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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 61  |  Issue : 4  |  Page : 545-548
Infective endocarditis due to Streptococci and Enterococci: A 3-year retrospective study


1 Department of Microbiology, Sree Chithra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
2 Department of Cardiology, Sree Chithra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India

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Date of Web Publication10-Oct-2018
 

   Abstract 


Introduction: Infective endocarditis (IE) is an infection of the heart valves with an aggregation of bacteria in a fibrin plaque called vegetation. Aims and Objectives: This is a retrospective study of all infective endocarditis cases due to alpha haemolytic streptococci and enterococci. Methods: All cases of infective endocarditis cases due to alpha haemolytic streptococci and enterococci in a period of three years from 1st January 2010 to 31st December 2012 were included. Isolation of the same organism from more than one set of blood cultures was taken as a confirmed case of infective endocarditis. Clinical and serological parameters were recorded using a proforma. Results: Native valve endocarditis was more common with only five prosthetic valves being involved. Out of 89 clinically suspected cases of IE in the three years from Jan 2010 to Dec 2012, for which blood was sent for culture, 63(70.78%) samples were positive by culture. Of these, 42/63(66.66%) were due to alpha-lytic Streptococci, enterococci and rare gram positive cocci. The rare ones included Enterococcus gallinarum, abiotropha defective, Vagococcus fluvialis and Nutritionally Variant Streptococci(NVS). High level Aminoglycoside resistance(HLAR) was also encountered. The varied and important features of these isolates are discussed. Complications and treatment are described. Conclusion: From a clinical microbiology point of view, the major challenge faced by the microbiologist in diagnosis of IE is proper aseptic collection of sample before starting antibiotics with a need for multiple samples to detect and also to prove the causative organism. Sensitivity reporting can be a difficult task in the context of NVS, HLAR and gram positives that are slow growing. Congestive failure and embolisation occurs even when the antibiotic treatment is successful.When patients go in for complications, it is very rarely due to wrong antibiotics.

Keywords: Alpha lytic streptococci, enterococci, Infective endocarditis

How to cite this article:
Raja K, Antony M, Harikrishnan S. Infective endocarditis due to Streptococci and Enterococci: A 3-year retrospective study. Indian J Pathol Microbiol 2018;61:545-8

How to cite this URL:
Raja K, Antony M, Harikrishnan S. Infective endocarditis due to Streptococci and Enterococci: A 3-year retrospective study. Indian J Pathol Microbiol [serial online] 2018 [cited 2018 Dec 15];61:545-8. Available from: http://www.ijpmonline.org/text.asp?2018/61/4/545/242967





   Introduction Top


Infective endocarditis (IE) is an infection of the heart valves with an aggregation of bacteria in a fibrin plaque called vegetation. The commonest causative agents are the streptococci that are commensals of the oropharyngeal cavity. IE is treated based on blood culture report if positive and empirically if negative.

Viridans Streptococci form the largest group that causes IE. Though clubbed together, the individual species are varied with different growth requirements and antibiotic sensitivity patterns. Enterococci are also sometimes mistaken for viridans Streptococci; hence they have also been included in this retrospective cohort study.

This study aims to raise awareness regarding IE due to viridans Streptococci and the reasons for lack of response to treatment in few cases by enumerating the isolates during a period of 3 years in a premier tertiary care center for cardiology and cardiac surgery and reviewing the treatment and diagnostic methods adopted in these cases.

Aims and objectives

A retrospective study that includes all cases of IE cases due to alpha-hemolytic Streptococci and Enterococci in a period of 3 years from January 1, 2010 to December 31, 2012 at a tertiary center for cardiology and cardiac surgery.

Objectives:

  1. Characterization of the Streptococci and Enterococci isolated from blood of cases of IE
  2. Treatment given and follow-up of the patients.



   Materials and Methods Top


Blood culture isolates from all cases of IE where alpha-hemolytic Streptococci or Enterococci were isolated were included in the study. Period was 3 years from January 2010 to December 2012. Patients were those attending the cardiology clinic of a tertiary level referral center in Thiruvananthapuram, Kerala, India.

For IE, 5 ml blood is collected with aseptic precautions and inoculated into aerobic and anaerobic culture bottles provided with the BacT/Alert System (bioMerieux). At least two sets are collected for each patient at half-an-hour to one-hour interval. When more than one blood sample was positive for Streptococci or Enterococci, full clinical history and treatment history were noted with follow-up till discharge or death. This was done for clinically confirmed cases of IE. Complete identification was done using VITEK 2 system.

