobeck K. Antibiotic and prednisolone therapy of erysipelas: a randomized, double blind, placebo-controlled study. Scandinavian journal of infectious diseases. 1997;29(4):377–82. .
    1. Crisp JG, Takhar SS, Moran GJ, Krishnadasan A, Dowd SE, Finegold SM, et al. Inability of Polymerase Chain Reaction, Pyrosequencing, and Culture of Infected and Uninfected Site Skin Biopsy Specimens to Identify the Cause of Cellulitis. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2015. August 3 10.1093/cid/civ655
    1. Jeng A, Beheshti M, Li J, Nathan R. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation. Medicine. 2010. July;89(4):217–26. 10.1097/MD.0b013e3181e8d635
    1. Lawlor MT, Crowe HM, Quintiliani R. Cellulitis due to Streptococcus pneumoniae: case report and review. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 1992. January;14(1):247–50. .
    1. Leppard BJ, Seal DV, Colman G, Hallas G. The value of bacteriology and serology in the diagnosis of cellulitis and erysipelas. The British journal of dermatology. 1985. May;112(5):559–67. .
    1. Miller LG, Eells SJ, Taylor AR, David MZ, Ortiz N, Zychowski D, et al. Staphylococcus aureus colonization among household contacts of patients with skin infections: risk factors, strain discordance, and complex ecology. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2012. June;54(11):1523–35. Pubmed Central PMCID: 3348950. 10.1093/cid/cis213
    1. Albrecht VS, Limbago BM, Moran GJ, Krishnadasan A, Gorwitz RJ, McDougal LK, et al. Staphylococcus aureus Colonization and Strain Type at Various Body Sites among Patients with a Closed Abscess and Uninfected Controls at U.S. Emergency Departments. Journal of clinical microbiology. 2015. November;53(11):3478–84. 10.1128/JCM.01371-15
    1. Fritz SA, Hogan PG, Hayek G, Eisenstein KA, Rodriguez M, Krauss M, et al. Staphylococcus aureus colonization in children with community-associated Staphylococcus aureus skin infections and their household contacts. Archives of pediatrics & adolescent medicine. 2012. June 1;166(6):551–7. Pubmed Central PMCID: 3596005. 10.1001/archpediatrics.2011.900
    1. Ellis Simonsen SM, van Orman ER, Hatch BE, Jones SS, Gren LH, Hegmann KT, et al. Cellulitis incidence in a defined population. Epidemiology and infection. 2006. April;134(2):293–9. Pubmed Central PMCID: 2870381. 10.1017/S095026880500484X
    1. Martinez-Lopez LE, Friedl KE, Moore RJ, Kramer TR. A longitudinal study of infections and injuries of Ranger students. Military medicine. 1993. July;158(7):433–7. .
    1. Dupuy A, Benchikhi H, Roujeau JC, Bernard P, Vaillant L, Chosidow O, et al. Risk factors for erysipelas of the leg (cellulitis): case-control study. Bmj. 1999. June 12;318(7198):1591–4. . Pubmed Central PMCID: 28138.
    1. Semel JD, Goldin H. Association of athlete's foot with cellulitis of the lower extremities: diagnostic value of bacterial cultures of ipsilateral interdigital space samples. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 1996. November;23(5):1162–4. .
    1. Nakatsuji T, Chiang HI, Jiang SB, Nagarajan H, Zengler K, Gallo RL. The microbiome extends to subepidermal compartments of normal skin. Nature communications. 2013;4:1431 Pubmed Central PMCID: 3655727. 10.1038/ncomms2441

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa