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Open AccessArticle

Determinants of Inadequate Empiric Antimicrobial Therapy in ICU Sepsis Patients in Al-Madinah Al-Munawwarah, Saudi Arabia: A Comparison of Artificial Neural Network and Regression Analysis

by Ahmad Habeeb Hattab Dala Ali, Sabariah Noor Harun, Noordin Othman, Baharudin Ibrahim, Omer Elhag Abdulbagi, Ibrahim Abdullah and Indang Ariati Ariffin

Antibiotics 2023, 12(8), 1305; https://doi.org/10.3390/antibiotics12081305 - 10 Aug 2023

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Abstract

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and [...] Read more.

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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10 pages, 645 KiB

Open AccessArticle

Drug Utilization Evaluation and Impact of Pharmacist Interventions on Optimization of Piperacillin/Tazobactam Use: A Retrospective Analysis and Prospective Audit

by Savera Arain, Fahad Khalawi, Sainul Abideen Parakkal, Hassan S. AlHamad, Shabeer Ali Thorakkattil, Faisal Fahad J. Alghashmari, Bader AlHarbi, Nujud Bakhashwain, Weaam Mustafa Alzawad and Ali AlHomoud

Antibiotics 2023, 12(7), 1192; https://doi.org/10.3390/antibiotics12071192 - 15 Jul 2023

Cited by 1 | Viewed by 2463

Abstract

(1) Background: Piperacillin/tazobactam is a broad-spectrum antimicrobial encompassing most Gram-positive and Gram-negative aerobic and anaerobic bacteria. The inappropriate use of such broad-spectrum antibiotics is an important contributor to the rising rates of antimicrobial drug resistance worldwide. Drug utilization evaluation studies and pharmacists’ interventions [...] Read more.

(1) Background: Piperacillin/tazobactam is a broad-spectrum antimicrobial encompassing most Gram-positive and Gram-negative aerobic and anaerobic bacteria. The inappropriate use of such broad-spectrum antibiotics is an important contributor to the rising rates of antimicrobial drug resistance worldwide. Drug utilization evaluation studies and pharmacists’ interventions are vital to assess, develop, and promote the rational use of antibiotics. This drug utilization study aimed to evaluate the current utilization practice of piperacillin/tazobactam in a hospital setting and assess the impact of pharmacist intervention in improving its appropriate use. (2) Methodology: In this study, we used a retrospective cohort and a prospective cohort, a cross-sectional, observational method. It included a retrospective (Cycle A/pre-intervention-CycA) phase followed by an educational interventional phase conducted by the pharmacists. During the 2 months of educational intervention, pharmacists used several methods, including workshops, lectures, oral presentations, and the development and reinforcement of clinical pathways to promote the judicious use of piperacillin/tazobactam. This was followed by a prospective (Cycle B/post-intervention-CycB) phase to improve piperacillin/tazobactam usage appropriateness. The appropriateness criteria for this drug utilization evaluation were established based on antimicrobial guidelines, the published literature, the institutional antibiogram, consultation from the antimicrobial stewardship committee, and the product monograph (Tazocin). The appropriateness of CycA and CycB patients was compared using the measurable elements, including indication and dose based on renal function, timely order for cultures, de-escalation, and use of extended infusion protocol. (3) Results: The study population comprised 100 patients in both CycA and CycB. The mean age of the patients was 66.28 ± 16.15 and 67.35 ± 17.98, and the ratios of men to women were found to be 49:51 and 61:39 in CycA and CycB, respectively. It was observed that inappropriate usage was high in CycA patients, and the appropriateness was improved in CycB patients. A total of 31% of inappropriate empirical broad-spectrum use was found in CycA, and it was reduced to 12% in CycB patients. The transition of appropriateness was observed in all measurable criteria, which includes the optimized dose according to the renal function (CycA = 49% to CycB = 94%), timely bacterial culture orders (CycA = 47% to CycB = 74%), prompt de-escalation (CycA = 31% to CycB = 53%), and adherence to extended infusion institutional guidelines (CycA = 34% to CycB = 86%). (4) Conclusions: The study highlighted important aspects of inappropriate piperacillin/tazobactam use. This can be considerably improved by proper education and timely interventions based on the pharmacists’ vigilant approach. The study results emphasized the need for surveillance of piperacillin/tazobactam usage by conducting similar drug utilization evaluations and practice to improve quality and safety in healthcare organizations globally. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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11 pages, 529 KiB

