Despite medical advances, acute bacterial meningitis (ABM) constitutes a global public health problem, especially in developing countries with poor health facilities due to high rates of malnutrition, poor living conditions, and lack of access to appropriate preventive and curative services that may predispose people to the disease and reduce their chances of receiving optimal treatment [
Accurate information on important etiologic agents and populations at risk is needed to determine public health measures and ensure appropriate management of ABM [
This retrospective descriptive study, which involved all in-patients with ABM, was conducted at Hamad General Hospital between January 1, 2009, and December 31, 2013. This hospital is a 603-bed tertiary care center that covers all specialties except for hematology-oncology, cardiology, and obstetrics and it has been Joint Commission International (JCI) accredited since 2006 and is the first hospital system in the region to achieve institutional accreditation from the Accreditation Council for Graduate Medical Education-International (ACGME-I). Currently, there are three adult ICUs in Hamad General Hospital, namely, Medical ICU (MICU) with 22 beds, Surgical ICU (SICU) with 12 beds, and Trauma ICU (TICU) with 15 beds.
ABM was diagnosed on the basis of at least one of the following compatible clinical pictures with no other apparent cause: fever (38°C), headache, meningeal signs, cranial nerve signs, and impaired mental status, plus one of the following [ Positive cerebrospinal fluid (CSF) culture Positive CSF bacterial antigen test (with latex agglutination counterimmunoelectrophoresis) associated with pleocytosis mainly neutrophilic, defined as absolute WBC ≥ 100 cells/mm3, with a decreased glucose level ≤ 40 mg/dL and an increased protein concentration ≥ 60 mg/dL.
ABM was considered nosocomial if the diagnosis was made after more than 48 hours of hospitalization or within a short period of time (i.e., usually within one month after discharge from the hospital where the patient had received an invasive procedure, especially a neurosurgical procedure) [
Viral, fungal, mycobacterial, polymicrobial, and drug induced meningitis were excluded. ABM episodes with the same organism were included only once. Coagulase-negative staphylococci and viridans streptococci are considered as causative agents if CSF showed pleocytosis mainly neutrophilic, defined as absolute WBC ≥ 100 cells/mm3, or a decreased glucose level ≤ 40 mg/dL or an increased protein concentration ≥ 60 mg/dL. The primary outcome was in-hospital mortality which included all causes of death during admission.
Identification of isolates was based on colony morphology, Gram stain, oxidase, catalase, VITEK 2 Compact (bioMérieux, Durham, USA), and Phoenix (Becton Dickinson, NJ, USA). The antimicrobial minimal inhibitory concentrations (MICs) for the isolates were determined by using Phoenix (Becton Dickinson, NJ, USA) for GNB and staphylococci and enterococci (among Gram-positive cocci). For fastidious bacteria, susceptibility was determined with a gradient strip method (
Cases were identified via hospital’s discharge records, infection control records, and cerebrospinal fluid records maintained by the microbiology unit. These records were reviewed carefully by two investigators, in order not to miss any case. Records of all patients with bacterial meningitis were reviewed retrospectively to retrieve data on patients’ demography, sign-symptoms, underlying medical conditions, investigations, names of microorganisms and their drug susceptibility, name and duration of therapy offered, appropriateness of therapy, and outcome.
Quantitative variables were expressed as mean ± SD. Univariate logistic regression was performed to determine the probable predictors of in-hospital mortality. All potential risk factors at ≤0.1 level in the univariate analysis were entered in the multiple logistic regression to identify the independent predictors of mortality at
Ethical approval (#13254/13) and a waiver of informed consent were obtained from the medical research ethical committee at Hamad Medical Corporation, Qatar.
During the study period, we identified 117 episodes of ABM in 110 patients. There were 43, 22, 21, 12, and 18 episodes in 2009, 2010, 2011, 2012, and 2013, respectively. The study sample comprised 81 (69.2%) male and 29 (30.8%) female patients. Their mean age was
Demographic and clinical data of the 117 patients involved in this study.
