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Microbiology Spectrum May 2024Broad-spectrum ampicillin-resistant and third-generation cephalosporin-resistant Enterobacteriaceae, particularly and that have pathological features in humans, have...
UNLABELLED
Broad-spectrum ampicillin-resistant and third-generation cephalosporin-resistant Enterobacteriaceae, particularly and that have pathological features in humans, have become a global concern. This study aimed to investigate the prevalence, antimicrobial susceptibility, and molecular genetic features of extended-spectrum beta-lactamase (ESBL)-producing and isolates in Southern Thailand. Between January and August 2021, samples ( = 199) were collected from a tertiary care hospital in Southern Thailand. ESBL and AmpC-lactamase genes were identified using multiplex polymerase chain reaction (PCR). The genetic relationship between ESBL-producing and was determined using the enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction. ESBL-producing and isolates were mostly collected from catheter urine samples of infected female patients. The ESBL production prevalence was highest in the medical wards ( = 75, 37.7%), followed by that in surgical wards ( = 64, 32.2%) and operating rooms ( = 19, 9.5%). Antimicrobial susceptibility analysis revealed that all isolates were resistant to ampicillin, cefotaxime, ceftazidime, ceftriaxone, and cefuroxime; 79.4% were resistant to ciprofloxacin; and 64.3% were resistant to trimethoprim-sulfamethoxazole. In ESBL-producing and , ( = 57, 72.2%) and ( = 61, 50.8%) genes were prominent; however, no , , or were found in any of these isolates. Furthermore, only ESBL-producing had co-harbored and genes at 11.6%. The ERIC-PCR pattern of multidrug-resistant ESBL-producing strains demonstrated that the isolates were clonally related (95%). Notably, the presence of multidrug-resistant and extremely resistant ESBL producers was 83.4% and 16.6%, respectively. This study highlights the presence of , , and co-harbored genes in ESBL-producing bacterial isolates from hospitalized patients, which are associated with considerable resistance to beta-lactamase and third-generation cephalosporins.
IMPORTANCE
We advocate for evidence-based guidelines and antimicrobial stewardship programs to encourage rational and appropriate antibiotic use, ultimately reducing the selection pressure for drug-resistant bacteria and lowering the likelihood of ESBL-producing bacterial infections.
PubMed: 38809095
DOI: 10.1128/spectrum.00213-24 -
Open Forum Infectious Diseases May 2024This trial tested the effectiveness of a novel regimen to prevent malaria and sexually transmitted infections (STIs) among pregnant women with HIV in Cameroon. Our... (Clinical Trial)
Clinical Trial
Trimethoprim-Sulfamethoxazole Plus Azithromycin to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV (PREMISE): A Randomized, Double-Masked, Placebo-Controlled, Phase IIB Clinical Trial.
BACKGROUND
This trial tested the effectiveness of a novel regimen to prevent malaria and sexually transmitted infections (STIs) among pregnant women with HIV in Cameroon. Our hypothesis was that the addition of azithromycin (AZ) to standard daily trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis would reduce malaria and STI infection rates at delivery.
METHODS
Pregnant women with HIV at gestational age <28 weeks were randomized to adjunctive monthly oral AZ 1 g daily or placebo for 3 days and both groups received daily standard oral TMP-SMX through delivery. Primary outcomes were (1) positive peripheral malaria infection by microscopy or polymerase chain reaction and (2) composite bacterial genital STI (, or syphilis) at delivery. Relative risk and 95% confidence intervals were estimated using 2 × 2 tables with significance as < .05.
