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. 1998 Mar 28;316(7136):1015.
Clinical management of meningococcal disease
Coning may occur without lumbar puncture being done
Editor—Wylie et al do not give the ages of their 252 patients with meningococcal disease, but their recommendation for fewer lumbar punctures should be interpreted cautiously in children.1 Four deaths were attributed to lumbar puncture, which was done in 198 patients. Two patients deteriorated after lumbar puncture, and postmortem examination showed brainstem herniation. Even when lumbar puncture is not performed, however, patients with meningococcal disease can deteriorate after admission and can cone secondary to raised intracranial pressure. A causal relation in these two cases is not proved.
In two patients antibiotic treatment was delayed because initial examination of cerebrospinal fluid was normal. This is a criticism of clinicians, not a risk of lumbar puncture. The risk of cerebrospinal fluid initially giving false negative results and the difficulty of diagnosing meningitis clinically in young children are both recognised. If an ill child warrants a lumbar puncture then he or she should receive antibiotics for 48 hours pending the results of culture, irrespective of the initial results of microscopy.
Lumbar puncture may be dangerous if patients have hypotension, coma, raised intracranial pressure, or focal signs and is unnecessary if there is a typical rash. In a series of 445 children with meningitis, the two children with meningococcal infection and cerebral herniation had contraindications to lumbar puncture.2 Lumbar puncture must be performed more readily in children than adults because of the difficulty of diagnosing meningitis clinically. In 86 children with meningococcal meningitis, only 34 had a typical haemorrhagic rash, and not always at presentation.3
In Wylie et al’s series, lumbar puncture gave a positive result initially in 177 of 198 cases and an overall positive result in 186. In children, a clinical diagnosis of meningitis is unlikely to have a similar sensitivity of 89-94%. Moreover, it is unclear how often a positive culture was obtained from another site in the 120 cases that yielded meningococci; molecular biological techniques give no information on antibiotic sensitivity. If fewer lumbar punctures are done in children with meningitis some will be missed and the start of treatment will be delayed. This increases the risk of death,4 possibly above the 2% attributable to lumbar puncture in this series. Wylie et al have shown a high sensitivity and low mortality from lumbar puncture. Before recommending that the procedure be used less we need to be reassured that clinical diagnosis alone does not result in worse sensitivity and mortality, particularly in children.
References
1.Wylie PAL, Stevens D, Drake W, Stuart J, Cartwright K. Epidemiology and clinical management of meningococcal disease in west Gloucestershire: retrospective, population based study. BMJ. 1997;315:774–779. doi: 10.1136/bmj.315.7111.774. . (27 September.) [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Rennick G, Shann F, Campo J. Cerebral herniation during bacterial meningitis in children. BMJ. 1993;306:953–955. doi: 10.1136/bmj.306.6883.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. BMJ. 1992;305:143–147. doi: 10.1136/bmj.305.6846.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
BMJ. 1998 Mar 28;316(7136):1015.
Lumbar puncture is still performed in patients with contraindications
Editor—The editorial by Cartwright and Kroll and the paper by Wylie et al discuss some of the issues surrounding the management of both meningococcal disease and meningitis in general.1-1,1-2 Two of the points raised—prehospital use of benzylpenicillin and the risks associated with lumbar puncture—require emphasis because optimum practice is rare.
Prehospital administration of benzylpenicillin by general practitioners is the current recommendation. ln Wylie et al’s paper the proportion of cases in which this occurred was initially 18%, increasing to 40% during the study period. In a similar study this figure in our locality was only 10%, which may be explained by the low frequency of presentation of this disease to any individual general practitioner. Early presentation to the general practitioner for treatment is, however, important and relies on the recognition of purpura at home. A previous study identified a lack of awareness among health professionals in recognising meningococcal purpura.1-3 Similarly, in a survey of 200 parents or carers attending a variety of paediatric medical and surgical clinics at this hospital, 64% were unaware of either the significance of purpura or the use of the glass test to detect purpura as promoted by the Health Education Authority1-4 despite recent media publicity. Only 15% of parents were able to perform this test.
Wylie et al found that lumbar puncture had been a contributory factor in the death of four patients. Despite widespread recognition of the contraindications to lumbar puncture they remain poorly recognised in everyday clinical practice. In a retrospective analysis of cases of meningitis at this hospital, lumbar puncture was performed in the presence of a contraindication in a third of patients, although no adverse outcomes were noted. Subsequent alterations to unit protocols have reduced this figure considerably.
Both of these issues revolve around improved education of both public and health professionals.
References
1-1.Cartwright K, Kroll S. Optimising the investigation of meningococcal disease. BMJ. 1997;315:757–758. doi: 10.1136/bmj.315.7111.757. . (27 September.) [DOI] [PMC free article] [PubMed] [Google Scholar]
1-2.Wylie PAL, Stevens D, Drake W, Stuart J, Cartwright K. Epidemiology and clinical management of meningococcal disease in West Gloucestershire: retrospective population study. BMJ. 1997;315:774–779. doi: 10.1136/bmj.315.7111.774. . (27 September.) [DOI] [PMC free article] [PubMed] [Google Scholar]
1-3.Riordan FAI, Thomson APJ, Sills JA, Hart CA. Who spots the spots? Diagnosis and treatment of early meningococcal disease in children. BMJ. 1996;313:1255–1256. doi: 10.1136/bmj.313.7067.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
1-4.Health Education Authority. A guide to childhood immunisations including advice on recognising meningitis. London: HEA and Department of Health, 1996.
Editor—We agree with Stephenson that coning may occur in meningococcal meningitis with or without the added insult of lumbar puncture. For ethical reasons, prospective trials to clarify the respective contributions of disease and clinical investigation to cerebral herniation are unlikely. We also agree that children ill enough to warrant lumbar puncture should receive antibiotics for 48 hours regardless of findings on initial examination of cerebrospinal fluid. We believe that the high frequency of misleading initial negative findings on examination of cerebrospinal fluid in meningococcal meningitis (8%) is insufficiently well appreciated. If meningococcal disease is suspected then our view is that antibiotic treatment must be started immediately, regardless of any investigations undertaken. Meningococci in Britain, as elsewhere, are sensitive to penicillin, at least at present.
In our article we were at pains to avoid prescriptive advice on the need for, and the place of, lumbar puncture in suspected meningococcal infection. Before performing a lumbar puncture clinicians must ask themselves: “Will the results influence clinical management?” and “Am I likely to harm the patient?” If meningococcal disease is overwhelmingly likely on clinical and epidemiological grounds then a lumbar puncture may add little, whereas this may not be the case if alternative diagnoses are being entertained seriously. Our series of patients with meningococcal disease included both adults and children; though Neisseria meningitidis is by far the most common cause of bacterial meningitis in children under 5 years, the epidemiology of bacterial meningitis is more varied in adults.
We wished to emphasise in our paper that lumbar puncture, though often invaluable, may be hazardous. It should be undertaken only when deemed really necessary and in the absence of contraindications. Winrow confirms the continuing high frequency with which lumbar puncture is performed in patients with contraindications. We were encouraged that in his unit successful measures were implemented to reduce the overuse of this investigation.
Encouragingly, case fatality rates for meningococcal disease are falling (M Ramsay, personal communication). In common with Winrow, we believe that while effective vaccines are awaited, further reductions in mortality can be achieved by enhancing public and professional awareness and by optimising early recognition and management of meningococcal disease through audit and education in both primary and secondary care.
Editor—Cartwright and Kroll discuss the investigation of suspected cases of meningococcal infection,3-1 but evidence suggests that previous advice on this matter3-2 is not being implemented. From April 1996 to March 1997, 81 Birmingham residents were either notified to the consultants for communicable disease control or discharged from hospital with a diagnosis of meningococcal infection. We carried out a retrospective analysis of the investigations performed on these patients.
In 22 cases the diagnosis was confirmed by culture or Gram staining of blood or cerebrospinal fluid. In a further three cases it was confirmed from a nasopharyngeal swab. Only one patient had a bleb aspiration carried out (which was negative for meningococcus). In the remaining 56 cases, DNA from blood was amplified with the polymerase chain reaction in 13 (yielding positive results for meningococcus in five), DNA from cerebrospinal fluid was amplified with the polymerase chain reaction in nine (three results were positive), and blood samples were sent for serological testing in eight (five results were positive). In total, the diagnosis was confirmed microbiologically in 34 of the 81 cases.
The importance of ensuring that the optimal process for managing a case or outbreak of meningococcal infection is in place and adhered to is recognised locally. The early management of this infection is one of seven clinical effectiveness initiatives in Birmingham. As a result, data collection tools to facilitate the audit of both preadmission and early hospital management of meningococcal infection have been developed.
Laboratory confirmation of clinical suspicion plays an important part in the management of meningococcal infection in the community.3-3 Until such investigations as polymerase chain reaction and serological testing become more established, the difficulties in dealing with “definite,” “probable,” or “possible” cases and outbreaks of this serious infection will remain.
References
3-1.Cartwright K, Kroll S. Optimising the investigation of meningococcal disease. BMJ. 1997;315:757–758. doi: 10.1136/bmj.315.7111.757. . (27 September.) [DOI] [PMC free article] [PubMed] [Google Scholar]
3-2.Kaczmarski EB, Cartwright KAV. Control of meningococcal disease: guidance for microbiologists. Commun Dis Rep CDR Rev. 1995;5:R196–R198. [PubMed] [Google Scholar]
3-3.Stuart JM, Monk PN, Lewis DA, Constantine C, Kaczmarski EB, Cartwright KAV. Management of clusters of meningococcal disease. Commun Dis Rep CDR Rev. 1997;7:R3–R5. [PubMed] [Google Scholar]
BMJ. 1998 Mar 28;316(7136):1015.
Prospective international registration of patients may be needed
Editor—The prognosis for meningococcal disease has not improved since the introduction of antibiotic treatment. Prehospital antibiotic treatment has been recommended4-1 because of the combined evidence from five health districts in Britain,4-2–4-4 but conflicting data from a similar Danish study4-5 have been ignored. In the Danish study the case fatality rate was higher when treatment with parenteral antibiotics started before hospital admission (figure). The overall case fatality rate was 9.7% when the British data were used and 6.2% in the Danish study.
Results of observational studies of effect of prehospital antibiotic treatment of meningococcal disease and results of meta-analysis
No randomised trials of the effect of prehospital antibiotic treatment have been carried out, and the published results are undoubtedly subject to confounding by indication. Prehospital treatment may be beneficial, because confounding by indication would tend to mask a possible effect. The empirical evidence is not, however, convincing when all published results are pooled (Mantel-Haenszel weighted odds ratio 0.82; 95% confidence interval 0.43 to 1.56 (figure)). The proponents of prehospital penicillin find support in the observation that penicillin may reduce the concentration of bacterial lipopolysaccharides in the blood of the patients with meningococcal disease. These lipopolysaccharides seem to be the main toxic element of meningococci and are a strong predictor of death. It is impossible, however, to exclude the possibility that antibiotic treatment without appropriate resuscitation may be detrimental to a subset of patients with an advanced stage of septic shock or disseminated intravascular coagulation.
For various reasons it is not possible to conduct a randomised trial to clarify the situation and the existing studies do not identify the patients who benefit from prehospital treatment. Prospective international registration of patients with meningococcal disease, including information on clinical status and indications for prehospital treatment, may be needed.
References
4-1.Cartwright K, Kroll S. Optimising the investigation of meningococcal disease. BMJ. 1997;315:757–758. doi: 10.1136/bmj.315.7111.757. . (27 September.) [DOI] [PMC free article] [PubMed] [Google Scholar]
4-2.Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. BMJ. 1992;305:143–147. doi: 10.1136/bmj.305.6846.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
4-3.Strang JR, Pugh EJ. Meningococcal infections: reducing case fatality rate by giving penicillin before admission to hospital. BMJ. 1992;305:141–143. doi: 10.1136/bmj.305.6846.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
4-4.Gossain S, Constantine CE, Webberly JM. Early parenteral penicillin in meningococcal disease. BMJ. 1992;305:523–524. doi: 10.1136/bmj.305.6852.523-c. [DOI] [PMC free article] [PubMed] [Google Scholar]
4-5.Sørensen HT, Møller-Petersen J, Krarup HB, Pedersen H, Hansen H, Hamburger H. Early treatment of meningococcal disease. BMJ. 1992;305:774. doi: 10.1136/bmj.305.6856.774-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
