RESEARCH ARTICLE
Pneumococcal meningitis in childhood: a longitudinal prospective
study
Pasquale Pagliano1, Ugo Fusco1, Vittorio Attanasio1, Marco Rossi1, Annalisa Pantosti2, Marco Conte3 &
Francesco Saverio Faella1
1
Department of Emergency, I Division of Infectious Diseases, ‘D. Cotugno’ Hospital, Naples, Italy; 2Department of Microbiology, Istituto Superiore di
Sanità, Rome, Italy; and 3Department of Microbiology, ‘D. Cotugno’ Hospital, Naples, Italy
Correspondence: Pasquale Pagliano,
Department of Emergency, I Division of
Infectious Diseases, c/o ‘‘D. Cotugno’’
Hospital Via G. Quagliariello 54, 80131
Napoli, Italy. Tel./fax: 139 0815908292;
e-mail: ppagliano@libero.it
Received 25 January 2007; revised 19 July
2007; accepted 27 July 2007.
First published online 18 September 2007.
DOI:10.1111/j.1574-695X.2007.00324.x
Editor: Ewa Sadowy
Keywords
meningitis; CSF; children; outcome;
Streptococcus pneumoniae ; penicillin
susceptibility.
Introduction
The epidemiology of bacterial meningitis in childhood has
changed significantly during the past few years, mainly
because of programmes for routine immunization of infants
with conjugate Haemophilus influenzae b (Hib) vaccine. In
developed countries, where immunization programmes
against Hib were strongly sustained, Hib meningitis has
declined dramatically and Streptococcus pneumoniae and
Neisseria meningitidis have become the most common
agents of bacterial meningitis in childhood (Schuchat et al.,
1997; Dawson et al., 1999).
Despite continuous improvements in antibiotic therapy
and intensive treatment, pneumococcal meningitis remains
a severe and life-threatening disease. In fact, large trials
performed during the past 20 years, involving adult or
paediatric cases, report case–fatality rates ranging between
4% and 16% and neurological sequelae in over 30% of the
c 2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
Abstract
After implementation of programmes for active immunization against Haemophi-
lus influenzae b, Streptococcus pneumoniae and Neisseria meningitidis became the
most common agents of bacterial meningitis in childhood. Over a 9-year period,
children showing clinical and laboratory findings of meningitis on the basis of
their positive cultures of blood or cerebro-spinal fluid (CSF) for S. pneumoniae
were enrolled. Predisposing conditions, clinical and laboratory findings, and
microbiological and imaging studies were considered. Meningitis-related death or
neurological sequelae defined an unfavourable outcome. Sixty-four patients met
the inclusion criteria. Thirty-one (48%) children had predisposing conditions to
pneumococcal meningitis. Fever and neck stiffness were the main symptoms; 14
patients (22%) reported seizures before admission. Twenty-one patients required
treatment in the intensive care unit (ICU). Streptococcus pneumoniae strains were
penicillin susceptible in 54 cases (84%). Forty-eight children (75%) showed
complete recovery. Two patients (3%) died, and 14 (22%) had sequelae. Patients
with a low CSF cell count, low neutrophils, early admission to ICU or infection by
penicillin-nonsusceptible strains of S. pneumoniae had an unfavourable outcome
more frequently. Low blood neutrophils, low CSF cell count, early admission to
ICU and infection by penicillin-nonsusceptible strains are the main factors
predicting an unfavourable outcome in children with pneumococcal meningitis.
survivors (Kornelisse et al., 1998; Arditi et al., 1998; Aubur-
tin et al., 2002; Kastenbauer & Pfister, 2003).
Identification of the factors predicting the outcome of
pneumococcal meningitis is of great value as it permits the
identification of patients at a higher risk of intracranial
complications who may benefit from early diagnosis and
intensive treatment. Among the baseline characteristics, the
prognostic value of penicillin susceptibility was suspected on
the basis of some case reports describing the poor efficacy of
monotherapy with third-generation cephalosporins, when
penicillin- or cephalosporin-resistant strains were involved,
but was not confirmed by adult or paediatric studies of
patients with pneumococcal meningitis (Bradley & Scheld,
1997; Kaplan, 2002; Kellner et al., 2002; McMaster et al., 2002).
The aim of the present study was to investigate the
baseline clinical and laboratory features of childhood pneu-
mococcal meningitis and their influence on outcome, and
also to evaluate the role of penicillin susceptibility.
FEMS Immunol Med Microbiol 51 (2007) 488–495
Pneumococcal meningitis in childhood 489

Methods conventional methods (e.g. optochine susceptibility test).

