scholarly journals Time-Kill Evaluation of Antibiotic Combinations Containing Ceftazidime-Avibactam against Extensively Drug-Resistant Pseudomonas aeruginosa and Their Potential Role against Ceftazidime-Avibactam-Resistant Isolates

2021 ◽  
Author(s):  
María M. Montero ◽  
Sandra Domene Ochoa ◽  
Carla López-Causapé ◽  
Sonia Luque ◽  
Luisa Sorlí ◽  
...  
Keyword(s):  
Public Health ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Health Problem ◽  
Potential Role ◽  
Public Health Problem ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Time Kill ◽  
Emergence Of Resistance

The emergence of resistance to antibiotics is a serious public health problem worldwide and can be a cause of mortality. For this reason, antibiotic treatment is compromised, and we have few therapeutic options to treat infections.

scholarly journals In VitroActivity of Polymyxin B in Combination with Various Antibiotics against Extensively Drug-Resistant Enterobacter cloacae with Decreased Susceptibility to Polymyxin B

2016 ◽  
Vol 60 (9) ◽  
pp. 5238-5246 ◽  
Author(s):  
Yiying Cai ◽  
Tze-Peng Lim ◽  
Jocelyn Teo ◽  
Suranthran Sasikala ◽  
Winnie Lee ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Polymyxin B ◽  
Infection Model ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Dosing Regimens ◽  
Time Kill ◽  
Emergence Of Resistance

ABSTRACTAgainst extensively drug-resistant (XDR)Enterobacter cloacae, combination antibiotic therapy may be the only option. We investigated the activity of various antibiotics in combination with polymyxin B using time-kill studies (TKS). TKS were conducted with four nonclonal XDRE. cloacaeisolates with 5 log10CFU/ml bacteria against maximum, clinically achievable concentrations of polymyxin B alone and in two-drug combinations with 10 different antibiotics. A hollow-fiber infection model (HFIM) simulating clinically relevant polymyxin B and tigecycline dosing regimens was conducted for two isolates over 240 h. Emergence of resistance was quantified using antibiotic-containing (3× MIC) media. Biofitness and stability of resistant phenotypes were determined. All XDRE. cloacaeisolates were resistant to all antibiotics except for polymyxin B (polymyxin B MIC, 1 to 4 mg/liter). All isolates harbored metallo-β-lactamases (two with NDM-1, two with IMP-1). In single TKS, all antibiotics alone demonstrated regrowth at 24 h, except amikacin against two strains and polymyxin B and meropenem against one strain each. In combination TKS, only polymyxin B plus tigecycline was bactericidal against all four XDRE. cloacaeisolates at 24 h. In HFIM, tigecycline and polymyxin B alone did not exhibit any killing activity. Bactericidal kill was observed at 24 h for both isolates for polymyxin B plus tigecycline; killing was sustained for one isolate but regrowth was observed for the second. Phenotypically stable resistant mutants with reducedin vitrogrowth rates were observed. Polymyxin B plus tigecycline is a promising combination against XDRE. cloacae. However, prolonged and indiscriminate use can result in resistance emergence.

scholarly journals Chronic Respiratory Infections by Mucoid Carbapenemase-Producing Pseudomonas aeruginosa Strains, a New Potential Public Health Problem

2008 ◽  
Vol 52 (6) ◽  
pp. 2285-2286 ◽  
Author(s):  
Carlos Juan ◽  
Olivia Gutiérrez ◽  
Feliu Renom ◽  
Margarita Garau ◽  
Sebastián Albertí ◽  
...  
Keyword(s):  
Public Health ◽  
Pseudomonas Aeruginosa ◽  
Health Problem ◽  
Respiratory Infections ◽  
Public Health Problem ◽  
Potential Public Health

scholarly journals A Review: Lantibiotics, a Promising Antimicrobial Agent

2016 ◽  
Vol 21 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Shradha Basi-Chipalu
Keyword(s):  
Public Health ◽  
Antimicrobial Agent ◽  
Health Problem ◽  
Posttranslational Modification ◽  
Public Health Problem ◽  
Probiotic Bacteria ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Food Preservatives ◽  
Drug Resistant Bacteria

