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The Journal of Allergy and Clinical... 2019Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly... (Review)
Review
Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly common with a wide range of immunopathologic mechanisms. Cephalosporins are one of the leading causes for perioperative anaphylaxis and severe cutaneous adverse reactions. Patients allergic to cephalosporins tend to tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains. Skin testing for cephalosporins has not been well validated but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains. In vitro tests including basophil activation tests have lower sensitivity when compared with skin testing. Rapid drug desensitization procedures are safe and effective and have been used successfully for immediate and some nonimmediate cephalosporin reactions. Many gaps in knowledge still exist regarding cephalosporin hypersensitivity.
Topics: Anaphylaxis; Basophil Degranulation Test; Cephalosporins; Cross Reactions; Desensitization, Immunologic; Drug Eruptions; Drug Hypersensitivity; Humans; Perioperative Period; Pharmacogenomic Variants; Serum Sickness; Skin Tests; beta-Lactams
PubMed: 31495420
DOI: 10.1016/j.jaip.2019.06.001 -
Clinical Pharmacokinetics Jul 2022Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion... (Review)
Review
Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion over 30-60 min or as a prolonged infusion with infusion times from 3 h to continuous administration. Cefepime is widely distributed in biological fluids and tissues with an average volume of distribution of ~ 0.2 L/kg in healthy adults with normal renal function. Protein binding is relatively low (20%), and elimination is mainly renal. About 85% of the dose is excreted unchanged in the urine, with an elimination half-life of 2-2.3 h. The pharmacokinetics of cefepime is altered under certain pathophysiological conditions, resulting in high inter-individual variability in cefepime volume of distribution and clearance, which poses challenges for population dosing approaches. Consequently, therapeutic drug monitoring of cefepime may be beneficial in certain patients including those who are critically ill, have life-threatening infections, or are infected with more resistant pathogens. Cefepime is generally safe and efficacious, with a goal exposure target of 70% time of the free drug concentration over the minimum inhibitory concentration for clinical efficacy. In recent years, reports of neurotoxicity have increased, specifically in patients with impaired renal function. This review summarizes the pharmacokinetics, pharmacodynamics, and toxicodynamics of cefepime contemporarily in the setting of increasing cefepime exposures. We explore the potential benefits of extended or continuous infusions and therapeutic drug monitoring in special populations.
Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Critical Illness; Humans; Microbial Sensitivity Tests
PubMed: 35764774
DOI: 10.1007/s40262-022-01137-y -
Clinical Infectious Diseases : An... Nov 2019The emergence of antimicrobial resistance is a significant public health issue worldwide, particularly for healthcare-associated infections caused by... (Review)
Review
The emergence of antimicrobial resistance is a significant public health issue worldwide, particularly for healthcare-associated infections caused by carbapenem-resistant gram-negative pathogens. Cefiderocol is a novel siderophore cephalosporin targeting gram-negative bacteria, including strains with carbapenem resistance. The structural characteristics of cefiderocol show similarity to both ceftazidime and cefepime, which enable cefiderocol to withstand hydrolysis by β-lactamases. The unique chemical component is the addition of a catechol moiety on the C-3 side chain, which chelates iron and mimics naturally occurring siderophore molecules. Following the chelation of iron, cefiderocol is actively transported across the outer membrane of the bacterial cell to the periplasmic space via specialized iron transporter channels. Furthermore, cefiderocol has demonstrated structural stability against hydrolysis by both serine- and metallo-β-lactamases, including clinically relevant carbapenemases such as Klebsiella pneumoniae carbapenemase, oxacillin carbapenemase-48, and New Delhi metallo-β-lactamase. Cefiderocol has demonstrated promising in vitro antibacterial and bactericidal activity, which correlates with its in vivo efficacy in several animal models. This article reviews the discovery and chemistry of cefiderocol, as well as some of the key microbiological and in vivo findings on cefiderocol from recently conducted investigations.
Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Bacterial; Gram-Negative Bacteria; History, 20th Century; Humans; Microbial Sensitivity Tests; Models, Molecular; Siderophores; Cefiderocol
PubMed: 31724047
DOI: 10.1093/cid/ciz826 -
Drugs Sep 2021Intravenous cefiderocol (Fetroja; Fetcroja) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections.... (Review)
Review
Intravenous cefiderocol (Fetroja; Fetcroja) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of β-lactamases (including metallo-β-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options.
Topics: Anti-Bacterial Agents; Cephalosporins; Double-Blind Method; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Healthcare-Associated Pneumonia; Humans; Randomized Controlled Trials as Topic; Urinary Tract Infections; Cefiderocol
PubMed: 34427896
DOI: 10.1007/s40265-021-01580-4 -
Revista Espanola de Quimioterapia :... Apr 2022Cefiderocol is a new siderophore cephalosporin with potent in vitro activity against gram-negative bacilli including Enterobacterales that produce all kinds of... (Review)
Review
Cefiderocol is a new siderophore cephalosporin with potent in vitro activity against gram-negative bacilli including Enterobacterales that produce all kinds of carbapenemases and non-fermenting Gram-negative with difficult-to-treat resistance. As a β-lactam, its efficacy is optimized in extended-perfusion and requires dose adjustment in renal dysfunction and hyperclearance. Its efficacy has been validated in three clinical trials, one of them in the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia. The clinical trial aimed at difficult-to-treat gram-negatives achieved the clinical and microbiological target, but the increase in mortality observed in the cefiderocol arm makes it necessary to demonstrate efficacy in real clinical practice. Cefiderocol is a good option among the new β-lactams for the treatment of pneumonia caused by Gram-negative bacilli carbapenem-resistant.
Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Gram-Negative Bacteria; Humans; Cefiderocol
PubMed: 35488822
DOI: 10.37201/req/s01.07.2022 -
Revista Espanola de Quimioterapia :... Apr 2022Ceftobiprole medocaril is a broad-spectrum 5th-generation cephalosporin with activity against Gram-positives such as methicillin-resistant Staphylococcus aureus and... (Review)
Review
Ceftobiprole medocaril is a broad-spectrum 5th-generation cephalosporin with activity against Gram-positives such as methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, and against Gram-negatives such as Pseudomonas aeruginosa. The recommended dose is 500 mg every 8 h in 2-hour infusions. Various clinical trials have demonstrated its usefulness in the treatment of community-acquired pneumonia and nosocomial pneumonia, with the exception of ventilator-associated pneumonia. In summary, it is a very useful antibiotic for the treatment of pneumonia.
Topics: Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Humans; Methicillin-Resistant Staphylococcus aureus
PubMed: 35488820
DOI: 10.37201/req/s01.05.2022 -
Revista Espanola de Quimioterapia :... Sep 2022Gram-negative bacilli are intrinsically resistant to many antibiotics due to the low permeability of their outer membrane. The most effective strategy to solve this... (Review)
Review
Gram-negative bacilli are intrinsically resistant to many antibiotics due to the low permeability of their outer membrane. The most effective strategy to solve this problem has been the design of antibiotics that cross the membrane using specific transport systems. This is the case of cefiderocol, which, unlike cefepime or ceftazidime, has a chlorocatechol group at the end of the C-3 side chain. This group is recognized by transporters located in the outer membrane that allow cefiderocol to accumulate in the periplasmic space. Furthermore, cefiderocol is not a substrate for efflux pumps and the configuration of the side chains at C-7 and in particular at C-3 confer it a high stability against hydrolysis by most beta-lactamases of clinical interest including class A (KPC, BLEEs), C (ampC) or D (OXA-48) serine beta-lactamases and metallo-betalactamases (NDM, VIM. IMP). In order to better understand the mechanism of action of cefiderocol, the importance of iron in bacterial metabolism and the competition for iron between bacteria and host are reviewed.The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance.
Topics: Animals; Cattle; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cefepime; Ceftazidime; Cephalosporins; Gram-Negative Bacteria; Iron; Quinolones; Serine; Tetracyclines; Cefiderocol
PubMed: 36193980
DOI: 10.37201/req/s02.02.2022 -
The New Microbiologica Feb 2023Cefditoren is an oral third-generation cephalosporin with a large spectrum activity against Gram-negative and Gram-positive bacteria which are reported to be responsible... (Review)
Review
Cefditoren is an oral third-generation cephalosporin with a large spectrum activity against Gram-negative and Gram-positive bacteria which are reported to be responsible for respiratory tract and skin and skin structure infections. In this work we reviewed the pharmacodynamics, pharmacokinetics, and the main clinical indications of cefditoren. Similarly to other beta-lactams, cefditoren is a time-dependent antibiotic, and its "best" PK/PD target is probably 40% dosing interval time > 4- 5-fold MIC and 40-70% dosing interval time > 4- 5-fold MIC for bacteriostatic and bactericidal effect, respectively. In fasting patients oral bioavailability is low and increases when the drug is taken with food. This cephalosporin has significant bactericidal activity against S. pneumoniae (both penicillin-susceptible and penicillin-resistant strains), S. pyogenes, H. Influenzae and M. catarrhalis, as well as methicillin-susceptible S. aureus (MSSA). Regarding Enterobacterales, cefditoren has very low MICs90 against K. pneumoniae andE. coli but is not active against AmpC-, ESBL- and carbapenemase-producer' strains. Licensed indications are treatment of exacerbations of chronic bronchitis,acute rhinosinusitis, otitis media, upper respiratory tract infections (pharyngitis/tonsillitis), lower community-acquired respiratory tract infections (LRTIs), and skin and skin-structure infections (SSTI). Cefditoren might have a role in switching from parenteral to oral therapy in acute pyelonephritis and LRTIs. with a reduction of adverse effects and hospital costs. Eventually, due to its supposed binding to enterococcal penicillin binding proteins (PBPs) cefditoren, in combination with other beta-lactams, might have a role in partial oral enterococcal endocarditis treatment..
Topics: Humans; Staphylococcus aureus; Cephalosporins; Anti-Bacterial Agents; Monobactams; Respiratory Tract Infections
PubMed: 36853812
DOI: No ID Found -
Revista Espanola de Quimioterapia :... Sep 2021Ceftobiprole is a broad-spectrum, fifth-generation cephalosporin currently approved for community-acquired and non-ventilator-associated hospital-acquired pneumonia.... (Review)
Review
Ceftobiprole is a broad-spectrum, fifth-generation cephalosporin currently approved for community-acquired and non-ventilator-associated hospital-acquired pneumonia. High bactericidal and anti-biofilm activity has been exhibited in in vitro and animal models. This, together with its synergism with other antibiotics against gram-positive bacteria, makes it an ideal candidate for treatment of complex infections, such as those associated with devices or infective endocarditis. More clinical data are needed to achieve drug positioning.
Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Endocarditis, Bacterial; Gram-Positive Bacteria
PubMed: 34598421
DOI: 10.37201/req/s01.09.2021 -
Revista Espanola de Quimioterapia :... Apr 2022Severe community-acquired pneumonia (SCAP) is associated with high mortality. Factor such as early adequate antibiotic therapy, delay in intensive care unit (ICU) care... (Review)
Review
Severe community-acquired pneumonia (SCAP) is associated with high mortality. Factor such as early adequate antibiotic therapy, delay in intensive care unit (ICU) care and pneumonia caused by resistant pathogens are associated with worse outcomes in SCAP patients. Ceftaroline is a fifth-generation cephalosporin with bactericidal activity against Gram-positive pathogens (including methicillin-resistant Staphylococcus aureus [MRSA] and multidrug-resistant Streptococcus pneumoniae) and common Gram-negative organisms. The efficacy and safety for the treatment of pneumonia was evaluated in three randomized control trials were ceftaroline demonstrated superiority against ceftriaxone for the treatment of pneumonia in hospitalized patients with Pneumonia Severity Index (PSI) III - IV.
Topics: Cephalosporins; Community-Acquired Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Pneumonia; Ceftaroline
PubMed: 35488821
DOI: 10.37201/req/s01.06.2022