Infective Endocarditis Caused by Neisseria Sicca Species 10 Years After Mechanical Aortic Valve Implantation

Introduction

Neisseria mucosa/sicca, a gram-negative diplococcus of the Neisseria (N). genus, is typically regarded as a nonpathogenic species that inhabits the oropharyngeal mucosa of healthy individuals. Usually, infective endocarditis (IE) is caused by gram-positive pathogens, gram-negative organisms, including HACEK group bacilli, are rarely reported. IE caused by gram-negative organisms is rare, especially for other Neisseria species, except for N. menigitidis and N. gonorrhoeae.¹ Here, we report a rare case of Neisseria sicca mechanical aortic valve infective endocarditis, offering valuable insights for clinical diagnosis and treatment.

Case Presentation

A 44-year-old man was admitted to our department after experiencing a 10-day history of fever (highest temperature 39.0°C) accompanied by chills and headache. He denied cough, sputum production, hemoptysis, or any other discomfort. He had a history of aortic stenosis, had received mechanical aortic valve replacement 10 years prior, and had taken warfarin as an anticoagulant. The patient denied any history of hypertension, diabetes, needle-sharing, intravenous drug use, or other systemic diseases.

On admission, the patient was febrile with a temperature of 38.7°C, a heart rate of 102 beats per minute, a blood pressure of 100/70 mmHg, a respiratory rate of 21 breaths per minute, and an oxygen saturation of 97% in room air. A physical examination revealed poor dentition and a holosystolic murmur at the right sternal border without radiation. Janeway’s lesions, Osler’s nodes, Roth’s spots, and conjunctival hemorrhage were not observed. Laboratory examination showed the following: white blood cell, 12.74×10⁹/L (normal: 4–10×10⁹/L) with a neutrophil rate of 89.3%, hemoglobin level of 129 g/L (normal: 120–160 g/L), and platelet count of 303×10⁹/L (normal:100–300×10⁹/L). Blood chemistry showed an erythrocyte sedimentation rate (ESR) of 15 mm/h (normal <20 mm/h), C-reactive protein (CRP) was 45.93 mg/L (normal <20 mg/L), procalcitonin (PCT) was 9.19 ng/mL (normal <0.05 ng/mL). His chest, abdomen, and head CT showed no abnormalities. And his vascular ultrasound also showed no abnormalities. Transthoracic echocardiography (TTE) revealed a slight increase in the forward flow rate of the mechanical valve after the aortic mechanical valve replacement. No significant perivalvular leakage was observed (Figure 1).

Figure 1 Transthoracic echocardiogram revealed a slight increase in the forward flow rate of the mechanical valve after aortic mechanical valve replacement. Abbreviations: Vmax, maximum speed; Vmean, average speed; Max PG, maximum pressure gradient; Mean PG, average pressure gradient; VTI, velocity-time integral.

