Reversed halo sign caused by huge tricuspid native valve infective endocarditis associated with community-acquired methicillin-resistant Staphylococcus aureus

IP: 54.70.40.11 On: Wed, 12 Dec 2018 21:15:22 Case Report Reversed halo sign caused by huge tricuspid native valve infective endocarditis associated with community-acquired methicillin-resistant Staphylococcus aureus Takeshi Saraya, Ken Kikuchi, Koji Araki, Yuki Uehara, Hiroshi Makino, Masaki Tamura, Ichiro Hirukawa, Kojiro Honda, Takuma Yokoyama, Daisuke Kurai, Haruyuki Ishii, Masachika Fujiwara, Hajime Takizawa and Hajime Goto


Introduction
This case presented with pulmonary embolization caused by community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA), but also revealed a hospital-acquired (HA) MRSA-like pattern on drug susceptibility tests.A reversed halo sign (RHS) has diverse differential diagnoses; however, the present case showed that this sign can be caused by massive infective endocarditis (IE), and we describe here a novel phenotype of CA-MRSA belonging to clonal complex (CC) 509.

Case report
A 43-year-old man was transferred to our hospital in a critical condition of unknown cause.He was admitted to another hospital 1 month prior to his current presentation.At that time, he complained of chest pain, pyrexia and general fatigue.At that hospital, he was diagnosed with pneumonia and concomitant idiopathic thrombocytic purpura and underwent treatment for 1 month with various antibiotics and high-dose corticosteroids.He had a Abbreviations: Abbreviations: CC, clonal complex; CT, computed tomography; IE, infective endocarditis; RHS, reversed halo sign; ST, sequence type; SSCmec, staphylococcal cassette chromosome mec.smoking history of 30 pack years, no history of illicit drug use and no medical history, with the exception of chronic otitis media with cholesteatoma 13 years previously.He had been in good health until recently.On admission to our facility, he was critically ill with mild impairment in his level of consciousness; his Glasgow Coma Scale score was 12 (E4V3M5: E, eye opening; V, verbal response; M, motor response).His vital signs were as follows: body temperature, 36.8 u C; blood pressure, 96/44 mmHg; pulse rate, 124 beats min 21 ; respiration, 36 beats min 21 ; and oxygen saturation, 96 % measured while on a 100 % 6 l min 21 oxygen mask.These vital signs were suggestive of preshock status.He had cyclic oscillations of tidal volume and respiratory rate with periods of hyperpnoea (up to 50 beats min 21 ) alternating with hypopnoea (12 beats min 21 ), suggestive of Cheyne-Stokes respiration.On physical examination, although his lungs were clear to auscultation, conjunctival anaemia and bilateral lowerextremity oedema were present.Furthermore, he had left conjunctival petechiae and flat, painless, red to bluish-red spots on his left second finger pad, which was recognized as a Janeway's lesion.He also had exfoliative skin on both palms and a Levine II/VI systolic murmur at the left sternal border in the fifth and fourth intercostal spaces.These findings were consistent with tricuspid IE possibly caused by an unknown toxin-producing pathogen.His laboratory data showed elevation of his white blood cell count to 13 000610 3 ml 21 , a C-reactive protein level of 23 mg dl 21 , blood urea nitrogen of 98 mg dl 21 and a creatinine level of 1.3 mg dl 21 .The haemoglobin value and platelet count were decreased to 8.0 mg dl 21 and 1.8610 4 ml 21 , respectively.Non-enhanced thoracic computed tomography (CT) performed 30 days prior to coming to our hospital (the day of admission to his local hospital) depicted multiple cavitary lesions throughout the lung (Fig. 1a-c).The cavitary lesion showed a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation, the so-called RHS.However, the RHS had atypical aspects in that the consolidation rim was very thick, the central groundglass opacity was narrow, and the ground-glass opacity surrounded a thick rim of consolidation like a double rim.Thoracic enhanced CT on admission to our facility showed scattered necrotic cavity lesions (Fig. 1d-f) as well as filling defects in the bilateral main pulmonary arteries, suggestive of embolization.Urgent echocardiography showed severe tricuspid regurgitation with massive vegetation.Thus, he was diagnosed with tricuspid native valve IE complicated by bacterial embolization to the lung and pulmonary arteries.Two hours after arrival at our hospital, he underwent an emergency operation for tricuspid valve replacement as well as extraction of the component of bacterial embolization located in the main pulmonary arteries.On Gram staining and histological evaluation, the resected tricuspid valves were found to have been destroyed and were replaced by numerous clusters of Gram-positive cocci (Fig. 2a-c), and two huge vegetations (as large as 8 cm; Fig. 2d, arrow heads) were noted, which were derived from the tricuspid valve together with multiple tiny vegetations (Fig. 2d, arrow), suggestive of massive IE.Thereafter, MRSA was cultured from the tricuspid valve, blood and sputum (two samples).

