Barriers and facilitators for isoniazid preventive therapy (IPT) administration in children under 5 years of age in the Dominican Republic.

INTRODUCTION: Throughout the world tuberculosis (TB) is the second leading cause of death due to an infectious agent. The World Health Organization promotes Isoniazid Preventive Therapy (IPT) in children under 5 years who are contacts of persons diagnosed with smear-positive pulmonary TB (SPPTB). In 2019, 33% of children identified as contacts received IPT globally, while in the Americas 11 countries reached coverages ≥ 75%, only 35% did so in the Dominican Republic (DR). The aim of this study was to identify barriers and facilitators for IPT administration in children under 5 in the Area IV Directorate of Health of the DR's National District. METHODS: Descriptive study, using mixed methods and sequential explanatory approach. We characterized children under 5 years who were contacts of a person with SPPTB. Later, semi-structured interviews and content analysis allowed identification of barriers and facilitators for IPT administration in children who were contacts of a person diagnosed with SPPTB, as perceived by relatives and health system personnel. RESULTS: A total of 238 children were identified as contacts of 174 persons with SPPTB: 36% of these received IPT while no data on IPT administration was found for 11% of them. The proportion of children who had a tuberculin skin test (TST) done was < 20%. However, those who had the test done had a greater opportunity to receive IPT (OR: 8.12, CI 95%: 1.60-41.35). Barriers identified include socioeconomic conditions of children and families, stigma, lack of information in clinical and follow-up records, lack of coordination between public and private providers and lack of coherence within national regulations. Facilitators include home based care of persons with TB and their contacts, transfer of treatment to a health centre near household, isoniazid availability, provision of information by health-workers and economic support for food and transportation. CONCLUSIONS: Incomplete data, lack of use of TST to rule out active TB, socioeconomic and cultural conditions, were barriers for IPT administration. Implementation of a person centred approach to care was found to be the main facilitator for IPT uptake. Administration of IPT depends predominantly on modifiable health system factors. This allows rapid identification of strategies to improve IPT administration.

Risk factors and survival of patients infected with carbapenem-resistant Klebsiella pneumoniae in a KPC endemic setting: a case-control and cohort study.

BACKGROUND: Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy. METHODS: A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy. RESULTS: A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37). CONCLUSION: Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.