J Infect Chemother 26 (2020) 101e106

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Journal of Infection and Chemotherapy

journal homepage: http://www.elsevier.com/locate/jic

Original Article

Epidemiology and risk factors of neurosurgical bacterial meningitis/

encephalitis induced by carbapenem resistant Enterobacteriaceae*
Zheng Guanghui a, Liu Jing b, Zhang Guojun a, **, Lv Hong a, *
a
Department of Clinical Diagnosis Laboratory of Beijing Tiantan Hospital, Capital Medical University, China
b
Department of Clinical Diagnosis Laboratory of Beijing Jishuitan Hospital, China

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: This is a retrospective observational study conducted in one of the largest clinical center of
Received 24 March 2019 neurosurgery in China. Our aim was to determine the epidemiological characteristics of carbapenem-
Received in revised form resistant Enterobacteriaceae (CRE) related meningitis/encephalitis and to elucidate the risk factors for
7 July 2019
CRE neurosurgical infections.
Accepted 31 July 2019
Available online 21 August 2019
Patients and methods: We performed a retrospective study between January 2012 and December 2017 of
patients who underwent neurosurgery. The medical records of each patient were reviewed, and 20
clinical variables on risk factors were extracted and evaluated by Multivariate logistic analysis for CRE-
Keywords:
Risk factors
meningitis/encephalitis.
Meningitis/encephalitis Results: In 2012e2017, the positive rate of neurosurgical meningitis/encephalitis was 7.9% (2947/29605),
Carbapenem resistant Enterobacteriaceae Enterobacteriaceae accounted for 6.3% (185/2947) of all bacterial infections. Totally, 133 Enterobacteri-
Infection aceae include 26 CRE isolates were available in this study. Of them, Univariate analysis showed that the
risk factors of CRE meningitis were ventilator, bacteremia, Intensive Care Unit (ICU) admission, hospital
acquired pneumonia and mortality attribute to infection. Multivariate logistic analysis showed that
hospital acquired pneumonia and mortality attribute to infection were independent risk factors for CRE
meningitis.
Conclusion: CRE is one of the most serious drug-resistant bacteria published by World Health Organi-
zation (WHO) in 2016, and meningitis/encephalitis caused by CRE is an important sign of the failure of
the neurosurgery, which demands the physician's immediate attention.
© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction meningitis rate following neurosurgeries has not decreased as

Meningitis caused by neurosurgery has posed a formidable
challenge, resulting in severe morbidity with a prolonged length of
hospital stay and higher hospital costs [1,2]. Significantly varied
rates of meningitis caused by neurosurgery have been reported,
ranging from 0.72 to >8% [3e5]. Despite the increasing advance-
ment in neurosurgical technology and postoperative care, the
*
All authors meet the ICMJE authorship criteria.
* Corresponding author. Beijing Tiantan Hospital, Capital Medical University,
Nansihuan west road NO.119, Fengtai district, Beijing, 100070, China.
** Corresponding author. Beijing Tiantan Hospital, Capital Medical University,
Nansihuan west road NO.119, Fengtai district, Beijing, 100070, China.
E-mail addresses: tiantanzgj@163.com (Z. Guojun), tiantanlvhong@126.com
(L. Hong).
much as expected in recent years.
Therefore, it's an essential part to identify the epidemiology and
risk factors of meningitis to provide proper treatment. In recent
decades, nosocomial meningitis caused by Enterobacteriaceae,
particularly carbapenem-resistant Enterobacteriaceae (CRE), has
become a major threat all over the world, with high morbidity and
mortality rates [6,7]. Understanding the risk factors of CRE men-
ingitis in neurosurgical patients are of the utmost clinical
significance.
Several comprehensive studies have been published on the risk
factors for neurosurgical meningitis [8,9], however, no study
considered specific risk factors for meningitis/encephalitis caused
by CRE, which prompted the need for our study. We retrospectively
investigated the epidemiology of neurosurgical meningitis/en-
cephalitis in 2012e2017 from Beijing Tiantan hospital to analysis
the risk factors of CRE related meningitis/encephalitis in

https://doi.org/10.1016/j.jiac.2019.07.023
1341-321X/© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
102 Z. Guanghui et al. / J Infect Chemother 26 (2020) 101e106

