‘Azole Menace’ – An underappreciated trigger perpetuating the epidemic of antifungal therapeutic failure in cutaneous mycoses

One of the most common neurological disorders, which occurs among 1% of the population worldwide, is epilepsy. Therapeutic failure is common with epilepsy and nearly about 30% of patients fall in this category. Seizure suppression should not be the only goal while treating epilepsy but associated comorbidities, which can further worsen the condition, should also be considered. Treatment of such comorbidities such as depression, anxiety, cognition, attention deficit hyperactivity disorder and, various other disorders which co-exist with epilepsy or are caused due to epilepsy should also be treated. Novel targets or the existing targets are needed to be explored for the dual mechanism which can suppress both the disease and the comorbidity. New therapeutic targets such as IDO, nNOS, PAR1, NF-κb are being explored for their role in epilepsy and various comorbidities. This review explores recent therapeutic targets for the treatment of comorbidities associated with epilepsy.

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Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

Studies in the Economic History of Southern Africa ◽

10.22201/fm.24484865e.2020.63.2.02 ◽

2020 ◽

Vol 63 (2) ◽

pp. 7-17

Author(s):

Evelyn Rivera-Toledo ◽

Alan Uriel Jiménez-Delgadillo ◽

Patricia Manzano-Gayosso

Keyword(s):

Antifungal Activity ◽

Key Words ◽

Secondary Metabolism ◽

Amphotericin B ◽

Antifungal Agents ◽

Fungal Infections ◽

Variable Number ◽

Therapeutic Failure ◽

Morbidity And Mortality ◽

Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

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Artemeter-Lumefantrine therapeutic efficacy, safety and plasma levels in patients with uncomplicated falciparum malaria from the Colombian Pacific región

Infectio ◽

10.22354/in.v22i4.738 ◽

2018 ◽

Vol 22 (4) ◽

pp. 199

Author(s):

Alberto Tobón-Castaño ◽

Luisa Garcés-Murillo ◽

Alexandra Ríos-Orrego ◽

Jehidys Montiel-Ramos ◽

Briegel De Las Salas ◽

...

Keyword(s):

Clinical Trial ◽

Falciparum Malaria ◽

Therapeutic Efficacy ◽

Plasma Concentrations ◽

Plasmodium Falciparum Malaria ◽

Therapeutic Failure ◽

World Health ◽

Blood Levels ◽

Drug Clinical Trial ◽

Parasitological Response

Introduction: In Colombia, the published studies for the treatment of uncomplicated Plasmodium falciparum malaria with Artemether-Lumefantrine are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination.Methods: A clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28-day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy endpoint was the clinical and parasitological response. Safety was assessed through adverse events surveillance and plasmatic levels of antimalarial drugs were measured.Results: 88 patients were included. Adequate clinical and parasitological response rate of 100% on day 28 was achieved in 84 patients, diagnosed by thick blood smear examination. There were four parasitological therapeutic failures (5%) detected by polymerase chain reaction.Discusion: Therapeutic efficacy similar to previous studies was established with a slight increase in therapeutic failure. The serum levels of the antimalarials were adequate and the few cases of therapeutic failure were not related.Conclusion: Treatment of uncomplicated P. falciparum malaria with Artemeter-Lumefantrine was effective and safe in the study population. All patients reached adequate plasma concentrations of the drugs; therapeutic failures were not associated with low blood levels of the drug clinical trial.

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935 Potential role of an IRE1α/XBP1 inhibitor in preventing therapeutic failure of intravesical BCG in bladder cancer

European Urology Supplements ◽

10.1016/s1569-9056(16)60937-5 ◽

2016 ◽

Vol 15 (3) ◽

pp. e935

Author(s):

P. Lewicki ◽

H. Liu ◽

D. Golombos ◽

P. O'Malley ◽

J. Cubillos-Ruiz ◽

...

Keyword(s):

Bladder Cancer ◽

Potential Role ◽

Therapeutic Failure ◽

Intravesical Bcg

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Anthropometric and Pharmacotherapeutic Variables on Acute Emesis Induced by Cisplatin-Containing Chemotherapy

Annals of Pharmacotherapy ◽

10.1345/aph.19188 ◽

2000 ◽

Vol 34 (5) ◽

pp. 573-579 ◽

Cited By ~ 2

Author(s):

José Luis Catalán Arlandis ◽

N Víctor Jiménez Torres

Keyword(s):

Prognostic Factors ◽

Odds Ratio ◽

Logistic Model ◽

Therapeutic Failure ◽

High Dose ◽

Anthropometric Parameters ◽

Cycle Number ◽

Chemotherapeutic Regimen ◽

Acute Emesis ◽

First Choice

OBJECTIVE: To characterize the effects of anthropometric and pharmacotherapeutic variables on acute emesis induced by cisplatin-containing regimens with dosages ·50 mg·m−2. METHODS: A prospective, cross-sectional, noncontrolled study was performed to analyze acute vomiting during the first 24 hours in patients treated in a Spanish hospital. The patients received an intravenous combination of drugs (2 doses of metoclopramide 3 mg/kg, dexamethasone 20 mg) as first-choice antiemetic therapy. Intravenous ondansetron 8 mg and dexamethasone 20 mg served as an alternative regimen in patients <30 years old with a history of extrapyramidal manifestations or emesis in previous cycles. Therapeutic failure was used as a dependent variable, defined as three or more vomiting episodes documented by the patients. Other variables were the chemotherapeutic regimen; antiemetic regimen; patient gender, age, weight, and height; and cycle number. The reference logistic model and two reduced-models derived from the latter were designed. The logistic models were subsequently validated by means of receiving operating characteristic curves. RESULTS: A total of 319 cycles involving 106 patients were studied. The metoclopramide regimen was administered in 66% of the cycles. The therapeutic failure rate was 21% for the metoclopramide regimen and 32% for the ondansetron treatment. The logistic model developed identified the type of chemotherapeutic regimen provided as the most significant prognostic variable (p < 0.0001). Patient weight (odds ratio 1.64) and height (odds ratio 1.28) were identified as prognostic factors related with therapeutic failure. CONCLUSIONS: The type of chemotherapeutic regimen administered and the anthropometric characteristics of the patients exert a clear conditioning effect on risks associated with therapeutic failure against acute emesis following high-dose cisplatin therapy. Such anthropometric parameters have not been previously identified as prognostic factors.

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Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.8.3171-3177.2005 ◽

2005 ◽

Vol 49 (8) ◽

pp. 3171-3177 ◽

Cited By ~ 120

Author(s):

Cornelius J. Clancy ◽

Victor L. Yu ◽

Arthur J. Morris ◽

David R. Snydman ◽

M. Hong Nguyen

Keyword(s):

Therapeutic Response ◽

Geometric Mean ◽

Therapeutic Failure ◽

Response To Therapy ◽

Success Rates ◽

Therapeutic Success ◽

Data Set ◽

In Vitro Susceptibility ◽

Dose Dependent

ABSTRACT We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (≤200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 μg/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 μg/ml and 219.36 [P = 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC ≤ 8 μg/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 μg/ml), and resistant (MIC ≥ 64 μg/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio ≤50 (P = 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.

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Early Identification of Therapeutic Failure in Nonseminomatous Germ Cell Tumors by Assessing Serum Tumor Marker Decline During Chemotherapy: Still Not Ready for Routine Clinical Use

Journal of Clinical Oncology ◽

10.1200/jco.2004.06.923 ◽

2004 ◽

Vol 22 (19) ◽

pp. 3842-3845 ◽

Cited By ~ 8

Author(s):

Guy C. Toner

Keyword(s):

Germ Cell ◽

Tumor Marker ◽

Early Identification ◽

Germ Cell Tumors ◽

Therapeutic Failure ◽

Clinical Use ◽

Serum Tumor Marker ◽

Nonseminomatous Germ Cell Tumors

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Early Experiences in Switching between Monoclonal Antibodies in Patients with Nonresponsive Migraine in Spain: A Case Series

European Neurology ◽

10.1159/000518899 ◽

2021 ◽

pp. 1-4

Author(s):

Ignacio Patier Ruiz ◽

Javier Sánchez-Rubio Ferrández ◽

Alba Cárcamo Fonfría ◽

Teresa Molina García

Keyword(s):

Clinical Trials ◽

Monoclonal Antibodies ◽

Therapeutic Targets ◽

Case Series ◽

Similar Efficacy ◽

Migraine Prophylaxis ◽

Therapeutic Failure ◽

Related Peptide ◽

Early Experiences ◽

Calcitonin Gene

Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

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