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Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (1 December 2020) | Viewed by 43604

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Special Issue Editors

Dr. Islam M. Ghazi

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Guest Editor

Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA
Interests: preclinical models; bacterial drug-resistance determinants; stewardship; pharmacokinetics/pharmacodynamics
Special Issues, Collections and Topics in MDPI journals

Dr. Kamilia Abdelraouf

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Guest Editor

Center for Anti-Infective Research and Development at Hartford Hospital, USA
Interests: Animal infection models, drug development, pharmacokinetics/pharmacodynamics

Special Issue Information

Dear Colleagues,

As the incidence of bacterial resistance to antibiotics continues to increase, multi-faceted research is necessary to combat difficult-to-treat infections and improve patient outcomes. Characterization of bacterial antibiotic-resistant genotypes/phenotypes assists drug discovery and develomental research, guides clinicians to devise optimal therapy regimens, provides insights into infection prevention and control, as well as impacts stewardship policies. All of which are aspects contributing to better patient care. The following types of research would be applicable for this special issue:

Basic laboratory or animal research focusing on antibiotic resistance among gram-positive and gram-negative bacteria: characterization, development or prevention
Advances in diagnostic methodoligies for early detection of antibiotic-resistant genotypes and phenotypes
Case reports describing novel antibiotic resistance mechanisms
Surveillance studies detailing prevelance of antibiotic resistance
Evaluation of stewardship policies and strategies
Review articles summarizing recent literature pertaining to antibiotic resistance
Clinical trials or retrospective analyses investigating treatment outcomes for patients with infections due to antibiotic resistant phenotypes

Dr. Islam M Ghazi
Dr. Kamilia Abdelraouf
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

Drug development
Antibiotic resistance evolution
Antibiotic-resistance
Multidrug-resistance
Phenotypic identification
Genotypic identification
Diagnositics
Antibacterial stewardship
Resistance mechanisms
Patient outcomes

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Published Papers (9 papers)

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Research

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12 pages, 260 KiB

Open AccessArticle

Acinetobacter baumannii Infections in Hospitalized Patients, Treatment Outcomes

by Diaa Alrahmany, Ahmed F. Omar, Gehan Harb, Wasim S. El Nekidy and Islam M. Ghazi

Antibiotics 2021, 10(6), 630; https://doi.org/10.3390/antibiotics10060630 - 25 May 2021

Cited by 14 | Viewed by 4028

Abstract

Background Acinetobacter baumannii (AB), an opportunistic pathogen, could develop into serious infections with high mortality and financial burden. The debate surrounding the selection of effective antibiotic treatment necessitates studies to define the optimal approach. This study aims to compare the clinical outcomes of commonly used treatment regimens in hospitalized patients with AB infections to guide stewardship efforts. Material and methods: Ethical approval was obtained, 320 adult patients with confirmed AB infections admitted to our tertiary care facility within two years were enrolled. The treatment outcomes were statistically analyzed to study the relation between antibiotic regimens and 14, 28, and 90-day mortality as the primary outcomes using binary logistic regression—using R software—in addition to the length of hospitalization, adverse events due to antibiotic treatment, and 90-day recurrence as secondary outcomes. Results: Among 320 patients, 142 (44%) had respiratory tract, 105 (33%) soft tissue, 42 (13%) urinary tract, 22 (7%) bacte iemia, and other infections 9 (3%). Nosocomial infections were 190 (59%) versus community-acquired. Monotherapy was significantly associated with lower 28-day (p < 0.05, OR:0.6] and 90-day (p < 0.05, OR:0.4) mortality rates, shorter length of stay LOS (p < 0.05, Median: −12 days] and limited development of adverse events (p < 0.05, OR:0.4). Subgroup analysis revealed similar results ranging from lower odds of mortality, adverse events, and shorter LOS to statistically significant correlation to monotherapy. Meropenem (MEM) and piperacillin/tazobactam (PIP/TAZ) monotherapies showed non-significant high odd ratios of mortalities, adverse events, and disparate LOS. There was a statistical correlation between most combined therapies and adverse events, and longer LOS. Colistin based and colistin/meropenem (CST/MEM) combinations were superior in terms of 14-day mortality (p = 0.05, OR:0.4) and (p < 0.05, OR:0.4) respectively. Pip/Taz and MEM-based combined therapies were associated with statistically non-significant high odd ratios of mortalities. Tigecycline (TGC)-based combinations showed a significant correlation to mortalities (p < 0.05, OR:2.5). Conclusion: Monotherapy was associated with lower mortality rates, shorter LOS, and limited development of adverse events compared to combined therapies. Colistin monotherapy, colistin/meropenem, and other colistin combinations showed almost equivalent mortality outcomes. Patients on combined therapy were more susceptible to adverse events and comparable LOS. The possible adverse outcomes of PIP/TAZ and MEM-based therapies in the treatment of MDRAB infections and the association of TGC with a higher mortality rate raise doubts about their treatment role. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

