Skip Navigation

Acute Bacterial, Nonnecrotizing Cellulitis in Finland: Microbiological Findings

  1. Tuula Siljander1,
  2. Matti Karppelin4,
  3. Susanna Vähäkuopus1,
  4. Jaana Syrjänen4,
  5. Maija Toropainen2,
  6. Juha Kere3,7,
  7. Risto Vuento5,
  8. Tapio Jussila6, and
  9. Jaana Vuopio-Varkila1
  1. 1Department of Bacterial, National Public Health Institute, University of Helsink, Helsink
  2. 2Department of Vaccines, National Public Health Institute, University of Helsink, Helsink
  3. 3Department of Medical Genetics, University of Helsinki, Helsinki
  4. 4Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
  5. 5Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland
  6. 6Hatanpää City Hospital, Tampere, Finland
  7. 7Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
  1. Reprints or correspondence: Tuula Siljander, National Public Health Institute, Dept. of Bacterial and Inflammatory Diseases, Mannerheimintie 166, FIN-00300 Helsinki, Finland (tuula.siljander{at}ktl.fi).

  1. Presented in part: 16th European Congress of Clinical Microbiology and Infectious Diseases, Nice, France, April 2006 (poster number P1866).

 
Next Section

Abstract

Background. Bacterial, nonnecrotizing cellulitis is a localized and often recurrent infection of the skin. The aim of this study was to identify the β-hemolytic streptococci that cause acute nonnecrotizing cellulitis infection in Finland.

Methods. A case-control study of 90 patients hospitalized for acute cellulitis and 90 control subjects was conducted during the period of April 2004–March 2005. Bacterial swab samples were obtained from skin lesions or any abrasion or fissured toe web. Blood culture samples were taken for detection of bacteremia. The patients, their household members, and control subjects were assessed for pharyngeal carrier status. β-Hemolytic streptococci and Staphylococcus aureus were isolated and identified, and group A and G streptococcal isolates were further analyzed by T serotyping and emm and pulsed-field gel electrophoresis typing.

Results. β-Hemolytic streptococci were isolated from 26 (29%) of 90 patients, 2 isolates of which were blood-culture positive for group G streptococci, and 24 patients had culture-positive skin lesions. Group G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) was found most often and was isolated from 22% of patient samples of either skin lesions or blood, followed by group A Streptococcus, which was found in 7% of patients. Group G streptococci were also carried in the pharynx of 7% of patients and 13% of household members but was missing from control subjects. Several emm and pulsed-field gel electrophoresis types were present among the isolates. Six patients (7%) had recurrent infections during the study. In 2 patients, the group G streptococcal isolates recovered from skin lesions during 2 consecutive episodes had identical emm and pulsed-field gel electrophoresis types.

Conclusions. Group G streptococci, instead of group A streptococci, predominated in bacterial cellulitis. No clear predominance of a specific emm type was seen. The recurrent nature of cellulitis became evident during this study.

Bacterial cellulitis and erysipelas refer to diffuse, spreading skin infections, excluding infections associated with underlying suppurative foci, such as cutaneous abscesses, necrotizing fasciitis, septic arthritis, and osteomyelitis [1]. Cellulitis usually refers to a more deeply situated skin infection, and erysipelas can be considered to be a superficial form of it. However, the distinction between these entities is not clear cut, and the 2 conditions share the typical clinical features—for example, sudden onset, usually with a high fever, and the tendency to recur. Streptococcus pyogenes (group A Streptococcus [GAS]) has been considered to be the main causative agent of these infections, although streptococci of group G (GGS), group C (most importantly, Streptococcus dysgalactiae subsp. equisimilis), group B, and, rarely, staphylococci can also cause these diseases [2–4].

The predominant infection site is on the lower extremities, and the face or arms are more rarely affected [2, 3]. Lymphedema and disruption of the cutaneous barrier, which serves as a site of entry for the pathogens, are risk factors for infections [5–8]. Twenty percent to 30% of patients have a recurrence during a 3-year follow-up period [4, 9]. Results of patient blood cultures are usually positive for β-hemolytic streptococci in <5% of cases [2–4]. Although cellulitis is usually not a life-threatening disease, it causes remarkable morbidity, especially in elderly persons [10]. This clinical study aims for a better understanding of acute bacterial cellulitis infections and focuses specifically on the characterization of β-hemolytic streptococci involved in the infection, infection recurrences, and pharyngeal carriage.

