Microbiological examination of the CSF specimen is an important basis for the diagnosis and treatment of CNS infections. We retrospectively analyzed the patients with positive CSF culture and aimed to explore the etiology, antibiotic sensitivity and risk factors affecting the clinical outcomes of patients with CNS infections. Due to a lack of standardization of the available assays and uncertainty about sample collection and processing. False positive CSF culture can be discovered in some studies [11, 19]. In our study, 111 positive CSF culture specimens were identified.
According to the results of retrospective analysis, 26 samples from 26 patients were considered to be false positive in our 8-year study.
Of the 86 isolates detected from patients confirmed with CNS infections, the general pathogens distribution of Gram-positive, Gram-negative and Eumycetes in the paper were 59.3, 30.2 and 10.5%, respectively. Which was approximate to the results of the previous studies [11, 20]. In our study, the top seven pathogens were CoNS (43.0%), Acinetobacter baumannii (7.0%), Escherichia coli (7.0%), Cryptococcus neoformans (7.0%), Enterococcus faecium (5.8%), Streptococcus pneumoniae (5.8%) and Klebsiella (5.8%). Which was not differ significantly from the multicenter study of positive CSF isolates from China Antimicrobial Surveillance Network (CHINET, www.chinets.com), as they showed that CoNS was the most frequent isolates (> 44.97%), followed by Acinetobacter baumannii (12.43%), Klebsiella pneumoniae (8.23%), Enterococcus faecium (3.95%), Escherichia coli (3.92%), Staphylococcus aureus (2.61%) and Enterococcus faecalis (2.42%) in 2019. Whereas, Cryptococcus neoformans accounted for a higher percentage in our study, thus fungal CNS infections should be considered when conventional empirical treatment is ineffective.
With respect to the pathogens distribution in different periods, we found that the proportion of Gram-negative bacteria increased markedly from 15.4% in 2012–2015 years to 43.5% in 2016–2019 years. In the last decades, Gram-negative bacteria had attracted more attention from clinicians, especially MDR/XDR Acinetobacter baumannii and Enterobacteriaceae [21–25]. In our study, Acinetobacter baumannii and Klebsiella were the significantly increased strains and the most frequent causative Gram-negative strains in the later period, accounting for 21.2% of the total isolates. Of the Gram-positive bacteria, CoNS were still the predominant organism although the percentage of it reduced dramatically from 61.5–27.7%. In addition, compare to 2012–2015 years, the species and quantities of isolated strains increased during 2016–2019 years, the Streptococcus pneumoniae and Klebsiella were identified merely in the later period. Cultivation of Streptococcus pneumoniae has been challenging because autolysis resulted in decreased viability , the discovery of it could be associated with the development of the laboratory and microbiological inspection techniques. The elevated microbial species in the later period might also demonstrate this opinion.
As for the results of antibiotic sensitivity in this study, Gram-positive bacteria was still 100% sensitive to vancomycin, teicoplanin and linezolid. Of them, 81.1% (30/37) of the CoNS were methicillin-resistant strains. This finding was higher than the other studies, which were reported 75% and approximately 55%-75% respectively [11, 26]. Additionally, CoNS was 80% sensitive to rifampicin. However, rifampicin is usually used to destroy the tuberculosis bacilli, monotherapy might develop drug resistance easily. The use of rifampicin as part of a combination therapy for CoNS infections of the CNS might be worth considering. Of the Streptococcus pneumoniae, 60% (3/5) strains were resistance to penicillin in our study, the result was lower than an Ethiopian study , which showed that 100% resistance to penicillin. Moreover, there were several studies reported about vancomycin-resistant Enterococcus faecium [28–30], yet, no vancomycin-resistant strains were identified at the present study.
For the Gram-negative isolates, XDR strains accounted for 20.8% of the Acinetobacter in an Indian study , yet, 83.3% (5/6) of the Acinetobacter baumannii strains were XDR bacteria as we showed. An obvious distinction was the sensibility to cefoperazone-sulbactum, approximately 74% of the Acinetobacter isolates were found to be sensitive to it in Indian . However, Acinetobacter baumannii strains were all resistant to it in our study. One possible cause may be the different region and medical conditions. The data presented by two Chinese hospitals about Acinetobacter baumannii indicated low sensitivity to cefoperazone-sulbactum, which were 5.3%, 16.3% respectively [20, 23]. It is possibly indicated that the antibiotic resistance of Acinetobacter baumannii is relatively severe among Acinetobacter. In the meantime, meningitis caused by Enterobacteriaceae, particularly carbapenem-resistant Enterobacteriaceae (CRE) remains a therapeutic challenge worldwide . Among the Enterobacteriaceae strains in our study, carbapenem-resistant species appeared only in the Klebsiella. Four isolates of five Klebsiella showed resistance to carbapenems antibiotics, in which three Klebsiella pneumoniae were all carbapenem-resistant strains. With regards to the Escherichia coli, our findings presented low sensibility to cephalosporins, but they were 100% sensitive to carbapenems antibiotics. This phenomenon might demonstrated that the major resistance mechanism of the Escherichia coli in our hospital is the production of beta- lactamase enzymes rather than carbapenemases.
Antimicrobial agents have been used successfully to treat infectious diseases for a long time. Unfortunately, the misuse and overuse of antibiotics has led to increased antibiotic resistance . Antimicrobial therapy for CNS infections is complicated due to the emergence of MDR strains. Particularly, for Gram-negative bacteria, tigecycline, polymyxin/colistin are usually used for the treatment of MDR/XDR Acinetobacter baumannii and Klebsiella pneumoniae infections [24, 33]. Nevertheless, due to the existence of the BBB, CNS infections does not show any improvement when treated with them by intravenous administration. Hence, the intrathecal (ITH) or intraventricular (IVT) administration of antibiotics had been performed in recent years [34–37]. Whereas, ITH and IVT antibiotic therapy has not been standardized . Further work is needed to explore the antimicrobial therapy through ITH/IVT approach, this might significantly improve the outcomes of patients with CNS infections.
A previous study showed that mortality due to bacterial meningitis ranges from 10 to 20% in high resource settings and as high as 50% in lower resource settings . Our study showed the mortality rate of CNS infections was 30.6% in our hospital. Therefore, it is important to determine the risk factors affecting the outcomes of patients with bacterial CNS infections, particularly in developing countries. Previous studies predicted survival following CNS infections and suggested that age > 40 years, presence of external ventricular drainage, low CSF glucose levels, high CSF protein levels, CSF leukocyte count > 200 cells/mm3, ICU admission, and the presence of comorbidities were risk factors for mortality [31, 38, 39]. In our analysis, age > 50, comorbidity (pulmonary infection) and CSF glucose < normal value were independent risk factors for mortality. Older patients are usually characterised by marked altered organ and physiological functions that often requires distinct treatment, such as individual drug administration and extracorporeal therapies. Thus, comprehensive assessment of the patients status is necessary before the treatment, especially for older patients. Concurrent pulmonary infections might complicate the antibiotic therapy and lead to a poor prognosis at last. Low glucose level in CSF is a crucial diagnostic criterion of CNS infections. Our findings showed that this indicator is not only important indicator of diagnosis, but also crucial indicator to judge the prognosis of patients. The decreased level of CSF glucose might related to the severity of CNS infections. We believe that exploring the risk factors for mortality could help clinicians to pay particular attention to this clinical condition and improve the patients outcomes.
The present study has some limitations. First, this was a single-center study with a small sample size, characteristics that may restrict the applicability of its findings to all patients with CNS infections. Second, due to the limitation of retrospective study, drug sensitivity results were not acquired in some antibiotics. Finally, we did not analyze the cause of CNS infections, whether it was related to surgery.