10 pages, 516 KiB

Open AccessArticle

Selective Decontamination of the Digestive Tract to Prevent Postoperative Pneumonia and Anastomotic Leakage after Esophagectomy: A Retrospective Cohort Study

by Robin Janssen, Frans Van Workum, Nikolaj Baranov, Harmen Blok, Jaap ten Oever, Eva Kolwijck, Alma Tostmann, Camiel Rosman and Jeroen Schouten

Antibiotics 2021, 10(1), 43; https://doi.org/10.3390/antibiotics10010043 - 5 Jan 2021

Cited by 5 | Viewed by 2905

Abstract

Infectious complications occur frequently after esophagectomy. Selective decontamination of the digestive tract (SDD) has been shown to reduce postoperative infections and anastomotic leakage in gastrointestinal surgery, but robust evidence for esophageal surgery is lacking. The aim was to evaluate the association between SDD and pneumonia, surgical-site infections (SSIs), anastomotic leakage, and 1-year mortality after esophagectomy. A retrospective cohort study was conducted in patients undergoing Ivor Lewis esophagectomy in four Dutch hospitals between 2012 and 2018. Two hospitals used SDD perioperatively and two did not. SDD consisted of an oral paste and suspension (containing amphotericin B, colistin, and tobramycin). The primary outcomes were 30-day postoperative pneumonia and SSIs. Secondary outcomes were anastomotic leakage and 1-year mortality. Logistic regression analyses were performed to determine the association between SDD and the relevant outcomes (odds ratio (OR)). A total of 496 patients were included, of whom 179 received SDD perioperatively and the other 317 patients did not receive SDD. Patients who received SDD were less likely to develop postoperative pneumonia (20.1% vs. 36.9%, p < 0.001) and anastomotic leakage (10.6% vs. 19.9%, p = 0.008). Multivariate analysis showed that SDD is an independent protective factor for postoperative pneumonia (OR 0.40, 95% CI 0.23–0.67, p < 0.001) and anastomotic leakage (OR 0.46, 95% CI 0.26–0.84, p = 0.011). Use of perioperative SDD seems to be associated with a lower risk of pneumonia and anastomotic leakage after esophagectomy. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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16 pages, 3725 KiB

Open AccessArticle

Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

by Hao Lu, Wenjia Lu, Yongwei Zhu, Chenchen Wang, Liming Shi, Xiaodan Li, Zhaoyuan Wu, Gaoyan Wang, Wenqi Dong, Chen Tan and Manli Liu

Antibiotics 2021, 10(1), 26; https://doi.org/10.3390/antibiotics10010026 - 30 Dec 2020