Previous SectionNext Section

Methods

Study design and population. During 1 year (April 2004–March 2005), patients (age, ⩾18 years) hospitalized for acute bacterial cellulitis were recruited into the study from 2 infectious diseases wards, 1 at Tampere University Hospital (Tampere, Finland) and 1 at Hatanpää City Hospital (Tampere, Finland). After receiving informed consent, each patient's diagnosis of cellulitis was confirmed by a specialist of infectious diseases (M.K.) within 4 days after admission to the hospital. The patients were subsequently interviewed and were clinically examined.

For each patient, 1 control subject living in Tampere who was matched for age (same year and month of birth) and sex was recruited. For each patient, as many as 6 control candidates were randomly sampled from the Finnish Population Register Centre and, in random order, asked by letter, sent at 2-week intervals until the first response was obtained, to participate in the study. The recruited control subject was excluded if he or she had been affected with any cellulitis episode, and a new control subject was asked to participate. The reason for nonparticipation was not recorded. Interview and examination procedures were the same for control subjects as for patients.

To study the pharyngeal carriage and possible transmission of β-hemolytic streptococci, family members sharing the same household with the patients were recruited. The study was approved by the Ethical Review Board of Pirkanmaa District, Tampere, Finland.

Case definition and exclusion criteria. Nonnecrotizing bacterial cellulitis was defined (1) as an acute onset of fever or chills and a localized, more-or-less well-demarcated erythema of the skin in 1 extremity or (2) as a typical appearance of well-demarcated skin eruption on the face, with or without fever or chills. Thus, the case definition includes acute bacterial cellulitis and the superficial form of cellulitis (erysipelas). Patients with cutaneous abscesses, necrotizing fasciitis, septic arthritis, and osteomyelitis were excluded.

Sample collection and culture and isolation of bacteria. Samples were collected from the patients at admission to the hospital. Sterile swabs (Technical Service Consultants) were used for sampling and transportation. Samples were taken in duplicate from any existing wound or blister in the affected skin or, if the infection area was intact, from any abrasion or fissured toe web. Furthermore, a throat swab culture specimen was taken from all patients, household members, and control subjects.

The sample swab was first inoculated on a primary plate of sheep blood agar and then was placed in sterile water, to obtain a bacterial suspension, which was serially diluted and plated on sheep blood agar. Plates were incubated in 5% CO2 at 35°C, and bacterial growth was determined at 24 h and 48 h.

β-Hemolytic bacterial growth was visually examined, and the number of colony-forming units per milliliter (cfu/mL) was calculated. Up to 10 suspected β-hemolytic streptococcal colonies and 1 suspected Staphylococcus aureus colony per sample were chosen for isolation.

In addition to the swabs, 2 sets (for an aerobic bottle and an anaerobic bottle) of blood samples were drawn from each patient. The culturing and identification of blood cultures were performed using Bactec 9240 (BD Diagnostic Systems) culture systems, with standard culture media.

Identification of β-hemolytic streptococci and S. aureus. β-Hemolytic streptococcal isolates were tested for sensitivity to bacitracin and were identified by detection of Lancefield group antigens A, B, C, D, F, and G, with use of the Streptex latex agglutination test (Remel Europe). Antimicrobial susceptibility testing of blood isolates was performed according to the Clinical Laboratory Standards Institute (the former National Committee on Clinical Laboratory Standards) guidelines. S. aureus was identified by the Staph Slidex Plus latex agglutination test (bioMárieux). The API ID 32 Strep test (bioMárieux) was used to determine the species of groups A, B, and G streptococci. Isolates identified as β-hemolytic streptococci and S. aureus were stored at −70°C. Group A (S. pyogenes) and group G (S. dysgalactiae subsp. equisimilis) isolates were further analyzed by T serotyping, emm typing, and PFGE.

