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
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Antimicrobial Peptides MeSH
- Cephalosporins pharmacology MeSH
- Hepcidins pharmacology therapeutic use MeSH
- Humans MeSH
- Linezolid pharmacology therapeutic use MeSH
- Meropenem pharmacology therapeutic use MeSH
- Methicillin-Resistant Staphylococcus aureus * MeSH
- Mesenchymal Stem Cells * MeSH
- Microbial Sensitivity Tests MeSH
- Pseudomonas aeruginosa genetics MeSH
- Staphylococcal Infections * microbiology MeSH
- Vancomycin MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Pneumonie patří v dětském věku mezi častá infekční onemocnění. Jejich průběh může být nekomplikovaný, avšak mohou také vést k respiračnímu selhání, které vyžaduje hospitalizaci na jednotce intenzivní a resuscitační péče. Součástí léčby respiračního selhání je podpora či náhrada plicních funkcí pomocí oxygenoterapie, neinvazivní a invazivní umělé plicní ventilace a dále postupy zahrnující aplikaci inhalačního oxidu dusnatého, či pronační polohu. V případech, kdy tyto metody selhávají, je nezbytná mimotělní podpora životních funkcí. V následující kazuistice popisujeme komplikovaný průběh pneumonie u šestiletých dvojčat, jejichž zdravotní stav vyžadoval z důvodu kritických plicních funkcí připojení na mimotělní oběh s membránovou oxygenací.
Pneumonia is a common infectious disease in childhood. Its course may be uncomplicated, but it can also lead to respiratory failure requiring hospitalisation in the paediatric intensive care unit. The treatment of respiratory insufficiency includes support or replacement of lung function by oxygen therapy, non-invasive and invasive mechanical ventilation, and procedures such as inhaled nitric oxide or prone positioning. In situations where these methods fail, extracorporeal life support is necessary. In the following case report, we discuss the complicated course of pneumonia in six-year-old twins whose medical condition required connection to extracorporeal membrane oxygenation due to critical lung function.
- MeSH
- Ceftriaxone pharmacology therapeutic use MeSH
- Child MeSH
- Twins MeSH
- Respiratory Syncytial Virus Infections diagnosis drug therapy classification complications MeSH
- Coinfection etiology classification microbiology MeSH
- Humans MeSH
- Linezolid pharmacology therapeutic use MeSH
- Extracorporeal Membrane Oxygenation * methods MeSH
- Pneumonia, Pneumococcal diagnosis drug therapy complications MeSH
- Pneumonia * diagnosis etiology drug therapy classification microbiology MeSH
- Radiography, Thoracic methods MeSH
- Respiratory Insufficiency diagnosis etiology complications therapy MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
AIM: To investigate the epidemiology of Clostridioides difficile infection (CDI) in Slovakian hospitals after the emergence of ribotype 176 (027-like) in 2016. METHODS: Between 2018 and 2019, European Centre for Disease Control and Prevention CDI surveillance protocol v2.3 was applied to 14 hospitals, with additional data collected on recent antimicrobial use and the characterization of C. difficile isolates. RESULTS: The mean hospital incidence of CDI was 4.1 cases per 10,000 patient bed-days. One hundred and five (27.6%) in-hospital deaths were reported among the 381 cases. Antimicrobial treatment within the previous 4 weeks was recorded in 90.5% (333/368) of cases. Ribotype (RT)176 was detected in 50% (n=185/370, 14 hospitals) and RT001 was detected in 34.6% (n=128/370,13/14 hospitals) of cases with RT data. Overall, 86% (n=318/370) of isolates were resistant to moxifloxacin by Thr82Ile in GyrA (99.7%). Multi-locus variable tandem repeat analysis showed clonal relatedness of predominant RTs within and between hospitals. Seven of 14 sequenced RT176 isolates and five of 13 RT001 isolates showed between zero and three allelic differences by whole-genome multi-locus sequence typing. The majority of sequenced isolates (24/27) carried the erm(B) gene and 16/27 also carried the aac(6')-aph(2'') gene with the corresponding antimicrobial susceptibility phenotypes. Nine RT176 strains carried the cfr(E)gene and one RT001 strain carried the cfr(C) gene, but without linezolid resistance. CONCLUSIONS: The newly-predominant RT176 and endemic RT001 are driving the epidemiology of CDI in Slovakia. In addition to fluoroquinolones, the use of macrolide-lincosamide-streptogramin B antibiotics can represent another driving force for the spread of these epidemic lineages. In C. difficile, linezolid resistance should be confirmed phenotypically in strains with detected cfr gene(s).
- MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Clostridioides difficile * genetics MeSH
- Clostridioides genetics MeSH
- Fluoroquinolones pharmacology MeSH
- Clostridium Infections * epidemiology drug therapy MeSH
- Humans MeSH
- Linezolid MeSH
- Macrolides MeSH
- Microbial Sensitivity Tests MeSH
- Multilocus Sequence Typing MeSH
- Ribotyping MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Slovakia MeSH
Notwithstanding the fact that streptomycetes are overlooked in clinical laboratories, studies describing their occurrence in disease and potential pathogenicity are emerging. Information on their species diversity in clinical specimens, aetiology and appropriate therapeutic treatment is scarce. We identified and evaluated the antibiotic susceptibility profile of 84 Streptomyces clinical isolates from the Czech Republic. In the absence of appropriate disk diffusion (DD) breakpoints for antibiotic susceptibility testing (AST) of Streptomyces spp., we determined DD breakpoints by correlation with the broth microdilution method and by the distribution of zone diameters among isolates. Correlation accuracy was high for 9 antibiotics, leading to the establishment of the most valid DD breakpoints for Streptomyces antibiotic susceptibility evaluation so far. Clinical strains belonged to 17 different phylotypes dominated by a cluster of strains sharing the same percentage of 16S rRNA gene sequence identity with more than one species (S. albidoflavus group, S. hydrogenans, S. resistomycificus, S. griseochromogenes; 70% of isolates). AST results showed that Streptomyces exhibited intrinsic resistance to penicillin, general susceptibility to amikacin, gentamycin, vancomycin and linezolid, and high percentage of susceptibility to tetracyclines and clarithromycin. For the remaining antibiotics, AST showed inter- and intra-species variations when compared to available literature (erythromycin, trimethoprim-sulfamethoxazole), indicating a region-dependent rather than species-specific patterns.
Linezolid is an antibiotic increasingly used for treatment of resistant Gram-positive infections, which blocks bacterial proteosythesis through direct inhibition of mitochondrial ribosomes. The most common adverse effects of linezolid include gastrointestinal symtoms, peripheral neuropathy, bone marrow depression and lactic acidosis. Here we present a rare case of a 9-year-old female, a survivor of acute lymphoblastic leukemia (ALL) and a hematopoietic stem cell transplant (HSCT), who developed life-threatening lactic acidosis with vomiting, impaired consciousness and Kussmaul breathing after 51 days of intravenous linezolid administration due to mycobacterial infection. She fully recovered after drug discontinuation and normalization of the plasma levels. We conclude that plasma lactate concentrations should be monitored closely during any linezolid treatment, particularly in patients with hepatic or renal dysfunction.
- MeSH
- Acidosis, Lactic * chemically induced MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma * drug therapy MeSH
- Anti-Bacterial Agents adverse effects MeSH
- Bacteria MeSH
- Child MeSH
- Humans MeSH
- Linezolid adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Nekrotizující pneumonie způsobená kmenem Staphylococcus aureuss produkcí Panton-Va-lentinova leukocidinu (PVL-SA) je v České republice prozatím raritní diagnóza, ovšem kvůlifulminantnímu průběhu s vysokou mortalitou představuje závažný problém. Vzhledem k ros-toucí celosvětové incidenci je pravděpodobné, že se s touto diagnózou budeme v budoucnupotýkat častěji. Postihuje většinou mladší jedince v návaznosti na virovou respirační infekcis rychlým vznikem septického šoku a respiračním selháním. Základem pro diagnostiku jedůkaz genů pro PVL metodou PCR. Neexistují jednoznačné doporučené postupy pro léčbu,jako lék volby se jeví linezolid a klindamycin. V kazuistice přinášíme první potvrzený případv historii našeho pracoviště.
Necrotizing pneumonia caused by Staphylococcus aureuswith Panton-Valentine leukocidinproduction is a temporary and rare diagnosis in the Czech Republic. It is a serious problemdue to the fulminant course with high mortality. Given the increasing worldwide incidence,it is likely that we will have to deal with this diagnosis more often in the future. It primarilyaffects younger individuals following a viral respiratory infection with rapid septic shock andrespiratory failure. The proof of PVL genes by PCR method is the basis for diagnosis. Thereare no guidelines for treatment, but for now linezolid and clindamycin appear to be the drugof choice. In the case report we introduce the first confirmed case in the history of our work-place.