Open AccessArticle

Addressing Antimicrobial Stewardship in Primary Care—Developing Patient Information Sheets Using Co-Design Methodology

by Ruby Biezen, Stephen Ciavarella, Jo-Anne Manski-Nankervis, Tim Monaghan and Kirsty Buising

Antibiotics 2023, 12(3), 458; https://doi.org/10.3390/antibiotics12030458 - 24 Feb 2023

Cited by 2 | Viewed by 1769

Abstract

Antibiotic resistance is a threat to global health, and inappropriate antibiotic use can be associated with adverse effects. Developing tools to encourage better communication between patients and general practitioners may reduce inappropriate use of antibiotics. The aim of the study was to develop [...] Read more.

Antibiotic resistance is a threat to global health, and inappropriate antibiotic use can be associated with adverse effects. Developing tools to encourage better communication between patients and general practitioners may reduce inappropriate use of antibiotics. The aim of the study was to develop shared decision support tools on common infections using a co-design methodology to address antimicrobial stewardship (AMS) in primary care. Three co-design/interview sessions were conducted with primary care providers and consumers between October 2019–April 2020 in Melbourne, Australia. Participants critiqued existing AMS tools, identified key elements required and optimised resulting prototypes. Primary care providers and consumers prioritised information to include in the AMS tools, such as when to see a doctor, management options, disease symptoms and cause of infection differently. However, both agreed content should be communicated in a plain, concise and logical manner, using inclusive and simple language accompanied by illustrations. Information sheets should be single-sided and A4-sized, appropriate for use before, during or after consultations. Co-design provided a collaborative forum to systematically design and develop products that meet the needs of both primary care providers and consumers. This resulted in the development of seven patient information sheets on common infections that encourage discussion of these infections, conservative management options and appropriate antibiotic use in primary care. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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12 pages, 1314 KiB

Open AccessArticle

Case Study: Using a Shared International Database to Document Veterinary Consumption of Antibiotics in Pakistan

by Mashkoor Mohsin, Umar Farooq, Maria Hartmann, Sandra Brogden, Lothar Kreienbrock and Julia Stoffregen

Antibiotics 2023, 12(2), 394; https://doi.org/10.3390/antibiotics12020394 - 15 Feb 2023

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Abstract

In this paper, we present a case study of Pakistan documenting the use of antimicrobial drugs in poultry flocks in the VetCAb-ID database. Unlike other databases, this system allows international users to upload their data directly. Based on expert interviews and a review [...] Read more.

In this paper, we present a case study of Pakistan documenting the use of antimicrobial drugs in poultry flocks in the VetCAb-ID database. Unlike other databases, this system allows international users to upload their data directly. Based on expert interviews and a review of the latest publications on the topic, we provide an alternative approach to harmonizing data collection among countries. This paper will provide impetus to formulate joint requirement documentation for an AMU database on a global level that international users can adapt for their own purposes and projects. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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16 pages, 946 KiB

Open AccessArticle

Evaluation of Systemic Antifungal Prescribing Knowledge and Practice in the Critical Care Setting among ICU Physicians and Clinical Pharmacists: A Cross-Sectional Study

by Sahar Mohamed Ibrahim, Nosiyba Adlan, Sufyan Mohammed Alomair, Ibrahim Butaiban, Ahmed Alsalman, Abdulmajeed Bawazeer, Monahi Alqahtani, Dalia Mohamed and Promise Madu Emeka

Antibiotics 2023, 12(2), 238; https://doi.org/10.3390/antibiotics12020238 - 23 Jan 2023

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Abstract

Management of invasive fungal infections (IFI) and subsequent treatment choices remain challenging for physicians in the ICU. Documented evidence shows increased practice of the inappropriate use of antifungal agents in the ICU. Continuous education of healthcare providers (HCPs) represents the cornerstone requirement for [...] Read more.

