Antibiotics in the pipeline: a literature review (2017-2020).

INTRODUCTION: Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity and strains healthcare systems. Health care professionals can counter the rising AMR by promoting antibiotic stewardship and facilitating new drug development. Even with the economic and scientific challenges, it is reassuring that new agents continue to be developed. METHODS: This review addresses new antibiotics in the pipeline. We conducted a review of the literature including Medline, Clinicaltrials.org, and relevant pharmaceutical companies for approved and in pipeline antibiotics in phase 3 or new drug application (NDA). RESULTS: We found a number of new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in the healthcare settings. The number of these agents is limited against high priority organisms. The identified antibiotics were based mainly on previously known molecules or pre-existing antimicrobial agents. CONCLUSION: There are a limited number of antibiotics against high priority organisms such as multi-drug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. New antimicrobial agents directed against the top priority organisms as classified by the World Health Organization are urgently needed.

Safety and Outcome of Pharmacy-Led Vancomycin Dosing and Monitoring.

BACKGROUND: Therapeutic vancomycin trough levels correlate with therapeutic success and the development of renal failure. In this study, we aimed to describe the safety and outcome of pharmacy-led vancomycin dosing and monitoring. METHODS: We included adults requiring vancomycin for >48 h and who had a vancomycin trough level drawn near steady state. The primary outcome of the comparison was the achievement of therapeutic trough levels, defined as 10-20 µg/ml. Secondary outcome included acute renal failure. We compared these outcomes before and after the implementation of pharmacy-led vancomycin dosing and monitoring. RESULT: During the study period, a total of 278 patients were in the preimplementation phase and 286 were in the postintervention phase. There was a clear increase in the percentage of patients achieving the therapeutic range (50.5 vs. 79.7%, p = 0.0001) and an increase in the percentage of levels within the therapeutic range (31.6 vs. 59.1%; p = 0.0001). The number of cases receiving vancomycin increased by 5% and the duration of therapy decreased by 19.5%. More patients attained a therapeutic range of 10-20 µg/ml (i.e. the level was 31.6% in the preintervention and 59.1% in the postintervention phase). CONCLUSIONS: A higher percentage of patients achieved a therapeutic range and less nephrotoxicity when using a pharmacy-led protocol for vancomycin dosing.

Implementation of pharmacist-managed anticoagulation clinic in a saudi arabian health center.

BACKGROUND: During the past 2 decades, a paradigm shift in the management of oral anticoagulation therapy has occurred. A multidisciplinary approach has been used and has proved beneficial from both a cost and quality perspective. However, this approach to anticoagulation therapy is not well established in Saudi Arabia and the Middle East, and the traditional way of managing anticoagulation patients is still the mainstay of care. The Pharmacy Services Division (PSD) in collaboration with physician, nursing, and medical support enterprises at the Dhahran Health Center established the pharmacy-managed anticoagulation clinic (ACC). OBJECTIVE: To describe the implementation process of the first pharmacist-managed anticoagulation clinic in the eastern province of Saudi Arabia and its impact on patient care. METHODS: The PSD in collaboration with medical staff successfully created a care delivery model utilizing clinical pharmacists' expertise to provide comprehensive anticoagulation management services at Saudi Aramco Medical Services Organization (SAMSO). Planning included analyzing existing practices, reviewing the relevant literature, obtaining physician input, formulating a business proposal, and developing clinical protocols and guidelines. Collaborative relationships were established with the center laboratory, scheduling services, and nursing and medical departments. Clinic services include patient assessment, anticoagulation monitoring, warfarin dosage adjustment, medication dispensing at the clinic, patient education, and feedback to referring physicians. Data (2 years before and after clinic inception) for all patients enrolled at the anticoagulation clinic were reviewed to evaluate the impact of the clinic on anticoagulation management, adverse events, and patient satisfaction. RESULTS: A total of 578 patients were enrolled in the ACC. The total percentage of international normalized ratio (INR) within the target range was 59% versus 48% when compared to the previous traditional practice. The number of INR tests per patient dropped by 19%. Minor and major adverse events occurred in 10% and 1.5% of patients, respectively. Overall, the patients were very satisfied with the new clinic compared to the previous practice. CONCLUSION: Implementation of the pharmacist-managed ACC in the eastern province of Saudi Arabia had a positive impact on patient care based on the improvements in the number of patients whose INR was within therapeutic range and patient satisfaction scores.

Robotic Pharmacy Implementation and Outcomes in Saudi Arabia: A 21-Month Usability Study.

