Minocycline-Rifampin Impregnated IV Catheters Superior
Abstract & Commentary
Synopsis: Central venous catheters impregnated with minocycline and rifampin (MR) were compared to catheters impregnated with chlorhexidine and silver sulfadiazine (SS) and found to be superior with respect to the rates of catheter colonization and bloodstream infection (BSI). Colonization rates were 7.9% for the MR and 22.8% for the SS groups. Only one BSI occurred with the 356 MR catheters (0.3%), as compared to 13 BSIs with the 382 SS catheters (3.4%) (P < 0.002).
Source: Darouiche RO, et al. N Engl J Med 1999; 340:1-8.
Patients at 12 university teaching hospitals who needed central venous catheters inserted as part of their management and were predicted to need the venous access for more than three days were randomized to receive a 20-cm-long, triple-lumen, polyurethane catheter impregnated with either minocycline-rifampin (MR) or chlorhexidine-silver sulfadiazine (SS). Only catheters placed with a new percutaneous stick were entered into the study, not those changed over a wire. At the time of catheter removal, the tip and subcutaneous segments were cultured. If a bloodstream infection (BSI) was suspected, blood was cultured and the catheter removed. Organisms obtained from more than one site were DNA typed for identification. Clinical indications directed catheter removal.
A total of 865 study catheters were placed in 817 patients; complete data were collected for 738 catheters (85%) in 689 patients. The two groups were similar in important characteristics: the catheters were in place an average of 8.2 (SS) and 8.4 (MR) days; 67% of patients were in an ICU; 16% were receiving hyperalimentation; and the patients were an average of 56 years old in both groups. Catheter colonization and BSI rates were significantly lower in the MR group (7.9% and 0.3%) than in the SS group (22.8% and 1.3%). In 71% of patients with a BSI, the same organism was found on the skin, on the catheter, and in the blood. Two patients died as a result of a BSI, both of them in the SS group. No local or systemic hypersensitivity reactions were noted with any catheter.
Comment by Charles G. Durbin, Jr., MD, FCCM
This is an impressive and important study—the first head-to-head comparison of these expensive but effective special catheters. The variety of institutions that participated and the large number of catheters studied supports Darouiche and colleagues’ contention of the superiority of the MR over the SS-impregnated catheter. Both types of impregnated catheters have been shown to reduce nosocomial infection and colonization rates when compared to unimpregnated controls. The large difference between them in this study is surprising.
The colonization rate for SS catheters found in this study is high—so high, in fact, that one might wonder if the SS catheters were defective. This rate is the same as those reported for controls in many previous studies of SS catheters. The highest colonization rate for SS catheters was reported by one of the authors of this study—40% with 52% of control catheters becoming colonized (Heard SO, et al. Arch Intern Med 1998;158:81-87). Heard reported little difference in BSI, 3.3% as compared with 3.8% in that study. Most other studies of the SS catheter against controls show advantages, and a well-designed meta-analysis of 12 reported studies including more than 2000 catheters demonstrated more than 50% reduction in colonization and BSI rates with SS catheters (Veenstra DL, et al. JAMA 1999;281[3]:261-267).
A problem with this study is the MR catheter used. As compared to previous studies, this "new" catheter was impregnated on the internal as well as external surface with the antibiotics. Approximately three to five times the amount of antibiotic was found on these catheters as on catheters used in previous studies. Although no complications related to antibiotic resistance were found in any of the catheter-related nosocomial infections, antibiograms of the patients’ other organisms were not carried out in this study. Whether this higher dose of antibiotic will create a resistance problem is not yet known.
The technique used to identify colonization used in this study was not standard. Darouiche et al sonicated the catheter tips in broth after rolling them on plates. This was thought to release trapped organisms from the inside of the catheter, identifying hidden colonization. The validity and reliability of this technique has not been widely tested. Darouiche et al state that using conventional definitions of colonization (more than 15 colony-forming units from the rolled tip) did not change their results, although they did not report this information for independent confirmation. The sonication culture technique probably overestimates the actual colonization rate. Despite this criticism, the BSI rate is impressively reduced with these MR catheters.
Finally, cost information was only indirectly mentioned. The MR catheters cost approximately $9.00 more per unit, and about $60.00 more than conventional central venous catheters. To make cost-effectiveness decisions it is necessary to know the exact cost of the devices to an individual institution. Limiting the use of these effective but expensive catheters to those patients at high risk is the appropriate initial strategy. The catheters must be left in
place through a fever and only suspected as the source when all other causes of infection are ruled out. If local practice is to change the catheter at the first temperature rise, then no benefit will be realized. The mechanical risks of changing catheters (which includes death) outweigh the benefits of preventing a small number of BSIs resulting from leaving the antibiotic catheter in place a few days longer. Patients developing fevers should have an evaluation for the presence of an infection. Infrequently, after a workup, the central venous line will be found to be the source. Only if positive blood cultures are found should the catheter be thought to be the primary source.
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