The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Case
Severe Acute Otitis Media Caused by Mucoid Streptococcus Pyogenes in a Previously Healthy Adult
Risako KakutaHisakazu YanoHiroshi HidakaHiromitsu MiyazakiMihoko IrimadaKiyoshi OdaKazuaki AraiDaiki OzawaTakashi TakahashiMitsuo KakuYukio Katori
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2014 Volume 232 Issue 4 Pages 301-304

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Abstract

Streptococcus (S.) pyogenes is well recognized as the most common pathogen causing pharyngotonsillitis in school-age children. In Japan, mucoid Streptococcus pneumoniae is well known as a causative agent of severe acute otitis media (AOM); however, mucoid S. pyogenes has rarely been reported. To the best of our knowledge, this is the first report of an AOM patient caused by mucoid S. pyogenes in Japan. A 36-year-old previously healthy female was referred to our hospital with suspicion of cerebrospinal otorrhea due to increasing otalgia accompanied by headache following myringotomy. Bacterial cultures of middle ear secretions were performed, and mucoid-form colonies surrounded by zones of complete β-hemolysis were produced on sheep’s blood agar. Antigen-agglutination test results were positive for S. pyogenes, and thus the patient received treatment with panipenem-betamipron 2.0 g/day for 10 days, which resolved nearly all symptoms. The bacteriological features of this strain were then investigated. The M-protein genotype encoded by the emm gene, the major virulence factor of S. pyogenes, was determined to be emm75. Generally, S. pyogenes forms colonies having non-mucoid matt appearances based on β-hemolysis of sheep’s blood agar. The mucoid phenotype results from abundant production of hyaluronic acid capsular polysaccharide, a key virulence determinant. emm75 is common in noninvasive, but less common in invasive disease. In conclusion, mucoid S. pyogenes can cause severe infection even in previously healthy persons. Emergence of mucoid S. pyogenes and drug resistance trends should be monitored in the future.

Introduction

Streptococcus (S.) pyogenes is a Gram-positive coccus that is by far the most common cause of acute bacterial pharyngitis, accounting for 15-30% of cases in children and 5-10% in adults (Alós et al. 2003). S. pyogenes is one of the most common human pathogens and causes both invasive and noninvasive infections. Invasive S. pyogenes infections include bacteremia, pneumonia, puerperal sepsis, cellulitis, necrotizing fasciitis, and streptococcal toxic shock syndrome. Noninvasive infections, predominantly tonsillitis and impetigo, account for a significant number of general practice consultations (Ekelund et al. 2005).

S. pyogenes has also been fairly consistently the fourth-most predominant pathogen causing pediatric acute otitis media (AOM), after S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis (Shulman and Tanz 2005). There have been reports of bacterial meningitis as a complication of otitis media or mastoiditis due to S. pyogenes (Cohen-Kerem and Lavon 2002; Laupland and Bosch 2006). Generally, S. pyogenes forms non-mucoid colonies with a matt surface and causes β-hemolysis on sheep’s blood agar medium (Chang et al. 2011; Wozniak et al. 2012). In Japan, mucoid S. pyogenes has rarely been reported because of the quite low detection rate of mucoid type isolates, and the epidemiological features of mucoid S. pyogenes infection are not fully understood. There has never been a report of mucoid β-hemolytic S. pyogenes causing AOM. Here, we report first case of severe AOM caused by mucoid S. pyogenes in a previously healthy adult.