Sensitivity of the isolates was done manually on blood agar using antibiotic discs (HiMedia) and measuring zone diameter. High-level aminoglycoside resistance (HLAR) strains were detected using e-test strips (bioMerieux). For gentamicin, minimum inhibitory concentration (MIC) >500 μg/ml was considered HLAR and MIC >1000 μg/ml for Streptomycin.[1]


   Results Top


Out of 89 clinically suspected cases of IE in the 3 years from January 2010 to December 2012, for which blood was sent for culture, 63 (70.78%) samples were positive by culture. Of these, 42/63 (66.66%) were due to alpha-hemolytic Streptococci, Enterococci, and rare Gram-positive cocci (GPC). Their distribution is given in [Table 1].
Table 1: Streptococcal isolates and their species

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Demographic profile

There were 25 males and 17 females. Enterococci had a slight predilection for females, i.e., 6/8 were females (62.5%), of whom one patient had a definite cyst in the pouch of Douglas, while only 2/8 (25%) were male patients. Age distribution is given in [Table 2].
Table 2: Age distribution

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Valves involved

Native valve endocarditis was more common with only five prosthetic valves being involved. Mitral valve (17) was most commonly involved. Both valves, i.e., mitral and aortic were involved in six cases and aortic in eight cases. Rare cases were the involvement of five cases of ventricular septal defect (VSD) and one case where there was a ruptured sinus of Valsalva and tricuspid valve vegetation. It was interesting to note that the size of vegetation on first echo ranged from no definite vegetation seen, to more than 20 mm size.

Antibiotic sensitivity

Sensitivity was done manually with the help of antibiotic discs (HiMedia) and e-test strips (bioMerieux). Of the 31 alpha-hemolytic Streptococci, one was resistant to penicillin. Enterococci were all sensitive to Ampicillin, except one. Enterococcus gallinarum is inherently resistant to vancomycin. Of the three rare GPC, Vagococcus fluvialis was sensitive only to vancomycin. Abiotrophia defectiva, though it appeared sensitive to penicillin due to slow growth, did not respond clinically, and the nutritionally variant streptococci (NVS) were difficult to grow and hence sensitivity could not be reliably reported.

High-level Aminoglycoside Resistance

Out of the 31 viridans Streptococci, four and out of five Enterococcus faecalis, three, showed HLAR to gentamicin. One E. gallinarum showed HLAR to gentamicin. To streptomycin, HLAR was shown by one E. faecalis and one E. gallinarum.

Treatment

For 18 typical alpha-hemolytic Streptococci with sensitivity to penicillin and gentamicin, crystalline penicillin in the standard dose of 5 mill units was given sixth hourly and gentamicin 1.5 mg/kg twice daily. Duration was 42 days with gentamicin being stopped after 2–3 weeks. All 18 patients recovered.

For those with HLAR to gentamicin, streptomycin was used in two cases of viridans Streptococci and the other two were managed with ceftriaxone added to penicillin. Of these, one had a high MIC to penicillin; hence this was later changed to vancomycin with ceftriaxone. All cases recovered uneventfully.

For five cases of enterococcal endocarditis that showed sensitivity to ampicillin, standard regimen of 4 g eighth hourly intravenous was given with gentamicin. However, two of these showed HLAR to gentamicin and were successfully managed with streptomycin.

Complications

The complications that developed and the corresponding organisms are given in [Table 3].
Table 3: Complications due to the different types of streptococci

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   Discussion Top


Streptococci of the oral cavity, namely Streptococcus mitis, Streptococcus oralis, Streptococcus sanguis, and Streptococcus gordonii, colonize the tooth surfaces as well as mucosal membranes. They enter the blood stream during dental procedures and vigorous brushing, especially when the gingiva is inflamed. Such bacteria of low virulence are cleared from circulation within 1 hour in an otherwise healthy individual. However, in a person with a defective valve, it deposits in a niche not frequented by the macrophages, namely the damaged heart valves. Here they multiply and cause vegetations. They may disrupt to get into circulation to cause embolic abscesses in various tissues, especially the brain.[2]

IE is generally a disease of the valvular endocardium, rather than the mural endocardium. Histological examination of the valve tissue remains the gold standard for confirming IE. The mitral valve is the most frequently affected, followed by the aortic valve.[3] In this study also mitral valve was predominantly involved, but there were cases where both valves were involved. Involvement of cases of VSD and vegetations in the tricuspid valve were the rare entities.

In this study, the aim was to find the incidence of IE due to viridans Streptococci and Enterococci, complications that occur, and the management options.

Viridans Streptococci contributed to 49.21% (31/63) of the total endocarditis in 3 years, while Enterococci made up 12.70% (8/63). In a recent study in Chennai, South India, a similar incidence of 55.5% (15/27) was recorded for viridans Streptococci among all culture positive cases in a period of 2 years.[4] Enterococci have emerged as a major cause of Gram-positive IE. The source is obviously the genitourinary tract as opposed to the oropharyngeal flora for viridans Streptococci. This was shown in a retrospective cohort study on risk factors for enterococcal IE, where the genitourinary tract was the most common source of the infection (29.7%).[5] However, here this could not be proved. One female patient had an ovarian cyst that had to be excised due to recurrent IE due to E. faecalis. Three patients with alpha-hemolytic Streptococci, sensitive to penicillin and gentamicin, died of coronary congestive failure, renal failure, and aortic valve perforation. Of these one had a large vegetation (20 × 10 mm) which embolized to kidney with renal shutdown. One patient with E. faecalis died of cardiac arrest within 24 h of admission. Patients with NVS and A. defectiva died in spite of treatment with crystalline penicillin and valve repair. In case of the NVS infection, emergency surgery had to be performed due to heart failure and the valves when cultured also grew the NVS.

