Non-Canonical Aspects of Antibiotics and Antibiotic Resistance.

The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The "canonical" mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess their activity upon bacteria, have not changed in decades; the same applies to the definition, acquisition, selective pressures, and drivers of resistance. As a consequence, the strategies to improve antibiotic usage and overcome resistance have ultimately failed.

Ascorbate and Antibiotics, at Concentrations Attainable in Urine, Can Inhibit the Growth of Resistant Strains of Cultured in Synthetic Human Urine.

There are conflicting reports on the antibacterial activity of ascorbate; all at concentrations much higher than the typical in human plasma, but that can be reached in urine. The effect of 10 mM ascorbate (in itself not inhibitory) along with antibiotics, was tested both in Mueller-Hinton broth (MHb) and in synthetic human urine (SHU), against resistant isolates of from lower urinary infections. The activity of nitrofurantoin and sulfamethoxazole was higher in SHU than in MHb; minimal inhibitory concentrations (MICs) in SHU with ascorbate were below typical urinary concentrations.

Macrolides at Clinically-Relevant Concentrations May Induce Biofilm Formation in Macrolide-Resistant .

Macrolides inhibit biofilm formation in several Gram-negative, intrinsically-resistant bacterial species. However, the effect of macrolides upon biofilm formation by susceptible Gram-positive bacteria has been much less explored as such concentrations also inhibit cell growth. To circumvent this problem, the effect of macrolides (erythromycin, clarithromycin and azithromycin) at 0.

Phage Therapies: Lessons (Not) Learned from the "Antibiotic Era".

The use of phages as therapeutic or prophylactic approaches is gaining increased interest amid the growing menace of antibiotic resistance. Phages, along with other new anti-infective strategies, are certainly welcome as much needed additions to the medicinal arsenal. However, we can easily make with phages the same mistakes we made with antibiotics, which caused the current resistance crisis.

Myths and Misconceptions around Antibiotic Resistance: Time to Get Rid of Them.

The antibiotic resistance arena is fraught with myths and misconceptions, leading to wrong strategies to combat it. It is crucial to identify them, discuss them in light of current evidence, and dispel those that are unequivocally wrong. This article proposes some concepts that may qualify as misconceptions around antibiotic resistance: the susceptible-resistant dichotomy; that incomplete antibiotic courses cause resistance; that resistance "emerges" in patients and hospitals; that antibiotics are mostly abused clinically; that resistance is higher in countries that use more antibiotics; that reducing antibiotic usage would reduce resistance; that financial incentives would "jumpstart" research and development of antibiotics; that generic and "original" antibiotics are the same; and that new anti-infective therapies are just around the corner.

Metallo-beta-lactamase-producing in the sewage of Mexico City: where do they come from?

While monitoring the presence of antibiotic resistance in municipal wastewater bacteria from Mexico City, five isolates were found to be resistant to carbapenems, antibiotics of "last resort" used mostly in hospitals. Further analysis revealed that these carbapenem-resistant isolates carried the gene encoding a metallo-beta-lactamase, NDM-5. The gene was found to be beared by a large, ∼145 kb conjugative plasmid, which also carries putative genes encoding resistance to sulfonamides, trimethoprim, tetracycline, ciprofloxacin, and chloramphenicol (although no phenotypic chloramphenicol resistance was detected) and quaternary-ammonium compounds.

Antibiotic usage and resistance in Mexico: an update after a decade of change.

Ten years ago, a review on the status of resistance in Mexico was bleak: with antibiotics freely sold over the counter and poor regulation of generic drugs, among other conditions, resistance among relevant pathogens often ranked top, either among Latin American countries, or even worldwide. Since then, there have been some regulatory changes, along a decline in antibiotics usage: antibiotics are (supposedly) no longer sold without prescription, generic drugs (supposedly) have to demonstrate bioequivalence, and antibiotic usage has drop, from about 13 defined daily doses per 1,000 inhabitants per day, to 7. While these changes may sound encouraging, an analysis show that regulatory changes are incomplete at best, and usage decline may be the consequence of factors such as growing poverty.

Selection of Amikacin Hyper-Resistant Pseudomonas aeruginosa After Stepwise Exposure to High Amikacin Concentrations.

Aerosolized amikacin reaches high concentrations in lung fluids, which are well above the minimum inhibitory concentrations (MICs) of resistant strains of Pseudomonas aeruginosa. However, P. aeruginosa can gain resistance to amikacin through different cumulative mechanisms; amikacin MICs are seldom reported beyond values of 1,000 μg/ml, as tested in clinical microbiology assays.

Characterization of Escherichia coli Isolates from an Urban Lake Receiving Water from a Wastewater Treatment Plant in Mexico City: Fecal Pollution and Antibiotic Resistance.

The presence of enteric bacteria in water bodies is a cause of public health concerns, either by directly causing water- and food-borne diseases, or acting as reservoirs for antibiotic resistance determinants. Water is used for crop irrigation; and sediments and aquatic plants are used as fertilizing supplements and soil conditioners. In this work, the bacterial load of several micro-environments of the urban lake of Xochimilco, in Mexico City, was characterized.

Sublethal exposure to commercial formulations of the herbicides dicamba, 2,4-dichlorophenoxyacetic acid, and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium.

Unlabelled: Biocides, such as herbicides, are routinely tested for toxicity but not for sublethal effects on microbes. Many biocides are known to induce an adaptive multiple-antibiotic resistance phenotype. This can be due to either an increase in the expression of efflux pumps, a reduced synthesis of outer membrane porins, or both.