Investigations
We applied the MRSA samples to the Gram-positive BBL Crystal identification system (Becton, Dickinson and Co.), which characterized three different kinds of MRSA biotypes (data not shown).Interestingly, the biotypes obtained from the tricuspid valve and blood culture were the same biotype, whilst the biotype obtained from the sputum sample #1 had the additional characteristic of producing exfoliative toxin B. Furthermore, the biotype from sputum sample #2 was of an entirely different character.These findings were confirmed by PFGE, which showed proximity banding patterns between the strains from the tricuspid valve, blood and sputum sample #1 but not in that from sputum sample #2 (data not shown).The antibiotic susceptibilities of the isolated strains (numbered 1-4) are shown as Table 1.To accurately characterize these strains further, we performed multilocus sequence typing (MLST) (Table 2) using seven housekeeping genes, as described previously (Enright et al., 2000).An allelic profile (allele number) was obtained from the MLST website (http://www.mlst.net/),and the sequence type (ST) was determined using eBURST software (Feil et al., 2004) to determine the CC to which each ST belonged.The staphylococcal cassette chromosome mec (SCCmec) types (I-IV) were analysed by PCR as described previously (Oliveira & de Lencastre, 2002) using reference strains.All four MRSA isolates were uniformly resistant to all b- lactam antibiotics and had no Panton-Valentine leukocidin gene (pvl).This was consistent with HA-MRSA.However, isolates no. 1 (tricuspid valve) and no. 2 (blood) matched completely (SCCmec II, ST91, CC509) and were consistent with CA-MRSA, which commonly presents as impetigo in Japan (Takizawa et al., 2005).Isolate no. 3 (sputum sample #1) showed a partially different pattern of the triosephosphate isomerase (tpi) allele, one of the house keeping genes, whilst isolate no. 4 (sputum sample #2) revealed an entirely different pattern of SCCmec II, ST5 and CC5, corresponding to the pandemic New York/ Japan clone (Oliveira et al., 2002) HA-MRSA infection.Thus, the present case was diagnosed as IE caused by CA-MRSA with pulmonary embolization presenting as RHS but also revealed an HA-MRSA-like pattern on drug susceptibility testing.Despite the intensive treatment, the patient died of septic shock on the 10th hospital day.Kim et al. (2003) first described the RHS and considered it to be a relatively specific sign of cryptogenic organizing pneumonia.Later, the presence of this sign was reported in various other diseases, such as fungal, bacterial and mycobacterial infections, and in systemic and neoplastic diseases.The present case showed a somewhat different RHS from that originally described in that (i) the consolidation rim was very thick and the central ground-glass opacity was narrow, and (ii) the ground-glass opacity surrounding the thick rim of consolidation seemed to be double rimmed.This appearance has been reported in cases with invasive mycosis, which may be related to angioinvasive organisms (Godoy et al., 2012;Marchiori et al., 2012).In these cases, the central portion of the lesion tended to be necrotic and form a cavity during the course of the disease (Choo et al., 2014), as in the present case.The present case had some signs that were characteristic of IE, such as conjunctival petechiae, Janeway's lesion and a systolic murmur in the tricuspid valve area.Moreover, the presence of Cheyne-Stokes respiration and pre-shock status suggested that MRSA IE provoked acute decompensated heart failure, and sample no. 3 isolated from sputum sample #1 probably caused the exfoliated skin on both palms by production of exfoliative toxin B (Table 2).HA-MRSA is typically defined as MRSA isolated from in-patients that were MRSA negative at the start of hospitalization or as MRSA isolated from inpatients 48 h or more after hospitalization.CA-MRSA is defined as MRSA isolated from out-patients with no history of hospitalization within the past year and who present with no other established risk factors for MRSA infection.In this regard, the present case seemed to be classified as CA-MRSA, regardless of its unknown portal site of infection, such as skin or soft tissue, and growth of isolate no. 4 was considered as colonization due to long-term hospitalization in his local hospital.In Japan, the New York/Japan clone (ST5/SCCmec II) is a typical HA-MRSA clone, whilst ST8/ SCCmec IV is a major CA-MRSA clone and often presents as bullous impetigo.Generally speaking, SCCmec I, II and III are HA-MRSA, whilst SCCmec IV and V are CA-MRSA (Yamamoto et al., 2010).The present case was categorized as CA-MRSA with SCCmec II, which seems to be an extremely rare type of CA-MRSA.Interestingly, on MLST analysis, isolate no. 3 was also categorized as CC509, but two changes in the base sequence (G142A, A159T) were found in the tpi  allele (Table 2).This unique MLST allele pattern (1-26-28-18-18-UNQ-50) has never been reported (Oliveira et al., 2002).In Japan, most CA-MRSA do not have the pvl gene, as in the present case, and pvl is found in approximately 17-20 % of S. aureus from bullous impetigo.Takizawa et al. (2005) reported that pvl-CA-MRSA can be divided into one of three STs (89, 8 and 91).Our case was clinically consistent with CA-MRSA, and this new ST (isolate no. 3) might have been derived from ST91 (isolate no. 1 and/or no. 2) via some genetic rearrangement and plasmid elimination, thereby resulting in increased virulence presenting as exfoliated skin lesions in both palms.Although the new ST was not isolated from blood culture or vegetations, exfoliative skin on both palms could be caused by haematological spread of the new ST, which possessed exfoliative toxin (TSST-1).

Discussion
In conclusion, we have described a case of CA-MRSA IE together with atypical RHS on thoracic CT, and the new phenotype of this CA-MRSA was shown to be a new ST that belongs to CC509.

Fig. 1 .
Fig. 1.Non-enhanced thoracic CT taken 30 days prior to coming to our hospital (the day of admission to his local hospital) depicting multiple cavitary lesions randomly distributed through the lungs (a, b, c).The cavity lesion showed a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation (d, e, f), the so-called RHS.

Fig. 2 .
Fig. 2. Gram staining and histopathological evaluation showing that the resected tricuspid valves had been destroyed and replaced by numerous clusters of Gram-positive cocci [magnification: 620 (a), 6200 (b); 61000 (c)], and two huge vegetations as large as 8 cm in diameter (d; arrow heads) and tiny multiple vegetations (d; arrow) were noted at the tricuspid valve.

Table 1 .
Antibiotic susceptibility of MRSA strains identified from the patient samples

Table 2 .
Multilocus sequence typing of the four isolated S. aureus strains UNQ means a novel ST type that did not include in the S. aureus MLST database (http://eburst.mlst.net/v3/mlst_datasets/).