Guidelines for the Prevention of Central Venous Catheter-Related Bloodstream Infections with Prostanoid Therapy for Pulmonary Arterial Hypertension

The inception and completion of this document is the work of a collection of dedicated healthcare providers in the field of pulmonary hypertension medicine. It should be used as a guideline for best clinical practice. Every attempt was made to ensure the relevance and timeliness of the information included.Intravenous prostanoids are the backbone of therapy for advanced pulmonary arterial hypertension (PAH) and have improved long-term outcome and quality of life.1–4 Currently, two prostanoids are approved by the US Food and Drug administration for parenteral administration: epoprostenol (Flolan) and treprostinil (Remodulin).5 Chronic intravenous therapy presents considerable challenges for patients and caregivers who must learn sterile preparation of the medication, operation of the pump, and care of the central venous catheter. Central line infections and bacteremia are well-documented risks of long-term intravenous therapy and may significantly contribute to morbidity and mortality.The incidence of catheter-related bloodstream infection (CR-BSI) in 192 patients treated with epoprostenol at two pulmonary hypertension centers (335,285 medicine days) was 0.15 per 1000 medicine days, with Staphylococcus aureus and Micrococcus spp being the most common pathogens identified.6 Recently, the Centers for Disease Control and Prevention investigated a possible increase in Gram-negative CR-BSI in patients treated with treprostinil. In a retrospective evaluation of seven centers with 51,183 intravenous prostanoid medicine days, the BSI incidence by pooled mean was higher for patients receiving treprostinil than for those receiving epoprostenol (1.11 vs 0.43). In addition, treprostinil patients had a higher incidence of Gram-negative bacteremia (0.73 vs 0.06).7 Retrospective evaluation at two centers of 224 patients with 146,093 treatment days found the incidence of BSI for patients receiving epoprostenol and treprostinil was 0.55 cases per 1000 medicine days; Gram-negative pathogens were reported in 0.18 cases per 1000 medicine days. Patients treated with treprostinil had a higher incidence of BSI in comparison with epoprostenol (1.13 vs 0.42 per 1000 treatment days) and a higher incidence of CR-BSI due to Gram-negative pathogens (0.81 vs 0.04 BSI per 1000 treatment days).8The mechanisms for the presumed increase in Gram-negative CR-BSIs in patients receiving intravenous prostacyclins are unknown. From the literature, it is clear that Gram-negative pathogens predominate in patients with malignancies or compromised mucosal barriers because of transmigration of gut bacteria.9 In the case of pulmonary hypertension patients it is unclear if prostacyclin therapy affects mucosal integrity or if gut edema from right heart failure is contributing. These will be active areas of ongoing investigation. The catheter hub is known to be an important source of CR-BSI. It is also suggested that the infusion system connections may be exposed to hydrophilic Gram-negative pathogens such as Pseudomonas, Stenotrophomonas, Acinetobacter and Serratia during bathing or showering. A closed-hub system may decrease bacterial contamination of the hub;1011 however, the type of needleless catheter connector may also impact the incidence of CR-BSI.1213 It is important that treating physicians keep these potential mechanisms in mind when implementing and using these guidelines.Italics indicate direct quotes from Guidelines for the Prevention of Intravascular Catheter-Related Infections developed by the Healthcare Infection Control Practices Advisory Committee of the Centers for Disease Control and Prevention (HICPAC/CDC).14The HICPAC/CDC system for categorizing recommendations is as follows:Do not routinely use antibiotic lock solutions. Use prophylactic antibiotic lock solution only in special circumstances (eg, in treating a patient with a long-term cuffed or tunneled catheter or port who has a history of multiple CRBSIs despite optimal maximal adherence to aseptic technique). Category IIDo not administer intranasal or systemic antimicrobial prophylaxis routinely before insertion or during use of an intravascular catheter to prevent catheter colonization or BSI. Category 1AConduct surveillance to determine CR-BSI rates, monitor trends in those rates, and assist in identifying lapses in infection control practices. Category 1AWe would like to acknowledge and thank the Scientific Leadership Council of the Pulmonary Hypertension Association and the Centers for Disease Control and Prevention for their review of these guidelines.Ms. Doran is a consultant for Actelion, Gilead, and United Therapeutics. Dr Ivy is a consultant for Actelion, Pfizer, Gilead, and United Therapeutics. Dr Barst is a consultant for Actelion, Pfizer, Gilead, Lung Rx, Novartis, Eli Lilly, and MondoBiotech. Dr Hill receives research grants from Actelion, Encysive, EPIX, Gilead, Lung Rx, Pfizer, United Therapeutics, and Lilly/ICOS and is on the Medical Advisory Boards for all except EPIX and Lilly. Dr Murali receives research grants from Actelion, Pfizer, and United Therapeutics and is a consultant for Actelion, Gilead, and United Therapeutics. Dr Benza is a consultant for Actelion, Pfizer, Gilead, and United Therapeutics.