Outcome following postneurosurgical Acinetobacter meningitis: an institutional experience of 72 cases

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OBJECTIVE

The authors aimed to evaluate the antimicrobial susceptibility pattern of Acinetobacter isolates responsible for nosocomial meningitis/ventriculitis in the neurosurgical ICU. The authors also sought to identify the risk factors for mortality following Acinetobacter meningitis/ventriculitis.

METHODS

This was a retrospective study of 72 patients admitted to the neurosurgical ICU between January 2014 and December 2018 with clinical and microbiological diagnosis of nosocomial postneurosurgical Acinetobacter baumanii meningitis/ventriculitis. Electronic medical data on clinical characteristics, underlying pathology, CSF cytology, antibiotic susceptibilities, and mortality were recorded. To evaluate the outcome following nosocomial postneurosurgical Acinetobacter meningitis/ventriculitis, patients were followed up until discharge or death in the hospital. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to compute factors affecting survival.

RESULTS

The study population was divided into two groups depending on the final outcome of whether the patient died or survived. Forty-three patients (59.7%) were included in the survivor group and 29 patients (40.3%) were included in the nonsurvivor group. Total in-hospital mortality due to Acinetobacter meningitis/ventriculitis was 40.3% (29 cases), with a 14-day mortality of 15.3% and a 30-day mortality of 25%. The 43 (59.7%) patients who survived had a mean length of hospital stay of 44 ± 4 days with a median Glasgow Outcome Scale–Extended score at discharge of 6. On univariate analysis, age > 40 years (p = 0.078), admission Glasgow Coma Scale (GCS) score ≤ 8 (p = 0.003), presence of septic shock (p = 0.011), presence of external ventricular drain (EVD) (p = 0.03), CSF white blood cell (WBC) count > 200 cells/mm3 (p = 0.084), and comorbidities (diabetes, p = 0.036; hypertension, p = 0.01) were associated with poor outcome. Carbapenem resistance was not a risk factor for mortality. According to a multivariable Cox proportional hazards model, age cutoff of 40 years (p = 0.016, HR 3.21), GCS score cutoff of 8 (p = 0.006, HR 0.29), CSF WBC count > 200 cells/mm3 (p = 0.01, HR 2.76), presence of EVD (p = 0.001, HR 5.42), and comorbidities (p = 0.017, HR 2.8) were found to be significant risk factors for mortality.

CONCLUSIONS

This study is the largest case series reported to date of postneurosurgical Acinetobacter meningitis/ventriculitis. In-hospital mortality due to Acinetobacter meningitis/ventriculitis was high. Age older than 40 years, GCS score less than 8, presence of EVD, raised CSF WBC count, and presence of comorbidities were risk factors for mortality.

ABBREVIATIONS EVD = external ventricular drain; GCS = Glasgow Coma Scale; GOS-E = Glasgow Outcome Scale–Extended; ltEVD = long-tunneled EVD; MDR = multidrug resistant; PDR = pandrug resistant; stEVD = short-tunneled EVD; VPS = ventriculoperitoneal shunt; WBC = white blood cell; XDR = extremely drug resistant.

OBJECTIVE

The authors aimed to evaluate the antimicrobial susceptibility pattern of Acinetobacter isolates responsible for nosocomial meningitis/ventriculitis in the neurosurgical ICU. The authors also sought to identify the risk factors for mortality following Acinetobacter meningitis/ventriculitis.

METHODS

This was a retrospective study of 72 patients admitted to the neurosurgical ICU between January 2014 and December 2018 with clinical and microbiological diagnosis of nosocomial postneurosurgical Acinetobacter baumanii meningitis/ventriculitis. Electronic medical data on clinical characteristics, underlying pathology, CSF cytology, antibiotic susceptibilities, and mortality were recorded. To evaluate the outcome following nosocomial postneurosurgical Acinetobacter meningitis/ventriculitis, patients were followed up until discharge or death in the hospital. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to compute factors affecting survival.

