Case Report 89
Recurrent Infective Endocarditis due to Aggregatibacter aphrophilus and Staphylococcus lugdunensis Rezidivierende infektiöse Endokarditis verursacht durch Aggregatibacter aphrophilus und Staphylococcus lugdunensis Authors
L. Hidalgo-García1, A. Hurtado-Mingo2, P. Olbrich1, A. Moruno-Tirado1, O. Neth1, I. Obando1
Affiliations
1
Key words ▶ infectious endocarditis ● ▶ congenital heart disease ● ▶ Staphylococcus lugdunensis ● ▶ Aggregatibacter aphrophilus ●
Abstract
Zusammenfassung
Uncommon microorganisms are increasingly being recognized as causative agents of paediatric infectious endocarditis (IE). We report a 4-year old girl with congenital heart disease, who suffered from 2 IE episodes secondary to Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus) and Staphylococcus lugdunensis, both rarely reported pathogens in this age group. The patient was initially successfully treated with prolonged intravenous antibiotic courses, however removal of the Contegra valved conduit during the second episode was required due to recurrence of fever and development of pulmonary embolism despite completion of antibiotic therapy. A. aphrohilus is a member of the fastidious gram negative microorganisms of the HACEK group (Haemophilus spp., Aggregatibacter spp, Cardiobaterium hominis, Eikenella corrodens and Kingella kingae), that colonize the oropharynx and are a recognised cause of IE. Prognosis of children with IE due to HACEK group members varies, half of them suffering from complications and mortality rates of 10–12.5 %. Although S. lugdunensis belongs to coagulase negative staphylococci (CONS), it behaves more like S. aureus species rather than CONS. This microorganism is a well-described cause of endocarditis in adult patients, associated with high requirements of surgical procedures and mortality (42–78 %). In conclusion, paediatric IE can be caused by uncommon microorganisms associated with severe complications and potential fatality. The isolation of S. lugdunensis or A. aphrophilus in febrile patients should be considered clinically relevant and cardiac involvement must be ruled out. Those patients with proved IE will require prolonged intravenous antibiotic courses and in complicated cases surgical intervention.
Ungewöhnliche Mikroorganismen, als Ursache pädiatrischer infektiöser Endokarditiden (IE) werden zunehmend berichtet. Wir berichten über ein 4 Jahre altes Mädchen mit angeborenem strukturellem Herzfehler, welche zwei sekundäre, durch A. aphrophilus (früher Haemophilus aphrophilus) und Staphylococus lugdunensis verursachte, IE erlitt, wobei die kausale Identifizierung dieser Keime sehr ungewöhnlich in dieser Altersgruppe ist. Bei diesem Kind war ein konservativer Therapieansatz mit langdauernder intravenöser Antibiotikagabe inital erfolgreich, erneute Fieberschübe und Auftreten einer pulmonarer Embolien während der zweiten IE Episode machten jedoch die Enfernung des “Contegra valved conduit” erforderlich. A. Aphrophilus gehört zu den Gram-negativen Mikroorganismen der HACEK Gruppe (Haemophilus spp., Aggretatbacter spp., Cardiobacterium hominis, Eikenella corrodens und Kingella kingae), welche den Oropharynx kolonisieren und als Erreger der IE bekannt sind. Die Prognose für HACEK bedingte IE im Kindesalter ist sehr variable mit Folgeschäden in der Hälfte der Patienten und einer Mortalitätsrate von 10-12.5%. Obwohl S. lugdunensis zu den koagulase negativen Staphylokokken gehört, zeigt dieser Mikroorganismus ein S. aureus ähnliches Virulenzverhalten. Bei S. lugdunensis handelt es sich um einen gut beschriebenen Verursacher der IE im Erwachsenenalter, welcher gehäuft chirurgische Interventionen benötigt und mit hohen Mortalitätsraten (42-78%) verbunden ist. Pädiatrische IE können durch ungewöhnliche Keime verursacht und mit schweren Komplikationen und potentieller Letalität assoziert sein. Zusammenfassend sollte die Identifikation von S. lugdunensis oder A. aphrophilus in Blutkulturen febriler Kinder als klinisch relevant betrachtet und kardiologische Untersuchungen erwägt werden. Patienten mit bestätigter IE erfordern eine prolongierte antibio tische Behandlung und möglicherweise kardiochirurgischer Interventionen.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1398536 Klin Padiatr 2015; 227: 89–92 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Ignacio Obando Hospital Universitario Virgen del Rocío Pediatrc Infectious Diseases and Immunopathology Manuel Siurot s/n Seville 41013 Spain Tel.: + 34/660/522 448 Fax: + 34/955/012 921 [email protected]
Hospital Universitario Virgen del Rocío, Pediatric Infectious Diseases and Immunopathology, Seville, Spain Hispalense Institute of Pediatrics, Seville, Spain
