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The Science of the Total Environment Jul 2022Pseudomonas aeruginosa is a ubiquitous bacterium, successfully exploiting a variety of environmental niches due to its remarkable metabolic versatility. The World Health...
Pseudomonas aeruginosa is a ubiquitous bacterium, successfully exploiting a variety of environmental niches due to its remarkable metabolic versatility. The World Health Organization classifies P. aeruginosa as a "priority pathogen" due to its a great ability to overcome the action of antimicrobials, including carbapenems. Hitherto, most studies have focused on clinical settings from humans, but much less on animal and environmental settings, particularly on wildlife. In this work, we report the isolation of a carbapenem-resistant Pseudomonas aeruginosa strain recovered from the faeces of a red deer adult female sampled in a humanized area. This isolate was obtained during a nationwide survey on antimicrobial resistance in wildlife aimed to determine the occurrence of carbapenem-resistant bacteria among 181 widely distributed wild ungulates. This P. aeruginosa isolate was found to be a high-risk clone, belonging to the sequence type (ST) 274. The genomic analysis of P. aeruginosa isolate UP4, classified this isolate as belonging to serogroup O3, which was also found to harbour the genes bla, bla, bla (encoding resistance to beta-lactams), aph(3')-IIb (aminoglycosides resistance), fosA (fosfomycin resistance) and catB7 (chloramphenicol resistance). Antimicrobial susceptibility screening, according to EUCAST, showed resistance to imipenem and intermediate resistance to meropenem and doripenem. To our knowledge, this is the first description of carbapenem-resistant P. aeruginosa in deer in Europe. Our results highlight the importance of wild ungulates either as victims of human activity or amplifiers of AMR, either way with potential impacts on animal, human and ecosystem health, since excretion of AMR bacteria might directly or indirectly contaminate other animals and the surrounding environment, perpetuating the spill-over and chain dissemination of AMR determinants.
Topics: Animals; Anti-Bacterial Agents; Carbapenems; Clone Cells; Deer; Ecosystem; Female; Microbial Sensitivity Tests; Portugal; Pseudomonas Infections; Pseudomonas aeruginosa; beta-Lactamases
PubMed: 35318052
DOI: 10.1016/j.scitotenv.2022.154699 -
Nanomaterials (Basel, Switzerland) Jan 2022The synthesis of bacterial cellulose (BC) by strain B-12068 was investigated on various C-substrates, under submerged conditions with stirring and in static surface...
The synthesis of bacterial cellulose (BC) by strain B-12068 was investigated on various C-substrates, under submerged conditions with stirring and in static surface cultures. We implemented the synthesis of BC on glycerol, glucose, beet molasses, sprat oil, and a mixture of glucose with sunflower oil. The most productive process was obtained during the production of inoculum in submerged culture and subsequent growth of large BC films (up to 0.2 m and more) in a static surface culture. The highest productivity of the BC synthesis process was obtained with the growth of bacteria on molasses and glycerol, 1.20 and 1.45 g/L per day, respectively. We obtained BC composites with silver nanoparticles (BC/AgNPs) and antibacterial drugs (chlorhexidine, baneocin, cefotaxime, and doripenem), and investigated the structure, physicochemical, and mechanical properties of composites. The disc-diffusion method showed pronounced antibacterial activity of BC composites against E. coli ATCC 25922 and S. aureus ATCC 25923.
PubMed: 35055211
DOI: 10.3390/nano12020192 -
Antibiotics (Basel, Switzerland) Jan 2022Fosfomycin-based combination therapy has emerged as an attractive option in our armamentarium due to its synergistic activity against carbapenem-resistant Gram-negative...
