Mycoplasma hominis, a Rare but True Cause of Infective Endocarditis

Abstract

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 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.

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

Antibiotic	MIC (mg/liter) determined by:
	SIR mycoplasma kit	Etest
Clindamycin	<2	<0.016
Doxycycline	<2	<0.016
Tetracycline	<2
Azithromycin	>4	>256
Erythromycin	>4
Josamycin	<2
Clindamycin	<2
Pristinamycin	<2
Ofloxacin	<1
Moxifloxacin		0.016

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 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 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.

TABLE 2.

Characteristics of cases of Mycoplasma infective endocarditis reported in the literature

Reference(s) or source	Sexa	Age (yrs)	History of cardiac surgery	Delay between cardiac surgery and Infective endocarditis	Species identified (method[s])	Treatment	Outcome
Cohen (7), DiSesa (8)	F	25	Aortic and mitral replacement for systemic lupus	Several yrs	Mycoplasma hominis (culture)	Clindamycin and rifampin (6 wks) and doxycycline (4 wks), heart transplant	Survival
Blasco (9)	M	46	Mitral replacement	15 days	Mycoplasma hominis (culture)	Vancomycin and amikacin	Death
Dominguez (10)	F	4	Biventricular repair	22 days	Mycoplasma hominis (culture)	Clindamycin and levofloxacin	Death
Fenollar (11)	M	33	Annuloplasty for valve mitral prolapses	15 days	Mycoplasma hominis (16S rDNA PCR)	Doxycycline	Survival
	F	57	Aortic replacement	13 yrs	Ureaplasma parvum (16S rDNA PCR)	Vancomycin, gentamicin, and ceftriaxone	Death
Scapini (12)	M	15	No	0	Mycoplasma pneumoniae (culture)	Ceftriaxone and clarithromycin	Survival
Jamil (13)	M	40	Aortic and mitral replacement	9 yrs	Mycoplasma hominis (16S rDNA PCR, culture)	Doxycycline and clindamycin (8 wks)	Survival
Hussain (14)	M	57	Aortic valve replacement with a bioprosthetic valve	1 yr	Mycoplasma hominis (16S rDNA PCR)
Our case	M	74	Aortic and mitral valve replacement	6 mo	Mycoplasma hominis (16S rDNA PCR, culture)	Doxycycline and clindamycin (9 wks)	Survival

^aF, female; M, male.

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 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. Broad-range 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).