Intramuscular therapeutic doses of enrofloxacin affect microbial community structure but not the relative abundance of fluoroquinolones resistance genes in swine manure.

Livestock manure is a major source of veterinary antibiotics and antibiotic resistance genes (ARGs). Elucidation of the residual characteristics of ARGs in livestock manure following the administration of veterinary antibiotics is critical to assess their ecotoxicological effects and environmental contamination risks. Here, we investigated the effects of enrofloxacin (ENR), a fluoroquinolone antibiotic commonly used as a therapeutic drug in animal husbandry, on the characteristics of ARGs, mobile genetic elements, and microbial community structure in swine manure following its intramuscular administration for 3 days and a withdrawal period of 10 days. The results revealed the highest concentrations of ENR and ciprofloxacin (CIP) in swine manure at the end of the administration period, ENR concentrations in swine manure in groups L and H were 88.67 ± 45.46 and 219.75 ± 88.05 mg/kg DM, respectively. Approximately 15 fluoroquinolone resistance genes (FRGs) and 48 fluoroquinolone-related multidrug resistance genes (F-MRGs) were detected in swine manure; the relative abundance of the F-MRGs was considerably higher than that of the FRGs. On day 3, the relative abundance of qacA was significantly higher in group H than in group CK, and no significant differences in the relative abundance of other FRGs, F-MRGs, or MGEs were observed between the three groups on day 3 and day 13. The microbial community structure in swine manure was significantly altered on day 3, and the altered community structure was restored on day 13. The FRGs and F-MRGs with the highest relative abundance were qacA and adeF, respectively, and Clostridium and Lactobacillus were the dominant bacterial genera carrying these genes in swine manure. In summary, a single treatment of intramuscular ENR transiently increased antibiotic concentrations and altered the microbial community structure in swine manure; however, this treatment did not significantly affect the abundance of FRGs and F-MRGs.

Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones.

BACKGROUND: Fluoroquinolones lack approval for treatment of tularemia but have been used extensively for milder illness. Here, we evaluated fluoroquinolones for severe illness. METHODS: In an observational study, we identified case-patients with respiratory tularemia from July to November 2010 in Jämtland County, Sweden. We defined severe tularemia by hospitalization for >24 hours and severe bacteremic tularemia by Francisella tularensis subsp. holarctica growth in blood or pleural fluid. Clinical data and drug dosing were retrieved from electronic medical records. Chest images were reexamined. We used Kaplan-Meier curves to evaluate time to defervescence and hospital discharge. RESULTS: Among 67 case-patients (median age, 66 years; 81% males) 30-day mortality was 1.5% (1 of 67). Among 33 hospitalized persons (median age, 71 years; 82% males), 23 had nonbacteremic and 10 had bacteremic severe tularemia. Subpleural round consolidations, mediastinal lymphadenopathy, and unilateral pleural fluid were common on chest computed tomography. Among 29 hospitalized persons with complete outcome data, ciprofloxacin/levofloxacin (n = 12), ciprofloxacin/levofloxacin combinations with doxycycline and/or gentamicin (n = 11), or doxycycline as the single drug (n = 6) was used for treatment. One disease relapse occurred with doxycycline treatment. Treatment responses were rapid, with median fever duration 41.0 hours in nonbacteremic and 115.0 hours in bacteremic tularemia. Increased age-adjusted Charlson comorbidity index predicted severe bacteremic tularemia (odds ratio, 2.7 per score-point; 95% confidence interval, 1.35-5.41). A 78-year-old male with comorbidities and delayed ciprofloxacin/gentamicin treatment died. CONCLUSIONS: Fluoroquinolone treatment is effective for severe tularemia. Subpleural round consolidations and mediastinal lymphadenopathy were typical findings on computed tomography among case-patients in this study.

Magnetic activated carbon from spent coffee grounds: iron-catalyzed CO2 activation mechanism and adsorption of antibiotic lomefloxacin from aqueous medium.

