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Journal of Medical Microbiology Jun 2024Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have...
Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS). We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones. All admissions for HCT in a tertiary centre between January 2020 and December 2022 ( = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures. Allo-HCT was performed for 43.3 % (173/400) of patients and auto-HCT was performed for 56.7 % (227/400). A bacteraemia was documented in 28.3 % (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability ( for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.
PubMed: 38922673
DOI: 10.1099/jmm.0.001847 -
Expert Review of Anti-infective Therapy Jun 2024Non-typhoidal (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation... (Review)
Review
INTRODUCTION
Non-typhoidal (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation cephalosporins, and multi-drug resistance (MDR) in NTS human isolates from sub-Saharan Africa.
METHODS
A systematic review was conducted using a search in Ovid Medline, Embase, and African Index Medicus of publications between 2000 and 2021. A random-effects model meta-analysis was performed using data from 66 studies that included 29,039 NTS blood and 1,065 stool isolates.
RESULTS
The pooled prevalence proportions of MDR were 0.685 (95% CI 0.574-0.778) and 0.214 (0.020-0.785) in blood vs. stool isolates. The corresponding estimates of fluoroquinolones resistance were 0.014 (0.008-0.025) vs. 0.021 (0.012-0.036) and third-generation cephalosporins resistance 0.019 (0.012-0.031) vs. 0.035 (0.006-0.185). Similar results were found for children and adults. Resistance prevalence to these antibiotics in blood isolates increased between 2000-2010 and 2011-2021. The guidelines employed to determine antimicrobial resistance and epidemiological characteristics (e.g. sample size, study duration) correlated with the resistance prevalence.
CONCLUSIONS
The prevalence of MDR and resistance to fluoroquinolones and third-generation cephalosporins in NTS in sub-Saharan Africa is alarming.
EXPERT OPINION
Standardized surveillance of antimicrobial drug resistance in NTS in sub-Saharan Africa is warranted to guide healthcare policymaking and antibiotic stewardship programs.
PubMed: 38922636
DOI: 10.1080/14787210.2024.2368989 -
Drug Delivery and Translational Research Jun 2024The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug...
The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug (Cel-CSO) by conjugating chitosan oligosaccharides (CSO) to Cel for reversing Taxol resistance in chemotherapy, followed by self-assembly with Taxol into a novel nanoplatform of Cel-CSO/Taxol nanoparticles (termed NPs). NPs showed a suitable size (about 153 nm), excellent stability and prolonged release of Cel and Taxol in a manner that depended on both pH and time. NPs effectively inhibited the overexpression of multidrug resistance-related protein P-gp, hypoxia inducible factor-1α (HIF-1α), and triggered the MCF-7/Taxol cell apoptosis through inhibiting the PI3K/AKT/NF-κB/HIF-1α pathway. In tumor-bearing mice, NPs exhibited significant curative effects in inducing apoptosis of MCF-7/Taxol tumors which showed a low expression level of P-gp, microtubule-related proteins TUBB3 and Tau. The results indicated that NPs may be a promising strategy to overcome drug resistance caused by P-gp, which improve the antitumor effects in drug-resistant breast cancer.
PubMed: 38922561
DOI: 10.1007/s13346-024-01653-3 -
Revista Brasileira de Parasitologia... 2024Ticks are parasitic arthropods that cause significant economic losses to livestock production worldwide. Although Rhipicephalus (Boophilus) microplus, the cattle tick,... (Review)
Review
Ticks are parasitic arthropods that cause significant economic losses to livestock production worldwide. Although Rhipicephalus (Boophilus) microplus, the cattle tick, occurs throughout the Brazilian territory, there is no official program to control this tick, which is the vector of tick fever pathogens. We address the situation of R. (B.) microplus resistance to synthetic acaricides in Brazil, including cattle tick management; the status of tick resistance per Brazilian state; the history of resistance occurrence of different acaricides; multiple resistance occurrence; and the main strategies for integrated tick management. Tick control in Brazil is characterized by management errors. Local laboratories affiliated with federal and state research institutions and universities employ the Adult Immersion Test as a primary diagnostic method to assess acaricide resistance to topically applied drugs. Only three states (Acre, Amapá, and Amazonas) have no reports on resistant populations. Misinformation on tick control strategies, misuse of available products for tick control, no adoption of Integrated Parasite Management (IPM) practices, low technical support to producers, and the high-speed emergence of acaricide-resistant tick populations are the main problems. We also propose a list of needs and priorities for cattle tick control regarding communication, research, and policies.
Topics: Animals; Rhipicephalus; Brazil; Tick Control; Acaricides; Cattle; Tick Infestations; Cattle Diseases; Forecasting; Drug Resistance
PubMed: 38922203
DOI: 10.1590/S1984-29612024026 -
Toxins Jun 2024Extensively drug-resistant infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism's inherent properties of...
