Antibiotics — Open Access Journal

Lyme disease is the most common vector borne-disease in the United States (US). While the majority of the Lyme disease patients can be cured with 2–4 weeks antibiotic treatment, about 10–20% of patients continue to suffer from persisting symptoms. While the cause of this condition is unclear, persistent infection was proposed as one possibility. It has recently been shown that B. burgdorferi develops dormant persisters in stationary phase cultures that are not killed by the current Lyme antibiotics, and there is interest in identifying novel drug candidates that more effectively kill such forms. We previously identified some highly active essential oils with excellent activity against biofilm and stationary phase B. burgdorferi. Here, we screened another 35 essential oils and found 10 essential oils (Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Cuminum cyminum L. seeds, Cymbopogon martini var. motia Bruno grass, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers, Amyris balsamifera L. wood, Thymus vulgaris L. leaves, Litsea cubeba (Lour.) Pers. fruits, Eucalyptus citriodora Hook. leaves) and the active component of cinnamon bark cinnamaldehyde (CA) at a low concentration of 0.1% have strong activity against stationary phase B. burgdorferi. At a lower concentration of 0.05%, essential oils of Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Cymbopogon martini var. motia Bruno grass and CA still exhibited strong activity against the stationary phase B. burgdorferi. CA also showed strong activity against replicating B. burgdorferi, with a MIC of 0.02% (or 0.2 μg/mL). In subculture studies, the top five essential oil hits Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers, and Litsea cubeba (Lour.) Pers. fruits completely eradicated all B. burgdorferi stationary phase cells at 0.1%, while Cymbopogon martini var. motia Bruno grass, Eucalyptus citriodora Hook. leaves, Amyris balsamifera L. wood, Cuminum cyminum L. seeds, and Thymus vulgaris L. leaves failed to do so as shown by visible spirochetal growth after 21-day subculture. At concentration of 0.05%, only Allium sativum L. bulbs essential oil and CA sterilized the B. burgdorferi stationary phase culture, as shown by no regrowth during subculture, while Pimenta officinalis Lindl. berries, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers and Litsea cubeba (Lour.) Pers. fruits essential oils all had visible growth during subculture. Future studies are needed to determine if these highly active essential oils could eradicate persistent B. burgdorferi infection in vivo. Full article

Background: The prevalence of disinfectant resistance in Pseudomonas aeruginosa is on the rise. P. aeruginosa is the most common bacteria isolated from cases of microbial keratitis. Many multi-purpose contact lens disinfectant solutions are available to decontaminate contact lenses before use and to help reduce the incidence of infections. However, with increasing disinfectant resistance, the effect of multi-purpose disinfectant solutions may diminish. The goal of this study was to examine genes associated with disinfectant resistance in ocular isolates of P. aeruginosa and understand the strain’s susceptibility to different multipurpose disinfectant solutions. Methods: Seven potential disinfectant resistance genes were used in BLASTn searches against the whole genomes of 13 eye isolates of P. aeruginosa. A microdilution broth method was used to examine susceptibility to four different multipurpose disinfectant solutions. Results: All strains possessed the sugE2, sugE3 and emrE (qacE) genes. The sugE1 and qacEdelta1 genes were present in 6/13 isolates. No strains contained the qacF or qacG genes. All tested disinfectant solutions had the ability to kill all test strains at 100% concentration, with some strains being susceptible at 1:8 dilutions of the disinfecting solutions. However, the presence of disinfectant resistance genes was not associated with susceptibility to multi-purpose disinfectants. Conclusion: All four tested contact lens disinfectant preparations are effective against P. aeruginosa isolates regardless of the presence of disinfectant resistance genes. Full article

Infections involving diabetic foot ulcers (DFU) are a major public health problem and have a substantial negative impact on patient outcomes. Osteomyelitis in an ulcerated foot substantially increases the difficulty of successful treatment. While literature suggests that osteomyelitis in selected patients can sometimes be treated conservatively, with no, or minimal removal of bone, we do not yet have clear treatment guidelines and the standard treatment failure fallback remains amputation. The authors report on the successful treatment, with a long term follow up, of a 63 YO diabetic female with distal phalangeal osteomyelitis using bacteriophage, a form of treatment offering the potential for improved outcomes in this era of escalating antibiotic resistance and the increasingly recognized harms associated with antibiotic therapy. Full article

