Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization.

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

A simple accurate method for concentration-QTc analysis in preclinical animal models.

INTRODUCTION: In preclinical cardiovascular safety pharmacology studies, statistical analysis of the rate corrected QT interval (QTc) is the focus for predicting QTc interval changes in the clinic. Modeling of a concentration/QTc relationship, common clinically, is limited due to minimal pharmacokinetic (PK) data in nonclinical testing. It is possible, however, to relate the average drug plasma concentration from sparse PK samples over specific times to the mean corrected QTc. We hypothesize that averaging drug plasma concentration and the QTc-rate relationship over time provides a simple, accurate concentration-QTc relationship bridging statistical and concentration/QTc modeling. METHODS: Cardiovascular telemetry studies were conducted in non-human primates (NHP; n = 48) and canines (n = 8). Pharmacokinetic samples were collected on separate study days in both species. Average plasma concentrations for specific intervals (CAverage0-X) were calculated for moxifloxacin in canines and NHP using times corresponding to super-intervals for the QTc data statistical analysis. The QTc effect was calculated for each super-interval using a linear regression correction incorporating QT and HR data from the whole super-interval. The concentration QTc effects were then modeled. RESULTS: In NHP, a 10.9 ± 0.06 ms (mean ± 95% CI) change in QTc was detected at approximately 1.5× the moxifloxacin plasma concentration that causes a 10 ms QTc change in humans, based on a 0-24 h super-interval. When simulating a drug without QT effects, mock, no effect on QTc was detected at up to 3× the clinical concentration. Similarly, in canines, a 16.6 ± 0.1 ms change was detected at 1.7× critical clinical moxifloxacin concentration, and a 0.04 ± 0.1 ms change was seen for mock. CONCLUSIONS: While simultaneous PK and QTc data points are preferred, practical constraints and the need for QTc averaging did not prevent concentration-QTc analyses. Utilizing a 0-24 h super-interval method illustrates a simple and effective method to address cardiovascular questions when preclinical drug exposures exceed clinical concentrations.

Optimized J to T peak and T peak to T end measurements in nonclinical species administered moxifloxacin and amiodarone.

INTRODUCTION: Cardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug development. TdP is associated with a delayed ventricular repolarization represented by QT interval prolongation in the electrocardiogram (ECG), typically due to block of the potassium channel encoded by the human ether-a-go-go related gene (hERG). Importantly however, not all drugs that prolong the QT interval are torsadagenic and not all hERG blockers prolong the QT interval. Recent clinical reports suggest that partitioning the QT interval into early (J to T peak; JTp) and late repolarization (T peak to T end; TpTe) components may be valuable for distinguishing low-risk mixed ion channel blockers (hERG plus calcium and/or late sodium currents) from high-risk pure hERG channel blockers. This strategy, if true for nonclinical animal models, could be used to de-risk QT prolonging compounds earlier in the drug development process. METHODS: To explore this, we investigated JTp and TpTe in ECG data collected from telemetered dogs and/or monkeys administered moxifloxacin or amiodarone at doses targeting relevant clinical exposures. An optimized placement of the Tpeak fiducial mark was utilized, and all intervals were corrected for heart rate (QTc, JTpc, TpTec). RESULTS: Increases in QTc and JTpc intervals with administration of the pure hERG blocker moxifloxacin and an initial QTc and JTpc shortening followed by prolongation with the mixed ion channel blocker amiodarone were detected as expected, aligning with clinical data. However, anticipated increases in TpTec by both standard agents were not detected. DISCUSSION: The inability to detect changes in TpTec reduces the utility of these subintervals for prediction of arrhythmias using continuous single­lead ECGs collected from freely moving dogs and monkeys.

Deleterious effects of a combination therapy using fluoroquinolones and tetracyclines for the treatment of Japanese spotted fever: a retrospective cohort study based on a Japanese hospital database.

