Showing papers on "Quinolone published in 2022"

Quinolone antibiotics in sewage treatment plants with activated sludge treatment processes: A review on source, concentration and removal

Abstract: According to the existing research results, this paper reviews the influent and effluent concentrations , migration and transformation, and influencing factors of quinolone antibiotics in sewage treatment plants (STPs) with activated sludge treatment processes. Animal breeding and slaughtering wastewater, pharmaceutical wastewater and medical and domestic sewage may be the main sources of quinolone antibiotics. The compounds and concentrations of quinolone antibiotics in influents and effluents around the world are quite different, which is generally due to the difference in social and environmental factors in different regions, and the different treatment processes and operating parameters adopted. The migration and transformation of quinolone antibiotics is usually the result of the synergistic effect of sludge adsorption, biodegradation and photolysis. Sludge adsorption based on electrostatic interaction, hydrophobic forces and other mechanisms is the dominant route to remove quinolone antibiotics, but it does not reduce the total amount of the target antibiotics. An appropriate selection of conditions and control of process variables are beneficial to improve the removal of quinolone antibiotics by biodegradation with co-metabolism. Sources control, treatment processes improvement, fate understanding and prediction, monitoring strategies and risks assessment are potential options for improving the elimination and controlling the pollution of quinolone antibiotics in the future.

Sulfonamide and quinolone antibiotics contaminated wastewater treatment by constructed rapid infiltration: efficiency and microbial community structure

Abstract: Four antibiotics common in wastewater, namely sulfadiazine (SD), sulfamethoxazole (SMX), ciprofloxacin (CIP), and norfloxacin (NOR), were used in the treatment of wastewater by constructed rapid infiltration (CRI), using coke as filler material. Results showed that the removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N) and the total phosphorus (TP) of the sulfonamide antibiotics infiltration column reached 75.01%, 40.79% and 91.22%, respectively, which were 6.61%, 12.13% and 2.68% lower than those of the quinolone antibiotics infiltration column. With increasing antibiotic concentration (2–10 mg/L), the removal of SD showed a downward trend. The average removal rates of CIP and NOR by the CRI reached 34.65% and 43.57%, respectively. Oxygen-containing functional groups of the coke played a positive role in the removal of antibiotics. The dehydrogenase (DH) activity in the sulfonamide infiltration column was 0.62 μg/(g·mL), which was 0.48 μg/(g·mL) lower than that of the quinolone infiltration column. Meanwhile, the activity of phosphatase (AKP) in the sulfonamide infiltration column was 0.06 mg/(g·h), 0.30 mg/(g·h) lower compared to that of the quinolone infiltration column. Microbial community was dominated by Actinomycetes (38.52–55.93%) at the phylum level and by Arthrobacter (34.00–49.20%) at the genus level, especially in the sulfonamide infiltration column. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis, carbohydrate (10.79–11.52%) and amino acid metabolism (10.79–11.27%) were the main bacterial pathways. Overall, sulfonamide antibiotics more negative impacted wastewater treatment by the CRI than quinolone antibiotics.

A new exploration toward adamantane derivatives as potential anti‐MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors

Abstract: Developing novel antimicrobial agents has become a necessitate due to the increasing rate of microbial resistance to antibiotics. All the newly adamantane derivatives were evaluated for their antimicrobial activities against six MDR clinical pathogenic isolates. The results exhibited that 13 compounds have from potent to good activity. Among those, five derivatives (6, 7, 9, 14a, and 14b) displayed the potent activities against the different isolates tested (MIC < 0.25 µg/ml with bacteria and <8 µg/ml with fungi) compared with Ciprofloxacin (CIP) and Fluconazole (FCA). Additionally, the potent adamantanes showed bactericidal and fungicidal effects based on (MBCs and MFCs) and the time‐kill assay. The most active adamantane derivatives 7 and 14b exhibited a synergistic effect of ΣFIC ≤ 0.5 with CIP and FCA against the bacterial and fungal isolates. Moreover, no antagonistic effect appeared for the tested derivatives. Additionally, the interaction of DNA gyrase and topoisomerase IV enzymes with the compounds 6, 7, 9, 14a, and 14b exhibited potent antimicrobial activity using in vitro biochemical assays and gel‐based DNA‐supercoiling inhibition method. The activity of DNA gyrase and topoisomerase IV enzymes showed inhibitory activity (IC50) of 6.20 µM and 9.40 µM with compound 7 and 10.14 µM and 13.28 µM with compound 14b, respectively. Surprisingly, exposing compound 7 to gamma irradiation sterilized and increased its activity. Finally, the in‐silico analysis predicted that the most active derivatives had good drug‐likeness and safe properties. Besides, molecular docking and quantum chemical studies revealed several important interactions inside the active sites and showed the structural features necessary for activity.