T serotyping. T serotyping was performed using anti-T-agglutination sera (Sevac), as described elsewhere [11, 12]. With multiple isolates per sample, isolates with the same T serotype were considered to be a single strain, and 1 isolate of each serotype was selected for further analysis.

emmTyping. The emm gene was amplified using primers MF1 and MR1, as described elsewhere [11], or primer 1 (5′-TAT T(C/G)G CTT AGA AAA TTA A-3′) and primer 2 (5′-GCA AGT TCT TCA GCT TGT TT-3′) [13]. With primer 1 and primer 2, PCR conditions were as follows: at 95°C for 10 min; 30 cycles at 94°C for 1 min, at 46°C for 1 min, and at 72°C for 2.5 min; and 1 cycle at 72°C for 7 min [14]. PCR products were purified with QIAquick PCR purification Kit (Qiagen). emm Sequencing was performed with primer MF1 [11] or emmseq2 [13] with use of BigDye chemistry (Applied Biosystems), with cycling times of 30 cycles at 96°C for 20 s, at 55°C for 20 s, and at 60°C for 4 min. Sequence data were analyzed with ABI Prism 310 Genetic Analyzer (Applied Biosystems) and were compared against the Centers for Disease Control and Prevention Streptococcus emm sequence database to assign emm types [15].

PFGE. PFGE was performed using standard methods [16]. DNA was digested with SmaI (Roche) and was separated with CHEF-DR II (Bio-Rad), with pulse times of 10–35 s for 23 h. Restriction profiles were analyzed using Bionumerics software (Applied Maths). Strains with ⩾90% similarity were considered to be the same PFGE type. Types including ⩾2 strains were designated by Roman numerals (for GGS) or uppercase letters (for GAS). Individual strains were named “unique.”

Data handling and statistical analysis. For calculating percentages, 1 episode per patient was considered, unless otherwise specified. A patient was considered to be culture positive for a given bacterial group if the patient culture sample was positive for that bacterial group at any time during the study. This rule was applied separately for clinical and pharyngeal data.

Data were analyzed using Intercooled Stata 9.1 for Windows (StataCorp). Categorical data were compared using the χ2 test with Stata, GraphPad software [17], or an interactive calculation tool for χ2 tests [18]. McNemar's test was used in comparing differences between the findings of patients and control subjects. Differences were considered to be significant when P<.05.

Previous SectionNext Section

Results

Research subjects and disease episodes. A total of 104 patients received the diagnosis of acute bacterial cellulitis during the study period. Eight eligible patients refused to participate (the reason for refusal was not recorded). Six patients were excluded from the study after recruitment because of obvious alternative diagnosis (3 patients) or not fulfilling the case definition (3 patients). Therefore, 90 patients (58 men and 32 women) were included in the study. Correspondingly, 90 control subjects and 38 family members were recruited. Of the control subjects, 34 (38%) of 90 were the first invited individuals of 6 eligible candidates. Six patients had recurrences during the study period; therefore, a total of 98 disease episodes were recorded (table 1). Sixteen of these 98 cellulitis episodes could be classified as classic erysipelas with a sharply demarcated area of inflammation. 44 (49%) of the 90 patients had a history of cellulitis infection before our study. The median age of the patients was 58 years (range, 21–90 years). More episodes occurred in July–September than in other periods (P⩽.05).

Figure 1
View larger version:
Figure 1

Throat swab samples that were culture positive for β-hemolytic streptococcus in different study groups. n, Total number of samples taken in each study group, including only 1 sample from patients with recurrent episodes. The total number of isolates for each bacterial group is shown. GAS, GBS, GCS, GDS, GFS, and GGS, group A, B, C, D, F, and G Streptococcus, respectively.

Table 1
View larger version:
Table 1

Acute bacterial cellulitis episodes, patients, samples, and bacterial findings, by 3-month study periods.

