Meningitis Association of
Due to Combined Infections
Haemophilus influenzae Type
B and Clostridium
perfringens
Richard C. Gehrz, MD; Robert M. Ward, MD; Richard H. Lien, MD; H. Rosalie Thompson; Charles W. Jarvis, MD
\s=b\ Haemophilus
influenzae
type
B and
perfringens were recovered simultaneously from the cerebrospinal fluid of a patient with purulent meningitis. No antecedent history of head trauma was present to explain the coexistence of the anaerobe with Haemophilus organisms. Clostridium
A review of the literature on mixed that no previous cases of anaerobes have been reported in uncomplicated meningitis due to multiple
meningitis indicates
identification of anaerobic in due to has to our knowledge, previously been reported. In the following case, the fortuitous demonstration of large, Gram-posi¬ tive rods on a Gram stain of the cerebrospinal fluid (CSF) resulted in the eventual recovery of Clostridium
The organisms meningitis not, multiple organisms
perfringens.
REPORT OF A CASE A 1-year-old male infant was admitted to St Paul Children's Hospital with a oneweek history of upper respiratory tract
Accepted for publication April 5, 1976. From the Department of Pediatrics (Drs Gehrz and Ward), University of Minnesota, and the departments of pediatrics (Drs Gehrz and Lien) and pathology (Ms Thompson and Dr Jarvis), St Paul Children's Hospital, St Paul. Reprint requests to Department of Pediatrics, Children's Hospital, 311 Pleasant Ave, St Paul, MN 55102 (Dr Gehrz).
organisms. In addition, the recovery of clostridia is extremely unusual in the absence of an identifiable portal of entry. We have identified two additional cases of clostridia infection in the central nervous system and recommend that anaerobic organisms be considered in selected cases of meningitis. (Am J Dis Child 130:877-879, 1976)
symptoms. A temperature of 38.9 C devel¬
oped on the day prior to admission. On the day of admission, he was noted to be lethargic and irritable. There was no ante¬ cedent history of head trauma or penetrat¬ ing head wounds. On examination, the patient was pale, with circumoral cyanosis and mottling of the extremities. Vital signs included a temperature of 40.4 C, pulse rate of 240 beats per minute, shallow respirations at 80 per minute, and an initial blood pressure of 180/110 mm Hg. The infant was lethar¬ gic, with profound nuchal rigidity. The anterior fontanel was fibrous but full, and funduscopic examination showed no evi¬ dence of papilledema. There was no evidence of trauma to the head. The deep tendon reflexes were normal. An equivocal Babinski sign was noted on the right side, and a slight ptosis of the left eyelid was also present. Lumbar puncture
on admission produced cloudy CSF. Laboratory values are listed in
the Table. A Gram stain of the CSF showed numerous
Gram-negative, pleomorphic
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/12/2015
rods. In addition, large intracellular and extracellular Gram-positive rods were seen, but regarded as likely contaminants until confirmed by additional experienced observers. A period of two hours elapsed before the Gram-positive organism was reported and believed to be most consistent with clostridia. At that time, anaerobic cultures of the CSF were established.
Haemophilus influenzae type
was
recovered from cultures of CSF and blood, and was sensitive to ampicillin sodium and chloramphenicol. The anaerobic culture of the CSF was observed for seven days before it demonstrated growth. The orga¬ nism was identified as Clostridium and subsequently typed as C perfringens, sensitive to ampicillin and chlorampheni¬ col. Anaerobic and aerobic cultures of subsequent specimens of blood, CSF, and subdural fluid were sterile. The patient's peripheral perfusion im¬ proved clinically with fluids given intrave¬ nously and 0., by mask. Therapy consisted of ampicillin sodium at 400 mg/kg admin¬ istered intravenously after an initial loading dose of 200 mg/kg. Chloramphen¬ icol was initiated one hour later intrave¬ nously at 100 mg/kg/24 hr. Fluids were restricted to 1,000 ml/sq m/24 hr. The patient's temperature fell to 37.5 to 38.5 C within 24 hours. Subsequent exami¬ nations of CSF were free of bacteria and had fewer leukocytes, a higher percentage of lymphocytes, and correction of glucose and protein levels toward normal (Table). Spiking fevers developed on day 5. Transil¬ lumination at that time was increased on the right side, but the occipitofrontal circumference was unchanged from admis-
sion. Subdurai aspirations yielded 5 ml of xanthochromic fluid from the right side, with an elevated leukocyte count as described in the Table. Aspirations of the left subdural space produced no fluid. Spiking fevers continued, and subdural aspiration two days later yielded only 3 ml of similar fluid on the right side. All cultures of the subdural fluid were sterile. Ampicillin was discontinued on the day of the second subdural aspiration, since the fevers were considered to possibly repre¬ sent a drug reaction. The fever spikes resolved the following day, and chloram¬ phenicol was continued for six afebrile days (total of 17 days). No fluid was obtained from a subdural aspiration per¬ formed five days after the second positive
Laboratory Data Day 13
Temperature, C_404_38^8_39.5
39.9
Lumbar cerebrospinal fluid Red blood cell
17
37.4_37.3
_count_537_10_3_._._1_49,000 White blood cell count
12,550
2.675
1,987
% Polymorpho-
165
125
...