OBJECTIVES: Tetracyclines are the standard treatment for rickettsiosis, including Japanese spotted fever (JSF), a tick-borne rickettsiosis caused by Rickettsia japonica. While some specialists in Japan advocate combining fluoroquinolones with tetracyclines for treating JSF, the negative aspects of combination therapy have not been thoroughly evaluated. Whether fluoroquinolones should be combined with tetracyclines for JSF treatment is controversial. The study aimed to evaluate the disadvantages of fluoroquinolones combined with tetracyclines for JSF treatment. METHODS: This retrospective cohort study was conducted using a Japanese database comprising claims data from April 2008 to December 2020. The combination therapy group (tetracyclines and fluoroquinolones) was compared with the monotherapy group (tetracycline only) regarding mortality and the incidence of complications. RESULTS: A total of 797 patients were enrolled: 525 received combination therapy, and 272 received monotherapy. The adjusted odds ratio (OR) for mortality was 2.30 [95% confidence interval (CI): 0.28-18.77] in the combination therapy group with respect to the monotherapy group. According to the subgroup analysis, patients undergoing combination therapy with ciprofloxacin experienced higher mortality rates compared with those receiving monotherapy (adjusted OR = 25.98, 95% CI = 1.71-393.75). Additionally, 27.7% of the combination therapy group received NSAIDs concurrently with fluoroquinolones. The combination therapy with NSAIDs group was significantly more likely to experience convulsions than the monotherapy without NSAIDs group (adjusted OR: 5.44, 95% CI: 1.13-26.30). CONCLUSIONS: This study found no evidence that combination therapy improves mortality outcomes and instead uncovered its deleterious effects. These findings facilitate a fair assessment of combination therapy that includes consideration of its disadvantages.

Amoxicillin, gemifloxacin and rabeprazole, as first-line Helicobacter pylori therapy in clinical practice: A pilot study.

Success in eradication of H. pylori is decreasing due to increasing resistant strains. In particular, side-effects due to 4-agent treatment multiple drug use are observed and treatment compliance decreases. The aim of this study was to evaluate the efficacy, reliability, and side-effect profile of the combination of amoxicillin and rabeprazole with gemifloxacin, which is a new generation quinolone, in the treatment of H. pylori infection. This study was conducted on 71 naive patients who received H. pylori eradication. All the patients were administered treatment of Amoxicillin (1000 mg twice a day) + Gemifloxacin (320 mg once a day) + rabeprazole (20 mg twice a day) for 7 days. Drug compliance and treatment tolerance were evaluated after finishing the treatment. At 1 month after the end of the treatment, H. pylori eradication was evaluated in all the patients by examining H. pylori antigen in the feces. In the evaluation after treatment, H. pylori eradication was obtained in 63 (88.7%) patients and eradication was not obtained in 8 (11.3%) patients. The treatment was not completed by 2 patients because of side-effects and noncompliance, so after exclusion of these 2 patients, successful H. pylori eradication was obtained in 63 (91.3%) of 69 patients who completed the treatment. Side-effects were seen in a total of 9 (12.7%) patients. Diarrhea, bloating, abdominal pain, and nausea-vomiting were seen in some patients, but no reflux, constipation, skin rash, listlessness-fatigue, headache, dizziness, palpitations, dry mouth, or weight loss was seen in any patient. In regions with high resistance to clarithromycin and metronidazole in particular, the combination of gemifloxacin with amoxicillin and rabeprazole can be considered for use in first-stage treatment as both the efficacy and tolerability are high.

Transzonular moxifloxacin and dexamethasone delivery in phacoemulsification: A novel dropless regimen.

PURPOSE: To assess the safety and efficacy of transzonular moxifloxacin and dexamethasone versus standard postoperative topical drug regimen in phacoemulsification. DESIGN: Nonrandomized prospective study. METHODS: The study included 100 eyes of 100 age and gender-matched individuals with senile cataract undergoing routine phacoemulsification. The patients were consecutively divided into transzonular (TZ = 50) and topical (TP = 50) groups. Both the groups were followed up for 4 weeks and assessed for intraocular inflammation, visual acuity, changes in intraocular pressure (IOP), and any adverse events. RESULTS: The grades of inflammation were significantly lower in TZ as compared to the TP group ( P < 0.001). The IOP remained normal and comparable in both the groups. Most of the patients in the two groups attained a visual acuity of 0.2 or better at the end of the follow-up. No adverse effects and increased rate of endophthalmitis were noted in TZ group. CONCLUSION: A one-time peroperative TZ moxifloxacin and dexamethasone combination is a safe and effective method to control postoperative inflammation after cataract surgery. A word of caution though, due precautions to be exercised to prevent the risk of inflammation and endophthalmitis.

