Antibiotics

3 pages, 211 KiB

Open AccessEditorial

Bacterial Pathogenesis and Antimicrobial Strategy

by Juan C. Vázquez-Ucha and Marta Martínez-Guitián

Antibiotics 2023, 12(12), 1750; https://doi.org/10.3390/antibiotics12121750 - 18 Dec 2023

Viewed by 837

Abstract

Antimicrobial resistance and multidrug resistance are major global health concerns [...] Full article

(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)

23 pages, 1716 KiB

Open AccessReview

Virulence Factors and Pathogenicity Mechanisms of Acinetobacter baumannii in Respiratory Infectious Diseases

by Yake Yao, Qi Chen and Hua Zhou

Antibiotics 2023, 12(12), 1749; https://doi.org/10.3390/antibiotics12121749 - 18 Dec 2023

Viewed by 1640

Abstract

Acinetobacter baumannii (A. baumannii) has become a notorious pathogen causing nosocomial and community-acquired infections, especially ventilator-associated pneumonia. This opportunistic pathogen is found to possess powerful genomic plasticity and numerous virulence factors that facilitate its success in the infectious process. Although the [...] Read more.

Acinetobacter baumannii (A. baumannii) has become a notorious pathogen causing nosocomial and community-acquired infections, especially ventilator-associated pneumonia. This opportunistic pathogen is found to possess powerful genomic plasticity and numerous virulence factors that facilitate its success in the infectious process. Although the interactions between A. baumannii and the pulmonary epitheliums have been extensively studied, a complete and specific description of its overall pathogenic process is lacking. In this review, we summarize the current knowledge of the antibiotic resistance and virulence factors of A. baumannii, specifically focusing on the pathogenic mechanisms of this detrimental pathogen in respiratory infectious diseases. An expansion of the knowledge regarding A. baumannii pathogenesis will contribute to the development of effective therapies based on immunopathology or intracellular signaling pathways to eliminate this harmful pathogen during infections. Full article

► Show Figures

Figure 1

12 pages, 1935 KiB

Open AccessArticle

Genomic Profiling of Multidrug-Resistant Swine Escherichia coli and Clonal Relationship to Human Isolates in Peru

by Luis Alvarez, Dennis Carhuaricra, Joel Palomino-Farfan, Sonia Calle, Lenin Maturrano and Juan Siuce

Antibiotics 2023, 12(12), 1748; https://doi.org/10.3390/antibiotics12121748 - 18 Dec 2023

Viewed by 2083

Abstract

The misuse of antibiotics is accelerating antimicrobial resistance (AMR) in Escherichia coli isolated from farm animals. The genomes of ten multidrug-resistant (MDR) E. coli isolates from pigs were analyzed to determine their sequence types, serotypes, virulence, and AMR genes (ARGs). Additionally, the relationship [...] Read more.

The misuse of antibiotics is accelerating antimicrobial resistance (AMR) in Escherichia coli isolated from farm animals. The genomes of ten multidrug-resistant (MDR) E. coli isolates from pigs were analyzed to determine their sequence types, serotypes, virulence, and AMR genes (ARGs). Additionally, the relationship was evaluated adding all the available genomes of Peruvian E. coli from humans using the cgMLST + HierCC scheme. Two aEPEC O186:H11-ST29 were identified, of which H11 and ST29 are reported in aEPEC isolates from different sources. An isolate ETEC-O149:H10-ST100 was identified, considered a high-risk clone that is frequently reported in different countries as a cause of diarrhea in piglets. One ExPEC O101:H11-ST167 was identified, for which ST167 is an international high-risk clone related to urinary infections in humans. We identified many ARGs, including extended-spectrum β-lactamase genes, and one ETEC harboring the mcr-1 gene. CgMLST + HierCC analysis differentiated three clusters, and in two, the human isolates were grouped with those of swine in the same cluster. We observed that Peruvian swine MDR E. coli cluster with Peruvian E. coli isolates from healthy humans and from clinical cases, which is of great public health concern and evidence that AMR surveillance should be strengthened based on the One Health approach. Full article

► Show Figures

Figure 1

13 pages, 530 KiB

Open AccessReview

Pharmacokinetic and Pharmacodynamic Considerations of Antibiotic Use in Neonates

by Mario Regazzi, Alberto Berardi, Simonetta Picone and Chryssoula Tzialla

Antibiotics 2023, 12(12), 1747; https://doi.org/10.3390/antibiotics12121747 - 18 Dec 2023

Viewed by 1320

Abstract

The selection of an appropriate dose of a given antibiotic for a neonate not only requires knowledge of the drug’s basic pharmacokinetic (PK) and pharmacodynamic (PD) properties but also the profound effects that organ development might have on the volume of distribution and [...] Read more.

The selection of an appropriate dose of a given antibiotic for a neonate not only requires knowledge of the drug’s basic pharmacokinetic (PK) and pharmacodynamic (PD) properties but also the profound effects that organ development might have on the volume of distribution and clearance, both of which may affect the PK/PD of a drug. Interest has grown in alternative antibiotic dosing strategies that are better aligned with the antibiotic’s PK and PD properties. These strategies should be used in conjunction with minimum inhibitory concentration measurements and therapeutic drug monitoring to measure their potential success. They can also guide the clinician in tailoring the delivery of antibiotics to suit an individual patient’s needs. Model-informed precision dosing, such as Bayesian forecasting dosing software (which incorporates PK/PD population models), may be utilized to optimize antibiotic exposure in neonatal populations. Consequently, optimizing the antibiotic dose and exposure in each newborn requires expertise in different fields. It drives the collaboration of physicians together with lab technicians and quantitative clinical pharmacologists. Full article

► Show Figures

Figure 1

21 pages, 1573 KiB

Open AccessReview

Strategies to Name Metallo-β-Lactamases and Number Their Amino Acid Residues

by Peter Oelschlaeger, Heba Kaadan and Rinku Dhungana

Antibiotics 2023, 12(12), 1746; https://doi.org/10.3390/antibiotics12121746 - 16 Dec 2023

Viewed by 1392

Abstract

Metallo-β-lactamases (MBLs), also known as class B β-lactamases (BBLs), are Zn(II)-containing enzymes able to inactivate a broad range of β-lactams, the most commonly used antibiotics, including life-saving carbapenems. They have been known for about six decades, yet they have only gained much attention [...] Read more.

