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Objective: To define the susceptibilities of the common causative pathogens of neonatal sepsis in the UK., Design: Retrospective analysis of the prospectively collected neonIN infection surveillance network data between 2005 and 2014., Setting: 30 neonatal units in the UK., Patients: Newborns admitted to participating neonatal units who return a positive blood, cerebrospinal fluid or urine culture and are treated with at least 5 days of appropriate antibiotics., Results: 1568 isolates with recorded antimicrobial data were collected including 328 early-onset sepsis (EOS) isolates and 1240 late-onset sepsis (LOS) isolates. The majority of EOS pathogens (>92%) were susceptible to the four empirical commonly used antimicrobial combinations (eg, 93% for benzylpenicillin/gentamicin), while LOS pathogens demonstrated higher levels of resistance (eg, 89% for flucloxacillin/gentamicin). Among infants<1500 g and <32 weeks gestation, an amoxicillin/gentamicin combination demonstrated a trend towards improved coverage of EOS isolates than benzylpenicillin/gentamicin (93% vs 86%, p=0.211)., Conclusions: This analysis provides insights into the patterns of antimicrobial resistance among UK neonatal pathogens. These data will inform areas of future research and can be used to update national evidence-based guidelines on antimicrobial usage., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested., Aim: To describe the efficacy and safety of FMT for the treatment of recurrent CDI., Patients and Methods: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction., Results: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary., Conclusions: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

Thiopeptides are members of the ribosomally synthesized and post-translationally modified peptide family of natural products. Most characterized thiopeptides display nanomolar potency toward Gram-positive bacteria by blocking protein translation with several being produced at the industrial scale for veterinary and livestock applications. Employing our custom bioinformatics program, RODEO, we expand the thiopeptide family of natural products by a factor of four. This effort revealed many new thiopeptide biosynthetic gene clusters with products predicted to be distinct from characterized thiopeptides and identified gene clusters for previously characterized molecules of unknown biosynthetic origin. To further validate our data set of predicted thiopeptide biosynthetic gene clusters, we isolated and characterized a structurally unique thiopeptide featuring a central piperidine and rare thioamide moiety. Termed saalfelduracin, this thiopeptide displayed potent antibiotic activity toward several drug-resistant Gram-positive pathogens. A combination of whole-genome sequencing, comparative genomics, and heterologous expression experiments confirmed that the thioamide moiety of saalfelduracin is installed post-translationally by the joint action of two proteins, TfuA and YcaO. These results reconcile the previously unknown origin of the thioamide in two long-known thiopeptides, thiopeptin and Sch 18640. Armed with these new insights into thiopeptide chemical-genomic space, we provide a roadmap for the discovery of additional members of this natural product family.

Antimicrobial resistance among staphylococci of animal origin is based on a wide variety of resistance genes. These genes mediate resistance to many classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. In addition, numerous mutations have been identified that confer resistance to specific antimicrobial agents, such as ansamycins and fluoroquinolones. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents, including agents approved solely for human use. The resistance genes code for all three major resistance mechanisms: enzymatic inactivation, active efflux, and protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate not only the exchange of resistance genes among members of the same and/or different staphylococcal species, but also between staphylococci and other Gram-positive bacteria. The observation that plasmids of staphylococci often harbor more than one resistance gene points toward coselection and persistence of resistance genes even without direct selective pressure by a specific antimicrobial agent. This chapter provides an overview of the resistance genes and resistance-mediating mutations known to occur in staphylococci of animal origin.

Mycoplasmas are intrinsically resistant to antimicrobials targeting the cell wall (fosfomycin, glycopeptides, or β-lactam antibiotics) and to sulfonamides, first-generation quinolones, trimethoprim, polymixins, and rifampicin. The antibiotics most frequently used to control mycoplasmal infections in animals are macrolides and tetracyclines. Lincosamides, fluoroquinolones, pleuromutilins, phenicols, and aminoglycosides can also be active. Standardization of methods used for determination of susceptibility levels is difficult since no quality control strains are available and because of species-specific growth requirements. Reduced susceptibility levels or resistances to several families of antimicrobials have been reported in field isolates of pathogenic Mycoplasma species of major veterinary interest: M. gallisepticum and M. synoviae in poultry; M. hyopneumoniae , M. hyorhinis , and M. hyosynoviae in swine; M. bovis in cattle; and M. agalactiae in small ruminants. The highest resistances are observed for macrolides, followed by tetracyclines. Most strains remain susceptible to fluoroquinolones. Pleuromutilins are the most effective antibiotics in vitro . Resistance frequencies vary according to the Mycoplasma species but also according to the countries or groups of animals from which the samples were taken. Point mutations in the target genes of different antimicrobials have been identified in resistant field isolates, in vitro -selected mutants, or strains reisolated after an experimental infection followed by one or several treatments: DNA-gyrase and topoisomerase IV for fluoroquinolones; 23S rRNA for macrolides, lincosamides, pleuromutilins, and amphenicols; 16S rRNAs for tetracyclines and aminoglycosides. Further work should be carried out to determine and harmonize specific breakpoints for animal mycoplasmas so that in vitro information can be used to provide advice on selection of in vivo treatments.

Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.

Background: Appropriate antibiotic use has become an important issue. However, collecting data on the use of all antibiotics in a hospital is difficult without an advanced computerized system and dedicated staff. This paper examines if 1-3 antibiotics can satisfactorily represent the total antibiotic consumption at the hospital level., Methods: We collected antibiotic data from six large university hospitals in Korea for some years between 2004 and 2012. Since the total antibiotics consist of a few chosen representative antibiotics and the rest, we used those chosen antibiotics along with additional variables constructed only with t (time) such as t, t 2 , and t 3 to capture the time trend and whether t belongs to each month or not to capture the monthly variations. The ordinary least squares method was used to explain the total antibiotic amount with these variables, and then the estimated model was employed to predict the use for 2013. To determine which antibiotics were the most representative in tracking general trends in antibiotic use over time, we tried various combinations of antibiotics to find the combination that best minimized the 2013 prediction error., Results: We found that fluoroquinolones and aminoglycosides were the most representative, followed by beta-lactam/beta-lactamase inhibitors and 4th-generation and 3rd-generation cephalosporins. The mean prediction error over 12 months in 2013 with these few antibiotics was only 1-3% of the monthly antibiotic consumption amount., Conclusions: The total antibiotic consumption amount at the hospital level can be represented sufficiently by a few antibiotics, such as fluoroquinolones and aminoglycosides, which means that hospitals can save resources by tracing only the usage of those few antibiotics instead of the entire inventory. Since the choice of fluoroquinolones and aminoglycosides is based solely on our Korean data, other hospitals may follow the same modelling methodology to find their own representative antibiotics.

Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA ('poisoning') in an analogous fashion to fluoroquinolones, but without the requirement for the water-metal-ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase-DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate. These involve movement at the GyrA interface and tilting of the TOPRIM domains toward the scissile phosphate coupled to capture of the catalytic metal ion. Our experiments show that these structural transitions are involved generally in poisoning of gyrase by therapeutic compounds and resemble those undergone by the enzyme during its adenosine triphosphate-coupled strand-passage cycle. In addition to resistance mutations affecting residues that directly interact with the compounds, we characterized a mutant (D82N) that inhibits formation of the cleavage complex by the unpoisoned enzyme. The D82N mutant appears to act by stabilizing the binary conformation of DNA gyrase with uncleaved DNA without direct interaction with the compounds. This provides general insight into the resistance mechanisms to antibiotics targeting bacterial type II topoisomerases.

Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2018 by Daedalus Enterprises.)

This case reports the findings and management of a late preterm female infant born with congenital bilateral eyelid eversion with chemosis. The pathogenic process remains unknown but typically presents at birth, predominantly affecting the upper eyelid of both eyes. Black males, patients with trisomy 21, and collodion infants have a higher incidence of eyelid eversion. Treatment modalities range from conservative therapy including eye patching with antibiotic and lubricating ointment to invasive surgical eyelid suturing. In this case report, successful resolution of chemosis and eyelid inversion occurred with conservative management.

We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a systematic literature review of published, randomized, controlled trials (RCTs) that compared a bacteriostatic agent to a bactericidal agent in the treatment of clinical, bacterial infections. Of 56 identified trials published since 1985, 49 found no significant difference in efficacy between bacteriostatic and bactericidal agents. In 6 trials it was found that the bacteriostatic agent was superior to the bactericidal agent in efficacy. Only 1 trial found that the bactericidal agent was superior; in that case, the inferiority of the static agent was explainable by underdosing of the drug based on pharmacokinetic-pharmacodynamic analysis. Thus, virtually all available data from high-quality, RCTs demonstrate no intrinsic superiority of bactericidal compared to bacteriostatic agents. Other drug characteristics such as optimal dosing, pharmacokinetics, and tissue penetration may be more important efficacy drivers.

The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin-antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production. Here, we demonstrate post-transcriptional autoregulation of mazF expression dynamics by MazF cleaving its own transcript. Single-cell analyses of bacterial populations during ectopic MazF production indicated that two-level autoregulation of mazEF expression influences cell-to-cell growth rate heterogeneity. The increase in growth rate heterogeneity is governed by the MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both autoregulatory features grant rapid exit from the stress caused by mazF overexpression. Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads to increased temporal variability in length of individual cells during ectopic mazF overexpression, as explained by a stochastic model indicating that mazEF mRNA cleavage underlies temporal fluctuations in MazF levels during stress.

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Background: Recently awareness of the importance of Aspergillus colonization in the airway of patients with chronic obstructive pulmonary disease (COPD) was rising. The aim of this study was to investigate the clinical features and short-term outcomes of COPD patients with Aspergillus colonization during acute exacerbation., Methods: A pair-matched retrospective study on patients presenting with COPD exacerbation was conducted from January 2014 to March 2016 in Beijing Hospital, China., Results: Twenty-three patients with Aspergillus colonization and 69 patients as controls, diagnosed of COPD exacerbation, were included in this study at a pair-matched ratio of 1:3. In stable stage, the percentage of patients with high-dose corticosteroids inhalation in the Aspergillus colonization group is higher than that of in control group (65.5% vs 33.3%, p = 0.048). Multivariate analysis showed that corticosteroids use was the risk factor for isolation of Aspergillus. In acute exacerbation stage, patients in Aspergillus colonization group received higher dose of inhaled corticosteroids and more types of antibiotics than control group. The short-time outcome hinted that the remission time and the duration of hospitalization were longer in the Aspergillus colonization group than in the control group (remission time: 11 ± 4 days vs 7 ± 4 days, p = 0.001; duration: 15 ± 5 days vs 12 ± 4 days, p = 0.011)., Conclusions: Aspergillus colonization in the lower respiratory tract of COPD patients showed typical clinical manifestations, affected their short time outcome and provided a dilemma of clinical treatment strategy.

Introduction: Campylobacter is an important agent of diarrhea in humans. In Ecuador, the information on Campylobacter is scarce and there are not antecedents about antimicrobial susceptibility., Objective: To describe Campylobacter prevalence in children with diarrhea and their behavior against five antimicrobials in vitro., Method: We studied 253 children with diarrhea aging 7 months to 9 years who consulted for diarrhea in two hospitals in the city of Loja. Fecal samples were cultured and identification by tests by phenotypic tests and multiplex PCR. Susceptibility to 5 antibiotics was determined by the disc-diffusion method., Results: Campylobacter was found in 16 (6.3%) children, being C. jejuni the most frequent one (5.1%), followed by C. coli (1.2%). All strains were susceptible to gentamicin and ampicillin/clavulanic acid, being found low resistance to ampicillin and erythromycin and high resistance to ciprofloxacin.

Campylobacter is a major foodborne pathogen and has become increasingly resistant to clinically important antimicrobials. To cope with the selection pressure from antimicrobial use in both veterinary and human medicine, Campylobacter has developed multiple mechanisms for antibiotic resistance, including modification or mutation of antimicrobial targets, modification or inactivation of antibiotics, and reduced drug accumulation by drug efflux pumps. Some of these mechanisms confer resistance to a specific class of antimicrobials, while others give rise to multidrug resistance. Notably, new antibiotic resistance mechanisms continuously emerge in Campylobacter , and some examples include the recently discovered multidrug resistance genomic islands harboring multiple genes involved in the resistance to aminoglycosides and macrolides, a novel Cfr(C) conferring resistance to phenicols and other drugs, and a potent multidrug efflux pump CmeABC variant (RE-CmeABC) that shows a significantly enhanced function in multidrug resistance and is associated with exceedingly high-level resistance to fluoroquinolones. These newly emerged resistance mechanisms are horizontally transferable and greatly facilitate the adaptation of Campylobacter in the food-producing environments where antibiotics are frequently used. In this article, we will discuss how Campylobacter resists the action of various classes of antimicrobials, with an emphasis on newly discovered mechanisms.

OBJECTIVE Because antibacterial history is difficult to obtain, especially when the exposure occurred at an outside hospital, we assessed whether infection-related diagnostic billing codes, which are more readily available through hospital discharge databases, could infer prior antibacterial receipt. DESIGN Retrospective cohort study. PARTICIPANTS This study included 121,916 hospitalizations representing 78,094 patients across the 3 hospitals. METHODS We obtained hospital inpatient data from 3 Chicago-area hospitals. Encounters were categorized as "infection" if at least 1 International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code indicated a bacterial infection. From medication administration records, we categorized antibacterial agents and calculated total therapy days using Centers for Disease Control and Prevention (CDC) definitions. We evaluated bivariate associations between infection encounters and 3 categories of antibacterial exposure: any, broad spectrum, or surgical prophylaxis. We constructed multivariable models to evaluate adjusted risk ratios for antibacterial receipt. RESULTS Of the 121,916 inpatient encounters (78,094 patients) across the 3 hospitals, 24% had an associated infection code, 47% received an antibacterial, and 13% received a broad-spectrum antibacterial. Infection-related ICD-9-CM codes were associated with a 2-fold increase in antibacterial administration compared to those lacking such codes (RR, 2.29; 95% confidence interval [CI], 2.27-2.31) and a 5-fold increased risk for broad-spectrum antibacterial administration (RR, 5.52; 95% CI, 5.37-5.67). Encounters with infection codes had 3 times the number of antibacterial days. CONCLUSIONS Infection diagnostic billing codes are strong surrogate markers for prior antibacterial exposure, especially to broad-spectrum antibacterial agents; such an association can be used to enhance early identification of patients at risk of multidrug-resistant organism (MDRO) carriage at the time of admission. Infect Control Hosp Epidemiol 2018;39:377-382.

The genus Streptococcus includes Gram-positive organisms shaped in cocci and organized in chains. They are commensals, pathogens, and opportunistic pathogens for humans and animals. Most Streptococcus species of veterinary relevance have a specific ecological niche, such as S. uberis , which is almost exclusively an environmental pathogen causing bovine mastitis. In contrast, S. suis can be considered as a true zoonotic pathogen, causing specific diseases in humans after contact with infected animals or derived food products. Finally, Streptococcus species such as S. agalactiae can be sporadically zoonotic, even though they are pathogens of both humans and animals independently. For clarification, a short taxonomical overview will be given here to highlight the diversity of streptococci that infect animals. Several families of antibiotics are used to treat animals for streptococcal infections. First-line treatments are penicillins (alone or in combination with aminoglycosides), macrolides and lincosamides, fluoroquinolones, and tetracyclines. Because of the selecting role of antibiotics, resistance phenotypes have been reported in streptococci isolated from animals worldwide. Globally, the dynamic of resistance acquisition in streptococci is slower than what is experienced in Enterobacteriaceae , probably due to the much more limited horizontal spread of resistance genes. Nonetheless, transposons or integrative and conjugative elements can disseminate resistance determinants among streptococci. Besides providing key elements on the prevalence of resistance in streptococci from animals, this article will also largely consider the mechanisms and molecular epidemiology of the major types of resistance to antimicrobials encountered in the most important streptococcal species in veterinary medicine.