Specialized metabolites are of great interest due to their possible industrial and clinical applications. The increasing number of antimicrobial resistant infectious agents is a major health threat and therefore, the discovery of chemical diversity and new antimicrobials is crucial. Extensive genomic data from Streptomyces spp. confirm their production potential and great importance. Genome sequencing of the same species strains indicates that specialized metabolite biosynthetic gene cluster (SMBGC) diversity is not exhausted, and instead, a pool of novel specialized metabolites still exists. Here, we analyze the genome sequence data from six phylogenetically close Streptomyces strains. The results reveal that the closer strains are phylogenetically, the number of shared gene clusters is higher. Eight specialized metabolites comprise the core metabolome, although some strains have only six core gene clusters. The number of conserved gene clusters common between the isolated strains and their closest phylogenetic counterparts varies from nine to 23 SMBGCs. However, the analysis of these phylogenetic relationships is not affected by the acquisition of gene clusters, probably by horizontal gene transfer events, as each strain also harbors strain-specific SMBGCs. Between one and 15 strain-specific gene clusters were identified, of which up to six gene clusters in a single strain are unknown and have no identifiable orthologs in other species, attesting to the existing SMBGC novelty at the strain level. Full article

The current spread of multi-drug resistance in a number of key pathogens and the lack of therapeutic solutions in development to address most of the emerging infections in the clinic that are difficult to treat have become major concerns. Microbial natural products represent one of the most important sources for the discovery of potential new antibiotics and actinomycetes have been one of the most relevant groups that are prolific producers of these bioactive compounds. Advances in genome sequencing and bioinformatic tools have collected a wealth of knowledge on the biosynthesis of these molecules. This has revealed the broad untapped biosynthetic diversity of actinomycetes, with large genomes and the capacity to produce more molecules than previously estimated, opening new opportunities to identify the novel classes of compounds that are awaiting to be discovered. Comparative genomics, metabolomics and proteomics and the development of new analysis and genetic engineering tools provide access to the integration of new knowledge and better understanding of the physiology of actinomycetes and their tight regulation of the production of natural products antibiotics. This new paradigm is fostering the development of new genomic-driven and culture-based strategies, which aims to deliver new chemical classes of antibiotics to be developed to the clinic and replenish the exhausted pipeline of drugs for fighting the progression of infection diseases in the near future. Full article

Antibiotics are the most frequent prescription drugs used by pregnant women. Our objective was to investigate if the dispensation of antibiotics and antiasthmatics in children less than 1 year of age is associated with prenatal antibiotic exposure. A secondary aim was to explore the incidence of dispensed antibiotics in pregnancy and dispensed antibiotics and antiasthmatics in children. We conducted an observational study using the Peer Academic Detailing study database to select patients eligible for match in the Medical Birth Registry of Norway, a total of 7747 mother-and-child pairs. Details on antibiotic and antiasthmatic pharmacy dispensations were obtained from the Norwegian Prescription Database. One quarter (1948 of 7747) of the mothers in the study had been dispensed antibiotics during pregnancy. In their first year of life, 17% (1289) of the children had had an antibiotic dispensation, 23% (1747) an antiasthmatic dispensation, and 8% (619) of the children had had both. We found a significant association between dispensed antibiotics in pregnancy and dispensed antibiotics to the child during their first year of life; OR = 1.16 (95% CI: 1.002–1.351). The association was stronger when the mothers were dispensed antibiotics at all, independent of the pregnancy period; OR = 1.60 (95% CI: 1.32–1.94). We conclude that the probability for dispensation of antibiotics was increased in children when mothers were dispensed antibiotics, independent of pregnancy. Diagnostic challenges in the very young and parental doctor-seeking behavior may, at least in part, contribute to the association between dispensations in mothers and children below the age of one year. Full article

