A subacute presentation of Mycoplasma hominis prosthetic valve endocarditis

Abstract

Mycoplasma hominis is a rare but important cause of prosthetic valve endocarditis. It is usually associated with acute progression of symptoms and can be difficult to diagnose as it does not grow in standard culture media. We report a case of an immunocompetent man in his 70s who presented with 14-month subacute decline with shortness of breath and evidence of a splenic infarct. Following a redo aortic valve replacement and diagnosis of M. hominis through 16S ribosomal ribonucleic acid PCR, he improved clinically with oral doxycycline therapy. He remained well at follow-up 2 years post-cessation of antibiotics. We present a literature review highlighting the role of PCR testing in the microbiological identification of M. hominis.

Background

Mycoplasma is a genus of bacteria that belongs to the Mycoplasmataceae family in the Mollicutes class. They are slow-growing species characterised by the absence of a cell wall, small genome and high nutritional demand, which makes them a challenge for the culture.¹ Mycoplasma hominis is frequently associated with urogenital infections but has been isolated in other settings, such as joint, respiratory, central nervous system and even endovascular infections.² The increasing use of molecular technology with broad-range 16S ribosomal ribonucleic acid (rRNA) PCR has improved the diagnostic yield of ‘culture-negative’ endocarditis. M. hominis infection is important to diagnose as it is resistant to standard empirical antibiotic therapy for endocarditis.

Case presentation

A man in his 70s was investigated for subacute shortness of breath and fevers 14 months following a bovine aortic valve replacement for a bicuspid aortic valve. Three months prior he had developed left upper quadrant pain and a CT abdomen demonstrated a splenic infarct. His previous medical history was significant for urinary tract infections, osteomyelitis of the shoulder and recurrent tonsillitis requiring tonsillectomy. He had type II diabetes, hypertension, a prior pulmonary embolus, gastro-oesophageal reflux and osteoarthritis but he was fully independent. Transoesophageal echocardiography showed moderate–severe transvalvular regurgitation with pannus formation and disintegration of the prosthesis causing prolapse, consistent with endocarditis. In retrospect, the splenic infarct was likely an embolic phenomenon from infective endocarditis. Blood cultures were negative, and he was commenced empirically on vancomycin and gentamicin. He proceeded to redo aortic valve replacement due to persisting fevers and heart failure refractory to medical management. 16S rRNA PCR was performed on the explanted valve which was positive for M. hominis. The gentamicin was ceased, and doxycycline at 100 mg two times daily orally was added for 8 weeks along with completion of 6 weeks of vancomycin with the resolution of symptoms.

Investigations

M. hominis is the cause of culture-negative endocarditis due to its high nutritional demand prohibiting the growth in standard media.¹ It also cannot be identified on Gram stain due to the absence of a cell wall. Since the 1990s, broad-range 16S rRNA PCR on valvular tissue has substantially changed the diagnostic yield in blood culture–negative endocarditis due to M. hominis. These assays target the highly conserved 16S ribosomal subunit which is common to all bacterial ribosomal genes. These genes are interspersed with variable regions which are genus or species specific.³ Nucleotide sequencing of the PCR product and comparison of known gene sequences with high-quality databases allows the identification of the organism to species level. Positive broad-range PCR for an organism consistent with infective endocarditis is now included as a minor diagnostic criterion for infective endocarditis in British guidelines.⁴ PCR is extremely sensitive, giving it a predilection to contamination and persistence of genetic material. However, it can provide a definitive diagnosis through the identification of M. hominis in the context of valve or endovascular prosthetic tissue collected aseptically. This molecular technique is important when patients have been pretreated with antibiotics or have an infection caused by non-cultivable or highly fastidious pathogens such as Mycoplasma species.³

Outcome and follow-up

Our patient returned to his daily activity of normal living after the cessation of antibiotics. He remained well on his follow-up telehealth appointment 2 years postsurgery and reported no issues.

Discussion

M. hominis is a rare but important cause of infective endocarditis in patients with prior valvular surgery or repair with 10 cases documented in the literature, as outlined in table 1. Two cases without valvular surgery were also identified. The first patient was a girl in her early childhood with a congenital heart malformation requiring biventricular repair who developed a right atrial and perivalvular abscess and died.⁵ The second patient was a man in his 60s who had an implantable cardioverter defibrillator (ICD) inserted following sustained monomorphic ventricular tachycardia secondary to structural heart disease.⁶ He developed M. hominis endocarditis requiring explantation of the ICD and improved clinically with moxifloxacin and doxycycline.

Table 1.

