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Multiple recurrences and relapse of Streptococcus pneumoniae meningitis
could be done. The diagnosis of aortic dissection was but postmortem confirmation could not be obtained because the family refused. Proven spontaneous coronary dissections are rare, especially when multiple. They tend to occur at a single site with only 17 reported patients with multiple, coronary artery dissections." Furthermore, proven serial arterial dissections of coronary and peripheral arteries are exceptional. In this patient, the number of vascular sites affected included two cerebral arteries, two coronary arteries, one iliac artery, and
suspected
the aorta. We thank Dr P Godeau, Dr C Frances, and their team for help in the diagnosis of Ehlers-Danlos syndrome (Service de Medecine Interne,
Figure:
Groupe Hospitalier Pitie-Salpetriere, Paris, France).
S
*Hélène Eltchaninoff, Alain Cribier, Brice Letac *Department of Cardiology, Hôpital Charles Nicolle, Vacomed Research Group, 76000 Rouen, France
left, primer 1 De Maio SJ, Kinsella SH, Silverman MK. Clinical course and longterm prognosis of spontaneous coronary artery dissection. Am J Cardiol 1989; 64: 471-74. 2 Antoniucci D, Magi Diligenti L. Spontaneous dissection of the three major coronary arteries. Eur Heart J 1990; 11: 1130-34. 3 Yeoh JK, Choo HH, Soo CS, Lim YT, Yan CH. Spontaneous coronary dissection in a young man with anterior myocardial infarction. Cathet Cardiovasc Diagn 1991; 24: 186-88. 4 Desseigne P, Tabib A, Loire R. Spontaneous coronary artery dissection: a rare cause of sudden death: two case reports. Arch Mal Coeur 1992; 85: 1031-33. 5 Pita JP, Gonzales NV, Alvarez LP, Rodriguez JMV, Beiras AC. Spontaneous coronary artery dissection. Cathet Cardiovasc Diagn 1994; 32: 27-32.
Multiple recurrences and relapse of Streptococcus pneumoniae meningitis Six-Patients with multiple attacks of Streptococcus pneumoniae meningitis are rare and usually have immunodeficiency or anatomical abnormalities.’ Because pathogenic mechanisms and clinical implications differ, it is important to distinguish a relapse due to the same organism
infection with another strain. Cases of P-lactam-resistant pneumococcal meningitis with failure of cefotaxime or ceftriaxone therapy have been reported.2 Thus, a combination of high doses of a third-generation cephalosporin and vancomycin is recommended for the initial treatment of pneumococal meningitis,3 but the optimum duration of treatment is unknown. In April, 1995, an 11-year-old girl with a petrosphenoidal fluid fistula contracted meningitis due to penicillin-resistant pneumococci. Since the age of 18 months, she had recovered from seven attacks of meningitis caused by five penicillin-sensitive pneumococcal strains and two Haemophilus influenzae strains. Three unsuccessful surgical treatments were done. A lumboperitoneal shunt was installed. Vaccinations with the 23-valent pneumococcal vaccine were done in 1988 and 1993. Prophylaxis with amoxycillin (40 mg/kg daily) was instituted in March, 1988. During this new episode, cerebrospinal fluid (CSF) culture yielded S pneumoniae serotype 23F resistant to penicillin (strain Sl). The patient was treated with cefotaxime (300 mg/kg daily) and vancomycin (60 mg/kg daily). Clinical improvement was observed. CSF culture 36 h after beginning treatment remained sterile. Minimum inhibition concentrations with the agar dilution method were penicillin 2 mg/L and cefotaxime 1 mg/L. After 5 days, the therapeutic regimen was changed to cefotaxime alone (200 mg/kg per day). 2 days later, the patient became febrile. S pneumoniae serotype 23F strain (S2) was isolated from CSF with the from
same
a recurrent
susceptibility profile
as
previously.
