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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 -
F1000Research 2020of the many staphylococcal species is the most common cause of both skin and soft tissue infection and severe staphylococcal infections including bacteremia (SAB).... (Review)
Review
of the many staphylococcal species is the most common cause of both skin and soft tissue infection and severe staphylococcal infections including bacteremia (SAB). Many antibiotics are active against the staphylococci, yet over the last 40 years antibiotic resistance, particularly resistance to beta-lactam antibiotics, has plagued antimicrobial therapy. The term "methicillin resistance" is a historic term and now refers to the ability of staphylococci, in particular methicillin-resistant (MRSA), to resist the action of beta-lactam antibiotics. This resistance is encoded by the A gene carried in a complex genetic cassette, SCC . Vancomycin and old antibiotics remain the keystone of treatment for resistant staphylococci. Other newer agents, and some older agents, show good activity against resistant staphylococci which are the focus of this review: trimethoprim-sulfamethoxazole, ceftaroline, daptomycin, fosfomycin, linezolid, dalbavancin, televancin, and omadacycline. Other agents with novel mechanisms of action are under development, for use as single anti-staphylococcal agents or for combination use to augment the action of the primary anti-staphylococcal agent. Vancomycin therapy carries specific risks, particularly renal dysfunction, but despite its foibles, vancomycin remains the standard of care for the treatment of resistant staphylococcal infections. Some clinicians implement an early switch from vancomycin at the earliest signs of renal dysfunction. The near horizon holds promise also of augmentation of both cellular and humoral responses to staphylococcal infection. Pending newer clinical trials that show clear superiority of one anti-staphylococcal agent over another or over vancomycin, it will remain to expert clinical judgment in determining antibiotic choice and duration of anti-staphylococcal therapy.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections
PubMed: 32148777
DOI: 10.12688/f1000research.17718.1 -
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 -
Veterinary Research Nov 2022Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig... (Review)
Review
Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig production. The lack of effective vaccines to prevent the disease has promoted the extensive use of antibiotics worldwide. This has been followed by the emergence of resistance against different classes of antibiotics. The rates of resistance to tetracyclines, lincosamides, and macrolides are extremely high, and resistance has spread worldwide. The genetic origin of S. suis resistance is multiple and includes the production of target-modifying and antibiotic-inactivating enzymes and mutations in antibiotic targets. S. suis genomes contain traits of horizontal gene transfer. Many mobile genetic elements carry a variety of genes that confer resistance to antibiotics as well as genes for autonomous DNA transfer and, thus, S. suis can rapidly acquire multiresistance. In addition, S. suis forms microcolonies on host tissues, which are associations of microorganisms that generate tolerance to antibiotics through a variety of mechanisms and favor the exchange of genetic material. Thus, alternatives to currently used antibiotics are highly demanded. A deep understanding of the mechanisms by which S. suis becomes resistant or tolerant to antibiotics may help to develop novel molecules or combinations of antimicrobials to fight these infections. Meanwhile, phage therapy and vaccination are promising alternative strategies, which could alleviate disease pressure and, thereby, antibiotic use.
Topics: Humans; Swine; Animals; Streptococcus suis; Streptococcal Infections; Anti-Bacterial Agents; Macrolides; Swine Diseases
PubMed: 36371221
DOI: 10.1186/s13567-022-01111-3 -
Molecules (Basel, Switzerland) Apr 2022Quercetin, an essential plant flavonoid, possesses a variety of pharmacological activities. Extensive literature investigates its antimicrobial activity and possible... (Review)
Review
Quercetin, an essential plant flavonoid, possesses a variety of pharmacological activities. Extensive literature investigates its antimicrobial activity and possible mechanism of action. Quercetin has been shown to inhibit the growth of different Gram-positive and Gram-negative bacteria as well as fungi and viruses. The mechanism of its antimicrobial action includes cell membrane damage, change of membrane permeability, inhibition of synthesis of nucleic acids and proteins, reduction of expression of virulence factors, mitochondrial dysfunction, and preventing biofilm formation. Quercetin has also been shown to inhibit the growth of various drug-resistant microorganisms, thereby suggesting its use as a potent antimicrobial agent against drug-resistant strains. Furthermore, certain structural modifications of quercetin have sometimes been shown to enhance its antimicrobial activity compared to that of the parent molecule. In this review, we have summarized the antimicrobial activity of quercetin with a special focus on its mechanistic principle. Therefore, this review will provide further insights into the scientific understanding of quercetin's mechanism of action, and the implications for its use as a clinically relevant antimicrobial agent.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Quercetin
PubMed: 35458691
DOI: 10.3390/molecules27082494 -
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 -
Journal of Clinical Microbiology Mar 2023Mycoplasma genitalium is an important sexually transmitted pathogen affecting both men and women. Its extremely slow growth and very demanding culture requirements... (Review)
Review
Mycoplasma genitalium is an important sexually transmitted pathogen affecting both men and women. Its extremely slow growth and very demanding culture requirements necessitate the use of molecular-based diagnostic tests for its detection in clinical specimens. The recent availability of U.S. Food and Drug Administration (FDA)-cleared commercial molecular-based assays has enabled diagnostic testing to become more widely available in the United States and no longer limited to specialized reference laboratories. Advances in the knowledge of the epidemiology and clinical significance of M. genitalium as a human pathogen made possible by the availability of molecular-based testing have led to updated guidelines for diagnostic testing and treatment that have been published in various countries. This review summarizes the importance of M. genitalium as an agent of human disease, explains the necessity of obtaining a microbiological diagnosis, describes currently available diagnostic methods, and discusses how the emergence of antimicrobial resistance has complicated treatment alternatives and influenced the development of diagnostic tests for resistance detection, with an emphasis on developments over the past few years.
Topics: Male; Humans; Female; Anti-Bacterial Agents; Mycoplasma genitalium; Laboratories; Drug Resistance, Bacterial; Mycoplasma Infections; Macrolides; Urethritis
PubMed: 36598247
DOI: 10.1128/jcm.00790-21 -
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