WWW.JPHARMTECHNOL.COMSeveral health benefits of cranberries have been proposed, from urinary tract infection prophylaxis, possibly related to an anti-adhesion mechanism of bacteria in the bladder, to a cardioprotective effect by inhibiting lowdensity lipoprotein (LDL) oxidation and inducing LDL receptor expression. 1-3 The growing interest in alternative therapies, including phytonutrients, may lead to concomitant use of cranberry juice or products in patients receiving warfarin.Close monitoring of patients who consume cranberry juice is recommended based on warnings of its possible interaction with warfarin. 4-8 We report a case of an elevated international normalized ratio (INR) believed to be caused by consumption of cranberry juice.

Doripenem is the latest carbapenem on the market to date. Although not an antibiotic in a new class, it offers a glimmer of hope in combating serious infections secondary to multidrug-resistant Gram-negative bacteria when we have not seen a new class of antibacterial, particularly for Gram-negative bacteria, for more than 10 years. In vitro, doripenem exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including extended-spectrum β-lactamase (ESBL) and Amp-C β-lactamase producing Enterobacteriaceae and anaerobes. Doripenem also exhibits better in vitro activity against Pseudomonas aeruginosa compared to other anti-pseudomonal carbapenems. It combines the desirable activities of both imipenem and meropenem. It has similar activity to imipenem against Gram-positive pathogens and has the antimicrobial spectrum of meropenem against Gram-negative organisms. Several randomized clinical trials have demonstrated that doripenem is non-inferior to meropenem, imipenem, piperacillin/tazobactam, or levofloxacin in its efficacy and safety profile in treating a wide range of serious bacterial infections including intra-abdominal infection, complicated urinary tract infection, and nosocomial pneumonia. Due to its wide spectrum of activity and good safety profile it is susceptible to misuse leading to increasing rates of resistance. Judicious use should be considered when using doripenem as a first-line agent or drug of choice for serious infections. Doripenem is a well-tolerated drug with common adverse effects including headache, nausea and diarrhea. Caution should be used in patients with hypersensitivity to carbapenems and adverse reactions to β-lactam agents. Dosage adjustment is needed for patients with renal impairment. Doripenem has demonstrated economic and clinical benefits. It has been shown to reduce hospital length of stay and duration of mechanical ventilation for intensive care unit (ICU) patients. Therefore, doripenem is a welcome addition to our limited armamentarium of antibiotics available to treat serious bacterial infections in hospitalized patients.

Despite alarming data showing the ever increasing number of bacteria becoming resistant to different classes of antibiotics through various mechanisms, the carbapenems remain a unique class of antibiotics that possess the broadest spectrum against Gram-positive, Gram-negative, aerobic and anaerobic organisms. However, bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, carry mechanisms that can inactivate the carbapenems. This article gives a review of the carbapenems that are currently in clinical use as well as discusses the new carbapenems that are in clinical trials. These new carbapenems show promising potential to overcome the resistance against the presently existing carbapenems. The present article shows the recent patents using carbapenems as an effective antibiotic.

Background There are data suggesting a possible association of serum digoxin concentrations (SDC) and risk of mortality in patients treated with digoxin. Objective To determine whether SDCs in the therapeutic range of 1.2 to 2 ng/mL increase the risk of mortality when compared to a lower range of 0.5 to 1.1 ng/mL. Methods Retrospective cohort study to compare the risk of mortality in male patients with SDCs less than 1.2 ng/mL to patients with SDCs of 1.2 to 2 ng/mL. Results A total of 261 male patients were included, 191 (73%) had SDCs in the low range (0.5 to 1.1 ng/mL), and 70 (27%) had SDCs in the high range (at least 1.2 to 2 ng/mL). A high SDC showed a significant increase in risk for mortality with a hazard ratio (HR) of 1.656; 95 % HR confidence interval, 1.153 to 2.38; P = 0.0063. Conclusion Our results showed an increased risk of mortality in the high SDC group (1.2 to 2 ng/mL). This study's findings are consistent with the results of a post hoc evaluation of SDC in male patients in the DIG trial.1 A prospective trial is warranted to confirm our findings.

Background The manufacturer of simvastatin recommends a dose limitation of 10 mg daily when used in combination with gemfibrozil, due to increased risk of myopathy and rhabdomyolysis. Little information is available regarding the risk of adverse effects of atorvastatin when used in combination with gemfibrozil. Purpose To compare the rate of discontinuation or dose reduction due to adverse effects with simvastatin and gemfibrozil versus atorvastatin and gemfibrozil. Methods Retrospective review of patients taking gemfibrozil in combination with simvastatin 10 mg, simvastatin 80 mg, or atorvastatin 40 mg for at least 6 months. Results A total of 166 patients were included; 59 were taking simvastatin 10 mg (S10), 47 were taking simvastatin 80 mg (S80), and 60 were taking atorvastatin 40 mg (A40). There was no significant difference in the rate of discontinuation or dose reduction due to adverse effects among the groups (10.2% for S10, 21.2% for S80, and 10% for A40, P = 0.159). A paired comparison of discontinuation or dose reduction due to adverse effects between the simvastatin 80 mg and atorvastatin 40 mg groups approached a trend toward a difference ( P = 0.104). Severe adverse effects occurred in the simvastatin 80 mg and atorvastatin 40 mg groups. Conclusion Our results did not show a significant difference in discontinuation or dose reduction due to adverse effects between patient groups taking gemfibrozil in combination with simvastatin 10 mg, simvastatin 80 mg, or atorvastatin 40 mg. However, the rate of this outcome in the S80 group was approximately double that for the S10 and A40 groups. Further studies are needed to compare the safety of these statin-gemfibrozil combinations.