One Health is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and our environment. The drivers of antimicrobial resistance include antimicrobial use and abuse in human, animal, and environmental sectors and the spread of resistant bacteria and resistance determinants within and between these sectors and around the globe. Most of the classes of antimicrobials used to treat bacterial infections in humans are also used in animals. Given the important and interdependent human, animal, and environmental dimensions of antimicrobial resistance, it is logical to take a One Health approach when addressing this problem. This includes taking steps to preserve the continued effectiveness of existing antimicrobials by eliminating their inappropriate use and by limiting the spread of infection. Major concerns in the animal health and agriculture sectors are mass medication of animals with antimicrobials that are critically important for humans, such as third-generation cephalosporins and fluoroquinolones, and the long-term, in-feed use of medically important antimicrobials, such as colistin, tetracyclines, and macrolides, for growth promotion. In the human sector it is essential to prevent infections, reduce over-prescribing of antimicrobials, improve sanitation, and improve hygiene and infection control. Pollution from inadequate treatment of industrial, residential, and farm waste is expanding the resistome in the environment. Numerous countries and several international agencies have included a One Health approach within their action plans to address antimicrobial resistance. Necessary actions include improvements in antimicrobial use regulation and policy, surveillance, stewardship, infection control, sanitation, animal husbandry, and alternatives to antimicrobials. WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicrobials routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antimicrobials that are important for human medicine by reducing their use in animals.

Infection in surgical incision often results in poor wound healing, and one of the main factors for wound infection is the use of antimicrobial agents. Rational use of antibiotics is one of the key factors to prevent incision infection in general surgery. The number of current clinical studies on antibiotic use before and during surgery is greater than that of systematic studies on antibiotic use after surgery. For the rational use of antibiotics and improvement of wound healing rate, researchers around the world have gradually focused on the use of antibiotics after surgery. Despite the familiarity on the concept of "rational use of antibiotics", few clear and systematic studies were conducted to elucidate the effect of different antibiotics on wound healing. Therefore, this review focuses on the use of different types of antimicrobial agents in surgical wounds.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) worked together on the development of specific recommendations for the diagnosis, treatment and prevention of ventilator-associated pneumonia (VAP). The methodology used was the analysis of the literature published in the last 15 years, complemented with the opinion of experts and local data. This document aims to offer basic tools to optimize diagnosis based on clinical and microbiological criteria, orientation in empirical and targeted antibiotic schemes, news on posology and administration of antibiotics in critical patients and to promote effective measures to reduce the risk of VAP. It also offers a diagnostic and treatment algorithm and considerations on inhaled antibiotics. The joint work of both societies -infectious diseases and intensive care- highlights the concern for the management of VAP and the importance of ensuring improvement in daily practices. This guideline established recommendations to optimize the diagnosis, treatment and prevention of VAP in order to reduce morbidity and mortality, days of hospitalization, costs and resistance to antibiotics due to misuse of antimicrobials.

Background: Empiric treatment for Helicobacter pylori is influenced by antibiotic susceptibility of infecting strains. A rise in the resistance rate to clarithromycin and metronidazole has been reported in pediatric populations., Objectives: To assess the primary and secondary antibiotic resistance of H. pylori isolates in Israeli children and adolescents., Methods: A retrospective review of H. pylori isolates cultured from antral biopsies of consecutive children aged 1 to 18 years, who were referred to the Pediatric Gastroenterology Unit, Kaplan Medical Center, over a 2.8 year period, was performed. Antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was determined by E-test. Data on the age of the patient, indication for endoscopy, and antibiotic treatment for H. pylori in previously treated children was collected., Results: Cultures for H. pylori yielded 123 isolates. In children not previously treated (n=95), the primary global resistance was 38% with resistance to clarithromycin 9.5%, metronidazole 32.6 %, and to both 4.2%. Respective rates of resistance in previously treated children (n=28) were 71% (P = 0.002), 29% (P = 0.02), and 61% (P = 0.007). Simultaneous resistance to both drugs was found in 18% (P = 0.02). All H. pylori strains were susceptible to amoxicillin, tetracycline, and levofloxacin. Past eradication treatment was the only independent risk factor for antibiotic resistance in multivariate analysis., Conclusions: Significantly higher resistance rates were found in previously treated patients, stressing the need to refrain from empiric treatment using the "test and treat strategy." Culture-based treatment strategy should be considered in all previously treated children.

Peer comparison has potential as an effective antimicrobial stewardship intervention in the inpatient setting. We report a new metric, days of therapy per 100 service days, for comparing antibiotic utilization. Among 14 prescribers on the primary infectious diseases service during a 6-month period, we identified 1 outlier for each anti-MRSA agent. Infect Control Hosp Epidemiol 2017;38:1506-1508.

There is currently only limited information on the antimicrobial susceptibility and resistance of Corynebacterium spp., Arcanobacterium spp., and Trueperella pyogenes from animals. The comparability of the data is hampered by the use of different antimicrobial susceptibility testing methods and interpretive criteria. To date, standard broth microdilution methods and clinical breakpoints that are approved by the Clinical and Laboratory Standards Institute and are applicable to Corynebacterium spp., Arcanobacterium spp., and T. pyogenes are available. The lack of species-specific clinical breakpoints for the different animal species reduces the explanatory power of the data. Among the isolates of the three genera, elevated MICs for different classes of antimicrobial agents (e.g., β-lactams, macrolides, lincosamides, tetracyclines, aminoglycosides, phenicols, sulfonamides/diaminopyrimidines, and fluoroquinolones) have been described. The most comprehensive data set is available for T. pyogenes , which also includes information about genes and mutations involved in antimicrobial resistance. In T. pyogenes isolates, the macrolide-lincosamide-streptogramin B resistance genes erm (B) and erm (X) were identified. Tetracycline resistance in T. pyogenes was based on the resistance genes tet (W), tet (Z), and tet (33), whereas the aminoglycoside resistance genes aacC , aadA1 , aadA2 , aadA5 , aadA24 , and aadB have been described in T. pyogenes . So far, only single genes conferring either phenicol resistance ( cmlA6 ), trimethoprim resistance ( dfrB2a ), or β-lactam resistance ( blaP1 ) are known to occur in T. pyogenes isolates. Various 23S rRNA mutations, including A2058T, A2058G, and G2137C, were identified in macrolide/lincosamide-resistant T. pyogenes .