Extensively drug-resistant infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism's inherent properties of developing antibiotic resistance, we sought to investigate alternative strategies such as identifying "high value" antigens for immunotherapy-based purposes. Through extensive database mining, we discovered that numerous Gram-negative bacterial (GNB) genomes, many of which are known multidrug-resistant (MDR) pathogens, including , horizontally acquired the evolutionarily conserved gene encoding Zonula occludens toxin (Zot) with a substantial degree of homology. The toxin's genomic footprint among so many different GNB stresses its evolutionary importance. By employing in silico techniques such as proteomic-based phylogenetic tracing, in conjunction with comparative structural modeling, we discovered a highly conserved intermembrane associated stretch of 70 amino acids shared among all the GNB strains analyzed. The characterization of our newly identified antigen reveals it to be a "high value" vaccine candidate specific for . This newly identified antigen harbors multiple non-overlapping B- and T-cell epitopes exhibiting very high binding affinities and can adopt identical tertiary structures among the least genetically homologous strains. Taken together, using proteomic-driven reverse vaccinology techniques, we identified multiple "high value" vaccine candidates capable of eliciting a polarized immune response against all the genetic variants tested.
Topics: Pseudomonas aeruginosa; Phylogeny; Pseudomonas Infections; Humans; Epitopes, T-Lymphocyte; Pseudomonas Vaccines; Epitopes, B-Lymphocyte
PubMed: 38922165
DOI: 10.3390/toxins16060271 -
Pathogens (Basel, Switzerland) Jun 2024is a concerning pathogen, responsible for hospital-associated outbreaks. Multi drug resistant (MDR) strains are especially hard to treat. We conducted whole-genome...
Complete Genome Sequence of a Strain Carrying Novel Variant , Cross-Resistant to Ceftazidime/Avibactam and Cefiderocol, but Susceptible to Carbapenems, Isolated in Italy, 2023.
BACKGROUND
is a concerning pathogen, responsible for hospital-associated outbreaks. Multi drug resistant (MDR) strains are especially hard to treat. We conducted whole-genome sequencing on a MDR strain in order to identify genomic features potentially linked to its phenotype.
METHODS
DNA sequencing was performed on the Illumina iSeq 100 platform. Genome assembly was carried out with SPAdes. The genome was annotated with RASTtk. Typing was performed with MLST and Kaptive. Antibiotic resistance genes were detected with AMRFinderPlus and Abricate, and further verified with BLAST.
RESULTS
The strain exhibited resistance to ceftazidime/avibactam and cefiderocol, but remained susceptible to carbapenems. The strain belonged to sequence type ST101, serotype O1:K17. The analysis of antibiotic resistance genes indicated that the strain carried a novel KPC variant, designated as KPC-203, featuring a EL deletion at amino acid position 166-167, within the Ω-loop, and a nine-amino-acid insertion (LAVYTRAPM) at position 259. Sequence alterations were found in porin genes and . Unlike molecular testing, which was able to detect the KPC-203 variant, all phenotypic carbapenemase detection methods achieved negative results.
CONCLUSIONS
KPC-203, a novel KPC variant, showed a sequence modification in a cephalosporin resistance-associated hotspot. Interestingly, such alterations typically correlate with the restoration of carbapenem susceptibility. We hypothesize that KPC-203 likely led to resistance to ceftazidime/avibactam and cefiderocol, while maintaining susceptibility to carbapenems.
PubMed: 38921804
DOI: 10.3390/pathogens13060507 -
Marine Drugs Jun 2024Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of...
Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of deepsea-derived SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains CCARM 5172 and CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 μg/mL.
Topics: Streptomyces; Lipopeptides; Microbial Sensitivity Tests; Anti-Bacterial Agents; Enterococcus faecalis; Peptides, Cyclic; Enterococcus faecium; Drug Resistance, Multiple, Bacterial; Bacterial Proteins
PubMed: 38921573
DOI: 10.3390/md22060262 -
MBio Jun 2024This study examined the diversity and persistence of in the surface waters of agricultural regions of Brazil, Chile, and Mexico. Research groups (three in 2019-2020 and...
