Acinetobacter Meningitis: A Retrospective Study on its Incidence and Mortality Rates in Postoperative Patients at a Tertiary Care Centre in Northern India
Correspondence Address :
Dr. Chinmoy Sahu,
Additional Professor, Department of Microbiology, C-Block, Second Floor, SGPGI, Lucknow-226012, Uttar Pradesh, India.
E-mail: csahu78@rediffmail.com
Introduction: Acinetobacter is a non fermenting, Gram negative bacillus, a causative pathogen of hospital-acquired infections due to its inherent Multidrug-Resistant (MDR) property. It is held responsible for the majority of nosocomial meningitis in patients undergoing neurosurgical procedures.
Aim: To identify the clinical characteristics, drug-resistance and mortality rate among the patients suffering from meningitis caused by Acinetobacter baumannii.
Materials and Methods: This retrospective, single-centre study was carried out in the Bacteriology section of the Department of Microbiology at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, from February 2019 to February 2022. A total of 150 Cerebrospinal Fluid (CSF) samples from routine bacterial culture-confirmed patients were included in the study. All clinical data were extracted from the Hospital Information System (HIS). All the isolates were identified by Matrix Assisted Laser Desorption/Ionisation-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) assay and antibiotic sensitivity testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines.
Results: The study included 150 (7.55%) cases of culture-proven bacterial meningitis among 1986 CSF samples collected from February 2019 to February 2022. There were 45 (30.0%) cases of Acinetobacter meningitis. Thirty-five (77.8%) patients had undergone neurosurgical procedures for the removal of space-occupying lesions from the brain parenchyma. Forty-two (93.3%) isolates were resistant to amikacin and a cumulative resistance of almost 93.3-95.6% was observed among cephalosporins. Fluoroquinolone resistance was observed in 43 (95.6%) patients and carbapenem resistance was observed in 42 (93.33%) isolates. Overall, 12 (26.7%) succumbed to their infections.
Conclusion: Acinetobacter meningitis causes delay in the recovery of the patient undergoing intracranial surgery, amounting to a delay in brain parenchyma healing in the case of neurosurgical patients.
Bacterial meningitis, Gram negative bacilli, Mass spectrometry, Neurosurgical procedures, Nosocomial meningitis
Hospital-acquired meningitis is the most common morbidity faced by patients undergoing neurosurgical procedures (1). The causative microorganisms responsible for these nosocomially acquired infections include a wide range of Gram negative and Gram positive microorganisms but this scenario has changed over the past decade to include many polydrug-resistant microorganisms in the list of causative pathogens of nosocomial meningitis. Among all other Gram negative bacilli, Acinetobacter species have been held responsible for the majority of nosocomial meningitis in patients undergoing neurosurgical procedures and critical patients admitted to the neurosurgery ward (2).
Acinetobacter species is a non fermenting, Gram negative bacillus which is the known causative pathogen of hospital-acquired infections due to its inherent MDR property (3). It is an opportunistic pathogen that is capable of causing infection in old and debilitated patients admitted to the hospital for a prolonged period. The common array of infections caused by it includes pneumonia, meningitis, bacteraemia, and rarely wound infections (4),(5). Acinetobacter species is known as the most common pathogenic bacteria isolated from patients who have undergone craniotomy or other neurosurgical procedures (2).
The presence of Extraventricular Drain (EVD) and Ventriculo-Peritonial (VP) shunt usually after the intracranial procedure for CSF diversion deems the patient susceptible to bacterial meningitis by MDR microorganisms like Acinetobacter species (6).
The study aimed to demonstrate the incidence of Acinetobacter meningitis among known cases of bacterial meningitis and also include the propensity of the microorganism to cause infection in neurosurgical patients. An overtime increase in the incidence of Acinetobacter meningitis among the patients admitted to the study hospital prompted the authors to conduct this study to analyse the accurate incidence of Acinetobacter meningitis among all inpatients, recognise the rate of drug resistance among these isolates and identify the group of patients that were more susceptible to this infection at our centre.
