Trial design and current evidence for antibiotics-impregnated ventricular catheters in reducing infections
To the editor,
We thank Dr. Marini and colleagues for their interest in our article.1 They commented on the use of nosocomial infections as primary outcome and the randomised yet non-double-blinded study design. Secondarily, they shared their disappointing results from the utilization of antibiotics-impregnated ventricular catheters.
In our centers, we have achieved a ventricular-catheter-related cerebrospinal fluid infection rate of less than 5%, with protocol-driven ventricular catheter care, no catheter exchange every 5 days, adequate subcutaneous tunneling, and dual prophylactic antibiotcs.2,3,4 However, one criticism of this successful policy is that dual prophylactic antibiotics increase antibiotic pressure and cause a surge of resistant infections, especially in intensive care units. The application of antibiotics-impregnated catheters as local antibiotic prophylaxis, without the need for repeated cerebrospinal fluid instillations, seemed to be a perfect solution and thus we designed the study. The catheters were unblinded as no available plain catheters were of similar colors as antibiotics-impregnated catheters. The same methodology was applied in a recently completed multi-center study sponsored by Codman & Shurtleff, Inc., a Johnson & Johnson Company (Establishment of Baseline and Comparative Infection Rates for the Codman BACTISEALTM External Ventricular Drainage System).
In centers with background ventricular-catheter-related cerebrospinal fluid infection rates of more than 5%, antibiotics-impregnated catheters reduced cerebrospinal fluid infection in both randomized controlled trial and historical cohort studies.5,6,7 Similar to Dr. Marini and colleagues, Harrop and colleagues indeed carried out a 1961-patient study between 2003 and 2008. They were able to show that the institution, discontinuation, and reinstitution of antibiotics-impregnated catheters were the most important determinants ventricular-catheter-related cerebrospinal fluid infections.7
Dr. Marini and colleagues described their cohort study of 55 patients, in which two-thirds of the 67 catheters used were impregnated with antibiotics. They reported a high cerebrospinal fluid infection rate of 13.4%, half of which was caused by gram-positive cocci and half caused by gram-negative bacilli. The exact infection rates and organisms responsible were not described for each group, though we presume that the infection in the antibiotics-impregnated catheters was mostly caused by gram-negative bacilli. The weakness is that their results are likely to be underpowered to detect any difference between cerebrospinal fluid infection rates. One must remember that other aspects of infection control are important in bringing down infection rates, such as antibiotic cover during surgery, adequate subcutaneous tunneling and protocol-driven ventricular catheter care. Unfortunately, with the data provided by Dr. Marini and colleagues, we are afraid that their conclusion is invalid.
1. Wong GK, Ip M, Poon WS, et al. Antibiotics-impregnated ventricular catheter versus systemic antibiotics for prevention of nosocomial CSF and non-CSF infections: a prospective randomised clinical trial. J Neuro Neurosurgery Psychiatry (2010). Doi:10.1136/jnnp.2009.198523 2. Poon WS, Ng S, Wai S. CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomized study. Acta Neurochir Suppl (Wien) 1998; 71:146-148. 3. Wong GK, Poon WS, Wai S, et al. Failure of regular external ventricular drain exchange to reduce cerebrospinal fluid infection: result of a randomized controlled trial. J Neurol Neurosurg Psychiatry 2002; 73:759- 761. 4. Wong GK, Poon WS. Failure of regular external ventricular exchange to reduce CSF infection: authorsÃÃÃÃÃÃ¢ÃÃÂ¢ÃÃÃÃ¢ÃÃÂ¢ÃÃ¢ÃÃÂ¬ÃÃÃÃ¢ÃÃÂ¢ÃÃ¢ÃÃÂ¢ reply. J Neurol Neurosurg Psychiatry 2003; 74:1599. 5. Zabramski JM, Whiting D, Darouiche RO, et al. Efficacy of antimicrobial -impregnated external ventricular drain catheters: a prospective, randomized, controlled trial. J Neurosurg 2003; 98:725-730. 6. Muttaiyah S, Ritchie S, John S, et al. Efficacy of antibiotic- impregnated external ventricular drain catheters. Journal of Clinical Neuroscience 2010; 17:296-298. 7. Harrop JS, Sharan AD, Ratliff J, et al. Impact of a standardized protocol and antibiotic-impregnated catheters on ventriculostomy infection rates in cerebrovascular patients. Neurosurgery 2010; 67(1):187-191.
Conflict of Interest: