Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are major causes of hospital-acquired infections and sepsis. Due to increasing antibiotic resistance, new treatments are needed. Mesenchymal stem cells (MSCs) have antimicrobial effects, which can be enhanced by preconditioning with antibiotics. This study investigated using antibiotics to strengthen MSCs against MRSA and P. aeruginosa. MSCs were preconditioned with linezolid, vancomycin, meropenem, or cephalosporin. Optimal antibiotic concentrations were determined by assessing MSC survival. Antimicrobial effects were measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antimicrobial peptide (AMP) gene expression. Optimal antibiotic concentrations for preconditioning MSCs without reducing viability were 1 μg/mL for linezolid, meropenem, and cephalosporin and 2 μg/mL for vancomycin. In MIC assays, MSCs preconditioned with linezolid, vancomycin, meropenem, or cephalosporin inhibited MRSA or P. aeruginosa growth at lower concentrations than non-preconditioned MSCs (p ≤ 0.001). In MBC assays, preconditioned MSCs showed enhanced bacterial clearance compared to non-preconditioned MSCs, especially when linezolid and vancomycin were used against MRSA (p ≤ 0.05). Preconditioned MSCs showed increased expression of genes encoding the antimicrobial peptide genes hepcidin and LL-37 compared to non-preconditioned MSCs. The highest hepcidin expression was seen with linezolid and vancomycin preconditioning (p ≤ 0.001). The highest LL-37 expression was with linezolid preconditioning (p ≤ 0.001). MSCs' preconditioning with linezolid, vancomycin, meropenem, or cephalosporin at optimal concentrations enhances their antimicrobial effects against MRSA and P. aeruginosa without compromising viability. This suggests preconditioned MSCs could be an effective adjuvant treatment for antibiotic-resistant infections. The mechanism may involve upregulation of AMP genes.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antimikrobiální peptidy MeSH
• cefalosporiny farmakologie   MeSH
• hepcidiny farmakologie   terapeutické užití   MeSH
• lidé MeSH
• linezolid farmakologie   terapeutické užití   MeSH
• meropenem farmakologie   terapeutické užití   MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• mezenchymální kmenové buňky * MeSH
• mikrobiální testy citlivosti MeSH
• Pseudomonas aeruginosa genetika   MeSH
• stafylokokové infekce * mikrobiologie   MeSH
• vankomycin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: The objective of this study was to develop a population pharmacokinetic model of meropenem in a heterogeneous population of patients with a serious bacterial infection in order to propose dosing optimisation leading to improved achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target. METHODS: A total of 174 meropenem serum levels obtained from 144 patients during therapeutic drug monitoring were analysed using a non-linear mixed-effects modelling approach and Monte Carlo simulation was then used to compare various dosing regimens in order to optimise PK/PD target attainment. RESULTS: The meropenem volume of distribution of the patient population was 54.95 L, while clearance started at 3.27 L/hour and increased by 0.91 L/hour with each 1 mL/s/1.73 m2 of estimated glomerular filtration rate. Meropenem clearance was also 0.31 L/hour higher in postoperative patients with central nervous system infection. Meropenem administration by continuous infusion showed a significantly higher probability of attaining the PK/PD target than a standard 30 min infusion (95.3% vs 49.5%). CONCLUSIONS: A daily meropenem dose of 3 g, 6 g and 10.5 g administered by continuous infusion was shown to be accurate for patients with moderate to severe renal impairment, normal renal function to mild renal impairment and augmented renal clearance, respectively.

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• bakteriální infekce * farmakoterapie   MeSH
• biologické modely * MeSH
• dospělí MeSH
• intravenózní infuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem * farmakokinetika   aplikace a dávkování   MeSH
• metoda Monte Carlo MeSH
• monitorování léčiv metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Delftia acidovorans je gramnegatívna aeróbna tyčinkovitá baktéria. Ochorenia u ľudí vyvoláva len raritne. Spôsobuje predovšetkým nozokomiálne nákazy, opisované častejšie u imunokompromitovaných pacientov v rámci všetkých vekových skupín. V odbornej literatúre bolo v posledných rokoch publikovaných niekoľko prípadov, v rámci ktorých sa uplatnila pri vzniku infekcií postihujúcich rôzne orgánové systémy. S ohľadom na častú rezistenciu voči aminoglykozidom a polymyxínom, ktoré mnohokrát slúžia ako záchranné liečivá pri komplikovaných infekciách gramnegatívnymi baktériami, nastáva nevyhnutne potreba jej rýchlej identifikácie s následne správne zvolenou liečbou. V kazuistike opisujeme prípad pacientky s rozsiahlym fluidothoraxom hrudníka v dôsledku infekcie baktériou Delftia acidovorans a sumarizujeme aktuálne dostupné informácie o infekciách spôsobených týmto zriedkavým patogénom.

