Bacterial Meningitis among Intracranial Surgery Patients at a University Hospital in Northern India

HIGHLIGHTS

• This study denotes the incidence of bacterial cerebrospinal infections among the patients who underwent intracranial surgeries.

• We discuss the risk factors, underlying comorbidities that render susceptibility to bacterial cerebrospinal infections, and drug resistance among the pathogens isolated from cerebrospinal shunt infections.

BACKGROUND

Meningitis is a dreaded complication that increases morbidity, mortality, and the length and cost of hospitalization after intracranial surgical intervention.¹ Other studies also describe it to have the highest incidence among all the patients who underwent neurosurgical interventions.^2,3 Meningitis remains the main reason for poor prognosis in postoperative intracranial surgeries in patients after neurosurgery.⁴ The patients included in this study have undergone craniotomies and other endoscopic intracranial surgeries due to both benign and malignant lesions, and isolation of postoperative meningeal infections further delays the improvement in neurological functions of the patient and may progress to cause disability or death.⁵

The prevalence of intracranial bacterial infections was found to be 3% by the American National Nosocomial Infections Surveillance System, which assessed 43,135 neurosurgical cases between 1992 and 2004, and a similar incidence of 2.89–5.35% was found in bacterial meningitis patients who underwent intracranial surgeries at various hospitals in China.^5,6 Indian studies suggest a 0.7–8.9% incidence of meningitis in post-neurosurgical patients.⁷ Although bacterial meningitis causes a potential threat to the life of the postoperative patients, the histopathological findings of the lesions, the stage and time of diagnosis, more importantly in malignant intracranial lesions, and the administration of appropriate antibiotics play a major role in the prognosis of the disease.⁸

OBJECTIVES

It is the need of the hour for the neurosurgeons to know the incidence, risk factors, and the spectrum of pathogenic microorganisms and appropriate antibiotic susceptibility causing bacterial meningitis among the patients who underwent intracranial surgery. The main aim of the study was to observe the incidence of bacterial cerebrospinal infections in post-neurosurgery patients.

The objectives of this study include the following:

• Identification of the risk factors and underlying comorbidities that render susceptibility to bacterial cerebrospinal infections in post-neurosurgery patients.

• Analysis of the spectrum of pathogenic bacteria and drug resistance among the pathogens isolated from cerebrospinal shunt infections.

MATERIALS AND METHODS

RESULTS

DISCUSSION

This study demonstrates the clinical and microbiological profiles of the patients who developed cerebrospinal infections following neurosurgical procedures at a tertiary care center in Northern India. We studied the cases of 96 nosocomially acquired cerebrospinal infection post neurosurgery and evaluated their demographics, underlying comorbidities, risk factors, spectrum of pathogenic microorganisms, and their drug-resistance patterns. The incidence of postsurgical cerebrospinal infections at our center was 4.83% (96/1986, 4.83%), which is in agreement with the studies conducted by Reichert et al.,¹ Blomstedt,¹⁶ Patir et al.,¹⁷ and Korinek et al.³ A male predominance (57/96, 59.4%) was observed in our study cohort, which could be attributed to more male patients visiting the OPD or emergency department of the hospital, seeking treatment which correlates with studies by Zhou et al.⁴

The incidence of cerebrospinal infection at our center was 7.55% (150/1986, 7.55%), which is estimated to be lower in comparison to the incidence of cerebrospinal infection that was noted to be in the range of 32–94% in an analysis performed by McClelland et al.,¹⁸ Kourbeti et al.,¹⁰ Korinek et al.,³ and Dashti et al.¹⁹ This difference in incidence could be attributed to the regular use of preoperative prophylactic administration of antibiotics before every surgery performed at our tertiary care center. Although prophylactically all the intraoperative CSF samples were sent for culture at our institute, it is highly recommended that samples from highly symptomatic patients are sent for microscopic examination and culture.