Diabetic foot infections are a common and serious problem for all health systems worldwide. The aim of this study was to examine the resistance to antibiotics of microorganisms isolated from infected soft tissues of diabetic foot ulcers, using tissue cultures. We included 113 consecutive patients (70 men, 43 women) with a mean age of 66.4 ± 11.2 years and a mean diabetes duration of 14.4 ± 7.6 years presenting with diabetic foot soft tissue infections. Generally, no high antibiotic resistance was observed. Piperacillin-tazobactam exhibited the lowest resistance in Pseudomonas, as well as in the other Gram-negative pathogens. In methicillin-resistant Staphylococcus aureus isolates, there was no resistance to anti-Staphylococcus agents. Of note, clindamycin, erythromycin, and amoxycillin/clavulanic acid exhibited high resistance in Gram-positive cocci. These results suggest that antibiotic resistance in infected diabetic foot ulcers in our area is not high and they are anticipated to prove potentially useful in the initial choice of antibiotic regimen.

The biofilm life cycle is characterized by the transition of planktonic cells exhibiting high susceptibly to antimicrobial agents to a biofilm mode of growth characterized by high tolerance to antimicrobials, followed by dispersion of cells from the biofilm back into the environment. Dispersed cells, however, are not identical to planktonic cells but have been characterized as having a unique transitionary phenotype relative to biofilm and planktonic cells, with dispersed cells attaching in a manner similar to exponential-phase cells, but demonstrating gene expression patterns that are distinct from both exponential and stationary-phase planktonic cells. This raised the question whether dispersed cells are as susceptible as planktonic cells and whether the dispersion inducer or the antibiotic class affects the drug susceptibility of dispersed cells. Dispersed cells obtained in response to dispersion cues glutamate and nitric oxide (NO) were thus exposed to tobramycin and colistin. Although NO-induced dispersed cells were as susceptible to colistin and tobramycin as exponential-phase planktonic cells, glutamate-induced dispersed cells were susceptible to tobramycin but resistant to colistin. The difference in colistin susceptibility was independent of cellular c-di-GMP levels, with modulation of c-di-GMP failing to induce dispersion. Instead, drug susceptibility was inversely correlated with LPS modification system and the biofilm-specific transcriptional regulator BrlR. The susceptibility phenotype of glutamate-induced dispersed cells to colistin was found to be reversible, with dispersed cells being rendered as susceptible to colistin within 2 h postdispersion, though additional time was required for dispersed cells to display expression of genes indicative of exponential growth., (Copyright © 2017 American Society for Microbiology.)

Background and Objective: Pneumonia is a common admitting diagnosis in the intensive care unit (ICU). When aspiration is suspected, antibiotics to cover anaerobes are frequently used, but in the absence of clear risk factors, current guidelines have questioned their role. It is unknown how frequently these guidelines are followed., Methods: We conducted a single-centre observational study on practice patterns of anaerobic antibiotic use in consecutive patients admitted to the ICU with aspiration pneumonia (Asp), community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP)., Results: A total of 192 patients were studied (Asp: 20, HCAP: 107, CAP: 65). Overall, 59 patients received anaerobic antibiotics (Asp: 90%, HCAP: 28%, CAP 17%) but a significant proportion of these patients did not meet criteria to receive them. Inappropriate anaerobic antibiotic use was 12/20 for Asp, 27/107 for HCAP and 9/65 for CAP. Mortality probability model III at zero hours (MPM0) score and a diagnosis of Asp were predictors of receiving inappropriate anaerobic antibiotics. Receiving inappropriate anaerobic antibiotics was associated with a longer ICU length of stay (LOS; 7 days (interquartile range (IQR): 7-21) vs 4 days (IQR:2-9), P = 0.017)., Conclusion: For patients in the ICU admitted with pneumonia, there is a high occurrence of inappropriately prescribed anaerobic antibiotics, the use of which was associated with a longer ICU LOS., (© 2017 Asian Pacific Society of Respirology.)