Metallo-β-lactamases (MBLs), also known as class B β-lactamases (BBLs), are Zn(II)-containing enzymes able to inactivate a broad range of β-lactams, the most commonly used antibiotics, including life-saving carbapenems. They have been known for about six decades, yet they have only gained much attention as a clinical problem for about three decades. The naming conventions of these enzymes have changed over time and followed various strategies, sometimes leading to confusion. We are summarizing the naming strategies of the currently known MBLs. These enzymes are quite diverse on the amino acid sequence level but structurally similar. Problems trying to describe conserved residues, such as Zn(II) ligands and other catalytically important residues, which have different numbers in different sequences, have led to the establishment of a standard numbering scheme for BBLs. While well intended, the standard numbering scheme is not trivial and has not been applied consistently. We revisit this standard numbering scheme and suggest some strategies for how its implementation could be made more accessible to researchers. Standard numbering facilitates the comparison of different enzymes as well as their interaction with novel antibiotics and BBL inhibitors. Full article

(This article belongs to the Special Issue Feature Review Papers on β-Lactam and β-Lactam-β-Lactamase Inhibitor Combinations and Resistance Mechanisms to β-Lactam and β-Lactam-β-Lactamase Inhibitor Combinations)

► Show Figures

Figure 1

23 pages, 580 KiB

Open AccessArticle

Whole-Genome Investigation of Zoonotic Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 398 Isolated from Pigs and Humans in Thailand

by Pawarut Narongpun, Pattrarat Chanchaithong, Junya Yamagishi, Jeewan Thapa, Chie Nakajima and Yasuhiko Suzuki

Antibiotics 2023, 12(12), 1745; https://doi.org/10.3390/antibiotics12121745 - 16 Dec 2023

Cited by 1 | Viewed by 1473

Abstract

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been widespread globally in pigs and humans for decades. Nasal colonization of LA-MRSA is regarded as an occupational hazard to people who are regularly involved in livestock production. Our previous study suggested pig-to-human transmission caused by LA-MRSA [...] Read more.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been widespread globally in pigs and humans for decades. Nasal colonization of LA-MRSA is regarded as an occupational hazard to people who are regularly involved in livestock production. Our previous study suggested pig-to-human transmission caused by LA-MRSA clonal complex (CC) 398, using traditional molecular typing methods. Instead, this study aimed to investigate the zoonotic transmission of LA-MRSA CC398 using whole genome sequencing (WGS) technologies. A total of 63 LA-MRSA isolates were identified and characterized in Thailand. Further, the 16 representatives of LA-MRSA CC9 and CC398, including porcine and worker isolates, were subjected to WGS on the Illumina Miseq platform. Core-genome single nucleotide polymorphism (SNP)-based analyses verify the zoonotic transmission caused by LA-MRSA CC398 in two farms. WGS-based characterization suggests the emergence of a novel staphylococcal cassette chromosome (SCC) mec type, consisting of multiple cassette chromosome recombinase (ccr) gene complexes via genetic recombination. Additionally, the WGS analyses revealed putative multi-resistant plasmids and several cross-resistance genes, conferring resistance against drugs of last resort used in humans such as quinupristin/dalfopristin and linezolid. Significantly, LA-MRSA isolates, in this study, harbored multiple virulence genes that may become a serious threat to an immunosuppressive population, particularly for persons who are in close contact with LA-MRSA carriers. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Veterinary Science)

► Show Figures

Figure 1

15 pages, 1030 KiB

Open AccessSystematic Review

Antimicrobial Prophylaxis in Robot-Assisted Laparoscopic Radical Prostatectomy: A Systematic Review

by Eva Falkensammer, Ece Erenler, Truls E. Bjerklund Johansen, Lazaros Tzelves, Laila Schneidewind, Yuhong Yuan, Tommaso Cai, Bela Koves and Zafer Tandogdu

Antibiotics 2023, 12(12), 1744; https://doi.org/10.3390/antibiotics12121744 - 16 Dec 2023

Cited by 1 | Viewed by 1309

Abstract

It remains unclear whether antibiotic prophylaxis (AP) should be recommended or discouraged in robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer (PCa). The development of microbial resistance and side effects are risks of antibiotic use. This systematic review (SR) investigates the evidence base [...] Read more.

It remains unclear whether antibiotic prophylaxis (AP) should be recommended or discouraged in robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer (PCa). The development of microbial resistance and side effects are risks of antibiotic use. This systematic review (SR) investigates the evidence base for AP in RALP. A systematic literature search was conducted until 12 January 2023, using Embase, MEDLINE, Cochrane CENTRAL, Cochrane CDSR (via Ovid) and CINAHL for studies reporting the effect of AP on postoperative infectious complications in RALP. Of 436 screened publications, 8 studies comprising 6378 RALP procedures met the inclusion criteria. There was no evidence of a difference in the rate and severity of infective complications within 30 days after RALP surgery between different AP protocols. No studies omitted AP. For patients who received AP, the overall occurrence of postoperative infectious complications varied between 0.6% and 6.6%. The reported urinary tract infection (UTI) rates varied from 0.16% (4/2500) to 8.9% (15/169). Wound infections were reported in 0.46% (4/865) to 1.12% (1/89). Sepsis/bacteraemia and hyperpyrexia were registered in 0.1% (1/1084) and 1.6% (5/317), respectively. Infected lymphoceles (iLC) rates were 0.9% (3 of 317) in a RALP cohort that included 88.6% pelvic lymph node dissections (PLND), and 3% (26 of 865) in a RALP cohort where all patients underwent PLND. Our findings underscore that AP is being administered in RALP procedures without scientifically proven evidence. Prospective studies that apply consistent and uniform criteria for measuring infectious complications and antibiotic-related side effects are needed to ensure the comparability of results and guidance on AP in RALP. Full article

(This article belongs to the Special Issue Antibiotics Use in Infection and Public Health)

► Show Figures

Figure 1

23 pages, 2217 KiB

Open AccessArticle

Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters

by Nesrine Bouhrour, Tanny J. K. van der Reijden, Michella M. Voet, Bep Schonkeren-Ravensbergen, Robert A. Cordfunke, Jan Wouter Drijfhout, Farida Bendali and Peter H. Nibbering

Antibiotics 2023, 12(12), 1743; https://doi.org/10.3390/antibiotics12121743 - 16 Dec 2023

Viewed by 1382

Abstract

The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) [...] Read more.

The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on E. coli and K. pneumoniae biofilms but not on A. baumannii biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. Full article

(This article belongs to the Special Issue Bacterial-Associated Infections: Epidemiology, Antimicrobial Resistance and Its Impact on Health)

► Show Figures

Graphical abstract

15 pages, 358 KiB

Open AccessArticle

Knowledge and Perceptions of Final-Year Nursing Students Regarding Antimicrobials, Antimicrobial Resistance, and Antimicrobial Stewardship in South Africa: Findings and Implications to Reduce Resistance

by Elisma Teague, Selente Bezuidenhout, Johanna C. Meyer, Brian Godman and Deirdré Engler

Antibiotics 2023, 12(12), 1742; https://doi.org/10.3390/antibiotics12121742 - 16 Dec 2023

Viewed by 1133

Abstract

Antimicrobial resistance (AMR) is being increasingly seen as the next pandemic due to high morbidity and mortality rates, with Sub-Saharan Africa currently having the highest mortality rates driven by high rates of inappropriate prescribing in ambulatory care. In South Africa, nurses typically provide [...] Read more.