The facile fabrication of low-cost adsorbents possessing high removal efficiency and convenient separation property is an urgent need for water treatment. Herein, magnetic activated carbon was synthesized from spent coffee grounds (SCG) by Fe-catalyzed CO2 activation at 800 °C for 90 min, and magnetization and pore formation were simultaneously achieved during heat treatment. The sample was characterized by N2 adsorption-desorption, XRD, VSM, SEM, and FTIR. Batch adsorption experiments were conducted using lomefloxacin (LMO) as the probing pollutant. Preparation mechanism was revealed by TG-FTIR and XRD. Experimental results showed that Fe3O4 derived from Fe species can be reduced to Fe by carbon at high temperatures, followed by subsequent reoxidation to Fe3O4 by CO2, and the redox cycle between Fe and Fe3O4 favored the formation of pores. The promotion effects of Fe species on CO2 activation can be quantitatively reflected by the yield of CO as the signature gaseous product, and the suitable activation temperate range was determined to be 675 to 985 °C. The BET surface area, total pore volume, and saturated magnetization value of the product were 586 m2 g-1, 0.327 cm3 g-1, and 11.59 emu g-1, respectively. The Langmuir model was applicable for the adsorption isotherm data for LMO with the maximum adsorption capacity of 95 mg g-1, and thermodynamic analysis revealed that the adsorption process was endothermic and spontaneous. This study demonstrated that Fe-catalyzed CO2 activation was an effective method of converting SCG into magnetic separable adsorbent for LMO removal from aqueous medium.

Rifampicin does not reduce moxifloxacin concentrations at the site of infection and may not improve treatment outcome of a one-stage exchange surgery protocol of implant-associated osteomyelitis lesions in a porcine model.

We aimed to evaluate moxifloxacin steady-state concentrations in infected bone and soft tissue and to explore the additive microbiological and pathological treatment effect of rifampicin to standard moxifloxacin treatment of implant-associated osteomyelitis (IAO). 16 pigs were included. On Day 0, IAO was induced in the proximal tibia using a susceptible Staphylococcus aureus strain. On Day 7, the pigs underwent one-stage exchange surgery of the IAO lesions and were randomized to receive seven days of intravenous antibiotic treatment of either rifampicin combined with moxifloxacin or moxifloxacin monotherapy. On Day 14, microdialysis was applied for continuous sampling (8 h) of moxifloxacin concentrations. Microbiological, macroscopical pathology, and histopathological analyses were performed postmortem. Steady-state moxifloxacin area under the concentration-time curve was lower in the combination therapy group in plasma (total) and subcutaneous tissue compartments (infected and noninfected) (p < 0.04), while no differences were found in bone compartments. No additional treatment effect of rifampicin to moxifloxacin treatment was found (p = 0.57). Conclusive, additive rifampicin treatment does not reduce moxifloxacin concentrations at the infection site. Rifampicin treatment may not be necessary in a one-stage exchange treatment of IAO. However, our sample size and treatment period may have been too small and short to reveal true clinical differences.

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation.

Hematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin (CIP) or levofloxacin (LVX), with the cell-penetrating peptide transportan 10 (TP10). Here, we demonstrate that the resultant compounds display promising biologic activities in preclinical studies. These novel conjugates not only exhibit potent antimicrobial effects but are also selective against leukemia cells. The cytotoxic mechanism involves rapid disruption of cell membrane asymmetry leading to membrane damage. Importantly, these conjugates penetrated mammalian cells, accumulating within the nuclear membrane without significant effect on cellular architecture or mitochondrial function. Molecular simulations elucidated the aggregation tendencies of TP10 conjugates within lipid bilayers, resulting in membrane disruption and permeabilization. Moreover, mass spectrometry analysis confirmed efficient reduction of disulfide bonds within TP10 conjugates, facilitating release and activation of the fluoroquinolone derivatives. Intriguingly, these compounds inhibited human topoisomerases, setting them apart from traditional fluoroquinolones. Remarkably, TP10 conjugates generated lower intracellular levels of reactive oxygen species compared with CIP and LVX. The combination of antibacterial and antileukemic properties, coupled with selective cytostatic effects and minimal toxicity toward healthy cells, positions TP10 derivatives as promising candidates for innovative therapeutic approaches in the context of antileukemic HCT. This study highlights their potential in search of more effective leukemia treatments. SIGNIFICANCE STATEMENT: Fluoroquinolones are commonly used antibiotics, while transportan 10 (TP10) is a cell-penetrating peptide (CPP) with anticancer properties. In HCT, microbial infections are the primary cause of illness and death. Combining TP10 with fluoroquinolones enhanced their effects on different cell types. The dual pharmacological action of these conjugates offers a promising proof-of-concept solution for leukemic patients undergoing HCT. Strategically designed therapeutics, incorporating CPPs with antibacterial properties, have the potential to reduce microbial infections in the treatment of malignancies.

Fluoroquinolone resistance mutations among Mycobacterium tuberculosis and their interconnection with treatment outcome.