BACKGROUND: We describe the introduction, use, and evaluation of an automation and integration pharmacy development program in a private facility in Saudi Arabia. The project was specifically undertaken to increase throughput, reduce medication dispensing error rates, improve patient satisfaction, and free up pharmacists' time to allow for increased face-to-face consultations with patients. OBJECTIVE: We forecasted growth of our outpatient service at 25% per annum over 5- and 10-year horizons and set out to prepare our outpatient pharmacy service to meet this demand. Initial project goals were set as a 50% reduction in the average patient wait time, a 15% increase in patient satisfaction regarding pharmacy wait time and pharmacy services, a 25% increase in pharmacist productivity, and zero dispensing errors. This was expected to be achieved within 10 months of go-live. Realignment of pharmacist activity toward counseling and medication review with patients was a secondary goal, along with the rapid development of a reputation in the served community for patient-centered care. METHODS: Preimplementation data for patient wait time for dispensing of prescribed medications as a specific measure of patient satisfaction was gathered as part of wider ongoing data collection in this field. Pharmacist activity and productivity in terms of patient interaction time were gathered. Reported and discovered dispensing errors per 1000 prescriptions were also aggregated. All preimplementation data was gathered over an 11-month period. RESULTS: From go-live, data were gathered on the above metrics in 1-month increments. At the 10-month point, there had been a 53% reduction in the average wait time, a 20% increase in patient satisfaction regarding pharmacy wait time, with a 22% increase in overall patient satisfaction regarding pharmacy services, and a 33% increase in pharmacist productivity. A zero dispensing error rate was reported. CONCLUSIONS: The robotic pharmacy solution studied was highly effective, but a robust upstream supply chain is vital to ensure stock levels, particularly when automated filling is planned. The automation solution must also be seamlessly and completely integrated into the facility's software systems for appointments, medication records, and prescription generation in order to garner its full benefits. Overall patient satisfaction with pharmacy services is strongly influenced by wait time and follow-up studies are required to identify how to use this positive effect and make optimal use of freed-up pharmacist time. The extra time spent by pharmacists with patients and the opportunity for complete overview of the patient's medication history, which full integration provides, may allow us to address challenging issues such as medication nonadherence. Reduced wait times may also allow for smaller prescription fill volumes, and more frequent outpatient department visits, allowing patients to have increased contact time with pharmacists.

Empiric Antibiotic Therapy in the Treatment of Community-acquired Pneumonia in a General Hospital in Saudi Arabia.

BACKGROUND: Guideline-based empiric antimicrobial therapy is recommended for the treatment of community-acquired pneumonia (CAP). In this study, we evaluate the pattern of empiric antibiotics of CAP patients. MATERIALS AND METHODS: Patients with CAP were retrieved from the health information unit using the International Classification of Diseases, Ninth Revision. The electronic pharmacy database was used to retrieve prescribed antibiotics and the duration of therapy for each antibiotic. RESULTS: A total of 1672 adult patients were included in the study and 868 (52%) were male. Of all the patients, 47 (2.8%) were admitted to the intensive care unit (ICU). The most frequently used antibiotics were levofloxacin (68.12%), ceftriaxone (37.7%), imipenem-cilastatin (32.5%), and azithromycin (20.6%). The mean days of therapy of each of these antibiotics were 3.2, 2.8, 4.4, and 2.9, respectively. A combination therapy of levofloxacin and imipenem-cilastatin was prescribed for 355 (21.8%) of non-ICU patients versus 20 (60.6%) of ICU patients (P = 0.0007). Imipenem-cilastatin was prescribed for 518 (31.8%) of non-ICU patients versus 25 (56.8%) of ICU patients (P = 0.0009). Levofloxacin was prescribed for 1106 (68%) of non-ICU patients versus 33 (75%) of ICU patients (P = 0.412). Ceftriaxone use decreased significantly from 40.9% in 2013 to 25.9% in 2016 (P = 0.034). In addition, levofloxacin use increased from 63.7% to 75% (P = 0.63). CONCLUSION: The most commonly used antibiotics were levofloxacin, ceftriaxone, imipenem-cilastatin, and azithromycin. The data call for further refinement and prospective audit of antibiotic use in CAP, especially in non-ICU settings.

A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. The disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy. METHOD: We searched MEDLINE, Science Direct, Embase and Scopus databases for relevant papers published till March 2019 describing in vitro, in vivo or human therapy of MERS. RESULTS: Initial search identified 62 articles: 52 articles were from Medline, 6 from Embase, and 4 from Science Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta- 1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta- 1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. CONCLUSION: Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.

