Olivia Ferrández

Changes in the Prescription of Psychotropic Drugs in the Palliative Care of Advanced Cancer Patients Over a Seven-Year Period

CONTEXT Psychiatric disorders are frequently underdiagnosed and undertreated in advanced cancer patients. OBJECTIVES To assess changes in the prescription of psychotropic drugs in terminally ill patients. METHODS All patients with advanced disease receiving palliative care between 2002 and 2009 were eligible. The consumption of benzodiazepines, antipsychotics, and antidepressants for the years 2002, 2006, and 2009 was compared. Data on the percentage and profile of psychotropic drugs prescribed were collected. RESULTS The study population included 840 patients (241 in 2002, 274 in 2006, and 325 in 2009). The percentage of patients treated with psychotropic drugs increased from 82.2% in 2002 to 90.2% in 2009 (P = 0.006) and the mean number of drugs per patient from 1.66 in 2002 to 2.16 in 2006 (P = 0.003), and to 2.35 in 2009 (P<0.001). Benzodiazepines were prescribed to 72.6% of patients in 2002 and 84% in 2009 (P = 0.001), with lorazepam and midazolam as the most frequently used medications. The use of antipsychotics increased from 26.1% in 2002 to 37.2% in 2006 (P = 0.007) and to 40% in 2009 (P = 0.001), with haloperidol and risperidone as the most commonly prescribed. Antidepressants were prescribed to 17.8% in 2002, 28.1% in 2006 (P = 0.006), and 27.1% in 2009 (P = 0.010), with mirtazapine, citalopram, escitalopram, and duloxetine as the most frequent. CONCLUSION Between 2002 and 2009, there was a significant increase in the use of psychotropic drugs and a change in the profile of drugs prescribed.

Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections

Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need.

Design of a score to identify hospitalized patients at risk of drug‐related problems

The potential impact of drug‐related problems (DRP) on morbidity and mortality is a serious concern in hospitalized patients. This study aimed to design a risk score to identify patients most at risk of a DRP.

Characteristics of doripenem: a new broad-spectrum antibiotic

Doripenem (S-4661) is a new parenteral antibiotic from the carbapenem class; similarly to imipenem and meropenem, it has a broad-spectrum activity against Gram-positive, Gram-negative, and anaerobic bacteria. It is active against multiresistant Gram-negative bacilli such as extended-spectrum beta-lactamase-producing (ESBL) Gram-negative Enterobacteriaceae and nonfermentative Gram-negative bacilli including some strains of Pseudomonas aeruginosa that are resistant to other carbapenems. Doripenem’s chemical structure is similar to that of meropenem (substitution of one sulfamoxil-aminomethyl chain for the dimethyl-carboxyl chain), and has one 1-beta-methyl chain which provides resistance to dehydropeptidase-I enzyme. The clinical trials conducted so far have focused on the treatment of severe infections such as complicated intra-abdominal infections, complicated urinary tract infections and pyelonephritis, nosocomial pneumonia, and ventilator-associated pneumonia. Given its activity profile and the results from the clinical trials, this antibiotic may be used for empirical treatment of multibacterial infections produced by potentially multiresistant Gram-negative bacilli. In 2007, the US Food and Drug Administration approved the use of doripenem for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. The European Medicines Agency has approved the use of doripenem for the same indications in addition to nosocomial pneumonia regardless of whether it is ventilator-associated or not.

Long-term treatment with linezolid in a patient with osteomyelitis undergoing hemodialysis.

Abstract Anemia and/or thrombocytopenia are the most relevant adverse effects of linezolid treatment. We report the case of a patient under hemodialysis who developed osteomyelitis involving the amputation stump of the left limb due to a vancomycin-resistant and teicoplanin-resistant Enterococcus faecium successfully treated with linezolid for 6 months. Close monitorization of the patient probably contributed to maintenance of treatment with linezolid despite hematological alterations observed, which could be attributed to either the underlying patient’s clinical condition or antimicrobial treatment.