RESULTS

The study population was divided into two groups depending on the final outcome of whether the patient died or survived. Forty-three patients (59.7%) were included in the survivor group and 29 patients (40.3%) were included in the nonsurvivor group. Total in-hospital mortality due to Acinetobacter meningitis/ventriculitis was 40.3% (29 cases), with a 14-day mortality of 15.3% and a 30-day mortality of 25%. The 43 (59.7%) patients who survived had a mean length of hospital stay of 44 ± 4 days with a median Glasgow Outcome Scale–Extended score at discharge of 6. On univariate analysis, age > 40 years (p = 0.078), admission Glasgow Coma Scale (GCS) score ≤ 8 (p = 0.003), presence of septic shock (p = 0.011), presence of external ventricular drain (EVD) (p = 0.03), CSF white blood cell (WBC) count > 200 cells/mm3 (p = 0.084), and comorbidities (diabetes, p = 0.036; hypertension, p = 0.01) were associated with poor outcome. Carbapenem resistance was not a risk factor for mortality. According to a multivariable Cox proportional hazards model, age cutoff of 40 years (p = 0.016, HR 3.21), GCS score cutoff of 8 (p = 0.006, HR 0.29), CSF WBC count > 200 cells/mm3 (p = 0.01, HR 2.76), presence of EVD (p = 0.001, HR 5.42), and comorbidities (p = 0.017, HR 2.8) were found to be significant risk factors for mortality.

CONCLUSIONS

This study is the largest case series reported to date of postneurosurgical Acinetobacter meningitis/ventriculitis. In-hospital mortality due to Acinetobacter meningitis/ventriculitis was high. Age older than 40 years, GCS score less than 8, presence of EVD, raised CSF WBC count, and presence of comorbidities were risk factors for mortality.

Meningitis is one of the most common complications in neurosurgical patients.15 The etiology of nosocomial meningitis/ventriculitis includes a wide spectrum of gram-positive and gram-negative bacteria, and since the last decade there has been a change in the trend toward antibiotic resistance, with carbapenem-resistant strains being predominant in the current era.6,15 Among the gram-negative bacteria, Acinetobacter baumanii is one of the most common pathogens responsible for nosocomial meningitis/ventriculitis leading to increased morbidity and mortality in neurosurgical patients.6 Management of multidrug-resistant (MDR) and extremely drug-resistant (XDR) Acinetobacter strains is challenging.3,8 Mortality following Acinetobacter meningitis/ventriculitis ranges from 15% to 70% and it is particularly high in developing countries.14 Despite such high mortality rates, literature on factors predicting survival following Acinetobacter meningitis/ventriculitis is sparse. Herein, we present what is to our knowledge the largest case series on postneurosurgical Acinetobacter meningitis/ventriculitis and attempt to evaluate the crucial risk factors affecting mortality following this challenging nosocomial infection.

Methods

This study was performed at the Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India, a tertiary care apex referral center. We identified the patients admitted in the neurosurgical ICU between January 2014 and December 2018 with microbiological evidence of Acinetobacter baumanii infection using culture reports and antimicrobial susceptibility test results. We included only postneurosurgical nosocomial meningitis cases in our study. Nosocomial Acinetobacter meningitis was identified according to Centers for Disease Control and Prevention (CDC) criteria in patients with clinical, biochemical, cytological, and microbiological evidence of meningitis developing at least 48 hours following any neurosurgical procedure within the same admission setting. Diagnosis of Acinetobacter meningitis/ventriculitis was made on the basis of CDC criteria,5 which include isolation of Acinetobacter species from CSF, fever (≥ 38°C) in the absence of another cause, and any one of the following: increased number of white blood cells (WBCs; > 10/mm3 with > 50% polymorphonuclear leukocytes), raised protein levels (> 45 mg/dl), and/or decreased glucose levels (< 40 mg/dl) in the CSF.

Electronic medical records and laboratory data on the demographic characteristics, clinical characteristics, underlying pathology, comorbidities, CSF cell counts, antibiotic susceptibilities, presence of septic shock, and mortality were retrospectively investigated. Antibiotic susceptibility of Acinetobacter isolates was assessed according to the CLSI (Clinical and Laboratory Standards Institute) guidelines.16 To evaluate the outcome following Acinetobacter meningitis/ventriculitis, patients were followed up until discharge or death in the hospital. Cases with mortality caused by preexisting illnesses after the patient was cured of Acinetobacter meningitis/ventriculitis were excluded. This study was a retrospective subgroup evaluation of a large ongoing audit of nosocomial infections at the Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, and was approved by the Institutional Ethics Committee.

