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      Evaluation of the Use of Antimicrobial Therapy for Treating Diabetic Foot Infections in an Indonesia Referral Hospital: A Retrospective Cohort Study

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          Abstract

          Background

          Diabetic foot infection (DFI) is a common complication of hyperglycemia and is related to prolongation of hospitalization, mortality, high hospitalization costs and decreased quality of life. Antibiotic therapy is one of the most critical factors in the eradication of infection. This study aims to determine the appropriateness of antibiotic use based on the local and international clinical guidelines and its short-term effect on patients’ clinical improvement.

          Materials and Methods

          This retrospective cohort study was conducted using secondary data from DFI inpatients from 1 January 2018 to 31 May 2020, from Dr. Cipto Mangunkusumo Hospital (RSCM), the National Referral Hospital of Indonesia. The Gyssens algorithm was used to help assess the appropriateness of antibiotics. All subjects were type 2 Diabetes Mellitus (T2DM) adult patients diagnosed with DFI. The primary outcome was a clinical improvement of infection after 7 - 14 days of antibiotic use. The clinical improvement of infection was defined by a minimum of three of these criteria: reduced or no purulent secretions, no fever, the area around the wound did not feel warm, no or reduced local oedema, no local pain, reduced redness or erythema, and decreased leukocytes count.

          Results

          A total of 113 (63.5%) eligible subjects from a total of 178 were recruited. Among the patients, 51.4% had a duration of T2DM for ≥10 years, 60.2% had uncontrolled hyperglycemia, 94.7% had a history of complications, 22.1% had a history of amputation, and 72.6% had ulcer grade ≥3. Based on the Gyssens algorithm, 54.0% of the subjects were given antibiotics appropriately, while the other 46.0% were not. The proportion of improved patients in the appropriate antibiotics group was higher but not statistically significant than those in the inappropriate group (60.7% vs. 42.3%, P = 0.079). However, the results of the multivariate analysis demonstrated that the appropriate use of antibiotics would increase clinical improvement by 2.6 times, compared to inappropriate use after controlling for the covariates (adjusted odds ratio: 2.616, 95% confidence interval: 1.117 - 6.126, P = 0.027).

          Conclusion

          Only half of the patients with DFI received appropriate antibiotics, although an appropriate antibiotics usage was independently associated with better short-term clinical improvement in DFI. This suggests that we should effort to improve appropriateness in antibiotics usage in DFI.

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          Most cited references29

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          A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

          Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Conclusions Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients.
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            2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections.

            Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.
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              Variable selection strategies and its importance in clinical prediction modelling

              Clinical prediction models are used frequently in clinical practice to identify patients who are at risk of developing an adverse outcome so that preventive measures can be initiated. A prediction model can be developed in a number of ways; however, an appropriate variable selection strategy needs to be followed in all cases. Our purpose is to introduce readers to the concept of variable selection in prediction modelling, including the importance of variable selection and variable reduction strategies. We will discuss the various variable selection techniques that can be applied during prediction model building (backward elimination, forward selection, stepwise selection and all possible subset selection), and the stopping rule/selection criteria in variable selection (p values, Akaike information criterion, Bayesian information criterion and Mallows’ Cp statistic). This paper focuses on the importance of including appropriate variables, following the proper steps, and adopting the proper methods when selecting variables for prediction models.
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                Author and article information

                Journal
                Infect Chemother
                Infect Chemother
                IC
                Infection & Chemotherapy
                The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS
                2093-2340
                2092-6448
                March 2023
                23 February 2023
                : 55
                : 1
                : 80-89
                Affiliations
                [1 ]Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
                [2 ]Division of Endocrinology, Department of Internal Medicine Dr. Cipto Mangunkusumo National Referral Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
                Author notes
                Corresponding Author: Rani Sauriasari, BPharm, MMedSci, PhD. Faculty of Pharmacy, Universitas Indonesia, Building A, 3rd Floor, Kampus Baru UI Depok, 16424, West Java Province, Indonesia. Tel: +62-1-727-0031, Fax: +62-1-786-3433, rani@ 123456farmasi.ui.ac.id
                Corresponding Author: Em Yunir, MD, PhD. Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta 10430, Indonesia. Tel: +62-21-390-7703, e.yunir@ 123456ui.ac.id

                *These authors are contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-8087-1110
                https://orcid.org/0000-0001-7861-4369
                https://orcid.org/0000-0002-2004-9050
                https://orcid.org/0000-0002-8000-6992
                Article
                10.3947/ic.2022.0084
                10079441
                36864766
                4f28fb70-6637-4d6a-981a-0b721a51557a
                Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 June 2022
                : 26 December 2022
                Funding
                Funded by: Ministry of Research and Higher Education
                Award ID: NKB-93/UN2.RST/HKP.05.00/2020
                Award ID: NKB-2692/UN2.RST/HKP.05.00/2020
                Categories
                Original Article

                antibiotics,clinical improvement,diabetic foot,infection

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