nuclear leuko¬
79 95 cytes Glucose, mg/dl_17_54_60_.___49_52 Protein, Subdural effusion
mg/dl_1J35_56_68_._._57_149
White blood cell
count_.___„._197_.___300_.__
% Polymorpho-
aspiration.
nuclear leuko-
At the time of discharge, the patient demonstrated no neurologic deficits. No area of abnormal transillumination was noted, and his occipitofrontal circumfer¬ ence was unchanged from admission. Findings from examination of the CSF were essentially normal, except for a persistent pleocytosis. Findings from fol¬ low-up physical examinations at 7, 14, and 28 days after discharge have been normal. A brain scan and a computerized axial tomogram were performed 16 days and 19 days after admission, and failed to demon¬ strate an abscess, residual subdural effu¬ sion, or enlarged ventricles.
COMMENT
The isolation and identification of than one organism from pa¬ tients with meningitis is unusual. In a review of 1,535 patients with meningi¬ tis, Neal1 found only six cases due to more
multiple organisms. Subsequently, Vaden et al- and Herweg et al' have reported simultaneous, mixed infec¬
tion in ten of 124 and 20 of 534 patients with meningitis. Eleven of the patients in the report of Herweg and co-workers were less than 6 months of age, suggesting an in¬ creased susceptibility to polymicrobial infections in infancy. Forty-three cases of mixed meningitis wore iden¬ tified over a 16-year period at the Mayo Clinic.4 Multiple organisms were isolated from the initial CSF specimen in only five patients in this study, all of whom had underlying neurologic diseases. In the remaining cases, a second organism was isolated during the course of treatment of meningitis due to a single organism. Bacteria isolated most frequently
_cytes_.___.„_22_„._26_ Glucose, mg/dl_„_._.„_88_^_78_ Protein, mg/dl_.¡,_ _365_.¡,_.„_
from patients with mixed meningitis include Neisseria meningitidis, Diplococcus pneumoniae, H influenzae, and
hemolytic streptococci.l:i·5-7 negative coliform organisms
Gramwere
recovered from a considerable number of infants,1 and Streptococcus faecalis and Staphylococcus aureus predomi¬ nated in patients with underlying central nervous system (CNS) abnor¬ malities.4 Polymicrobial infections of the me¬ ninges have included simultaneous isolation of pyogenic bacteria with Mycobacterium tuberculosis"''- and en tero viruses.1314 A case of tubercu¬ lous meningitis complicated by cryptococcal infection has also been reported.15 However, there have been no
previous
case
reports involving
anaerobic bacteria. Clostridium perfringens is recov¬ ered most frequently from intraabdominal infections or contaminated soft tissue injuries.1617 A variety of clinical syndromes are associated with this organism, including septicemia, massive hemolytic anemia, and cellulitis with myonecrosis. Central ner¬ vous system infection due to clostridia is uncommon, and most cases reported have been associated with primary brain abscess or penetrating injuries to the skull.1824 Conomy and Dalton,-5 Ganchrow and Brief,26 and Mackay and co-workers-7 have reported cases of purulent clostridial meningitis in which a primary intra-abdominal
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/12/2015
lesion nous
presumably lead to hematogespread of enteric organisms to
the CNS. In addition to the case reported here, we have isolated C perfringens from the CNS in two other patients. The first was a 16-month-old male infant who had developed a brain abscess and meningitis after a super¬ ficial corneal laceration. A second case involved a 10-year-old boy who was found at postmortem examination to have had multiple brain abscesses after acute sodium arsenite ingestion. Mucosal ulcérations and microabscesses were demonstrated on histo¬ logie examination of the gastrointes¬ tinal tract, presumably providing a portal of entry for the organism. In our present case, no portal of entry for clostridia could be demon¬ strated. Physical examination and radiologie studies failed to show evidence of head trauma, fracture, sinusitis, or mastoiditis. There was no
apparent gastrointestinal
or
genito¬
and the orga¬ nism could not be recovered from the blood or urine. A small subdural effu¬ sion was demonstrated on the fifth hospital day. Although some inflam¬ matory cells were present, no orga¬ nisms were demonstrable on Gram stain or culture. The effusion may have provided an anaerobic environ¬ ment for secondary infection by the clostridia, although the simultaneous isolation of C perfringens with H
urinary abnormality,
from the initial cultures that the anaerobe involved suggests the CNS early in the course of this child's illness.
influenzae
CONCLUSION It has not been our practice to rou¬ collect CSF for anaerobic cultures in patients with purulent meningitis. In this case, identification of Gram-positive bacilli alerted us to the possibility of an anaerobic infec¬ tion. However, reliance on microscop¬ ical identification may result in failure to pick up small numbers of organisms or organisms that are morphologically similar to the aerobic
tinely
pathogen. Therefore, primary incuba¬
tion of the CSF under anaerobic conditions is essential. Anaerobic organisms have been iso¬ lated from a variety of infections in which a primary aerobic pathogen has been identified, although the path¬ ogenic significance of the anaerobe in these cases is uncertain. Furthermore, anaerobes have been isolated success¬ fully from intra-abdominal, pulmo¬ nary, and CNS infections as a primary pathogen when meticulous techniques of specimen collection and culturing are employed. Therefore, the possi¬ bility of anaerobic infection should always be considered in cases of
if associated cranial trauma or intraabdominal abnormality is suspected, or in cases in which no aerobic organism is identified.
pyogenic meningitis, particularly
The Minnesota State Board of Health did the confirmation and specific typing of the Clos¬ tridium perfringens. Marietta Sattler helped in the preparation of the manuscript.
Nonproprietary Name and Trademarks of
Drug
Ampicillin sodium-Alpen-N, Amcill-S, Omnipen-N, Penbriton-S, Principen-N, Totacillin-N.
References 1. Neal JB:
Meningitis: Distribution according
to age and etiology. JAMA 82:1429, 1924. 2. Vaden EB, Rice EC, Stadnichenko V: Meningitis due to simultaneous double infections in children. JAMA 143:1402-1404, 1950. 3. Herweg JC, Middelkamp JN, Hartmann AF: Simultaneous mixed bacterial meningitis in children. J Pediatr 63:76-83, 1963. 4. Keys TF, Wellman WE, Needham GM, et al: Bacterial meningitis: IV. Infections caused by multiple organisms. Mayo Clin Proc 41:179-185, 1966. 5. Ashmun SH: Pneumococcic meningitis combined with streptococcus and Diplococcus catarrhalis. Ohio State Med J 29:243-246, 1933. 6. Cunningham AA: Mixed meningococcal and streptococcal meningitis. Lancet 1:198-199, 1937. 7. Gaffney JC: Mixed infection of the meninges with H influenzae and the pneumococcus. Br Med J 1:346, 1940. 8. Todesco J: A case of meningitis due to the tubercle bacillus and a diplococcus closely allied to Micrococcus tetragenes. Lancet 2:338, 1927. 9. Fiddes J: Combined forms of meningitis: Mixed infection of the meninges by the tubercle bacillus and meningococcus. Arch Dis Child 16:140-144, 1941. 10. Rosenthal IM, Linker M, Golomb J: Tuber-
meningitis complicated by pyogenic meningitis caused by Streptococcus faecalis. Am
culous
Rev Tuberc 62:441, 1950. 11. Williams MJ, Clapp MP: Mixed meningitis: Association of Mycobacterium tuberculosis, alpha hemolytic streptococcus, and Neisseria meningitidis. JAMA 151:732-734, 1953. 12. Riley EA: Combined pneumococcal and tuberculous meningitis. Am Rev Tuberc 71:584, 1955. 13. Wright HT, McAllister RM, Ward R: "Mixed" meningitis: Report of a case with isolation of Hemophilus influenzae type B and ECHO virus type 9 from the cerebrospinal fluid. N Engl J Med 267:142-144, 1962. 