Antibiotics

13 pages, 1339 KiB

Open AccessReview

Antimicrobial Stewardship Strategies Including Point-of-Care Testing (POCT) for Pediatric Patients with Upper-Respiratory-Tract Infections in Primary Care: A Systematic Review of Economic Evaluations

by Costanza Vicentini, Lorenzo Vola, Christian Previti, Valerio Brescia, Francesca Dal Mas, Carla Maria Zotti and Fabrizio Bert

Antibiotics 2022, 11(8), 1139; https://doi.org/10.3390/antibiotics11081139 - 22 Aug 2022

Cited by 8 | Viewed by 2562

Abstract

Upper-respiratory-tract infections (URTIs) are among the main causes of antibiotic prescriptions in pediatric patients. Over one-third of all antibiotic prescriptions for URTIs in children are estimated to be inappropriate, as the majority of URTIs are caused by viral agents. Several strategies, including clinical [...] Read more.

Upper-respiratory-tract infections (URTIs) are among the main causes of antibiotic prescriptions in pediatric patients. Over one-third of all antibiotic prescriptions for URTIs in children are estimated to be inappropriate, as the majority of URTIs are caused by viral agents. Several strategies, including clinical scoring algorithms and different point-of-care tests (POCTs) have been developed to help discriminate bacterial from viral URTIs in the outpatient clinical setting. A systematic review of the literature was conducted following PRISMA guidelines with the objective of summarizing evidence from health–economic evaluations on the use of POCT for URTIs in pediatric outpatients. A total of 3375 records identified from four databases and other sources were screened, of which 8 met the inclusion criteria. Four studies were classified as being of high reporting quality, and three were of medium quality. Five out of eight studies concluded in favor of strategies that included POCTs, with an additional study finding several POCTs to be cost-effective compared to usual care but over an acceptable WTP threshold. This review found POCT could be a valuable tool for antimicrobial stewardship strategies targeted towards childhood URTIs in primary care. Full article

(This article belongs to the Special Issue Antibiotic Prescribing and Antimicrobial Resistance Patterns in Pediatric Patients)

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9 pages, 489 KiB

Open AccessArticle

Incidence and Determinants of Piperacillin/Tazobactam-Associated Hypokalemia: A Retrospective Study

by Heenam Seo and Eunyoung Kim

Antibiotics 2022, 11(8), 1138; https://doi.org/10.3390/antibiotics11081138 - 22 Aug 2022

Cited by 2 | Viewed by 3350

Abstract

Piperacillin/tazobactam (TZP) is a commonly used antibiotic for treating moderate-to-severe infections because of its broad-spectrum activity and recommendation as an alternative to carbapenem. TZP-associated severe hypokalemia has been consistently reported; however, related studies are very rare. This study aimed to evaluate the incidence [...] Read more.

Piperacillin/tazobactam (TZP) is a commonly used antibiotic for treating moderate-to-severe infections because of its broad-spectrum activity and recommendation as an alternative to carbapenem. TZP-associated severe hypokalemia has been consistently reported; however, related studies are very rare. This study aimed to evaluate the incidence and risk factors of TZP-associated hypokalemia (TAH). A retrospective cohort study was conducted on hospitalized adult patients who received TZP from 1 January 2015 to 31 December 2017 at a tertiary teaching hospital. Of the 713 patients, 13.9% had TAH. As a result of multivariate logistic regression analysis, older age (OR 1.03, 95% CI: 1.02–1.05, p < 0.001), female sex (OR 1.88, 95% CI: 1.18–3.00, p = 0.008), longer duration of TZP therapy (OR 1.08, 95% CI: 1.04–1.13, p < 0.001), and higher TZP daily dose (OR 1.10, 95% CI: 1.01–1.20, p = 0.049) were independently associated with TAH. In contrast, higher baseline serum potassium level (OR 0.13, 95% CI: 0.07–0.26, p < 0.001) was related to lower TAH. Furthermore, hypokalemia mostly occurred in the early days of TZP therapy (median onset time: 4 days). Thus, close monitoring of serum potassium levels, especially upon therapy initiation, is essential to prevent TAH. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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3 pages, 200 KiB

Open AccessEditorial

Optimization of Veterinary Antimicrobial Treatment in Companion and Food Animals

by Nikola Puvača

Antibiotics 2022, 11(8), 1137; https://doi.org/10.3390/antibiotics11081137 - 22 Aug 2022

Cited by 1 | Viewed by 1531

Abstract

Several international strategies for antimicrobial stewardship have been developed in response to the global crisis of antimicrobial resistance [...] Full article

11 pages, 308 KiB

Open AccessArticle

In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy

by Bernardetta Segatore, Alessandra Piccirilli, Sabrina Cherubini, Luigi Principe, Giovanni Alloggia, Maria Lina Mezzatesta, Mario Salmeri, Stefano Di Bella, Roberta Migliavacca, Aurora Piazza, Elisa Meroni, Paolo Fazii, Daniela Visaggio, Paolo Visca, Venere Cortazzo, Giulia De Angelis, Arianna Pompilio and Mariagrazia Perilli

Antibiotics 2022, 11(8), 1136; https://doi.org/10.3390/antibiotics11081136 - 22 Aug 2022

Cited by 8 | Viewed by 2427

Abstract

In the present study, the in vitro activity of the sulbactam–durlobactam (SUL–DUR) combination was evaluated against 141 carbapenem-resistant A. baumannii (CRAb) clinical strains collected from six Italian laboratories. Over half (54.6%) of these isolates were resistant to colistin. The SUL–DUR combination [...] Read more.

In the present study, the in vitro activity of the sulbactam–durlobactam (SUL–DUR) combination was evaluated against 141 carbapenem-resistant A. baumannii (CRAb) clinical strains collected from six Italian laboratories. Over half (54.6%) of these isolates were resistant to colistin. The SUL–DUR combination was active against these CRAb isolates with MIC₅₀ and MIC₉₀ values of 0.5 mg/L and 4 mg/L, respectively. Only eleven isolates were resistant to SUL–DUR with MIC values ranging from 8 to 128 mg/L. The SUL–DUR resistant A. baumannii exhibited several antimicrobial resistance genes (ARGs) such as bla_OXA-20, bla_OXA-58, bla_OXA-66, bla_ADC-25, aac(6′)-Ib3 and aac(6′)-Ib-cr and mutations in gyrA (S81L) and parC (V104I, D105E). However, in these isolates, mutations Q488K and Y528H were found in PBP3. Different determinants were also identified in these CRAb isolates, including adeABC, adeFGH, adeIJK, abeS, abaQ and abaR, which encode multidrug efflux pumps associated with resistance to multiple antibacterial agents. This is the first report on the antimicrobial activity of SUL–DUR against carbapenem-resistant A. baumannii isolates selected from multiple regions in Italy. Full article

(This article belongs to the Special Issue Antibiotic Resistance of Acinetobacter baumannii)

11 pages, 1118 KiB

Open AccessArticle

Anticandidal and Antibiofilm Effect of Synbiotics including Probiotics and Inulin-Type Fructans

by Ricardo García-Gamboa, Miguel Domínguez-Simi, Misael S. Gradilla-Hernández, Jorge Bravo, Andrés Moya, Blanca Ruiz-Álvarez and Marisela González-Avila

Antibiotics 2022, 11(8), 1135; https://doi.org/10.3390/antibiotics11081135 - 21 Aug 2022

Cited by 7 | Viewed by 2588

Abstract

Background: There is great interest in the search for new alternatives to antimicrobial drugs, and the use of synbiotics is a promising approach to this problem. This study evaluated the growth inhibition and antibiofilm activity of the short-chain fatty acids produced by Lacticaseibacillus [...] Read more.

