Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin.

BACKGROUND: Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment. METHODS: We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI. RESULTS: Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant-days; p =  .8) and multidrug-resistant gram-negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant-days; p =  .08) were not significantly higher in comparison to patients who did not receive moxifloxacin. CONCLUSION: A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.

Successful maintenance treatment of disseminated nocardiosis with cerebral abscess in a severely immunocompromised patient allergic to trimethoprim-sulfamethoxazole using moxifloxacin and high-dose minocycline: A case report.

Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although trimethoprim-sulfamethoxazole (TMP/SMX) remains the cornerstone of nocardiosis treatment, optimal alternative therapies for patients intolerant to TMP/SMX are not well-established. Herein, we report a case of disseminated nocardiosis with bacteremia and multiple lesions in the lungs and brain caused by Nocardia farcinica, in a 60-year-old man who had previously undergone allogeneic HSCT and was receiving immunosuppressants for severe chronic graft-versus-host disease. The patient received atovaquone for the prophylaxis of Pneumocystis pneumonia because of a previous serious allergic reaction to TMP/SMX. The patient was initially treated with imipenem/cilastatin and amikacin, which were later switched to ceftriaxone and amikacin based on the results of antimicrobial susceptibility testing. After switching to oral levofloxacin and a standard dose of minocycline, the patient experienced a single recurrence of brain abscesses. However, after switching to oral moxifloxacin and high-dose minocycline, the patient did not experience any relapses during the subsequent two years and seven months of treatment. In treating nocardiosis with brain abscesses, it is crucial to select oral antibiotics based on the antimicrobial susceptibility test results and pharmacokinetics, especially when TMP/SMX is contraindicated. A combination of oral moxifloxacin and high-dose minocycline could be a promising alternative therapy.

Eco-friendly approach for the determination of moxifloxacin in pharmaceutical formulations and biological fluids based on fluorescence quenching of l-tryptophan.

A rapid, novel and cost-effective spectrofluorimetric method developed to determine moxifloxacin (MFX) in pharmaceutical preparations because MFX in a pH 10 medium could reduce the fluorescence intensity of l-tryptophan. The maximum fluorescence excitation and emission wavelengths were found to be 280 and 363 nm respectively. A range of factors affecting fluorescence quenching and the effect of co-existing substances were investigated. Fluorescence quenching values (ΔF = FL-tryptophan - FMoxi-L-tryptophan ) displayed a strong linear relationship with the MFX concentration ranging from 0.2 to 8.0 µg/ml under optimum conditions. The limit of detection was found to be 6.1 × 10-4  µg/ml. The proposed method was shown to be suitable for MFX determination in pharmaceutical tablets and biological fluids by the linearity, recovery and limit of detection. The spectrofluorimetric approach that has been developed is extremely eco-friendly, as evidenced by the fact that all the experimental components and solvents were safe for the environment.

Moxifloxacin HCl -loaded Cellulose Acetate Butylate In Situ Forming Gel for Periodontitis Treatment.

Periodontitis presents significant treatment challenges due to its complexity and potential complications. In response, an in situ forming gel (ISG) loaded with moxifloxacin HCl (Mx) and cellulose acetate butyrate (CAB) was developed for targeted periodontitis therapy. Mx-loaded 10-45% CAB-based ISGs were developed, and their physicochemical properties such as rheology, viscosity, contact angle, gel morphology and gel formation, interface interaction were investigated. Moreover, the formulation performance studies including drug release and kinetics, in vitro degradation, and antimicrobial activities were also evaluated. The Mx-loaded ISGs containing 25-45% CAB demonstrated rapid matrix formation in both macroscopic and microscopic examinations and presented plastic deformation matrix. Tracking with sodium fluorescein and Nile red fluorescence probes indicated delayed solvent movement owing to CAB matrix formation. Adequate CAB content sustained Mx release for one week, following Peppas-Sahlin model and indicating a predominantly Fickian diffusion mechanism. Higher CAB content likely contributed to a denser matrix structure, leading to a slower in vitro degradation rate. Synchrotron radiation X-ray tomographic and SEM imaging provided insights into the CAB matrix structure and porous network formation. These ISG formulations effectively inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, and Porphyromonas gingivalis. The Mx-loaded 40% CAB-based ISG shows promise as a dosage form for treating periodontitis. Further clinical trials are necessary to ensure the safety of this new ISG formulation, despite existing safety data for other medicinal uses of CAB. HIGHLIGHTS: Moxifloxacin HCl-loaded 10-45% cellulose acetate butyrate (CAB)-based in situ forming gels (ISG) were developed. They were evaluated for physicochemical properties, drug release, in vitro degradation, and antimicrobial activities. ISGs with 25-45% CAB showed swift matrix formation and plastic deformation Adequate CAB content sustained Mx release with Fickian diffusion mechanism They promise for periodontitis treatment because of effective inhibition of related pathogens.