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Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
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Schlüsselwörter ▶ infektiöse Endokarditis ● ▶ angeborene Herzfehler ● ▶ Staphylococcus lugdunensis ● ▶ Aggregatibacter aphrophilus ●
2
Introduction
▼
Infective endocarditis (IE) is an infection of the cardiac endothelium associated with high morbidity and mortality rates. Although the incidence of IE in the paediatric population is low, an increasing number of paediatric IE cases has been reported over the last years, probably related to improved survival rates of children suffering from congenital heart disease [7, 18]. HACEK group members (Haemophilus spp, Aggregatibacter spp, Cardiobaterium hominis, Eikenella corrodens and Kingella kingae), are increasingly being recognized in paediatric IE cases and represent the most common gram negative IE pathogens in childhood [5, 6, 8]. Although Streptococcus viridans was the leading microorganism causing endocarditis, Staphylococcus aureus and coagulase-negative staphylococci (CONS) are now increasingly reported [5, 9, 15, 22]. Staphylococcus lugdunensis is an emergent member of the CONS group in the context of IE due to its high destructive potential both, on prosthetic as well as on native valves [14, 23]. Here, we report a young child suffering from 2 IE episodes secondary to Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus) and S. lugdunensis, both very rarely reported pathogens in this age group.
Case report
▼
A 4-year old girl was admitted with a 3-week history of fever and respiratory distress. At 2 years of age a D-transposition of the great arteries with ventricular septal defect and pulmonary stenosis was corrected according to the Rastelli procedure with Contegra valved conduit (CVC) placement. On admission signs of cardiac insufficiency, anemia (hemoglobin 7.4 g/dl) and raised acute phase reactants (CRP 118 mg/l) were noted. Bacterial endocarditis was suspected and empirical treatment with penicillin G (300 00 IU/kg/d in 4 doses) and gentamicin (3 mg/kg/24 h) was started. A. aphrophilus (HACEK group) was isolated and antimicrobial management was modified accordingly to intravenous ceftriaxone (100 mg/kg/24 h). An echocardiography revealed a 4 × 5 mm vegetation at the pulmo▶ Fig. 1). Due to the nary side of the prosthetic valved conduit ( ● prompt clinical response (remitting fever and decreased inflammatory markers), the prosthetic material was not removed. She was discharged after an 8 week course of intravenous antibiotics although only a minimal decrease of the vegetation (2 × 2 mm) was documented in a control echocardiography.
Fig. 1 Echocardiogram showing a 4 × 5 mm vegetation related to the pulmonary side of the Contegra valved conduit.
2 years later she became readmitted with a 16 days history of fever (39.9 ºC), being otherwise asymptomatic. Echocardiography at admission revealed an 8 × 10 mm vegetation of the CVC, contiguous to the outflow-tract of the right ventricle. Serial echocardiography disclosed 2 new vegetations. A full blood count (FBC) revealed anaemia (haemoglobin 9.2 g/dl), leucocytosis (15 870/mcl) with neutrophilia (79 %) and a markedly raised CRP (221 mg/L). Intravenous ceftriaxone and gentamicin were started empirically and after isolation of S. lugdunensis, (CMI to penicillin ≤ 0.03 mg/ml) therapy was switched to iv pencillin G (200 00 IU/kg/d in 4 doses), rifampicin (20 mg/kg/d) both for 6 weeks, and gentamicin (3 mg/kg/d) for 2 weeks resulting in an excellent clinical response with decreased inflammatory markers, negative blood cultures, resolution of one vegetation and size reduction of the vegetation related to the pulmonary side of the CVC (4 × 5 mm). One week after discharge the patient was readmitted with high fever, cough and respiratory distress. FBC revealed leukocytosis (15 200/mcl), raised CRP 157 mg/L, and DDimers 107 968 mcg/L. Blood culture was negative. The echocardiography showed 2 vegetations (3 × 6 and 5 × 6 mm respectively). A chest CT scan was suggestive of a pulmonary embolism. At this stage removal of the foreign material with placement of a new CVC was decided. due to the fact that there was not an available pulmonary homograft for the patient at that time. Prolonged culturing and histopathology of the removed prosthetic material did not identify microorganisms. The patient was discharged in excellent clinical state without showing infectious complications over the last 2 years. However, 9 months after her last admission she developed severe left ventricular dysfunction due to compression of the anterior descending right coronary artery by the prosthetic material, requiring CVC replacement.
