u-62840 and Bacteremia

Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH). It is commonly administered through a central venous catheter (CVC). Treprostinil is associated with the incidence of Gram-negative bacterial bloodstream infections (BSI), a susceptibility that has been associated with a diluent used for treprostinil. We report the case of a 14-year-old boy with idiopathic PAH on continuous intravenous treprostinil therapy who presented with fever and fatigue. A blood culture drawn from his CVC was positive for the rare Gram-negative organism Chryseomonas luteola. The patient made a complete recovery with antibacterial treatment. This is the only documented case of a C. luteola BSI in a PAH patient receiving continuous intravenous treprostinil. We recommend maintaining a high index of suspicion for both common and rare Gram-negative pathogens and the early administration of appropriate antibiotic therapy in this population. The use of an alternate diluent solution, such as Sterile Diluent for Flolan, further decreases the infection risk.

Topics: Adolescent; Anti-Bacterial Agents; Antihypertensive Agents; Bacteremia; Blood; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Male; Pseudomonas; Pseudomonas Infections; Treatment Outcome

Recent studies have reported an increase in catheter-related bloodstream infections (BSIs) and gram-negative BSIs among patients with pulmonary arterial hypertension treated with IV treprostinil. One possible explanation is the neutral pH of the treprostinil diluent compared with the basic pH of epoprostenol. We hypothesized that administering IV treprostinil with epoprostenol diluent will lower the rate of gram-negative BSI.. We prospectively enrolled patients treated with IV treprostinil and changed the diluent from native diluent to epoprostenol diluent. We compared the incidence of BSI and gram-negative BSI between those receiving IV treprostinil with epoprostenol diluent (n = 25) and those actively receiving IV epoprostenol (n = 61), as well as with a cohort of patients who received IV treprostinil in native diluent (n = 34). Incidence rates of BSI were expressed as a fraction of 1,000 medicine treatment days.. There were similar rates of BSI in those treated with treprostinil with epoprostenol diluent and those treated with epoprostenol (0.32 of 1,000 vs 0.40 of 1,000; P = .79). Also, there were similar rates of gram-negative BSI in these two cohorts (0.08 of 1,000 vs 0.20 of 1,000; P = .46). BSI rates were not statistically different between those treated with treprostinil with epoprostenol diluent and those treated with treprostinil (0.32 of 1,000 vs 0.90 of 1,000; P = .06). However, gram-negative BSIs were significantly lower in patients treated with treprostinil with epoprostenol diluent than in those treated with treprostinil (0.08 of 1,000 vs 0.71 of 1,000, respectively; P = .01).. Patients treated with treprostinil with epoprostenol diluent have a lower incidence of gram-negative BSI than do those treated with treprostinil and a similar rate to those treated with epoprostenol. Changing the diluent of treprostinil to epoprostenol diluent, in combination with the use of water-tight seals throughout the delivery system, appears to be an effective safety measure.

Topics: Antihypertensive Agents; Bacteremia; Catheter-Related Infections; Catheterization, Peripheral; Catheters; Dose-Response Relationship, Drug; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Hydrogen-Ion Concentration; Hypertension, Pulmonary; Illinois; Incidence; Injections, Intravenous; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors

An excessive risk for bacteremia has recently been reported in patients with pulmonary arterial hypertension (PAH) treated with intravenous treprostinil. We aimed to assess this association in a cohort of patients from a Spanish referral center.. We performed a retrospective cohort study that included 55 patients diagnosed with PAH who received a continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil) for ≥1month at our center between January 1991 and December 2011. The risk factors associated with the incidence of bacteremia were analyzed with the log-rank test.. After a total follow-up of 64,453 treatment days, we found 12 episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram-negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118 episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938 episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037). All episodes of bacteremia due to Gram-negative bacilli were diagnosed in patients on treprostinil. In the univariate analysis the treatment with intravenous treprostinil was associated with the incidence of bacteremia (hazard ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of events prevented us from performing a multivariate analysis.. Therapy with intravenous treprostinil is associated with a higher risk for bacteremia, especially due to non-fermenting Gram-negative bacilli. This association should be taken in consideration when choosing empirical antibiotic therapy for patients with PAH and sepsis.

Topics: Adult; Antihypertensive Agents; Bacteremia; Cohort Studies; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Gram-Negative Bacteria; Humans; Hypertension, Pulmonary; Incidence; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies

To evaluate the rate of and potential risk factors for bloodstream infections (BSIs) using data from the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension [PAH] Disease Management) REGISTRY(®), which provides current information about patients with PAH.. Patients were enrolled from March 30, 2006, through December 8, 2009, and data on reported BSIs were collected through the third quarter of 2010. Bloodstream infection rates were calculated per 1000 patient-days of risk.. Of 3518 patients enrolled, 1146 patients received intravenous (IV) prostanoid therapy for more than 1 day (no BSI, n=1023; ≥1 BSI, n=123; total BSI episodes, n=166). Bloodstream infections rates were significantly increased in patients receiving IV treprostinil vs IV epoprostenol (0.36 vs 0.12 per 1000 treatment days; P<.001), primarily due to gram-negative organisms (0.20 vs 0.03 per 1000 treatment days; P<.001). Multivariate analysis adjusting for age, causes of PAH, and year of BSI found that treatment with IV treprostinil was associated with a 3.08-fold increase (95% confidence interval, 2.05-4.62; P<.001) in BSIs of any type and a 6.86-fold increase (95% confidence interval, 3.60-13.07; P<.001) in gram-negative BSIs compared with treatment with IV epoprostenol.. Compared with IV epoprostenol therapy, treatment with IV treprostinil is associated with a significantly higher rate of gram-negative BSIs; observed differences in BSI rate did not seem to be due to any other analyzed factors.. clinicaltrials.gov Identifier: NCT00370214.

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Bacteremia; Chi-Square Distribution; Child; Cross Infection; Epoprostenol; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Prostaglandins; Registries; Risk Factors; Survival Rate; United States

Intravenous prostanoids (epoprostenol and treprostinil) are effective therapies for pulmonary arterial hypertension but carry a risk of catheter-related bloodstream infection (CR-BSI). Prevention of CR-BSI during long-term use of indwelling central venous catheters is important.. To evaluate whether using a closed-hub system and waterproofing catheter hub connections reduces the rate of CR-BSI per 1,000 catheter-days.. Single-center open observational study (January 2003-December 2008).. Pediatric patients with pulmonary arterial hypertension who received intravenous prostanoids.. In July 2007, CR-BSI preventive measures were implemented, including the use of a closed-hub system and the waterproofing of catheter hub connections during showering. Rates of CR-BSI before and after implementing preventive measures were compared with respect to medication administered and type of bacterial infection.. Fifty patients received intravenous prostanoid therapy for a total of 41,840 catheter-days. The rate of CR-BSI during the study period was 0.51 infections per 1,000 catheter-days for epoprostenol and 1.38 infections per 1,000 catheter-days for treprostinil, which differed significantly (P < .01). CR-BSIs caused by gram-negative pathogens occurred more frequently with treprostinil than with epoprostenol (0.91 infections per 1,000 catheter-days vs 0.08 infections per 1,000 catheter-days; P < .01). Patients treated with treprostinil after the implemented changes had a significant decrease in CR-BSI rate (1.95 infections per 1,000 catheter-days vs 0.19 infections per 1,000 catheter-days; P < .01).. The closed-hub system and the maintenance of dry catheter hub connections significantly reduced the incidence of CR-BSI (particularly infections caused by gram-negative pathogens) in patients receiving intravenous treprostinil.

Topics: Antihypertensive Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Epoprostenol; Equipment Contamination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Hypertension, Pulmonary; Incidence; Infusions, Intravenous; Risk Reduction Behavior

In September 2006, the Centers for Disease Control and Prevention was notified of cases of gram-negative bloodstream infection (BSI) occurring among outpatients who received an intravenous formulation of the prostanoid treprostinil. An investigation was conducted to determine rates of prostanoid-associated BSI in this patient population and possible risk factors for infection.. We performed a retrospective cohort study of patients who had received intravenous formulations of at least 1 of the 2 approved prostanoids (epoprostenol and treprostinil) from January 1, 2004, through late 2006. Chart reviews were conducted at 2 large centers for pulmonary arterial hypertension, and a survey of infection control practices was conducted at 1 center.. A total of 224 patients were given intravenous prostanoid treatment, corresponding to 146,093 treatment-days during the study period. Overall, there were 0.55 cases of BSI and 0.18 cases of BSI due to gram-negative organisms per 1,000 treatment-days. BSI rates were higher for patients who received intravenous treprostinil than for patients who received intravenous epoprostenol (1.13 vs. 0.42 BSIs per 1,000 treatment-days; P < .001), as were rates of BSI due to gram-negative organisms (0.81 vs. 0.04 BSIs per 1,000 treatment-days; P < .001). Adjusted hazard ratios for all BSIs and for BSIs due to gram-negative organisms were higher among patients given treatment with intravenous treprostinil. The survey identified no significant differences in medication-related infection control practices.. At 2 centers, BSI due to gram-negative pathogens was more common than previously reported and was more frequent among patients given treatment with intravenous treprostinil than among patients given treatment with intravenous epoprostenol. Whether similar results would be found at other centers for pulmonary arterial hypertension warrants further investigation. This investigation underscores the importance of surveillance and evaluation of healthcare-related adverse events in patients given treatment primarily as outpatients.

Topics: Adolescent; Adult; Antihypertensive Agents; Bacteremia; Catheters, Indwelling; Centers for Disease Control and Prevention, U.S.; Cohort Studies; Cross Infection; Epoprostenol; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Home Infusion Therapy; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Proportional Hazards Models; Prostaglandins; Retrospective Studies; Risk Factors; Surveys and Questionnaires; United States