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Fatal Streptococcus equi subsp. ruminatorum infection in a man.

To the Editor: Streptococcus equi belongs to the pyogenic group of streptococci and to group C of the Lancefield classification. It consists of 3 subspecies of zoonotic agents rarely reported as human pathogens (1,2): S. equi subsp, equi, S. equi subsp, zooepidemicus, and S. equi subsp, ruminatorum. We report here a case of human infection caused by S. equi subsp, ruminatorum. (3).

A 53-year-old man was admitted to an intensive care unit of our hospital (University Teaching Hospital, Montpellier, France) on April 28, 2006, with a high fever and in a comatose state. The day before, he had experienced headache and neck pain. He had been infected with HIV for 9 years but had not had an opportunistic infection. His ongoing HIV treatment consisted of ritonavir, lopinavir, abacavir, lamivudine, and co-trimoxazole; 3 weeks before admission, his blood CD4+ T-cell count was 133/[micro]L, and viral load was 118,000 copies/mL. At the time of admission, his body temperature was 38.9[degrees]C, heart rate was 105 beats/rain, and blood pressure was 55/35 mmHg. He exhibited a fixed pupil in 1 eye, neck stiffness, and was nonresponsive. He had bilateral pulmonary infiltrates and severe hypoxemia. Treatment consisted of mechanical ventilation, fluid therapy, and norepinephrine. Laboratory investigations found the following: leukocyte count 9,600/[mm.sup.3] with 90% neutrophils, hemoglobin level 9.0 g/dL, platelet count 32,000/[mm.sup.3], C-reactive protein value 159 mg/L, and blood lactate concentration 3.2 mmol/ L. Computed tomographic scanning of the brain showed no hemorrhage or edema. Lumbar puncture produced turbid cerebrospinal fluid (CSF) with 300 leukocytes/[mm.sup.3] (95% neutrophils), protein 5.6 g/L, glucose <0.1 mmol/L, and gram-positive cocci. Three sets of aerobic-anaerobic blood cultures and bronchial aspirates were sampled, and intravenous treatment with dexamethasone (10 mg/6 h/day), cefotaxime (2 g/4 h/day), and vancomycin (30 mg/kg/day) was initiated. On day 2, the hemodynamic state was stabilized, but brain death occurred.

All sets of aero-anaerobic blood cultures, CSF, and bronchial aspirate fluid yielded the growth of a catalase-negative, [beta]-hemolytic, gram-positive cocci belonging to the Lancefield group C of streptococci. Antimicrobial susceptibility testing showed a bacterium fully susceptible to antibiotics tested. MICs of penicillin, amoxicillin, and cefotaxime were 0.047, 0.125, and 0.125 mg/L, respectively. The isolates were identified as S. equi by using the Vitek2 system, rapid ID32 STREP, and API 20 STREP strips (bioMerieux, Marcy l'Etoile, France), but phenotype was inconclusive for subspecies identification. The strains were identified as S. equi subsp. zooepidemicus by Vitek2, but aesculin was not hydrolyzed, and D-ribose fermentation was noted, as previously described for S. equi subsp, ruminatorum. 16S rRNA gene--based identification was performed as previously described (4) on strain ADV 6048.06 from blood. The 1,396-bp sequence (GenBank accession no. EF362949) was compared with databases by using the BLAST program (5); the sequence differed by only 1 nucleotide position (>99.9% identity) from the sequence of S. equi subsp, ruminatorum CECT 577[2.sup.T]. Other primarily related sequences were from S. equi subsp. ruminatorum strains of animal origin (99.5%-99.9% identity) and from S. equi subsp, zooepidemicus, (98.7% identity). Phylogenetic trees clustered the clinical isolate with S. equi subsp. ruminatorum strains to form a robust lineage, well separated from other strains of S. equi and supported by a high bootstrap value (Figure).


S. equi subsp, equi and S. equi subsp, zooepidemicus are zoonotic agents implicated in diverse animal infections such as strangles, mastitis, abscesses, wounds, and respiratory and uterine infections. Human infections caused by S. equi subsp, equi, and S. equi subsp, zooepidemicus included outbreaks of foodborne diseases (6,7), meningitis, septicemia, arthritis, pneumonia, glomerulonephritis, and streptococcal toxic shock syndrome, in both immunocompromised and immunocompetent patients (1,2,8,9). S. equi subsp, ruminatorum was described in 2004 in domestic sheep and goats with mastitis (3). More recently, it was isolated during severe infections in spotted hyenas and zebras (10). No human isolate has been reported to date. Moreover, none of the 3 subspecies of S. equi has been isolated from HIV-infected patients. The current case underlines the conclusion that molecular identification of S. equi subsp, ruminatorum is essential. S. equi subsp, ruminatorum could have been underestimated due to its potential misidentification as S. equi subsp. zooepidemicus by phenotypic tools. Despite the rare occurrence of group C streptococci in human infections, a high death rate is reported for invasive infections (7-9). S. equi subsp, zooepidemicus produce superantigen exotoxin that may have been implicated in the pathogenesis of fatal infection (2); S. equi subsp, ruminatorum should also be investigated for potential virulence factors for humans.