Susceptibility assays of penicillin, cefotaxime, rifampin,
This was a prospective study of children with pneumococcal
vancomycin and erythromycin were performed using an
meningitis referred to the Department of Emergency and
E-test with the Clinical Laboratory Standard Institute inter-
Infectious Diseases at the D. Cotugno Hospital (Naples,
pretative criteria for minimum inhibitory concentration
Italy) between January 1997 and December 2005. Approval
(MIC). Susceptibility of the pneumococcal strains obtained
for the study was obtained from the internal review board,
during the course of the study was evaluated by the authors’
and all patients’ legal representatives gave written informed
laboratory and confirmed using an E-test by the reference
consent to participate in the study.
laboratory of the ‘Istituto Superiore di Sanità’ in Rome, Italy,
as part of a national surveillance programme of bacterial
Patients
meningitis. The serotyping of the strains of S. pneumoniae
Consecutive children affected by bacterial meningitis were was performed by the authors’ Laboratory of Microbiology
evaluated if they tested positive either on urine or on or by the Laboratory of Microbiology of the Istituto Super-
cerebro-spinal fluid (CSF) for pneumococcal antigens. A iore di Sanità (ISS), as reported elsewhere (Pantosti et al.,
case of pneumococcal meningitis was defined by character- 2000).
istic clinical signs and symptoms (i.e. neck stiffness, a
bulging fontanel, headache or vomiting), CSF pleocytosis Imaging studies
(4 10 cells mL 1), detection of pneumococcal antigens in
A computed tomographic (CT) scan of the brain was
either urine or in CSF samples or isolation of S. pneumoniae
scheduled at admission. During the hospital stay and the 8-
from blood or CSF cultures. If lumbar puncture was not
week follow-up period, repeated CT or magnetic resonance
performed at admission, the diagnosis of pneumococcal
imaging (MRI) scans of the brain were performed for
meningitis was based on clinical signs and symptoms and
patients with either positive findings on admission or
isolation of S. pneumoniae from blood cultures. The inclu-
suspicion of cerebral oedema, or in the presence of focal
sion criteria for the study were: (1) positive blood or CSF
neurological deficit. A CT scan of the brain was performed
cultures for S. pneumoniae; (2) availability of the S. pneu-
immediately before discharge in all cases, regardless of the
moniae susceptibility assay performed by an E-test; and (3)
CT findings on admission.
ages ranging from 1 month to 14 years. The exclusion
criterion was HIV coinfection.
Treatment
Data collection A 14-day course of antimicrobial therapy was scheduled.
During the first 3 years of the study, children received third-
Demographic data, detailed information about previous or
generation cephalosporin (ceftriaxone 100 mg kg 1 intra-
underlying diseases, presenting signs and symptoms (fever,
venously every 24 h or cefotaxime 100 mg kg 1 intravenously
defined as a body temperature 4 38 1C, neck stiffness, focal
every 8 h), as empirical therapy. In this period, a multidrug
neurological deficit, coma), findings of the CSF exam (cell
therapy containing third-generation cephalosporin and
count, protein and glucose concentrations) and evidence
vancomycin (15 mg kg 1 intravenously every 6 h) or rifam-
obtained from laboratory and neuroradiographic studies
pin (8 mg kg 1 intravenously every 12 h) was administered
were recorded on admission. The data obtained from
only to comatose or immunodepressed patients. During the
clinical evaluation, laboratory exams and neuroradiographic
last 6 years of the study, because of the increasing diffusion
studies performed during hospitalization, as well as the
of penicillin-nonsusceptible strains of S. pneumoniae, study
findings of a complete clinical evaluation performed 8 weeks
protocol changed (Pantosti et al., 2000; Whitney et al.,
after treatment were recorded for each subject on a standar-
2000). Therefore, the empirical therapy was changed to
dized case report form.
third-generation cephalosporin plus rifampin or vancomy-
cin (vancomycin was given additionally to children aged 6
Microbiological studies
months or less). When microbiological studies were avail-
Blood and CSF samples were obtained for microbiological able, antibiotic treatment was continued on the basis of the
studies, including pneumococcal antigen detection before susceptibility test, and monotherapy with ceftriaxone or
starting any antibiotic treatment. Blood and CSF samples cefotaxime was administered only to children with pneumo-
were inoculated in a BACTEC Plus Aerobic/F (Becton- coccal meningitis due to a penicillin-susceptible strain.
Dickinson) and were incubated in BACTEC 9240 device Besides antibiotic therapy, children received dexamethasone
(Becton-Dickinson). Positive cultures were inoculated in (0.15 mg kg 1 intravenously every 6 h). The latter was ad-
sheep blood agar and chocolate agar and incubated in 5% ministered 1 h before the antibiotics on four consecutive
CO2. The identification of the strains was confirmed by days starting on admission.

