Disponibilidad de antibióticos en tiendas de Guatemala.

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Availability of over-the-counter antibiotics in Guatemalan corner stores.

Widespread availability of antibiotics without prescription potentially facilitates overuse and contributes to selection pressure for antimicrobial resistant bacteria. Prior to this study, anecdotal observations in Guatemala identified corner stores as primary antibiotic dispensaries, where people purchase antibiotics without prescriptions. We carried out a cross sectional study to document the number and types of antibiotics available in corner stores, in four study areas in Guatemala. A total of 443 corner stores were surveyed, of which 295 (67%) sold antibiotics. The most commonly available antibiotics were amoxicillin, found in 246/295 (83%) stores, and tetracycline, found in 195/295 (66%) stores. Over the counter sales result from laissez-faire enforcement of antibiotic dispensing regulations in Guatemala combined with patient demand. This study serves as a baseline to document changes in the availability of antibiotics in informal establishments in light of new pharmacy regulations for antibiotic dispensing, which were adopted after this study was completed.

Antibiotic use and hygiene interact to influence the distribution of antimicrobial-resistant bacteria in low-income communities in Guatemala.

To examine the effects of poor sanitation and hygiene on the prevalence of antimicrobial-resistant bacteria, we surveyed households in two rural and two urban communities in Guatemala (N = 196 randomly selected households). One adult (≥ 18-years old) and, when available, one child (≤ 5 years-old) provided a stool sample. Up to 48 presumptive Escherichia coli isolates were collected from each stool sample (n = 21,256 total) and were subjected to breakpoint assays for ten antibiotics. Mixed-effects logistic models were used to identify potential factors influencing the likelihood of harboring antibiotic-resistant bacteria. For nine out of ten antibiotics, the odds of detecting resistant bacteria decreased by ~ 32% (odds ratios, OR 0.53-0.8, P < 0.001) for every unit of improvement of a hygiene scale. Hygiene differences between households had a greater impact on prevalence compared to antibiotic use differences. The likelihood of detecting resistant isolates was lower for five antibiotics among households that boiled raw milk before consumption (OR 0.31-0.69), and higher for nine antibiotics in urban households (OR > 1.89-9.6). Poor hygiene conditions likely obscure effects of individual antibiotic use, presumably due to enhanced microbial transmission. Consequently, efforts to improve antibiotic stewardship should be coupled with improving hygiene conditions.

NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort.

OBJECTIVE: Blau syndrome and early-onset sarcoidosis are NOD2 gene-associated chronic autoinflammatory diseases characterized by skin rash, arthritis, and/or eye involvement, with noncaseating granulomata as their pathologic hallmark. This study was undertaken to describe the expanded clinical phenotype, treatment outcomes, and NOD2 gene mutation analysis in a Spanish cohort with pediatric granulomatous arthritis, a chronic disease resembling Blau syndrome/early-onset sarcoidosis. METHODS: Clinical, laboratory, and treatment data on the 12 patients in the cohort were obtained through direct interviews. NOD2 gene analysis was performed in a central laboratory, by bidirectional sequencing. Cytokine levels were measured using the human Flex-Set cytokine bead array. RESULTS: The classic Blau syndrome/early-onset sarcoidosis triad of skin rash, arthritis, and recurrent uveitis was identified in 5 patients (41.7%), whereas 7 patients (58.3%) presented with fewer than 3 of the classic features. Novel atypical manifestations such as persistent fever and myocardiopathy were also observed. NOD2 analysis revealed 1 heterozygous mutation in each patient, and familial studies confirmed its full penetrance. Of the 12 cases, 58.3% were sporadic, due to de novo mutations. Four different missense mutations on exon 4 were detected. Two of them (R334W and R334Q) were recurrent mutations and were found in 77.8% of the Spanish families, whereas the other 2 (C495Y and R587C) were novel. In the patient who received anakinra treatment, all clinical inflammatory symptoms improved and plasma cytokine levels normalized. CONCLUSION: These findings indicate that the expanding clinical heterogeneity of the disease (that is, the presentation of incomplete forms of the classic triad and atypical manifestations) and the high prevalence of sporadic cases should alert clinicians to the possible genetic basis of the condition and support the inclusion of DNA analysis as a diagnostic test. The positive response to anakinra observed in 1 patient suggests a new potential therapeutic approach that merits further investigation, and suggests that the pathogenesis of pediatric granulomatous arthritis may involve interleukin-1-mediated events.