Fosfomycin-based combination therapy has emerged as an attractive option in our armamentarium due to its synergistic activity against carbapenem-resistant Gram-negative bacteria (CRGNB). The ability to simultaneously measure fosfomycin and other antibiotic drug levels will support in vitro and clinical investigations to develop rational antibiotic combination dosing regimens against CRGNB infections. We developed an analytical assay to measure fosfomycin with nine important antibiotics in human plasma and cation-adjusted Mueller-Hinton II broth (CAMHB). We employed a liquid-chromatography tandem mass spectrometry method and validated the method based on accuracy, precision, matrix effect, limit-of-detection, limit-of-quantification, specificity, carryover, and short-term and long-term stability on U.S. Food & Drug Administration (FDA) guidelines. Assay feasibility was assessed in a pilot clinical study in four patients on antibiotic combination therapy. Simultaneous quantification of fosfomycin, levofloxacin, meropenem, doripenem, aztreonam, piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam, cefepime, and tigecycline in plasma and CAMHB were achieved within 4.5 min. Precision, accuracy, specificity, and carryover were within FDA guidelines. Fosfomycin combined with any of the nine antibiotics were stable in plasma and CAMHB up to 4 weeks at -80 °C. The assay identified and quantified the respective antibiotics administered in the four subjects. Our assay can be a valuable tool for in vitro and clinical applications.
PubMed: 35052932
DOI: 10.3390/antibiotics11010054 -
Frontiers in Microbiology 2021Carbapenem-resistant (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus,...
Carbapenem-resistant (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 logCFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.
PubMed: 34970239
DOI: 10.3389/fmicb.2021.779988 -
Antibiotics (Basel, Switzerland) Dec 2021Traditionally, the antibacterial activity of β-lactam antibiotics in the presence of β-lactamase inhibitors is determined at the fixed inhibitor concentration. This...
Predicting the Effects of Carbapenem/Carbapenemase Inhibitor Combinations against KPC-Producing in Time-Kill Experiments: Alternative versus Traditional Approaches to MIC Determination.
Traditionally, the antibacterial activity of β-lactam antibiotics in the presence of β-lactamase inhibitors is determined at the fixed inhibitor concentration. This traditional approach does not consider the ratio of antibiotic-to-inhibitor concentrations achieved in humans. To explore whether an alternative pharmacokinetically based approach to estimate MICs in combinations is predictive of antimicrobial efficacy, the effects of imipenem and doripenem alone and in combination with relebactam were studied in time-kill experiments against carbapenemase-producing . The carbapenem-to-relebactam concentration ratios in time-kill assays were equal to the therapeutic 24-h area under the concentration-time curve (AUC) ratios of the drugs (1.5/1). The simulated levels of carbapenem and relebactam were equal to their concentrations achieved in humans. When effects of combined regimens were plotted against respective C/MICs, a sigmoid relationship was obtained only with MICs determined by pharmacokinetically based method. The effectiveness of both carbapenems in the presence of relebactam was comparable by the results of time-kill experiments. These findings suggest that (1) antibiotic/inhibitor MICs determined at a pharmacokinetically based concentration ratio allow an adequate assessment of carbapenem susceptibility in carbapenemase-producing strains and can be used to predict antibacterial effects; (2) in time-kill experiments, the effects of imipenem and doripenem in the presence of relebactam are comparable.
PubMed: 34943731
DOI: 10.3390/antibiotics10121520 -
European Journal of Hospital Pharmacy :... Mar 2023Outpatient parenteral antimicrobial therapy (OPAT) services using continuous infusions (CIs) of antimicrobial agents in elastomeric devices require evidence of... (Review)
Review
Widening the net: a literature review of antimicrobial agents with potential suitability for outpatient parenteral antimicrobial therapy services-the importance of storage and stability.
OBJECTIVES
Outpatient parenteral antimicrobial therapy (OPAT) services using continuous infusions (CIs) of antimicrobial agents in elastomeric devices require evidence of acceptable stability of the agent over the infusion period. A period of refrigerated storage of filled devices, followed by the CI period, is useful for OPAT services but can present a significant challenge to the stability of drugs. The aims of this study were to review fresh-filled stability data on antimicrobials which would be useful for OPAT services and to identify suitable candidates for further assessment.
METHODS
Searches identified papers relating to stability assessments of antimicrobials for immediate use tested above 31°C using a stability-indicating method.
RESULTS
We identified 18 stability studies published in 12 papers between 2015 and 2020, assessing the stability of 10 agents. Aminopenicillins like ampicillin and amoxicillin appear too unstable for CI, while benzylpenicillin may benefit from buffering to improve its stability. Cephalosporins vary in their stability and CI periods of 24 hours may not be achievable. Of the carbapenems, there are insufficient data for doripenem but meropenem has been extensively studied and is unsuitable for CI longer than 6 hours. Voriconazole may be suitable for CI but needs further investigation.
