CASE REPORT

Mycoplasma hominis, a Rare but True Cause of Infective Endocarditis Amandine Gagneux-Brunon,a Florence Grattard,b Jerome Morel,c Florence Suy,d Jean-François Fuzellier,e Paul Verhoeven,b Celine Cazorla,a Claire Guglielminotti,a Anne Fresard,a Frederic Lucht,a Elisabeth Botelho-Neversa

Mycoplasma spp. are rarely recognized agents of infective endocarditis. We report a case of Mycoplasma hominis prosthetic valve endocarditis diagnosed by 16S ribosomal DNA (rDNA) PCR and culture of valves in a 74-year-old man. We reviewed the literature and found only 8 other cases reported.

CASE REPORT

A

74-year-old man, with a history of hypertension and mitral and aortic biological prosthetic valve replacement since June 2013 and stroke in August 2013, was admitted in December 2013 to the intensive care unit of the University Hospital of Saint Etienne, Saint-Etienne, France, for dizziness and cardiac and kidney failure. Physical examination revealed a low-grade fever (38.2°C) and an aortic murmur. A first transthoracic echocardiography procedure showed a decrease in the left ventricular ejection function fraction (LVEF) to 35% compared to anterior data (LVEF, 45% to 50% in June 2013), whereas the prosthetic valves appeared functional. The results of a second transthoracic echocardiography procedure, performed only 2 days later, were consistent with aortic prosthetic endocarditis associated with grade IV aortic insufficiency, a decrease in the LVEF to 25%, and an abscess of mitroaortic intervalvular fibrosa. Four days later, 2 of 6 blood cultures grew with the same strain of Staphylococcus epidermidis after 19 and 23 h, respectively (blood culture system, Bactec FX40; Becton Dickinson). Both positive blood cultures were obtained through an arterial catheter. The results of peripheral blood cultures obtained through vein and central venous catheters remained negative. Diagnosis of infective endocarditis (IE) was based on Duke’s criteria (1 major criterion [valvular abscess] and 3 minor criteria [fever over 38°C, blood culture positive for S. epidermidis, and predisposing heart condition, i.e., history of valvular replacement]). The initial antibiotic regimen included vancomycin (20 mg/kg of body weight/day) and linezolid (600 mg twice a day). Cardiac surgery was performed 24 h after the diagnosis of infective endocarditis. Cardiac surgeons observed destruction of the mitroaortic intervalvular fibrosa, with dehiscence of the aortic prosthesis, and multiple abscesses. Aortic valve replacement with a biologic prosthesis associated with a reconstruction of the mitroaortic fibrosa was performed. After surgery, linezolid was replaced by daptomycin (8 mg/kg every 48 h) due to acute kidney injury. Serological testing for Bartonella spp. and Coxiella burnetii was negative. Broad-range 16S ribosomal DNA (rDNA) PCR was performed on the cardiac valve, using the primers described by Harris and Hartley (1), followed by sequencing; the results were positive for Mycoplasma hominis. Initially, routine cultures of the cardiac valve performed on standard media, including blood agar and chocolate agar for 48 h and Schaedler broth for 15 days, remained sterile. After the results

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of the PCR were seen, a culture of the valve was plated on chocolate agar for longer and led to the growth of translucent and tiny colonies after 5 days. A piece of the agar was then transferred onto A7 medium (Eurobio), which led to the growth of typical M. hominis colonies. Identification of the culture was confirmed by 16S rDNA sequencing and comparison with sequences available from the GenBank nucleotide database. Definitive diagnosis of M. hominis IE was done. Antibiotic susceptibility was initially determined using a S.I.R. mycoplasma kit (Bio-Rad) (Table 1). Since the in vitro activity of moxifloxacin or levofloxacin against M. hominis had been shown to be superior to that of ofloxacin, moxifloxacin at 400 mg/day was added to the daptomycin treatment (2, 3). Two days after beginning moxifloxacin therapy, the patient developed jaundice (total bilirubin, 200 mg/liter), justifying stopping the antibiotic. Moxifloxacin was replaced by clindamycin (2,400 mg a day) and doxycycline (200 mg a day). Antibiotic susceptibility was determined by E tests on A7 media (Eurobio), as described by Waites et al. (2), and the results are presented in Table 1. An antibiotic regimen effective for S. epidermidis was discontinued after 6 weeks of treatment. Clindamycin and doxycycline treatments were maintained for 9 weeks. The course of antibiotics was complicated by Clostridium difficile colitis, and the patient was cured with oral metronidazole (1,500 mg a day until clindamycin cessation). The patient was discharged from our hospital to a rehabilitation center after 6 weeks of hospitalization. After 4 months of follow-up, the echocardiography results were stable, with grade II aortic insufficiency (without vegetation) and a LVEF value of 65%. The patient had no fever and did not exhibit inflammatory

