Correspondence
364
gococcus versus therapeutic treatment of early bacteremia. Second, it is problematic to use historical controls. Assuming that more rapid antibiotic treatment of serious bacterial infections can only be beneficial, we recently examined another aspect of this problem. In a retrospective study of 122 emergency department patients admitted for suspected bacterial meningitis, we attempted to determine the factors associated with delays of initiating parenteral antibiotic therapy [4]. We found that the overriding factors associated with delays of therapy were deferral of initiation of antibiotics until after the patient was admitted to a hospital bed (as opposed to treatment in the emergency department) and the practice of withholding antibiotics until the completion of head computerized tomography or until results of formal laboratory evaluation of cerebrospinal fluid had returned. The presence or absence of ostensibly overt signs of meningitis was not significantly associated with more rapid treatment. We suspect that the issue of the effect of antimicrobial delays on patient outcome will never be fully elucidated. For now it may be more worthwhile to concentrate on methods of optimizing the rapidity of recognition and treatment of these infections.
In the future as other lessestablished therapeutic modalities are evaluated for effectiveness (e.g., corticosteroids for bacterial meningitis, immunotherapy for gram-negative bacillary lipopolysaccharide, or tumor necrosis factor for bacteremia), issues of timing should be addressed. DAVID GARY
D.
A.
TALAN
OVERTURF
Olive View/UCLA Medical Center Sylmar, California References
1. Talan DA, Hoffman JR, Yoshikawa TT, Overturf GD. Role of empiric parental antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art. Rev Infect Dis 1988;10:365-76 2. Young LS, Gascon R, Alam S, Bermudez LEM. Monoclonal antibodies for treatment of gram-negative infections. Rev Infect Dis 1989;11(Suppl 7):SI564-71 3. LevelMH, Freij BJ, Syrogiannopoulos GA, Chrane DF, Hoyt MJ, Stewart SM, Kennard BD, Olsen KD, McCracken GH. Dexamethasone therapy for bacterial meningitis. N Engl J Med 1988;319:964-71 4. Talan DA, Guterman JT, Overturf GD, Singer C, Hoffman JR, Lambert B. Analysis of emergencydepartment management of suspected bacterial meningitis. Ann Emerg Med 1989;18:856-62
REVIEWS OF INFECTIOUS DISEASES • VOL. 12, NO.2. MARCH-APRIL 1990 © 1990 by The University of Chicago. All rights reserved. 0162-0886/90/1202-0021$02.00
Bacteroides fragiiis Meningitis: Report of 1\vo Cases SIR - We read with interest Feder's recent report on meningitis due to Bacteroides fragilis [1]. We have observed two cases of B. jragilis meningitis in adults during the last 10 years in our hospital. Case 1. A 68-year-old patient had arteritic dementia. One and one-half months after her left leg was amputated, she presented in a coma with fever and complete hemiplegia. Physical examination showed nuchal rigidity and a sacral scab. Spinal puncture revealed cloudy CSF with 6,800 polymor- . phonuclear cells (PMNs)/mm3 , 7.0 g of protein/L, and gram-negative bacilli. CSF culture was positive for an ampicillin- and metronidazole-sensitive B. fragilts. 1\vo blood cultures were also positive for an ampicillin-resistant and metronidazole-sensitive B. jragi/is strain. Cutaneous scab cultures revealed
a third B. jragi/is strain. Therapy was begun with ampicillin and gentamicin, then continued with intravenous ornidazole. The patient became apyretic within 8 days, with a subnormal consciousness; hemiplegia persisted. Further CSF cultures weresterile (table 1). Case 2. A 51-year-old woman was hospitalized for lumbar pains and left sciatica 3 months after undergoing surgery for a genital and rectal prolapsus; this intervention was complicated by an impaction of the bowel. Three days after hospitalization the patient demonstrated severe sepsis, with shock and meningitis. The first spinal puncture showed pus, with anaerobic bacteria (three different Bacteroides species - B. fragilis, B. distasonis, B. thetaiotaomicron) and a nongroupable Streptococcus. Twenty-
Correspondence
365
Table 1. Laboratory findings for a patient with B. fragilis
Table 2. Serum and CSF concentrations of omidazole in
meningitis.
a patient with B. fragilis meningitis. Day of hospitalization 0
Finding
8
12
19
26
Blood WBCs/mm 3
% PMNs Protein concentration (giL) CSF culture for B. fragilis NOTE. available.
