High Frequency Of Resistance Research Articles

Antimicrobial susceptibilities of oral Neisseria from men on HIV pre-exposure prophylaxis in Hanoi, Vietnam

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG) is an urgent global health concern. Commensal Neisseria species in the oropharynx are an important reservoir of AMR genes that are transferred to NG, yet few data about AMR among commensal Neisseria in populations at risk for AMR exist. From May 2022 - December 2023, men in a HIV pre-exposure prophylaxis program in Hanoi, Vietnam, were recruited. Participants self-collected oral specimens using phosphate buffer solution (PBS), for culture on LB agar media containing sucrose, vancomycin and trimethoprim (LBVT.SNR). Oxidase-positive gram-negative diplococci were identified using Remel RapID NH system. Minimum inhibitory concentrations (MICs) to azithromycin, ceftriaxone, cefixime, and doxycycline were determined using Etests. There were 42 male participants, the median age was 26 years and 29% (n=12) reported using antibiotics in the past 6 months. In total, 48 Neisseria isolates were recovered; N. sicca/subflava was the most common species (50%; n=24), followed by N. mucosa (38%; n=18). For azithromycin, 85% (n=41) of isolates were resistant with MICs ≥1 ug/ml, including 25% (n=12) with high-level resistance (MICs ≥ 256 ug/mL of which 67% (8/12) were N. mucosa. Among non-gonococcal Neisseria isolates, the prevalence of resistance was 6% (n=3) for ceftriaxone, 6% (n=3) for cefixime, and 54% (n=26) for doxycycline; most non-susceptible isolates were N. mucosa. A High frequency of azithromycin resistance, moderate doxycycline resistance, and low cephalosporin resistance was found in oropharyngeal Neisseria isolates from MSM in a PrEP program in Hanoi, Vietnam. N. mucosa was over-represented among resistant isolates.

Antimicrobial resistance, virulence factors and phylogenetic profiles of Vibrio parahaemolyticus in the eastern coast of Shenzhen.

Vibrio parahaemolyticus (V. parahaemolyticus) is a major food-borne pathogen which causes human gastroenteritis. Since the characteristics of V. parahaemolyticus remain unknown, 220 isolates selected from clinical and environmental samples in Dapeng of Shenzhen were tested for the presence of two hemolysin-expressing genes tdh and trh. Among 27 clinical isolates, 26 carrired the tdh gene, and the other one carried both tdh and trh genes, however neither genes were detected in environmental isolates. Meanwhile, antimicrobial susceptibility profiles revealed the isolates with high frequency of resistance to ampicillin (77.73%) and colistin (71.82%) and medium to streptomycin (57.27%). Genetically, by whole genome sequencing (WGS), comparative genomics studies was performed on isolates from various districts and GenBank. Data analysis showed that antimicrobial resistance genes (ARGs) blaCARB, tet(34) and tet(35) were harbored in all genomes and other ARGs was absent in the genomes of 27 clinical isolates. Besides, little regional difference was observed. As for virulence factors, MAM7, T3SS1, T3SS1 secret effector, T3SS2, T3SS2 secret effector, and VpadF were carried by most isolates. Two isolates from other districts were tdh gene positive which clustered with clinical isolates from Dapeng in the same clade, indicating close genetic distance. This study revealed the widely distribution of V. parahaemolyticus in Shenzhen and the diverse ARGs and virulence genes it carried. Furthermore, pathways that pathogen disseminated through were discussed.

Plasminogen Activator Inhibitor-1 in the Pathophysiology of Late Life Depression.

Late life depression (LLD) is characterized by specific clinical features including a high frequency of vascular form and frequent antidepressant treatment resistance. The expression and functions of the serine protease inhibitor, Plasminogen Activator Inhibitor-1 (PAI-1) is known to be altered by aging, vascular damage, insulin levels associated with a sedentary lifestyle, chronic stress leading to hypercortisolemia, and inflammatory changes linked to stress responses. These phenomena would be implicated in LLD like vascular depression. This article thus aims to review the existing literature regarding the association between LLD and plasmatic levels of PAI-1, a marker of hypofibrinolysis. We hypothesize that increased age would be associated with changes in PAI-1 plasma level and function which influence LLD pathogenesis and its treatment. Although a large number of studies on PAI-1 changes in the elderly exist, studies about its implications in LLD are sparse. Despite heterogeneous findings regarding the direction of variation in plasmatic PAI-1 levels among elderly participants with LLD, all studies demonstrated an association between PAI-1 levels and current or remitted depressive symptoms. Moreover, disruptions in the concentrations of other biological markers influencing PAI-1 expression, such as cytokines or adipokines, were also observed, notably an increase in the levels of interleukins 6 and 8. LLD genesis appears to be influenced by PAI-1 regulatory loops which are implicated in senescence or cell death. The resistance to antidepressant treatment appears to be linked to distinct biological profiles involving inflammatory and fibrinolytic factors. Taken together these data suggest that PAI-1 pathway may be a promising target of treatment development efforts for LLD, and depression in general.

