Resumo em Inglês:

Abstract BACKGROUND Diabetic foot ulcers are a common diabetic complication leading to alarming figures of amputation, disability, and early mortality. The diabetic glucooxidative environment impairs the healing response, promoting the onset of a ‘wound chronicity phenotype’. In 50% of ulcers, these non-healing wounds act as an open door for developing infections, a process facilitated by diabetic patients’ dysimmunity. Infection can elicit biofilm formation that worsens wound prognosis. How this microorganism community is able to take advantage of underlying diabetic conditions and thrive both within the wound and the diabetic host is an expanding research field. OBJECTIVES 1) Offer an overview of the major cellular and molecular derangements of the diabetic healing process versus physiological cascades in a non-diabetic host. 2) Describe the main immunopathological aspects of diabetics’ immune response and explore how these contribute to wound infection susceptibility. 3) Conceptualize infection and biofilim in diabetic foot ulcers and analyze their dynamic interactions with wound bed cells and matrices, and their systemic effects at the organism level. 4) Offer an integrative conceptual framework of wound–dysimmunity–infection–organism damage. EVIDENCE AQUISITION We retrieved 683 articles indexed in Medline/PubMed, SciELO, Bioline International and Google Scholar. 280 articles were selected for discussion under four major subheadings: 1) normal healing processes, 2) impaired healing processes in the diabetic population, 3) diabetic dysimmunity and 4) diabetic foot infection and its interaction with the host. DEVELOPMENT The diabetic healing response is heterogeneous, torpid and asynchronous, leading to wound chronicity. The accumulation of senescent cells and a protracted inflammatory profile with a pro-catabolic balance hinder the proliferative response and delay re-epithelialization. Diabetes reduces the immune system’s abilities to orchestrate an appropriate antimicrobial response and offers ideal conditions for microbiota establishment and biofilm formation. Biofilm–microbial entrenchment hinders antimicrobial therapy effectiveness, amplifies the host's pre-existing immunodepression, arrests the wound’s proliferative phase, increases localized catabolism, prolongs pathogenic inflammation and perpetuates wound chronicity. In such circumstances the infected wound may act as a proinflammatory and pro-oxidant organ superimposed onto the host, which eventually intensifies peripheral insulin resistance and disrupts homeostasis. CONCLUSIONS The number of lower-limb amputations remains high worldwide despite continued research efforts on diabetic foot ulcers. Identifying and manipulating the molecular drivers underlying diabetic wound healing failure, and dysimmunity-driven susceptibility to infection will offer more effective therapeutic tools for the diabetic population.

Resumo em Inglês:

Abstract INTRODUCTION Carbapenem-resistant Acinetobacter baumannii is a complex health problem, causing difficulties in clinical–therapeutic management worldwide. It is of particular concern in Latin America, the Caribbean and China, where it is an emerging health problem. Carbapenemases produced by these organisms inactivate carbapenem antibiotics. Monitoring circulating genotypes’ geographic dispersion contributes to more effective control measures. However, exhaustive studies on carbapenem-resistant A. baumannii are scarce. OBJECTIVES Study the production of carbapenemases in clinical isolates of A. baumannii resistant to carbapenem antibiotics and the geographic distribution of the sequences circulating in China, Latin America and the Caribbean. DATA ACQUISITION We followed PRISMA indications. We carried out a systematic search in Pubmed, BVS and CKNI on papers on A. baumannii and carbapenemases published during 2015–2020 in English, Spanish and Chinese, and selected 29 cross-sectional studies that met the search criteria. Studies were evaluated using JBI Critical Appraisal tools, and quantitative data were collated for meta-analysis using the Metaprop library in Stata15. DEVELOPMENT OXA-type carbapenemases were detected in all studies; among A. baumannii resistant to carbapenem antibiotics, predominant types were OXA-23, OXA-24, OXA-54 and OXA-72; metallobetalactamases were identified less frequently than OXA carbapenemases. Only one clinical isolate producer of Class A carbapenemases (KPC) was identified in Colombia. In total, 41 sequence types were identified; in Latin America and the Caribbean the most common types were: ST79, ST25, ST1 and ST15; in China, the sequences ST195, ST208, ST191, ST368 and ST369 were the most prevalent. ST2 was found in both regions. CONCLUSIONS The most prevalent carbapenemases and sequence types vary by region, indicating different ancestral strains. Microbiological surveillance, antibiotic use optimization, adequate infection treatment and timely control strategies are essential for carbapenem-resistant A. baumannii prevention and control in geographies such as Latin America, the Caribbean and China where such resistance is an emerging health problem.