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Annals of Intensive Care Jun 2023Appropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and... (Review)
Review
Appropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and mortality. Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Phase 1 studies established that cefiderocol achieves adequate concentration in the epithelial lining fluid in the lung and requires dosing adjustment for renal function, including patients with augmented renal clearance and continuous renal-replacement therapy (CRRT); no clinically significant drug-drug interactions are expected. The non-inferiority of cefiderocol versus high-dose, extended-infusion meropenem in all-cause mortality (ACM) rates at day 14 was demonstrated in the randomized, double-blind APEKS-NP Phase 3 clinical study in patients with nosocomial pneumonia caused by suspected or confirmed Gram-negative bacteria. Furthermore, the efficacy of cefiderocol was investigated in the randomized, open-label, pathogen-focused, descriptive CREDIBLE-CR Phase 3 clinical study in its target patient population with serious carbapenem-resistant Gram-negative infections, including hospitalized patients with nosocomial pneumonia, bloodstream infection/sepsis, or complicated urinary tract infections. However, a numerically greater ACM rate with cefiderocol compared with BAT led to the inclusion of a warning in US and European prescribing information. Cefiderocol susceptibility results obtained with commercial tests should be carefully evaluated due to current issues regarding their accuracy and reliability. Since its approval, real-world evidence in patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections suggests that cefiderocol can be efficacious in certain critically ill patient groups, such as those requiring mechanical ventilation for COVID-19 pneumonia with subsequently acquired Gram-negative bacterial superinfection, and patients with CRRT and/or extracorporeal membrane oxygenation. In this article, we review the microbiological spectrum, pharmacokinetics/pharmacodynamics, efficacy and safety profiles and real-world evidence for cefiderocol, and look at future considerations for its role in the treatment of critically ill patients with challenging Gram-negative bacterial infections.
PubMed: 37322293
DOI: 10.1186/s13613-023-01146-5 -
Trends in Microbiology Jan 2024is a Gram negative, facultative intracellular bacterium that resides in the rhizosphere of tropical soils. causes melioidosis, which is transmitted by cutaneous entry,...
is a Gram negative, facultative intracellular bacterium that resides in the rhizosphere of tropical soils. causes melioidosis, which is transmitted by cutaneous entry, ingestion, or inhalation of contaminated soil or water. Infection with can cause a wide array of clinical symptoms such as pneumonia, bone, joint, skin, genitourinary, and central nervous system infections, as well as parotid abscesses in children. Mammalian virulence is linked to the intracellular life cycle, which begins with attachment and internalization by host cells. can infect a wide range of eukaryotic cells, including macrophages, monocytes, and neutrophils, as well as nonphagocytic cells. Once internalized, a type 3 secretion system (T3SS) facilitates escape from the phagosome, and the bacteria replicate in the cytoplasm. Autotransporter protein BimA mediates actin polymerization, enabling to spread, cell to cell, using actin-based motility. This process, coupled with the activity of a type 6 secretion system (T6SS-5), results in host membrane fusion and the formation of multinucleated giant cells. Capsule polysaccharides also contribute to virulence and evasion of host innate immunity. Treatment of infections is complicated by the organism’s intrinsic resistance to multiple classes of antimicrobials, largely due to an abundance of efflux pumps and reduced outer membrane permeability. While is commonly associated with endemic ‘hotspots’ in southeast Asia and northern Australia, there is increasing evidence that it is likely endemic in a large range of tropical and subtropical areas, including regions in Africa, South America, the Middle East, Central America, and the Caribbean. Soil and climate conditions favorable for survival are also found in additional areas worldwide. Consequently, it is important for clinical and public health laboratories located outside of high-endemicity areas to be aware of , as well as for improved diagnostic and reporting methods.
Topics: Burkholderia pseudomallei; Burkholderia
PubMed: 37634974
DOI: 10.1016/j.tim.2023.07.008 -
The American Journal of Tropical... Jun 2023
Topics: Humans; Burkholderia pseudomallei; Melioidosis
PubMed: 37160279
DOI: 10.4269/ajtmh.23-0223 -
Cureus May 2023Point-of-care ultrasound is widely used in hospitalized patients. Hospital-acquired infections attributed to contaminated multiuse ultrasound gel bottles have been...
Point-of-care ultrasound is widely used in hospitalized patients. Hospital-acquired infections attributed to contaminated multiuse ultrasound gel bottles have been increasingly reported, including , , and species. Surgilube's chemical properties and sterile single-use packaging make it an appealing alternative to multi-use ultrasound gel bottles.
PubMed: 37398720
DOI: 10.7759/cureus.39666 -
Journal of Clinical Medicine Sep 2023Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate... (Review)
Review
Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate oxidase, the enzyme that generates the phagocyte respiratory burst responsible for intracellular killing of engulfed micro-organisms. Patients present with infectious or inflammatory complications. Common bacterial pathogens include and complex. Fungal pathogens include species, particularly . Inflammatory complications most commonly manifest as inflammatory bowel disease or lung disease. Granulomata are the distinguishing histological feature. Haematopoietic stem cell transplantation (HSCT) was first considered for CGD in the early 1970's. Since then, refinements in transplant technique, donor selection, conditioning regimens, and graft engineering have widened the option of HSCT to most patients with CGD. This review charts the progress made in HSCT for CGD.
PubMed: 37763024
DOI: 10.3390/jcm12186083 -
Frontiers in Microbiology 2023
PubMed: 37346750
DOI: 10.3389/fmicb.2023.1226865 -
Frontiers in Cellular and Infection... 2024Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where... (Review)
Review
Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population. The common marmoset (), a Neotropical new-world (platyrrhines) non-human primate, has gained increasing attention as an animal model for a number of diseases given its small size, availability and evolutionary proximity to humans. This review aims to (i) discuss the pros and cons of the common marmoset as an animal model by providing a brief snapshot of how marmosets are currently utilized in biomedical research, (ii) summarize and evaluate relevant aspects of the marmoset immune system to the study of infectious diseases, (iii) provide a historical backdrop, outlining the significance of infectious diseases and the importance of developing reliable animal models to test novel therapeutics, and (iv) provide a summary of infectious diseases for which a marmoset model exists, followed by an in-depth discussion of the marmoset models of two studied bacterial infectious diseases (tularemia and melioidosis) and one viral infectious disease (viral hepatitis C).
Topics: Animals; Humans; Callithrix; Disease Models, Animal; Communicable Diseases; Tularemia; Bacterial Infections
PubMed: 38465237
DOI: 10.3389/fcimb.2024.1340017