Background: There is great interest in the search for new alternatives to antimicrobial drugs, and the use of synbiotics is a promising approach to this problem. This study evaluated the growth inhibition and antibiofilm activity of the short-chain fatty acids produced by Lacticaseibacillus rhamnosus and Pediococcus acidilactici in combination with inulin-type fructans against Candida albicans. Methods: The growth inhibition of Candida was evaluated using microdilution analysis in 96-well microtiter plates; different concentrations of cell-free supernatants of Lacticaseibacillus rhamnosus and Pediococcus acidilactici were exposed to Candida albicans. The antibiofilm assessment was carried out using the crystal violet staining assay. The short-chain fatty acids were analyzed by gas chromatography. Results: The clinically isolated Candida albicans interacted with supernatants from Lacticaseibacillus rhamnosus and Pediococcus acidilactici and showed significant growth inhibition and antibiofilm formation versus the controls. Lactate and acetic acid were elevated in the supernatants. The results suggest that the supernatants obtained from the synbiotic combinations of Lacticaseibacillus rhamnosus and Pediococcus acidilactici with inulin-type fructans can inhibit the growth and biofilm formation against a clinically isolated Candida albicans strain. Conclusions: These results suggest that synbiotic formulations could be a promising alternative to antifungal drugs in candidiasis therapy. Full article

(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)

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13 pages, 1045 KiB

Open AccessArticle

A Wash of Ethyl Acetoacetate Reduces Externally Added Salmonella enterica on Tomatoes

by Shelley M. Horne and Birgit M. Prüß

Antibiotics 2022, 11(8), 1134; https://doi.org/10.3390/antibiotics11081134 - 21 Aug 2022

Cited by 1 | Viewed by 1693

Abstract

The continuously high numbers of food-borne disease outbreaks document that current intervention techniques are not yet satisfactory. This study describes a novel wash for tomatoes that can be used as part of the food processing chain and is designed to prevent contamination with [...] Read more.

The continuously high numbers of food-borne disease outbreaks document that current intervention techniques are not yet satisfactory. This study describes a novel wash for tomatoes that can be used as part of the food processing chain and is designed to prevent contamination with serovars of Salmonella enterica. The wash contains ethyl acetoacetate (EAA) at a concentration of 8% in H₂O. This wash reduced live bacterial counts (on Salmonella Shigella agar) of externally added S. Newport MDD14 by 2.3 log, counts of S. Typhimurium ATCC19585 by 1.5 log, and counts of S. Typhimurium FSL R6-0020 by 3.4 log. The naturally occurring background flora of the tomatoes was determined on plate count agar. The log reduction by EAA was 2.1. To mimic organic matter in the wash, we added 1% tomato homogenate to the 8% EAA solution. Prior to using the wash, the tomato homogenate was incubated with the EAA for 2 h. In the presence of the tomato homogenate, the log reductions were 2.4 log for S. Newport MDD14 and 3 log for S. Typhimurium FSL R6-0020. It seems like tomato homogenate did not reduce the efficacy of the EAA wash in the two S. enterica serovars tested. We propose the use of EAA as a wash for tomatoes to reduce bacterial counts of S. enterica well as naturally occurring background flora. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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14 pages, 4973 KiB

Open AccessArticle

Knowledge and Attitudes about Antibiotics and Antibiotic Resistance of 2404 UK Healthcare Workers

by Diane Ashiru-Oredope, Ella Casale, Eleanor Harvey, Eno Umoh, Sagar Vasandani, Jacqui Reilly and Susan Hopkins

Antibiotics 2022, 11(8), 1133; https://doi.org/10.3390/antibiotics11081133 - 21 Aug 2022

Cited by 10 | Viewed by 3990

Abstract

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs’) knowledge, attitudes and behaviours towards antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented here. Methods: A 43-item questionnaire was developed through a [...] Read more.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs’) knowledge, attitudes and behaviours towards antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented here. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1315 respondents. Results: In total, 2404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic-resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic-resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the previous week to responding to the survey due to a fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals. Full article

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

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14 pages, 2960 KiB

Open AccessArticle

Both Manuka and Non-Manuka Honey Types Inhibit Antibiotic Resistant Wound-Infecting Bacteria

by Samantha R. Hewett, Stephany D. Crabtrey, Esther E. Dodson, C. Alexander Rieth, Richard M. Tarkka and Kari Naylor

Antibiotics 2022, 11(8), 1132; https://doi.org/10.3390/antibiotics11081132 - 20 Aug 2022

Cited by 5 | Viewed by 4969

Abstract

Postoperative infections are a major concern in United States hospitals, accounting for roughly 20% of all hospital-acquired infections yearly. Wound-infecting bacteria, in particular, have a high rate of drug resistance (up to 65%), creating life-threatening complications. Manuka honey, native to New Zealand, has [...] Read more.

Postoperative infections are a major concern in United States hospitals, accounting for roughly 20% of all hospital-acquired infections yearly. Wound-infecting bacteria, in particular, have a high rate of drug resistance (up to 65%), creating life-threatening complications. Manuka honey, native to New Zealand, has been FDA-approved for wound treatment in the United States after studies demonstrated its ability to inhibit a variety of bacterial species and facilitate wound healing. The aim of this study was to identify alternative (non-manuka) honey types that can be specifically used against antibiotic resistance bacteria in wound infections. We utilized a honey-plate method to measure the minimum inhibitory concentration (MIC) of honey to avoid the limitations of agar diffusion, where large, nonpolar polyphenols (which will not diffuse efficiently) play an important role in bioactivity. This study demonstrated that there are several alternative (non-manuka) honey types, particularly fresh raw Arkansas wildflower honeys, that comparably inhibit the growth of the antibiotic-resistant bacterial species specifically implicated in wound infections. Concentrations of 10–30% honey inhibited the growth of the highly antibiotic-resistant organisms colloquially referred to as “superbugs”, which the WHO declared in 2017 to be in critical need of new antibiotics. There was no statistical difference between manuka honey and fresh summer Arkansas wildflower honey in overall bacterial inhibition. These results could transform wound care in the United States, where manuka honey can be expensive and difficult to obtain and where antibiotic resistance remains a troubling concern for wound treatment. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Healthcare Associated Infections)

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11 pages, 1196 KiB

Open AccessArticle

Biochemical Characterizations of the Putative Endolysin Ecd09610 Catalytic Domain from Clostridioides difficile

by Hiroshi Sekiya, Hina Yamaji, Ayumi Yoshida, Risa Matsunami, Shigehiro Kamitori and Eiji Tamai

Antibiotics 2022, 11(8), 1131; https://doi.org/10.3390/antibiotics11081131 - 20 Aug 2022

Cited by 3 | Viewed by 2328

Abstract

Clostridioides difficile is the major pathogen of pseudomembranous colitis, and novel antimicrobial agents are sought after for its treatment. Phage-derived endolysins with species-specific lytic activity have potential as novel antimicrobial agents. We surveyed the genome of C. difficile strain 630 and identified an [...] Read more.

Clostridioides difficile is the major pathogen of pseudomembranous colitis, and novel antimicrobial agents are sought after for its treatment. Phage-derived endolysins with species-specific lytic activity have potential as novel antimicrobial agents. We surveyed the genome of C. difficile strain 630 and identified an endolysin gene, Ecd09610, which has an uncharacterized domain at the N-terminus and two catalytic domains that are homologous to glucosaminidase and endopeptidase at the C-terminus. Genes containing the two catalytic domains, the glucosaminidase domain and the endopeptidase domain, were cloned and expressed in Escherichia coli as N-terminal histidine-tagged proteins. The purified domain variants showed lytic activity almost specifically for C. difficile, which has a unique peptide bridge in its peptidoglycan. This species specificity is thought to depend on substrate cleavage activity rather than binding. The domain variants were thermostable, and, notably, the glucosaminidase domain remained active up to 100 °C. In addition, we determined the optimal pH and salt concentrations of these domain variants. Their properties are suitable for formulating a bacteriolytic enzyme as an antimicrobial agent. This lytic enzyme can serve as a scaffold for the construction of high lytic activity mutants with enhanced properties. Full article

(This article belongs to the Special Issue Discovery and Development of Novel Antibacterial Agents)

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9 pages, 1615 KiB

Open AccessArticle

Rapid Detection of Plasmid AmpC Beta-Lactamases by a Flow Cytometry Assay

by Inês Martins-Oliveira, Blanca Pérez-Viso, Ana Silva-Dias, Rosário Gomes, Luísa Peixe, Ângela Novais, Rafael Cantón and Cidália Pina-Vaz

Antibiotics 2022, 11(8), 1130; https://doi.org/10.3390/antibiotics11081130 - 19 Aug 2022

Cited by 3 | Viewed by 1991

Abstract

Plasmidic AmpC (pAmpC) enzymes are responsible for the hydrolysis of extended-spectrum cephalosporins but they are not routinely investigated in many clinical laboratories. Phenotypic assays, currently the reference methods, are cumbersome and culture dependent. These methods compare the activity of cephalosporins with and without [...] Read more.

Plasmidic AmpC (pAmpC) enzymes are responsible for the hydrolysis of extended-spectrum cephalosporins but they are not routinely investigated in many clinical laboratories. Phenotypic assays, currently the reference methods, are cumbersome and culture dependent. These methods compare the activity of cephalosporins with and without class C inhibitors and the results are provided in 24–48 h. Detection by molecular methods is quicker, but several genes should be investigated. A new assay for the rapid phenotypic detection of pAmpC enzymes of the Enterobacterales group-I (not usually AmpC producers) based on flow cytometry technology was developed and validated. The technology was evaluated in two sites: FASTinov, a spin-off of Porto University (Portugal) where the technology was developed, and the Microbiology Department of Ramón y Cajal University Hospital in Madrid (Spain). A total of 100 strains were phenotypically screened by disk diffusion for the pAmpC with the new 2 h assay. Molecular detection of the pAmpC genes was also performed on discrepant results. Forty-two percent of the strains were phenotypically classified as pAmpC producers using disk diffusion. The percentage of agreement of the flow cytometric assay was 93.0%, with 95.5% sensitivity and 91.1% specificity. Our proposed rapid assay based on flow cytometry technology can, in two hours, accurately detect pAmpC enzymes. Full article

(This article belongs to the Special Issue Epidemiology of Acquired AmpC Type β-Lactamases in Enterobacteriaceae from a One Health Perspective)

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15 pages, 3661 KiB

Open AccessArticle

Analysis of a Library of Escherichia coli Transporter Knockout Strains to Identify Transport Pathways of Antibiotics

by Lachlan Jake Munro and Douglas B. Kell

Antibiotics 2022, 11(8), 1129; https://doi.org/10.3390/antibiotics11081129 - 19 Aug 2022

Cited by 4 | Viewed by 2543

Abstract

Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics. Targeting [...] Read more.

Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics. Targeting these transporters is a potential avenue to combat antibiotic resistance. In this study, we used an automated screening pipeline to evaluate the growth of a library of 447 Escherichia coli transporter knockout strains exposed to sub-inhibitory concentrations of 18 diverse antimicrobials. We found numerous knockout strains that showed more resistant or sensitive phenotypes to specific antimicrobials, suggestive of transport pathways. We highlight several specific drug-transporter interactions that we identified and provide the full dataset, which will be a useful resource in further research on antimicrobial transport pathways. Overall, we determined that transporters are involved in modulating the efficacy of almost all the antimicrobial compounds tested and can, thus, play a major role in the development of antimicrobial resistance. Full article

(This article belongs to the Special Issue Clinical Pharmacology and Pharmacy of Antimicrobial Agents)

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12 pages, 823 KiB

Open AccessArticle

Ventilator-Associated Pneumonia, Multidrug-Resistant Bacteremia and Infection Control Interventions in an Intensive Care Unit: Analysis of Six-Year Time-Series Data

by Amalia Papanikolopoulou, Helena C. Maltezou, Athina Stoupis, Anastasia Pangalis, Christos Kouroumpetsis, Genovefa Chronopoulou, Yannis Kalofissoudis, Evangelos Kostares, Fotini Boufidou, Maria Karalexi, Vasiliki Koumaki, Nikos Pantazis, Athanasios Tsakris and Maria Kantzanou

Antibiotics 2022, 11(8), 1128; https://doi.org/10.3390/antibiotics11081128 - 19 Aug 2022

Cited by 5 | Viewed by 2700

Abstract

Ventilator-associated pneumonia (VAP) occurs more than 48h after mechanical ventilation and is associated with a high mortality rate. The current hospital-based study aims to investigate the association between VAP rate, incidence of bacteremia from multidrug-resistant (MDR) pathogens, and infection control interventions in a [...] Read more.