Emerging quinoline‐ and quinolone‐based antibiotics in the light of epidemics

Abstract: Pandemics are large‐scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Quinoline and quinolone antibiotics exhibit extensive activities approved by FDA in the treatment of the several ailments such as gastrointestinal infections, urinary tract infections, prostate inflammation, malaria, gonorrhea, skin infection, colorectal cancer, respiratory tract infections. These are active against both gram‐negative and gram‐positive bacteria. This basic core of quinoline and quinolone is vital due to its capability of targeting the pathogen causing disease and beneficial in treating the infectious disease. They inhibit the synthesis of nucleic acid of bacteria which results in the rupture of bacterial chromosome due to the interruption of enzymes such as DNA gyrase and topoisomerase IV. There are various quinoline and quinolone compounds that are synthetically derived by applying different synthesis approaches which show a wide range of pharmacological activities in several diseases. The most commonly used are fluoro, chloro, and hydroxychloro derivatives of quinoline and quinolone. These compounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life‐threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID‐19 (currently). In this chapter, the research and advancements of quinoline‐ and quinolone‐based antibiotics in epidemic management are briefly discussed.

Sublethal concentrations of heavy metals Cu2+ and Zn2+ can induce the emergence of bacterial multidrug resistance

Abstract: The emergence of multidrug resistance has become an environmental safety issue of worldwide concern. Numerous studies have confirmed that heavy metals can promote the spread of bacterial resistance. However, in addition to co-resistance plasmids, the role and mechanism of metals at sublethal levels (< minimum inhibitory concentration [MIC]) on antibiotic resistance remain poorly defined. Here we investigated the alteration of resistance phenotype under Cu2+ and Zn2+ exposure and explored the molecular mechanism by which heavy metals affect antibiotic resistance. The results showed that the MIC of Escherichia coli and Staphylococcus aureus on antibiotics, especially norfloxacin and tetracyclines, was significantly increased after seven consecutive days of exposure to Cu2+ and Zn2+ and exhibited a higher cross-resistance rate, which meant that heavy metals can induce bacteria to develop antibiotic resistances that were not previously available. It was observed the downregulation of outer membrane protein gene ompC after heavy metal exposure, while the expression of other efflux pump and resistance genes in E. coli was upregulated, especially tetB, tolC and arcAB genes, suggesting that heavy metals might enhance antibiotic resistance by altering the expression of efflux pump genes. Moreover, many point mutations were found in the efflux system of resistant mutant strains. In particular, quinolone-resistant mutant strains showed a point mutation in the conversion of serine (Ser) to phenylalanine (Phe) at residue 464 of the gyrB gene, which may also be an important cause of increased quinolone resistance. This study provides an explanation for the effect of heavy metals on bacterial resistance.

Preliminary Studies of Antimicrobial Activity of New Synthesized Hybrids of 2-Thiohydantoin and 2-Quinolone Derivatives Activated with Blue Light

Abstract: Thiohydantoin and quinolone derivatives have attracted researchers’ attention because of a broad spectrum of their medical applications. The aim of our research was to synthesize and analyze the antimicrobial properties of novel 2-thiohydantoin and 2-quinolone derivatives. For this purpose, two series of hybrid compounds were synthesized. Both series consisted of 2-thiohydantoin core and 2-quinolone derivative ring, however one of them was enriched with an acetic acid group at N3 atom in 2-thiohydantoin core. Antibacterial properties of these compounds were examined against bacteria: Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antimicrobial assay was carried out using a serial dilution method to obtain the MIC. The influence of blue light irradiation on the tested compounds was investigated. The relative yield of singlet oxygen (1O2*, 1Δg) generation upon excitation with 420 nm was determined by a comparative method, employing perinaphthenone (PN) as a standard. Antimicrobial properties were also investigated after blue light irradiation of the suspensions of the hybrids and bacteria placed in microtitrate plates. Preliminary results confirmed that some of the hybrid compounds showed bacteriostatic activity to the reference Gram-positive bacterial strains and a few of them were bacteriostatic towards Gram-negative bacteria, as well. Blue light activation enhanced bacteriostatic effect of the tested compounds.

