https://www.espen.org/files/ESPEN-Guidelines/1__ESPEN_guidelines_on_chronic_intestinal_failure_in_adults.pdf

ESPEN guidelines on chronic intestinal failure in adults

The insertion or implantation of foreign bodies has become an indispensable part in almost all fields of medicine. However, medical devices are associated with a definitive risk of bacterial and fungal infections. Foreign body-related infections (FBRIs), particularly catheter-related infections, significantly contribute to the increasing problem of nosocomial infections. While a variety of micro-organisms may be involved as pathogens, staphylococci account for the majority of FBRIs. Their ability to adhere to materials and to promote formation of a biofilm is the most important feature of their pathogenicity. This biofilm on the surface of colonised foreign bodies is regarded as the biological correlative for the clinical experience with FBRI, that is, that the host defence mechanisms often seem to be unable to handle the infection and, in particular, to eliminate the micro-organisms from the infected device. Since antibacterial chemotherapy is also frequently not able to cure these infections despite the use of antibacterials with proven in vitro activity, removal of implanted devices is often inevitable and has been standard clinical practice. However, in specific circumstances, such as infections of implanted medical devices with coagulase-negative staphylococci, a trial of salvage of the device may be justified. All FBRIs should be treated with antibacterials to which the pathogens have been shown to be susceptible. In addition to systemic antibacterial therapy, an intraluminal application of antibacterial agents, referred to as the 'antibiotic-lock' technique, should be considered to circumvent the need for removal, especially in patients with implanted long-term catheters. To reduce the incidence of intravascular catheter-related bloodstream infections, specific guidelines comprising both technological and nontechnological strategies for prevention have been established. Quality assurance, continuing education, choice of the catheter insertion site, hand hygiene and aseptic techniques are aspects of particular interest. Furthermore, all steps in the pathogenesis of biofilm formation may represent targets against which prevention strategies may be directed. Alteration of the foreign body material surface may lead to a change in specific and nonspecific interactions with micro-organisms and, thus, to a reduced microbial adherence. Medical devices made out of a material that would be antiadhesive or at least colonisation resistant would be the most suitable candidates to avoid colonisation and subsequent infection. Another concept for the prevention of FBRIs involves the impregnation of devices with various substances such as antibacterials, antiseptics and/or metals. Finally, further studies are needed to translate the knowledge on the mechanisms of biofilm formation into applicable therapeutic and preventive strategies.

Infections associated with medical devices: pathogenesis, management and prophylaxis.

Pseudomonas aeruginosa is the predominant cause of chronic airway infection in cystic fibrosis (CF). CF airway isolates are often tested for antibiotic susceptibility but are rarely eradicated by the antibiotics identified as potentially effective. The growth state of P. aeruginosa in CF airways is probably different from that exhibited under conventional susceptibility testing conditions and may represent a bacterial biofilm. Biofilm susceptibility testing methods were adapted to create an assay for implementation in a clinical microbiology laboratory. This assay gave reproducible results when examined in 300 paired determinations with 12 antimicrobial agents, with a serious error rate of 5.7%. The biofilm assay was used retrospectively to test these 12 agents against 94 isolates from 41 CF patients. The biofilm inhibitory concentrations (BICs) were much higher than the corresponding conventionally determined MICs for the β-lactam antibiotics (median values: aztreonam, >128 μg/ml versus 4 μg/ml; ceftazidime, 128 μg/ml versus 2 μg/ml; piperacillin-tazobactam, 256 μg/ml versus 4 μg/ml; and ticarcillin-clavulanate, 512 μg/ml versus 16 μg/ml, respectively) and doxycycline (>64 μg/ml versus 16 μg/ml); and similar for meropenem (4 μg/ml versus ≤ 1 μg/ml), ciprofloxacin (0.5 μg/ml versus 1 μg/ml), and the aminoglycosides amikacin (32 μg/ml versus 16 μg/ml), gentamicin (16 μg/ml versus 8 μg/ml), and tobramycin (4 μg/ml versus 2 μg/ml). The median BIC for azithromycin was 2 μg/ml, whereas isolates were uniformly resistant when tested by standard methods. This demonstrates the feasibility of adapting biofilm susceptibility methods to the clinical microbiology laboratory and opens the way to examining whether biofilm testing might be used to select more effective antibiotic combinations for CF airway infections than methods in current use.

Clinically Feasible Biofilm Susceptibility Assay for Isolates of Pseudomonas aeruginosa from Patients with Cystic Fibrosis

https://www.ajkd.org/article/S0272-6386(04)01078-9/pdf

Dialysis catheter-related bacteremia: Treatment and prophylaxis

Heparin, known for its anticoagulant activity, is commonly used in catheter locks. Staphylococcus aureus, a versatile human and animal pathogen, is commonly associated with catheter-related bloodstream infections and has evolved a number of mechanisms through which it adheres to biotic and abiotic surfaces. We demonstrate that heparin increased biofilm formation by several S. aureus strains. Surface coverage and the kinetics of biofilm formation were stimulated, but primary attachment to the surface was not affected. Heparin increased S. aureus cell-cell interactions in a protein synthesis-dependent manner. The addition of heparin rescued biofilm formation of hla, ica, and sarA mutants. Our data further suggest that heparin stimulation of biofilm formation occurs neither through an increase in sigB activity nor through an increase in polysaccharide intracellular adhesin levels. These finding suggests that heparin stimulates S. aureus biofilm formation via a novel pathway.

Heparin Stimulates Staphylococcus aureus Biofilm Formation

Intravascular catheter-associated bloodstream infections significantly increase rates of morbidity and hospital costs. Microbial colonization and development of biofilms, which are known to be recalcitrant to antibiotic therapy, often lead to the loss of otherwise patent vascular access systems. We evaluated a new taurolidine- and citrate-based catheter lock solution (Neutrolin; Biolink Corporation, Norwell, Mass.) for its activity against planktonic microbes, antimicrobial activity in a catheter model, and biofilm eradication activity. In studies of planktonic microbes, after 24 h of contact, 675 mg of taurolidine-citrate solution per liter caused > 99% reductions in the initial counts of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Entercoccus faecalis. A solution of 13,500 mg/liter was cidal for Candida albicans. Ports and attached catheters inoculated with 50 to 600 CFU of these bloodstream isolates per ml were locked with heparin or the taurolidine-citrate solution. After 72 h, there was no growth in the taurolidine-citrate-treated devices but the heparin-treated devices exhibited growth in the range of 6 x 10(2) to 5 x 10(6) CFU/ml. Biofilms were developed on silicone disks in modified Robbins devices with broth containing 6% serum (initial counts, 10(6) to 10(8) CFU/cm(2)). The axenic biofilms were treated for 24 h with taurolidine-citrate or heparin. Taurolidine-citrate exposure resulted in a median reduction of 4.8 logs, whereas heparin treatment resulted in a median reduction of 1.7 logs (P < 0.01). No significant differences in the effects of the two treatments against P. aeruginosa and C. albicans were observed. These findings suggest that taurolidine-citrate is a promising combination agent for the prevention and treatment of intravascular catheter-related infections.

Michael Pelak

Papers

Antimicrobial activity of a novel catheter lock solution.