Introduction
Beta-hemolytic groups A (Streptococcus pyogenes) and B (Streptococcus agalactiae) streptococci of the Lancefield classification are considered etiological agents of mild to severe infectious diseases. S. pyogenes causes purulent tonsillitis, skin and soft tissue infections, scarlet fever, non-cutaneous infections (myositis, myonecrosis, pharyngitis, pneumonia, postpartum endometritis), and streptococcal toxic shock syndrome (STSS). S. agalactiae is most commonly associated with perinatal infections 1-3.
Different reports have shown other streptococci groups (C, G, F, and L) as a frequent cause of human infections. In recent years, groups C and G streptococci (GCS-GGS) have emerged as serious pathogens. Moreover, their frequency is similar or could exceed group A streptococcus (GAS) as a cause of invasive diseases in some countries 4-7.
Group G includes Streptococcus dysgalactiae subsp. equisimilis (SDSE), Streptococcus anginosus, and Streptococcus canis4-6. Vandamme et al. 8 proposed two main subspecies of S.dysgalactiae in 1996: S.dysgalactiae subsp. equisimilis (SDSE) (associated with human infections) and S. dysgalactiae subsp. dysgalactiae (SDSD). Due to its agglutination reaction when exposed to Lancefield group C and G antigens, SDSE has been considered within both ß-hemolytic groups C (GCS) and G (GGS).
During the present century, an increase in case reports of severe infections by SDSE has been described worldwide, and a similar frequency with those caused by groups A and B in some countries. Therefore, SDSE invasive diseases are now considered an emerging health problema 4-7,9,10. Some authors define an SDSE invasive infection when these bacteria are isolated from a sterile site or isolated on several occasions from non-sterile sites in a patient with necrotizing fasciitis or streptococcal toxic shock síndrome 10,11.
The most severe infections caused by SDSE (cellulitis, pneumonia, urosepsis, bacteremia, osteoarticular infections, skin and soft tissue infections, and STSS) are observed in the adult population, particularly those over 60 years of age. These infections are infrequent in children, in which STSS is a rare evento 7,9-13.
In this report, a clinical case of a severe infection caused by SDSE in a preschool child that fulfilled streptococcal toxic shock syndrome criteria is presented.
Clinical case
A 3-year-old previously healthy female started her condition with a history of three days with malaise, fever (38°C), hyporexia, irritability, and vomiting. An upper respiratory tract infection of viral etiology was diagnosed, and symptomatic treatment was prescribed. As the patient showed a poor evolution, she was brought to the hospital due to a state of altered consciousness in the last hours. At admission, she showed adequate alertness and awareness with a Glasgow scale of 14. However, during the first hours, the Glasgow scale score decreased in three 3 points. Physical examination revealed a red maculopapular rash (thorax, abdomen and lower extremities), tachypnea, tachycardia (200/min), hypotension (BP 68/40 mmHg), capillary filling of 7 s; in thorax auscultation, right basal hypoventilation was detected. Intensive care management included crystalloid and vasoactive amines administration, orotracheal intubation, and mechanical ventilation. Ceftriaxone and vancomycin were started. Due to neurological deterioration, neuroinfection was suspected and a lumbar puncture was requested; however, it was delayed due to the patient’s hemodynamic instability. Despite the intensive management, tachycardia and hypotension persisted. Eight hours after admission, she presented cardiorespiratory arrest with no response to advanced resuscitation maneuvers and died.
Admission laboratory tests reported 13.3 g/dl hemoglobin, 39.6% hematocrit, 3,210/mm3 leukocytes, 73% neutrophils, 16% lymphocytes, 6% monocytes, 5% eosinophils, 17% bands, 323,000/mm3 platelets. C-reactive protein, 390 mg/l; Na+, 130 mEq/l; K+, 5.48 mEq/l; Cl-, 95.4 mEq/l. Total protein, 4.4 g/dl; albumin, 2.5 g/dl; globulin, 1.9 g/dl; DB (direct bilirubin), 0.4 mg/dl; IB (indirect bilirubin), 0.10 mg/dl; GOT (glutamic-oxalacetic transaminase), 213 U/l; GPT (glutamic-pyruvic transaminase), 97 U/l; ALP (alkaline phosphatase), 141 U/l; LDH (lactate dehydrogenase), 1855 U/l. Blood urea nitrogen, 49.8 mg/dl; creatinine, 1.4 mg/dl; urea, 109.3 mg/dl. Venous gasometry showed pH 6.8, pCO2 (partial CO2 pressure) 84, PO2 (partial O2 pressure) 45, HCO3 19.8, BEb (base excess) -11.8, O2 saturation 53, lactate 2 mmol/l. Coagulation tests were not performed. At admission, two blood cultures were collected.
Blood cultures were processed in the Bact/Alert system® (bioMérieux Mexico). Subsequently, bacterial identification was made with the Vitek® 2 system (bioMérieux Mexico). Results from blood cultures were obtained 48 h after the patient died, and S. pyogenes was identified. As part of the surveillance system for streptococcal infections, the strain was referred to the National Institute of Public Health, where it was sent for MALDI-TOF system confirmation. The results confirmed Streptococcus dysgalactiae subspecies equisimilis14,15.
Discussion
The case of a previously healthy preschool child, with an upper respiratory tract infection that in a short time developed toxic shock syndrome (hypotension, erythematous macular rash, and multi-organ failure: renal and hepatic dysfunction and acute respiratory distress syndrome), and a rapidly lethal outcome is presented. The initial bacterial identification of the blood culture was S. pyogenes, which was changed to S. dysgalactiae subspecies equisimilis according to MALDI-TOF results. The VITEK 2 system, which is considered as one of the most reliable systems, is the most commonly used bacterial identification method in clinical microbiology laboratories. Several authors have found that the Vitek 2 system has a lower identification capacity than the MALDI-TOF MS system in the identification of beta-hemolytic Streptococcus (BHS), particularly in the discrimination of S. dysgalactiae. It is considered that the MALDI-TOF MS system can be a powerful and cost-effective tool for the identification of BHS in routine clinical microbiology laboratories 16,17.
To the present date, no reports of serious infections caused by S. dysgalactiae subspecies equisimilis can be found in Mexico. Since the late 1980s, STSS caused by S. pyogenes (group A streptococcus) has become a serious problem in many countries. It is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. Although STSS is mainly caused by S. pyogenes, the group G streptococcus, identified as S. dysgalactiae subsp. equisimilis (SDSE), has also been associated with STSS. The first cases of STSS caused by SDSE were reported in the 90s in Japan 18. Currently, the number of reports have been increasing worldwide. More than 50 types of the emm gene in SDSE have been found. These genes encode the M protein, which is the main virulence factor of GAS that could be associated with the pathogenesis of streptococcal infections and could be responsible for the development of STSS 19.
More than 90% of cases of bacteremia and invasive diseases caused by S. dysgalactiae subsp equisimilis are detected in elderly patients suffering from some comorbidity (diabetes mellitus, cardiovascular diseases, immunosuppression, cancer), but pediatric infections are scarce. The primary site of the infection cannot be identified in all cases. The patient in this report started with an upper respiratory tract infection that led to the lethal form of toxic shock syndrome in a few days. In a recent study, SDSE has been identified in 2% of cases of acute pharyngitis, predominantly in schoolchildren 20, apparently with a favorable course.
According to the medical literature, the participation of SDSE in Mexico has not been reported. However, the identification of this species in a preschool patient suggests that it is probably circulating in other areas of the country. It is essential to alert microbiology laboratories and pediatricians to consider that some of the isolates identified as S. pyogenes under traditional methods may correspond to S. dysgalactiae subspecies equisimilis. Due to the fulminate course of these bacterial infections, it is necessary to improve their appropriate identification.