© Borgis - New Medicine 1/2001, s. 5-9
Zofia Rajtar-Leontiew1, Teresa Wernik2
The aetiology of cns bacterial infections in neonates, infants, and children hospitalised in the Clinical Hospital of the Medical University of Warsaw between 1988-1998
1Department of Naonatal Pathology, the Medical University of Warsaw
Head: Zofia Rajtar-Leontiew
2Bacteriological Laboratory, Clinical Hospital, the Medical University of Warsaw
Head: Teresa Wernik
Summary
The authors discuss the aetiology of CNS bacterial infections in neonates, infants, and children. The results of this investigation are presented in eight tables.
Bacterial meningitis occurs in children at every age, and is most frequently due to septicaemia, although it is not always easy to confirm the disease on bacteriological examination (15).
The younger the child, the lower the sensitivity of bacterial strains causing the disease, and the more postponed the treatment, the poorer the prognosis as to survival and complete recovery (9, 10).
The absence of bacteriological evidence renders the situation difficult for the patient, since the treatment is based only on morphological and chemical assessment of the cerebrospinal fluid, a physician´s experience and intuition, and nonspecific laboratory parameters (ESR, a complete blood count, platelets, leukocytosis, young forms/ /neutrophils ratio, coagulations system, CRP) (1, 2).
Complications following previous, inappropriately - diagnosed and inadequately - treated bacterial meningitis are difficult to predict, but they are always associated with the child´s further vital physical and intellectual development (9).
The culture growth of bacteria causing meningitis, precise evaluation of their sensitivity and resistance to popular antibiotics, and preserving them for further investigations are the factors which contribute to a targeted treatment, an efficient control of the infection, and a better prognosis (8).
An efficient microbiological laboratory obtains a higher percentage of culture yields if their co-operative with clinicians is more effective. This is expressed as an adequate exchange of information about a patient, appropriate collection of material for study and handing it over to the examiner (according to accepted rules) and on the other hand, the results are immediately interpreted and sent back to the physicians.
At the Clinical Hospital Bacteriological Laboratory over a period of 10.5 years (from the beginning of 1988 until the end of July 1998) positive bacteriological results from CSF examinations were obtained in 115 patients with meningitis. (Detailed data are shown in Table 1). As can be seen from the data, approximately 30% of cases of meningitis in children were caused by N. meningitidis, 14% jointly by S. epidermidis and S. aureus, 11% by all streptococcal groups(Streptococcus spp), and 8% by H. influenzae. The results are similar to the national figures reported by Grzybowska (6).
Table 1. Incidence of bacterial meningitis in children.
| No. | Pathogen/years | 1988 | 89 | 90 | 91 | 92 | 93 | 94 | 95 | 96 | 97 | 98 | Total | % |
