Active Antimicrobial Agents Research Articles

High Prevalence of Multi-Drug Resistance and Extended Spectrum Beta Lactamase Production in Non-Fermenting Gram-Negative Bacilli in Ethiopia.

Background:Emergence of resistance to multiple antimicrobial agents in Non-Fermenting Gram-Negative Bacilli is a major problem to public health, as it limits drug treatment options against infections. The aim of this study was to determine the prevalence of multi-drug resistance and extended spectrum beta lactamase production in Non-Fermenting Gram-Negative Bacilli.Materials and methods:Different clinical samples were collected and processed following standard procedures. Each sample was then inoculated onto culture media. Identification, drug susceptibility testing, and extended spectrum beta lactamase production of the isolates were carried out by using the VITEK 2 compact system.Results:Among 996 clinical samples, 135 samples yielded Non-Fermenting Gram-Negative Bacilli of which Pseudomonas and Acinetobacter species were the commonest isolates. The overall drug resistance rates of Non-Fermenting Gram-Negative Bacilli were above 80% against ampicillin (89.6%), cefuroxime axetil (88.9%), nitrofurantoin (85.9%), cefalotin (84.4%), cefoxitin (83.7%), cefazolin (83.0%), and cefuroxime (83.0%). Tobramycin with a resistance rate of 19.3% was the most active antimicrobial agent. Out of 135 isolates, 81.5% were multi-drug resistant of which 13.3% were extensively drug resistant and 10.4% were pandrug resistant. Extended spectrum beta lactamase production was detected in 48.9% of the isolates.Conclusions:The spectrum of bacterial species isolated was diverse. The isolates demonstrated high level of drug resistance in different classes of antibiotics. The magnitude of multi-drug resistance and the level of extended spectrum beta lactamase production were high. Hence, further studies on multi-drug resistant and extended spectrum beta lactamase producing Non-Fermenting Gram-Negative Bacilli both in the community and in hospital setting are essential.

Distribution and antibiotic resistance of 532 bacterial panthogens in blood culture in a hematology department

Objective To analyze the distribution and antibiotic resistance of bacterial pathogens in blood culture in the Department of Hematology of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2017. Methods BACTEC FX automatic blood culture instrument was used for blood culture. VITEK-2 Compact automatic microbial identification and drug susceptibility system was used for bacterial identification, drug sensitivity testing and fungal identification. K-B and ATB FUNGUS 3 methods were used for Streptococcus and fungi susceptibility testing, respectively. WHONET5.6 software was used for statistical analysis. Results The positive results of blood culture accounted for 7.6% during 2013 to 2017 and the top five isolated pathogenic bacteria were Escherichia coli (20.9%), Klebsiella pneumoniae (18.0%), coagulase negative Staphylococcus (12.4%), Pseudomonas aeruginosa (11.5%) and Enterobacter cloacae (3.6%). Carbapenems (94.4%) were the most active antibiotics against Enterobacteriaceae. Pseudomonas aeruginosa strains were sensitive to all antibacterial dugs except aztreonam. Acinetobacter baumannii strains had a lower sensitivity to almost all antibacterial dugs. Vancomycin, linezolid and teicoplanin were active antimicrobial agents against gram-positive cocci. Conclusion Patients with hematological diseases are more susceptible to nosocomial infection, which should be paid more attention to in clinical and laboratory practice. Rational antimicrobial therapy is an effective way for control of antimicrobial resistance. Key words: Blood culture; Pathogenic bacteria; Antibiotic; Antimicrobial susceptibility

Combination therapy with polymyxin B for carbapenemase-producing Klebsiella pneumoniae bloodstream infection

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) bloodstream infections (BSIs) are related to high mortality rates, and combination therapy has been associated with lower mortality in patients treated mostly with colistin. There is a paucity of studies addressing polymyxin B (PMB) treatment for KPC-KP infections. This was a retrospective cohort study of patients with monomicrobial KPC-KP BSIs. The primary outcome was 30-day mortality. Antimicrobial therapy was defined as empirical (started within the first 48 h) or definitive (initiated after >48 h) and was evaluated as follows: monotherapy (only one in vitro active agent or combination therapy of one in vitro active agent plus one or more in vitro non-active agents); and combination therapy with two or more in vitro active agents. A total of 82 KPC-KP BSIs were included; 40 patients (48.8%) died in the first 30 days. Mortality of patients treated with the combination of two in vitro active antimicrobial agents, mostly PMB plus amikacin, was significantly lower (37.5%) compared with monotherapy (64.7%) (P= 0.01). Combination therapy [adjusted hazard ratio (aHR) = 0.40, 95% confidence interval (CI) 0.22-0.83; P = 0.01] was independently associated with lower 30-day survival when controlled for non-surgical admission (aHR = 2.33, 95% CI 1.14-4.80; P = 0.02) and use of vasoactive drugs (aHR = 7.37, 95% CI 3.01-18.02; P < 0.01). In conclusion, combination therapy with two in vitro active agents, mostly PMB plus amikacin, showed a survival benefit compared with other regimens.

Results from the Canadian Nosocomial Infection Surveillance Program for detection of carbapenemase-producing Acinetobacter spp. in Canadian hospitals, 2010-16.

Globally there is an increased prevalence of carbapenem-resistant Acinetobacter spp. (CRAs) and carbapenemase-producing Acinetobacter spp. (CPAs) in the hospital setting. This increase prompted the Canadian Nosocomial Infection Surveillance Program (CNISP) to conduct surveillance of CRA colonizations and infections identified from patients in CNISP-participating hospitals between 2010 and 2016. Participating acute care facilities across Canada submitted CRAs from 1 January 2010 to 31 December 2016. Patient data were collected from medical records using a standardized questionnaire. WGS was conducted on all CRAs and data underwent single nucleotide variant analysis, resistance gene detection and MLST. The 7 year incidence rate of CRA was 0.02 per 10 000 patient days and 0.015 per 1000 admissions, with no significant increase observed over the surveillance period (P > 0.73). Ninety-four CRA isolates were collected from 58 hospitals, of which 93 (98.9%) were CPA. Carbapenemase OXA-235 group (48.4%) was the most common due to two separate clusters, followed by the OXA-23 group (41.9%). Patients with a travel history were associated with 38.8% of CRA cases. The all-cause 30 day mortality rate for infected cases was 24.4 per 100 CRA cases. Colistin was the most active antimicrobial agent (95.8% susceptibility). CRA remains uncommon in Canadian hospitals and the incidence did not increase from 2010 to 2016. Almost half of the cases were from two clusters harbouring OXA-235-group enzymes. Previous medical treatment during travel outside of Canada was common.

In Vitro and in Vivo Antimicrobial Evaluation of Graphene-Polyindole (Gr@PIn) Nanocomposite against Methicillin-Resistant Staphylococcus aureus Pathogen.

Nowadays, the infection caused by the methicillin-resistant Staphylococcus aureus (MRSA) and countless different types of bacterial infection cause the death of millions of people worldwide. Thereby, several strategies have explored for the advancement of better and active antimicrobial agents; one of these lies in the form of two-dimensional carbon-based nanocomposites. Herein, we demonstrate the synthesis of the graphene–polyindole (Gr@PIn) nanocomposite and polyindole (PIn) and significantly enhance the proficiency against MRSA strains which are immune to most antibiotics. The synthesized Gr@PIn and PIn have been characterized by the various biophysical techniques, especially X-ray diffraction (XRD), electron microscopy [scanning electron microscopy (SEM) and transmission electron microscopy (TEM)], Fourier transform infrared, Raman, UV–vis spectroscopy, and thermogravimetric analysis. Electron microscopic investigations unveiled the disintegration of bacterial cell wall upon interaction with Gr@PIn. Significantly, the Gr@PIn found to be very potent in the eradication of the MRSA strain with minimal toxicity to the mammalian cells. Assessment of the antibacterial mechanism revealed that the Gr@PIn adhered toward the bacterial surface, irreversibly interrupted the membrane layer structure of the bacteria, eventually penetrated cells, and efficiently impeded protein activity, which inherently turns into bacterial apoptosis in vitro. Moreover, last, the synthesized Gr@PIn efficiently treated the S. aureus-mediated experimental skin infection in BALB/c mice as well. This work magnifies our comprehending antibacterial mechanism of nonmetallic graphene-based PIn nanocomposite and provides the support to activity anticipation.

