Teena Abraham

Daptomycin: evaluation of a high-dose treatment strategy

With a decreasing pipeline of novel antibiotics and increasing antibacterial resistance, the need to optimise the current antibiotics in our armamentarium has become vitally important. Daptomycin is a novel lipopeptide antibiotic that exhibits concentration-dependent activity. Currently, the daptomycin dosage is 4 mg/kg/day for treatment of complicated skin and soft-tissue infections and 6 mg/kg/day for Staphylococcus aureus bloodstream infections, including those with right-sided endocarditis, however higher doses (>6 mg/kg/day) have been explored as a possible alternative. A comprehensive review of published data identified through a MEDLINE search of the literature from 1967-2011 and a manual search of references was performed with the primary objective of critically evaluating the safety and efficacy of high-dose daptomycin. Search results yielded two prospective trials, three retrospective reviews, case reports and in vitro simulation studies on high-dose daptomycin. To date, clinical trials, retrospective reviews, case reports and in vitro simulation models have documented the safety and tolerability of high-dose daptomycin, even when administered for a prolonged duration. Additionally, in vitro benefits observed include suppression of the emergence of daptomycin resistance and increased rapidity of bactericidal activity.

A comprehensive comparative review of adenosine diphosphate receptor antagonists

Introduction: Thrombosis risk necessitates dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist, in patients who have acute coronary syndrome. Current guidelines emphasize the critical role of dual antiplatelet therapy in both medical management and invasive strategy, especially in patients undergoing percutaneous coronary intervention. With the availability of multiple ADP-receptor antagonists, it is crucial to select the most appropriate agent for each patient. Areas covered: The pertinent trials were identified through a MEDLINE search, in addition to a manual search from the articles retrieved. This review examines the differences between clopidogrel, prasugrel and ticagrelor in terms of their pharmacological/pharmacokinetic properties, clinical efficacy, drug interactions and safety parameters. Expert opinion: Prasugrel and ticagrelor exhibit greater platelet inhibition and superior efficacy compared with clopidogrel, at the expense of higher bleeding risk. Prasugrel and ticagrelor should be preferred over clopidogrel in patients who are at a high risk of thrombotic events with low risk of bleeding. Additionally, these two agents may offer advantage over clopidogrel in those patients who might have risk for drug resistance due to CYP2C19 polymorphism. In selecting the ideal agent for patients, clinicians should tailor the antiplatelet regimen by considering individual risk factors and medication characteristics.

Role of combination therapy in the treatment of pulmonary arterial hypertension.

As a result of the multimechanistic pathology of pulmonary arterial hypertension (PAH), combination therapy is emerging as a potential treatment option. Recent guidelines from the American College of Chest Physicians and expert consensus from the American College of Cardiology Foundation and American Heart Association do not definitively support or disapprove of combination pharmacotherapy for the treatment of PAH. Published trials have investigated different combinations including endothelin receptor antagonists with prostanoids, prostanoids with phosphodiesterase inhibitors, and phosphodiesterase inhibitors with endothelin receptor antagonists. Pertinent trials on combination pharmacotherapy for PAH were identified through a MEDLINE search of literature from 1967–2009 in addition to a manual search of references from the articles retrieved. Search results identified 12 trials that evaluated combination therapy for PAH; some included an add‐on agent for patients who failed treatment with monotherapy and others were placebo controlled. Even with the published data, the overall consensus is unclear. Well‐designed, larger trials with validated end points are needed to further identify when to initiate combination therapy for the treatment of PAH. Meanwhile, perhaps the most appropriate situation for using combination pharmacotherapy may be in the setting of a lack of clinical improvement or deterioration.