neurosurgical patients in order to better understand possibilities to occurring after an episode of meningitis/encephalitis but result in
decrease carbapenem resistance rates. In this study, to minimize causes independent of the infectious process).
deviation, carbapenem-susceptible Enterobacteriaceae (CSE) and
CRE were chosen for comparison, and 20 clinical variables that
2.3. Statistical analysis
might relate to CRE neurosurgical infection were included. In
addition, clinical treatment and outcome were also embedded into
WHONET 5.5 and SPSS 20.0 (IBM New York, US) were used for
this study. As far as we know, this is the first study of such risk
the all statistical analysis. Continuous data were expressed as mean
factors in China, and the data in this paper have great clinical
and standard deviations (SD) or median and range, whereas cate-
significance.
gorical data were expressed as numbers and percentages. A t-test/
Mann-Whitney U test was used to perform two group comparisons
2. Materials and methods
for continuous quantitative variables and chi-square or Fisher's
exact test were performed for the categorical data. Univariate
This study was done at the Beijing Tiantan Hospital & Capital
analysis was employed to calculate the P values for all variables, a
Medical University between 2012 and 2017. Beijing Tiantan Hos-
multivariate model was performed to take into account differences
pital is a tertiary hospital with 1850 beds and more than 15000
between the two groups, variables were included as candidates in
annual surgeries. The protocol for this study was approved by the
the multivariable model when one univariate analysis P
clinical diagnosis department of the Beijing Tiantan Hospital &
value < 0.10, significance was defined as a P-value of <0.05 (two-
Capital Medical University. Patients were eligible if they were at
tailed).
least 18 years of age and survived at least 7 days after neurosurgery;
neurosurgical operations included craniotomy, trans sphenoidal,
and spinal surgeries. Patients discharged without new surgery, 3. Results
anti-infective operations not done in this hospital, and incomplete
medical records were excluded from our study. 3.1. Microbiology

2.1. Definitions and data abstraction From Jan 2012 to Dec 2017, a total of 2947 isolates were collected
from CSF with a 7.9% (2947/29605) positive culture ratio. Among
For patients with Enterobacteriaceae meningitis/encephalitis them, 6.3% patients with non-duplicate Enterobacteriaceae (185/
was identified by cerebrospinal fluid (CSF) bacteria cultures on 29605) were gathered. The respective microorganisms are pre-
standard media. Epidemiological data included distribution and sented in Table 1. No multiple organism infections were found, and
antimicrobial susceptibility tests of bacteria. Antimicrobial testing antimicrobial susceptibility test results are shown in Table 2.
of susceptibility to the antimicrobial drug categories were per-
formed by the disc diffusion method and broth microdilution
method, according to the Clinical and Laboratory Standards Insti- 3.2. Patient demographics and clinical characteristics