Mining of Egypt's Red Sea invertebrates for potential bioactive producers.

The objective of this work was to isolate bacteria from Red Sea invertebrates, determine their antimicrobial activity, and screen for the biosynthetic gene clusters [polyketides (PKs) and nonribosomal peptides (NRPs)] which could be involved in the production of bioactive secondary metabolites. Eleven different samples of marine invertebrates' were collected from Egypt's Red Sea (El-Tor-Sharm El-Sheikh and Hurghada) by scuba diving, and a total 80 isolates of the associated microorganisms were obtained from the cultivation on six different cultural medium. Seven isolates of them showed an antimicrobial activity against five pathogenic reference strains, while the most active antimicrobial agent was isolate number HFF-8 which was 99% identical to Bacillus amyloliquefaciens. HFF-8's extract showed positive results against Gram negative bacteria, Gram positive bacteria and yeast. Moreover, the isolates gave positive bands when screened for the presence of PK synthase (PKS) I and II and NRP synthetase (NRPS) I and II biosynthetic genes, those biosynthetic fragments when cloned and sequenced were primitively predicted as biosynthetic fragments for kirromycin and leinamycin production by NaPDoS program with 56 and 55%, respectively. The Red Sea can provide a sustainable solution to combat bacterial resistance. The contribution of this work is that B. amyloliquefaciens was isolated from Heteroxenia fuscescens, Red Sea, Egypt. Moreover, the bacterial extract showed a broad spectrum with a potent antimicrobial activity.

Molecular detection of SHV-Type ESBL in E. coli and K.pneumoniae and their antimicrobial resistance profile

Background and objective: The increase in the incidence of Beta-lactam resistance in Gram-negative bacteria has become a main clinical problem worldwide that limits therapeutic options. The production of extended-spectrum blactamases is the major source of resistance to newer beta-lactam antibiotics in Enterobacteriaceae. This study aimed to check the presence of extended-spectrum β-lactamase producing K. pneumoniae and E. coli and the evaluation of ESBL among those isolates. Methods: A total of 120 E. coli and K. pneumoniae clinical isolates were obtained from Rizgary Teaching Hospital in Erbil City, Iraqi Kurdistan Region, during the first six months of 2016. All isolates were identified and checked for the production of ESBL using Vitek 2 automated system. The technique of PCR was performed for the detection of the presence of blaSHV gene from these isolates. The antibiotic resistant profiles for these isolates were also investigated. Results: The overall proportion of ESBL-producing E. coli and K. pneumoniae isolates, 77 (76.2%) and 15 (78.9%) isolates were ESBL producers, respectively. ESBL-producing isolates were significantly more resistant than Non-ESBL-producers (P < 0.05). PCR performed on 30 ESBL positive isolates, 21(70%) isolates were of E. coli, and 9 (30%) isolates were of K.pneumoniae. The ESBL B-lactamase related SHV gene was detected only in 11 (36.6%) isolates, 6 (28.5 %) of E. coli and 5(55.5%) of K. pneumoniae isolates respectively. All isolates were susceptible to carbapenems. Conclusion: The great diversity of ESBL and the prevalences of clinical isolates of E. coli and K. pneumoniae producing these enzymes indicate that this is an important problem in our region. The most active antimicrobial agent against isolates used in this study was carbapenem. It is, therefore strongly recommended to consider carbapenems as the drug of choice for such multi-drug resistant ESBL-producing microorganisms.

CONSUMPTION AND BACTERIAL RESISTANCE TO AMINOGLYCOSIDES AT SUDANESE UNIVERSITY HOSPITAL

Objectives: The objective of this study was to describe patterns of antimicrobial resistance to gentamicin (Gen) and amikacin (Ak) among Gram-negative aerobic bacteria during 1-year period and to determine the association between antibiotic resistance and the consumption of Gen.Methods: Aminoglycosides consumption at Soba University Hospital wards was measured and susceptibility of Gram-negative bacteria for the same period was evaluated. Consumption data were converted to defined daily doses (DDDs)/100 bed days based on DDD/anatomical therapeutic chemical the WHO system. The association between the frequency of strains resistant to Gen and Ak and their consumption was assessed by linear regression analysis using Spearman’s correlation. The level of statistical significance was set at p&lt;0.05.Results: A total of 973 Gram-negative isolates were identified and tested for antimicrobial susceptibility to Gen and Ak. Resistance to Gen alone was found to be 19.42%; n=189, resistance to Ak alone was found to be 3.08%; n=30, and resistance to Gen plus Ak was found to be 5.24%; n=51. Pseudomonas aeruginosa was the most resistant pathogen to Ak plus Gen (2.26%; n=22). A positive correlation between the increases in the use of Gen and the prevalence of bacterial resistance among hospital wards was found (correlation coefficient r=0.6; p=0.04).Conclusion: Gen and Ak are still highly active antimicrobial agents for the treatment of aerobic Gram-negative bacteria at times of intensified resistance to other antimicrobial agents. Monitoring the use of aminoglycosides is very important too.

Multifunctional TiO2 microspheres-rGO as highly active visible light photocatalyst and antimicrobial agent

Multifunctional TiO₂ microspheres-rGO as highly active visible light photocatalyst and antimicrobial agent

Mechanical, barrier, and color properties of banana starch edible films incorporated with nanoemulsions of lemongrass ( Cymbopogon citratus) and rosemary ( Rosmarinus officinalis) essential oils.

Edible films are among the most promising fields in food science over the last decade due to their versatility (they can be made from a wide array of materials) and because they can be used as carriers of different active substances, like antioxidants, antimicrobial agents, and essential oils from plants. In the case of the essential oils, their inclusion in edible films is limited by their low water solubility. Nanoemulsions are thermodynamically stable and transparent systems that can be used as a way of incorporating essential oils into edible film matrices. In this paper, we developed lemongrass and rosemary essential oil nanoemulsions by using a low-energy method, observing the effect of the surfactant/oil ratio in their physicochemical properties. Then we studied the effect of the nanoemulsions concentration incorporated into banana starch edible films. We observed that essential oils' nanoemulsions have a plasticizing effect increasing the film's water vapor permeability, transparency, and elongation at break, while the hydrophobic nature of the essential oils lead to a decrease in their water solubility.

Antifungal activity of Cardiospermum halicacabum L. (Sapindaceae) against Trichophyton rubrum occurs through molecular interaction with fungal Hsp90.

IntroductionDermatophytosis is a superficial fungal infection limited to the stratum corneum of the epidermis, or to the hair and nails, and constitutes an important public health problem because of its high prevalence and associated morbidity. Dermatophyte fungi, especially 2 species, Trichophyton rubrum and Trichophyton mentagrophytes, are the predominant pathogens. Topical antifungal drugs, mainly azoles or allyamines, are currently used for the treatment of dermatophytoses, although in some cases, such as in nail and hair involvement, systemic treatment is required. However, therapeutic efficacy of current antifungal agents can be limited by their side effects, costs, and the emergence of drug resistance among fungi. Plant extracts represent a potential source of active antimicrobial agents, due to the presence of a variety of chemical bioactive compounds. In the present work, we evaluated in silico and in vitro the antifungal activity of an extract of the medicinal plant Cardiospermum halicacabum against T. rubrum suggesting a potential interaction with Hsp90 as playing an important role in both pathogenicity and drug susceptibility of T. rubrum.MethodsWe investigated in vitro the effect of different concentrations of C. halicacabum (from 500 to 31.25 µg) against a clinical isolate of T. rubrum. Furthermore, using a computational assessment, the interaction between different C. halicacabum active compounds and the fungal Hsp90 was also investigated.ResultsOur results indicate a clear-cut antifungal activity of the total plant extract at the highest concentrations (500 and 250 µg). Among all tested C. halicacabum compounds, the luteolin and rutin molecules have been identified in silico as the most important potential inhibitors of Hsp90. Based on these data, luteolin and rutin were also individually assessed for their antifungal activity. Results demonstrate that both substances display an antifungal effect, even if lower than that of the total plant extract.ConclusionOur data indicate a strong fungistatic effect of C. halicacabum against T. rubrum, suggesting its potential therapeutic efficacy in the treatment of dermatophytoses. Additionally, C. halicacabum compounds, and particularly luteolin and rutin, are all possible Hsp90 interactors, explaining their fungistatic activity.