Antimicrobial resistance (AMR) is being increasingly seen as the next pandemic due to high morbidity and mortality rates, with Sub-Saharan Africa currently having the highest mortality rates driven by high rates of inappropriate prescribing in ambulatory care. In South Africa, nurses typically provide a range of services, including prescribing, in public ambulatory care clinics. However, little is currently known about the perception of final-year nursing students regarding antibiotic use, AMR, and antimicrobial stewardship (AMS). Consequently, we sought to address this important evidence gap. A quantitative descriptive study using a self-administered online questionnaire via Google Forms^® was undertaken among six universities in South Africa offering a Baccalaureus of Nursing. Knowledge on the classes of antibiotics, organisms covered, and mechanism of action was lacking. The sample size to achieve a confidence interval of 95% with a 5% error margin was 174, increased to 200 to compensate for possible attrition. Only 15.3% of nurses knew that ceftazidime is not a fourth-generation cephalosporin, and only 16.1% knew that clavulanic acid does not decrease inflammation at the site of infection. In addition, only 58.9% and 67.7% agreed that the prescribing of broad-spectrum antibiotics and poor infection control, respectively, increase AMR. AMS was also not a well-known concept among final-year nurses. The lack of knowledge regarding antibiotics, AMR, and AMS among final-year nurses could have important repercussions in practice once these nurses are qualified. Consequently, this information gap needs to be urgently addressed going forward with updated curricula and post-qualification educational activities to reduce AMR in South Africa Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Clinical Infection and Antibiotic Stewardship)

18 pages, 1890 KiB

Open AccessArticle

Exploring Facilitators and Barriers to Delayed Antibiotic Prescribing in Rural Northwest China: A Qualitative Study Using the Theoretical Domains Framework and Behavior Change Wheel

by Haishaerjiang Wushouer, Weihsin Ko, Kexin Du, Wanmeng Zhang, Lin Hu, Junxuan Yu, Kairui Zhang, Luwen Shi and Xiaodong Guan

Antibiotics 2023, 12(12), 1741; https://doi.org/10.3390/antibiotics12121741 - 15 Dec 2023

Viewed by 1164

Abstract

Background: Antimicrobial resistance, exacerbated by antibiotic misuse, poses a global threat. Though delayed antibiotic prescribing (DAP) can mitigate antibiotic overuse, its adoption in developing nations, such as China, is limited. This study probed barriers and facilitators to DAP in Xinjiang, characterized by extensive [...] Read more.

Background: Antimicrobial resistance, exacerbated by antibiotic misuse, poses a global threat. Though delayed antibiotic prescribing (DAP) can mitigate antibiotic overuse, its adoption in developing nations, such as China, is limited. This study probed barriers and facilitators to DAP in Xinjiang, characterized by extensive rural landscapes and primary care institutions (PCIs). Methods: Adopting a qualitative methodology, we conducted key informant interviews with thirty participants across six county hospitals in Xinjiang using VooV Meeting. Employing a two-stage sampling method targeting economically diverse areas, our interviews spanned physicians, pharmacists, patients, and caregivers. We organized the data according to the Theoretical Domains Framework (TDF) and the Behavior Change Wheel (BCW), spotlighting behavioral and policy elements impacting DAP. Results: Our research included thirty interviewees. Twelve physicians contemplated delayed prescriptions, while five adult patients and six caregivers encountered recommendations for delayed antibiotic prescriptions. Six patients sought pharmacists’ advice on antibiotic necessity. Prominent TDF domains were memory, attention, and beliefs about consequences. Critical intervention functions included education and environmental restructuring, while vital policy categories encompassed communication/marketing and guidelines. Conclusions: Countering antibiotic misuse and resistance in China necessitates overcoming barriers through strategic resource distribution, comprehensive education, rigorous training, and consistent monitoring, thereby promoting DAP adoption. The adoption of DAP in rural healthcare settings in China has the potential to significantly reduce antibiotic misuse, thereby mitigating the global threat of antimicrobial resistance. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship and Prescribing Practice)

► Show Figures

Figure 1

17 pages, 3055 KiB

Open AccessArticle

Evaluating the In Vivo Virulence of Environmental Pseudomonas aeruginosa Using Microinjection Model of Zebrafish (Danio rerio)

by Edit Kaszab, Dongze Jiang, István Szabó, Balázs Kriszt, Béla Urbányi, Sándor Szoboszlay, Rózsa Sebők, Illés Bock and Zsolt Csenki-Bakos

Antibiotics 2023, 12(12), 1740; https://doi.org/10.3390/antibiotics12121740 - 15 Dec 2023

Viewed by 1312

Abstract

(1) Background: Microinjection of zebrafish (Danio rerio) embryos offers a promising model for studying the virulence and potential environmental risks associated with Pseudomonas aeruginosa. (2) Methods: This work aimed to develop a P. aeruginosa infection model using two parallel exposition [...] Read more.

(1) Background: Microinjection of zebrafish (Danio rerio) embryos offers a promising model for studying the virulence and potential environmental risks associated with Pseudomonas aeruginosa. (2) Methods: This work aimed to develop a P. aeruginosa infection model using two parallel exposition pathways on zebrafish larvae with microinjection into the yolk and the perivitelline space to simultaneously detect the invasive and cytotoxic features of the examined strains. The microinjection infection model was validated with 15 environmental and clinical strains of P. aeruginosa of various origins, antibiotic resistance profiles, genotypes and phenotypes: both exposition pathways were optimized with a series of bacterial dilutions, different drop sizes (injection volumes) and incubation periods. Besides mortality, sublethal symptoms of the treated embryos were detected and analyzed. (3) Results: According to the statistical evaluation of our results, the optimal parameters (dilution, drop size and incubation period) were determined. (4) Conclusions: The tested zebrafish embryo microinjection infection model is now ready for use to determine the in vivo virulence and ecological risk of environmental P. aeruginosa. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach)

► Show Figures

Figure 1

19 pages, 5562 KiB

Open AccessArticle

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus

by José B. de Araújo-Neto, Cícera D. de M. Oliveira-Tintino, Gildênia A. de Araújo, Daniel S. Alves, Fernanda R. Ribeiro, Guilherme A. Brancaglion, Diogo T. Carvalho, Clara Mariana Gonçalves Lima, Hani S. H. Mohammed Ali, Irfan A. Rather, Mohmmad Y. Wani, Talha B. Emran, Henrique D. M. Coutinho, Valdir de Q. Balbino and Saulo R. Tintino

Antibiotics 2023, 12(12), 1739; https://doi.org/10.3390/antibiotics12121739 - 15 Dec 2023

Cited by 2 | Viewed by 1474

Abstract

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent [...] Read more.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study’s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus. Full article

(This article belongs to the Special Issue Antibiotic Adjuvants: An Approach to Overcoming Multi-Drug Resistance and Biofilm Infections)

► Show Figures

Figure 1

21 pages, 1654 KiB

Open AccessReview

Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics

by Sheryl A. Zelenitsky

Antibiotics 2023, 12(12), 1738; https://doi.org/10.3390/antibiotics12121738 - 14 Dec 2023

Viewed by 1281

Abstract

Appropriate surgical antimicrobial prophylaxis (SAP) is an important measure in preventing surgical site infections (SSIs). Although antimicrobial pharmacokinetics–pharmacodynamics (PKPD) is integral to optimizing antibiotic dosing for the treatment of infections, there is less research on preventing infections postsurgery. Whereas clinical studies of SAP [...] Read more.

Appropriate surgical antimicrobial prophylaxis (SAP) is an important measure in preventing surgical site infections (SSIs). Although antimicrobial pharmacokinetics–pharmacodynamics (PKPD) is integral to optimizing antibiotic dosing for the treatment of infections, there is less research on preventing infections postsurgery. Whereas clinical studies of SAP dose, preincision timing, and redosing are informative, it is difficult to isolate their effect on SSI outcomes. Antimicrobial PKPD aims to explain the complex relationship between antibiotic exposure during surgery and the subsequent development of SSI. It accounts for the many factors that influence the PKs and antibiotic concentrations in patients and considers the susceptibilities of bacteria most likely to contaminate the surgical site. This narrative review examines the relevance and role of PKPD in providing effective SAP. The dose–response relationship i.e., association between lower dose and SSI in cefazolin prophylaxis is discussed. A comprehensive review of the evidence for an antibiotic concentration–response (SSI) relationship in SAP is also presented. Finally, PKPD considerations for improving SAP are explored with a focus on cefazolin prophylaxis in adults and outstanding questions regarding its dose, preincision timing, and redosing during surgery. Full article

(This article belongs to the Special Issue Perioperative Antibiotic Prophylaxis)

► Show Figures

Figure 1

17 pages, 594 KiB

Open AccessSystematic Review

Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies

by Gianpiero Tebano, Giulia la Martire, Luigi Raumer, Monica Cricca, Davide Melandri, Federico Pea and Francesco Cristini

Antibiotics 2023, 12(12), 1737; https://doi.org/10.3390/antibiotics12121737 - 14 Dec 2023

Viewed by 1256

Abstract

Background: Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the [...] Read more.

Background: Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population. Methods: We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients. We extracted and synthetized data on drug regimens and their ability to attain adequate PK/PD targets. Results: We selected 35 studies for analysis. Overall, studies showed that both high doses and the continuous infusion (CI) of broad-spectrum beta-lactams were needed to achieve internationally-recognized PK/PD targets, ideally with therapeutic drug monitoring guidance. The most extensive evidence concerned meropenem, but similar conclusions could be drawn about piperacillin-tazobactam, ceftazidime, cefepime, imipenem-clinastatin and aztreonam. Insufficient data were available about new beta-lactam-beta-lactamase inhibitor combinations, ceftaroline, ceftobiprole and cefiderocol. Conclusions: Both high doses and CI of broad-spectrum beta-lactams are needed when treating burn patients due to the peculiar changes in the PK/PD of antibiotics in this population. Further studies are needed, particularly about newer antibiotics. Full article

(This article belongs to the Special Issue Antibiotics in the Critically Ill Patient)

► Show Figures

Figure 1

15 pages, 1571 KiB

Open AccessArticle

Could an Optimized Joint Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin-Tazobactam Be a Valuable Innovative Approach for Maximizing the Effectiveness of Monotherapy Even in the Treatment of Critically Ill Patients with Documented Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections and/or Ventilator-Associated Pneumonia?

by Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Pierluigi Viale and Federico Pea

Antibiotics 2023, 12(12), 1736; https://doi.org/10.3390/antibiotics12121736 - 14 Dec 2023

Cited by 3 | Viewed by 1286

Abstract

(1) Background: Piperacillin-tazobactam represents the first-line option for treating infections caused by full- or multi-susceptible Enterobacterales and/or Pseudomonas aeruginosa in critically ill patients. Several studies reported that attaining aggressive pharmacokinetic/pharmacodynamic (PK/PD) targets with beta-lactams is associated with an improved microbiological/clinical outcome. We aimed [...] Read more.

(1) Background: Piperacillin-tazobactam represents the first-line option for treating infections caused by full- or multi-susceptible Enterobacterales and/or Pseudomonas aeruginosa in critically ill patients. Several studies reported that attaining aggressive pharmacokinetic/pharmacodynamic (PK/PD) targets with beta-lactams is associated with an improved microbiological/clinical outcome. We aimed to assess the relationship between the joint PK/PD target attainment of continuous infusion (CI) piperacillin-tazobactam and the microbiological/clinical outcome of documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP) of critically ill patients treated with CI piperacillin-tazobactam monotherapy. (2) Methods: Critically ill patients admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 treated with CI piperacillin-tazobactam monotherapy optimized by means of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program for documented Gram-negative BSIs and/or VAP were retrospectively retrieved. Steady-state plasma concentrations (C_ss) of piperacillin and of tazobactam were measured, and the free fractions (f) were calculated according to respective plasma protein binding. The joint PK/PD target was defined as optimal whenever both the piperacillin fC_ss/MIC ratio was >4 and the tazobactam fC_ss/target concentration (C_T) ratio was > 1 (quasi-optimal or suboptimal whenever only one or none of the two weas achieved, respectively). Multivariate logistic regression analysis was performed for testing variables potentially associated with microbiological outcome. (3) Results: Overall, 43 critically ill patients (median age 69 years; male 58.1%; median SOFA score at baseline 8) treated with CI piperacillin-tazobactam monotherapy were included. Optimal joint PK/PD target was attained in 36 cases (83.7%). At multivariate analysis, optimal attaining of joint PK/PD target was protective against microbiological failure (OR 0.03; 95%CI 0.003–0.27; p = 0.002), whereas quasi-optimal/suboptimal emerged as the only independent predictor of microbiological failure (OR 37.2; 95%CI 3.66–377.86; p = 0.002). (4) Conclusion: Optimized joint PK/PD target attainment of CI piperacillin-tazobactam could represent a valuable strategy for maximizing microbiological outcome in critically ill patients with documented Gram-negative BSI and/or VAP, even when sustained by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. In this scenario, implementing a real-time TDM-guided ECPA program may be helpful in preventing failure in attaining optimal joint PK/PD targets among critically ill patients. Larger prospective studies are warranted to confirm our findings. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring in Intensive Care)

► Show Figures

Figure 1

23 pages, 4098 KiB

Open AccessArticle

Unveiling the Microbiome Landscape: A Metagenomic Study of Bacterial Diversity, Antibiotic Resistance, and Virulence Factors in the Sediments of the River Ganga, India

by Ajaya Kumar Rout, Partha Sarathi Tripathy, Sangita Dixit, Dibyajyoti Uttameswar Behera, Bhaskar Behera, Basanta Kumar Das and Bijay Kumar Behera

Antibiotics 2023, 12(12), 1735; https://doi.org/10.3390/antibiotics12121735 - 14 Dec 2023

Cited by 2 | Viewed by 1311

Abstract

The global rise in antibiotic resistance, fueled by indiscriminate antibiotic usage in medicine, aquaculture, agriculture, and the food industry, presents a significant public health challenge. Urban wastewater and sewage treatment plants have become key sources of antibiotic resistance proliferation. The present study focuses [...] Read more.