Management of invasive fungal infections (IFI) and subsequent treatment choices remain challenging for physicians in the ICU. Documented evidence shows increased practice of the inappropriate use of antifungal agents in the ICU. Continuous education of healthcare providers (HCPs) represents the cornerstone requirement for starting an antifungal stewardship program (AFS). This study aimed at evaluating knowledge gaps in systemic antifungal prescribing among physicians and clinical pharmacists in a critical care setting. A cross-sectional, multi-center, survey-based study was conducted in five tertiary hospitals located in Al-Ahsaa, Saudi Arabia between January and May 2021. A self-administered questionnaire was distributed among the targeted clinicians. A total of 63 clinicians were involved (65.5% ICU physicians and 34.5% clinical pharmacists). It was noted that a minority of the participating HCPs (3.2%) had overall good knowledge about antifungal prescribing, but the majority had either moderate (46%) or poor (50.8%) knowledge. The difference in overall knowledge scores between the ICU physicians and the clinical pharmacists (p = 0.925) was not significant. However, pharmacists showed better scores for the pharmacokinetics of antifungal therapy (p = 0.05). This study has revealed a significant gap in the knowledge and practice of clinicians as regards prescribing antifungal therapy in our area. Although the results cannot be generalized, the outcome of this study has exposed the need for a tailored training program essential for carrying out an AFS program. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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12 pages, 261 KiB

Open AccessArticle

WHO Point Prevalence Survey to Describe the Use of Antimicrobials at a Tertiary Care Center in Pakistan: A Situation Analysis for Establishing an Antimicrobial Stewardship Program

by Quratulain Shaikh, Samreen Sarfaraz, Anum Rahim, Aneela Hussain, Shameem Behram, Aamir Sikander Kazi, Mujahid Hussain and Naseem Salahuddin

Antibiotics 2022, 11(11), 1555; https://doi.org/10.3390/antibiotics11111555 - 04 Nov 2022

Cited by 4 | Viewed by 1549

Abstract

Antimicrobial stewardship is a systematic approach for promoting and monitoring responsible antimicrobial use globally. We conducted a prospective point prevalence survey of antimicrobial utilization among hospitalized adult patients during September 2021. The survey instrument was adapted from the WHO methodology for point prevalence [...] Read more.

Antimicrobial stewardship is a systematic approach for promoting and monitoring responsible antimicrobial use globally. We conducted a prospective point prevalence survey of antimicrobial utilization among hospitalized adult patients during September 2021. The survey instrument was adapted from the WHO methodology for point prevalence surveys, and it was conducted at The Indus Hospital and Health Network, Karachi. Among the 300 admitted patients, 55% were males and the mean age was 44 (±18) years. At least 67% of the patients received one antimicrobial agent and the most common indication was surgical prophylaxis (40%). The most frequently used were antibacterial agents (97%) among all antimicrobials. Amoxicillin/Clavulanic acid and Ceftriaxone were the most frequently used antibacterial agents, i.e., 14% each. At least 56% of the antibacterial agents were amenable to antimicrobial stewardship when reviewed by infectious disease (ID) experts. Reasons for stewardship were: antibacterial not indicated (n = 39, 17.0%), unjustified prolonged duration of antibacterial (n = 32, 13.9%), extended surgical prophylaxis (n = 60, 26.2%), non-compliance to surgical prophylaxis guidelines (n = 30, 13.1%), and antibacterial not needed on discharge (n = 27, 11.7%). Median days of therapy (DOT) per agent was 3 days (IQR 2–4), while median DOT per patient was 2 days (IQR 1–4). These data have described the pattern of antimicrobial utilization in our institute. We found a higher prevalence of antimicrobial use overall as compared to the global figures, but similar to other low- and middle-income countries. Two important areas identified were the use of antimicrobials on discharge and extended surgical prophylaxis. As a result of these data, our institutional guidelines were updated, and surgical teams were educated. A post-intervention survey will help us to further determine the impact. We strongly recommend PPS at all major tertiary care hospitals in Pakistan for estimating antimicrobial utilization and identifying areas for stewardship interventions. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