Received 27 March 2015 Returned for modification 29 April 2015 Accepted 18 June 2015 Accepted manuscript posted online 1 July 2015 Citation Gagneux-Brunon A, Grattard F, Morel J, Suy F, Fuzellier J-F, Verhoeven P, Cazorla C, Guglielminotti C, Fresard A, Lucht F, Botelho-Nevers E. 2015. Mycoplasma hominis, a rare but true cause of infective endocarditis. J Clin Microbiol 53:3068 –3071. doi:10.1128/JCM.00827-15. Editor: P. H. Gilligan Address correspondence to Amandine Gagneux-Brunon, [email protected]. Copyright © 2015, American Society for Microbiology. All Rights Reserved. doi:10.1128/JCM.00827-15

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Infectious Disease Department, University Hospital of Saint Etienne, Saint-Etienne, Francea; Laboratory of Infectious Agents and Hygiene, University Hospital of SaintEtienne, Saint-Etienne, Franceb; Anesthesia and Intensive Care Department, University Hospital of Saint Etienne, Saint-Etienne, Francec; Médecine Interne Infectieuse Tropicale, Lyon, Franced; Cardiac Surgery Department, University Hospital of Saint Etienne, Saint-Etienne, Francee

Case Report

TABLE 1 MICs of the M. hominis strain isolated from the prosthetic valve, as determined by the use of a SIR mycoplasma kit and E tests MIC (mg/liter) determined by: SIR mycoplasma kit

Etest

Clindamycin Doxycycline Tetracycline Azithromycin Erythromycin Josamycin Clindamycin Pristinamycin Ofloxacin Moxifloxacin

⬍2 ⬍2 ⬍2 ⬎4 ⬎4 ⬍2 ⬍2 ⬍2 ⬍1

⬍0.016 ⬍0.016 ⬎256

0.016

syndrome (C-reactive protein ⬍ 1 mg/liter and blood culture negative in April 2014).

We report here a rare case of M. hominis infective endocarditis of a prosthetic valve diagnosed using 16S rDNA PCR and confirmed by valve culture. M. hominis is frequently responsible for urogenital tract infections but has been also isolated in other settings such as pneumonia, wound infections, joint infections, bacteremia, and central nervous system infections (4). During the past decade, the development of PCR analysis targeting the 16S rDNA sequence improved the method of etiological diagnosis of infective endocarditis (IE) (5). Consequently, unusual pathogens have been described in cases of IE. We report a case of M. hominis prosthetic valve endocarditis diagnosed by 16S rDNA PCR sequencing and confirmed by culture. This report emphasizes the exceptional role of Mycoplasma species in IE but

TABLE 2 Characteristics of cases of Mycoplasma infective endocarditis reported in the literature

Reference(s) or source

Delay between cardiac surgery and Infective endocarditis

Sexa

Age (yrs)

History of cardiac surgery

Species identified (method[s]) Treatment

Outcome

Cohen (7), DiSesa (8)

F

25

Several yrs

Mycoplasma hominis (culture)

M F

46 4

15 days 22 days

Mycoplasma hominis (culture) Mycoplasma hominis (culture)

Clindamycin and rifampin (6 wks) and doxycycline (4 wks), heart transplant Vancomycin and amikacin Clindamycin and levofloxacin

Survival

Blasco (9) Dominguez (10)

Aortic and mitral replacement for systemic lupus Mitral replacement Biventricular repair

Fenollar (11)

M

33

15 days

Survival

57

M

15

No

0

Vancomycin, gentamicin, and ceftriaxone Ceftriaxone and clarithromycin

Death

Scapini (12) Jamil (13)

M

40

9 yrs

Doxycycline and clindamycin (8 wks)

Survival

Hussain (14)

M

57

Our case

M

74

Aortic and mitral replacement Aortic valve replacement with a bioprosthetic valve Aortic and mitral valve replacement

Mycoplasma hominis (16S rDNA PCR) Ureaplasma parvum (16S rDNA PCR) Mycoplasma pneumoniae (culture) Mycoplasma hominis (16S rDNA PCR, culture) Mycoplasma hominis (16S rDNA PCR)

Doxycycline

F

Annuloplasty for valve mitral prolapses Aortic replacement

Mycoplasma hominis (16S rDNA PCR, culture)

Doxycycline and clindamycin (9 wks)

Survival

a

13 yrs

1 yr

6 mo

Death Death

Survival

F, female; M, male.