Variable | Number (%), mean ± SD (range) |
---|---|
|
|
M | 81 (69.2) |
F | 29 (30.8) |
|
26.4 ± 22.3 (2–74) |
|
|
<1 | 26 (22.2) |
1–5 | 11 (9.4) |
6–14 | 6 (5.1) |
15–24 | 12 (10.3) |
25–34 | 13 (11.1) |
35–44 | 17 (14.5) |
45–54 | 23 (19.7) |
55–64 | 6 (5.1) |
≥65 | 3 (2.6) |
|
|
Qatari | 28 (23.9) |
Non-Qatari | 82 (76.1) |
|
|
Diabetes mellitus | 9 (7.7) |
Hypertension | 26 (22.2) |
Head injury | 6 (5.1) |
Neurosurgery | 54 (46.2) |
Alcoholic | 4 (3.4) |
Prematurity | 7 (6.0) |
Liver cirrhosis | 1 (0.9) |
Otitis media | 5 (4.3) |
Malignancy | 8 (6.8) |
Immunosuppression | 2 (1.7) |
|
|
Fever | 110 (94) |
Mental alteration | 55 (47) |
Headache | 43 (36.8) |
Vomiting | 35 (29.9) |
Meningism | 31 (26.5) |
Seizures | 23 (19.7) |
Bulging fontanel | 16 (13.7) |
Hypotension (BP < 90/60 mmHg) | 12 (10.2) |
Focal signs | 11 (9.4) |
Photophobia | 7 (6.0) |
Behavioral changes | 3 (2.6) |
Petechial rash | 3 (2.6) |
|
|
Hydrocephalus | 19 (16.2) |
Ischemic stroke | 5 (4.3) |
Brain abscess | 4 (3.4) |
Subdural empyema | 1 (0.9) |
Adrenal insufficiency | 1 (0.9) |
Vasculitis | 1 (0.9) |
The most frequent underlying conditions were neurosurgery (54, 46.2%), hypertension (26, 22.2%), and diabetes mellitus (9, 7.7%) (see Table
The CSF findings of the 117 ABM episodes are listed in Table
Clinical data of the 117 patients involved in this study.
Variable | Number (%), mean ± SD (range) |
---|---|
|
|
Community-acquired | 59 (50.4) |
Nosocomial | 58 (49.6) |
|
|
Cells/ |
3880.4 ± 8654.6 (20–66000) |
Neutrophils% | 74.1 ± 26.1 (1–99) |
Lymphocytes% | 22.9 ± 24.8 (1–98) |
Protein (g/dL) | 222.8 ± 205.9 (38–936) |
Glucose (mmol/L) | 2.1 ± 1.6 (0.1–6) |
Positive Gram stain | 93 (79.5) |
Positive culture | 112 (95.7) |
Positive latex agglutination | 23 (19.7) |
|
|
Gram-positive | 62 (53) |
Gram-negative | 55 (47) |
|
37 (31.6) |
|
|
Appropriate | 97 (82.9) |
Inappropriate | 20 (17.1) |
|
|
Died | 14 (12.0) |
Alive | 103 (88.0) |
Fifty-nine episodes (50.4%) were community-acquired and the other 58 (49.6%) were nosocomially acquired ABM (see Table
Distribution of different isolates in relation to setting of acquisition of meningitis.
Microorganism | Setting of acquisition | Total | |
---|---|---|---|
Nosocomial |
Community-acquired |
||
Gram-positive | |||
|
1 (100) | 0 | 1 |
|
5 (71.4) | 2 (28.6) | 7 |
|
1 (100) | 0 | 1 |
|
1 (100) | 0 | 1 |
|
1 (100) | 0 | 1 |
|
0 | 3 (100) | 3 |
|
0 | 1 (100) | 1 |
|
2 (100) | 0 | 2 |
|
14 (87.5) | 2 (12.5) | 16 |
|
2 (100) | 0 | 2 |
|
0 | 3 (100) | 3 |
|
0 | 1 (100) | 1 |
|
0 | 1 (100) | 1 |
|
0 | 1 (100) | 1 |
|
0 | 1 (100) | 1 |
|
0 | 19 (100) | 19 |
|
0 | 1 (100) | 1 |
Gram-negative | |||
|
8 (100) | 0 | 8 |
|
2 (66.7) | 1 (33,3) | 3 |
|
0 | 1 (100) | 1 |
|
0 | 1 (100) | 1 |
|
0 | 1 (100) | 1 |
|
1 (100) | 0 | 1 |
|
3 (100) | 0 | 3 |
|
3 (75) | 1 (25) | 4 |
|
1 (50) | 1 (50) | 2 |
|
7 (58.3) | 5 (41.7) | 12 |
|
0 | 11 (100) | 11 |
|
5 (100) | 0 | 5 |
|
1 (100) | 0 | 1 |
|
0 | 1 (100) | 1 |
|
0 | 1 (100) | 1 |
Total |
|
|
|
Distribution of microorganisms in relation to the age group.