This retrospective, single-centre study was carried out in the Bacteriology section of the Department of Microbiology at a tertiary care centre, where data of Acinetobacter meningitis patients from February 2019 to February 2022 was extracted from the laboratory records and HIS and was analysed from March 2022 to May 2022. The study was performed under the project with Reference number 2020-100-EMP-EXP-16 which was approved by the Institutional Ethics Committee (IEC) of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
A total of 150 non repeat culture-proven bacterial meningitis samples were included in the study and all clinical data of the patients was extracted from the HIS of the institute.
Inclusion criteria: All CSF samples with culture confirmed bacterial meningitis, from the inpatient department at the centre, without any specific age group and gender were included in the study.
Exclusion criteria: Contaminated samples and samples with delay in transportation for more than two hours were excluded from the study.
Study Procedure
Processing of samples: All CSF samples were collected at a combined receiving station and sent to the bacteriology section of the Department of Microbiology for processing in laboratory according to the standard protocols. The Gram’s stain and bacterial culture were performed for each sample. The Blood agar, MacConkey agar, and Robertsons’ Cooked Meat broth (RCM) were used for the bacterial culture of the samples. The samples were incubated for 72 hours at 37º C and isolated Acinetobacter species colonies were observed on the Blood and MacConkey agar plates. After completion of the incubation period, turbidity was observed in the RCM and identification of the Acinetobacter species was facilitated using standard biochemical tests, and MALDI-TOF-MS, (Bruker Daltonics, Germany) assay (7).
Antimicrobial susceptibility testing: The Kirby-Bauer Disc Diffusion method and Epsilometeric test were used for conducting antibiotic susceptibility testing for each of the bacterial isolates, according to the CLSI 2019 guidelines (8). Antibiotic discs containing amikacin (30 μg), ceftazidime (30 μg), ceftriaxzone (30 μg), cefoperazone-sulbactam (75/10 μg), ciprofloxacin (5 μg), imipenem (10 μg), meropenem (30 μg), and colistin (0.016-256 μg) Epsilometeric test strips were obtained from bioMérieux. Standard inoculums for each bacterial isolate were prepared and set to 0.5 McFarland and a lawn culture was applied on cation-adjusted Muller-Hinton agar plates. The above mentions E-test strips and antibiotic discs were manually placed on the lawn cultured plates and incubated overnight at 37º C. The measurement of zones of inhibition for each antibiotic against each isolate was done and classified as sensitive, intermediate, and resistant according to the tables and guidelines by CLSI 2019 (Table/Fig 1) (8).
Microbiological characteristics and drug resistance patterns were analysed for all the Acinetobacter species isolated from CSF samples included in the study. The study further demonstrated the risk of isolating MDR-Acinetobacter spp, which includes microorganisms resistant to three different classes of antibiotics (9). The study also assessed the risk factors associated with Acinetobacter meningitis in patients with and without shunts.
Statistical Analysis
Quantitative variables were articulated as mean±standard deviation. While analysing of risk factors of acquiring MDR-Acinetobacter spp, the comparison between groups for categorical variables was estimated by using χ2 tests. The results were presented as 95% Confidence Intervals. Statistical analysis was facilitated by the software program International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) Statistics version 20.0 (IBM Corp., Armonk, NY, USA), with p-value <0.05 considered statistically significant.
The study included 150 (7.55%) cases of culture-proven bacterial meningitis among the 1986 CSF samples collected from February 2019 to February 2022. Forty-five (30.0%) cases of Acinetobacter meningitis among the culture-positive bacterial meningitis patients were reported in this study and thus Acinetobacter spp. has been deemed the predominant microorganism among the patients suffering predominantly from nosocomial bacterial meningitis. The mean age of the patients was 26.60±18.32 years (range 1-68), and 28 (62.22%) were males. The mean length of hospitalisation was 38.98±22.13 days. The demographic characteristics, presenting complaints, and risk factors of acquiring Acinetobacter meningitis are demonstrated in (Table/Fig 2).
