- Determination of 14 aminoglycosides by LC-MS/MS using molecularly imprinted polymer solid phase extraction for clean-up. [Journal Article]
- FAFood Addit Contam Part A Chem Anal Control Expo Risk Assess 2018 Feb 16
- A LC-MS/MS method for screening fourteen aminoglycosides in foodstuffs of animal origin is presented. Its scope includes raw materials and processed ingredients but also finished products composed of...
A LC-MS/MS method for screening fourteen aminoglycosides in foodstuffs of animal origin is presented. Its scope includes raw materials and processed ingredients but also finished products composed of milk, meat, fish, egg or fat. Aminoglycosides are extracted in an acidic aqueous solution, which is first recovered after centrifugation, then diluted with a basic buffer and finally purified by molecularly imprinted polymer-solid phase extraction (MIP-SPE). Analytes are detected within 8 min by ion-pair reversed phase LC-MS/MS. Due to the large range of foodstuffs involved, the variability of matrix effects led to significant MS signal variations. This was circumvented by systematically extracting each sample twice i.e. "unspiked" and "spiked" at the screening target concentration of 50 µg kg-1. The method was validated according to the European Community Reference Laboratories Residues Guidelines (CRL 20/1/2010) giving false-negative and false-positive rates ≤ 3 % for all compounds. Ruggedness of the method was further demonstrated in quality control operations by a second laboratory. The fourteen aminoglycosides in water-based standard solutions were stable for up to six months when stored at either -80 °C, -20 °C or at 4 °C storage temperatures.
- Extended-spectrum β-lactamase-producing Enterobacteriaceae, national study of antimicrobial treatment for pediatric urinary tract infection. [Journal Article]
- MMMed Mal Infect 2018 Feb 12
- CONCLUSIONS: Antimicrobial treatment for ESBL-producing UTI greatly varies, and carbapenems are excessively prescribed. Specific guidelines for ESBL infections are required.
- Antimicrobial Prophylaxis with Combat-Related Open Soft-Tissue Injuries. [Journal Article]
- MMMil Med 2018 Feb 13
- CONCLUSIONS: Use of non-guideline directed EGN-based post-trauma antibiotic prophylaxis does not improve infectious outcomes nor does it shorten hospital stay.
- Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. [Review]
- CMClin Microbiol Rev 2018; 31(2)
- Therapy of invasive infections due to multidrug-resistantEnterobacteriaceae(MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactam...
Therapy of invasive infections due to multidrug-resistantEnterobacteriaceae(MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producingEnterobacteriaceae(CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.
- [Urosepsis]. [Journal Article]
- MKMed Klin Intensivmed Notfmed 2018 Feb 07
- Urosepsis is defined as a severe disease due to organ failure caused by a urinary tract infection. An empirical antibiotic therapy should be instigated within the first hour after diagnosis. Urine cu...
Urosepsis is defined as a severe disease due to organ failure caused by a urinary tract infection. An empirical antibiotic therapy should be instigated within the first hour after diagnosis. Urine cultures and blood cultures should be performed before antibiotic treatment. Further diagnostics should be carried out at an early stage to enable an interventional focus control in the case of urinary tract obstruction or abscess formation, if necessary. Gram-negative pathogens are most frequently isolated. Extended spectrum beta-lactamase (ESBL) forming bacteria as a cause of urosepsis are increasing. Carbapenemase-forming Enterobacteriaceae, on the other hand, are still rare. The empirical treatment consists of a broad spectrum beta-lactam antibiotic. While piperacillin/tazobactam, carbapenems and the new cephalosporin/beta-lactamase inhibitor (BLI) combinations are given as monotherapy, cephalosporins should be combined with aminoglycosides (preferred) or fluoroquinolones. If a combination therapy is given, it should be de-escalated to a monotherapy after 48-72 h.
- Alanine Enhances Aminoglycosides-Induced ROS Production as Revealed by Proteomic Analysis. [Journal Article]
- FMFront Microbiol 2018; 9:29
- Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose incr...
Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remains to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion ofnagEandfadLdecreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS) production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production.