The global rise in antibiotic resistance, fueled by indiscriminate antibiotic usage in medicine, aquaculture, agriculture, and the food industry, presents a significant public health challenge. Urban wastewater and sewage treatment plants have become key sources of antibiotic resistance proliferation. The present study focuses on the river Ganges in India, which is heavily impacted by human activities and serves as a potential hotspot for the spread of antibiotic resistance. We conducted a metagenomic analysis of sediment samples from six distinct locations along the river to assess the prevalence and diversity of antibiotic resistance genes (ARGs) within the microbial ecosystem. The metagenomic analysis revealed the predominance of Proteobacteria across regions of the river Ganges. The antimicrobial resistance (AMR) genes and virulence factors were determined by various databases. In addition to this, KEGG and COG analysis revealed important pathways related to AMR. The outcomes highlight noticeable regional differences in the prevalence of AMR genes. The findings suggest that enhancing health and sanitation infrastructure could play a crucial role in mitigating the global impact of AMR. This research contributes vital insights into the environmental aspects of antibiotic resistance, highlighting the importance of targeted public health interventions in the fight against AMR. Full article

(This article belongs to the Special Issue Insights into Antibiotics in Human, Animal, and Agriculture: Resistance, Determinant, and Treatment)

► Show Figures

Figure 1

12 pages, 725 KiB

Open AccessArticle

Adaptive Phage Therapy for the Prevention of Recurrent Nosocomial Pneumonia: Novel Protocol Description and Case Series

by Fedor Zurabov, Marina Petrova, Alexander Zurabov, Marina Gurkova, Petr Polyakov, Dmitriy Cheboksarov, Ekaterina Chernevskaya, Mikhail Yuryev, Valentina Popova, Artem Kuzovlev, Alexey Yakovlev and Andrey Grechko

Antibiotics 2023, 12(12), 1734; https://doi.org/10.3390/antibiotics12121734 - 14 Dec 2023

Viewed by 1470

Abstract

Nowadays there is a growing interest worldwide in using bacteriophages for therapeutic purposes to combat antibiotic-resistant bacterial strains, driven by the increasing ineffectiveness of drugs against bacterial infections. Despite this fact, no novel commercially available therapeutic phage products have been developed in the [...] Read more.

Nowadays there is a growing interest worldwide in using bacteriophages for therapeutic purposes to combat antibiotic-resistant bacterial strains, driven by the increasing ineffectiveness of drugs against bacterial infections. Despite this fact, no novel commercially available therapeutic phage products have been developed in the last two decades, as it is extremely difficult to register them under the current legal regulations. This paper presents a description of the interaction between a bacteriophage manufacturer and a clinical institution, the specificity of which is the selection of bacteriophages not for an individual patient, but for the entire spectrum of bacteria circulating in the intensive care unit with continuous clinical and microbiological monitoring of efficacy. The study presents the description of three clinical cases of patients who received bacteriophage complex via inhalation for 28 days according to the protocol without antibiotic use throughout the period. No adverse effects were observed and the elimination of multidrug-resistant microorganisms from the bronchoalveolar lavage contents was detected in all patients. A decrease in such inflammatory markers as C-reactive protein (CRP) and procalcitonin was also noted. The obtained results demonstrate the potential of an adaptive phage therapy protocol in intensive care units for reducing the amount of antibiotics used and preserving their efficacy. Full article

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

► Show Figures

Figure 1

17 pages, 1540 KiB

Open AccessEditor’s ChoiceReview

How We Treat Drug-Susceptible Pulmonary Tuberculosis: A Practical Guide for Clinicians

by Niccolò Riccardi, Sara Occhineri, Elisa Vanino, Roberta Maria Antonello, Agostina Pontarelli, Francesca Saluzzo, Tiziana Masini, Giorgio Besozzi, Marina Tadolini, Luigi Codecasa and on behalf of StopTB Italia

Antibiotics 2023, 12(12), 1733; https://doi.org/10.3390/antibiotics12121733 - 14 Dec 2023

Viewed by 1312

Abstract

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis [...] Read more.

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript. Full article

(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)

► Show Figures

Figure 1

15 pages, 1112 KiB

Open AccessReview

Gut-Antimicrobial Peptides: Synergistic Co-Evolution with Antibiotics to Combat Multi-Antibiotic Resistance

by Piyush Baindara and Santi M. Mandal

Antibiotics 2023, 12(12), 1732; https://doi.org/10.3390/antibiotics12121732 - 14 Dec 2023

Cited by 2 | Viewed by 1517

Abstract

Due to huge diversity and dynamic competition, the human gut microbiome produces a diverse array of antimicrobial peptides (AMPs) that play an important role in human health. The gut microbiome has an important role in maintaining gut homeostasis by the AMPs and by [...] Read more.

Due to huge diversity and dynamic competition, the human gut microbiome produces a diverse array of antimicrobial peptides (AMPs) that play an important role in human health. The gut microbiome has an important role in maintaining gut homeostasis by the AMPs and by interacting with other human organs via established connections such as the gut–lung, and gut–brain axis. Additionally, gut AMPs play a synergistic role with other gut microbiota and antimicrobials to maintain gut homeostasis by fighting against multi-antibiotic resistance (MAR) bacteria. Further, conventional antibiotics intake creates a synergistic evolutionary pressure for gut AMPs, where antibiotics and gut AMPs fight synergistically against MAR. Overall, gut AMPs are evolving under a complex and highly synergistic co-evolutionary pressure created by the various interactions between gut microbiota, gut AMPs, and antibiotics; however, the complete mechanism is not well understood. The current review explores the synergistic action of gut AMPs and antibiotics along with possibilities to fight against MAR bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: An Emerging Hope in the Era of New Infections and Resistance)

► Show Figures

Figure 1

11 pages, 2029 KiB

Open AccessArticle

Colistin Effects on Emphysematous Lung in an LPS-Sepsis Model

by Rodopi Stamatiou, Anna Vasilaki, Dimitra Tzini, Konstantina Deskata, Konstantina Zacharouli, Maria Ioannou, Markos Sgantzos, Epaminondas Zakynthinos and Demosthenes Makris

Antibiotics 2023, 12(12), 1731; https://doi.org/10.3390/antibiotics12121731 - 14 Dec 2023

Viewed by 1045

Abstract

Emphysema is prevalent in various respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD) and cystic fibrosis. Colistin and vasoconstrictive drugs are crucial for treating these patients when diagnosed with sepsis in the ICU. This study examines colistin impact in ether-induced emphysematous septic and [...] Read more.

Emphysema is prevalent in various respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD) and cystic fibrosis. Colistin and vasoconstrictive drugs are crucial for treating these patients when diagnosed with sepsis in the ICU. This study examines colistin impact in ether-induced emphysematous septic and non-septic animals, focusing on lung pathophysiology and inflammatory responses, including IL-1β, TNF-α, AMPK, caspase-3, cyclin-D1, and colistin levels in lung tissue. All animals exhibited significant emphysematous changes, accentuated by LPS-induced septic conditions, validating the emphysema model and highlighting the exacerbating effect of sepsis on lung pathology. Colistin, alone or with vasoconstrictive drugs, stimulated immune responses through increased inflammatory cell infiltration and the presence of lymphocytes, indicating potential immunomodulatory effects. Vasoconstriction did not alter the effects of colistin or sepsis but correlated with increased colistin levels in the lungs of septic animals. These observations suggest a potential interplay between vasoconstrictive drugs and colistin distribution/metabolism, leading to enhanced local concentrations of colistin in the lung microenvironment. The findings suggest the need for further investigations to optimize colistin and vasoconstrictive drug delivery in critically ill patients with lung pathologies. Understanding these complexities may guide more effective management of inflammatory responses and lung pathologies in these critical conditions. Full article

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

► Show Figures

Figure 1

15 pages, 1343 KiB

Open AccessArticle

Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure

by Stephan Schmid, Chiara Koch, Katharina Zimmermann, Jonas Buttenschoen, Alexander Mehrl, Vlad Pavel, Sophie Schlosser-Hupf, Daniel Fleischmann, Alexander Krohn, Tobias Schilling, Martina Müller and Alexander Kratzer

Antibiotics 2023, 12(12), 1730; https://doi.org/10.3390/antibiotics12121730 - 14 Dec 2023

Cited by 1 | Viewed by 1110

Abstract

(1) Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing disease in patients with liver cirrhosis. Meropenem is crucial for treating severe infections. Therapeutic drug monitoring (TDM) offers an effective means to control drug dosages, especially vital for bactericidal antibiotics like meropenem. [...] Read more.