tute 2016. Based on the antimicrobial susceptibility testing (AST)
results, Enterobacteriaceae were classified using the most-current During the study period, 185 patients who underwent neuro-
standard definitions: CRE and CSE, and strains with intermediate surgery and were infected by Enterobacteriaceae were included.
susceptibility to carbapenem were classified as the CRE. There were 15 patients younger than 18 years old, 8 patients who
All of the patients' eligible daily progress notes were extracted were discharged from hospital directly without antimicrobial
from the standard database. We recorded 20 characteristics such as treatment, 9 patients hospitalized less than 7 days, 7 patients that
patients' routine information (age, male%), length of hospitalization died within 7 days, and 13 patients with incomplete medical re-
stay (LOS), Positive culture time, hypertension, diabetes mellitus, cords who were all (52) excluded from our study. A flow sheet is
site of surgery, surgical wound classification, extra ventricular shown in Fig. 1. In the remaining 133 cases, 26 had CRE infections
drainage (EVD), lumbar drainage (LD), ventilation rate, cerebro- and 107 had CSE infections.
spinal fluid (CSF) leakage, the lowest point during hospitalization
Glasgow coma scale (GCS score), surgical approach, bacteremia,
intensive care unit (ICU) admission, malignancy, craniotomy, hos-
Table 1
pital acquired pneumonia and mortality attribute to infection Species found in Enterobacteriaceae related meningitis/encephalitis during
[8e10]. Clinical treatment includes antibiotic prophylaxis, received 2012e2017.
empirical antibiotics, received definitive therapy as well as clinical
Bacterial isolates Numbers Percentage
outcome.
Citrobacter freundii 1 0.5%
Citrobacter koseri 3 1.6%
2.2. Patient antimicrobial drugs therapy and outcomes Enterobacter aerogenes 19 10.3%
Enterobacter cloacae 19 10.3%
Antibiotic therapies were classified as 3 categories: 1) Antibiotic Enterobacter gergoviae 1 0.5%
prophylaxis: patients receive antibiotic 0.5 h before the neurosur- Enterobacter sakazakii 1 0.5%
Escherichia coli 32 17.3%
gery; 2) Empirical antibiotics: patients receive antibiotics ahead the Klebsiella oxytoca 10 5.4%
microbiological AST result; 3) Received definitive therapy: patients Klebsiella pneumoniae ss. pneumoniae 75 40.5%
receive antibiotics in line with the microbiological AST result. Kluyvera ascorbata 1 0.5%
Clinical outcomes were assessed at 7 days after the end of Leclercia adecarboxylata 1 0.5%
Morganella morganii ss. morganii 1 0.5%
therapy. The clinical outcomes were defined as follows: 1)
Pantoea agglomerans 6 3.2%
Improved and cured (complete resolution of fever, clinical signs and Proteus mirabilis 1 0.5%
other relevant investigations); 2) Dead. Mortality was assessed at Proteus rettgeri 3 1.6%
28 days after patients completed therapy. It was classified as: 1) Providencia stuartii 1 0.5%
Mortality attribute to infection (death with clinical evidence of an Serratia marcescens 9 4.9%
Serratia plymuthica 1 0.5%
active infection) and 2) Mortality not attribute to infection (death
 Z. Guanghui et al. / J Infect Chemother 26 (2020) 101e106 103