FEMS Immunol Med Microbiol 51 (2007) 488–495

c 2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
490 P. Pagliano et al.

Outcome cluded because of negative cultures despite positive CSF

pneumococcal antigen, three because of lack of susceptibil-
An adverse clinical outcome was defined as meningi-
ity data, and one because of HIV coinfection. Overall, 64
tis-related death or evidence of neurological sequelae in
children were included in the study; the sex ratio (male :
survivors. The latter included motor deficit, hearing loss,
female) was 1.9 : 1, and the median (IQR) age was 26 (7–89)
behavioural or language disturbance and hydrocephalus.
months. No patient had previously received antipneumo-
These conditions were diagnosed by means of a complete
coccal vaccine.
clinical exam of sensory and motor functions performed 8
One or more predisposing conditions to pneumococcal
weeks after the end of the therapy. The clinical examination
meningitis were recognized in 31 (48%) children. Eighteen
was integrated by audiological evaluation and CT or MRI
reported recurrent ear/sinus infections, seven had a CSF leak
scan of the brain, when required.
or experienced a severe head trauma or underwent neuro-
surgery (Table 1). Predisposing conditions were not found
Statistical analysis in 21 (68%) of 31 patients younger than 24 months and in
The Fisher exact test and a two-tailed w2 test were used to 12 (36%) of 33 patients older than 24 months (P = 0.01;
compare qualitative variables. Quantitative data were ex- odds ratio 3.7, confidence interval 1.2–11.9).
pressed as medians [interquartile range (IQR)] and com- The length of general symptoms of illness before the
pared using the Mann–Whitney U-test. Two-tailed P-values administration of intravenous antibiotic therapy ranged
of o 0.05 were considered to be statistically significant. between 1 and 4 days (median 1 day). On admission, 60
Variables achieving statistical significance at a 90% level in (94%) patients had fever, 55 (86%) had neck stiffness and 16
the univariate analysis were simultaneously considered by (25%) were comatose. Seizures before admission were
multivariate logistic regression analysis to determine inde- reported in 14 (22%) patients, 12 had generalized seizures
pendent factors of adverse outcome. The results of the and two had focal seizures. Twenty-one patients were
multivariate analysis are presented as estimated odds ratio, admitted to the intensive care unit (ICU) because of a
with corresponding 95% confidence intervals. SPSS 13.0 rapidly deteriorating clinical condition; 13 patients required
software was used for statistical analysis. mechanical ventilation. All ICU admissions occurred within
48 h from the diagnosis of meningitis.
Lumbar puncture was performed on admission in 61
Results
(95%) children, while in three it was delayed because of CT
Eighty-six children with pneumococcal meningitis were evidence of increased intracranial pressure. The findings of
observed during the study period. Of these, 18 were ex- the CSF exam revealed a high cell count, high protein and
low glucose concentration in all patients (Table 2).
Table 1. Predisposing conditions in 31 of 64 children with pneumococ-
CT scan performed on admission showed abnormalities
cal meningitis in 14 (22%) patients: brain oedema in 14, arterial infarction
in two, and sinus thrombosis in two.
Conditions Number of cases %
Empirical therapy included third-generation cephalos-
Recurrent ear or sinus infections 18 28
porin monotherapy in 15 patients and a combined admin-
Common variable immunodeficiency 3 5
istration of cephalosporin plus vancomycin (six patients) or
Recent or remote head trauma 3 5
Previous neurosurgery 2 3 rifampin (43 patients) in the remaining 49 cases. Two
CSF leak 2 3 patients had a maculopapular skin eruption because of an
Status post splenectomy 1 2 allergic reaction to ceftriaxone, respectively, 2 and 7 days
Diabetes mellitus 1 2 after administration of the first dose. Both received mer-
Bone marrow transplantation 1 2 openem (120 mg kg 1 day 1, divided in three doses) to
Chronic hepatitis 1 2
complete the course of therapy. No other toxicity was
Asthma 1 2
reported, and, no case of bleeding occurred after dexa-
CSF, cerebrospinal fluid. methasone therapy. Time from evidence of symptoms and