| 1. | N. meningitidis | 8 | 8 | 4 | 4 | 1 | 2 | 1 | 1 | 3 | 1 | 1 | 34 | 29.6 |
| 2. | E. coli | | 2 | 1 | 1 | 1 | 2 | 2 | 1 | 1 | | | 11 | 9.6 |
| 3. | H. influenzae | | 1 | 1 | 1 | | | 1 | 1 | 1 | | 3 | 9 | 7.8 |
| 4. | S. epidermidis | | | | 1 | 3 | | 2 | 1 | 1 | 1 | | 9 | 7.8 |
| 5. | S. pneumoniae | | | 1 | 1 | | 1 | 1 | 1 | 2 | | | 7 | 6.0 |
| 6. | S. aureus | 2 | | | | 2 | 1 | 1 | | 1 | | | 7 | 6.0 |
| 7. | P. aeruginosa | 1 | 1 | | | 1 | | 1 | 1 | | | | 5 | 4.3 |
| 8. | E. cloacae | | 2 | | | | 1 | | | 1 | | 1 | 5 | 4.3 |
| 9. | S. agalactiae (B) | | | 1 | | | 1 | | | | 2 | | 4 | 3.5 |
| 10. | C. albicans | 1 | 2 | | | 1 | | | | | | | 4 | 3.5 |
| 11. | L. monocytogenes | | | | | | 1 | | 2 | 1 | | | 4 | 3.5 |
| 12. | S. marcescens | | | 1 | | 1 | 1 | | | | | | 3 | 2.6 |
| 13. | K. pneumoniae | | | | | | 1 | 1 | | | 1 | | 3 | 2.6 |
| 14. | P. mirabilis | | | 1 | | 1 | | | | | | | 2 | 1.7 |
| 15. | Strept. Spp. | | | | | | | 1 | 1 | | | | 2 | 1.7 |
| 16. | P. morgani | 1 | | | | | | | | | | | 1 | 0.9 |
| 17. | P. cepacia | 1 | | | | | | | | | | | 1 | 0.9 |
| 18. | Citrob. freundi | | | | | 1 | | | | | | | 1 | 0.9 |
| 19. | Citrob. intermed. | | | | | | | | | | 1 | | 1 | 0.9 |
| 20. | Flavobact. breve | | | | | | 1 | | | | | | 1 | 0.9 |
| 21. | Acinobact. baumani | | | | | | | | | | 1 | | 1 | 0.9 |
| Total | 14 | 16 | 10 | 8 | 12 | 12 | 11 | 9 | 11 | 7 | 5 | 115 | 100.0 |
Different strains of G(-) bacteria are definitely the most frequent pathogenic factors in bacterial meningitis (Table 2) and they amount to almost 68% (78 out of 115 culture yields), whereas G(+) bacteria account for only 32% (37 out of 115). Among the G(-) bacteria the most frequent were N. meningitidis (44%), followed by E. coli (14%) and H. influenzae (12%). Among the G(+) bacteria the most common were S. epidermidis and S. aureus (43%) followed up by Streptococci (35%) and L. monocytogenes and C. albicans (approximately 11% each) (Table 3).
Table 2. Bacterial meningitis in children caused by Gram - negative pathogens.
| No. | Pathogens/year | 1988 | 89 | 90 | 91 | 92 | 93 | 94 | 95 | 96 | 97 | 98 | Total | % |
| 1. | N. meningitidis | 8 | 8 | 4 | 4 | 1 | 2 | 1 | 1 | 3 | 1 | 1 | 34 | 43.6 |
| 2. | E. coli | | 2 | 1 | 1 | 1 | 2 | 2 | 1 | 1 | | | 11 | 14.1 |
| 3. | H. influenzae | | 1 | 1 | 1 | | | 1 | 1 | 1 | | 3 | 9 | 11.5 |
| 4. | P. aeruginosa | 1 | 1 | | | 1 | | 1 | 1 | | | | 5 | 6.4 |
| 5. | E. cloacae | | 2 | | | | 1 | | | 1 | | 1 | 5 | 6.4 |
| 6. | S. marcescens | | | 1 | | 1 | 1 | | | | | | 3 | 3.8 |
| 7. | K. pneumoniae | | | | | | 1 | 1 | | | 1 | | 3 | 3.8 |
| 8. | P. mirabilis | | | 1 | | 1 | | | | | | | 2 | 2.6 |
| 9. | P. morgani | 1 | | | | | | | | | | | 1 | 1.3 |
| 10. | P. cepacia | 1 | | | | | | | | | | | 1 | 1.3 |
| 11. | Citrob. freundi | | | | | 1 | | | | | | | 1 | 1.3 |
| 12. | Flavobact. breve | | | | | | 1 | | | | | | 1 | 1.3 |
| 13. | Acinobact. baumani | | | | | | | | | | 1 | | 1 | 1.3 |
| 14. | Citrob. intermed | | | | | | | | | | 1 | | 1 | 1.3 |
| Total | 11 | 14 | 8 | 6 | 6 | 8 | 6 | 4 | 6 | 4 | 5 | 78 | 100.0 |
Table 3. Bacterial meningitis in children caused by Gram - positive pathogens.
