Aortic valve infective endocarditis due to Streptococcus pyogenes : A case report

Abstract

Group A Streptococcus is a common cause of pharyngitis, scarlet fever, glomerulonephritis, and various skin infections. However, there have only been a few reports of Group A Streptococcus (GAS) associated with infective endocarditis. We present a case of a 31-year-old male who presented to the hospital with a few days of weakness and myalgias after recently receiving treatment with azithromycin for GAS pharyngitis as an outpatient. The patient was admitted to the intensive care unit in septic shock from Group A beta-hemolytic Streptococcus bacteremia and acute hypoxic respiratory failure. He was found to have new severe aortic insufficiency from infective endocarditis. He underwent urgent partial aortic valve annuloplasty reconstruction and incision and drainage of root abscess with intraoperative cultures growing gram positive cocci consistent with GAS. The majority of cases of infective endocarditis are caused by Staphylococcus aureus, virdians group Streptococci and Streptococcus gallolyticus, while Streptococcus pneumoniae and Streptococcus pyogenes have the lowest prevalence of infective endocarditis. Penicillin remains the first line treatment for GAS pharyngitis. However, in cases of severe penicillin allergy, macrolides should be avoided given the increasing rate of macrolide resistance GAS strains. This case emphasizes the importance of using beta-lactams as first line therapy for GAS pharyngitis to avoid harmful complications and infection recurrence.

Highlights

• •Group A Streptococcus is associated with pharyngitis, glomerulonephritis and skin infections, rarely bacteremia and infective endocarditis.
• •Penicillin remains the first line treatment for Group A streptococcal pharyngitis.
• •Given the increasing macrolide resistance, cephalosporins and clindamycin are recommended in the case of severe penicillin allergy.

Background

Group A Streptococcus is a gram positive bacterium that colonizes the throat and skin and is associated with many common infections from pharyngitis and scarlet fever, to glomerulonephritis, and various skin conditions including cellulitis, impetigo, necrotizing fasciitis, streptococcal toxic shock syndrome. However, Group A Streptococcus (GAS) is a rare cause of infective endocarditis and has rarely been reported in medical literature. A PubMed search found 39 cases reported globally of endocarditis from Group A Streptococcus since 1940 [1]. Since the 1980 s, there has been an increase in the incidence of invasive GAS infections, especially among 20–35 year olds [2]. The overall increased rates of GAS bacteremia are thought to be from the emergence of new serotypes of GAS [3]. While invasive GAS infections can occur at any age, incidence is highest among adults older than 50 years of age, followed by children less than 1 year old [3]. We report a young patient who was diagnosed with group A pharyngitis and completed a full course of azithromycin as an outpatient, who presented to the hospital 1 week later in septic shock and acute hypoxic respiratory failure. He was found to have group A beta-hemolytic streptococcus bacteremia resistant to erythromycin causing severe aortic insufficiency. He was ultimately treated with ceftriaxone and underwent valve replacement with good recovery and without any complications. Given increasing rates of macrolide resistance GAS strains, penicillin remains the first line treatment for GAS pharyngitis. In the case of penicillin allergy, macrolides should be avoided if possible to prevent recurrence and sequalae. In the case of a diagnosed Group A streptococcal infective endocarditis, there should be a high clinical suspicion for predisposing risk factors including immunosuppression from HIV, intravenous drug use, or cardiac abnormalities.

Case presentation

A 31-year-old Caucasian male with a past medical history of alcohol use disorder who presented to an outside hospital with a few days of generalized fatigue, weakness and myalgias. Four weeks prior, the patient presented to a walk-in clinic for throat pain and was subsequently diagnosed with GAS pharyngitis based on a positive throat culture. He completed a five-day course of azithromycin in the setting of a reported severe penicillin allergy. Despite completing a full course of antibiotics, the patient started to feel unwell again a week later with fever, chills, nausea, vomiting, arthralgias, myalgias, fatigue and weakness. He presented to the hospital and was found to be febrile to 102.6 F and tachycardic to 110 bpm. Physical exam was remarkable for an ill appearing male but otherwise unremarkable cardiac, pulmonary, abdominal exam. Blood tests demonstrated a neutrophilic leukocytosis (white blood cell count: 12 ×103/ul; neutrophils 76.7 %) as well as thrombocytopenia (platelet 70 k/mm3), hyponatremia (129 mmol/L), abnormal liver enzymes (alkaline phosphatase 211 units/L, AST 301 units/L, ALT 398 units/L, total bilirubin 2.0 mg/dL), significantly elevated Nt-ProBNP (11,232 pg/mL), negative HIV, and elevated troponin T 0.51 ng/mL. COVID-19 test was negative. Right upper quadrant ultrasound demonstrated hepatic steatosis. A follow-up acute viral hepatitis panel was negative. CT of the abdomen and pelvis with intravenous contrast showed bilateral striated nephrograms with perinephric fat stranding suspicious for bilateral pyelonephritis with mild hepatosplenomegaly.