Table 2 3.3. Treatments and outcomes

Antimicrobial susceptibility test of species found in Enterobacteriaceae related
meningitis/encephalitis during 2012e2017 (R: Resistance; I: Intermediate; S:
Sensitive).
The clinical treatment and outcomes of the Enterobacteriaceae
infections are at Table 3. The majority of patients (76.7%, 102/133)
Antibiotics No. %R %I %S were given antibiotic prophylaxis medication. Patients in the two
Ampicillin 185 78.9 10.8 10.3 groups received the empirical antibiotics rates (100.0% VS 86.0%,
Piperacillin 183 44.8 6.6 48.6 P ¼ 0.043) are statistical significance. Empirical and definitive
Amoxicillin/clavulanic acid 179 46.4 6.7 46.9
therapy with combination antibiotics were frequently prescribed in
Ampicillin/Sulbactam 183 38.3 18.0 43.7
Piperacillin/tazobactam 182 19.3 2.7 78.0 both groups. For Enterobacteriaceae meningitis/encephalitis, the
Ceftazidime 185 38.9 1.6 59.5 most commonly prophylactic use of antibiotics is cefuroxime and
Cefotaxime 179 38.0 5.0 57.0 ceftriaxone. In addition, vancomycin plus meropenem are the most
Cefepime 185 35.2 1.6 63.2
commonly used empirical antibiotics. Meropenem plus colstin
Aztreonam 183 39.9 1.1 59.0
Imipenem 183 16.4 0.0 83.6
were the most frequently prescribed drugs in the CRE-meningitis/
Meropenem 183 16.4 0.0 83.6 encephalitis group. Finally, in this study, the overall mortality
Amikacin 183 9.8 0.0 90.2 attribute to infection rate was 23.3% (31/133), and it was signifi-
Gentamicin 185 27.1 0.5 72.4 cantly higher in CRE group than CSE group (69.2% VS 12.1%,
Ciprofloxacin 183 27.9 4.4 67.7
P < 0.001).
Levofloxacin 185 27.0 1.6 71.4
Sulfamethoxazole/Trimethoprim 184 32.1 0.0 67.9
Polymyxin B 173 0.0 0.0 100.0
Chloramphenicol 175 16.6 14.3 69.1
3.4. Risk factors associate with CRE-meningitis/encephalitis
Tetracycline 176 34.1 1.1 64.8
Of the 20 risk factors we selected, univariate analysis is shown in
Table 4; 13 characteristics showed higher proportions in CRE vs CSE
meningitis/encephalitis; they include hypertension, diabetes mel-
litus, spinal surgery, surgical wound classification: clean, LD,
Patients with Enterobacteriaceae meningitis/encephalitis had a
ventilation rate, CSF leakage, craniotomy, bacteremia, ICU admis-
median age of 43.9 ± 13.9 years, 54.9% (73/133) patients were male.
sion, hospital acquired pneumonia, malignancy, and mortality
Average LOS of the patients was 35.1 days and the median time of
attribute to infection. In addition, the mean LOS and positive cul-
CSF positive culture was 7.4 days. There were 54.9% (73/133) of
ture time were higher than those of CSE meningitis/encephalitis.
patients suffering from a malignant tumor, and 27.8% (37/133) pa-
Factors with P value < 0.05 in univariate analysis include sur-
tients who underwent bacteremia comorbidity; other common
gical wound classification, ventilation rate, craniotomy, bacteremia,
comorbidities were hypertension 12.8% (17/133), diabetes mellitus
ICU admission, hospital acquired pneumonia and mortality attri-
3.8% (5/133), and hospital acquired pneumonia 18.0% (24/133).
bute to infection. We included all the factors with P value < 0.10 in
There were 33.1% (43/133) cases with a clean surgical wound
the univariate analysis into the logistic multivariate analysis. All of
operation and the remainder had a clean-contaminated surgical
the multivariate analysis variables included in the model are listed
wound operation. In 133 cases, 77 (57.9%) have EVD, 57 (42.8%)
in Table 5. Hospital acquired pneumonia and mortality attribute to
have LD and 48 patients (36.1%) were admitted into the ICU. Inci-
infection were determined as the independent risk factors for CRE
dence of CSF leakage was 24.8% (33/133) and the lowest point
meningitis/encephalitis. Species found in hospital acquired pneu-
during hospitalization Glasgow coma scale was 8.1. All variables are
monia with Enterobacteriaceae related meningitis/encephalitis are
shown in Table 4.
listed in Table 6.

Fig. 1. Flow sheet for diagnosing Enterobacteriaceae meningitis/encephalitis.

104 Z. Guanghui et al. / J Infect Chemother 26 (2020) 101e106

Table 3
Treatment, and clinical and microbiological outcomes, of patients with CRE-related meningitis/encephalitis.

