Antimicrobial susceptibility of clinical isolates collected from sites in central Europe in 2019 was tested by CLSI broth microdilution method and EUCAST breakpoints. Most active were amikacin, ceftazidime-avibactam and colistin; respectively, susceptibility rates among P. aeruginosa (n = 701) were 89.2%, 92.2% and 99.9%; difficult-to-treat (DTR) isolates, 62.5%, 37.5% and 100%; multidrug-resistant (MDR) isolates, 68.3%, 72.9% and 99.5%; meropenem-resistant (MEM-R), metallo-β-lactamase-negative (MBL-negative) isolates, 72.8%, 78.6% and 100%. Among Enterobacterales (n = 1639), susceptibility to ceftazidime-avibactam, colistin and tigecycline was ≥ 97.9%; MDR Enterobacterales, 96.8%, 94.4% and 100%, respectively; DTR isolates, ≥ 76.2% to ceftazidime-avibactam and colistin; MEM-R, MBL-negative isolates, ≥ 90.0% to ceftazidime-avibactam and colistin.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- azabicyklické sloučeniny MeSH
- ceftazidim farmakologie MeSH
- Enterobacteriaceae MeSH
- fixní kombinace léků MeSH
- kolistin * farmakologie MeSH
- lidé MeSH
- meropenem MeSH
- mikrobiální testy citlivosti MeSH
- Pseudomonas aeruginosa * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Chorvatsko MeSH
- Litva MeSH
- Lotyšsko MeSH
- Maďarsko MeSH
- Polsko MeSH
- Klíčová slova
- avibaktam, infekce neznámého původu,
- MeSH
- antibakteriální látky * farmakologie terapeutické užití MeSH
- azabicyklické sloučeniny farmakologie terapeutické užití MeSH
- ceftazidim * farmakologie terapeutické užití MeSH
- fixní kombinace léků MeSH
- infekce spojené se zdravotní péčí farmakoterapie MeSH
- infekce * farmakoterapie MeSH
- lidé MeSH
- mladiství MeSH
- mozková obrna komplikace MeSH
- septický šok farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Recently, new combinations of β-lactams and β-lactamase inhibitors became available, including ceftazidime-avibactam, and increased the ability to treat infections caused by carbapenem-resistant Enterobacterales (CRE). Despite the reduced time of clinical use, isolates expressing resistance to ceftazidime-avibactam have been reported, even during treatment or in patients with no previous contact with this drug. Here, we detailed review data on global ceftazidime-avibactam susceptibility, the mechanisms involved in resistance, and the molecular epidemiology of resistant isolates. Ceftazidime-avibactam susceptibility remains high (≥ 98.4%) among Enterobacterales worldwide, being lower among extended-spectrum β-lactamase (ESBL) producers and CRE. Alterations in class A β-lactamases are the major mechanism involved in ceftazidime-avibactam resistance, and mutations are mainly, but not exclusively, located in the Ω loop of these enzymes. Modifications in Klebsiella pneumoniae carbapenemase (KPC) 3 and KPC-2 have been observed by many authors, generating variants with different mutations, insertions, and/or deletions. Among these, the most commonly described is Asp179Tyr, both in KPC-3 (KPC-31 variant) and in KPC-2 (KPC-33 variant). Changes in membrane permeability and overexpression of efflux systems may also be associated with ceftazidime-avibactam resistance. Although several clones have been reported, ST258 with Asp179Tyr deserves special attention. Surveillance studies and rationale use are essential to retaining the activity of this and other antimicrobials against class A CRE.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- azabicyklické sloučeniny MeSH
- bakteriální proteiny genetika MeSH
- beta-laktamasy genetika MeSH
- ceftazidim farmakologie MeSH
- fixní kombinace léků MeSH
- infekce bakteriemi rodu Klebsiella * farmakoterapie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Between 2014 and 2017, 6,662 Enterobacterales and 1,953 P. aeruginosa isolates were collected by 19 centers in four central European countries and Israel. A further 2,585 Enterobacterales and 707 P. aeruginosa isolates were collected in 2018 by 28 centers in seven European countries and Israel as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) study. A central laboratory performed antimicrobial susceptibility testing using broth microdilution panels according to Clinical Laboratory Standards Institute (CLSI) guidelines. Susceptibility rates among Enterobacterales were highest to ceftazidime-avibactam (≥98.5%), colistin (≥97.3%), and meropenem (≥95.8%). Ceftazidime-resistant and multidrug-resistant (MDR) Enterobacterales subsets were highly susceptible to ceftazidime-avibactam (≥94.9%) and colistin (≥94.7%). Susceptibility rates to colistin among all P. aeruginosa were ≥97.4% and were ≥96.3% among ceftazidime-resistant and MDR subsets. Susceptibility rates to ceftazidime-avibactam were 91.9% (2014-2017), 86.3% (2018) and, in common with comparator agents, were lower among ceftazidime-resistant (≥51.7%) and MDR isolates (≥57.1%).
