Bacteremia caused by group G streptococci, Taiwan.

A retrospective observational study in Taiwan, 19982004, identified 92 patients with group G streptococcal bacteremia; 86 had Streptococcus dysgalactiae subspecies equisimilis. The most common diagnosis was cellulitis (48 cases), followed by primary bacteremia (34 cases). Infection recurred in 9 patients. Mortality rate was low (3.3%); resistance to quinupristin-dalfopristin was high.

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Group G streptococci (GGS) are part of the normal microbial flora of the gastrointestinal tract, vagina, and skin and cause a variety of infections (1). Major underlying illnesses in patients with GGS bacteremia are malignancy, cardiovascular disease, diabetes mellitus, bone and joint diseases, and cirrhosis (1,2). Reported mortality rates for patients with GGS bacteremia also vary, ranging from 5% to 30% (1-3). Recent studies of [beta]-hemolytic streptococci isolates carrying Lancefield group G antigen showed that they consist of Streptococcus dysgalactiae subspecies equisimilis, S. anginosus, and S. canis (2,4-6). To supplement the limited clinical information about bacteremia caused by GGS strains identified to the species level (2-4), we conducted a retrospective observational study.

The Study

We included all patients with GGS-positive blood cultures who had been treated from April 1998 through August 2004 at National Taiwan University Hospital, a 2,000-bed teaching hospital in northern Taiwan. We recorded demographic parameters, underlying illness, clinical diagnosis, and outcome for each patient. Clinical diagnosis was based on the attending physician's judgment and examination results. Recurrence of bacteremia was defined as repeated positive blood culture after complete treatment (at least 14 days) of previous bacteremia.

Differentiation of GGS was based on colony size, hemolytic reaction, Voges-Proskauer reaction, and [beta]-glucuronidase activity. All [beta]-hemolytic streptococci, whether large or small colonies, were tested for Lancefield group by using an agglutination kit (Streptex; Murex Bio tech Ltd., Dartford, UK). PCR to differentiate between S. anginosus and S. dysgalactiae subsp, equisimilis was performed for all GGS isolates as described (7). For identification of S. canis, a probable isolate was identified by a negative [beta]-glucuronidase result and further confirmed with the 16sRNA method as described (8). Susceptibilities of these isolates were tested by using the broth microdilution method as defined by the Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards) (9).

To determine the similarity of isolates in cases of recurrence, we used pulsed-field gel electrophoresis (PFGE) as described (10). The emm typing of isolates in cases of recurrence were also determined as described (11). The first 160 bases sequenced by emmseq2 that had [greater than or equal to] 95% identity were defined as having the same genotype (11).

During the study period, 106 episodes of GGS bacteremia in 92 patients had been recorded; 56 episodes occurred during the first half of the study period (before June 2001) and 50 episodes during the second half. The causative agent was X dysgalactiae subsp, equisimilis for 99 episodes, S. anginosus for 5, and S. canis for 2. Bacteremia recurred for 9 patients (1 had 4 episodes, and 3 had 3 episodes); bacteremia was nosocomial for 7 patients and polymicrobial for 5. The clinical characteristics of the patients are summarized in Table 1. All 3 patients who died had a diagnosis of the primary bacteremia caused by S. dysgalactiae subsp, equisimilis.

Among the 9 patients with recurrent bacteremia, the causative agent was S. dysgalactiae subsp, equisimilis for 8 and S. canis for 1. PFGE performed with all 13 available isolates from recurrent cases showed that 10 were identical to that of the initial episode, including 1 in a patient with recurrence of S. canis bacteremia. Sequence typing showed emm type stG485 for 4 patients. The clinical characteristics of the patients and emm typing results are shown in Table 2; PFGE results are shown in the Figure. The underlying diseases of patients with recurrent episodes included genital cancer (4 [44.4%] patients) and history of cellulitis (6 [66.7%]), each of which was significantly correlated with the likelihood of recurrence (p<0.01 for each). Further analysis showed that a previous history of cellulitis was significantly correlated with female sex (p = 0.01), genital cancer (p<0.01), tissue edema (p = 0.02), heart disease (p = 0.04), and post-coronary artery bypass graft (p = 0.03).

