Antimicrobial susceptibility was determined for clinical gram-negative isolates from Czech Republic, Hungary, and Poland, where published data for ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL) is scarce. C/T was active against 94.3% of Enterobacterales, 10-18% higher than the tested cephalosporins and piperacillin/tazobactam. IMI/REL was the most active tested agent against non-Morganellaceae Enterobacterales (99.7% susceptible). C/T was the most active among all studied agents except colistin against Pseudomonas aeruginosa (96.0% susceptible); susceptibility to IMI/REL was 90.7%. C/T maintained activity against 73.7-85.3% of β-lactam-resistant or multidrug-resistant P. aeruginosa subsets. C/T and IMI/REL could represent important treatment options for patients from these countries.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- cefalosporiny terapeutické užití MeSH
- imipenem farmakologie terapeutické užití MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- pseudomonádové infekce * farmakoterapie mikrobiologie MeSH
- Pseudomonas aeruginosa MeSH
- tazobaktam farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Maďarsko MeSH
- Polsko MeSH
Predkladaný článok popisuje využitie rezervného karbapenemového antibiotika imipeném v kombinácii s novým inhibítorom b-laktamázy relebaktámom v liečbe ventilátorovej pneumónie vznikajúcej v teréne infekcie SARS-CoV-2 u mladej gravidnej pacientky. V úvode stručne popisuje mechanizmus a spektrum účinku antibiotika, vrátane jeho dávkovania.
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- Klíčová slova
- relebaktam,
- MeSH
- antibakteriální látky aplikace a dávkování MeSH
- císařský řez MeSH
- COVID-19 komplikace terapie MeSH
- farmakoterapie COVID-19 MeSH
- fixní kombinace léků MeSH
- inhibitory beta-laktamasy aplikace a dávkování farmakologie MeSH
- kombinace léků imipenem a cilastatin * aplikace a dávkování farmakologie MeSH
- komplikace těhotenství farmakoterapie terapie MeSH
- lidé MeSH
- mladý dospělý MeSH
- pneumonie etiologie farmakoterapie terapie MeSH
- těhotenství MeSH
- ventilátorová pneumonie * etiologie farmakoterapie terapie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Aims: To describe the aetiology and microbial susceptibility profile of endophthalmitis cases treated at an ophthalmological referral centre in Colombia. Material and Methods: A retrospective descriptive study was carried out with all endophthalmitis cases referred to the Fundación Oftalmológica de Santander FOSCAL (Floridablanca, Colombia) from 1 January 2012 to 31 December 2015. Results: 121 eyes of 121 patients were evaluated. 77.7% of them were male and the mean age was 42.9 years. Five of them (4.1%) corresponded to endogenous endophthalmitis, and 116 (95.9%) to exogenous endophthalmitis. Of the latter, 66.9% were associated with trauma (almost one-half of them associated with intraocular foreign body), and 29.5% with intraocular surgery. The most common isolated microorganisms in the exogenous endophthalmitis group corresponded to methicillin-resistant and methicillin-sensitive strains of Staphylococcus epidermidis and Staphylococcus aureus, which were mostly susceptible to imipenem, vancomycin and moxifloxacin and resistant to ceftazidime. Conclusion: Endophthalmitis is a potentially sight-threatening condition, especially in cases of inadequate treatment. Therefore, antimicrobial therapy should be guided by vitreous humour culture to assure that the causative microorganism is susceptible to the selected agent. The results of our study lead us to propose vancomycin, moxifloxacin or imipenem as first-line antimicrobial options.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- endoftalmitida * epidemiologie etiologie MeSH
- imipenem terapeutické užití MeSH
- lidé MeSH
- moxifloxacin terapeutické užití MeSH
- oční infekce bakteriální farmakoterapie komplikace MeSH
- retrospektivní studie MeSH
- vankomycin terapeutické užití MeSH
- Check Tag
- lidé MeSH
This study sought to reveal the proteomic profiling of methicillin-resistant Staphylococcus aureus (MRSA)-derived extracellular vesicles (EVs) after exposure to imipenem. The advanced isobaric tags for relative and absolute quantitation (iTRAQ®) proteomic approach were used to analyze the alterations in MRSA-derived EV protein patterns upon exposure to imipenem. A total of 1260 EV proteins were identified and quantified. Among these, 861 differentially expressed exosome proteins (P < 0.05) were found. Multivariate analysis, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the identified proteins. Enrichment analysis of GO annotations indicated that imipenem primarily regulated the metabolic processes in MRSA. The metabolism of differentially expressed proteins was found to be the most significant in the combined analysis of the KEGG pathway analysis. Based on the results from the STRING analysis, 50S ribosomal protein L16 (RplP) and 30S ribosomal protein S8 (RpsH) were involved in the imipenem-induced MRSA-derived EVs. These results provide vital information on MRSA-derived EVs, increasing our knowledge of the proteome level changes in EVs upon exposure to imipenem. Moreover, these results pave the way for developing novel MRSA treatments.
1. The underlying microbial metabolic activity toward xenobiotics is among the least explored factors contributing to the inter-individual variability in drug response. 2. Here, we analyzed the effect of microbiota on a non-steroidal anti-inflammatory drug nabumetone. 3. First, we cultivated the drug with the selected gut commensal and probiotic bacteria under both aerobic and anaerobic conditions and analyzed its metabolites by high-performance liquid chromatography (HPLC) with UV detection. To analyze the effect of microbiota on nabumetone pharmacokinetics in vivo, we administered a single oral dose of nabumetone to rodents with intentionally altered gut microbiome - either rats treated for three days with the antibiotic imipenem or to germ-free mice. Plasma levels of its main active metabolite 6 methoxy-2-naphthylacetic acid (6-MNA) were analyzed at pre-specified time intervals using HPLC with UV/fluorescence detection. 4. We found that nabumetone is metabolized by bacteria to its non-active metabolites and that this effect is stronger under anaerobic conditions. Although in vivo, none of the pharmacokinetic parameters of 6-MNA was significantly altered, there was a clear trend towards an increase of the AUC, Cmax and t1/2 in rats with reduced microbiota and germ-free mice.
- MeSH
- anaerobióza MeSH
- antibakteriální látky farmakologie MeSH
- antiflogistika nesteroidní metabolismus farmakokinetika MeSH
- biologická dostupnost MeSH
- imipenem farmakologie MeSH
- kyseliny naftalenoctové metabolismus farmakokinetika MeSH
- myši inbrední BALB C MeSH
- nabumeton metabolismus farmakokinetika MeSH
- organismy bez specifických patogenů MeSH
- potkani Wistar MeSH
- střevní mikroflóra účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
BACKGROUND: Sepsis is a life-threatening organ dysfunction caused the dysregulation of host inflammatory response and immunosuppression to infection Early recognition and intervention are hence of paramount importance. In this respect the "sepsis bundle" was proposed in 2004 to be instituted in cases of suspected sepsis. OBJECTIVE AND HYPOTHESIS: We hypothesised that a combination treatment of the sepsis bundle with cyclophosphamide would improve the function of the intestinal mucosa and enhance survival in rats with induced sepsis. METHODS AND RESULTS: Sprague-Dawley rats were divided into 5 different groups: sham, cecal ligation and puncture (CLP), cyclophosphamide (CTX), imipenem+normal saline (NS) and imipenem+NS+CTX. Cecal ligation and puncture were used for inducing the polymicrobial sepsis. Western-blot was used to measure the occludin protein, and ELISA for examining the plasma level of cytokines IL-6, IL-10 and TNF-α. TUNEL assay for testing the intestinal mucosal apoptosis, and hematoxylin-eosin staining for observing the intestinal mucosal changes. The permeability of intestinal mucosa was determined by the plasma level of FD-70. The results showed that the combination treatment of the sepsis bundle with cyclophosphamide attenuated cytokine levels, inhibited epithelial cell apoptosis and improved the function of the intestinal barrier. The survival rate of the group treated with the combined therapy was significantly higher than that of the other groups. CONCLUSION: The combination treatment of sepsis bundle with cyclophosphamide improves the function of the intestinal barrier and enhances survival in septic rats.
- MeSH
- antibakteriální látky farmakologie MeSH
- apoptóza účinky léků MeSH
- chlorid sodný farmakologie MeSH
- cyklofosfamid farmakologie MeSH
- cytokiny metabolismus MeSH
- fixní kombinace léků MeSH
- imipenem farmakologie MeSH
- imunosupresiva farmakologie MeSH
- okludin metabolismus MeSH
- permeabilita účinky léků MeSH
- potkani Sprague-Dawley MeSH
- sepse farmakoterapie mortalita MeSH
- střevní sliznice účinky léků mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A comparison of carbapenem molecules for the detection of carbapenemase-producing bacteria by MALDI-TOF MS showed that imipenem exhibited higher sensitivity (97%) and specificity (100%) scores for Pseudomonas aeruginosa than meropenem. However, meropenem was more efficient (98% sensitivity and 100% specificity) against Enterobacteriaceae.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální proteiny analýza metabolismus MeSH
- bakteriologické techniky metody MeSH
- beta-laktamasy analýza metabolismus MeSH
- Enterobacteriaceae účinky léků enzymologie MeSH
- imipenem farmakologie MeSH
- karbapenemy farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- Pseudomonas aeruginosa účinky léků enzymologie MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice metody MeSH
- thienamyciny farmakokinetika MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT>MIC, 40%fT>MIC and 100%fT>MIC. For the target of 40%fT>MIC, all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT>MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT>MIC and 100%fT>MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary.
- MeSH
- antibakteriální látky aplikace a dávkování farmakokinetika MeSH
- bakteriální pneumonie farmakoterapie MeSH
- časové faktory MeSH
- gramnegativní bakterie účinky léků MeSH
- imipenem aplikace a dávkování farmakokinetika MeSH
- infekce spojené se zdravotní péčí farmakoterapie MeSH
- intravenózní infuze metody MeSH
- krevní plazma chemie MeSH
- kritický stav MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- senioři MeSH
- Staphylococcus aureus účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
VIM-39, a VIM-1-like metallo-β-lactamase variant (VIM-1 Thr33Ala His224Leu) was identified in a clinical isolate of Klebsiella pneumoniae belonging to sequence type 147. VIM-39 hydrolyzed ampicillin, cephalothin, and imipenem more efficiently than did VIM-1 and VIM-26 (a VIM-1 variant with the His224Leu substitution) because of higher turnover rates.
- MeSH
- ampicilin metabolismus farmakologie MeSH
- antibakteriální látky metabolismus farmakologie MeSH
- beta-laktamasy genetika metabolismus MeSH
- beta-laktamová rezistence genetika MeSH
- biotransformace MeSH
- cefalothin metabolismus farmakologie MeSH
- exprese genu MeSH
- hydrolýza MeSH
- imipenem metabolismus farmakologie MeSH
- infekce bakteriemi rodu Klebsiella farmakoterapie mikrobiologie MeSH
- izoenzymy genetika metabolismus MeSH
- kinetika MeSH
- Klebsiella pneumoniae účinky léků enzymologie genetika izolace a purifikace MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární sekvence - údaje MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- techniky typizace bakterií MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Řecko MeSH
Syndromem diabetické nohy označujeme destruktivní postižení tkání dolních končetin diabetiků distálně od kotníku, jehož následkem jsou rozsáhlé ulcerace, gangrény a v krajních případech i nutnost amputace končetiny. Hlavní faktory, které vedou ke vzniku diabetické nohy, jsou diabetická neuropatie (senzomotorická a viscerální), ischemie končetiny (angiopatie), snížení kloubní pohyblivosti a působení tlaku na plosku nohy. Na vzniku a obtížném hojení ulcerací se často podílí infekce. Z přítomnosti těchto faktorů potom vyplývá i léčebná strategie, v níž se významně uplatňuje i použití farmakoterapie. Jedná se zejména o antibiotickou, antiagregační/antikoagulační léčbu a ovlivnění mikrocirkulace. V textu rozebíráme jednotlivé možnosti farmakoterapie.
Diabetic foot syndrome refers to a foot that exhibits pathological changes below the ankle – ulcerations or gangrenes that result directly from diabetes mellitus. The major factors that can cause the diabetic foot syndrome are diabetic neuropathy, limb ischaemia (angiopathy), limited joint mobility, and plantar pressure. Healing is complicated by infection. These factors should be targeted in our treatment strategy that includes pharmacotherapy as well. Antimicrobial, antiplatelet/anticoagulant treatment and drugs improving microcirculation are mainly used
- Klíčová slova
- trimetoprim - cotrimoxazol, ciprofloxacin - metronidazol, kyselina acetylsalicylová - clopidogrel, diabetická makroangiopatie,
- MeSH
- alprostadil aplikace a dávkování farmakologie terapeutické užití MeSH
- amoxicilin * terapeutické užití MeSH
- ampicilin * analogy a deriváty aplikace a dávkování farmakologie terapeutické užití MeSH
- antibakteriální látky * aplikace a dávkování farmakologie terapeutické užití MeSH
- aztreonam * terapeutické užití MeSH
- cefalexin * terapeutické užití MeSH
- cefalosporiny * aplikace a dávkování farmakologie terapeutické užití MeSH
- ceftazidim * terapeutické užití MeSH
- ciprofloxacin * terapeutické užití MeSH
- diabetes mellitus * MeSH
- diabetická noha * diagnóza etiologie farmakoterapie terapie MeSH
- hojení ran * MeSH
- hypolipidemika aplikace a dávkování farmakologie terapeutické užití MeSH
- imipenem * terapeutické užití MeSH
- infekce * diagnóza farmakoterapie mikrobiologie MeSH
- inhibitory agregace trombocytů * terapeutické užití MeSH
- klindamycin * terapeutické užití MeSH
- levofloxacin * terapeutické užití MeSH
- lidé MeSH
- mikrocirkulace fyziologie účinky léků MeSH
- oxacilin * aplikace a dávkování farmakologie terapeutické užití MeSH
- piperacilin * terapeutické užití MeSH
- prostaglandiny * aplikace a dávkování farmakologie terapeutické užití MeSH
- vankomycin * terapeutické užití MeSH
- vazodilatancia aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