Is the fluoroquinolone combination necessary for empirical antibiotic regimen in severe community-acquired pneumonia?

OBJECTIVES: This study aimed to assess whether superior clinical outcomes can be attained through piperacillin/tazobactam (TZP)+fluoroquinolone (FQ) combination therapy for severe community-acquired pneumonia (CAP) compared to TZP monotherapy. METHODS: This retrospective study was conducted at a tertiary care hospital in Korea. Adult inpatients diagnosed with pneumonia within 48 hours of hospitalization were included. Severe CAP was defined as a CURB-65 score of ≥ 3 or based on the 2007 guidelines of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) definition. Only patients who received either TZP and FQ combination or TZP as initial empirical therapy were included. RESULTS: The final analysis included 145 patients; 57.9% received combination therapy and 42.1% received monotherapy. In the combination therapy group, body mass index (20.67 ± 3.28 vs. 22.26 ± 4.80, p = 0.030) and asthma prevalence (0 vs. 8.3%, p = 0.022) were significantly higher; initial symptoms, clinical severity, and causative pathogens were not significantly different between groups. White blood cell counts (12,641.64 ± 6,544.66 vs. 12,491.67 ± 10,528.24, p = 0.008), and C-reactive protein levels (18.78 ± 11.47 vs. 26.58 ± 14.97, p < 0.001) were significantly higher in the combination therapy group. Clinical outcomes, including all-cause in-hospital mortality rate (26.2 vs. 33.3%, p = 0.358), were not significantly different between the groups. Multivariate analysis identified no significant association between FQ combination and all-cause in-hospital mortality. CONCLUSION: In patients with severe CAP, there were no differences in the clinical outcomes, including mortality, between the TZP and FQ combination therapy and TZP monotherapy. FQ combination was not significantly associated with in-hospital mortality.

Continuous evaluation of single-dose moxifloxacin concentrations in brain extracellular fluid, cerebrospinal fluid, and plasma: a novel porcine model.

BACKGROUND: Knowledge regarding CNS pharmacokinetics of moxifloxacin is limited, with unknown consequences for patients with meningitis caused by bacteria resistant to beta-lactams or caused by TB. OBJECTIVE: (i) To develop a novel porcine model for continuous investigation of moxifloxacin concentrations within brain extracellular fluid (ECF), CSF and plasma using microdialysis, and (ii) to compare these findings to the pharmacokinetic/pharmacodynamic (PK/PD) target against TB. METHODS: Six female pigs received an intravenous single dose of moxifloxacin (6 mg/kg) similar to the current oral treatment against TB. Subsequently, moxifloxacin concentrations were determined by microdialysis within five compartments: brain ECF (cortical and subcortical) and CSF (ventricular, cisternal and lumbar) for the following 8 hours. Data were compared to simultaneously obtained plasma samples. Chemical analysis was performed by high pressure liquid chromatography with mass spectrometry. The applied PK/PD target was defined as a maximum drug concentration (Cmax):MIC ratio >8. RESULTS: We present a novel porcine model for continuous in vivo CNS pharmacokinetics for moxifloxacin. Cmax and AUC0-8h within brain ECF were significantly lower compared to plasma and lumbar CSF, but insignificantly different compared to ventricular and cisternal CSF. Unbound Cmax:MIC ratio across all investigated compartments ranged from 1.9 to 4.3. CONCLUSION: A single dose of weight-adjusted moxifloxacin administered intravenously did not achieve adequate target site concentrations within the uninflamed porcine brain ECF and CSF to reach the applied TB CNS target.

Achromobacter xylosoxidans keratitis in a LASIK flap treated with intrastromal antibiotics: a case report.

