Department of Neurology and The Netherlands Reference Laboratory for Bacterial Meningitis/Department of Medical Microbiology, Academic Medical Centre, PO Box 22660, 1100 DD Amsterdam, The Netherlands
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Abstract |
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Introduction |
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Materials and methods |
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Daily, the NRLBM provided the investigators with the names of the physicians and hospitals where adult patients with bacterial meningitis had been admitted 26 days earlier. Physicians were contacted by telephone, and were informed about the study. All patients received written information concerning the study and were asked to give informed consent for participation. Subsequently, data on patient's history, microbiological features and treatment were collected by questionnaire [case record form (CRF)]. According to the national guidelines, patients were classified into four categories depending on patient's age and underlying health status (Table 1). The antibiotic therapy started on admission to the hospital was assumed to be the initial therapy. This observational study with anonymous patient data was carried out in accordance with the Dutch privacy legislation. Written informed consent to use data made anonymous was obtained from the patient (if possible) or from the patient's legal representative.
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Initial antimicrobial treatment was defined as compliant if antibiotics were used as recommended in the national guidelines. The microbiological coverage for Neisseria meningitidis, Streptococcus pneumoniae and H. influenzae was based on the results of in vitro antibiotic susceptibility testing. Intermediate resistance for penicillin was categorized as inadequate coverage if penicillin monotherapy was given. For the other isolates, coverage was based on the antimicrobial spectrum of the antibiotic agents, as mentioned previously.14
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Results |
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The distribution according to species of the 263 meningitis patients for each category formulated in the guidelines (Table 1) is shown in Table 2
. N. meningitidis, the most common causative microorganism of community-acquired meningitis in the category of adult patients
60 years of age without risk factors, accounted for 54% of all species in this category. S. pneumoniae occurred particularly in the elderly and in patients with risk factors, and accounted for 61% and 58% of all species in these two categories, respectively. Gram-negative enteric bacteria (Escherichia coli and Klebsiella pneumoniae) were isolated from three patients >60 years old without risk factors (3%) and from one patient with a history of recent neurosurgery (6%). Listeria monocytogenes was isolated from the CSF in six patients with risk factors (19%). From meningitis patients with a history of recent neurosurgery, Staphylococcus aureus was isolated from six patients (33%); Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium were each isolated from one patient, accounting for 6% in this category. Results of Gram staining were available for 227 CSF specimens from 264 patients (86%). In 189 of 227 (83%) cases, microscopic examination of the Gram-stained CSF specimens revealed the presence of the microorganism cultured later on.
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On the first day of hospitalization the most frequently prescribed antibiotics were amoxicillin and penicillin (44%), a third-generation cephalosporin (18%) and a combination of penicillin or amoxicillin with a third-generation cephalosporin (14%) (Table 3). Of the patients without risk factors and
60 years old and of those aged >60 years, 39% and 30%, respectively, were initially treated with a third-generation cephalosporin with or without amoxicillin or penicillin. Of the patients with risk factors, 38% received a third-generation cephalosporin.
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Despite the low compliance in these three categories, evaluation of microbiological coverage showed that 249 of 263 (95%) patients received treatment that provided adequate coverage (Table 4). Of the 87 patients treated in compliance with the guidelines, the microbiological coverage was 98%; 12 of 176 (7%) patients not treated in compliance with the guidelines received antibiotics with an insufficient spectrum. Six of the 11 (55%) patients with meningitis due to L. monocytogenes and not treated in compliance with the guidelines received inappropriate antibiotics.
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Discussion |
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The highest compliance was found in the first patient category (patients <60 years old without risk factors): 49% of them were treated according to the recommendations. Penicillin, recommended as the initial treatment in this patient category, covered isolates from all except five of the 127 patients. H. influenzae was cultured from four of these patients, and S. aureus from one. In the UK and USA, a combination of amoxicillin and cephalosporins has been recommended for the treatment of patients 1660 years old.5,79 A major reason for the usage of third-generation cephalosporins is the emerging problem of microbial resistance, found particularly among S. pneumoniae.5,7 In the USA, Spain, Hungary and other countries, antibiotic-resistant S. pneumoniae strains have become prevalent and have emerged as a major problem in the treatment of patients with bacterial meningitis.18 In a recent surveillance study in the USA on antimicrobial resistance of invasive S. pneumoniae strains, 24% were resistant to penicillin.18 In the UK, a trend analysis revealed the prevalence of penicillin-resistance among pneumococci causing bacteraemia ranging from 1% in 1990 to 3.6% in 1998.19 In The Netherlands, the recommendation to treat this patient group with penicillin is still valid for patients with meningitis due to N. meningitidis and S. pneumoniae. For the small minority of patients in this category with meningitis due to other bacteria, this recommendation will not be optimal for all cases, and a third-generation cephalosporin would usually have been more appropriate. For the other categories the compliance was rather low, ranging from 17% to 18%.