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The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

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.

Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349).

BACKGROUND: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the prespecified subgroup of people with human immunodeficiency virus (HIV) (PWH). METHODS: PWH and CD4+ counts ≥100 cells/µL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months after randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% noninferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV status. PWH were enrolled in a staged fashion to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz. RESULTS: A total of 2516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4+ count was 344 cells/µL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was noninferior to control (absolute difference in unfavorable outcomes -7.4%; 95% confidence interval [CI] -20.8% to 6.0%); the rifapentine regimen was not noninferior to control (+7.5% [95% CI, -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%). CONCLUSIONS: In people with HIV-associated DS-PTB with CD4+ counts ≥100 cells/µL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was noninferior to the 6-month control regimen and was safe. CLINICAL TRIALS REGISTRATION: NCT02410772.

Optimizing Moxifloxacin Dose in MDR-TB Participants with or without Efavirenz Coadministration Using Population Pharmacokinetic Modeling.

Moxifloxacin is included in some treatment regimens for drug-sensitive tuberculosis (TB) and multidrug-resistant TB (MDR-TB). Aiming to optimize dosing, we described moxifloxacin pharmacokinetic and MIC distribution in participants with MDR-TB. Participants enrolled at two TB hospitals in South Africa underwent intensive pharmacokinetic sampling approximately 1 to 6 weeks after treatment initiation. Plasma drug concentrations and clinical data were analyzed using nonlinear mixed-effects modeling with simulations to evaluate doses for different scenarios. We enrolled 131 participants (54 females), with median age of 35.7 (interquartile range, 28.5 to 43.5) years, median weight of 47 (42.0 to 54.0) kg, and median fat-free mass of 40.1 (32.3 to 44.7) kg; 79 were HIV positive, 29 of whom were on efavirenz-based antiretroviral therapy. Moxifloxacin pharmacokinetics were described with a 2-compartment model, transit absorption, and elimination via a liver compartment. We included allometry based on fat-free mass to estimate disposition parameters. We estimated an oral clearance for a typical patient to be 17.6 L/h. Participants treated with efavirenz had increased clearance, resulting in a 44% reduction in moxifloxacin exposure. Simulations predicted that, even at a median MIC of 0.25 (0.06 to 16) mg/L, the standard daily dose of 400 mg has a low probability of attaining the ratio of the area under the unbound concentration-time curve from 0 to 24 h to the MIC (fAUC0-24)/MIC target of >53, particularly in heavier participants. The high-dose WHO regimen (600 to 800 mg) yielded higher, more balanced exposures across the weight ranges, with better target attainment. When coadministered with efavirenz, moxifloxacin doses of up to 1,000 mg are needed to match these exposures. The safety of higher moxifloxacin doses in clinical settings should be confirmed.

Drug-ionic surfactant interactions: density, sound speed, spectroscopic, and electrochemical studies.

The failure of antibiotics against infectious diseases has become a global health issue due to the incessant use of antibiotics in the community and a lack of entry of new antibacterial drugs onto the market. The limited knowledge of biophysical interactions of existing antibiotics with bio-membranes is one of the major hurdles to design and develop more effective antibiotics. Surfactant systems are the simplest biological membrane models that not only mimic the cell membrane functions but are also used to investigate the biophysical interactions between pharmaceutical drugs and bio-membranes at the molecular level. In this work, volumetric and acoustic studies were used to investigate the molecular interactions of moxifloxacin (MXF), a potential antibacterial drug, with ionic surfactants (dodecyl-tri-methyl-ammonium bromide (DTAB), a cationic surfactant and sodium dodecyl sulfate (SDS), an anionic surfactant) under physiological conditions (phosphate buffer, pH 7.4) at T = 298.15-313.15 K at an interval of 5 K. Various volumetric and acoustic parameters were computed from the density and sound speed data and interpreted in terms of MXF-ionic surfactant interaction using electrostriction effect and co-sphere overlap model. Absorption spectroscopy and cyclic voltammetry were further used to determine the binding, partitioning, and related free energies of MXF with ionic micelles.

A randomized, double-blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women.