Fluoroquinolone sales in food animals and quinolone resistance in non-typhoidal Salmonella from retail meats - United States, 2009-2018.

Abstract: Antimicrobial-resistant non-typhoidal Salmonella (NTS) infections are associated with worse health outcomes compared to antimicrobial-susceptible infections. Misuse of antimicrobials in food animals can amplify the emergence of antimicrobial resistance. The objective of this study was to examine the association between fluoroquinolone sales in food animals and the prevalence of quinolone-resistant NTS isolated from retail meats.We reviewed data for 4318 NTS isolates from retail meat samples collected from 2009 to 2018 through the FDA National Antimicrobial Resistance Monitoring System programs. The Pearson's correlation was used to examine the correlation between the prevalence of quinolone-resistant NTS and standardised fluoroquinolone sales.After adjusting for the increase in beef and pork production, fluoroquinolone sales increased by 41.67% from 2013 to 2018. The prevalence of quinolone-resistant NTS from retail ground beef increased from 5% in 2014 to 11% in 2018. The increase of quinolone-resistant isolates in retail meats since 2016 was mostly related to Salmonella Infantis and Salmonella enteritidis.One Health integrated surveillance for NTS isolates from food of animal origin and human sources is necessary to elucidate trends in resistance to critical drugs. The study also underscores the need for judicious use of antimicrobials in agricultural settings.

Design, Synthesis, in vitro and in silico Characterization of 2‐Quinolone‐L‐alaninate‐1,2,3‐triazoles as Antimicrobial Agents

Abstract: Due to the ever‐increasing antimicrobial resistance there is an urgent need to continuously design and develop novel antimicrobial agents. Inspired by the broad antibacterial activities of various heterocyclic compounds such as 2‐quinolone derivatives, we designed and synthesized new methyl‐(2‐oxo‐1,2‐dihydroquinolin‐4‐yl)‐L‐alaninate‐1,2,3‐triazole derivatives via 1,3‐dipolar cycloaddition reaction of 1‐propargyl‐2‐quinolone‐L‐alaninate with appropriate azide groups. The synthesized compounds were obtained in good yield ranging from 75 to 80 %. The chemical structures of these novel hybrid molecules were determined by spectroscopic methods and the antimicrobial activity of the compounds was investigated against both bacterial and fungal strains. The tested compounds showed significant antimicrobial activity and weak to moderate antifungal activity. Despite the evident similarity of the quinolone moiety of our compounds with fluoroquinolones, our compounds do not function by inhibiting DNA gyrase. Computational characterization of the compounds shows that they have attractive physicochemical and pharmacokinetic properties and could serve as templates for developing potential antimicrobial agents for clinical use.

Occurrence of plasmid-mediated quinolone resistance genes in Pseudomonas aeruginosa strains isolated from clinical specimens in southwest Iran: a multicentral study

Abstract: This study aimed to assess the presence of qnrA, qnrB, qnrC, qnrD, qnrS, qepA, and aac(6')-Ib-cr determinants as well as quinolone resistance pattern of clinical isolates of P. aeruginosa in Ahvaz, southwest Iran. A total of 185 clinical isolates of P. aeruginosa were collected from 5 university-affiliated hospitals in Ahvaz, southwest Iran. The disk diffusion method was applied to assess the quinolone resistance pattern. The presence of qnrA, qnrB, qnrC, qnrD, qnrS, qepA, and aac(6')-Ib-cr genes was investigated by the polymerase chain reaction (PCR) method. Overall, 120 (64.9%) isolates were non-susceptible to quinolones. The most and the less quinolone resistance rates were observed against ciprofloxacin (59.4%) and ofloxacin (45.9%), respectively. The prevalence rates of qnr genes were as follows: qnrA (25.8%), qnrB (29.2%), and qnrS (20.8%). The qnrB gene was the most common type of qnr genes. The qnr genes were occurred in 37.5% (n = 45/120) of quinolne-resistant isolates, simultaneously. The qnrC, qnrD, qepA, and aac(6')-Ib-cr genes were not recognized in any isolates. In conclusion, the ofloxacin was the most effective quinolone. This study was the first to shed light on the prevalence of PMQR genes among P. aeruginosa isolates in southwest Iran.

