Journal Watch: Recent studies of note

Recent studies about early routine eptifibatide for ACS, predicting C. diff infections, and other topics.

Early routine eptifibatide has no benefit in ACS

Early, routine use of eptifibatide 12 hours or more before angiography is not superior to delayed, provisional administration after angiography but before percutaneous coronary intervention in patients with acute coronary syndromes (ACS) without ST-segment elevation, a recent study found.

Although glycoprotein IIb/IIIa inhibitors are recommended in conjunction with an invasive procedure in patients with ACS, existing evidence guiding the timing of this therapy is inconclusive. The EARLY ACS Investigators compared early, routine use and delayed, provisional use of eptifibatide in 9,492 ACS patients undergoing angiography. The primary end point was a composite of death, myocardial infarction, recurrent ischemia requiring urgent revascularization, or the occurrence of a thrombotic complication during intervention that required bolus infusion opposite the study group assignment (“thrombotic bailout”) at 96 hours. The secondary end point was a composite of death or myocardial infarction in the first 30 days. Safety end points were bleeding and transfusion 120 hours or less after random group assignment. The study results were published early online by The New England Journal of Medicine on March 30.

Rates of the primary end point did not differ significantly between the early and delayed therapy groups (9.3% vs. 10.0%; odds ratio, 0.92 [95% CI, 0.80 to 1.06]; P= 0.23). The secondary end point occurred in 11.2% of the early therapy group and 12.3% of the delayed therapy group (odds ratio, 0.89 [95% CI, 0.79 to 1.01]; P= 0.08). Bleeding and red cell transfusion were significantly more common in those receiving early therapy, but severe bleeding and other serious adverse events did not differ between groups. A trend toward fewer ischemic events at 30 days was noted in patients who received early eptifibatide.

The authors pointed out that their patient population was older and higher-risk and received more aggressive concomitant therapy than those in previous studies. They concluded that early, routine use of eptifibatide was not superior to delayed, provisional use in high-risk ACS patients without ST-segment elevation and may increase bleeding and transfusion risk. Although fewer ischemic events were noted in those receiving early therapy, “a routine strategy of administering eptifibatide in patients early after presentation cannot be recommended,” they wrote.

Simple rule predicts patients at risk for recurrent c. diff infections

A simple clinical rule predicts which patients are at risk for recurrent infections of Clostridium difficile, a recent study reported.

In an independent validation cohort of 89 patients with C. diff infection, 64 of whom had complete follow-up and were analyzed for the study, the rule correctly classified 71.9% (95% CI, 59.2% to 82.4%) of patients with recurrent infections, researchers reported in the April issue of Gastroenterology. The clinical rule assigned one point for each of three risk factors: age greater than 65 years, severe or fulminant illness (by the Horn index), and additional antibiotic use after initial therapy. Patients with two or more risk factors were considered high risk for recurrence, whereas patients with fewer than two risk factors were low risk. The sensitivity and specificity for stratifying risk were 53.8% (95% CI, 25.1% to 80.8%) and 76.5% (95% CI, 62.5% to 87.2%), respectively.

Researchers noted that the rule could facilitate faster recognition, diagnosis and treatment of recurrent C. diff infection in a high-risk population. These patients are most likely to benefit from interventions that prevent recurrence, they added, such as infection control measures, prudent use of antibiotics, prolongation of metronidazole or vancomycin therapy, and use of probiotics. The study was limited by the relatively small number of patients who had recurrent C. diff (13 out of the 64 patients).

Combining GFR, albuminuria predicts progression to end-stage renal disease

Estimated glomerular filtration rate (eGFR) and urinary albumin may predict who will develop end-stage renal disease (ESRD) and allow physicians to intervene earlier, according to Norwegian researchers. In the U.S., ESRD is expected to affect 785,000 people by 2020, or more than double the number in 2007. The disease currently costs $32 billion a year to treat.

Norwegian researchers analyzed data from 65,589 adults in a population-based study and found 124 people who developed ESRD after 10 years of follow-up. Hazard ratios for eGFR of 45 to 59 mL/min per 1.73 m2, 30 to 44 mL/min per 1.73 m2, and 15 to 29 mL/min per 1.73 m2 were 6.7, 18.8, and 65.7, respectively (P< 0.001 for all). Hazard ratios for micro- and macroalbuminuria were 13.0 and 47.2 (P< 0.001 for both).

Referrals to specialists based only on current chronic kidney disease stage 3 to 4 would include 4.7% of the general population and identify 69.4% of all individuals progressing to ESRD. Referrals using both eGFR and albuminuria would include 1.4% of the general population without losing predictive power, detecting 65.6% of those expected to progress to ESRD. Using these combined measurements might help reduce the number of patients referred to specialists without eliminating the ability to detect future ESRD cases, as well as improve efficient handling of this large group of patients, authors said in the Journal of the American Society of Nephrology. Generalizability of the study may be limited by its homogeneous population.

Asymptomatic catheter-associated bacteriuria treated inappropriately, study suggests

Patients with catheter-associated asymptomatic bacteriuria (CAABU) often receive inappropriate antibiotic treatment, according to a recent study.

Evidence-based guidelines call for no antibiotic treatment in patients with asymptomatic bacteriuria. The authors hypothesized that patients with indwelling and condom catheters who receive a diagnosis of catheter-associated urinary tract infection (CAUTI) may actually have CAABU and therefore should not receive antibiotic treatment. They performed a retrospective study of urine cultures obtained at a Veterans Affairs Medical Center over a three-month period to see how many patients with CAABU were treated with antibiotics. Infections associated with indwelling catheters or condom collection systems were classified as CAABUs or CAUTIs; antibiotic therapy was considered appropriate for the latter but not for the former. The results were published in the May Clinical Infectious Diseases.

Of 164 episodes of CAABU, 111 (68%) were not treated with antibiotics but 53 (32%) were. Patients who were older, had predominantly gram-negative bacteriuria and had more white blood cells in their urine were significantly more likely to receive inappropriate treatment for CAABU. Although the study was retrospective and looked at only one medical center, the authors concluded that better recognition of CAABU can help reduce inappropriate antibiotic use in hospitals. They suggested the first strategy for decreasing the number of reported cases of CAUTI may be to simply not screen for CAABU.

An accompanying editorial called attention to the study's flaws, noting that “there is no reason to assume that the long-term outcomes of patients with CAABU and those with CAUTI would be different or that treatment would alter the natural history of catheter-associated infections—so long as the instrument remains in place.” The editorialist also noted that the authors extrapolated results from earlier studies of patients with uncomplicated UTIs to patients with catheter-associated UTIs, and that the study design did not allow the researchers to adjust for antibiotics given for reasons besides a positive urine culture. Nevertheless, the editorialist wrote that the study, “despite its defects, is helpful because it reminds us that antibiotics continue to be used inappropriately for patients with urinary collection devices” and “compels us to reconsider how best to evaluate and manage urosepsis in patients with indwelling catheters.”