After blood cultures were drawn, the patient was started on empirical antimicrobial therapy with vancomycin, gentamicin, and rifampicin. However, the patient showed no signs of recovery after the application of antibiotics, in terms of temperature and inflammatory markers. By 48 h of culture, two aerobic bottles in the BACTEC system (Becton Dickinson) grew gram-negative diplococci with dry and wrinkled colonies on chocolate agar, which were later identified as Neisseria mucosa/sicca using VITEK MS (Biomérieux). Further evaluation with a transesophageal echocardiogram (TEE) revealed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve and a mild increase in regurgitant flow through the prosthetic aortic valve compared with TTE (Figure 2). The patient was evaluated by cardiothoracic surgery but refused surgical intervention. The therapy was then switched to ceftriaxone and rifampicin. However, the patient temperature and biological parameters have not yet been alleviated. A further antibiotic susceptibility test (AST) for Neisseria mucosa/sicca was performed in the clinical laboratory (Table 1). Because there were no antimicrobial breakpoints for Neisseria mucosa/sicca, we used the antimicrobial breakpoint of the Clinical and Laboratory Standards Institute (CLSI) for Neisseria meningitidis as a reference. The results indicated that meropenem, TMP-SMX, chloramphenicol, and minocycline were susceptible, penicillin, azithromycin, ciprofloxacin, and cefotaxime were resistant or unsusceptible, and rifampicin was intermediate. Therefore, treatment was switched to meropenem and minocycline. Thereafter, the patient’s condition rapidly improved. Two weeks later, the patient’s biological parameters recovered, and reinspection blood cultures were negative; however, a repeat TTE still revealed an increase in the size of the aortic valve vegetation (0.7 cm × 0.2 cm). Rifampicin was added to synergize the anti-infective effects of meropenem and minocycline. After six weeks of therapy, the patient’s biological parameters had almost returned to normal, repeat blood cultures were negative, and a repeat TTE revealed smaller vegetation. The patient was discharged with oral treatment of rifampicin, TMP-SMX, and minocycline. After eight weeks of therapy, the patient’s blood cultures remained negative, and a repeat TEE (Figure 3) showed no vegetation. Therefore, the antibiotic therapy was discontinued. After more than one year of follow-up, the patient remained in good condition, and the patient’s TTE was negative (Figure 4). Here we made a timeline of patient events and treatment decisions to facilitate readers to better inform the diagnosis and treatment process (Table 2).

Table 1 Antibiotic Susceptibility Test for Neisseria Mucosa/Sicca

Table 2 The Timeline of Events and Therapeutic Decisions

Figure 2 Transesophageal echocardiogram showed a 0.5*0.3cm vegetation attached to the aortic valve (yellow arrow) complicated by mild aortic regurgitation.

Figure 3 Three-dimensional transesophageal echocardiography showed no vegetation attached to the aortic valve (yellow arrow).

Figure 4 Transthoracic echocardiogram showed no vegetation attached to the aortic valve, and the forward flow rate of the mechanical valve after aortic mechanical valve replacement is normal. Abbreviations: Vmax, maximum speed; Vmean, average speed; Max PG, maximum pressure gradient; Mean PG, average pressure gradient; VTI, velocity-time integral.

Discussion

In the genus Neisseria, N. meningitidis and N. gonorrhoeae are the only species that cause serious infectious diseases. N. gonorrhoeae infections can also cause infective endocarditis. N. meningitidis is the main cause of bacterial meningitis, but rarely causing infective endocarditis. Worldwide, infective endocarditis caused by commensal Neisseria (such as N. elongata, N. subflava, N. lactamica, N. cinerea, N. skkuensis, or N. mucosa) is rare.² Among these, N. elongate was the most common cause of IE (38.4% of the patients described in the literature), followed by N. mucosa (36.4%).² N. sicca is phenotypically similar to N. mucosa and is thought to be a variant of N. mucosa.³ However, it is difficult to identify these two species using phylogenetic taxonomic methods. In our case, we observed dry and wrinkled colonies on chocolate agar and identified them as N. mucosa/sicca using VITEK MS (Biomérieux). Thus, we hypothesized that the organism in our case was N. sicca based on colony morphology. However, our results may need to be carefully verified as we did not conduct whole-genome sequencing or biochemical tests on these bacteria. Furthermore, these two species typically exhibit variable phenotypic characteristics.

Only 26 cases of N. sicca endocarditis have been previously reported.^4–6 All patients except one (96.1%) received β-lactam based therapy: penicillin (n = 4), penicillin and gentamicin (n = 9), penicillin and streptomycin (n = 2), penicillin and netilmicin (n = 1), ceftriaxone (n = 2), ceftriaxone and gentamicin (n = 3), ceftriaxone and gentamicin and ciprofloxacin (n = 3), ceftriaxone and gentamicin and rifampicin (n = 1), and ciprofloxacin (n = 1). There is no resistance to β-lactam in these patients. Death was reported in 23.1% of cases (6/26) after therapy.^4–7 Most reports have described intravenous drug abuse, underlying heart disease, poor dentition, and prosthetic valves as the main risk factors of N. sicca endocarditis.⁷ In our case, poor dentition and prosthetic valves made the patient susceptible to infection with this organism. Typically, N. sicca causes severe endocarditis of the mitral valve.⁸ Our case showed aortic valve vegetation. To our knowledge, endocarditis involving this valve usually causes fatal outcomes and poor prognosis. Approximately 90% of the literature reports that N. sicca causes severe endocarditis with embolic events.⁹ In this patient, embolic phenomena did not occur in the skin, conjunctives, or other main organs.