AIM: The voltage-gated potassium channel Kv 11.1 is important for repolarizing the membrane potential in excitable cells such as myocytes, pancreatic α- and ß-cells. Moxifloxacin blocks the Kv 11.1 channel and increases the risk of hypoglycaemia in patients with diabetes. We investigated glucose regulation and secretion of glucoregulatory hormones in young people with and without moxifloxacin, a drug known to block the Kv 11.1 channel. MATERIALS AND METHODS: The effect of moxifloxacin (800 mg/day for 4 days) or placebo on glucose regulation was assessed in a randomized, double-blind, crossover study of young men and women (age 20-40 years and body mass index 18.5-27.5 kg/m2 ) without chronic disease, using 6-h oral glucose tolerance tests and continuous glucose monitoring. RESULTS: Thirty-eight participants completed the study. Moxifloxacin prolonged the QTcF interval and increased heart rate. Hypoglycaemia was more frequently observed with moxifloxacin, both during the 8 days of continuous glucose monitoring and during the oral glucose tolerance tests. Hypoglycaemia questionnaire scores were higher after intake of moxifloxacin. Moxifloxacin reduced the early plasma-glucose response (AUC0-30 min ) by 7% (95% CI: -9% to -4%, p < .01), and overall insulin response (AUC0-360 min ) decreased by 18% (95% CI: -24% to -11%, p < .01) and plasma glucagon increased by 17% (95% CI: 4%-33%, p = .03). Insulin sensitivity calculated as the Matsuda index increased by 11%, and MISI, an index of muscle insulin sensitivity, increased by 34%. CONCLUSIONS: In young men and women, moxifloxacin, a drug known to block the Kv 11.1 channel, increased QT interval, decreased glucose levels and was associated with increased muscle insulin sensitivity and more frequent episodes of hypoglycaemia.

A mouth watering case of Mycoplasma salivarium native mitral valve endocarditis: 'case report'.

BACKGROUND: Mycoplasma salivarium is part of our commensal oral flora and readily resides in dental plaque. Although considered indolent, few case reports have documented its pathogenic potential in humans. To this day no case of Mycoplasma salivarium infectious endocarditis has ever been described. CASE PRESENTATION: Our report describes a challenging case of Mycoplasma salivarium endocarditis, with a patient presenting with oligoarticular joint swelling, and later on in the course of his disease developed signs of right-sided heart failure. The diagnosis was initially mistaken for septic gonarthritis and was later established on the basis of echocardiography and eubacterial PCR of joint fluid. CONCLUSION: This report describes a first documented case of Mycoplasma salivarium culture negative endocarditis that was successfully treated with targeted antimicrobial therapy. Specific antimicrobial therapy targeting Mycoplasma spp, lead to clinical improvement, with radiological regression of the lesion and the resolution of the serum inflammation biomarkers.

Rifampin-moxifloxacin-metronidazole combination therapy for severe Hurley stage 1 hidradenitis suppurativa: prospective short-term trial and 1-year follow-up in 28 consecutive patients.

BACKGROUND: Severe Hurley stage 1 hidradenitis suppurativa (HS1) is a difficult-to-treat form of the disease. OBJECTIVE: To assess the efficacy and tolerance of the oral combination of rifampin (10 mg/kg once daily)/moxifloxacin (400 mg once daily)/metronidazole (250-500 mg 3 times daily) (RMoM) treatment strategy in patients with severe HS1. METHODS: Prospective, open-label, noncomparative cohort study in 28 consecutive patients. Nineteen patients were treated for 6 weeks by RMoM, followed by 4 weeks of rifampin/moxifloxacin alone, then by cotrimoxazole after remission. Moxifloxacin was replaced by pristinamycin (1 g 3 times daily) in 9 patients because of contraindications or intolerance. The primary endpoint was a Sartorius score of 0 (clinical remission) at week 12. RESULTS: The median Sartorius score dropped from 14 to 0 (P = 6 × 10-6) at week 12, with 75% of patients reaching clinical remission. A low initial Sartorius score was a prognosis factor for clinical remission (P = .049). The main adverse effects were mild gastrointestinal discomfort, mucosal candidiasis, and asthenia. At 1 year of follow-up, the median number of flares dropped from 21/year to 1 (P = 1 × 10-5). LIMITATIONS: Small, monocentric, noncontrolled study. CONCLUSIONS: Complete and prolonged remission can be obtained in severe HS1 by using targeted antimicrobial treatments.