14. Chia W, Berriman P: A case of "mixed meningitis" in a neonate due to Proteus mirabilis and Coxsackie virus group b type 4. Med J Aust 1:209-210, 1971. 15. Nanda SP, Kass I, Cohn M, et al: Coexistence of tuberculous and cryptococcal meningitis. Pediatrics 20:45, 1957. 16. Bornstein DL, Weinberg AN, Swartz MN, et al: Anaerobic infections: Review of current experience. Medicine 43:207-232, 1964. 17. Gorbach SL, Bartlett JG: Anaerobic infections: Medical progress. N Engl J Med 290:1177\x=req-\ 1183, 1237-1245, 1289-2394, 1974. 18. Gas infection of brain as one form of serious complications of cerebrocranial injuries, Committee of Soviet Scientists. Br Med J 1:785\x=req-\ 788, 1943.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/12/2015
19. Cairns H, Calvert CA, Daniel P: Complications of head wounds with special reference to infection. Br J Surg 35(War Surg suppl)1:198\x=req-\ 243, 1947. 20. Henderson JK, Kennedy WFC, Potter JM: Recovery from acute Clostridium welchii meningitis. Br Med J 2:1400-1401, 1954. 21. Moller B: Purulent Clostridium welchii meningitis originating from penetrating cranial wounds. Acta Chir Scand 109:394-399, 1955. 22. Colwell FG, Sullivan J, Shuman HH: Acute purulent meningitis due to Clostridium perfringens. N Engl J Med 262:618-619, 1960. 23. Willis AT, Jacob SI: A case of meningitis due to Clostridium welchii. J Pathol Bacteriol
88:312-314, 1964. 24. Samson DS, Clark K: A current review of brain abscess. Am J Med 54:201-210, 1973. 25. Conomy JP, Dalton JW: Clostridium
perfringens meningitis: Report of a case with neuropathological observations. Arch Neurol 21:44-50, 1969. 26. Ganchrow MI, Brief DK: A case of meningitis secondary to Clostridium welchii. J Trau11:444-446, 1971. 27. Mackay NNS, Gruneberg RN, Harries BJ, et al: Primary Clostridium welchii meningitis. Br Med J 1:591-592, 1971. ma
Due to Combined Infections
Haemophilus influenzae Type
B and Clostridium
perfringens
Richard C. Gehrz, MD; Robert M. Ward, MD; Richard H. Lien, MD; H. Rosalie Thompson; Charles W. Jarvis, MD
\s=b\ Haemophilus
influenzae
type
B and
perfringens were recovered simultaneously from the cerebrospinal fluid of a patient with purulent meningitis. No antecedent history of head trauma was present to explain the coexistence of the anaerobe with Haemophilus organisms. Clostridium
A review of the literature on mixed that no previous cases of anaerobes have been reported in uncomplicated meningitis due to multiple
meningitis indicates
identification of anaerobic in due to has to our knowledge, previously been reported. In the following case, the fortuitous demonstration of large, Gram-posi¬ tive rods on a Gram stain of the cerebrospinal fluid (CSF) resulted in the eventual recovery of Clostridium
The organisms meningitis not, multiple organisms
perfringens.
REPORT OF A CASE A 1-year-old male infant was admitted to St Paul Children's Hospital with a oneweek history of upper respiratory tract
Accepted for publication April 5, 1976. From the Department of Pediatrics (Drs Gehrz and Ward), University of Minnesota, and the departments of pediatrics (Drs Gehrz and Lien) and pathology (Ms Thompson and Dr Jarvis), St Paul Children's Hospital, St Paul. Reprint requests to Department of Pediatrics, Children's Hospital, 311 Pleasant Ave, St Paul, MN 55102 (Dr Gehrz).
