Antibiotics

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widespread in European pig production, and an increasing number of humans attract infections with this bacterium. Although most infections occur in humans with direct livestock contact, an increasing number of infections occur in humans without any established livestock contact. There have been speculations that at least some of these infections may be connected to the exposure of liquid pig manure for example spread as fertilizers. The present study therefore undertook to measure the presence of LA-MRSA in liquid pig manure and on the surface of soils fertilized with liquid manure and investigate the survival of the bacterium in manure. The results showed that LA-MRSA could be detected in 7 out of 20 liquid manure samples and in 12 out of 186 soil samples. However, the bacterium was not more frequently detected in samples collected after compared to before the spreading of liquid manure on the fields, thus suggesting that other sources of LA-MRSA on agriculture fields likely exist. The decimation time in liquid manure was >32 days at 5 °C in vitro but decreased with increasing temperature. Based on these results, liquid manure does not appear to be an important risk factor for human exposure to LA-MRSA. Full article

The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were most commonly isolated from urine samples. E. coli was significantly more frequent in women (58.6%) (p = 0.0089) and in the age group 0–18, while K. pneumoniae was more frequent in men (24.4%) (p = 0.0119) and in individuals aged 40–60 and >60. Gram-negative species showed resistance to ampicillin. K. pneumoniae were resistant to amoxicillin plus clavulanic acid (75.0%), piperacillin plus tazobactam (76.2%), cefotaxime (76.2%), cefuroxime (81.0%), ciprofloxacin (81.0%), and trimethoprim plus sulphamethoxazole (81.0%). Carbapenems were effective against all E. coli and P. mirabilis. Some K. pneumoniae (13.6%) produced metallo-β-lactamases (MBLs). E. coli (22.6%), K. pneumoniae (81.8%), and all E. faecium were multidrug-resistant (MDR). Some E. coli (26.2%), K. pneumoniae (63.6%), and P. mirabilis (14.3%) isolates produced extended-spectrum beta-lactamases (ESBL). Vancomycin-resistant E. faecium was also found. This study showed that the possibilities of UTIs therapy using available antibiotics become limited due to the increasing number of antibiotic-resistant uropathogens. Full article

Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection Unit of the Hospital Universitari Bellvitge (January 2014–December 2018). To identify risk factors for DEP, cases were divided into two groups: those who developed DEP and those without DEP. Results: Among the whole cohort (n = 229) we identified 11 DEP cases (4.8%) and this percentage almost doubled in the subgroup of patients ≥70 years (8.1%). The risk factors for DEP were age ≥70 years (HR 10.19, 95%CI 1.28–80.93), therapy >14 days (7.71, 1.98–30.09) and total cumulative dose of daptomycin ≥10 g (5.30, 1.14–24.66). Conclusions: Clinicians should monitor cumulative daptomycin dosage to minimize DEP risk, and be cautious particularly in older patients when the total dose of daptomycin exceeds 10 g. Full article

Antimicrobial resistance (AMR) is a pressing threat to public and animal health. There is evidence that antimicrobial prescribing and stewardship behaviors by veterinarians (vets) are influenced by non-clinical factors, such as psychological, social, and environmental factors. This study explored the role of context, beliefs, and values on vets’ antimicrobial prescribing decisions. UK-based practicing farm vets (n = 97) were recruited to an online study. Using an experimental vignette methodology, vets were randomly assigned across four conditions, to examine the effects of different contexts (pressure on farm economics, the farmer, or the vet-farmer relationship, compared to a control condition) on vets’ likelihood of prescribing antibiotics. Vets’ beliefs about different groups’ responsibility for causing and preventing AMR and vets’ values were also measured. Key findings were that context alone, values, and beliefs about groups’ responsibilities for causing AMR were not predictive of vets’ likelihood of prescribing antibiotics. However, vets’ beliefs about groups’ responsibilities for preventing AMR were predictive of an increased likelihood of prescribing antibiotics, when vets were exposed to the experimental condition of the vignette in which the vet–farmer relationship was under pressure. Farm vets also believed that different groups have different levels of responsibility for causing and preventing AMR. Results should be interpreted cautiously, given the smaller than planned for sample size, and the possibility for both false negatives and false positives. Further research is needed to explore how these findings could inform antimicrobial stewardship interventions in veterinary medicine. Full article

