In vitro activity of tigecycline, a new glycylcycline, tested against 1,326 clinical bacterial strains isolated from Latin America

The in vitro activity of tigecycline (former GAR-936), a new semisynthetic tetracycline, was evaluated in comparison with tetracycline and other antimicrobial agents. MATERIAL AND METHODS: A total of 1,326 contemporary clinical isolates collected from the Latin American region were collected in 2000-2002 period and tested with microdilution broth according to the CLSI guidelines. The bacterial pathogens evaluated included Staphylococcus aureus (505), Streptococcus pneumoniae (269), coagulase-negative staphylococci (CoNS; 227), Haemophilus influenzae (129), Enterococcus spp. (80), Moraxella catarrhalis (54), beta-haemolytic streptococci (28), viridans group streptococci (26), and Neisseria meningitidis (8) RESULTS:Tigecycline demonstrated excellent activity against all Gram-positive cocci, with 90% of penicillin-resistant S. pneumoniae strains being inhibited at 0.12 µg/mL, while the same isolates had an MIC90 of > 16 µg/mL for tetracycline. All Enterococcus spp. were inhibited at 0.25 µg/mL of tigecycline. Tigecycline (MIC50, 0.25 µg/mL) was eight-fold more potent than minocycline (MIC50, 2 µg/mL) against oxacillin-resistant S. aureus (ORSA); all ORSA were inhibited at < 2 µg/mL of tigecycline. Tigecycline demonstrated excellent activity (MIC50, 0.5 µg/mL) against CoNS with reduced susceptibility to teicoplanin (MIC, 16 µg/mL). Tigecycline also showed high potency against respiratory pathogens such as M. catarrhalis (MIC50, 0.12 µg/mL) and H. influenzae (MIC50, 0.5 µg/mL). No tigecycline resistant isolates were detected when the proposed susceptible breakpoints (< 4 µg/mL) was applied. CONCLUSIONS: This results indicate that tigecycline has potent in vitro activity against clinically important pathogenic bacteria, including Gram-positive isolates resistant to both tetracycline and minocycline.Federal University of São Paulo Division of Infectious DiseasesDepartment of MedicineThe JMI LaboratoriesUNIFESP, Division of Infectious DiseasesSciEL

Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine

Background Antimicrobial resistance has become a major challenge in veterinary medicine, particularly in the context of bacterial pathogens that play a role in both humans and animals. Objectives This review serves as an update on acquired resistance mechanisms in bacterial pathogens of human and animal origin, including examples of transfer of resistant pathogens between hosts and of resistance genes between bacteria. Results Acquired resistance is based on resistance-mediating mutations or on mobile resistance genes. Although mutations are transferred vertically, mobile resistance genes are also transferred horizontally (by transformation, transduction or conjugation/mobilization), contributing to the dissemination of resistance. Mobile genes specifying any of the three major resistance mechanisms – enzymatic inactivation, reduced intracellular accumulation or modification of the cellular target sites – have been found in a variety of bacteria that may be isolated from animals. Such resistance genes are associated with plasmids, transposons, gene cassettes, integrative and conjugative elements or other mobile elements. Bacteria, including zoonotic pathogens, can be exchanged between animals and humans mainly via direct contact, but also via dust, aerosols or foods. Proof of the direction of transfer of resistant bacteria can be difficult and depends on the location of resistance genes or mutations in the chromosomal DNA or on a mobile element. Conclusion The wide variety in resistance and resistance transfer mechanisms will continue to ensure the success of bacterial pathogens in the future. Our strategies to counteract resistance and preserve the efficacy of antimicrobial agents need to be equally diverse and resourceful. This article is based on a State of the Art presentation at the 8th World Congress of Veterinary Dermatology held May 2016 in Bordeaux, France

Characterization of Antibiotic and Biocide Resistance Genes and Virulence Factors of Staphylococcus Species Associated with Bovine Mastitis in Rwanda

The present study was conducted from July to August 2018 on milk samples taken at dairy farms in the Northern Province and Kigali District of Rwanda in order to identify Staphylococcus spp. associated with bovine intramammary infection. A total of 161 staphylococcal isolates originating from quarter milk samples of 112 crossbred dairy cattle were included in the study. Antimicrobial susceptibility testing was performed and isolates were examined for the presence of various resistance genes. Staphylococcus aureus isolates were also analyzed for the presence of virulence factors, genotyped by spa typing and further phenotypically subtyped for capsule expression using Fourier Transform Infrared (FTIR) spectroscopy. Selected S. aureus were characterized using DNA microarray technology, multi-locus sequence typing (MLST) and whole-genome sequencing. All mecA-positive staphylococci were further genotyped using dru typing. In total, 14 different staphylococcal species were detected, with S. aureus being most prevalent (26.7%), followed by S. xylosus (22.4%) and S. haemolyticus (14.9%). A high number of isolates was resistant to penicillin and tetracycline. Various antimicrobial and biocide resistance genes were detected. Among S. aureus, the Panton–Valentine leukocidin (PVL) genes, as well as bovine leukocidin (LukM/LukF-P83) genes, were detected in two and three isolates, respectively, of which two also carried the toxic shock syndrome toxin gene tsst-1 bovine variant. t1236 was the predominant spa type. FTIR-based capsule serotyping revealed a high prevalence of non-encapsulated S. aureus isolates (89.5%). The majority of the selected S. aureus isolates belonged to clonal complex (CC) 97 which was determined using DNA microarray based assignment. Three new MLST sequence types were detected

Contribution of Efflux Pumps, Porins, and B-Lactamases to Multidrug Resistance in Clinical Isolates of Acinetobacter baumannii

