Potential drugs used in the antibody-drug conjugate (ADC) architecture for cancer therapy.

Cytotoxic small-molecule drugs have a major influence on the fate of antibody-drug conjugates (ADCs). An ideal cytotoxic agent should be highly potent, remain stable while linked to ADCs, kill the targeted tumor cell upon internalization and release from the ADCs, and maintain its activity in multidrug-resistant tumor cells. Lessons learned from successful and failed experiences in ADC development resulted in remarkable progress in the discovery and development of novel highly potent small molecules. A better understanding of such small-molecule drugs is important for development of effective ADCs. The present review discusses requirements making a payload appropriate for antitumor ADCs and focuses on the main characteristics of commonly-used cytotoxic payloads that showed acceptable results in clinical trials. In addition, the present study represents emerging trends and recent advances of payloads used in ADCs currently under clinical trials.

Evaluation of vancomycin use in university-affiliated hospitals in Southern Khorasan Province (East Iran) based on HICPAC guidelines.

BACKGROUND: Vancomycin resistance has raised concerns about its effectiveness prospect in the treatment of patients with Gram-positive infections. The Healthcare Infection Control Practices Advisory Committee (HICPAC) has recently established guidelines to delineate improper use of vancomycin. In this light, we sought out to determine the appropriateness of vancomycin prescription using the HICPAC guidelines. SETTING: The study was carried out in two university-affiliated hospitals, Valiasr and Imam Reza, with 297 and 234 beds, respectively, from May 2012 to May 2013. METHODS: This retrospective study evaluated the vancomycin prescription and usage in the hospitals. Total vancomycin use was determined and expressed as vancomycin courses per 298 admitted patients. The patient information was collected on a data collection sheet as follows: demographic variables, etiology and localization of infection, microbiological data, duration of vancomycin treatment, reasons for vancomycin prescription, prescribed antibiotic dosing, and patient regimen. RESULTS: The average age of the patients and vancomycin treatment duration were 55.965 years and 10.5 days, respectively. Septicemia (15.7%) was the most common cause of vancomycin administration. Vancomycin use was documented to be appropriate and inappropriate in 236 (89.4%) and 28 (10.6%) patients, respectively. No statistically significant differences were found among the wards and hospitals (P values =0.66 and 0.54, respectively) in terms of appropriateness of vancomycin use based on the HICPAC criteria. In addition, 29.21% and 62% of all patients exhibited complete and partial recovery, respectively. We found that 90% of the cases showed compliance with the HICPAC recommendations. CONCLUSION: Comprehensive programs are required to improve the vancomycin use in the hospitals. Vancomycin use should be monitored due to its large-scale empiric use. The rate of improper use of vancomycin in the infection and intensive care unit services may be high, and pharmacists must take appropriate action to optimize the use of the drug.

Evaluation of vancomycin therapy in the adult ICUs of a teaching hospital in southern Iran.

BACKGROUND: Vancomycin resistance in intensive care units (ICUs) accounts for significant morbidity and excess costs. The objective of the present study was to determine the appropriateness of vancomycin use in the various ICUs of Nemazee Hospital, Shiraz, Iran. METHODS: This prospective study was performed on 95 critically ill patients (48 males and 47 females) who were treated with vancomycin for at least 3 subsequent doses in 6 ICUs during 12 months. Required demographic, clinical, and paraclinical data were collected by a pharmacist. Fifteen indexes were considered for evaluation of vancomycin use. RESULTS: Ventilator-associated hospital-acquired pneumonia (22.6%), sepsis (22.1%) and CNS infection (12.6%) were found to be the most important indications for vancomycin prescription. Vancomycin was prescribed empirically in 81% of patients. None of the patients received loading dose, and most of the patients received fixed dose. The rate of prolonged empiric antibiotic therapy was 68.5% in patients who received vancomycin. The mean score of vancomycin use in the ICUs of Nemazee Hospital was 7.1±0.6 out of 15, implying that the rate of vancomycin use was in accordance with the guideline proposed by the Department of Clinical Pharmacy of Nemazee Hospital based on Infectious Diseases Society of America by 47.3%. CONCLUSION: Based on our results, the weakness in using vancomycin was related to not administering loading dose, the practice of prescribing fixed-dose vancomycin and prolonged duration of empiric therapy. Efforts to improve the pattern of vancomycin prescription and utilization in these ICUs should be undertaken.