Impact of Generic Entry on Hospital Antimicrobial Use: A Retrospective Quasi-Experimental Interrupted Time Series Analysis.

BACKGROUND: The impact of antimicrobials generic entry (GE) is controversial. Their introduction could provide an economic benefit yet may also increase their consumption, leading to a higher risk of resistance. Our aim was to analyze the impact of GE on trends of antimicrobial consumption in an acute-care hospital. METHODS: A retrospective quasi-experimental interrupted time series analysis was conducted at a 400-bed tertiary hospital in Barcelona, Spain. All antimicrobials for systemic use for which a generic product entered the hospital from January 2000 to December 2019 were included. Antimicrobial consumption was expressed as DDD/100 bed days. RESULTS: After GE, the consumption of cefotaxime (0.09, p < 0.001), meropenem (0.54, p < 0.001), and piperacillin-tazobactam (0.13, p < 0.001) increased, whereas the use of clindamycin (-0.03, p < 0.001) and itraconazole (-0.02, p = 0.01) was reduced. An alarming rise in cefepime (0.004), daptomycin (1.02), and cloxacillin (0.05) prescriptions was observed, despite not achieving statistical significance. On the contrary, the use of amoxicillin (-0.07), ampicillin (-0.02), cefixime (-0.06), fluconazole (-0.13), imipenem-cilastatin (-0.50) and levofloxacin (-0.35) decreased. These effects were noticed beyond the first year post GE. CONCLUSIONS: GE led to an increase in the consumption of broad-spectrum molecules. The potential economic benefit of generic antibiotics could be diluted by an increase in resistance. Antimicrobial stewardship should continue to monitor these molecules despite GE.

Evolution of Antimicrobial Consumption During the First Wave of COVID-19 Pandemic.

Background: The first wave of COVID-19 pandemic may have significantly impacted antimicrobial consumption in hospitals. The objective of this study was to assess the evolution of antimicrobial consumption during this period. Methods: A retrospective quasi-experimental before-after study was conducted in a Spanish tertiary care hospital. The study compared two periods: pre-pandemic, from January 2018 to February 2020, and during the COVID-19 pandemic from March to June 2020. Antimicrobial consumption was analyzed monthly as defined daily doses (DDD)/100 bed-days and overall hospital and ICU consumption were evaluated. Results: An increase in the hospital consumption was noticed. Although only ceftaroline achieved statistical significance (p = 0.014), a rise was observed in most of the studied antimicrobials. A clear temporal pattern was detected. While an increase in ceftriaxone and azithromycin was observed during March, an increment in the consumption of daptomycin, carbapenems, linezolid, ceftaroline, novel cephalosporin/ß-lactamase inhibitors or triazoles during April-May was noticed. In the ICU, these findings were more evident, namely ceftriaxone (p = 0.029), carbapenems (p = 0.002), daptomycin (p = 0.002), azithromycin (p = 0.030), and linezolid (p = 0.011) but followed a similar temporal pattern. Conclusion: An increase in the antimicrobial consumption during the first wave of COVID-19 pandemic was noticed, especially in the ICU. Availability of updated protocols and antimicrobial stewardship programs are essential to optimize these outcomes.

Design of a relative value unit-based tool for the measurement and reimbursement of pharmacy services for clinical trials.

OBJECTIVE: To develop a relative value unit (RVU)-based tool for the measurement and reimbursement of pharmacy services for clinical trials. METHODS: A portfolio of activities was agreed by consensus in four tertiary hospitals. Related activities were pooled into several categories or intermediate products. We recorded the duration of each activity by multiple determinations. We then calculated the average time of all determinations. The reference activity was assigned a value of 1. All other activities were compared to the reference activity to obtain the RVU. To establish which items should be invoiced to third parties for the activities performed, we defined the final products (different types of clinical trials according to their complexity). RESULTS: Ten intermediate products and five final products were differentiated. Six intermediate products could be repeated over the course of a clinical trial and seven were performed whether or not the clinical trial had included patients. Each final product consisted of different categories. The total number of RVUs produced for a clinical trial was the sum of each constant category value plus the repetitive category values multiplied by the number of repetitions. CONCLUSION: The application of RVU methodology in investigational drug services allows a more precise quantification of services performed. After a prospective validation to confirm the applicability of this tool, it may contribute to more appropriate invoicing to third parties for these services.

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

PURPOSE: 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. METHODS: Data from patients admitted to a tertiary university hospital between January and August 2009 were used to design the risk score (training set). DRP were detected through a pharmacy warning system integrated in the computerized medical history. The variables associated with developing a DRP were identified through a binary multivariate logistic regression analysis and were used to compute the DRP risk score, which was subsequently validated in patients admitted between September and December 2009 (validation set). RESULTS: Of the 8713 patients included in the training set, at least one DRP was detected in 2425 (27.8%). Prescription of a higher number of drugs, higher comorbidity, advanced age, certain groups of the Anatomical Therapeutic Chemical classification system, and some major diagnostic categories were associated with risk of DRP. These variables were used to compute the DRP risk score. The area under the receiver operator characteristic curve was 0.778 (95%CI [0.768, 0.789]). Of the 4058 admissions included in the validation set, at least one DRP was detected in 876 (21.6%). The area under the receiver operator characteristic curve was 0.776 (95%CI [0.759, 0.792]). CONCLUSIONS: Knowledge of the variables associated with DRP could aid their early detection in at-risk patients. The use of an application that can be continually updated in daily clinical practice helps to optimize resources.

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 patient's 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.

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.

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

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.

Novetats farmacològiques en pediatria a Espanya: any 2008 / No disponible

No disponible