Background: Fluoroquinolone (FQ) antibiotics are among the most potent second-line antitubercular drugs these days. The aim of the study was to analyze the frequency and pattern of genetic mutation in preextensive (pre-XDR) and extensively drug-resistant Mycobacterium tuberculosis using second-line line probe assay (LPA) and to compare drug-resistant mutations with different treatment outcomes. Methods: Sputum, lymph node aspirate, and cold accesses from patients with rifampicin-resistant Tuberculosis (TB) were subjected to first-line and second-line LPA (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluoroquinolones (levofloxacin and moxifloxacin). Final treatment outcomes as per the National TB Elimination Program were assessed and compared with the mutation profile. Results: One hundred and fifty subjects were observed to have mutations associated with resistance to FQs and constituted the final study population. The most frequent mutation observed among GyrA drug resistance mutation was D94G (Gyr A MUT3C, 44/150, 66%) corresponding to high-level resistance to levofloxacin and moxifloxacin. The same mutation was associated with poor treatment outcome as died or treatment failure (odds ratio 2.50, relative risk 1.67, P = 0.043). The most common hetero-resistance mutation pattern observed in GyrA gene was wild type plus Asp94Gly mutation in 24.6% of isolates. Conclusions: GyrA MUT3C hybridization corresponding to single-point mutation of aspartic acid to glycine at codon 94 constitutes the most common mutation in GyrA gene locus in M. tuberculosis with significant association with treatment outcome as died compared to those with treatment outcome as cured.

Polymer based dual drug delivery system for targeted treatment of fluoroquinolone resistant Staphylococcus aureus mediated infections.

The present study attempts to treat S. aureus-induced soft skin infections using a combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, an efflux pump inhibitor molecule is synthesized and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP-loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained drug release for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation-solvent evaporation method, which showed optimum average particle size of 230-280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide a synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidence that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. The research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system for treating S. aureus-induced skin infections.

Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: An alert for empirical treatment.

BACKGROUND: Bacterial resistance to extended-spectrum beta-lactamases (ESBL) is present worldwide. Empirical antibiotic therapy is often needed, and the use of fluoroquinolones, such as ciprofloxacin and norfloxacin, is common. This study aimed to analyze the urine cultures from 2,680 outpatients in January 2019, 2020, 2021, and 2022, with bacterial counts above 100,000 CFU/mL in which Escherichia coli was the etiological agent. METHODS: We monitored the resistance of ESBL-positive and ESBL-negative strains to ciprofloxacin and norfloxacin and evaluated resistance rates. RESULTS: Significantly higher fluoroquinolone resistance rates were observed among ESBL-positive strains in all years studied. Furthermore, a significant increase in the rate of fluoroquinolone resistance was observed between 2021 and 2022 in ESBL-positive and -negative strains, as well as from 2020 to 2021 among the ESBL-positive strains. CONCLUSIONS: The data obtained in the present study showed a tendency towards an increase in fluoroquinolone resistance among ESBL-positive and -negative E. coli strains isolated from urine cultures in Brazil. Since empirical antibiotic therapy with fluoroquinolones is commonly used to treat diverse types of infections, such as community-acquired urinary tract infections, this work highlights the need for continuous monitoring of fluoroquinolone resistance among E. coli strains circulating in the community, which can mitigate the frequency of therapeutic failures and development of widespread multidrug-resistant strains.

gyrA Mutations in Mycoplasma genitalium and Their Contribution to Moxifloxacin Failure: Time for the Next Generation of Resistance-Guided Therapy.

BACKGROUND: Although single nucleotide polymorphisms (SNPs) in Mycoplasma genitalium parC contribute to fluoroquinolone treatment failure, data are limited for the homologous gene, gyrA. This study investigated the prevalence of gyrA SNPs and their contribution to fluoroquinolone failure. METHODS: Samples from 411 patients (male and female) undergoing treatment for M. genitalium infection (Melbourne Sexual Health Centre, March 2019-February 2020) were analyzed by Sanger sequencing (gyrA and parC). For patients treated with moxifloxacin (n = 194), the association between SNPs and microbiologic treatment outcome was analyzed. RESULTS: The most common parC SNP was G248T/S83I (21.1% of samples), followed by D87N (2.3%). The most common gyrA SNP was G285A/M95I (7.1%). Dual parC/gyrA SNPs were found in 8.6% of cases. One third of infections harboring parC G248T/S83I SNP had a concurrent SNP in gyrA conferring M95I. SNPs in gyrA cooccurred with parC S83I variations. Treatment failure was higher in patients with parC S83I/gyrA dual SNPs when compared with infections with single S83I SNP alone from analysis of (1) 194 cases in this study (81.2% vs 45.8%, P = .047), and (2) pooled analysis of a larger population of 535 cases (80.6% vs 43.2%; P = .0027), indicating a strong additive effect. CONCLUSIONS: Compared with parC S83I SNP alone, M. genitalium infections with dual mutations affecting parC/gyrA had twice the likelihood of failing moxifloxacin. Although antimicrobial resistance varies by region globally, these data indicate that gyrA should be considered as a target for future resistance assays in Australasia. We propose a strategy for the next generation of resistance-guided therapy incorporating parC and gyrA testing.