13 pages, 1388 KiB

Open AccessArticle

A Threshold Logistic Modelling Approach for Identifying Thresholds between Antibiotic Use and Methicillin-Resistant Staphylococcus aureus Incidence Rates in Hospitals

by Mamoon A. Aldeyab, Stuart E. Bond, Barbara R. Conway, Jade Lee-Milner, Jayanta B. Sarma and William J. Lattyak

Antibiotics 2022, 11(9), 1250; https://doi.org/10.3390/antibiotics11091250 - 15 Sep 2022

Cited by 3 | Viewed by 1673

Abstract

The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also [...] Read more.

The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also aimed to assess the impact of exceeding those thresholds that resulted in increased MRSA rates. The study was undertaken in a 700-bed hospital in England between January 2015 and December 2021 (84 monthly observations). By employing the threshold logistic modelling approach, we: (i) determined the cut-off percentile value of MRSA incidence that defines a critical level of MRSA; (ii) identified thresholds for fluoroquinolone and co-amoxiclav use that would accelerate MRSA incidence rates and increase the probability of reaching critical incidence levels; (iii) enabled a better understanding of the effect of antibiotic use on the probability of reaching a critical level of resistant pathogen incidence; (iv) developed a near real-time performance monitoring feedback system; (v) provided risk scores and alert signals for antibiotic use, with the ability to inform hospital policies, and control MRSA incidence; and (vi) provided recommendations and an example for the management of pathogen incidence in hospitals. Threshold logistic models can help hospitals determine quantitative targets for antibiotic usage and can also inform effective antimicrobial stewardship to control resistance in hospitals. Studies should work toward implementing and evaluating the proposed approach prospectively, with the aim of determining the best counter-measures to mitigate the risk of increased resistant pathogen incidence in hospitals. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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14 pages, 1600 KiB

Open AccessArticle

Identifying Antibiotic Use Targets for the Management of Antibiotic Resistance Using an Extended-Spectrum β-Lactamase-Producing Escherichia coli Case: A Threshold Logistic Modeling Approach

by Mamoon A. Aldeyab, Stuart E. Bond, Barbara R. Conway, Jade Lee-Milner, Jayanta B. Sarma and William J. Lattyak

Antibiotics 2022, 11(8), 1116; https://doi.org/10.3390/antibiotics11081116 - 17 Aug 2022

Cited by 4 | Viewed by 2047

Abstract

The aim of this study was to develop a logistic modeling concept to improve understanding of the relationship between antibiotic use thresholds and the incidence of resistant pathogens. A combined approach of nonlinear modeling and logistic regression, named threshold logistic, was used to [...] Read more.

The aim of this study was to develop a logistic modeling concept to improve understanding of the relationship between antibiotic use thresholds and the incidence of resistant pathogens. A combined approach of nonlinear modeling and logistic regression, named threshold logistic, was used to identify thresholds and risk scores in hospital-level antibiotic use associated with hospital-level incidence rates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli). Threshold logistic models identified thresholds for fluoroquinolones (61.1 DDD/1000 occupied bed days (OBD)) and third-generation cephalosporins (9.2 DDD/1000 OBD) to control hospital ESBL-producing E. coli incidence. The 60th percentile of ESBL-producing E. coli was determined as the cutoff for defining high incidence rates. Threshold logistic analysis showed that for every one-unit increase in fluoroquinolones and third-generation cephalosporins above 61.1 and 9.2 DDD/1000 OBD levels, the average odds of the ESBL-producing E. coli incidence rate being ≥60th percentile of historical levels increased by 4.5% and 12%, respectively. Threshold logistic models estimated the risk scores of exceeding the 60th percentile of a historical ESBL-producing E. coli incidence rate. Threshold logistic models can help hospitals in defining critical levels of antibiotic use and resistant pathogen incidence and provide targets for antibiotic consumption and a near real-time performance monitoring feedback system. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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11 pages, 1289 KiB

