zithromax and Breast-Neoplasms

Legionella species are a common cause of community-acquired pneumonia, infrequently complicated by cavitary disease. We describe Legionella pneumophila pneumonia and abscess formation in an immunosuppressed patient receiving corticosteroid therapy for metastatic breast carcinoma. The predisposing role of corticosteroids is discussed and the management of this complication is reviewed.

Topics: Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Australia; Azithromycin; Brain Neoplasms; Breast Neoplasms; Ceftriaxone; Combined Modality Therapy; Cranial Irradiation; Dexamethasone; Diagnosis, Differential; Drainage; Female; Humans; Immunocompromised Host; Legionella pneumophila; Legionnaires' Disease; Lung Abscess; Lung Neoplasms; Metronidazole; Roxithromycin; Thoracic Surgery, Video-Assisted; Thoracostomy; Tomography, X-Ray Computed

Delayed breast cellulitis is an infrequently reported entity after conservation therapy for breast cancer. We describe our experience with this entity at Naval Medical Center, San Diego.. Eight patients who presented with delayed cellulitis after wide local excision/axillary dissection and breast radiotherapy (RT) are presented. Their clinical characteristics and therapy are described and possible causative factors are analyzed.. The latency of breast cellulitis is variable after breast conservation therapy, although most cases in our experience and in the literature occur within a year post-RT. These infections are frequently refractory to a single course of antibiotics (n = 4 cases in our experience). Some patients suffer multiple episodes separated by months.. Breast cancer patients are at risk for delayed cellulitis after conservative surgery and RT. The mechanism of such events probably involves lymph stasis, however, therapy is no different from the more frequently occurring cases of cellulitis presenting perioperatively.

Topics: Aged; Amoxicillin; Azithromycin; Breast Diseases; Breast Neoplasms; Cellulitis; Clavulanic Acid; Combined Modality Therapy; Dicloxacillin; Drug Therapy, Combination; Female; Humans; Lymph Node Excision; Mastectomy, Segmental; Middle Aged; Postoperative Complications; Radiotherapy Dosage

Macrolides are widely used for the long-term treatment of infections and chronic inflammatory diseases. The pharmacokinetic features of macrolides include extensive tissue distribution because of favorable membrane permeability and accumulation within lysosomes. Trastuzumab emtansine (T-DM1), a HER2-targeting antibody-drug conjugate (ADC), is catabolized in the lysosomes, where Lys-SMCC-DM1, a potent cytotoxic agent, is processed by proteinase degradation and subsequently released from the lysosomes to the cytoplasm through the lysosomal membrane transporter SLC46A3, resulting in an antitumor effect. We recently demonstrated that erythromycin and clarithromycin inhibit SLC46A3 and attenuate the cytotoxicity of T-DM1; however, the effect of other macrolides and ketolides has not been determined. In this study, we evaluated the effect of macrolide and ketolide antibiotics on T-DM1 cytotoxicity in a human breast cancer cell line, KPL-4. Macrolides used in the clinic, such as roxithromycin, azithromycin, and josamycin, as well as solithromycin, a ketolide under clinical development, significantly attenuated T-DM1 cytotoxicity in addition to erythromycin and clarithromycin. Of these, azithromycin was the most potent inhibitor of T-DM1 efficacy. These antibiotics significantly inhibited the transport function of SLC46A3 in a concentration-dependent manner. Moreover, these compounds extensively accumulated in the lysosomes at the levels estimated to be 0.41-13.6 mM when cells were incubated with them at a 2 μM concentration. The immunofluorescence staining of trastuzumab revealed that azithromycin and solithromycin inhibit the degradation of T-DM1 in the lysosomes. These results suggest that the attenuation of T-DM1 cytotoxicity by macrolide and ketolide antibiotics involves their lysosomal accumulation and results in their greater lysosomal concentrations to inhibit the SLC46A3 function and T-DM1 degradation. This suggests a potential drug-ADC interaction during cancer chemotherapy.

Topics: Ado-Trastuzumab Emtansine; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Azithromycin; Breast Neoplasms; Clarithromycin; Female; Humans; Immunoconjugates; Ketolides; Lysosomes; Maytansine; Receptor, ErbB-2; Trastuzumab