This study examined the diversity and persistence of in the surface waters of agricultural regions of Brazil, Chile, and Mexico. Research groups (three in 2019-2020 and five in 2021-2022) conducted a long-term survey of surface water across 5-8 months annually ( = 30 monthly). On-site, each team filtered 10-L water samples with modified Moore Swabs to capture which were then isolated and identified using conventional microbiological techniques. isolates were sequenced on Illumina platforms. was present in 1,493/3,291 water samples (45.8%), with varying isolation rates across countries and years. Newport, Infantis, and Typhimurium were the most frequent among the 128 different serovars. Notably, 22 serovars were found in all three countries, representing almost half of the 1,911 different isolates collected. The resistome comprised 72 antimicrobial resistance (AMR) genes and six point mutations in three genes. At least one AMR determinant was observed in 33.8% (646/1,911) of the isolates, of which 47.4% (306/646) were potentially multidrug resistant. Phylogeny based on core genome multilocus sequence typing (cgMLST) showed that most isolates clustered according to sequence type and country of origin. Only 14 cgMLST multi-country clusters were detected among the 275 clusters. However, further analysis confirmed that close genetic relatedness occurred mostly among isolates from the same country, with three exceptions. Interestingly, isolates closely related phylogenetically were recovered over multiple years within the same country, indicating the persistence of certain in those areas. In conclusion, surface waters in these regions are consistently contaminated with diverse , including strains that persist over time.IMPORTANCE is a leading foodborne pathogen responsible for millions of illnesses, hospitalizations, and deaths annually. Although -contaminated water has now been recognized as an important contamination source in the agrifood chain, there is a lack of knowledge on the global occurrence and diversity of in surface water. Moreover, there has been insufficient research on in surface waters from Latin American countries that are major producers and exporters of agricultural products. Incorporating genetic profiling of isolates from underrepresented regions, such as Latin America, enhances our understanding of the pathogen's ecology, evolution, antimicrobial resistance, and pathogenicity. Moreover, leveraging genomic data derived from pathogens isolated from diverse geographical areas is critical for assessing the potential public health risk posed by the pathogen and expediting investigations of foodborne outbreaks. Ultimately, global efforts contribute significantly to reducing the incidence of foodborne infections.
PubMed: 38920393
DOI: 10.1128/mbio.00777-24 -
AIMS Microbiology 2024Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB...
Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB control and treatment. Stratified data on MDR-TB, particularly in the high-burden western Kenya region, remain unknown. This data is important to monitor the efficacy of TB control and treatment efforts. Herein, we determined the molecular epidemiology of drug-resistant TB and associated risk factors in western Kenya. This was a non-experimental, population-based, cross-sectional study conducted between January and August 2018. Morning sputum samples of individuals suspected of pulmonary TB were collected, processed, and screened for (Mtb) and drug resistance using line probe assay (LPA) and growth indicator tubes (MGIT) culture. MGIT-positive samples were cultured on brain heart infusion (BHII) agar media, and the presence of Mtb was validated using Immunochromatographic assay (ICA). Drug sensitivity was performed on MGIT and ICA-positive but BHI-negative samples. Statistical significance was set at < 0.05. Of the 622 Mtb isolates, 536 (86.2%) were susceptible to RIF and INH. The rest, 86 (13.83%), were resistant to either drugs or both. A two-sample proportional equality test revealed that the MDR-TB prevalence in western Kenya (5%) did not vary significantly from the global MDR-TB estimate (3.9%) (P = 0.196). Men comprised the majority of susceptible and resistant TB (75.9% and 77.4%%, respectively). Also, compared with healthy individuals, the prevalence of HIV was significantly higher in MDR-TB patients (35.9% vs 5.6%). Finally, TB prevalence was highest in individuals aged 25-44 years, who accounted for 58.4% of the total TB cases. Evidently, the prevalence of MDRTB in western Kenya is high. Particular attention should be paid to men, young adults, and those with HIV, who bear the greatest burden of resistant TB. Overall, there is a need to refine TB control and treatment programs in the region to yield better outcomes.
PubMed: 38919722
DOI: 10.3934/microbiol.2024014 -
Journal of Anaesthesiology, Clinical... 2024Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high morbidity and mortality. This study was undertaken to monitor the trend of the...
Antimicrobial resistance pattern in aerobic bacteria isolated from endotracheal aspirate in ventilator-associated pneumonia: Ten years observation from a tertiary care hospital.
BACKGROUND AND AIMS
Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high morbidity and mortality. This study was undertaken to monitor the trend of the demographical details, comorbid conditions, bacterial etiological agents, and their antibiogram causing VAP in adults in the year 2008, 2013 and 2018.
MATERIAL AND METHODS
A retrospective study conducted at the Department of Microbiology, Hospital Infection control and Quality Control at a tertiary care teaching hospital. All the adult patients with more than 48 h of the mechanical ventilator with endotracheal intubation with Clinical Pulmonary infection Score >6 with suspicion of VAP were included in the study at a difference of 5 years, i.e., 2008, 2013, and 2018.
RESULTS
A total of 338 patients were included in the study, of which males accounted for more than two-third of the patients studied. Nearly 45% of the patients belonged to geriatric (>60 years) age group. The most common comorbid conditions were chronic obstructive pulmonary disease, hypertension and diabetes mellitus. Among the gram-negative isolates, , species, and were the most common. There is an emergence of resistance to most commonly administered antimicrobial agents like aminoglycosides, levofloxacin, piperacillin/tazobactum, and carbapenems during the study period.
CONCLUSION
This is a ten-year study on the antibiotic resistance pattern of organisms causing VAP. As far as the authors are aware, this is the first study addressing the pattern of change in drug resistance in the organisms causing VAP over a decade. The emergence of multi-drug resistant (MDR) MDR pathogens, especially in intensive care unit (ICU), is a great concern for the intensivist and infection control physicians. Preventive measures need to be undertaken to control the spread of these pathogens to the patients in the ICU.
PubMed: 38919443
DOI: 10.4103/joacp.joacp_410_22