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Case report: Azithromycin-meropenem combination therapy as a low-cost approach to combat PDR gram-negative infections of war wounds in Ukraine.

ABSTRACT: Antimicrobial resistance recognised as a major global health problem and it poses a significant challenge in conflict zones, such as the Russia-Ukraine war. This case study focuses on a 32-year-old soldier who sustained combat-related injuries, including extensive wound infections caused by multidrug-resistant and pan-resistant bacteria and was successfully treated with azithromycin-meropenem combination therapy. The emergence of pan-resistant bacteria, particularly a pandrug-resistant strain of Pseudomonas aeruginosa, highlights the severity of the problem and the limited treatment options available. Additionally, the financial burden posed by reserve antibiotics further complicates the management of these infections. The case study demonstrates the effectiveness of including azithromycin-meropenem combination therapy in the treatment regimen, which resulted in improvements in the patient's condition and the eradication of the resistant strains. The findings underscore the need for effective antimicrobial stewardship, infection control measures, and alternative treatment strategies to combat antimicrobial resistance in conflict zones.

SUBMITTER: Kryzhevskyi V

PROVIDER: S-EPMC10566362 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Case report: Azithromycin-meropenem combination therapy as a low-cost approach to combat PDR gram-negative infections of war wounds in Ukraine.

Kryzhevskyi Vadym V Strokous Viktor V Lifshyts Yurii Y Rybianets Yurii Y Oberniak Artem A Krikunov Alexey A Iungin Olga O Potochilova Viktoria V Rudnieva Kateryna K Petakh Pavlo P Kamyshnyi Aleksandr A Moshynets Olena O

Frontiers in medicine 20230922

Antimicrobial resistance recognised as a major global health problem and it poses a significant challenge in conflict zones, such as the Russia-Ukraine war. This case study focuses on a 32-year-old soldier who sustained combat-related injuries, including extensive wound infections caused by multidrug-resistant and pan-resistant bacteria and was successfully treated with azithromycin-meropenem combination therapy. The emergence of pan-resistant bacteria, particularly a pandrug-resistant strain of ...[more]

PMID: 37828939

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Project description:BackgroundInfection with extensive-drug-resistant (XDR) carbapenem-resistant (CR) Gram-negative bacteria (GNB) are viewed as a serious threat to human health because of the limited therapeutic options. This imposes the urgent need to find agents that could be used as adjuvants or combined with carbapenems to enhance or restore the susceptibility of XDR CR- GNB. Therefore, this study aimed to examine the effect of propranolol (PR) in combination with Meropenem (MEM) on the susceptibility profile of XDR CR-GNB recovered from severely infected patients as well as to evaluate combining MEM with either tigecycline (TGC) or amikacin (AK).MethodsA total of 59 non-duplicate CR- GNB were investigated for carbapenemase production by the major phenotypic methods. Molecular identification of five major carbapenemase-coding genes was carried out using polymerase chain reactions (PCR). Antimicrobial susceptibility tests were carried out using standard methods. Phenotypic and genotypic relatedness was carried out using the heatmap and ERIC PCR analysis. PR, 0.5 -1 mg/mL against the resulting non-clonal XDR CR-GNB pathogens were evaluated by calculating the MIC decrease factor (MDF). A combination of MEM with either AK or TGC was performed using the checkerboard assay.ResultsA total of 21 (35.6%) and 38 (64.4%) CR-GNB isolates were identified as enterobacterial isolates (including 16 (27.1%) Klebsiella Pneumoniae and 5 (8.5%) Escherichia coli) and non-fermentative bacilli (including, 23 (39%), Acinetobacter baumannii, and 15 (25.4%) Pseudomonas aeruginosa). The heatmap and ERIC PCR analysis resulted in non-clonal 28 XDR CR isolates. PR, at a concentration of 0.5 mg /ml, decreased MICs values of the tested XDR CR isolates (28; 100%) and restored susceptibility of only 4 (14.3%) isolates. However, PR (1 mg/mL) when combined with MEM has completely (28; 100%) restored the susceptibility of the tested XDR CR- GNB to MEM. The MEM + AK and MEM + TGC combination showed mostly additive effects (92.8% and 71.4%, respectively).ConclusionPR at a concentration of 1 mg/mL restored the susceptibility of XDR CR- GNB to MEM which is considered a promising result that should be clinically investigated to reveal its suitability for clinical use in patients suffering from these life-threatening pathogens.

Project description:BackgroundMicrobiology of modern war wounds is unique for each military conflict. Climatic and geographical features of the theater of war, contemporary warfare as well as wound management affect the microbial flora of wounds. This study was designed to determine time-specific microbial flora of combat wounds of upper and lower extremities obtained during the war in eastern Ukraine.MethodsThe patients enrolled in study had combat wounds of upper or lower extremities which were treated in the Military Medical Clinical Center of Central Region. The wounds were swab-cultured and measured at each surgical debridement. The recovered microorganisms were identified and their antimicrobial resistance profiles were evaluated by disc diffusion method.ResultsForty-nine patients with battle-field wounds were enrolled in the study from July to November 2014; all patients were male with a mean Injury Severity Score and arrival APACHE II scores of 16.2 ± 10.7 and 7.4 ± 4.2 respectively. Among 128 swab cultures, 100 swab cultures were positive. Swab cultures were obtained from 57 wounds of 49 patients. The results of the test showed that 87.7% of all positive swab cultures contained a single-organism while the rest of the swab-culture results showed polymicrobial growth. Among the isolated microorganisms 65% (76 strains) were Gram-negative rods, 22.2% (26 strains) of Gram-positive cocci, followed by Gram-positive rods (12.8%, 15 strains). We found that epidemiology of wound infection changes with the time after injury. The most common bacterial isolates cultured during the first week were Gram-positive microbes with low pathogenicity. The number of Gram-negative rods increased during the wound healing process. The incidence of Gram-positive microorganisms' growth fell after the first week and increased after third week. During wound healing, bacterial microflora of wounds changes with increasing number of Gram-negative rods with predominance of Acinetobacter species. Predominant microorganisms in positive swab-cultures after first week were nonfermentative Gram-negative bacilli (68% of swab-cultures), which in 53% of the swab-cultures belonged to the genus Acinetobacter, and in 15% to the genus Pseudomonas. The incidence of polymicrobial wound cultures increased from first week to second post-injury week. The most frequent microbial mixture were Acinetobacter baumannii with Enterobacteriaceae or other nonfermentative Gram negative rods with Enterococcus spp. We observed bacteria recovery from wounds during proliferation phase. These wounds had no pure inflammation signs and were free of devitalized tissues.ConclusionsAny wound is at some risk of becoming infected. In the event of infection, a wound fails to heal, treatment costs rise, and general wound management practices become more resource demanding. Determining the microorganisms which colonize battle wounds and cause wound infection is paramount. This information can help to treat battle wound infections or even changes infection control strategies. The fact of shifting in wound microbiology in the favor of bacteria responsible for healthcare-associated infections support to the proposition that these changes are nosocomially related [4, 14]. For Ukrainian military medicine this study is the first time-specified assessment of battle wound colonization from the World War II.

Project description:IntroductionOn 24 February 2022, Russia launched a large-scale offensive in Ukraine, resulting in significant casualties to civilians, including children. As part of a seven-stream trauma education initiative, a novel pediatric trauma fundamentals course (PTF) was developed to provide standalone pediatric trauma education by our academic/NGO partnership. The objective of the program was to develop, implement, and evaluate a novel PTF educational course in the active armed conflict zone of Ukraine.MethodsA novel two-day PTF course was internally developed, translated into Ukrainian, and implemented across eight Oblasts (regions) in Ukraine from November 2022 to December 2023. Participants completed pre-and post-assessments in knowledge and self-confidence, and critical skills were assessed against objective skill checklists. Change in knowledge and self-confidence were analyzed, respectively, with the nonparametric Wilcoxon matched-pairs signed-rank test and McNemar's test for paired data. Anonymous course evaluations were solicited after each course. Six to eight-week follow-up surveys were conducted to assess skill utilization and stewardship.ResultsFour hundred and forty-six Ukrainian health care providers were trained during 30 courses across 8 Oblasts in Ukraine during the intervention period. Aggregated knowledge and self-confidence significantly improved across all measures. Ukrainian instructors of courses received higher raw scores across all evaluation points on instructor feedback surveys as compared to international instructors. Six to eight-week follow-up surveys demonstrated participants had positive views of the training, have used the training on patients, and have taught the material to other health care providers.DiscussionOur novel PTF intervention demonstrates a successful partnership-based model for implementing pediatric trauma education in an active conflict zone in Ukraine. Challenges to implementing such programs can be mitigated through strategic partnership-based models between academic institutions and organizations with local knowledge and expertise. Ukrainian instructors provide course experiences similar or superior to international instructors, likely due to multiple factors related to language, culture, and context.

Dataset Information

Case report: Azithromycin-meropenem combination therapy as a low-cost approach to combat PDR gram-negative infections of war wounds in Ukraine.

Publications

Case report: Azithromycin-meropenem combination therapy as a low-cost approach to combat PDR gram-negative infections of war wounds in Ukraine.

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