The enteropathogen Yersinia pseudotuberculosis causes gastrointestinal infections in humans. Although this species is usually susceptible to antibiotics active against Gram-negative bacteria, we identified three multidrug resistant (MDR) strains of Y. pseudotuberculosis that were isolated from the environment in Russia and from a patient in France. The resistance traits of the two Russian isolates were transferable at high frequencies (≈2×10 -1 /donor CFU) to Y. pseudotuberculosis. In contrast no transfer of the antibiotic resistances carried by the French strain was observed. Sequencing of the plasmid extracts of the Y. pseudotuberculosis transconjugants for the Russian isolates revealed the presence of conjugative plasmids of the IncN group that carried genes conferring resistance to four to six classes of antibiotics. The French strain harbored a large MDR plasmid of the IncHI2 group that carried resistance genes to six families of antibiotics, and contained a truncated set of transfer genes, accounting for the lack of plasmid transfer. All three Y. pseudotuberculosis plasmids were homologous to MDR plasmids found in various enterobacteria. A phylogenetic analysis showed that the two Russian strain plasmids were closely related to each other and were more distant from the French plasmid. To the best of our knowledge, this is the first molecular characterization of MDR plasmids in Y. pseudotuberculosis. Due to the propensity of this species to acquire exogenous plasmids, the risk of emergence of new MDR Y. pseudotuberculosis isolates should be seriously taken into consideration., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Pediatric stewardship programs have been successful at reducing unnecessary antibiotic use. Data from nonfreestanding children's hospitals are currently limited. This study is an analysis of antibiotic use after implementation of an antimicrobial stewardship program at a community nonfreestanding children's hospital., Methods: In April 2013, an antimicrobial stewardship program that consisted of physician-group engagement and pharmacist prospective auditing and feedback was initiated. We compared antibiotic use in the preintervention period (April 2012 to March 2013) with that in the postintervention period (April 2013 to March 2015) in all units except the neonatal intensive care unit and the emergency department. In addition, drug-acquisition costs, antibiotic-specific use, death, length of stay, and case-mix index were examined., Results: Antibiotic use decreased by 16.8% (95% confidence interval, 18.0% to -9.2%; P < .001) in the postintervention period. Vancomycin use decreased by 38% (P = .001), whereas antipseudomonal β-lactam use was unaltered. Drug-acquisition cost savings were estimated to be $67 000/year over the 2-year postintervention period. Lengths of stay and mortality rates were unchanged in the postintervention period after adjusting for case-mix index., Conclusions: Implementation of a simple stewardship initiative with limited resources at a community nonfreestanding children's hospital effectively reduced antibiotic use without an overt negative impact on overall clinical outcomes. The results of this study suggest that nonfreestanding children's hospitals can achieve substantial reductions in antibiotic use despite limited resources., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The development of antimicrobial resistance is triggered by the use of antibiotic drugs. Therefore, the consumption of antibiotics in livestock is monitored, and different measures may be applied if the usage of antibiotic drugs seems inappropriate. Unfortunately, the surveillance of antibiotic consumption is not standardised, and surveillance systems differ. In Germany, the food quality assurance system QS Qualität und Sicherheit GmbH (QS) began the documentation of antibiotic drug usage in pigs in 2012 in a private economic based database, and for its members, documentation has been mandatory in all pig age groups since 2014. In this investigation, we calculated the distribution of the antibiotics use per pig age group and half-year, and the percentage of the active substances used from overall treatments within German pig holdings from 1 July, 2013 to 30 June, 2015. In fattening pigs, the median of the treatment frequency is 4.3 in 2013-2 and exhibits a decreasing trend in this time period up to 2.1 in 2015-1. In weaners the median ranged between 11.3 in 2014-2 and 5.8 in 2013-2. The median of sucklers varies between 21.6 and 25.0. In sucklers and weaners, a clear temporal trend is not seen to date. The share of the active substances differs between the age groups. In fattening pigs, mostly tetracyclines and penicillines were used, occurring in approximately 60% of the total treatments. In weaners, amoxicillin and colistin have the highest shares of the treatment frequency, at approximately 60%. The treatment frequencies of macrolides and penicillines have the highest share in sucklers.

Background and Objectives: Cefotaxime is a class III drug according to the Biopharmaceutical Classification System due to low intestinal permeability based on poor oral bioavailability. Bile salt compounds have been shown to be effective additive for drug permeation through several biological membranes. The main purpose of this study was to investigate the ability of a mixed micelles made of phosphatidylcholine, sodium deoxycholate, and loaded with a cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex to enhance the oral bioavailability of cefotaxime in rats., Methods: Thin-film hydration method was used to prepare cefotaxime-loaded mixed micelles using different bile salt concentrations (0.87-25 mM of sodium deoxycholate). Overall, micelle sizes ranging from 86.9 to 155.6 nm were produced with negative zeta potential values from -15.9 to -19.5 mV and drug loading from 10.5 to 18.9 %. The oral bioavailability of cefotaxime in mixed micellar formulation was assessed and the pharmacokinetic parameters were compared with cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex and cefotaxime aqueous solution. 24 Male Wistar rats were randomly allocated into four groups (n = 6, per group) to receive the following: (1) a single intravenous dose of cefotaxime (25 mg/kg) in sterilized normal saline solution for injection; (2) a single oral dose of mixed micelles (100 mg/kg of cefotaxime) in phosphate buffered saline administered by oral gavage; (3) a single oral dose of cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex (100 mg/kg of cefotaxime) in phosphate buffered saline administered by oral gavage; (4) a single oral dose of free cefotaxime (100 mg/kg) in aqueous solution administered by oral gavage. Blood samples were collected for up to 24 h and cefotaxime analyzed using a validated HPLC assay., Results: Pharmacokinetic data showed that the oral bioavailability of cefotaxime in mixed micelles was found to be 4.91 % higher compared to the cefotaxime in aqueous solution (1.30 %). Maximum concentration (C max ) of cefotaxime in mixed micellar formulation was higher (1.08 ± 0.1 µg/ml) compared to the cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex (0.69 ± 0.1 µg/ml) and cefotaxime in aqueous solution (0.52 ± 0.1 µg/ml). Similarly, the mean values for area under the plasma concentration-time curve extrapolated to infinity (AUC 0-∞ ) of cefotaxime in the mixed micellar formulation was higher (3.89 ± 0.9 μg·h/mL) compared to the cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex (1.52 ± 0.2 μg·h/mL) and cefotaxime in aqueous solution (1.03 ± 0.4 μg·h/mL), respectively., Conclusion: The mixed micellar formulation was able to increase the oral bioavailability of the BCS Class III drug cefotaxime up to fourfold by enhancing drug permeation through the mucosal membrane of the small intestine.

Objective: To examine the timing and microbiology of neonatal sepsis in a population-based surveillance in the Indian community setting., Study Design: All live born infants in 223 villages of Odisha state were followed at home for 60 days. Suspect sepsis cases were referred to study hospitals for further evaluation including blood culture., Results: Of 12 622 births, 842 were admitted with suspected sepsis of whom 95% were 4 to 60 days old. Culture-confirmed incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high level of resistance to penicillin and ampicillin, moderate resistance to cephalosporins and extremely low resistance to Gentamicin and Amikacin was observed., Conclusion: The bacterial burden of sepsis in the Indian community is not high. Judicious choice of empiric antibiotics, antibiotic stewardship and alternate modalities should be considered for the management or prevention of neonatal sepsis in India.