A thiol-reactive Ru(II) ion, not CO release, underlies the potent antimicrobial and cytotoxic properties of CO-releasing molecule-3

Carbon monoxide (CO)-releasing molecules (CORMs), mostly metal carbonyl compounds, are extensively used as experimental tools to deliver CO, a biological ‘gasotransmitter’, in mammalian systems. CORMs are also explored as potential novel antimicrobial drugs, effectively and rapidly killing bacteria in vitro and in animal models, but are reportedly benign towards mammalian cells. Ru-carbonyl CORMs, exemplified by CORM-3 (Ru(CO)3Cl(glycinate)), exhibit the most potent antimicrobial effects against Escherichia coli. We demonstrate that CORM-3 releases little CO in buffers and cell culture media and that the active antimicrobial agent is Ru(II), which binds tightly to thiols. Thus, thiols and amino acids in complex growth media – such as histidine, methionine and oxidised glutathione, but most pertinently cysteine and reduced glutathione (GSH) – protect both bacterial and mammalian cells against CORM-3 by binding and sequestering Ru(II). No other amino acids exert significant protective effects. NMR reveals that CORM-3 binds cysteine and GSH in a 1:1 stoichiometry with dissociation constants, Kd, of about 5 μM, while histidine, GSSG and methionine are bound less tightly, with Kd values ranging between 800 and 9000 μM. There is a direct positive correlation between protection and amino acid affinity for CORM-3. Intracellular targets of CORM-3 in both bacterial and mammalian cells are therefore expected to include GSH, free Cys, His and Met residues and any molecules that contain these surface-exposed amino acids. These results necessitate a major reappraisal of the biological effects of CORM-3 and related CORMs.

Sanitary-hygienic evaluation of meat processing enterprises productions and their sanation

The results in the determination microbiocinosis level of the objects of veterinary supervision at meat processing enterprises are presented. It was experimentally established that in 3 hours of the slaughter workshop working process, the total number of microorganisms is higher more than 5 times of the established standard, and by the end of the working shift the amount of MAFAnM on the floor and walls is (1.6 ± 0.23)×10 6 and (8.2 ± 1.1)×10 5 CFU/cm 2 , respectively, which is significantly more of the regulated indicators. It is determined, that the most contaminated in the production process is the table to wash stomach, the gutter to move off stomach, the table to disassemble intestinal kit and the gutter to move off intestinal kits. The gained results indicate the necessity for thorough and timely sanitization of contaminated surfaces. It has been established that the daily use of «Anti-Jermi SR S 25» detergent (2.0 % – 30 minutes) provides the high level of sanitation in the meat industry enterprises. The disinfectant «Germicidan FF Plus» ensures the complete destruction of sanitary-indicative microorganisms at veterinary supervision sites of meat-processing plants when applied at 0.5 % concentration with an exposure of 60 minutes. The obtained results broaden the spectrum of highly active antimicrobial agents, which are promising to use in the processing and food industries.

Resveratrol-Inspired Benzo[b]selenophenes Act as Anti-Oxidants in Yeast.

Resveratrol is a natural (poly)phenol primarily found in plants protecting them against pathogens, as well as harmful effects of physical and chemical agents. In higher eukaryotic cells and organisms, this compound displays a remarkable range of biological activities, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, cardio- and neuro-protective properties. Here, biological activities of synthetic selenium-containing derivatives of resveratrol—benzo[b]selenophenes—have been studied in lower eukaryotes Saccharomyces cerevisiae. Their toxicity, as well as DNA damaging and reactive oxygen species (ROS) inducing potencies, manifested through their ability to act as redox active anti-microbial agents, have been examined. We show that some benzo[b]selenophenes can kill yeast cells and that the killing effects are not mediated by DNA damage types that can be detected as DNA double-strand breaks. These benzo[b]selenophenes could potentially be used as anti-fungal agents, although their concentrations relevant to application in humans need to be further evaluated. In addition, most of the studied benzo[b]selenophenes display redox-modulating/anti-oxidant activity (comparable or even higher than that of resveratrol or Trolox) causing a decrease in the intracellular ROS levels in yeast cells. Therefore, after careful re-evaluation in other biological systems these observations might be transferred to humans, where resveratrol-inspired benzo[b]selenophenes could be used as supra-anti-oxidant supplements.

Spectrum and Drug Susceptibility Profile of Bacteria Recovered from Patients with Wound Infection Referred to Arsho Advanced Medical Laboratory

Wound infection still remains a significant cause of morbidly and mortality. Hence, studying the spectrum of bacterial etiological agents and their drug susceptibility profile is critical. A prospective study was conducted at Arsho Advanced Medical Laboratory from June 2016 to July 2017. Wound specimens were collected from 366 patients following standard procedures. Specimens were plated and incubated at 37°C for 48 hours. Identification and drug susceptibility testing of cultures were carried out by using the VITEK 2 compact system. Among 366 wound samples cultured, bacteria grew in 271(74%) samples. The highest (81.9%) wound infections were documented among patients with an age group of 15-64 years. Two hundred twenty one bacterial isolates were recovered of which 43.2% were Gram-negative while, 56.8% were Gram-positive. Staphylococcus aureus and Coagulase-Negative Staphylococci were major Gram-positive bacteria while Escherichia coli and Pseudomonas spp. were the commonest Gram-negative bacteria. Gram-negative bacteria had the highest overall drug resistance rate against ampicillin. Tobramycin and piperacillin/tazobactam combination were effective antimicrobial agents against Gram-negative bacteria. The highest overall resistance rate to Gram-positive bacteria was observed against erythromycin. Vancomycin and linezolid were the most active antimicrobial agents against Gram-positive bacteria. High culture positivity rate of wound infections reported in the present study initiates many similar studies to be conducted on wound in the country. High level of drug resistance to the commonly prescribed drugs dictates a search for better choices.

Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present.

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (-) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (-) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease.

PYOGENIC LIVER ABSCESS – ETIOLOGICAL SPECTRUM AND SENSITIVITY TO ANTIBIOTICS

Introduction: Pyogenic liver abscess (PLA) is a serious challenge in modern medical practice. The aim of this study was to investigate the etiology and antimicrobial susceptibility of PLA-associated microbial pathogens, diagnosed in hospitalized patients at St. Marina University Hospital of Varna during the period between 2001 and 2016. Materials and Methods: A total of 84 clinical samples (pus aspirates, n=72, bile samples, n=7, and blood cultures, n=5), collected from PLA patients, hospitalized in the Second Surgery Clinic were analyzed. Species identification was performed by conventional methods. Antimicrobial susceptibility was studied by disk diffusion method and Phoenix 100 (BD). The results were interpreted according to CLSI and EUCAST standards. Results: Causative bacterial agents belonging to 15 different species were isolated in 59 cases (in 70%). E. coli (23.7%) , K. pneumoniae (20%) , E. cloacae (13.5%) , E. faecalis (8.5%) , P. mirabilis (5%) and P. aeruginosa (5%) dominated in the etiological spectrum. E. coli demonstrated the following levels of antimicrobial susceptibility: imipenem, amikacin, piperacillin/tazobactam, 100%; ceftazidime, cefepime, 90.9%; cefuroxime, 83.3%; amoxicillin/clavulanic acid, 77.8%; gentamicin, 75%; levofloxacin, cefalothin, 66.6%; ciprofloxacin, 63.6%; piperacillin, 58.3%; ampicillin, 45.5%. The following antimicrobial susceptibility rates were determined for K. pneumoniae : imipenem, 100%; amikacin, 92.3%; ceftazidime, cefepime, 80%; cefalothin, cefuroxime, 75%; levofloxacin, gentamicin, 66.6%; ciprofloxacin, 62.5%; piperacillin/tazobactam, 57.1%; piperacillin, 25% and amoxicillin/clavulanic acid, 22.2%. Conclusions: E. coli and K. pneumonia are the predominant pathogens in PLA patients. Carbapenems are the most active antimicrobial agents followed by ceftazidime and cefepime. In the aminoglycoside group, amikacin demonstrates the best in vitro activity.

In vitro analysis of a local polymeric device as an alternative for systemic antibiotics in Dentistry.

The development of a biodegradable material with antimicrobial properties for local applications is required in the prevention and treatment of infectious diseases. The objective of this study was to produce blends of poly-L-lactide acid (PLLA) synthetic polymer associated with several antimicrobials, as an alternative in the prevention and treatment of infections, as well as to evaluate its cytotoxicity, release of antimicrobials and inhibit bacteria growth. Blends of PLLA added with 20% Amoxicillin, Metronidazole, Clindamycin or Azithromicyn were used to produce Films (F) or Meshs (M) by casting and electrospinning methods, respectively. Standardized discs of the films and meshs were stored in buffer solutions (pH 5 or 7.4) and aliquots were analyzed by high performance chromatography (HPLC) during 168 hours. Cytotoxicity on human gingival fibroblasts was tested after 24, 48 and 72h by MTT reaction. The antimicrobial capacity was determined against P. gingivalis and S. pyogenes. The specimens were weighed after 3 and 6 months of storage for degradation analysis. SEM was performed to control interfaces and degradation. Antimicrobials presented a continuous and exponential drug release. Analysis showed that both M and F were able to inhibit S. pyogenes and P. gingivalis growth, indicating the release of active antimicrobial agents. The products were not toxic to the fibroblasts. Amoxicillin-film showed more degradation than PLLA at both pHs (p < 0.05), whereas Azithromycin-meshes were more degraded than PLLA at pH 7.4 (p < 0.05). PLLA association with antimicrobials is biocompatible and may represent a potential tool for the local delivery of antimicrobials.

The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single-Center Study Over a Period of 12 Years.

Despite global efforts to tackle resistance in extended-spectrum beta-lactamase (ESBL)-producing isolates via old antibiotics, there are limited data on the efficacy of fosfomycin-an old oral antibiotic-against Enterobacteriaceae in the Middle East. The purpose of this study was to evaluate the in vitro activity of fosfomycin against urinary ESBL-producing isolates of Enterobacteriaceae. Between 2004 and 2015, 363 isolates of ESBL-producing Enterobacteriaceae were recovered from high-risk patients suffering from cardiac disorders and were subjected to polymerase chain reaction using specific primers for the blaTEM, blaSHV, and blaCTX-M genes. Antibiotic susceptibility testing was performed for fosfomycin and other antibiotic comparators. For the isolates considered nonsusceptible to fosfomycin by disk diffusion, the minimum inhibitory concentration (MIC) was determined. The susceptibility rate to fosfomycin remained almost steady (90-100%) over a 12-year period, although it fluctuated vis-à-vis ciprofloxacin (0-54%), trimethoprim/sulfamethoxazole (9.1-31.7%), and nitrofurantoin (41.7-100%). Of all the antibiotics tested, fosfomycin was the most active antimicrobial agent (97%) against the ESBL-positive isolates. Fosfomycin maintained higher activity against ESBL-Escherichia coli than against ESBL-Klebsiella pneumoniae. Only 11 (3%) isolates were not susceptible to fosfomycin according to disk diffusion and they had MICs greater than 1,024 mg/ml. All of the fosfomycin-nonsusceptible isolates were positive for the blaCTX-M gene (100%), while 5 (45.4%) and 3 (27.3%) of the isolates harbored the blaTEM and blaSHV genes, respectively. We showed that fosfomycin had a numerically higher susceptibility rate than the other antibiotics against the ESBL-producing isolates of the most common Enterobacteriaceae. Given its low resistance rate and oral administration, fosfomycin may be deemed a promising antibiotic for the treatment of urinary tract infections caused by ESBL-producing Enterobacteriaceae.

Antimicrobial peptides: Coming to the end of antibiotic era, the most promising agents

Recently, because of the rising in multidrug resistance from infectious agents, there is a prompted interest for the development of new antimicrobial agents and new therapeutic strategies to combat the infections caused by the resistant bacteria. Among them, the natural bactericidal compounds, such as antimicrobial cationic peptides (AMPs) seems very promising agents. AMPs are the important component of the innate immune response to the surrounding microorganisms. This substances which can be isolated from most of the living organisms, have various activity like broad spectrum antibacterial, antifungal, antiviral, and antiprotozoal. However there are some resistance mechanisms that affects the AMPs, because of the rapid action and existing more than one mechanism of action, development of resistance to AMPs is quite rare. Due to their many advantages and characteristics, AMPs looks like a good candidate for being a new generation, active antimicrobial agent for antimicrobial chemotherapy against especially multi drug resistant bacteria and biofilms, either alone or in combination.