Tricuspid Valve Endocarditis Partly Due to a Penicillin Susceptible, Ceftriaxone-Resistant Streptococcus anginosus Isolate

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To the Editor:
A 26-year-old man with a history of intravenous (IV) heroin and cocaine abuse presents to the emergency department with several days of fevers, nausea, and nonproductive cough. On hospital arrival, he was febrile to 104.4 and hypotensive. Blood cultures were obtained and various empiric antimicrobials were initiated. His white blood cell count was 8 × 103/μL with 90% neutrophils, creatinine was 1.66 mg/dL, Blood Urea Nitrogen was 25 mg/dL, and lactate was 4.0 mg/dL. A transthoracic echocardiogram revealed a 1.3-cm tricuspid valve vegetation. Chest roentgenogram revealed multiple bilateral, pulmonary nodules. His admission blood cultures revealed Prevotella denticola, Eikenella corrodens, and beta-hemolytic group C Streptococcus. His beta-hemolytic group C Streptococcus revealed an intermediate susceptibility to cefotaxime with a minimum inhibitory concentration (MIC) E-test of 64 μg/mL. This organism was further identified as Streptococcus anginosus. He was transferred to our institution for cardiothoracic surgical evaluation on ceftriaxone and metronidazole.
A transesophageal echocardiogram revealed a tricuspid valve vegetation with severe tricuspid regurgitation (Figure 1). Repeat blood cultures grew S. anginosus. The susceptibilities for our institution's S. anginosus revealed an E-test MIC to penicillin of 0.032 mg/dL and to ceftriaxone of 6 mg/dL (Table 1). With finalization of cultures, his antibiotics were modified to penicillin G 4 million units IV every 4 hours plus metronidazole 500 mg IV every 8 hours. His hospital course was complicated by the development of a pulmonary abscess along with a bronchopleural fistula requiring an endobronchial valve. The patient was continued on IV antibiotics for 3 weeks and subsequently discharged home.
The S. anginosus group (or Streptococcus milleri group) consisting of S. anginosus, Streptococcus intermedius, and Streptococcus constellatus are considered a subgroup of viridans-group Streptococci.1 These species are uniquely identified by their virulence and propensity to cause abscesses.2,3S. anginosus is the species most commonly associated with polymicrobial infections.3–5 Management of these infections requires surgical drainage and antimicrobial therapy. Studies have reported continued susceptibility to penicillins and cephalosporins, making these preferred agents. However, emergence of resistance to beta-lactams has been described, in addition to increasing resistance to macrolides and fluoroquinolones.5–7
Belko et al evaluated pediatric patients with S. milleri infections. Twelve of 106 isolates were intermediately susceptible to penicillin, (11%) whereas only 3 of 97 were intermediately susceptible to cefotaxime (3.1%).2 Tracy et al evaluated 44 clinically significant isolates of S. milleri group. Four were intermediate to penicillin (9%), and all were fully susceptible to ceftriaxone. None of the isolates were fully resistant to penicillin, ampicillin, or ceftriaxone.7
Although penicillin resistance is well described, cephalosporin resistance in viridans-group Streptococci is less common, particularly in penicillin susceptible strains. Marron et al evaluated 89 episodes of viridans-group Streptococci bacteremias in neutropenic cancer patient over 10 years. Thirty-five (39%) had elevated penicillin MICs ranging from 0.25 to 16 mg/L and 20 (22%) were highly resistant. Twenty isolates (22%) were also resistant to ceftriaxone. This study correlated previous beta-lactam exposure with beta-lactam resistance.5 Doern et al found that among 352 diverse viridans-group streptococci bacteremia isolates, 13.4% had high-level penicillin resistance and 42.9% had intermediate resistance to penicillin. Ceftriaxone resistance was found in 15% of isolates. However, among S. milleri, only 2% were either ceftriaxone or penicillin resistant.6
We were not able to find other reports of highly penicillin susceptible but ceftriaxone resistant viridans-group Streptococci isolates similar to ours. This phenomenon has been reported rarely in Streptococcus pneumoniae.8 Penicillin resistance in pneumococci generally requires alteration in 3 penicillin-binding proteins (PBPs), including 2X, 2B, and 1A, whereas third-generation cephalosporin resistance only requires 2 PBP alterations including PBP 2X and 1A.
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