PEDIATRICS Vol. 110 No. 5 November 2002, pp. 1028
Lumbar Punctures and Meningitis
To the Editor.—In their article about the timing of lumbar puncture (LP) in bacterial meningitis, Kanegaye et al1 recommend delaying administration of antibiotics until cultures have been taken. We would like to point out that where meningococcal meningitis is suspected, this potentially life-threatening delay may be neither appropriate nor necessary.
In the United Kingdom, patients suspected of having invasive meningococcal disease are investigated using polymerase chain reaction (PCR) assay of plasma and, where available, cerebrospinal fluid (CSF). This service is provided nationally by the Public Health Laboratory Service (PHLS) Meningococcal Reference Unit (MRU) in Manchester.2
The use of PCR by the PHLS has markedly increased the rate of microbiological confirmation in suspected cases of meningococcal disease. In a review of 103 such cases, 89% were found to be positive by PCR assay, compared with only 44% by more traditional tests such as culture and microscopy.3 It is important to note that PCR detected meningococci even after antibiotics had been administered. Of samples tested >12 hours after initiation of antibiotics, 10 (59%) of 17 were still positive by PCR, whereas only 3 (14%) of 21 samples were positive by culture or microscopy.
For obvious methodologic and ethical reasons, it is difficult to demonstrate rigorously that early treatment improves the outcome in meningococcal disease. However, common sense dictates that treatment should not be delayed unnecessarily. Where postantibiotic diagnosis is available, treatment can be commenced even before hospital admission. This is reflected in practice in the United Kingdom, where family doctors administer intramuscular benzylpenicillin immediately upon suspicion of meningococcal disease and before sending the patient to hospital.
For the hospital doctor, there is less pressure to perform an early LP, with the possible complications that might ensue.4 The current view of many pediatricians in the United Kingdom is that LP should not be performed acutely in patients who are suspected of having meningococcal disease.5 If LP is felt to be necessary, it may be performed electively once the patient is stable.
The ability to offer both early treatment and reliable identification of Neisseria meningitidis is the ideal. Almost a third of the patients studied by Kanegaye et al had meningococcal meningitis. We would urge them to consider the possibilities afforded by PCR in their patients.
A.J. Kvalsvig, MD
D.J. Unsworth, MD
Department of Immunology
Southmead Hospital
Bristol, United Kingdom
REFERENCES
- Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment.
Pediatrics.2001; 108
:1169
–1174
[Abstract/Free Full Text] - Carrol ED,Thomson APJ, Shears P, Gray SJ, Kaczmarski EB, Hart CA. Performance characteristics of the polymerase chain reaction assay to confirm clinical meningococcal disease.
Arch Dis Child.2000; 83
:271
–273
[Abstract/Free Full Text] - Ragunathan L, Ramsay M, Borrow R, Guiver M, Gray S, Kaczmarski E. Clinical features, laboratory findings, and management of meningococcal meningitis in England and Wales: report of 1997 survey. J Infect.2000; 40 :74 –79[CrossRef][Web of Science][Medline]
- Rennick G, Shann F, de Campo J. Cerebral herniation during bacterial meningitis in children. BMJ.1993; 306 :953 –955
- Pathan N, Nadel S, Levin M. Pathophysiology and management of meningococcal septicaemia. J R Coll Physicians Lond.2000; 34 :436 –444[Medline]
To the Editor.—
We read with interest the recent article by Kanegaye et al on recovery of cerebrospinal fluid (CSF) pathogens after parenteral antibiotic treatment.1 Kanegaye et al provide useful objective data that should replace the anecdotal information often cited regarding the time interval between administration of antibiotics and sterilization of CSF.2,3 However, we do not agree that the data support their conclusion that antibiotic administration should be deferred until after lumbar puncture (LP) in children at risk for meningitis, except for those with obvious hemodynamic instability or evidence of cerebral edema.