Intrastromal antibiotic injections are a type of treatment that can be very useful in bacterial keratitis refractory to topical antibiotics. We present the case of a 44-year-old woman with an infiltrate in a laser in situ keratomiuleusis (LASIK) flap and growth of Achromobacter xylosoxidans, who was treated with topical ceftazidime for 1 month. However, after discontinuation of the antibiotic, there was a worsening with growth of the same germ. Topical treatment was reintroduced and, due to suspicion of germ reservoir, it was decided to give three cycles of intrastromal ceftazidime injections, the last one also with moxifloxacin, with good results. After 4 months asymptomatic and without treatment at the moment, no signs of recurrence have been observed. This case supports the usefulness of intraestromal injections in refractory cases to the topical medication.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Bioavailability of flumequine and diclofenac in mice exposed to a metal-drug chemical cocktail. Evaluation of the protective role of selenium.

BACKGROUND AND PURPOSE: Organisms, including humans, are subjected to the simultaneous action of a wide variety of pollutants, the effects of which should not be considered in isolation, as many synergies and antagonisms have been found between many of them. Therefore, this work proposes an in vivo study to evaluate the effect of certain metal contaminants on the bioavailability and metabolism of pharmacologically active compounds. Because the most frequent entry vector is through ingestion, the influence of the gut microbiota and the possible protective effects of selenium has been additionally evaluated. EXPERIMENTAL APPROACH: A controlled exposure experiment in mammals (Mus musculus) to a "chemical cocktail" consisting of metals and pharmaceuticals (diclofenac and flumequine). The presence of selenium has also been evaluated as an antagonist. Mouse plasma samples were measured by UPLC-QTOF. A targeted search of 48 metabolites was also performed. KEY RESULTS: Metals significantly affected the FMQ plasma levels when the gut microbiota was depleted. Hydroxy FMQ decreased if metals were present. Selenium minimized this decrease. The 3-hydroxy DCF metabolite was not found in any case. Changes in some metabolic pathways are discussed. CONCLUSIONS AND IMPLICATIONS: The presence of metals in the mouse diet as well as the prior treatment of mice with an antibiotic mixture (Abxs), which deplete the gut microbiota, has a decisive effect on the bioavailability and metabolism of the tested pharmaceuticals and dietary selenium minimize some of their effects.

Phenotypic and molecular characterization of fluoroquinolone resistant Pseudomonas aeruginosa isolates in Palestine / Caracterização fenotípica e molecular de isolados de Pseudomonas aeruginosa resistentes a fluoroquinolonas na Palestina

Fluoroquinolones are important antimicrobial agents for the treatment of Pseudomonas infections. A total of 11 isolates of P. aeruginosa were collected from different clinical samples from different medical centers in the North West Bank-Palestine during 2017. In this study, resistance to fluoroquinolones and secretions of β-lactamases were detected by phenotypic methods, while presence of β-lactamase gene sequences and other virulence factors were detected by PCR technique. PCR product for gyrA, parC and parE genes were sequenced for further analyses. The phylogenetic analyses, population diversity indices and haplotypes determination were conducted using computer programs MEGA version 6, DnaSP 5.1001 and median-joining algorithm in the program Network 5, respectively. Results of this study showed that the MIC for ciprofloxacin and norfloxacin had a range of 32-256 µg/ml. In addition, all isolates carried either exoT or exoT and exoY genes, different β-lactamase genes and 82% of these isolates harbored class 1 integrons. Analyses of the gyrA, parC and parE sequences were found to be polymorphic, had high haplotype diversity (0.945-0.982), low nucleotide diversity (0.01225-0.02001) and number of haplotypes were 9 for each gyrA and parE genes and 10 haplotypes for parC gene. The founder haplotypes being Hap-1 (18%), Hap-2 (27.3%) and Hap-6 (9.1%) for gyrA, parC and parE genes, respectively. Two of ParE haplotypes were detected as indel haplotypes. The Median-joining- (MJ) networks constructed from haplotypes of these genes showed a star-like expansion. The neutrality tests (Tajima’s D test and Fu’s Fs test) for these genes showed negative values. Palestinian fluoroquinolone resistant P. aeruginosa strains showed high MIC level for fluoroquinolones, β-lactamase producers, carried type III secretion exotoxin-encoding genes, most of them [...].

