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1.
Invest Ophthalmol Vis Sci ; 65(11): 38, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39325471

RESUMO

Purpose: The purpose of this study was to investigate the bacterial composition in the conjunctiva and to determine the relationship between fluoroquinolone resistance and mutations in the quinolone resistance-determining region (QRDR) in Corynebacterium macginleyi (C. macginleyi). Methods: Bacteria isolated from conjunctival swabs of patients awaiting ophthalmic surgery or patients with presumed keratoconjunctivitis were included in this study. For C. macginleyi isolates from 49 samples, the minimum inhibitory concentrations (MICs) of second- to fourth-generation fluoroquinolones were determined by broth microdilution. Additionally, we determined the sequence of the QRDR in the gyrA gene of C. macginleyi-positive isolates by direct sequencing and investigated the relationship between the QRDR mutation and the MICs of fluoroquinolones for C. macginleyi. Results: Among 423 eyes of 296 preoperative patients who underwent conjunctival culture testing, 105 eyes of 89 patients were culture-positive, and among 148 eyes of 147 patients with keratoconjunctivitis, 55 eyes of 54 patients were culture-positive. C. macginleyi accounted for the largest proportion of cultured organisms (34.8%). C. macginleyi-positive isolates were found in 45 eyes of 37 preoperative patients and in 4 eyes of 4 patients with keratoconjunctivitis. Direct sequencing revealed that 91.8% of C. macginleyi-positive isolates had amino acid mutations in the QRDR and 95.5% of mutations were found at Ser-87 and Asp-91. Isolates harboring double mutations at Ser-87 and Asp-91 were resistant to second- to fourth-generation fluoroquinolones. One isolate with double mutations at Ser-87 and Ala-88 but no mutation in Asp-91 showed intermediate susceptibility to moxifloxacin, a fourth-generation fluoroquinolone. Conclusions: C. macginleyi isolated from conjunctiva harboring QRDR amino acid mutations were resistant to second- to fourth-generation fluoroquinolones.


Assuntos
Antibacterianos , Túnica Conjuntiva , Infecções por Corynebacterium , Corynebacterium , DNA Girase , Farmacorresistência Bacteriana , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Mutação , Humanos , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Corynebacterium/genética , Corynebacterium/efeitos dos fármacos , Corynebacterium/isolamento & purificação , Túnica Conjuntiva/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Corynebacterium/microbiologia , Infecções por Corynebacterium/tratamento farmacológico , DNA Girase/genética , Masculino , Feminino , Ceratoconjuntivite/microbiologia , Ceratoconjuntivite/tratamento farmacológico , Ceratoconjuntivite/genética , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Idoso , DNA Bacteriano/genética , Moxifloxacina/farmacologia , Moxifloxacina/uso terapêutico
2.
Can Vet J ; 65(9): 900-905, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39219608

RESUMO

A 10-year-old spayed female mixed-breed dog was brought to the Ohio State University Veterinary Medical Center because of a suspected mass located to the right kidney. The mass was diagnosed by abdominal ultrasound following a recurrent lower urinary tract infection. Abdominal computed tomography revealed 2 isoattenuating, peripherally hypoattenuating, and centrally non-contrast-enhancing nodules in the right kidney; the larger one measured 1.9 cm. Initial attempts at fine-needle aspiration were unsuccessful. The dog was returned and the mass was aspirated using ultrasound guidance under heavy sedation. Cytology confirmed the presence of septic inflammation, consistent with a renal corticomedullary abscess. The dog was administered oral enrofloxacin (15 mg/kg, q24h) after diagnosis. Ultrasound guidance was used 2 wk later, under general anesthesia, to achieve percutaneous drainage of ~0.25 mL of fluid and instillation of 5.7 mg (0.25 mL) of enrofloxacin into the abscess capsule. Two weeks after percutaneous drainage, ultrasound examination showed complete resolution of the renal corticomedullary abscess. Urine culture confirmed resolution of the urinary tract infection. To the authors' knowledge, kidney-sparing medical management has never been successfully reported in a dog with a renal corticomedullary abscess. Key clinical message: Renal corticomedullary abscesses occur infrequently in dogs. Medical management is feasible and can result in complete resolution of clinical signs and imaging abnormalities.


Diagnostic et prise en charge médicale réussie d'un abcès corticomédullaire rénal chez un chienUne chienne croisée de 10 ans, stérilisée, a été amenée au centre médical vétérinaire de l'Ohio State University en raison d'une masse suspectée située au niveau du rein droit. La masse a été diagnostiquée par échographie abdominale à la suite d'une infection récurrente du tractus urinaire inférieur. La tomodensitométrie abdominale a révélé 2 nodules isoatténuants, hypoatténuants en périphérie et centralement sans contraste dans le rein droit; le plus grand mesurait 1,9 cm. Les premières tentatives d'aspiration à l'aiguille fine ont échoué. Le chien est revenu et la masse a été aspirée sous guidage échographique sous sédation lourde. La cytologie a confirmé la présence d'une inflammation septique, compatible avec un abcès corticomédullaire rénal. Le chien a reçu de l'enrofloxacine par voie orale (15 mg/kg, toutes les 24 heures) après le diagnostic. Le guidage échographique a été utilisé 2 semaines plus tard, sous anesthésie générale, pour obtenir un drainage percutané d'environ 0,25 mL de liquide et l'instillation de 5,7 mg (0,25 mL) d'enrofloxacine dans la capsule de l'abcès. Deux semaines après le drainage percutané, l'échographie a montré une résolution complète de l'abcès corticomédullaire rénal. La culture urinaire a confirmé la résolution de l'infection des voies urinaires. À la connaissance des auteurs, une prise en charge médicale préservant les reins n'a jamais été rapportée avec succès chez un chien présentant un abcès corticomédullaire rénal.Message clinique clé:Les abcès corticomédullaires rénaux surviennent rarement chez le chien. La prise en charge médicale est réalisable et peut aboutir à une résolution complète des signes cliniques et des anomalies d'imagerie.(Traduit par Dr Serge Messier).


Assuntos
Abscesso , Antibacterianos , Doenças do Cão , Enrofloxacina , Animais , Cães , Doenças do Cão/tratamento farmacológico , Doenças do Cão/diagnóstico , Doenças do Cão/diagnóstico por imagem , Feminino , Abscesso/veterinária , Abscesso/tratamento farmacológico , Abscesso/diagnóstico , Enrofloxacina/uso terapêutico , Enrofloxacina/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Infecções Urinárias/veterinária , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/diagnóstico , Nefropatias/veterinária , Nefropatias/tratamento farmacológico , Nefropatias/diagnóstico , Drenagem/veterinária , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagem , Ultrassonografia/veterinária
3.
J Antimicrob Chemother ; 79(10): 2413-2416, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39178118

RESUMO

This article discusses the recent regulatory restrictions on the use of fluoroquinolones and their impact on treating orthopaedic infections. We focus on the balance between the benefits and risks of fluoroquinolones in scenarios involving severe infections where alternative antibiotics may be less effective. The discussion includes a summary of recent evidence on adverse effects and the implications for clinical practice.


Assuntos
Antibacterianos , Fluoroquinolonas , Humanos , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Medição de Risco , Infecções Bacterianas/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico
4.
J Antimicrob Chemother ; 79(10): 2554-2560, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090969

RESUMO

BACKGROUND: Over the years, reports have associated fluoroquinolones (FQ) with seizures. The incidence and whether FQ compared to non-epileptogenic antibiotic are associated with increased risk of seizures has yet to be examined. METHODS: A retrospective observational study of hospitalized patients treated with FQ (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin) or macrolides (MA: azithromycin or roxithromycin) between January 2009 and January 2021 in a large tertiary academic medical centre. The outcome was the occurrence of a seizure during treatment. The Naranjo scale was used to assess causality between FQ treatment and seizures. Comparative analysis was conducted using propensity score matching to correct for possible bias due to non-random selection, followed by inverse probability weighting (IPW) to estimate the difference in seizure risk between FQ and MA. RESULTS: Overall, 52 722 patients were treated with FQ during a total of 178 982 days. Mean age was 65 (±19) years and 47% were females. Thirty-three patients (0.06%) experienced a seizure, yielding an incidence of 1:5422 treatment days. Causality was deemed probable and possible among 9/33 and 24/33, respectively. The MA group composed of 8522 patients treated during 17 954 treatment days. Mean age was 65 (±21) years, 49% were females. Six (0.07%) patients experienced each a single seizure. IPW estimated OR for seizures among the FQ versus MA group was 1.44 (95%CI 0.59-3.5, P = 0.42). DISCUSSION: The incidence of FQ associated seizures among hospitalized patients is low and the risk did not significantly exceed that under macrolides. Our results provide evidence for clinicians and decision-makers when balancing fluoroquinolones risks and benefits.


Assuntos
Antibacterianos , Fluoroquinolonas , Convulsões , Humanos , Feminino , Masculino , Estudos Retrospectivos , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Idoso , Convulsões/induzido quimicamente , Convulsões/epidemiologia , Pessoa de Meia-Idade , Antibacterianos/efeitos adversos , Idoso de 80 Anos ou mais , Incidência , Fatores de Risco , Macrolídeos/efeitos adversos , Macrolídeos/uso terapêutico , Adulto
5.
BMC Infect Dis ; 24(1): 856, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179971

RESUMO

BACKGROUND: Fluoroquinolones are the most commonly prescribed antibiotics. Because of their known tendency to drive antimicrobial resistance, their prescribing patterns need to be more restricted. This study aimed to describe the clinical practice of fluoroquinolone prescription, dose adjustments for renal impairment patients and bacterial resistance profiles, eventually providing evidence-based recommendations to optimize antibiotic prescribing practices in the local population. METHODS: This retrospective, cross-sectional study was conducted at An-Najah National University Hospital in Palestine. The data were collected from admitted patients who were given ciprofloxacin or levofloxacin from July 2021 to June 2023. Data from 692 inpatients across various hospital departments were examined (409 for levofloxacin and 283 for ciprofloxacin). Statistical analysis was performed via IBM SPSS version 23.0 to summarize the demographic, clinical, and epidemiological data. RESULTS: The sociodemographic profile revealed diverse age distributions, with 25.4% and 39% older than 50 years for ciprofloxacin and levofloxacin, respectively. Ciprofloxacin was predominantly used in the oncology department (28.2%), with surgical prophylaxis (22.6%) and febrile or afebrile neutropenia (21.1%) being the most common indications. Levofloxacin was predominantly used in the medical ward (45.7%), mainly for lower respiratory tract infection (58.8%) and prophylaxis for bone marrow transplantation (16.5%). Enterococcus and methicillin-resistant Staphylococcus aureus were the most commonly isolated pathogens, with 62.5% of the isolates demonstrating resistance to ciprofloxacin. Moreover, extended-spectrum beta-lactamase-producing Enterobacterales were the most common pathogen isolated, with 33.3% being resistant to levofloxacin. Statistical analysis revealed a significant association between the choice of antibiotic and the approach to therapy. Levofloxacin was significantly more likely than ciprofloxacin to be used as empiric therapy (p < 0.001), whereas ciprofloxacin was more likely to be used as targeted therapy (p < 0.001). CONCLUSIONS: This study investigated prescribing practices and resistance to levofloxacin and ciprofloxacin in a large hospital in a developing country. According to the bacterial resistance profiles, we conclude that there is a need for hospital departments to exercise greater restraint on the use of these antibiotics. To this end, further studies addressing the clinical efficacy of fluoroquinolones against the current treatment guidelines to evaluate their appropriateness should be carried out.


Assuntos
Antibacterianos , Fluoroquinolonas , Levofloxacino , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Feminino , Centros de Atenção Terciária/estatística & dados numéricos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/farmacologia , Idoso , Levofloxacino/uso terapêutico , Levofloxacino/farmacologia , Ciprofloxacina/uso terapêutico , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Padrões de Prática Médica/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Oriente Médio/epidemiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação
6.
J Vet Med Sci ; 86(9): 974-978, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39111849

RESUMO

Malakoplakia is a rare granulomatous inflammation that has mainly been reported in the urinary bladder of dogs. Only one case of canine colonic malakoplakia has been reported to date; however, successful treatment of this disease has not been reported. Here, we report a case of colonic malakoplakia in a 5-month-old spayed female French Bulldog. The dog was referred to a veterinarian because of chronic diarrhea and mucinous blood feces; empirical treatment did not improve its condition. Histologically, numerous macrophages containing periodic acid-Schiff-positive granules infiltrated the lamina propria of the large intestine. Furthermore, targetoid basophilic inclusion bodies (Michaelis-Gutmann bodies) were observed. Complete clinical remission was achieved after 8 months of enrofloxacin treatment and favorable progress after 2 months of medication.


Assuntos
Doenças do Cão , Enrofloxacina , Malacoplasia , Animais , Malacoplasia/veterinária , Malacoplasia/tratamento farmacológico , Malacoplasia/patologia , Feminino , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Enrofloxacina/uso terapêutico , Fluoroquinolonas/uso terapêutico , Antibacterianos/uso terapêutico , Doenças do Colo/veterinária , Doenças do Colo/tratamento farmacológico , Doenças do Colo/patologia
7.
J Microbiol Immunol Infect ; 57(5): 791-800, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39160114

RESUMO

BACKGROUND: Bedaquiline, delamanid and fluoroquinolones are associated with increased QTcF. Whether clofazimine is associated with QTcF prolongation is less clear. METHODS: All patients with rifampicin-resistant TB enrolled between May 2017 and Dec 2019 were included. ECGs were performed at baseline, month 1, month 3 and month 6 for patients treated with conventional regimens, and at additional timepoint for patients treated with bedaquiline, delamanid and short regimen. We estimated the maximum increase of QTcF and constructed cox proportional hazards models to assess factors associated with QTcF≥501ms. RESULTS: Among 321 patients, 59 (18.4%) patients had QTcF≥501ms during a mean follow-up of 242 days (median 189, range 4-1091). The median maximum increase of QTcF was 43.4 ms (IQR 31.3-65.9) in patients treated with clofazimine. Treatment with clofazimine was significantly associated with QTcF≥501ms as compared to without clofazimine (adjusted hazards ratio (adjHR) 4.35, 95% confidence interval (CI) 2.01-9.44). Among patients not treated with bedaquiline and delamanid, those treated with clofazimine and a fluoroquinolone (adjHR 3.43, 95% CI 1.61-7.34) and those treated with clofazimine and high dose moxifloxacin (adjHR 6.54, 95% CI 2.43-17.60) had a significantly higher risk of QTcF≥501ms as compared to those treated with a fluoroquinolone without other QTcF prolonging agents. Four (1.6%) patients had documented ventricular tachycardia, in which one was Torsade de pointes. One patient was found to have sudden death during hospitalization. CONCLUSIONS: Clofazimine was significantly associated with an increased risk of QTcF prolongation. QTcF≥501ms was potentially associated with fatal event and needed to be managed cautiously.


Assuntos
Antituberculosos , Clofazimina , Diarilquinolinas , Síndrome do QT Longo , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Clofazimina/efeitos adversos , Clofazimina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Síndrome do QT Longo/induzido quimicamente , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Taiwan/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Diarilquinolinas/efeitos adversos , Nitroimidazóis/efeitos adversos , Nitroimidazóis/uso terapêutico , Oxazóis/efeitos adversos , Oxazóis/uso terapêutico , Eletrocardiografia , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Idoso , Modelos de Riscos Proporcionais
8.
Sci Rep ; 14(1): 19719, 2024 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-39181942

RESUMO

Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34-20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25-3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.


Assuntos
Antituberculosos , Fluoroquinolonas , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Tuberculose Resistente a Múltiplos Medicamentos/genética , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Masculino , Feminino , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto , Mutação , Medição de Risco , Pessoa de Meia-Idade , Testes de Sensibilidade Microbiana , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Idoso
9.
Antimicrob Agents Chemother ; 68(8): e0069824, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-38953622

RESUMO

In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of Clostridioides difficile isolates recovered from first-episode C. difficile infection (CDI) cases, BI represented 19% of first-episode CDI isolates in 2013-2015. Two additional REA group strains accounted for 31% of isolates (Y, 16%; DH, 12%). High-level resistance to fluoroquinolones and azithromycin was more common among BI isolates than among DH, Y, and non-BI/DH/Y isolates. Multivariable analysis revealed that BI cases were 2.47 times more likely to be associated with fluoroquinolone exposure compared to non-BI cases (95% confidence interval [CI]: 1.12-5.46). In addition, the odds of developing a CDI after third- or fourth-generation cephalosporin exposure was 2.83 times for DH cases than for non-DH cases (95% CI: 1.06-7.54). Fluoroquinolone use in the hospital decreased from 2005 to 2015 from a peak of 113 to a low of 56 antimicrobial days/1,000 patient days. In contrast, cephalosporin use increased from 42 to 81 antimicrobial days/1,000 patient days. These changes correlated with a decrease in geometric mean MIC for ciprofloxacin (61.03 to 42.65 mg/L, P = 0.02) and an increase in geometric mean MIC for ceftriaxone (40.87 to 86.14 mg/L, P < 0.01) among BI isolates. The BI strain remained resistant to fluoroquinolones, but an overall decrease in fluoroquinolone use and increase in cephalosporin use were associated with a decrease in the prevalence of BI, an increased diversity of C. difficile strain types, and the emergence of strains DH and Y.


Assuntos
Antibacterianos , Clostridioides difficile , Infecções por Clostridium , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/tratamento farmacológico , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Masculino , Feminino , Idoso , Prevalência , Pessoa de Meia-Idade , Proibitinas , Hospitais , Surtos de Doenças , Azitromicina/uso terapêutico , Azitromicina/farmacologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Idoso de 80 Anos ou mais , Cefalosporinas/uso terapêutico , Cefalosporinas/farmacologia
11.
Indian J Tuberc ; 71 Suppl 1: S37-S43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39067953

RESUMO

BACKGROUND & OBJECTIVES: The purpose of present study is to analyse the distribution and pattern of genetic mutations in PRE-XDR-TB and extensive drug resistant Mycobacterium tuberculosis (XDR-TB) using second-line line probe assay and to compare them with different parameters. METHOD: Sputum, Lymph node aspirate and cold accesses from patients with rifampicin resistant Tuberculosis were subjected to first line and second line Probe Assay (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluroquinolones (Levofloxacin & Moxifloxacin) and Aminoglycosides (Amikacin, Ofloxacin and Kanamycin). The genetic mutation pattern was analysed and compared with demographic, clinical and other parameters. RESULTS: The final study population included 123 fluoroquinolone resistant isolates including 14 isolates with additional second line aminoglycosides drug resistance. The most frequent mutation observed among Gyr A drug resistance mutation was D94G (Gyr A MUT3C, 50/123,40%) corresponding to high level resistance to levofloxacin and moxifloxacin. The most frequent wild type mutant among Gyr A gene locus was WT 3 (85/123,69%). The most common mutation among second line aminoglycoside resistant isolates was at eis WT2 (7/14,50%) followed by rrs MUT 2 (4/14,29%). CONCLUSIONS: GyrA MUT3C (Asp94Gly) was the most common mutation in Gyr A gene locus in M. tuberculosis causing high level levofloxacin and moxifloxacin resistance. Patients with Asp94Gly mutation was significantly associated with underweight body mass index (p = 0.026). This study also observed that history of anti-tuberculosis therapy is a risk factor for FQ drug resistance mutations (p < 0.001).


Assuntos
Antituberculosos , Mutação , Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Masculino , Feminino , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Pessoa de Meia-Idade , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Testes de Sensibilidade Microbiana , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Moxifloxacina/uso terapêutico , Moxifloxacina/farmacologia , Adulto Jovem
12.
BMJ Open Qual ; 13(3)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39053916

RESUMO

BACKGROUND: The US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms. OBJECTIVE: To evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population. METHODS: This cross-sectional study with an interrupted time series (ITS) analysis (January 2018-December 2019) used a 25% random sample of IQVIA PharMetrics® Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population. RESULTS: From 2018 to 2019, both study populations saw a decrease in the year-over-year percent change of FQ prescriptions per 100 000 beneficiaries (-11%, from 14 227 to 12 662, targeted; -15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01-0.13), but there were no significant changes in level or post-warning trend. CONCLUSION: We did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.


Assuntos
Antibacterianos , Aneurisma Aórtico , Dissecção Aórtica , Fluoroquinolonas , United States Food and Drug Administration , Humanos , Estados Unidos/epidemiologia , Estudos Transversais , Dissecção Aórtica/epidemiologia , United States Food and Drug Administration/estatística & dados numéricos , Aneurisma Aórtico/epidemiologia , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Análise de Séries Temporais Interrompida , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Padrões de Prática Médica/normas , Prescrições de Medicamentos/estatística & dados numéricos , Adulto
13.
J Pediatric Infect Dis Soc ; 13(9): 486-492, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39073450

RESUMO

There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Levofloxacino , Humanos , Criança , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Guias de Prática Clínica como Assunto , Neoplasias/tratamento farmacológico , Bacteriemia/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/tratamento farmacológico
14.
Congenit Anom (Kyoto) ; 64(5): 199-206, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38936845

RESUMO

Given the paucity of safety data on fluoroquinolone antibiotics in pregnancy, a prospective observational cohort study was conducted in pregnant women who sought help and advice on drug use at two teratology information institutes in Japan. The primary endpoint of the study was the incidence of major congenital anomalies. The study population included pregnant women exposed to (i) fluoroquinolones (fluoroquinolone group), (ii) ß-lactams (infectious control group), or (iii) other agents considered to be nonteratogenic in humans (nonteratogenic control group) during the first trimester. The frequency of major congenital anomalies was compared across groups using a logistic regression model that adjusted for maternal age, smoking status, drinking status, facility consulted, and time of consultation. The fluoroquinolone group consisted of 411 women who had 383 children born alive. The infectious control and nonteratogenic control groups consisted of 1416 and 1482 women who had 1322 and 1401 children born alive, respectively. The incidence of major congenital anomalies was 1.5%, 2.0%, and 1.6% in the fluoroquinolone group, infectious control, and nonteratogenic control groups, respectively. Logistic regression showed that fluoroquinolone exposure is not a significant risk factor for major congenital anomalies. In conclusion, first-trimester exposure to fluoroquinolone antibiotics was not associated with increased maternal or fetal risks.


Assuntos
Anormalidades Induzidas por Medicamentos , Antibacterianos , Fluoroquinolonas , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Adulto , Feminino , Humanos , Gravidez , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Bases de Dados Factuais , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Incidência , Japão/epidemiologia , Exposição Materna/efeitos adversos , Resultado da Gravidez/epidemiologia , Estudos Prospectivos , Fatores de Risco
15.
J Antimicrob Chemother ; 79(8): 1962-1968, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38863370

RESUMO

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.


Assuntos
Antibacterianos , Quimioterapia Combinada , Fluoroquinolonas , Tetraciclinas , Humanos , Estudos Retrospectivos , Feminino , Masculino , Japão , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Tetraciclinas/uso terapêutico , Tetraciclinas/administração & dosagem , Tetraciclinas/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Pessoa de Meia-Idade , Idoso , Adulto , Bases de Dados Factuais , Rickettsiose do Grupo da Febre Maculosa/tratamento farmacológico , Hospitais/estatística & dados numéricos , População do Leste Asiático
17.
Indian J Dermatol Venereol Leprol ; 90(5): 632-635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38899414

RESUMO

Background Increasing rates of macrolide and fluroquinolone resistance in Mycoplasma genitalium (MG) are being reported worldwide with resultant treatment failure. Aim We aimed to determine the level of antibiotic resistance of MG in men who have sex with men (MSM) attending a sexually transmitted infections (STIs) clinic in New Delhi, India. Methods Real-time polymerase chain reaction (PCR) assays targeting MgPa and pdhD genes were performed to detect MG rectal, urogenital or oropharyngeal infections in 180 MSM between January 2022 and June 2023. Macrolide resistance-associated mutations (MRM) and quinolone resistance-associated mutations (QRM) were detected by specific amplification of domain V of 23SrRNA gene and appropriate regions of parC and gyrA genes respectively followed by sequencing. PCR-based screening for Chlamydia trachomatis (CT) infection was also performed. Results A total of 13 (7.2%) MSM were positive for MG infection. The most common site of infection was anorectum (8/13; 61.5%) followed by the urethra (5/13; 38.5%). None of the patients had infection at both the sites, and no oropharyngeal MG infection was detected. CT infection was detected in 37 (20.6%) MSM. Of the 13 MG-infected MSM, 6 (46.2%) were co-infected with CT. MRM and QRM were found in five (46.2%) and two (15.4%) strains, respectively. Both Quinolone resistance mutation (QRM)-harbouring strains also harboured MRM. All the five MG isolates carried the MRM A2071G. Both the QRM isolates co-harboured the parC and gyrA single-nucleotide polymorphisms. There was no correlation between the presence of antibiotic resistance and co-infection with CT (P = 0.52). Limitation Because all patients in the study were MSM, the high rate of resistance to macrolides and fluoroquinolones could not be extrapolated for non-MSM patients. Conclusion This is a report of an initial survey of antibiotic resistance to MG in a country where its diagnosis and treatment are not routinely available. We found a high prevalence of MG-carrying MRM, QRM and dual-class resistance in MSM in the absence of antibiotic exposure. This study mandates the need for both screening and detection of antimicrobial resistance against MG.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Fluoroquinolonas , Macrolídeos , Mutação , Infecções por Mycoplasma , Mycoplasma genitalium , Humanos , Mycoplasma genitalium/genética , Mycoplasma genitalium/efeitos dos fármacos , Masculino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Projetos Piloto , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologia , Índia/epidemiologia , Adulto , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Homossexualidade Masculina , Adulto Jovem , Pessoa de Meia-Idade
19.
Eur J Gen Pract ; 30(1): 2362693, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38881418

RESUMO

BACKGROUND: Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance. OBJECTIVES: The objective of this qualitative study was to explore general practitioners' (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs. METHODS: GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs' experiences and behaviours were recorded and analysed using an interpretive phenomenological approach. RESULTS: From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: 'male cystitis does not exist'. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be 'potent' antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system. CONCLUSIONS: GPs' experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs' antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed.KEY MESSAGESDefining a male urinary tract infection represents a diagnostic challenge for GPs.A diagnosis based on clinical evidence alone is insufficient and complementary tests are required.A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.


Assuntos
Antibacterianos , Cistite , Clínicos Gerais , Padrões de Prática Médica , Pesquisa Qualitativa , Infecções Urinárias , Humanos , Masculino , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/diagnóstico , França , Cistite/tratamento farmacológico , Cistite/diagnóstico , Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Pessoa de Meia-Idade , Adulto , Feminino , Gestão de Antimicrobianos , Atenção Primária à Saúde
20.
Ned Tijdschr Geneeskd ; 1682024 06 25.
Artigo em Holandês | MEDLINE | ID: mdl-38888389

RESUMO

OBJECTIVE: Risk minimisation measures (RMM) are put in place to ensure safe and effective use of medicines. This study assessed whether RMM for five medicines are implemented in Dutch clinical guidelines. DESIGN: Descriptive study. METHOD: Dutch clinical guidelines where treatment with valproate, fluoroquinolones, methotrexate, metformin or fluorouracil was recommended were identified. In those guidelines that had been updated after publication of the RMM, we determined whether RMM-information was included in the guideline. RESULTS: Out of 50 identified guidelines recommending treatment with one of the five medicines, only 21 (42%) were revised after RMM-implementation. Of these 21 guidelines, 12 (n = 57%) included RMM-related information. CONCLUSION: Uptake of RMM information in Dutch clinical guidelines is limited and RMM-publication does not prompt guideline updates. This suggests that guidelines alone are not an optimal way to inform health care professionals of new safety warnings.


Assuntos
Guias de Prática Clínica como Assunto , Humanos , Países Baixos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metotrexato/uso terapêutico , Metotrexato/efeitos adversos , Ácido Valproico/uso terapêutico , Ácido Valproico/efeitos adversos , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/efeitos adversos , Metformina/uso terapêutico , Metformina/efeitos adversos , Gestão de Riscos
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