Lumbar Punctures and MAJ Gerald W.
Fischer, MC, USA;
MAJ Ronald W.
Four patients, with an additional seven from the literature, had meningitis following a lumbar puncture (LP) that disclosed normal cerebrospinal fluid (CSF). Animal studies demonstrate that perforation of the meninges in the presence of bacteremia enhances the development of meningitis. Simultaneous blood cultures should be obtained with all LPs. Regardless of the results of the initial LP, a second CSF examination is recommended in any patient whose clinical condition is deteriorating. If the initial blood culture is positive, a second LP should be strongly considered in all newborn and very young infants.
lumbar puncture (LP) is an abso¬ lute necessity in the exami¬ nation of any infant suspected of having a central nervous system in¬ fection. Since the possibility of men¬ ingitis is generally not considered after an initial LP shows normal cer¬ ebrospinal fluid (CSF), a second CSF examination is often done with reluc¬ tance. The rapid emergence of men¬ ingitis after an LP has shown normal CSF is well documented.1·2 That LPs might contribute to the development of meningitis was suggested clini¬ cally and experimentally as early as
A
Received for publication May 21, 1974; accepted Sept 16. From the Department of Pediatrics, Madigan Army Medical Center, Tacoma, Wash (Drs. Fischer, Brenz, and Alden); and Children's Orthopedic Hospital and Medical Center, Seattle (Dr. Beckwith). Dr. Fischer is now with Tripler Army Medical Center, Honolulu. Reprint requests to Department of Pediatrics, Tripler Army Medical Center, Honolulu, HI 96819 (Dr. Fischer).
Meningitis
Brenz, MC, USA; LTC Errol R. Alden, MC, USA; J. Bruce Beckwith, MD
1919.3"5 We wish to describe four pa¬ tients and to review seven from the literature who were found to have meningitis shortly after an LP showed normal CSF. The develop¬ ment of meningitis after an LP is considered, and the clinical conditions necessitating a second CSF examina¬ tion are discussed. REPORT OF CASES Case 1.—An 8-month-old
girl had a tem¬
perature of 41.1 C (106 F) and lethargy for
days prior to admission. Because of vomiting and continued lethargy, the child was brought to the hospital and admitted. The physical examination showed a mildly lethargic child with a temperature of 39.4 C (103 F) and a full fontane! A fine, erythematous, macular rash was present over the extremities, but no petechiae were noted. Neurologic examination two
showed no abnormalities. Results of the initial LP and laboratory studies were nor¬ mal (Table 1). During the next 24 hours the child developed petechiae and purpura with increased lethargy. The second LP disclosed purulent fluid that contained Neisseria meningitidis by Gram stain and culture. The initial blood culture done on admission was also positive for meningococcus, as was the second culture. Case 2.—A 15-month-old boy had a fever of nine days' duration and symptoms of an upper-respiratory tract infection. The child's condition did not improve on erythromycin therapy, and he had a tempera¬ ture of 40.5 C (104.9 F) and became irri¬ table and lethargic. On admission to the hospital, the physical examination showed no abnormalities except for irritability and a temperature of 40.5 C. Results of the ini-