Factors Total (133) CRE (26) CSE(107) P

Antibiotic prophylaxis 102 (76.7%) 22 (84.6%) 80 (74.8%) 0.287

Ceftazidime 12 (9.0%) 3 (11.5%) 9 (8.4%) 0.249
Ceftriaxone 25 (18.8%) 11 (42.3%) 14 (13.1%) 0.001
Cefuroxime 61 (45.8%) 8 (30.8%) 53 (49.5%) 0.085
Meropenem 1 (0.8%) 0 (0.0%) 1 (0.9%) 0.621
Vancomycin 2 (1.5%) 0 (0.0%) 2 (1.9%) 0.482
Cefoperazone/Sulbactam 1 (0.8%) 0 (0.0%) 1 (0.9%) 0.621
Received empirical antibiotics 118 (86.5%) 26 (100.0%) 92 (86.0%) 0.043
Single antibiotics 39 (29.3%) 12 (46.2%) 27 (25.2%) 0.036
Ceftriaxone 12 (9.0%) 7 (26.9%) 5 (4.7%) <0.001
Meropenem 17 (12.8%) 5 (19.2%) 12 (11.2%) 0.272
Cefuroxime 7 (5.3%) 0 (0.0%) 7 (6.5%) 0.180
Vancomycin 3 (2.3%) 0 (0.0%) 3 (2.8%) 0.388
Combination antibiotics (2) 67 (50.4%) 11 (42.3%) 56 (52.3%) 0.359
Vancomycin þ Meropenem 54 (40.6%) 8 (30.8%) 46 (43.0%) 0.255
Meropenem þ Ceftazidime 5 (3.8%) 3 (11.5%) 2 (1.9%) 0.020
Others 8 (6.0%) 0 (0.0%) 8 (7.5%) 0.150
Combination antibiotics (3) 12 (9.0%) 3 (11.5%) 9 (8.4%) 0.618
Vancomycin þ Meropenem þ Ceftazidime 10 (7.5%) 3 (11.5%) 7 (6.5%) 0.386
Others 2 (1.5%) 0 (0.0%) 2 (1.9%) 0.482
Received definitive therapy 130 (97.7%) 26 (100.0%) 104 (97.2%) 0.388
Single antibiotics 37 (27.8%) 3 (11.5%) 34 (31.8%) 0.039
Meropenem 36 (27.1%) 2 (7.7%) 34 (31.8%) 0.013
Colistin 1 (0.8%) 2 (7.7%) 0 (0.0%) 0.004
Combination antibiotics (2) 81 (60.9%) 16 (61.5%) 65 (60.7%) 0.590
Vancomycin þ Meropenem 53 (39.8%) 3 (11.5%) 50 (46.7%) 0.001
Meropenem þ Colistin 18 (13.5%) 13 (50.0%) 5 (4.7%) <0.001
Meropenem þ Cefoperazone/Sulbactam 5 (3.8%) 0 (0.0%) 5 (4.7%) 0.261
Others 5 (3.8%) 0 (0.0%) 5 (4.7%) 0.261
Combination antibiotics (3) 12 (9.0%) 7 (26.9%) 5 (4.7%) <0.001
Colistin þ Meropenem þ Trimethoprim 5 (3.8%) 3 (11.5%) 2 (1.9%) 0.020
Colistin þ Tigecycline þ Meropenem 4 (3.0%) 4 (15.4%) 0 (0.0%) <0.001
Others 3 (2.3%) 0 (0.0%) 3 (2.8%) 0.388
Clinical Outcome
Improved and cured 96 (72.2%) 8 (30.8%) 88 (82.2%) <0.001
Mortality attribute to infection 31 (23.3%) 18 (69.2%) 13 (12.1%) <0.001
Mortality not attribute to infection 6 (4.5%) 0 (0.0%) 6 (5.6%) 0.217

Table 4
Univariate analysis of risk factors for the development of CRE related meningitis/encephalitis.

Factors Total (133) CRE (26) CSE(107) P

Age (years) 43.9 ± 13.9 41.3 ± 12.9 44.4 ± 12.6 0.857

Male (%) 73 (54.9%) 13 (50.0%) 60 (57.9%) 0.577
Length of hospitalization stay (LOS) 35.1 days 47.8 days 33.3 days 0.211
Positive culture time 7.4 days 11.9 days 6.9 days 0.219
Hypertension 17 (12.8%) 5 (19.2%) 12 (11.2%) 0.272
Diabetes mellitus 5 (3.8%) 2 (7.8%) 3 (2.8%) 0.240
Site of surgery
Head 122 (91.7%) 23 (88.5%) 99 (92.5%) 0.500
Spinal 11 (8.3%) 3 (11.5%) 8 (7.5%) 0.500
Surgical wound classification
Clean 44 (33.1%) 13 (50.0%) 31 (29.0%) 0.041
Clean -contaminated 89 (66.9%) 13 (50.0%) 76 (71.0%) 0.041
Extra ventricular drainage (EVD) 77 (57.9%) 15 (57.7%) 62 (57.9%) 0.981
Lumbar drainage (LD) 57 (42.8%) 15 (57.7%) 42 (39.3%) 0.088
Ventilation rate 32 (24.1%) 15 (57.7%) 17 (15.9%) <0.001
CSF leakage 33 (24.8%) 7 (26.9%) 26 (24.3%) 0.781
Glasgow Coma Scale 8.1 4.0 8.3 0.716
Craniotomy 59 (44.4%) 16 (61.5%) 43 (40.2%) 0.049
Bacteremia 37 (27.8%) 15 (57.7%) 22 (20.6%) <0.001
ICU admission 48 (36.1%) 18 (69.2%) 30 (29.9%) <0.001
Hospital acquired pneumonia 24 (18.0%) 13 (50.0%) 11 (10.3%) <0.001
malignancy 73 (54.9%) 18 (69.2%) 55 (51.4%) 0.101
Mortality attribute to infection 31 (23.3%) 18 (69.2%) 13 (12.1%) <0.001