6,800 390 100 100 7
2.7
230 81 1.25
110 60
8
2.5 1.3
+
Drug Interval concentration after iv (ug/ml.) infusion (h) Serum CSF 1 8
72 46
92 86
Inhibitory titer
Bactericidal titer
Serum
CSF
Serum
CSF
1:64 1:32
1:64 1:32
1:16 1:8
ND 1:8
ND = not done.
+ = positive; - = negative; blank indicates data not
four hours later, consciousness was impaired, and the patient developed a bilateral pneumonia in spite of treatment with ampicillin, gentamicin, and ornidazole. A second spinal puncture showed the same bacteria. Recovery took place within a few days with the combination of tiophenicol and metronidazole. The primary infectious localization was probably L5SI spondylitis. Anaerobic bacterial meningitis is indeed very uncommon [2]. In 1979, Heerema et al. [3] reported 86 cases of anaerobic bacterial meningitis published in the English-language literature. Bacteroides species were present in 22 cases. The authors reported four patients, three of them with Bacteroides meningitis (two B. fragilis and one other Bacteroides species), all in adults. CSF is routinely cultured in anaerobic medium in our laboratory; yet we have only observed two cases of anaerobic bacterial meningitis among 128documented cases of bacterial meningitis in adults (1.6070), both with B. fragills [4]. No B.fragilis mengingitis was observed during the same 15-year period in the pediatrics department, which includes a neonatal unit. We have not found a high prevalence of this infection in premature infants. On the other hand, in a cooperative study with our bacterioides survey center (Groupe d'Etudes Epidemiologiques et Prophylactiques) in 1987, we received from 43 laboratories of microbiology more than 200 strains of B. fragilis isolated from normally sterile fluids and surgical pus. Only one B. fragilis was isolated from the CSF of an infant. We found predispos-
ing factors in those two patients (abdominal surgery and anaerobic cutaneous lesions). The 5-nitroimidazoles remain the best therapy for these anaerobic infections, in spite of the emergence of Bacteroides strains with less sensitivity to these antibiotics [5]. They have a good penetration in the CSF, as shown in table 2 (ornidazole in case 1). O.
PATEY
J. BREUIL A. FISCH C. BURNAT F. VINCENT-BALLEREAU
A. DuBLANCHET Department of Infectious and Tropical Diseases and the Laboratory of Microbiology Villeneuve Saint Georges Hospital and the Pharmacie Centrale Angers, France References
1. Feder M Jr. Bacteroides fragilis meningitis. Rev Infect Dis 1987;9:783-6 2. Finland M, Barnes MW. Acute bacterial meningitis at Boston City Hospital during 12 selected years, 1935-1972. J Infect Dis 1977;136:400-15 3. Heerema MS, Ein ME, Musher DM, Bradshaw MW, Williams TW Jr. Anaerobic bacterial meningitis. Am J Med 1979;67:219-27 4. Cadoz M, Deborne B, Lafaix C, Langlois-Zantain 0, DuBlanchet A. Traitement par 1'0rnidazoie injectable d'une meningite it Bacteroides. Presse Med 1977;6:2438-9 5. DuBlanchet A, Caillon J, Emond JP, Chardon H, Drugeon H. Isolation of Bacteroides strains with reduced sensitivity to 5 nitroimidazoles. Eur J Clin Microbiol 1986; 5:346-7
364
gococcus versus therapeutic treatment of early bacteremia. Second, it is problematic to use historical controls. Assuming that more rapid antibiotic treatment of serious bacterial infections can only be beneficial, we recently examined another aspect of this problem. In a retrospective study of 122 emergency department patients admitted for suspected bacterial meningitis, we attempted to determine the factors associated with delays of initiating parenteral antibiotic therapy [4]. We found that the overriding factors associated with delays of therapy were deferral of initiation of antibiotics until after the patient was admitted to a hospital bed (as opposed to treatment in the emergency department) and the practice of withholding antibiotics until the completion of head computerized tomography or until results of formal laboratory evaluation of cerebrospinal fluid had returned. The presence or absence of ostensibly overt signs of meningitis was not significantly associated with more rapid treatment. We suspect that the issue of the effect of antimicrobial delays on patient outcome will never be fully elucidated. For now it may be more worthwhile to concentrate on methods of optimizing the rapidity of recognition and treatment of these infections.