Only one-third of the physicians adhered to the recommendations contained within the guidelines. The microbiological coverage for the 87 patients who were treated in compliance with the guidelines was almost complete (98%). Although guidelines can be varied by a clinician according to the circumstances, the question arises why was the compliance so poor? First, national guidelines are often of limited efficacy because medical practices are most often locally driven.20 In The Netherlands, >70% of hospitals have antibiotic formularies recommending antibiotic treatment.21 Local hospital committees preparing guidelines for antibiotic treatment should have been aware of the existence of the national consensus, since after the consensus meeting in 1997 a booklet containing the guidelines was widely disseminated. However, the current antibiotic policies of the eight Dutch academic hospitals still recommend a considerable diversity of antibiotics for the initial treatment of bacterial meningitis. Secondly, the meningitis guidelines have probably not been disseminated effectively. Dissemination must be supported by various interventions. Simply publishing guidelines has been associated with low rates of compliance before.20 In 1997, all medical specialists in The Netherlands involved in the treatment of patients with bacterial meningitis were invited to participate in the consensus meeting, and received a booklet with the guidelines. At this meeting the recommendations were approved by experts in the field of bacterial meningitis. However, other interventions have not been made, and the guidelines were not published in a national medical journal until 2001.22 Thirdly, despite the availability of the guidelines, the individual doctor has to decide which antibiotic to prescribe. Leibovici et al.23 clearly describe the dilemma of the individual doctor in making the decision about which antibiotic should be used. Doctors fear that the recommended initial treatment will not match the antibiotic susceptibility of the bacteria and feel uneasy in prescribing a drug that affords less than the maximum coverage. Following antibiotic guidelines may well slow down the development of resistance, and give future patients a better chance of an uneventful recovery, but the main duty of a doctor is to treat the present patient. This dilemma may also explain why so few physicians adhere to the national guidelines. Although Dutch doctors receive annual information about antibiotic susceptibility of isolates causing meningitis,16 the great majority do not use the guidelines.
Treatment of adult meningitis patients was not according to the guidelines in 167 of 273 (61%) cases. The microbiological coverage in these 167 patients was 93%. Twelve (7%) of them were treated inappropriately according to our criteria. Six of these patients (50%) had meningitis due to L. monocytogenes and received inappropriate therapy, since treatment consisted of a third-generation cephalosporin only. The other patients had meningitis due to S. aureus, Pseudomonas aeruginosa, E. faecalis, E. coli and S. epidermidis.
In this study only the compliance of the initial antibiotic treatment, recommended in the Dutch guidelines for treatment of adult meningitis patients, was analysed. Therapy can be modified when results of CSF Gram staining and CSF culture and antibiotic susceptibility testing become available. Analysis of the step-down therapy, narrowing the initial treatment, and the outcome of this approach has been carried out. The results will be presented separately.
In conclusion, 1 year after national consensus-based guidelines for the initial treatment of adult patients with bacterial meningitis in The Netherlands were provided, only one-third of the Dutch physicians were adhering to the guidelines. The microbiological coverage for the patients who were treated in compliance with the guidelines was almost complete (98%), whereas of the patients who were not treated in compliance with the guidelines, 7% received inappropriate antibiotic therapy.
Conflict of interest
This study was financially supported by means of a research grant from Roche Pharmaceuticals, The Netherlands, and was designed, conducted and analysed independently of any company and without any financial interests of investigators.
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Acknowledgements |
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Notes |
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References |
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23
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Received 10 May 2001; returned 24 October 2001; revised 21 November 2001; accepted 29 November 2001