Discussion
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In this case report a child experienced 2 episodes of IE related to prosthetic material caused by 2 unusual pathogens known to be associated with high morbidity and potential mortality. S. lugdunensis generally colonizes the skin and infrequently causes invasion [10]. Although it belongs to CONS, it is far more virulent with a behaviour more similar to S. aureus [1, 10, 14]. Virulence factors that contribute to the increased pathogenic potential have not been fully elucidated but include a heat-stable δ-like haemolysin produced by most S. lugdunensis isolates, agr and slush loci, as well as OatA, a membrane bound acetyltransferase, that confers resistance to lysozyme and adhesins, such as fbl and vWbl [1, 10]. S. lugdunensis has been mostly isolated from adult patients in context with a wide spectrum of clinical diseases including cardiovascular, urinary tract, CONS, bone and joint and soft-tissue infections, bacteremia, endophtalmitis and peritonitis [1, 10]. S. lugdunensis is a well-described cause of endocarditis affecting both native and prosthetic valves in adults [1, 10, 14]. As in our case, these infections may produce suppurative complications, heart failure and peripheral embolisms. Manifestations of IE are not typically caused by CONS, and are associated with high requirements of surgical procedures and mortality rates; being 42 % in case of native and 78 % of prosthetic valve IE [1, 10]. To date only 4 patients younger than 18 years with IE due to S. lugdunensis have been reported with a median age of 11 years (range 5 to 16 years) [13, 15, 17, 23]. Site of infection involved native valve in 3 patients, predominantly affecting the left side
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
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90 Case Report
Case Report 91 Contributorʼs statement
▼
L. Hidalgo-García: acquistion of data and drafting the manuscript, A. Hurtado-Mingo: acquisition of data and drafting the manuscript, P. Olbrich: drafting and revising the manuscript, A. Moruno-Tirado: acquistion of data, O. Neth: revising the manuscrpt, I. Obando: study design, drafting and revising the manuscript
Conflict of interest: I have read and understood the document “Conflict of Interest”. Being the corresponding author of the manuscript, I declare that my co-authors informed me that they did not have economic or personal relations according to the explanations given in the document “Conflict of Interest” within the past 3 years. Nor did I myself have such relationships within the past 3 years. References
1 Babu E, Oropello J. Staphylococcus lugdunensis: the coagulase-negative staphylococcus you don’t want to ignore. Expert Rev Anti Infect Ther 2011; 9: 901–907 2 Baddour LM, Wilson WR, Bayer AS et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005; 111: e394–e434 3 Bieger RC, Brewer NS, Washington JA. Haemophilus aphrophilus: a microbiologic and clinical review and report of 42 cases. Medicine 1978; 57: 345–354 4 Chambers ST, Murdoch D, Morris A et al. Hacek infective endocarditis: characteristics and outcomes from a large, multi-national cohort. PLoS One 2013; 8: e63181 5 Di Filippo S, Delahaye F, Semiond B et al. Current patterns of infective endocarditis in congenital heart disease. Heart 2006; 92: 1490–1495 6 Feder HM, Roberts JC, Salazar JC et al. HACEK endocarditis in infants and children: two cases and a literature review. Pediatr Infect Dis J 2003; 22: 557–562 7 Ferrieri P, Gewitz MH, Gerber MA et al. Unique features of infective endocarditis in childhood. Pediatrics 2002; 109: 931–943 8 Foster MA, Walls T. High rates of complications following Kingella kingae infective endocarditis in children: a case series and review of the literature. Pediatr Infect Dis J 2014; 33: 785–786 9 Fowler VG Jr, Miro JM, Hoen B et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 2005; 293: 3012–3021 10 Frank KL, Del Pozo JL, Patel R. From clinical microbiology to infection pathogenesis: how daring to be different works for Staphylococcus lugdunensis. Clin Microbiol Rev 2008; 21: 111–133 11 Geraci JE, Wilkowske CJ, Wilson WR et al. Haemophilus endocarditis: report of 14 patients. Mayo Clin Proc 1977; 52: 209–215 12 Habib G, Hoen B, Tornos P et al. 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 2009; 30: 2369–2413 13 Jones RM, Jackson MA, Ong C et al. Endocarditis caused by Staphylococcus lugdunensis. Pediatr Infect Dis J 2002; 21: 265–268 14 Lin Y-T, Hsieh K-S, Chen Y-S et al. Staphylococcus lugdunensis infective endocarditis: a literature review and analysis of risk factors. J Microbiol Immunol Infect 2010; 43: 478–484 15 Lin Y-T, Hsieh K-S, Chen Y-S et al. Infective endocarditis in children without underlying heart disease. J Microbiol Immunol Infect 2013; 46: 121–128 16 Mesko ZG, Bauza J, Vinas C. Bacterial endocarditis due to Hemophilus aphrophilus with cerebral embolism. J Pediatr 1976; 89: 1031–1032 17 Murillo J, McMahon C, Starr J. Large vegetations in Staphylococcus lugdunensis endocarditis. Heart Lung 2008; 37: 479–480
