title: Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study.
abstract: Reports of therapeutic failure to meglumine antimoniate (MA) and miltefosine in cutaneous leishmaniasis (CL) varies between species, populations and geographic regions. This study aimed to determine the clinical, drug-related factors, and Leishmania species associated with treatment failure in children and adults with cutaneous leishmaniasis.
  
  
  
  A cohort study was performed with children (2-12 years old) and adults (18-65 years old) with CL, who have participated in clinical studies at CIDEIM Cali, Tumaco and Chaparral. Incidence of therapeutic failure was estimated by treatment and age groups. Descriptive, bivariate, and multiple logistic regression analyses were performed for the complete cohort and pediatric patients.
  
  
  
  Two hundred and thirty patients were included (miltefosine: 112; MA: 118), of which 60.4% were children and 83.9% were infected with L.V. panamensis. Overall incidence of therapeutic failure was 15.65% (95%CI: 10.92-20.38), and was lower for miltefosine than for MA (8.92%, 95%CI: 3.59-14.26 versus 22.03%, 95%CI:14.48-29.58, p = 0.006). Treatment failure was associated with age ≤8 years (OR: 3.29; 95%CI: 1.37-7.89), disease duration ≤1 month (OR: 3.29; 95%CI: 1.37-7.89), regional lymphadenopathy (OR: 2.72; 95%CI: 1.10-6.70), treatment with MA (OR: 3.98; 95%CI: 1.66-9.50), and adherence <90% (OR: 3.59; 95%CI: 1.06-12.11). In children, higher Z-score of height/age was a protective factor (OR: 0.58; 95%CI: 0.36-0.93), while treatment with MA was a risk factor (OR: 40.82; 95%CI: 2.45-677.85), demonstrating significant interaction with age (p = 0.03).
  
  
  
  Clinical and drug-related factors determine therapeutic failure in CL. High risk of failure in children treated with MA indicates the need to reconsider this drug as first line treatment in this population.
  
  
  
  Clinical trial registration: NCT00487253 Clinical trial registration: NCT01462500 Clinical trial registration: NCT01464242.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.|Escuela de Salud Pública, Universidad del Valle, Cali, Colombia.
authors.forename: Maria Del Mar
authors.identifier: 0000-0002-0485-2919
authors.initials: MDM
authors.lastname: Castro
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cossio
authors.affiliation: Departamento de Pediatría, Universidad del Valle, Cali, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Velasco
authors.affiliation: Escuela de Salud Pública, Universidad del Valle, Cali, Colombia.
authors.forename: Lyda
authors.initials: L
authors.lastname: Osorio
mesh_terms: D000293:Adolescent; D000328:Adult; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003105:Colombia; D005260:Female; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008536:Meglumine / Q000494:pharmacology / Q000627:therapeutic use*; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate