New-Generation Antibiotics for Treatment of Gram-Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis

Bloem, Annemieke; Bax, Hannelore I.; Yusuf, Erlangga; Verkaik, Nelianne J.

doi:10.3390/jcm10081743

Cited by 24 publications

(16 citation statements)

References 121 publications

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“…Gram-positive bacteria have thick cell walls, which can cause clinical infections of various diseases. 103 The emergence of drug-resistant Gram-positive bacteria has raised concerns, and methicillin-sensitive Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and highly resistant strains to Streptococcus penicillin pneumoniae infections are a growing concern to human health. 104 As a gene defense system, CRISPR-Cas has been widely used to combat drug resistance in Gram-positive bacteria.…”

Section: Crispr-cas System’s Role In the Development Of Antibiotic Re...mentioning

confidence: 99%

The Application of the CRISPR-Cas System in Antibiotic Resistance

Tao¹,

Chen²,

Li³

et al. 2022

IDR

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The emergence and global epidemic of antimicrobial resistance (AMR) poses a serious threat to global public health in recent years. AMR genes are shared between bacterial pathogens mainly via horizontal gene transfer (HGT) on mobile genetic elements (MGEs), thereby accelerating the spread of antimicrobial resistance (AMR) and increasing the burden of drug resistance. There is an urgent need to develop new strategies to control bacterial infections and the spread of antimicrobial resistance. The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) are an RNA-guided adaptive immune system in prokaryotes that recognizes and defends against invasive genetic elements such as phages and plasmids. Because of its specifically target and cleave DNA sequences encoding antibiotic resistance genes, CRISPR/Cas system has been developed into a new gene-editing tool for the prevention and control of bacterial drug resistance. CRISPR-Cas plays a potentially important role in controlling horizontal gene transfer and limiting the spread of antibiotic resistance. In this review, we will introduce the structure and working mechanism of CRISPR-Cas systems, followed by delivery strategies, and then focus on the relationship between antimicrobial resistance and CRISPR-Cas. Moreover, the challenges and prospects of this research field are discussed, thereby providing a reference for the prevention and control of the spread of antibiotic resistance.

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Section: Crispr-cas System’s Role In the Development Of Antibiotic Re...mentioning

confidence: 99%

The Application of the CRISPR-Cas System in Antibiotic Resistance

Tao¹,

Chen²,

Li³

et al. 2022

IDR

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“…Tedizolid ( 29 ) is an oxazolidinone‐class antibacterial drug approved in 2014 as its phosphate prodrug in injection and tablet dosage forms. It is specifically used to treat acute bacterial skin infections caused by susceptible isolates of the following gram‐positive methicillin‐resistant and methicillin‐susceptible Staphylococcus aureus (Bloem et al, 2021). Remdesivir ( 30 ) is a prodrug that gets hydrolyzed to its active metabolite, GS‐441524 which is a broad‐spectrum antiviral nucleoside.…”

Section: Phosphate Prodrugsmentioning

confidence: 99%

Phosphate moiety in FDA‐approved pharmaceutical salts and prodrugs

Fulmali

Bharate

2022

Drug Development Research

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The salification and prodrug approaches modulate the physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity parameters of drugs and lead candidates. The "phosphate" is one of the key counterions/promoiety used in the salt formation and prodrug synthesis. Salification with phosphoric acid enhances the aqueous solubility and thereby facilitates the administration of a drug by the parenteral route. Phosphate moiety in prodrug synthesis mainly improves permeability by lipophilic substitution. Histamine phosphate is the first phosphate salt, and hydrocortisone phosphate was the first prodrug approved by FDA in 1939 and 1952, respectively. The orange book enlists 12 phosphate salts and 17 phosphate prodrugs.Phosphate prodrugs, namely combretastatin A-4 diphosphate, combretastatin A-4 phosphate, lufotrelvir, TP-1287, pyridoxal phosphate, riboflavin phosphate, and psilocybin are clinical candidates. This review focuses on the FDA-approved phosphate salts and prodrugs from 1939 to 2021. The biopharmaceutical advantage of phosphate salts and prodrugs over the parent molecule is also deliberated.

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“…They have also been used off-label for the continuation phase of treatment of deep-seated gram-positive infections requiring a long duration of therapy, such as endocarditis, osteomyelitis, osteosynthesis-associated infections, and septic arthritis. 114 -122 Oritavancin has been found to prolong certain coagulation tests, and the use of intravenous heparin is contraindicated for 5 days after oritavancin administration. 30 In addition, caution should be taken when oritavancin is administered with warfarin because of the potential for artificially increased international normalized ratio.…”

Section: Antibiotics and Related Biologics Approved By The Fda From J...mentioning

confidence: 99%

Antibiotic Approvals in the Last Decade: Are We Keeping Up With Resistance?

et al. 2021

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Objective: To review the spectrum of activity, efficacy, safety, and role in therapy of all antibiotics and related biologics approved by the Food and Drug Administration (FDA) in the last decade. Data Sources: A literature search was performed using PubMed and Google Scholar (2010 to end May 2021) with the search terms’ name of the antibiotic or the biologic. Data were also obtained from the prescribing information, FDA, and ClinicalTrials.gov websites. Study Selection: All relevant English-language, late phase clinical trials assessing the safety and efficacy of the identified drugs were included. Review articles and references of retrieved articles were evaluated for relevant data. Data Synthesis: Antibiotic resistance is a public health crisis, and antibiotic development is imperative to outpace the ability of bacteria to develop resistance. Only 17 new systemic antibiotics and 1 related biologic have been approved by the FDA since 2010. Among these drugs, 14 were approved for common bacterial infections, 1 was approved for Clostridioides difficile infection (CDI), 1 was licensed to prevent CDI recurrence, and 2 were approved for drug-resistant tuberculosis. Very few antibiotics are in clinical development. Relevance to Patient Care and Clinical Practice: The arrival of these new antibiotics was welcomed with great enthusiasm, particularly when they met previously unmet medical needs. Unfortunately, the majority of them represent modifications to existing chemical structures rather than new drug classes. Despite the availability of these antibiotics, managing patients with deep-seated infections and those with extensively resistant gram-negative organisms remains challenging. Conclusions: The number of new antibiotics and their indications are not keeping up with resistance and the needs of the patients.

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New-Generation Antibiotics for Treatment of Gram-Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis

Cited by 24 publications

References 121 publications

The Application of the CRISPR-Cas System in Antibiotic Resistance

The Application of the CRISPR-Cas System in Antibiotic Resistance

Phosphate moiety in FDA‐approved pharmaceutical salts and prodrugs

Antibiotic Approvals in the Last Decade: Are We Keeping Up With Resistance?

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