Table 2. CSF exam findings and their relationship with disease severity
Findings ICU admission (19 patients) No ICU admission (42 patients) All cases
1
Proteins [mg dL ; median (IQR)] 338 (250–328) 319 (181–482) 320 (200–530)
Glucose [mg dL 1; median (IQR)] 32 (5–61) 17 (5–48) 19 (19–45)
Cell count [  103 cells mL 1; median (IQR)] 900 (150–4000) 1900 (900–6650) 1600 (600–6250)

CSF, cerebro-spinal fluid; ICU, intensive care unit.

c 2007 Federation of European Microbiological Societies FEMS Immunol Med Microbiol 51 (2007) 488–495
Published by Blackwell Publishing Ltd. All rights reserved
Pneumococcal meningitis in childhood 491

start of i.v. antimicrobial therapy ranged between 24 and The median (IQR) time of defervescence was 4 (2–6)
70 h and was quite similar for cases infected by nonsuscep- days. No difference occurred in patients infected by
tible strains of S. pneumoniae and for those infected by penicillin-susceptible or -nonsusceptible strains of S. pneu-
susceptible strains. moniae. During hospitalization, 11 (17%) patients had
Streptococcus pneumoniae was isolated from CSF cultures meningitis-associated intracranial complications: eight had
in 16 patients, from blood cultures in seven patients and subdural hygroma, two had hydrocephalus and one had
from both blood and CSF cultures in 41 patients. Overall, sinus thrombosis. One of these cases needed permanent CSF
two strains were fully resistant to penicillin (MIC 3 mg mL 1) drainage.
and eight showed intermediate resistance (MIC Forty-eight (75%) children did not show sequelae. Two
0.1–1 mg mL 1). Two strains had intermediate resistance to (3%) children died: one 3 days after admission because of
cefotaxime (MIC 2 mg mL 1); both strains were fully resis- severe septic shock, and the other after 14 days because of
tant to penicillin. Twenty-one strains were resistant to cardiac arrest. The latter children had no electroencephalo-
erythromycin; none was resistant to vancomycin or rifam- graphic activity 48 h after admission. The case–fatality ratio
pin. One (7%) of 15 patients observed during the first 3 was 2% for patients infected by penicillin-susceptible strains
years of the study and nine (18%) of 49 cases observed and 10% for those infected by nonsusceptible strains. One
during the last 6 years were infected by penicillin-nonsus- or more sequelae were reported in 14 (22%) patients (six
ceptible strains of S. pneumoniae (P = 0.28). All cases in- were infected by penicillin-nonsusceptible strains). Seven
fected by nonsusceptible strains received combined reported paresis, four hearing loss, two hydrocephalus and
treatment since admission. two cognitive impairment.
Association through serotypes and outcome for 52 strains Table 4 reports the baseline findings vs. outcome, as
of S. pneumoniae are reported in Table 3. Serotypes were assessed by univariate analysis. The CSF cell count
analysed by the Laboratory of Microbiology of the ISS in an (P = 0.001), peripheral white blood cells (P = 0.001) and
earlier study and by the authors’ Laboratory of Microbiol- blood neutrophils (P = 0.0001) were lower in patients with
ogy during the last period of the study. The overall coverage unfavourable outcome. ICU admission within 48 h from the
of pneumococcal conjugate vaccines (PCV) was 54% for the onset of symptoms (P o 0.00001) and infection sustained