Bacteriological findings of clinical samples. A skin swab sample was taken for culture from 66 patients, who presented with 73 disease episodes (table 1). β-Hemolytic streptococci were isolated from 24 patients. The most common finding was GGS (S. dysgalactiae subsp. equisimilis), which was recovered from 18 (20%) of the 90 patients, 12 of whom also harbored S. aureus. GAS (S. pyogenes) was isolated from 6 patients (7%), always concomitantly with S. aureus. Group B streptococcus (S. agalactiae [GBS]) was isolated from 1 patient. S. aureus was isolated as the only bacterium from 10 patients. A blood culture sample was obtained from 88 (98%) of the patients, 2 (2%) of whom had a blood culture result positive for GGS (S. dysgalactiae subsp. equisimilis). The median ages of patients whose cultures were positive for GGS and GAS were 58 and 65 years, respectively.

From 9 (33%) of 27 patients, β-hemolytic streptococci were isolated from the infection focus; from 15 (38%) of 39 patients, they were isolated from a suspected site of entry—for example, from a wound, intertrigo, or between the toes. Isolates from the infection foci were diverse, yielding 5 GGS isolates, 4 GAS isolates, and 1 GBS isolate, whereas isolates from the probable portals of entry were more uniform, with 13 GGS and 2 GAS isolates. In 27 episodes, antibiotic treatment (penicillin, cephalexin, or clindamycin) had been started before admission to the hospital, but the treatment did not significantly affect the amount of culture-positive findings (data not shown).

β-Hemolytic streptococcal growth could be quantitated in 23 samples. The viable counts in samples with a GGS isolate had a range of 103–107 cfu/mL (mean, 3×106 cfu/mL) and, with a GAS isolate, 103–105 cfu/mL (mean, 2×105 cfu/mL).

Eleven emm types among GGS isolates and 4 emm types among GAS isolates were found (table 2). Three patients harbored the most common emm type of GGS, stG643.0. We identified a cluster of 3 cellulitis cases among patients in a nursing home, and the patients had the same clone of GAS in their affected skin: emm81.0 with PFGE profile type A. One of these patients also harbored a GGS emm type stC6979.0 at the infection site.

Table 2
View larger version:
Table 2

Molecular characteristics of group G (Streptococcus dysgalactiae subsp. equisimilis) and group A (Streptococcus pyogenes) streptococci isolated from patients with acute bacterial cellulitis.

Recurrent infections. Six patients (median age, 48 years) had recurrences during the study period; 4 patients had 2, and 2 patients had 3 disease episodes (table 3). The median time between recurrences was 81 days. All of these patients had a history of at least 1 cellulitis infection before the time of this study. The infection site remained the same in all episodes, but the site of sampling varied. GGS combined with S. aureus was isolated from 3 patients, none of whom had any visible abrasion or wound at the infection site, and the sample was taken from another site, such as the toe area or heel. In 2 patients, the GGS recovered from cutaneous swabs in 2 consecutive episodes had identical emm (stG6.0 and stG11.0) and PFGE types (table 2). All of these patients had negative blood culture results.

Table 3
View larger version:
Table 3

Bacterial findings for patients who had recurrent infections during this study.

Pharyngeal findings. A total of 225 throat swab samples were taken: 97 samples from 89 patients, 38 from household members, and 90 from control subjects. β-Hemolytic streptococci were carried in the pharynx by 12 (13%) of the 89 patients, 8 (21%) of the 38 household members, and 9 (10%) of the 90 control subjects (figure 1). GGS was significantly more commonly found in patients (7%) and household members (13%) than in control subjects (0%) (P⩽.04, by McNemar's test). S. aureus was present in ⩽10% of the samples of these groups (data not shown).

Of the GGS isolated from patients, 4 of 6 isolates were S. dysgalactiae subsp. equisimilis (table 2), 1 was S. anginosus, and 1 could not be characterized. Two patients harbored GAS (S. pyogenes) strains. The household members harbored 5 GGS isolates (S. dysgalactiae subsp. equisimilis), with emm types stG6.1 (2 isolates), stG166b.0, stG480.0, and stG652.0. On 2 occasions, the same strain was shared within the household: 1 patient and a household member harbored the same clone of GGS: emm type stG480.0 with PFGE type II. Two household members of the nursing home cluster carried an identical clone of a GGS strain: emm type stG6.1.

One of the 90 patients had the same streptococcal strain (GGS, emm type stG245.0 with an identical PFGE type III) in the pharynx and affected skin (toe web; not the actual infection site).

Previous SectionNext Section

Discussion

To our knowledge, this is the first case-control study of acute bacterial cellulitis in Finland. Within 1 year, 90 patients presenting with 98 disease episodes were included in the study. Strikingly, GGS (S. dysgalactiae subsp. equisimilis) instead of GAS was the most common finding. Some patients and household members also carried GGS in the pharynx, whereas it was not detected in the control subjects. We could also confirm in 2 cases of recurrences that the consecutive episodes were caused by the same clone of GGS.

A limitation of our study is that the patient population comprised hospitalized patients with cellulitis of intermediate severity. The proportion of patients treated on an outpatient basis is not known. However, a Finnish treatment recommendation is to hospitalize febrile patients with cellulitis, for initial parenteral antibiotic treatment. The most severe cases—for example, patients requiring intensive care treatment or surgery—were treated in other wards and therefore were not eligible for this study. This may have decreased the observed rate of bacteremia, as well as the rate of recurrence, which may also be underestimated because of the short study period and lack of follow-up data [19].

GGS was isolated either from skin lesion or blood from 22% of patients, whereas GAS was isolated from 7% of patients, in proportions similar to those reported in a recent case-control study [5]. The proportion of patients with a positive blood culture result (2%) was in the expected range for this disease, with GGS as the cause of bacteremia. GAS has been regarded as the main causative agent of streptococcal cellulitis, as well as the cause of bacteremia in patients with cellulitis [3, 4]. Nonetheless, a stronger role of GGS in cellulitis [4, 5, 20] and, with increasing recent frequency, in nonfocal bacteremia [21–24] has been noticed.

With a noninvasive sampling method, we could isolate β-hemolytic streptococci from one-third of the samples. We cannot exclude the possibility that the choice of sampling method and, in some cases, antibiotic treatment before our sampling may have had an effect on the findings. The findings differed by sampling site, and more than one-half of the isolates were obtained from the suspected site of entry, which may or may not be the actual site of entry of the pathogen. Nevertheless, recent findings support the role of toe webs as a potential site of entry, and colonization of toe webs by pathogens is a risk factor for lower-limb cellulitis [5, 25].

Only 1 patient harbored the same streptococcal clone in both the pharynx and affected skin. The skin is a more likely origin of the infection than is the respiratory tract, and presence of streptococci on the intact skin before cellulitis onset has been reported [26]. The causal relationship with anal GGS colonization and bacterial cellulitis has also been studied [27].

There was no clear predominance of a specific emm type in GGS or GAS that associated with the disease, although it is difficult to draw conclusions from relatively few isolates. Of the emm types in GAS isolates, emm28 was common among Finnish invasive strains during the same time period [11]. In contrast, very little is known of the emm types of GGS that cause cellulitis. Many of the emm types that we found in GGS isolates have been related to invasive disease, bacteremia, and toxic shock syndrome [28–31].

Of patients with bacterial cellulitis, 20%–30% are prone to recurrences [4, 9]. Even within this short study period, 7% of the patients had a recurrence, and 50% of all patients reported having previous cellulitis infections. In 2 patients, the GGS strains that were isolated in the consecutive episodes only 2 months apart had identical emm and PFGE types, suggesting that these infections were relapses. Recurrent GGS bacteremia has also been reported [28]. The pathogen's persistence in the tissue, despite antibiotic treatment, contributes to the rate of recurrence. The question remains as to whether recurrences are specifically associated with a streptococcal species or strain. The median age of patients with recurrences was 10 years younger than the median age of the other case patients. Younger patients may be at a high risk of recurrence, and a previous cellulitis infection seems to be a strong predisposing factor to future episodes [4, 5, 8, 32]. Various general and local risk factors play a role in recurrences, as does the patient's increased susceptibility to infection, such as the inability of the immune system to clear the bacteria from the infection site.

Relatively little is known of the unique characteristics of GGS in relation to its pathogenic potential. The bacterial load and the magnitude and type of cytokine expression correlate with the severity of GAS soft-tissue infection [33]. Toxins have a critical role in streptococcal pathogenesis, and their distribution varies among GAS strains [2, 33, 34]. There is strong support that horizontal transfer of virulence genes between GAS and GGS occurs and may lead to clones with enhanced pathogenic potential [35–40]. Thus, further research targeted to the group A and group G streptococcal virulence determinants and genome is warranted.