Treatment Protocol

All patients undergoing an elective/emergency neurosurgical procedure (without any indwelling CSF catheters) were given postoperative antibiotic prophylaxis for 24 hours (intravenous cefuroxime and amikacin) according to the department antibiotic policy. For patients having an external CSF diversion procedure or clinically suspected meningitis, initially cefoperazone-sulbactum and amikacin were given empirically while the culture sensitivity reports were awaited. Once the antimicrobial susceptibility results were available, appropriate antibiotics were started. The culture sensitivity–based antibiotic therapy was given for at least 14 days or until culture results were negative, whichever was longer (except in patients who died before the completion of the antibiotic course). In patients who developed Acinetobacter meningitis with an existing indwelling catheter, appropriate culture sensitivity–based antibiotics were started, and the indwelling catheter was removed in cases where CSF diversion was no longer required.

In cases where the continuation of CSF diversion was needed, the short-tunneled external ventricular drain (stEVD) was replaced by either a fresh Ommaya reservoir or a long-tunneled EVD (ltEVD) for CSF drainage and/or instillation of intraventricular antibiotics, depending upon the surgeon’s preference. After 3 consecutive sterile CSF cultures, the Ommaya reservoir or ltEVD was replaced by a ventriculoperitoneal shunt (VPS). According to the departmental policy, in patients having external CSF diversion (stEVD/ltEVD/externalized abdominal end of VPS) or Ommaya reservoir, CSF was sent for biochemical, cytological, and microbiological analysis once daily using strict aseptic precautions. For patients not having external CSF diversion, CSF was collected using lumbar puncture with aseptic precautions whenever there was clinical suspicion of meningitis and repeated only if there was a clinical indication of nonresponsiveness to ongoing antibiotics.

Statistical Analysis

The baseline data were recorded as number (%), mean ± SD, or median [IQR] as appropriate, based on normalcy of distribution. To compare the baseline characteristics between the two groups of patients (survivors and nonsurvivors), chi-square test or Fisher’s exact test was used for categorical variables and Student t-test was used for continuous variables with normal distribution. Continuous variables with nonnormal distribution were compared by using the independent samples Kruskal-Wallis test. For all statistical tests, a p value < 0.05 was considered to be statistically significant. Univariate analyses were done with the final outcome as the dependent variable. To further substantiate the validity of the associations found on univariate analysis, survival analysis was conducted for all identified predictors by using Kaplan-Meier analysis, and median survival was compared using a log-rank test. Kaplan-Meier plots were made to represent survival across strata. In addition, for factors found significant on univariate analysis, a multivariable adjusted Cox proportional hazards model was constructed, and hazard ratios based on multivariate analysis were computed. The data were entered using Microsoft Excel 2011 and analyzed using the IBM SPSS Statistics package version 20 (IBM Corp.) and R Studio. In addition to the base packages in R, ggplot2, survival, survminer, dplyr, and tidyr packages were used.

Results

Clinical Characteristics

This was a retrospective study of 72 patients (26.18%) with Acinetobacter meningitis/ventriculitis out of 275 patients who developed postneurosurgical nosocomial meningitis/ventriculitis between January 2014 and December 2018. Two patients were excluded who had Acinetobacter meningitis and were cured of it but died due to some other cause. One patient had aspiration pneumonitis and consequently succumbed to ARDS (acute respiratory distress syndrome), while the other patient had an ileostomy from a previous abdominal surgery and developed stoma necrosis followed by sepsis. Male patients made up 63.9% of the study population. All collected data were divided into two groups depending on the final outcome of whether the patient died or survived; 43 patients (59.7%) were included in the survivor group and 29 patients (40.3%) were included in the nonsurvivor group. Fifty-seven (79.2%) subjects were adult patients and the rest were pediatric patients (<18 years old). There was no statistically significant difference between the two groups with regard to age group. The mean age of the survivor group (30.6 ± 2.8) was significantly lower than that of the nonsurvivor group (47.5 ± 3.7) (p value < 0.001). There were no significant differences in the age and sex distributions between the two groups. The median time between the neurosurgical procedure and infection was 7 days (IQR 6–10 days). This did not differ when the groups were compared on the basis of final outcome: median 7 days (IQR 5–10 days) for the survivor group and median 7 days (IQR 6–10 days) for the nonsurvivor group (p = 0.8) (Table 1).

