|Year : 2015 | Volume
| Issue : 1 | Page : 148-151
Profile of fatal Streptococcal bacteraemia at a tertiary care Indian hospital
P Punia, N Bhardwaj, P Mathur, G Gupta, MC Misra
Department of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Center Trauma Centre, All India Institutes of Medical Sciences, Delhi - 110 029, India
|Date of Submission||06-Dec-2013|
|Date of Acceptance||19-Mar-2014|
|Date of Web Publication||5-Jan-2015|
Department of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Center Trauma Centre, All India Institutes of Medical Sciences, Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Streptococcus pyogenes causes mild to acutely life-threatening diseases. Herein, we report our experience with five cases of fatal bacteraemia due to various groups of Streptococci, three of them due to Group G Streptococcus and one case each due to Group A Streptococcus and Group F Streptococcus. The peculiarity of all these cases was the rapidity of deaths occurring in these patients despite all the strains being sensitive to Penicillin. Hence, timely intervention in all suspected cases is strongly advocated. All isolates of beta-haemolytic Streptococci should be identified up till the species level and antimicrobial susceptibility be performed so that proper and early management can be done.
Keywords: Bacteraemia, fatal cases, Non Group A Streptococci
|How to cite this article:|
Punia P, Bhardwaj N, Mathur P, Gupta G, Misra M C. Profile of fatal Streptococcal bacteraemia at a tertiary care Indian hospital. Indian J Med Microbiol 2015;33:148-51
|How to cite this URL:|
Punia P, Bhardwaj N, Mathur P, Gupta G, Misra M C. Profile of fatal Streptococcal bacteraemia at a tertiary care Indian hospital. Indian J Med Microbiol [serial online] 2015 [cited 2019 Sep 19];33:148-51. Available from: http://www.ijmm.org/text.asp?2015/33/1/148/148424
| ~ Introduction|| |
Streptococcus pyogenes is a notorious organism, causing mild to acutely life-threatening diseases. Invasive S. pyogenes infections have increased in the past two decades in the west; the fatality rates of such cases being extremely high.  Non-group A Streptococci, traditionally considered to be commensal and non-pathogenic have also come a far way and now have been implicated from mild to serious infections. In this study, we report our experience withfive cases of fatal bacteraemia due to various groups of streptococci.
| ~ Materials and Methods|| |
All the isolates of beta-haemolytic were identified by standard microbiological methods.The confirmation of identity was also done by the Vitek 2 (Biomerix, France). Grouping of the Streptococci was performed by agglutination test (HiMedia Labs, India) according to the manufacturer's instructions.
The antimicrobial susceptibility testing of Streptococci was performed by the disk diffusion method on Mueller Hinton agar with 5% sheep blood according to the recommendations of the CLSI.  The E test was performed on 5% sheep blood agar according to manufacturer's recommendations (Biomeriux Ltd., formerly AB Biodisk, Sweden).
Exotoxin genes, including speA, speB, speC, speF, smeZ, ssa, speG, speH, speJ, speL, speMand speI were tested by PCR as per published protocol. 
The emm types of isolates of S. pyogenes were determined by sequencing the variable 5' end of emm gene after amplification by PCR as per published protocol.  ATCC 12347 (emm5) was used as positive control for emm typing. Molecular typing was done for epidemiological purposes to see the most prevalent strain causing infections.
| ~ Results|| |
Among the five fatal cases that we came across, three were caused by group G streptococci (GGS), and one case each was caused by group A Streptococcus (GAS) and group F Streptococcus (GFS). A detailed clinical history and treatment regimens were collected from the electronic surveillance software of the hospital and reviewed. All the Streptococci isolated were found to be sensitive to penicillin, vancomycin, teicoplanin, erythromycin, linezolid, amoxicillin and clindamycin. The exotoxin gene profile of the isolates is shown in [Table 1].
| ~ Case Synopsis|| |
A 38-year-old male patient was admitted to our hospital after a road traffic accident with a history of loss of consciousness, inability to move both lower limbs and weakness of grip of both hands. His past medical history was unremarkable and there was no family history suggestive of any significant illness. He was diagnosed as having cervical spine fracture, for which C-7 corpectomy, and cage and tricorticate iliac crest graft placement with a metal plate and screw fixation was done under general anaesthesia. The patient had slow recovery due to the spinal cord injury and was finally discharged after a month. The patient came for follow up and complained of respiratory distress and difficulty in swallowing. He was readmitted following development of prevertebral abscess around the cervical area. The abscess was drained and the aspirated pus along with the blood sample of the patient was sent to the microbiology laboratory. The patient was started empirically on cefotaxime and clindamycin.The patient was in clinical sepsis and his condition deteriorated fast. He succumbed a day after, due to the development of septic shock. Culture of the pus sample as well as the blood sample yielded beta-haemolytic colonies identified as Streptococcusdysgalactiaesspequisimilis (Group G Streptococcus).