Ventilator-associated pneumonia (VAP) occurs more than 48h after mechanical ventilation and is associated with a high mortality rate. The current hospital-based study aims to investigate the association between VAP rate, incidence of bacteremia from multidrug-resistant (MDR) pathogens, and infection control interventions in a single case mix ICU from 2013 to 2018. Methods: The following monthly indices were analyzed: (1) VAP rate; (2) use of hand hygiene disinfectants; (3) isolation rate of patients with MDR bacteria; and (4) incidence of bacteremia/1000 patient-days (total cases, total carbapenem-resistant cases, and carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae cases separately). Results: Time trends of infection control interventions showed increased rates in isolation of patients with MDR pathogens (p <0.001) and consumption of hand disinfectant solutions (p =0.001). The last four years of the study an annual decrease of VAP rate by 35.12% (95% CI: −53.52 to −9.41; p =0.01) was recorded, which significantly correlated not only with reduced trauma and cardiothoracic surgery patients (IRR:2.49; 95% CI: 2.09–2.96; p <0.001), but also with increased isolation rate of patients with MDR pathogens (IRR: 0.52; 95% CI: 0.27–0.99; p = 0.048), and hand disinfectants use (IRR: 0.40; 95% CI: 0.18–0.89; p =0.024). Conclusions: Infection control interventions significantly contributed to the decrease of VAP rate. Constant infection control stewardship has a stable time-effect and guides evidence-based decisions. Full article

(This article belongs to the Special Issue Antibiotics Research in Europe)

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9 pages, 1040 KiB

Open AccessArticle

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units

by Kesia Esther da Silva, Gleyce Hellen de Almeida de Souza, Quézia Moura, Luana Rossato, Letícia Cristina Limiere, Nathalie Gaebler Vasconcelos and Simone Simionatto

Antibiotics 2022, 11(8), 1127; https://doi.org/10.3390/antibiotics11081127 - 19 Aug 2022

Cited by 5 | Viewed by 2430

Abstract

This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility [...] Read more.

This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility profile was confirmed using broth microdilution. The strains displayed a multidrug resistant profile and were subjected to whole-genome sequencing. Bioinformatic analysis revealed a variety of antimicrobial resistance genes, including the bla_KPC-2. No plasmid-mediated colistin resistance gene was identified. Nonetheless, nonsynonymous mutations in mgrB, pmrA, pmrB, and eptA were detected, justifying the colistin resistance phenotype. Virulence genes encoding yersiniabactin, colibactin, and aerobactin were also found, associated with ICEKp4 and ICEKp10, and might be related to the high mortality observed among the patients. In fact, this is the first time ICEKp is identified in K. aerogenes in Brazil. Phylogenetic analysis grouped the strains into two clonal groups, belonging to ST93 and ST16. In summary, the co-existence of antimicrobial resistance and virulence factors is deeply worrying, as it could lead to the emergence of untreatable invasive infections. All these factors reinforce the need for surveillance programs to monitor the evolution and dissemination of multidrug resistant and virulent strains among critically ill patients. Full article

(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)

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25 pages, 5047 KiB

Open AccessArticle

Design, Synthesis and Mechanistic Studies of Novel Isatin-Pyrazole Hydrazone Conjugates as Selective and Potent Bacterial MetAP Inhibitors

by Iram Irfan, Asghar Ali, Bharati Reddi, Mohd. Abrar Khan, Phool Hasan, Sarfraz Ahmed, Amad Uddin, Magdalena Piatek, Kevin Kavanagh, Qazi Mohd. Rizwanul Haque, Shailja Singh, Anthony Addlagatta and Mohammad Abid

Antibiotics 2022, 11(8), 1126; https://doi.org/10.3390/antibiotics11081126 - 19 Aug 2022

Cited by 8 | Viewed by 3073

Abstract

Methionine aminopeptidases (MetAPs) are attractive drug targets due to their essential role in eukaryotes as well as prokaryotic cells. In this study, biochemical assays were performed on newly synthesized Isatin-pyrazole hydrazones (PS1–14) to identify potent and selective bacterial MetAPs inhibitors. [...] Read more.

Methionine aminopeptidases (MetAPs) are attractive drug targets due to their essential role in eukaryotes as well as prokaryotic cells. In this study, biochemical assays were performed on newly synthesized Isatin-pyrazole hydrazones (PS1–14) to identify potent and selective bacterial MetAPs inhibitors. Compound PS9 inhibited prokaryotic MetAPs, i.e., MtMetAP1c, EfMetAP1a and SpMetAP1a with K_i values of 0.31, 6.93 and 0.37 µM, respectively. Interestingly, PS9 inhibited the human analogue HsMetAP1b with Ki (631.7 µM) about ten thousand-fold higher than the bacterial MetAPs. The in vitro screening against Gram-positive (Enterococcus faecalis, Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial strains also exhibited their antibacterial potential supported by minimum bactericidal concentration (MBC), disk diffusion assay, growth curve and time-kill curve experiments. Additionally, PS6 and PS9 had synergistic effects when combined with ampicillin (AMP) and ciprofloxacin (CIP) against selective bacterial strains. PS9 showed no significant cytotoxic effect on human RBCs, HEK293 cells and Galleria mellonella larvae in vivo. PS9 inhibited the growth of multidrug-resistant environmental isolates as it showed the MIC lower than the standard drugs used against selective bacterial strains. Overall, the study suggested PS9 could be a useful candidate for the development of antibacterial alternatives. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

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8 pages, 256 KiB

Open AccessArticle

Microbiology of Diabetic Foot Infections in a Tertiary Care Hospital in São Paulo, Brazil

by Amanda Thurler Palomo, Ana Paula Maia Pires, Marcelo Fernando Matielo, Rafael de Athayde Soares, Christiano Pecego, Roberto Sacilotto, Alexandre Inacio de Paula, Nair Hosino, Cristiano de Melo Gamba, Cibele Lefreve Fonseca, Daniela K. S. Paraskevopoulos, Augusto Yamaguti, João Silva de Mendonça, Silvia Figueiredo Costa and Thaís Guimarães

Antibiotics 2022, 11(8), 1125; https://doi.org/10.3390/antibiotics11081125 - 19 Aug 2022

Cited by 5 | Viewed by 2211

Abstract

Diabetic foot infections (DFIs) are one of the causes of hospitalization in diabetic patients and, when this occurs, empirical antibiotic therapy is necessary. We have conducted a retrospective study of patients with DFI that required hospitalization to evaluate microbiologic profile and the susceptibility [...] Read more.

