Probenecid & Abx
- Probenecid inhibits excretion of weak organic acids in the proximal and distal convoluted tubules, altering the pharmacokinetics of many drugs. It also inhibits glucuronidation of some drugs. Probenecid inhibits renal tubular excretion of many β-lactam antibacterial agents (e.g., cephalosporins and penicillins), an interaction that has been exploited clinically to maintain serum levels of the antibacterial agent, thereby reducing the frequency of administration. Probenecid does not alter serum levels of ceftriaxone or ceftazidime. Probenecid does not alter the pharmacokinetics of digoxin or theophylline.
- According to the 2008 update of the Canadian guidelines on sexually transmitted infections, the combination of oral probenecid and cefoxitin, as a single dose in combination with doxycycline for 14 days, is used as an alternative to ceftriaxone for outpatient treatment regimen for pelvic inflammatory disease [www.phac-aspc.gc.ca/std-mts/sti_2006/pdf/404_Pelvic_Inflammatory_Disease.pdf].
- According to the 2005 Anti-infective guidelines for community-acquired infections, the combination of cefazolin with oral probenecid (given 30 minutes prior to cefazolin) is used as an alternative treatment regimen for severe non-facial uncomplicated cellulitis [Clin Infect Dis 2002;34(11):1440-8].
- According to the 2009 Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, oral probenecid is administered in combination with cidofovir (administered iv) for the prevention of cidofovir-related nephrotoxicity. Cidofovir is used for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS in whom other drugs are inappropriate [www.cdc.gov/mmwr/pdf/rr/rr5804.pdf].
Bisphosphonate
steonecrosis of the jaw has been reported in patients receiving bisphosphonate therapy. Although the majority of patients affected receive either pamidronate or zoledronic acid for the management of metastatic cancer to the bone, there have been reports of osteonecrosis in patients receiving oral bisphosphonate therapy for the treatment of osteoporosis, including risedronate.[30737] Most of the reported cases have appeared after dental tooth extraction; however, some cases have appeared spontaneously. It is not possible to determine if the reported events are related to bisphosphonates, concomitant drugs or other therapies (e.g., chemotherapy, radiotherapy, corticosteroid), a patient’s underlying disease state, or other comorbid risk factors (e.g., anemia, infection, preexisting oral disease). Typical signs and symptoms of osteonecrosis of the jaw include pain, swelling, infection, or poor healing of the gums, loosening of the teeth, numbness or a feeling of heaviness in the jaw, and drainage of exposed bone. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. The treating physician and dentist should use their best clinical judgment to guide the management plan of each patient based on individual benefit and risk assessments. Based on a review of the available literature, treatments that have been used include local debridement, bone resection or other surgery, antimicrobials, antiseptic mouthwash, and hyperbaric oxygen.[33138] While a consensus on the best treatment strategies does not exist, the American Academy of Oral Medicine recommends prevention. Preventive measure include evaluation by a dentist prior to intravenous bisphosphonate initiation and within 3 months of oral bisphosphonate initiation, correction of dental complications prior to drug initiation, and continued regular follow-up with a dentist. For the treatment of osteonecrosis, recommendations include superficial debridement, bone resection when indicated, systemic antimicrobial for infections with culture-directed therapy or penicillin, amoxicillin, or clindamycin empirically, or use of chlorhexidine mouthwash 3—4 times daily. Discontinuation of the bisphosphonate once osteonecrosis occurs is controversial as the half-life of bisphosphonates within the bone is estimated to be years
- cefazolin
- better gram positive coverage
- useful for cellulitis
- cefuroxime
- more respiratory
- more gram negative coverage
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