Cited by 10 | Viewed by 3101

Abstract

Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the Streptococcus suis (S. suis) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortality despite adequate treatment. A number of antibiotics exhibit excellent bactericidal effects in vivo, such as fluoroquinolones, aminoglycosides (gentamicin) and β-lactams (penicillin G, ceftiofur, or amoxicillin), but are less effective for treating STSLS. Therefore, there is an urgent need to identify new compounds that can reduce the damage caused by STSLS. In the present study, we identified auranofin, an orally bioavailable FDA-approved anti-rheumatic drug as a candidate repurposed drug to treat severe S. suis infections. Our results showed that auranofin can bind to the functional domain of bacterial thioredoxin reductase, decreasing the reducing redox-responsive capacity of target bacteria and allowing for the killing of S. suis cells. We also observed that auranofin has antibacterial activity against other gram-positive bacteria, such as multidrug resistant Streptococcus pneumoniae (MDRSP), Streptococcus agalactiae, and vancomycin-resistant strains of Staphylococcus aureus. Additionally, auranofin is capable of eradicating intracellular S.suis present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with S. suis. Compared to the ampicillin treatment group, the survival rate of mice in the auranofin treatment group in severely infected model mice was significantly improved. These results suggest that auranofin has the potential for use as an effective antibiotic against S. suis. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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22 pages, 967 KiB

Open AccessArticle

Antimicrobial Resistance, Pharmacists, and Appreciative Inquiry: Development of a Novel Measurement Tool

by Rojjares Netthong, Keivan Ahmadi and Ros Kane

Antibiotics 2020, 9(11), 798; https://doi.org/10.3390/antibiotics9110798 - 11 Nov 2020

Cited by 5 | Viewed by 4336

Abstract

Antimicrobial resistance (AMR) is a threat to achieving the United Nation’s (UN) sustainable development goals (SDGs). The behavior of stakeholders has directly influenced the extent of AMR and understanding underpinning knowledge and attitudes is an important step towards understanding these behaviors. The aim of this study was to develop and validate a novel questionnaire, utilizing the theory of Appreciative Inquiry, to measure knowledge and attitudes around antibiotic resistance amongst community pharmacists throughout Thailand. A survey tool was developed using the Appreciative Inquiry theory, and was piloted in a non-probability sample of practicing community pharmacists. Descriptive and inferential statistics were applied and the tool validated, using a three-step psychometric validation process. A total of 373 community pharmacists participated in the study. The survey tool was found to be valid and reliable. The “Knowledge” domain of the survey tool showed an acceptable level of reliability (Cronbach’s alpha 0.64); while the “Attitude” domain showed an excellent reliability level (Cronbach’s alpha 0.84). This new survey tool has been designed to measure attitudes and knowledge of antibiotic resistance by utilizing the Discovery phase of Appreciative Inquiry theory amongst community pharmacists in Thailand. This survey tool has the potential to be used by other researchers across different settings. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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9 pages, 226 KiB

Open AccessArticle

Fluoroquinolone Versus Nonfluoroquinolone Treatment of Bloodstream Infections Caused by Chromosomally Mediated AmpC-Producing Enterobacteriaceae

by Sarah Grace Gunter, Katie E. Barber, Jamie L. Wagner and Kayla R. Stover

Antibiotics 2020, 9(6), 331; https://doi.org/10.3390/antibiotics9060331 - 17 Jun 2020

Cited by 2 | Viewed by 2419

Abstract

Objectives: Chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) display high susceptibility to fluoroquinolones; minimal clinical data exist supporting comparative clinical outcomes. The objective of this study was to compare treatment outcomes between fluoroquinolone and nonfluoroquinolone definitive therapy of bloodstream infections caused by CAE. Methods: This retrospective cohort assessed adult patients with positive blood cultures for CAE that received inpatient treatment for ≥48 h. The primary outcome was difference in clinical failure between patients who received fluoroquinolone (FQ) versus non-FQ treatment. Secondary endpoints included microbiological cure, infection-related length of stay, 90-day readmission, and all-cause inpatient mortality. Results: 56 patients were included in the study (31 (55%) received a FQ as definitive therapy; 25 (45%) received non-FQ). All non-FQ patients received a beta-lactam (BL). Clinical failure occurred in 10 (18%) patients, with 4 (13%) in the FQ group and 6 (24%) in the BL group (p = 0.315). Microbiological cure occurred in 55 (98%) patients. Median infection-related length of stay was 10 (6–20) days, with a significantly longer stay occurring in the BL group (p = 0.002). There was no statistical difference in 90-day readmissions between groups (7% FQ vs. 17% BL; p = 0.387); one patient expired. Conclusion: These results suggest that fluoroquinolones do not adversely impact clinical outcomes in patients with CAE. When alternatives to beta-lactam therapy are needed, fluoroquinolones may provide an effective option. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