Diabetic foot infections (DFIs) are one of the causes of hospitalization in diabetic patients and, when this occurs, empirical antibiotic therapy is necessary. We have conducted a retrospective study of patients with DFI that required hospitalization to evaluate microbiologic profile and the susceptibility pattern of these infections. We evaluated 320 patients, of which 223 (69.7%) were male with a media age of 71 years with 276 isolates. Gram-positive bacteria were responsible for 188 (68.1%) of the isolates, while Gram-negative bacilli were responsible for 88 (31.9%). E. faecalis was the most prevalent pathogen, followed by S. aureus and coagulase negative Staphylococci. Among Gram-negative pathogens, P. aeruginosa was the most prevalent agent. Regarding the susceptibility profile, we found ampicillin-sensitive enterococci in 89% of the cases, oxacillin-sensitive S. aureus in 47%, but in coagulase-negative staphylococci, oxacillin was sensible only in 20%. The susceptibility profile of Gram-negatives was very good with 76% susceptibility of P. aeruginosa to ceftazidime and meropenem. The other prevalent Enterobacterales had great susceptibility to ceftazidime, piperacillin-tazobactam and 100% susceptibility to meropenem, with the exception of K. pneumoniae, which had 75% susceptibility to meropenem. Knowledge of microbiological profile and susceptibility patterns of patients with DFIs is useful to guide empirical therapy. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Healthcare Associated Infections)

24 pages, 1452 KiB

Open AccessEditor’s ChoiceReview

Successful Integration of Clinical Pharmacists in an OPAT Program: A Real-Life Multidisciplinary Circuit

by Sara Ortonobes, Abel Mujal-Martínez, María de Castro Julve, Alba González-Sánchez, Rafael Jiménez-Pérez, Manuel Hernández-Ávila, Natalia De Alfonso, Ingrid Maye-Pérez, Teresa Valle-Delmás, Alba Rodríguez-Sánchez, Jessica Pino-García and Mònica Gómez-Valent

Antibiotics 2022, 11(8), 1124; https://doi.org/10.3390/antibiotics11081124 - 19 Aug 2022

Cited by 7 | Viewed by 4747

Abstract

Outpatient parenteral antimicrobial therapy (OPAT) programs encompass a range of healthcare processes aiming to treat infections at home, with the preferential use of the intravenous route. Although several barriers arise during the implementation of OPAT circuits, recent cumulative data have supported the effectiveness [...] Read more.

Outpatient parenteral antimicrobial therapy (OPAT) programs encompass a range of healthcare processes aiming to treat infections at home, with the preferential use of the intravenous route. Although several barriers arise during the implementation of OPAT circuits, recent cumulative data have supported the effectiveness of these programs, demonstrating their application in a safe and cost-effective manner. Given that OPAT is evolving towards treating patients with higher complexity, a multidisciplinary team including physicians, pharmacists, and nursing staff should lead the program. The professionals involved require previous experience in infectious diseases treatment as well as in outpatient healthcare and self-administration. As we describe here, clinical pharmacists exert a key role in OPAT multidisciplinary teams. Their intervention is essential to optimize antimicrobial prescriptions through their participation in stewardship programs as well as to closely follow patients from a pharmacotherapeutic perspective. Moreover, pharmacists provide specialized counseling on antimicrobial treatment technical compounding. In fact, OPAT elaboration in sterile environments and pharmacy department clean rooms increases OPAT stability and safety, enhancing the quality of the program. In summary, building multidisciplinary teams with the involvement of clinical pharmacists improves the management of home-treated infections, promoting a safe self-administration and increasing OPAT patients’ quality of life. Full article

(This article belongs to the Special Issue Antibiotic Use and Stewardship in Hospital)

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12 pages, 1561 KiB

Open AccessArticle

The Effect of Heavy Metals on Conjugation Efficiency of an F-Plasmid in Escherichia coli

by Martin Palm, Alfred Fransson, Julia Hultén, Karolina Búcaro Stenman, Amina Allouche, Oscar E. Chiang, Mirthe L. Constandse, Karlijn J. van Dijk, Suheda Icli, Bela Klimesova, Emma Korhonen, Gema Martínez-Crespo, Dominik Meggers, Margarita Naydenova, Maria An. Polychronopoulou, Dominik B. Schuntermann, Havva Unal, Agnieszka Wasylkowska and Anne Farewell

Antibiotics 2022, 11(8), 1123; https://doi.org/10.3390/antibiotics11081123 - 19 Aug 2022

Cited by 9 | Viewed by 3920

Abstract

Conjugation, the process by which conjugative plasmids are transferred between bacteria, is regarded as a major contributor to the spread of antibiotic resistance, in both environmental and clinical settings. Heavy metals are known to co-select for antibiotic resistance, but the impact of the [...] Read more.

Conjugation, the process by which conjugative plasmids are transferred between bacteria, is regarded as a major contributor to the spread of antibiotic resistance, in both environmental and clinical settings. Heavy metals are known to co-select for antibiotic resistance, but the impact of the presence of these metals on conjugation itself is not clear. Here, we systematically investigate the impact that five heavy metals (arsenic, cadmium, copper, manganese, and zinc) have on the transfer of an IncF conjugative plasmid in Escherichia coli. Our results show that two of the metals, cadmium and manganese, have no significant impact, while arsenic and zinc both reduce conjugation efficiency by approximately 2-fold. Copper showed the largest impact, with an almost 100-fold decrease in conjugation efficiency. This was not mediated by any change in transcription from the major Py promoter responsible for transcription of the conjugation machinery genes. Further, we show that in order to have this severe impact on the transfer of the plasmid, copper sulfate needs to be present during the mating process, and we suggest explanations for this. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

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25 pages, 399 KiB

Open AccessArticle

Management of Pediatric Urinary Tract Infections: A Delphi Study

by Giovanni Autore, Luca Bernardi, Claudio La Scola, Filippo Ghidini, Federico Marchetti, Andrea Pasini, Luca Pierantoni, Claudia Castellini, Claudia Gatti, Cristina Malaventura, Gabriella Pelusi, Francesco Antodaro, Andrea Bergomi, Franco Mazzini, Giovanni Parente, Roberto Pillon, Francesca Cusenza, Giacomo Biasucci, Alessandro De Fanti, Lorenzo Iughetti, Serafina Perrone, Andrea Pession, Mario Lima, Susanna Esposito and The UTI-Ped-ER Study Group Show full author list Hide full author list

Antibiotics 2022, 11(8), 1122; https://doi.org/10.3390/antibiotics11081122 - 18 Aug 2022

Cited by 13 | Viewed by 5627

Abstract

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to [...] Read more.

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Pediatrics)

16 pages, 882 KiB

Open AccessArticle

Risk Factors for Persistent Infection of Non-Typhoidal Salmonella in Poultry Farms, North Central Nigeria

by Abdullahi O. Sanni, Joshua Onyango, Abdulkadir Usman, Latifah O. Abdulkarim, Annelize Jonker and Folorunso O. Fasina

Antibiotics 2022, 11(8), 1121; https://doi.org/10.3390/antibiotics11081121 - 18 Aug 2022

Cited by 7 | Viewed by 2699

Abstract

Salmonellosis is a bacterial zoonosis causing an array of health conditions. Non-typhoidal salmonellosis (NTS) has a discrete adaptation to certain animals; in poultry, pullorum and fowl typhoid are its primary disease manifestations. The diseases are prevalent in Nigerian poultry and have been well-studied [...] Read more.