organisms. In addition, the recovery of clostridia is extremely unusual in the absence of an identifiable portal of entry. We have identified two additional cases of clostridia infection in the central nervous system and recommend that anaerobic organisms be considered in selected cases of meningitis. (Am J Dis Child 130:877-879, 1976)
symptoms. A temperature of 38.9 C devel¬
oped on the day prior to admission. On the day of admission, he was noted to be lethargic and irritable. There was no ante¬ cedent history of head trauma or penetrat¬ ing head wounds. On examination, the patient was pale, with circumoral cyanosis and mottling of the extremities. Vital signs included a temperature of 40.4 C, pulse rate of 240 beats per minute, shallow respirations at 80 per minute, and an initial blood pressure of 180/110 mm Hg. The infant was lethar¬ gic, with profound nuchal rigidity. The anterior fontanel was fibrous but full, and funduscopic examination showed no evi¬ dence of papilledema. There was no evidence of trauma to the head. The deep tendon reflexes were normal. An equivocal Babinski sign was noted on the right side, and a slight ptosis of the left eyelid was also present. Lumbar puncture
on admission produced cloudy CSF. Laboratory values are listed in
the Table. A Gram stain of the CSF showed numerous
Gram-negative, pleomorphic
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/12/2015
rods. In addition, large intracellular and extracellular Gram-positive rods were seen, but regarded as likely contaminants until confirmed by additional experienced observers. A period of two hours elapsed before the Gram-positive organism was reported and believed to be most consistent with clostridia. At that time, anaerobic cultures of the CSF were established.
Haemophilus influenzae type
was
recovered from cultures of CSF and blood, and was sensitive to ampicillin sodium and chloramphenicol. The anaerobic culture of the CSF was observed for seven days before it demonstrated growth. The orga¬ nism was identified as Clostridium and subsequently typed as C perfringens, sensitive to ampicillin and chlorampheni¬ col. Anaerobic and aerobic cultures of subsequent specimens of blood, CSF, and subdural fluid were sterile. The patient's peripheral perfusion im¬ proved clinically with fluids given intrave¬ nously and 0., by mask. Therapy consisted of ampicillin sodium at 400 mg/kg admin¬ istered intravenously after an initial loading dose of 200 mg/kg. Chloramphen¬ icol was initiated one hour later intrave¬ nously at 100 mg/kg/24 hr. Fluids were restricted to 1,000 ml/sq m/24 hr. The patient's temperature fell to 37.5 to 38.5 C within 24 hours. Subsequent exami¬ nations of CSF were free of bacteria and had fewer leukocytes, a higher percentage of lymphocytes, and correction of glucose and protein levels toward normal (Table). Spiking fevers developed on day 5. Transil¬ lumination at that time was increased on the right side, but the occipitofrontal circumference was unchanged from admis-
sion. Subdurai aspirations yielded 5 ml of xanthochromic fluid from the right side, with an elevated leukocyte count as described in the Table. Aspirations of the left subdural space produced no fluid. Spiking fevers continued, and subdural aspiration two days later yielded only 3 ml of similar fluid on the right side. All cultures of the subdural fluid were sterile. Ampicillin was discontinued on the day of the second subdural aspiration, since the fevers were considered to possibly repre¬ sent a drug reaction. The fever spikes resolved the following day, and chloram¬ phenicol was continued for six afebrile days (total of 17 days). No fluid was obtained from a subdural aspiration per¬ formed five days after the second positive
Laboratory Data Day 13
Temperature, C_404_38^8_39.5
39.9
Lumbar cerebrospinal fluid Red blood cell
17
37.4_37.3
_count_537_10_3_._._1_49,000 White blood cell count
12,550
2.675
1,987
% Polymorpho-
165
125
...
nuclear leuko¬
79 95 cytes Glucose, mg/dl_17_54_60_.___49_52 Protein, Subdural effusion
mg/dl_1J35_56_68_._._57_149
White blood cell
count_.___„._197_.___300_.__
% Polymorpho-
aspiration.
nuclear leuko-
At the time of discharge, the patient demonstrated no neurologic deficits. No area of abnormal transillumination was noted, and his occipitofrontal circumfer¬ ence was unchanged from admission. Findings from examination of the CSF were essentially normal, except for a persistent pleocytosis. Findings from fol¬ low-up physical examinations at 7, 14, and 28 days after discharge have been normal. A brain scan and a computerized axial tomogram were performed 16 days and 19 days after admission, and failed to demon¬ strate an abscess, residual subdural effu¬ sion, or enlarged ventricles.