Investigation of plasmid‐mediated quinolone resistance genes among clinical isolates of Klebsiella pneumoniae in southwest Iran

Abstract: Extensive and inappropriate use of quinolones has led to growing resistance rates to these broad‐spectrum antibiotics. The present study purposed to investigate the prevalence of plasmid‐mediated quinolone resistance (PMQR) genes in Klebsiella pneumoniae clinical isolates.

Controlling Antimicrobial Activity of Quinolones Using Visible/NIR Light-Activated BODIPY Photocages

Abstract: Controlling the activity of a pharmaceutical agent using light offers improved selectivity, reduction of adverse effects, and decreased environmental build-up. These benefits are especially attractive for antibiotics. Herein, we report a series of photoreleasable quinolones, which can be activated using visible/NIR light (520–800 nm). We have used BODIPY photocages with strong absorption in the visible to protect two different quinolone-based compounds and deactivate their antimicrobial properties. This activity could be recovered upon green or red light irradiation. A comprehensive computational study provides new insight into the reaction mechanism, revealing the relevance of considering explicit solvent molecules. The triplet excited state is populated and the photodissociation is assisted by the solvent. The light-controlled activity of these compounds has been assessed on a quinolone-susceptible E. coli strain. Up to a 32-fold change in the antimicrobial activity was measured.

Recognition of quinolone antibiotics by the multidrug efflux transporter MexB of Pseudomonas aeruginosa

Abstract: The drug/proton antiporter MexB is the engine of the major efflux pump MexAB-OprM in Pseudomonas aeruginosa. This protein is known to transport a large variety of compounds, including antibiotics, thus conferring a multi-drug resistance phenotype. Due to the difficulty of producing co-crystals, only two X-ray structures of MexB in a complex with ligands are available to date, and mechanistic aspects are largely hypothesized based on the body of data collected for the homologous protein AcrB of Escherichia coli. In particular, a recent study (Ornik-Cha, Wilhelm, Kobylka et al., Nat. Commun., 2021, 12, 6919) reported a co-crystal structure of AcrB in a complex with levofloxacin, an antibiotic belonging to the important class of (fluoro)-quinolones. In this work, we performed a systematic ensemble docking campaign coupled to the cluster analysis and molecular-mechanics optimization of docking poses to study the interaction between 36 quinolone antibiotics and MexB. We additionally investigated surface complementarity between each molecule and the transporter and thoroughly assessed the computational protocol adopted against the known experimental data. Our study reveals different binding preferences of the investigated compounds towards the sub-sites of the large deep binding pocket of MexB, supporting the hypothesis that MexB substrates oscillate between different binding modes with similar affinity. Interestingly, small changes in the molecular structure translate into significant differences in MexB–quinolone interactions. All the predicted binding modes are available for download and visualization at the following link: https://www.dsf.unica.it/dock/mexb/quinolones.

Rapid Detection of Quinolone Resistance Mutations in gyrA of Helicobacter pylori by Real-Time PCR

Abstract: The treatment of infections by the gastric pathogen Helicobacter pylori (H. pylori) has become more difficult due to increased rates of resistances against various antibiotics. Typically, atriple therapy, employing a combination of at least two antibiotics and a proton pump inhibitor, is used to cure H. pylori infections. In case of first-line therapy failure, quinolones are commonly applied in a second-line therapy. To prevent second-line treatment failures, we developed an improved method to detect the most common quinolone-resistance mutations located in the quinolone-resistance-determining region (QRDR) of the bacterial gyrA gene. Biopsy material from the gastric mucosa of infected patients was used to identify quinolone-resistant strains before the onset of drug administration. Two different wild-type and six mutant QRDR sequences were included. Melting curve analyses were performed with corresponding gyrA plasmid DNAs using a real-time polymerase chain reaction (RT-PCR) assay. By applying a combination of only two different fluorescent probes, this assay allows wild-type sequences to be unambiguously distinguished from all known mutant QRDR sequences of H. pylori. Next, the Tm values of patient DNAs were established, and the genotypes were confirmed by sequencing. Thus, quinolone-resistant H. pylori strains can be easily and quickly diagnosed before treatment, which will help to avoid the administration of ineffective drug regimes.