Benchmarking of antibiotic usage: An adjustment to reflect antibiotic stewardship program outcome in a hospital in Saudi Arabia.

Antimicrobial stewardship program aims to reduce antibiotic use. Periodic measurement and monitoring of antibiotic use and comparison within the institution as well as with other organizations are important indicators. We analyzed antibiotic usage in a general hospital in Saudi Arabia. Antibiotic data were collected retrospectively for 2011 and from 2013 to 2015, and only adult patients (>15year of age) were included in the study. Data were presented as days of therapy (DOT) and defined daily dose (DDD). DDD was adjusted per 100 bed-days and according to the case mix index (CMI). The total DDD was 37,557 in 2013, 36,550 in 2014 and 38,738 in 2015. The DDD per 100 patient-days was 90.7-94.5. There was a discordant findings of antibiotic measurements based on the DDD compared to DOT, and DDD/100 bed-days compared to DOT/100 bed-days. There was a negative correlation between CMI and DDD per 100 bed days (r -0.696), but a positive correlation of CMI with DOT (r +0.93). Adjusted DDD/100 bed-days showed decrease in the usage of antibiotics, reflecting activities of the antibiotic stewardship program. The increase in DOT/100 bed-days may indicate the favorable utilization of combination therapy. Antibiotic usage needs to be adjusted per 100 bed-days and correlated with CMI for better reflection of optimal antibiotic utilization, activities of the antibiotic stewardship program, and to allow benchmarking.

Restrictive reporting of selected antimicrobial susceptibilities influences clinical prescribing.

BACKGROUND: Cascade and restrictive reporting are useful strategies to enhance antibiotic stewardship programs. METHODS: We combined both strategies to improve the prescribing of antibiotics aimed at Gram-negative infections. RESULTS: For Enterobacter aerogenes, the susceptibility rates to amikacin increased from 10% to 100%; for third generation cephalosporins, these rates increased from 55% to 89%. The susceptibility rates of E. aerogenes to cefepime and piperacillin-tazobactam changed little, and the ampicillin susceptibility decreased from 30% in 2009 to 11% in 2010. For Proteus mirabilis, the susceptibility rates increased for third-generation cephalosporins (48% vs. 92%) and piperacillin-tazobactam (10% vs. 98%), with minimal changes for cefepime (96% vs. 93%), ampicillin (69% vs. 73%) and amikacin (96% vs. 84%). For Pseudomonas aeruginosa, the susceptibility rates improved slightly for third-generation cephalosporins (81% vs. 91%) but reduced for piperacillin-tazobactam (99% vs. 59%). Hospital-acquired Clostridium difficile infections decreased from 0.11 to 0.07 per 1000 patient days. CONCLUSIONS: Selective reporting helps physicians choose the most appropriate antibiotics for their patients within a stewardship program, with reduced C. difficile infection.

Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) has been reported to have a high case-fatality rate. Currently, there is no specific therapy or vaccine with proven effectiveness for MERS-CoV infections. METHODS: A combination of ribavirin and interferon therapy was used for the treatment of five MERS-CoV-positive patients. We reviewed the therapeutic schedule and the outcome of these patients. RESULTS: All patients were critically ill with acute respiratory distress syndrome treated with adjunctive corticosteroids and were on mechanical ventilation at the time of initiation of therapy. The median time from admission to therapy with ribavirin and interferon was 19 (range 10-22) days. None of the patients responded to the supportive or therapeutic interventions and all died of their illness. CONCLUSIONS: While ribavirin and interferon may be effective in some patients, our practical experience suggests that critically ill patients with multiple comorbidities who are diagnosed late in the course of their illness may not benefit from combination antiviral therapy as preclinical data suggest. There is clearly an urgent need for a novel effective antiviral therapy for this emerging global threat.

Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy.

The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been detected in a number of countries in the Middle East and Europe with an apparently high mortality rate. It is phylogenetically related to the SARS coronavirus and has also been associated with severe respiratory illness as well as nosocomial transmission in healthcare settings. Current international recommendations do not support any specific therapies; however, there are a number of agents, which were used during the SARS epidemic of 2003. It is possible that these might be active against the related MERS coronavirus. We have reviewed the literature on the safety and efficacy of therapies used in patients with SARS with a view to their potential use in patients with MERS-CoV infections.