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BRIEF COMMUNICATION
Year : 2017  |  Volume : 35  |  Issue : 1  |  Page : 120-123
 

Coagulase-negative staphylococci: Emerging pathogen in central nervous system shunt infection


Department of Microbiology, Grant Government Medical College and Sir J.J. Group of Hospitals, Byculla, Mumbai, Maharashtra, India

Date of Web Publication16-Mar-2017

Correspondence Address:
Sunil Lilani
Department of Microbiology, Grant Government Medical College and Sir J.J. Group of Hospitals, Byculla, Mumbai - 400 008, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_16_157

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 ~ Abstract 


Central nervous system (CNS) shunts are commonly used to treat patients with hydrocephalus. Its placement is associated with increased risk of infection. The study was intended to evaluate infection rate associated with CNS shunt surgeries and identify risk factors for shunt infection. The frequency and characterisation of aetiological agents along with their antibiotic resistance pattern were also studied. A prospective study of 86 patients who underwent 97 surgeries over a period of 18 months was conducted. One hundred seventy-six cerebrospinal fluid samples and 44 shunt tips obtained were processed using standard microbiological techniques. Of 86 patients, 39 (45.35%) operated for shunt revision were infected while 47 patients operated for shunt insertion were not found to be infected. Methicillin-resistant Staphylococcus epidermidis was the predominant isolate. 57.58% isolates of Staphylococci were found to be biofilm producers. Mortality of 15% was observed among infected patients. Shunt infection remains a serious issue in the patients undergoing shunt surgery. Accurate diagnosis, treatment and prevention of infection are essential in such patients.


Keywords:  Central nervous system shunt infections, cerebrospinal fluid, methicillin-resistant Staphylococcus epidermidis, shunt revision


How to cite this article:
Bhatia PL, Lilani S, Shirpurkar R, Chande C, Joshi S, Chowdhary A. Coagulase-negative staphylococci: Emerging pathogen in central nervous system shunt infection. Indian J Med Microbiol 2017;35:120-3

How to cite this URL:
Bhatia PL, Lilani S, Shirpurkar R, Chande C, Joshi S, Chowdhary A. Coagulase-negative staphylococci: Emerging pathogen in central nervous system shunt infection. Indian J Med Microbiol [serial online] 2017 [cited 2017 Jun 25];35:120-3. Available from: http://www.ijmm.org/text.asp?2017/35/1/120/202333





 ~ Introduction Top


Central nervous system (CNS) shunt surgery is the most common treatment modality in diagnosed cases of hydrocephalus.[1] Shunt infection is one of the devastating complications associated with shunt placement, responsible for significant morbidity leading to shunt malfunction and chronic ill-health.[2] Different figures for CNS shunt infection have been reported in literature, and there are considerable variations worldwide. Post-operative infection of cerebrospinal fluid (CSF) shunts have varied from a low of 2% to high of 27%.[2],[3],[4],[5],[6] Shunt infection is defined as isolation of organism from shunt fluid, shunt tube, reservoir and/or blood culture along with the clinical signs and symptoms suggestive of shunt infection or malfunction such as fever, peritonitis, meningitis, signs of infection along the shunt tract, or non-specific signs and symptoms of headache, vomiting or altered sensorium.[2]

Coagulase-negative Staphylococci (CONS), most important being Staphylococcus epidermidis, are reported to be the most common aetiological agents responsible for shunt infection.[2],[4],[5] Several other species have now been reported, and these agents are increasingly being recognised as important opportunistic pathogens in hospitalised patients following invasive procedures and with indwelling plastic devices. The more commonly implicated CONS species include Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus schleiferi, Staphylococcus warneri, Staphylococcus hominis, Staphylococcus simulans and Staphylococcus saccharolyticus.[5]

Despite technological advances and administration of new antibiotics, infection continues to be one of the most frequent and serious complications of CSF shunts.[6] Hence, the present study was undertaken to study (i) infection rate associated with CNS shunt surgery; (ii) underlying risk factors; (iii) the frequency of pathogens along with their antibiotic resistance pattern and (iv) the therapeutic outcomes of patients.