COMMENT
The isolation and identification of than one organism from pa¬ tients with meningitis is unusual. In a review of 1,535 patients with meningi¬ tis, Neal1 found only six cases due to more
multiple organisms. Subsequently, Vaden et al- and Herweg et al' have reported simultaneous, mixed infec¬
tion in ten of 124 and 20 of 534 patients with meningitis. Eleven of the patients in the report of Herweg and co-workers were less than 6 months of age, suggesting an in¬ creased susceptibility to polymicrobial infections in infancy. Forty-three cases of mixed meningitis wore iden¬ tified over a 16-year period at the Mayo Clinic.4 Multiple organisms were isolated from the initial CSF specimen in only five patients in this study, all of whom had underlying neurologic diseases. In the remaining cases, a second organism was isolated during the course of treatment of meningitis due to a single organism. Bacteria isolated most frequently
_cytes_.___.„_22_„._26_ Glucose, mg/dl_„_._.„_88_^_78_ Protein, mg/dl_.¡,_ _365_.¡,_.„_
from patients with mixed meningitis include Neisseria meningitidis, Diplococcus pneumoniae, H influenzae, and
hemolytic streptococci.l:i·5-7 negative coliform organisms
Gramwere
recovered from a considerable number of infants,1 and Streptococcus faecalis and Staphylococcus aureus predomi¬ nated in patients with underlying central nervous system (CNS) abnor¬ malities.4 Polymicrobial infections of the me¬ ninges have included simultaneous isolation of pyogenic bacteria with Mycobacterium tuberculosis"''- and en tero viruses.1314 A case of tubercu¬ lous meningitis complicated by cryptococcal infection has also been reported.15 However, there have been no
previous
case
reports involving
anaerobic bacteria. Clostridium perfringens is recov¬ ered most frequently from intraabdominal infections or contaminated soft tissue injuries.1617 A variety of clinical syndromes are associated with this organism, including septicemia, massive hemolytic anemia, and cellulitis with myonecrosis. Central ner¬ vous system infection due to clostridia is uncommon, and most cases reported have been associated with primary brain abscess or penetrating injuries to the skull.1824 Conomy and Dalton,-5 Ganchrow and Brief,26 and Mackay and co-workers-7 have reported cases of purulent clostridial meningitis in which a primary intra-abdominal
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/12/2015
lesion nous
presumably lead to hematogespread of enteric organisms to
the CNS. In addition to the case reported here, we have isolated C perfringens from the CNS in two other patients. The first was a 16-month-old male infant who had developed a brain abscess and meningitis after a super¬ ficial corneal laceration. A second case involved a 10-year-old boy who was found at postmortem examination to have had multiple brain abscesses after acute sodium arsenite ingestion. Mucosal ulcérations and microabscesses were demonstrated on histo¬ logie examination of the gastrointes¬ tinal tract, presumably providing a portal of entry for the organism. In our present case, no portal of entry for clostridia could be demon¬ strated. Physical examination and radiologie studies failed to show evidence of head trauma, fracture, sinusitis, or mastoiditis. There was no
apparent gastrointestinal
or
genito¬
and the orga¬ nism could not be recovered from the blood or urine. A small subdural effu¬ sion was demonstrated on the fifth hospital day. Although some inflam¬ matory cells were present, no orga¬ nisms were demonstrable on Gram stain or culture. The effusion may have provided an anaerobic environ¬ ment for secondary infection by the clostridia, although the simultaneous isolation of C perfringens with H
urinary abnormality,
from the initial cultures that the anaerobe involved suggests the CNS early in the course of this child's illness.
influenzae
CONCLUSION It has not been our practice to rou¬ collect CSF for anaerobic cultures in patients with purulent meningitis. In this case, identification of Gram-positive bacilli alerted us to the possibility of an anaerobic infec¬ tion. However, reliance on microscop¬ ical identification may result in failure to pick up small numbers of organisms or organisms that are morphologically similar to the aerobic
tinely
pathogen. Therefore, primary incuba¬
tion of the CSF under anaerobic conditions is essential. Anaerobic organisms have been iso¬ lated from a variety of infections in which a primary aerobic pathogen has been identified, although the path¬ ogenic significance of the anaerobe in these cases is uncertain. Furthermore, anaerobes have been isolated success¬ fully from intra-abdominal, pulmo¬ nary, and CNS infections as a primary pathogen when meticulous techniques of specimen collection and culturing are employed. Therefore, the possi¬ bility of anaerobic infection should always be considered in cases of
if associated cranial trauma or intraabdominal abnormality is suspected, or in cases in which no aerobic organism is identified.
pyogenic meningitis, particularly
The Minnesota State Board of Health did the confirmation and specific typing of the Clos¬ tridium perfringens. Marietta Sattler helped in the preparation of the manuscript.
Nonproprietary Name and Trademarks of
Drug
Ampicillin sodium-Alpen-N, Amcill-S, Omnipen-N, Penbriton-S, Principen-N, Totacillin-N.