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
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of the heart. All but one patient, with a previous history of recurrent skin and soft tissue infections, had congenital heart disease. These 3 cases were treated with surgery and combined intra venous antibiotics (median 56 days (range 42 to 62 days) with a good overall outcome, except for one patient who had a residual tricuspid valve regurgitation. No information was available regarding management and outcome of the fourth patient. In our patient repeated prolonged treatment with a combination of 2 antibiotics, according to the IE guidelines for staphylococci infections of prosthetic valves was administered [2, 12]. How ever, removal of the prosthetic material was necessary in order to clear the infection. A. aphrophilus is a member of the HACEK group, which are fastidious gram negative microorganisms that colonize the oropharynx and have long been recognised as a cause of IE [4, 19]. This manifestation and cerebral abscesses are the most frequent invasive infections due to A. aphrophilus. The most prevalent risk factor of IE due to A. aphrophilus and other members of the HACEK group is congenital heart diseases, however a significant proportion of paediatric IE caused by these microorganisms occurred in patients with normal hearts [6, 8]. Current guidelines recommend the use of ceftriaxone as the first line therapy for IE due to the HACEK group, taking into account their potential to produce beta lactamases and the difficulty in the interpretation of the antibiotic sensitivity [2, 12]. In the subgroup of paediatric IE, A. aphrophilus is the 3rd most relevant HACEK pathogen after K. kingae and H. parainfluenzae with 6 cases reported [3, 11, 16, 20, 21, 24]. Median age was 11,5 years (range 7 to 13 years) and a previous history of congenital heart disease was identified in 5 patients. IE localizations were identified in 2 patients (native mitral and/or tricuspid valve), whereas no details regarding infection sites were available in the remaining 4 patients. All cases were managed with long term antibiotics (median 62 days, range 56 to 78 days) and surgical intervention was only performed in one patient. Outcome was favourable for 5 of the 6 patients and the remaining one was left with severe residual mitral regurgitation. Although the reported patient recovered uneventfully with medical management after the first episode of IE due to A. aphrophilus, the outcome and prognosis of children with IE due to HACEK group members is variable; with half of them suffering from important complications and mortality rates of 10– 12.5 % [6, 8]. Stroke and septic embolisms were the most common complications and occurred in up to 28 and 17.5 % of cases, respectively. Surgical procedures were required in one third of the patients, increasing to 54 % in those children who developed complications [6]. Mortality rate of HACEK endocarditis in adults is significantly lower compared to IE due to no HACEK (4 vs. 18 %), but a high rate of stroke (25 vs. 17 %) and immunologic and/or vascular manifestations (32 vs. 20 %) have been observed [4]. In conclusion, paediatric IE can be caused by uncommon microorganisms producing severe complications and being potentially fatal. Therefore, the isolation of S. lugdunensis or A. aphrophilus from blood cultures in febrile children should be considered relevant and cardiac involvement has to be ruled out. Those patients with proved IE will require prolonged intravenous anti biotic courses and in complicated cases surgical intervention may be needed. Early diagnosis and initiation of appropriate management is mandatory for a good clinical outcome of these patients.
92 Case Report 22 Rosenthal LB, Feja KN, Levasseur SM et al. The changing epidemiology of pediatric endocarditis at a children’s hospital over seven decades. Pediatr Cardiol 2010; 31: 813–820 23 Sotutu V, Carapetis J, Wilkinson J et al. The “Surreptitious Staphylococcus”: Staphylococcus lugdunensis endocarditis in a child. Pediatr Infect Dis J 2002; 21: 984–985 24 Webb CH, Hogg GM. Haemophilus aphrophilus endocarditis. Br J Clin Pract 1990; 44: 329–331
Downloaded by: Rutgers University. Copyrighted material.