Post-intracranial surgery, all patients were managed on either EVD or VP shunt. The presence of any shunts increases the risk of cerebrospinal infections. The patients were managed on the shunts for at least 10–15 days in most cases, and most of the patients showed positive CSF cultures within the same timeframe, which correlates with the study conducted by Scheithauer et al.²⁰ According to early studies, the rate of cerebrospinal shunt infections was reported to be 1.5–39%, however, the rate seems to have dropped to 2–9%,²¹ which corresponds with the rate of CSF shunt infections, which was reported to be 4.83% (96/1986, 4.83%) in our study.

In literature, post-neurosurgery cerebrospinal infections were commonly reported to be caused by Staphylococcus aureus, Propionibacterium acnes, and coagulase-negative Staphylococcus.²² In contrast to early reports, our study observed the major pathogenic bacteria causing infection among post-neurosurgery patients to be Acinetobacter spp. (33/96, 34.375%) followed by K. pneumoniae (18/96, 18.75%). The shunts used in neurosurgery are premedicated with antibiotics such as minocycline, clindamycin, and rifampin, and silver coating is active mainly against gram-positive bacteria and significantly reduces the chances of shunt infections by them.²³ Notably, some recent studies have reported the emergence of gram-negative bacilli as a major pathogen in many neurosurgical units, especially A. baumannii,²⁴ which mirrors the results of our observations.

Our study dealt mainly with nosocomial infections and hospital-acquired microorganisms causing bacterial meningitis. Acinetobacter spp. (33/96, 34.375%) was the most commonly isolated bacteria followed by Staphylococcus species (20/96, 20.83%), which is in agreement with the study conducted by Khan et al.²⁵ Gram-negative bacilli, mostly belonging to the Enterobacteriaceae group, were observed in our study as K. pneumoniae was isolated in 18.75% (18/96, 18.75%) cases, E. cloacae was isolated in 11.4% (11/96, 11.4%), and E. coli was isolated in 2.1% (2/96, 2.1%) cases as observed in studies conducted in 1992 by Federico et al.² and Erdem et al.²⁶

The rate of isolation of MDROs was high among the patients who had undergone craniotomy with shunt placement in our study. The risk of isolating MDROs in patients who had undergone craniotomy with shunt placement in our study is statistically significant, as described in Table 4. The ESBL and carbapenem resistance in the intensive care unit was in concordance with a study conducted at our center by Sahu et al.²⁷ Owing to the high drug resistance among gram-negative isolates, intrathecal colistin administration was observed in 31.25% (30/96) of patients with neurosurgical bacterial meningitis with favorable outcomes due to poor CSF penetration of intravenous colistin which is similar to a study conducted by Rao et al.²⁸

The mean length of hospitalization in patients who underwent intracranial surgery and developed bacterial meningitis was 36.99 ± 20.42 days, and the length of hospital stay among the patients suffering from intracranial malignant lesions was 36.25 ± 18.50 days, which corroborates our findings with the study by Zhou et al.⁴ that the patients had a length of hospital stay more than 15 days in case of malignant lesions due to prolonged treatment. The increased total cell count of CSF, low CSF glucose, high CSF protein, increased length of hospital stay, the GCS, and low CSF/blood glucose ratio as a risk for isolation of MDROs are statistically significant in our study, as described in Table 4.

The factors that limit the information conveyed by our study are that it is a retrospective, single-center study, so firstly we had to depend upon the HIS for the clinical data and charting, thus representing a selection bias. The drawback of it being a single-center study is that it does not represent the rate of isolation of postsurgical bacterial meningitis in the population of Northern India. There were factors that we did not take into consideration, including the prophylactic antibiotics administered and catheter insertion and removal of shunts.

CONCLUSION

This study determines gram-negative bacteria as the budding cause of post-neurosurgery infection and the emergence of Acinetobacter spp. as the most common organism causing cerebrospinal shunt infections. Presence of shunts predisposes the postoperative patients to many MDR microorganisms. There is a high incidence of MDR organisms reported from our study as prophylactic antibiotics are already administered before a surgical procedure.