- MeSH
- antibakteriální látky farmakologie MeSH
- azabicyklické sloučeniny farmakologie MeSH
- bakteriální léková rezistence účinky léků MeSH
- ceftazidim farmakologie MeSH
- Enterobacteriaceae účinky léků izolace a purifikace MeSH
- enterobakteriální infekce mikrobiologie MeSH
- fixní kombinace léků MeSH
- inhibitory beta-laktamasy farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- pseudomonádové infekce mikrobiologie MeSH
- Pseudomonas aeruginosa účinky léků izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Izrael MeSH
Non-thermal plasma (NTP), generated at atmospheric pressure by DC cometary discharge with a metallic grid, and antibiotics (gentamicin-GTM, ceftazidime-CFZ and polymyxin B-PMB), either alone or in combination, were used to eradicate the mature biofilm of Pseudomonas aeruginosa formed on Ti-6Al-4V alloy. Our aim was to find the conditions for NTP pre-treatment capable of enhancing the action of the antibiotics and thus reducing their effective concentrations. The NTP treatment increased the efficacy of relatively low concentrations of antibiotics. Generally, the highest effect was achieved with GTM, which was able to suppress the metabolic activity of pre-formed P. aeruginosa biofilms in the concentration range of 4-9 mg/L by up to 99%. In addition, an apparent decrease of biofilm-covered area was confirmed after combined NTP treatment and GTM action by SYTO®13 staining using fluorescence microscopy. Scanning electron microscopy confirmed a complete eradication of P. aeruginosa ATCC 15442 mature biofilm from Ti-6Al-4V alloy when using 0.25 h NTP treatment and subsequent treatment by 8.5 mg/L GTM. Therefore, NTP may be used as a suitable antibiofilm agent in combination with antibiotics for the treatment of biofilm-associated infections caused by this pathogen.
- MeSH
- antibakteriální látky farmakologie MeSH
- atmosférický tlak MeSH
- biofilmy účinky léků MeSH
- ceftazidim farmakologie MeSH
- gentamiciny farmakologie MeSH
- mikroskopie elektronová rastrovací MeSH
- plazmové plyny MeSH
- polymyxin B farmakologie MeSH
- Pseudomonas aeruginosa účinky léků metabolismus MeSH
- titan chemie MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ceftazidim aplikace a dávkování farmakologie terapeutické užití MeSH
- cilastatin farmakologie terapeutické užití MeSH
- injekce intravenózní MeSH
- klinické laboratorní techniky MeSH
- krev mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- meningitida vyvolaná Escherichia coli * diagnóza etiologie mikrobiologie MeSH
- počítačová rentgenová tomografie využití MeSH
- vankomycin aplikace a dávkování farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Bacterial resistance to conventional antibiotics is currently one of the most important healthcare issues, and has serious negative impacts on medical practice. This study presents a potential solution to this problem, using the strong synergistic effects of antibiotics combined with silver nanoparticles (NPs). Silver NPs inhibit bacterial growth via a multilevel mode of antibacterial action at concentrations ranging from a few ppm to tens of ppm. Silver NPs strongly enhanced antibacterial activity against multiresistant, β-lactamase and carbapenemase-producing Enterobacteriaceae when combined with the following antibiotics: cefotaxime, ceftazidime, meropenem, ciprofloxacin and gentamicin. All the antibiotics, when combined with silver NPs, showed enhanced antibacterial activity at concentrations far below the minimum inhibitory concentrations (tenths to hundredths of one ppm) of individual antibiotics and silver NPs. The enhanced activity of antibiotics combined with silver NPs, especially meropenem, was weaker against non-resistant bacteria than against resistant bacteria. The double disk synergy test showed that bacteria produced no β-lactamase when treated with antibiotics combined with silver NPs. Low silver concentrations were required for effective enhancement of antibacterial activity against multiresistant bacteria. These low silver concentrations showed no cytotoxic effect towards mammalian cells, an important feature for potential medical applications.