The patient was initially admitted for concern of alcoholic hepatitis and alcohol withdrawal; however, his hospital course was complicated by continued high fevers for an additional week in the setting of worsening myalgias, nausea, vomiting, leukocytosis, and thrombocytopenia. His hospital course was further complicated by acute hypoxic respiratory failure, after desaturation to SpO2 78 %. Chest x-ray and CT chest showed extensive diffuse and bilateral interstitial and alveolar markings with predominantly ground-glass airspace consolidations concerning for diffuse infection versus alveolar damage versus pulmonary edema. Two sets of blood cultures drawn on admission yielded GAS, resistant to erythromycin with inducible clindamycin resistance. The decision was made to start broad spectrum antibiotics with vancomycin, cefepime, and doxycycline as the source of his bacteremia was unclear. He continued to have high fevers, increasing oxygen requirements, requiring non-invasive positive pressure ventilation and was ultimately transferred to our hospital for a higher level of care. He was evaluated by pulmonary medicine and infectious diseases teams. Transthoracic echocardiogram was obtained and demonstrated left ventricular ejection fraction 55–60 %, mildly thickened aortic valve, possibly bicuspid with severe aortic regurgitation, and was not able to exclude vegetation. Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5.

Fig. 1.

TTE with parasternal long axis view of aortic valve.

Fig. 2.

TTE with severe aortic insufficiency.

Fig. 3.

Janeway lesions on first right toe.

Fig. 4.

Splinter hemorrhages on fingernails.

Fig. 5.

desquamative rash over his bilateral palms.

Given the patient’s severe aortic insufficiency with labile respiratory status and blood pressure, the decision was made to transfer him to the cardiac intensive care unit by the cardiothoracic surgeons. At this time, the patient was noted to have stigmata of infective endocarditis on physical exam with Janeway lesions on his feet, splinter hemorrhages, conjunctival hemorrhages, and a desquamative rash over his palms.

The patient’s hemodynamically instability with worsening vital signs, worsening heart failure and respiratory distress prompted urgent valve surgery. Intraoperatively, the patient was found to have an aortic root abscess at the noncoronary sinus, extending into the left ventricle. The patient underwent urgent partial aortic valve annuloplasty reconstruction, incision and drainage of root abscess, and partial root repair. Intraoperative culture of the aortic valve demonstrated gram positive cocci consistent with GAS. The patient recovered well following surgery. His repeat blood cultures were sterile, and he was discharged home to complete six weeks of ceftriaxone.

Discussion

Invasive group A streptococcal infections include bacteremia, pneumonia, and necrotizing fasciitis. The most common sources of GAS bacteremia are skin and soft tissue infections. Less common sources of GAS bacteremia include respiratory tract infections, or pregnancy-associated infection [2]. Approximately 80 % of cases of infective endocarditis are caused by Staphylococcus aureus, viridans group Streptococci and Streptococcus gallolyticus [4]. However, infective endocarditis is a rare and severe presentation of GAS. A case series from Denmark looked at all cases of Streptococcal bacteremia from 2008 to 2017 and found Streptococcus pneumoniae and Streptococcus pyogenes had the lowest prevalence of infective endocarditis at 1.2 % and 1.9 %, respectively [5]. Streptococcus gallolyticus and viridans group Streptococci had the highest prevalence and risk of infective endocarditis after adjusting for risk factors [5]. Despite its rarity, infective endocarditis from GAS is associated with lower mortality compared to group B, C, and G beta-hemolytic infections [6]. A PubMed analysis identified 39 cases globally of endocarditis caused by GAS in children and adults since 1940 [1]. Of these cases, five patients were intravenous drug users and 22.2 % had known pre-existing heart defects [7]. Additionally, skin lesions were the primary source of infection, followed by pharyngitis [7]. In this study, the mortality rate was 24 % and mainly due to cardiac failure or septic shock; however, most patients recovered with antibiotic therapy [7]. In our case, the source of his GAS bacteremia was likely his streptococcal pharyngitis a few weeks prior, as there was no other obvious source identified. The patient had no known predisposing risk factors and no reported history of intravenous drug use. He was found to have a bicuspid aortic valve at surgery, but this was not well identified on echocardiogram.