Group G streptococci, instead of group A streptococci, seem to predominate in skin lesions of patients with bacterial cellulitis. A predominance of GGS was also seen in the throat of patients and their family members, whereas it was not detected in control subjects. Several emm types were present in GGS and GAS isolates, with no clear predominance of a specific type. The recurrent nature of cellulitis became evident during this study.

Previous SectionNext Section

Acknowledgments

We thank research nurses Päivi Aitos and Eeva Pursiainen (University of Helsinki) and laboratory technicians Aila Soininen, Saija Perovuo, and Suvi Kavenius (National Public Health Institute, Helsinki), for excellent technical assistance. We greatly acknowledge the staff of the hospital wards where the study was performed, for their invaluable input in the study. Researcher Minna Kardán-Lilja (National Public Health Institute, Helsinki) kindly advised in the analyzing of PFGE gels and assigning types.

Financial support. Grants from the Academy of Finland/Microbes and Man Research Programme 2003–2005, and a travel grant (to T.S.) from the Finnish Society for Study of Infectious Diseases for the poster presentation at the European Congress of Clinical Microbiology and Infectious Diseases.

Potential conflicts of interest. All authors: no conflicts.

  • Received May 22, 2007.
  • Accepted October 24, 2007.
Previous Section
 

References

  1. ↵
    1. Stevens DL,
    2. Bisno AL,
    3. Chambers HF,
    4. et al
    . Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005;41:1373-406.
    FREE Full Text
  2. ↵
    1. Bonnetblanc JM,
    2. Bedane C
    . Erysipelas: recognition and management. Am J Clin Dermatol 2003;4:157-63.
    CrossRefMedlineWeb of Science
  3. ↵
    1. Chartier C,
    2. Grosshans E
    . Erysipelas. Int J Dermatol 1990;29:459-67.
    MedlineWeb of Science
  4. ↵
    1. Eriksson B,
    2. Jorup-Ronstrom C,
    3. Karkkonen K,
    4. Sjoblom AC,
    5. Holm SE
    . Erysipelas: clinical and bacteriologic spectrum and serological aspects. Clin Infect Dis 1996;23:1091-8.
    Abstract/FREE Full Text
  5. ↵
    1. Bjornsdottir S,
    2. Gottfredsson M,
    3. Thorisdottir AS,
    4. et al
    . Risk factors for acute cellulitis of the lower limb: a prospective case-control study. Clin Infect Dis 2005;41:1416-22.
    Abstract/FREE Full Text
    1. Dupuy A,
    2. Benchikhi H,
    3. Roujeau JC,
    4. et al
    . Risk factors for erysipelas of the leg (cellulitis): case-control study. BMJ 1999;318:1591-4.
    Abstract/FREE Full Text
    1. Mokni M,
    2. Dupuy A,
    3. Denguezli M,
    4. et al
    . Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study. Dermatology 2006;212:108-12.
    CrossRefMedlineWeb of Science
  8. ↵
    1. Roujeau JC,
    2. Sigurgeirsson B,
    3. Korting HC,
    4. Kerl H,
    5. Paul C
    . Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study. Dermatology 2004;209:301-7.
    CrossRefMedlineWeb of Science
  9. ↵
    1. Jorup-Ronstrom C,
    2. Britton S
    . Recurrent erysipelas: predisposing factors and costs of prophylaxis. Infection 1987;15:105-6.
    CrossRefMedlineWeb of Science
  10. ↵
    1. Bisno AL,
    2. Stevens DL
    . Streptococcal infections of skin and soft tissues. N Engl J Med 1996;334:240-5.
    CrossRefMedlineWeb of Science
  11. ↵
    1. Siljander T,
    2. Toropainen M,
    3. Muotiala A,
    4. Hoe NP,
    5. Musser JM,
    6. Vuopio-Varkila J
    . emm Typing of invasive T28 group A streptococci, 1995–2004, Finland. J Med Microbiol 2006;55:1701-6.