18 Niwa K, Nakazawa M, Tateno S et al. Infective endocarditis in congenital heart disease: Japanese national collaboration study. Heart 2005; 91: 795–800 19 Nørskov-Lauritsen N. Classification, identification, and clinical significance of Haemophilus and Aggregatibacter species with host specificity for humans. Clin Microbiol Rev 2014; 27: 214–240 20 Page MI, King EO. Infection due to Actinobacillus actinomycemcomitans and Haemophilus aphrophilus. N Engl J Med 1966; 275: 181–188 21 Pereira RM, Bucaretchi F, Tresoldi AT. Infective endocarditis due to Haemophilus aphrophilus: a case report. J Pediatr (Rio J) 2008; 84: 178–180
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
Recurrent Infective Endocarditis due to Aggregatibacter aphrophilus and Staphylococcus lugdunensis Rezidivierende infektiöse Endokarditis verursacht durch Aggregatibacter aphrophilus und Staphylococcus lugdunensis Authors
L. Hidalgo-García1, A. Hurtado-Mingo2, P. Olbrich1, A. Moruno-Tirado1, O. Neth1, I. Obando1
Affiliations
1
Key words ▶ infectious endocarditis ● ▶ congenital heart disease ● ▶ Staphylococcus lugdunensis ● ▶ Aggregatibacter aphrophilus ●
Abstract
Zusammenfassung
Uncommon microorganisms are increasingly being recognized as causative agents of paediatric infectious endocarditis (IE). We report a 4-year old girl with congenital heart disease, who suffered from 2 IE episodes secondary to Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus) and Staphylococcus lugdunensis, both rarely reported pathogens in this age group. The patient was initially successfully treated with prolonged intravenous antibiotic courses, however removal of the Contegra valved conduit during the second episode was required due to recurrence of fever and development of pulmonary embolism despite completion of antibiotic therapy. A. aphrohilus is a member of the fastidious gram negative microorganisms of the HACEK group (Haemophilus spp., Aggregatibacter spp, Cardiobaterium hominis, Eikenella corrodens and Kingella kingae), that colonize the oropharynx and are a recognised cause of IE. Prognosis of children with IE due to HACEK group members varies, half of them suffering from complications and mortality rates of 10–12.5 %. Although S. lugdunensis belongs to coagulase negative staphylococci (CONS), it behaves more like S. aureus species rather than CONS. This microorganism is a well-described cause of endocarditis in adult patients, associated with high requirements of surgical procedures and mortality (42–78 %). In conclusion, paediatric IE can be caused by uncommon microorganisms associated with severe complications and potential fatality. The isolation of S. lugdunensis or A. aphrophilus in febrile patients should be considered clinically relevant and cardiac involvement must be ruled out. Those patients with proved IE will require prolonged intravenous antibiotic courses and in complicated cases surgical intervention.
Ungewöhnliche Mikroorganismen, als Ursache pädiatrischer infektiöser Endokarditiden (IE) werden zunehmend berichtet. Wir berichten über ein 4 Jahre altes Mädchen mit angeborenem strukturellem Herzfehler, welche zwei sekundäre, durch A. aphrophilus (früher Haemophilus aphrophilus) und Staphylococus lugdunensis verursachte, IE erlitt, wobei die kausale Identifizierung dieser Keime sehr ungewöhnlich in dieser Altersgruppe ist. Bei diesem Kind war ein konservativer Therapieansatz mit langdauernder intravenöser Antibiotikagabe inital erfolgreich, erneute Fieberschübe und Auftreten einer pulmonarer Embolien während der zweiten IE Episode machten jedoch die Enfernung des “Contegra valved conduit” erforderlich. A. Aphrophilus gehört zu den Gram-negativen Mikroorganismen der HACEK Gruppe (Haemophilus spp., Aggretatbacter spp., Cardiobacterium hominis, Eikenella corrodens und Kingella kingae), welche den Oropharynx kolonisieren und als Erreger der IE bekannt sind. Die Prognose für HACEK bedingte IE im Kindesalter ist sehr variable mit Folgeschäden in der Hälfte der Patienten und einer Mortalitätsrate von 10-12.5%. Obwohl S. lugdunensis zu den koagulase negativen Staphylokokken gehört, zeigt dieser Mikroorganismus ein S. aureus ähnliches Virulenzverhalten. Bei S. lugdunensis handelt es sich um einen gut beschriebenen Verursacher der IE im Erwachsenenalter, welcher gehäuft chirurgische Interventionen benötigt und mit hohen Mortalitätsraten (42-78%) verbunden ist. Pädiatrische IE können durch ungewöhnliche Keime verursacht und mit schweren Komplikationen und potentieller Letalität assoziert sein. Zusammenfassend sollte die Identifikation von S. lugdunensis oder A. aphrophilus in Blutkulturen febriler Kinder als klinisch relevant betrachtet und kardiologische Untersuchungen erwägt werden. Patienten mit bestätigter IE erfordern eine prolongierte antibio tische Behandlung und möglicherweise kardiochirurgischer Interventionen.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1398536 Klin Padiatr 2015; 227: 89–92 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Ignacio Obando Hospital Universitario Virgen del Rocío Pediatrc Infectious Diseases and Immunopathology Manuel Siurot s/n Seville 41013 Spain Tel.: + 34/660/522 448 Fax: + 34/955/012 921 [email protected]
Hospital Universitario Virgen del Rocío, Pediatric Infectious Diseases and Immunopathology, Seville, Spain Hispalense Institute of Pediatrics, Seville, Spain
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▼
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
Downloaded by: Rutgers University. Copyrighted material.