One patient with E. gallinarum which was both penicillin and vancomycin resistant initially responded to teicoplanin and rifampicin, but developed gangrene of the leg due to embolization and later died after amputation.

Speciating streptococci has now become very much easier with automated systems such as VITEK. The importance of speciating is when organisms like E. gallinarum are isolated. In an ordinary method of identification, the isolate would have been reported as Enterococcus species sensitive to vancomycin and resistant to ampicillin. However, it is resistant to vancomycin inherently and since it was resistant to ampicillin also with HLAR to gentamicin and streptomycin, an alternative regime had to be given. Teicoplanin and rifampicin proved effective in reducing fever and vegetations, but embolization to leg occurred followed by gangrene and patient died due to complications of amputation of the leg. In case of the other patient, E. gallinarum was sensitive to ampicillin and complete cure was achieved. A similar situation is described in a case report, where initial treatment with vancomycin was changed when the identification was made and MIC to vancomycin proved to be on the higher side.[6]

The need for detecting HLAR is also obvious from the fact that in this study out of four cases of HLAR for gentamicin among viridans Streptococci, two were successfully treated with streptomycin and the other two with ceftriaxone. The e-test (bioMerieux) has proved to be a blessing as it is rapid and less tedious. The authors recommend the use of e-test strips in IE due to GPC for testing penicillin, ampicillin, gentamicin, and streptomycin.

The three most important complications described in the literature are congestive heart failure, embolization to major organs and periannular abscesses.[7] Such complications are relatively rare in IE due to GPC (other than Staphylococci). In this study, we had all three complications with embolization being the commonest.

The role of histology in IE is not very well defined. To get a specimen for histology, the valve has to be excised. In most of our cases the patients either got cured or died of complications without undergoing any surgery or valve replacement. In four cases where cure was achieved with antibiotics, the valve was replaced for reasons other than IE. Of these, three were sent for histopathological evaluation. In one of these, a “few cocci of doubtful significance” was reported by the pathologist. In case of NVS, the cocci were not seen in tissue, but the same growth occurred on culture of the tissue, thus corroborating the significance of the growth in blood culture. Postmortem evaluation of valve tissue remains the gold standard for IE because blood culture does not detect organisms in about one-third of the cases. However, during life, blood culture is the standard method and aids in targeted therapy.


   Conclusion Top


From a clinical microbiology point of view, the major challenge faced by the microbiologist in diagnosis of IE is proper aseptic collection of sample before starting antibiotics with a need for multiple samples to detect and also to prove the causative organism. Sensitivity reporting can be a difficult task in the context of NVS, HLAR, and Gram-positives that are slow growing. A few additional antibiotics such as rifampicin, teicoplanin, ceftriaxone, clindamycin, and streptomycin may come in handy for resistant cases. E-test is very useful and in cases of high MIC, dose modification is essential. It is necessary to make sure that the patient gets the right dose recommended for IE. When patients go in for complications, it is very rarely due to wrong antibiotics. Congestive failure and embolization occurs even when the antibiotic treatment is successful. This study gives an indication of the common Gram-positives encountered in IE, problems in reporting their sensitivity pattern, clinical features of IE and outcome after antibiotic treatment based on culture. The above conclusions are only a pointer to the path for further research in this field.

Acknowledgements

All staff of Department of Microbiology and doctors and nurses in the cardiology unit at SCTIMST for their cooperation in helping with the collection of records.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 24th Informational Supplement 2014;M100-S24:140.  Back to cited text no. 1
    
2.
Greenwood D, Slack RCB, Peutherer JF. In: Medical microbiology: A guide to microbial infections. 16th ed, Indian reprint. New Delhi: Elsevier; 2006; Ch. 16: 183-4.  Back to cited text no. 2
    
3.
Brusch JL. Infective endocarditis and its mimics in the critical care unit. In: Burke A Cunha, editor. Infectious Diseases in Critical Care Medicine. 2nd ed, Informa Health Care: NY; 2007. p. 242-4.  Back to cited text no. 3
    
4.
Senthilkumar S, Menon T, Subramanian G. Epidemiology of infective endocarditis in Chennai, South India. Indian J Med Sci 2010;64:187-91.  Back to cited text no. 4
  [Full text]  
5.
Fernández Guerrero ML, Goyenechea A, Verdejo C, Roblas RF, de Górgolas M. Enterococcal endocarditis on native and prosthetic valves: A review of clinical and prognostic factors with emphasis on hospital-acquired infections as a major determinant of outcome. Medicine (Baltimore) 2007;86:363-77.  Back to cited text no. 5
    
6.
Dargere S, Vergnaud M, Verdon R, Saloux E, Le Page O, Leclercq R, et al. Enterococcus gallinarum endocarditis occurring on native heart valves. J Clin Microbiol 2002;40:2308-10.  Back to cited text no. 6
    
7.
Mocchegiani R, Nataloni M. Complications of infective endocarditis. Cardiovasc Hematol Disord Drug Targets 2009;9:240-8.  Back to cited text no. 7
    

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Correspondence Address:
Kavita Raja
Department of Microbiology, Sree Chithra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_205_17

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