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Antibiotic

also the need to identify them accurately, especially by molecular methods such as 16S rDNA sequencing, as the prognosis of Mycoplasma IE is poor and specific treatment is needed. As Mycoplasma spp. are recognized as agents of IE (6), in order to evaluate their significance, we performed a review of literature on the PubMed database with the following key words: Mycoplasma and infective endocarditis. Only studies published in English were considered. Mycoplasma spp. are rarely responsible for IE. Indeed, we retrieved data for only 8 cases published in the literature (Table 2). All the cases, except one, occurred in patients with a history of cardiac surgery, particularly, of valve replacement (7–11, 13, 14). All the cases were due to M. hominis but one. The only case not related to cardiac surgery was due to Mycoplasma pneumoniae (12). In half of the cases, IE appeared in the first year following cardiac surgery, as reported in our case, suggesting possible nosocomial infection. Despite the fact that M. hominis nosocomial IE was never previously reported, M. hominis wound infections have been described after a caesarian procedure (15, 16) and sternotomy and may be responsible for mediastinitis (17–22). Eight cases of M. hominis mediastinitis (6 occurring after coronary artery bypass) were reported previously (21). In contrast to endocarditis, mediastinitis occurred only a few days after the surgery. Moreover, one report described three consecutive cases of wound infection due to M. hominis, suggesting nosocomial transmission of this pathogen (23). These observations therefore addressed the possibility of nosocomial transmission of M. hominis. Identification of Mycoplasma spp. is difficult, and the use of broad-range bacterial PCR is helpful to identify emerging pathogens in IE (24). In the cases previously reported, 4 of 8 species were identified by 16S rDNA PCR. In our case, the identification of M. hominis by PCR encouraged microbiologists to cultivate an aliquot of the resected valve stored at ⫺80°C both on nonspecific

Case Report

3.

4. 5.

6.

7. 8. 9.

10. 11. 12. 13.

14.

15.

16.

17.

ACKNOWLEDGMENTS

18.

We thank William Caule (Eurobio) for providing the media and broth used for mycoplasma cultures and Martine Maisonneuve for excellent technical assistance.

19.

REFERENCES 1. Harris KA, Hartley JC. 2003. Development of broad-range 16S rDNA PCR for use in the routine diagnostic clinical microbiology service. J Med Microbiol 52:685– 691. http://dx.doi.org/10.1099/jmm.0.05213-0. 2. Waites KB, Canupp KC, Kenny GE. 1999. In vitro susceptibilities of

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20. 21.