tial CSF examination were normal (Table 1). The onset of meningismus with contin¬ ued lethargy prompted a second LP to be taken approximately 24 hours later; it dis¬ closed grossly purulent CSF. Haemopkilus influenzae was cultured from the blood and CSF. Case 3.-A 2,863-gm (6.3-lb) girl was ex¬ amined shortly after birth because of ma¬ ternal fever. An LP and blood culture were obtained, and kanamycin sulfate and am¬ picillin sodium therapy was begun. Results of the first LP were normal (Table 1), al¬ though Escherichia coli grew from the original blood culture. The child's condition deteriorated with increasing lethargy and irritability. A second CSF examination was done, and although no organisms were cultured after antibiotic therapy was insti¬ tuted, the presence of cells in the CSF and the clinical course suggested meningitis. Case 4.—A 4-year-old boy was admitted two weeks after the onset of chickenpox with ataxia, vomiting, and headache. The admission temperature was 38.4 C (101.2 F) and a postnasal discharge was noted, but the ears were normal. There was facial weakness on the left side and an abnormal finger-to-nose test. The LP showed clear fluid and an opening pressure of 180 mm H20. The glucose and protein levels were normal, and the Gram stain and culture were negative (Table 1). The initial im¬
pression
was
postchickenpox encephalitis
with cerebellar ataxia. A blood culture the following day was positive for H influ¬ enzae. Despite antimicrobial therapy, the child's condition continued to deteriorate and he developed seizures and vomiting. A second LP four days later disclosed grossly purulent fluid with the Gram stain and cul¬ ture both positive for H influenzae. On autopsy the child was found to have
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Table 1.—Patients With
Meningitis After Initial Discovery of Normal Cerebrospinal Fluid Patient 1 day 12 (100%
4 yr 2 (50%
88 14
68 154
44 44
24 hr
24 hr
E coli 24 hr
4
4,250 (98% segmented cells & 2% lymphocytes)
2,554 (99%
55 46
30 98
8 mo
Age
15 mo
Initial CSF values
WBCs/cu
Glucose level, mg/100 ml Protein level, mg/100 ml Gram stain Initial culture results CSF Blood Interval between examinations Second CSF values
WBCs/cu
mm
Glucose level, mg/100 ml Protein level, mg/100 ml Gram stain Second culture results CSF Blood *
segmented cells &50% lymphocytes)
lymphocytes)
mm
72 8
meningitidis
segmented cells & 1% lymphocytes)
influenzae
days 3,970 (87%
1,880 (10% segmented cells
& 92 124
segmented cells & 13% lymphocytes)
90% lymphocytes)
930
influenzae
influenzae influenzae
meningitidis meningitidis
Exúdate and bacteria limited to cord at autopsy.
pus limited grossly and microscopically to the area of the spinal cord near the site of the LP (Figure). There was associated varicella encephalitis with cerebral swell¬ ing and tonsillar herniation, but there was no evidence of a bacterial infection involv¬ ing the brain.
COMMENT
Lumbar punctures are performed each year on thousands of febrile chil¬ dren to exclude meningitis, but a single negative LP is not absolute confirmation of normal CSF. Al¬ though the pathophysiologic charac¬ teristics of meningitis are not well understood, there are two explana¬ tions for the rapid development of meningitis after an LP has deter¬ mined that the CSF is normal. The first and most obvious possibility is that the patient was bacteremic and had seeded the meninges prior to the initial examination, but that a host response had not yet occurred. Three of the four patients whose cases we described had bacteremias at the time of the initial LP. Seven other patients whose cases were collected from the literature also demonstrated bactere¬ mia with an initial CSF examination and later developed meningitis1-2 (Table 2). The fact that most of these patients are quite ill and have pre¬
senting signs
or
symptoms
sugges-
Localization of
purulent
material is noted
tive of meningitis further strength¬ ens this hypothesis. However, septic infants without meningitis look se¬ verely ill and may die without ever developing meningitis, ie, menin-
gococcemia.
An alternate
explanation is that meningeal damage caused by the LP predisposes the patient to meningitis
when bacteremia is present at the time of CSF sampling. Petersdorf et al5 demonstrated in dogs that when 109 bacteria were given intravenously
over
spinal cord
near
site of initial LP.