In the future as other lessestablished therapeutic modalities are evaluated for effectiveness (e.g., corticosteroids for bacterial meningitis, immunotherapy for gram-negative bacillary lipopolysaccharide, or tumor necrosis factor for bacteremia), issues of timing should be addressed. DAVID GARY
D.
A.
TALAN
OVERTURF
Olive View/UCLA Medical Center Sylmar, California References
1. Talan DA, Hoffman JR, Yoshikawa TT, Overturf GD. Role of empiric parental antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art. Rev Infect Dis 1988;10:365-76 2. Young LS, Gascon R, Alam S, Bermudez LEM. Monoclonal antibodies for treatment of gram-negative infections. Rev Infect Dis 1989;11(Suppl 7):SI564-71 3. LevelMH, Freij BJ, Syrogiannopoulos GA, Chrane DF, Hoyt MJ, Stewart SM, Kennard BD, Olsen KD, McCracken GH. Dexamethasone therapy for bacterial meningitis. N Engl J Med 1988;319:964-71 4. Talan DA, Guterman JT, Overturf GD, Singer C, Hoffman JR, Lambert B. Analysis of emergencydepartment management of suspected bacterial meningitis. Ann Emerg Med 1989;18:856-62
REVIEWS OF INFECTIOUS DISEASES • VOL. 12, NO.2. MARCH-APRIL 1990 © 1990 by The University of Chicago. All rights reserved. 0162-0886/90/1202-0021$02.00
Bacteroides fragiiis Meningitis: Report of 1\vo Cases SIR - We read with interest Feder's recent report on meningitis due to Bacteroides fragilis [1]. We have observed two cases of B. jragilis meningitis in adults during the last 10 years in our hospital. Case 1. A 68-year-old patient had arteritic dementia. One and one-half months after her left leg was amputated, she presented in a coma with fever and complete hemiplegia. Physical examination showed nuchal rigidity and a sacral scab. Spinal puncture revealed cloudy CSF with 6,800 polymor- . phonuclear cells (PMNs)/mm3 , 7.0 g of protein/L, and gram-negative bacilli. CSF culture was positive for an ampicillin- and metronidazole-sensitive B. fragilts. 1\vo blood cultures were also positive for an ampicillin-resistant and metronidazole-sensitive B. jragi/is strain. Cutaneous scab cultures revealed
a third B. jragi/is strain. Therapy was begun with ampicillin and gentamicin, then continued with intravenous ornidazole. The patient became apyretic within 8 days, with a subnormal consciousness; hemiplegia persisted. Further CSF cultures weresterile (table 1). Case 2. A 51-year-old woman was hospitalized for lumbar pains and left sciatica 3 months after undergoing surgery for a genital and rectal prolapsus; this intervention was complicated by an impaction of the bowel. Three days after hospitalization the patient demonstrated severe sepsis, with shock and meningitis. The first spinal puncture showed pus, with anaerobic bacteria (three different Bacteroides species - B. fragilis, B. distasonis, B. thetaiotaomicron) and a nongroupable Streptococcus. Twenty-
Correspondence
365
Table 1. Laboratory findings for a patient with B. fragilis
Table 2. Serum and CSF concentrations of omidazole in
meningitis.
a patient with B. fragilis meningitis. Day of hospitalization 0
Finding
8
12
19
26
Blood WBCs/mm 3
% PMNs Protein concentration (giL) CSF culture for B. fragilis NOTE. available.