(1) Background: nasopharynx colonization by resistant Staphylococcus aureus and Streptococcus pneumoniae can lead to serious diseases. Emerging resistance to antibiotics commonly used to treat infections due to these pathogens poses a serious threat to the health system. The present study aimed to determine the antibiotic susceptibility of S. aureus and S. pneumoniae isolates from the febrile children’s nasopharynx under 5 years in Nanoro (Burkina Faso). (2) Methods: bacterial isolates were identified from nasopharyngeal swabs prospectively collected from 629 febrile children. Antibiotic susceptibility of S. aureus and S. pneumoniae isolates was assessed by Kirby–Bauer method and results were interpreted according to the Clinical and Laboratory Standard Institute guidelines. (3) Results: bacterial colonization was confirmed in 154 (24.5%) of children of whom 96.1% carried S. aureus, 3.2% had S. pneumoniae, and 0.6% carried both bacteria. S. aureus isolates showed alarming resistance to penicillin (96.0%) and S. pneumoniae was highly resistant to tetracycline (100%) and trimethoprim–sulfamethoxazole (83.3%), and moderately resistant to penicillin (50.0%). Furthermore, 4.0% of S. aureus identified were methicillin resistant. (4) Conclusion: this study showed concerning resistance rates to antibiotics to treat suspected bacterial respiratory tract infections. The work highlights the necessity to implement continuous antibiotic resistance surveillance. Full article

This study quantified the potential of farm-scale composting to degrade antibiotics in dairy manure. The compost windrow, consisting of sick cow bedding from a 1000-cow US dairy farm, was managed using the dairy farm’s typical practices and monitored for tetracycline and nutrient composition. Samples were collected over 33 days, which was the time from compost pile formation to land application as fertilizer, and analyzed for solids, antibiotics, and nutrient content. Average tetracycline concentrations at the beginning of the study (452 ng/g DW) were lower than at the end of composting (689 ng/g DW), illustrating that antibiotic degradation was not greater than degradation of the compost solids. Total Kjeldahl nitrogen (TKN) increased from 15.3 to 18.4 g/kg during the composting period due to decreases in solids and likely inhibition of N-mineralization due to the presence of antibiotics. The results indicated that antibiotics were not completely degraded when using the farm’s compost pile management techniques, with antibiotics possibly impacting nitrogen transformation in the compost, which should be considered in nutrient management when using sick cow bedding. Additionally, the results showed that antibiotic degradation during farm-scale composting can vary from reported laboratory-scale due to differences in management, composting duration, and temporal conditions, illustrating the need for more extensive on-farm research including common farm practices and real-world conditions. Full article

Multidrug resistant Staphylococcus aureus is a severe threat, responsible for most of the nosocomial infections globally. This resistant strain is associated with a 64% increase in death compared to the antibiotic-susceptible strain. The prokaryotic protein FtsZ and the cell division cycle have been validated as potential targets to exploit in the general battle against antibiotic resistance. Despite the discovery and development of several anti-FtsZ compounds, no FtsZ inhibitors are currently used in therapy. This work further develops benzodioxane-benzamide FtsZ inhibitors. We seek to find more potent compounds using computational studies, with encouraging predicted drug-like profiles. We report the synthesis and the characterization of novel promising derivatives that exhibit very low MICs towards both methicillin-susceptible and -resistant S. aureus, as well as another Gram positive species, Bacillus subtilis, while possessing good predicted physical-chemical properties in terms of solubility, permeability, and chemical and physical stability. In addition, we demonstrate by fluorescence microscopy that Z ring formation and FtsZ localization are strongly perturbed by our derivatives, thus validating the target. Full article

