The most recent CDC guidelines recommended two antimicrobial CVCs that were shown to be highly effective in preventing biofilm colonization and highly efficacious in preventing CLABSI through multiple prospective randomized trials (13
). These two FDA-approved antimicrobial CVCs consisted of M/R-coated CVCs and those treated with CHX/SS. According to our data, we have demonstrated that a novel antimicrobial catheter that combines the same active antimicrobial ingredients (chlorhexidine and minocycline-rifampin) used in the two prior traditional antimicrobial CVCs is highly and uniquely effective in completely preventing the biofilm colonization of MRSA, multidrug-resistant P. aeruginosa
, and Candida
sp. organisms that cause CLABSI. In addition, the antimicrobial activity and durability of this novel antimicrobial CVC (CHX/MR) were significantly superior to those of the traditional M/R and CHX/SS CVCs in preventing biofilm colonization of MRSA and P. aeruginosa
after 3 weeks of immersion in serum. Furthermore, the extended-spectrum CHX-M/R PICC was superior to CHX PICCs in preventing biofilm formation of two Candida
species in addition to the bacteria tested. Finally, the novel CHX-M/R CVC and PICC retained antimicrobial activity after 1 year of shelf life.
Preventive measures such as a bundle of aseptic procedures during insertion have been instituted to reduce the risk of CLABSI. This bundle of aseptic procedures has become the standard of care in the United States and is currently recommended through the CDC guidelines (13
). This recommendation is based largely on a multicenter prospective crossover study in Michigan, conducted by Pronovost et al., that demonstrated that the use of a bundle of aseptic procedures (referred to as “the bundle”)—consisting of maximal sterile barriers, hand washing, and cleaning of the skin insertion site with chlorhexidine, as well as avoidance of the femoral vein insertion site and removal of unnecessary catheters—resulted in a significant decrease in the incidence of CLABSI in critically ill patients (15
). In the Pronovost study, the rate of CLABSI decreased from the baseline rate of 7.7 cases per 1,000 catheter days to 1.4 cases per 1,000 catheter days 6 to 12 months after the introduction of the aseptic procedure bundle (15
). However, the Pronovost study has limitations due to its crossover design, the lack of assessment of compliance, the lack of assessment of confounding variables (such as the introduction of antimicrobial-coated catheters), and the poor definitions of bacteremia and catheter-related bloodstream infections.
A more recent and larger study by Furuya et al. that involved 250 National Healthcare Safety Network (NHSN) hospitals demonstrated the difficulty of compliance with all the elements of the bundle of aseptic procedures (6
). In this large study, only 38% of hospitals that monitored compliance reported compliance with all components of the bundle. Furthermore, compliance with all bundle elements was not necessary to show a decrease in CLABSI, and the CLABSI rates in the study ranged from 1.69 to 2.7 cases per 1,000 catheter days, irrespective of the degree of compliance.
The CDC, as well as the Center for Medical Services, has called for zero tolerance for CLABSI because of the seriousness of catheter-related bloodstream infections, which are thought to be completely preventable (20
). Based on all of the studies that have used the bundle, the level of CLABSI could not be reduced below 1.4 cases/1,000 catheter days in critically ill patients (6
). However, there are hints in the literature that if the aseptic bundle is used with a combination of antimicrobial CVCs, the rate of CLABSI could be lowered to a level below 0.5 case/1,000 catheter days, to as low as 0.25 case/1,000 catheter days (9
Based on the data derived from this study, it is possible that highly effective, novel antimicrobial CVCs such as the CHX-M/R catheter, combined with the aseptic technique bundle, might bring the CLABSI rate to a level that is as close as possible to zero.
Using an in vitro
biofilm colonization model, we tested the antimicrobial activity and durability of M/R-, CHX/SS-, and CHX-M/R-coated CVCs against MRSA. MRSA represents the most resistant and virulent form of staphylococci. Staphylococci and Gram-positive organisms are the cause of 60% to 70% of CLABSI (5
). A large multicenter study conducted by the CDC that evaluated CLABSI from 1997 to 2007 determined that the majority (61%) of the 4,088 S. aureus
CLABSI nationwide were caused by MRSA (3
). Traditionally, M/R catheters have been shown to be significantly more effective at preventing biofilm colonization of staphylococci than CHX/SS catheters, with superior antimicrobial durability (18
). Because the majority of CLABSI are caused by staphylococci, these prior findings could have contributed to the clinical superiority of the M/R CVC over the first-generation CHX/SS-coated CVC in a multicenter clinical trial (16
). In the current study, M/R-coated CVCs were significantly superior to control uncoated CVCs in preventing biofilm colonization of MRSA. However, the M/R-coated CVC showed equivalent antimicrobial activity and durability to those of the second-generation CHX/SS CVC, even though it showed superior activity in previous studies. On the other hand, the CHX-M/R CVC showed superior antimicrobial activity and durability to those of the two other traditional CVCs, M/R- and CHX/SS-coated CVCs, with complete inhibition of biofilm colonization of MRSA over a 3-week period of incubation in serum.
A multidrug-resistant P. aeruginosa
strain was chosen to be tested because it reflects the most resistant and virulent form of Gram-negative bacteria, which contribute to 17% to 24% of all CLABSI. Traditionally, the M/R CVC showed little activity against MDR P. aeruginosa
), but it showed superior activity compared to the CHX/SS-coated CVC in preventing the adherence of biofilm colonies of other common Gram-negative bacteria, such as Stenotrophomonas maltophilia
). However, in the current study, both the M/R and CHX/SS CVCs showed limited equivalent activity and durability against P. aeruginosa
, which were superior to those of uncoated catheters but significantly inferior to those of the CHX-M/R CVC. The M/R and CHX/SS CVC durability was limited to some baseline activity against P. aeruginosa
, which was lost in a week given the resistant nature of this organism.
Finally, catheter-related candidemia has been on the rise, particularly with the emergence of fluconazole-resistant Candida glabrata
as one of the leading causes of health care-associated candidemia nationwide (10
). The use of a CVC has been shown to be an independent risk factor for candidemia by multivariate analysis (1
), and the attributable mortality of health care-associated candidemia has been reported to be in the range of 38% to 49% (7
species contribute to around 10% to 15% of all CLABSI. Other studies have shown that the M/R and CHX/SS CVCs failed to completely inhibit the biofilm colonization of Candida
organisms on the surfaces of the catheters (8
). However, according to our data, the novel CHX-M/R CVC completely inhibits the biofilm colonization of Candida
, even after 3 weeks of immersion and incubation in serum, and it was shown to have superior antimicrobial activity and durability compared to the M/R CVC, as well as the CHX/SS-coated CVC, in preventing the biofilm colonization of both C. albicans
and C. glabrata
The novel extended-spectrum CVC and PICC impregnated with CHX-M/R were shown to be superior to other traditional antimicrobial CVCs and PICCs currently approved by the FDA and recommended by the CDC for preventing the biofilm colonization of resistant pathogens that often cause CLABSI. The CHX-M/R CVC was significantly more efficacious in completely inhibiting the biofilm colonization of resistant bacteria and fungi, with prolonged antimicrobial durability. Future comparative in vivo testing and clinical trials of these antimicrobial catheters are needed to determine their relative contributions to reducing bloodstream infections.