The aggregate data presented demonstrate identification of a pathogen in 125 (97%) of 129 patients studied. Although finding pathogen sensitivities is important, we cannot agree that this consideration should delay early initiation of therapy. Because of the potentially catastrophic consequences from delayed treatment, many physicians have a low threshold for initiation of antibiotics in children at risk for meningitis. In fact, one facility has described a protocol intended to reduce time to treatment in which a significant proportion of febrile young infants (26%) received parenteral antibiotics before LP.4 The article by Kanegaye et al did not address the subjective appearance or relative hemodynamic stability of patients at the time of antibiotic administration. We suspect that review of this information would demonstrate that potentially unstable infants and children were much more likely to receive antibiotics before LP.
We agree with the authors’ implication that febrile but otherwise well-appearing infants and young children at risk for meningitis should undergo LP before antibiotic administration. We also recognize the practicalities of providing optimum emergency care may include administration of antibiotics before LP in a significant proportion of infants and young children at risk for meningitis.
CPT Todd Arkava, MD
LTC Michael Luszczak, DO
Department of Emergency Medicine
Darnall Army Community Hospital
Fort Hood, TX 76544, USA
REFERENCES
- Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic treatment. Pediatrics.2000; 108 :1169 –1174
- Kookier JC. Spinal puncture and cerebrospinal fluid examination. In: Roberts JR, Hedges JR, eds. Clinical Procedures in Emergency Medicine. 3rd ed. Philadelphia, PA: WB Saunders; 1998: 1054–1077
- Lipton JD, Shafermeyer RW. Evolving concepts in pediatric bacterial meningitis—part II: current management and therapeutic research. Ann Emerg Med.1993; 22 :1616 –1629[CrossRef][Web of Science][Medline]
- Sharieff GQ, Hoecker C, Silva PD. Effect of a pediatric emergency department febrile infant protocol on time to antibiotic therapy. J Emerg Med.2001; 21 :1 –6[Medline]
Reply.—
We thank Drs Kvalsvig and Unsworth and Arkava and Luszczak for their interest. Drs Kvalsvig and Unsworth note that many (29%) of the patients in our study1 had meningococcal disease and recommend early antibiotic treatment because of the availability of polymerase chain reaction (PCR) assays. Drs Arkava and Luszczak argue that the "practicalities of providing optimum emergency care" warrant parenteral pretreatment of pediatric patients "at risk for meningitis."
Our intention was not to encourage unnecessary delay in the treatment of bacterial meningitis, but to encourage timely performance of lumbar puncture (LP) when it is readily available and if the child is clinically stable (lacks signs of septic shock, intracranial hypertension, or mass lesion). When the technical skills, equipment, or laboratory facilities for collection of cerebrospinal fluid (CSF) are lacking, we agree that antibiotics should be administered promptly after collection of a blood culture if there is a high clinical suspicion for meningitis—even in hemodynamically and neurologically stable children. This is particularly true when a patient with highly suspected meningitis requires transport to a pediatric facility. However, when the child is in a medical facility, such as a hospital emergency department (ED) or pediatric inpatient ward, where LPS can be readily performed, we feel that antibiotics may be given immediately after the procedure.
Our discussion recognized the potential utility of PCR in the evaluation of pretreated patients. However, the technique is not without pitfalls,2 and, at this time, its availability remains limited to major medical centers and regional laboratories in the United States. Even the service available in the United Kingdom requires transport of specimens to a single reference laboratory, with results available in 3 to 4 days.3 In the cited study, blood PCR had a sensitivity of only 47%, and 14% of assays were negative when blood cultures were positive.3 In their own discussion, Carroll et al acknowledge that PCR results may not influence clinical management in pretreated, clinically defined meningococcal disease and may be more useful to public health authorities than to the individual patient. Because the majority of our patients had nonmeningococcal disease (and thus lacked the cutaneous findings used by Carrol et al3 and likely helpful to Kvalsvig and Unsworth), the interpretation of negative cultures and PCR in a pretreated patient would be even more difficult. Because at least 25% of blood cultures obtained before parenteral antibiotics may be negative,1 the CSF may be the only source of bacterial identification. Even with antibiotic pretreatment, a Gram-stained smear of CSF may provide useful diagnostic information, and is available universally.