9 pages, 1234 KiB

Open AccessArticle

A Prediction Tool for the Presence of Ceftriaxone-Resistant Uropathogens upon Hospital Admission

by Nancy Yanzhe Li, Gang Quan Poh, Gladys Chung Wei Teng, Hui Hiong Chen, Douglas Su Gin Chan, Siew-Pang Chan, Paul Anantharajah Tambyah, Natasha Bagdasarian and Jia En Wu

Antibiotics 2020, 9(6), 316; https://doi.org/10.3390/antibiotics9060316 - 10 Jun 2020

Cited by 4 | Viewed by 2906

Abstract

Antimicrobial resistance among uropathogens is a particularly pressing problem in the Asia-Pacific region. The objectives of this study were to determine the incidence and susceptibility of uropathogens upon hospital admission and to develop a risk-scoring model to predict the presence of ceftriaxone-resistance uropathogens (CrP). This was a retrospective observational cohort study of patients with a positive urine culture within 48 h of presentation at National University Hospital, Singapore between June 2015 and August 2015. Escherichia coli was the most common uropathogen isolated (51.7%), followed by Klebsiella pneumonia (15.1%) and Pseudomonas aeruginosa (8.2%). Overall, 372 out of 869 isolates (42.8%) were resistant to ceftriaxone. Hospitalization for ≥2 days within past 30 days, antibiotic use within the past 3 months and male gender were associated with the presence of CrP. A risk score based on these parameters successfully predicted CrP with an area under the curve of 0.68. The risk score will help clinicians to accurately predict antibiotic resistance at the individual patient level and allow physicians to safely prescribe empiric ceftriaxone in patients at low risk of CrP, thus reducing the antibiotic selection pressure that is driving carbapenem resistance in hospitals throughout Asia. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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11 pages, 833 KiB

Open AccessArticle

Effects of Antibiotics on the Intestinal Microbiota of Mice

by Frederik Boetius Hertz, Andries E. Budding, Malieka van der Lugt-Degen, Paul H. Savelkoul, Anders Løbner-Olesen and Niels Frimodt-Møller

Antibiotics 2020, 9(4), 191; https://doi.org/10.3390/antibiotics9040191 - 17 Apr 2020

Cited by 23 | Viewed by 6259

Abstract

Studies on human and mouse gastrointestinal microbiota have correlated the composition of the microbiota to a variety of diseases, as well as proved it vital to prevent colonization with resistant bacteria, a phenomenon known as colonization resistance. Antibiotics dramatically modify the gut community and there are examples of how antibiotic usage lead to colonization with resistant bacteria [e.g., dicloxacillin usage selecting for ESBL-producing E. coli carriage], as shown by Hertz et al. Here, we investigated the impact of five antibiotics [cefotaxime, cefuroxime, dicloxacillin, clindamycin, and ciprofloxacin] on the intestinal microbiota in mice. Five different antibiotics were each given to groups of five mice. The intestinal microbiotas were profiled by use of the IS-pro analysis; a 16S–23S rDNA interspace [IS]-region-based profiling method. For the mice receiving dicloxacillin and clindamycin, we observed dramatic shifts in dominating phyla from day 1 to day 5. Of note, diversity increased, but overall bacterial load decreased. For ciprofloxacin, cefotaxime, and cefuroxime there were few overall changes. We speculate that antibiotics with efficacy against the abundant anaerobes in the gut, particularly Bacteroidetes, can in fact be selected for resistant bacteria, disregarding the spectrum of activity. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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14 pages, 1595 KiB