heptavalent (PCV-7) and nanovalent (PCV-9) vaccines, 57% by a nonsusceptible strain of S. pneumoniae (P = 0.012)
for the nanovalent vaccine (PCV-11) and 67% for the resulted more frequently in an adverse clinical outcome.
13-valent vaccine (PCV-13). Children infected by S. pneu- When variables achieving significance at a 90% level by
moniae serotype 9 had the highest incidence of unfavourable univariate analysis were simultaneously evaluated by multi-
outcome. variate logistic analysis, only admission to ICU was asso-
ciated with an increased risk of unfavourable outcome (odds
Table 3. Serotype distribution and outcome of 52 patients with
ratio 23.6, 95% confidence limits 3.12–178.9, P = 0.0001). To
pneumococcal meningitis
better observe the prognostic value of laboratory and
Favourable Unfavourable microbiological findings, a multivariate model was used
Serotype outcome outcome Sequelae
where the continuous variables achieving significance by
3 1 1 Hydrocephalus univariate analysis were dichotomized according to the 25th
4 2 0
percentile value. Both CSF cell count below 600 mL 1 (odds
6A 3 0
ratio 10.4, 95% confidence intervals 2.6–52.6, P = 0.002) and
6B 3 1 Hearing loss
8 3 0 penicillin nonsusceptibility (odds ratio 11.2, 95% confi-
9N 0 2 Hearing loss, hemi paresis dence intervals 1.6–83.9, P = 0.009) were predictive of an
9V 1 2 Death, hemi paresis unfavourable outcome (Table 5).
11 A 3 0
14 4 2 Hemi paresis, hearing loss
15 B 2 0 Discussion
18 A 2 0
Pneumococcal meningitis in childhood is a life-threatening
18 C 3 1 Cognitive impairment
19 A 1 1 Hemi paresis disease determining a high incidence of neurological seque-
19 F 2 1 Hearing loss lae in survivors. The case–fatality ratio and sequelae re-
23 A 1 1 Hemi paresis ported in this study were lower than those observed in other
23 F 4 1 Cognitive impairment European and North-American series (Arditi et al., 1998;
31 1 0 Auburtin et al., 2002; Kellner et al., 2002; McMaster et al.,
33 1 0
2002). Many factors, including wide use of combined
NT 2 0
antimicrobial therapy and administration of dexametha-
NT, nontypeable. sone, may have favoured the better outcome (Bradley &

FEMS Immunol Med Microbiol 51 (2007) 488–495

c 2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
492 P. Pagliano et al.

Table 4. Base-line findings in respect to outcome

Favourable outcome Unfavourable outcome
Findings (48 patients) (16 patients) P
Age o 24 months 20 11 0.09
Age 4 24 months 29 5
Treatment within 48 h 34 12 0.51
Treatment after 48 h 14 4
PNSP 4 6 0.012
PSSP 44 10
ICU admission 8 13 0.00001
No ICU admission 40 3
CSF cell count # [cells mL 1; median (IQR)] 2000 (1100–6500) 550 (142–1325) 0.001
CSF glucosew [mg dL 1; median (IQR)] 31 (5–46.5) 10 (3–22) 0.13
CSF proteinsw [mg dL 1; median (IQR)] 347 (200–1090) 315 (254–512) 0.39
Blood leucocytes [  103 cells mL 1; median (IQR)] 22.5 (16.1–27.5) 14.1 (7.5–19.0) 0.001
Blood neutrophils [  103 cells mL 1; median (IQR)] 19.1 (13.4–24.6) 12.6 (6.1–16.1) 0.0001
P are calculated by Mann–Whitney U-test and by Fisher’s exact test as appropriate.
w
The analysis was done for 61 patients, because three, respectively one with favourable and two with unfavourable outcome did not undergo to lumbar
puncture at admission.
PNSP, Penicillin-nonsusceptible Streptococcus pneumoniae; PSSP, penicillin-susceptible Streptococcus pneumoniae; CSF, cerebro-spinal fluid;
ICU, intensive care unit.

