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Current Opinion in Infectious Diseases Dec 2023In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of... (Review)
Review
PURPOSE OF REVIEW
In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines in terms on their recommendations/suggestions for the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii infections.
RECENT FINDINGS
Treatment of severe infections caused by nonfermenting gram-negative bacteria (NF-GNB) is posing both novel hopes and novel challenges to physicians worldwide, and both the IDSA and the ESCMID have recently updated/released their guidelines or guidance documents, based on different philosophies and providing recommendations for the treatment of NF-GNB infections. In order to correctly exploit recent advances in the treatment of such infections, IDSA and ESCMID approaches should be viewed as complementary and evolving, and should not preclude further revision based on accumulating evidence on the use of novel β-lactams and β-lactam/β-lactamase inhibitor combinations.
SUMMARY
A joint consideration of both philosophies should leave the door opened for the wise use of novel agents, ultimately building precious experience on their use that could favorably influence future guidelines revisions.
Topics: Humans; Anti-Bacterial Agents; Gram-Negative Bacteria; beta-Lactamase Inhibitors; beta-Lactams; Acinetobacter Infections; Monobactams; Communicable Diseases
PubMed: 37769165
DOI: 10.1097/QCO.0000000000000982 -
European Journal of Medicinal Chemistry Mar 2016A series of monobactam derivatives were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative strains, taking...
A series of monobactam derivatives were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative strains, taking Aztreonam and BAL30072 as the leads. Six conjugates (12a-f) bearing PIH-like siderophore moieties were created to enhance the bactericidal activities against Gram-negative bacteria based on Trojan Horse strategy, and all of them displayed potencies against susceptible Gram-negative strains with MIC ≤ 8 μg/mL. SAR revealed that the polar substituents on the oxime side chain were beneficial for activities against resistant Gram-negative bacteria. Compounds 19c and 33a-b exhibited the promising potencies against ESBLs-producing E. coli and Klebsiella pneumoniae with MICs ranging from 2 μg/mL to 8 μg/mL. These results offered powerful information for further strategic optimization in search of the antibacterial candidates against MDR Gram-negative bacteria.
Topics: Anti-Bacterial Agents; Aztreonam; Drug Design; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Models, Molecular; Monobactams; Structure-Activity Relationship; Thiazoles
PubMed: 26827160
DOI: 10.1016/j.ejmech.2016.01.024 -
Applied Microbiology and Biotechnology Dec 2022Antibiotics are antibacterial compounds that interfere with bacterial growth, without harming the infected eukaryotic host. Among the clinical agents, beta-lactams play... (Review)
Review
Antibiotics are antibacterial compounds that interfere with bacterial growth, without harming the infected eukaryotic host. Among the clinical agents, beta-lactams play a major role in treating infected humans and animals. However, the ever-increasing antibiotic resistance crisis is forcing the pharmaceutical industry to search for new antibacterial drugs to combat a range of current and potential multi-resistant bacterial pathogens. In this review, we provide an overview of the development, innovation, and current status of therapeutic applications for beta-lactams with a focus on semi-synthetic cephalosporins. Cephalosporin C (CPC), which is a natural secondary metabolite from the filamentous fungus Acremonium chrysogenum, plays a major and demanding role in both producing modern antibiotics and developing new ones. CPC serves as a core compound for producing semi-synthetic cephalosporins that can control infections with different resistance mechanisms. We therefore summarize our latest knowledge about the CPC biosynthetic pathway and its regulation in the fungal host. Finally, we describe how CPC serves as a key lead generation source for the in vitro and better, in vivo synthesis of 7-aminocephalosporanic acid (7-ACA), the major core compound for the pharmaceutical synthesis of current and future semi-synthetic cephalosporins. KEY POINTS: • Latest literature on cephalosporin generations • Biotechnical production of cephalosporins • In vivo production of 7-ACA.
Topics: Animals; Humans; Monobactams; Cephalosporins; Anti-Bacterial Agents; Drug Industry
PubMed: 36401643
DOI: 10.1007/s00253-022-12272-8 -
Enfermedades Infecciosas Y... Jan 2003Betalactams, which act by inhibiting the last phase of bacterial cell wall synthesis, constitute the largest family of antimicrobial agents and the most extensively used...
Betalactams, which act by inhibiting the last phase of bacterial cell wall synthesis, constitute the largest family of antimicrobial agents and the most extensively used in current clinical practice. These drug have a slow bactericidal action that is relatively independent of plasma concentrations, little toxicity and a broad therapeutic margin. Their spectrum has increased over the years with the incorporation of new molecules having greater activity against gram-negative bacilli. Nevertheless, the progressive emergence of acquired resistance has limited the empirical use of betalactams and their efficacy in certain situations. Despite this problem, penicillin is still the treatment of choice for a large number of classic infections, cephalosporins are widely used in surgical prophylaxis and severe community-acquired infections, carbapenems are the choice for mixed nosocomial and multiresistant bacterial infections and betalactamase inhibitors permit the effective use of amino- and ureido-penicillins in highly significant infections.
Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Endocarditis, Bacterial; Humans; Molecular Structure; Monobactams; Neutropenia; Penicillins; Respiratory Tract Infections; Soft Tissue Infections; Staphylococcal Skin Infections; Urinary Tract Infections; beta-Lactam Resistance; beta-Lactamase Inhibitors
PubMed: 12550043
DOI: 10.1016/s0213-005x(03)72873-0 -
Current Opinion in Microbiology Oct 2010In the 80 years since their discovery the β-lactam antibiotics have progressed through structural generations, each in response to the progressive evolution of... (Review)
Review
In the 80 years since their discovery the β-lactam antibiotics have progressed through structural generations, each in response to the progressive evolution of bacterial resistance mechanisms. The generational progression was driven by the ingenious, but largely empirical, manipulation of structure by medicinal chemists. Nonetheless, the true creative force in these efforts was Nature, and as the discovery of new β-lactams from Nature has atrophied while at the same time multi-resistant and opportunistic bacterial pathogens have burgeoned, the time for empirical drug discovery has passed. We concisely summarize recent developments with respect to bacterial resistance, the identity of the new β-lactams, and the emerging non-empirical strategies that will ensure that this incredible class of antibiotics has a future.
Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cephalosporins; Monobactams; beta-Lactam Resistance; beta-Lactamases; beta-Lactams
PubMed: 20888287
DOI: 10.1016/j.mib.2010.09.008 -
The Journal of Antimicrobial... Oct 2016The monobactam aztreonam is currently being re-examined as a therapeutic agent in light of the global spread of carbapenem resistance in aerobic Gram-negative bacilli... (Review)
Review
The monobactam aztreonam is currently being re-examined as a therapeutic agent in light of the global spread of carbapenem resistance in aerobic Gram-negative bacilli and aztreonam's stability to Ambler class B metallo-β-lactamases. Of particular interest are the pharmacokinetic and pharmacodynamic properties of aztreonam alone and in combination with β-lactamase inhibitors. The choice of inhibitor may vary depending on the spectrum of β-lactamases produced by Enterobacteriaceae. The monobactam ring is also being used to produce new developmental monobactams. Thus, a greater understanding of aztreonam pharmacokinetics and dynamics is of great relevance in drug development. This review summarizes the pharmacokinetic profile of aztreonam in man and its pharmacodynamics in human and pre-clinical studies when studied alone and with β-lactamase inhibitors.
Topics: Aztreonam; Clinical Trials as Topic; Drug Therapy, Combination; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; beta-Lactamase Inhibitors; beta-Lactamases
PubMed: 27334663
DOI: 10.1093/jac/dkw231 -
Journal of Clinical Pharmacology Feb 1988The discovery of the monobactams led to the successful development of aztreonam as the first of this novel class of beta-lactam antibiotics to enter the clinical field....
The discovery of the monobactams led to the successful development of aztreonam as the first of this novel class of beta-lactam antibiotics to enter the clinical field. Continued structural modification on the monobactam nucleus has resulted in two additional compounds from this class that show interesting biologic properties. The first, SQ 83,360, is like aztreonam in exhibiting high activity against members of the Enterobacteriaceae but has the added characteristic of being exceptionally active against strains of Pseudomonas aeruginosa. Also, significant gains are made with SQ 83,360 in activity against Pseudomonas spp. and Acinetobacter. The second compound, tigemonam, is also like aztreonam, having good activity against Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae and showing good beta-lactam stability. Tigemonam differs from aztreonam in being well absorbed orally by experimental laboratory animals.
Topics: Bacteria; Chemical Phenomena; Chemistry; Monobactams
PubMed: 3360965
DOI: 10.1002/j.1552-4604.1988.tb05734.x -
The Journal of Allergy and Clinical... Apr 2020
Topics: Anti-Bacterial Agents; Carbapenems; Clindamycin; Humans; Monobactams; Penicillins; Retrospective Studies
PubMed: 32276693
DOI: 10.1016/j.jaip.2020.01.027 -
Pharmacotherapy 1986Aztreonam is a new, totally synthetic beta-lactamase agent--the first monobactam. It is highly resistant to hydrolytic inactivation caused by plasmid-mediated (except... (Review)
Review
Aztreonam is a new, totally synthetic beta-lactamase agent--the first monobactam. It is highly resistant to hydrolytic inactivation caused by plasmid-mediated (except PSE-2 enzyme found in some Pseudomonas species) or chromosomally mediated beta-lactamases (except for K1 produced by rare strains of Klebsiella oxytoca). Accordingly, aztreonam remains active against many pathogens that are resistant to other beta-lactam antibiotics. The drug exhibits directed antibacterial activity against gram-negative organisms and is effective as monotherapy against most Enterobacteriaceae and Hemophilus and Neisseria species, including beta-lactamase-producing strains; it is not active against anaerobes or gram-positive organisms. Before culture results are known, it may be necessary to administer the agent empirically in combination with other antibiotics. Aztreonam is rapidly distributed to most body tissues and fluids when administered parenterally. Its serum half-life is 1.7 hours, suggesting a dosing interval of 6-8 hours for severe or life-threatening infections and 8-12 hours for moderately severe infections and urinary tract infections. It is primarily eliminated unchanged in the urine and in much lesser amounts as a microbiologically inactive metabolite; slight biliary excretion may occur. Aztreonam is well-tolerated, lacking any serious adverse hematologic, otic, or renal system effects. Its lack of effect on anaerobes helps to maintain resistance against colonization. Particularly in light of its safety and unique properties, aztreonam promises to be a useful alternative to aminoglycoside therapy.
Topics: Aztreonam; Bacterial Infections; Bone Diseases; Female; Genital Diseases, Female; Gonorrhea; Gram-Negative Bacteria; Humans; Immune System Diseases; Joint Diseases; Respiratory Tract Infections; Sepsis; Skin Diseases; Urinary Tract Infections
PubMed: 3534798
DOI: 10.1002/j.1875-9114.1986.tb03468.x -
Journal of Pharmacy Practice Dec 2014Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This... (Review)
Review
Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.
Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cross Reactions; Drug Hypersensitivity; Humans; Monobactams; Penicillins
PubMed: 25124380
DOI: 10.1177/0897190014546109