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Clostridium sordellii as a cause of constrictive pericarditis with 1

pyopericardium and tamponade 2

Rama Chaudhry,1* Nishant Verma,

1 Tej Bahadur,

1 Parul Chaudhary,

1 Pallavi Sharma,

1 and 3

Nidhi Sharma1 4

All India Institute of Medical Sciences, New Delhi, India1

5

*Corresponding author. Mailing address. Department of Microbiology, All India Institute 6

of Medical Sciences, New Delhi 110029, India. Phone: 91-11-2659 4795. Fax: 91-11-2658 7

8641. Email id: drramach@gmail.com. 8

Abstract 9

Systemic infections caused by Clostridium sordellii is a rare entity. They are usually 10

reported in skin, soft tissue infections and sometimes toxic shock syndrome involving 11

exotoxins. We report here, the first case of Clostridium sordellii infection associated with 12

acute constrictive pericarditis with pyopericardium and tamponade. 13

Case Report 14

The patient, an eight months old infant, was admitted in a local hospital with history of fever 15

of about 2 months and an abscess in right thigh which had developed following hepatitis-B 16

vaccination. The abscess was drained and the pus culture revealed Staphylococcus aureus for 17

which the patient was given vancomycin intravenously as per the antimicrobial susceptibility 18

report. The abscess subsequently healed, however, the patient continued to remain sick with 19

development of dry cough and swelling of legs. Echocardiography and chest x-ray showed 20

pericardial effusion with increased cardio-thoracic ratio and the patient was referred to our 21

institute. On admission, the patient was afebrile with mild pedal edema, tender hepatomegaly, 22

and liver palpable till 4 cm below costal margin. Routine investigations showed 23

Copyright © 2011, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.J. Clin. Microbiol. doi:10.1128/JCM.00933-11 JCM Accepts, published online ahead of print on 3 August 2011

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haemoglobin-12.8 g/dL; total leukocyte count-14,100/µL; differential leukocyte count of 24

Neutrophils 50 , Lymphocytes 46, Eosinophils 3, Monocytes 1; erythrocyte sedimentation 25

rate-5 mm in first hour; blood urea-35 mg/dL; serum creatinine-0.4 mg/dL; serum sodium- 26

128 mEq/L; serum potassium-4.3 mEq/L; SGOT-115 U/L; SGPT-235 U/L; total bilirubin-1.8 27

mg/dL; total protein-5.1 g/dL; serum albumin-2.8 g/dL. The urine output was within normal 28

limits. Central nervous system and respiratory system examination showed no abnormalities. 29

Heart rate was 128 beats per minute. Electrocardiogram showed low voltage complexes and 30

echocardiography revealed organized pericardial effusion with features of tamponade. The x-31

ray of chest showed a cardio-thoracic ratio of 0.65. Computerized tomography (CT) scan of 32

chest showed features suggestive of effusive constrictive pericarditis and a diagnosis of 33

constrictive pericarditis with pyopericardium and tamponade was made. Pigtail drainage of 34

pericardial pus was performed and patient was administered empirically with intravenous 35

piperacillin-tazobactam and linezolid. On examination, pericardial fluid was turbid with 36

protein-40 mg/dL; sugar-45 mg/dL; total leukocyte count of 2600/µL; differential leukocyte 37

count of Neutrophils 90 and Lymphocytes 10. Gram staining on direct smear showed no 38

organisms and Ziehl-Neelsen staining showed no acid fast bacilli. Aerobic cultures of 39

pericardial fluid and blood were sterile, however, pericardial fluid was not sent for anaerobic 40

culture. Meanwhile the patient had stabilized. Follow-up Computerized tomography-41

angiogram showed a localized constriction at atrio-ventricular groove and pericardiectomy 42

was performed. Post-operative period was uneventful and the patient was discharged with 43

oral amoxycillin-clavulanic acid. 44

The excised pericardial tissue was sent for both aerobic and anaerobic culture. Aerobic 45

culture showed no growth. On anaerobic culture, odourless, flat, greyish, non-hemolytic 46

colonies were seen with irregular margin. They were metronidazole sensitive. Gram staining 47

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showed gram-positive bacilli with sub terminal non-bulging spores. The isolate was further 48

identified biochemically, and tested positive for lecithinase, urease, gelatin liquefaction, 49

indole production, glucose fermentation, and esculin hydrolysis. The isolate was identified as 50

C. sordellii. The isolate was also tested using API 20A (Biomeurix, France) and was 51

identified as C. sordellii. 52

A polymerase chain reaction (PCR) using published primers for 16S ribosomal RNA was 53

also done. Briefly, DNA was extracted from the culture by QIAmp kit (QIAGEN, Germany) 54

and was amplified using broad range PCR primers i.e., forward primer (F8) 5’-55

AGTTTGATCCTGGCTCAG-3’ and reverse primer (357R) 5’-CTGCTGCCTCCCGTA-3’ 56

(6, 14) and C. sordellii specific forward primer (C1SOR-F) 5’-TCGAGCGACCTTCGG-3’ 57

and reverse primer (C1SOR-R) 5’-CACCACCTGTCACCAT-3’ respectively, targeting the 58