Open AccessArticle

Study the Effect of Conjugate Novel Ultra-Short Antimicrobial Peptide with Silver Nanoparticles against Methicillin Resistant S. aureus and ESBL E. coli

by Rula M. Darwish and Ali H. Salama

Antibiotics 2022, 11(8), 1024; https://doi.org/10.3390/antibiotics11081024 - 30 Jul 2022

Cited by 5 | Viewed by 1778

Abstract

Background: Bacterial resistance is a challenging limitation in infection treatment. This work evaluates the potential antibacterial activity of conjugation of Tryasine peptide with silver nanoparticles against selected pathogens. Materials and Methods: The peptide Tryasine was produced using three subunits of tryptophan and three [...] Read more.

Background: Bacterial resistance is a challenging limitation in infection treatment. This work evaluates the potential antibacterial activity of conjugation of Tryasine peptide with silver nanoparticles against selected pathogens. Materials and Methods: The peptide Tryasine was produced using three subunits of tryptophan and three lysine amino acids, then its purity was determined by reverse-phase high-performance liquid chromatography. The peptide was confirmed using mass spectrometry and electrospray ionization mass spectrometry. Silver nanoparticles conjugate with Tryasine was synthesized by adding Tryasine-silver nitrate solution in the presence of the reducing agent sodium borohydride. The presence of Tryasine-silver nanoparticles was indicated by the yellow-brown color and was further confirmed through ultraviolet-visible spectrophotometry. The minimum inhibitory and minimum bactericidal concentrations for Tryasine nanoparticles were determined against Staphylococcus aureus, Escherichia coli, methicillin resistant Staphylococcus aureus, and ESBL Escherichia coli using the microdilution method. Toxicity for nanoparticles conjugated with Tryasine was determined using erythrocyte hemolytic assay. Results: Tryasine alone was effective (MIC around 100 and 200 μM) against standard and resistant strains of bacteria used. However, Tryasine-silver nanoparticles were more effective with MICs ranging from 30 to 100 μM depending on the bacterial strain used. Tryasine-silver nanoparticles at concentration of 100 μM only caused 1% hemolysis on human erythrocytes after 30 min of incubation. Conclusions: The findings indicate that Tryasine-silver nanoparticles had good antibacterial activity against pathogenic strains of Gram-positive and Gram-negative bacteria. Additionally, the conjugate showed low hemolytic activity and cytotoxicity. Therefore, conjugation of Tryasine with silver nanoparticles is a promising treatment candidate for bacterial infection with low toxicity. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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23 pages, 675 KiB

Open AccessSystematic Review

A Systematic Review on Antimicrobial Pharmacokinetic Differences between Asian and Non-Asian Adult Populations

by Eko Setiawan, Menino Osbert Cotta, Jason A. Roberts and Mohd Hafiz Abdul-Aziz

Antibiotics 2023, 12(5), 803; https://doi.org/10.3390/antibiotics12050803 - 23 Apr 2023

Cited by 2 | Viewed by 1598

Abstract

While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential [...] Read more.

While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed. Thirty studies on meropenem, imipenem, doripenem, linezolid, and vancomycin were included in the final descriptive summaries. In studies recruiting hospitalised patients, inconsistent differences in the volume of distribution (V_d) and drug clearance (CL) of the studied antimicrobials between Asian and non-Asian patients were observed. Additionally, factors other than ethnicity, such as demographic (e.g., age) or clinical (e.g., sepsis) factors, were suggested to better characterise these pharmacokinetic differences. Inconsistent differences in pharmacokinetic parameters between Asian and non-Asian subjects/patients may suggest that ethnicity is not an important predictor to characterise interindividual pharmacokinetic differences between meropenem, imipenem, doripenem, linezolid, and vancomycin. Therefore, the dosing regimens of these antimicrobials should be adjusted according to patients’ demographic or clinical characteristics that can better describe pharmacokinetic differences. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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