(1) Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing disease in patients with liver cirrhosis. Meropenem is crucial for treating severe infections. Therapeutic drug monitoring (TDM) offers an effective means to control drug dosages, especially vital for bactericidal antibiotics like meropenem. We aimed to assess the outcomes of implementing TDM for meropenem using an innovative interprofessional approach in ACLF patients on a medical intensive care unit (ICU). (2) Methods: The retrospective study was conducted on a medical ICU. The outcomes of an interprofessional approach comprising physicians, hospital pharmacists, and staff nurses to TDM for meropenem in critically ill patients with ACLF were examined in 25 patients. Meropenem was administered continuously via an infusion pump after the application of an initial loading dose. TDM was performed weekly using high-performance liquid chromatography (HPLC). Meropenem serum levels, implementation of the recommendations of the interprofessional team, and meropenem consumption were analyzed. (3) Results: Initial TDM for meropenem showed a mean meropenem serum concentration of 20.9 ± 9.6 mg/L in the 25 analyzed patients. Of note, in the initial TDM, only 16.0% of the patients had meropenem serum concentrations within the respective target range, while 84.0% exceeded this range. Follow-up TDM showed serum concentrations of 15.2 ± 5.7 mg/L (9.0–24.6) in Week 2 and 11.9 ± 2.3 mg/L (10.2–13.5) in Week 3. In Week 2, 41.7% of the patients had meropenem serum concentrations that were within the respective target range, while 58.3% of the patients were above this range. In Week 3, 50% of the analyzed serum concentrations of meropenem were within the targeted range, and 50% were above the range. In total, 100% of the advice given by the interprofessional team regarding meropenem dosing or a change in antibiotic therapy was implemented. During the intervention period, the meropenem application density was 37.9 recommended daily doses (RDD)/100 patient days (PD), compared to 42.1 RDD/100 PD in the control period, representing a 10.0% decrease. (4) Conclusions: Our interprofessional approach to TDM significantly reduced meropenem dosing, with all the team’s recommendations being implemented. This method not only improved patient safety but also considerably decreased the application density of meropenem. Full article

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

► Show Figures

Figure 1

19 pages, 1476 KiB

Open AccessReview

Cefiderocol and Sulbactam-Durlobactam against Carbapenem-Resistant Acinetobacter baumannii

by Arta Karruli, Antonella Migliaccio, Spyros Pournaras, Emanuele Durante-Mangoni and Raffaele Zarrilli

Antibiotics 2023, 12(12), 1729; https://doi.org/10.3390/antibiotics12121729 - 14 Dec 2023

Viewed by 1763

Abstract

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal β-lactam–β-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. [...] Read more.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal β-lactam–β-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. baumannii infections. In this review, we discuss the mechanisms of action of and resistance to cefiderocol and sulbactam-durlobactam, the antimicrobial susceptibility of A. baumannii isolates to these drugs, as well as the clinical effectiveness of cefiderocol and sulbactam/durlobactam-based regimens against CRAB. Overall, cefiderocol and sulbactam-durlobactam show an excellent antimicrobial activity against CRAB. The review of clinical studies evaluating the efficacy of cefiderocol therapy against CRAB indicates it is non-inferior to colistin/other treatments for CRAB infections, with a better safety profile. Combination treatment is not associated with improved outcomes compared to monotherapy. Higher mortality rates are often associated with prior patient comorbidities and the severity of the underlying infection. Regarding sulbactam-durlobactam, current data from the pivotal clinical trial and case reports suggest this antibiotic combination could be a valuable option in critically ill patients affected by CRAB infections, in particular where no other antibiotic appears to be effective. Full article

(This article belongs to the Special Issue Molecular Characterization of Gram-Negative Bacteria: Antimicrobial Resistance, Virulence and Epidemiology)

► Show Figures

Figure 1

18 pages, 2862 KiB

Open AccessArticle

In Vitro Microevolution and Co-Selection Assessment of Florfenicol Impact on Escherichia coli Resistance Development

by Ádám Kerek, Bence Török, Levente Laczkó, Gábor Kardos, Krisztián Bányai, Zoltán Somogyi, Eszter Kaszab, Krisztina Bali and Ákos Jerzsele

Antibiotics 2023, 12(12), 1728; https://doi.org/10.3390/antibiotics12121728 - 14 Dec 2023

Cited by 1 | Viewed by 1162

Abstract

The issue of antimicrobial resistance is becoming an increasingly serious challenge in both human and veterinary medicine. Prudent antimicrobial use in veterinary medicine is warranted and supported by international guidelines, with the Antimicrobial Advice Ad Hoc Expert Group (AMEG) placing particular emphasis on [...] Read more.

The issue of antimicrobial resistance is becoming an increasingly serious challenge in both human and veterinary medicine. Prudent antimicrobial use in veterinary medicine is warranted and supported by international guidelines, with the Antimicrobial Advice Ad Hoc Expert Group (AMEG) placing particular emphasis on the critically important group B antimicrobials. These antimicrobials are commonly employed, especially in the poultry and swine industry. The impact of florfenicol, a veterinary antibiotic, was studied on the resistance development of Escherichia coli. The aim of the study was to investigate the effect of the use of florfenicol on the development of phenotypic and genomic resistances, not only to the drug itself but also to other drugs. The minimum inhibitory concentrations (MICs) of the antibiotics were investigated at 1×, 10×, 100× and 1000× concentrations using the adapted Microbial Evolution and Growth Arena (MEGA-plate) method. The results demonstrate that florfenicol can select for resistance to fluoroquinolone antibiotics (167× MIC value increase) and cephalosporins (67× MIC value increase). A total of 44 antimicrobial resistance genes were identified, the majority of which were consistent across the samples. Chromosomal point mutations, including alterations in resistance-associated and regulatory genes (acrB, acrR, emrR and robA), are thought to trigger multiple drug efflux pump activations, leading to phenotypically increased resistance. The study underscores the impact of florfenicol and its role in the development of antimicrobial resistance, particularly concerning fluoroquinolone antibiotics and cephalosporins. This study is the first to report florfenicol’s dose-dependent enhancement of other antibiotics’ MICs, linked to mutations in SOS-box genes (mdtABC-tolC, emrAB-tolC and acrAB-tolC) and increased multidrug efflux pump genes. Mutations in the regulatory genes acrR, emrR and rpbA support the possibility of increased gene expression. The results are crucial for understanding antimicrobial resistance and its development, highlighting the promising potential of in vitro evolutionary and coselection studies for future research. Full article