TABLE 1.

Comparison of characteristics of the nonsurvivor group versus the survivor group

CharacteristicTotal (n = 72)Nonsurvivor (n = 29)Survivor (n = 43)p Value
Age, yrs37.4 ± 2.547.5 ± 3.730.6 ± 2.8<0.001
Sex0.461
 Male46 (63.9%)20 (43.4%)26 (56.6%)
 Female26 (36.1%)9 (34.6%)17 (65.4%)
Age group0.078
 Adult57 (79.2%)26 (45.6%)31 (55.4%)
 Pediatric15 (20.8%)3 (20%)12 (80%)
Comorbidities
 Diabetes mellitus6 (8.3%)5 (83.4%)1 (16.6%)0.036
 Hypertension12 (16.7%)9 (75%)3 (25%)0.01
 Immunocompromised1 (1.4%)1 (100%)00.403
Primary pathology0.998
 Tumor39 (54.2%)12 (30.7%)27 (69.3%)
 Vascular22 (30.6%)15 (68.1%)7 (31.9%)
 Trauma1 (1.4%)01 (2.3%)
 Congenital5 (6.9%)1 (20%)4 (80%)
 Tuberculosis2 (2.8%)1 (50%)1 (50%)
 Spinal3 (4.2%)03 (100%)
Admission GCS score11.5 ± 0.59.8 ± 0.812.6 ± 0.50.003
Time from procedure to infection, days7 [6–10]7 [6–10]7 [5–10]0.8
CSF diversion procedure
 VPS28 (39.4%)8 (28.6%)20 (71.4%)0.131
 EVD38 (53.5%)21 (55.3%)17 (44.7%)0.03
 Ommaya reservoir12 (16.9%)5 (41.6%)7 (58.4%)0.862
 Shunt revision20 (27.7%)7 (35%)13 (65%)0.632
Time for CSF to become sterile, days7.8 ± 0.76.8 ± 1.58.1 ± 0.70.255
CSF WBC count, cells/mm3492 ± 1131031.9 ± 248128 ± 27.40.0084
Length of hospital stay, days35 [30–49]20 [8–41]45 [34–59]0.001
GOS-E at death/discharge2 [1–6]1 [1–1]6 [2–7]<0.001
Presence of septic shock19 (26.38%)14 (73.6%)5 (26.4%)0.011
Carbapenem resistance0.98
 Resistant to meropenem5 (6.94%)2 (40%)3 (60%)
 Resistant to imipenem4 (5.55%)2 (50%)2 (50%)
 Resistant to both55 (76.3%)22 (40%)33 (60%)
 Sensitive to both8 (11.11%)3 (37.5%)5 (62.5%)

Data are presented as number (%) of patients, mean ± SD, or median [IQR] unless indicated otherwise.

CSF Diversion Procedures

For ease of analysis, all of the external CSF diversion procedures (n = 38) were grouped under a single category of EVD (including stEVD, ltEVD, and externalized abdominal end of VPS).

Primary stEVDs were placed in patients requiring CSF diversion due to hydrocephalus with or without intraventricular hemorrhage (n = 25), and in all of these patients Acinetobacter meningitis was diagnosed after stEVD placement. In patients with stEVD in situ who developed meningitis and in whom CSF diversion was no longer required, the stEVD was removed (n = 2). In cases in which patients developed meningitis with stEVD in situ and CSF diversion was still needed, the stEVD was replaced by either an ltEVD (n = 11) or an Ommaya reservoir (n = 12), according to the treating surgeon’s discretion. After 3 consecutive sterile cultures were obtained, the ltEVD/Ommaya reservoir was replaced with a VPS. Because this was a retrospective study involving multiple surgeons, the choice of ltEVD versus Ommaya reservoir was made according to the surgeon’s preference. However, in all cases VPSs were placed only after 3 consecutive CSF cultures were sterile.

There were 13 patients in whom a primary VPS was placed for hydrocephalus secondary to various reasons. These patients presented with shunt malfunction and required further interventions (externalization in 7 patients or fresh stEVD placement in 6 patients, depending on the site of obstruction). Acinetobacter meningitis was diagnosed after one of these interventions was performed. Of the patients with an externalized VPS, 1 patient was confirmed not to have meningitis and directly underwent VPS placement. Four patients in this group who had persistent infection required change to an ltEVD. After 3 serial sterile cultures were obtained in these patients, the ltEVD was replaced with a VPS.

The median duration of stEVD placement was 4 days (IQR 3.5–4.5 days) in the nonsurvival group and 4 days (IQR 3.5–4.5 days) in the survival group, with no significant difference between the two groups (p = 0.762). With respect to ltEVD placement, the median duration was 11 days (IQR 9.25–13.75 days) in the nonsurvival group and 11 days (IQR 9.25–13.75 days) in the survival group, with no significant difference between the groups (p = 1.00).

Antibiogram

More than 80% of the Acinetobacter isolates were found to be resistant to amikacin (86%), amoxicillin–clavulanic acid (94%), cefotaxime (94%), ceftazidime (94%), chloramphenicol (93%), ciprofloxacin (89%), netilmicin (90%), and piperacillin-tazobactum (85%). Carbapenem resistance (resistance to both meropenem and imipenem) was seen in 76.3% of the isolates. However, 74% of the isolates were sensitive to cefoperazone-sulbactum. Fifteen (20.8%) isolates were categorized as XDR Acinetobacter species sensitive only to colistin and tigecycline. No isolates were found to be resistant to colistin and/or tigecycline (pandrug resistant [PDR]). Individual antimicrobial susceptibility is illustrated in Fig. 1.

FIG. 1.
FIG. 1.

Antibiogram showing antimicrobial susceptibility patterns of the 72 isolates.

Outcome

None of the patients had abscess/empyema formation after the initial meningitis/ventriculitis was detected. Total in-hospital mortality due to Acinetobacter meningitis/ventriculitis was 40.3% (29 cases), with 14-day mortality of 15.3% and 30-day mortality of 25%. Forty-three (59.7%) patients who survived had a median length of hospital stay of 45 days (IQR 34–59 days), with a median Glasgow Outcome Scale–Extended (GOS-E) score at discharge of 6 (IQR 2–7). Out of the 15 (20.8%) patients with XDR isolates, 7 patients survived, with a median GOS-E of 6.

Factors Affecting Survival

On univariate analysis, age > 40 years, admission Glasgow Coma Scale (GCS) score ≤ 8, presence of septic shock, presence of EVD, CSF WBC count > 200 cells/mm3, and comorbidities (diabetes mellitus and hypertension) were associated with poor outcome. Carbapenem resistance was not a risk factor for mortality. In comparison to Ommaya reservoir placement (p = 0.862) and VPS (p = 0.131), the presence of an EVD was a significant risk factor for mortality (p = 0.03). Various risk factors evaluated in univariate analysis have been summarized in Table 1. Kaplan-Meier survival analysis for the abovementioned risk factors has been illustrated in Fig. 2. Factors that were found to be significant on univariate analysis were further evaluated using a Cox proportional hazards model, and hazard ratios were calculated. On multivariate analysis, age cutoff of 40 years, GCS score cutoff of 8, CSF WBC count > 200 cells/mm3, presence of EVD, and comorbidities were found to be significant risk factors for mortality (Table 2).

FIG. 2.
FIG. 2.

Kaplan-Meier survival analyses for age (cutoff > 40 years) (A), presence of EVD (B), CSF total leukocyte count (TLC [equivalent to WBC]) (C), and presence of septic shock (D).

TABLE 2.