- MeSH
- antibakteriální látky farmakologie MeSH
- beta-laktamasy genetika metabolismus MeSH
- cefotaxim farmakologie MeSH
- ceftazidim farmakologie MeSH
- ciprofloxacin farmakologie MeSH
- Escherichia coli účinky léků enzymologie genetika růst a vývoj MeSH
- exprese genu MeSH
- gentamiciny farmakologie MeSH
- Klebsiella pneumoniae účinky léků enzymologie genetika růst a vývoj MeSH
- kovové nanočástice chemie toxicita MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence účinky léků genetika MeSH
- stříbro farmakologie MeSH
- synergismus léků MeSH
- thienamyciny farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pseudomonas aeruginosa is one of the most frequent and dangerous pathogens involved in the etiology of severe nosocomial infections. A retrospective observational study was conducted at all intensive care units of the University Hospital in Olomouc, Czech Republic (155 ICU beds). Complete antibiotic utilization data of the ICUs in the period of 1999 to 2008 were processed according to ATC/DDD system and expressed in defined daily doses per 100 bed-days (DBD). Utilization of meropenem, imipenem, ciprofloxacin, ofloxacin, pefloxacin, gentamicin, amikacin, ceftazidime, cefoperazone, cefoperazone/sulbactam and piperacillin/tazobactam was measured. Pseudomonas aeruginosa strains were isolated from clinical material obtained from patients hospitalized in ICUs. During the ten-year period, utilization of the entire group of antibiotics monitored grew. It increased from 23.52 DBD in 1999 to 27.48 DBD in 2008 with a peak of 33.04 DBD in 2007. P. aeruginosa accounted for as much as 42% of pneumonias and 23% of surgical wound infections. Our results show that P. aeruginosa strains became gradually resistant to all antibiotics used in the treatment of the infections caused by them, with the exception of amikacin and piperacillin/tazobactam.
- MeSH
- amikacin farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- cefoperazon farmakologie MeSH
- ceftazidim farmakologie MeSH
- ciprofloxacin farmakologie MeSH
- gentamiciny farmakologie MeSH
- jednotky intenzivní péče MeSH
- kyselina penicilanová analogy a deriváty farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence MeSH
- piperacilin farmakologie MeSH
- Pseudomonas aeruginosa účinky léků MeSH
- sulbaktam farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The efficacy of the agents was evaluated on the basis of minimum inhibitory concentration (MIC) and time-kill curve analysis in Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Mycobacterium smegmatis, and Citrobacter braakii; MIC was found to be 0.5, 4.0, 0.015625, 0.0078125, and 0.0625 mg/L in FDC of ceftazidime + sulbactam, respectively, which is lower than ceftazidime and sulbactam individually. Time-kill curve analysis demonstrated maximum killing of bacteria after 4 h. A fixed dose combination of ceftazidime + sulbactam was found to have stronger antibacterial properties than ceftazidime and sulbactam alone at in vitro analysis.