Seasonal distribution and dynamic evolution of antibiotics and evaluation of their resistance selection potential and ecotoxicological risk at a wastewater treatment plant in Jinan, China.

The seasonal distribution and dynamic evolution of antibiotics in wastewater from main treatment areas and in sludge and their resistance selection potential and ecotoxicological risk were studied at a municipal wastewater treatment plant in Jinan, East China. Ten antibiotics were selected, and all were detected in wastewater and sludge samples, with fluoroquinolones showing the highest detection concentrations and frequencies. Seasonal fluctuations in the antibiotic concentrations in the influent, effluent, and sludge were observed, with the highest values in winter in most cases. The dynamic evolution of antibiotics during the treatment process differed among the seasons. The antibiotic removal efficiencies were incomplete, ranging from - 40.47 to 100%. Mass balance analysis showed that sulfonamides, roxithromycin, and metronidazole were mainly removed through biological processing, whereas fluoroquinolones, doxycycline, and chloramphenicol were removed through sludge adsorption. Levofloxacin, as well as a mixture of the 10 antibiotics from the effluent, could pose a low ecotoxicological risk to Daphnia in the receiving waters. Additionally, levofloxacin and ciprofloxacin in the effluent and ciprofloxacin and metronidazole in the sludge may facilitate the selection of antibiotic-resistant bacteria in the environment.

Safety and Efficacy of Black Tea Extract in the Treatment of Acute Bacterial Conjunctivitis: A Rabbit Model.

PURPOSE: To determine the safety and efficacy of black tea extract in the treatment of bacterial conjunctivitis in a rabbit model and compare it with that of gatifloxacin drops. METHODS: Black tea extract was tested in vitro on bacterial cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Forty-two rabbit eyes were cultured with either MRSA (n=21) or P. aeruginosa (n=21) and further divided into a control group (n=5), a tea group (n=8) treated with black tea extract, and a gatifloxacin group (n=8) treated with 0.3% gatifloxacin eye drops. Conjunctival swabs were collected on the third and fifth days. RESULTS: The tea extract successfully inhibited the growth of both organisms at a concentration of 400 mg/mL. Rabbits in the treatment groups showed a reduction in the clinical index on day 2 (P<0.01), unlike the control group (P=0.1), for both organisms. Resolution of conjunctivitis was achieved on days 4 and 5 in the tea and gatifloxacin groups, respectively. On days 3 and 5, while the control group still showed considerable bacterial growth, the tea and gatifloxacin groups showed its inhibition. CONCLUSION: Tea extract has antimicrobial effects similar to those of gatifloxacin in a rabbit model of conjunctivitis.

A Literature-Based Review and Analysis of the Pharmacodynamics of the Dose Frequency of Topical 0.3% Ciprofloxacin and 0.3% Ofloxacin in the Day-1 Treatment of Bacterial Keratitis.

Purpose: To determine the appropriate dose frequency for the second-generation fluoroquinolones (2FQs), ciprofloxacin 0.3% and ofloxacin 0.3%, in the day-1 treatment of bacterial keratitis (BK) based on the corneal concentrations achievable and required Minimum Inhibitory Concentration90 (MIC90) of common BK isolates. Methods: Literature-based ocular MIC90 required to treat bacterial isolates of BK patients were determined for each fluoroquinolone. Published corneal concentrations for each 2FQ, and the drop regimens used to reach these concentrations, were then analyzed to determine the relationship between the corneal 2FQ concentration and the amount of drug applied per hour and the total amount applied. Results: Significant relationships were found to exist for corneal concentrations of both ciprofloxacin and ofloxacin and the amount of drug applied per hour (both P = 0.005), and the total amount of drug applied (P = 0.003 and P = 0.0004, respectively). Derived ciprofloxacin drops/hour corneal concentrations agreed well with both a literature-based regimen and the manufacturers' day-1 drop regimen for various MIC90. Derived ofloxacin drops per hour indicated a higher rate than that suggested by the manufacturer. Conclusions: Both a literature-based and the manufacturers' drop regimens for the day-1 treatment of BK using 0.3% ciprofloxacin have a pharmacodynamic basis, which is related to the required MIC90 of commonly encountered isolates in BK. Dose frequency for 0.3% ofloxacin should be in line with the manufacturers' maximum suggested drop regimen. Commonly suggested drop regimens below these recommendations for either FQ may need to be revised in view of these findings.

Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins.

BACKGROUND: Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. OBJECTIVES: To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. MAIN RESULTS: We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones.  We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.

The treatment effect of Levofloxacin, Moxifloxacin, and Gatifloxacin contained in the conventional therapy regimen for pulmonary tuberculosis: Systematic review and network meta-analysis.

BACKGROUND: Tuberculosis (TB) is one of the serious epidemics that highly threaten the global public health. To explore the treatment effect of Levofloxacin, Moxifloxacin, and Gatifloxacin contained in the conventional therapy regimen for pulmonary tuberculosis. METHODS: Medline, PubMed, Embase, and Cochrane Library were searched with the keyword such as "Levofloxacin," "Moxifloxacin," "Gatifloxacin," and "tuberculosis", through June 1992 to 2017. According to the inclusion and exclusion criteria, 2 researchers independently screened the literature, extracted the data, and evaluated the quality of the included studies. The Cochrane system was evaluated by RevMan5.2 and the network meta-analysis was performed by Stata 15. RESULTS: A total of 891 studies were included, with a total of 6565 patients. The results of network meta-analysis showed that Moxifloxacin + conventional therapy (CT) regimen was superior to CT regimen only on the spectrum culture negative. Both Levofloxacin + CT and Moxifloxacin + CT were superior to the CT regimen in treatment success rate. For the adverse events, the Levofloxacin + CT showed much safer results than CT group, while Moxifloxacin + CT had more adverse events than CT group. CONCLUSION: Levofloxacin, Moxifloxacin, and Gatifloxacin have different superiority, comparing to CT regimen in spectrum culture negative, treatment success rate, and adverse events. Hence, combined utilization of these quinolone is important on the clinical treatment for tuberculosis.

Green and Efficient Determination of Fluoroquinolone Residues in Edible Green Fruits and Leafy Vegetables by Ultrasound-Assisted Extraction Followed by HPLC-MS/MS.

In this work, a simple, quick and efficient analytical method for determination of human and veterinary fluoroquinolone antimicrobial residues in lettuce, cucumber and spinach is developed. The procedure entails a 6 min ultrasound-assisted extraction (UAE, 3 × 2 min) in an alkaline (2% v/v NH3) aqueous solution containing Mg2+ ions (3 × 6 mL), with no need for organic solvents. The extract is submitted to cleanup on the HLB™ cartridge and the fluoroquinolones are separated and quantified by HPLC-MS/MS in a 10 min chromatographic run, using a small amount of acetonitrile in the mobile phase. The method, entirely developed in real matrices, is validated according to the updated analytical guidelines and provided suitable recoveries in the range of 67-116% and precision (RSD ≤ 20%, n = 3) at different concentrations (15, 70 and 150 ng g-1), with method quantification limits of 2-10 ng g-1. Fluoroquinolones were detected and quantified at concentrations from few to hundreds of nanograms per gram in vegetables from supermarkets, demonstrating the applicability of the method for monitoring residues of these pharmaceuticals.

Mechanochemical treatment for degradation of ciprofloxacin (CIP) in solutions.

Ciprofloxacin (CIP) is a kind of widely used fluoroquinolone antibiotic, and the widespread presence of CIP in aquatic environment has become a serious issue. Mechanochemical treatment (MCT), as an effective approach to degrade persistent organic pollutants, has many advantages of low cost, simplicity, and being environmentally innocuous. However, little attention has been paid to employing MCT to treat effluents containing CIP. In this study, MCT was introduced to degrade CIP in aquatic solutions. A series of CIP degradation experiments were conducted by a planetary ball mill, and the influences of main parameters on CIP degradation efficiency were investigated. Furthermore, an optimum combination was selected through orthogonal experiments, and CIP degradation efficiency could reach as high as 99% in certain conditions. Besides, the biotoxicity of CIP solution was also studied. MCT exhibits satisfying performance for degrading CIP in solutions, which makes MCT a promising approach to CIP elimination and also encourages further applications in treating effluents containing other organic pollutants.