6,800 390 100 100 7
2.7
230 81 1.25
110 60
8
2.5 1.3
+
Drug Interval concentration after iv (ug/ml.) infusion (h) Serum CSF 1 8
72 46
92 86
Inhibitory titer
Bactericidal titer
Serum
CSF
Serum
CSF
1:64 1:32
1:64 1:32
1:16 1:8
ND 1:8
ND = not done.
+ = positive; - = negative; blank indicates data not
four hours later, consciousness was impaired, and the patient developed a bilateral pneumonia in spite of treatment with ampicillin, gentamicin, and ornidazole. A second spinal puncture showed the same bacteria. Recovery took place within a few days with the combination of tiophenicol and metronidazole. The primary infectious localization was probably L5SI spondylitis. Anaerobic bacterial meningitis is indeed very uncommon [2]. In 1979, Heerema et al. [3] reported 86 cases of anaerobic bacterial meningitis published in the English-language literature. Bacteroides species were present in 22 cases. The authors reported four patients, three of them with Bacteroides meningitis (two B. fragilis and one other Bacteroides species), all in adults. CSF is routinely cultured in anaerobic medium in our laboratory; yet we have only observed two cases of anaerobic bacterial meningitis among 128documented cases of bacterial meningitis in adults (1.6070), both with B. fragills [4]. No B.fragilis mengingitis was observed during the same 15-year period in the pediatrics department, which includes a neonatal unit. We have not found a high prevalence of this infection in premature infants. On the other hand, in a cooperative study with our bacterioides survey center (Groupe d'Etudes Epidemiologiques et Prophylactiques) in 1987, we received from 43 laboratories of microbiology more than 200 strains of B. fragilis isolated from normally sterile fluids and surgical pus. Only one B. fragilis was isolated from the CSF of an infant. We found predispos-
ing factors in those two patients (abdominal surgery and anaerobic cutaneous lesions). The 5-nitroimidazoles remain the best therapy for these anaerobic infections, in spite of the emergence of Bacteroides strains with less sensitivity to these antibiotics [5]. They have a good penetration in the CSF, as shown in table 2 (ornidazole in case 1). O.
PATEY
J. BREUIL A. FISCH C. BURNAT F. VINCENT-BALLEREAU
A. DuBLANCHET Department of Infectious and Tropical Diseases and the Laboratory of Microbiology Villeneuve Saint Georges Hospital and the Pharmacie Centrale Angers, France References
1. Feder M Jr. Bacteroides fragilis meningitis. Rev Infect Dis 1987;9:783-6 2. Finland M, Barnes MW. Acute bacterial meningitis at Boston City Hospital during 12 selected years, 1935-1972. J Infect Dis 1977;136:400-15 3. Heerema MS, Ein ME, Musher DM, Bradshaw MW, Williams TW Jr. Anaerobic bacterial meningitis. Am J Med 1979;67:219-27 4. Cadoz M, Deborne B, Lafaix C, Langlois-Zantain 0, DuBlanchet A. Traitement par 1'0rnidazoie injectable d'une meningite it Bacteroides. Presse Med 1977;6:2438-9 5. DuBlanchet A, Caillon J, Emond JP, Chardon H, Drugeon H. Isolation of Bacteroides strains with reduced sensitivity to 5 nitroimidazoles. Eur J Clin Microbiol 1986; 5:346-7