 ~ Materials and Methods Top


The study was a prospective one approved by the Institutional Ethics Committee and conducted in a tertiary care hospital from January 2012 to July 2013. Patients undergoing shunt insertion or revision surgery were included in the study while those with external ventricular drainage system were excluded from the study. Besides demographic data, the clinical condition requiring shunt procedure, date of admission and operation, past and present history, prophylactic and therapeutic antibiotics administered and condition of patient at time of discharge were noted. Each patient was followed up from the time of admission till discharge and also for 30 days post-operatively.

A total of 176 CSF specimens were collected from 86 patients either by lumbar puncture or percutaneous tapping of the fluid from shunt reservoir. One CSF specimen was received at the time of surgery and additional as and when infection was suspected clinically. Forty-four shunt tips (ventricular or peritoneal end) from 39 patients who underwent shunt revision were also received. Both CSF and shunt tips were processed and isolates were identified by standard microbiological protocol.[7] Staphylococcus strains isolated from infected shunts were tested for beta-lactamase production using nitrocefin disc (BD Diagnostic Systems: BBL cefinase paper discs).[8] A qualitative assessment of biofilm formation was determined in Staphylococci as previously described by Mathur, et al.[9] Loopful of isolates were inoculated into tubes containing 10 ml glucose broth. The tubes were then incubated at 37°C for 24 h. After the incubation, the broth was aspirated out and walls of the tubes were stained with 1% safranine. Tubes were then kept still for 7 min. Safranine then was removed and tubes were examined for biofilm production with naked eyes. Formation of pink coloured ring on the level of inoculated broth surface in the tube was considered as the organism to be a biofilm producer.

Antibiotic susceptibility was tested by modified Kirby-Bauer disc diffusion method.[10],[11] Commercially available discs from HiMedia Laboratories Pvt. Ltd with known potency were used according to the antibiotics preferred in clinical settings. For Gram-positive cocci (GPC), antibiotics discs used were penicillin (10 units), gentamicin (10 µg), amikacin (30 µg), linezolid (30 µg) and teicoplanin (30 µg). For Gram-negative bacilli (GNB), antibiotics such as ampicillin (10 µg), amoxycillin-clavulanic acid (20/10 µg), piperacillin (100 µg), piperacillin-tazobactam (100/10 µg), ceftazidime (30 µg), ceftriaxone (30 µg), cefepime (30 µg), gentamicin (10 µg), amikacin (30 µg), aztreonam (30 µg), imipenem (10 µg), meropenem (10 µg) were used. For Pseudomonas aeruginosa, additional antibiotics used were ticarcillin (75 µg), polymyxin B (300 units) and colistin (10 µg). Both CONS and Staphylococcus aureus were tested for vancomycin sensitivity by determining minimum inhibitory concentration by macrobroth dilution method.[8] Methicillin resistance in Staphylococci and extended spectrum beta lactamase (ESBL) production in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were tested using disc diffusion method.[11]


 ~ Results Top


Twenty out of 86 patients developed shunt infection of which 12 were males and 8 were females. Although infection rate was higher in males (28.57%) as compared to females (18.18%), the results were statistically insignificant (P = 0.31, Fisher's exact test). Highest infection rate was seen in children (1–15 years) and infants (<1 year), that is, 27.27% and 24%, respectively, compared to elderly patients (>50 years) and adults (16–50 years), that is, 20% and 17.39%, respectively. The differences in shunt infection rate for the various age groups were found to be statistically insignificant (P = 0.85, Chi-square test). Infection rate in various aetiological conditions of hydrocephalus is shown in [Table 1].
Table 1: Infection rate in various aetiological conditions of hydrocephalus

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Of 176 samples, only 24 (13.64%) and of 44 shunt tips 22 (50%) were culture positive. When culture reports of CSF and shunt tip samples were compared with each other, the difference was found to be statistically significant (P < 0.0001, Fisher's exact test). Of these 86 patients, 39 underwent shunt revision surgery, of which shunt of 29 patients were revised once while remaining, that is, 10 patients had to undergo multiple shunt revisions. It was found that 6 of 10 patients (60%) with multiple shunt revisions were infected compared to 14 of 29 patients (48.28%) with one shunt revision.

