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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 -
European Review For Medical and... Apr 2019Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years,...
Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years, with relapses and failures. The optimal type, route of administration, and duration of antibiotic treatment remain controversial, and the emergence of multi-drug resistant organisms poses major therapeutic challenges. Identification of the causative agent and subsequent targeted antibiotic treatment has a major impact on patients' outcome. In this review, we summarize which intravenous and oral antibiotics are the best options available for the treatment of chronic osteomyelitis, according to specific aetiologies.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Chronic Disease; Humans; Osteomyelitis
PubMed: 30977893
DOI: 10.26355/eurrev_201904_17500 -
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 :... 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 Molecular... Jul 2021Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The... (Review)
Review
Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as and . The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cell Line; Drug Development; Drug Resistance, Bacterial; Escherichia coli; Humans; Metal Nanoparticles; Microbial Sensitivity Tests; Nanotechnology; Pseudomonas aeruginosa; Silver; Staphylococcus aureus
PubMed: 34281254
DOI: 10.3390/ijms22137202 -
Antimicrobial Agents and Chemotherapy May 2016The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to... (Review)
Review
The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of ≥400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of ≥400 for a MIC of ≤1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated.
Topics: Anti-Bacterial Agents; Drug Administration Schedule; Humans; Microbial Sensitivity Tests; Staphylococcus aureus; Vancomycin
PubMed: 26856841
DOI: 10.1128/AAC.03147-14 -
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 Infectious Diseases : An... Apr 2018We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a...
We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a systematic literature review of published, randomized, controlled trials (RCTs) that compared a bacteriostatic agent to a bactericidal agent in the treatment of clinical, bacterial infections. Of 56 identified trials published since 1985, 49 found no significant difference in efficacy between bacteriostatic and bactericidal agents. In 6 trials it was found that the bacteriostatic agent was superior to the bactericidal agent in efficacy. Only 1 trial found that the bactericidal agent was superior; in that case, the inferiority of the static agent was explainable by underdosing of the drug based on pharmacokinetic-pharmacodynamic analysis. Thus, virtually all available data from high-quality, RCTs demonstrate no intrinsic superiority of bactericidal compared to bacteriostatic agents. Other drug characteristics such as optimal dosing, pharmacokinetics, and tissue penetration may be more important efficacy drivers.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29293890
DOI: 10.1093/cid/cix1127 -
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 -
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