Dose Optimization of Colistin: A Systematic Review

Colistin is considered a last treatment option for multi-drug and extensively resistant Gram-negative infections. We aimed to assess the available data on the dosing strategy of colistin. A systematic review was performed to identify all published studies on the dose optimization of colistin. Grey literature and electronic databases were searched. Data were collected in a specified form and the quality of the included articles was then assessed using the Newcastle-Ottawa scale for cohort studies, the Cochrane bias tool for randomized clinical trials (RCT), and the Joanna Briggs Institute (JBI) critical checklist for case reports. A total of 19 studies were included, of which 16 were cohort studies, one was a RCT, and two were case reports. A total of 18 studies proposed a dosing regimen for adults, while only one study proposed a dosing schedule for pediatric populations. As per the available evidence, a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h was considered the most appropriate dosing strategy to optimize the safety and efficacy of treatment and improve clinical outcomes. This review supports the administration of a loading dose followed by a maintenance dose of colistin in severe and life-threatening multi-drug Gram-negative bacterial infections

Gender Differences in Adverse Drug Reactions during HAART Therapy in HIV/AIDS Patients at a Tertiary Care Hospital Penang, Malaysia

Aims and objective: Current study is aimed to explore and observe adverse drug reactions occurrence of antiretroviral therapy and to examine the gender differences in treatment outcomes of HIV/AIDS patients during HAART therapy. Method: An observational retrospective study of all patients on HAART therapy diagnosed with HIV infection from January 2007 to December 2012 was conducted at infectious disease department of Hospital Pulau Pinang, Malaysia. Patients socio-demographic, clinical and laboratory data was retrieved via self developed validated data collection form. Results: Out of 743 patients 571 (76.8%) were male and 172 (23.1%) were female patients. A total number of 425 (57.2%) adverse drug reactions were reported among which 311 (73.1%) occurred in males and 114 (26.8%) in female patients, with a significant statistical relationship (p=0.02, OR=1.21). Out of total ADRs (57.2%) observed in both genders, a significant association was observed in Lipodystrophy (p=0.05), anemia (p=0.02), Peripheral Neuropathy (p=0.02) and pancreatitis (p=0.01). A total of 455 (79.6%) male and 139 (80.8%) female patients have improvement in CD4 cells count at the final follow up, a significant association (p=0.05) was observed among the mode of transmission and treatment outcome. Conclusion: Overall, the ADRs observed in both gender emphasize the importance of developing safer HAART regimens and managing these adverse effects in a timely manner in order to avoid long-term health consequences

Antimicrobial Usage and Resistance in Makkah Region Hospitals: A Regional Point Prevalence Survey of Public Hospitals

(1) Background: Inappropriate use of antimicrobials and subsequently rise of antimicrobial resistance (AMR) remains a major public health priority. Over-prescribing of broad-spectrum antibiotics is one of the main contributing factors for the emergence of AMR. We sought to describe antimicrobial prescribing trends among patients in public hospitals in Makkah hospitals. (2) Method: We undertook a point prevalence survey (PPS) in six hospitals in Makkah, Saudi Arabia, from January 2019 to July 2019. The survey included all the inpatients receiving antimicrobials on the day of PPS. Data was collected using the Global point prevalence survey (PPS) tool developed by the University of Antwerp, Belgium. (3) Results: Of 710 hospitalized patients, 447 patients (61.9%) were treated with one or more antimicrobials during the study period. The average bed occupancy among six hospitals was 74.4%. The majority of patients received antimicrobials parenterally (90.3%). Of the total prescribed antimicrobials, 415 (53.7%) antimicrobials were used in medical departments, 183 (23.7%) in surgical departments, and 175 (22.6%) in ICUs. Pneumonia (17.3%), skin and soft tissue infections (10.9%), and sepsis (6.6.%) were three common clinical indications. Ceftriaxones were the most commonly used antibiotics that were prescribed in 116 (15%) of patients, followed by piperacillin, with an enzyme inhibitor in 84 (10.9%). (4) Conclusion: There was a high prevalence of antibiotic use in the hospitals of Makkah, which could be a potential risk factor for the incidence of resistant strains, particularly MRSA infection. Public health decision-makers should take these findings into consideration to update national policies for antibiotic use in order to reduce the risks of further increases of AMR

Dose optimization of β-lactams antibiotics in pediatrics and adults:A systematic review

Background: β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses

Threat of antimicrobial resistance among pilgrims with infectious diseases during Hajj : lessons learnt from COVID-19 pandemic

Hajj pilgrimage is a large mass gathering global event that may facilitate the spread and emergence of various infectious diseases as well as antimicrobial resistance (AMR) in a local and global scenario. Planning and preparing for these public health issues is a challenging and complex process for the Kingdom of Saudi Arabia (KSA) health authorities. Despite multiple efforts for the prevention and treatment of infectious diseases through longtime funding in education and medical care, the prevalence of infectious disease is still high among Hajj pilgrims. The commonly observed infectious diseases during Hajj include respiratory tract infections (influenza and pneumonia), urinary tract infections and skin infections that may necessitate the use of antimicrobials. Beta-lactams are used as a first-line treatment for hospital acquired infections as well as community acquired infections due to their broad-spectrum activity. However, most of the bacterial isolates such as Staphylococcus spp., Pseudomonas spp. and E. coli are resistant to beta-lactams. Irrational use of anti-microbials, lack of infection prevention practices and suboptimal healthcare access further exacerbate the risk of spreading AMR among Hajj pilgrims. Enhanced collaboration between countries, sharing of best practices and international cooperation are crucial in addressing AMR threats among pilgrims. Consequently, robust surveillance systems for early detection and monitoring of AMR, collaboration with national as well as international healthcare agencies, effective infection prevention and control measures, public awareness, and rational use of antimicrobials via antimicrobial stewardship programs are required to mitigate the risk of AMR and ensure the health and well-being of pilgrims during Hajj

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients

Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: “vancomycin”, “safety”, “efficacy” and “loading dose” combined with the Boolean operator “AND” or “OR”. Results: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. Conclusions: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions

Antimicrobial resistance among pilgrims: a retrospective study from two hospitals in Makkah, Saudi Arabia

Objective: To identify commonly reported community-acquired organisms and antimicrobial resistance patterns exhibited by Gram-positive and Gram-negative pathogens among pilgrims visiting emergency care departments in Makkah. Method: The study was designed as a retrospective audit of all patients (pilgrims) admitted to two hospitals and residing in the city of Makkah, Saudi Arabia. Results: Among 374 isolates, Gram-negative pathogens accounted for 280 (75%), while the remaining 94 (25%) were Gram-positive organisms. Among all isolated pathogens, the highest resistance was observed for amoxicillin–clavulanic acid. Klebsiella pneumoniae had the highest resistance to amoxicillin–clavulanic acid and ampicillin. Most of the organisms were sensitive to tobramycin except Acinetobacter baumannii (n = 3, 50%), Escherichia coli (n = 4, 57%), and K. pneumoniae (n = 6, 46%). Conclusion: Overall, a high resistance was observed for beta-lactam antibiotics. In addition, a high resistance was noted for ceftazidime with A. baumannii species (n = 16, 77%). However, for quinolones, the highest resistance to ciprofloxacin was observed for E. coli, A. baumannii, methicillin-resistant Staphylococcus aureus, and K. pneumoniae

Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review

(1) Background: Pneumocystis jirovecii pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal dosing strategies of Trimethoprim–Sulfamethoxazole (TMP-SMX). Therefore, to ensure the safety of TMP-SMX, there is a high demand to review current evidence in PCP patients with a focus on dose optimization strategies; (2) Methods: Various databases were searched from January 2000 to December 2021 for articles in English, focusing on the dose optimization of TMP-SMX. The data were collected in a specific form with predefined inclusion and exclusion criteria. The quality of each article was evaluated using a Newcastle–Ottawa Scale (NOS) for retrospective studies, Joanna Briggs Institute (JBI) critical checklist for case reports, and Cochrane bias tool for randomized clinical trials (RCTs); (3) Results: Thirteen studies met the inclusion criteria for final analysis. Of the 13 selected studies, nine were retrospective cohort studies, two case reports, and two randomized controlled trials (RCT). Most of the studies compared the high-dose with low-dose TMP-SMX therapy for PCP. We have found that a low dose of TMP-SMX provides satisfactory outcomes while reducing the mortality rate and PCP-associated adverse events. This strategy reduces the economic burden of illness and enhances patients’ compliance to daily regimen plan; (4) Conclusions: The large-scale RCTs and cohort studies are required to improve dosing strategies to prevent initial occurrence of PCP or to prevent recurrence of PCP in immune compromised patients