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Experimental and Therapeutic Medicine Jan 2023Diabetic foot ulcers infected with microorganisms increase the risk of amputation. The presence of drug-resistant bacteria in diabetic foot ulcers creates a big...
Diabetic foot ulcers infected with microorganisms increase the risk of amputation. The presence of drug-resistant bacteria in diabetic foot ulcers creates a big challenge during the treatment. The objective of the present study was to determine the bacterial prevalence and antibiotic resistance among bacteria isolated from Chinese patients with diabetic foot ulcers. The present study studied the microbial colonization of diabetic foot ulcers of patients from a single center in China. Wound swabs from 89 patients with diabetic foot ulcers were collected and the presence of microorganisms detected. The isolated microorganisms were subjected to antibiotic susceptibility testing by the disk diffusion method. Of 89 patients, 56 (62.9%) were male and 33 (37.1%) were female, the mean age of patients was 53.2±5.4 years, the mean duration of diabetes was 14.8±2.9 years, the mean random blood sugar was 301±87 mg/dl, mean HbA1c was 7.9±1.4%. Patients with Wanger ulcer grade III (36.0%; P=0.034) and patients within the weight range of 51-75 kg (59.6%; P=0.012) were significantly higher. The prevalence rate of diabetic foot ulcers was 11.3%. Among 153 microorganisms, gram-positive bacteria (52.3%) were more prevalent than gram-negative bacteria (44.4%). Most of the patients with polymicrobial infection were classified to have Wanger III ulcer grade diabetic foot ulcers. (38.2%) was the most predominant bacteria isolated followed by (29.2%) and (28.1%). Most of the gram-positive and gram-negative bacteria were resistant to dicloxacillin (73.8%, P=0.021) and cefotaxime (50%), respectively and ~53.4% of the isolates were multi-drug resistance isolates, 61.8% of the were identified as methicillin-resistant and 61.8% of the gram-negative bacteria were extended-spectrum -lactamase producers. and were the predominant gram-positive and gram-negative bacteria isolated, respectively. Penicillin resistance was significantly higher among the gram-negative bacteria (P=0.019). and were the predominant gram-positive and gram-negative bacteria isolated and levofloxacin and nitrofurantoin were the most effective antibiotics among the gram-positive and gram-negative bacterial isolates, respectively.
PubMed: 36588808
DOI: 10.3892/etm.2022.11752 -
Antibiotics (Basel, Switzerland) Dec 2021Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance,...
Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance, quorum-sensing, virulence and can influence the rate of mutations on the chromosome. Multidrug RND efflux systems are often characterized by a wide substrate specificity. Similarly to many other RND efflux pump systems, AcrAD-TolC confers resistance toward SDS, novobiocin and deoxycholate. In contrast to the other pumps, however, it in addition confers resistance against aminoglycosides and dianionic β-lactams, such as sulbenicillin, aztreonam and carbenicillin. Here, we could show that AcrD from confers resistance toward several hitherto unreported AcrD substrates such as temocillin, dicloxacillin, cefazolin and fusidic acid. In order to address the molecular determinants of the AcrD substrate specificity, we conducted substitution analyses in the putative access and deep binding pockets and in the TM1/TM2 groove region. The variants were tested in ΔΔ against β-lactams oxacillin, carbenicillin, aztreonam and temocillin. Deep binding pocket variants N136A, D276A and Y327A; access pocket variant R625A; and variants with substitutions in the groove region between TM1 and TM2 conferred a sensitive phenotype and might, therefore, be involved in anionic β-lactam export. In contrast, lower susceptibilities were observed for cells harbouring deep binding pocket variants T139A, D176A, S180A, F609A, T611A and F627A and the TM1/TM2 groove variant I337A. This study provides the first insights of side chains involved in drug binding and transport for AcrD from .
PubMed: 34943706
DOI: 10.3390/antibiotics10121494 -
Journal of Analytical Methods in... 2021Novel, accurate, selective, and rapid high-performance liquid chromatography mass spectrometry method was developed for simultaneous analysis of amoxicillin trihydrate,...
Novel, accurate, selective, and rapid high-performance liquid chromatography mass spectrometry method was developed for simultaneous analysis of amoxicillin trihydrate, dicloxacillin sodium, and their official impurity 6-aminopenicillanic acid. The chromatographic separation was carried out by applying the mixture on a C column (3.5 m ps, 100 mm × 4.6 mm id) using acetonitrile:water (65 : 35 by volume) as a mobile phase within only 4 min. The quantitative analysis was executed using single quadrupole mass spectrometer in which electrospray ionization, selected ion monitoring, and negative mode were operated. The retention times were 1.61, 2.54, and 3.50 mins for amoxicillin, 6-aminopenicillanic acid, and dicloxacillin, respectively. The method was validated in linear ranges of 2-28 g mL, 2-35 g mL, and 1-10 g mL for amoxicillin, dicloxacillin, and 6-aminopenicillanic acid, respectively. The results obtained from the suggested HPLC/MS were statistically compared with those obtained from the reported HPLC method, where no significant difference appeared respecting accuracy and precision. According to the analytical eco-scale assessment method, the proposed method was proved to be greener than the reported one, where the analysis time and the amount of the wasted effluent decreased.
PubMed: 34221533
DOI: 10.1155/2021/5570938 -
Journal of Infection in Developing... Feb 2022Dynamic movement in the hospital environment promotes the transmission of nosocomial pathogens and multidrug resistance mechanisms through the dissemination of organisms...
INTRODUCTION
Dynamic movement in the hospital environment promotes the transmission of nosocomial pathogens and multidrug resistance mechanisms through the dissemination of organisms that carry genetic determinants. Healthcare workers play an important role in the spread of pathogens; however, the role of visitors in this environment is poorly understood.
OBJECTIVE
This study aimed to molecularly identify and examine the antibiotic resistance of the palmar microbiota of patients' companions in a hospital waiting room.
METHODOLOGY
Twenty-five palmar surface and interdigital space sample swabs were randomly collected and cultured on blood agar plates, and 19 colonies with different macro- and microscopic characteristics were isolated. The V4 and V6 hypervariable regions of the 16S rRNA gene from each isolate were amplified by PCR and sequenced. Maximum likelihood- and Bayesian inference-based phylogenetic analyses were performed to determine taxonomic relationships. Antibiotic resistance was evaluated by disk diffusion and broth microdilution.
RESULTS
Among the isolates, 52.6% were related to Bacillus, 36.8% to Staphylococcus, 5.3% to Enterococcus and 5.3% to Atlantibacter. All of the isolates exhibited ampicillin and penicillin resistance, while 94.7% also exhibited dicloxacillin resistance. Staphylococcus aureus was resistant to penicillins but sensitive to the remaining drugs. Bacteria identified as Bacillus subtilis (MLM14B99), Bacillus pumilus (MLM23B07 and MLM25B06), Staphylococcus epidermidis (MLM24S31 and MLM29S04), and Enterococcus (MLM22E08) showed resistance to at least 46.7% of the antibiotics.
CONCLUSIONS
To decrease the transmission of pathogenic bacteria with an antibiotic resistance profile, re-evaluation of hand cleaning measures and their application by people who visit hospital centres is needed.
Topics: Bayes Theorem; Drug Resistance, Microbial; Hospitals; Humans; Phylogeny; RNA, Ribosomal, 16S; Staphylococcus epidermidis
PubMed: 35298428
DOI: 10.3855/jidc.15252 -
Microbiology Spectrum Feb 2023New strategies are urgently needed to address the public health threat of antimicrobial resistance. Synergistic agent combinations provide one possible pathway toward...
New strategies are urgently needed to address the public health threat of antimicrobial resistance. Synergistic agent combinations provide one possible pathway toward addressing this need and are also of fundamental mechanistic interest. Effective methods for comprehensively identifying synergistic agent combinations are required for such efforts. In this study, an FDA-approved drug library was screened against methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) in the absence and presence of sub-MIC levels of ceftobiprole, a PBP2a-targeted anti-MRSA β-lactam. This screening identified numerous potential synergistic agent combinations, which were then confirmed and characterized for synergy using checkerboard analyses. The initial group of synergistic agents (sum of the minimum fractional inhibitory concentration ∑FIC ≤0.5) were all β-lactamase-resistant β-lactams (cloxacillin, dicloxacillin, flucloxacillin, oxacillin, nafcillin, and cefotaxime). Cloxacillin-the agent with the greatest synergy with ceftobiprole-is also highly synergistic with ceftaroline, another PBP2a-targeted β-lactam. Further follow-up studies revealed a range of ceftobiprole synergies with other β-lactams, including with imipenem, meropenem, piperacillin, tazobactam, and cefoxitin. Interestingly, given that essentially all other ceftobiprole-β-lactam combinations showed synergy, ceftaroline and ceftobiprole showed no synergy. Modest to no synergy (0.5 < ∑FIC ≤ 1.0) was observed for several non-β-lactam agents, including vancomycin, daptomycin, balofloxacin, and floxuridine. Mupirocin had antagonistic activity with ceftobiprole. Flucloxacillin appeared particularly promising, with both a low intrinsic MIC and good synergy with ceftobiprole. That so many β-lactam combinations with ceftobiprole show synergy suggests that β-lactam combinations can generally increase β-lactam effectiveness and may also be useful in reducing resistance emergence and spread in MRSA. Antimicrobial resistance represents a serious threat to public health. Antibacterial agent combinations provide a potential approach to combating this problem, and synergistic agent combinations-in which each agent enhances the antimicrobial activity of the other-are particularly valuable in this regard. Ceftobiprole is a late-generation β-lactam antibiotic developed for MRSA infections. Resistance has emerged to ceftobiprole, jeopardizing this agent's effectiveness. To identify synergistic agent combinations with ceftobiprole, an FDA-approved drug library was screened for potential synergistic combinations with ceftobiprole. This screening and follow-up studies identified numerous β-lactams with ceftobiprole synergy.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Floxacillin; Staphylococcal Infections; Anti-Bacterial Agents; beta-Lactams; Cloxacillin; Microbial Sensitivity Tests; Ceftaroline
PubMed: 36519895
DOI: 10.1128/spectrum.03726-22 -
The British Journal of Dermatology Oct 2022Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's...
BACKGROUND
Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear.
OBJECTIVES
To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy.
METHODS
We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables.
RESULTS
A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin].
CONCLUSIONS
Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.
Topics: Acitretin; Anti-Bacterial Agents; Biological Factors; Biological Products; Clindamycin; Dapsone; Dicloxacillin; Drug Utilization; Hidradenitis Suppurativa; Humans; Isotretinoin; Rifampin; Tetracyclines
PubMed: 35603888
DOI: 10.1111/bjd.21673 -
Microorganisms Dec 2021Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This...
Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5-7 days of antibiotic therapy ( = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray-Curtis dissimilarities were significant between the pre- and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre- and the post-treatment microbial composition. We did not find significant differences between pre- and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.
PubMed: 34946144
DOI: 10.3390/microorganisms9122542 -
Microorganisms May 2023Skin and soft tissue infections are one of the main causes of consultations worldwide. The objective was to determine the treatment of a group of patients with...
Skin and soft tissue infections are one of the main causes of consultations worldwide. The objective was to determine the treatment of a group of patients with uncomplicated skin and soft tissue infections in Colombia. Follow-up study of a cohort of patients with skin infections who were treated in the Colombian Health System. Sociodemographic, clinical and pharmacological variables were identified. Treatments were evaluated using clinical practice guidelines for skin infections. A total of 400 patients were analyzed. They had a median age of 38.0 years and 52.3% were men. The most commonly used antibiotics were cephalexin (39.0%), dicloxacillin (28.0%) and clindamycin (18.0%). A total of 49.8% of the subjects received inappropriate antibiotics, especially those with purulent infections (82.0%). Being cared for in an outpatient clinic (OR: 2.09; 95% CI: 1.06-4.12), presenting pain (OR: 3.72; 95% CI: 1.41-9.78) and having a purulent infection (OR: 25.71; 95% CI: 14.52-45.52) were associated with a higher probability of receiving inappropriate antibiotics. Half of patients with uncomplicated skin and soft tissue infections were treated with antibiotics that were not recommended by clinical practice guidelines. This inappropriate use of antibiotics occurred in the vast majority of patients with purulent infections because the antimicrobials used had no effect on methicillin-resistant .
PubMed: 37374871
DOI: 10.3390/microorganisms11061369 -
Microorganisms Jun 2023is considered a microorganism with probiotic potential, which has been extensively studied, but these probiotic effects are strain dependent. This work aims to...
is considered a microorganism with probiotic potential, which has been extensively studied, but these probiotic effects are strain dependent. This work aims to characterize the probiotic potential, based on the biochemical and genomic functionality, of LBUX23, isolated from neonates' feces. LBUX23 contains one circular genome of 2,287,838 bp with a G+C content of 60.05%, no plasmids, no CRISPR-Cas operon, possesses 56 tRNAs, 9 rRNAs, 1 tmRNA and 1776 coding sequences (CDSs). It has chromosomally encoded resistance genes to ampicillin and dicloxacillin, non-hemolytic activity, and moderate inhibition of ATCC 25922 and to some emergent pathogen's clinical strains. LBUX23 was able to utilize lactose, sucrose, fructooligosaccharides (FOS), and lactulose. The maximum peak of bacterial growth was observed in sucrose and FOS at 6 h; in lactose and lactulose, it was shown at 8 h. LBUX23 can survive in gastrointestinal conditions (pH 4 to 7). A decrease in survival (96.5 and 93.8%) was observed at pH 3 and 3.5 during 120 min. , , and genes could be involved in this tolerance. LBUX23 can also survive under primary and secondary glyco- or tauro-conjugated bile salts, and a mixture of bile salts due to the high extracellular bile salt hydrolase (BSH) activity (67.3 %), in taurocholic acid followed by taurodeoxycholic acid (48.5%), glycocholic acid (47.1%), oxgall (44.3%), and glycodeoxycholic acid (29.7%) probably due to the presence of the and genes which form an operon (start: 119573 and end: 123812). Low BSH activity was determined intracellularly (<7%), particularly in glycocholic acid; no intracellular activity was shown. LBUX23 showed antioxidant effects in DPPH radical, mainly in intact cells (27.4%). In the case of hydroxyl radical scavenging capacity, cell debris showed the highest reduction (72.5%). In the cell-free extract, superoxide anion radical scavenging capacity was higher (90.5%). The genome of LBUX23 contains , , , and genes, which could be involved in this activity. Regarding adherence, it showed adherence up to 5% to Caco-2 cells. LBUX23 showed in vitro potential probiotic properties, mainly in BSH activity and antioxidant capacity, which indicates that it could be a good candidate for antioxidant or anti-cholesterol tests using in vivo models.
PubMed: 37512821
DOI: 10.3390/microorganisms11071648 -
BMJ Open Feb 2023Lesional skin of atopic dermatitis (AD) is often colonised by and the bacterial abundance increases during a flare. However, the role of and the skin microbiome in the...
Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis: protocol of a Danish intervention study.
INTRODUCTION
Lesional skin of atopic dermatitis (AD) is often colonised by and the bacterial abundance increases during a flare. However, the role of and the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD.
METHODS AND ANALYSIS
This clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologous , staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression.
ETHICS AND DISSEMINATION
The scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov: NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications.
TRIAL REGISTRATION NUMBER
NCT05578482, EudraCT 2021-006883-2.
Topics: Adult; Humans; Dermatitis, Atopic; Staphylococcus aureus; Skin; Immunity; Denmark
PubMed: 36806068
DOI: 10.1136/bmjopen-2022-068395