(This article belongs to the Special Issue Epidemiology, Impact and Mitigation of Antimicrobial Resistance in Veterinary Medicine, 2nd Volume)

► Show Figures

Figure 1

11 pages, 1201 KiB

Open AccessArticle

Interhospital Spread of bla_VIM-1- and bla_CTX-M-15-Producing K. pneumoniae ST15 on an IncR Plasmid in Southern Spain

by Patricia Pérez-Palacios, Ana Gual-de-Torrella, Ines Portillo-Calderón, Esther Recacha-Villamor, Francisco Franco-Álvarez de Luna, Lorena Lopez-Cerero and Alvaro Pascual

Antibiotics 2023, 12(12), 1727; https://doi.org/10.3390/antibiotics12121727 - 13 Dec 2023

Viewed by 919

Abstract

In 2014–2015, the main CTX-M-15- and OXA-48-producing clone in our region was ST15. Recently, K. pneumoniae ST15 isolates co-producing VIM-1 and CTX-M-15 were detected in several hospitals. The aim was to study the emergence and acquisition of this carbapenemase. Between 2017 and 2019, [...] Read more.

In 2014–2015, the main CTX-M-15- and OXA-48-producing clone in our region was ST15. Recently, K. pneumoniae ST15 isolates co-producing VIM-1 and CTX-M-15 were detected in several hospitals. The aim was to study the emergence and acquisition of this carbapenemase. Between 2017 and 2019, four hospitals submitted twenty-nine VIM-1- and CTX-M-15-producing K. pneumoniae ST15 isolates to our laboratory. Seven representatives of each XbaI PFGE pulsotype were sequenced using short- and long-read technologies. RAST, CGE databases, and Pathogenwatch were used for resistance determinants and capsule-type analysis. Plasmid comparison was performed with Easyfig2.1. Phylogenetic analysis included other contemporary ST15 isolates from Spain. The 29 isolates were clustered into seven different pulsotypes. The selected genomes, from three hospitals in two different provinces, were clustered together (fewer than 35 alleles) and differed by more than 100 alleles from other ST15 isolates obtained in the region. These seven isolates harbored one IncR plasmid (200–220 kb) with a common backbone and four regions flanked by IS26: one contained bla_VIM-1, another contained bla_CTX-M-15, the third contained bla_OXA-1, and the fourth harbored heavy-metal-tolerance genes. The two initial plasmids, from two different centers, were identical, and rearrangement of four regions was observed in the five subsequent plasmids. Our findings showed the first intercenter dissemination of IncR plasmids carrying bla_VIM-1, bla_CTX-M-15, and metal-tolerance genes mediated by a new lineage of K. pneumoniae ST15. Two different capture events of the bla_VIM-1 gene or different IS26-mediated plasmid rearrangements from a common ancestor may explain plasmid variations. Full article

(This article belongs to the Special Issue Antibiotics Resistance and Molecular Epidemiology of Carbapenem-Resistance Bacteria)

► Show Figures

Figure 1

12 pages, 2620 KiB

Open AccessArticle

Susceptibility Profile and Epidemiological Cut-Off Values Are Influenced by Serotype in Fish Pathogenic Streptococcus agalactiae

by Carlos Augusto Gomes Leal, Brendhal Almeida Silva and Salene Angelini Colombo

Antibiotics 2023, 12(12), 1726; https://doi.org/10.3390/antibiotics12121726 - 13 Dec 2023

Viewed by 943

Abstract

Streptococcus agalactiae is a major health concern in tilapia farming worldwide. In contrast to the availability of susceptibility profile results, interpretative criteria for disk diffusion assays and the influence of serotypes on resistance profiles are not available. To address this, sixty isolates (thirty [...] Read more.

Streptococcus agalactiae is a major health concern in tilapia farming worldwide. In contrast to the availability of susceptibility profile results, interpretative criteria for disk diffusion assays and the influence of serotypes on resistance profiles are not available. To address this, sixty isolates (thirty of each serotype, Ib and III) were evaluated using the disk diffusion assay against six antibiotics, and the epidemiological cut-off value (ECV) was calculated. All the isolates were classified as non-wild type (NWT) for sulfamethoxazole (SUT) and norfloxacin (NOR). The inhibition zones for oxytetracycline (OXY) and doxycycline (DOX) were largely distinct; all serotype Ib and III isolates were classified as wild-type (WT) and NWT, respectively. The results for serotype III of fish group B Streptococcus (GBS) were comparable to the NWT tetracycline profile of human GBS available in EUCAST, suggesting the presence of resistance mechanisms in these fish isolates. The calculation of the cut-off wild type (CO_WT) values for OXY and DOX was appropriate for both serotypes. Differences between the distribution of florfenicol (FLO) and amoxicillin (AMO) were found, and we attribute this to the faster growth rate of serotype III, which promotes smaller inhibition zones. Therefore, using separate CO_WT for each serotype is necessary. In conclusion, the serotype of fish GBS affects its susceptibility profile, and it is recommended to use serotype-specific CO_WT values as interpretative criteria for disk diffusion assays against FLO and AMO. Full article

► Show Figures

Figure 1

16 pages, 1538 KiB

Open AccessReview

European Wild Carnivores and Antibiotic Resistant Bacteria: A Review

by Andreia Garcês and Isabel Pires

Antibiotics 2023, 12(12), 1725; https://doi.org/10.3390/antibiotics12121725 - 13 Dec 2023

Cited by 1 | Viewed by 954

Abstract

Antibiotic resistance is a global concern that affects not only human health but also the health of wildlife and the environment. Wildlife can serve as reservoirs for antibiotic-resistant bacteria, and antibiotics in veterinary medicine and agriculture can contribute to the development of resistance [...] Read more.

Antibiotic resistance is a global concern that affects not only human health but also the health of wildlife and the environment. Wildlife can serve as reservoirs for antibiotic-resistant bacteria, and antibiotics in veterinary medicine and agriculture can contribute to the development of resistance in these populations. Several European carnivore species, such as wolves, foxes, otters, and bears, can be exposed to antibiotics by consuming contaminated food, water, or other resources in their habitats. These animals can also be indirectly exposed to antibiotics through interactions with domestic animals and human activities in their environment. Antibiotic resistance in wildlife can harm ecosystem health and also impact human health indirectly through various pathways, including zoonotic disease transmission. Moreover, the spread of resistant bacteria in wildlife can complicate conservation efforts, as it can threaten already endangered species. This review aims to describe the presence of antibiotic-resistant bacteria in wild carnivores in Europe. Full article

(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment)

► Show Figures

Figure 1

7 pages, 233 KiB

Open AccessCommunication

Application of Octenidine into Nasal Vestibules Does Not Influence SARS-CoV-2 Detection via PCR or Antigen Test Methods

by Ojan Assadian, Fabiola Sigmund, Daniela Herzog, Karin Riedl and Christoph Klaus

Antibiotics 2023, 12(12), 1724; https://doi.org/10.3390/antibiotics12121724 - 13 Dec 2023

Viewed by 885

Abstract

The targeted or universal decolonization of patients through octenidine for nasal treatment and antiseptic body wash for 3 to 5 days prior elective surgery has been implemented in several surgical disciplines in order to significantly reduce surgical site infections (SSIs) caused by Staphylococcus [...] Read more.