4. Discussion and the incidence of neurosurgical bacterial meningitis/encepha-

Meningitis/encephalitis in neurosurgery has posed a formidable
challenge, resulting in severe morbidity and mortality [11]. To
address our data, more than 2000 neurosurgical positive infections
were reviewed in one of the largest neurosurgical centers of China
litis was 7.6%. Prevalence of infection was roughly the same with
median reported in the literature [12,13].
Meningitis/encephalitis caused by Enterobacteriaceae remains a
therapeutic challenge as the effective antibiotic is severely limited.
The number of Enterobacteriaceae meningitis/encephalitis in
 Z. Guanghui et al. / J Infect Chemother 26 (2020) 101e106
Table 5
Multivariate logistic analysis of risk factors for the development of CRE-related meningitis/encephalitis.
Factors B S.E,
Surgical wound classification 0.528 0.557
Ventilation rate 0.882 0.627
Craniotomy 0.107 0.572
Bacteremia 1.02 0.583
ICU admission 0.279 0.655
Hospital acquired pneumonia 1.829 0.573
Mortality attribute to infection 1.921 0.653
neurosurgery patients have increased in recent years [1,2]. In this
retrospective study, Enterobacteriaceae, and especially CRE, played
a significant role in neurosurgical bacterial meningitis/encephalitis
with strong invasiveness, high toxicity, high morbidity and mor-
tality rates. Overall, the microbiological findings in this study are
consistent with the majority of previous reports [14]. Of these,
Klebsiella pneumoniae (75, 40.5%), Escherichia coli (32, 17.3%),
Enterobacter cloacae (19, 10.3%) and Enterobacter aerogenes (19,
10.3%) were the four most prevalent species. Carbapenem have
been considered one of the last lines of defense against infections
due to Enterobacteriaceae, but CRE are resistant to nearly all b-lac-
tam antimicrobials. Other classes of antimicrobials, such as fosfo-
mycin, tigecycline, polymyxin and aminoglycoside were commonly
used for CRE infections. Unfortunately, these types of antibiotics
possess severe adverse effects, which blocked substantial clinical
applications. From this study, for carbapenems, the susceptibility
was 83.6%, and despite the low ratio of CRE (16.4%), it can result in
extremely grievous consequences [15].
Depending on the present study, antibiotic prophylaxis and
empirical are routine manipulation during the neurosurgery
operation. For empirical antibiotics therapy, difference of the CRE
and CSE-meningitis/encephalitis patients were statistically signifi-
cant. According to the present study, colistin seems to be the most
active agent for combating infections caused by CRE. Several pub-
lished data reveal that in response to CRE infections, combination
therapy is more efficient than single-agent therapy [16,17]. In this
study, antibiotics combination seems the better choice for CRE
meningitis/encephalitis, and colistin appears to be the most effec-
tive antibiotics for combating CRE infections in post-neurosurgical
patients, and several combinations require colistin for
compatibility.
Several risk factors associated with neurosurgical infection have
been identified in previous studies; different literature reports vary
widely due to different data inclusion criteria. According to a case-
controlled study with 4578 cases, CSF leakage, male%, surgical
diagnosis, surgeon, early reoperation, surgical duration and
absence of prophylaxis were independent risk factors [18]. In
another report, EVD was the risk factor for neurosurgical infection
[19]. Chen's study suggests that EVD, LD, and diabetes were
neurosurgical infection risk factors [20]. In Univariate analysis of
risk factors for the development of CRE meningitis/encephalitis,
surgical wound classification, ventilation rate, craniotomy, bacter-
emia, ICU admission, hospital acquired pneumonia and mortality
Table 6
Species found in hospital acquired pneumonia with Enterobacteriaceae related
meningitis/encephalitis.
Bacterial isolates Total CRE
Klebsiella pneumoniae 10 7 3
Acinetobacter baumannii 2 1
Pseudomonas aeruginosa 6 2
Staphylococcus aureus 6 3
Total 24 13
105
Wals OR 95% confidence interval P Hosmer-Lemeshow test(P)
0.897 1.696 0.484e4.873 0.344 0.141
1.981 2.415 0.318e4.84 0.159
0.035 1.113 0.314e3.4 0.851
3.057 2.772 0.418e5.55 0.08
0.181 1.322 0.362e4.99 0.67
10.185 6.227 1.568e17.091 0.001
8.657 6.825 1.899e24.533 0.003
attribute to infection were risk factors. In multivariate logistic