Salmonellosis is a bacterial zoonosis causing an array of health conditions. Non-typhoidal salmonellosis (NTS) has a discrete adaptation to certain animals; in poultry, pullorum and fowl typhoid are its primary disease manifestations. The diseases are prevalent in Nigerian poultry and have been well-studied in Nigeria, but less so in North Central Nigeria (NCN). Using field sampling, laboratory methods and a semi-structured questionnaire for 1000 poultry farms in NCN, we explored the incidence and risk factors for the persistence of NTS infection in poultry. Approximately 41.6% of the farms had experienced NTS over the last 18 months. Farm experience of NTS moderately predicted awareness of salmonellosis. Increasing stock in smallholder farms, self-mixing of concentrate on the farm, usage of stream water, pen odour, non-adherence and partial adherence of farms to recommended poultry vaccination against pullorum and fowl typhoid and lack of and non-adherence to biosecurity were identified risk factors that increased the odds of NTS infection in poultry. Antibiotic use practice may have reduced the isolation rate of NTS, yet NTS continues to challenge poultry farms in Nigeria. Identified risk practices must be mitigated intentionally and biosecurity and hygiene must be improved to reduce the burden of NTS. Full article

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12 pages, 3560 KiB

Open AccessArticle

Characteristics of Antibiotic Resistance and Tolerance of Environmentally Endemic Pseudomonas aeruginosa

by Seryoung Kim, Satomi Masai, Keiji Murakami, Momoyo Azuma, Keiko Kataoka, Mayu Sebe, Kazuya Shimizu, Tomoaki Itayama, Niwooti Whangchai, Kanda Whangchai, Ikko Ihara and Hideaki Maseda

Antibiotics 2022, 11(8), 1120; https://doi.org/10.3390/antibiotics11081120 - 18 Aug 2022

Cited by 3 | Viewed by 2110

Abstract

Antibiotic-resistant bacteria remain a serious public health threat. In order to determine the percentage of antibiotic-resistant and -tolerant Pseudomonas aeruginosa cells present and to provide a more detailed infection risk of bacteria present in the environment, an isolation method using a combination of [...] Read more.

Antibiotic-resistant bacteria remain a serious public health threat. In order to determine the percentage of antibiotic-resistant and -tolerant Pseudomonas aeruginosa cells present and to provide a more detailed infection risk of bacteria present in the environment, an isolation method using a combination of 41 °C culture and specific primers was established to evaluate P. aeruginosa in the environment. The 50 strains were randomly selected among 110 isolated from the river. The results of antibiotic susceptibility evaluation showed that only 4% of environmental strains were classified as antibiotic-resistant, while 35.7% of clinical strains isolated in the same area were antibiotic-resistant, indicating a clear difference between environmental and clinical strains. However, the percentage of antibiotic-tolerance, an indicator of potential resistance risk for strains that have not become resistant, was 78.8% for clinical strains and 90% for environmental strains, suggesting that P. aeruginosa, a known cause of nosocomial infections, has a high rate of antibiotic-tolerance even in environmentally derived strains. It suggested that the rate of antibiotic-tolerance is not elicited by the presence or absence of antimicrobial exposure. The combination of established isolation and risk analysis methods presented in this study should provide accurate and efficient information on the risk level of P. aeruginosa in various regions and samples. Full article

(This article belongs to the Special Issue Antibiotic Tolerance in Pseudomonas aeruginosa)

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15 pages, 1342 KiB

Open AccessArticle

Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection

by Irene Muñoz-Gallego, María Ángeles Meléndez-Carmona, Jaime Lora-Tamayo, Carlos Garrido-Allepuz, Fernando Chaves, Virginia Sebastián and Esther Viedma

Antibiotics 2022, 11(8), 1119; https://doi.org/10.3390/antibiotics11081119 - 18 Aug 2022

Cited by 6 | Viewed by 1912

Abstract

Background: Persistent and relapsing prosthetic joint infection (PJI) due to Staphylococcus aureus presents a clinical challenge. This study aimed to provide an extensive description of phenotypic and genomic changes that could be related to persistence or relapse. Methods: Initial and second S. aureus [...] Read more.

Background: Persistent and relapsing prosthetic joint infection (PJI) due to Staphylococcus aureus presents a clinical challenge. This study aimed to provide an extensive description of phenotypic and genomic changes that could be related to persistence or relapse. Methods: Initial and second S. aureus isolates from 6 cases of persistent and relapsing PJI, along with clinical isolates from 8 cases, with favorable outcome were included. All isolates were studied by phenotypic and genotypic approaches. Results: Recurrent S. aureus isolates exhibited a significant increase in adhesive capacity, invasion and persistence compared to resolved isolates. No association was found for the presence or absence of certain genes with the persistence or relapse of PJI. All sequential isolates showed identical sequence type (ST). Resistance gene loss during the infection and a great diversity of variants in different virulence genes between the pair of strains, mainly in genes encoding adhesins such as fnbA, were observed. Conclusions: S. aureus-caused relapse and persistence PJI is associated with bacterial phenotypical and genotypical adaptation. The main paths of adaptation were persistence in the intracellular compartment, and the loss of antibiotic resistance genes and variant acquisition, especially in genes encoding adhesins. Full article

(This article belongs to the Special Issue Prosthetic Joint Infection: The Challenges of Prevention, Diagnosis and Treatment and Opportunities for Future Research - 2nd Volume)

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10 pages, 886 KiB

Open AccessArticle

Resistance towards Critically Important Antimicrobials among Enterococcus faecalis and E. faecium in Poultry Farm Environments in Selangor, Malaysia

by Sakshaleni Rajendiran, Yuvaneswary Veloo, Syahidiah Syed Abu Thahir and Rafiza Shaharudin

Antibiotics 2022, 11(8), 1118; https://doi.org/10.3390/antibiotics11081118 - 18 Aug 2022

Cited by 5 | Viewed by 2545

Abstract

Multidrug resistant (MDR) enterococci pose significant public health challenges. However, the extent of resistance in the environment is less explored. This study aimed to determine the antibiotic resistance in a poultry farm environment. Eighty enterococcal isolates recovered from the soil and effluent water [...] Read more.

Multidrug resistant (MDR) enterococci pose significant public health challenges. However, the extent of resistance in the environment is less explored. This study aimed to determine the antibiotic resistance in a poultry farm environment. Eighty enterococcal isolates recovered from the soil and effluent water of 28 poultry farms in Selangor state were included in the study for further bacterial identification and antibiotic susceptibility testing using a VITEK 2 system. Data were analyzed using Statistical Package for Social Science (SPSS) version 27. The resistance rate and MDR of enterococcal isolates were reported. Out of 80 isolates recovered, 72 (90%) exhibited resistance to at least one antibiotic, with 50 isolates (62.5%) being found to be MDR. All linezolid-resistant enterococci (LRE) exhibit MDR, which constituted 40% of resistance among all the isolates recovered from poultry environment. Since linezolid is listed as critically important antibiotics for clinical use by the World Health Organization (WHO), the higher resistance towards it and other critically important antibiotic for human use is a serious concern. Hence, relevant agencies need to investigate the use of clinically important antimicrobials in poultry farms paying special attention towards linezolid or any other antibiotics that can facilitate the development of LRE. Full article

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15 pages, 3167 KiB

Open AccessArticle

Microbial Profiling of Potato-Associated Rhizosphere Bacteria under Bacteriophage Therapy

by Samar Mousa, Mahmoud Magdy, Dongyan Xiong, Raphael Nyaruabaa, Samah Mohamed Rizk, Junping Yu and Hongping Wei

Antibiotics 2022, 11(8), 1117; https://doi.org/10.3390/antibiotics11081117 - 18 Aug 2022

Cited by 6 | Viewed by 3110

Abstract

Potato soft rot and wilt are economically problematic diseases due to the lack of effective bactericides. Bacteriophages have been studied as a novel and environment-friendly alternative to control plant diseases. However, few experiments have been conducted to study the changes in plants and [...] Read more.

Potato soft rot and wilt are economically problematic diseases due to the lack of effective bactericides. Bacteriophages have been studied as a novel and environment-friendly alternative to control plant diseases. However, few experiments have been conducted to study the changes in plants and soil microbiomes after bacteriophage therapy. In this study, rhizosphere microbiomes were examined after potatoes were separately infected with three bacteria (Ralstonia solanacearum, Pectobacterium carotovorum, Pectobacterium atrosepticum) and subsequently treated with a single phage or a phage cocktail consisting of three phages each. Results showed that using the phage cocktails had better efficacy in reducing the disease incidence and disease symptoms’ levels when compared to the application of a single phage under greenhouse conditions. At the same time, the rhizosphere microbiota in the soil was affected by the changes in micro-organisms’ richness and counts. In conclusion, the explicit phage mixers have the potential to control plant pathogenic bacteria and cause changes in the rhizosphere bacteria, but not affect the beneficial rhizosphere microbes. Full article

(This article belongs to the Special Issue Bacteriophage Therapy: Recent Developments and Applications of a Renaissance Weapon)

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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 2609

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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26 pages, 5526 KiB

Open AccessArticle

Development of Dicationic Bisguanidine-Arylfuran Derivatives as Potent Agents against Gram-Negative Bacteria

by Catarina Bourgard, Diego Rodríguez-Hernández, Anastasia Rudenko, Carolin Rutgersson, Martin Palm, D. G. Joakim Larsson, Anne Farewell, Morten Grøtli and Per Sunnerhagen

Antibiotics 2022, 11(8), 1115; https://doi.org/10.3390/antibiotics11081115 - 17 Aug 2022

Cited by 6 | Viewed by 3274

Abstract

Antibiotic resistance among bacteria is a growing global challenge. A major reason for this is the limited progress in developing new classes of antibiotics active against Gram-negative bacteria. Here, we investigate the antibacterial activity of a dicationic bisguanidine-arylfuran, originally developed as an antitrypanosomal [...] Read more.

Antibiotic resistance among bacteria is a growing global challenge. A major reason for this is the limited progress in developing new classes of antibiotics active against Gram-negative bacteria. Here, we investigate the antibacterial activity of a dicationic bisguanidine-arylfuran, originally developed as an antitrypanosomal agent, and new derivatives thereof. The compounds showed good activity (EC₅₀ 2–20 µM) against antibiotic-resistant isolates of the Gram-negative members of the ESKAPE group (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and Escherichia coli with different antibiotic susceptibility patterns, including ESBL isolates. Cytotoxicity was moderate, and several of the new derivatives were less cytotoxic than the lead molecule, offering better selectivity indices (40–80 for several ESKAPE isolates). The molecular mechanism for the antibacterial activity of these molecules is unknown, but sensitivity profiling against human ESKAPE isolates and E. coli collections with known susceptibility patterns against established antibiotics indicates that it is distinct from lactam and quinolone antibiotics. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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10 pages, 1708 KiB

Open AccessArticle

Effects of Levofloxacin, Aztreonam, and Colistin on Enzyme Synthesis by P. aeruginosa Isolated from Cystic Fibrosis Patients

by Arianna Pani, Valeria Lucini, Silvana Dugnani, Alice Schianchi and Francesco Scaglione

Antibiotics 2022, 11(8), 1114; https://doi.org/10.3390/antibiotics11081114 - 17 Aug 2022

Cited by 2 | Viewed by 1931

Abstract

(1) Background: Cystic fibrosis (CF) is characterized by chronic pulmonary inflammation and persistent bacterial infections. P. aeruginosa is among the main opportunistic pathogens causing infections in CF. P. aeruginosa is able to form a biofilm, decreasing antibiotic permeability. LOX, a lipoxygenase enzyme, is [...] Read more.

(1) Background: Cystic fibrosis (CF) is characterized by chronic pulmonary inflammation and persistent bacterial infections. P. aeruginosa is among the main opportunistic pathogens causing infections in CF. P. aeruginosa is able to form a biofilm, decreasing antibiotic permeability. LOX, a lipoxygenase enzyme, is a virulence factor produced by P. aeruginosa and promotes its persistence in lung tissues. The aim of this study is to evaluate if antibiotics currently used for aerosol therapy in CF are able to interfere with the production of lipoxygenase from open isolates of P. Aeruginosa from patients with CF. (2) Methods: Clinical isolates of P. aeruginosa from patients with CF were grown in Luria broth (LB). Minimum inhibitory concentration (MIC) was performed and interpreted for all isolated strains according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. We selected four antibiotics with different mechanisms of action: aztreonam, colistin, amikacin, and levofloxacin. We used human pulmonary epithelial NCI-H929 cells to evaluate LOX activity and its metabolites according to antibiotic action at increasing concentrations. (3) Results: there is a correlation between LOX secretion by clinical isolates of P. aeruginosa and biofilm production. Levofloxacin exhibits highly significant inhibitory activity compared to the control. Amikacin also exhibits significant inhibitory activity against LOX production. Aztreonam and colistin do not show inhibitory activity. These results are also confirmed for LOX metabolites. (4) Conclusions: among the evaluated antibiotics, levofloxacin and amikacin have an activity on LOX secretion. Full article

(This article belongs to the Special Issue Clinical Pharmacology and Pharmacy of Antimicrobial Agents)

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11 pages, 2018 KiB

Open AccessArticle

Cerebrospinal Fluid System Infection in Children with Cancer: A Retrospective Analysis over 14 Years in a Major European Pediatric Cancer Center

by Antonia Diederichs, Evelyn Pawlik, Anke Barnbrock, Stefan Schöning, Jürgen Konczalla, Tobias Finger, Thomas Lehrnbecher, Stephan Göttig and Konrad Bochennek

Antibiotics 2022, 11(8), 1113; https://doi.org/10.3390/antibiotics11081113 - 17 Aug 2022

Cited by 1 | Viewed by 2045

Abstract

Infection of a cerebrospinal fluid system is a serious medical complication. We performed a retrospective monocentric analysis on temporary and permanent cerebrospinal fluid devices in children with and without cancer, covering a period of over 14 years. Between 2004 and 2017, 275 children [...] Read more.

