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Re: Neonatal meningitis

We read with interest the study by Holt et al,[1] which provides very useful data regarding the current status of neonatal meningitis in England and Wales, where it appears that the incidence of the disease has remained practically unchanged. In a retrospective study of 72 cases of Gram negative bacterial meninitis (GNBM) in term neonates from a single centre in Greece, covering a 15-year period,[2] we too did not observe a significant yearly variation or trend. With respect to antibiotic regimen, since 1983 we have been using third generation cephalosporins (cefotaxime except for the few cases of Pseudomonas meningitis where ceftazidime was used) in combination with amikacin for the treatment of GNBM. Survival of our term neonates with this disease was 97.2%.

However, before attributing any improvements solely to antibiotics used, other factors should be taken into account. We would like to stress the importance of such a factor which could influence prognosis, namely the time interval between onset of symptoms and institution of appropriate therapy. This is not frequently reported. In the report by Anderson and Gilbert[3] symptoms had been noted for more than two days in 50% of their cases before the diagnosis of meningitis was made, while in the study by Unhanand et al[4] the mean interval between symptoms and diagnosis was 1.7 days. It is worth commenting that in that study 8% of their neonates with GNBM had nuchal rigidity.

In our series of term neonates[2] this interval was less than 14 hours and no baby, the vast majority of whom had been admitted from home, had received antibiotics prior to admission to our Unit, reflecting the attitude of primary care physicians who advised hospital evaluation.

In the study by Holt et al[1] the aforementioned time interval is not mentioned, which we think it would of importance to know, particularly as the relatively high death rate due to gram negative enteric bacilli found in their study continued. Also in the same study 21% of neonates admitted from home had received antibiotics in the 48 hours preceding hospital admission, figure which was no different compared with their previous study.[5] Presumably these were term or near term neonates and it would be interesting to know in what way if any, these antibiotics had influenced diagnosis and/or outcome. We think there is a potentially important issue here.

Should primary care physicians prescribe antibiotics to neonates in the immediate postnatal period, particularly when there is no readily identifiable site of bacterial infection and/or no appropriate investigations have been performed? We sould be grateful for the authors' comments on these issues.

Dr H D Dellagrammaticas MD, FRCPCH
Dr N Iacovidou MD
NICU, 2nd Department of Paediatrics
University of Athens
Aglaia Kyriakou Children's Hospital
115 27 Athens, Greece

References
(1) Holt DE, Halket S, de Louvois J, Harvey D. Neonatal meningitis in England and Wales: 10 years on. Arch Dis Child Fetal Neonatal Ed 2001;84:F85-9.

(2) Dellagrammaticas HD, Christodoulou Ch, Megaloyanni E, Papadimitriou M, Kapetanakis J, Kourakis G. Biol Neonate 2000;77:139-146.

(3) Anderson SG, Gilbert GL. Neonatal gram nefative meningitis. A 10 year review with reference to outcome and relapse of infection. J Pediatr Child Health 1990;26:212-16.

(4) Unhanand M, Mustafa M, Mc Cracken GH, Nelson JD. Gram-negative enteric bacillary meningitis. A twenty-one year experience. J Pediatr 1993;122:15-21.

Send letter to journal:
Re: A closer look at neonatal bacterial meningitis

Editor,

Bacterial meningitis has its peak incidence in the neonatal period, but there are few data regarding factors affecting outcome. Like Holt and colleagues [1], we studied infants with meningitis, but focused on bacterial culture-proven cases [2]. Prognostic factors were identified by multivariate analysis in 101 infants with bacterial meningitis admitted between 1979 and 1998 to the Hospital for Sick Children, Toronto [2]. Outcome data were available for all infants. Mortality rates declined from 17.4% in the first decade to 9.0% in the second, rates similar to those observed by Holt and colleagues between 1985 and 1997 (19.8% and 6.6% respectively) [1].

A number of issues arise from comparison of the two studies. Firstly, combining the outcomes of viral with bacterial meningitis provides data, which are not relevant to the outcomes of each type of meningitis alone (respective mortality rates were 0 and 10%)[1]. The mortality rates of the two main pathogens, Group B Streptococci (GBS) and E Coli, (15% and 12% respectively) may give a more accurate mortality estimate for the individual patient with bacterial meningitis.

Secondly, a decrease in the mortality rate may be attributable to secular changes in antibiotic therapy. The bacteria isolated in our cases were sensitive to the initial antibiotics given in all infants. Thus, we found no evidence that changes in management influenced outcomes.

Thirdly, our two studies differ in the secular trends of the proportion of meningitis caused by GBS (increase from 38 to 48% of infants1, compared with a decrease from 59 to 42%2 that we observed). GBS infection in the neonate has been targeted by preventive strategies [3]. The widespread implementation of this strategy may have changed over time and may differ between countries, explaining the differences between our two studies.

Lastly, the cardinal question is whether the fall in mortality rate has been accompanied by a similar reduction in morbidity, or has occurred at the expense of an increase in the number of handicapped survivors. We found no significant change over time in the rate of survival with adverse neurological outcome (11% in the first period vs. 13% in the second). The results of similar analyses of morbidity data from the U.K. are awaited with interest.

Gil Klinger, MD Division of Neonatology, Schneider Children’s Medical Center, Petah Tiqva, Israel and the Sackler School of Medicine, Tel Aviv University

Max Perlman MB, BS, FRCP (Lond), FRCPC Division of Neonatology, The Hospital for Sick Children, 555 University Avenue, Toronto, Canada and The University of Toronto

References