The chemical analysis of insect-associated Actinobacteria has attracted the interest of natural product chemists in the past years as bacterial-produced metabolites are sought to be crucial for sustaining and protecting the insect host. The objective of our study was to evaluate the phylogeny and bioprospecting of Actinobacteria associated with fungus-growing termites. We characterized 97 Actinobacteria from the gut, exoskeleton, and fungus garden (comb) of the fungus-growing termite Macrotermes natalensis and used two different bioassays to assess their general antimicrobial activity. We selected two strains for chemical analysis and investigated the culture broth of the axenic strains and fungus-actinobacterium co-cultures. From these studies, we identified the previously-reported PKS-derived barceloneic acid A and the PKS-derived rubterolones. Analysis of culture broth yielded a new dichlorinated diketopiperazine derivative and two new tetracyclic lanthipeptides, named rubrominins A and B. The discussed natural products highlight that insect-associated Actinobacteria are highly prolific natural product producers yielding important chemical scaffolds urgently needed for future drug development programs. Full article

Patients’ expectations of being prescribed antibiotics can have an important influence on inappropriate prescribing. Therefore, it is important to understand the drivers of patients’ antibiotic expectations. The 2015/16 New Zealand Attitudes and Values Study measured sense of entitlement to antibiotics in a nationally representative sample of New Zealanders (n = 13,484). Participants were asked to rate their agreement with the statement “If I go to my doctor/GP with a minor illness (e.g., sore throat, cough, runny nose, etc.), I think that I should be prescribed antibiotics by default.” Eighty percent of participants showed low feelings of antibiotic entitlement, while 18.5% exhibited moderate and 3.7% high feelings of entitlement. People of ethnic minority, lower socio-economic status, and with diabetes expressed higher expectations of being prescribed antibiotics. This may be partially based on a higher risk of rheumatic fever or other complications. Men, religious people, those with lower educational attainment and self-rated health, but greater psychological distress and feelings of control over their health exhibited higher feelings of antibiotic entitlement. Those high on Extraversion, Conscientiousness, and Narcissism, but low on Agreeableness and Openness, also showed greater feelings of entitlement. Our findings help identify key characteristics of those more likely to express inappropriate expectations of antibiotic prescription. Full article

Most antibiotics are prescribed in primary care, and commonly for respiratory tract infections (RTIs). Narrow-spectrum phenoxymethylpenicillin is the antibiotic of choice for RTIs in the Scandinavian countries, while broader spectrum amoxicillin is used in most other European countries. This review summarizes the knowledge of the effect of phenoxymethylpenicillin versus amoxicillin for infections treated in ambulatory care. We searched PubMed/Medline and Embase for trials comparing the clinical effect of phenoxymethylpenicillin and amoxicillin. The Norwegian Knowledge Centre for the Health Services’ checklist was used to assess risk of bias. In total, 1687 studies were identified, and 18 of these fulfilled the inclusion criteria. One additional study was found as a reference. The randomized controlled trials revealed no significant differences in clinical effect in acute sinusitis (three RCTs), GAS tonsillitis (11 RCTs) and Lyme borreliosis (two RCTs). One RCT on community-acquired pneumonia found amoxicillin to be superior, while the results were conflicting in the two RCTs on acute otitis. The results suggest that non-Scandinavian countries should consider phenoxymethylpenicillin as the treatment of choice for RTIs because of its narrower spectrum. More studies should be conducted on the clinical effect of phenoxymethylpenicillin versus amoxicillin for acute otitis and lower RTIs. Full article

In this article, a series of silver-containing dressings are prepared by metal-vapor synthesis (MVS), and their antibacterial properties are investigated. The antibacterial activity of the dressings containing silver nanoparticles (AgNPs) against some Gram-positive, and Gram-negative microorganisms (Staphylococcus aureus, Staphylococcus haemolyticus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Moraxella spp.) has been determined. Based on the plasmon resonance frequency of these nanoparticles, the frequency of laser irradiation of the dressing was chosen. The gauze bandage examined showed pronounced antibacterial properties, especially to Staphylococcus aureus strain. When 470 nm laser radiation, with a power of 5 mW, was applied for 5 min, 4 h after inoculating the Petri dish, and placing a bandage containing silver nanoparticles on it, the antibacterial effect of the latter significantly increased—both against Gram-positive and Gram-negative microorganisms. The structure and chemical composition of the silver-containing nanocomposite were studied by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and extended X-ray absorption fine structure (EXAFS). The synthesized AgNPs demonstrate narrow and monomodal particle size distribution with an average size of 1.75 nm. Atoms of metal in Ag/bandage system are mainly in Ag⁰ state, and the oxidized atoms are in the form of Ag-Ag-O groups. Full article

The therapeutic arsenal against bacterial infections is rapidly shrinking, as drug resistance spreads and pharmaceutical industry are struggling to produce new antibiotics. In this review we cover the efficacy of silver as an antibacterial agent. In particular we recall experimental evidences pointing to the multiple targets of silver, including DNA, proteins and small molecules, and we review the arguments for and against the hypothesis that silver acts by enhancing oxidative stress. We also review the recent use of silver as an adjuvant for antibiotics. Specifically, we discuss the state of our current understanding on the potentiating action of silver ions on aminoglycoside antibiotics. Full article

Urgent need for innovative and effective antibacterial coatings in different fields seems to have triggered the development of numerous strategies for the production of such materials. As shown in this short overview, plasma based techniques arouse considerable attention that is connected with the possibility to use these techniques for the production of advanced antibacterial Ag/plasma polymer coatings with tailor-made functional properties. In addition, the plasma-based deposition is believed to be well-suited for the production of novel multi-functional or stimuli-responsive antibacterial films. Full article

The increasing rates of gonorrhea infections and the global emergence and spread of multi-drug-resistant Neisseria gonorrhoeae (NG) threaten the successful management of gonorrhea. In the era of nucleic acid amplification tests (NAATs), surveillance projects are urgently needed to monitor prevalence and trends in the antimicrobial susceptibility of NG. In this study, we retrospectively determined the susceptibility profile of NG isolates to previously and currently prescribed antimicrobials. NG isolates collected in Baltimore, Maryland between January and October 2016 were evaluated by the E-test method and/or molecular methods for susceptibility to ceftriaxone, azithromycin, ciprofloxacin, tetracycline, gentamicin, and penicillin. One-hundred and forty-three NG isolates from African-American males (98.6%), primarily heterosexual (88.8%), ranging in age from 15 to 69 years of age were included in the study. Ciprofloxacin resistance was observed in 44.1% of isolates. Plasmid-mediated resistance to penicillin and tetracycline resistance was detected in 22.4% and 10.1% of isolates, respectively. Three isolates (2.1%) displayed high-level resistance to azithromycin (minimum inhibitory concentration (MIC) > 256 μg/mL). Forty-three percent of isolates were resistant or had decreased susceptibility to three antimicrobials (ciprofloxacin, tetracycline, and penicillin). All isolates were susceptible to ceftriaxone and gentamicin. Overall, the epidemiology of antimicrobial resistant NG in Baltimore continues to evolve, and the emergence of azithromycin resistance in this population emphasizes the need for continued sentinel surveillance programs to monitor susceptibility trends and aid in treatment recommendations. Full article

Phytophthora cinnamomi, responsible for “root rot” or “dieback” plant disease, causes a significant amount of economic and environmental impact. In this work, the fungicide action of nanocomposites based on silver nanoparticles and polyphenol inclusion compounds, which feature enhanced bioavailability and water solubility, was assayed for the control of this soil-borne water mold. Inclusion compounds were prepared by an aqueous two-phase system separation method through extraction, either in an hydroalcoholic solution with chitosan oligomers (COS) or in a choline chloride:urea:glycerol deep eutectic solvent (DES). The new inclusion compounds were synthesized from stevioside and various polyphenols (gallic acid, silymarin, ferulic acid and curcumin), in a [6:1] ratio in the COS medium and in a [3:1] ratio in the DES medium, respectively. Their in vitro response against Phytophthora cinnamomi isolate MYC43 (at concentrations of 125, 250 and 500 µg·mL⁻¹) was tested, which found a significant mycelial growth inhibition, particularly high for the composites prepared using DES. Therefore, these nanocomposites hold promise as an alternative to fosetyl-Al and metalaxyl conventional systemic fungicides. Full article

Antimicrobial use (AMU) in animal production is a key contributor to antimicrobial resistance (AMR) worldwide. As consumption of animal protein and associated animal production is forecast to increase markedly over coming years in low- and middle-income countries (LMICs), accurate monitoring of AMU has become imperative. We summarized data from 89 scientific studies reporting AMU data in animal production published in English since 1998, identified through the ‘ISI Web of Knowledge’ search engine. The aims were as follows: (a) to describe methodologies and metrics used to quantify AMU; (b) to summarize qualitative (on-farm prevalence of use) and quantitative (amounts of antimicrobial active principle) data, in order to identify food animal species at the highest risk of AMU; and (c) to highlight data gaps from LMICs. Only 17/89 (19.1%) studies were conducted in LMICs. Sixty (67.3%) reported quantitative data use, with ‘daily doses per animal-time’ being the most common metric. AMU was greatest in chickens (138 doses/1000 animal-days [inter quartile range (IQR) 91.1–438.3]), followed by swine (40.2 [IQR 8.5–120.4]), and dairy cattle (10.0 [IQR 5.5–13.6]). However, per kg of meat produced, AMU was highest in swine, followed by chickens and cattle. Our review highlights a large deficit of data from LMICs, and provides a reference for comparison with further surveillance and research initiatives aiming to reduce AMU in animal production globally. Full article

Human burial in cemeteries facilitates the decomposition of corpses without posing a public health danger. However, the role of cemeteries as potential environmental reservoirs of drug-resistant pathogens has not been studied. Thus, we investigated cemeteries as potential environmental reservoirs of multi-drug resistant (MDR) pathogenic Escherichia coli. E. coli isolates were obtained from water samples (collected from surface water bodies and boreholes in three cemeteries) after isolation using the Colilert^® 18 system. Pathogenic potentials of the isolates were investigated using real-time polymerase chain reactions targeting seven virulence genes (VGs) pertaining to six E. coli pathotypes. The resistance of isolates to eight antibiotics was tested using the Kirby–Bauer disc diffusion method. The mean E. coli concentrations varied from <1 most probable number (MPN)/100 mL to 2419.6 MPN/100 mL with 48% of 100 isolates being positive for at least one of the VGs tested. Furthermore, 87% of the isolates were resistant to at least one of the antibiotics tested, while 72% of the isolates displayed multi-drug resistance. Half of the MDR isolates harboured a VG. These results suggest that cemeteries are potential reservoirs of MDR pathogenic E. coli, originating from surrounding informal settlements, which could contaminate groundwater if the cemeteries are in areas with shallow aquifers. Full article

The bacterial primase—an essential component in the replisome—is a promising but underexploited target for novel antibiotic drugs. Bacterial primases have a markedly different structure than the human primase. Inhibition of primase activity is expected to selectively halt bacterial DNA replication. Evidence is growing that halting DNA replication has a bacteriocidal effect. Therefore, inhibitors of DNA primase could provide antibiotic agents. Compounds that inhibit bacterial DnaG primase have been developed using different approaches. In this paper, we provide an overview of the current literature on DNA primases as novel drug targets and the methods used to find their inhibitors. Although few inhibitors have been identified, there are still challenges to develop inhibitors that can efficiently halt DNA replication and may be applied in a clinical setting. Full article

About 10% of U.K. patients believe that they are allergic to penicillin and have a “penicillin allergy label” in their primary care health record. However, around 90% of these patients may be mislabelled. Removing incorrect penicillin allergy labels can help to reduce unnecessary broad-spectrum antibiotic use. A rapid review was undertaken of papers exploring patient and/or clinician views and experiences of penicillin allergy testing (PAT) services and the influences on antibiotic prescribing behaviour in the context of penicillin allergy. We reviewed English-language publications published up to November 2017. Limited evidence on patients’ experiences of PAT highlighted advantages to testing as well as a number of concerns. Clinicians reported uncertainty about referral criteria for PAT. Following PAT and a negative result, a number of clinicians and patients remained reluctant to prescribe and consume penicillins. This appeared to reflect a lack of confidence in the test result and fear of subsequent reactions to penicillins. The findings suggest lack of awareness and knowledge of PAT services by both clinicians and patients. In order to ensure correct penicillin allergy diagnosis, clinicians and patients need to be supported to use PAT services and equipped with the skills to use penicillins appropriately following a negative allergy test result. Full article