without further manipulation, the an¬ imals did not develop meningitis. However, 81% of the dogs with more than 103 bacteria in the bloodstream at the time of cisternal puncture de¬ veloped meningitis.3 These data sug¬ gest that meningeal damage facil¬ itates the development of meningitis. Previously, it was believed that pa¬ tients rarely reached the level of bac¬ teremia utilized by Petersdorf et al in their meningitis studies. However, a recent study by Dietzman et al6 dem-
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Table 2.—Patients With Normal CSF After Initial LP and Purulent CSF After Second LP Initial Culture
Patient & Sex
1.F2
Results
Symptoms
CSF
Blood
Temp, 40 C (104 F);
D pneumon/ae
Temp, 39.5 C (103.1 F); diarrhea, vomiting for 1 wk Meningismus, pneumonia, stupor, tachypnea
D pneumon/ae
Second CSF Examination Purulent
seizure, rhinitis
2, F2 3, M'
4, M1 Mi
6, Ml 7, M'
D
pneumon/ae
Purulent; D pneumon/ae
1,200/ protein level elevated; glucose level, 0 mg/100 ml; D pneumon/ae Leptomeningitis at autopsy; D pneumon/ae Meningitis at autopsy
WBC count, cu mm;
pneumon/ae
Pneumonia, headache
D
Temp, 39.5 C (103.1 F); purpuric rash; back, leg, & joint pains; headache Temp, 39.5 C (103.1 F); pneumonia, leg pain, headache, petechiae Temp, 40 C (104 F); pneumonia & macular rash
Meningococcus Meningococcus
Purulent; intracellular & extracellular
organisms present Meningococcus
4,320/ meningitis
WBC count, cu mm;
cated
if the initial blood culture negative and a CSF examination, obtained only a few hours before, was normal. When meningitis is sus¬ pected, a blood culture should be ob¬ tained in any patient who has an LP. If the blood culture is positive, careful observation of the patient is essen¬ tial. If the child's course does not follow expectations, a second CSF examination is warranted. Because newborn and very young infants are often difficult to evaluate clinically for meningitis, they should have a re¬ peated CSF examination, not only af¬ ter clinical deterioration, but when the initial blood culture is positive for a pathogen. A delay of several hours in the diagnosis and treatment of meningitis may be greatly detrimen¬ tal to the patient.
with intracellular
Name and Trademarks of Drug
Nonproprietary
organisms present at
onstrated that in septic newborns, 30% had greater than 103 bacteria per milliliter of blood and 60% (6/10) of them had meningitis. In contrast, when bacteria counts were less than 103 per milliliter of blood, only 5% (1/20) of patients had meningitis. It seems reasonable to assume, there¬ fore, that the production of a defect in the meninges by a needle could al¬ low some blood to enter the subarachnoid space. If bacteria were in the blood, seeding of the CSF might eas¬ ily occur. Three of the four patients had bacteremia at the time of the ini¬ tial LP. In case 4, the infection was limited to the spinal cord. It is pos¬ sible that the tonsillar herniation served to localize the exúdate and demonstrate its origin near the site of the LP. The patients reported by Wegeforth and Latham1 and Torphy and Ray2 also all had bacteremia recorded at the time of the first LP (Table 2). Pray,7 however, found no increased incidence of meningitis in
autopsy_
children who have an LP during pneumococcal bacteremia when com¬ pared to bacteremic patients not hav¬ ing a prior CSF examination. No single organism can be incrimi¬ nated in the process presented, since three different bacteria are reported. The young ages of the children in our series suggest that the young child is at greatest risk, but when one consid¬ ers that this is also the age group re¬ ceiving most of the CSF examina¬ tions and in whom febrile illnesses are particularly common, this proba¬ bly reflects a sampling bias. Conclusion
The
importance of recognizing that single LP does not rule out men¬ ingitis cannot be overemphasized. The reluctance of many physicians to a
reexamine a child's CSF because an LP had recently shown it to be nor¬ mal is unwarranted. If the patient's clinical course deteriorates or sug¬ gests meningitis, a second LP is indi-
even
was
Ampicillin sodium—Alpen-N, Amcill-S, Omnipen-N. References
Wegeforth P, Latham JR: Lumbar as a factor in the causation of meningitis. Am J Med Sci 148:183-202, 1919. 2. Torphy DE, Ray CG: Occult pneu1.
puncture
mococcal bacteremia. Am J Dis Child 119:336-338, 1970. 3. Weed LH, Wegeforth P, Ayer JB, et al: A study of experimental meningitis: IV. The influence of certain experimental procedures upon the production of meningitis by intravenous inoculation. Monogr Rockefeller Inst Med Res 12:57-114, 1920. 4. Weed LH, Wegeforth P, Ayer JB, et al: The production of meningitis by release of cerebrospinal fluid during an experimental septicemia: Preliminary note. JAMA 72:190-193, 1919. 5. Petersdorf RG, Swarner DR, Garcia M: Studies on the pathogenesis of meningitis: II. Development of meningitis during pneumococcal bacteremia. J Clin Invest 41:320-327, 1962. 6. Dietzman DE, Fischer GW, Schoenknecht FD: Neonatal Escherichia coli septicemia: Bacterial counts in blood. J Pediatr 85:128-130, 1974. 7. Pray LG: Lumbar puncture as a factor in the pathogenesis of meningitis. Am J Dis Child 62:295-308, 1941.
