Closed-hub systems with protected connections and the reduction of risk of catheter-related bloodstream infection in pediatric patients receiving intravenous prostanoid therapy for pulmonary hypertension.

Treatment with continuous intravenous (IV) prostanoids (ie, epoprostenol and treprostinil) has been shown to improve exercise capacity,1-3 hemodynamics,1-3 and survival rates1,2 in patients with pulmonary arterial hypertension (PAH). Administration of IV formulations of prostanoids involves continuous infusion of medication through a central venous catheter (CVC).4 Although CVCs are common vehicles for drug delivery (an estimated 5 million CVCs are implanted annually in the United States), they are associated with a risk of complications.5 Indeed, more than 15% of patients with CVCs develop catheter-related complications, including mechanical, thrombotic, and infectious complications.5 Catheter-related bloodstream infections (CR-BSIs) are caused by a wide range of opportunistic pathogens, including gram-negative and gram-positive bacterial species.4,6 The mean rate of CR-BSI in medical intensive care units is 2.9 infections per 1,000 catheter-days,7 and the reported incidence of CR-BSI among patients with long-term, indwelling CVCs for various diseases and conditions ranges from 0.3 infections per 1,000 catheter-days to 9.1 infections per 1,000 catheter-days.6,8-10 The use of CVCs in patients with PAH has been associated with CR-BSI rates reportedly ranging from 0.1 infections per 1,000 catheter-days to 1.1 infections per 1,000 catheter-days.6,11,12 In the largest review of patients with PAH and CR-BSI, the Centers for Disease Control and Prevention conducted a retrospective evaluation of CR-BSIs in patients who had received IV prostanoids from 7 major PAH centers.12 A total of 57 CR-BSIs were identified during 51,183 catheter-days among patients receiving IV treprostinil, and 87 CR-BSIs were noted during 201,158 catheter-days among patients receiving IV epoprostenol. Thus, CR-BSI rates were found to be higher among patients receiving treprostinil than among patients receiving epoprostenol (1.11 infections per 1,000 catheter-days vs 0.43 infections per 1,000 catheter-days; pooled incidence rate ratio [IRR], 2.57; 95% confidence interval [CI], 1.81–3.64). However, the incidence of CR-BSI at individual centers varied widely; reported CR-BSI rates ranged from 0.28 to 2.10 infections per 1,000 catheter-days for treprostinil and from 0.23 to 1.02 infections per 1,000 catheter-days for epoprostenol, reflecting an approximate 2-fold difference between centers. The increased incidence of CR-BSI with treprostinil may be associated with higher rates of infection caused by gram-negative pathogens.4,12 The Centers for Disease Control and Prevention report identified a significantly higher pooled mean rate of CR-BSI caused by gram-negative pathogens among patients who received treprostinil than among patients who received epoprostenol (0.76 infections per 1,000 catheter-days vs 0.06 infections per 1,000 catheter-days; pooled IRR, 12.77; 95% CI, 6.55–26.80).12 Higher rates of CR-BSI and the increased frequency of infection caused by gram-negative pathogens associated with treprostinil, compared with epoprostenol, were also reported in a separate publication detailing CR-BSI rates at 2 of the 7 PAH centers and that retrospectively evaluated a total of 224 patients during 146,093 catheter-days.4 Thus, CR-BSIs are rare but significant events in PAH, and infections caused by gram-negative pathogens are more commonly associated with IV treprostinil. The catheter hub is generally the suspected point of entry for pathogens causing CR-BSI in patients receiving long-term treatment.13,14 Akagi et al11 evaluated the effect of adopting a closed-hub system on CR-BSI rates among 20 patients with PAH who were receiving continuous IV epoprostenol. Eleven patients started to receive epoprostenol therapy before introduction of the closed-hub system. During the 6.5-year study period, a total of 7 CR-BSIs occurred in 6 patients, resulting in a CR-BSI rate of 1.2 infections per 1,000 catheter-days in the non–closed-hub system group. Thirteen patients received IV epoprostenol via a closed-hub system, including 4 patients who were switched from the non–closed-hub system. Catheter-related BSIs in the closed-hub system group included 2 infections that occurred in 1 patient, and the CR-BSI rate in this patient population was 0.23 infections per 1,000 catheter-days. Thus, the closed-hub system significantly reduced the risk for CR-BSI among patients with PAH who were receiving IV epoprostenol (P = .04). The infusion line connections also may represent a point of entry for bacterial pathogens present in tap water or transferred from the shower head. Therefore, interventions designed to prevent the exposure of infusion system connections to tap water, such as during bathing, may further reduce the risk of CR-BSI. In this context, the objective of the current study was to evaluate whether the incidence of CR-BSI among patients with PAH receiving IV prostanoids could be reduced through the introduction of 2 new preventive measures: the introduction of a closed-hub system and the waterproofing of catheter hub connections during showering.