Fluoroquinolonas são agentes antimicrobianos importantes para o tratamento de infecções por Pseudomonas. Um total de 11 bacilos isolados de P. aeruginosa foram coletados de diferentes amostras clínicas provenientes de diferentes centros médicos na Cisjordânia-Palestina durante o ano de 2017. Neste estudo, resistência a fluoroquinolonas e secreções de β-lactamases foram detectadas por métodos fenotípicos, enquanto a presença de sequências do gene β-lactamase e outros fatores de virulência foram detectados pela técnica de PCR (Proteína C-reativa). O produto de PCR para os genes gyrA, parC e parE foram sequenciados para análises posteriores. As análises filogenéticas, os índices de diversidade populacional e a determinação de haplótipos foram realizados utilizando os softwares MEGA versão 6, DnaSP 5.1001 e o algoritmo de junção de mediana do programa Network 5, respectivamente. Os resultados deste estudo mostraram que a MIC para ciprofloxacina e norfloxacina tinha um intervalo de 32-256 µg/ml. Além disso, todos os bacilos isolados carregavam genes exoT ou exoT e exoY, genes de β-lactamase diferentes e 82% desses isolados continham integrons de classe 1. As análises das sequências gyrA, parC e parE foram consideradas polimórficas, com alta diversidade de haplótipos (0,945-0,982), baixa diversidade de nucleotídeos (0,01225-0,02001) e o número de haplótipos foi de 9 para cada gene de gyrA e parE e 10 haplótipos para o gene parC. Os haplótipos fundadores são Hap-1 (18%), Hap-2 (27,3%) e Hap-6 (9,1%) para os genes gyrA, parC e parE, respectivamente. Dois dos haplótipos parE foram detectados como haplótipos InDel. As redes Median-joining (MJ) construídas a partir de haplótipos desses genes mostraram uma expansão semelhante à de uma estrela. Os testes de neutralidade (teste D de Tajima e teste Fs de Fu) para esses genes apresentaram valores negativos. As cepas palestinas de P. aeruginosa resistentes a fluoroquinolonas mostraram alto nível de MIC para [...].

Protocolo de desensibilización a levofloxacino en paciente con infección osteoarticular. A propósito de un caso / Desensitization protocol with levofloxacin in patient with osteoarticual infection. Report of clinical case

Las reacciones alérgicas y cutáneas para fluoroquinolonas las presentan entre el 0,4% y el 2,2% de los pacientes. Se presenta un protocolo de desensibilización por vía intravenosa que se desarrolla en 4 horas con dosis de 0,05 mg hasta una dosis acumulada de 750 mg

Allergic and cutaneous reactions to fluoroquinolones are shown among 0.4% and 2.2% of the patients. A protocol of intravenous desensitization is presented, which develops in 4 hours with a dose of 0.05 mg to a cumulative dose of 750 mg

Cambios en las prescripciones y el consumo de antimicrobianos, luego de la implementación de recomendaciones de uso: experiencia en un hospital universitario / Changes in prescriptions and antibiotic consumption after the implementation of recommendations for use: experience in a university hospital

Resumen Introduccion: Actualmente cerca de la mitad de las prescripciones de antimicrobianos son inadecuadas, lo que aumenta la resistencia bacteriana. Tanto cefalosporinas como fluoroquinolonas se asocian con este fenomeno: aumento de bacterias productoras de β-lactamasas e infecciones por Clostridioides difficile, por lo que las agencias reguladoras buscan racionalizar su uso. Objetivo: Evaluar el efecto de recomendaciones para el uso adecuado de antimicrobianos en la proporcion de prescripciones inadecuadas de ceftriaxona y fluoroquinolonas. Metodologia: Se desarrollo un estudio de antes y despues, prospectivo e intervencional, que comparo la calidad y la cantidad de uso de ceftriaxona y fluoroquinolonas antes y despues de la implementacion de recomendaciones de uso para tratamientos de enfermedades infecciosas adquiridas en la comunidad. Los parametros medidos fueron: proporcion de prescripciones inadecuadas y DDD. Los datos se analizaron por medio del test de χ2, correccion de Fisher y test de Student. Resultados: Se evaluaron 206 pacientes, observandose una disminucion de 35% en las prescripciones inadecuadas, una reduccion del consumo de ceftriaxona y levofloxacina y un aumento significativo de la utilizacion de ampicilina/sulbactam. Conclusiones: La implementacion de recomendaciones de uso basadas en evidencia cientifica y susceptibilidad local, permitieron disminuir la proporcion de prescripciones inadecuadas y reducir el consumo de ceftriaxona y fluoroquinolonas.