    Abstract/FREE Full Text
  12. ↵
    1. Moody MD,
    2. Padula J,
    3. Lizana D,
    4. Hall CT
    . Epidemiologic characterization of group A streptococci by T-agglutination and M-precipitation tests in the public health laboratory. Health Lab Sci 1965;2:149-62.
    Medline
  13. ↵
    Centers for Disease Control and Prevention. Streptococcus pyogenes emm sequence database: protocol for emm typing. Available at: http://www.cdc.gov/ncidod/biotech/strep/protocol_emm-type.htm. Accessed 3 September 2007.
  14. ↵
    1. Tanna A,
    2. Emery M,
    3. Dhami C,
    4. Arnold E,
    5. Efstratiou A
    . Molecular characterization of clinical isolates of M non-typable group A streptococci from invasive disease cases. J Med Microbiol 2006;55:1419-23.
    Abstract/FREE Full Text
  15. ↵
    Centers for Disease Control and Prevention. Streptococcus pyogenes emm sequence database: Blast 2.0 server. Available at: http://www.cdc.gov/ncidod/biotech/strep/strepblast.htm. Accessed 3 September 2007.
  16. ↵
    1. Stanley J,
    2. Linton D,
    3. Desai M,
    4. Efstratiou A,
    5. George R
    . Molecular subtyping of prevalent M serotypes of Streptococcus pyogenes causing invasive disease. J Clin Microbiol 1995;33:2850-5.
    Abstract/FREE Full Text
  17. ↵
    GraphPad Software. Online calculators for scientists. Available at: http://www.graphpad.com/quickcalcs/index.cfm. Accessed 3 September 2007.
  18. ↵
    1. Preacher KJ
    . Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence. April. 2001. Available at: http://www.quantpsy.org. Accessed 3 September 2007.
  19. ↵
    1. Cox NH
    . Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow-up. Br J Dermatol 2006;155:947-50.
    CrossRefMedlineWeb of Science
  20. ↵
    1. Hugo-Persson M,
    2. Norlin K
    . Erysipelas and group G streptococci. Infection 1987;15:184-7.
    CrossRefMedlineWeb of Science
  21. ↵
    1. Ekelund K,
    2. Skinhoj P,
    3. Madsen J,
    4. Konradsen HB
    . Invasive group A, B, C and G streptococcal infections in Denmark 1999–2002: epidemiological and clinical aspects. Clin Microbiol Infect 2005;11:569-76.
    CrossRefMedlineWeb of Science
    1. Hindsholm M,
    2. Schonheyder HC
    . Clinical presentation and outcome of bacteraemia caused by beta-haemolytic streptococci serogroup G. APMIS 2002;110:554-8.
    CrossRefMedlineWeb of Science
  23. Health Protection Agency U.K. Pyogenic and non-pyogenic streptococcal bacteraemias, England, Wales and Northern Ireland: 2005. Commun Dis Rep Wkly 2006;16. HCAI. Available at: http://www.hpa.org.uk/infections/topics_az/strepto/HPAStreptococcalInfectionsEpidemiologicaldata.htm. Accessed 3 September 2007.
  24. ↵
    1. Sylvetsky N,
    2. Raveh D,
    3. Schlesinger Y,
    4. Rudensky B,
    5. Yinnon AM
    . Bacteremia due to beta-hemolytic streptococcus group G: increasing incidence and clinical characteristics of patients. Am J Med 2002;112:622-6.
    CrossRefMedlineWeb of Science
  25. ↵
    1. Hilmarsdottir I,
    2. Valsdottir F
    . Molecular typing of beta-hemolytic streptococci from two patients with lower-limb cellulitis: identical isolates from toe web and blood specimens. J Clin Microbiol 2007;45:3131-2.
    Abstract/FREE Full Text
  26. ↵
    1. Jorup-Ronstrom C
    . Epidemiological, bacteriological and complicating features of erysipelas. Scand J Infect Dis 1986;18:519-24.
    MedlineWeb of Science
  27. ↵
    1. Eriksson BK