CONCLUSIONS
Some drugs identified in our review are unlikely to be suitable for continuous infusion in OPAT services due to instability. Using a 'fresh-fill' approach, without refrigerated storage, may make some drugs useful while other agents should be considered for further assessment to Yellow Cover Document standards. The impact of buffering for penicillins should be assessed further.
Topics: Humans; Outpatients; Anti-Infective Agents; Meropenem; Ambulatory Care; Ampicillin
PubMed: 34862256
DOI: 10.1136/ejhpharm-2021-002937 -
Infection and Drug Resistance 2021Antibiotic combination is commonly used to treat multidrug-resistant pathogens. Reports have indicated that tigecycline use is associated with hypofibrinogenemia....
BACKGROUND
Antibiotic combination is commonly used to treat multidrug-resistant pathogens. Reports have indicated that tigecycline use is associated with hypofibrinogenemia. However, whether the bleeding risk of tigecycline is higher than that of other antibiotics remains unknown. The aim of this study was to compare the bleeding risk between colistin-tigecycline and colistin-carbapenem treatment.
METHODS
This retrospective cohort study enrolled adult patients treated with colistin along with tigecycline or carbapenems (doripenem, imipenem-cilastatin, or meropenem) for ˃72 hours during hospitalization. The primary outcome was major bleeding events, which were determined by a hemoglobin drop of ≥2 g/d and receipt of blood transfusions with whole blood or packed red blood cells. Multivariate logistic regression was applied to determine risk factors for bleeding events.
RESULTS
In total, 106 and 268 patients in the colistin-tigecycline and colistin-carbapenem groups met the criteria for analysis, respectively. The two groups did not differ significantly in demographic data, except for alanine aminotransferase (ALT), serum creatinine (S) and ulcer disease. The colistin-tigecycline group had a higher ALT, S and a lower proportion of ulcer disease. Major bleeding events did not differ significantly between the colistin-tigecycline and colistin-carbapenem groups (12.26% vs 9.33%, = 0.40). Antibiotic duration [OR = 1.06 (1.02-1.11), =0.007)] and anticoagulant use [OR = 2.16 (1.05-4.42), =0.04] were associated with major bleeding events.
CONCLUSION
Colistin-tigecycline treatment was not associated with a higher bleeding risk. Antibiotic duration and concurrent use of anticoagulant were the risk factors of bleeding events.
PubMed: 34858035
DOI: 10.2147/IDR.S339188 -
PloS One 2021The relatively high frequency of marine mammal stranding events in the Philippines provide many research opportunities. A select set of stranders (n = 21) from 2017 to...
The relatively high frequency of marine mammal stranding events in the Philippines provide many research opportunities. A select set of stranders (n = 21) from 2017 to 2018 were sampled for bacteriology and histopathology. Pertinent tissues and bacteria were collected from individuals representing eight cetacean species (i.e. Feresa attenuata, Kogia breviceps, Globicephala macrorhynchus, Grampus griseus, Lagenodelphis hosei, Peponocephala electra, Stenella attenuata and Stenella longirostris) and were subjected to histopathological examination and antibiotic resistance screening, respectively. The antibiotic resistance profiles of 24 bacteria (belonging to genera Escherichia, Enterobacter, Klebsiella, Proteus, and Shigella) that were isolated from four cetaceans were determined using 18 antibiotics. All 24 isolates were resistant to at least one antibiotic class, and 79.17% were classified as multiple antibiotic resistant (MAR). The MAR index values of isolates ranged from 0.06 to 0.39 with all the isolates resistant to erythromycin (100%; n = 24) and susceptible to imipenem, doripenem, ciprofloxacin, chloramphenicol, and gentamicin (100%; n = 24). The resistance profiles of these bacteria show the extent of antimicrobial resistance in the marine environment, and may inform medical management decisions during rehabilitation of stranded cetaceans. Due to inadequate gross descriptions and limited data gathered by the responders during the stranding events, the significance of histopathological lesions in association with disease diagnosis in each cetacean stranding or mortality remained inconclusive; however, these histopathological findings may be indicative or contributory to the resulting debility and stress during their strandings. The findings of the study demonstrate the challenges faced by cetacean species in the wild, such as but not limited to, biological pollution through land-sea movement of effluents, fisheries interactions, and anthropogenic activities.