16S ribosomal RNA (rRNA) gene (10). Amplified products i.e., 330 bp (Fig. 1) for broad 59

range and 944 bp (Fig. 2) for Clostridium sordellii specific PCR, were purified by using 60

QIAGEN Gel extraction kit. The purified products were commercially sequenced and 61

compared with sequences available in the Gene Bank database by Basic Local Alignment 62

Search Tool (BLAST). The 16S rRNA gene sequences amplified from isolate showed 99% 63

identity with C. sordellii (Accession no. dbj|AB448946.1|) sequence available in the 64

database. Thus, C. sordellii was identified as the cause of constrictive pericarditis with 65

pyopericardium and tamponade. Patient responded favourably to the therapy. 66

______________________________________________________ 67

Anaerobes are now being recognized as etiological agents for infections of almost any body 68

site including pericardium (4). Pericarditis refers to inflammation of the pericardium and the 69

proximal part of great blood vessels. It may either be asymptomatic or may present as a 70

fulminating, life threatening condition. Brahan et al (3), Francois et al (8), and Pigrau et al 71

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(12) have reported the association of C. septicum infection with pericarditis in patients with 72

underlying carcinoma. Skiest et al (13) have given a brief review of anaerobic pericarditis 73

occurring in children in which Bacteroides species was highlighted as the predominant cause. 74

Pericarditis was also associated with C. perfringens (9). C. difficile pericarditis complicating 75

pseudomembranous colitis in patient hospitalized after multiple trauma was first reported by 76

Koehler et al (11). It is to be noted that C. difficile resembles C. sordellii phenotypically and 77

since more virulent strains of C. difficile such as NAP1 are being reported worldwide, there is 78

a need to carefully differentiate between them genotypically (7). Although few other cases of 79

pericarditis caused by genus clostridia have been reported, to our knowledge, this is the first 80

case where Clostridium sordellii infection is associated with pericarditis. C. sordellii is a 81

gram-positive anaerobe; an infrequent human pathogen associated with skin and soft tissue 82

infections. The exotoxins produced by the bacteria are associated with toxic shock syndrome 83

with high mortality rate following childbirth, medically induced abortion, and routine 84

gynaecological procedures (1, 2). Recently, C. sordellii has been reported as a cause of brain 85

abscess (15). 86

In the case reported here, there was no clinical suspicion of anaerobic infection initially. 87

Since all other reasons were ruled out systematically the clinicians finally decided to send the 88

excised pericardial tissue for anaerobic culture. The sample was transported in anaerobic 89

transport medium with sterile precautions. A pure culture of C.sordellii was confirmed 90

phenotypically and genotypically. 91

Prevailing local conditions, host factors, and rapid administration of appropriate antimicrobial 92

treatment could have decreased the clinical severity of the infection which led to good 93

prognosis in the case reported here. The possibility of low virulence of the pathogen could 94

not be ruled out (5). 95

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Present case demonstrates that C.sordellii can cause acute constrictive pericarditis. Moreover, 96

expanding clinical spectrum of C. sordellii necessitates application of rapid identification 97

methods such as PCR and gene sequencing and increased clinical awareness of this 98

unrecognized human pathogen. 99

References 100

1. Aldape, M. J., A. E. Bryant, and D. L. Stevens. 2006. Clostridium 101

sordellii infections: epidemiology, clinical findings, and current perspectives on 102

diagnosis and treatment. Clin. Infect. Dis. 43:1436-1446. 103

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syndrome. Lancet Infect. Dis. 9:725-726. 105

3. Brahan, R. B., and R. C. Kahler. 1990. Clostridium septicum as a cause of 106

pericarditis and mycotic aneurysm. J. Clin. Microbiol. 28:2377-2378. 107

4. Brook, I., 2009. Pericarditis caused by anaerobic bacteria. Int. J. Antimicrob. 108

Agents. 33:297-300. 109

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extrachromosomal elements in pathogenicity. Curr. Opin. Microbiol. 8:601-605. 111

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8. Francois, B. L., P. Delare, L. Vignon, Niquet R, Gobeaux F, and Gay R. 1994. 118

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tracts. Microbiol. Immunol. 46:353-358. 125

11. Koehler, R., M. Mone, E. Kimball , D. Vargo, N. Leonardo , and R. Barton. 126

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trauma patient. J. Trauma. 55:771-773. 128

12. Pigrau, C. M., P. Ruiz, and J. Sagrista. 1995. Purulent pericarditis due to 129

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pericarditis: case report and review. Clin. Infect. Dis. 19:435-440. 133

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Figure 1:

Broad range PCR assay showing 330 bp sequence of 16S rRNA gene of genus clostridia.

Lane 1: 100 bp ladder

Lane 2: Pericardial isolate

Lane 3: C. sordellii lab isolate

Lane 4: C. difficile ATCC 9689

Lane 5: C. perfringens lab solate

Lane 6: Negative control

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FIGURE 2:

Clostridium sordellii specific PCR showing 944 bp sequence of 16S rRNA gene.

Lane 1: 100 bp ladder

Lane 2: Negative control

Lane 3: C.sordellii pericardial isolate

Lane 4 and 5: C.sordellii lab isolate

Lane 6: 100 bp ladder

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