| No. | Pathogens/years | 1988 | 89 | 90 | 91 | 92 | 93 | 94 | 95 | 96 | 97 | 98 | Total | % |
| 1. | S. epidermidis | | | | 1 | 3 | | 2 | 1 | 1 | 1 | - | 9 | 24.3 |
| 2. | S. aureus | 2 | | | | 2 | 1 | 1 | | 1 | | - | 7 | 18.9 |
| 3. | S. pneumoniae | | | 1 | 1 | | 1 | 1 | 1 | 2 | | - | 7 | 18.9 |
| 4. | S. agalactiae | | | 1 | | | 1 | | | | 2 | - | 4 | 10.8 |
| 5. | Streptococc. spp. | | | | | | | 1 | 1 | | | - | 2 | 5.4 |
| 6. | L. monocytogenes | | | | | | 1 | | 2 | 1 | | - | 4 | 10.8 |
| 7. | C. albicans | 1 | 2 | | | 1 | | | | | | - | 4 | 10.8 |
| | Total | 3 | 2 | 2 | 2 | 6 | 4 | 5 | 5 | 5 | 3 | - | 37 | 100.0 |
The type of pathogens cultured might have been associated with age. In our study 23.5% of yields concerned neonates, 40% infants and 36.5% children over 1 year age.
In neonates the G(-) bacteria were responsible for 62.0% of cases, in infants the figure was 73.3% and in older children it was 63.4% (Table 4). The increased number of G(-) bacterial infections in neonates and older children was due to N. meningitidis infections, prevalent at that age. In neonates the pathogens were other G (-) bacterial strains highly resistant to treatment, e.g., S. marcescens, P. mirabilis, Citrobacter freundi, Enterobacter cloacae, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In no one neonate did the CSF culture grow H. influenzae; in infants the pathogen was present in 4.4% of cases and in children over 1 year of age it accounted for 17%. We believe that such a distribution of H. influenzae might have been due to the presence of natural maternal antibodies and their loss after six monthg of age (4). None of the children with meningitis caused by H. influenzae had previously been vaccinated with HIB (against H. influenzae).
Table 4. Children´s age in bacterial meningitis.
| | Years | Total | % |
| 1988 | 89 | 90 | 91 | 92 | 93 | 94 | 95 | 96 | 97 | 98 |
| Newborns | 2 | 2 | 3 | | 3 | 5 | 4 | 3 | 1 | 3 | 1 | 27 | 23.4 |
| Infants | 7 | 10 | 2 | 7 | 1 | 5 | 3 | 3 | 3 | 2 | 3 | 46 | 40.0 |
| Toddlers >= 1 year old) | 4 | 4 | 6 | 1 | 8 | 2 | 6 | 2 | 6 | 1 | 2 | 42 | 36.5 |
| Total | 13 | 16 | 11 | 8 | 12 | 12 | 13 | 8 | 10 | 6 | 6 | 115 | 100.0 |
Parallel growths of the same bacterial strains were obtained from blood and CSF cultures in 46 children (46%); most frequently: H. influenzae (8 out of 9), E. coli (5 out of 11) and N. meningitidis (10 out of 34) (Table 5). With a division only into two groups, septicaemia was due to the G(-) and G(+) bacteria - twice as many systemic infection were caused by the G(-) bacteria. Out of 78 cases of bacterial meningitis due to G(-) bacterial septicaemia was diagnosed in 34 children (43.5%); out of 37 cases due to the G(+) bacteria, septicaemia was found in 12 children (32.4%) (Table 6 - page 8).
Table 5. Bacterial meningitis in sepsis.
| No. | Pathogen | CSF culture- positive | Sepsis (CSF and bloodcultures positive) | Sepsis
(%) |
| 1. | N. meningitidis | 34 | 10 | 29.4 |
| 2. | E. coli | 11 | 5 | 45.5 |
| 3. | H. influenzae B | 9 | 8 | 88.9 |
| 4. | S. epidermidis | 9 | 3 | 33.3 |
| 5. | S. pneumoniae | 7 | 3 | 42.8 |
| 6. | S. aureus | 7 | 2 | 28.6 |
| 7. | P. aeruginosa | 5 | 1 | 20.0 |
| 8. | E. cloacae | 5 | 2 | 40.0 |
| 9. | S. agalactiae | 4 | 2 | 50.0 |
| 10. | C. albicans | 4 | - | - |
| 11. | L. monocytogenes | 4 | 2 | 50.0 |
| 12. | S. marcescens | 3 | 2 | 66.6 |
| 13. | K. pneumoniae | 3 | 1 | 33.3 |
| 14. | Str. spp. | 2 | - | - |
| | Other G(-) 7 strains | 8 | 5 | 62.5 |
| Total | 115 | 46 | 40.0 |
Table 6. Sepsis due to Gram - negative vs. Gram - positive bacteria.
| Pathogen | No.meningitis | Sepsis (number) | Sepsis (%) |
| Gram negative | 78 | 34 | 43.5 |
| Gram positive | 37 | 12 | 32.4 |
| Total | 115 | 46 | 40.0 |
Boys were more frequently affected with meningitis than girls. The girls to boys ratio was 1/3 (to the disadvantage of males: 49 to 69). The comparison of results obtained for the first five years (1988-1992) with a consecutive 5-year period (1993-1997) shows a slight downward trend in the total number of meninigitis cases, mainly those due to the G(-) bacteria (Table 7). The `gap´ is filled with G(+) infections caused mainly by streptococci and staphylococci.
Table 7. Comparative assessment (1988-92 vs. 1993-97).
| Years | Gram negative | % | Gram positive | % | Total | % |
| 1988-92 | 45 | 61.6 | 15 | 40.5 | 60 | 54.5 |
| 1993-97 | 28 | 38.3 | 22 | 59.5 | 50 | 45.4 |
| 1988-98 | 73 | 100.0 | 37 | 100.0 | 110 | 100.0 |
Considering the age (Table 8) it seems that an increased number of meningitis cases occur in group of infants and children over 1 year of age, but the number of affected neonates seems to be increasing. In our study, C. albicans was obtained from CSF samples only in the first 5 years (Table 1) and was found only in 3 neonates and 1 child with neoplasia. In cases with likely mycoses, early administration of an efficient and least toxic medication e.g., flucozanole, may be considered to reduce the number of severe cases of the disease, including meningitis (3, 7). All four cases of isolating L. monocytogenes concern the year 1993-1997. The number of CNS infections due to that bacterium in our study does not differ from the international data, and it seems that isolation of the bacteria resulted from a more efficient co-operation between microbiologists and clinicians, but it is not a danger signal indicating an increased morbidity from that type of infection (8).
Table 8. Comparative assessment of bacterial infection incidence according to children´s age (1988-92 vs. 1993-97).
| Years | Newborns | % | Infants | % | Children(> 1 year old) | % | Total | % |
| 1988-92 | 10 | 38.5 | 27 | 62.8 | 23 | 59 | 60 | 55.6 |
| 1993-97 | 16 | 61.5 | 16 | 37.2 | 16 | 41.0 | 48 | 44.4 |
| 1988-97 | 26 | 100.0 | 43 | 100.0 | 39 | 100.0 | 108 | 100.0 |
An assessment of the total number of 115 positive cultures of CSF in children performed at the same microbiological laboratory over 10.5 years renders the following conclusions:
1. G(-) bacteria are the most frequent cause of meningitis in children at any age;
2. the three most common G(-) bacterial infections are due to N. meningitidis, E. coli and H. influenzae, and those due to the G(+) bacteria include S. epidermis with S. aureus and all the streptococcal strains;
3. division into five-year periods shows a slight downward trend in the incidence of meningitis, mainly those due to G(-) bacteria, including N. meningitidis but excluding H. influenzae; however, there is a simultaneous increase in G(+) bacterial infections caused mainly by staphylococci;
4. the decreased incidence of meningitis refers to children and infants; however, the neonate group shows a significantly rising trend to get the disease (Table 8);
5. septicaemia in the course of bacterial meningitis was diagnosed during bacteriological examination in 40% of cases. Similar results have been obtained in well-established microbiological laboratories worldwide;
6. septicaemia was most frequently found in the course of infections due to H. influenzae, E. coli and N. meningitidis;
7. septicaemia is more frequently caused by G(-) than G(+) bacteria;
8. in the group of G(+) infections streptococcal meningitis was more frequently complicated by septicaemia than those due to staphylococci;
9. bacterial meningitis affects boys more frequently than girls (3 to 1 ratio);
10. the age of the child clearly predisposes to bacterial meningitis (Table 4).
Piśmiennictwo
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