References 1. Neal JB:
Meningitis: Distribution according
to age and etiology. JAMA 82:1429, 1924. 2. Vaden EB, Rice EC, Stadnichenko V: Meningitis due to simultaneous double infections in children. JAMA 143:1402-1404, 1950. 3. Herweg JC, Middelkamp JN, Hartmann AF: Simultaneous mixed bacterial meningitis in children. J Pediatr 63:76-83, 1963. 4. Keys TF, Wellman WE, Needham GM, et al: Bacterial meningitis: IV. Infections caused by multiple organisms. Mayo Clin Proc 41:179-185, 1966. 5. Ashmun SH: Pneumococcic meningitis combined with streptococcus and Diplococcus catarrhalis. Ohio State Med J 29:243-246, 1933. 6. Cunningham AA: Mixed meningococcal and streptococcal meningitis. Lancet 1:198-199, 1937. 7. Gaffney JC: Mixed infection of the meninges with H influenzae and the pneumococcus. Br Med J 1:346, 1940. 8. Todesco J: A case of meningitis due to the tubercle bacillus and a diplococcus closely allied to Micrococcus tetragenes. Lancet 2:338, 1927. 9. Fiddes J: Combined forms of meningitis: Mixed infection of the meninges by the tubercle bacillus and meningococcus. Arch Dis Child 16:140-144, 1941. 10. Rosenthal IM, Linker M, Golomb J: Tuber-
meningitis complicated by pyogenic meningitis caused by Streptococcus faecalis. Am
culous
Rev Tuberc 62:441, 1950. 11. Williams MJ, Clapp MP: Mixed meningitis: Association of Mycobacterium tuberculosis, alpha hemolytic streptococcus, and Neisseria meningitidis. JAMA 151:732-734, 1953. 12. Riley EA: Combined pneumococcal and tuberculous meningitis. Am Rev Tuberc 71:584, 1955. 13. Wright HT, McAllister RM, Ward R: "Mixed" meningitis: Report of a case with isolation of Hemophilus influenzae type B and ECHO virus type 9 from the cerebrospinal fluid. N Engl J Med 267:142-144, 1962. 14. Chia W, Berriman P: A case of "mixed meningitis" in a neonate due to Proteus mirabilis and Coxsackie virus group b type 4. Med J Aust 1:209-210, 1971. 15. Nanda SP, Kass I, Cohn M, et al: Coexistence of tuberculous and cryptococcal meningitis. Pediatrics 20:45, 1957. 16. Bornstein DL, Weinberg AN, Swartz MN, et al: Anaerobic infections: Review of current experience. Medicine 43:207-232, 1964. 17. Gorbach SL, Bartlett JG: Anaerobic infections: Medical progress. N Engl J Med 290:1177\x=req-\ 1183, 1237-1245, 1289-2394, 1974. 18. Gas infection of brain as one form of serious complications of cerebrocranial injuries, Committee of Soviet Scientists. Br Med J 1:785\x=req-\ 788, 1943.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/12/2015
19. Cairns H, Calvert CA, Daniel P: Complications of head wounds with special reference to infection. Br J Surg 35(War Surg suppl)1:198\x=req-\ 243, 1947. 20. Henderson JK, Kennedy WFC, Potter JM: Recovery from acute Clostridium welchii meningitis. Br Med J 2:1400-1401, 1954. 21. Moller B: Purulent Clostridium welchii meningitis originating from penetrating cranial wounds. Acta Chir Scand 109:394-399, 1955. 22. Colwell FG, Sullivan J, Shuman HH: Acute purulent meningitis due to Clostridium perfringens. N Engl J Med 262:618-619, 1960. 23. Willis AT, Jacob SI: A case of meningitis due to Clostridium welchii. J Pathol Bacteriol
88:312-314, 1964. 24. Samson DS, Clark K: A current review of brain abscess. Am J Med 54:201-210, 1973. 25. Conomy JP, Dalton JW: Clostridium
perfringens meningitis: Report of a case with neuropathological observations. Arch Neurol 21:44-50, 1969. 26. Ganchrow MI, Brief DK: A case of meningitis secondary to Clostridium welchii. J Trau11:444-446, 1971. 27. Mackay NNS, Gruneberg RN, Harries BJ, et al: Primary Clostridium welchii meningitis. Br Med J 1:591-592, 1971. ma