Bacteremia caused by [beta]-hemolytic S. anginosus with group G antigen was identified for 5 patients, none of whom had cellulitis, compared with 48 (55.8%) of the 86 patients with S. dysgalactiae subsp, equisimilis who did have cellulitis (p = 0.03). Polymicrobial bacteremia and nosocomial bacteremia were found in a higher percentage of patients with S. anginosus (60% and 40.0%, respectively) than of patients with S. dysgalactiae subsp, equisimilis bacteremia (4.7% and 5.8%, respectively); p<0.01 and p = 0.02, respectively. The 1 patient with S. canis bacteremia was a 33-year-old man with no history of dog bite. He had alcoholassociated liver cirrhosis of Child C (severe) classification and leg edema. He had 2 episodes of S. canis bacteremia 1 month apart. Echocardiogram results showed no evidence of valvular vegetation. For the first episode, the patient received a 14-day course of cefotaxime.

Antimicrobial drug-susceptibility testing showed decreased susceptibility to only macrolides (susceptibity rates: azithromycin 67.4%, clarithromycin 73.9%), clindamycin (87.0%), and quinupristin-dalfopristin (33.7%) (online Appendix Table, available from www.cdc.gov/EID/content/14/5/837-appT.htm). No clinical factor correlated with macrolide resistance. All isolates of recurrent bacteremia were susceptible to macrolides.

Conclusions

We documented 5 cases of primary bacteremia caused by [beta]-hemolytic group G S. anginosus and unintentionally documented recurrence of S. canis bacteremia. S. canis bacteremia in humans was first clearly described in 1997 (12).

Our finding of 5 [beta]-hemolytic S. anginosus isolates and 1 S. canis isolate in patients with GGS bacteremia in this study differs from findings of previous studies (2,3). Factors that may have contributed to this discrepancy include serotype determination and PCR method. Serotype determination was performed for all [beta]-hemolytic streptococci isolated in our hospital, whether colonies were large or small, which might have led to the detection of more streptococcal isolates with G antigen. The PCR method developed in our hospital and used in this study could effectively differentiate S. anginosus from S. dysgalactiae subsp, equisimilis (7).

Information about clinical infection with S. milleri with group G antigen is limited (4). In a previous study of GGS bacteremia, Cohen-Poradosu et al. reported that 6 of 84 patients had recurrence of bacteremia (3). We found recurrence in 9 of the 92 patients. Risk factors were similar to those previously reported for non--group A streptococcal cellulitis (13). PFGE of these isolates showed that a high percentage of recurrence was caused by identical strains. Although Cohen-Poradosu et al. reported that emm type stG840 was the most common strain (3), we found emm type stG485 to be most common.

[FIGURE OMITTED]

For years in Taiwan, macrolide resistance of streptococci has been a major health problem (14,15). A previous study found erythromycin resistance in 23.5% of GGS strains (14). Although we did not test for erythromycin resistance, we found some resistance even to new macrolides. Since restriction of macrolide use in Taiwan, a linear relationship has been noted between the decline in erythromycin use and the decline in erythromycin resistance in S. pyogenes (15). Our study, however, found no decline in macrolide resistance from first half of the study period (27.1%) to the second half (37.0%).

In summary, in our study, infection with S. dysgalactiae subsp, equisimilis was the most common cause of GGS bacteremia. Infection recurred for [approximately equal to] 10%. The mortality rate for patients with GGS bacteremia was relatively low (< 10%), but resistance to quinupristin-dalfopristin was extremely high.

References

(1.) Auckenthaler R, Hermans PE, Washington JA II. Group G streptococcal bacteremia: clinical study and review of the literature. Rev Infect Dis. 1983;5:196-204.

(2.) Woo PC, Fung AM, Lau SK, Wong SS, Yuen KY. Group G betahemolytic streptococcal bacteremia characterized by 16S ribosomal RNA gene sequencing. J Clin Microbiol. 2001;39:3147-55.

(3.) Cohen-Poradosu R, Jaffe J, Lavi D, Grisariu-Greenzaid S, Nir-Paz R, Valinsky L, et al. Group G streptococcal bacteremia in Jerusalem. Emerg Infect Dis. 2004;10:1455-60.

(4.) Facklam R. What happened to the streptococci: overview of taxonomic and nomenclature changes. Clin Microbiol Rev. 2002;15: 613-30.

