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
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
The objective of this study was to assess the susceptibility of cefiderocol against multidrug-resistant carbapenemase-producing and nonproducing bacteria. The panel comprised 182 isolates of the order Enterobacterales, and 40 strains of Pseudomonas aeruginosa. Antimicrobial susceptibility testing has been performed using broth microdilution method according to the European Committee on Antimicrobial Susceptibility Testing recommendations. Mass spectrometry matrix-assisted laser desorption/ionization-time of flight mass spectrometry and carbapenemase-producing test were used to verify the presence of carbapenemases in clinical isolates. The genetic expression of single carbapenemases (blaKPC, blaOXA-48, blaNDM, blaVIM, blaIMP, blaGES) was determined by real-time polymerase chain reaction. Cefiderocol exhibited a good activity against the majority of strains tested in this study. Altogether, growth of 81.9% (n = 149) strains of the order Enterobacterales and 77.5% (n = 31) of P. aeruginosa isolates were inhibited at minimal inhibitory concentration (MIC) ≤2 mg/L. Values MIC50/MIC90 were 0.5/8 mg/L for enterobacteria, and 1/8 mg/L for P. aeruginosa. One isolate (Klebsiella pneumoniae) harboring two carbapenemases (blaOXA-48, blaNDM) had cefiderocol MIC 0.5 mg/L. In enterobacteria resistant to cefiderocol, blaNDM carbapenemase prevailed (43.3%, n = 29), followed by blaOXA-48 (31.3%, n = 21) and blaKPC (4.5%, n = 3). blaIMP (n = 8) and blaVIM (n = 1) metallo-β-lactamases dominated in cefiderocol-resistant P. aeruginosa (n = 9) isolates. Very good susceptibility (100%) to this drug showed blaGES-positive strains of P. aeruginosa (n = 8) and isolates resistant to meropenem without confirmed carbapenemase gene (n = 10). In this study, cefiderocol demonstrated potent activity against important nosocomial pathogens, therefore, therapeutic options of this drug against multidrug-resistant bacteria should be considered.
PURPOSE: In this review we present the status of the prevalence of bacteria resistant to antibiotics and the main antibiotic resistance genes that are reported in infections acquired in intensive care units (ICU) around the world. METHODS: A systematic review based on the PRISMA guide was carried out, from the Science Direct, Redalyc, Scopus, Hinari, Scielo, Dialnet, PLOS, ProQuest, Taylor, Lilacs and PubMed/Medline databases. Inclusion criteria of this review were original research study published in a scientific journal in a 10-year time span from 1 January 2017 and 30 April 2022. RESULTS: A total of 1686 studies were identified, but only 114 studies were considered eligible for inclusion. Klebsiella pneumoniae and Escherichia coli resistant to carbapenems and producers of extended-spectrum β-lactamases (ESBL) are the most frequently isolated pathogens in ICUs in Asia, Africa and Latin America. The blaOXA and blaCTX were antibiotic resistance genes (ARG) most commonly reported in different geographic regions (in 30 and 28 studies, respectively). Moreover, multidrug-resistant (MDR) strains were reported in higher frequency in hospital-acquired infections. Reports of MDR strains vary between continents, with the majority of publications being in Asia and between countries, with Egypt and Iran being highlighted. There is a predominance of few bacterial clones with MDR phenotype, for example, clonal complex 5 Methicillin-Resistant Staphylococcus aureus (CC5-MRSA) circulates frequently in hospitals in the United States, clone ST23-K. pneumoniae is reported in India and Iran, and clone ST260 carbapenemase-producing P. aeruginosa in the United States and Estonia. CONCLUSION: Our systematic review reveals that ESBL- and carbapenemase-producing K. pneumoniae and E. coli are the most problematic bacteria that are reported, mainly in tertiary hospitals in Asia, Africa, and Latin America. We have also found propagation of dominant clones with a high degree of MDR, becoming a problem due to its high capacity to cause morbidity, mortality and additional hospital costs.
