Opioid exposure as a potential risk factor for vancomycin-resistant enterococci colonization in the absence of antimicrobial exposure.

BACKGROUND: Antimicrobial exposure leads to an increased risk of colonization and spread of vancomycin-resistant enterococci. Studies have also implicated exposure to nonantimicrobial medications as a potential risk factor for an increased risk of colonization with these pathogens. METHODS: A matched case-control study was performed to determine specific nonantimicrobial medications associated with vancomycin-resistant enterococci rectal colonization. Cases and controls were defined as persons who were not exposed to antimicrobials in the preceding 12 months and in whom vancomycin-resistant enterococci rectal colonization was and was not detected at hospital admission, respectively. Matching was performed by the date of admission. Data were extracted from electronic medical records and included patient demographics, clinical data, and exposure to non-antimicrobial medications in the preceding 90 days. RESULTS: Vancomycin-resistant enterococci colonization was identified among 2,919 (4.8%) patients during their first admission among 59,986 admissions. Among these patients, 27 cases were identified and were matched to 63 controls. Exposure to opioids was the only independent risk factor associated with colonization (adjusted odds ratio 3.8 [95% confidence interval 1.4-10.8], P-value = .01). CONCLUSIONS: Opioid exposure may increase the risk of vancomycin-resistant enterococci colonization. Preventing the acquisition of these pathogens may require infection-prevention efforts targeting persons exposed to opioids.

Brucella Species Staining as Gram-Positive Rod and Gram-Positive Cocci in Chains.

Two cases of Brucellosis were identified at a hospital in Rhode Island. In both cases, the organisms were isolated from the blood cultures. The bacteria did not appear as the classical textbook description of Brucella spp. as short, Gram-negative rods; instead, Gram-positive rods and Gram-positive cocci in chains were observed. Due to the atypical Gram stain morphology, Brucella spp. were not initially considered as a possible pathogen. Antimicrobial prophylaxes were offered to the technologists who were exposed to the organisms.

Preclinical Efficacy of Ron Kinase Inhibitors Alone and in Combination with PI3K Inhibitors for Treatment of sfRon-Expressing Breast Cancer Patient-Derived Xenografts.

PURPOSE: Recent studies have demonstrated that short-form Ron (sfRon) kinase drives breast tumor progression and metastasis through robust activation of the PI3K pathway. We reasoned that upfront, concurrent inhibition of sfRon and PI3K might enhance the antitumor effects of Ron kinase inhibitor therapy while also preventing potential therapeutic resistance to tyrosine kinase inhibitors (TKI). EXPERIMENTAL DESIGN: We used patient-derived breast tumor xenografts (PDX) as high-fidelity preclinical models to determine the efficacy of single-agent or dual Ron/PI3K inhibition. We tested the Ron kinase inhibitor ASLAN002 with and without coadministration of the PI3K inhibitor NVP-BKM120 in hormone receptor-positive [estrogen receptor (ER)(+)/progesterone receptor (PR)(+)] breast PDXs with and without PIK3CA gene mutation. RESULTS: Breast PDX tumors harboring wild-type PIK3CA showed a robust response to ASLAN002 as a single agent. In contrast, PDX tumors harboring mutated PIK3CA demonstrated partial resistance to ASLAN002, which was overcome with addition of NVP-BKM120 to the treatment regimen. We further demonstrated that concurrent inhibition of sfRon and PI3K in breast PDX tumors with wild-type PIK3CA provided durable tumor stasis after therapy cessation, whereas discontinuation of either monotherapy facilitated tumor recurrence. CONCLUSIONS: Our work provides preclinical rationale for targeting sfRon in patients with breast cancer, with the important stipulation that tumors harboring PIK3CA mutations may be partially resistant to Ron inhibitor therapy. Our data also indicate that tumors with wild-type PIK3CA are most effectively treated with an upfront combination of Ron and PI3K inhibitors for the most durable response. Clin Cancer Res; 21(24); 5588-600. ©2015 AACR.