Scheld, 1997; Kaplan, 2002; McMaster et al., 2002; Bucking-
ham et al., 2006).
The prognostic value of the CSF cell count emerging from
the analysis of the present data may be sustained on the basis
of clinical and experimental evidences and may have a
therapeutic impact. The association between CSF cell count
and outcome was reported in a retrospective study of adult
pneumococcal meningitis and was related to the serotype
involved in another retrospective study considering the
outcome of pneumococcal meningitis cases sustained by
serotypes 1, 3 and 9 V (Kastenbauer & Pfister, 2003; Oster-
gaard et al., 2004). Similar findings were reported in a model
of pneumococcal meningitis demonstrating that the bacter-
ial growth within CSF and the outcome were influenced by
the increase of peripheral neutrophils obtained by granulo-
cyte colony-stimulating factor or by the attenuation of CSF
pleocytosis obtained by fucoidin (Brandt et al., 2004; Brandt
et al., 2005). On the basis of these clinical and laboratory
findings, it may be supposed that an insufficient inflamma-
tory response against pneumococcal antigens during the
first hours of the disease permits a bacterial overgrowth
Table 5. Prognostic value of laboratory and microbiological findings as
assessed by multivariate analysis
Findings Odds ratio 95% CI
CSF cell count o 600 mL 1 10.4 2.6–52.6
Penicillin nonsusceptibility 11.2 1.6–83.9
1
White blood cell count o 13 850 mL 1.945 0.017–225.9
Blood neutrophils o 11 950 mL 1 1.945 0.017–225.9
Continuous variables achieving significance by univariate analysis were
dichotomised according to 25th percentile value.
within the CSF. In these cases, when antimicrobial therapy is
administered, the considerable bacterial lysis results in more
pronounced inflammatory changes within the meninges
and vascular complications are favoured. Children with a
relatively low CSF cell count have to receive high-dose
steroids and combined antimicrobial therapy to reduce the
bacterial load, meningeal inflammation and, consequently,
neurological complications as quickly as possible (Kornelisse
et al., 1995; Müller et al., 1995; Ries et al., 1997; Waterer
et al., 2001).
The spread of antibiotic-resistant pneumococcus strains
with high-level penicillin resistance and multidrug resis-
tance represents a concrete threat. Indeed, when penicillin-
nonsusceptible strains were involved, about half of the cases
reported an unfavourable outcome, unless an antimicrobial
therapy active against penicillin-nonsusceptible strains of
S. pneumoniae was firmly adopted. The association between
penicillin susceptibility and outcome has not been reported
in any previous study of pneumococcal meningitis, but was
reported in studies evaluating the outcome of patients
affected by pneumococcal pneumonia, as confirmed by a
large meta-analysis (Tleyjeh et al., 2006). It is believed that
the larger definition of unfavourable outcome adopted in
this study, including both mortality and sequelae, gave more
statistical efficacy to the sample and permitted the observa-
P tion of the influence of penicillin susceptibility on outcome.
0.002 However, because other factors, such as the pneumococcal
0.009 strain involved and the patients’ underlying conditions, may
0.784 influence the outcome of pneumococcal meningitis, the
0.784
prognostic value of penicillin susceptibility needs further
investigation by larger multicentre trials (Bradley & Scheld,
1997; Aronin et al., 1998; Cabellos et al., 2000; Kaplan, 2002;

c 2007 Federation of European Microbiological Societies FEMS Immunol Med Microbiol 51 (2007) 488–495
Published by Blackwell Publishing Ltd. All rights reserved
Pneumococcal meningitis in childhood
Kellner et al., 2002; Martinez-Lacasa et al., 2002; McMaster
et al., 2002; Ostergaard et al., 2004; Tunkel et al., 2004; van
de Beek et al., 2004).
Although children affected by pneumococcal meningitis
frequently suffer a transient hearing loss and regain normal
hearing over the weeks or months following meningitis, a
number of them still show hearing sequelae. The present
study highlighted an incidence of hearing loss lower than
other studies of patients receiving third-generation cepha-
losporin and vancomycin. As an association between pre-
cocious vancomycin administration and hearing loss was
reported, it is believed that, in the cases in this study, the
wide use of rifampin, whose penetrability within the inner
ear and the cochlear aqueduct is relatively high, may have
favoured the better outcome (Bhatt et al., 1993; Richardson
et al., 1997; Arditi et al., 1998; Buckingham et al., 2006).
These findings, coupled with the relatively low number of
patients showing an unfavourable outcome reported in this
study, suggests that the use of rifampin in combination with
ceftriaxone or cefotaxime is a potentially attractive thera-
peutic strategy for children with pneumococcal meningitis.
Of note, rifampin penetration within CSF is not affected by
concomitant use of dexamethasone, and experimental evi-
dence demonstrates lower mortality rates and lower levels
of CSF lipoteichoic acids in animals with pneumococcal
meningitis receiving rifampin (Nau et al., 1999; Gerber et al.,
2003).
In an immunocompetent host, immune defence mechan-
isms, mainly secretory IgA and an efficacious antibody- and
complement-mediated phagocytosis, do not permit the
invasion of pneumococcus in the intravascular space and
its survival within the bloodstream. Younger children show
a relatively lower ability to contain the infection and
frequently acquire pneumococcal meningitis by an uncon-
trolled haematogenous diffusion of S. pneumoniae. In this
study, there is no evidence of extrameningeal foci of infec-
tion (e.g. sinus or middle ear infection) in 21 (68%) of 31
children aged 24 months or less. This finding is a strong
argument for the administration of the PCV during the first
2 years of life, because it promotes an efficient cell-mediated
immune response against more common strains of
S. pneumoniae (Janoff et al., 1999; Black et al., 2000;
Hausdorff et al., 2000; Koedel et al., 2002; Obaro &
Adegbola, 2002; Klugman et al., 2003; Whitney et al., 2003;
Bogaert et al., 2004). PCV is not routinely administered by
the local national health system, and heptavalent vaccine-
type strains of S. pneumoniae accounted for 54% of sero-
typed strains. It is estimated that the large use of PCV-7 (the
only conjugate vaccine available in Italy) had prevented at
least half of the cases observed in children aged 24 months or
less (Lebel et al., 2003). The value of the pneumococcal
vaccine is greater if it is considered that serotypes covered by
PCV-7 are involved in the more severe cases and that many
FEMS Immunol Med Microbiol 51 (2007) 488–495
493
younger children having bacterial meningitis experience
neurobehavioural sequelae, also if evaluated many years
after the illness (Anderson et al., 2004).
In conclusion, pneumococcal meningitis in childhood is a
severe but preventable disease, either by conjugate vaccine or
early treatment of extrameningeal foci of infection. CSF and
haematological findings are useful in identifying more
severe cases requiring prompt intensive care. On the basis
of the incidence of penicillin-nonsusceptible strains and the
beneficial effect of dexamethasone on mortality and neuro-
logical sequelae, use of combined protocols, containing
drugs with a good blood–brain barrier penetrability regard-
less of meningeal inflammation and steroids use, such as
rifampin or linezolid, may become an excellent therapeutic
strategy (McIntyre et al., 1997; Yogev & Guzman-Cottrill,
2005; Faella et al., 2006).
Disclaimer
The authors have reported no conflict of interest.
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