Background: Nowadays about half of antibiotic prescriptions are inadequate, increasing bacterial resistance. Both cephalosporins and fluoroquinolones are associated with this phenomenon: increase of β-lactamase producing bacteria and Clostridioides difficile infections, which is why regulatory agencies seek to rationalize their use. Aim: To evaluate the effect of use recommendations on the proportion of inadequate prescriptions of ceftriaxone and fluoroquinolones. Methods: A prospective and interventional study was developed, comparing the quality and quantity of use of ceftriaxone and fluoroquinolones before and after the implementation of use recommendations for treatments of infectious diseases acquired at the community. The outcomes were: proportion of inadequate prescriptions and defined daily dose (DDD). Data were analyzed using the Chi-square test, Fisher's correction and Student's test. Results: A total of 206 patients were evaluated, a 35% decrease in inadequate prescriptions, a decline in the consumption of ceftriaxone and levofloxacin, and a significant increase in the use of ampicillin/ sulbactam was observed. Conclusions: The implementation of use recommendations based on scientific evidence and local susceptibility allowed to reduce the proportion of inadequate prescriptions and to reduce de consumption of ceftriaxone and fluoroquinolones.

Role of moxifloxacin-dexamethasone in cardiac histomorphometric findings among Wistar rats from infected mothers

Abstract Purpose: To investigate cardiac changes in young rats, whose mothers underwent autogenic fecal peritonitis, during organogenesis phase and to evaluate the role of intravenous administration of moxifloxacin and dexamethasone in preventing infection-related cardiac changes. Methods: A prospective histomorphometric study was performed on 29 hearts of Wistar four-month old rats. Animals were divided into three groups: Negative Control Group (NCG) included 9 subjects from healthy mothers; Positive Control Group (PCG) included 10 subjects from mothers with fecal peritonitis (intra-abdominal injection of 10% autogenic fecal suspension in the gestational period) and did not receive any treatment; and Intervention Group (IG), with 10 animals whose infected mothers received moxifloxacin and dexamethasone treatment 24 hours after induction of fecal peritonitis. Results: Nuclear count was higher in the IG group as compared to PCG (p = 0.0016) and in NCG as compared to PCG (p = 0.0380). There was no significant difference in nuclear counts between NCG and IG. Conclusion: Induced autogenic fecal peritonitis in pregnant Wistar rats determined myocardial changes in young rats that could be avoided by the early administration of intravenous moxifloxacin and dexamethasone.

Comentarios al tratamiento de la tuberculosis con resistencia / Comments On The Treatment Of Resistant Tuberculosis

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Intracameral moxifloxacin after cataract surgery: a prospective study / Moxifloxacino intracameral após cirurgia da catarata: estudo prospectivo

ABSTRACT Objective: To study the safety parameters associated with intracameral moxifloxacin application five weeks after cataract surgery. Methods: The study was a prospective case series set in a private hospital in Recife, Pernambuco, Brazil. A consecutive sample of 1,016 cataract surgeries was evaluated. The inclusion criteria were patients with indications for cataract surgery, a minimum of 55 years of age, and no history of allergy to quinolones. Patients were prepared for surgery using a 5% povidone solution diluted as a topical antiseptic agent. The operative technique was phacoemulsification with intraocular lens implantation. A 0.3-mL syringe was partially filled with moxifloxacin and 150 µg/0.03 mL of moxifloxacin was administered through the surgical incision at the end of the surgery. Postoperatively, patients were prescribed: (1) 0.5% moxifloxacin eyedrops 5 times daily for 1 week, and (2) 1% prednisolone acetate eyedrops 5 times daily for 1 week, followed by 4 times daily for 1 week and, subsequently, 2 times daily for 3 weeks. The outcomes were incidence of acute endophthalmitis, mean changes from baseline to 5 postoperative weeks in corneal endothelial cell density, corrected distance visual acuity and intraocular pressure. Results: The mean age was 67 ± 5 years, and 56.2% of the patients were female. There were no cases of endophthalmitis. The mean preoperative corrected distance visual acuity was 58 letters ± 10 (SD), and the mean postoperative corrected distance visual acuity was 80 letters ± 4 (SD). The mean change in corneal endothelial cell density was 249 cells/mm (-10.3%). There was almost no difference in intraocular pressure. No study-related adverse events were observed. Conclusion: The results suggest moxifloxacin is a safe option for intracameral use after cataract surgery.