Weinvestigated the mechanisms of resistance to carbapenems, aminoglycosides, glycylcyclines, tetracyclines, and quinolones in 90 multiresistant clinical strains of Acinetobacter baumannii isolated from two genetically unrelated A. baumannii clones: clone PFGEROC- 1 (53 strains producing the OXA-58B-lactamase enzyme and 18 strains with the OXA-24B-lactamase) and clone PFGE-HUI-1 (19 strains susceptible to carbapenems).Weused real-time reverse transcriptase PCR to correlate antimicrobial resistance (MICs) with expression of genes encoding chromosomalB-lactamases (AmpC and OXA-51), porins (OmpA, CarO, Omp33, Dcap-like, OprB, Omp25, OprC, OprD, and OmpW), and proteins integral to six efflux systems (AdeABC, AdeIJK, AdeFGH, CraA, AbeM, and AmvA). Overexpression of the AdeABC system (level of expression relative to that by A. baumannii ATCC 17978, 30- to 45-fold) was significantly associated with resistance to tigecycline, minocycline, and gentamicin and other biological functions. However, hyperexpression of the AdeIJK efflux pump (level of expression relative to that by A. baumannii ATCC 17978, 8- to 10-fold) was significantly associated only with resistance to tigecycline and minocycline (to which the TetB efflux system also contributed). TetB and TetA(39) efflux pumps were detected in clinical strains and were associated with resistance to tetracyclines and doxycycline. The absence of the AdeABC system and the lack of expression of other mechanisms suggest that tigecycline-resistant strains of the PFGE-HUI-1 clone may be associated with a novel resistance-nodulation-cell efflux pump (decreased MICs in the presence of the inhibitor Phe-ArgB-naphthylamide dihydrochloride) and the TetA(39) system

Escherichia coli and Antibiotic Resistance to Tetracycline Antibiotics

Escherichia coli cells growing under ideal conditions are able to complete one reproduction cycle in as little as every twenty minutes. Since so many generations are able to be observed, one should theoretically be able to observe thousands of generations and determine evolution’s effects over a short period of time. In this experiment, E. coli K12 cells were cultured under ideal growth conditions but in the presence of antibiotics as a selective environmental stress in order to select for resistance. This was accomplished by serially passing colonies that were in close contact with two different, but similar antibiotics over a period of more than 4,000 generations. The goal was to improve research in the antibiotic sensitivity properties of E. coli and to determine if the data are in agreement with the theory that bacteria or other species will accumulate new phenotypic traits via development of genotypic changes that will enhance the survival of the organism, especially under selective pressure (e.g. growth with the presence of an antibiotic). The diameter of E. coli colonies’ zones of inhibition decreased over time in response to the antibiotics Doxycycline and Tetracycline indicating decreased sensitivity to these antibiotics. The cultures, however, appeared to have increased fitness cost as compared to the wild type

Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types : treating cancer like an infectious disease

Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated

Rational use of antimicrobials in dentistry during pregnancy

The use of medicines during pregnancy deserves special attention from dentists due to the potential risks to fetal development. The prescription of antimicrobial drugs during this period must be based not only on the etiology of the disease but also on the drug?s effect on the embryo, which may be toxic, possibly leading to irreversible lesions. Interest in studies of the teratogenic effects of drugs increased in response to reports of the high incidence of phocomelia in patients treated with thalidomide. Although teratogenicity has long been known, pregnant women today are still exposed to this risk. The effects of drugs depend on the level of susceptibility of the fetus and on the period of exposure during pregnancy. In this context, and considering the paucity of studies on this subject in dentistry, the aim of this review was to offer an up-to-date compilation of data on the antimicrobial drugs most frequently used during pregnancy and the effects of their use

NEUROPSYCHIATRIC ADVERSE EFFECTS OF ANTIBACTERIAL AGENTS

Anti-bacterial are agents that inhibit bacterial growth or kills bacteria and are a sub-type of antimicrobials. These are drugs used to treat infections, but they sometimes pose a threat of adverse events. Some of these adverse events are neuropsychiatric, which are generally hard to diagnose and is often paid less attention. They account for about 30% of total Adverse drug reactions (ADRs) caused by drugs in patients without mental abnormalities. The spectrum ranges from episodes of seizure to acute psychosis. The article emphasizes the frequency of such adverse events and means to raise awareness among medical practitioners regarding the same. The various neuropsychiatric adverse effects and the agents responsible have been reviewed, along with their possible mechanisms and general management. The information for writing this review was selected by searching for keywords such as Neurotoxicity, GABA, Psychosis, Naranjo scale, and Antibiomania in databases such as Google Scholar, PubMed, Elsevier, etc. After searching the articles in the above-mentioned databases, the articles were screened concerning their importance with our work and according to their title and abstract. Additional articles were discovered by checking the references in the current study's citations. Using this method, the various neuropsychiatric adverse effects of Antibacterial agents were summarized in this review

Chronic Osteomyelitis

Chronic osteomyelitis is a multifaceted bacterial infection with common features. It absolutely requires surgery for remission. The duration and form of concomitant administration of antibiotic agents for adult patients is still based on expert opinion. The traditional recommendation of 6-12weeks of antibiotic therapy, where, for at least the first 2-6weeks, antibiotics should be administered intravenously, is more and more challenged in favor of an oral antibiotic treatment with selected agents from the start. There is no evidence that the total duration of antibiotic therapy for more than 4-6weeks improves outcome, when compared with shorter regimens. Hopefully, the future will show randomized trials in the adult population, allowing optimal timing of surgical and medical therapy and sparing of unnecessary prescription, with concomitant development of antibiotic resistance. External advice from an expert team with combined surgeons and infectious disease physicians may help to reduce antibiotic consumption in a cost-effective wa