An outpatient antimicrobial stewardship program (O-ASP) was developed and implemented to promote appropriate antibiotic therapy in outpatient settings. As active patient involvement is a critical component of an effective O-ASP, this study aimed to develop and validate a questionnaire addressing patient awareness for appropriate antibiotic therapy and the need for pharmaceutical care services (PCS) in the O-ASP in Korea. The questionnaire was drafted based on ASPs and PCS guidelines and validated for content and construct validity using the item-content validity index (I-CVI) and Cronbach’s alpha, respectively. The estimated I-CVI and Cronbach’s alpha were considered excellent or adequate (≥0.8 and 0.70–0.90, respectively) for most of the survey items (17 out of 23 items). The validated questionnaire was utilized in a pilot survey study, including 112 individuals (37% male) with the mean ± SD age of 37 ± 13 years. Among the survey participants, 68% responded that antibiotics had been prescribed appropriately; however, ≥50% showed a lack of knowledge regarding their antibiotic therapy. The participants expressed the need for PCS as part of an O-ASP in the questionnaire (average Likert score ≥3.4/5). In conclusion, our newly validated questionnaire successfully measured patient awareness and knowledge of antimicrobial use and the need for PCS in the O-ASP. Full article

Candida albicans is a common overgrowth in people wearing dentures. Long-term use of antifungal chemicals carries a risk of toxic side effects. This study focused on the edible Piper betle extract because of its safety. The broth dilution method was applied for antifungal determination of the ethyl acetate fractionated extract (fEA) and fEA-loaded polymeric micelles (PMF). The PMF was prepared by thin-film hydration using poloxamer 407 as a polymer base. The results found that the weight ratio of fEA to polymer is the main factor to obtain PMF system as a clear solution, nanoparticle sizes, narrow size distribution, negative zeta potential, and high entrapment efficiency. The activity of PMF against C. albicans is significantly higher than fEA alone, with a minimum fungicidal concentration of 1.5 mg/mL. PMF from 1:3 ratio of fEA to polymer is used to develop a denture-soaking solution contained 1.5 mg fEA/mL (PMFS). A clinical study on dentures of 15 volunteers demonstrated an 86.1 ± 9.2% reduction of C. albicans after soaking the dentures in PMFS daily for 14 days. Interestingly, PMFS did not change the hardness and roughness of the denture base resins. The developed PMFS may serve as a potential natural denture-soaking solution against candidiasis in denture wearers. Full article

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation. Full article

Antibiotic resistance is spreading worldwide and it has become one of the most important issues in modern medicine. In this context, the bacterial RNA degradation and processing machinery are essential processes for bacterial viability that may be exploited for antimicrobial therapy. In Staphylococcus aureus, RnpA has been hypothesized to be one of the main players in these mechanisms. S. aureus RnpA is able to modulate mRNA degradation and complex with a ribozyme (rnpB), facilitating ptRNA maturation. Corresponding small molecule screening campaigns have recently identified a few classes of RnpA inhibitors, and their structure activity relationship (SAR) has only been partially explored. Accordingly, in the present work, using computational modeling of S. aureus RnpA we identified putative crucial interactions of known RnpA inhibitors, and we used this information to design, synthesize, and biologically assess new potential RnpA inhibitors. The present results may be beneficial for the overall knowledge about RnpA inhibitors belonging to both RNPA2000-like thiosemicarbazides and JC-like piperidine carboxamides molecular classes. We evaluated the importance of the different key moieties, such as the dichlorophenyl and the piperidine of JC2, and the semithiocarbazide, the furan, and the i-propylphenyl ring of RNPA2000. Our efforts could provide a foundation for further computational-guided investigations. Full article