AUTHORS’ CONTRIBUTIONS

MK and CS: Protocol development. AD and AJ: Data collection. CS and SSP: Data analysis and Supervision. MK: Writing—original draft. MK, AJ, AD, CS, and SSP all authors read and approved the final version of the manuscript.

ACKNOWLEDGMENTS

The author thanks the contribution of Mr. Malay Ghar, Mr. Aman, Mr. Ramesh, and all other laboratory staff for providing technical and logistic support.

ORCID

Mitra Kar https://orcid.org/0000-0001-9744-9653

Ashima Jamwal https://orcid.org/0000-0003-4497-8388

Akanksha Dubey https://orcid.org/0000-0002-5546-6110

Chinmoy Sahu https://orcid.org/0000-0002-5440-7717

Sangram Singh Patel https://orcid.org/0000-0001-5344-0729

REFERENCES

1. Reichert MC, Medeiros EA, Ferraz FA. Hospital-acquired meningitis in patients undergoing craniotomy: Incidence, evolution, and risk factors. Am J Infect Control 2002;30(3):158–164. DOI: 10.1067/mic.2002.119925.

2. Federico G, Tumbarello M, Spanu T, Rosell R, Iacoangeli M, Scerrati M, et al. Risk factors and prognostic indicators of bacterial meningitis in a cohort of 3580 post neurosurgical patients. Scand J Infect Dis 2001:33(7):533–537. DOI: 10.1080/00365540110026557.

3. Korinek AM, Golmard J-L, Elcheick A, Bismuth R, van Effenterre R, Coriat P, et al. Risk factors for neurosurgical site infections after craniotomy: A critical reappraisal of antibiotic prophylaxis on 4,578 patients. Br J Neurosurg 2005;19(2):155–162. DOI: 10.1080/02688690500145639.

4. Zhou H, Zhang X. Intracranial malignant lesions correlate with the requirement for a long treatment course in a postoperative central nervous system infection. Neuropsychiatr Dis Treat 2014;10:2071–2077. DOI: 10.2147/NDT.S71836.

5. Xu G, Zhang F, Chen QX. Analysis of high-risk factors correlated to the associated intracranial infection postcraniotomy. Chin J Clin Neurosurg 2008;13(6):362–364.

6. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32(8):470–485. DOI: 10.1016/S0196655304005425.

7. Srinivas D, Veena Kumari HB, Somanna S, Bhagavatula I, Anandappa CB. The incidence of postoperative meningitis in neurosurgery: An institutional experience. Neurol India 2011;59(2):195–198. DOI: 10.4103/0028-3886.79136.

8. Wang KW, Chang WN, Huang CR, et al. Post-neurosurgical nosocomial bacterial meningitis in adults: Microbiology, clinical features, and outcomes. J Clin Neurosci 2005;12(6):647–650. DOI: 10.1016/j.jocn.2004.09.017.

9. Yang ZJ, Zhong HL, Wang ZM, Zhao F, Liu PN. Prevention of postoperative intracranial infection in patients with cerebrospinal fluid rhinorrhea. Chin Med J (Engl) 2011;124(24):4189–4192. PMID: 22340385.

10. Kourbeti IS, Jacobs AV, Koslow M, Karabetsos D, Holzman RS. Risk factors associated with post craniotomy meningitis. Neurosurgery 2007;60(2):317–325; discussion 325–326. DOI: 10.1227/01.NEU.0000249266.26322.25.

11. Kurtaran B, Kuscu F, Ulu A. The causes of post-operative meningitis: the comparison of gram-negative and gram-positive pathogens. Turkish Neurosurg 2018;28(4):589–596. DOI: 10.1155/2021/9923015.

12. Hu Y, He W, Yao D, Dai H. Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical intracranial infection due to multidrug-resistant and extensively drug-resistant gram-negative bacteria: A systematic review and meta-analysis. Int J Antimicrob Agents 2019;54(5):556–561. DOI: 10.1016/j.ijantimicag.2019.08.002.

13. Saklad M. Grading of patients for surgical procedures. Anesthesia 1941;2:281–284. DOI: 10.1097/00000542-194105000-00004.