- High rate of association of 16S rRNA methylases and carbapenemases in Enterobacteriaceae recovered from hospitalized children, Angola. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 12
- Acquired 16S rRNA methylases (RMTase) conferring pandrug resistance to aminoglycosides were searched among enterobacterial isolates recovered in Angola. A total of 36 hospitalized children were scree...
Acquired 16S rRNA methylases (RMTase) conferring pandrug resistance to aminoglycosides were searched among enterobacterial isolates recovered in Angola. A total of 36 hospitalized children were screened for rectal colonization using the SuperAminoglycoside medium selective. Twenty-two pan-aminoglycoside-resistant enterobacterial isolates were recovered, all of them producing RMTases, namely RmtB, ArmA, and RmtC. A high diversity of genetic backgrounds was identified either forEscherichia coliandKlebsiella pneumoniaeisolates, most of them co-producing carbapenemases NDM-1 or NDM-5, respectively.
- Novel Tn916-like elements confer aminoglycoside/macrolide co-resistance in clinical isolates of Streptococcus gallolyticus ssp. gallolyticus. [Journal Article]
- JAJ Antimicrob Chemother 2018 Feb 09
- CONCLUSIONS: Previously unknown Tn916-like mobile genetic elements conferring aminoglycoside/macrolide co-resistance make Sgg, collectively with other gut Firmicutes such as enterococci and eubacteria, a potential laterally active reservoir of these antibiotic resistance determinants among the mammalian gastrointestinal microbiota.
- Evolution of thePseudomonas aeruginosaaminoglycoside mutational resistome in vitro and in the cystic fibrosis setting. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 05
- Inhaled administration of high doses of aminoglycosides is a key maintenance treatment ofPseudomonas aeruginosachronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mec...
Inhaled administration of high doses of aminoglycosides is a key maintenance treatment ofPseudomonas aeruginosachronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of step-wise high-level tobramycin resistance developmentin vitroand compared the results with those of isogenic pairs of susceptible-resistant clinical isolates. Resistance development correlated withfusA1mutationsin vitroandin vivopmrBmutations, conferring polymyxin resistance, were also frequently selectedin vitroIn contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed inin vitroevolution experiments.
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- Analysis of Aminoglycoside Modifying Enzyme Genes Responsible for High-Level Aminoglycoside Resistance among Enterococcal Isolates. [Journal Article]
- JPJ Pathog 2017; 2017:3256952
- Enzymatic modification results in high-level resistance to aminoglycoside (HLAR), which eliminates the synergistic bactericidal effect of combined exposure to a cell wall-active agent and an aminogly...
Enzymatic modification results in high-level resistance to aminoglycoside (HLAR), which eliminates the synergistic bactericidal effect of combined exposure to a cell wall-active agent and an aminoglycoside. So aim of the study was to determine prevalence of HLAR enterococcal isolate and to study distribution of aminoglycoside modifying enzyme genes in them. A total of 100 nonrepeat isolates of enterococci from various clinical samples were analyzed. As per Clinical and Laboratory Standards Institute guidelines enterococci were screened for HLAR by Kirby-Bauer disc diffusion method. Minimum inhibitory concentration of all isolates for gentamicin and streptomycin was determined by E-test. Multiplex polymerase chain reaction (PCR) was carried out for HLAR enterococcal isolates to identify aminoglycoside modifying enzymes genes responsible for resistance. 60% isolates were found to be high-level gentamicin resistant (HLGR) whereas 45% isolates were found to be high-level streptomycin resistant (HLSR). By multiplex PCR 80% HLGR isolates carried bifunctional aminoglycoside modifying enzyme gene aac(6')-Ie-aph(2'')-Ia whereas 18 out of 45 high-level streptomycin resistant, that is, 40%, isolates carried aph(3')-IIIa. However, aph(2'')-Ib, aph(2'')-Ic, aph(2'')-Id, and ant(4')-Ia genes which encode other aminoglycosides modifying enzymes were not detected. Bifunctional aminoglycoside modifying enzyme gene aac(6')-Ie-aph(2'')-Ia is the predominant gene responsible for HLAR.