Background and aims: Only a few antimicrobials are effective against H. pylori, and antibiotic resistance is an increasing problem for eradication therapies. In 2017, the World Health Organization categorized clarithromycin resistant H. pylori as a “high-priority” bacterium. Standard antimicrobial susceptibility testing can be used to prescribe appropriate therapies but is currently recommended only after the second therapeutic failure. H. pylori is, in fact, a “fastidious” microorganism; culture methods are time-consuming and technically challenging. The advent of molecular biology techniques has enabled the identification of molecular mechanisms underlying the observed phenotypic resistance to antibiotics in H. pylori. The aim of this literature review is to summarize the results of original articles published in the last ten years, regarding the use of Next Generation Sequencing, in particular of the whole genome, to predict the antibiotic resistance in H. pylori.Methods: a literature research was made on PubMed. The research was focused on II and III generation sequencing of the whole H. pylori genome. Results: Next Generation Sequencing enabled the detection of novel, rare and complex resistance mechanisms. The prediction of resistance to clarithromycin, levofloxacin and amoxicillin is accurate; for other antimicrobials, such as metronidazole, rifabutin and tetracycline, potential genetic determinants of the resistant status need further investigation. Full article

Hemipteran insects, such as whiteflies, aphids and planthoppers, resemble one of the most important pest groups threating food security. While many insecticides have been used to control these pests, many issues such as insecticide resistance have been found, highlighting the urgent need to develop novel insecticides. Here, we first observed that a commercial tetramycin solution was highly effective in killing whitefly. The major bioactive constituents were identified to be isothiazolinones, a group of biocides. We then tested the toxicity of several isothiazolinones to five hemipteran insects. The results show that Kathon, a widely used biocide against microorganisms, and its two constituents, chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT), can cause considerable levels of mortality to whiteflies and aphids when applied at concentrations close to, or lower than, the upper limit of these chemicals permitted in cosmetic products. The results also indicate that two other isothiazolinones, benzisothiazolinone (BIT) and octylisothiazolinone (OIT) can cause considerable levels of mortality to whitefly and aphids but are less toxic than Kathon. Further, we show that Kathon marginally affects whitefly endosymbionts, suggesting its insecticidal activity is independent of its biocidal activity. These results suggest that some isothiazolinones are promising candidates for the development of a new class of insecticides for the control of hemipteran pests. Full article

Antimicrobial resistance is a significant threat to human health worldwide, forcing scientists to explore non-traditional antibacterial agents to support rapid interventions and combat the emergence and spread of drug resistant bacteria. Many new antibiotic-free approaches are being developed while the old ones are being revised, resulting in creating unique solutions that arise at the interface of physics, nanotechnology, and microbiology. Specifically, physical factors (e.g., pressure, temperature, UV light) are increasingly used for industrial sterilization. Nanoparticles (unmodified or in combination with toxic compounds) are also applied to circumvent in vivo drug resistance mechanisms in bacteria. Recently, bacteriophage-based treatments are also gaining momentum due to their high bactericidal activity and specificity. Although the number of novel approaches for tackling the antimicrobial resistance crisis is snowballing, it is still unclear if any proposed solutions would provide a long-term remedy. This review aims to provide a detailed overview of how bacteria acquire resistance against these non-antibiotic factors. We also discuss innate bacterial defense systems and how bacteriophages have evolved to tackle them. Full article

AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection. Full article

Type B dihydrofolate reductase (dfrb) genes were identified following the introduction of trimethoprim in the 1960s. Although they intrinsically confer resistance to trimethoprim (TMP) that is orders of magnitude greater than through other mechanisms, the distribution and prevalence of these short (237 bp) genes is unknown. Indeed, this knowledge has been hampered by systematic biases in search methodologies. Here, we investigate the genomic context of dfrbs to gain information on their current distribution in bacterial genomes. Upon searching publicly available databases, we identified 61 sequences containing dfrbs within an analyzable genomic context. The majority (70%) of those sequences also harbor virulence genes and 97% of the dfrbs are found near a mobile genetic element, representing a potential risk for antibiotic resistance genes. We further identified and confirmed the TMP-resistant phenotype of two new members of the family, dfrb10 and dfrb11. Dfrbs are found both in Betaproteobacteria and Gammaproteobacteria, a majority (59%) being in Pseudomonas aeruginosa. Previously labelled as strictly plasmid-borne, we found 69% of dfrbs in the chromosome of pathogenic bacteria. Our results demonstrate that the intrinsically TMP-resistant dfrbs are a potential emerging threat to public health and justify closer surveillance of these genes. Full article

Antimicrobial-resistant (AMR) bacteria affect human and animal health worldwide. Here, CTX-M-14-producing Escherichia coli isolates were isolated from Siberian weasels (Mustela sibirica) that were captured on a veterinary campus. To clarify the source of bacteria in the weasels, we examined the domestic animals reared in seven facilities on the campus. Extended-spectrum β-lactamase (ESBL)-producing E. coli were isolated on deoxycholate hydrogen sulfide lactose agar, containing cephalexin (50 μg/mL) or cefotaxime (2 μg/mL), and were characterized with antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), replicon typing, and β-lactamase typing analyses. Next-generation sequencing of the ESBL-encoding plasmids was also performed. CTX-M-14 producers isolated from both domestic animals and weasels were classified into six clusters with seven PFGE profiles. The PFGE and antimicrobial resistance profiles were characterized by the animal facility. All CTX-M-14 plasmids belonged to the IncI1 type with a similar size (98.9–99.3 kb), except for one plasmid that was 105.5 kb in length. The unweighted pair group method with arithmetic mean (UPGMA) revealed that the CTX-M-14 plasmid in the weasel isolates might have the same origin as the CTX-M-14 plasmid in the domestic animals. Our findings shed further light on the association of antimicrobial resistance between wild and domestic animals. Full article

Health surveillance systems are considered vital for combatting antimicrobial resistance (AMR); however, the evidence-base on the effectiveness of these systems in providing information that can be used by healthcare professionals, or the acceptability of these systems by users, has not been reviewed. A systematic review was conducted of a number of databases to synthesise the evidence. The review identified 43 studies that met the inclusion criteria, conducted in 18 countries and used 11 attributes in their assessment of surveillance systems. The majority of systems evaluated were for monitoring the incidence of tuberculosis. The studies found that most surveillance systems were underperforming in key attributes that relate to both effectiveness and acceptability. We identified that two features of systems (ease of use and users’ awareness of systems) were associated with greater acceptability and completeness of systems. We recommend prioritising these for the improvement of existing systems, as well as ensuring consistency in the definition of attributes studied, to allow a more consistent approach in evaluations of surveillance systems, and to facilitate the identification of the attributes that have the greatest impact on the utility of data produced. Full article

Resistance mechanisms occur in almost all clinical bacterial isolates and represent one of the most worrisome health problems worldwide. Bacteria can form biofilms and communicate through quorum sensing (QS), which allow them to develop resistance against conventional antibiotics. Thus, new therapeutic candidates are sought. We focus on alkylglycerols (AKGs) because of their recently discovered quorum sensing inhibition (QSI) ability and antibiofilm potential. Fifteen natural enantiopure AKGs were tested to determine their effect on the biofilm formation of other clinical bacterial isolates, two reference strains and their QSI was determined using Chromobacterium violaceum ATCC 12472. The highest biofilm inhibition rates (%) and minimum QS inhibitory concentration were determined by a microtiter plate assay and ciprofloxacin was used as the standard antibiotic. At subinhibitory concentrations, each AKG reduced biofilm formation in a concentration-dependent manner against seven bacterial isolates, with values up to 97.2%. Each AKG displayed QSI at different levels of ability without affecting the growth of C. violaceum. AKG (2S)-3-O-(cis-13’-docosenyl)-1,2-propanediol was the best QS inhibitor (20 μM), while (2S)-3-O-(cis-9’-hexadecenyl)-1,2-propanediol was the least effective (795 μM). The results showed for the first time the QSI activity of this natural AKG series and suggest that AKGs could be promising candidates for further studies on preventing antimicrobial resistance. Full article