Streptococcus dysgalactiae subsp. dysgalactiae presents with progressive weakness in limbs: a case report and literature review

Abstract

Background

Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome.

Case presentation

She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month.

Conclusion

Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.

Background

There are only 12 documented cases of Streptococcus dysgalactiae subsp. Dysgalactiae (SDSD) infection in humans, so information characterizing the clinical picture and therapeutic protocol of SDSD is still in the exploratory stage. In this area, case profiles involving multisystem dysfunction syndromes, especially neuromuscular symptoms, have not been well described. We report the first case of SDSD infection identified in our department. This study details the clinical progression of muscle weakness and the course of antibiotic treatment. The case report was written in accordance with the CARE Guidelines [1].

Case presentation

The patient, a 31-year-old female, presented to our emergency department with complaints of fatigue and muscle pain in both lower extremities for two days, which had worsened a day earlier and manifested difficulties with daily activities. She initially presented to the local hospital with chills, fever, and headache. In response to treatment, the symptoms were temporarily relieved (unavailable medication information). Blood results showed thrombocytopenia and compromised liver function. Given the complexity of her condition, the primary care physician recommended a referral to an advanced hospital. The patient underwent a medication abortion and curettage at 11 weeks’ gestation five days ago. There was no discomfort during the operation or in the postoperative period, except for a very small amount of brown secretion. She had a cesarean section in 2005. There was an absence of exposure to grass or animals recently. It was evident from the physical examination that both lower extremities were tender and that bilateral tonsils were enlarged to a first degree. Vital signs were a temperature of 37.4 °C, a pulse of 119 bpm, 28 breaths per minute, 98% oxygen saturation (in room air), and normal blood pressure. The results reported tachycardia on electrocardiogram, normal echocardiogram, and mild enlargement of the liver on abdominal computed tomography (CT) scan.

By CARE guidelines, the timeline in Table 1 illustrates the chronological sequence of pertinent events in the patient's medical file [1].

Table 1 The manifestations, diagnostic testing, and interventions in the patient's medical file

Gynecologic evaluation revealed a small amount of brown secretion and an enlarged uterus with slight tenderness. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) of the brain were free of abnormalities. In the cases of human SDSD, clinical documentations are not well defined. The results of multi-specimen cultures were decisive in confirming the diagnosis of SDSD. The application of piperacillin-tazobactam (a broad-spectrum antibiotic) failed to improve the clinical picture. There was a parallel improvement in clinical symptoms and laboratory values with the switch to penicillin, which is effective against streptococci. Differentiation of polymyositis presenting as progressive muscle weakness is necessary because the initial treatment regimen includes high doses of corticosteroids rather than antibiotics. We strongly recommended a muscle biopsy for polymyositis, which was rejected by the patient and her husband for financial reasons.

She complained of dry mouth, blurred vision, orbital pain in both eyes, as well as decreased urine output and hypotension. The ophthalmic examination was unremarkable, and the serum-specific antibody test was negative, hence the epidemic hemorrhagic fever was exonerated. The lumbar puncture procedure revealed clear cerebrospinal fluid and an open pressure of 220 mm Hg. Meanwhile, neurologists helped to identify Guillain-Barré syndrome or other neurological disorders. Because SDSD symptoms overlap with multiple diseases, clinicians need to make the necessary differential diagnosis and select agents depending on illness progression and exam findings. Penicillin is an effective treatment for SDSD infections, but one should be wary of the incidence of multidrug resistance.

It is essential to collect specimens for laboratory culture and identification prior to initiating empirical antibiotic therapy. Antibiotics should be altered according to one’s symptoms, inflammatory markers, and susceptibility testing results. In terms of treatment, she received nutritional support and albumin infusion to correct hypoalbuminemia, as well as multidisciplinary consultation for clinical diagnosis and medication direction. To facilitate the management of her condition, central venous catheters and urinary catheters are inserted to monitor fluid intake and output. It was initially prescribed with Doxycycline Hydrochloride at 0.2 g every 12 h and later switched to Moxifloxacin at 0.4 g daily. Drug sensitivity test confirmed that SDSD was sensitive to penicillin G, vancomycin, linezolid, ampicillin, and levofloxacin, but resistant to clindamycin and tetracycline. Accordingly, an alternative dose of piperacillin-tazobactam sodium 4.5 g every 8 h was administered. There was an improvement in muscle strength with piperacillin-tazobactam sodium, while the fever had not resolved. It was eventually shifted to a dose of 4.8 million units of penicillin twice daily through multidisciplinary consultation and discussion. With nine days of penicillin monotherapy, the condition improved remarkably, and the laboratory values normalized. She was discharged on the 19th day of admission. Table 2 illustrates the relevant laboratory results and antibiotic profiles.

Table 2 Antibiotics Administration and Important Laboratory Results

Multidisciplinary consultation and laboratory results helped to discriminate the condition. Neurologists and rheumatologists indicated that myalgia and elevated creatine kinase were signs of multisystem involvement in the setting of severe infection, and multiple cultures were SDSD, further ruling out polymyositis. Endocrinologist confirmed that a lack of endocrine dysfunction affected her muscle strength. In the absence of a history of thyroid disease, hypothyroidism due to T3 syndrome was related to her current underlying disease and hypoproteinemia. For the full treatment period, the patient has not received corticosteroids and recovered completely within one month of follow-up. She developed generalized oedema upon admission, sudden onset of chest tightness and shortness of breath at night, and a significant rise in NT-proBNP. It was noted that the decreased creatinine value remained at a high level, so the sharp increase in NT-proBNP was linked to renal compromise. Moreover, the failure of diuretics to increase urine output, coupled with low CVP, was highly assumed to be multi-organ dysfunction. In a further, there was a pressure injury to the sacrococcygeal skin due to being bedridden for eight days. A final multidrug resistance to extended-spectrum beta-lactamases (ESBLs) produced by Escherichia coli was detected in midstream urine cultures. The retained urinary catheter was considered for possible colonizing bacterial infection due to the absence of symptoms of urinary tract irritation.

There were 534 reads of Streptococcus dysgalactiae from peripheral blood detected by comparison with the reference database. The NGS-related information is shown in Table 3 and Fig. 1.

Table 3 Metagenomic Testing Report of Pathogenic Organisms IN Peripheral Blood

Fig. 1

Reads Distribution In The Genome Of The Organisms

Discussion

Depending on the hemolytic patterns, Streptococcus dysgalatiae (SD) is divided into two subspecies, Streptococcus dysgalactiae subspecies dysgalactiae (SDSD) and Streptococcus dysgalactiae subspecies equisimilis (SDSE) [2]. A human pathogen (SDSE) that causes various infections similar to Streptococcus pyogenes [3], and an animal pathogen (SDSD) that is thought to occur only in animal populations [4]. A genuine and practical issue of SDSD infections is that it is challenging to identify in laboratory samples. Jensen and Kilian have found that SDSD can be identified as SDSE based on the presence of the β-hemolysis property [5]. In humans [6] and animals [5], both α- and ß-hemolytic isolates have been detected. The blood culture isolates from one patient were α-hemolytic, consistent with the case report by Bansal et al. [7], while isolates from the other one were ß-hemolytic [6]. In a study by Koh et al. of three cases, blood cultures showed weak ß-hemolytic in case 1, β-hemolytic in wound cultures in case 2, and α-hemolytic in blood culture in case 3 [8]. It is likely that the incidence of SDSD human infection is underestimated by the failure to accurately determine the classification of SD subspecies from the hemolytic patterns [9]. To date, the methods employed for SDSD identification in the available case reports include the following, ranging from the 16S rRNA gene [8], a combination of phenotypic features, MALDI-TOF MS (matrix-assisted laser desorption ionization-time of flight mass spectrometry), and 16S rRNA analysis [10], to whole-genomic DNA sequencing [6]. Researchers concluded that the multigene approach is the only way to identify SDSD [6]. Both this study and the two former reports [7, 11] identified the isolate as SDSD through an automated system. Metagenomic next-generation sequencing (mNGS), also known as high-throughput genetic testing, is increasingly being applied to enhance the detection, investigation and diagnosis of infectious diseases [12]. The blood mNGS was sent to a third-party laboratory to gather additional information and it confirmed the presence of Streptococcus dysgalactiae. We have not conducted further analysis of this isolate from the results of mNGS, as laboratory tests on the second day confirmed the SDSD. The mNGS as a non-routine test is not reimbursable by Medicare. Patients must bear the cost of expensive tests, which can be a burden in some cases. In fact, mNGS is essential to better understand the pathogenicity and transmission of SDSD. It may be beneficial that genetic analysis will be able to identify factors associated with virulence and host specificity [13].

As shown in Table 4, information on clinical symptoms, detection methods, and antibiotic treatment is provided in case reports of SDSD infections in humans.

Table 4 Summary of patients' symptoms, testing methods and antibiotic treatment details from case reports of human infections due to Streptococcus dysgalactiae subspecies dysgalactiae

It is critical to note that the severity of the clinical symptoms of SDSD can range from mild localized pain to severe, life-threatening conditions. Some cases of this pathogen manifesting fever and pain have been reported in the literature [1,2,3,4,5,6,7], including two cases with visual abnormalities [3, 5] and one case with generalized myalgia [7]. Currently, three cases of ocular problems associated with SDSD infection result in impaired vision. One case involved a 65-year-old male with inaccurate vision [3], another involved a 22-day-old neonate with a visual path abnormality [15] and the 32-year-old female, in this case, had blurred vision. In terms of laboratory findings, elevated total creatinine kinase (CK) fraction could predict rhabdomyolysis or myositis among patients with cellulitis. However, excessive creatine kinase levels were not expected in patients with cellulitis [7]. The myoglobin level on admission was 675.9 ng/mL (0–110 ng/mL) and the CK level (41–186 U/L) increased from 533 u/L to 762 u/L on day five. With progressive muscle weakness in the extremities, polymyositis may have been present. However, the consensus from the multidisciplinary consultation was that muscle weakening and soreness were associated with sepsis and that polymyositis was not considered. Furthermore, the patient refused a muscle biopsy to confirm the presence of muscle inflammation typical of polymyositis. There was ultimately a lack of clear evidence for the diagnosis of polymyositis. It was conclusively excluded when the patient had recovered to the pre-onset state without further medical intervention. Despite mentioned conditions, SDSD-induced hematological disorders are equally noteworthy, such as the reduction of hemoglobin and platelets 76 g/L and 37*10^9/L, respectively.

Regarding the management of serious infections, effective and immediate intravenous empirical antibiotic therapy may be appropriate in the absence of pathogens. The combination of antibiotics is usually common in practice. Notably, the overuse of antibiotics has contributed to the persistence of antibiotic-resistance genes and the emergence of multi-drug resistance in populations, which poses a threat to the cure of common infections and results in long-term illness and death [17]. Of these patients, all but one died of irreversible septic shock [16], and the others benefited from the antibiotic combination and survived. In these cases, vancomycin and ceftriaxone were the most prescribed antibiotics [10, 11, 14, 16]. This case differs from prior cases of antibiotic combination in that each course of treatment is a single antibiotic. Therefore, it is worthwhile to further investigate whether human SDSD strains require antibiotic combinations. To maximize the effectiveness of treatment, clinicians should correctly and appropriately prescribe antibiotics in line with the laboratory pathogen profile and drug sensitivity data. It is assumed that the treatment of SDSE infections applies to SDSE infections as well [18]. Penicillin G currently remains the first-line agent, followed by second- and third-generation cephalosporins [19]. The resistance profile of human SDSD to tetracycline antibiotics seen in this case is consistent with the resistance of bovine SDSD isolates [20] and the results of Alves-Barroco et al. [21].

Conclusion

Given the increasing number of pathogens rarely associated with causing human diseases and the proportion of immunocompromised individuals, clinicians need to be aware of the pathogenic potential of such isolates. The pathogenicity of SDSD and its clinical features should empower clinicians to formulate the optimal treatment plan for their patients. Next-generation sequencing technology detects thousands of pathogens, minimizing the incidence of erroneous or omitted identifications. Such technology is now well-established and is widely deployed as a powerful diagnostic tool for pathogens [22].