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Antimicrobial Agents and Chemotherapy Jul 2021Bacterial resistance to carbapenem agents has reached alarming levels. Accordingly, collaborative efforts between national and international organizations and the... (Review)
Review
Bacterial resistance to carbapenem agents has reached alarming levels. Accordingly, collaborative efforts between national and international organizations and the pharmaceutical industry have led to an impressive expansion of commercially available β-lactam agents in recent years. No available agent comes close to the broad range of activity afforded by cefiderocol, a novel siderophore-cephalosporin conjugate. The novelty of and need for cefiderocol are clear, but available clinical data are conflicting, leaving infectious diseases specialists puzzled as to when to prescribe this agent in clinical practice. After a brief overview of cefiderocol pharmacokinetics and pharmacodynamics, safety data, cefiderocol susceptibility testing, and putative mechanisms of cefiderocol resistance, this review focuses on determining cefiderocol's role in the management of specific pathogens, including carbapenem-resistant Acinetobacter baumannii complex, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant , and less commonly identified glucose-nonfermenting organisms such as Stenotrophomonas maltophilia, species, and species. Available preclinical, clinical trial, and postmarketing data are summarized for each organism, and each section concludes with our opinions on where to position cefiderocol as a clinical therapeutic.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Cefiderocol
PubMed: 34031052
DOI: 10.1128/AAC.02171-20 -
Journal of Clinical Laboratory Analysis Jun 2022Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial... (Review)
Review
BACKGROUND
Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide.
METHODS
Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies.
RESULTS
AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections.
CONCLUSIONS
Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.
Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Cystic Fibrosis; Humans
PubMed: 35447019
DOI: 10.1002/jcla.24427 -
Clinical Microbiology and Infection :... Apr 2021Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
BACKGROUND
Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
OBJECTIVES
Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection.
SOURCES
We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals.
CONTENT
Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression.
IMPLICATIONS
We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions.
Topics: Algorithms; Anti-Bacterial Agents; Humans; Nocardia; Nocardia Infections
PubMed: 33418019
DOI: 10.1016/j.cmi.2020.12.019 -
International Journal of Antimicrobial... Sep 2022Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients.... (Review)
Review
Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum β-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime-avibactam (CZA, a cephalosporin-β-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T) and imipenem-relebactam (I-R). Cefiderocol is a recent siderophore β-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many β-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I-R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new β-lactam-β-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel β-lactam approaches for treatment of MDR-GNB infections.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; beta-Lactamase Inhibitors
PubMed: 35787918
DOI: 10.1016/j.ijantimicag.2022.106633 -
Clinical Microbiology and Infection :... May 2020Standard treatments against bacterial infections are becoming ineffective due to the rise of antibacterial resistance worldwide. Classical approaches to develop new... (Review)
Review
BACKGROUND
Standard treatments against bacterial infections are becoming ineffective due to the rise of antibacterial resistance worldwide. Classical approaches to develop new antibacterial agents are not sufficient to fulfil the current pipeline, therefore new strategies are currently being devised in the field of antibacterial discovery.
OBJECTIVES
The objective of this narrative review is to compile the most successful strategies for drug discovery within the antibacterial context that are currently being pursued.
SOURCES
Peer-reviewed publications from the MEDLINE database with robust data addressing the discovery of new antibacterial agents in the current pipeline have been selected.
CONTENT
Several strategies to discover new antibacterials are described in this review: (i) derivatives of known antibacterial agents; the activity of a known antimicrobial agent can be improved through two strategies: (a) the modification of the original chemical structure of an antimicrobial agent to circumvent antibacterial resistance mechanisms and (b) the development of a compound that inhibits the mechanisms of resistance to an antibacterial agent; (ii) new antibacterial agents targeting new proteins; (iii) inhibitors of virulence factors; (iv) nanoparticles; (v) antimicrobial peptides and peptidomimetics; (vi) phage therapy and enzybiotics; and (vii) antisense oligonucleotides.
IMPLICATIONS
This review intends to provide a positive message affirming that several different strategies to design new antibacterial agents are currently being developed, and we are therefore confident that in the near future some of the most promising approaches will come to fruition.
Topics: Anti-Bacterial Agents; Bacterial Infections; Bacterial Proteins; Drug Discovery; Drug Resistance, Bacterial; Humans; Nanoparticles; Oligonucleotides, Antisense; Peptidomimetics; Phage Therapy; Pore Forming Cytotoxic Proteins; Virulence
PubMed: 31574341
DOI: 10.1016/j.cmi.2019.09.015 -
Drugs Sep 2021Contezolid (Youxitai ), an orally administered oxazolidinone antibacterial agent, is being developed by Shanghai MicuRx Pharmaceutical Co., Ltd. for the treatment of... (Review)
Review
Contezolid (Youxitai ), an orally administered oxazolidinone antibacterial agent, is being developed by Shanghai MicuRx Pharmaceutical Co., Ltd. for the treatment of multidrug-resistant (MDR) Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. In June 2021, it was approved by the National Medical Products Administration of China for the treatment of complicated skin and soft tissue infections (cSSTI), including, but not limited to, methicillin-susceptible S. aureus, MRSA, Streptococcus pyogenes and Streptococcus agalactiae. The recommended dosage of contezolid is 800 mg (i.e. two 400 mg tablets) every 12 h for 7-14 days. Contezolid is also undergoing clinical development for acute bacterial skin and skin structure infections (ABSSSI) in the USA, and for diabetic foot infections. This article summarizes the milestones in the development of contezolid leading to this first approval for the treatment of cSSTI.