Echocardiographic positivity is a major clinical criterion for IE diagnosis. Transesophageal echocardiography commonly has a higher rate of valve vegetation detection than transthoracic echocardiography (96–100% vs 77%).¹⁰ The initial transthoracic echocardiography for the patient described did not show valve vegetation, but a repeat transesophageal echocardiogram (TEE) revealed a 0.5 cm × 0.3 cm aortic valve vegetation. Thus, a repeat TEE is warranted if there remains high suspicion of IE even the initial TTE is negative. Blood culture and excised valve tissue culture are other major clinical criteria for IE. In our case, two separate aerobic bottles grew N. sicca in 48h after culture, excluding contamination. However, N. sicca is not a typical IE bacterium according to the modified Duke criteria, which has made it difficult to definitively diagnose IE.

In our case, an antibiotic susceptibility test (AST) for Neisseria mucosa/sicca was performed. Because there was no antimicrobial breakpoint for this strain, we used the antimicrobial breakpoint of CLSI for Neisseria meningitidis as a reference. The results showed Neisseria mucosa/sicca has different antibiotic susceptibilities to Neisseria meningitidis; meropenem, TMP-SMX, chloramphenicol, and minocycline were susceptible, whereas penicillin, azithromycin, ciprofloxacin, and cefotaxime were resistant or unsusceptible, and rifampicin was intermediate. Few studies have reported the antibiotic susceptibility of Neisseria mucosa/sicca. A previous study reported that the strain was susceptible to penicillin in high-dose treatment; however, they found that the mitral valve mass increased in size after penicillin treatment.¹¹ Our patient’s vegetation decreased after receiving intravenous rifampicin, meropenem, and minocycline followed by oral rifampicin, TMP-SMX, and minocycline. No vegetation was observed after eight weeks of therapy.

The current European Society of Cardiology (ESC) and American Association for Thoracic Surgery (AATS) guidelines suggest that surgical intervention for IE should be considered in patients with congestive heart failure, uncontrolled infection, repeated embolic events, or right-sided IE.¹² According to the literature, approximately half of IE patients with Neisseria species infection undergo surgical replacement.¹³ Although the patient we reported had no symptoms of heart failure and the aortic valve vegetation did not exceed 10 mm in size, he had surgical indications that IE was triggered by an extensively resistant N. sicca. Upon Discussion with the patient, he refused surgical therapy. We could only add rifampicin to synergize the anti-infective effects of meropenem and minocycline when the repeat TTE showed an increased vegetation size. Several studies have shown that Neisseria species cause IE with a high degree of destruction of the native valve.¹⁴ And death have been reported in a patient with aortic valve IE due to N. sicca.⁹ Therefore, early surgical therapy may be a rational choice for such patients.

Conclusion

This report presents a rare case of infective endocarditis of the mechanical aortic valve caused by Neisseria sicca. There is insufficient clinical experience in the diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics. Patients with IE should consider Neisseria strain infection when primary empirical anti-infectious treatment is ineffective, especially when the following high-risk factors are present: intravenous drug abuse, underlying heart disease, poor dentition, or prosthetic valves. Although the reported mortality of the Neisseria strain is low, vegetation of the aortic valve may cause a fatal outcome. Early surgical therapy may still be a rational choice for N. sicca causing IE, because this strain exhibits extensive resistance to antibiotics.