Successful Use of Ceftolozane-Tazobactam to Treat a Pulmonary Exacerbation of Cystic Fibrosis Caused by Multidrug-Resistant Pseudomonas aeruginosa.

Ceftolozane-tazobactam, a novel ß-lactam/ß-lactamase inhibitor, was recently approved for the treatment of complicated urinary tract and intraabdominal infections, as monotherapy and in combination with metronidazole, respectively. Ceftolozane-tazobactam exhibits a wide spectrum of activity against both gram-positive bacteria, gram-negative bacteria including multidrug-resistant (MDR) Pseudomonas aeruginosa, and some anaerobic bacteria. Although not currently approved for any pulmonary indication, studies have demonstrated excellent distribution to epithelial lining fluid, indicating that it may be an alternative agent to use in the treatment of respiratory tract infections caused by MDRP. aeruginosa. Unfortunately, data are lacking regarding the use of ceftolozane-tazobactam in the treatment of respiratory tract infections including patients with cystic fibrosis (CF). We describe the first case report, to our knowledge, of a 25-year-old white man successfully treated with ceftolozane-tazobactam for a pulmonary exacerbation of his CF caused by MDRP. aeruginosa. He was admitted for his fourth hospitalization in 7 months for a pulmonary exacerbation of his CF. After blood and sputum were cultured, prednisone, cefepime, inhaled tobramycin, and intravenous ciprofloxacin were started. On day 4, after no signs of clinical improvement, respiratory cultures revealed nonmucoid MDRP. aeruginosa, susceptible only to colistin. ß-Lactam therapy was subsequently changed to ceftolozane-tazobactam 3 g intravenously every 8 hours while continuing ciprofloxacin and inhaled tobramycin. Ceftolozane-tazobactam susceptibility was determined by the Etest method (minimum inhibitory concentration 1.5 µg/ml). By day 3 of therapy, the patient showed signs of clinical improvement and was discharged after completion of a 12-day course of antibiotics. Until additional research is available, we hope this evidence will provide consideration of ceftolozane-tazobactam for this novel off-label indication.

Mitiglinide: a novel agent for the treatment of type 2 diabetes mellitus.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide, a rapid-acting insulin secretion-stimulating agent to determine its potential role in therapy for the treatment of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1966-May 2010) was conducted for English-language, human studies using the terms mitiglinide, KAD 1229, S 21403, and meglitinide analogs. Abstracts presented at the American Association and European Association for the Study of Diabetes annual meetings from 2005 to 2009 were also evaluated for relevant data. STUDY SELECTION AND DATA EXTRACTION: Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide were reviewed. DATA SYNTHESIS: Mitiglinide has been shown through small clinical studies (N <400) to modestly decrease hemoglobin A(1c), postprandial hyperglycemia, and oxidative stress and inflammatory markers associated with postprandial hyperglycemia. Mitiglinide exerts its hypoglycemic activity by closing adenosine triphosphate (ATP)-sensitive potassium channels in the ß-islet cells of the pancreas. This agent has a rapid onset and short duration of action, mimicking a physiologic pattern of insulin release in nondiabetic people. Studies suggest a starting dose of 5 mg 3 times daily with meals and a maximum dose of 20 mg 3 times daily. Overall, mitiglinide is well tolerated, with the most common adverse effect being hypoglycemia. CONCLUSIONS: Mitiglinide is the third agent in the class of meglitinides that targets postprandial hyperglycemia. Because of a more intensive dosing regimen, potential cost, and lack of studies assessing the clinical impact of mitiglinide therapy on oxidative stress and inflammatory markers secondary to postprandial hyperglycemia, we cannot recommend this therapy over currently approved therapies.

A possible case of saw palmetto-induced pancreatitis.

A 65-year-old male with a history of diabetes, hypertension, hyperlipidemia, gout, Barrett esophagitis, and chronic gastritis developed acute pancreatitis after taking one week of the herbal medicine, saw palmetto, for symptoms related to benign prostatic hyperplasia (BPH). Ultrasound and computed tomography ruled out cholelithiasis and obstruction, triglycerides were normal, and he had no recent infection or trauma. He had a history of occasional alcohol consumption, though there was no recent increased intake. The most likely cause of pancreatitis in this case was saw palmetto. Saw palmetto (Serenoa repens) is an herbal medication used primarily in the treatment of symptoms related to BPH. It has a high content of fatty acids and phytosterols which are thought to exert their effects by inhibiting the enzyme 5-alpha-reductase, thereby preventing the conversion of testosterone into dihydrotestosterone (DHT). It has been postulated that saw palmetto directly stimulates estrogenic receptors and inhibits progesterone receptors in the prostate tissue. A previous report implicated the estrogen/antiandrogen properties of saw palmetto as inducing hepatotoxicity in a patient. Additionally, it has also been postulated that stimulation of the estrogenic receptors may lead to increased triglyceride levels or induction of a hypercoagulable state that leads to pancreatic necrosis. Finally, inhibition of cyclooxygenase, a property of saw palmetto, may be linked to acute pancreatitis. Acute pancreatitis, a serious and sometimes fatal disorder may occur secondary to medications. Although the mechanism is not fully known, this is the second case of acute pancreatitis that has been documented secondary to the herbal medication saw palmetto. It is important for clinicians to obtain detailed medication histories, including over-the-counter and herbal medications, in order to prevent further complications from occurring.

Cannabinoid-induced pancreatitis: a case series.

CONTEXT: There is only one previously published case report of acute pancreatitis secondary to the use of tetrahydrocannabinoid. While drugs, in general, account for 2% of all the causes of acute pancreatitis, we add to the literature three additional cases of cannabis-induced pancreatitis. CASES: The first case occurred in a 22-year-old man who admitted to smoking tetrahydrocannabinoid heavily over the days prior to admission. The second case involved a 23-year-old man with multiple admissions for tetrahydrocannabinoid-induced pancreatitis. The third case involved a 20-year-old female who admitted to smoking tetrahydrocannabinoid heavily over a period of two weeks prior to admission. In all cases, other causes of pancreatitis were ruled out. Furthermore, the symptoms associated with the acute pancreatitis subsided upon discontinuation of the drug. CONCLUSION: Cannabis is the world's most popular illicit drug with over 4% of the world's population using it each year. Despite this, acute pancreatitis is a rarely reported adverse effect of cannabis use. This case series adds to the literature that cannabis does in fact cause pancreatitis and it may be dose related, although the exact mechanism remains unknown.