Multivariate Cox proportional hazards model

VariableHR (95% CI)p Value
Age cutoff, ≤40 or >40 yrs3.21 (1.24–8.3)0.016
GCS score cutoff, ≤8 or >80.29 (0.12–0.7)0.006
EVD5.42 (1.94–15.1)0.001
Septic shock1.54 (0.69–3.4)0.293
Comorbidities2.80 (1.20–6.5)0.017
CSF WBC count >200 cells/mm32.76 (1.202–6.35)0.01

Discussion

Nosocomial meningitis/ventriculitis following neurosurgical procedures is showing an upward trend, and the increasing prevalence of MDR pathogens affects outcomes following nosocomial meningitis.15 Acinetobacter baumanii, a gram-negative bacillus, has been reported to be one of the most common pathogens responsible for nosocomial meningitis/ventriculitis worldwide.6 Along with meningitis/ventriculitis, Acinetobacter baumanii is also a major cause of other infections occurring in neurosurgical ICUs.13 A recent systemic review by Sipahi et al.12 reported that Acinetobacter species were responsible for around 30% of nosocomial meningitis/ventriculitis. This is concordant with the results of our study, where Acinetobacter contributed to 26.18% of nosocomial meningitis/ventriculitis.

The major challenge in the management of Acinetobacter meningitis/ventriculitis is the ability of this pathogen to develop resistance against commonly used antibiotics for surgical prophylaxis, and such resistance patterns can compound surgical morbidity and mortality.3,6,8 In our study, more than 80% of the Acinetobacter isolates were found to be resistant to amikacin, amoxicillin–clavulanic acid, cefotaxime, chloramphenicol, ceftazidime, ciprofloxacin, netilmicin, and piperacillin-tazobactum. Carbapenem resistance (to both meropenem and imipenem) was seen in 76.3% of patients; however, it was not associated with worse outcome. About 74% of the isolates were found to be sensitive to cefoperazone-sulbactum, suggesting that this combination can be used for surgical prophylaxis in patients with a high propensity to develop meningitis/ventriculitis, especially patients with EVD in situ. A study by Niu et al.11 has shown that cefoperazone-sulbactum is an effective therapy for the treatment of carbapenem-resistant strains. As a part of our neurosurgical ICU antibiotic policy, all patients with external CSF diversion procedures are given intravenous cefoperazone-sulbactum and we attempt to remove the stEVD as soon as feasible or convert it to an ltEVD or Ommaya reservoir if CSF diversion is still needed. Fifteen (20.8%) isolates were found to fulfill the criteria of XDR Acinetobacter species sensitive to only colistin and/or tigecycline. This is in concordance with the recent series which shows increasing prevalence of XDR Acinetobacter species that must be treated with colistin and/or tigecycline.3,4,7 However, no PDR isolates were found in our study.

Our study showed a high rate of in-hospital mortality (40.3%), with 15.3% of the deaths occurring within 14 days of diagnosis of Acinetobacter meningitis/ventriculitis. Tuon et al.14 recently reported in-hospital mortality rates as high as 72%. Such high mortality rates can be explained on the basis of increasing prevalence of MDR and XDR species. However, carbapenem resistance was not found to increase the risk of mortality in our study. Out of the 15 patients with XDR isolates, 7 patients survived, suggesting that timely diagnosis and intervention using appropriate antibiotics can also allow management of such difficult cases. All cases of XDR isolates were treated with combinations of intravenous and intraventricular colistin and/or tigecycline.

Literature regarding factors predicting survival following Acinetobacter meningitis/ventriculitis is sparse.14 Many previous studies have shown the impact of carbapenem resistance on mortality; however, as per our study, carbapenem resistance was not associated with worse outcome.1,9 Patients younger than 40 years were found to have higher survival rates. Admission GCS scores greater than 8 were associated with better outcomes. Presence of EVD, septic shock, comorbidities, and CSF WBC count greater than 200 cells/mm3 were risk factors for poor survival. A recent study by Ceylan et al.1 reported that old age and failure to provide CSF sterilization were risk factors for increased mortality. The impact of the presence of EVD, which was found to be a significant risk factor for mortality in our study, was not evaluated in that study. We also compared various CSF diversion procedures, such as VPS, VPS revision, external CSF diversion procedures, and Ommaya reservoir placement. In our experience, Acinetobacter meningitis typically follows external CSF diversion procedures. We found that among all these CSF diversion procedures, external CSF diversion procedures were associated with increased risk of mortality following Acinetobacter meningitis/ventriculitis. This finding highlights the need to tailor antibiotic prophylaxis for patients who have an EVD in the neurosurgical ICU and to convert the EVD into an alternate form of CSF diversion as early as possible.