Open AccessArticle

Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia

by Noriyuki Ishihara, Nobuhiro Nishimura, Kazuro Ikawa, Fumi Karino, Kiyotaka Miura, Hiroki Tamaki, Takahisa Yano, Takeshi Isobe, Norifumi Morikawa and Kohji Naora

Antibiotics 2020, 9(3), 113; https://doi.org/10.3390/antibiotics9030113 - 6 Mar 2020

Cited by 9 | Viewed by 4586

Abstract

The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.5 g) was infused intravenously three times daily to Japanese patients over 75 years old. The plasma concentrations of PIPC and TAZ were determined using high-performance liquid chromatography and modeled using the NONMEM program. PK/PD analysis with a random simulation was conducted using the final population PK model to estimate the probability of target attainment (PTA) profiles for various PIPC/TAZ-regimen–minimum-inhibitory-concentration (MIC) combinations. The PTAs for PIPC and TAZ were determined as the fraction that achieved at least 50% free time > MIC and area under the free-plasma-concentration–time curve over 24 h ≥ 96 μg h/mL, respectively. A total of 18 cases, the mean age of which was 86.5 ± 6.0 (75–101) years, were investigated. The plasma-concentration–time profiles of PIPC and TAZ were characterized by a two-compartment model. The parameter estimates for the final model, namely the total clearance, central distribution volume, peripheral distribution volume, and intercompartmental clearance, were 4.58 + 0.061 × (CL_cr − 37.4) L/h, 5.39 L, 6.96 L, and 20.7 L/h for PIPC, and 5.00 + 0.059 × (CL_cr − 37.4) L/h, 6.29 L, 7.73 L, and 24.0 L/h for TAZ, respectively, where CL_cr is the creatinine clearance. PK/PD analysis using the final model showed that in drug-resistant strains with a MIC > 8 μg/mL, 4.5 g of PIPC/TAZ every 6 h was required, even for the patients with a CL_cr of 50–60 mL/min. The population PK model developed in this study, together with MIC value, can be useful for optimizing the PIPC/TAZ dosage in the over-75-year-old patients, when they are administered PIPC/TAZ. Therefore, the findings of present study may contribute to improving the efficacy and safety of the administration of PIPC/TAZ therapy in late elderly patients with pneumonia. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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Review

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15 pages, 939 KiB

Open AccessReview

Intolerable Burden of Impetigo in Endemic Settings: A Review of the Current State of Play and Future Directions for Alternative Treatments

by Solomon Abrha, Wubshet Tesfaye and Jackson Thomas

Antibiotics 2020, 9(12), 909; https://doi.org/10.3390/antibiotics9120909 - 15 Dec 2020

Cited by 8 | Viewed by 12199

Abstract

Impetigo (school sores) is a common superficial bacterial skin infection affecting around 162 million children worldwide, with the highest burden in Australian Aboriginal children. While impetigo itself is treatable, if left untreated, it can lead to life-threatening conditions, such as chronic heart and kidney diseases. Topical antibiotics are often considered the treatment of choice for impetigo, but the clinical efficacy of these treatments is declining at an alarming rate due to the rapid emergence and spread of resistant bacteria. In remote settings in Australia, topical antibiotics are no longer used for impetigo due to the troubling rise of antimicrobial resistance, demanding the use of oral and injectable antibiotic therapies. However, widespread use of these agents not only contributes to existing resistance, but also associated with adverse consequences for individuals and communities. These underscore the urgent need to reinvigorate the antibiotic discovery and alternative impetigo therapies in these settings. This review discusses the current impetigo treatment challenges in endemic settings in Australia and explores potential alternative antimicrobial therapies. The goals are to promote intensified research programs to facilitate effective use of currently available treatments, as well as developing new alternatives for impetigo. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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