Frequency of antimicrobial resistance among invasive and colonizing Group B Streptococcal isolates

BACKGROUND: Group B Streptococcus (GBS) remains susceptible to penicillin, however, resistance to second-line antimicrobials, clindamycin and erythromycin, has increased since 1996. We describe the age-specific antibiotic susceptibility profile and capsular type distribution among invasive and colonizing GBS strains. METHODS: We tested 486 invasive GBS isolates from individuals of all ages collected by a Wisconsin surveillance system between 1998 and 2002 and 167 colonizing strains collected from nonpregnant college students during 2001 in Michigan. Antimicrobial susceptibility testing was performed by disk diffusion or Etest and capsular typing was performed using DNA dot blot hybridization RESULTS: 20.0% (97/486) of invasive and 40.7% (68/167) of colonizing isolates were resistant to clindamycin (P < .001) and 24.5% (119/486) of invasive and 41.9% (70/167) of colonizing isolates were resistant to erythromycin (P < .001). Similarly, 19.8% (96/486) of invasive and 38.3% (64/167) of colonizing isolates were resistant to both antimicrobial agents (P < .001). 29.4% (5/17) of invasive isolates from persons 18–29 years of age and 24.3% (17/70) of invasive isolates from persons 30–49 years of age were resistant to clindamycin. Similarly, 35.3% (6/17) of invasive isolates from persons 18–29 years of age and 31.4% (22/70) of invasive isolates from persons 30–49 years of age were resistant to erythromycin. 34.7% (26/75) of invasive isolates from persons < 1 year of age were capsular type Ia, whereas capsular type V predominated among isolates from adults. CONCLUSION: Clindamycin and erythromycin resistance rates were high among isolates colonizing nonpregnant college students and invasive GBS isolates, particularly among the colonizing isolates. Susceptibility profiles were similar by age although the proportion of clindamycin and erythromycin resistance among invasive isolates was highest among persons 18–49 years of age. Increasing antimicrobial resistance has implications for GBS disease treatment and intrapartum prophylaxis among penicillin intolerant patients

Bone Marrow Stromal Cells Modulate Mouse ENT1 Activity and Protect Leukemia Cells from Cytarabine Induced Apoptosis

BACKGROUND: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS: Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML

Phase II trial of fenretinide in advanced renal carcinoma

Purpose : Fenretinide, a synthetic form of retinoid, induced apoptosis even in chemotherapy resistant cell lines. A phase II study was hence conducted to evaluate toxicity and efficacy of fenretinide in metastatic renal cancer. Methods : Eligibility included unresectable or metastatic renal cell carcinoma (RCC), adequate organ function and Zubrod performance status ≦2. Prior immunotherapy and a maximum of one prior chemotherapy regimen were allowed. Fenretinide was administered at a dose of 900 mg/m 2 twice daily orally for 7 days in a 21-day cycle. Toxicity was assessed at the start of each cycle, and response every 2 cycles. Results : Nineteen eligible patients enrolled of which fifteen had visceral/bone metastases. Seventeen patients had prior nephrectomy and 11 had prior immunotherapy. 76 cycles of therapy were delivered. Therapy was very well tolerated with few severe toxicities consisting of thrombosis in 1 individual and grade 3 fatigue, nausea and diarrhea in 1 patient. 5 patients had grade 2 nyctalopia and 3 patients had transient grade 2 visual toxicity. No objective responses were noted. Stable disease was seen in seven of nineteen cases (37%, 90% C.I. 0.21–0.59). Median time to progression was 1.5 months and median duration of stable disease was 5.8 months (90% C.I. 3.0–8.4). Median survival was 10 months. Tumor fenretinide levels were obtained in three patients and were in the lower end of the therapeutic range. Conclusion : Fenretinide was well tolerated but demonstrated minimal activity that was consistent with results of intratumoral drug measurements. Strategies are needed that will increase systemic and tumor levels of fenretinide.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45264/1/10637_2005_Article_5864.pd