A 40-year-old male presented to our hospital with a history of fever and chest pain. He was investigated upon and was diagnosed to have para-aortic abscess. During the hospital stay he developed features of septicaemia. His abscess was drained and the pus collected was sent to the microbiology laboratory along with his blood sample. The organism from blood and pus was identified as Streptococcus porcinus (Group G Streptococcus). The patient expired before the specific antibiotics could be initiated.
A 28-year-old male, known to have non-Hodgkin lymphoma, developed an ulcerative lesion on the right arm. He complained of severe pain in the lesion and soon developed fever and hypotension. Rest of the clinical findings, including examination of oral cavity, abdomen, chest and other systems were unrevealing. He was provisionally diagnosed as having toxic shock syndrome and was started empirically on vancomycin and piperacillin-tazobactam. But the patient's clinical condition deteriorated rapidly and he succumbed to the infection even before his culture reports could be communicated. His wound and blood samples grew Streptococusdysgalactaespp (Group G Streptococcus).
An 85-year-old male was brought to our hospital after a fall in the bathroom. He was diagnosed as having a fracture of the humerus for which he was managed conservatively. There were no external injuries and he showed no other significant signs and symptoms. Thus he was discharged home on an arm pouch. He came back after 2 days with complaints of difficulty in breathing, which was thought to be probably due to aspiration. On physical examination, he had black blotches on his skin at back and chest. His blood sample was taken for culture. He was given amoxicillin-clavulanic acid and clindamycin and referred to another hospital due to lack of beds for further management. The patient expired withing a few hours of reaching the hospital. His blood samples grew Streptococcus pyogenes (Group A Streptococcus), emmtype 110. The results showing emm typing are shown in [Figure 1] and [Figure 2].
|Figure 2: Gel picture shown for the emm typing Gel picture showing PCR amplification of emm gene by conventional PCR, Lane 1:100 plus bp ladder, Lane 2-6: Clinical Isolates showing presence of emm gene, Lane 7: ATCC 12347 (positive control for emm gene) and Lane 8: Negative control|
Click here to view
A previously healthy, 40-year-old male was admitted following severe head injury in the right fronto-temporo-parietal region associated with subdural haematoma. The patient was unconscious and had poor Glasgow coma scale score. Right decompressivecraniectomy and lax duroplasty was done on this patient. Appropriate samples were collected and sent to the microbiology laboratory and the patient was started empirically on ceftriaxone and amoxicillin-clavulanic acid. The patient expired within a span of 3 days following development of septicaemia. The cause of death in this patient was identified to be septicaemia. The blood sample on culture grew beta-haemolytic colonies, which were identified as Streptococcus constellatussspconstellatus (Group F Streptococcus).
| ~ Discussion|| |
The peculiar features observed in this study was the rapidity of deaths occurring in the patients with streptococcal bacteraemia and the high frequency of isolation of non-Group A Streptococci isolates that are emerging as a causes of fatal bacteraemia.
GGS are part of the normal microbial flora of the gastrointestinal tract, vagina and skin and can cause a variety of infections. Reported mortality rates for patients with GGS bacteraemia also vary, ranging from 5% to 30%.  There have been a number of reports of bacteraemia due to GGS across the world and it has been seen that GGS bacteraemia is usually associated with major underlying illnesses in patients such as malignancy, cardiovascular disease, diabetes mellitus, bone and joint diseases and cirrhosis.  In the three cases of GGS bacteraemia that we report here, one of the patients had underlying non-Hodgkin lymphoma, but in the rest, only immobilization as the risk factor could be ascertained. In all the three cases, the source of bacteraemia could be identified as either an abscess or a wound infection. Despite the three strains being sensitive to most of the commonly available drugs, the patients succumbed to septicaemia even before the specific treatment could be started. Although most of the studies indicate satisfactory responses to antimicrobial therapy in patients with GGS infections, there have been reports of erythromycin and clindamycin resistance in these isolates which undermines the necessity for identification and susceptibility testing of these bacteria.  The rapidly fatal outcomes also emphasise the need for early workup and diagnosing streptococcal infection before it invades the bloodstream so that appropriate antimicrobial treatment can be initiated.
GAS is known to cause invasive infections, which are associated with a high morbidity and mortality. Overall case fatality rate of invasive GAS is estimated to be from 10% to 15%.  One of the cases in this series was an old patient, who succumbed to GAS septicaemia in less than 48 hours. Age is a risk factor for fatality due to GAS bacteraemia as observed by Lamagani et al. who described that older patients had poor survival. 
Like GGS, GFS are also part of normal microbial flora and have been associated with brain, dental and hepatic abscesses, occasional endocarditis and wound infections. They are unique among the Streptococci in their proclivity for abscess formation but are not a frequent cause of bacteraemia. In a study of all bacteraemias at Mayo Clinic-affiliated hospitals, GFS accounted for only 2% of all beta-haemolytic streptococcal isolates.  In our case with GGS bacteraemia, no source of bacteraemia could be identified but the patient succumbed rapidly, pointing to the severe fatality of the organism.
Streptococcal pyrogenic exotoxins (SPEs) contribute to the pathogenesis of severe invasive diseases by acting as superantigens.  Not many studies have demonstrated the presence of SPEs in streptococci other than GAS. In the present study, the isolates of GGS did not produce spe A or C. Kalia et al. in their study had observed three GGS strains positive for Spe A and one strain positive for Spe C.  The Group A isolate in our study was found to be positive for Spe B, Spe F, Spe G and Sme Z.
These cases illustrate rapid fatality of the patients who presented with streptococcal septicemia despite them being incredibly susceptible to penicillin, highlighting the essence of strict vigilance and timely intervention in suspected cases. Congruent with our observation, Kristen et al. observed that 57% of GAS and 43% of GGS bacteraemia cases expired in less than 24 hours of sending the blood culture.  All the above cases of group-G streptococcal infection with a fatal outcome emphasise the need for cognizance of this erstwhile non-pathogen emerging as lethal pathogenic bacteria, and hence the importance of isolation of this bacterium should not be undermined. Most of these cases were caused by health care post-op infections so more needs to be done to address the quality around surgery. There should be a persistent diligent search for the possible isolation of this organism as early as possible before it invades the bloodstream with repeated clinical examination as well as laboratory investigations so that timely antimicrobial therapy can be initiated based on the susceptibility testing. This study would be helpful in assessing the fatal nature of Streptococci other than Streptococcus pyogenes and the importance of identification of Streptococci upto species level.
| ~ Acknowledgements and Source of Funding|| |
The work on molecular epidemiology of Streptococcus wasfunded through an ongoing research grant from the Indian Council of Medical Research. The Hospital Infection Surveillance work is being funded by another research grant from the Indian Council of Medical Research. We acknowledge the financial support of ICMR for the performance of this study.
| ~ References|| |
Lamagni TL, Neal S, Keshishian C, Powell D, Potz N, Pebody R, et al.
Predictors of death after severe Streptococcus pyogenes
infection. Emerg Infect Dis 2009;15:1304-7.
CLSI. Performance standards for antimicrobial susceptibility testing: 19 th
informational supplement. CLSI document M100-S19. Clinical and Laboratory Standards Institute, Wayne; 2009
Jing HB, Ning BA, Hao HJ, Zheng YL, Chang D, Jiang W, et al
. Epidemiological analysis of group A streptococci recovered from patients in China. J Med Microbiol 2006;55:1101-7.
Beall B, Facklam R, Thompson T. Sequencing emm
-specific PCR products for routine and accurate typing of group Astreptococci. J Clin Microbiol 1996;34:953-8.
Liao CH, Liu LC, Huang YT, Teng LJ, Hsueh PR. Bacteremia caused by group G Strepococci, Taiwan. Emerg Infect Dis 2008;14:837-40.
Woo PC, Fung AM, Lau SK, Wong SS, Yuen KY. Group G beta-hemolytic streptococcal bacteremia characterized by 16S ribosomal RNA gene sequencing. J Clin Microbiol 2001;39:3147-55.
Factor SH, Levine OS, Schwartz B, Harrison LH, Farley MM, McGeer A, et al
. Invasive group Astreptococcal disease: Risk factors for adults. Emerg Infect Dis 2003;9:970-7.
Libertin CR, Hermans PE, Washington JA 2 nd
. Beta-hemolytic group F streptococcal bacteremia: A study and review of the literature. Rev Infect Dis1985;7:498-503.
Kalia A, Bessen DE. Presence of streptococcal pyrogenic exotoxin A and C genes in human isolates of group G streptococci. FEMS Microbiol Lett 2003;219:291-5.
Kristensen B, Schbnheyder HC. A 13-year survey of bacteraemia due to beta-haemolytic streptococci in a Danish county. J Med Microbiol 1995;43:63-7.
[Figure 1], [Figure 2]