The survival rate in our study was 59.7%, with a mean length of hospital stay of 44 ± 4 days among the survivor group. The median GOS-E score at discharge for the survivor group was 6. Out of the 15 (20.8%) patients with XDR isolates, 7 patients survived, with a median GOS-E score of 6. This finding suggests that early diagnosis of Acinetobacter meningitis and intervention with appropriate antibiotics and timely conversion of EVD into an alternative CSF diversion procedure can result in good functional outcome even in cases with MDR and XDR isolates.

To our knowledge, our study includes the largest available database on Acinetobacter meningitis/ventriculitis, with most cases categorized as infection with MDR or XDR Acinetobacter species. The previously available studies on postneurosurgical MDR/XDR Acinetobacter meningitis/ventriculitis are mostly case reports or small case series.1,2,10 This in turn reflects the very high burden of nosocomial meningitis/ventriculitis in developing countries like India. Our study is unique as it has clearly demonstrated the factors associated with mortality following postneurosurgical Acinetobacter meningitis/ventriculitis. It is the first study to compare various CSF diversion procedures and their impact on survival following Acinetobacter meningitis/ventriculitis.

However, the current study has several limitations, mainly owing to the retrospective design. This investigation was a single-center tertiary care hospital experience from a developing country, characteristics that may restrict the applicability of its findings to management of nosocomial Acinetobacter meningitis/ventriculitis patients worldwide. We could not study the effect of the duration of antibiotic treatment on mortality, as in many cases the treatment could not be completed because of the patient’s death. Our study did not compare the use of intraventricular versus intravenous colistin and/or tigecycline for XDR isolates because all of the patients received drugs via both routes. Since this was a retrospective review of patients suffering from Acinetobacter meningitis, it was not feasible to calculate the incidence of Acinetobacter infections for different durations of EVD, although it would have made for an interesting comparison. We did not include any patients in this study who did not have Acinetobacter meningitis, so this analysis was not feasible in our study. In the light of the above limitations, there is a need for a well-designed prospective study in the future.

Conclusions

In the current study we evaluated the largest database of postneurosurgical Acinetobacter meningitis/ventriculitis. Most cases were caused by MDR species, with around one-fifth of the cases caused by XDR species. Around 76% of the isolates were sensitive to cefoperazone-sulbactum, and no isolates were resistant to colistin and/or tigecycline. This nosocomial meningitis/ventriculitis was associated with high mortality. Age > 40 years, GCS score < 8, presence of EVD, CSF WBC count > 200 cells/mm3, and presence of comorbidities were risk factors for mortality. Carbapenem resistance was not a risk factor for mortality. Among various CSF diversion procedures, only EVD was found to increase the risk of mortality, suggesting the need for appropriate antibiotic prophylaxis in patients with EVD in situ and conversion of EVD to alternate CSF diversion procedures. Patients whose infection is diagnosed in a timely manner and treated with appropriate culture-based antibiotics have good functional outcome at discharge.

Acknowledgments

We would like to acknowledge the members of the departmental infection control team (Jyotsna Dabral, BSc, Shally George, BSc, and Bindu Jijumon, RNRM) for contributing to the retrospective audit and helping the authors in collecting the data on Acinetobacter meningitis.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Borkar, Sharma, Suri. Acquisition of data: Sharma, Goda, Kapil, Kumar, Mohapatra. Analysis and interpretation of data: Katiyar, Kumar, Mohapatra. Drafting the article: Borkar, Sharma, Goda, Kumar, Mohapatra. Critically revising the article: Borkar, Sharma, Katiyar, Suri, Kumar, Mohapatra. Reviewed submitted version of manuscript: Borkar, Katiyar, Suri, Kumar, Mohapatra. Approved the final version of the manuscript on behalf of all authors: Borkar. Statistical analysis: Katiyar, Agarwal. Administrative/technical/material support: Borkar, Kapil, Suri, Kale. Study supervision: Borkar, Sharma, Katiyar, Kapil, Suri, Kale.