Nitrofurantoin, phenazopyridine, and the superoxide-response regulon soxRS of Escherichia coli.

Nitrofurantoin and phenazopyridine are two drugs commonly used against urinary tract infections. Both compounds exert oxidative damage in patients deficient in glucose-6-phosphate dehydrogenase. This study was done to assess the interactions of these drugs with the soxRS regulon of Escherichia coli, a superoxide-defense system (that includes a nitroreductase that yields the active metabolite of nitrofurantoin) involved in antibiotic multi-resistance.

Basis for a cheap method for detecting bacteria and assessing their antibiotic susceptibility in urine samples.

Although molecular methods can now provide fast identification and the antibiotic susceptibility profile of infecting pathogens, these techniques are not affordable by a large majority of clinical laboratories in developing countries and can be considered excessive for simple, community-acquired infections. Most antibiotics are therefore prescribed empirically, which tends to avoid those drugs that face high resistance prevalence but that could still be used in a significant number of patients. This is a description of the basis for a fast, cheap method for assessing the presence of bacterial infection and its susceptibility to antibiotics in body fluids that are normally sterile, such as urine.

Antibiotic resistance: from Darwin to Lederberg to Keynes.

The emergence and spread of antibiotic-resistant bacteria reflects both, a gradual, completely Darwinian evolution, which mostly yields slight decreases in antibiotic susceptibility, along with phenotypes that are not precisely characterized as "resistance"; and sudden changes, from full susceptibility to full resistance, which are driven by a vast array of horizontal gene transfer mechanisms. Antibiotics select for more than just antibiotic resistance (i.e.

"Ten Commandments" for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting.

A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients' compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically - but intelligently; know local susceptibility trends, and also surveillance limitations.

Serotypes and antibiotic susceptibility of Streptococcus pneumoniae isolates causative of invasive diseases in Mexican children.

Introduction: Streptococcus pneumoniae is a worldwide leading cause of morbidity and mortality, while susceptibility towards penicillin and macrolides can be less than 50% in many regions.

Methodology: A total of 150 isolates of S. pneumoniae causative of invasive diseases in children were characterized, of which 24.

Susceptibility of Mexican isolates of yeasts and moulds to amphotericin B and triazole antifungals.

Background: Resistance to antifungal drugs, especially towards triazoles, is commonly referred to by clinicians, but data on its prevalence in developing countries is limited.

Methodology: To determine the prevalence of triazole-resistance amongst pathogenic yeasts and moulds, we assessed the in vitro susceptibility of 250 isolates from hospitalized patients at five Mexican cities towards amphotericin B, fluconazole and voriconazole, by E-test.

Results: All yeasts were susceptible to voriconazole, according to E-test interpretive criteria (MIC < or = 1 microg/mL), and all filamentous or dimorphic fungi also had voriconazole MIC < or = 1 microg/mL, except for one isolate each of Mucor sp.

An analysis of the evolutionary relationships of integron integrases, with emphasis on the prevalence of class 1 integrons in Escherichia coli isolates from clinical and environmental origins.

Integrons are genetic elements that allow the mobilization and expression of smaller elements called gene cassettes, and are considered to be key elements in the evolution of antibiotic resistance among enteric bacteria. Although in nature integrons appear to be abundant, the presence of class 1 integrons in Escherichia coli has been reported to be much less frequent among isolates of non-human origin than among clinical ones. Searching for integrons in a wide variety of E.

High resistance prevalence towards ampicillin, co-trimoxazole and ciprofloxacin, among uropathogenic Escherichia coli isolates in Mexico City.

Background: The prevalence of antimicrobial resistance among uropathogenic E. coli varies widely worldwide; to guide empirical therapy is necessary to have local, up-to-date susceptibility data.

Methodology: We tested 907 isolates from patients in Mexico City by disk diffusion and further characterized ciprofloxacin, cephalosporin and nitrofurantoin resistant strains.

Moxifloxacin vs amoxicillin/clavulanate in the treatment of acute sinusitis.

Purpose: The aim of this study was to compare the efficacy and safety of moxifloxacin with that of amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults.

Materials And Methods: Five hundred seventy-five patients from Latin American countries were randomized to receive oral moxifloxacin 400 mg once daily for 7 days, or oral amoxicillin/clavulanate 500/125 mg 3 times daily for 10 days, in a prospective, open study.

Results: At the test-of-cure visit (7-14 days after the end of therapy), the clinical success rate in the moxifloxacin group was 93.

Urban dust fecal pollution in Mexico City: antibiotic resistance and virulence factors of Escherichia coli.

Fecal pollution of settled dust samples from indoor and outdoor urban environments, was measured and characterized by the presence of fecal coliforms (FC), and by the characterization of Escherichia coli virulence genes, adherence and antibiotic resistance traits as markers. There were more FC indoors than outdoors (mean values 1089 and 435MPN/g). Among indoor samples, there were more FC in houses with carpets and/or pets.

Moxifloxacin versus levofloxacin against acute exacerbations of chronic bronchitis: the Latin American Cohort.

We compared the efficacy and safety of moxifloxacin and levofloxacin for the treatment of patients with acute exacerbations of chronic bronchitis (AECB) using a prospective, randomized, double blind, parallel-group clinical trial design. A total of 563 patients with AECB were enrolled (437 efficacy-valid) at 34 centers in Mexico, Argentina, Brazil, Colombia, and Peru. Patients were randomized to oral therapy with either moxifloxacin 400 mg once daily for 5 days or levofloxacin 500 mg once daily for 7 days.