RESUMO Objetivo: Estudar alguns parâmetros de segurança da moxifloxacino intracameral nas cinco semanas após a cirurgia de catarata. Métodos: O estudo foi uma série de casos prospectivos. O cenário era um hospital privado em Recife, Pernambuco, Brasil. Foi considerada uma amostra consecutiva de 1.016 cirurgias de catarata. Os critérios de inclusão foram pacientes com indicação para cirurgia de catarata, com pelo menos 55 anos de idade e sem história de alergia a quinolonas. Os pacientes foram preparados para cirurgia usando uma solução de povidona a 5% diluída como agente anti-séptico tópico. A técnica operatória foi a facoemulsificação com implante de lente intraocular. Uma seringa de 0,3 mL foi parcialmente preenchida com moxifloxacino. Os pacientes receberam 150 µg/0,03 mL de moxifloxacino através da incisão cirúrgica no final da cirurgia. No pós-operatório, os pacientes foram prescritos: (1) moxifloxacino 0,5% 5 vezes ao dia durante 1 semana e (2) colírio de acetato de prednisolona a 1% 5 vezes ao dia durante 1 semana, seguido de 4 vezes ao dia durante 1 semana e, posteriormente, 2 vezes diariamente por 3 semanas. Os desfechos foram a incidência de endoftalmite aguda, variações entre os valores basais e os na 5ª semana pós-operatória referente à densidade celular endotelial corneana, acuidade visual corrigida para longe e pressão intraocular. Resultados: A média da idade foi de 67 ± 5 anos, e 56,2% dos pacientes eram do sexo feminino. Não houve casos de endoftalmite. A acuidade visual corrigida para longe préoperatório médio foi de 58 letras ± 10 (SD), e a acuidade visual corrigida para longe pósoperatório médio foi de 80 letras ± 4 (SD). A alteração média na densidade celular endotelial corneana foi de 249 células/mm (10,3%). Não houve diferença na pressão intraocular. Não foram observados eventos adversos relacionados ao estudo. Conclusão: Os resultados sugerem que o moxifloxacino é uma opção segura para o uso intracameral após a cirurgia de catarata.

Seguridad de las fluoroquinolonas: riesgos habitualmente olvidados para el clínico / Safety of fluoroquinolones: risks usually forgotten for the clinician

Resumen Las quinolonas constituyen una familia de antimicrobianos de amplio uso y si bien son consideradas segura para los pacientes, el conocimiento del perfil de seguridad es necesario para que los profesionales estén alertas a lo que deben vigilar. Sobre el sistema músculo-esquelético, las quinolonas tienen el potencial de dañar cartílagos, provocando incluso muy excepcionalmente rotura de tendón. A nivel endocrino se ha observado hipoglicemia/hiperglicemia, por lo que en pacientes diabéticos se recomienda el control cuidadoso de la glicemia. Las reacciones adversas cardiovasculares son poco frecuentes, pero pueden ir desde alteraciones del ECG como prolongación del QT sin traducción clínica a graves arritmias que pueden ser de riesgo vital. En el sistema nervioso, destaca la aparición de alteraciones del sistema nervioso central y la neuropatía periférica. Durante la evaluación de la seguridad de las quinolonas es importante considerar las potenciales interacciones con otros medicamentos. En niños se prefiere no usar las fluoroquinolonas debido al potencial riesgo de daño a los cartílagos de crecimiento, efectos que no parecen ser tan dramáticos a la luz de la evidencia actual. A pesar del optimismo se debe evaluar la seguridad del tratamiento de estos antimicrobianos en todo paciente pediátrico.