Appraisal of ICH E14/S7B Q&As adopted in February 2022 using thorough QT/QTc study data for α4-integrin antagonist carotegrast methyl in Japanese healthy subjects.

We investigated how a lack of placebo control affects the interpretation of results of thorough QT/QTc (TQT) study. Results of TQT study in 48 healthy Japanese subjects assessing the effects of 480 and 960 mg of carotegrast methyl (test drug) and 400 mg of moxifloxacin (positive control) on the time-matched changes in corrected QT from baseline (ΔQTcF) and the placebo-adjusted ΔQTcF (ΔΔQTcF) were analyzed with central-tendency and concentration-response analyses. In central-tendency analysis, moxifloxacin prolonged ΔQTcF and ΔΔQTcF with the largest mean values (90% confidence interval) of 12.1 ms (9.3, 14.8) and 15.4 ms (12.6, 18.1), respectively. Meanwhile, carotegrast methyl hardly altered ΔQTcF and ΔΔQTcF with the largest mean values of 0.8 ms (-2.3, 3.9) and 2.1 ms (-0.7, 4.8) for the low dose, and -0.2 ms (-3.4, 3.0) and 1.6 ms (-0.9, 4.2) for the high dose, respectively. In concentration-response analysis, moxifloxacin attained the estimated mean values for ΔQTcF and ΔΔQTcF of 11.4 ms (8.5, 14.4) and 16.7 ms (14.0, 19.4) at the mean Cmax, whereas carotegrast methyl provided those of -4.6 ms (-7.3, -1.9) and 0.7 ms (-1.4, 2.8), respectively. Thus, lack of placebo control did not influence the interpretation of TQT study with either of the analysis in line with updated E14/S7B Q&As.

Right hip gonococcal septic arthritis treatment with successful transition to oral fluoroquinolone.

We present a case of gonococcal septic arthritis of the right hip diagnosed via synovial fluid cultures. Antimicrobial susceptibility testing of the synovial fluid demonstrated susceptibility to tetracycline, ciprofloxacin, cefixime and ceftriaxone. Our patient was initially treated with ceftriaxone and was successfully de-escalated to oral levofloxacin to complete the treatment. This case is interesting given the rarity of disseminated gonococcal infections in the 21st century and that most clinical isolates of Neisseria gonorrhoeae are increasingly resistant to fluoroquinolones.

Susceptibility of caprine mastitis pathogens to tildipirosin, gamithromycin, oxytetracycline, and danofloxacin: effect of serum on the in vitro potency of current macrolides.

Mastitis is a significant disease in dairy ruminants, causing economic losses to the livestock industry and severe risks to public health. Antibiotic therapy is one of the most crucial practices to treat mastitis, although the susceptibility of caprine mastitis pathogens to current antibiotics has not been tested under standard or modified incubation conditions. This work evaluated the in vitro activity of tildipirosin, gamithromycin, oxytetracycline, and danofloxacin against caprine mastitis pathogens incubated following standard conditions of Clinical and Laboratory Standards Institute (CLSI) and deviation method by 25% supplementation with goat serum. Mycoplasma agalactiae, Escherichia coli, Staphylococcus aureus, Streptococcus spp., and coagulase-negative Staphylococci (CNS) were isolated from dairy goats with mastitis in Spain. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution technique. The lowest MIC90 under standard conditions was obtained with danofloxacin for mastitis-causing pathogens. An exception was M. agalactiae, where danofloxacin and oxytetracycline obtained low values. However, after adding serum, gamithromycin showed the lowest MIC50 for S. aureus, Streptococcus spp., and CNS. The lowest MIC50 was obtained with all the antibiotics tested (< 0.125 µg/ml) against M. agalactiae. Supplementing with serum resulted in a significant variation in tildipirosin and gamithromycin MIC values for CNS, S. aureus, M. agalagtiae, and E. coli. In brief, the MIC for antibiotics used against mastitis should be determined under conditions closely resembling intramammary infections to obtain representative susceptibility patterns against mastitis pathogens. Caprine mastitis pathogens were broadly susceptible to danofloxacin under standard conditions. The potency of macrolides against caprine mastitis pathogens increases when serum is present in culture media.