Correspondence
Antimicrobial-Impregnated Central Venous Catheters
N Engl J Med 1999; 340:1761-1762June 3, 1999
- Article
To the Editor:
Dr. Darouiche and colleagues (Jan. 7 issue)1 conclude that the use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of catheter-related bloodstream infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine. They defined a catheter-related bloodstream infection by the isolation of the same organism from the vascular catheter and from peripheral blood in a patient with sepsis and no other apparent source of bloodstream infection. However, residual antimicrobial activity in the removed catheter sufficient to prevent growth from the cultured catheter segments would substantially reduce the apparent rate of catheter-related bloodstream infections (since a catheter-related bloodstream infection cannot occur on the basis of this definition if no growth is recorded from the cultured catheter segments).
The authors found no significant difference between groups in the proportion of catheters removed for suspected infection (14 percent of minocycline–rifampin catheters and 13 percent of chlorhexidine–silver sulfadiazine catheters), the proportion receiving vancomycin (23 percent vs. 25 percent), or the mean duration of stay in the intensive care unit (8.7 vs. 8.6 days). Thus, could it be that use of minocycline–rifampin impregnation prevents growth from catheters in the microbiology laboratory but does not eliminate the clinical syndrome of catheter-related bloodstream infection?
1 ReferencesDavid L. Paterson, M.B., B.S.
Veterans Affairs Medical Center, Pittsburgh, PA 152401
Darouiche RO ,Raad II ,Heard SO , et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med 1999;340:1-8
Full Text | Web of Science | Medline
To the Editor:
The results of the study by Darouiche and colleagues may be flawed, because they did not address the potential effect of antibiotics released from the catheters during roll-plate and sonication procedures on the subsequent culture results. For example, an in vitro study has shown that antiinfective compounds elute into culture medium, affecting quantitative catheter cultures.1 The release of antiinfective compounds from catheters in vitro results in a higher concentration (since the volume of distribution is limited) than it does in vivo, where the bloodstream continuously dilutes the concentration. This in vitro effect could result in falsely low or negative culture results.1 The addition of inhibitors to the culture medium to prevent such interference has been suggested1 and used in a clinical study.2 . . .
Furthermore, the authors used a commercially available antiseptic catheter whose entire outer surface is blue; therefore, it seems questionable whether the study was completely blinded. This factor adds the possibility of observer bias.
2 ReferencesAlfons Bach, M.D.
University of Heidelberg, D-69120 Heidelberg, Germany1
Schmitt SK ,Knapp C ,Hall GS ,Longworth DL ,McMahon JT ,Washington JA . Impact of chlorhexidine-silver sulfadiazine-impregnated central venous catheters on in vitro quantitation of catheter-associated bacteria. J Clin Microbiol 1996;34:508-511
Web of Science | Medline2
Bach A ,Schmidt H ,Bottiger B , et al. Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters. J Antimicrob Chemother 1996;37:315-322
CrossRef | Web of Science | Medline
To the Editor:
Darouiche et al. demonstrated that the use of catheters impregnated with minocycline and rifampin was associated with a lower rate of colonization of catheters than the use of catheters impregnated with chlorhexidine and silver sulfadiazine (7.9 percent vs. 22.8 percent). We are surprised by the very high rate of colonization of catheters impregnated with chlorhexidine and silver sulfadiazine, which is similar to the rate of colonization reported with the use of standard catheters.1,2
It would be interesting to know what the colonization rate was among catheters removed for suspected infection.
2 ReferencesEric Maury, M.D.
Georges Offenstadt, M.D.
Hôpital Saint-Antoine, 75571 Paris CEDEX 12, France1
Maki DG ,Stolz SM ,Wheeler S ,Mermel LA . Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter: a randomized, controlled trial. Ann Intern Med 1997;127:257-266
Web of Science | Medline2
Timsit JF ,Sebille V ,Farkas JC , et al. Effect of subcutaneous tunneling on internal jugular catheter-related sepsis in critically ill patients: a prospective randomized multicenter study. JAMA 1996;276:1416-1420
CrossRef | Web of Science | Medline
To the Editor:
We would like to highlight a rare but life-threatening complication of the use of antimicrobial-impregnated catheters. Twelve cases of severe anaphylaxis associated with the use of these catheters have been reported in Japan,1,2 where 170,000 such catheters have been used. In our hospital, a 52-year-old patient died postoperatively of refractory shock despite treatment with vasoactive drugs and fluid replacement. He went into shock immediately after a central venous catheter impregnated with chlorhexidine and silver sulfadiazine was placed in the right jugular vein. Since this patient died before the reports of this complication were issued, we were unaware of the possibility of anaphylactic reactions. Therefore, the catheter was kept in place and resuscitative drugs were administered through the catheter.
