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1.
Braz J Infect Dis ; : 103867, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39305936

RESUMO

The aim of this study was to compare the in vitro activity of delafloxacin with other fluoroquinolones against bacterial pathogens recovered from inpatients with osteomyelitis, Acute Bacterial Skin and Skin-Structure Infections (ABSSSI). In total, 100 bacterial isolates (58 % Gram-negative and 42 % Gram-positive) recovered from inpatients between January and April 2021, were reidentified at species level by MALDI-TOF MS. Antimicrobial susceptibility testing was conducted using the broth microdilution method and the detection of biofilm formation was assessed through the microtiter plate assay. The screening for mecA was carried out by PCR, while mutations in the Quinolone Resistance Determining Regions (QRDR), specifically gyrA and parC, were analyzed using PCR followed by Sanger sequencing. Results showed that delafloxacin exhibited greater in vitro potency (at least 64-times) than the other tested fluoroquinolones (levofloxacin and ciprofloxacin) when evaluating Staphylococcus aureus (MIC50 ≤0.008 mg/L) and coagulase-negative Staphylococcus (MIC50 0.06 mg/L). Furthermore, delafloxacin (MIC50 0.25 mg/L) was at least 4 times more potent than other tested fluoroquinolones (MIC50 1 mg/L) against P. aeruginosa. No difference in delafloxacin activity (MIC50 0.03 mg/L) was observed against Enterobacter cloacae when compared with ciprofloxacin (MIC50 0.03 mg/L). Despite presenting low activity against K. pneumoniae isolates (22.2 %), delafloxacin exhibited twice the activity compared to both levofloxacin and ciprofloxacin. Delafloxacin also exhibited a strong activity (71.4 %‒85.7 %.) against biofilm producing bacterial pathogens tested in this study. Interestingly, 82.14 % of the staphylococci tested in this study harbored mecA gene. In addition, the gyrA and parC genes in fluoroquinolone-resistant Gram-negative isolates displayed different mutations (substitutions and deletions). Herein, we showed that delafloxacin was the most active fluoroquinolone against staphylococci (including MRSA) and P. aeruginosa when compared to other fluoroquinolones such as ciprofloxacin and levofloxacin.

2.
Diagn Microbiol Infect Dis ; 110(4): 116518, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39241665

RESUMO

Susceptibility of delafloxacin on 199 osteoarticular levofloxacin-resistant staphylococci strains was reported in 49% and 1% using SSTI S. aureus breakpoint (0.25 mg/L) and general S. aureus breakpoint (0.016 mg/L) respectively. Fifty percents levofloxacin-resistant staphylococci showed resistance to delafloxacin using CA-SFM/EUCAST recommendations. Microbiological societies should define new breakpoints especially for CoNS.

3.
Anal Chim Acta ; 1327: 343175, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39266065

RESUMO

BACKGROUND: Carbon quantum dots (CQDs) have gained much interest recently for being efficient probes. Their cost-effectiveness, eco-friendliness, and unique photocatalytic activities made them distinctive alternatives to other luminescent approaches like fluorescent dyes and luminous derivatization. Meanwhile, delafloxacin (DLF) is a recently approved antibacterial medicine. DLF has been authorized for the treatment of soft-tissue and skin infections as well as pneumonia. Therefore, new eco-friendly, cost-effective, and sensitive tools are needed its estimation in different matrices. RESULTS: In the proposed study, green copper and nitrogen carbon dots (Cu-N@CDs) were synthesized from a green source (plum juice with copper sulphate). Cu-N@CQDs were then characterized using multiple tools including X-ray photon spectroscopy (XPS), FTIR and UV-VIS spectroscopy, Zeta potential measurements, High-resolution transmission electron microscopy (HRTEM), and fluorescence spectroscopy. After gradually adding DLF, the developed quantum dots' fluorescence was significantly enhanced within the working range of 0.5-100.0 ng mL-1. The limits of detection and quantification were 0.08 and 0.27 ng mL-1, respectively. The accuracy of the proposed method ranged from 96.00 to 99.12 % in recovery%, when recovered from milk and plasma samples. SIGNIFICANCE: Cu-N@CDs were utilized and validated for selectively determining DLF in several matrices including pharmaceutical forms, human plasma and in milk samples using spectrofluorimetric technique. The bio-analytical method is simple and could be used in content uniformity testing as well as in therapeutic drug monitoring in human plasma.