Infection of a cerebrospinal fluid system is a serious medical complication. We performed a retrospective monocentric analysis on temporary and permanent cerebrospinal fluid devices in children with and without cancer, covering a period of over 14 years. Between 2004 and 2017, 275 children with a cerebrospinal fluid system were seen at our institution. Thirty-eight children suffered from 51 microbiologically proven infectious episodes of the cerebrospinal fluid system (12 children with cancer and 26 children without cancer). Independently of the cerebrospinal fluid system used, the incidence of infection did not significantly differ between children with and without cancer and was the highest in children younger than one year. Infection occurred earlier in external ventricular drain (EVD) than ventriculoperitoneal (VP) shunt, and in EVD significantly earlier in children with cancer compared with patients without cancer. The pathogens isolated were mainly Gram-positive bacteria, in particular Staphylococcus spp., which should be taken into account for empirical antimicrobial therapy. Full article

(This article belongs to the Special Issue Antimicrobial Use in Pediatrics)

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13 pages, 1715 KiB

Open AccessArticle

A Randomized Controlled Trial of Colistin Combined with Sulbactam: 9 g per Day versus 12 g per Day in the Treatment of Extensively Drug-Resistant Acinetobacter baumannii Pneumonia: An Interim Analysis

by Chutchawan Ungthammakhun, Vasin Vasikasin and Dhitiwat Changpradub

Antibiotics 2022, 11(8), 1112; https://doi.org/10.3390/antibiotics11081112 - 17 Aug 2022

Cited by 7 | Viewed by 4065

Abstract

Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB [...] Read more.

Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB pneumonia were randomly assigned (1:1) to receive colistin in combination with sulbactam at either 9 g/day or 12 g/day. The primary outcome was the 28-day mortality rate in the intention-to-treat population. A total of 88 patients received colistin in combination with sulbactam at a dosage of either 12 g/day (n = 45) or 9 g/day (n = 43). Trends toward a lower mortality rate were observed in the 12 g/day group at 7 days (11.1% vs. 23.3%), 14 days (33.3% vs. 41.9%), and 28 days (46.7% vs. 58.1%). The microbiological cure rate at day 7 was significantly higher in the 12 g/day group (90.5% vs. 58.1%; p = 0.02). Factors associated with mortality at 28 days were asthma, cirrhosis, APACHEII score ≥ 28, and a dosage of sulbactam of 9 g/day for mortality at any timepoint. Treatment with colistin combined with sulbactam at 12 g/day was not superior to the combination treatment with sulbactam at 9 g/day. However, due to being an interim analysis, this trial was underpowered to detect mortality differences. Full article

(This article belongs to the Special Issue Approaches to Navigating Multi-Drug Resistance in Gram-Negative Pathogens)

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16 pages, 2958 KiB

Open AccessArticle

Effects of Ciprofloxacin Alone or in Mixture with Sulfamethoxazole on the Efficiency of Anaerobic Digestion and Its Microbial Community

by Valentina Mazzurco Miritana, Luisa Patrolecco, Anna Barra Caracciolo, Andrea Visca, Flavia Piccinini, Antonella Signorini, Silvia Rosa, Paola Grenni, Gian Luigi Garbini, Francesca Spataro, Jasmin Rauseo and Giulia Massini

Antibiotics 2022, 11(8), 1111; https://doi.org/10.3390/antibiotics11081111 - 17 Aug 2022

Cited by 8 | Viewed by 2043

Abstract

Some livestock farms rely on anaerobic digestion (AD) technology for manure disposal, thus obtaining energy (biogas) and fertilizer (digestate). Mixtures of antibiotics used for animal health often occur in organic waste and their possible synergistic/antagonistic effects on microorganisms involved in AD are still [...] Read more.

Some livestock farms rely on anaerobic digestion (AD) technology for manure disposal, thus obtaining energy (biogas) and fertilizer (digestate). Mixtures of antibiotics used for animal health often occur in organic waste and their possible synergistic/antagonistic effects on microorganisms involved in AD are still poorly studied. This work focuses on the effects of adding ciprofloxacin, alone (5 mg L⁻¹) and in combination with sulfamethoxazole (2.5–5–10 mg L⁻¹), on AD efficiency and microbial community structure. The experiment consisted of 90-day cattle manure batch tests and antibiotic removal percentages were assessed. Adding antibiotics always promoted CH₄ and H₂ production compared to untreated controls; however, CH₄ production was lowered with the highest ciprofloxacin (CIP) concentrations. The overall results show antibiotic degradation caused by acidogenic Bacteria, and CH₄ was mainly produced through the hydrogenotrophic-pathway by methanogenic Archaea. Shifts in microbial community abundance (DAPI counts) and composition (Illumina-MiSeq and FISH analyses) were observed. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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17 pages, 2461 KiB

Open AccessArticle

Salmonella enterica Serovar Dublin from Cattle in California from 1993–2019: Antimicrobial Resistance Trends of Clinical Relevance

by Heather M. Fritz, Richard V. Pereira, Kathy Toohey-Kurth, Edie Marshall, Jenna Tucker and Kristin A. Clothier

Antibiotics 2022, 11(8), 1110; https://doi.org/10.3390/antibiotics11081110 - 17 Aug 2022

Cited by 7 | Viewed by 2844

Abstract

Salmonella enterica subsp. enterica serovar Dublin (S.Dublin) is a cattle-adapted pathogen that has emerged as one of the most commonly isolated and multidrug resistant (MDR) serovars in cattle. S.Dublin may be shed in feces, milk, and colostrum and persist [...] Read more.

Salmonella enterica subsp. enterica serovar Dublin (S.Dublin) is a cattle-adapted pathogen that has emerged as one of the most commonly isolated and multidrug resistant (MDR) serovars in cattle. S.Dublin may be shed in feces, milk, and colostrum and persist in asymptomatic cattle, leading to spread and outbreaks in herds. Though infections with S.Dublin in humans are rare, they are frequently severe, with extraintestinal spread that requires hospitalization and antimicrobial therapy. To determine minimum inhibitory concentration (MIC) and antimicrobial resistance (AMR) patterns and trends in cattle in California, broth microdilution testing was performed on 247 clinical S. Dublin isolates recovered from cattle at the California Animal Health and Food Safety Laboratory System (CAHFS) over the last three decades (1993–2019). Mean MICs and classification of resistance to antimicrobial drugs using a clinical livestock panel and the National Antimicrobial Resistance Monitoring System (NARMS) Gram-negative drug panels were utilized to assess prevalence and trends in AMR. Findings indicate an increase in AMR for the years 1993 to 2015. Notably, compared to the baseline year interval (1993–1999), there was an increase in resistance among quinolone and cephalosporin drugs, as well as an increased number of isolates with an MDR profile. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Livestock)

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