The targeted or universal decolonization of patients through octenidine for nasal treatment and antiseptic body wash for 3 to 5 days prior elective surgery has been implemented in several surgical disciplines in order to significantly reduce surgical site infections (SSIs) caused by Staphylococcus aureus carriage. However, as most healthcare facilities also screen patients on admission for pilot infection, it is imperative that a prophylactic nasal decolonization procedure not yield a false negative SARS-CoV-2 status in otherwise positive patients. We assessed the effect of a commercially available octenidine-containing nasal gel on two different screening methods—antigen (Ag) detection based on colloidal gold immunochromatography and RT-PCR—in a prospective-type accuracy pilot study in asymptomatic SARS-CoV-2-positive inpatients. All patients still showed a positive test result after using the octenidine-containing nasal gel for about 3 days; therefore, its application did not influence SARS-CoV-2 screening, which is of high clinical relevance. Of note is that Ag detection was less sensitive, regardless of the presence of octenidine. From an infection prevention perspective, these results favor octenidine-based decolonization strategies, even during seasonal SARS-CoV-2 periods. As only asymptomatic patients are considered for elective interventions, screening programs based on RT-PCR technology should be preferred. Full article

(This article belongs to the Special Issue Membranes to Fight Drug-Resistant Microbes)

11 pages, 314 KiB

Open AccessArticle

Bloodstream Infections by Pantoea Species: Clinical and Microbiological Findings from a Retrospective Study, Italy, 2018–2023

by Roberto Casale, Matteo Boattini, Gabriele Bianco, Sara Comini, Silvia Corcione, Silvia Garazzino, Erika Silvestro, Francesco Giuseppe De Rosa, Rossana Cavallo and Cristina Costa

Antibiotics 2023, 12(12), 1723; https://doi.org/10.3390/antibiotics12121723 - 13 Dec 2023

Viewed by 1843

Abstract

(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, Pantoea species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on [...] Read more.

(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, Pantoea species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on a few anecdotal reports. (2) Methods: We conducted this five-year (2018–2023) single-center study aimed at investigating the prevalence and clinical and microbiological findings of Pantoea species bloodstream infections. (3) Results: Among the 4996 bloodstream infection Gram-negative isolates collected during the study period, Pantoea species accounted for 0.4% (n = 19) of isolates from 19 different patients, 5 of them being pediatric cases. Among Pantoea species isolates, P. agglomerans was the most frequently detected (45%; n = 9) followed by P. eucrina (30%; n = 6) and P. septica (15%; n = 3). Malignancy (35.7%) in adults and malignancy (40%) and cerebrovascular disease following meconium aspiration (40%) in pediatric patients as comorbidities and shivering and/or fever following parenteral infusion (36.8%) as a symptom/sign of Pantoea species bloodstream infection onset were the most frequently observed clinical features. Among adults, primary bloodstream infection was the most frequent (50%), whereas among pediatric patients, the most commonly identified sources of infection were catheter-related (40%) and the respiratory tract (40%). Overall, Pantoea species bloodstream infection isolates displayed high susceptibility to all the antibiotics except for ampicillin (63.2%), fosfomycin (73.7%), and piperacillin/tazobactam (84.2%). Targeted antibiotic treatment was prescribed as monotherapy for adults (71.4%) and combination therapy for pediatric patients (60%). The most prescribed antibiotic regimens were piperacillin/tazobactam (21.4%) in adults and meropenem- (40%) and aminoglycoside-containing (40%) antibiotics in pediatric patients. The overall 28-day all-cause mortality rate was 5.3% (n = 1). (4) Conclusions: The prevalence and 28-day mortality rate of Pantoea species bloodstream infections were low. The prescription of targeted therapy including broad-spectrum antibiotics could indicate an underestimation of the specific involvement of the Pantoea species in the onset of the disease, warranting further studies defining their pathogenic potential. Full article

(This article belongs to the Special Issue Bacteremia: Clinical Diagnostics and Epidemiology)

11 pages, 284 KiB

Open AccessArticle

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients

by Valeria Castelli, Enric Sastre-Escolà, Pedro Puerta-Alcalde, Leyre Huete-Álava, Júlia Laporte-Amargós, Alba Bergas, Mariana Chumbita, Mar Marín, Eva Domingo-Domenech, Ana María Badia-Tejero, Paula Pons-Oltra, Carolina García-Vidal, Jordi Carratalà and Carlota Gudiol

Antibiotics 2023, 12(12), 1722; https://doi.org/10.3390/antibiotics12121722 - 13 Dec 2023

Viewed by 1020

Abstract

Objectives: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. Methods: episodes of bacteremic SSTIs [...] Read more.

Objectives: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. Methods: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. Results: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. Conclusions: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population. Full article

(This article belongs to the Special Issue Infections in Immunocompromised Hosts and Antimicrobial Therapy)

19 pages, 11638 KiB

Open AccessArticle

Improving the Antibacterial Properties of Dental Bonding Materials Loaded with Silver Compounds

by Elena Ferrando-Magraner, Verónica García-Sanz, Carlos Bellot-Arcís, Anna Marín-Gozalbo, Luís Cabedo-Mas, Gladys Mínguez-Vega and Vanessa Paredes-Gallardo

Antibiotics 2023, 12(12), 1721; https://doi.org/10.3390/antibiotics12121721 - 13 Dec 2023

Viewed by 1011

Abstract

Biofilm accumulation, the appearance of white spot lesions and the development of secondary caries are the main complications in orthodontic patients. A promising approach to fight this situation is the development of adhesive cements with improved antibacterial properties. The aim of the present [...] Read more.

Biofilm accumulation, the appearance of white spot lesions and the development of secondary caries are the main complications in orthodontic patients. A promising approach to fight this situation is the development of adhesive cements with improved antibacterial properties. The aim of the present study was to evaluate the possibility of improving the antibacterial properties of glass ionomer cements by incorporating different types of antimicrobial compounds without altering their physical and mechanical properties. Different concentrations of silver carbonate (SC) and an inorganic glass with encapsulated silver were added to the glass ionomer cement, as well as chitosan, to achieve synergistic antibacterial activity. Variations in the antibacterial capacity were evaluated using the agar diffusion test; the potential alteration of the physical and mechanical properties of the material was analyzed by the shear bond strength test. SEM characterization and colorimetric evaluation were also conducted. Samples of SC up to 1% and inorganic glass with encapsulated silver up to 5% showed significant improvement in their antibacterial ability without compromising shear strength. The highest antimicrobial activity was observed for Lactobacillus acidophilus, with inhibition zones of 3.8 and 3.1 mm for SC and inorganic glass, respectively. The characterization of the samples did not detect any major structural changes between the different samples. The only group that underwent a noticeable color change was the group with SC. The results show that the incorporation of silver carbonate and inorganic glass with encapsulated silver provided the glass ionomer cement with an antibacterial capacity without compromising the bond strength and without modifying the structure of the material. Full article

(This article belongs to the Topic Antimicrobial Agents and Nanomaterials)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Antibiotics, Volume 12, Issue 12 (December 2023) – 105 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI