Burden of severe infections due to carbapenem-resistant pathogens in intensive care unit

Intensive care units(ICU)for various reasons,including the increasing age of admitted patients,comorbidities,and increasingly complex surgical procedures(e.g.,transplants),have become"the epicenter"of nosocomial infections,these are characterized by the presence of multidrug-resistant organisms(MDROs)as the cause of infection.Therefore,the perfect match of fragile patients and MDROs,as the cause of infection,makes ICU mortality very high.Furthermore,carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs;unfortunately,nowadays carbapenem resistance,mainly among Gram-negative pathogens,is a matter of the highest concern for worldwide public health.This comprehensive review aims to outline the problem from the intensivist's perspective,focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs(Acinetobacter baumannii,Pseudomonas aeruginosa and Enterobacterales)to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.

Susceptibility of Mixed Infection of Ureaplasma Urealyticum and Mycoplasma Hominis to Seven Antimicrobial Agents and Comparison with that of Ureaplasma Urealyticum Infection

In order to investigate the susceptibility of mixed infection of Ureaplasma Urealyticum (UU) and Mycoplasma Hominis (MH) to 7 kinds of antimicrobial agents and comparison with that of UU infection in NGU patients, the in vitro susceptibility was determined by using microdilution method. The positive results were analyzed. The results showed that the sequence of susceptibility to 7 kinds of antimicrobial agents for both UU infection group and UU-MH mixed infection group was almost the same from the highest susceptibility to the lowest accordingly: Josamycin, Doxycycline, Minocycline, Sparfloxacin, Roxithromycin, Ofloxacin and Azithromycin. The total drug resistance rate for UU-MH mixed infection group (97. 67 %) was significantly higher than that for UU infection group (44. 67 %, P<.0. 01). The highest drug resistance rate in UU group and UU-MH mixed infection group was 31. 33 % (Ofloxacin) and 90. 48 % (Azithromycin) respectively. UU-MH mixed infection showed an increased drug resistance and changes of drug resistance spectrum.

Structure, properties and application to water-soluble coatings of complex antimicrobial agent Ag-carboxymethyl chitosan-thiabendazole

The structure, properties and application to water-soluble coatings of a new complex antimicrobial agent Ag-carboxylmethyl citosan-thiabendazole （Ag-CMCTS-TBZ） prepared from different materiel ratios were reported. The silver ions were preferably coordinated with the free-NH2 groups and the -OH groups of secondary alcohol and carboxyl in CMCTS. TBZ preferably bonded to carboxyl group in CMCTS by electrostatic force and hydrogen bonding. Increase in silver ions content in the complex agent improved to some limited extent the antibacterial activity, but enhanced coloring and cost of the complex agent. Increase in TBZ content resulted in increase of antifungal activity, but decrease of water solubility of the complex agent. The antimicrobial MICs of the complex agent to Esherichia coil, Staphylococcus aureus, Candida albicans, Aspergillus niger, Mucor sp. were 20 -80, 15 -60, 20 - 55, 40 - 250, and 400 - 1700 mg/kg, respectively. Addition of 0.1% of this complex agent to acrylic emulsion paint made the paint without substantial change in color, luster, viscosity, odor or pH value, but with an excellent and chronically persisting broad-spectra antimicrobial activity.

In vitro drug resistance of clinical isolated Brucella against antimicrobial agents

Objective:To explore the antibiotic resistance of Brucella melitensis and instruct rational use of antimicrobial agents in clinical treatment of Brucella infection.Methods:Bacteria were cultured and identified by BACTEC9120 and VTTEK Ⅱ automicrobic system.E-test was used to detect the minimal inhibitory concentration(MIC) of antimicrobial agents in the drug susceptivity experiment.Results:A total of 19 brucella strains(all Brucella melitensis) were isolated from 19 patients,who had fever between January 2010 and June 2012,and 17 samples were blood,one was bone marrow,the other sample was cerebrospinal fluid.The MIC range of ceftazidime was 2.0-8.0 mg/L,rifampicin was 0.06-2.0 mg/L,amikacin was 4.0-12.0 mg/L,levofloxacin was 2.0-8.0 mg/ L,doxycycline was 8.0-32.0 mg/L,sulfamethoxazole-trimethoprim was 4.0-16.0 mg/L,ampicillin was 1.5-2.0 mg/L and gentamicin was 0.50-0.75 mg/L.Conclusions:The drugs used in this experiment cover common drugs for treating Brcella.Meanwhile,the results are consistent with clinical efficacy.It is suggested personalized regimen according to patients' status in treatment of Brucella.

Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.

Pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma in vitro

AIM: To understand the pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma (FBGT) in vitro, and to provide laboratory evidence for diagnosis. METHODS: The FBGT pathogens were isolaated and cultured with reformed rabbit-brain anaerobic enriched broth (RRAB), and identified by ATB/API 20A system. The minimum inhibiting concentration (MIC) was determined by anaerobic broth dilution method. RESULTS: A total of 22 strains of pathogen were separated from 21 patients with FBGT and identified as Propionibacterium acnes (PA) by ATB/API 20A system. The MIC of ciprofloxacin for 22 PA strains was 0.0625-0.5mg/L, the MIC of penicillin, ampicillin, ampicillin/sulbactam, cefoperazone, lincomycin, and imipenem/cilastatin were 0.125-0.5mg/L, the MIC of ticarcillin/clavulanic acid was 0.250-1.000mg/L, and the MIC of metronidazole was 64-256mg/L. The pathogen of FBGT was strictly anaerobic PA, which growed slowly and better in nutritious RRAB broth. All PA were resistant to metronidazole, but susceptive to other routine antimicrobial agents, such as penicillin, ampicillin and lincomycin. CONCLUSION: FBGT should not be treated with metronidazole. Clinicians should choose combined use of drugs or operation to treat FBGT according to patients' individual condition and the results of drug sensitivity test.

Optimization of four types of antimicrobial agents to increase the inhibitory ability of marine Arthrobacter oxydans KQ 11 dextranase mouthwash

We adopted the response surface methodology using single factor and orthogonal experiments to optimize four types of antimicrobial agents that could inhibit biofilm formation by Streptococcus mutans, which is commonly found in the human oral cavity and causes tooth decay. The objective was to improve the function of marine Arthrobacter oxydans KQll dextranase mouthwash （designed and developed by our laboratory）. The experiment was conducted in a three-level, four-variable central composite design to determine the best combination of ZnSO4, lysozyme, citric acid and chitosan. The optimized antibacterial agents were 2.16 g/L ZnSO4, 14 g/L lysozyme, 4.5 g/L citric acid and 5 g/L chitosan. The biofilm formation inhibition reached 84.49%. In addition, microscopic observation of the biofilm was performed using scanning electron microscopy and confocal laser scanning microscopy. The optimized formula was tested in marine dextranase Arthrobacter oxydans KQ11 mouthwash and enhanced the inhibition of S. mutans. This work may be promoted for the design and development of future marine dextranase oral care products.

Effects of water-aging for 6 months on the durability of a novel antimicrobial and protein-repellent dental bonding agent

Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate(DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine(MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent(MPC) and antibacterial agent(DMAHDM) were added to a Scotchbond multi-purpose(SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days(d).At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control(P < 0.05). The SBMP + MPC + DMAHDM group had protein adhesion that was only 1/20 of that of the SBMP control(P < 0.05). Incorporation of MPC and DMAHDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d(P > 0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.

Synthesis of New Type Antimicrobial agent CL and Its Application in Fabric Finish

Amino - functional silicone oil was used as a raw material to synthesize antimicrobial agent by means of alkyla-tion. Through synthetically judging every possible influential factor, a new method was developed to synthesize antimicrobial agent CL under moderate condition. Then, antimicrobial agent CL was emulsified with surfactants AEO - 9 and AEO - 3 in appropriate proportion. Practical properties of antimicrobial fabric were tested.