Assuntos
Carbono , Cobre , Fluoroquinolonas , Nitrogênio , Pontos Quânticos , Pontos Quânticos/química , Nitrogênio/química , Cobre/química , Carbono/química , Fluoroquinolonas/análise , Fluoroquinolonas/sangue , Fluoroquinolonas/química , Humanos , Animais , Fluorometria/métodos , Limite de Detecção , Espectrometria de Fluorescência , Leite/química , Antibacterianos/sangue , Antibacterianos/análise , Antibacterianos/química
4.
Antibiotics (Basel) ; 13(7)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39061323

RESUMO

High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1 mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates recovered from blood cultures. Susceptibility to DLX was determined in 75 MRSA isolates by E-test, and an rt-PCR was developed to detect mutations affecting position 84 of ParC to screen a further 185 MRSA isolates. The genomes of 48 isolates, including all DLX-R isolates or with alterations at position 84, and also a subset of DLX-susceptible isolates were analyzed. Among the 75 isolates studied, 77.34% were DLX-susceptible and only 4 H-L DLX-R isolates were found. Seven (3.8%) isolates with alterations at position 84 of ParC were detected by rt-PCR. Genomic analysis showed that 89.9% (8/9) of isolates with the substitution E84K/G in ParC, together with other mutations in gyrA and parC, were H-L DLX-R. However, the E84K substitution in ParC alone or with other alterations was found in two isolates without H-L DLX-R. Alterations at position 84 of ParC are rare but play a key role in H-L DLX resistance in MRSA but only when other alterations in GyrA are present.

5.
J Appl Microbiol ; 135(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39066496

RESUMO

AIMS: Staphylococcus aureus is an opportunistic pathogen whose treatment is further complicated by its ability to form biofilms. In this study, we examine the impact of growing S. aureus biofilms on different polymerizing surfaces, specifically agar and agarose, on the pathogen's tolerance to fluoroquinolones. METHODS AND RESULTS: Biofilms of two methicillin-resistant strains of S. aureus were grown on agar or agarose in the presence of the same added nutrients, and their antibiotic susceptibility to two fluoroquinolones, moxifloxacin (MXF) and delafloxacin (DLX), were measured. We also compared the metabolism and extracellular polymeric substances (EPS) production of biofilms that were grown on agar and agarose. CONCLUSIONS: Biofilms that were grown on agarose were consistently more susceptible to antibiotics than those grown on agar. We found that in biofilms that were grown on agar, extracellular protein composition was higher, and adding EPS to agarose-grown biofilms increased their tolerance to DLX to levels that were comparable to agar-grown biofilms.


Assuntos
Ágar , Antibacterianos , Biofilmes , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Sefarose , Staphylococcus aureus , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Fluoroquinolonas/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Staphylococcus aureus/crescimento & desenvolvimento , Meios de Cultura/química , Moxifloxacina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia
6.
Antimicrob Agents Chemother ; 68(7): e0042824, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38899925

RESUMO

Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC0-24h in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant Staphylococcus aureus (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.


Assuntos
Antibacterianos , Fluoroquinolonas , Voluntários Saudáveis , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Humanos , Fluoroquinolonas/farmacocinética , Fluoroquinolonas/farmacologia , Fluoroquinolonas/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Adulto , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Feminino , Pessoa de Meia-Idade , Administração Intravenosa , Adulto Jovem , Área Sob a Curva , Peso Corporal/efeitos dos fármacos
7.
Rev Esp Quimioter ; 37(2): 158-162, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38226580

RESUMO

OBJECTIVE: We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). METHODS: A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. RESULTS: Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. CONCLUSIONS: CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method.


Assuntos
Cefotaxima , Fluoroquinolonas , Infecções Pneumocócicas , Humanos , Cefotaxima/farmacologia , Streptococcus pneumoniae , Antibacterianos/farmacologia , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Sorotipagem
8.
Anaerobe ; 85: 102816, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145709

RESUMO

The aim of this study was to describe the in vitro activity of delafloxacin against 230 anaerobic isolates and compare it with the activity of other antimicrobials used against infections caused by anaerobic microorganisms. Minimal inhibitory concentrations (MICs) were lower for delafloxacin than for all other antibiotics tested with the exception of piperacillin-tazobactam and meropenem against Gram-positive anaerobic cocci. Only two (0.8 %) isolates of Bacteroides spp. showed a MIC ≥4 µg/mL. With some exceptions, the present results show lower MICs for delafloxacin in comparison to the other antibiotics used against anaerobes.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Fluoroquinolonas , Cocos Gram-Positivos , Humanos , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Bactérias Anaeróbias , Testes de Sensibilidade Microbiana
11.
Heliyon ; 9(11): e21216, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37954372