(5.) Vandamme P, Pot B, Falsen E, Kersters K, Devriese LA. Taxonomic study of Lancefield streptococcal groups C, G, and L (Streptococcus dysgalactiae) and proposal of S. dysgalactiae subsp, equisimilis subsp, nov. Int J Syst Bacteriol. 1996;46:774-81.

(6.) Lawrence J, Yajko DM, Hadley WK. Incidence and characterization of beta-hemolytic Streptococcus milleri and differentiation from S. pyogenes (group A), S. equisimilis (group C), and large-colony group G streptococci. J Clin Microbiol. 1985;22:772-7.

(7.) Liu LC, Tsai JC, Hsueh PR, Teng LJ. Rapid differentiation between members of the anginosus group and Streptococcus dysgalactiae subsp, equisimilis within beta-hemolytic group C and G streptococci by PCR. J Clin Microbiol. 2006;44:1836-8.

(8.) Whatmore AM, Engler KH, Gudmundsdottir G, Efstratiou A. Identification of isolates of Streptococcus canis infecting humans. J Clin Microbiol. 2001;39:4196-9.

(9.) National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A6. 5th ed. Wayne (PA): The Committee, 2004.

(10.) Hsueh PR, Teng LJ, Lee LN, Yang PC, Ho SW, Luh KT. Dissemination of high-level penicillin-, extended-spectrum cephalosporin-, and erythromycin-resistant Streptococcus pneumoniae clones in Taiwan. J Clin Microbiol. 1999;37:221-4.

(11.) Facklam R, Beall B, Efstratiou A, Fischetti V, Johnson D, Kaplan E, et al. emm typing and validation of provisional M types for group A streptococci. Emerg Infect Dis. 1999;5:247-53.

(12.) Bert F, Lambert-Zechovsky N. Septicemia caused by Streptococcus canis in a human. J Clin Microbiol. 1997;35:777-9.

(13.) Baddour LM, Bisno AL. Non-group A beta-hemolytic streptococcal cellulitis. Association with venous and lymphatic compromise. Am J Med. 1985;79:155-9.

(14.) Wu JJ, Lin KY, Hsueh PR, Liu JW, Pan HI, Sheu SM. High incidence of erythromycin-resistant streptococci in Taiwan. Antimicrob Agents Chemother. 1997;41:844-6.

(15.) Hsueh PR, Shyr JM, Wu JJ. Changes in macrolide resistance among respiratory pathogens after decreased erythromycin consumption in Taiwan. Clin Microbiol Infect. 2006; 12:296-8.

Chun-Hsing Liao, * Liang-Chun Liu, ([dagger]) Yu-Tsung Huang, ([dagger]) Lee-Jeng Teng, ([dagger]) and Po-Ren Hsueh ([dagger])

* Far-Eastern Memorial Hospital, Taipei, Taiwan; and ([dagger]) National Taiwan University College of Medicine, Taipei, Taiwan

Address for correspondence: Po-Ren Hsueh, National Taiwan University, No. 7, Chung-Shan South Road, 100 Taipei, Taiwan; email: [e-mail]

Dr Liao is an infectious diseases specialist in the Department of Internal Medicine, Far-Eastern Memorial Hospital. His major research interests are clinical and epidemiologic studies and pathogenesis of gram-positive bacterial infections, particularly streptococcal and methicillin-resistant Staphylococcus aureus infections.

Table 1. Clinical characteristic of 92 patients with group G
streptococcal bacteremia, April 1998-August 2004, Taiwan

Characteristic                             No. (%) patients

Age, y
  <10                                       1 (1.1)
  10-50                                    12 (13.0)
  51-75                                    68 (73.9)
  >75                                      11 (12.0)
  Median (range)                           72 (10-93)
Sex
  Male                                     58 (63.0)
  Female                                   34 (37.0)
Underlying diseases
  Malignancy                               35 (38.0)
  Genital                                  10 (10.9)
  Head and neck                             8 (8.7)
  Gastrointestinal                          6 (6.5)
  Hematologic                               3 (3.3)
  Tissue edema                             25 (27.2)
  Heart disease                            20 (21.7)
  Post-coronary artery bypass graft         6 (6.5)
  Diabetes mellitus                        16 (17.4)
  Central nervous system disease           15 (16.3)
  Liver cirrhosis                           9 (9.8)
  Chronic renal disease                     8 (8.7)
  Chronic lung disease                      6 (6.5)
  Bone disease                              5 (5.4)
  Deep venous thrombosis                    2 (2.2)
Type of infection
  Cellulitis                               48 (52.1) *
  Primary bacteremia                       34 (36.9)
  Deep-seated abscess                       4 (4.2) ([dagger])
  Neutropenia and fever                     3 (3.3)
  Septic arthritis                          2 (2.2)
  Urinary tract infection                   1 (1.1)
  Infective endocarditis                    1 (1.1)
  Pneumonia                                 1 (1.1)
Initial findings
  Fever                                    86 (93.5)
  Leukocytosis (>10,000 cells/[micro]L)    34 (37.0)
  Septic shock                              4 (5.4)
Outcome
  Death                                     3 (3.3)
  Recurrence of bacteremia                  9 (9.8)