14. Keats AS. The ASA classification of physical status – a recapitulation. Anesthesiology 1978;49(4):233–236. DOI: 10.1097/00000542-197810000-00001.

15. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-third informational supplement. Clinical and Laboratory Standards Institute. CLSI document M100-S29. Wayne, PA, USA; 2019.

16. Blomstedt GC. Infections in neurosurgery: A retrospective study of 1143 patients and 1517 operations. Acta Neurochir (Wien) 1985;78:81–90.

17. Patir R, Mahapatra AK, Banerji AK. Risk factors in postoperative neurosurgical infection. A prospective study. Acta Neurochir (Wien) 1992;119(1–4):80–84. DOI: 10.1007/BF01541786.

18. McClelland S 3rd, Hall WA. Postoperative central nervous system infection: Incidence and associated factors in 2111 neurosurgical procedures. Clin Infect Dis 2007;45(1):55–59. DOI: 10.1086/518580.

19. Dashti SR, Baharvahdat H, Spetzler RF, Sauvageau E, Chang SW, et al. Operative intracranial infection following craniotomy. Neurosurg Focus 2008;24(6):E10. DOI: 10.3171/FOC/2008/24/6/E10.

20. Scheithauer S, Bürgel U, Bickenbach J, Häfner H, Haase G, Waitschies B, et al. External ventricular and lumbar drainage-associated meningoventriculitis: Prospective analysis of time-dependent infection rates and risk factor analysis. Infection 2010;38(3):205–209. DOI: 10.1007/s15010-010-0006-3.

21. Crnich CJ, Safdar N, Maki DG. Infections associated with implanted medical devices. In: Finch RG, Greenwood D, Norrby SR, Whitley RJ (Eds.). Antibiotic and Chemotherapy: Anti-infective Agents and their Use in Therapy. Churchill Livingstone; 2003:575–618.

22. Hoefnagel D, Dammers R, Laak-Poort T, Avezaat CJ. Risk factors for infections related to external ventricular drainage. Acta Neurochir (Wein) 2008;150(3):209–214. DOI: 10.1007/s00701-007-1458-9.

23. Atkinson RA, Fikrey L, Vail A, Patel HC. Silver-impregnated external-ventricular-drain-related cerebrospinal fluid infections: A meta-analysis. J Hosp Infect 2016;92(3):263–272. DOI: 10.1016/j.jhin.2015.09.014.

24. Chen C, Zhang B, Yu S, Sun F, Ruan Q, Zhang W, et al. The incidence and risk factors of meningitis after major craniotomy in China: A retrospective cohort study. PLoS One 2014;9(7):e101961. DOI: 10.1371/journal.pone.0101961.

25. Khan FY, Abukhattab M, Baager K. Nosocomial post neurosurgical Acinetobacter baumannii meningitis: A retrospective study of six cases admitted to Hamad General Hospital, Qatar. J Hosp Infect 2012:80(2):176–179. DOI: 10.1016/j.jhin.2011.08.021.

26. Erdem I, Hakan T, Ceran N, Metin F, Akcay SS, Kucukercan M, et al. Clinical features, laboratory data, management and the risk factors that affect the mortality in patients with postoperative meningitis. Neurol India 2008:56(4):433–437. DOI: 10.4103/0028-3886.44629.

27. Sahu C, Patel SS, Singh A, Yaduvanshi N. A comparative in vitro sensitivity study of “Ceftriaxone–Sulbactam–EDTA” and various antibiotics against Gram-negative bacterial isolates from intensive care unit. Indian J Crit Care Med 2020;24(12):1213–1217. DOI: 10.5005/jp-journals-10071-23573.

28. Rao K, Rangappa P, Jacob I, Hiremath P. Cerebrospinal fluid lactate as a prognostic indicator in postneurosurgical bacterial meningitis and use of intrathecal colistin. Indian J Crit Care Med 2018;22(4):297–299. DOI: 10.4103/ijccm.IJCCM_418_17.