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    Moon CKwak YGKim BNKim ESLee CS: Implications of postneurosurgical meningitis caused by carbapenem-resistant Acinetobacter baumannii. J Infect Chemother 19:9169192013

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    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Ni SLi SYang NZhang SHu DLi Q: Post-neurosurgical meningitis caused by acinetobacter baumannii: case series and review of the literature. Int J Clin Exp Med 8:21833218382015

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Niu TLuo QLi YZhou YYu WXiao Y: Comparison of Tigecycline or Cefoperazone/Sulbactam therapy for bloodstream infection due to Carbapenem-resistant Acinetobacter baumannii. Antimicrob Resist Infect Control 8:522019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Sipahi ORNazli Zeka ATaşbakan MPullukçu HArda BYamazhan T: Pooled analysis of 899 nosocomial meningitis episodes from Turkey. Turk J Med Sci 47:29332017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Suri AMahapatra AKKapil A: Acinetobacter infection in neurosurgical intensive care patients. Natl Med J India 13:2963002000

  • 14

    Tuon FFPenteado-Filho SRAmarante DAndrade MABorba LA: Mortality rate in patients with nosocomial Acinetobacter meningitis from a Brazilian hospital. Braz J Infect Dis 14:4374402010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    van de Beek DDrake JMTunkel AR: Nosocomial bacterial meningitis. N Engl J Med 362:1461542010

  • 16

    Weinstein MP: Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testinged 29. Wayne, PA: Clinical and Laboratory Standards Institute2019

    • Search Google Scholar
    • Export Citation

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Article Information

Correspondence Sachin Anil Borkar: All India Institute of Medical Sciences, New Delhi, India. sachin.aiims@gmail.com.

INCLUDE WHEN CITING DOI: 10.3171/2019.5.FOCUS19278.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Antibiogram showing antimicrobial susceptibility patterns of the 72 isolates.

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    Kaplan-Meier survival analyses for age (cutoff > 40 years) (A), presence of EVD (B), CSF total leukocyte count (TLC [equivalent to WBC]) (C), and presence of septic shock (D).

References

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    Moon CKwak YGKim BNKim ESLee CS: Implications of postneurosurgical meningitis caused by carbapenem-resistant Acinetobacter baumannii. J Infect Chemother 19:9169192013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Ni SLi SYang NZhang SHu DLi Q: Post-neurosurgical meningitis caused by acinetobacter baumannii: case series and review of the literature. Int J Clin Exp Med 8:21833218382015

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Niu TLuo QLi YZhou YYu WXiao Y: Comparison of Tigecycline or Cefoperazone/Sulbactam therapy for bloodstream infection due to Carbapenem-resistant Acinetobacter baumannii. Antimicrob Resist Infect Control 8:522019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Sipahi ORNazli Zeka ATaşbakan MPullukçu HArda BYamazhan T: Pooled analysis of 899 nosocomial meningitis episodes from Turkey. Turk J Med Sci 47:29332017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Suri AMahapatra AKKapil A: Acinetobacter infection in neurosurgical intensive care patients. Natl Med J India 13:2963002000

  • 14

    Tuon FFPenteado-Filho SRAmarante DAndrade MABorba LA: Mortality rate in patients with nosocomial Acinetobacter meningitis from a Brazilian hospital. Braz J Infect Dis 14:4374402010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    van de Beek DDrake JMTunkel AR: Nosocomial bacterial meningitis. N Engl J Med 362:1461542010

  • 16

    Weinstein MP: Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testinged 29. Wayne, PA: Clinical and Laboratory Standards Institute2019

    • Search Google Scholar
    • Export Citation

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