- Metabolic Analyses Revealed Time-Dependent Synergistic Killing by Colistin and Aztreonam Combination Against Multidrug-Resistant Acinetobacter baumannii. [Journal Article]
- FMFront Microbiol 2018; 9:2776
- Background: Polymyxins are a last-line class of antibiotics against multidrug-resistant Acinetobacter baumannii; however, polymyxin resistance can emerge with monotherapy. Therefore, synergistic com...
Background: Polymyxins are a last-line class of antibiotics against multidrug-resistant Acinetobacter baumannii; however, polymyxin resistance can emerge with monotherapy. Therefore, synergistic combination therapy is a crucial strategy to reduce polymyxin resistance. Methods: This study conducted untargeted metabolomics to investigate metabolic responses of a multidrug-resistant (MDR) A. baumannii clinical isolate, AB090342, to colistin and aztreonam alone, and their combination at 1, 4, and 24 h. Metabolomics data were analyzed using univariate and multivariate statistics; metabolites showing ≥ 2-fold changes were subjected to bioinformatics analysis. Results: The synergistic action of colistin-aztreonam combination was initially driven by colistin via significant disruption of bacterial cell envelope, with decreased phospholipid and fatty acid levels at 1 h. Cell wall biosynthesis was inhibited at 4 and 24 h by aztreonam alone and the combination as shown by the decreased levels of two amino sugars, UDP-N-acetylglucosamine and UDP-N-acetylmuramate; these results suggested that aztreonam was primarily responsible for the synergistic killing at later time points. Moreover, aztreonam alone and the combination significantly depleted pentose phosphate pathway, amino acid, peptide and nucleotide metabolism, but elevated fatty acid and key phospholipid levels. Collectively, the combination synergy between colistin and aztreonam was mainly due to the inhibition of cell envelope biosynthesis via different metabolic perturbations. Conclusion: This metabolomics study is the first to elucidate multiple cellular pathways associated with the time-dependent synergistic action of colistin-aztreonam combination against MDR A. baumannii. Our results provide important mechanistic insights into optimizing synergistic colistin combinations in patients.
- Antibiotic-Induced Cell Chaining Triggers Pneumococcal Competence by Reshaping Quorum Sensing to Autocrine-Like Signaling. [Journal Article]
- CRCell Rep 2018 Nov 27; 25(9):2390-2400.e3
- Streptococcus pneumoniae can acquire antibiotic resistance by activation of competence and subsequent DNA uptake. Here, we demonstrate that aztreonam (ATM) and clavulanic acid (CLA) promote competenc...
Streptococcus pneumoniae can acquire antibiotic resistance by activation of competence and subsequent DNA uptake. Here, we demonstrate that aztreonam (ATM) and clavulanic acid (CLA) promote competence. We show that both compounds induce cell chain formation by targeting the d,d-carboxypeptidase PBP3. In support of the hypothesis that chain formation promotes competence, we demonstrate that an autolysin mutant (ΔlytB) is hypercompetent. Since competence is initiated by the binding of a small extracellular peptide (CSP) to a membrane-anchored receptor (ComD), we wondered whether chain formation alters CSP diffusion kinetics. Indeed, ATM or CLA presence affects competence synchronization by shifting from global to local quorum sensing, as CSP is primarily retained to chained cells, rather than shared in a common pool. Importantly, autocrine-like signaling prolongs the time window in which the population is able to take up DNA. Together, these insights demonstrate the versatility of quorum sensing and highlight the importance of an accurate antibiotic prescription.
- In vitro and in vivo bactericidal activity of ceftazidime-avibactam against Carbapenemase-producing Klebsiella pneumoniae. [Journal Article]
- ARAntimicrob Resist Infect Control 2018; 7:142
- CONCLUSIONS: This study indicated ceftazidime-avibactam therapy occupied significant bactericidal effects against KPC-2 and OXA-232 carbapenemase-producing Klebsiella pneumoniae. While combined with aztreonam, the stronger synergistic bactericidal effects against NDM carbapenemase-producing Klebsiella pneumoniae were achieved.
- Inpatient Beta-lactam test-dose Protocol promotes Antimicrobial Stewardship in Patients with History of Penicillin Allergy. [Journal Article]
- AAAnn Allergy Asthma Immunol 2018 Nov 19
- CONCLUSIONS: The antibiotic choice in patients admitted to the hospital with a reported penicillin allergy can be improved by better evaluation of the allergy history and the use of a risk stratification guideline.
- Effectiveness of empiric aztreonam compared to other beta-lactams for treatment of Pseudomonas aeruginosa infections. [Journal Article]
- IDInfect Drug Resist 2018; 11:1975-1981
- CONCLUSIONS: Empiric therapy failure occurred more often when initially using aztreonam vs a BL in a patient who subsequently had a P. aeruginosa infection. Only a third of patients within the aztreonam group had a documented BL allergy, demonstrating an inclination for clinicians to utilize this drug as an empiric therapy when there were more appropriate therapies available.
- Multiple clones of metallo-β-lactamase-producing Acinetobacter ursingii in a children hospital from Argentina. [Journal Article]
- IGInfect Genet Evol 2018 Nov 12; 67:145-149
- Acinetobacter spp. are opportunistic pathogens being A. baumannii the most frequently identified in nosocomial settings. A. ursingii was mainly described as causing bacteremia and outbreaks in neonat...