Epidemiologic investigations were unsuccessful in tracing the patient's infection to an animal source. The respiratory tract, from which S. equi subsp. ruminatorum was recovered in pure culture, could be considered the most probable portal of entry.

The mode of S. equi subsp, ruminatorum transmission to humans remains unknown. More information is needed on its reservoirs, but they likely resemble those of S. equi subsp. equi, and S. equi subsp, zooepidemicus (2,6,7). Prevention of human infections due to S. equi should include frequent microbiologic sampling of lactating animals and control measures for un-pasteurized dairy products (7). Better characterization of underlying conditions that increase risk of invasive S. equi infections is also needed. This knowledge could help define high-risk groups of persons and could lead to generation of specific preventive recommendations.

Helene Marchandin,* ([dagger]) Estelle Jumas-Bilak, ([dagger]) Abderrahmane Boumzebra,* Delphine Vidal,* Olivier Jonquet,* and Philippe Corne * ([double dagger])

* Centre Hospitalier Universitaire de Montpellier, Montpellier, France; ([dagger]) Unite de Formation et de Recherche des Sciences Pharmaceutiques, Montpellier, France; and ([double dagger]) Institut de Recherche pour le Developpement, Montpellier, France


(1.) Popescu GA, Fuerea R, Benea E. Meningitis due to an unusual human pathogen: Streptococcus equi subspecies equi. South Med J. 2006;99:190-1.

(2.) Korman TM, Boers A, Gooding TM, Curtis N, Visvanathan K. Fatal case of toxic shock-like syndrome due to group C Streptococcus associated with superantigen exotoxin. J Clin Microbiol. 2004;42:2866-9.

(3.) Fernandez E, Blume V, Garrido P, Collins MD, Mateos A, Dominguez L, et al. Streptococcus equi subsp, ruminatorum subsp, nov., isolated from mastiffs in small ruminants. Int J Syst Evol Microbiol. 2004;54:2291-6.

(4.) earlier JP, Marchandin H, Jumas-Bilak E, Lorin V, Henry C, Carriere C, et al. Anaeroglobus geminatus gen. nov., sp. nov., a novel member of the family Veillonellaceae. Int J Syst Evol Microbiol. 2002;52:983-6.

(5.) Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389-402.

(6.) Bordes-Benitez A, Sanchez-Onoro M, Suarez-Bordon P, Garcia-Rojas AJ, Saez-Nieto JA, Gonzalez-Garcia A, et al. Outbreak of Streptococcus equi subsp, zooepidemicus infections on the island of Gran Canaria associated with the consumption of inadequately pasteurized cheese. Eur J Clin Microbiol Infect Dis. 2006;25: 242-6.

(7.) Kuusi M, Lahti E, Virolainen A, Hatakka M, Vuento R, Rantala L, et al. An outbreak of Streptococcus equi subspecies zooepidemicus associated with consumption of fresh goat cheese. BMC infect Dis. 2006;6:36.

(8.) Bradley SF, Gordon JJ, Baumgartner DD, Marasco WA, Kauffman CA. Group C streptococcal bacteremia: analysis of 88 cases. Rev Infect Dis. 1991;13:270-80.

(9.) Bateman AC, Ramsay AD, Pallett AR Fatal infection associated with group C streptococci. J Clin Pathol. 1993;46:965-7.

(10.) Honer OP, Wachter B, Speck S, Wibbelt G, Ludwig A, Fyumagwa RD, et al. Severe Streptococcus infection in spotted hyenas in the Ngorongoro Crater, Tanzania. Vet Microbiol. 2006; 115:223-8.

Address for correspondence: Philippe Come, Service de Reanimation Medicale Assistance Respiratoire, Hopital Gui de Chauliac, 80 Avenue Augustin Fliche, 34295 Montpellier CEDEX 5, France; email:
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Title Annotation:LETTERS
Author:Marchandin, Helene; Jumas-Bilak, Estelle; Boumzebra, Abderrahmane; Vidal, Delphine; Jonquet, Olivier
Publication:Emerging Infectious Diseases
Article Type:Letter to the editor
Date:Dec 1, 2007
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