2 ReferencesTakeshi Yasukawa, M.D.
Yoshihisa Fujita, M.D.
Atsuo Sari, M.D.
Kawasaki Medical School, Okayama 701-0192, Japan1
An urgent announcement (No. 97-D2) from the Japan Ministry of Health and Welfare, Tokyo, August 14, 1998.
2
Oda T ,Hamasaki J ,Kanda N ,Mikami K . Anaphylactic shock induced by an antiseptic-coated central venous catheter. Anesthesiology 1997;87:1242-1244[Erratum, Anesthesiology 1998;88:560.]
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Drs. Paterson and Bach question whether residual antimicrobial activity in the impregnated catheter may prevent bacterial growth in vitro, thereby possibly reducing the apparent rate of catheter colonization and catheter-related bloodstream infection. Although in vitro studies1 of catheters impregnated with chlorhexidine and silver sulfadiazine showed that antimicrobial agents elute from catheters during culturing processes, clinical evidence indicates that this phenomenon does not significantly affect the results of cultures of catheters removed from patients. Scanning electron microscopy of catheters removed from patients showed that ultrastructural colonization was significantly less likely with catheters impregnated with minocycline and rifampin than with unimpregnated catheters.2 Furthermore, our finding of a trend toward a lower overall risk of nosocomial bacteremia with catheters impregnated with minocycline and rifampin than with catheters impregnated with chlorhexidine and silver sulfadiazine (6.7 percent vs. 10.2 percent) supports the likelihood of the accuracy of the observed differences in the rates of catheter-related bloodstream infection (0.3 percent vs. 3.4 percent). Therefore, we and other investigators3 believe that the elution of antimicrobial agents from the catheter's surface is a phenomenon that underscores the antimicrobial efficacy of impregnated catheters, which are able to inhibit bacterial growth even when artificial conditions are created in vitro specifically to encourage such growth.
To help ensure that enrolled patients continued to receive the usual care, we deliberately did not tell the patients' primary physicians our hypothesis (that catheters impregnated with minocycline and rifampin would have a superior antiinfective efficacy). Therefore, we did not expect to find differences between the two groups in the proportions receiving therapy with vancomycin or antibiotics in general and the proportions of catheters removed for suspected infection. Furthermore, when we analyzed only catheters removed for suspected infection, catheters impregnated with minocycline and rifampin were less likely to be colonized than those impregnated with chlorhexidine and silver sulfadiazine (7 of 50 catheters [14 percent] vs. 19 of 52 catheters [37 percent], P=0.01).
Variations in culturing methods could explain, at least in part, the differences in reported rates of colonization of catheters in different studies. For instance, the rate of colonization of catheters impregnated with chlorhexidine and silver sulfadiazine has been reported to be as high as 40 percent.4
The potential for anaphylaxis associated with the use of catheters impregnated with chlorhexidine and silver sulfadiazine pointed out by Dr. Yasukawa and colleagues was also recently acknowledged by the Food and Drug Administration.5
5 ReferencesRabih O. Darouiche, M.D.
Baylor College of MedicineIssam I. Raad, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX 770301
Schmitt SK ,Knapp C ,Hall GS ,Longworth DL ,McMahon JT ,Washington JA . Impact of chlorhexidine-silver sulfadiazine-impregnated central venous catheters on in vitro quantitation of catheter-associated bacteria. J Clin Microbiol 1996;34:508-511
Web of Science | Medline2
Raad II ,Darouiche RO ,Hachem R , et al. Antimicrobial durability and rare ultrastructural colonization of indwelling central catheters coated with minocycline and rifampin. Crit Care Med 1998;26:219-224
CrossRef | Web of Science | Medline3
Kamal GD ,Divishek D ,Kumar GC ,Porter BR ,Tatman DJ ,Adams JR . Reduced intravascular catheter-related infection by routine use of antibiotic-bonded catheters in a surgical intensive care unit. Diagn Microbiol Infect Dis 1998;30:145-152
CrossRef | Web of Science | Medline4
Heard SO ,Wagle M ,Vijayakumar E , et al. Influence of triple-lumen central venous catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia. Arch Intern Med 1998;158:81-87
CrossRef | Web of Science | Medline5
Center for Devices and Radiological Health. Potential hypersensitivity reactions to chlorhexidine-impregnated medical devices. Washington, D.C.: Food and Drug Administration, 1998. (Or see: http://www/fda.gov/cdrh/chlorhex.html.)
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