Cefotaxime
pneumoniae DNA fingerprinting by Random-PCR
Lane 1=size marker, lane 2=strain Sl, lane 3=strain S2, lane 4=strain S3, lane 5=strain S4, lane 6=unrelated cefotaxime-resistant S pneumoniae meningitis strain. Numbers on left are reference molecular size markers (basepairs). On
(300
was
5’-TGGGAGGTGTATAGTCTA-3’;
on
right primer was
5’-AGTTCAGCCAC-3’.
per day) and vancomycin (60 mg/kg per day) were reinstituted. The patient became afebrile and subsequent CSF cultures remained sterile. She was discharged after 30 days of therapy. Prophylaxis with rifampicin (20 mg/kg daily) and pristinamycin (50 mg/kg daily) was prescribed until a new surgical treatment could be done. To distinguish relapse from recurrence for this last episode, we used DNA fingerprinting by Random-PCR.4 It is known that capsular typing is not sufficient to establish genetic relatedness. The two resistant isolates were also compared with the two penicillin-sensitive S pneumoniae strains responsible for the sixth and seventh attacks of meningitis and which belonged to serotypes 17F (strain S3) and 21 (strain S4), respectively. The two penicillin-resistant isolates shared the same pattern, whereas the penicillinsusceptible strains produced patterns different from each other and from those of the resistant strains (figure). Thus, this approach clearly distinguished two episodes of recurrence from an episode of relapse. In this latter case, relapsing meningitis was attributed to inadequate duration of
mg/kg
therapy. Our findings lead us to suggest that: patients with cefotaxime-resistant pneumococci meningitis should receive high doses of cefotaxime plus vancomycin for more than 5 days; prevention based on vaccination and antibiotic prophylaxis may be inefficient; and it is probable that prophylaxis with amoxycillin has selected a resistant strain in the upper airway here. The features of this patient’s recurrent meningitis due to penicillin-susceptible and then to pencillin-resistant isolates are notable since they mimic the recent and dramatic world wide increase in penicillin resistance in pneumococcal meningitis. *E Bingen, C Doit, C Bouillie, B Blanchard, P Geslin, A Bourillon, J Elion *Service de Microbiologie, Hôpital Robert Debré, 75019 Paris, France; Service de Pédiatrie, Centre Hospitaler de Longjumeau, Longjumeau; and Centre National de Références des Pneumocoques, Créteil
1
2
3
4
Whitecar JP Jr, Reddin JL, Spink WW. Recurrent pneumococcal meningitis: a review of the literature and studies on a patient who recovered from eleven attacks caused by five serotype of Diplococcus pneumoniae. N Engl J Med 1966; 274: 1283-89. John CC. Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis 1994; 18: 188-93. Friedland IR, Paris M, Ehrett S, et al. Evaluation of antimicrobial regimens for the treatment of experimental penicillin- and cephalosporin-resistant pneumococal meningitis. Antimicrob Agents Chemother 1993; 37: 1630-31. Bingen E, Cavé H, Aujard Y, et al. Molecular analysis of multiple recurrent meningitis due to Escherichia coli K1 in an infant. Clin Infect Dis 1993; 16: 82-85.
311
suspected
the aorta. We thank Dr P Godeau, Dr C Frances, and their team for help in the diagnosis of Ehlers-Danlos syndrome (Service de Medecine Interne,
Figure:
Groupe Hospitalier Pitie-Salpetriere, Paris, France).
S
*Hélène Eltchaninoff, Alain Cribier, Brice Letac *Department of Cardiology, Hôpital Charles Nicolle, Vacomed Research Group, 76000 Rouen, France
left, primer 1 De Maio SJ, Kinsella SH, Silverman MK. Clinical course and longterm prognosis of spontaneous coronary artery dissection. Am J Cardiol 1989; 64: 471-74. 2 Antoniucci D, Magi Diligenti L. Spontaneous dissection of the three major coronary arteries. Eur Heart J 1990; 11: 1130-34. 3 Yeoh JK, Choo HH, Soo CS, Lim YT, Yan CH. Spontaneous coronary dissection in a young man with anterior myocardial infarction. Cathet Cardiovasc Diagn 1991; 24: 186-88. 4 Desseigne P, Tabib A, Loire R. Spontaneous coronary artery dissection: a rare cause of sudden death: two case reports. Arch Mal Coeur 1992; 85: 1031-33. 5 Pita JP, Gonzales NV, Alvarez LP, Rodriguez JMV, Beiras AC. Spontaneous coronary artery dissection. Cathet Cardiovasc Diagn 1994; 32: 27-32.
Multiple recurrences and relapse of Streptococcus pneumoniae meningitis Six-Patients with multiple attacks of Streptococcus pneumoniae meningitis are rare and usually have immunodeficiency or anatomical abnormalities.’ Because pathogenic mechanisms and clinical implications differ, it is important to distinguish a relapse due to the same organism
infection with another strain. Cases of P-lactam-resistant pneumococcal meningitis with failure of cefotaxime or ceftriaxone therapy have been reported.2 Thus, a combination of high doses of a third-generation cephalosporin and vancomycin is recommended for the initial treatment of pneumococal meningitis,3 but the optimum duration of treatment is unknown. In April, 1995, an 11-year-old girl with a petrosphenoidal fluid fistula contracted meningitis due to penicillin-resistant pneumococci. Since the age of 18 months, she had recovered from seven attacks of meningitis caused by five penicillin-sensitive pneumococcal strains and two Haemophilus influenzae strains. Three unsuccessful surgical treatments were done. A lumboperitoneal shunt was installed. Vaccinations with the 23-valent pneumococcal vaccine were done in 1988 and 1993. Prophylaxis with amoxycillin (40 mg/kg daily) was instituted in March, 1988. During this new episode, cerebrospinal fluid (CSF) culture yielded S pneumoniae serotype 23F resistant to penicillin (strain Sl). The patient was treated with cefotaxime (300 mg/kg daily) and vancomycin (60 mg/kg daily). Clinical improvement was observed. CSF culture 36 h after beginning treatment remained sterile. Minimum inhibition concentrations with the agar dilution method were penicillin 2 mg/L and cefotaxime 1 mg/L. After 5 days, the therapeutic regimen was changed to cefotaxime alone (200 mg/kg per day). 2 days later, the patient became febrile. S pneumoniae serotype 23F strain (S2) was isolated from CSF with the from
same
a recurrent
susceptibility profile
as
previously.
Cefotaxime
pneumoniae DNA fingerprinting by Random-PCR
Lane 1=size marker, lane 2=strain Sl, lane 3=strain S2, lane 4=strain S3, lane 5=strain S4, lane 6=unrelated cefotaxime-resistant S pneumoniae meningitis strain. Numbers on left are reference molecular size markers (basepairs). On
(300
was
5’-TGGGAGGTGTATAGTCTA-3’;
on
right primer was
5’-AGTTCAGCCAC-3’.
per day) and vancomycin (60 mg/kg per day) were reinstituted. The patient became afebrile and subsequent CSF cultures remained sterile. She was discharged after 30 days of therapy. Prophylaxis with rifampicin (20 mg/kg daily) and pristinamycin (50 mg/kg daily) was prescribed until a new surgical treatment could be done. To distinguish relapse from recurrence for this last episode, we used DNA fingerprinting by Random-PCR.4 It is known that capsular typing is not sufficient to establish genetic relatedness. The two resistant isolates were also compared with the two penicillin-sensitive S pneumoniae strains responsible for the sixth and seventh attacks of meningitis and which belonged to serotypes 17F (strain S3) and 21 (strain S4), respectively. The two penicillin-resistant isolates shared the same pattern, whereas the penicillinsusceptible strains produced patterns different from each other and from those of the resistant strains (figure). Thus, this approach clearly distinguished two episodes of recurrence from an episode of relapse. In this latter case, relapsing meningitis was attributed to inadequate duration of
mg/kg
therapy. Our findings lead us to suggest that: patients with cefotaxime-resistant pneumococci meningitis should receive high doses of cefotaxime plus vancomycin for more than 5 days; prevention based on vaccination and antibiotic prophylaxis may be inefficient; and it is probable that prophylaxis with amoxycillin has selected a resistant strain in the upper airway here. The features of this patient’s recurrent meningitis due to penicillin-susceptible and then to pencillin-resistant isolates are notable since they mimic the recent and dramatic world wide increase in penicillin resistance in pneumococcal meningitis. *E Bingen, C Doit, C Bouillie, B Blanchard, P Geslin, A Bourillon, J Elion *Service de Microbiologie, Hôpital Robert Debré, 75019 Paris, France; Service de Pédiatrie, Centre Hospitaler de Longjumeau, Longjumeau; and Centre National de Références des Pneumocoques, Créteil
1
2
3
4
Whitecar JP Jr, Reddin JL, Spink WW. Recurrent pneumococcal meningitis: a review of the literature and studies on a patient who recovered from eleven attacks caused by five serotype of Diplococcus pneumoniae. N Engl J Med 1966; 274: 1283-89. John CC. Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis 1994; 18: 188-93. Friedland IR, Paris M, Ehrett S, et al. Evaluation of antimicrobial regimens for the treatment of experimental penicillin- and cephalosporin-resistant pneumococal meningitis. Antimicrob Agents Chemother 1993; 37: 1630-31. Bingen E, Cavé H, Aujard Y, et al. Molecular analysis of multiple recurrent meningitis due to Escherichia coli K1 in an infant. Clin Infect Dis 1993; 16: 82-85.
311