Delftia acidovorans is a Gram-negative, aerobic, rod-shaped bacterium which causes infections in humans only rarely. It causes mostly nosocomial infections, described more frequently in immunocompromised patients across all age groups. In recent years, several cases involving this bacterium in infections affecting various organ systems have been published in the literature. With regard to its common resistance to aminoglycosides and polymyxins, which oftentimes serve as salvage therapy for complicated Gram-negative bacterial infections, there is inevitably a need for its quick identification followed by a correctly chosen treatment. This article describes a case of a patient with extensive pleural effusion due to Delftia acidovorans infection and also summarizes the currently available information on infections caused by this rare pathogen.

• MeSH
• Delftia acidovorans izolace a purifikace   MeSH
• empyém pleurální * diagnóza   etiologie   terapie   MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem aplikace a dávkování   terapeutické užití   MeSH
• mikrobiologické techniky metody   MeSH
• pleurální výpotek diagnóza   terapie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

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

The resistance to carbapenems is usually mediated by enzymes hydrolyzing β-lactam ring. Recently, an alternative way of the modification of the antibiotic, a β-lactone formation by OXA-48-like enzymes, in some carbapenems was identified. We focused our study on a deep analysis of OXA-48-like-producing Enterobacterales, especially strains showing poor hydrolytic activity. In this study, well characterized 74 isolates of Enterobacterales resistant to carbapenems were used. Carbapenemase activity was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), liquid chromatography/mass spectrometry (LC-MS), Carba-NP test and modified Carbapenem Inactivation Method (mCIM). As meropenem-derived β-lactone possesses the same molecular weight as native meropenem (MW 383.46 g/mol), β-lactonization cannot be directly detected by MALDI-TOF MS. In the spectra, however, the peaks of m/z = 340.5 and 362.5 representing decarboxylated β-lactone and its sodium adduct were detected in 25 out of 35 OXA-48-like producers. In the rest 10 isolates, decarboxylated hydrolytic product (m/z = 358.5) and its sodium adduct (m/z = 380.5) have been detected. The peak of m/z = 362.5 was detected in 3 strains co-producing OXA-48-like and NDM-1 carbapenemases. The respective signal was identified in no strain producing class A or class B carbapenemase alone showing its specificity for OXA-48-like carbapenemases. Using LC-MS, we were able to identify meropenem-derived β-lactone directly according to the different retention time. All strains with a predominant β-lactone production showed negative results of Carba NP test. In this study, we have demonstrated that the strains producing OXA-48-like carbapenemases showing false-negative results using Carba NP test and MALDI-TOF MS preferentially produced meropenem-derived β-lactone. We also identified β-lactone-specific peak in MALDI-TOF MS spectra and demonstrated the ability of LC-MS to detect meropenem-derived β-lactone.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny * analýza   MeSH
• beta-laktamasy analýza   MeSH
• Enterobacteriaceae * MeSH
• karbapenemy farmakologie   MeSH
• meropenem farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• Publikační typ
• časopisecké články 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

Carbapenem resistance observed in Klebsiella pneumoniae strains limits treatment options. Therefore, use of antibiotics combined with bioactive compounds may be an important strategy to control K. pneumoniae. The purpose of this study was to evaluate the activity of combination of carvacrol and meropenem on carbapenem-resistant K. pneumoniae (CRKP) strains. The presence of blaOXA-48 carbapenemase in all 25 CRKP strains was identified using the PCR technique. The combination of carvacrol and meropenem was tested for antimicrobial activity on CRKP strains. The minimum inhibitory concentrations of carvacrol and meropenem were detected within a range of 32-128 μg/mL using the broth microdilution method. Synergy between carvacrol and meropenem was observed on 8 of the 25 CRKP strains by checkerboard assay (FICI = 0.5) and confirmed by time-kill assay. According to the live-dead test results, the viability percentage of the cells exposed to synergistic combination was 35.47% at the end of 24 h. The membrane damage caused by the synergistic combination was spectrophotometrically measured (A = 0.21) and further confirmed by SEM analysis. According to the MTT assay, both carvacrol and meropenem did not show any statistically significant cytotoxic effect on Vero cells (p > 0.05). In conclusion, the results suggest that carvacrol and meropenem can act synergistically to inhibit the growth of CRKP.

• MeSH
• antibakteriální látky farmakologie   MeSH
• beta-laktamasy * genetika   MeSH
• Cercopithecus aethiops MeSH
• cymeny MeSH
• karbapenemy farmakologie   MeSH
• Klebsiella pneumoniae * MeSH
• meropenem farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• synergismus léků MeSH
• Vero buňky MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články 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

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

OBJECTIVES: In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated. METHODS: Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7-14 days after the end of therapy) in the microbiological ITT (mITT) population. RESULTS: The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: -4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: -18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: -4.51 to 19.38], respectively, were also comparable. CONCLUSIONS: In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.

• MeSH
• antibakteriální látky * terapeutické užití   MeSH
• bakteriální pneumonie * farmakoterapie   MeSH
• cefalosporiny terapeutické užití   MeSH
• lidé MeSH
• mechanické ventilátory MeSH
• meropenem terapeutické užití   MeSH
• mikrobiální testy citlivosti MeSH
• nemocnice MeSH
• prospektivní studie MeSH
• Pseudomonas aeruginosa MeSH
• tazobaktam terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH