The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.

Diltiazem coadministration resulted in a significant interaction with simvastatin, probably by inhibiting CYP3A-mediated metabolism. Concomitant use of diltiazem or other potent inhibitors of CYP3A with simvastatin should be avoided, or close clinical monitoring should be used.

No abstract

The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 106 U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. ql2h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. ql2h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin.In patients undergoing high-dose chemotherapy and autologous bone marrow transplantation (ABMT), mortality ranges from 5 to 20%, with the majority of deaths due to infectious complications. The use of prophylactic antibiotics directed against gram-negative, viral, and fungal pathogens has decreased the incidence of these infections (6,10,12,16). In particular, the use of the fluorinated quinolone antibiotics norfloxacin and ciprofloxacin has markedly decreased the incidence of gram-negative infections (5, 11, 21). Unfortunately, associated with the use of fluorinated quinolones has been a rise in the incidence of gram-positive infections and especially streptococcal infections (2-4, 14, 15, 18-20). These infections are felt to arise from the oral flora (9). A streptococcal septic shock syndrome manifested by hypotension and multiple organ failure with an associated mortality of 60% has been reported in this setting (2,17,19).The experience at Indiana University has been similar to that reported by others. Patients undergoing high-dose chemotherapy with ABMT are given a regimen of prophylactic antibiotics consisting of 5 mg of acyclovir per kg of body weight every 12 h (ql2h), 200 mg of fluconazole per day, and 400 mg of norf...