Case Series With Streptococcus pyogenes–related Toxic Shock Syndrome in the Post-COVID Period

To the Editors:

After the coronavirus disease 2019 pandemic restrictions are nullified, increasing bacterial infections are reported such as invasive pneumococcal diseases and Streptococcus pyogenes infections.^1,2 Streptococcal infections are common in children and usually have a mild clinical course. It can also cause life-threatening invasive infections such as streptococcal toxic shock syndrome (STSS). In this study, three patients with STSS who were followed in the Pediatric Intensive Care Unit with S. pyogenes growth in blood and pleural fluid cultures in the last 2 weeks are presented.

Case 1: A 9-year-old male patient was admitted with complaints of loss of appetite, weakness, headache, vomiting twice a day for 10 days, and nose-bleeds and bruises under his left eye for the last 2 days. The general condition of the patient on the physical examination was moderate–severe, sluggish and toxic. Among the vital signs, body temperature was 38.5°C, heart rate was 145/min, respiratory rate was 35/min and blood pressure was 85/55 mm Hg. Other pathological physical examination findings included sunken eyeballs, tenderness and ecchymosis in the left under-eye area and oral mucosal changes (dry and cracked lips). In the oropharynx examination, tonsillar grade 3 hyperemic, hypertrophic, intense postnasal purulent discharge was found. There was hyperemia, temperature increase and tenderness in the right arm supracondylar region, approximately 4 × 4 cm in size, consistent with cellulitis-myositis. Laboratory findings are summarized in Table 1. Ceftriaxone, clindamycin and vancomycin treatments were started intravenously. The patient was given intravenous immunoglobulin therapy at a dose of 1 g/kg. Contrast-enhanced cranial magnetic resonance imaging revealed pansinusitis, osteomyelitis associated with the left frontal sinus, and extra-axial empyema. S. pyogenes was grown in the blood culture of the patient’s cultures. Antibiotherapy was arranged as ceftriaxone clindamycin with de-escalation. The total treatment was completed in 6 weeks, and the patient was discharged.

TABLE 1. - Laboratory Characteristics of Patients

Laboratory Findings	Patient 1	Patient 2	Patient 3
White blood cell (4800–12,000/mm3)	11910	5740	5670
Hemoglobin (11.2–14.6 g/dL)	13.4	13.4	12.5
Platelets (180,000–415,000/mm3)	96000	260000	117000
Neutrophil count (/mm3)	10340	3790	5040
Lymphocyte count (/mm3)	720	1240	330
Aspartate aminotransferase (0–37 U/L)	149	356	39
Alanine aminotransferase (0–37 U/L)	206	194	44
Urea	18	62	77
Creatinine (mg/dL)	0.57	0.35	0.90
C-reactive protein (0–5 g/L)	1.7	141.3	350
Erythrocyte sedimentation rate (0–20 mm/h)	4	27	49
D-dimer (<0.55 mg/L)	3.13	3.77	10.47
INR 1.1 (0.8–1.2)	1.4	1.1	1.0
Fibrinogen (1.7–4.2 g/L)	0.57	4.66	5.30
Streptococcus pyogenes	Blood	Pleural fluid	x
Benzylpenicillin MİK (mg/L) ≤0.06	s	s
Clindamycin MİK (mg/L) ≤0.25	s	s
Erythromycin MİK (mg/L) ≤0.12	s	s

INR indicates international normalized ratio; MIK, minimum inhibitory concentration; s, sensitive; x, no reproduction.