- Keywords
- Pantonův-Valentinův leukocidin,
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Pneumonia, Bacterial etiology therapy MeSH
- Adult MeSH
- Humans MeSH
- Linezolid administration & dosage therapeutic use MeSH
- Pneumonia, Necrotizing * etiology drug therapy complications MeSH
- Critical Care MeSH
- Pleural Effusion etiology complications therapy MeSH
- Pulmonary Aspergillosis etiology complications MeSH
- Pneumonia, Staphylococcal * diagnosis complications therapy MeSH
- Pneumonia etiology drug therapy complications MeSH
- Radiography, Thoracic MeSH
- Heart Failure etiology complications therapy MeSH
- Staphylococcal Infections drug therapy complications physiopathology MeSH
- Staphylococcus aureus MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Antitubercular Agents MeSH
- Cycloserine administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Diarylquinolines administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Fluoroquinolones administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Clofazimine administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Humans MeSH
- Linezolid administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Tuberculosis, Multidrug-Resistant * drug therapy MeSH
- Check Tag
- Humans MeSH
Cancer cells are known to reprogram their metabolism to adapt to adverse conditions dictated by tumor growth and microenvironment. A subtype of cancer cells with stem-like properties, known as cancer stem cells (CSC), is thought to be responsible for tumor recurrence. In this study, we demonstrated that CSC and chemoresistant cells derived from triple negative breast cancer cells display an enrichment of up- and downregulated proteins from metabolic pathways that suggests their dependence on mitochondria for survival. Here, we selected antibiotics, in particular - linezolid, inhibiting translation of mitoribosomes and inducing mitochondrial dysfunction. We provided the first in vivo evidence demonstrating that linezolid suppressed tumor growth rate, accompanied by increased autophagy. In addition, our results revealed that bactericidal antibiotics used in combination with autophagy blocker decrease tumor growth. This study puts mitochondria in a spotlight for cancer therapy and places antibiotics as effective agents for eliminating CSC and resistant cells.
- MeSH
- Drug Resistance, Neoplasm * drug effects MeSH
- Humans MeSH
- Linezolid administration & dosage pharmacology MeSH
- Metabolic Networks and Pathways * drug effects MeSH
- Mitochondria drug effects metabolism MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells drug effects metabolism MeSH
- Tumor Microenvironment drug effects MeSH
- Cell Proliferation drug effects MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Neoplasm Transplantation MeSH
- Triple Negative Breast Neoplasms drug therapy metabolism pathology MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Laktátová acidóza je vzácnou, ale závažnou komplikací léčby oxazolidinonovým antibiotikem linezolidem. Prezentujeme kazuistiku 67letého muže léčeného 26 dnů linezolidem pro osteomyelitidu pravé nohy a následnou stafylokokovou sepsi. V průběhu léčby se vyvinula těžká laktátová acidóza s nutností hospitalizace na jednotce intenzivní péče (JIP). V příspěvku je popsán pravděpodobný mechanismus vzniku této potenciálně život ohrožující komplikace.
Lactic acidosis is a rare but serious adverse event linked to treatment with linezolid, an oxazolidinone antibiotic. Presented is a case of a 67-year-old man treated for 26 days with linezolid for staphylococcal osteomyelitis of the right foot with subsequent sepsis. During the course of treatment, severe lactic acidosis developed, requiring hospitalization in an intensive care unit. The likely mechanism of this potentially life-threatening complication is discussed.
- MeSH
- Acidosis, Lactic * etiology MeSH
- Humans MeSH
- Linezolid adverse effects MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Acute Disease MeSH
- Aminoglycosides administration & dosage pharmacology adverse effects MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Skin Diseases, Bacterial * drug therapy blood microbiology MeSH
- Bacterial Proteins administration & dosage pharmacology adverse effects MeSH
- Cephalosporins administration & dosage pharmacology adverse effects MeSH
- Cellulitis drug therapy blood microbiology MeSH
- Erysipelas drug therapy blood microbiology MeSH
- Drug Interactions MeSH
- Humans MeSH
- Linezolid administration & dosage pharmacology adverse effects MeSH
- Methicillin-Resistant Staphylococcus aureus drug effects MeSH
- Minocycline analogs & derivatives administration & dosage pharmacology adverse effects MeSH
- Drug Resistance, Multiple, Bacterial drug effects MeSH
- Staphylococcal Skin Infections drug therapy blood MeSH
- Teicoplanin analogs & derivatives administration & dosage pharmacology adverse effects MeSH
- Check Tag
- Humans MeSH
