Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenic Escherichia coli as a prophylactic against diarrhea.

BACKGROUND: . Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A. METHODS: . This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 1010 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD). RESULTS: . A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups. CONCLUSIONS: . Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrum-derived antibodies.

Risk factors for opioid overdose among hospitalized patients.

WHAT IS KNOWN AND OBJECTIVE: Hospitalized patients are at risk for opioid overdose. Little is known about the risk factors for these events. METHOD: Opioid overdose cases were identified by naloxone orders in computerized order entry system from a single institution. For each case, two controls were randomly selected. Data were collected on factors including age, gender, weight, opioid dose, route of administration, concomitant CNS depressants, renal function and comorbid conditions. RESULTS AND DISCUSSION: Between 2010 and 2013, we identified 44 cases of opioid overdose (OD), none of which were fatal, and matched these to 88 controls (no OD). Patients with a history of substance use disorder were excluded from the study. Factors associated with opioid overdose included age of 65 or older (40.9% OD vs 29.5% no OD, P = .026), being in an ICU (MICU/CICU 27.3% OD vs. 3.4% no OD, P < .001; SICU 18.1% OD vs 5.7% no OD, P = .031) and renal impairment (eGFR ≤60, 50.0% OD vs 28.4% no OD, P = .034). Total 24-hour opioid dose was lower in OD group, but the difference was not statistically significant (71.9 vs 107.2 mg morphine equivalent, P = .116). OD cases were more likely to have received concomitant CNS depressants, but the difference was statistically significant only for those who received 3 or more (15.9% OD vs 0% no OD, P = <.001). Heart disease was the only comorbidity significantly associated with an increased risk of opioid overdose (43.2% vs 20.5%, P = .025). Patient's BMI, duration of opioid use, route of administration and history of COPD and/or psychiatry were not associated with opioid overdoses. WHAT IS NEW AND CONCLUSION: Among hospitalized patients, risk factors of opioid overdose include age of 65 or greater, being in an ICU, renal impairment and concomitant administration of CNS depressant medications. These findings may help with the development and implementation of measures to prevent overdose.