Cases of Mycoplasma hominis prosthetic valve endocarditis in the literature

Case (Ref.)	Age/sex	Time from surgery	Duration of symptoms	Prosthetic valve involved	Diagnosis	Targeted treatment (duration in weeks)	Outcome
112	25/F	3 months	Weeks	Aortic+mitral	Culture of tissue	Clindamycin+rifampicin (6); doxycycline (4)	Alive—heart transplant
210	46/M	15 days	Days	Mitral	Culture of tissue	Vancomycin+amikacin (1)	Died
313	33/M	6 months	Days	Mitral (repair)	PCR	Doxycycline (4)	Alive
414	48/M	2 months	Weeks	Aortic	Culture of tissue	Doxycycline+levofloxacin (8)	Alive
515	40/M	9 years	Weeks	Mitral	PCR+culture of tissue	Doxycycline+clindamycin (8)	Alive
611	57/M	1 year	Months	Aortic	PCR	Doxycycline+moxifloxacin (duration ND)	Alive
716	74/M	6 months	Days	Aortic	PCR+culture of tissue	Clindamycin+doxycycline (9)	Alive
817	54/M	7 months	Days	Aortic	PCR	Doxycycline+levofloxacin (8)	Alive
918	ND/F	1 year	Weeks	Tricuspid	PCR	ND	Died
1019	28/M	13 months	Weeks	Aortic	PCR	Moxifloxacin (8)	Alive—heart transplant
This report	ND/M	14 months	Months	Aortic	PCR	Doxycycline	Alive

ND, not disclosed.

Only 3 out of the 11 cases were diagnosed through the culture of the valve tissue alone. Two other cases later cultured M. hominis after special media were set up in response to the 16S rRNA flagging positive for M. hominis. This supports the role of molecular testing, which is likely to become an increasingly critical tool in improving outcomes from culture-negative endocarditis and also contribute to an improved understanding of the aetiology.⁷ Current international guidelines on endocarditis with reference to Dukes criteria do not include molecular testing, although this may change as more evidence in the role of direct molecular identification arises.^{8 9}

M. hominis is important to identify because it is intrinsically structurally resistant to aminoglycosides and beta-lactam antibiotics used in the empirical treatment of endocarditis.¹ Of the 10 cases of prosthetic valve endocarditis, two cases resulted in death; in one of these, a diagnosis of M. hominis endocarditis was not made until after death, demonstrating the need for prompt diagnosis to target antibiotic therapy.¹⁰

Doxycycline is the antibiotic of choice for M. hominis endocarditis, with a recommended duration of treatment generally between 6 and 8 weeks.⁶ Most case reports document a combination antibiotic regimen of doxycycline with either clindamycin or quinolone. Response appears to be generally favourable when the infection is diagnosed early.

Nine out of 11 reports of M. hominis prosthetic valve endocarditis describe an acute presentation with fevers and cardiac failure necessitating early surgery. In this case, there was a gradual prodrome of breathlessness and a splenic infarct 3 months prior to the diagnosis of infective endocarditis, suggesting a more subacute presentation. Similarly, Hussain et al¹¹ describe a case with a 6-month history of fatigue, breathlessness, intermittent chest pain and weight loss prior to redo cardiac surgery and subsequent diagnosis of M. hominis endocarditis. These cases demonstrate that although M. hominis is most commonly associated with acute endocarditis, subacute presentations are also possible.

Patient’s perspective.

It is with great pleasure to be able to add my comments to the BMJ. Regarding my case of Mycoplasma hominis, I had good health after my initial heart valve replacement (bovine). Then I started to get frequent urinary tract infections along with fevers and chest pain. Finally, I had a second valve replacement (mechanical). Thanks to the relentless efforts of my doctor, he finally found the root cause of my infections. Once I was on the correct antibiotics I started to make a full recovery. I haven't looked back since. I realise that I am one of the lucky ones, of the 10 or so cases of M. hominis in the literature to survive and enjoy my retirement. I recently had a total knee replacement on my left leg which has also given me a new lease of life. Thank you.

Learning points.

• Mycoplasma hominis is a rare but an important cause of infective endocarditis in patients with prosthetic cardiac valves.

• Identification of M. hominis is critical because it is not covered by empirical antibiotics.

• 16S ribosomal ribonucleic acid PCR allows the identification of fastidious organisms and has significantly increased the diagnostic yield of ‘culture-negative’ endocarditis.

• Although M. hominis typically causes acute endocarditis, subacute presentations are also possible.

Ethics statements

Patient consent for publication

Obtained.