Demographic characteristics
From January 1, 2016 to December 3, 2018, 1161 patients (<18 years old) with BM were enrolled for screening. In accordance with the exclusion criteria, 1142 confirmed BM patients were included. A total of 283 pediatric intensive care unit (PICU) patients, 216 surgical patients and 643 patients from other departments had positive cerebrospinal fluid cultures. Less than half of the 1142 patients were boys (501/1142) and the median age was 3 months (range: 0 days to 17 years, 7 months). The enrolled confirmed meningitis case numbers varied annually, fluctuating between 386 cases in 2016 and 321 cases in 2018. The average number of confirmed cases each year was 380.7. Up to 65.9% (753/1142) of BM cases occurred in children under 1 year old, and more than two-fifths (513, 44.9%) were less than 3 months old. A sharp decline was observed with increasing age (Fig. 2).
Pathogen composition
From 2016 to 2018, 1193 bacterial pathogens were obtained from 1142 patients, 38 of whom had a mixture of infections. Gram-positive organisms accounted for nearly 69.6% (830/1193) of the isolates, and 30.4% (363/1193) were Gram-negative organisms. The predominant Gram-positive isolate was Staphylococcus epidermidis (S. epidermidis) (n=197, 16.5%), followed by S. pneumoniae (n=127, 10.6%) and Enterococcus faecium (E. faecium) (n=115, 9.6%). E. coli (n=148, 12.4%) was the most frequent Gram-negative organism causing PBM, followed by Klebsiella pneumoniae (K. pneumoniae) (n = 40, 3.4%) and Acinetobacter baumannii (A. baumannii) (n = 27, 2.3%) (Table 1). As shown in Table 1, S. epidermidis was the most prevalent pathogen in each year. E. coli was the second most commonly detected bacterium in 2016 and 2017, while S. pneumoniae was the second most frequently isolated bacterium in 2018.
In terms of clinical ward distribution, these common pathogens were detected in the PICU, surgical department and other departments (Fig. 3). S. epidermidis was detected more commonly in the surgical department (31.1%) than in the PICU (10.8%) and other departments (13.9%) (P<0.001). However, E. coli, S. pneumoniae, E. faecium, and Group B Streptococcus (GBS) were detected more frequently in the PICU and in the other departments than in the surgical department (all P<0.05).
The spectrum of pathogens causing PBM was highly variable in children of different ages (Fig. 4). Infants under 3 months of age were at a relatively high risk of infection by E. coli (116/523; 22.2%), E. faecium (75/523; 14.3%), S. epidermidis (57/523; 10.9%), and GBS (55/523; 10.5%). However, children more than 3 months of age were at a relatively high risk of infection by S. epidermidis (140/670; 20.9%), S. pneumoniae (117/670; 17.5%), and Staphylococcus hominis (S. hominis) (57/670; 8.5%). As shown in Figure 4, the other prevalent bacteria also varied by age group. Children less than one year old had the greatest abundance of pathogenic species, the leading pathogen among which was E. coli (134/776; 17.3%), followed by S. epidermidis (105/776; 13.5%) and E. faecium (88/776; 11.3%).
Antimicrobial susceptibilities of isolates
Coagulase-negative Staphylococcus
The three main species of CoNS, namely, S. epidermidis, S. hominis and S. haemolyticus, were isolated from CSF cultures. The resistance of these isolates to penicillin (PEN) and erythromycin (ERY) was greater than 71.0% (Table 2). The resistance to methicillin depended on oxacillin (OXA). Therefore, the overall detection rate of the methicillin-resistant CoNS (MRCoNS) isolates was approximately 80.0% and declined from 80.5% in 2016 to 72.3% in 2018 (Fig. 5). All three species of these isolates were susceptible to linezolid (LNZ) (100%) and vancomycin (VAN) (100%). Over 65.0% of the isolates, except S. haemolyticus, were also susceptible to aminoglycosides, fluoroquinolones, co-trimoxazole (SXT), rifampin (RIF) and tetracycline (TET) (Table 2).
Streptococcus pneumoniae
Isolates that were resistant to fluoroquinolones, LNZ, or VAN were not detected in this study. The susceptibility to amoxicillin (AMX) was 74.8%, and the susceptibility to cefotaxime (CTX) and ceftriaxone (CRO) was 59.0% and 50.0%, respectively. However, over 84% of the S. pneumoniae isolates were resistant to ERY, clindamycin (CLI), SXT, and TET (Table 2). The resistance of S. pneumoniae isolates to PEN was 82.8%, increasing from 75% in 2016 to 87.5% in 2018 (Fig. 5).
Enterococcus faecium
More than 95.0% of E. faecium isolates showed susceptibility to VAN, LNZ, and tigecycline (TGC) in the present study, but the resistance rates to other antibacterial drugs were over 62.9% (Table 2). The resistance of E. faecium strains to VAN was 0.9%, and this was detected at frequencies of 0%, 0%, and 2.7% in 2016, 2017, and 2018, respectively (Fig. 5).
Group B Streptococcus
GBS isolates showed resistance rates of 47.5% to LEV and 68.8% to TET. GBS also had high resistance levels to CLI (91.8%) and ERY (90.3%). However, our data found that GBS isolates exhibited relatively low resistance levels to PEN (1.7%), ampicillin (AMP) (3.7%), LNZ (0%) and VAN (0%) (Table 2).
Staphylococcus aureus
There were no LNZ- or VAN-resistant isolates found in the present study. The susceptibility rates of S. aureus isolates to aminoglycosides, fluoroquinolones, RIF, SXT and TET exceeded 74.0%. However, the susceptibility to PEN was only 3.4%, followed by the susceptibility to ERY (29.0%) (Table 2). The overall prevalence of methicillin-resistant S. aureus (MRSA) was 29.0% and ranged from 20.0% to 38.5% from 2016 to 2018 (Fig. 5).
Escherichia coli and Klebsiella pneumoniae
For E. coli isolates, more than 93.0% of isolates were sensitive to cefoxitin (FOX), piperacillin/tazobactam (TZP), cefoperazone/sulbactam (CSL), amikacin (AMK) and carbapenems, and the resistance rates for AMP and piperacillin (PIP) exceeded 82.0%. The sensitivities of E. coli to third-generation cephalosporins, aztreonam and fluoroquinolones were 47.6-73.6%, 65.3%, 44.3-46.4%, respectively (Table 3). Moreover, the detection rate of ESBL-producing E. coli was stable and fluctuated between 44.4% and 49.2% in 2016-2018. The proportion of carbapenem-resistant (CR) E. coli isolates was 5.0%, increasing from 2.2% in 2016 to 9.1% in 2018 (Fig. 5).
K. pneumoniae isolates exhibited susceptibility rates of greater than 50.0% to aminoglycosides, fluoroquinolones, TET, SXT, imipenem (IMP), and ertapenem (ETP), but the resistance rates to other antibiotics were greater than 50.0% (Table 3). The proportions of ESBL-producing K. pneumoniae and CR K. pneumoniae were 74.3% and 54.5%, respectively. The data from 2016 to 2018 demonstrated that ESBL-producing K. pneumoniae and CR K. pneumoniae showed an upward trend (Fig. 5).
Acinetobacter baumannii and Pseudomonas aeruginosa
The susceptibility rates of A. baumannii isolates to aminoglycosides, fluoroquinolones exceeded 55.0%. The susceptibility of isolates to cephalosporins and carbapenems ranged from 37.5% to 66.7% and 45.5% to 68.4%, respectively. The susceptibility rates of P. aeruginosa isolates to PIP, third-generation cephalosporins, TZP, aminoglycosides, fluoroquinolones, and carbapenems were greater than 60.0%, but the resistance of isolates to AMP and ampicillin/sulbactam (SAM) exceeded 92.0% (Table 3).