Case description
A 2-year-old boy was followed-up for severe Langerhans cell histiocytosis for which he received chemotherapy through a totally implantable venous access port. During follow-up, he was evaluated in the emergency department because of a 3-day fever. His general condition was good. His blood test showed a high inflammatory syndrome (C-reactive protein at 218 mg/L), and his chest X-ray showed bilateral alveolar infiltration suggestive of acute pneumonia. Four blood cultures were collected on day 4 of illness, and ceftriaxone was prescribed. Blood cultures were all positive for Staphylococcus lugdunensis. The first result was considered as a contaminant. The second led to treatment with vancomycin. The third led to a vancomycin lock on the implantable venous access port, suspecting a catheter-related infection. The child was sent to our university hospital on day 10 of illness. His general condition remained good despite fever. Transthoracic echocardiogram performed on day 11 showed two vegetations on the septal leaflet of the tricuspid valve (largest: 13.1×14.3 mm) associated with mild tricuspid regurgitation (grade I/IV). S. lugdunensis antibiogram revealed resistance to penicillin G and susceptibility to oxacillin, vancomycin, and aminoglycosides. The treatment was modified as follows: vancomycin was administered for 4 days, with gentamicin; and ceftriaxone was continued for 2 days and then switched to oxacillin. The implantable venous access port was removed on day 13 and was culture positive for S. lugdunensis. The blood culture cleared on day 13. Apyrexia appeared on day 15. On assessment, a CT scan showed a bilateral pneumonic lower lobe infarction and a left pulmonary artery embolism. In the following echocardiographies performed twice a week, the predominant tricuspid vegetation increased (21×14 mm) and tricuspid insufficiency worsened (grade II/IV). Surgical resection of the vegetations and tricuspid valvuloplasty were performed on day 30 because of the size of the vegetation and the risk of recurrent embolism. Oxacillin was continued for 6 weeks. After 3 years, limited mobility of the tricuspid septal leaflet with mild tricuspid insufficiency was persistent (Fig 1: per operative view).
Figure 1 Per operative view showing 2 vegetations (arrow) on the septal leaflet of the tricuspid valve
Materials and methods
Our literature review covered the period between 1988 and 2015 of S. lugdunensis-related endocarditis in children using the keywords “Staphylococcus lugdunensis”, “endocarditis”, “children” in PubMed, Medline, and Google Scholar databases. Symptoms at onset, diagnosis delay, co-morbidities, echocardiographic findings, embolic events, antibiotherapy, surgery, and outcome were evaluated. Synthesis of data is expressed as medians with quartiles or percentages.
A cursory review for S. lugdunensis endocarditis in adults was also undertaken.
Results
In all, nine patients were depicted including our case.Reference Jones, Jackson, Ong and Lofland 1 – Reference Chaparro, Murphy and Davis 6 We excluded two cases because of incomplete data. The median age was 13 years [6.0–15.5] with five males. In all, four patients had CHD, including aortic stenosis in three and a ventricular septal defect in one; two patients had associated conditions including sickle cell anaemia and Langerhans cell histiocytosis. The median duration of symptoms before diagnosis was 3.4 weeks (with a range from 2 to 6 weeks). No infection gateway was identified in five cases. Out of seven patients, five had positive blood cultures for S. lugdunensis, susceptible to penicillin and/or oxacillin. All were susceptible to vancomycin and aminoglycosides. In one case, S. lugdunensis was primarily misdiagnosed by routine technique. Echocardiographic findings showed large vegetations in all cases, with aggressive damage of the leaflets. Embolic events were documented in three cases (42.8%). Medical treatment was not sufficient although adequate antibiotherapy was conducted. Surgery was needed in all cases but was not performed in one patient because of neurological involvement. This patient died from brain herniation (Table 1).
Table 1 Clinical and microbiological features, treatment, and outcome of the seven children with Staphylococcus lugdunensis endocarditis identified in our review of the last 28 years.
AV=aortic valve; F=female; LV=left ventricle; M=male; MR=mitral regurgitation; MV=mitral valve; RA=right atrium; TIVAP=totally implantable venous access port; TR=tricuspid regurgitation; TV=tricuspid valve; VSD=ventricular septal defect; y=years of age
Discussion
S. lugdunensis is a novobiocin-susceptible, coagulase-negative Staphylococcus, a commensal of the skin and mucous membranes. In contrast to other coagulase-negative Staphylococcus, it has virulence factors similar to Staphylococcus aureus – toxin secretion, resistance to lysozyme, adhesion via binding protein, biofilm formation, etc. –leading to a destructive course with abscess formation and embolus.Reference Frank, Del Pozo and Patel 7 S. lugdunensis is responsible for serious infections including endocarditis or toxic shock syndrome. Owing to these virulence factors, it is recommended to search for other locations in case of bacteraemia with S. lugdunensis Reference Zinkernagel, Zinkernagel and Elzi 8 and not considering it as a contaminant when at least two blood cultures are positive.
It has been reported that S. lugdunensis bacteraemia is associated with endocarditis in 50% of cases,Reference Zinkernagel, Zinkernagel and Elzi 8 is responsible for 18% of infective endocarditis due to coagulase-negative Staphylococcus,Reference Frank, Del Pozo and Patel 7 and accounts for 1.1% of infective endocarditis.Reference Anguera, Del Rio and Miro 9 These numbers are probably underestimated because S. lugdunensis can be missed by routine identification procedures or can produce clumping factors and then be misidentified as S. aureus. Some authors have recommended sequencing the 16S ribosomal DNA specific to S. lugdunensis in patients with endocarditis,Reference Surinder, Lye, Leo and Barkham 10 especially when blood cultures are negative to avoid missing this bacterium. At present, optimisation of identification methods is helpful to increase the rate of S. lugdunensis detection. In our case, ignorance of these virulence factors was deleterious because of delay in antibiotics adaptation and the search for secondary locations. In endocarditis, S. lugdunensis affects cardiac structures with an aggressive course and a propensity for embolisation.
Less than 100 cases of S. lugdunensis endocarditis have been reported in adults. A study showed that S. lugdunensis mainly affected the native valves,Reference Anguera, Del Rio and Miro 9 and had high complication rates including heart failure, abscess formation, and embolism with a mortality rate of 42%. S. lugdunensis is usually susceptible to β-lactam agents, aminoglycosides, macrolides, and vancomycin, although antimicrobial resistance has been described even during treatment;Reference Kragsbjerg, Bomfim-Loogna, Tornqvist and Soderquist 11 however, despite appropriate antimicrobial therapy, S. lugdunensis infection progresses, and surgery is often required to improve the prognosis. Some authors have shown that surgery is necessary in 51% of cases, and patients treated with antibiotics and surgery had a better prognosis than those with medical treatment alone.Reference Anguera, Del Rio and Miro 9 Those authors have thus recommended early surgery.
Although our paediatric review reported only seven cases, the evolution was marked by a propensity for large vegetations, valve destruction, and embolic events despite appropriate antibiotherapy and the need for surgery as described in adults.
Conclusion
Blood cultures should be repeated even if one is positive for S. lugdunensis to confirm true infection, which should lead to search for secondary locations, particularly endocarditis. In endocarditis, early surgery associated with antimicrobial therapy is highly recommended. Delaying surgery could worsen the outcome because of the progression of cardiac damage and high risk for embolic events.
Acknowledgements
None.
Financial Support
This research received no specific grant from any funding agency or from commercial or not-for-profit sectors.
Conflicts of Interest
None.
Ethical Standards
The authors assert that all procedures reported comply with the ethical standards of the Helsinki convention, and consent for publication was obtained from the patient’s family.