RESULTS
Pregnant women with HIV (n = 308) were enrolled between March 2018 and August 2020: 155 women were randomized to TMP-SMX-AZ and 153 women to TMP-SMX-placebo. Groups were similar at baseline and loss to follow up was 3.2%. There was no difference in the proportion with malaria (16.3% in TMP-SMX-AZ vs 13.2% in TMP-SMX; relative risk, 1.24 [95% confidence interval, .71-2.16]) or STI at delivery (4.2% in TMP-SMX-AZ vs 5.8% in TMP-SMX; relative risk, 0.72 [95% confidence interval, .26-2.03]). Adverse birth outcomes were not significantly different, albeit lower in the TMP-SMX-AZ arm (preterm delivery 6.7% vs 10.7% [ = .3]; low birthweight 3.4% vs 5.4% [ = .6]).
CONCLUSIONS
The addition of monthly azithromycin to daily TMP-SMX prophylaxis in pregnant women living with HIV in Cameroon did not reduce the risk of malaria or bacterial STI at delivery.
PubMed: 38807754
DOI: 10.1093/ofid/ofae274 -
World Journal of Urology May 2024To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center... (Comparative Study)
Comparative Study
BACKGROUND
To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX).
METHODS
Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF).
RESULTS
Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7-2.6) for group-C vs. group-BF and 2.8 (CI 1.4-5.7) for group-F vs. group-BF respectively.
CONCLUSION
The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended.
Topics: Humans; Male; Fosfomycin; Ciprofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Antibiotic Prophylaxis; Aged; Middle Aged; Prostate; Anti-Bacterial Agents; Drug Therapy, Combination; Biopsy; Retrospective Studies; Rectum; Postoperative Complications
PubMed: 38806739
DOI: 10.1007/s00345-024-05048-4 -
BMC Veterinary Research May 2024Piggery production is highly constrained by diseases, with diarrhoea in piglets being a major cause of economic losses to smallholder farmers in Uganda. Enterotoxigenic...
BACKGROUND
Piggery production is highly constrained by diseases, with diarrhoea in piglets being a major cause of economic losses to smallholder farmers in Uganda. Enterotoxigenic Escherichia coli (ETEC) is thought to be one of the major etiologies of this diarrhoea. A cross-sectional study was carried out in two high pig-producing districts of Uganda with the aim of determining the significance of piglet diarrhoea and the pathogenic determinants of causative E. coli.
METHODOLOGY
A total of 40 households with piglets were visited in each district for a questionnaire survey and faecal sample collection. The questionnaire-based data collected included; demographic data and pig management practices. E. coli were isolated from diarrheic (43) and non-diarrheic (172) piglets and were subjected to antimicrobial susceptibility testing against nine commonly used antimicrobial agents. The E. coli isolates were further screened for the presence of 11 enterotoxin and fimbrial virulence gene markers using multiplex polymerase chain reaction. Data entry, cleaning, verification and descriptive statistics were performed using Microsoft Excel. Statistical analysis to determine any association between the presence of virulence markers and diarrhea in piglets was done using SPSS software (Version 23), with a p value of less than 0.05 taken as a statistically significant association.
RESULTS
Escherichia coli were recovered from 81.4% (175/215) of the faecal samples. All the isolates were resistant to erythromycin, and most showed high resistance to tetracycline (71%), ampicillin (49%), and trimethoprim sulfamethoxazole (45%). More than half of the isolates (58.3%) carried at least one of the 11 virulence gene markers tested. EAST1 was the most prevalent virulence marker detected (35.4%), followed by STb (14.8%). Expression of more than one virulence gene marker was observed in 6.2% of the isolates, with the EAST1/STa combination being the most prevalent. Three adhesins; F17 (0.6%), F18 (6.3%) and AIDA-I (0.6%) were detected, with F18 being the most encountered. There was a statistically significant association between the occurrence of piglet diarrhoea and the presence of the AIDA-1 (p value = 0.037) or EAST1 (p value = 0.011) gene marker among the isolates.
CONCLUSION AND RECOMMENDATION
The level of antimicrobial resistance among E. coli isolates expressing virulence markers were high in the sampled districts. The study established a significant association between presence of EAST1 and AIDA-I virulence markers and piglet diarrhea. Further studies should be carried out to elucidate the main adhesins borne by these organisms in Uganda and the actual role played by EAST1 in the pathogenesis of the infection since most isolates expressed this gene.