From 20 infected patients, total 46 isolates were recovered as shown in [Table 2]. S. epidermidis was the most common isolate (30.43%) followed by S. aureus (23.91%). Nineteen of 32 Staphylococci (59.38%) were found to be biofilm producers. 90.48% of CONS and 72.73% of S. aureus were methicillin resistant. All methicillin-sensitive CONS and Methicillin-sensitive S. aureus were beta-lactamase producers. Sixteen CONS (76.19%) and 7 S. aureus (63.64%) were resistant to gentamicin while 6 CONS (28.57%) and 4 S. aureus (36.37%) were resistant to amikacin. Single strain of Enterococcus faecalis was resistant to beta-lactams such as penicillin and ampicillin. All GPC were found to exhibit no resistance to glycopeptides (vancomycin and teicoplanin) and linezolid. Of the 4 isolates belonging to Enterobacteriaceae family, one was resistant to gentamicin (25%). All the 4 isolates were found to be ESBL producers and hence were resistant to third generation cephalosporins and aztreonam. Of 4 isolates, 2 (50%) were resistant to fourth generation cephalosporin such as cefepime. No resistance was observed to aminoglycosides such as amikacin and gentamicin, piperacillin-tazobactam combination, carbapenems. All pseudomonas were sensitive to lipopeptides such as polymyxin B and colistin. Antimicrobial prophylaxis with amikacin and ceftriaxone was initiated for all the patients preoperatively as well as intraoperatively and was continued in the post-operative period. Six of 20 GPC isolates were found to be resistant to amikacin and seven GNB were resistant to ceftriaxone.
Table 2: Frequency of pathogens isolated from shunt infected patients (n=46)

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Seventeen out of 20 infected patients survived well and were discharged according to their clinical condition. Three paediatric patients expired due to their underlying morbid condition and shunt infection was found to be an associated complication in them. One premature infant died due to shunt infection caused by methicillin-resistant S. epidermidis followed by septic shock. One infant with underlying congenital heart disease with hydrocephalus died whose shunt was infected by methicillin-resistant S. aureus. One child died because of shunt extrusion into the rectum followed by septicaemia where shunt was found to be infected by E. faecalis and P. mirabilis.


 ~ Discussion Top


Although CSF shunts contribute to significant improvement of management outcome of hydrocephalus, the shunt has severe complications including infection.[12] Shunt insertion for treatment of hydrocephalus are quite susceptible to bacterial infection.[3] Number of shunt revisions is considered to be one of the factors associated with an increased risk of CNS shunt infections, and the risk may be especially high in patients undergoing multiple shunt revisions.[12]

In the present study, S. epidermidis was the most common isolate responsible for shunt infection followed by S. aureus which is consistent with majority of studies.[4],[6] Organisms causing shunt-associated infection typically adhere to the device surface and form biofilms, thus making clinical and laboratory diagnosis difficult and antimicrobial treatment challenging.[13] In the present study, an attempt was made to detect the property of Staphylococcus isolates to form biofilms. 59.38% of Staphylococci were biofilm producers which suggest that along with anti-microbial treatment, removal of the entire colonised shunt is required to manage the case of shunt infection. 90.48% (19 out of 21) CONS, 72.73% (8 out of 11) and all GNB (100%) were multidrug-resistant showing resistance to more than two different classes of antibiotics.