Case 2: A 2-year and 8-month-old male patient was admitted with complaints of fever, cough, rapid breathing and widespread rash that had started 3 days ago. The general condition of the patient on the physical examination was moderate–severe, sluggish and toxic. Vital findings: his body temperature was 38.7°C, heart rate was 160/min, respiratory rate was 42/min, blood pressure was 70/50 mm Hg and oxygen-free saturation was 95%. In other pathological physical examination findings, his lips were cracked or erythematous, tonsillar hyperemic, hypertrophic and crypts were present in oropharynx examination. In respiratory system examination, respiratory sounds were decreased in the left lung. There was a widespread, fading maculopapular rash all over the body, and peeling on the basis of hyperemia in the genital area. Since the patient was hypotensive despite fluid supplementation, he was followed up in the pediatric intensive care unit with a preliminary diagnosis of septic shock and bacterial pneumonia. Laboratory findings are summarized in Table 1. Ceftriaxone, clindamycin and vancomycin treatments were started intravenously. Due to the detection of paracardiac consolidation and effusion in the left lung, and pleural effusion measuring 3.6 cm at its deepest point, extending to the apex surrounding the left lung, and compression atelectasis secondary to the effusion were observed on the thorax computed tomography. Thoracentesis was performed and pleural fluid was consistent with exudate. S. pyogenes was grown in the pleural fluid culture. Vancomycin was discontinued, and treatment with ceftriaxone and clindamycin was completed in 4 weeks.

Case 3: A 7-year-old male patient was admitted with complaints of fever, cough, vomiting, rapid breathing and rash that had started 3 days ago. In his anamnesis, it was learned that he was hospitalized in the center he had applied 2 days ago with the same complaints, and intravenous ceftriaxone and clarithromycin treatments were given for 2 days. Vital findings: body temperature was 38.9°C, heart rate was 150/min, respiratory rate was 35/min, blood pressure was 85/55 mm Hg and oxygen saturation was 98%. In other pathological physical examination findings, bilateral nonpurulent conjunctivitis and strawberry tongue were present. In the oropharyngeal examination, tonsils were hyperemic and cryptic. In the respiratory system examination, the patient had tachypneic and subcostal retractions. On auscultation, respiratory sounds were decreased in the left lung, and crepitant rales were present. There was a more prominent diffuse erythematous maculopapular rash (sandpaper-like) on the anterior aspect of the trunk. Laboratory findings of the patient are summarized in Table 1. Ceftriaxone, vancomycin, and clindamycin treatments were started intravenously. The patient was given intravenous immunoglobulin therapy at a dose of 1 g/kg. On the chest radiograph, pleural consolidation and effusion were seen on the left. Thorax ultrasonography revealed dense pleural fluid reaching a depth of 17 mm in the left hemithorax. The pleural fluid taken by thoracentesis was exudative. Echocardiographic examination performed on the patient was found to be normal. No microorganisms could be grown in the throat culture, blood culture and pleural fluid culture of the patient who received intravenous antibiotic therapy for 2 days before admission to our hospital. Probable staphylococcal/streptococcal toxic shock syndrome was considered in the foreground with clinical and laboratory findings in the patient (cryptic tonsillitis, scarlet rash, complicated pneumonia, being hypotensive, high urea creatinine, coagulopathy and thrombocytopenia). The patient was transferred to the pediatric infection service on the 11th day. Total treatment was completed in 6 weeks.

STSS is an acute and life-threatening serious complication of predominantly invasive Group A Streptococcal infections. Considering the case definition criteria for STSS determined by the Severe Streptococcal Infections Working Group in 1993, cases are divided into definite and probable.³ In our first case, S. pyogenes was isolated in the patient’s blood culture, and there were clinical and laboratory findings such as hypotension, soft tissue infection, increased liver enzymes, thrombocytopenia, low fibrinogen and increased fibrin degradation products. In our second case, S. pyogenes isolation in pleural fluid culture, pneumonia, hypotension, increase in liver enzymes and increase in fibrin degradation products were found. Our third case, who was treated with antibiotics in another center, had pneumonia and pleural effusion, hypotension, thrombocytopenia, elevated kidney function tests and diffuse erythematous maculopapular rash (sandpaper appearance). Considering the latest 2020 surveillance data reported by the Centers of Disease Control and Prevention, a total of 49 patients were reported as STSS and constituted 2.3% of the total invasive diseases.⁴ Although surveillance data are insufficient in our country, invasive streptococcal infections are seen with increasing frequency in our clinic in the postpandemic period, especially in the last weeks.