Schlüsselwörter ▶ infektiöse Endokarditis ● ▶ angeborene Herzfehler ● ▶ Staphylococcus lugdunensis ● ▶ Aggregatibacter aphrophilus ●
2
Introduction
▼
Infective endocarditis (IE) is an infection of the cardiac endothelium associated with high morbidity and mortality rates. Although the incidence of IE in the paediatric population is low, an increasing number of paediatric IE cases has been reported over the last years, probably related to improved survival rates of children suffering from congenital heart disease [7, 18]. HACEK group members (Haemophilus spp, Aggregatibacter spp, Cardiobaterium hominis, Eikenella corrodens and Kingella kingae), are increasingly being recognized in paediatric IE cases and represent the most common gram negative IE pathogens in childhood [5, 6, 8]. Although Streptococcus viridans was the leading microorganism causing endocarditis, Staphylococcus aureus and coagulase-negative staphylococci (CONS) are now increasingly reported [5, 9, 15, 22]. Staphylococcus lugdunensis is an emergent member of the CONS group in the context of IE due to its high destructive potential both, on prosthetic as well as on native valves [14, 23]. Here, we report a young child suffering from 2 IE episodes secondary to Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus) and S. lugdunensis, both very rarely reported pathogens in this age group.
Case report
▼
A 4-year old girl was admitted with a 3-week history of fever and respiratory distress. At 2 years of age a D-transposition of the great arteries with ventricular septal defect and pulmonary stenosis was corrected according to the Rastelli procedure with Contegra valved conduit (CVC) placement. On admission signs of cardiac insufficiency, anemia (hemoglobin 7.4 g/dl) and raised acute phase reactants (CRP 118 mg/l) were noted. Bacterial endocarditis was suspected and empirical treatment with penicillin G (300 00 IU/kg/d in 4 doses) and gentamicin (3 mg/kg/24 h) was started. A. aphrophilus (HACEK group) was isolated and antimicrobial management was modified accordingly to intravenous ceftriaxone (100 mg/kg/24 h). An echocardiography revealed a 4 × 5 mm vegetation at the pulmo▶ Fig. 1). Due to the nary side of the prosthetic valved conduit ( ● prompt clinical response (remitting fever and decreased inflammatory markers), the prosthetic material was not removed. She was discharged after an 8 week course of intravenous antibiotics although only a minimal decrease of the vegetation (2 × 2 mm) was documented in a control echocardiography.
Fig. 1 Echocardiogram showing a 4 × 5 mm vegetation related to the pulmonary side of the Contegra valved conduit.
2 years later she became readmitted with a 16 days history of fever (39.9 ºC), being otherwise asymptomatic. Echocardiography at admission revealed an 8 × 10 mm vegetation of the CVC, contiguous to the outflow-tract of the right ventricle. Serial echocardiography disclosed 2 new vegetations. A full blood count (FBC) revealed anaemia (haemoglobin 9.2 g/dl), leucocytosis (15 870/mcl) with neutrophilia (79 %) and a markedly raised CRP (221 mg/L). Intravenous ceftriaxone and gentamicin were started empirically and after isolation of S. lugdunensis, (CMI to penicillin ≤ 0.03 mg/ml) therapy was switched to iv pencillin G (200 00 IU/kg/d in 4 doses), rifampicin (20 mg/kg/d) both for 6 weeks, and gentamicin (3 mg/kg/d) for 2 weeks resulting in an excellent clinical response with decreased inflammatory markers, negative blood cultures, resolution of one vegetation and size reduction of the vegetation related to the pulmonary side of the CVC (4 × 5 mm). One week after discharge the patient was readmitted with high fever, cough and respiratory distress. FBC revealed leukocytosis (15 200/mcl), raised CRP 157 mg/L, and DDimers 107 968 mcg/L. Blood culture was negative. The echocardiography showed 2 vegetations (3 × 6 and 5 × 6 mm respectively). A chest CT scan was suggestive of a pulmonary embolism. At this stage removal of the foreign material with placement of a new CVC was decided. due to the fact that there was not an available pulmonary homograft for the patient at that time. Prolonged culturing and histopathology of the removed prosthetic material did not identify microorganisms. The patient was discharged in excellent clinical state without showing infectious complications over the last 2 years. However, 9 months after her last admission she developed severe left ventricular dysfunction due to compression of the anterior descending right coronary artery by the prosthetic material, requiring CVC replacement.