Topics: Animals; Uganda; Swine; Swine Diseases; Escherichia coli Infections; Diarrhea; Cross-Sectional Studies; Enterotoxigenic Escherichia coli; Virulence; Feces; Animals, Newborn; Anti-Bacterial Agents; Escherichia coli; Weaning; Microbial Sensitivity Tests
PubMed: 38802876
DOI: 10.1186/s12917-024-04092-x -
Journal of Family & Community Medicine 2024(. ), a forgotten pathogen that normally colonizes the upper respiratory mucosa, can be associated with severe and invasive infections. The objectives of this study...
Epidemiological characteristics of Klebsiella ozaenae infection and its antibiotic susceptibility: Experience of a tertiary care hospital in the Eastern Province of Saudi Arabia.
BACKGROUND
(. ), a forgotten pathogen that normally colonizes the upper respiratory mucosa, can be associated with severe and invasive infections. The objectives of this study were to determine the frequency of isolation of . at the microbiology laboratory in a tertiary hospital and the scope of diseases associated with it and to characterize its antimicrobial susceptibility pattern.
MATERIALS AND METHODS
This cross-sectional study analyzed the retrospective data, from 2002 to 2021, on cases with laboratory-confirmed isolation of . at a tertiary care hospital. The primary outcome was to identify the scope of . infections and their antimicrobial susceptibility patterns. . isolation was done by cultivation on microbiological culture media, whereas its identification and antimicrobial susceptibility pattern were performed using either Microscan or Vitek automated systems. Data was gathered and analyzed in Excel. The percentage of resistance was calculated as the number of resistant isolates from the total isolates multiplied by 100. Similarly, the percentage of sensitivity was calculated as the number of sensitive isolates from total isolates multiplied by 100.
RESULTS
. was detected in 59 cases during the study period. . was associated with urinary tract infections (39%), nasal infections (18.6%), other respiratory tract infections including sinusitis, bronchiectasis, and pneumonia (16.9%), and wound infections (15.3%). It was also associated with invasive infections such as bacteremia (3.4%) and abscesses (3.4%). . showed susceptibility to multiple antibiotic classes, but was resistant to ampicillin, piperacillin, nalidixic acid, and nitrofurantoin. . isolates from urinary tract infections had higher antibiotic resistance percentage than isolates from other infections, particularly to amoxicillin/clavulanic acid ( = 0.007, 95% confidence interval [CI]: 1.84-375), ciprofloxacin ( < 0.0001, 95% CI: 4.6-111.2), and trimethoprim/sulfamethoxazole ( < 0.001, 95% CI: 3.1-63.6).
CONCLUSION
Our data show that . is a pathogen with a spectrum of diseases wider than expected and a unique antibiotic susceptibility pattern in urinary tract infections.
PubMed: 38800796
DOI: 10.4103/jfcm.jfcm_280_23 -
Journal of Global Antimicrobial... May 2024The emergence of antimicrobial-resistant and mastitis-associated Enterococcus faecalis and Enterococcus faecium is of great concern due to the huge economic losses...
Draft genome sequences of clinical mastitis-associated Enterococcus faecalis and Enterococcus faecium carrying multiple antimicrobial resistance genes isolated from dairy cows.
OBJECTIVES
The emergence of antimicrobial-resistant and mastitis-associated Enterococcus faecalis and Enterococcus faecium is of great concern due to the huge economic losses associated with enterococcal infections. Here we report the draft genome sequences of Enterococcus faecalis and Enterococcus faecium strains which were isolated from raw milk samples obtained from mastitis-infected cows in Bangladesh.
METHODS
Strains were isolated, identified and Genomic DNA was sequenced using Illumina NextSeq 550 platform. The assembled contigs were analyzed for virulence, antimicrobial resistance genes, and multi-locus sequence type. The genomes were compared to previously reported Enterococcus faecalis and Enterococcus faecium genomes to generate core genome phylogenetic trees.
RESULTS
Enterococcus faecalis strain BR-MHR218Efa and Enterococcus faecium strain BR-MHR268Efe belonged to multilocus sequence type ST-190 and ST-22, respectively. Both sequence types seem to represent relatively rare sequence types. BR-MHR268Efe harbored only one antibiotic resistance gene encoding resistance towards macrolides (lsa(A)), while BR-MHR218Efa harbored ten different antibiotic resistance genes encoding resistance to aminoglycosides (ant[6]-Ia, aph(3')-III), sulphonamides (aac(6')-II), lincosamides (lnu(B)), macrolides (erm(B)), MLSB antibiotics (msr(C)), tetracyclines (tet(M), tet(L)), trimethoprim (dfrG) and pleuromutilin-lincosamide-streptogramin A (lsa(E)).The virulence gene composition was different in the two isolates. BR-MHR218Efa harbored only two virulence genes involved in adherence (acm, scm). BR-MHR268Efe harbored eight complete virulence operons including three operons involved in adherence (Ace, Ebp pili, EfaA), two operons involved in biofilm formation (BopD, Fsr) and three exoenzymes (gelatinase, hyaluronidase, SprE).
CONCLUSIONS
The genome sequences of strains BR-MHR268Efe and BR-MHR218Efa will serve as a reference point for molecular epidemiological studies of mastitis-associated Enterococcus faecalis and Enterococcus faecium. Additionally, the findings will help the understand the complex antimicrobial resistant livestock Enterococci.
PubMed: 38795772
DOI: 10.1016/j.jgar.2024.05.011 -
Microorganisms May 2024Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections...
Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections and reducing cerebral edema, respectively. Because the gut microbiota impacts the efficacy of cancer therapies, it is important to understand how these medications impact the gut microbiota of patients. Using mice that have been colonized with human microbiota, this study sought to examine how TMP-SMX and dexamethasone affect the gut microbiome. Two lines of humanized microbiota (HuM) Rag1 mice, HuM1Rag and HuM2Rag, were treated with either TMP-SMX or dexamethasone via oral gavage once a day for a week. Fecal samples were collected pre-treatment (pre-txt), one week after treatment initiation (1 wk post txt), and three weeks post-treatment (3 wk post txt), and bacterial DNA was analyzed using 16S rRNA-sequencing. The HuM1Rag mice treated with TMP-SMX had significant shifts in alpha diversity, beta diversity, and functional pathways at all time points, whereas in the HuM2Rag mice, it resulted in minimal changes in the microbiome. Likewise, dexamethasone treatment resulted in significant changes in the microbiome of the HuM1Rag mice, whereas the microbiome of the HuM2Rag mice was mostly unaffected. The results of our study show that routine medications used during glioblastoma treatment can perturb gut microbiota, with some microbiome compositions being more sensitive than others, and these treatments could potentially affect the overall efficacy of standard-of-care therapy.
PubMed: 38792844
DOI: 10.3390/microorganisms12051015 -
Microorganisms May 2024() poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions....
() poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions. This study investigated the prevalence, serotype distribution, virulence gene profiles, and antimicrobial resistance patterns of in ready-to-eat (RTE) food products from Romania. A total of 8151 samples were analyzed, including various processed dairy, bovine, poultry, pork, and fish products. Bacterial isolation was conducted using the classical standard method, followed by confirmation through biochemical and molecular testing. Among the isolated strains, serotypes 1/2a, 1/2b, and 1/2c were identified, with a prevalence of 75% for serotype 1/2a. Additionally, virulence genes specific to listeriolysin O (A) and regulatory factor A (A) were detected in all isolates. Antimicrobial susceptibility testing revealed varying resistance patterns among the strains. Trimethoprim-sulfamethoxazole and oxacillin showed the highest prevalence of resistance at 26.92% and 23.07%, respectively. However, all strains remained susceptible to ciprofloxacin, levofloxacin, and moxifloxacin. Notably, 23.07% of the isolates exhibited multidrug resistance, with the most common pattern being resistance to oxacillin, penicillin, and tetracycline. Analysis of antimicrobial resistance genes identified tetracycline resistance genes, particularly (C), (M), and (K), in a significant proportion of isolates. The presence of C and D genes was also notable, indicating potential mechanisms of resistance. These results emphasize the necessity for ongoing surveillance of in RTE foods and emphasize the importance of thorough monitoring of antimicrobial resistance to guide public health strategies within the European Union.
PubMed: 38792784
DOI: 10.3390/microorganisms12050954 -
Animals : An Open Access Journal From... May 2024This surveillance study aimed to estimate the proportion of antimicrobial resistant strains and antimicrobial resistance (AMR) profiles of isolates detected from the...
This surveillance study aimed to estimate the proportion of antimicrobial resistant strains and antimicrobial resistance (AMR) profiles of isolates detected from the intestinal contents of veal and dairy calves in the Veneto Region, Northeaster Italy. Additionally, we investigated the differences in AMR profiles between dairy and veal calves over the period 2017-2022. Overall 1150 isolates were tested from calves exhibiting enteric disease, with 868 from dairy and 282 from veal calves. The percentage of resistant isolates to nine antimicrobials was notably higher in veal calves compared to dairy calves, except for ampicillin. Throughout the study period, we observed a significant increase in the proportion of resistant isolates to florfenicol, gentamycin, paromomycin, tetracycline and trimethoprim/sulfamethoxazole in dairy calves, while we did not detect any significant increase in the proportion of resistant isolates among veal calves. A substantial proportion (75.9%) of the isolated exhibited multi-drug resistance (MDR). The proportion of multi-drug resistant isolates was significantly higher in veal calves (91.7%) compared to dairy calves (74.3%) all through the surveillance period (2017-2022), with no significant variation in MDR proportion among veal calves between 2017 and 2022 but a significant increase among dairy calves.
PubMed: 38791647
DOI: 10.3390/ani14101429 -
Biomedicines May 2024Human dihydrofolate reductase (DHFR) is an essential cellular enzyme, and inhibiting its activity is a promising strategy for cancer therapy. We have chosen the...
Human dihydrofolate reductase (DHFR) is an essential cellular enzyme, and inhibiting its activity is a promising strategy for cancer therapy. We have chosen the trimethoprim molecule () as a model compound in our search for a new class of DHFR inhibitors. We incorporated an amide bond, a structural element typical of netropsin, a ligand that binds selectively in the minor groove of DNA, into the molecules of analogs. In this work, we present previously obtained and evaluated eleven benzamides (-; , , ). Recently, these compounds were specifically projected as potential inhibitors of the enzymes acetylcholinesterase (AChE) and β-secretase (BACE1). was most active against AChE, with an inhibitory concentration of AChE IC = 0.056 µM, while the IC for donepezil was 0.046 µM. This compound was also the most active against the BACE1 enzyme. The IC value was 9.01 µM compared to that for quercetin, with IC = 4.89 µM. All the benzamides were active against DHFR, with IC values ranging from 4.72 to 20.17 µM, and showed activity greater than (55.26 µM). Quantitative results identified the derivatives and as the most promising. A molecular modeling study demonstrates that interacts strongly with the key residue Gly-117, while interacts strongly with Asn-64 and Arg-70. Furthermore, and demonstrate the ability to stabilize the DHFR enzyme, despite forming fewer hydrogen bonds with the protein compared to reference ligands. It can be concluded that this class of compounds certainly holds great promise for good active leads in medicinal chemistry.
PubMed: 38791041
DOI: 10.3390/biomedicines12051079