Print version ISSN 0021-7557
J. Pediatr. (Rio J.) vol.84 no.2 Porto Alegre Mar./Apr. 2008
Ricardo M. PereiraI; Fabio BucaretchiII; Antonia T. TresoldiIII
IDoutor. Médico assistente,
Enfermaria de Pediatria, Hospital de Clínicas, Universidade de Campinas
(UNICAMP), Campinas, SP, Brazil
IIDoutor. Professor assistente, Departamento de Pediatria, Faculdade de Ciências Médicas (FCM), UNICAMP, Campinas, SP, Brazil
IIIProfessor associado, Departamento de Pediatria, FCM, UNICAMP, Campinas, SP, Brazil
OBJECTIVE: To report the case of a child
with infective endocarditis caused by Haemophilus aphrophilus.
DESCRIPTION: Boy with 20 days of fever and chills. On admission, he was febrile, pale and with no signs of hemodynamic instability; on cardiac auscultation, a mitral-related holosystolic murmur was observed. Laboratory examination identified anemia (hemoglobin = 9.14 g/dL), total leukocytes of 11,920 mm3, platelets of 250,000 mm3, elevated sedimentation velocity of red cells and elevated C-reactive protein. The echocardiogram revealed image on mitral valve, resembling vegetation. Considering endocarditis, antibiotic therapy was started with crystalline penicillin (200,000 UI/kg/day) in association with gentamicin (4 mg/kg/day). On the third day of treatment, Haemophilus aphrophilus was identified in the blood cultures and the antibiotic scheme was replaced with ceftriaxone (100 mg/kg/day). On the 20th day of evolution, the patient was pale but with no fever or other complaints. Examinations showed hemoglobin = 7.0 g/dL, leukocytes = 2,190 mm3, platelets = 98,000 mm3, international normalized ratio = 1.95 and R = 1.89. Considering the hypothesis of adverse reaction to ceftriaxone, a 6-week replacement treatment with ciprofloxacin (20 mg/kg/day) was started. Examination results normalized after 72 hours of the replacement therapy. During ambulatory follow-up, patient presented with severe mitral regurgitation, undergoing a valve replacement with a metallic prosthetic valve 9 months after acute event. Patient has done well throughout the 3-year ambulatory follow-up.
COMMENTS: Identification of agents of the HACEK group (Haemophilus ssp, Actinobacillus actinomycetemcomitans,Cardiobacterium hominis, Eikenella corrodens and Kingella kingae) in children with infective endocarditis is rare. This case report, with no HACEK agent-related risk factors, reinforces the need for identification of the etiological agent of endocarditis to ensure adequate treatment.
Keywords: H. aphrophilus, endocarditis, ceftriaxone, ciprofloxacin, leukopenia, thrombocytopenia, hypoprothrombinemia.
The incidence of infective endocarditis (IE) has increased over the past years as survival rates of patients with congenital heart disease improve.1 Main agents of IE are: (i) Viridans group Streptococci (S. milleri, S. mitior, S. salivarius, S. mutans and S. sanguis), mainly on patients with congenital heart disease; (ii) Staphylococcus aureus, generally associated with placement of central venous catheter and use of injecting drugs; (iii) Staphylococcus epidermidis, usually affecting patients following cardiac surgery and catheterized premature newborns.1 On the other hand, the HACEK group of bacteria (Haemophilus ssp, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae) is responsible for 3% of IE in adults.1-3 The objective of this study is to report a case of rare occurrence of IE caused by Haemophilus aphrophilus in a child.
Report of case
The patient was a 12-year-old boy with a 20-day history of fever accompanied by chills and weight loss of 1 kg. On physical examination, he was febrile (40 ºC), pale 1+/4+, good peripheral perfusion, heart rate = 112 beats/min, respiratory rate = 24 breaths/min and blood pressure = 100/60 mmHg. During cardiac auscultation, he presented with a mitral-related harsh holosystolic murmur, with radiation throughout the precordium, the spleen was palpable 3 cm below the left costal margin, hard 1+/4+. Dental examination showed a good dental status, with no signs of gingivitis. Complete blood count revealed hemoglobin (Hb) = 9.14 g/dL, hematocrit = 27.56%, total leukocytes = 11,920 mm3 (9% band, 72% segmented, 7% lymphocytes, 12% monocytes), platelets = 250,000 mm3, sedimentation velocity of red cells = 120 mm, C-reactive protein = 15.6 mg/dL (reference value < 0.8 mg/dL) and no alterations in urine I. Chest radiograph was normal, echocardiogram revealed a 3mm image on the anterior surface of the anterior mitral valve leaflet, resembling vegetation. Due to hypothesis of IE, three blood samples were collected and antibiotic therapy was started with crystalline penicillin (200,000 UI/kg/day) in association with gentamicin (4 mg/kg/day). On the third day of treatment, H. aphrophilus susceptible to chloramphenicol, ciprofloxacin, and ceftriaxone was detected in the three blood cultures and the antibiotic scheme was replaced with ceftriaxone (100 mg/kg/day). After the eighth day of treatment, the patient remained afebrile. On the 20th day of evolution, the patient was pale but with no fever or other complaints. Screening examinations showed Hb = 7.0 g/dL, leukocytes = 2,190 mm3, platelets = 98,000 mm3, international normalized ratio = 1.95 and R = 1.89. Since the patient did not show other risk factors (only peripheral venous access was used), the hypothesis of an adverse reaction to ceftriaxone was considered. Ceftriaxone was then replaced with a 6-week treatment with ciprofloxacin (20 mg/kg/day). Leukocyte count, platelet count and coagulation normalized after 72 hours under the new scheme. During hospitalization, echocardiograms performed every 15 days demonstrated a progressive reduction in the vegetation size, with evidence of severe mitral regurgitation on the last echocardiography. At the end of the antibiotic therapy, patient was discharged from hospital to ambulatory follow-up. Due to the severe mitral regurgitation, the patient underwent a valve replacement with a metallic prosthetic valve 9 months after discharge, with no intercurrent events. Patient has done well throughout the 3-year ambulatory follow-up.