Alcohol Ingestion and Topical Tacrolimus: A Disulfiram-Like Interaction?

documented their search strategy, 5 used a broad-based approach, while 5 used only MEDLINE. Interestingly, the articles where search methods were not described had a higher percentage of bibliographic articles not indexed in MEDLINE (2%) compared with those articles describing >3 search methods (1%). McAlister et al.4 reviewed 158 review articles from 6 general medical journals in 1996. These authors found that only 28% of these articles (n = 44) described how evidence was located for their reviews. A similar study by Mulrow5 in 1987 reported that only 2% (1 in 50) of review articles described their literature-searching methods. Our small study shows a growing trend, 2% (1987), 28% (1996), to now 50% (2003) of academic reviews describing their literature-searching methods, but this is far short of what should be part of every review article. The small number of non-MEDLINE references utilized in these academic review articles is worth pondering. Why did authors find so few non–MEDLINE-indexed articles that were worthy of inclusion? Are authors biased toward MEDLINE-indexed articles or are non–MEDLINEindexed articles of poor quality? Are non-MEDLINE articles difficult to obtain and therefore not utilized? It is possible that the 88% of the literature not included in MEDLINE is not of sufficient quality to be included. It is also possible that authors are searching only what is available and familiar to them and ignoring that trove of the literature that is perhaps difficult to obtain, published in other countries, and/or not as recognizable to us. Further research is necessary to fully explore these issues. Larger studies comparing review article bibliographies in different databases, such as EMBASE and Science Citation Index, could also shed additional light on this subject.

Pharmacokinetics of micafungin in patients with pre-existing liver dysfunction: A safe option for treating invasive fungal infections.

In this prospective observational study performed in 12 hospitalized patients with proven or suspected invasive fungal infection treated for a mean of 14 days with micafungin (MCF), 8 of whom with pre-existing liver function impairment, plasma levels of MCF at steady state were not correlated with liver function tests at the beginning of treatment. Liver function remained stable or even improved in all patients, except in one in which MCF was discontinued due to liver toxicity.

Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

Tedizolid phosphate has high activity against the Gram-positive microorganisms mainly involved in acute bacterial skin and skin structure infections, such as strains of Staphylococcus aureus (including methicillin-resistant S. aureus strains and methicillin-sensitive S. aureus strains), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group, and Enterococcus faecalis, including those with some mechanism of resistance limiting the use of linezolid. The area under the curve for time 0–24 hours/minimum inhibitory concentration (MIC) pharmacodynamic ratio has shown the best correlation with the efficacy of tedizolid, versus the time above MIC ratio and the maximum drug concentration/minimum inhibitory concentration ratio. Administration of this antibiotic for 6 days has shown its noninferiority versus administration of linezolid for 10 days in patients with skin and skin structure infections enrolled in two Phase III studies (ESTABLISH-1 and ESTABLISH-2). Tedizolid’s more favorable safety profile and dosage regimen, which allow once-daily administration, versus linezolid, position it as a good therapeutic alternative. However, whether or not the greater economic cost associated with this antibiotic is offset by its shorter treatment duration and possibility of oral administration in routine clinical practice has yet to be clarified.

Normalization of creatine kinase values in a case of rhabdomyolysis during daptomycin treatment.

A 41-year-old woman presented in the Emergency Department with suspected compartment syndrome of lower left leg (creatine kinase [CK]: 12,502 IU/L, Cr: 4.31 mg/dL). Fasciotomy of the four limb compartments was conducted. By day 2, the patient presented oliguria during previous 24 h, so daily intermittent dialysis was carried out. On day 12, the patient presented an episode of bacteremia due to Staphylococcus hominis. Treatment with vancomycin was initiated and was changed after 4 days to daptomycin due to unsatisfactory clinical progression (6 mg/kg every 48 h, according to renal function and patients weight) (CK: 2,972 IU/L). After 15 days of treatment, the dose of daptomycin was increased to 6 mg/kg every 24 h (CrCL: 46 mL/min, CK: 83 IU/L). The antibiotic was continued for another 4 days. Fourteen days later, the patient was discharged (CK: 26 IU/L). Daptomycin could be prescribed in some patients with elevated CK values. A cut-off value of baseline CK for use of daptomycin needs to be determined.