The objective of this study was to evaluate the phenotypic and genotypic profile of antimicrobial susceptibility and the possible involvement of extended spectrum beta-lactamases (ESBLs) in the resistance profile of Salmonella Heidelberg (SH) isolated from chicken meat. We used 18 SH isolates from chicken meat produced in 2013 in the state of Paraná, Southern Brazil. The isolates were submitted to disk-diffusion tests and from these results it was possible to determine the number of isolates considered multiresistant and the index of multiple antimicrobial resistance (IRMA) against ten antimicrobials routinely used in human and veterinary medicine. It was considered multidrug resistant the isolate that showed resistance to three or more classes of antibiotics. Another test performed was the disc-approximation in order to investigate interposed zones of inhibition, indicative of ESBLs production. In the isolates that presented multidrug resistance (18/18), a search of resistance genes involved in the production of ESBLs was performed using PCR: blaCMY-2, blaSHV-1, blaTEM-1, blaCTX-M2, blaOXA-1, blaPSE-1 and AmpC. The overall antimicrobial resistance was 80.55%. The highest levels of resistance were observed for nalidixic acid and ceftiofur (100%). The most commonly resistance pattern found (42.1%) was A (penicillin-cephalosporin-quinolone-tetracycline). The results were negative for ghost zone formation, indicative of ESBLs. However, PCR technique was able to detect resistance genes via ESBLs where the blaTEM-1 gene showed the highest amplification (83.33%), and the second most prevalent genes were blaCMY-2 (38.88%) and AmpC gene (38.88%). The blaOXA-1 and blaPSE-1 genes were not detected. These results are certainly of concern since SH is becoming more prevalent in the South of Brazil and able to cause severe disease in immune compromised individuals, showing high antimicrobial resistance to those drugs routinely used in the treatment and control of human and animal salmonellosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To provide information on the prevalence and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and the distinction between community-associated MRSA and health care-associated MRSA., Quality of Evidence: The MEDLINE and EMBASE databases were searched from 2005 to 2016. Epidemiologic studies were summarized and the relevant treatment literature was based on level I evidence., Main Message: The incidence of community-associated MRSA infection is rising. Certain populations, including indigenous Canadians and homeless populations, are particularly affected. Community-associated MRSA can be distinguished from health care-associated MRSA based on genetic, epidemiologic, or microbiological profiles. It retains susceptibility to some oral agents including trimethoprim-sulfamethoxazole, clindamycin, and tetracyclines. Community-associated MRSA typically presents as purulent skin and soft tissue infection, but invasive infection occurs and can lead to severe, complicated disease. Treatment choices and the need for empiric MRSA coverage are influenced by the type and severity of infection., Conclusion: Community-associated MRSA is a common cause of skin and soft tissue infections and might be common in populations where overcrowding and limited access to clean water exist., (Copyright© the College of Family Physicians of Canada.)

Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

An ideal antibiotic is an antibacterial agent that kills or inhibits the growth of all harmful bacteria in a host, regardless of site of infection without affecting beneficial gut microbes (gut flora) or causing undue toxicity to the host. Sadly, no such antibiotics exist. What exist are many effective Gram-positive antibacterial agents as well as broad-spectrum agents that provide treatment of certain Gram-negative bacteria but not holistic treatment of all bacteria. However effectiveness of all antibacterial agents is being rapidly eroded due to resistance. This viewpoint provides an overview of today's antibiotics, challenges and potential path forward of discovery and development of new (ideal) antibiotics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Idiopathic pretracheal deep neck space infection is an extremely rare condition with potentially devastating complications. We present a series of 3 cases of pretracheal deep neck space infection that arose in the absence of trauma or a congenital lesion and that exhibited mediastinal spread. To the best of our knowledge, these cases represent the first reported series of this rare condition to be published in the English-language literature. All cultures grew Streptococcus milleri, and all patients had a favorable outcome. A high index of suspicion for a deep neck space infection is warranted in view of the devastating complications of this condition. Computed tomography is the investigation of choice. Treatment with intravenous antibiotics and surgical drainage, particularly when mediastinitis is present, is recommended. This rare presentation warrants a thorough investigation to identify the source of infection.

Objectives: Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade., Materials and Methods: This population-based study used data from the Swedish Prescribed Drug Register. From July 2005 until December 2014, all regimens that can eradicate H. pylori were identified and evaluated according to patients' age and sex and calendar year of eradication., Results: We identified 157,915 eradication episodes in 140,391 individuals (53.8% women, 42.6% older than 60 years), who correspond to 1.5% of the Swedish population. The absolute number and incidence of eradications decreased over the study period. Overall, 91.0% had one eradication and 0.1% had more than three. Of all eradications, 95.4% followed the recommended regimen, while 4.7% did not. The latter group was overrepresented among individuals aged ≥80 years (7.8%). Amoxicillin and clarithromycin were most frequently prescribed, while metronidazole was rarely used (0.01%). Other prescribed antibiotics were ciprofloxacin (2.4%), doxycycline (1.4%), nitrofurantoin (0.7%), norfloxacin (0.5%) and erythromycin (0.3%)., Conclusions: During the last decade in Sweden H. pylori eradication has been frequently prescribed, but the incidence of eradication has slowly declined. Most eradications followed the recommended regimen, including those occurring after a previous eradication.

Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.