Quinolones are a group of widely used antimicrobials. Although they are considered safe for patients, knowledge of the safety profile is necessary so that professionals become aware of what is necessary to monitor. At the musculoskeletal level, quinolones have the potential to damage cartilage, causing even tendon rupture in infrequent cases. Hypoglycemia / hyperglycemia has been observed at the endocrine level, thus, careful monitoring of glycemia in patients with quinolone is recommended in diabetic patients. At the cardiovascular level, arrhythmias induced by these antimicrobials are rare but severe. At the level of the nervous system, the appearance of alterations of the central nervous system and the peripheral neuropathy are emphasized. When assessing the safety of quinolones, it is important to consider potential interactions with other substances (medical products). In children it is preferred not to use fluoroquinolones because of the potential risk of cartilage damage and growth, effects that do not seem to be so dramatic in the face of new evidence. Despite optimism, the safety of the treatment of these antimicrobials should be evaluated in every pediatric patient.

Safety and efficacy of intracameral moxifloxacin injection for prophylaxis of endophthalmitis after phacoemulsification / Segurança e eficácia na injeção intracameral de moxifloxacino para profilaxia da endoftalmite após a facomeulsificação

ABSTRACT Purpose: To evaluate the safety and efficacy of 0.05 mL intracameral injection of moxifloxacin in patients who underwent phacoemulsification and intraocular lens (IOL) implant. Methods: Retrospective study comprising patients who underwent phacoemulsification and IOL implant between January 2009 and December 2013. Patients were divided into two groups. Group A followed standard endophthalmitis prevention protocol and group B followed the same protocol plus intracameral injection of 0.05 mL of moxifloxacin hydrochloride at 5.45 mg/mL, immediately after IOL implant. Results: Medical records from 7,195 eyes of 3,751 patients (median age: 67.8 ± 8.96, range: 48-83 years, 53.8% female) were evaluated. Group A included 3,515 eyes of 1,838 patients and group B included 3,680 eyes of 1,913 patients. The incidence of endophthalmitis in group A was 0.22% (8:3,515 eyes) and in group B was 0.03% (1:3,680 eyes, p=0.0198, Fischer's exact test). No toxicity or inflammation related to the use of moxifloxacin was observed. Conclusions: There was a 7.3-fold lower ratio of endophthalmitis in the group that received moxifloxacin intracameral injection. This study provides further evidence that moxifloxacin is an effective intracameral prophylactic antibiotic.

RESUMO Objetivo: Avaliar a segurança e a eficácia da injeção intracameral de 0,05 mL de moxifloxacina em pacientes que realizaram facoemulsificação e implante de lente intraocular. Métodos: Estudo retrospectivo envolvendo pacientes submetidos a facoemulsificação e implante de lente intraocular entre janeiro de 2009 a dezembro de 2013. Os pacientes foram divididos em dois grupos. O grupo A seguiu o protocolo padrão de prevenção de endoftalmite e o grupo B seguiu o mesmo protocolo associado à injeção intracameral de 0,05 mL de cloridrato de moxifloxacino a 5,45 mg/mL, imediatamente após o implante de lentes intra-oculares (LIO). Resultados: Foram avaliados registros clínicos de 7.195 olhos de 3.751 pacientes (mediana de idade de 67,8 ± 8,96, faixa de 48-83 anos, 53,8% de mulheres). O grupo A incluiu 3.515 olhos de 1.838 pacientes e o grupo B incluiu 3.680 olhos de 1.913 pacientes. A incidência de endoftalmite no grupo A foi de 0,22% (8:3.515 olhos) e no grupo B de 0,03% (1:3.680 olhos, p=0,0198, teste exato de Fischer). Não foi observada toxicidade ou inflamação relacionada com o uso de moxifloxacino intracameral. Conclusões: Houve uma proporção 7,3 vezes menor de endoftalmite no grupo que recebeu injeção de moxifloxacino. Este estudo fornece mais evidências que o moxifloxacino intracameral é um antibiótico profilático intracameral eficaz.