RESUMO

Objective: The resistance of Mycobacterium tuberculosis (Mtb) to currently available fluoroquinolones (FQs), namely ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), renders the treatment of TB infections less successful. In this study, we aimed to evaluate the susceptibility and intracellular killing assay of Mtb to next-generation FQs in vitro and determine the correlation of FQs resistance and newly detected mutations in gyrB by molecular docking. Methods: Antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations (MICs) of six FQs, including currently available FQs (OFX, LFX, and MFX) and next-generation FQs, i.e., sitafloxacin (SFX), finafloxacin (FIN) and delafloxacin (DFX) against Mtb clinical isolates obtained in 2015 and 2022, respectively. Quinolone-resistance-determining regions of gyrA and gyrB were subjected to DNA sequencing and the correlation of FQs resistance and new mutations in gyrB were determined by molecular docking. Furthermore, the intracellular antibacterial activity of the six FQs against Mtb H37Rv in THP-1 cells was evaluated. Results: SFX exhibited the highest antibacterial activity against Mtb isolates (MIC90 = 0.25 µg/mL), whereas DFX and OFX exhibited comparable activity (MIC90 = 8 µg/mL). A statistically significant difference was observed among the MICs of the new generation FQs (SFX, P = 0.002; DFX, P = 0.008). Additionally, a marked increase in MICs was found in strains isolated in 2022 compared with those isolated in 2015. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A. Cross-resistance rate between SFX and MFX was 40.6 % (26/64). At a concentration of 1 µg/mL, SFX exhibited high intracellular antibacterial activity (96.6 % ± 1.5 %) against the Mtb H37Rv, comparable with that of MFX at a concentration of 2 µg/mL. Conclusion: SFX exhibits the highest inhibitory activity against Mtb in vitro and THP-1 cell lines, which exhibits partial-cross resistance with MFX. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A.Our findings provide crucial insights into the potential clinical application of SFX and DFX in the treatment of Mtb infections.

12.
Antimicrob Agents Chemother ; 67(11): e0162522, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37882542

RESUMO

Understanding the resistance mechanisms of antibiotics in the micro-environment of the infection is important to assess their clinical applicability and potentially prevent resistance development. We compared the laboratory resistance evolution of Escherichia coli to delafloxacin (DLX) compared to ciprofloxacin (CIP), the co-resistance evolution, and underlying resistance mechanisms at different pHs. Three clones from each of the eight clinical E. coli isolates were subjected to subinhibitory concentrations of DLX or CIP in parallel at either pH 7.3 or 6.0. Minimum inhibitory concentrations (MICs) were regularly tested (at respective pHs), and the antibiotic concentration was adjusted accordingly. After 30 passages, MICs were determined in the presence of the efflux pump inhibitor phenylalanine-arginine-ß-naphthylamide. Whole genome sequencing of the parental isolates and their resistant derivatives (n = 54) was performed. Complementation assays were carried out for selected mutations. Quantitative PCR and efflux experiments were carried out for selected derivatives. For DLX-challenged strains, resistance to DLX evolved much slower in acidic than in neutral pH, whereas for CIP-challenged strains, the opposite was the case. Mutations in the quinolone resistance-determining region were mainly seen in CIP-challenged E. coli, whereas a multifactorial mechanism including mutations in efflux-related genes played a role in DLX resistance evolution (predominantly at pH 6.0). This work provides novel insights into the resistance mechanisms of E. coli to delafloxacin and highlights the importance of understanding micro-environmental conditions at the infection site that might affect the true clinical efficacy of antibiotics and challenges our current antibiotic susceptibility-testing paradigm.


Assuntos
Ciprofloxacina , Escherichia coli , Ciprofloxacina/farmacologia , Fluoroquinolonas/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética
13.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37765112

RESUMO

Antibiotic resistance is a public health problem with increasingly alarming data being reported. Gram-positive bacteria are among the protagonists of severe nosocomial and community infections. The objective of this review is to conduct an extensive examination of emerging treatments for Gram-positive infections including ceftobiprole, ceftaroline, dalbavancin, oritavancin, omadacycline, tedizolid, and delafloxacin. From a methodological standpoint, a comprehensive analysis on clinical trials, molecular structure, mechanism of action, microbiological targeting, clinical use, pharmacokinetic/pharmacodynamic features, and potential for therapeutic drug monitoring will be addressed. Each antibiotic paragraph is divided into specialized microbiological, clinical, and pharmacological sections, including detailed and appropriate tables. A better understanding of the latest promising advances in the field of therapeutic options could lead to the development of a better approach in managing antimicrobial therapy for multidrug-resistant Gram-positive pathogens, which increasingly needs to be better stratified and targeted.