Discussion
▼
In this case report a child experienced 2 episodes of IE related to prosthetic material caused by 2 unusual pathogens known to be associated with high morbidity and potential mortality. S. lugdunensis generally colonizes the skin and infrequently causes invasion [10]. Although it belongs to CONS, it is far more virulent with a behaviour more similar to S. aureus [1, 10, 14]. Virulence factors that contribute to the increased pathogenic potential have not been fully elucidated but include a heat-stable δ-like haemolysin produced by most S. lugdunensis isolates, agr and slush loci, as well as OatA, a membrane bound acetyltransferase, that confers resistance to lysozyme and adhesins, such as fbl and vWbl [1, 10]. S. lugdunensis has been mostly isolated from adult patients in context with a wide spectrum of clinical diseases including cardiovascular, urinary tract, CONS, bone and joint and soft-tissue infections, bacteremia, endophtalmitis and peritonitis [1, 10]. S. lugdunensis is a well-described cause of endocarditis affecting both native and prosthetic valves in adults [1, 10, 14]. As in our case, these infections may produce suppurative complications, heart failure and peripheral embolisms. Manifestations of IE are not typically caused by CONS, and are associated with high requirements of surgical procedures and mortality rates; being 42 % in case of native and 78 % of prosthetic valve IE [1, 10]. To date only 4 patients younger than 18 years with IE due to S. lugdunensis have been reported with a median age of 11 years (range 5 to 16 years) [13, 15, 17, 23]. Site of infection involved native valve in 3 patients, predominantly affecting the left side
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
Downloaded by: Rutgers University. Copyrighted material.
90 Case Report
Case Report 91 Contributorʼs statement
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L. Hidalgo-García: acquistion of data and drafting the manuscript, A. Hurtado-Mingo: acquisition of data and drafting the manuscript, P. Olbrich: drafting and revising the manuscript, A. Moruno-Tirado: acquistion of data, O. Neth: revising the manuscrpt, I. Obando: study design, drafting and revising the manuscript
Conflict of interest: I have read and understood the document “Conflict of Interest”. Being the corresponding author of the manuscript, I declare that my co-authors informed me that they did not have economic or personal relations according to the explanations given in the document “Conflict of Interest” within the past 3 years. Nor did I myself have such relationships within the past 3 years. References
1 Babu E, Oropello J. Staphylococcus lugdunensis: the coagulase-negative staphylococcus you don’t want to ignore. Expert Rev Anti Infect Ther 2011; 9: 901–907 2 Baddour LM, Wilson WR, Bayer AS et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005; 111: e394–e434 3 Bieger RC, Brewer NS, Washington JA. Haemophilus aphrophilus: a microbiologic and clinical review and report of 42 cases. Medicine 1978; 57: 345–354 4 Chambers ST, Murdoch D, Morris A et al. Hacek infective endocarditis: characteristics and outcomes from a large, multi-national cohort. PLoS One 2013; 8: e63181 5 Di Filippo S, Delahaye F, Semiond B et al. Current patterns of infective endocarditis in congenital heart disease. Heart 2006; 92: 1490–1495 6 Feder HM, Roberts JC, Salazar JC et al. HACEK endocarditis in infants and children: two cases and a literature review. Pediatr Infect Dis J 2003; 22: 557–562 7 Ferrieri P, Gewitz MH, Gerber MA et al. Unique features of infective endocarditis in childhood. Pediatrics 2002; 109: 931–943 8 Foster MA, Walls T. High rates of complications following Kingella kingae infective endocarditis in children: a case series and review of the literature. Pediatr Infect Dis J 2014; 33: 785–786 9 Fowler VG Jr, Miro JM, Hoen B et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 2005; 293: 3012–3021 10 Frank KL, Del Pozo JL, Patel R. From clinical microbiology to infection pathogenesis: how daring to be different works for Staphylococcus lugdunensis. Clin Microbiol Rev 2008; 21: 111–133 11 Geraci JE, Wilkowske CJ, Wilson WR et al. Haemophilus endocarditis: report of 14 patients. Mayo Clin Proc 1977; 52: 209–215 12 Habib G, Hoen B, Tornos P et al. 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 2009; 30: 2369–2413 13 Jones RM, Jackson MA, Ong C et al. Endocarditis caused by Staphylococcus lugdunensis. Pediatr Infect Dis J 2002; 21: 265–268 14 Lin Y-T, Hsieh K-S, Chen Y-S et al. Staphylococcus lugdunensis infective endocarditis: a literature review and analysis of risk factors. J Microbiol Immunol Infect 2010; 43: 478–484 15 Lin Y-T, Hsieh K-S, Chen Y-S et al. Infective endocarditis in children without underlying heart disease. J Microbiol Immunol Infect 2013; 46: 121–128 16 Mesko ZG, Bauza J, Vinas C. Bacterial endocarditis due to Hemophilus aphrophilus with cerebral embolism. J Pediatr 1976; 89: 1031–1032 17 Murillo J, McMahon C, Starr J. Large vegetations in Staphylococcus lugdunensis endocarditis. Heart Lung 2008; 37: 479–480
