Jpn. J. Infect. Dis., 60, 262-266, 2007 Original Article Epidemiology of Adult Staphylococcal Meningitis in Southern Taiwan: a Clinical Comparison of Staphylococcus aureus Infection and Coagulase-Negative Staphylococcal Infection Wen-Neng Chang*, Cheng-Hsien Lu, Chi-Ren Huang, Yao-Chung Chuang, Nai-Wen Tsai, Shu-Fang Chen, Chiung-Chih Chang, Hung-Chen Wang1, Chun-Chih Chien2 and Jiunn-Jong Wu3 Department of Neurology, 1Department of Neurosurgery and 2Department of Clinical Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung; and 3Department of Medical Technology, Medical College, National Cheng Kung University, Tainan, Taiwan (Received April 25, 2007. Accepted May 24, 2007) SUMMARY: The clinical and laboratory characteristics of 38 staphylococcal adult bacterial meningitis (ABM) cases (19 Staphylococcus aureus infections and 19 coagulase-negative staphylococcal [CoNS] infections), collected over a period of 6.5 years (July 1999-December 2005; total ABM cases = 181) were analyzed. The results were compared with those of our previous study (January 1986-June 1999; total ABM cases = 202: monomicrobial infection = 180, mixed infection = 22, staphylococcal infection = 27). The 38 staphylococcal meningitis cases were 21 men and 17 women. Fever and altered consciousness were the leading clinical mani- festations. A preceding postneurosurgical state was noted in 12 of the 19 S. aureus infections and all 19 CoNS infections. The ages of onset and mortality rates of S. aureus infection and CoNS infection were 58.21 ± 13.05 years and 36.8% (7/19), and 44.16 ± 17.57 and 5.3% (1/19), respectively. Eleven of the 19 implicated S. aureus strains and 18 of the 19 implicated CoNS strains were mecA gene-positive and methicillin-resistant; all the strains retained their susceptibility to linezolid. The therapeutic results showed a mortality rate of 21% (8/38). This study revealed an increase of methicillin-resistant, postneurosurgical staphylococcal infection in ABM. Patients with CoNS infection had a younger age at onset and a lower mortality rate. Gung Memorial Hospital (CGMH)-Kaohsiung over a period INTRODUCTION of 6.5 years (July 1999-December 2005). CGMH-Kaohsiung Staphylococcal species, including Staphylococcus aureus is the largest medical center in southern Taiwan. This facility and coagulase-negative staphylococci (CoNS), are not com- is a 2,482-bed acute-care teaching hospital, which provides mon pathogens of adult bacterial meningitis (ABM) (1-3). both primary and tertiary referral care. During this study Adult staphylococcal meningitis is usually seen in patients period, 181 adult patients were determined to have culture- with bacteremia, parameningeal infections or postneurosurgical proven bacterial meningitis, and the study period was chosen states (4-6). Among the preceding postneurosurgical states, to coincide with the time period (13.5 years: January 1986- insertion of an intracranial device is an important risk factor June 1999; 202 cases: 180 with monomicrobial infection, 27 for the development of staphylococcal meningitis (4,5,7, with monomicrobial staphylococcal infection) of our previ- 8). In recent years, adult meningitis caused by methicillin- ous study (3). resistant staphylococcal strains has increased, and resulted in In this study, the criteria for a definite diagnosis of bacte- a therapeutic challenge (4,5,9,10). In this study, the clinical rial meningitis, including the diagnosis of staphylococcal and laboratory characteristics of 38 adult staphylococcal meningitis (1,3-5) were as follows: (i) a positive CSF culture meningitis cases were analyzed, and a clinical comparison of of bacterial pathogen(s), including staphylococcal strains; (ii) S. aureus and CoNS infection was made. In addition, we also clinical features of meningitis, including fever, consciousness made a brief comparison of the clinical features between the disturbance, seizure, or signs of meningeal irritation; and (iii) staphylococcal ABM and non-staphylococcal meningitis. purulent CSF features including at least one of the following parameters: leukocytosis with a leukocyte count > 0.25×109/ L and predominant polymorphonuclear cells, lactate con- MATERIALS AND METHODS centration >3.5 mmol/L, glucose ratio (CSF glucose/serum We retrospectively reviewed the microbiological records glucose) <0.4 or glucose level <2.5 mmol/L if no simulta- of cerebrospinal fluid (CSF) and blood cultures, laboratory neous blood glucose level was determined. Because CoNS is data and medical records of adult patients (≧17 years old) a common contaminant of cultures, the diagnosis of CoNS with culture-proven bacterial meningitis admitted to Chang meningitis was defined with more strict criteria (1,5) only if repeated CSF cultures demonstrated positive results or if *Corresponding author: Mailing address: Department of Neurol- CoNS was cultured from the tip of an indwelling neurosurgical ogy, Chang Gung Memorial Hospital, #123, Ta Pei Road, Niao device. Patients with evidence of concomitant chronic men- Sung Hsiang, Kaohsiung Hsien, Taiwan. Tel: +886-7-731-7123 ingitis or encephalitis that was not due to bacterial pathogens ext. 2283, Fax: +886-7-733-3816, E-mail: cwenneng@ms19. were excluded from this study. Patients were considered to hinet.net have “mixed bacterial meningitis” if at least two bacterial 262 organisms were isolated from the initial CSF culture (11). infection was fatal were compared between these two patient In this study, staphylococcal ABM was classified as groups by means of a Chi-square test or Fisher’s exact test. being either nosocomial or community-acquired infection. Age was compared between the two patient groups by means “Nosocomial” infection was defined as a positive bacterial of a Student’s t test. CSF data for the WBC counts, glucose, infection not present when the patient was admitted to the total proteins and lactate concentrations for the two patient hospital, clinical evidence of an infection no sooner than 48 h groups were logarithmically transformed to improve normal- after admission, or clinical evidence of meningitis within a ity, and comparisons between the two patient groups were short period of time, usually within 1 month after a discharge made using the Student’s t test. Multiple logistic regression from the hospital where the patient had received an invasive analysis was used to evaluate the relationships among vari- procedure, especially a neurosurgical procedure. Otherwise, ables and the two patient groups adjusted for other potential the patient was considered to have “community-acquired” confounding factors. All statistical analyses were conducted infection. Patients who developed meningitis related to head using an SAS software package, version 9.1 (2002; SAS Sta- trauma with skull fractures or neurosurgical procedures were tistical Institute, Cary, N.C., USA). With the same statistical classified as having “postneurosurgical” meningitis. Other- methods, a clinical comparison of the clinical and laboratory wise, patients who demonstrated no clear distinctive disease features between the groups of staphylococcal meningitis and characteristics and who had not undergone any invasive non-staphylococcal meningitis was also made. procedures were classified as having “spontaneous” menin- gitis. RESULTS In this study, the initial consciousness level for adult patients was classified into two groups: (I) normal conscious- Of the 181 culture-proven ABM cases collected during this ness (Glasgow coma scale [GCS] score = 15); and (II) altered study period, 165 cases had monomicrobial infection, and consciousness (GCS < 15). “Leukocytosis” was defined as the other 16, mixed bacterial infection. Table 1 lists the causa- a peripheral white blood cell (WBC) count > 10 × 109/L, tive pathogens of the 181 cases. A postneurosurgical state as “leukopenia” as a WBC count < 5 × 109/L, and “thrombocy- the preceding event was found in 103 of the 181 ABM cases. topenia” as a platelet count < 140×109/L. Blood culture was Of the 165 monomicrobial ABM cases, 101 cases had Gram- carried out in all patients with clinical evidence of meningi- negative pathogen infection, and the other 64, Gram-positive tis and bacteremia was considered as “positive” only when pathogen infection. Among the 64 implicated Gram-positive multiple blood cultures grew the same bacterial pathogen. pathogens, staphylococcal strains were the most common, Over the study period, intravenous administration of peni- including 19 S. aureus strains and 19 CoNS strains. The sub- cillin G or vancomycin with one of the third generation types of the 19 CoNS strains were as follows: S. epidermidis cephalosporins (ceftriaxone, ceftazidime) or cefepime were (n = 13), S. haemolyticus (n = 5) and S. capitis (n = 1). the initial empiric antibiotics used in the treatment of adult The clinical and laboratory features of the 38 staphylococ- patients with clinical evidence of bacterial meningitis in our cal ABM cases are listed in Table 2. Of the 19 cases with S. hospital. Further antibiotic adjustment was guided by the aureus infection, 12 were of the postneurosurgical form and results of pathogenic identification and antibiotic suscepti- the other 7 were of the spontaneous form. Nine S. aureus bility tests, and the adjusted antibiotics included oxacillin, strains of the former 12 cases and 2 of the latter 7 cases were imipenem, and meropenem. Antibiotic susceptibility of the isolated pathogen was tested Table 1. Causative pathogens