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Fischer, MC, USA;
MAJ Ronald W.
Four patients, with an additional seven from the literature, had meningitis following a lumbar puncture (LP) that disclosed normal cerebrospinal fluid (CSF). Animal studies demonstrate that perforation of the meninges in the presence of bacteremia enhances the development of meningitis. Simultaneous blood cultures should be obtained with all LPs. Regardless of the results of the initial LP, a second CSF examination is recommended in any patient whose clinical condition is deteriorating. If the initial blood culture is positive, a second LP should be strongly considered in all newborn and very young infants.
lumbar puncture (LP) is an abso¬ lute necessity in the exami¬ nation of any infant suspected of having a central nervous system in¬ fection. Since the possibility of men¬ ingitis is generally not considered after an initial LP shows normal cer¬ ebrospinal fluid (CSF), a second CSF examination is often done with reluc¬ tance. The rapid emergence of men¬ ingitis after an LP has shown normal CSF is well documented.1·2 That LPs might contribute to the development of meningitis was suggested clini¬ cally and experimentally as early as
A
Received for publication May 21, 1974; accepted Sept 16. From the Department of Pediatrics, Madigan Army Medical Center, Tacoma, Wash (Drs. Fischer, Brenz, and Alden); and Children's Orthopedic Hospital and Medical Center, Seattle (Dr. Beckwith). Dr. Fischer is now with Tripler Army Medical Center, Honolulu. Reprint requests to Department of Pediatrics, Tripler Army Medical Center, Honolulu, HI 96819 (Dr. Fischer).
Meningitis
Brenz, MC, USA; LTC Errol R. Alden, MC, USA; J. Bruce Beckwith, MD
1919.3"5 We wish to describe four pa¬ tients and to review seven from the literature who were found to have meningitis shortly after an LP showed normal CSF. The develop¬ ment of meningitis after an LP is considered, and the clinical conditions necessitating a second CSF examina¬ tion are discussed. REPORT OF CASES Case 1.—An 8-month-old
girl had a tem¬
perature of 41.1 C (106 F) and lethargy for
days prior to admission. Because of vomiting and continued lethargy, the child was brought to the hospital and admitted. The physical examination showed a mildly lethargic child with a temperature of 39.4 C (103 F) and a full fontane! A fine, erythematous, macular rash was present over the extremities, but no petechiae were noted. Neurologic examination two
showed no abnormalities. Results of the initial LP and laboratory studies were nor¬ mal (Table 1). During the next 24 hours the child developed petechiae and purpura with increased lethargy. The second LP disclosed purulent fluid that contained Neisseria meningitidis by Gram stain and culture. The initial blood culture done on admission was also positive for meningococcus, as was the second culture. Case 2.—A 15-month-old boy had a fever of nine days' duration and symptoms of an upper-respiratory tract infection. The child's condition did not improve on erythromycin therapy, and he had a tempera¬ ture of 40.5 C (104.9 F) and became irri¬ table and lethargic. On admission to the hospital, the physical examination showed no abnormalities except for irritability and a temperature of 40.5 C. Results of the ini-
tial CSF examination were normal (Table 1). The onset of meningismus with contin¬ ued lethargy prompted a second LP to be taken approximately 24 hours later; it dis¬ closed grossly purulent CSF. Haemopkilus influenzae was cultured from the blood and CSF. Case 3.-A 2,863-gm (6.3-lb) girl was ex¬ amined shortly after birth because of ma¬ ternal fever. An LP and blood culture were obtained, and kanamycin sulfate and am¬ picillin sodium therapy was begun. Results of the first LP were normal (Table 1), al¬ though Escherichia coli grew from the original blood culture. The child's condition deteriorated with increasing lethargy and irritability. A second CSF examination was done, and although no organisms were cultured after antibiotic therapy was insti¬ tuted, the presence of cells in the CSF and the clinical course suggested meningitis. Case 4.—A 4-year-old boy was admitted two weeks after the onset of chickenpox with ataxia, vomiting, and headache. The admission temperature was 38.4 C (101.2 F) and a postnasal discharge was noted, but the ears were normal. There was facial weakness on the left side and an abnormal finger-to-nose test. The LP showed clear fluid and an opening pressure of 180 mm H20. The glucose and protein levels were normal, and the Gram stain and culture were negative (Table 1). The initial im¬
pression
was
postchickenpox encephalitis
with cerebellar ataxia. A blood culture the following day was positive for H influ¬ enzae. Despite antimicrobial therapy, the child's condition continued to deteriorate and he developed seizures and vomiting. A second LP four days later disclosed grossly purulent fluid with the Gram stain and cul¬ ture both positive for H influenzae. On autopsy the child was found to have
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Table 1.—Patients With
Meningitis After Initial Discovery of Normal Cerebrospinal Fluid Patient 1 day 12 (100%
4 yr 2 (50%
88 14
68 154
44 44
24 hr
24 hr
E coli 24 hr
4
4,250 (98% segmented cells & 2% lymphocytes)
2,554 (99%
55 46
30 98
8 mo
Age
15 mo
Initial CSF values
WBCs/cu
Glucose level, mg/100 ml Protein level, mg/100 ml Gram stain Initial culture results CSF Blood Interval between examinations Second CSF values
WBCs/cu
mm
Glucose level, mg/100 ml Protein level, mg/100 ml Gram stain Second culture results CSF Blood *
segmented cells &50% lymphocytes)
lymphocytes)
mm
72 8
meningitidis
segmented cells & 1% lymphocytes)
influenzae
days 3,970 (87%
1,880 (10% segmented cells
& 92 124
segmented cells & 13% lymphocytes)
90% lymphocytes)
930
influenzae
influenzae influenzae
meningitidis meningitidis
Exúdate and bacteria limited to cord at autopsy.
pus limited grossly and microscopically to the area of the spinal cord near the site of the LP (Figure). There was associated varicella encephalitis with cerebral swell¬ ing and tonsillar herniation, but there was no evidence of a bacterial infection involv¬ ing the brain.
COMMENT
Lumbar punctures are performed each year on thousands of febrile chil¬ dren to exclude meningitis, but a single negative LP is not absolute confirmation of normal CSF. Al¬ though the pathophysiologic charac¬ teristics of meningitis are not well understood, there are two explana¬ tions for the rapid development of meningitis after an LP has deter¬ mined that the CSF is normal. The first and most obvious possibility is that the patient was bacteremic and had seeded the meninges prior to the initial examination, but that a host response had not yet occurred. Three of the four patients whose cases we described had bacteremias at the time of the initial LP. Seven other patients whose cases were collected from the literature also demonstrated bactere¬ mia with an initial CSF examination and later developed meningitis1-2 (Table 2). The fact that most of these patients are quite ill and have pre¬
senting signs
or
symptoms
sugges-
Localization of
purulent
material is noted
tive of meningitis further strength¬ ens this hypothesis. However, septic infants without meningitis look se¬ verely ill and may die without ever developing meningitis, ie, menin-
gococcemia.
An alternate
explanation is that meningeal damage caused by the LP predisposes the patient to meningitis
when bacteremia is present at the time of CSF sampling. Petersdorf et al5 demonstrated in dogs that when 109 bacteria were given intravenously
over
spinal cord
near
site of initial LP.
without further manipulation, the an¬ imals did not develop meningitis. However, 81% of the dogs with more than 103 bacteria in the bloodstream at the time of cisternal puncture de¬ veloped meningitis.3 These data sug¬ gest that meningeal damage facil¬ itates the development of meningitis. Previously, it was believed that pa¬ tients rarely reached the level of bac¬ teremia utilized by Petersdorf et al in their meningitis studies. However, a recent study by Dietzman et al6 dem-
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Table 2.—Patients With Normal CSF After Initial LP and Purulent CSF After Second LP Initial Culture
Patient & Sex
1.F2
Results
Symptoms
CSF
Blood
Temp, 40 C (104 F);
D pneumon/ae
Temp, 39.5 C (103.1 F); diarrhea, vomiting for 1 wk Meningismus, pneumonia, stupor, tachypnea
D pneumon/ae
Second CSF Examination Purulent
seizure, rhinitis
2, F2 3, M'
4, M1 Mi
6, Ml 7, M'
D
pneumon/ae
Purulent; D pneumon/ae
1,200/ protein level elevated; glucose level, 0 mg/100 ml; D pneumon/ae Leptomeningitis at autopsy; D pneumon/ae Meningitis at autopsy
WBC count, cu mm;
pneumon/ae
Pneumonia, headache
D
Temp, 39.5 C (103.1 F); purpuric rash; back, leg, & joint pains; headache Temp, 39.5 C (103.1 F); pneumonia, leg pain, headache, petechiae Temp, 40 C (104 F); pneumonia & macular rash
Meningococcus Meningococcus
Purulent; intracellular & extracellular
organisms present Meningococcus
4,320/ meningitis
WBC count, cu mm;
cated
if the initial blood culture negative and a CSF examination, obtained only a few hours before, was normal. When meningitis is sus¬ pected, a blood culture should be ob¬ tained in any patient who has an LP. If the blood culture is positive, careful observation of the patient is essen¬ tial. If the child's course does not follow expectations, a second CSF examination is warranted. Because newborn and very young infants are often difficult to evaluate clinically for meningitis, they should have a re¬ peated CSF examination, not only af¬ ter clinical deterioration, but when the initial blood culture is positive for a pathogen. A delay of several hours in the diagnosis and treatment of meningitis may be greatly detrimen¬ tal to the patient.