    . Anal colonization of group G β-hemolytic streptococci in relapsing erysipelas of the lower extremity. Clin Infect Dis 1999;29:1319-20.
    Abstract/FREE Full Text
  28. ↵
    1. Cohen-Poradosu R,
    2. Jaffe J,
    3. Lavi D,
    4. et al
    . Group G streptococcal bacteremia in Jerusalem. Emerg Infect Dis 2004;10:1455-60.
    MedlineWeb of Science
    1. Hashikawa S,
    2. Iinuma Y,
    3. Furushita M,
    4. et al
    . Characterization of group C and G streptococcal strains that cause streptococcal toxic shock syndrome. J Clin Microbiol 2004;42:186-92.
    Abstract/FREE Full Text
    1. Kalia A,
    2. Enright MC,
    3. Spratt BG,
    4. Bessen DE
    . Directional gene movement from human-pathogenic to commensal-like streptococci. Infect Immun 2001;69:4858-69.
    Abstract/FREE Full Text
  31. ↵
    1. Lopardo HA,
    2. Vidal P,
    3. Sparo M,
    4. et al
    . Six-month multicenter study on invasive infections due to Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis in Argentina. J Clin Microbiol 2005;43:802-7.
    Abstract/FREE Full Text
  32. ↵
    1. Leclerc S,
    2. Teixeira A,
    3. Mahe E,
    4. Descamps V,
    5. Crickx B,
    6. Chosidow O
    . Recurrent erysipelas: 47 cases. Dermatology 2007;214:52-7.
    CrossRefMedlineWeb of Science
  33. ↵
    1. Norrby-Teglund A,
    2. Thulin P,
    3. Gan BS,
    4. et al
    . Evidence for superantigen involvement in severe group a streptococcal tissue infections. J Infect Dis 2001;184:853-60.
    Abstract/FREE Full Text
  34. ↵
    1. Banks DJ,
    2. Beres SB,
    3. Musser JM
    . The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence. Trends Microbiol 2002;10:515-21.
    CrossRefMedlineWeb of Science
  35. ↵
    1. Davies MR,
    2. McMillan DJ,
    3. Van Domselaar GH,
    4. Jones MK,
    5. Sriprakash KS
    . Phage 3396 (Π3396) from a Streptococcus dysgalactiae subsp equisimilis pathovar may have its origins in Streptococcus pyogenes. J Bacteriol 2007;189:2646-52.
    Abstract/FREE Full Text
    1. Davies MR,
    2. Tran TN,
    3. McMillan DJ,
    4. Gardiner DL,
    5. Currie BJ,
    6. Sriprakash KS
    . Inter-species genetic movement may blur the epidemiology of streptococcal diseases in endemic regions. Microbes Infect 2005;7:1128-38.
    CrossRefMedlineWeb of Science
    1. Igwe EI,
    2. Shewmaker PL,
    3. Facklam RR,
    4. Farley MM,
    5. van Beneden C,
    6. Beall B
    . Identification of superantigen genes speM, ssa, and smeZ in invasive strains of beta-hemolytic group C and G streptococci recovered from humans. FEMS Microbiol Lett 2003;229:259-64.
    CrossRefMedlineWeb of Science
    1. Kalia A,
    2. Bessen DE
    . Presence of streptococcal pyrogenic exotoxin A and C genes in human isolates of group G streptococci. FEMS Microbiol Lett 2003;219:291-5.
    CrossRefMedlineWeb of Science
    1. Kalia A,
    2. Bessen DE
    . Natural selection and evolution of streptococcal virulence genes involved in tissue-specific adaptations. J Bacteriol 2004;186:110-21.
    Abstract/FREE Full Text
  40. ↵
    1. Sachse S,
    2. Seidel P,
    3. Gerlach D,
    4. et al
    . Superantigen-like gene(s) in human pathogenic Streptococcus dysgalactiae, subsp equisimilis: genomic localisation of the gene encoding streptococcal pyrogenic exotoxin G (speGdys). FEMS Immunol Med Microbiol 2002;34:159-67.
    CrossRefMedlineWeb of Science
| Table of Contents

This Article

  1. Clin Infect Dis. (2008) 46 (6): 855-861. doi: 10.1086/527388
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most