Diabetic foot ulcers (DFUs) are a serious and common problem in patients with diabetes mellitus and constitute one of the major causes of lower extremity amputation. The microbiological profile of DFUs depends on the acute or chronic character of the wound. Aerobic gram-positive cocci are the predominant organisms isolated from DFUs. Diabetic foot biopsies from patients admitted to the Angiology and Vascular Surgery Hospital of the Northeast, in Reynosa, Tamaulipas from December 2011 to April 2016 were analyzed. The samples were processed using standard microbiology techniques. Antimicrobial susceptibility testing was carried out according to the protocol established by the Clinical & Laboratory Standards Institute (CLSI). We obtained 246 bacterial isolates, based on the results of phenotypic resistance. The least effective antibiotics for gram-positive bacteria were penicillin and dicloxacillin; for gram-negative bacteria, cefalotin and penicillin were the least effective. Levofloxacin, cefalotin, and amikacin were the most effective antibiotics for gram-positive and negative bacteria, respectively. Enterobacter genus was significantly associated with muscle biopsies ( P = .011) and samples without growth were significantly associated with specimens of pyogenic origin ( P = .000). In 215 DFU samples, we found that Staphylococcus aureus was the most commonly isolated pathogen followed by Enterobacter sp. This is consistent with previous reports. Enterobacter species may play an important role in the colonization/infection of certain tissues; however, further studies are needed in this regard.

The introduction of antibiotics into clinical practice revolutionized the treatment and management of infectious diseases. Before the introduction of antibiotics, these diseases were the leading cause of morbidity and mortality in human populations. This review presents a brief history of discovery of the main antimicrobial classes (arsphenamines, β-lactams, sulphonamides, polypeptides, aminoglycosides, tetracyclines, amphenicols, lipopeptides, macrolides, oxazolidinones, glycopeptides, streptogramins, ansamycins, quinolones, and lincosamides) that have changed the landscape of contemporary medicine. Given within a historical timeline context, the review discusses how the introduction of certain antimicrobial classes affected the morbidity and mortality rates due to bacterial infectious diseases in human populations. Problems of resistance to antibiotics of different classes are also extensively discussed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Helicobacter pylori ( H. pylori ) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori , which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori , infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori .

Background: To date, only few studies have examined the prognostic factors of community-acquired pneumonia (CAP) defined according to the latest criteria, which excludes healthcare-associated pneumonia (HCAP). Therefore, we aimed to investigate the factors that affect prognosis, and evaluate the usefulness of existing pneumonia severity scores for predicting the prognosis of CAP., Methods: We retrospectively analyzed patients with CAP, excluding HCAP, who were enrolled prospectively between April 2007 and February 2016. Four patients who used macrolides other than azithromycin (AZM) were excluded. We used age, sex, comorbidities, laboratory findings and antimicrobial therapy as prognostic variables. The primary outcome was 30-day mortality and secondary outcome was ICU admission. We also performed receiver operating characteristic curve analysis of Pneumonia Severity Index (PSI), Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe criteria, CURB-65 and A-DROP pneumonia severity scores., Results: Among 1834 CAP patients, mean age was 73.5 ± 14.3 years; 1281 (69.8%) were men; and 30-day mortality was 6.7% (122/1834). In total, 1830 patients were analyzed. Multivariate analysis identified age [Odds Ratio (OR): 1.04, 95% Confidence Interval (CI): 1.02-1.07], chronic obstructive pulmonary disease (COPD) [OR: 1.77, 95% CI: 1.13-2.76], malignancy (OR: 2.25, 95% CI: 1.25-4.06), body temperature (OR: 0.81, 95% CI: 0.67-0.99), respiratory rate (OR: 1.04, 95% CI: 1.01-1.07), PaO 2 /FiO 2  ≤ 250 (OR: 3.15, 95% CI: 1.93-5.14), Alb (OR: 0.27, 95% CI: 0.19-0.39), BUN (OR: 1.01, 95% CI: 1.00-1.02), and mechanical ventilation (OR: 2.99, 95% CI: 1.75-5.12) as prognostic factors. AZM and β-lactam combination therapy significantly reduced 30-day mortality (OR: 0.50, 95% CI: 0.26-0.97). Areas under the curve of PSI, IDSA/ATS severe criteria, CURB-65 and A-DROP were 0.759, 0.746, 0.754 and 0.764, respectively., Conclusions: Increasing age, presence of COPD and malignancy as comorbidities, hypothermia, tachypnea, PaO 2 /FiO 2 ratio ≤250 mmHg, low Alb level, high BUN level and mechanical ventilatory support predict a worse prognosis; AZM combination therapy should be considered for CAP, excluding HCAP. All four pneumonia severity scores are useful for assessing the severity of CAP defined by the latest criteria., Trial Registration: UMIN-CTR UMIN000004353 . Registered 7 October 2010. Retrospectively registered.

Pseudomonas aeruginosa develops profound population heterogeneity in CF airways. How changes in these populations relate to clinical status is unknown. In order to facilitate this understanding, frequent sampling of this community is required. To determine if the collection and storage of sputum at home may pose a viable option, we collected sputum from ten patients. Sputum samples were partitioned in two, with half immediately processed on MacConkey agar and half assessed after freezing for one week in a home-freezer. From each sample, 88 isolates were assessed for antibiotic susceptibility and virulence factor production. Freezing resulted in a 10 3 CFU/ml drop in P. aeruginosa. However, across 1760 isolates, no consistent difference in either antibiotic susceptibility nor virulence factors was observed suggesting freezing induced indiscriminate killing. Home collection and freezing of sputum will enable frequent and convenient assessment of P. aeruginosa population dynamics in CF., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)