Microorganism | Age group | Total | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
<1 | 1–5 | 6–14 | 15–24 | 25–34 | 35–44 | 45–54 | 55–64 | ≥65 | ||
|
0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 0 | 0 | 0 | 0 | 2 | 3 | 2 | 1 | 8 (6.8) |
|
0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 3 (2.6) |
|
0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 (0.8) |
|
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 3 (2.6) |
|
2 | 1 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 7 (5.9) |
|
0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 (0.8) |
|
2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 4 (3.4) |
|
0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 (1.6) |
|
2 | 0 | 0 | 2 | 1 | 1 | 4 | 2 | 0 | 12 (10.3) |
|
0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 (0.8) |
|
3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 (2.6) |
|
0 | 1 | 0 | 3 | 3 | 1 | 2 | 0 | 1 | 11 (9.4) |
|
0 | 0 | 1 | 0 | 2 | 1 | 1 | 0 | 0 | 5 (4.2) |
|
0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 2 (1.6) |
|
6 | 2 | 0 | 2 | 1 | 3 | 1 | 1 | 0 | 16 (13.6) |
|
0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 (1.6) |
|
2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 (2.6) |
|
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
3 | 2 | 3 | 2 | 3 | 2 | 4 | 0 | 0 | 19 (16.2) |
|
0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.8) |
|
||||||||||
Total | 26 (22.2) | 11 (9.4) | 6 (5.1) | 12 (10.3) | 13 (11.1) | 17 (14.5) | 23 (19.7) | 6 (5.1) | 3 (2.6) | 117 (100) |
Details of antimicrobial susceptibility are shown in Tables
Antimicrobial resistance rate of Gram-positive CSF isolates.
Microorganisms | TNP | pen | amp | oxc | eryt | clind | amclv | cotr | cfr | van | line | teic |
---|---|---|---|---|---|---|---|---|---|---|---|---|
|
1 | 0 | 0 | NT | 0 | 0 | 0 | 0 | NT | 0 | NT | NT |
|
7 | NT | 0 | NT | NT | NT | NT | NT | NT | 0 | 0 | 0 |
|
1 | NT | 0 | NT | NT | NT | NT | NT | NT | 1 (100) | 0 | 0 |
|
1 | 0 | 0 | NT | NT | NT | NT | NT | 0 | 0 | NT | NT |
|
1 | 0 | 0 | NT | NT | 0 | 0 | NT | 1 (100) | 1 (100) | 0 | 0 |
|
3 | 0 | 0 | NT | NT | NT | NT | 0 | NT | NT | NT | NT |
|
1 | 1 (100) | 1 (100) | NT | 0 | 0 | 0 | 0 | NT | 0 | 0 | 0 |
Coagulase-negative staphylococci | 20 | 20 (100) | 20 (100) | 19 (95) | 19 (95) | 10 (50) | 20 (100) | 9 (45) | NT | 0 | 0 | 0 |
|
8 | 1 (0.2) | 1 (0.2) | 0 | 1 (0.2) | 1 (0.2) | 0 | 1 (0.2) | 1 (0.2) | 0 | 0 | 0 |
|
19 | 6 (31.5) | 6 (31.5) | 6 (31.5) | 6 (31.5) | 6 (31.5) | 6 (31.5) | 3 (15.7) | 3 (15.7) | 0 | 0 | 0 |
TNP: total number of patients; pen: penicillin; amp: ampicillin; oxc: oxacillin; eryt: erythromycin; clind: clindamycin; amclv: amoxicillin/clavulanic acid; cotr: cotrimoxazole; cfr: ceftriaxone; van: vancomycin; line: linezolid; teic: teicoplanin; NT: not tested.
Antimicrobial resistance rate of Gram-negative cerebrospinal fluid isolates.