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
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of the heart. All but one patient, with a previous history of recurrent skin and soft tissue infections, had congenital heart disease. These 3 cases were treated with surgery and combined intra venous antibiotics (median 56 days (range 42 to 62 days) with a good overall outcome, except for one patient who had a residual tricuspid valve regurgitation. No information was available regarding management and outcome of the fourth patient. In our patient repeated prolonged treatment with a combination of 2 antibiotics, according to the IE guidelines for staphylococci infections of prosthetic valves was administered [2, 12]. How ever, removal of the prosthetic material was necessary in order to clear the infection. A. aphrophilus is a member of the HACEK group, which are fastidious gram negative microorganisms that colonize the oropharynx and have long been recognised as a cause of IE [4, 19]. This manifestation and cerebral abscesses are the most frequent invasive infections due to A. aphrophilus. The most prevalent risk factor of IE due to A. aphrophilus and other members of the HACEK group is congenital heart diseases, however a significant proportion of paediatric IE caused by these microorganisms occurred in patients with normal hearts [6, 8]. Current guidelines recommend the use of ceftriaxone as the first line therapy for IE due to the HACEK group, taking into account their potential to produce beta lactamases and the difficulty in the interpretation of the antibiotic sensitivity [2, 12]. In the subgroup of paediatric IE, A. aphrophilus is the 3rd most relevant HACEK pathogen after K. kingae and H. parainfluenzae with 6 cases reported [3, 11, 16, 20, 21, 24]. Median age was 11,5 years (range 7 to 13 years) and a previous history of congenital heart disease was identified in 5 patients. IE localizations were identified in 2 patients (native mitral and/or tricuspid valve), whereas no details regarding infection sites were available in the remaining 4 patients. All cases were managed with long term antibiotics (median 62 days, range 56 to 78 days) and surgical intervention was only performed in one patient. Outcome was favourable for 5 of the 6 patients and the remaining one was left with severe residual mitral regurgitation. Although the reported patient recovered uneventfully with medical management after the first episode of IE due to A. aphrophilus, the outcome and prognosis of children with IE due to HACEK group members is variable; with half of them suffering from important complications and mortality rates of 10– 12.5 % [6, 8]. Stroke and septic embolisms were the most common complications and occurred in up to 28 and 17.5 % of cases, respectively. Surgical procedures were required in one third of the patients, increasing to 54 % in those children who developed complications [6]. Mortality rate of HACEK endocarditis in adults is significantly lower compared to IE due to no HACEK (4 vs. 18 %), but a high rate of stroke (25 vs. 17 %) and immunologic and/or vascular manifestations (32 vs. 20 %) have been observed [4]. In conclusion, paediatric IE can be caused by uncommon microorganisms producing severe complications and being potentially fatal. Therefore, the isolation of S. lugdunensis or A. aphrophilus from blood cultures in febrile children should be considered relevant and cardiac involvement has to be ruled out. Those patients with proved IE will require prolonged intravenous anti biotic courses and in complicated cases surgical intervention may be needed. Early diagnosis and initiation of appropriate management is mandatory for a good clinical outcome of these patients.
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18 Niwa K, Nakazawa M, Tateno S et al. Infective endocarditis in congenital heart disease: Japanese national collaboration study. Heart 2005; 91: 795–800 19 Nørskov-Lauritsen N. Classification, identification, and clinical significance of Haemophilus and Aggregatibacter species with host specificity for humans. Clin Microbiol Rev 2014; 27: 214–240 20 Page MI, King EO. Infection due to Actinobacillus actinomycemcomitans and Haemophilus aphrophilus. N Engl J Med 1966; 275: 181–188 21 Pereira RM, Bucaretchi F, Tresoldi AT. Infective endocarditis due to Haemophilus aphrophilus: a case report. J Pediatr (Rio J) 2008; 84: 178–180
Hidalgo-García L et al. Recurrent Infective Endocarditis due … Klin Padiatr 2015; 227: 89–92