Topics: Animals; Cetacea; Liver; Lung; Muscle, Skeletal; Myocardium; Philippines
PubMed: 34762695
DOI: 10.1371/journal.pone.0243691 -
PloS One 2021The increasing incidence of carbapenem resistance in Acinetobacter baumannii is a critical concern worldwide owing to the limitations of therapeutic alternatives. The...
The increasing incidence of carbapenem resistance in Acinetobacter baumannii is a critical concern worldwide owing to the limitations of therapeutic alternatives. The most important carbapenem resistance mechanism for A. baumannii is the enzymatic hydrolysis mediated by carbapenemases, mostly OXA-type carbapenemases (class D) and, to a lesser extent, metallo-β-lactamases (class B). Therefore, early and accurate detection of carbapenemase-producing A. baumannii is required to achieve the therapeutic efficacy of such infections. Many methods for carbapenemase detection have been proposed as effective tests for A. baumannii; however, none of them are officially recommended. In this study, three carbapenemase detection methods, namely, CarbaAcineto NP test, modified carbapenem inactivation method (mCIM), and simplified carbapenem inactivation method (sCIM) were evaluated for phenotypic detection of clinically isolated A. baumannii. The MICs of imipenem, meropenem, and doripenem were determined for 123 clinically isolated A. baumannii strains before performing three phenotypic detections. The overall sensitivity and specificity values were 89.09%/100% for the carbAcineto NP test, 71.82%/100% for sCIM, and 32.73%/33.13% for mCIM. CarbAcineto NP test and sCIM performed excellently (100% sensitivity) when both Class B and Class D carbapenemases were present in the same isolate. Based on the results, the combined detection method of sCIM and CarbAcineto NP test was proposed to detect carbapenemase-producing A. baumannii rather than a single assay, significantly increasing the sensitivity of detection to 98.18%. The proposed algorithm was more reliable and cost-effective than the CarbAcineto NP test alone. It can be easily applied in routine microbiology laboratories for developing countries with limited resources.
Topics: Acinetobacter baumannii; Algorithms; Bacterial Proteins; Biological Assay; Carbapenems; Imipenem; Meropenem; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 34735533
DOI: 10.1371/journal.pone.0259686 -
The Journal of Hospital Infection Jan 2022Multi-drug-resistant (MDR) Gram-negative bacterial (GNB) infection remains a significant cause of morbidity and mortality among surgical patients. The objective of this...
BACKGROUND
Multi-drug-resistant (MDR) Gram-negative bacterial (GNB) infection remains a significant cause of morbidity and mortality among surgical patients. The objective of this study was to recognize the risk factors for MDR GNB infection in patients following abdominal surgery, and determine the predictors independently associated with death.
METHODS
From 2010 to 2017, a retrospective cohort study was conducted among patients with abdominal surgery admitted to the surgical intensive care unit (ICU). Patients with GNB infection were included for analyses.
RESULTS
In total, 364 patients experienced GNB infection following abdominal surgery. Of these, 117 (32.1%) were MDR GNB infection. Of 133 MDR GNB isolates, the most common isolate was Escherichia coli (45.1%). Patients with MDR GNB infection had significantly longer ventilator-days and hospital stay, as well as higher 30-day and in-hospital mortality compared with non-MDR GNB patients. Multi-variable analysis showed that longer length of pre-ICU stay, surgical re-exploration, receipt of group 2 carbapenems (e.g. imipenem, meropenem and doripenem) and fluoroquinolones, and higher total bilirubin were independent risk factors for the acquisition of MDR GNB infection. Predictors for 30-day mortality among patients with MDR GNB infection were chronic kidney disease, receipt of group 2 carbapenems and inappropriate empirical antimicrobial therapy.
CONCLUSIONS
This study provides important information about the risk factors for MDR GNB infection and 30-day mortality among patients following abdominal surgery.
Topics: Adult; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Pharmaceutical Preparations; Retrospective Studies; Risk Factors
PubMed: 34627933
DOI: 10.1016/j.jhin.2021.09.021