Microorganisms | TNP | cfr | gen | fep | taz | cip | amclv | ctz | amk | mem | pen | rif | col | tig |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
11 | 8 (72.7) | 8 (72.7) | 8 (72.7) | 8 (72.7) | 7 (63.6) | NT | 7 (63.6) | 7 (63.6) | 7 (63.6) | NT | NT | 0 | 0 |
|
1 | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT |
|
2 | 1 (50) | 2 (100) | 0 | 1 (50) | 0 | NT | 2 (100) | 2 (100) | 2 (100) | NT | NT | 2 (100) | 2 (100) |
|
4 | 3 (75) | 0 | 1 (25) | 3 (75) | 0 | 4 (100) | 3 (75) | 0 | 0 | NT | NT | NT | NT |
|
4 | 1 (25) | 1 (25) | 1 (25) | 0 | 1 (25) | 1 (25) | 1 (25) | 0 | 0 | NT | NT | NT | NT |
|
2 | 0 | NT | 0 | 0 | NT | 0 | NT | NT | NT | NT | NT | NT | NT |
|
12 | 3 (25) | 0 | 3 (25) | 2 (16.6) | 2 (16.6) | 7 (58.3) | 4 (33.3) | 0 | 0 | NT | NT | 0 | 0 |
|
8 | 0 | NT | 0 | 0 | 2 (25) | 0 | NT | NT | 0 | 0 | 2 (25) | NT | NT |
|
5 | NT | 0 | 0 | 0 | 0 | NT | 0 | 0 | 0 | NT | NT | 0 | 0 |
|
1 | NT | 0 | 0 | 0 | 0 | NT | 0 | 0 | 0 | NT | NT | 0 | 0 |
|
1 | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | NT | NT | NT | NT |
|
1 | 0 | 0 | 0 | 0 | 0 | 1 (100) | 0 | 0 | 0 | NT | NT | NT | NT |
TNP: total number of patients; cfr: ceftriaxone; gen: gentamicin; fep: cefepime; taz: piperacillin/tazobactam; cip: ciprofloxacin; amclv: amoxicillin/clavulanic acid; ctz: ceftazidime; amk: amikacin; mem: meropenem; pen: penicillin; rif: rifampicin; col: colistin; tig: tigecycline; NT: not tested.
Antimicrobial treatment was initiated for all patients. Ceftriaxone plus vancomycin combination was the most widely used antimicrobial treatment followed by meropenem. Empiric therapy was inappropriate in 20 (17.1%) episodes. The crude in-hospital mortality in our study was 14 (12%).
By the univariate analysis, the following variables were found to be probable predictors of in-hospital mortality: presence of underlying diseases, nosocomial infection, multidrug-resistant episodes, hypotension, mental alteration, and inappropriate treatments (see Table
Results of univariate analysis of in-hospital mortality predictors.
Variable | Unadjusted odds ratio (95% CI) |
|
---|---|---|
Presence of underlying diseases | 2.4 (1.4–3.9) | 0.001 |
Nosocomial infection | 3.2 (1.5–6.5) | 0.1 |
Multidrug-resistant episodes | 4.7 (3.8–5.7) | 0.08 |
Mental alteration | 4.9 (1.0–24.0) | 0.06 |
Hypotension | 2.3 (0.7–7.3) | 0.003 |
Inappropriate treatments | 1.9 (1.2–3.07) | 0.01 |
Results of multivariate analysis of in-hospital mortality independent factors.
Variable | Adjusted odds ratio (95% CI) |
|
---|---|---|
Presence of underlying diseases | 1.8 (1.03–3.2) | 0.02 |
Hypotension | 3.2 (1.4–7.3) | 0.04 |
Inappropriate treatments | 1.7 (1.0–2.8) | 0.01 |
Acute bacterial meningitis is a serious disease which necessitates early diagnosis and aggressive therapy to improve prognosis. Regional information regarding demographic data of patients, associated underlying conditions, etiology, and antimicrobial susceptibility is essential for correct and timely management of this disorder. Our study was the first to attempt to determine the clinical picture and the spectrum of pathogens of bacterial meningitis in patients of all ages in Qatar.
This retrospective series revealed some observations that deserve attention: firstly, in contrast with the previous study [
Secondly, sex distribution of the disease showed male predominance in agreement with the previous report [
Thirdly, compared with the previous studies [
Fourthly, drug resistance pattern showed that 95% of the implicated coagulase-negative staphylococci species were oxacillin-resistant and 63.3% of the implicated
Finally, in an attempt to identify independent predictors of mortality in patients with ABM, many studies had been conducted. The concluded prognostic factors among these studies were diverse [
This hospital-based study has the following limitations. First, the study was retrospective rather than prospective, and this design did not allow us to obtain additional details such as severity of the disease and long-term follow-up to evaluate the long-term sequelae of meningitis in our patients. Second, it was performed at a single hospital; the results may not be applicable to other hospitals. Third, we included patients who had a positive CSF culture or positive CSF bacterial antigen test.
Despite these limitations, we believe that our study remains the largest to date to provide comprehensive information on the epidemiology of ABM in Qatar.
In conclusion, our study revealed that there is a change in the predominantly affected age group and common causative agents of ABM. Coagulase-negative staphylococci species are the common causative agent in Qatar with majority of infections occurring nosocomially. More than 90% of all implicated coagulase-negative staphylococci strains were oxacillin-resistant. Thus, improving our infection control programs in addition to enhancing antimicrobial stewardship is essential to overcome this problem.
The authors declare that they have no conflicts of interest.