Antibiotic therapy is the mainstay of care for GAS infections. Penicillin and other beta-lactams remains the first line treatment for streptococcal pharyngitis. It has been proven to be effective against the bacteria with a narrow spectrum of activity, universally sensitive, safe, and low cost [2]. In our case, the patient had a severe allergy to penicillin and was initially treated with azithromycin as an outpatient. Two sets of the patient’s blood cultures revealed GAS was resistant to erythromycin and presumably other macrolides, which could explain the patient’s GAS bacteremia and infective endocarditis as sequalae from his pharyngitis. The rate of erythromycin resistance GAS infections has nearly tripled from 2010 to 2017 [8]. Single- center studies in the United States have shown rates of macrolide resistance in GAS as high as 48 % while multicenter surveillance studies have shown rates from 3% to 9% in 2000–2003 that rose to 12–15 % in the same centers in 2007 [9]. A multicenter study of children with GAS pharyngitis found a 3 day course of azithromycin was a clinically effective and safe treatment but inferior in eliminating GAS from the throat compared to traditional penicillin [1]. Two case reports described children diagnosed with streptococcal pharyngitis was diagnosed and treated with azithromycin [9]. They later presented with sequalae and complications of their pharyngitis [9]. In one case, a subsequent throat culture revealed erythromycin-resistant strain of GAS [9] and the second was presumed to be a macrolide resistance case but was not confirmed with a throat culture [9]. Given the increasing rates of macrolide resistant strains, cephalosporins and clindamycin can be used second line for patients with documented severe penicillin allergy.

Based on recommendations from the American Heart Association and Infectious Diseases Society of America, valve dysfunction with heart failure, fungal endocarditis, multi-drug resistant organisms, heart block, annular abscess, and persistent bacteremia are all indications for early surgery [10]. In this case, the patient underwent urgent aortic valve replacement due to hemodynamic instability and concern for potential heart failure given his severe aortic insufficiency. One prospective randomized trial compared conventional treatment versus early surgery in patients with infective endocarditis and large vegetations found reduced risk of death from any cause and embolic events in the early surgery group [11].

Conclusion

Our patient presented with fevers, myalgias, nausea, vomiting, and weakness in the setting of a recent pharyngitis infection. He subsequently developed signs of severe aortic insufficiency and septic shock secondary to GAS. GAS is a rare cause of infective aortic valve endocarditis but should be on the differential nonetheless, especially in someone with a pre-existing heart abnormality or intravenous drug use. The patient underwent urgent aortic valve replacement along with antibiotic therapy with resolution of his bacteremia and improvement in his symptoms. By presenting this case, we emphasize the importance of using beta-lactams as first line therapy for GAS pharyngitis to avoid harmful sequalae or infection recurrence given increasing rates of macrolide resistant strains.

Funding

No funding was sought to support this case report.

Ethical approval

Not required for this case report.

Consent

Written informed consent was obtained from the patient for the use of photographs for this journal without an identifiable date of publication.

Credit authorship contribution statement

Gabriella Primera was a major contributor in the writing of the manuscript. Karen Hogan obtained patient information for the case and was involved in the reviewing and editing. Hans Schlecht obtained patient information for the case and was involved in the reviewing and editing. Megan Gallagher was a major contributor in the writing of the manuscript. All authors read and approved the final manuscript.

Conflict of interest statement

All authors declare no conflicting interests.

Data availability

No data were used to support this study.