Clinical Course and Isolate Characterization

In March 2012, a 36-year-old previously healthy woman presented to the Ear, Nose and Throat (ENT) clinic of another institution. She complained of a sore throat and right otalgia. AOM was diagnosed and right myringotomy was performed. Because of continuous serous discharge, she was referred to the ENT department of a general hospital. She had severe otalgia accompanied by headache, and was referred to the ENT department of Tohoku University Hospital with suspected cerebrospinal fluid otorrhea on the same day. The patient was fully conscious and there was no neck rigidity. Physical examination was unremarkable. Vital signs were normal, except that her temperature was 37.2°C. Otoscopy revealed pulsating serous discharge from the right ear and circumferential bulging of the wall of the right external auditory canal, with little of the tympanic membrane being visible (Fig. 1A). The left ear was normal. She complained of severe pain even if her ear was touched softly. She had no previous history of ear discharge or significant illness, but her daughter had developed pharyngitis a few days before. Pure tone audiometry demonstrated conductive hearing loss on the right side (pure tone average: 36.3 dB) and normal hearing on the left. Laboratory tests revealed a white blood cell count of 18,200/μL with 93% neutrophils and elevation C reactive protein to 7.0 mg/dL. Serum electrolytes, renal function tests, and liver function tests were normal. Computed tomography of the temporal bone demonstrated opacification of the right tympanic cavity and mastoid air cells without bony destruction. A qualitative sugar test (Lifesticks®; Siemens Japan K.K., Tokyo, Japan) of middle ear secretions was negative. Therefore, we thought it was more likely that she had severe AOM rather than cerebrospinal fluid otorrhea or meningitis. Sampling of middle ear secretions for bacterial culture was performed before treatment was started. A smear of the middle ear secretions showed Gram-positive cocci and chains. Antimicrobial therapy was commenced with intravenous meropenem (1.0 g/day). Culture of middle ear secretions on sheep blood agar plates (Nissui Pharmaceutical Co., Tokyo, Japan) grew mucoid colonies surrounded by a zone of complete β-hemolysis (Fig. 2). The antigen-agglutination test was negative for Streptococcus pneumoniae (Slidex pneumo-Kit®; Sysmex-bioMérieux Japan, Tokyo, Japan), but was positive for S. pyogenes (Seroiden Strepto Kit Eiken®; Eiken Chemical Co., Tokyo, Japan). Accordingly, it was considered that mucoid S. pyogenes could be the causative pathogen, so the patient’s antimicrobial therapy was subsequently changed to panipenem-betamipron (2.0 g/day). After receiving antimicrobial therapy for a total of 10 days, all symptoms resolved other than slight persistent discharge from the right ear. Although middle ear fluid was seen after closure of the tympanic perforation, the right ear was normal (Fig. 1B) and the patient was asymptomatic (pure tone average: 13.8 dB) at her 4-month follow-up examination.

We confirmed infection due to S. pyogenes by 16S ribosomal RNA gene sequencing (Baker et al. 2003; Johansson et al. 2004; Woo et al. 2008). Antimicrobial susceptibility testing was performed for 11 antibiotics by the broth microdilution method as recommended by the Clinical and Laboratory Standards Institute (2009). The minimum inhibitory concentrations (MICs) of the antimicrobial agents were as follows: ≤ 0.016 μg/mL for penicillin G, ≤ 0.06 μg/mL for ampicillin, ≤ 0.12 μg/mL for amoxicillin/clavulanic acid, ≤ 0.06 μg/mL for amoxicillin/sulbactam, ≤ 0.03 μg/mL for ceftriaxone, ≤ 0.016 μg/mL for cefditoren, > 8 μg/mL for erythromycin, ≤ 0.12 μg/mL for clindamycin, ≤ 0.008 μg/mL for panipenem, ≤ 0.008 μg/mL for meropenem, and 1 μg/mL for levofloxacin. Polymerase chain reaction (PCR) analysis was done for detection of the ermA, ermB, and mefA genes mediating macrolide resistance, as described previously (Sutcliffe et al. 1996; Seppala et al. 1998), revealing mefA in the isolated strain. PCR for emm genotyping was carried out according to the method described previously (Beall et al. 1996; Arai et al. 2011), and the M-protein genotype was determined to be emm75 by comparison with the Centers for Disease Control and Prevention (CDC) emm database (http://www.cdc.gov/ncidod/biotech/strept/strepblast.htm). Multilocus sequence typing (MLST) analysis (Enright et al. 2001) revealed that this isolate belonged to ST49 by comparison with the MLST database (http://spyogenes.mlst.net/).

Fig. 1.

Appearance of the tympanic membrane.

(A) At the time of admission: The circumferential wall of the right external auditory canal was bulging with little of the tympanic membrane being visible.

(B) Four months’ after the treatment in our hospital: The right tympanic membrane became normal.

Fig. 2.

Appearance of bacterial colonies.

Culture of middle ear secretions resulted in growth of mucoid colonies on blood agar plates. The colonies are surrounded by a zone of complete (beta) hemolysis.

Discussion

In Japan, mucoid S. pyogenes has rarely been reported and there has never been a report of mucoid β-hemolytic S. pyogenes causing AOM. However, mucoid S. pyogenes has occasionally been reported to cause invasive disease in other countries (Tamayo et al. 2010; Wozniak et al. 2012). The mucoid phenotype is due to abundant production of the hyaluronic acid capsular polysaccharide, a key virulence factor associated with severe S. pyogenes infection (Gryllos et al. 2008). Tamayo et al. (2010) described the clinical and molecular characteristics of mucoid strains causing outbreaks of infection, and compared them with non-mucoid S. pyogenes isolated during the same period. They found that invasive disease was more often due to mucoid isolates than non-mucoid isolates at their hospital (3% vs. 0.21%, P = 0.001). In our patient, it is considered that severe AOM occurred because of infection with mucoid S. pyogenes.

The M protein encoded by the emm gene is a major virulence factor of S. pyogenes and marked variability of emm gene sequences among S. pyogenes strains is an important surveillance tool, with more than 200 emm types currently listed in the online CDC database (http://www.cdc.gov/ncidod/biotech/strep/strepindex.htm). In the present patient with severe AOM, S. pyogenes was isolated from middle ear secretions, which had a mucoid shape and was characterized as emm75. According to the CDC (http://www.cdc.gov/ncidod/biotech/strep/emmtype_proportions.htm), emm75 is the eighth most frequently isolated emm type causing disease in Asian countries, being the third most frequent emm type isolated in patients with pharyngeal disease and less common in invasive disease. Thus, S. pyogenes possessing emm75 is commonly noninvasive, but our case suggests that severe symptoms may be caused by its mucoid form.

Macrolide resistance has gradually increased in S. pyogenes isolates around the world, including Japan (Wajima et al. 2008; Arai et al. 2011). Resistance of S. pyogenes to macrolides is mainly caused by two mechanisms: one involving 23S ribosomal RNA methylase genes (ermB and ermA) and the other involving the efflux determinant mefA (Sutcliffe et al. 1996; Seppala et al. 1998). In Japan, macrolide-resistant strains have been reported to account for 16.2% of S. pyogenes isolates, with the resistance genes ermA, ermB, and mefA being found in 2.5%, 6.2%, and 7.5% of strains, respectively (Wajima et al. 2008). Hotomi et al. evaluated 272 strains of S. pyogenes isolated in Japan, and they found that strains belonging to the emm75 or emm12 types harbored macrolide resistance genes significantly more frequently than other emm types and that emm75 strains also had mefA (Hotomi et al. 2009). Ardanuy et al. performed molecular characterization of S. pyogenes isolates in Barcelona, and reported that emm75-ST49 (the same emm and ST types as the isolate in our patient) was one of the most frequent genotypes that possessed mefA (Ardanuy et al. 2010). To date, S. pyogenes remains universally susceptible to penicillin, which comprises the treatment of choice in non-allergic patients so we could have treated her with penicillin.

In conclusion, mucoid S. pyogenes can cause severe infection even in previously healthy persons. Emergence of mucoid S. pyogenes and drug resistance trends should be monitored in the future.

Conflict of Interest

The authors declare no conflict of interest.

References
 
© 2014 Tohoku University Medical Press
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