- MeSH
- antibakteriální látky MeSH
- Escherichia coli MeSH
- infekce spojené se zdravotní péčí * farmakoterapie epidemiologie MeSH
- karbapenemy MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- nemocnice MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Fosfomycin (FOS) has been recently reintroduced into clinical practice, but its effectiveness against multidrug-resistant (MDR) Enterobacterales is reduced due to the emergence of FOS resistance. The copresence of carbapenemases and FOS resistance could drastically limit antibiotic treatment. The aims of this study were (i) to investigate fosfomycin susceptibility profiles among carbapenem-resistant Enterobacterales (CRE) in the Czech Republic, (ii) to characterize the genetic environment of fosA genes among the collection, and (iii) to evaluate the presence of amino acid mutations in proteins involved in FOS resistance mechanisms. During the period from December 2018 to February 2022, 293 CRE isolates were collected from different hospitals in the Czech Republic. FOS MICs were assessed by the agar dilution method (ADM), FosA and FosC2 production was detected by the sodium phosphonoformate (PPF) test, and the presence of fosA-like genes was confirmed by PCR. Whole-genome sequencing was conducted with an Illumina NovaSeq 6000 system on selected strains, and the effect of point mutations in the FOS pathway was predicted using PROVEAN. Of these strains, 29% showed low susceptibility to fosfomycin (MIC, ≥16 μg/mL) by ADM. An NDM-producing Escherichia coli sequence type 648 (ST648) strain harbored a fosA10 gene on an IncK plasmid, while a VIM-producing Citrobacter freundii ST673 strain harbored a new fosA7 variant, designated fosA7.9. Analysis of mutations in the FOS pathway revealed several deleterious mutations occurring in GlpT, UhpT, UhpC, CyaA, and GlpR. Results regarding single substitutions in amino acid sequences highlighted a relationship between ST and specific mutations and an enhanced predisposition for certain STs to develop resistance. This study highlights the occurrence of several FOS resistance mechanisms in different clones spreading in the Czech Republic. IMPORTANCE Antimicrobial resistance (AMR) currently represents a concern for human health, and the reintroduction of antibiotics such as fosfomycin into clinical practice can provide further option in treatment of multidrug-resistant (MDR) bacterial infections. However, there is a global increase of fosfomycin-resistant bacteria, reducing its effectiveness. Considering this increase, it is crucial to monitor the spread of fosfomycin resistance in MDR bacteria in clinical settings and to investigate the resistance mechanism at the molecular level. Our study reports a large variety of fosfomycin resistance mechanisms among carbapenemase-producing Enterobacterales (CRE) in the Czech Republic. Our study summarizes the main achievements of our research on the use of molecular technologies, such as next-generation sequencing (NGS), to describe the heterogeneous mechanisms that reduce fosfomycin effectiveness in CRE. The results suggest that a program for widespread monitoring of fosfomycin resistance and epidemiology fosfomycin-resistant organisms can aide timely implementation of countermeasures to maintain the effectiveness of fosfomycin.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- beta-laktamasy genetika MeSH
- Escherichia coli MeSH
- fosfomycin * farmakologie MeSH
- karbapenemy farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika 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
Enterobacter spp. and Klebsiella aerogenes are rod-shaped Gram-negative opportunistic pathogens. This study aimed at the molecular and genomic characterization of multidrug resistant Enterobacter spp. and K. aerogenes isolates recovered from hospitalized patients in a tertiary care hospital in Lebanon. A total of 59 Enterobacter spp. clinical isolates consisting of 41 carbapenem-resistant and 18 susceptible by Etest were included in this study. Genotypic identification through whole-genome sequencing (WGS) was performed and confirmed in silico. Resistance and plasmid profiles were studied using ResFinder4.0 and Plasmid-Finder2.1. Multilocus sequence typing (MLST) was used to determine the isolates' clonality. Using the average nucleotide identity (ANI) we identified and confirmed that 47 (80%) isolates were E. hormaechei, 11 (18%) were Klebsiella aerogenes and 1 (2%) was an E. cloacae. Carbapenem-resistance was detected among 41 isolates all showing an MIC90 of ≥ 32 μg/mL for ertapenem, imipenem, and meropenem. blaNDM-1 (58.5%), blaACT-16 (54%), and blaOXA-1 (54%) were the most common detected β-lactamases, while blaCTX-M-15 (68%) was the main detected extended-spectrum β-lactamase (ESBL) encoding gene. Chromosomal ampC, carbapenemase encoding genes, and porin modifications were among the detected carbapenem resistance determinants. The carbapenemase encoding genes were linked to three well-defined plasmid Inc groups, IncFII/IncFIB, IncX3, and IncL. MLST typing revealed the diversity within the studied isolates, with ST114 being the most common among the studied E. hormaechei.: The spread of carbapenem-resistant isolates in clinical settings in Lebanon is a serious challenge. Screening and continuous monitoring through WGS analysis could effectively limit the dissemination of drug-resistant isolates in hospitalized patients. IMPORTANCE Drug resistance is an increasing global public health threat that involves most disease-causing organisms and antimicrobial drugs. Drug-resistant organisms spread in health care settings, and resistance to multiple drugs is common. Our study demonstrated the mechanisms leading to resistance against the last resort antimicrobial agents among members of the Enterobacteriaceae family. The spread of carbapenem-resistant bacteria in clinical settings is a serious challenge. Screening and continuous monitoring could effectively limit the dissemination of drug-resistant isolates in hospitalized patients.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- bakteriální proteiny genetika MeSH
- beta-laktamasy genetika MeSH
- Enterobacter aerogenes * genetika MeSH
- Enterobacter genetika MeSH
- karbapenemy farmakologie MeSH
- Klebsiella pneumoniae genetika MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Libanon 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 farmakoterapie komplikace terapie 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