with intracellular
Name and Trademarks of Drug
Nonproprietary
organisms present at
onstrated that in septic newborns, 30% had greater than 103 bacteria per milliliter of blood and 60% (6/10) of them had meningitis. In contrast, when bacteria counts were less than 103 per milliliter of blood, only 5% (1/20) of patients had meningitis. It seems reasonable to assume, there¬ fore, that the production of a defect in the meninges by a needle could al¬ low some blood to enter the subarachnoid space. If bacteria were in the blood, seeding of the CSF might eas¬ ily occur. Three of the four patients had bacteremia at the time of the ini¬ tial LP. In case 4, the infection was limited to the spinal cord. It is pos¬ sible that the tonsillar herniation served to localize the exúdate and demonstrate its origin near the site of the LP. The patients reported by Wegeforth and Latham1 and Torphy and Ray2 also all had bacteremia recorded at the time of the first LP (Table 2). Pray,7 however, found no increased incidence of meningitis in
autopsy_
children who have an LP during pneumococcal bacteremia when com¬ pared to bacteremic patients not hav¬ ing a prior CSF examination. No single organism can be incrimi¬ nated in the process presented, since three different bacteria are reported. The young ages of the children in our series suggest that the young child is at greatest risk, but when one consid¬ ers that this is also the age group re¬ ceiving most of the CSF examina¬ tions and in whom febrile illnesses are particularly common, this proba¬ bly reflects a sampling bias. Conclusion
The
importance of recognizing that single LP does not rule out men¬ ingitis cannot be overemphasized. The reluctance of many physicians to a
reexamine a child's CSF because an LP had recently shown it to be nor¬ mal is unwarranted. If the patient's clinical course deteriorates or sug¬ gests meningitis, a second LP is indi-
even
was
Ampicillin sodium—Alpen-N, Amcill-S, Omnipen-N. References
Wegeforth P, Latham JR: Lumbar as a factor in the causation of meningitis. Am J Med Sci 148:183-202, 1919. 2. Torphy DE, Ray CG: Occult pneu1.
puncture
mococcal bacteremia. Am J Dis Child 119:336-338, 1970. 3. Weed LH, Wegeforth P, Ayer JB, et al: A study of experimental meningitis: IV. The influence of certain experimental procedures upon the production of meningitis by intravenous inoculation. Monogr Rockefeller Inst Med Res 12:57-114, 1920. 4. Weed LH, Wegeforth P, Ayer JB, et al: The production of meningitis by release of cerebrospinal fluid during an experimental septicemia: Preliminary note. JAMA 72:190-193, 1919. 5. Petersdorf RG, Swarner DR, Garcia M: Studies on the pathogenesis of meningitis: II. Development of meningitis during pneumococcal bacteremia. J Clin Invest 41:320-327, 1962. 6. Dietzman DE, Fischer GW, Schoenknecht FD: Neonatal Escherichia coli septicemia: Bacterial counts in blood. J Pediatr 85:128-130, 1974. 7. Pray LG: Lumbar puncture as a factor in the pathogenesis of meningitis. Am J Dis Child 62:295-308, 1941.
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