Moxifloxacin monotherapy for treatment of uncomplicated pelvic inflammatory disease: A systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of moxifloxacin monotherapy for the treatment of uncomplicated pelvic inflammatory disease (uPID). METHODS: The literatures from PubMed, ScienceDirect, Google Scholar, Cochrane library and the http://clinicaltrials.gov/ were retrieved until February 2023. Only randomized controlled trials (RCTs) comparing the efficacy and safety of moxifloxacin with other antibiotics for treating uPID were included. The primary outcomes were clinical cure rate (CCR), bacteriological success rates (BSR) and risk of drug-related adverse events (AEs). We used random-effects modelled meta-analysis, trial sequential analysis, and the Grading of Recommendations Assessment, Development, and Evaluation. This study was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42023428751). RESULTS: A total of four RCTs that enrolled 3201 women patients with uPID were included. In the per-protocol populations, no significant difference was observed between patients given moxifloxacin and those given other antibiotics with regard to CCR at test-of-cure (TOC) (2485 patients, odds ratio [OR] = 0.84, 95% confidence interval [CI] 0.68-1.04, p = 0.12). Similarly, there was no statistically significant difference between patients given moxifloxacin and those given other antibiotics in terms of BSR at TOC (471 patients, OR = 1.17, 95% CI 0.70-1.96, p = 0.56) in the microbiologically valid population. However, drug-related AEs occurred less frequently with moxifloxacin than with other antibiotics (2973 patients, OR = 0.74, 95% CI 0.64-0.86, p < 0.0001), especially gastrointestinal AEs (2973 patients, OR = 0.59, 95% CI 0.47-0.74, p < 0.00001). CONCLUSIONS: In the treatment of uPID, moxifloxacin monotherapy can achieve similar efficacy as other combination therapy regimens. Moreover, moxifloxacin had a better safety profile than that of comparators. Based on its additional advantages (i.e., better safety profile, no dosage adjustment and better compliance), moxifloxacin may be a more fascinating option compared with the currently used regimens.

Feasibility of moxifloxacin and proflavine dual fluorescence imaging for detecting gastrointestinal neoplastic lesions: A prospective study.

OBJECTIVES: High-contrast and high-resolution imaging techniques would enable real-time sensitive detection of the gastrointestinal lesions. This study aimed to investigate the feasibility of novel dual fluorescence imaging using moxifloxacin and proflavine in the detection of neoplastic lesions of the human gastrointestinal tract. METHODS: Patients with the colonic and gastric neoplastic lesions were prospectively enrolled. The lesions were biopsied with forceps or endoscopically resected. Dual fluorescence imaging was performed by using custom axially swept wide-field fluorescence microscopy after topical moxifloxacin and proflavine instillation. Imaging results were compared with both confocal imaging with cell labeling and conventional histological examination. RESULTS: Ten colonic samples (one normal mucosa, nine adenomas) from eight patients and six gastric samples (one normal mucosa, five adenomas) from four patients were evaluated. Dual fluorescence imaging visualized detail cellular structures. Regular glandular structures with polarized cell arrangement were observed in normal mucosa. Goblet cells were preserved in normal colonic mucosa. Irregular glandular structures with scanty cytoplasm and dispersed elongated nuclei were observed in adenomas. Goblet cells were scarce or lost in the colonic lesions. Similarity analysis between moxifloxacin and proflavine imaging showed relatively high correlation values in adenoma compared with those in normal mucosa. Dual fluorescence imaging showed good detection accuracies of 82.3% and 86.0% in the colonic and the gastric lesions, respectively. CONCLUSIONS: High-contrast and high-resolution dual fluorescence imaging was feasible for obtaining detail histopathological information in the gastrointestinal neoplastic lesions. Further studies are needed to develop dual fluorescence imaging as an in vivo real-time visual diagnostic method.

A QbD-led simple and sensitive RP-UHPLC method for simultaneous determination of moxifloxacin, voriconazole, and pirfenidone: An application to pharmaceutical analysis.