Discovery of N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides as DNA gyrase B-targeted antibacterial agents

Abstract: Abstract Emerging drug resistance is generating an urgent need for novel and effective antibiotics. A promising target that has not yet been addressed by approved antibiotics is the bacterial DNA gyrase subunit B (GyrB), and GyrB inhibitors could be effective against drug-resistant bacteria, such as methicillin-resistant S. aureus (MRSA). Here, we used the 4-hydroxy-2-quinolone fragment to search the Specs database of purchasable compounds for potential inhibitors of GyrB and identified AG-690/11765367, or f1, as a novel and potent inhibitor of the target protein (IC50: 1.21 µM). Structural modification was used to further identify two more potent GyrB inhibitors: f4 (IC50: 0.31 µM) and f14 (IC50: 0.28 µM). Additional experiments indicated that compound f1 is more potent than the others in terms of antibacterial activity against MRSA (MICs: 4–8 µg/mL), non-toxic to HUVEC and HepG2 (CC50: approximately 50 µM), and metabolically stable (t1/2: > 372.8 min for plasma; 24.5 min for liver microsomes). In summary, this study showed that the discovered N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides are novel GyrB-targeted antibacterial agents; compound f1 is promising for further development.

Trifluoromethylated Quinolone-Hydantoin Hybrids: Synthesis and Antibacterial Evaluation

Abstract: A series of new trifluoromethyl-substituted quinolones and hydantoin hybrids has been synthesized and evaluated against Gram-positive bacterium (Staphylococcus aureus MTCC 96) and Gram-negative bacteria (Pseudomonas aeruginosa MTCC 441, Klebsiella pneumonia MTCC 109, and Escherichia coli MTCC 442). Compound 19c, having the 6-propene group on the quinolone ring, showed similar activity to a standard drug (chloramphenicol) by exhibiting MIC values of 50 µg/mL against S. aureus and P. aeruginosa. Physicochemical properties of compound 19c were also determined, which were in line with Lipinski’s rule of five, suggesting the suitability of compound 19c in biological systems. Various types of binding interactions of 19c within the active site of DNA gyrase of S. aureus were also streamlined by molecular docking studies, suggesting its capability to block the catalytic process of the DNA gyrase, which could be the possible reason for its antibacterial potential.

A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with Staphylococcus aureus DNA Gyrase

Abstract: Since 2000 some thirteen quinolones/fluoroquinolones have been developed and come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA-cleavage complexes with DNA gyrase and topo IV, the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here we report a 2.8 Å X-ray crystal structure which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA-cleavage site(s) as quinolones sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water-metal ion bridge to GyrA) suggesting it may be more difficult for bacteria to develop target mediated resistance. We found that zoliflodacin had an MIC of 4 µg/mL against Acinetobacter baumannii, an improvement of 4-fold over its progenitor QPT-1. The current phase III clinical trial of zoliflodacin for gonorrhea is due to be read out in 2023. Zoliflodacin, together with the unrelated novel bacterial topoisomerase inhibitor gepotidacin, are likely to become the first entirely novel chemical entities approved against Gram-negative bacteria in the 21st century. Zoliflodacin may also become the progenitor of a new safer class of antibacterial drugs against other problematic Gram-negative bacteria.

Phylogenomic Analysis of Salmonella enterica Serovar Indiana ST17, an Emerging Multidrug-Resistant Clone in China