Rise  in  multi  drug  resistant  bacteria  has  been  a  public  health  problem.  This has necessitated for the exploration of novel antimicrobials. Bacteriocins, probiotic bacteria, and bacteriophages are considered as alternatives to antibiotics. To this context, lantibiotics could be the future candidate for antimicrobial agent.Lantibiotics are synthesized ribosomally and  after posttranslational modification  active peptide is produced.Lantibiotics are lanthionine and methyllanthionine containing peptides exhibiting activity against multi drug resistant  pathogens. Besides its application  as  alternatives  to  old  antibiotics, they can be used as food preservatives, additives, probiotics, and prophylactics.Journal of Institute of Science and TechnologyVolume 21, Issue 1, August 2016, Page: 119-128

scholarly journals Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
María Montero ◽  
Sandra Domene Ochoa ◽  
Carla López-Causapé ◽  
Brian VanScoy ◽  
Sonia Luque ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Therapeutic Option ◽  
Drug Resistant ◽  
Chemostat Model ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Spanish Study ◽  
Time Kill

ABSTRACT Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

scholarly journals Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Yu-Wei Lin ◽  
Heidi H. Yu ◽  
Jinxin Zhao ◽  
Mei-Ling Han ◽  
Yan Zhu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Population Analysis ◽  
Polymyxin B ◽  
Infection Model ◽  
Limiting Factor ◽  
Drug Resistant ◽  
Limit Of Quantification ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Time Kill

ABSTRACT Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa . Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa , with ≥2 to 4 log 10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations.

Kindesmisshandlung und deren Langzeitfolgen – Analyse einer repräsentativen deutschen Stichprobe

2019 ◽  
Vol 67 (2) ◽  
pp. 100-111 ◽  
Author(s):  
Andreas Witt ◽  
Rebecca Brown ◽  
Paul L. Plener ◽  
Elmar Brähler ◽  
Jörg M. Fegert ◽  
...  
Keyword(s):  
Public Health ◽  
Health Problem ◽  
Public Health Problem ◽  
Nachhaltige Entwicklung

Zusammenfassung. Kindesmisshandlung stellt einen bedeutenden Risikofaktor für die Entwicklung dar. Einzelne Formen von Kindesmisshandlung treten häufig nicht isoliert auf, sondern das gemeinsame Auftreten verschiedener Formen von Kindesmisshandlung stellt eher die Regel als die Ausnahme dar. Neben den langfristigen und vielfältigen individuellen Folgen führt Kindesmisshandlung jährlich zu einer hohen gesamtgesellschaftlichen Belastung. Die WHO hat Kindesmisshandlung als großes Public Health Problem identifiziert und die Vereinten Nationen haben den Kampf gegen Kindesmisshandlung zum Ziel in ihrer Agenda für nachhaltige Entwicklung gemacht. In dem vorliegenden Beitrag werden die Häufigkeit sowie das gemeinsame Auftreten unterschiedlicher Formen von Kindesmisshandlung sowie deren Assoziation mit psychischen und somatischen Folgen auf Basis einer bevölkerungsrepräsentativen Stichprobe untersucht und dargestellt. Die Ergebnisse verdeutlichen den Zusammenhang zwischen der Kumulation verschiedener Formen von Misshandlung und negativen Folgen für die Betroffenen. So ist das Risiko für negative Konsequenzen beim Erleben von vier oder mehr Formen von Misshandlung um das bis zu 10-fache erhöht. Viel zu selten werden die kumulativen Effekte von mehreren Belastungen berücksichtigt. Gerade weil die Wirkweisen über die Misshandlung, die Gesundheit beeinflusst, zunehmend gut untersucht sind, muss dieses Wissen im Gesundheitswesen stärker bei der Konzeption von Präventions- und Interventionsmaßnahmen berücksichtigt werden.

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