A novel, quick and precise RP-UHPLC analytical method for the simultaneous determination of moxifloxacin (MFX), voriconazole (VCZ) and pirfenidone (PIR) was developed and validated according to the International Conference on Harmonization guidelines using a QbD-driven response surface Box-Behnken design. The developed method was validated considering the selectivity, sensitivity, linearity, accuracy-precision, robustness, stability, limit of detection and limit of quantification, respectively. Resolution between MFX, VCZ and PIR was achieved using a gradient elution protocol against a Waters Symmetry Shield C18 column (150 × 4.6 mm2 , 5 µm) using an Agilent 1290, Infinity II series LC system. The method was applied to quantitatively estimate proprietary and in-house prepared pharmaceutical topical ophthalmic formulations containing MFX, VCZ and PIR at wavelength (λmax ) of 296, 260 and 316 nm. The method is sensitive enough to detect up to 0.1 ppm of analytes in the formulation. The method was further exploited to study and identify the possible degradation products of the analytes. The proposed chromatographic method is simple, economical, reliable and reproducible. In conclusion, the developed method could be applicable for routine quality control analysis of single or combined MFX, VCZ and PIR-containing units or bulk dosage forms in pharmaceutical industries and research organizations working on drug discovery and development.

Protective effects of royal jelly and Echinacea against moxifloxacin-induced renal and hepatic injury in rats.

Antibiotic use, especially fluoroquinolones, has been linked to extensive renal and hepatic injury thus inflicts a considerable health problem. Fifty rats were allocated into five groups (n = 10). Group 1 represented the normal-control group. Group 2 received moxifloxacin only (MOX; 8 mg/kg/day, i.p.) for seven days and represented the MOX-control group. Groups 3, 4, and 5 received MOX for seven days accompanied by royal jelly (RJ; 100 mg/kg/day, p.o.), Echinacea (ECH; 40 mg/kg/day, p.o.), and a combination of both at the aforementioned doses respectively for 30 days. All groups were investigated for renal and hepatic function tests. Renal tissue content of kidney injury molecule-1 (KIM-1) along with renal and hepatic tissue contents of reduced glutathione (GSH) and malondialdehyde (MDA) were assessed for all groups. Histopathological examination was performed followed by immunohistochemical staining for caspase-3 in renal and hepatic tissues. MOX administration resulted in significant renal and hepatic damage. RJ and ECH significantly improved the serum parameters of renal and hepatic functions along with increasing GSH and decreasing MDA in renal and hepatic tissues. Renal contents of KIM-1 were also reduced. Moreover, RJ, ECH, and their combination amended MOX-induced histopathological changes and significantly reduced caspase-3 immunohistochemical staining in both renal and hepatic tissues. The current study is the first to elucidate the effect of RJ, ECH, and their combination against MOX-induced renal and hepatic injury in rats. The study suggests that these protective effects are mainly via the reduction of oxidative stress induced by MOX administration.

Transferrin decorated PLGA encumbered moxifloxacin nanoparticles and in vitro cellular studies.

PURPOSE: Complicated intra-abdominal infection (cIAI) management involves administering antibiotics that destroy the cell wall and the genesis of bacterial lipopolysaccharide (LPS). During the infectious state, the expression of transferrin receptors upregulates on the intestinal epithelial cells, which are considered the site of infection. In the present research, transferrin decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulated moxifloxacin (MOX) were developed for possible targeting of the receptors in the colon. SIGNIFICANCE: This study will explore more about the incorporation of transferrin as effective coating material in targeted drug delivery. METHODS: Nanoparticles were prepared using nano-emulsification and surface modification with transferrin was done by layer-by-layer methodology and evaluated by powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), FTIR, SEM, antibacterial activity, and cellular uptake studies. RESULTS: The formulated NPs exhibit a size of ≈170 nm, PDI ≈ 0.25, zeta potential ≈-4.0 mV, drug loading ≈ 6.8%, and entrapment efficiency of 82%. Transferrin-decorated NPs exhibit tailored release for almost 12 h and in vitro antibacterial activity for 14 h. The cellular uptake studies were done on a RAW264.7 cell line for better determination of transferrin uptake of fabricated NPs. CONCLUSION: The above study circumvents around the preparation of transferrin decorated PLGA encumbered MOX NPs intended for cIAI-induced sepsis. PLGA NPs provide tailored release of MOX with primary burst and followed by sustained release. These observations confines with antibacterial activity studies. The prepared transferrin-coated NPs were stable and effectively uptaken by RAW264.7 cells. However, future studies include the preclinical investigation of these NPs in sepsis-induced murine models.

Fluoroquinolone-Based Organic Salts (GUMBOS) with Antibacterial Potential.