Increasing Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae (ESBL) and the Relation to Consumption of Broad-Spectrum Antimicrobial Agents 2003-2011 in a Large Area of Copenhagen, Denmark

Purpose: To investigate 1) the development in the incidence of ESBL-producing bacteria in hospitals and primary health care, 2) the contribution of primary health care to the incidence of ESBL-producing bacteria, and 3) the development in resistance patterns for all Escherichia coli and Klebsiella pneumoniae isolates in relation to antimicrobial consumption in hospitals and primary health care. Methods: ESBL-data were retrospectively collected from bacterial isolates from all specimens received at the Department of Clinical Microbiology from 2003 to 2011 together with the corresponding patient data. ESBL-production was detected in isolates from 1067 of 59,373 patients (1.8%) with an E. coli infection and in 263 of 8660 patients (3.0%) with a K. pneumoniae infection. Results: From 2003 to 2009, an increase in patients with an ESBL-producing isolate occurred in both hospitals and primary health care at the same time as an increased consumption of broad-spectrum antimicrobial agents was seen. Interventions to reduce prescription of cephalosporins and ciprofloxacin at the hospitals from 2010 resulted in a remarkable decrease in patients with ESBL-producing K. pneumoniae whereas a continuing increase was seen in patients with ESBL-producing E. coli both at hospitals and in primary health care. The proportion of patients with community-acquired ESBL-producing E. coli was stable with an increase of only 1.4% from 2007 to 2011. Conclusions: Reduction in prescription of broad-spectrum antimicrobial agents at the hospital level had an important impact on the incidence of ESBL-producing K. pneumoniae, but not on ESBL-producing E. coli.

Synthesis of New Fluorinated Fused Heteropolycyclic Nitrogen Systems Containing a Pyrazolotriazine Moiety as Antimicrobial Agents Part I

A simple route to synthesize novel fluorinated fused hetero-polycyclic nitrogen systems containing a pyrazolotriazine moiety (5,8,11) have been deduced from cyclization of 2-aminothiocarbonyl-5-arylidene-3-phenyl-1,2,4-triazin-6(1H)one (2) with diethoxy-phosphine, diethyl carbonate and/or diethyl oxalate in boil THF followed by cyclo condensation with aryl sulfonic acid hydrazide in EtOH/piperidine and finally fluorination with trifluoroethyl acetate. Structures of the products have been established from their elemental analysis and spectral measurements. The antimicrobial activity of the targets has also been evaluated.

The Antimicrobial Activity of Wool Fabrics Treated with Crosslinking Agents and Polyhexamethylene Biguanide

In this study,we used citric acid(CA)as a crosslinking agent,mixed with polyhexamethylene biguanide,to perform a pad-dry-cure treatment on wool fabrics to study its antimicrobial effects and physical properties.

Evaluation of rational use of antimicrobial agents in a Brazilian intensive care unit

The present study sought to assess the rational use of antimicrobial agents in a Brazilian intensive care unit (ICU) and its association with antimicrobial resistance in elderly patients admitted to the unit. Results: Choice of empiric and sensitivity-guided therapy was inadequate in > 80% and 59% of cases respectively. Inadequate antimicrobial therapy, whether empiric or sensitivity-guided, was positively correlated with bacterial resistance (r = 0.316;p = 0.001). Sensitivity testing revealed a 46.5% resistance rate to eight out of the ten most commonly used antibiotics. Multiple drug-resistant organisms were found in 40.8% of patients. A significant increase was observed in the number of multidrug-resistant samples between 2006/2007 and 2008 (r = 0.41, p = 0.006), (r = 0.598, p = 0.001), (r = 0.688, p = 0.00). Conclusion: We found a high rate of antibiotic misuse in the study sample. Inadequate therapy was correlated with resistance to antimicrobial agents.

Antimicrobial susceptibility patterns of Streptococcus pneumoniae over 6 years at Gondar University Hospital, Northwest Ethiopia