Abstract: Fluoroquinolones and cephalosporins are the primary choices for severe salmonellosis treatment. S. Indiana has become one of the most prevalent serovars in breeding poultry and poultry meats in China in recent years. ST17 was recognized as the leading epidemiological importance in S. Indiana because of its high-level resistance to the most of common antibiotics, including ciprofloxacin and ceftriaxone. ABSTRACT Salmonella enterica serovar Indiana (S. Indiana) is an extremely expanded foodborne pathogen in China in recent years. This study aimed to elucidate the national prevalence and phylogenomic characterization of this pathogen in China. Among 5, 287 serotyped Salmonella isolates collected during 2002 to 2018, 466 S. Indiana isolates were found in 15 provinces, and 407 were identified to be ST17, and the rest were ST2040. Among 407 ST17 isolates, 372 (91.4%) were multidrug resistant, and 366 (89.9%) were resistant to ciprofloxacin, 235 (57.7%) were further resistant to ceftriaxone. Phylogenomic analysis revealed that ST17 isolates were classified into four clades (I, II, III and IV), which appeared in international clonal dissemination. ST17 isolates from China fell into Clade IV with part of isolates from the United Kingdom, the United States, South Korea, and Thailand, suggesting their close genetic relationship. Mutations in quinolone resistance-determining regions (QRDR) of GyrA and ParC, and plasmid-mediated quinolone resistance (PMQR) genes aac(6′)-Ib-cr, oqxAB, and qnrS as well as extended spectrum β-lactamases (ESBL) genes blaCTX-M, blaOXA, and blaTEM in isolates from Clade IV were much higher than those from other three clades. Various blaCTX-M subtypes (blaCTX-M-65, blaCTX-M-55, blaCTX-M-27, blaCTX-M-14, and blaCTX-M-123) with ISEcp1, IS903B, ISVsa5, and IS1R were found in ST17 isolates, especially Tn1721 containing ΔISEcp1-blaCTX-M-27-IS903B in P1-like bacteriophage plasmids. These findings on the prevalent and genomic characterization for the S. Indiana multidrug-resistant ST17 clone in China, which have not been reported yet, provide valuable insights into the potential risk of this high-resistant clone. IMPORTANCE Fluoroquinolones and cephalosporins are the primary choices for severe salmonellosis treatment. S. Indiana has become one of the most prevalent serovars in breeding poultry and poultry meats in China in recent years. ST17 was recognized as the leading epidemiological importance in S. Indiana because of its high-level resistance to the most of common antibiotics, including ciprofloxacin and ceftriaxone. However, the prevalence and phylogenomic characterization of ST17 isolates are unclear. Here, we did a retrospective screening on a large scale for S. Indiana in China, and performed its phylogenomic analysis. It was found that ST17 isolates had extensive spread in 15 provinces of China and became a multidrug-resistant clone. The international spread of the ST17 isolates was observed among several countries, especially China, the United Kingdom, and the United States. Our study emphasized the importance of surveillance of a high-resistant S. Indiana ST17 clone to combat its threat to public health.

High-Level Quinolone-Resistant Haemophilus haemolyticus in Pediatric Patient with No History of Quinolone Exposure

Abstract: The prevalence of antimicrobial resistance among Haemophilus spp. is a critical concern, but high-level quinolone-resistant strains had not been isolated from children. We isolated high-level quinolone-resistant H. haemolyticus from the suction sputum of a 9-year-old patient. The patient had received home medical care with mechanical ventilation for 2 years and had not been exposed to any quinolones for >3 years. The H. haemolyticus strain we isolated, 2019-19, shared biochemical features with H. influenzae. However, whole-genome analysis found this strain was closer to H. haemolyticus. Phylogenetic and mass spectrometry analyses indicated that strain 2019-19 was in the same cluster as H. haemolyticus. Comparison of quinolone resistance–determining regions showed strain 2019-19 possessed various amino acid substitutions, including those associated with quinolone resistance. This report highlights the existence of high-level quinolone-resistant Haemophilus species that have been isolated from both adults and children.

Characterization of Mutations in DNA Gyrase and Topoisomerase IV in Field Strains and In Vitro Selected Quinolone-Resistant Mycoplasma hyorhinis Mutants

Abstract: Mycoplasma hyorhinis is ubiquitous in swine, and it is a common pathogen of swine that causes polyserositis, arthritis, and maybe pneumonia. Fluoroquinolones are effective antimicrobials used for the treatment of mycoplasmal infection. However, a decrease in fluoroquinolones susceptibility in mycoplasma was observed. The molecular mechanisms have been studied in many mycoplasma species, while the mechanism in M. hyorhinis is still unknown. This study aimed to illustrate the in vitro development of fluoroquinolone resistance in M. hyorhinis and unveil the resistance mechanisms in both in vitro selected mutants and field strains. Seven ciprofloxacin-sensitive M. hyorhinis isolates were chosen to induce the fluoroquinolone resistance in vitro, and the point mutations in the quinolone resistance-determining regions (QRDRs) were characterized. The substitutions first occurred in ParC, resulting in a 2- to 8-fold increase in resistance, followed by additional mutations in GyrA and/or ParE to achieve a 32-fold increase. The mutations occurred in hot spots of QRDRs, and they were diverse and variable, including five in ParC (Ser80Phe, Ser80Tyr, Phe80Tyr, Glu84Gly, and Glu84Lys), four in GyrA (Ala83Val, Ser84Pro, Asp87Tyr, and Asp87Asn) and one in ParE (Glu470Lys). Target mutations in field strains were observed in the ParC (Ser80Phe, Ser81Pro, and Glu84Gln) of isolates with MICCIP = 2 μg/mL. This study characterized the point mutations in the QRDRs of M. hyorhinis and could be useful for the rapid detection of fluoroquinolone resistance in M. hyorhinis field isolates.