Antimicrobial resistance is a silent pandemic considered a public health concern worldwide. Strategic therapies are needed to replace antibacterials that are now ineffective. One approach entails the use of well-known antibacterials along with adjuvants that possess non-antibiotic properties but can extend the lifespan and enhance the effectiveness of the treatment, while also improving the suppression of resistance. In this regard, a group of uniform materials based on organic salts (GUMBOS) presents an alternative to this problem allowing the combination of antibacterials with adjuvants. Fluoroquinolones are a family of antibacterials used to treat respiratory and urinary tract infections with broad-spectrum activity. Ciprofloxacin and moxifloxacin-based GUMBOS were synthesized via anion exchange reactions with lithium and sodium salts. Structural characterization, thermal stability and octanol/water partition ratios were evaluated. The antibacterial profiles of most GUMBOS were comparable to their cationic counterparts when tested against Gram-positive S. aureus and Gram-negative E. coli, except for deoxycholate anion, which demonstrated the least effective antibacterial activity. Additionally, some GUMBOS were less cytotoxic to L929 fibroblast cells and non-hemolytic to red blood cells. Therefore, these agents exhibit promise as an alternative approach to combining drugs for treating infections caused by resistant bacteria.

The possible effect of topically applied azithromycin and moxifloxacin on the alleviation of uveitis.

PURPOSE: To investigate the inhibitory effect of topically administered azithromycin (AZM), and moxifloxacin (MXF) against tumor necrosis factor-α (TNF-α) production in a rat model of endotoxin-induced uveitis (EIU). METHODS: Thirty-six Wistar albino rats were divided into 6 equal groups. Groups 1, 2 and 3 were determined as sham, control group for topical AZM application and control group for topical MXF application, respectively. Sterile saline, topical AZM 1.5%, and topical MXF 0.5% were instilled 5 times daily for totally 6 days on both eyes of the rats in Group 4, Group 5, and Group 6, before and after inducing EIU by intravitreal injections of lipopolysaccharide, respectively. At 24 h after intravitreal injections, aqueous humor was collected from both eyes of each rat for the assessment of TNF-α concentration. Also, density of nuclear factor kappa B (NF-κB) in ciliary body, and the number of cells infiltrating the posterior segment of EIU rat eyes was assessed in one eye of each rat. RESULTS: There was a significant reduction in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical AZM in comparison with those pretreated with sterile saline (139 ± 38.6 in Group 4 vs. 72 ± 12.6 in Group 5, p = 0.006). There was also a marked decrease in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical MXF (139 ± 38.6 in Group 4 vs.86.1 ± 35.5 in Group 6, p = 0.025). Also, evident suppressions were determined in mean density of NF-κB, and in mean number of cells in EIU rats pretreated either with topical AZM, or topical MXF. CONCLUSIONS: Topically applied AZM or MXF may be beneficial in the suppression of TNF-α production in aqueous humor.

Moxifloxacin Pharmacokinetics, Cardiac Safety, and Dosing for the Treatment of Rifampicin-Resistant Tuberculosis in Children.

BACKGROUND: Moxifloxacin is a recommended drug for rifampin-resistant tuberculosis (RR-TB) treatment, but there is limited pediatric pharmacokinetic and safety data, especially in young children. We characterize moxifloxacin population pharmacokinetics and QT interval prolongation and evaluate optimal dosing in children with RR-TB. METHODS: Pharmacokinetic data were pooled from 2 observational studies in South African children with RR-TB routinely treated with oral moxifloxacin once daily. The population pharmacokinetics and Fridericia-corrected QT (QTcF)-interval prolongation were characterized in NONMEM. Pharmacokinetic simulations were performed to predict expected exposure and optimal weight-banded dosing. RESULTS: Eighty-five children contributed pharmacokinetic data (median [range] age of 4.6 [0.8-15] years); 16 (19%) were aged <2 years, and 8 (9%) were living with human immunodeficiency virus (HIV). The median (range) moxifloxacin dose on pharmacokinetic sampling days was 11 mg/kg (6.1 to 17). Apparent clearance was 6.95 L/h for a typical 16-kg child. Stunting and HIV increased apparent clearance. Crushed or suspended tablets had faster absorption. The median (range) maximum change in QTcF after moxifloxacin administration was 16.3 (-27.7 to 61.3) ms. No child had QTcF ≥500 ms. The concentration-QTcF relationship was nonlinear, with a maximum drug effect (Emax) of 8.80 ms (interindividual variability = 9.75 ms). Clofazimine use increased Emax by 3.3-fold. Model-based simulations of moxifloxacin pharmacokinetics predicted that current dosing recommendations are too low in children. CONCLUSIONS: Moxifloxacin doses above 10-15 mg/kg are likely required in young children to match adult exposures but require further safety assessment, especially when coadministered with other QT-prolonging agents.