Objective:To assess the magnitude and antimicrobial susceptibility patterns ofStreptococcus pneumoniaeisolates from various clinical specimens.Methods:A record based on retrospectivestudy was conducted at Gondar University Teaching Hospital from September 2007 to January 2012.All patients who visited Gondar University Hospital and provided clinical specimens(body fluids,discharge,swab and blood)for routine bacteriological culturing and antimicrobial susceptibilitytesting were taken for analysis.Clinical specimens were processed for bacterial culture accordingto the standard procedures.Antimicrobial susceptibility test for isolated organisms was doneusing agar disk diffusion method.The data were entered and analyzed using SPSS software version16 package.Results:One hundred and fifty threeStreptococcus pneumoniaewere isolated frompatients who visited Gondar University Teaching Hospital bacteriology laboratory for culture.Majority of the pneumococcal isolates were from inpatients[111(72.5%)],and 74(48.4%)were frombody fluids.Out of the total isolates,93(61%)were found to be resistant to at least one antibioticused for susceptibility testing.Forty eight(43.2%)of the isolates were multi-drug resistant(resistantto two or more drugs).The resistance rate noted for both ciprofloxacin 17(11.1%)and ceftriaxone15(9.8%)were alarming.Conclusions:High proportions of the isolates tend to be increasinglyresistant to the commonly prescribed drugs.The recommended drug of choice like ciprofloxacinand ceftriaxone were found to be less susceptible in the study area.Based on the findings,wetherefore recommend that antimicrobial agents should be inspected for acceptable activity beforethey are prescribed and administered empirically.Further study with a better design and surveyof antimicrobial susceptibility at large scale shoule be performed to draw advanced information.

Antibacterial activities of some plant extracts alone and in combination with different antimicrobials against multidrug-resistant Pseudomonas aeruginosa strains

Objective:To evaluate the possible in vitro interaction between ethanolic extracts of Rhus coriaria[R.coriaria)(seed),Sacropoterium spinosum(S.spinosum)(seed),Rosa damascena(R. damascene)(flower) and certain known antimicrobial drugs including oxytetracycline HCl, penicillin C,cephalexin,sulfadimethoxine as sodium,and enr of loxacin.This synergy study was carried out against 3 clinical strains of multidrug-resistant Pseudomonas aeruginosa (P.aeruginosa).Methods:Evaluation of synergy interaction between plant extracts and antimicrobial agents was carried out using microdilution method.Results:The results of this study showed that there is a decrease in the MIC in case of combination of ethanolic plant extracts and test antimicrobial agents.The most interesting result was that the combination between R. coriaria and these antibiotics,showed a high decrease in minimum inhibitory concentration(MIC), and a strong bactericidal activity against these strains.Conclusions:These results may indicate that combinations between R.coriaria extract and these antibiotics could be useful in fighting emerging drug-resistance P.aeruginosa,which may due to that R.coriaria extract contain natural inhibitors working by different mechanisms or inhibiting efflux pumps.Now we have experiments underway leading to the identification of the active molecules present in R.coriaria.Further,in vivo experiments are needed to confirm pseudomonal protection.

Synthesis and Antimicrobial Properties of the Novel Fluonnated Bis-ammonium Salts with Two Primary Amine Groups

In order to resolve the increasing resistance phenomena of the Gram-negative bacteria against single chain quaternary ammonium salts （QAS）, lysine with a pedant fluorinated bis-ammonium salts was synthesized and its antimicrobial properties were evaluated in this work. The novel fluorinated bis-ammonium salts shows similar activity with conventional single chain quaternary ammonium salts against Gram-positive bacteria but stronger activity against Gram-negative bacteria and yeast compared with the single chained counterpart.

Antimicrobial and Antioxidant Activity of Anacardium occidentale L. Flowers in Comparison to Bark and Leaves Extracts

Anacardium occidentale L., Anacardiaceae, is frequently used to treat infections. We evaluated the antimicrobial and antioxidant activity of extracts obtained from aerial parts of the plant in comparison with the extract prepared with the flowers. Ethanol extracts of the leaves (EEL), stem bark (EEB), and flowers (EEF) were prepared separately. The antimicrobial activity was evaluated by agar diffusion and broth dilution methods. The minimum bactericidal and fungicidal concentrations were determined against: Streptococcus mutans, Lactobacillus acidophilus, Staphylococcus aureus, MRSA, Enterococcus faecalis, Streptococcus pyogenes, Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli, Klebsiella pneumoniae, Helicobacter pylori, Salmonella choleraesuis, Candida albicans, and Candida tropicalis. The antioxidant activity of the extracts was evaluated based on their scavenger capacity of 2,2-diphenyl-1-picrylhydrazyle. The phytochemical profile was analyzed by colorimetric methods and by HPLC with UV detection. All extracts exhibited antioxidant and antimicrobial activity. Although, the EEF was the most effective since it inhibited the growth of all 14 microorganisms tested. Anacardic and galic acids were identified in all extracts as well phenolic compounds, triterpenes, flavones and xanthones. In conclusion, the extracts obtained from the aerial parts of A. occidentale, mainly the extract of flowers that was the most effective, are rich in bioactive metabolites that exert a potent antioxidant and antimicrobial effect. Taken together, the results indicate an important biotechnological potential of A. occidentale as a source of compounds with broad-spectrum antimicrobial and of antioxidant activity to be used in the food and cosmetics industry.

Antimicrobial resistance in clinically important biofilms

A biofilm contains a consortium of cohesive bacterial cells forming a complex structure that is a sedentary, but dynamic, community. Biofilms adhere on biotic and abiotic surfaces, including the surfaces of practically all medical devices. Biofilms are reported to be responsible for approximately 60% of nosocomial infections due to implanted medical devices, such as intravenous catheters, and they also cause other foreign-body infections and chronic infections. The presence of biofilm on a medical device may result in the infection of surrounding tissues and failure of the device, necessitating the removal and replacement ofthe device. Bacteria from biofilms formed on medical devices may be released and disperse, with the potential for the formation of new biofilms in other locations and the development of a systemic infection. Regardless of their location, bacteria in biofilms are tolerant of the activities of the immune system, antimicrobial agents, and antiseptics. Concentrations of antimicrobial agents sufficient to eradicate planktonic cells have no effect on the same microorganism in a biofilm. Depending on the microbial consortium or component of the biofilm that is involved, various combinations of factors have been suggested to explain the recalcitrant nature of biofilms toward killing by antibiotics. In this mini-review, some of the factors contributing to antimicrobial resistance in biofilms are discussed.

Bioguided isolation of antimicrobial polyphenols from Cuspidaria convoluta leaves and their synergistic effect with antibiotics

Objective:To identify and isolate phenolic compounds from Cuspidaria convoluta,and to evaluate their antibacterial activity and synergistic effect with antibiotics.Methods:The crude extract was prepared by maceration with methanol(5%).The dry extract was suspended in water and fractionated successively.The most active extract was selected by its antibacterial activity and its total phenol content was determined by spectrophotometry and by HPLC-MS/MS.Bioactive fractions of the most active extract were separated by column chromatography and evaluated by bioautography.Isolated compounds were identified.Minimum inhibitory concentration(MIC)of these compounds was determined by microdilution broth method,and synergism with antibiotics(ampicillin,gentamicin and oxacillin)was tested by checkerboard and time-kill assays.Results:Coumaric acid,catechin/epicatechin,and luteolin were purified and identified from the extract.There was an increase in the antibacterial activity of antibiotics when they were combined with these compounds.The combination of luteolin and ampicillin had the most potent antibacterial activities.The MICs of oxacillin for each of methicillin-resistant Staphylococcus aureus strains were reduced between 4 and 8-fold when these strains were coincubated with sub-MIC(≤?MIC)levels of these compounds,demonstrating that the combination had synergistic effect for all cases.Conclusions:Cuspidaria convoluta contains important pharmacologically active substances that can be used to improve antibiotic efficacy.

Ca (II)-EDTA shows antimicrobial activity against periodontopathic bacteria

Ethylenediamine-N,N,N’,N’-tetraacetic acid calcium (II) disodium salt (Ca (II)-EDTA) was investigated for its antibacterial activity against the periodontal pathogens Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Porphyromonas gingivalis. We determined the minimum inhibitory concentrations (MIC) of Ca (II)-EDTA and its bactericidal activity. Ethylenediamine-N,N,N’,N’-tetraacetic acid calcium (II) disodium salt inhibited the growth of all the periodontopathic bacteria tested in broth. An MIC of 60 mM was the most effective against P. gingivalis. An adenosine triphosphate bioluminescence assay revealed that Ca (II)-EDTA showed bactericidal activity against the bacteria tested in a time-dependent manner. To determine its safety in mammalian cells, we investigated the viability of murine L929 cells subjected to Ca (II)-EDTA treatment. At 75 mM, 93% ± 0.13% of the cells survived. These results indicate that Ca (II)-EDTA is a candidate chelating agent for prevention of infection by periodontopathic bacteria.