14.
Inn Med (Heidelb) ; 64(11): 1123-1128, 2023 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-37644177

RESUMO

Infections caused by pathogens with antimicrobial resistance (AMR) pose a threat to modern healthcare and have triggered the development of comprehensive national and global action plans against the spread of AMR. These include an increasing global network with the focus on rational antibiotic use, innovative strategies on antibiotic research and development, and new therapeutic approaches in antibacterial drug research. In Europe 671,689 infections associated with AMR pathogens and 33,110 deaths directly related to AMR were counted in just 1 year. Globally, resistant Staphylococcus aureus, Escherichia coli, pneumococci, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most common pathogens in the context of these deaths. Resistance to antibiotics in major drug classes such as beta-lactams and fluoroquinolones is particularly common. Strategies for overcoming the global AMR crisis address research on AMR emergence and spread, promoting campaigns for responsible antibiotic use, and improving infection prevention. The identification of new antibiotics and treatment approaches and the development of new strategies to contain the spread of AMR are essential. Newly approved substances include delafloxacin, lefamulin, and meropenem-vaborbactam. New antibiotics that are well advanced in clinical trials are aztreonam-avibactam, sulbactam-durlobactam, omadacycline, and type II topoisomerase inhibitors. Much interest is also being shown in the development of new therapeutic approaches such as bacteriophage treatment.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Farmacorresistência Bacteriana , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , beta-Lactamas
15.
Antibiotics (Basel) ; 12(6)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37370396

RESUMO

Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant Pseudomonas aeruginosa (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (p = 0.033) and Cmin (p = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (p = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF.

16.
Microorganisms ; 11(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37375104

RESUMO

Delafloxacin is a novel fluoroquinolone agent that is approved for clinical application. In this study, we analyzed the antibacterial efficacy of delafloxacin in a collection of 47 Escherichia coli strains. Antimicrobial susceptibility testing was performed by the broth microdilution method and minimum inhibitory concentration (MIC) values were determined for delafloxacin, ciprofloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, and imipenem. Two multidrug-resistant E. coli strains, which exhibited delafloxacin and ciprofloxacin resistance as well as extended-spectrum beta-lactamase (ESBL) phenotype, were selected for whole-genome sequencing (WGS). In our study, delafloxacin and ciprofloxacin resistance rates were 47% (22/47) and 51% (24/47), respectively. In the strain collection, 46 E. coli were associated with ESBL production. The MIC50 value for delafloxacin was 0.125 mg/L, while all other fluoroquinolones had an MIC50 value of 0.25 mg/L in our collection. Delafloxacin susceptibility was detected in 20 ESBL positive and ciprofloxacin resistant E. coli strains; by contrast, E. coli strains that exhibited a ciprofloxacin MIC value above 1 mg/L were delafloxacin-resistant. WGS analysis on the two selected E. coli strains (920/1 and 951/2) demonstrated that delafloxacin resistance is mediated by multiple chromosomal mutations, namely, five mutations in E. coli 920/1 (gyrA S83L, D87N, parC S80I, E84V, and parE I529L) and four mutations in E. coli 951/2 (gyrA S83L, D87N, parC S80I, and E84V). Both strains carried an ESBL gene, blaCTX-M-1 in E. coli 920/1 and blaCTX-M-15 in E. coli 951/2. Based on multilocus sequence typing, both strains belong to the E. coli sequence type 43 (ST43). In this paper, we report a remarkable high rate (47%) of delafloxacin resistance among multidrug-resistant E. coli as well as the E. coli ST43 international high-risk clone in Hungary.

18.
Pharmaceutics ; 15(3)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36986665

RESUMO

Antibacterial fluoroquinolones (FQs) are frequently used in treating infections. However, the value of FQs is debatable due to their association with severe adverse effects (AEs). The Food and Drug Administration (FDA) issued safety warnings concerning their side-effects in 2008, followed by the European Medicine Agency (EMA) and regulatory authorities from other countries. Severe AEs associated with some FQs have been reported, leading to their withdrawal from the market. New systemic FQs have been recently approved. The FDA and EMA approved delafloxacin. Additionally, lascufloxacin, levonadifloxacin, nemonoxacin, sitafloxacin, and zabofloxacin were approved in their origin countries. The relevant AEs of FQs and their mechanisms of occurrence have been approached. New systemic FQs present potent antibacterial activity against many resistant bacteria (including resistance to FQs). Generally, in clinical studies, the new FQs were well-tolerated with mild or moderate AEs. All the new FQs approved in the origin countries require more clinical studies to meet FDA or EMA requirements. Post-marketing surveillance will confirm or infirm the known safety profile of these new antibacterial drugs. The main AEs of the FQs class were addressed, highlighting the existing data for the recently approved ones. In addition, the general management of AEs when they occur and the rational use and caution of modern FQs were outlined.

19.
Int J Antimicrob Agents ; 61(6): 106795, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36965675

RESUMO

Delafloxacin is a new fluoroquinolone indicated for the treatment of complicated bacterial skin infections caused by Staphylococcus aureus. Despite its recent approval by the US Food and Drug Administration, the emergence of S. aureus-resistant strains has been reported. As such, this study aimed to investigate the activity of delafloxacin against a collection of S. aureus, and to determine the mechanisms of resistance. The activity of delafloxacin was measured in 59 S. aureus clinical isolates [40 methicillin-resistant S. aureus (MRSA) and 19 methicillin-susceptible S. aureus (MSSA)]. Whole-genome sequencing (WGS) was performed in the isolates resistant to delafloxacin. The minimum inhibitory concentrations required to inactivate 50% and 90% of the isolates (MIC50 and MIC90, respectively) were higher in MRSA (0.19 mg/L and 0.75 mg/L, respectively) than in MSSA (0.008 mg/L and 0.25 mg/L, respectively). Furthermore, 10 S. aureus clinical isolates (16.9%) were categorized as resistant to delafloxacin. Regarding the WGS data, several mutations were found in the quinolone resistance-determining region. Nevertheless, a mutation in the same position (E84K and E84V) of topoisomerase IV (ParC) was found exclusively in the four high-level delafloxacin-resistant isolates. Interestingly, a plasmid-encoded qacC gene (efflux pump) was found to be harboured by the isolate with the highest delafloxacin MIC value (32 mg/L). The use of a wide-spectrum efflux pump inhibitor revealed an important contribution of this system to the acquisition of delafloxacin resistance. In conclusion, delafloxacin has activity against S. aureus, including MRSA. However, this study showed that mutations in position 84 of ParC and the acquisition of a QacC efflux pump are key factors for the development of delafloxacin resistance in S. aureus.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade Microbiana
20.
Future Microbiol ; 18: 117-126, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722304

RESUMO

Aim: Meropenem-vaborbactam and delafloxacin activities were not assessed against Achromobacter spp. (Achr), Burkholderia cepacia complex (Bcc) and Stenotrophomonas maltophilia (Smal). Methodology: A total of 106 Achr, 57 Bcc and 100 Smal were tested with gradient diffusion test of meropenem-vaborbactam, delafloxacin and comparators. Results: Meropenem-vaborbactam MIC50 were 4 µg/ml for Achr, 1 µg/ml for B. cepacia, 2 µg/ml for B. cenocepacia and B. multivorans, and 32 µg/ml for Smal. Delafloxacin MIC50 were 4 µg/ml for Achr, 0.25 µg/ml for B. cepacia and B. multivorans, 2 µg/ml for B. cenocepacia, and 0.5 µg/m for Smal. meropenem-vaborbactam MICs were fourfold lower than meropenem for 28.3% Achr, 77.2% B. cepacia, 53.8% B. cenocepacia and 77.2% B. multivorans. Conclusion: Meropenem-vaborbactam and delafloxacin are in vitro active against Bcc and Achr.


We assess the efficacy of two new antibiotics, meropenem­vaborbactam and delafloxacin, to kill rarely encountered bacteria. These bacteria, Achromobacter, Burkholderia and Stenotrophomonas maltophilia, mainly cause respiratory tract infections. Both antibiotics are found active against Achromobacter and Burkholderia, but not S. maltophilia.


Assuntos
Complexo Burkholderia cepacia , Stenotrophomonas maltophilia , Meropeném/farmacologia , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana
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