analysis, hospital acquired pneumonia and the mortality attribute
to infection were the independent risk factors in neurosurgical CRE
infections. In this study, the distributions of patients infected with
Enterobacteriaceae with hospital acquired pneumonia were not in
the same ward, so the infection doesn't happen in endemic areas.
Neurosurgery nosocomial infection with hospital-acquired pneu-
monia can cause a huge clinical risk and several studies support
that co-infection is a number of clinical postoperative infection risk
factors [21]. Possible reasons may be the low immunity of neuro-
surgical patients after therapy with high-grade antibiotics;
carbapenem-susceptible strains that cannot directly invade the
patient's nervous system may lead to CRE infection, the specific
reasons for which still need further study for confirmation.
According to our study in multivariate logistic analysis, mor-
tality attribute to infection was another risk factor (P < 0.05).
However, as mortality is the result of neurosurgical infection; it
should not be considered as an independent risk factor. The rela-
tionship between carbapenem resistance and mortality is still
confusing [22]. Hussein's thesis reported that although mortality
rates of carbapenem resistant K. pneumoniae patients were signif-
icantly higher than those of carbapenem susceptible K. pneumoniae
patients, mortality was not connected to carbapenem resistance
[23]. In the study of Liu, mortality of carbapenem susceptible
K. pneumoniae bacteremia was lower than carbapenem non-
susceptible K. pneumoniae bacteremia but the overall in-hospital
mortality ratio for these two groups showed no obvious signifi-
cant difference [24]. We support the latter point of view; there is no
doubt that CRE meningitis/encephalitis can result in more difficult
treatment in comparison with CSE and it may also lead to increased
mortality, but mortality was associated with a variety of factors and
a large scale clinical study of CRE still needs to be carried out.
Although there are so many profits in this study, it is still having
inadequacies. First of all, this article is a retrospective analysis, and
it has congenital defects. If the patients from the two groups have
incomplete information when searching for risk factors, statistical
bias may occur. Secondly, the number of CRE is limited which may
lead to poor representation, and in addition, this study is a single-
center study with a single source of patients. However, despite
these limitations, these data represent current risk factors of CRE
meningitis/encephalitis. In our following work, we will conduct a
multi-center and prospective study to better understand the risk of
meningitis/encephalitis caused by CRE.
5. Conclusion
Epidemiological characteristics of Enterobacteriaceae infection
CSE and the risk factors of CRE meningitis/encephalitis in neurosurgical
patients were retrospectively studied. CRE was one of the most
1 serious microbes published by the WHO in 2016. In this study, we
4 observed that hospital acquired pneumonia was determined as the
3 independent risk factors for CRE meningitis/encephalitis, and in
11
addition, CRE meningitis/encephalitis can result in more difficult
106 Z. Guanghui et al. / J Infect Chemother 26 (2020) 101e106
treatment and it may lead to increased mortality. In total, CRE
meningitis/encephalitis is an important criterion for the success of
neurosurgery, which should prompt the clinician to be aware of its
importance.
Funding
This study was supported by research grant: QML20180502,
Beijing Municipal Administration of Hospitals' Youth Program.
Ethical approval
For this type of study formal consent is not required.
Informed consent
Informed consent was obtained from all individual participants
included in the study.
Conflicts of interest
We declare that we do not have any commercial or associative
interest that represents a conflict of interest in connection with the
work submitted.
Acknowledgements
I want to take this chance to thanks to Zhang Jiankun, colleague
of me in Beijing tiantan hospital. He gives me many academic and
precious suggestions at this section, and helps me to correct my
paper. This study was supported by research grant: QML20180502,
Beijing Municipal Administration of Hospitals' Youth Program.
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