* Includes 2 patients who also had septic arthritis.

([dagger]) Includes 2 patients with psoas muscle abscess, 1 with
epidural abscess, and 1 with deep neck infection.

Table 2. Summary of characteristics of patients with recurrence of
group G streptococcus bacteremia, April 1998-August 2004, Taiwan *

Patient  Age, y/                   Date of
no.        sex       Isolate      isolation      Underlying disease

1         67/F         A1        2001 May 28  Coronary heart disease,
                       A2        2002 Jul 18    post-coronary artery
                       A3        2003 Oct 14        bypass graft

2         33/M    B1 ([dagger])  2002 Nov 13      Alcoholic liver
                  B2 ([dagger])  2002 Oct 15     cirrhosis, child C

3         47/F         C1        1998 May 15    Vulvar cancer after
                       C2        2002 Jan 18  surgery and radiotherapy
                       C3        2002 Dec 19

4         49/M         D1        2000 May 24  Nasopharyngeal carcinoma
                       D2        2000 Aug 9    after chemotherapy and
                                                    radiotherapy

5         28/M         E1        1998 Dec 26  von Willebrand disease,
                       E2        1999 Aug 28           type I

6         72/F         F1        1998 Aug 24   Cervical cancer after
                       F2        1998 Oct 23        surgery and
                       F3        1999 Dec 3    radiotherapy, diabetes
                                                      mellitus

7         55/F         G1        1999 Oct 9    Cervical cancer after
                       G2        2000 Apr 18  surgery and radiotherapy
                       G3        2001 Sep 24
                       NA        2000 Jul 19

8         46/M         H1        2001 Aug 21       Acute myeloid
                       H2        2001 Sep 6        leukemia (M4)

9         80/F         I1        2003 May 5     Cervical cancer with
                       I2        2003 Nov 17    lung metastasis and
                                                obstructive uropathy

Patient     Date of                                        PFGE
no.        isolation    Clinical diagnosis   emm type     pattern

1         2001 May 28       Cellulitis        stG166b       --
          2002 Jul 18       Cellulitis        stG166b    Identical
          2003 Oct 14       Cellulitis        stG166b    Identical

2         2002 Nov 13   Primary bacteremia   STL1929.1      --
          2002 Oct 15   Primary bacteremia   STL1929.1   Identical

3         1998 May 15       Cellulitis        stG166b       --
          2002 Jan 18       Cellulitis        stG6.1      Related
          2002 Dec 19       Cellulitis        stG6.1     Identical

4         2000 May 24       Cellulitis        stG485        --
          2000 Aug 9        Cellulitis        stG485     Identical

5         1998 Dec 26       Cellulitis        stG485        --
          1999 Aug 28       Cellulitis        stG840     Different

6         1998 Aug 24       Cellulitis        stG485        --
          1998 Oct 23       Cellulitis        stG485     Identical
          1999 Dec 3        Cellulitis        stG840     Different

7         1999 Oct 9        Cellulitis        stG485        --
          2000 Apr 18       Cellulitis        stG485     Identical
          2001 Sep 24       Cellulitis        stG485     Identical
          2000 Jul 19       Cellulitis          NA          NA

8         2001 Aug 21   Primary bacteremia   stGLP 1.0      --
          2001 Sep 6    Primary bacteremia   stGLP 1.0   Identical

9         2003 May 5    Primary bacteremia   stG245.0
          2003 Nov 17   Primary bacteremia   stG245.0    Identical

* PFGE, pulsed-field gel electrophoresis; NA, not available.
([dagger]) Streptoccus canis.