Among these 45 cases of Acinetobacter meningitis, 35 (77.8%) had undergone neurosurgical procedures for the removal of space-occupying lesions from the brain parenchyma. Forty (88.89%) patients used shunts where, 27 (60.0%) patients used EVD, and 13 (28.89%) used VP shunts. The mean age of the patients with shunts and without shunts was 27.08±18.02 years and 22.8±22.5 years, respectively. The demographic characteristics and risk factors in patients suffering from Acinetobacter meningitis with and without shunt are described in (Table/Fig 3). The underlying co-morbidities like intracranial space-occupying lesions needing surgery, organ transplant, chronic obstructive pulmonary disease, heart disease, and nosocomial origin of infection is highly significant in patients with shunts in comparison to those without shunts is shown in (Table/Fig 3).
Among Acinetobacter spp isolates obtained from the CSF samples, Acinetobacter baumannii was the predominant microrganism isolated from 43 (43/45, 95.6%) samples and Acinetobacter lowffii was obtained from 2 (2/45, 4.4%) samples. Overall, a high drug resistance was observed among the Acinetobacter spp isolates from CSF samples. The antibiotic resistance among the Acinetobacter spp isolates is described in (Table/Fig 4) which demonstrates the percentage resistance of the isolates to a particular isolate. Amikacin was resistant among 42 (93.3%) isolates and among the cephalosporins, a cumulative resistance of almost 93.3-95.6% was observed. Thus, the extended-spectrum beta-lactam antibiotic resistance was thus observed in about 43 patients. Ciprofloxacin was used as a representative of the fluoroquinolone group of antibiotics and was found resistant among 43 patients. Carbapenem resistance was found in 42 isolates as seen in (Table/Fig 5).
Overall, 35 (77.8%) patients were administered appropriate antibiotics while among the rest of the 10 (22.2%) patients, 5 (11.11%) left against medical advice and 5 (11.11%) died before any treatment could be administered. Overall, 12 (26.7%) succumbed to their infections and could not be saved despite all efforts.
A rising trend of nosocomial bacterial meningitis, predominantly in patients after neurosurgical procedures has been observed and the presence of MDR complicates the recovery of infected patients (1). Among the Gram negative bacilli, Acinetobacter species are known to be the most common causative pathogen of nosocomial bacterial meningitis, especially in the case of post neurosurgical procedures and it is also a known cause of MDR infections among those admitted to neurosurgical Intensive Care Units (ICUs) (2),(10). Among the patients included in this study, all the CSF samples were sent to the Bacteriology Section of the Department of Microbiology from the Neurosurgical ward and ICU. The four year incidence of Acinetobacter meningitis among the bacterial meningitis patients included in this study was 30.0% (45/150). Acinetobacter meningitis was observed in 30% cases of bacterial meningitis and a similar incidence of Acinetobacter meningitis was observed in studies by Sipahi OR et al., and Sharma R et al., were the incidence of Acinetobacter meningitis was 30.7% and 26.18%, respectively (6),(11).
The challenge faced during the treatment of Acinetobacter meningitis includes the MDR property of the microorganism that complicates recovery among the patients. The mean age of the patients was 26.60±18.32 years which was in contrast with other studies by Sharma R et al., (6) and Tuon FF et al., (12), where the age of patients with Acinetobacter meningitis was in the range of 30-40 years of age, thus the rate of mortality was less in compared to the above-mentioned studies. The majority of patients included in the study had undergone neurosurgical procedures. Patients with hydrocephalus, intracranial bleeding and, CSF leak were managed using a shunt diversion. Thirty-five (87.5%) patients who had undergone intracranial surgeries needed shunt diversion after the procedure making them more susceptible to bacterial meningitis in agreement to a study by Sharma R et al., (6) where all the 25 (100.0%) patients with shunt diversion developed Acinetobacter meningitis.
The risk factors associated with Acinetobacter meningitis in patients with and without shunts is demonstrated in (Table/Fig 3). Presence of intracranial space occupying lesions, Chronic Obstructive Pulmonary Disease (COPD), heart disease and organ transplant had significant association with the use of shunts. The above finding of presence of intracranial space occupying lesion leading to neurosurgery corroborate with the finding of a study conducted by Sharma R et al., (6), where Acinetobacter meningitis was observed in all patients who underwent neurosurgery followed by shunt placement. Although none of the studies mentioned COPD, heart disease and organ transplant to be significant risk factor associated withAcinetobacter meningitis.
Although cefoperazone-sulbactam is universally accepted as antibiotic prophylaxis in many surgical procedures in a study by Niu T et al., (13), the present study suggested a resistance of 95.6% (43/45) to this antimicrobial agent. (Table/Fig 6) shows comparison with other similar published original articles directly or indirectly related to this study cohort (6),(11),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(26),(27),(28),(29),(30),(31),(32),(33),(34),(35),(36),(37). The presence of EVD and VP shunt also increases the risk of acquiring MDR infections. The MDR temperament of Acinetobacter isolates was significantly associated with chronic kidney disease, heart disease, and COPD in this study and authors did not come across any such association among the other co-morbidities in recently published studies by Sharma R et al., and Sipahi OR et al., (6),(11). Acinetobacter species were 93.3-95.6% resistant to amikacin, ceftazidime, ceftriaxone, ciprofloxacin, cefoperazone-sulbactam, imipenem, meropenem while other studies showed only about 20-80% (6),(12). A study by Moon C et al., suggests that the isolation of carbapenem-resistant isolates was directly proportional to the rate of mortality among the patients (14). The present study shows that carbapenem resistance was as high as 93.3% (42/45) which did not show a poor prognosis, due to the fact that being a tertiary care centre availability of newer and more effective antibiotic agents facilitated better outcome in comparison to other centres. Thus, the patients showed a higher incidence of resistance in this study, and most patients were treated with colistin infusion which is the drug of last resort and poses a high cost of treatment and morbidity.
The mortality rate in the present study was 26.7% (12/45) which was in agreement with the findings by Chen CH et al., (15), Sipahi OR et al., (16) and Chen FM et al., (17) where the mortality rates were 28.57%, 30% and 20%, respectively. On the other hand, it was much less in comparison to the study conducted by Tuon FF et al., (12) which reported a mortality rate of 72.7% and by Sharma R et al., (6) who reported about 40% mortality. This can be attributed to the early diagnosis and reporting of the antimicrobial resistance at present setting along with the fact that strict hospital infection control measures and prompt treatment with compliance to the antibiotic susceptibility report were followed at this centre.
Limitations(s)
Firstly, the study depicts the incidence of Acinetobacter meningitis at a single centre and does not mention about its incidence in the geographical area. Secondly, authors did not specify the groups of patients and found the incidence and mortality among the patients as a whole and not specifically in neonates or post neurosurgical meningitis. Thirdly, this was a retrospective study which is based mainly on previous records and HIS which may not clearly signify the incidence and mortality.
Acinetobacter meningitis causes a delay in the recovery of the patient from the operative procedures they had undergone, amounting to a delay in brain parenchyma healing in the case of neurosurgical patients. The associated morbidity and mortality of the disease due to the MDR nature of the microorganism and the nosocomial nature of the infection call for strict compliance to the infection control practices and drug susceptibility report to inhibit the rampant use of last resort antibiotics early in the treatment.
DOI: 10.7860/JCDR/2023/59248.17187
Date of Submission: Jul 24, 2022
Date of Peer Review: Aug 20, 2022
Date of Acceptance: Sep 29, 2022
Date of Publishing: Jan 01, 2023
Author declaration:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA
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