Drs Kvalsvig and Unsworth cite a series of 21 episodes of cerebral herniation in 19 children with bacterial meningitis.4 Our own data do not address the safety of LP in meningitis. However, review of the referenced article reveals that only 8 of the episodes occurred within 3 hours of a LP. Of these, 2 occurred in patients who experienced herniation at other times unrelated to LP, and only 3 occurred within 30 minutes of an LP. Six patients had severe neurologic abnormalities suggestive of herniation or intracranial hypertension at the time of their LPs. All other episodes occurred without LP, before LP, or >3 hours after LP. Thus, the relative roles of LP and natural disease progression in these cases of cerebral herniation remain undefined.
Because of safety concerns, the administration of parenteral antibiotics before computed tomography (CT) and subsequent LP has become common practice for adults with suspected meningitis. This is certainly sound practice if the initial physician examination strongly suggests a mass lesion or intracranial hypertension. However, the likelihood of a focal lesion mimicking meningitis is low among pediatric patients, and neurologic examination predicts clinically significant abnormalities in pediatric meningitis.5 Even among adults, careful examination has excellent sensitivity and negative predictive value for clinically important CT abnormalities.6
Drs Arkava and Luszczak cite the work of Sharieff et al7 and write that 26% of febrile infants "received parenteral antibiotics prior to lumbar puncture." In contrast, the paper reports the intramuscular route of administration in 26% of patients but provides neither data on nor recommendation for parenteral pretreatment. Indeed, the protocol, which was designed for very young (0–8 weeks) infants regardless of clinical appearance, specifically mandates collection of all culture specimens before parenteral antibiotic administration. Our data originate from the same "facility," and one of us (J. T. K.) supervised the committee that created and implemented the pathway.
Clinical appearance and hemodynamic stability are difficult to study retrospectively and were not reported. Also impossible to determine in a chart review are clinicians’ experience and level of comfort in managing sick pediatric patients. Even the number of years in practice or training may not correspond well to expertise in the management of pediatric meningitis. Although we agree with Drs Arkava and Luszczak that clinical appearance may dictate parenteral pretreatment, there are equally likely to be reasons related to clinicians’ practice patterns. Furthermore, we do not agree that the sampling of CSF before antibiotics should be limited to well-appearing infants and children. Indeed, the timely sampling of CSF in ill-appearing children will have the greatest yield in the diagnosis of central nervous system infection.
The importance of prompt recognition, stabilization, and rapid antibiotic administration for the child with suspected bacterial meningitis does not negate the benefit conferred by cultures obtained before parenteral pretreatment. In any ED, the child with meningitis will likely be one of the most ill patients and certainly the sickest child. Therefore, even in the busiest ED, "practicalities" should permit the appropriate personnel to be mobilized to facilitate the timely administration of parenteral antibiotics while allowing the blood cultures and a carefully but expeditiously performed LP.
John T. Kanegaye, MD, FAAP, FACEP*
John S. Bradley, MD, FAAP
* Division of Emergency Medicine Division of Infectious Diseases
Department of Pediatrics
Children’s Hospital and Health Center
San Diego, CA 92123 USA
REFERENCES
- Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics.2001; 108 :1169 –1174
- Isaacman DJ, Zhang Y, Reynolds EA, Ehrlich GD. Accuracy of a polymerase chain reaction-based assay for detection of pneumococcal bacteremia in children.
Pediatrics.1998; 101
:813
–816
[Abstract/Free Full Text] - Carrol ED, Thomson AP, Shears P, Gray SJ, Kaczmarski EB, Hart CA. Performance characteristics of the polymerase chain reaction assay to confirm clinical meningococcal disease. Arch Dis Child.2000; 83 :271 –273
- Rennick G, Shann F,de Campo J. Cerebral herniation during bacterial meningitis in children. BMJ.1993; 306 :953 –955
- Cabral DA, Flodmark O, Farrell K, Speert DP. Prospective study of computed tomography in acute bacterial meningitis. J Pediatr.1987; 111 :201 –205[CrossRef][Web of Science][Medline]
- Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis.
N Engl J Med.2001; 345
:1727
–1733
[Abstract/Free Full Text] - Sharieff GQ, Hoecker C, Silva PD. Effects of a pediatric emergency department febrile infant protocol on time to antibiotic therapy. J Emerg Med.2001; 21 :1 –6
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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