The patient's legal guardian signed a free and informed consent form.
The HACEK group bacteria are gram-negative bacilli of the normal oropharyngeal flora. Since these bacteria can be found in the dental plaque and in the gingiva, clinical features of infection, including respiratory tract infections, may follow dental manipulation.3-5 A case of H. aphrophilus endocarditis after tongue piercing in a patient with congenital heart disease was reported.6
These bacteria are slow growers that require special culture media for their identification.7 In a report of 46 cases of IE caused by microorganisms of the HACEK group, the mean time to blood culture positivity was 3,4 days.7
Feder et al., in a literature review, found 36 cases of pediatric patients with IE caused by HACEK bacteria (13 H. parainfluenzae, 13 K. kingae, five A. actinomycetemcomitans, four H. aphrophilus, one C. hominis) and 60% of these cases showed previous cardiac alteration.2
The suggested treatment for IE caused by HACEK bacteria is a 4-week administration of third- generation cephalosporin for native valves and a 6-week administration for prosthetic valves.2,3,8
The use of fluoroquinolones, especially ciprofloxacin, is an alternative since their pharmacokinetic properties allow eradication of bacteria that adhere to prostheses.8
The reported patient did not show the risk factors described for infection by bacteria of the HACEK group, since he did not have previous cardiac alteration, periodontal disease or previous dental manipulation. Despite the absence of known risk factors, H. aphrophilus is an oral bacteria and the oral cavity must have provided a port of entry for the bacteria. This fact reinforces the need for accurate identification of the etiological agent of IE to determine adequate treatment.
The probable adverse reaction to ceftriaxone, in particular, is worthy of attention. Severe hematological alterations, including death, have already been associated with the use of ceftriaxone, especially hemolytic anemia, in which presence of ceftriaxone antibodies has already been observed.9 Thrombocytopenia and hypoprothrombinemia have already been associated with ceftriaxone as well.9,10 Although in the present case specific antibodies against ceftriaxone were not researched, the complete recovery observed in the patient's examination results after drug withdrawal strongly suggests a possible adverse reaction to ceftriaxone.
1. Starke JR. Infective endocarditis. In: Feigin RD, Cherry JD, Demmier GJ, Kaplan SL. Textbook of pediatric infectious diseases. 5th ed. Philadelphia: WB Saunders; 2004. p. 355-80. [ Links ]
2. Feder HM Jr., Roberts JC, Salazar JC, Leoplod HB, Toro-Salazar O. HACEK endocarditis in infants and children: two cases and a literature review. Pediatr Infect Dis J. 2003;22:557-62. [ Links ]
3. Brouqui P, Raoult D. Endocarditis due to rare and fastidious bacteria. Clin Microbiol Rev. 2001;14:177-207. [ Links ]
4. Huang ST, Lee HC, Lee NY, Liu KH, Ko WC. Clinical characteristics of invasive Haemophilus aphrophilus infections. J Microbiol Immunol Infect. 2005;38:271-6. [ Links ]
5. Bieger RC, Brewer NS, Washington JA 2nd. Haemophilus aphrophilus: a microbiologic and clinical review and report of 42 cases. Medicine (Baltimore). 1978:57;345-55. [ Links ]
6. Akhondi H, Rahimi AR. Haemophilus aphrophilus endocarditis after tongue piercing. Emerg Infect Dis. 2002;8:850-1. [ Links ]
7. Das M, Badley AD, Cockerill FR, Steckelberg JM, Wilson WR. Infective endocarditis caused by HACEK microorganisms. Annu Rev Med. 1997;48;25-33. [ Links ]
8. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, 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:e 394-434. [ Links ]
9. Grossjohann B, Eichler P, Greinacher A, Santoso S, Kroll H. Ceftriaxone causes drug-induced immune thrombocytopenia and hemolytic anemia: characterization of targets on platelets and red blood cells. Transfusion. 2004;44:1033-40. [ Links ]
10. Agnelli G, Del Favero A, Parise P, Guerciolini R, Pasticci B, Nenci GG, et al. Cephalosporin-induced hypoprothrombinemia: is the N-methylthiotetrazole side chain the culprit? Antimicrob Agent Chemother. 1986;29:1108-9. [ Links ]
Ricardo Mendes Pereira
Rua Dr. Ruy Vicente de Mello, 240
Cidade Universitária, Barão Geraldo
CEP 13084-745 - Campinas, SP - Brazil
Manuscript received Jul 11 2007, accepted for publication Sep 03 2007.
No conflicts of interest declared concerning the publication of this article.