Mycoplasma hominis to six fluoroquinolones as determined by E test. Antimicrob Agents Chemother 43:2571–2573. Bébéar CM, de Barbeyrac B, Pereyre S, Renaudin H, Clerc M, Bébéar C. 2008. Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp., Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis. Clin Microbiol Infect 14:801– 805. http://dx.doi.org /10.1111/j.1469-0691.2008.02027.x. Taylor-Robinson D. 1996. Infections due to species of Mycoplasma and Ureaplasma: an update. Clin Infect Dis 23:671– 684. http://dx.doi.org/10 .1093/clinids/23.4.671. Breitkopf C, Hammel D, Scheld HH, Peters G, Becker K. 2005. Impact of a molecular approach to improve the microbiological diagnosis of infective heart valve endocarditis. Circulation 111:1415–1421. http://dx.doi .org/10.1161/01.CIR.0000158481.07569.8D. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, Moreillon P, de Jesus Antunes M, Thilen U, Lekakis J, Lengyel M, Müller L, Naber CK, Nihoyannopoulos P, Moritz A, Zamorano JL, ESC Committee for Practice Guidelines. 2009. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J 30: 2369 –2413. http://dx.doi.org/10.1093/eurheartj/ehp285. Cohen JI, Sloss LJ, Kundsin R, Golightly L. 1989. Prosthetic valve endocarditis caused by Mycoplasma hominis. Am J Med 86:819 – 821. http://dx.doi.org/10.1016/0002-9343(89)90479-8. DiSesa VJ, Sloss LJ, Cohn LH. 1990. Heart transplantation for intractable prosthetic valve endocarditis. J Heart Transplant 9:142–143. Blasco M, Torres L, Marco ML, Moles B, Villuendas MC, García Moya JB. 2000. Prosthetic valve endocarditis caused by Mycoplasma hominis. Eur J Clin Microbiol Infect Dis 19:638 – 640. http://dx.doi.org/10.1007 /s100960000333. Dominguez SR, Littlehorn C, Nyquist A-C. 2006. Mycoplasma hominis endocarditis in a child with a complex congenital heart defect. Pediatr Infect Dis J 25:851– 852. http://dx.doi.org/10.1097/01.inf.0000232639.81762.d4. Fenollar F, Gauduchon V, Casalta J-P, Lepidi H, Vandenesch F, Raoult D. 2004. Mycoplasma endocarditis: two case reports and a review. Clin Infect Dis 38:e21–24. http://dx.doi.org/10.1086/380839. Scapini JP, Flynn LP, Sciacaluga S, Morales L, Cadario ME. 2008. Confirmed Mycoplasma pneumoniae endocarditis. Emerg Infect Dis 14: 1664 –1665. http://dx.doi.org/10.3201/eid1410.080157. Jamil HA, Sandoe JAT, Gascoyne-Binzi D, Chalker VJ, Simms AD, Munsch CM, Baig MW. 2012. Late-onset prosthetic valve endocarditis caused by Mycoplasma hominis, diagnosed using broad-range bacterial PCR. J Med Microbiol 61:300 –301. http://dx.doi.org/10.1099/jmm.0 .030635-0. Hussain ST, Gordon SM, Tan CD, Smedira NG. 2013. Mycoplasma hominis prosthetic valve endocarditis: the value of molecular sequencing in cardiac surgery. J Thorac Cardiovasc Surg 146:e7– e9. http://dx.doi.org /10.1016/j.jtcvs.2013.03.039. Phillips LE, Faro S, Pokorny SF, Whiteman PA, Goodrich KH, Turner RM. 1987. Postcesarean wound infection by Mycoplasma hominis in a patient with persistent postpartum fever. Diagn Microbiol Infect Dis 7:193–197. http://dx.doi.org/10.1016/0732-8893(87)90004-6. Maccato M, Faro S, Summers KL. 1990. Wound infections after cesarean section with Mycoplasma hominis and Ureaplasma urealyticum. A report of three cases. Diagn Microbiol Infect Dis 13:363–365. http://dx.doi.org /10.1016/0732-8893(90)90002-D. Wilson ME, Dietze C. 1988. Mycoplasma hominis surgical wound infection: a case report and discussion. Surgery 103:257–260. Mossad SB, Rehm SJ, Tomford JW, Isada CM, Taylor PC, Rutherford I, Sorg S, McHenry MC. 1996. Sternotomy infection with Mycoplasma hominis: a cause of “culture negative” wound infection. J Cardiovasc Surg (Torino) 37:505–509. Marini H, Merle V, Frébourg N, Godier S, Bastit D, Benadiba L, Menguy E, Quesney M, Plissonnier D, Czernichow P. 2008. Mycoplasma hominis wound infection after a vascular allograft. J Infect 57:272– 274. http://dx.doi.org/10.1016/j.jinf.2008.06.003. Dan M, Robertson J. 1988. Mycoplasma hominis septicemia after heart surgery. Am J Med 84:976 –977. http://dx.doi.org/10.1016/0002-9343(88) 90085-X. Mattila PS, Carlson P, Sivonen A, Savola J, Luosto R, Salo J, Valtonen

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media (chocolate agar using a long time of incubation) and subsequently on specific Mycoplasma medium. The translucent colonies that initially grew on chocolate agar were subcultured on mycoplasma A7 medium and confirmed to be M. hominis by their typical fried-egg aspect and secondarily confirmed by 16S rDNA sequencing. In our case, since blood cultures were positive for Staphylococcus epidermidis, PCR performed directly on the valve contributed to the identification of M. hominis as the etiologic agent of this patient’s IE. S. epidermidis was retrospectively found to be responsible only for an arterial catheter infection. Broadrange PCR using primers for 16S rDNA and excised heart valves improves the diagnostic outcome of microbiological examinations (5, 25, 26). Consequently, British guidelines for IE management include positive results of broad-range PCR performed on excised heart valves as a minor criterion for IE (27). Physicians have to take into account the results of broad-range 16S rDNA PCR in IE for an appropriate choice of antibiotics (26). However, contamination and persistence of positive PCR several years after treatment of IE limit the use of broad-range PCR as a major criterion for IE diagnosis (28, 29). A delay between the appearance of clinical symptoms and identification of M. hominis as the causative agent was highlighted in a series of mediastinitis observations where the mean delay between obtaining sample and microbiological diagnosis was 9.1 days (21). In our case, a delay of 6 days occurred. In the published cases of IE and in our case, Mycoplasma spp. caused acute IE (7, 9–14), responsible for rapid hemodynamic failure. The prognosis of Mycoplasma IE is globally poor when adequate antibiotic is not administered, as summarized in Table 1. Only patients who received treatment with doxycycline and/or clindamycin survived (Table 2), as observed in our case, which is why we used this regimen. Of the 3 patients who died, 2 did not receive antibiotics active against Mycoplasma spp. Surprisingly, the European guidelines for management of infective endocarditis recommended treatment of Mycoplasma endocarditis with a new fluoroquinolone for a period of 6 months, but the evidence in support of such treatment is weak (6). In our case and in the other cases with favorable outcomes that we reviewed, doxycycline was usually used for 6 or 8 weeks (7, 8, 13). In conclusion, despite Mycoplasma IE being rare, with only 8 cases reported, it is a true cause of IE, notably in prosthetic heart valves in which nosocomial transmission of M. hominis is suspected. The prognosis of IE due to M. hominis remains poor, probably due to delays in diagnosis. 16S rDNA PCR performed on cardiac valves appeared very useful for diagnostic analysis. Our report and review suggest the use of doxycycline and/or clindamycin in Mycoplasma endocarditis and/or the adjunction of doxycycline in the recommended treatment for blood culture-negative IE (without prior antibiotic use).

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22.

23.

25.

26.

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Munthali P, NiRiain U, Hartley JC. 15 June 2014, posting date. Service evaluation to establish the sensitivity, specificity and additional value of broad-range 16S rDNA PCR for the diagnosis of infective endocarditis from resected endocardial material in patients from eight UK and Ireland hospitals. Eur J Clin Microbiol Infect Dis http://dx.doi.org/10.1007 /s10096-014-2145-4. 27. Gould FK, Denning DW, Elliott TSJ, Foweraker J, Perry JD, Prendergast BD, Sandoe JAT, Spry MJ, Watkin RW, Working Party of the British Society for Antimicrobial Chemotherapy. 2012. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 67:269 –289. http://dx.doi.org/10.1093/jac/dkr450. 28. Millar BC, Xu J, Moore JE. 2002. Risk assessment models and contamination management: implications for broad-range ribosomal DNA PCR as a diagnostic tool in medical bacteriology. J Clin Microbiol 40:1575– 1580. http://dx.doi.org/10.1128/JCM.40.5.1575-1580.2002. 29. Rovery C, Greub G, Lepidi H, Casalta J-P, Habib G, Collart F, Raoult D. 2005. PCR detection of bacteria on cardiac valves of patients with treated bacterial endocarditis. J Clin Microbiol 43:163–167. http://dx.doi .org/10.1128/JCM.43.1.163-167.2005.

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M. 1999. Life-threatening Mycoplasma hominis mediastinitis. Clin Infect Dis 29:1529 –1537. http://dx.doi.org/10.1086/313529. García-de-la-Fuente C, Miñambres E, Ugalde E, Sáez A, MartinezMartinez L, Fariñas MC. 2008. Post-operative mediastinitis, pleuritis and pericarditis due to Mycoplasma hominis and Ureaplasma urealyticum with a fatal outcome. J Med Microbiol 57:656 – 657. http://dx.doi.org/10 .1099/jmm.0.47632-0. Young H, Henao-Martínez AF, Miller A, Wilson M, Price CS. 2012. Cluster or coincidence? An unusual cause of surgical site infections in adult trauma patients. Am J Infect Control 40:e265– e267. http://dx.doi .org/10.1016/j.ajic.2012.06.007. Bosshard PP, Kronenberg A, Zbinden R, Ruef C, Böttger EC, Altwegg M. 2003. Etiologic diagnosis of infective endocarditis by broad-range polymerase chain reaction: a 3-year experience. Clin Infect Dis 37:167– 172. http://dx.doi.org/10.1086/375592. Fournier P-E, Thuny F, Richet H, Lepidi H, Casalta J-P, Arzouni J-P, Maurin M, Célard M, Mainardi J-L, Caus T, Collart F, Habib G, Raoult D. 2010. Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases. Clin Infect Dis 51:131– 140. http://dx.doi.org/10.1086/653675. Harris KA, Yam T, Jalili S, Williams OM, Alshafi K, Gouliouris T,

Mycoplasma hominis, a Rare but True Cause of Infective Endocarditis.

Mycoplasma spp. are rarely recognized agents of infective endocarditis. We report a case of Mycoplasma hominis prosthetic valve endocarditis diagnosed...
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