 ~ Conclusion Top


CSF shunt infection plays a significant role in outcome of patients with hydrocephalus. Early detection and management of shunt infection with appropriate antibiotics along with prompt removal and replacement of the alternative drainage system has provided best results.[2],[6] Identification of risk factors and causative agents may also help prevent shunt infection. In addition, it is important that surveillance of shunt infection should be done with feedback of appropriate data to surgeons in an attempt to reduce shunt infection rate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

1.
Hlatky R, Valadka AB, Robertson CS. Intracranial hypertension and cerebral ischaemia after severe traumatic brain injury. Neurosurg Focus 2003;14:1-4.  Back to cited text no. 1
    
2.
Sarguna P, Lakshmi V. Ventriculoperitoneal shunt infections. Indian J Med Microbiol 2006;24:52-4.  Back to cited text no. 2
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3.
Kaufman BA, McLone DG. Infection of cerebrospinal fluid shunts. In: Scheld WM, Whitley RJ, Durack DT, editors. Infection of the Central Nervous System. 2nd ed., Ch. 29. New York: Raven Press; 1997. p. 555-73.  Back to cited text no. 3
    
4.
Schoenbaum SC, Gardner P, Shillito J. Infections of cerebrospinal fluid shunts: Epidemiology, clinical manifestations, and therapy. J Infect Dis 1975;131:543-52.  Back to cited text no. 4
    
5.
Winn WC, Koneman EW, Allen SD, Procop GW, Janda WM, Woods GL. editors. Staphylococci and related Gram-positive cocci. In: Koneman's Colour Atlas and Textbook of Diagnostic Microbiology. 6th ed., Ch. 12. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 623-71.  Back to cited text no. 5
    
6.
Wang KW, Chang WN, Shih TY, Huang CR, Tsai NW, Chang CS, et al. Infection of cerebrospinal fluid shunts: Causative pathogens, clinical features, and outcomes. Jpn J Infect Dis 2004;57:44-8.  Back to cited text no. 6
    
7.
Winn WC, Koneman EW, Allen SD, Procop GW, Janda WM, Woods GL, editors. Introduction to microbiology: Part II: Guidelines for the collection, transport, processing, analysis, and reporting of cultures from specific specimen sources, In: Koneman's Colour Atlas and Textbook of Diagnostic Microbiology. 6th ed., Ch. 2. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 67-110.  Back to cited text no. 7
    
8.
Miles RS, Amyes SG. Laboratory control of antimicrobial therapy. In: Collee JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and McCartney Practical Medical Microbiology. 14th ed., Ch. 8. New York: Churchill Livingstone; 1996. p. 151-78.  Back to cited text no. 8
    
9.
Mathur T, Singhal S, Khan S, Upadhyay DJ, Fatma T, Rattan A. Detection of biofilm formation among the clinical isolates of staphylococci: An evaluation of three different screening methods. Indian J Med Microbiol 2006;24:25-9.  Back to cited text no. 9
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Jorgensen JH, Turnidge JD, Washington JA. Antibacterial susceptibility tests: Dilution and disk diffusion methods. In: Murray PR, Baron EJ, Pfaller MA, Landry ML, Jorgensen JH, editors. Manual of Clinical Microbiology. 9th ed., Ch. 73. Washington, DC: ASM Press; 2007. p. 1152-72.  Back to cited text no. 10
    
11.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. Twenty-second Informational Supplement. CLSI document M100-S21. Wayne, PA, USA: CLSI; 2012.  Back to cited text no. 11
    
12.
Tunkel AR, Kaufman BA. Cerebrospinal fluid shunt infections. In: Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 6th ed., Ch. 81. United States of America: Churchill Livingstone; 2005. p. 1126-30.  Back to cited text no. 12
    
13.
Conen A, Walti LN, Merlo A, Fluckiger U, Battegay M, Trampuz A. Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: A retrospective analysis over an 11-year period. Clin Infect Dis 2008;47:73-82.  Back to cited text no. 13
    



 
 
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