The Five Ds of Outpatient Antibiotic Stewardship for Urinary Tract Infections

Goebel, Melanie; Trautner, Barbara W.; Grigoryan, Larissa

doi:10.1128/cmr.00003-20

Cited by 63 publications

(43 citation statements)

References 197 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With an effective dose established, we aimed to evaluate fabimycin in a murine model of an infection with high translational value. Urinary tract infections (UTIs) represent one of the biggest risks for healthy individuals in terms of exposure to antibiotic-resistant bacteria with many individuals contracting one in their lifetime (roughly 1 in 2 women and 1 in 10 men); UTIs caused by Gram-negative pathogens, particularly those that are drug-resistant, are becoming more frequent and remain a major clinical challenge. − As E. coli is the causative agent in the vast majority of UTIs, fabimycin was evaluated in a murine UTI model with a challenging, extensively drug-resistant strain of carbapenem-resistant E. coli (fabimycin MIC = 2 μg/mL). When intravenously dosed at 33.3 mg/kg, three times a day, fabimycin was able to achieve 3.0, 2.8, 2.9, and 1.9 log 10 reductions in bacterial load relative to the vehicle in the spleen, bladder, liver, and kidney tissues, respectively (Figure ).…”

Section: Resultsmentioning

confidence: 99%

An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections

et al. 2022

View full text Add to dashboard Cite

Genomic studies and experiments with permeability-deficient strains have revealed a variety of biological targets that can be engaged to kill Gram-negative bacteria. However, the formidable outer membrane and promiscuous efflux pumps of these pathogens prevent many candidate antibiotics from reaching these targets. One such promising target is the enzyme FabI, which catalyzes the rate-determining step in bacterial fatty acid biosynthesis. Notably, FabI inhibitors have advanced to clinical trials for Staphylococcus aureus infections but not for infections caused by Gram-negative bacteria. Here, we synthesize a suite of FabI inhibitors whose structures fit permeation rules for Gram-negative bacteria and leverage activity against a challenging panel of Gram-negative clinical isolates as a filter for advancement. The compound to emerge, called fabimycin, has impressive activity against >200 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, and does not kill commensal bacteria. X-ray structures of fabimycin in complex with FabI provide molecular insights into the inhibition. Fabimycin demonstrates activity in multiple mouse models of infection caused by Gram-negative bacteria, including a challenging urinary tract infection model. Fabimycin has translational promise, and its discovery provides additional evidence that antibiotics can be systematically modified to accumulate in Gram-negative bacteria and kill these problematic pathogens.

show abstract

Section: Resultsmentioning

confidence: 99%

An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although most studies focus on adult patients, the principles are the same for all age groups. The five-D model includes correct diagnosis, the right drug, dose, and duration, and finally de-escalation (narrow spectrum antibiotics, or stopping antibiotics based on culture results) [ 27 ]. Anti- microbial stewardship programs have proven their effectiveness in urgent care [ 28 ] as well as in hospitalized patients with potentially fatal outcomes [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections

Novales

Flores-Moreno²,

López-Vidal³

et al. 2022

Antibiotics

View full text Add to dashboard Cite

The rise in antimicrobial resistance (AMR) has complicated the management of urinary tract infections (UTIs). The objective of this study was to evaluate the antimicrobial susceptibility patterns of Escherichia coli and Klebsiella pneumoniae. Design: prospective observational study. Bacteria were classified as susceptible or resistant to ampicillin-sulbactam, amikacin, gentamicin, ciprofloxacin, norfloxacin, nitrofurantoin, trimethoprim-sulfamethoxazole (TMP/SMZ), ertapenem, meropenem, and fosfomycin. The sensitivity to fosfomycin and chloramphenicol was evaluated by the disk diffusion method. Statistical analysis: the chi-square test and Fisher’s exact test were used to compare differences between categories. A p value < 0.05 was considered statistically significant. Isolates were collected from January 2019 to November 2020 from 21 hospitals and laboratories. A total of 238 isolates were received: a total of 156 E. coli isolates and 82 K. pneumoniae isolates. The majority were community-acquired infections (64.1%). Resistance was >20% for beta-lactams, aminoglycosides, fluoroquinolones, and TMP/SMZ. For E. coli isolates, resistance was <20% for amikacin, fosfomycin, and nitrofurantoin; for K. pneumoniae, amikacin, fosfomycin, chloramphenicol, and norfloxacin. All were susceptible to carbapenems. K. pneumoniae isolates registered a higher proportion of extensively drug-resistant bacteria in comparison with E. coli (p = 0.0004). In total, multidrug-resistant bacteria represented 61% of all isolates. Isolates demonstrated high resistance to beta-lactams, fluoro-quinolones, and TMP/SMZ.

show abstract

“…Although, antimicrobial stewardship programs that promote and focus on the appropriate use of antimicrobials and strategies to improve patient outcomes, and reduce antimicrobial resistance have been shown to be successful in many academic hospitals [7] [8], they are less-frequently implemented in community settings where most antibiotic prescribing takes place [9] [10], and gaps still remain in the knowledge of how to optimally design and sustain these programs.…”

Section: Introductionmentioning

confidence: 99%

Knowledge, Attitudes and Practices of Antibiotic Use and Antimicrobial Resistance among Medical Students in a Private University in Dominica, West Indies

Olatunde¹,

Owolabi²

2022

AiM

View full text Add to dashboard Cite

Antibiotics are indispensable to maintaining human health, however, their overuse has resulted in resistant organisms which present a significantly higher burden to the low to middle income countries, due to the high incidence of communicable diseases. Insufficient antimicrobial-related training for physicians during their undergraduate education could have a negative impact on their prescribing. This study assessed the knowledge, attitudes and practices of antibiotic use and antimicrobial resistance among medical students in a private university in Dominica, a resource-limited country, in order to facilitate more effective education of these future prescribers. A crosssectional study was undertaken with the medical students from February 2021 to April 2021 using a 36-item questionnaire. Data analysis was achieved using descriptive statistics. A total of 85 students participated in the study, majority (70%) were female, African, aged 23.8 ± 4.6 years and single. Between 64 and 99% of the respondents reported no risk factors for communicable diseases and demonstrated a low to moderate (10% -40%) negative response to knowledge-related questions. The majority (70%) of the respondents who had used antibiotics in the past 12 months reported efficacy and limited side-effects, but confirmed lack of knowledge about the classes of antibiotics prescribed to them. Almost half of the medical students (48%) reported having abused antibiotics, while about a third (35%) of the respondents reported sharing antibiotics with friends or loved ones in the past. There was no significant association between age, gender, and the medical students' knowledge of antibiotic resistance (p > 0.05). However, they reported that they would like more education on antimicrobial use and resistance. The medical students in this study showed knowledge of antimicrobial How to cite this paper: Olatunde, S.K. and Owolabi, J.B. (2022) Knowledge, Attitudes and Practices of Antibiotic Use and Antimicrobial Resistance among Medical Students in a Private University in Dominica,

show abstract

The Five Ds of Outpatient Antibiotic Stewardship for Urinary Tract Infections

Cited by 63 publications

References 197 publications

An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections

An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections

Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections

Knowledge, Attitudes and Practices of Antibiotic Use and Antimicrobial Resistance among Medical Students in a Private University in Dominica, West Indies

Contact Info

Product

Resources

About