Topics: Anti-Bacterial Agents; China; Drug Approval; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacterial Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Pyridones; Vancomycin Resistance
PubMed: 34365606
DOI: 10.1007/s40265-021-01576-0 -
Biomaterials Apr 2022Emerging antimicrobial resistance in infections asks for novel intervention strategies. Galacto-oligosaccharides (GOS) might be attractive alternatives to antibiotics...
Emerging antimicrobial resistance in infections asks for novel intervention strategies. Galacto-oligosaccharides (GOS) might be attractive alternatives to antibiotics due to their anti-inflammatory and anti-adhesive properties. Mannheimia haemolytica is one of the major Pasteurellaceae associated with bovine lung infections. Using M. haemolytica, we demonstrated that GOS have the capacity to reduce bacterial viability and can be used as adjuvant to improve antibiotic efficacy. Using M. haemolytica-treated primary bronchial epithelial cells (PBECs) of calves, we identified the anti-adhesive and anti-invasive activities of GOS. The observed inhibition of cytokine/chemokine release and the prevention of airway epithelial barrier dysfunction in M. haemolytica-treated PBECs by GOS might be related to the downregulation of "toll-like receptor 4/nuclear factor-κB" pathway and the anti-invasive and anti-adhesive properties of GOS. Particularly, GOS lowered lipopolysaccharides- but not flagellin-induced cytokine/chemokine release in calf and human airway epithelial cells. Finally, we performed in vivo experiments in calves and demonstrated for the first time that intranasal application of GOS can relieve lung infections/inflammation and lower M. haemolytica positivity in the lungs without affecting clinical performance. These findings not only shed light on the anti-inflammatory mechanisms of GOS during lung infections, but GOS might also be a promising anti-bacterial agent for preventing (lung) infections.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Cattle; Humans; Lung; Mannheimia haemolytica; Oligosaccharides; Pneumonia
PubMed: 35286857
DOI: 10.1016/j.biomaterials.2022.121461 -
Mini Reviews in Medicinal Chemistry 2021Phytocompounds are long known for their therapeutic uses due to their competence as antimicrobial agents. The antimicrobial activity of these bioactive compounds... (Review)
Review
Phytocompounds are long known for their therapeutic uses due to their competence as antimicrobial agents. The antimicrobial activity of these bioactive compounds manifests their ability as an antibiofilm agent and is thereby proved to be competent to treat the widespread biofilm-associated chronic infections. The rapid development of antibiotic resistance in bacteria has made the treatment of these infections almost impossible by conventional antibiotic therapy, which forced a switch-over to the use of phytocompounds. The present overview deals with the classification of a huge array of phytocompounds according to their chemical nature, detection of their target pathogen, and elucidation of their mode of action.
Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Biofilms; Fungi; Molecular Structure; Phytochemicals
PubMed: 32767942
DOI: 10.2174/1389557520666200807135243 -
Journal of Controlled Release :... Aug 2019The ever increasing scenario of bacterial resistance against commonly available antibiotics is becoming a global threat of major concern, which necessitates the... (Review)
Review
The ever increasing scenario of bacterial resistance against commonly available antibiotics is becoming a global threat of major concern, which necessitates the development of new strategies to overcome this hurdle. Conjugation of nanoparticles (NPs) with antimicrobial moieties, such as antibiotics, peptides or different biomolecules, has been one of the successful techniques in targeting antibiotic resistance. This review mainly focusses on the possible nanoparticle-drug conjugates with their activity against pathogenic bacterial infections. Nanoparticles play an array of roles, e.g. as a carrier, synergistically acting agent and as theranostic agent, henceforth facilitates the efficacy of therapy. Moreover, this review elaborates the studies with reported nanoparticles-drug conjugates that include their possible synthesis methodologies and applications. In most of the cases, the nanoparticles were found to increase the permeability of bacterial cell membrane, which enables higher uptake of antibiotics inside the bacterial cells which in return showed better effects. Even the conjugates were found to efficiently kill the antibiotic-resistant strains. Since several limitations are exerted by the biological systems, there is an urge for the advancement of nanoparticle-drug conjugates for better proficiency.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Humans; Nanoparticles
PubMed: 31226356
DOI: 10.1016/j.jconrel.2019.06.013 -
Journal of Medicinal Chemistry Nov 2020Daptomycin is a calcium-dependent cyclic lipodepsipeptide derived from the soil saprotroph , and its antibiotic properties make it a key agent for treatment of... (Review)
Review
Daptomycin is a calcium-dependent cyclic lipodepsipeptide derived from the soil saprotroph , and its antibiotic properties make it a key agent for treatment of drug-resistant Gram-positive infections. It is most commonly used clinically for the treatment of Gram-positive skin and skin structure infections (SSSI), bacteremia, and right-sided endocarditis infections associated with , including methicillin resistant (MRSA). It has also been used "off-label" for Enterococcal infections. There has been a tremendous amount of research investigating its mode of action, resistance mechanisms, and biosynthesis of this clinically important antimicrobial agent. Although we cover the latter aspects in detail, the primary focus of this review is to provide the most comprehensive and up-to-date reference for the medicinal chemist on the structure-activity-toxicity of this important class of lipopeptide antibiotics.
Topics: Animals; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Lipopeptides; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship
PubMed: 32687352
DOI: 10.1021/acs.jmedchem.0c00780