Dolutegravir for the treatment of adult patients with HIV-1 infection

Dolutegravir, is a second generation integrase inhibitor that had recently received United States Food and Drug Administration and European Commission approval for the treatment of adult patients with HIV-1 infection. Dolutegravir provides distinct advantages compared with first generation integrase inhibitors. Unlike raltegravir, dolutegravir can be given once daily for patients who are antiretroviral treatment naïve. Once-a-day dolutegravir dosing also does not require a pharmacokinetic booster like elvitegravir which minimizes the drug-drug interaction potential of dolutegravir. In Phase III clinical trials, dolutegravir-containing regimens have demonstrated either non-inferiority or superiority to current first line agents such as raltegravir, darunavir/ritonavir, and efavirenz containing regimens. Moreover, dolutegravir may be effective for patients with a history of raltegravir and/or elvitegravir resistance. Dolutegravir will likely play a major role in the management of patients with HIV-1 infection, and will be aided when coformulation with abacavir/lamivudine as a single pill, once-daily regimen is available.

Drug Dosage Adjustment Using Renal Estimation Equations: A Review of the Literature

Purpose To examine the factors affecting drug clearance and the available evidence for drug dosing based on the Cockcroft-Gault (CG) equation and the abbreviated Modification of Diet in Renal Disease (abbrMDRD) equation. Factors that would distort the accuracy of these formulas and the affect of this distortion on the use of either formula in drug dosage adjustment were reviewed. Methods An updated review of the literature was performed that pertained to the accuracy of the CG and abbrMDRD equations and their use in drug dosage adjustment. MEDLINE was searched using the OVIDSP database, from the inception of the database (1950) through June 2008. Discussion To cover the major issues concerning the use of renal estimation equations in drug dosing adjustment, various areas were examined. Topics included the accuracy of the CG and abbrMDRD formulas, variability in these equations because of patient and laboratory factors, the isotope dilution-mass spectrometry standardization initiative, and the applicability of each formula to modifying medication doses. Conclusion Although the abbrMDRD equation has many advantages as compared with the CG equation, too little research has been completed at this time to recommend the clinical use of the abbrMDRD equation in pharmacy practice.

Oritavancin, a single-dose, complete regimen, for the treatment of acute bacterial skin and skin structure infections

Oritavancin, a lipoglycopeptide antibiotic, recently received US FDA approval for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI). Oritavancin, unlike other intravenous antibiotics that are currently available for the treatment of ABSSSI (e.g., vancomycin, daptomycin, telavancin, dalbavancin), offers the option of a single-dose complete regimen. The dosing schedule of oritavancin eliminates the need for an indwelling catheter and introduces the possibility of avoidance of a hospital admission; although, treatment in non-hospital settings has not been adequately evaluated in clinical trials. The availability of oritavancin adds another agent to our antibiotic armamentarium providing dosing flexibility and an alternative treatment option for treatment of ABSSSI caused by susceptible bacteria, including methicillin-resistant Staphylococcus aureus.

Role of Tigecycline for the Treatment of Urinary Tract Infections

Objective: To review and critically analyze the literature for the use of tigecycline for the treatment of urinary tract infections (UTIs). Data Sources: A search of the MEDLINE database was performed (2004 to July 2013). Search terms included tigecycline, Tygacil, pyelonephritis, cystitis, and urinary tract infections in addition to a manual search of references from the articles retrieved. Study Selection and Data Exaction: All studies of humans, English-language articles, clinical studies, observational studies, and case reports were evaluated. Data Synthesis: Fourteen cases of tigecycline use for UTIs were identified. No clinical trials were identified via the search of the MEDLINE database. Twelve of the 14 cases described positive clinical outcomes with use of tigecycline for the treatment of UTI. Microbiological clearance was evaluable in 11 patients, of which 9 patients achieved documented microbiological clearance. None of the patients had mortality attributable to the use of tigecycline for the UTI. Two of the 14 cases reported had patients with subsequent cultures growing tigecycline-resistant organisms. Conclusion: Case reports have documented clinical improvement/success with the use of tigecycline for the treatment of UTIs. However, use of tigecycline for the treatment of UTIs remains controversial because of limited data and the lack of randomized control trials demonstrating efficacy. Tigecycline should be avoided for the treatment of UTIs when well-established options such as aminoglycosides and β-lactams are available. When alternative options are nonexistent, tigecycline can be considered.