Acinetobacter spp. are opportunistic pathogens being A. baumannii the most frequently identified in nosocomial settings. A. ursingii was mainly described as causing bacteremia and outbreaks in neonatal intensive care units. Ten A. ursingii isolates were recovered from rectal swab screening for carbapenemase-producing bacteria between June 2013 and December 2015 from a children hospital in Argentina. All ten isolates were metallo-β-lactamase-producing, nine were positive for blaIMP-1 and one for blaNDM-1. IMP-positive isolates were also positive for blaOXA-58 gene. All isolates were susceptible to ciprofloxacin, colistin and minocycline, and nine were susceptible to ampicillin-sulbactam and gentamicin. Two A. ursingii displayed high level of resistance to aztreonam associated with blaCTX-M-15 in one isolate, and blaVEB-1 in the other. Eight SmaI-PFGE patterns were recognized. We evaluated the usefulness of Acinetobacter MLST-Pasteur scheme, to analyse A. ursingii isolates, however the rpoB gene was not amplified. A new set of primers were designed for specific amplification and sequencing, allowing the analysis of rpoB gene for this species. New alleles and the sequence types 748, 749, 750, 751, 993, 1186, 1187, and 1189 were included at the Acinetobacter MLST-Pasteur database. Those isolates showing related PFGE patterns were assigned to the same ST. To the best of our knowledge, this is the first report of MBL-producing A. ursingii in Argentina. The inclusion of A. ursingii species to the Acinetobacter MLST-Pasteur scheme allows deeper molecular characterization and a better understanding about the epidemiology of this germen.
- Phenotypic and Genotypic Characterization of Carbapenem-resistant Enterobacteriaceae: Data From a Longitudinal Large-scale CRE Study in China (2012-2016). [Journal Article]
- CIClin Infect Dis 2018 Nov 13; 67(suppl_2):S196-S205
- CONCLUSIONS: The number of CRE strains harboring carbapenemase is increasing. KPC-ST11 K. pneumoniae, the predominant strain, shows a reduced susceptibility to most available antibiotics.
- Activity of ceftolozane/tazobactam against a collection of Pseudomonas aeruginosa isolates from bloodstream infections in Australia. [Journal Article]
- PPathology 2018 Nov 01
- Pseudomonas aeruginosa is a common pathogen causing nosocomial infection. In particular, bloodstream infection (BSI) is associated with a high rate of morbidity and mortality. Ceftolozane/tazobactam ...
Pseudomonas aeruginosa is a common pathogen causing nosocomial infection. In particular, bloodstream infection (BSI) is associated with a high rate of morbidity and mortality. Ceftolozane/tazobactam is a new β-lactam/β-lactamase antimicrobial with activity against P. aeruginosa as well as multidrug resistant (MDR) Gram negative Enterobacteriaceae. Ceftolozane/tazobactam has frequently been used in salvage therapy for MDR P. aeruginosa infections. The aim of this study was to determine the activity of ceftolozane/tazobactam against P. aeruginosa isolates from BSIs collected from three clinical microbiology laboratories in Queensland, Australia, with a high proportion of isolates demonstrating β-lactam resistance. Antimicrobial susceptibility testing was performed by broth microdilution using custom made sensititre plates sourced from ThermoFisher Scientific. In addition to ceftolozane/tazobactam, we also tested piperacillin/tazobactam, ceftazidime, cefepime, meropenem, doripenem, imipenem, aztreonam, ciprofloxacin, levofloxacin, gentamicin, amikacin, tobramycin and colistin. Overall, ceftolozane/tazobactam was the most active agent tested [(MIC50/90 = 1/2 μg/mL, 96% susceptible (S)]. Against 44 isolates with resistance to at least one other β-lactam agent, 40 were susceptible to ceftolozane/tazobactam. Three ceftolozane/tazobactam resistant isolates were susceptible to colistin, with one of those isolates also susceptible to levofloxacin but not to any other antimicrobials tested. One ceftolozane/tazobactam resistant isolate was susceptible only to meropenem and doripenem but was non-susceptible to imipenem. An association was found between fluoroquinolone resistance and aminoglycoside resistance but not with β-lactam resistance. In summary, ceftolozane/tazobactam was active against most strains tested, including those resistant to other β-lactams. Laboratories should consider testing P. aeruginosa against ceftolozane/tazobactam in suspected MDR or extensively drug resistant (XDR) infections.
- Changing drug resistance profile in Pseudomonas aeruginosa infection among HIV patients from 2010-2017 - A retrospective study. [Journal Article]
- JGJ Glob Antimicrob Resist 2018 Oct 30
- CONCLUSIONS: A constant increase in drug-resistant P. aeruginosa starins from HIV patients was observed, from the year 2010 to 2017. Findings from this study urge the need for periodical monitoring and surveillance of P.aeruginosa resistance profile, especially in hospitalized and immunocompromised patients from resource-limited settings.
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- Esculentin-1a Derived Antipseudomonal Peptides: Limited Induction of Resistance and Synergy with Aztreonam. [Journal Article]
- PPProtein Pept Lett 2018 Oct 31
- CONCLUSIONS: Both peptides represent promising candidates for the development of new antipseudomonal compounds, which do not induce resistance.