Diversity and antibiotic sensitivity of uropathogens from a regional hospital in Rwanda

Background: Urinary tract infections are a common cause for antibiotic consumption. Empirical treatment is common for community-acquired infections owing to predictability of pathogens. Objectives: Describe sensitivity profiles of uropathogens at a regional hospital in Rwanda. Methods: Hospital-based cross-sectional study in which clean-catch urine samples were analyzed. A two-stage process involving dipstick urinalysis and urine culture was used to identify true infections. The Kirby-Bauer disc diffusion method was used for antibiotic sensitivity analysis as per EUCAST guidelines. Results: Of 198 samples studied, 107 met criterion for UTI with 94 yielding significant growth. Klebsiella pneumoniae (35%), and Escherichia coli (32%) were the most common organisms isolated. Others included Staphylococcal species, Proteus spp, Enterobacter spp and Salmonella. Very high resistance frequencies (above 70%) were observed against amoxycillin, cotrimoxazole, trimethoprim, aztreonam and fosfomycin. Resistance to fluoroquinolones, aminoglycosides and cephalosporins varied between 40-60%. High levels of cross resistance were observed for drugs of the same class. Resistance to the potentiated penicillins, meropenem, cefoxitin and nitrofurantoin were less than 30%. Piperacillintazo bactum performed best with 91% sensitivity against all organisms tested. Conclusion: High levels of resistance were observed for most antibiotics studied. For empirical treatment of community-acquired UTI in our setting, nitrofurantoin remains effective while ciprofloxacin is not. Keywords: Diversity and antibiotic sensitivity; uropathogens; Rwanda.

The influence of efflux pump, outer membrane permeability and β-lactamase production on the resistance profile of multi, extensively and pandrug resistant Klebsiella pneumoniae

BackgroundAn important chance of nosocomial acquired infections are caused by the opportunistic bacterium Klebsiella pneumoniae. Urine, wound, sputum, and blood samples were collected from all patients. This study aimed to detect the antibiotic resistance profile, the frequency of MDR, XDR, PDR, and detection of efflux pump and outer membrane permeability genes in K. pneumoniae isolates. MethodsOne hundred twenty samples were collected from patients who were admitted to the Ramadi Teaching Hospitals in Al-Anbar Governorate. Fifty five of K. pneumoniae strains were collected from patients. The VITEK®2 Compact B System was used to detect the antibiotic resistance pattern of studied bacteria. The isolates were classified as MDR, XDR, or PDR based on established guidelines. The data were analyzed using Clinical and Laboratory Standards Institute (CLSI) breakpoints. PCR was used to detect the efflux pumps and porins genes. ResultsOut of the 120 samples studied, 45.83 % (55) tested positive for K. pneumoniae. The isolates displayed the greatest amount of resistance to cefazolin, ceftriaxone (98.2 %), ampicillin (100 %), and ceftazidime, cefepime (90.9 %). 20 % of the isolates were found to produce metallo-lactamases, and 41.81 % tested positive for extended-spectrum beta-lactamases. Overall, the rates of multi-drug resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) isolates were 57.2 %, 10.9 %, and 9.09 %, respectively. Additionally, the prevalence of efflux pump genes acrAB, mdtK, and tolC were 94.54 %, 14.54 %, and 89.09 %, respectively, while the porin-encoding genes ompK35 and ompK36 were found in 96.36 % and 98.18 % of the isolates. ConclusionThis investigation concluded that the study isolates had a high degree of antibiotic resistance heterogenicity. High frequencies of resistance to ampicillin, cefazolin, and ceftriaxone are present in study isolates. Most strains were categorized as MDR strains, with six being XDR strains and five being PDR strains. One of the main routes of antibiotic resistance in multidrug-resistant K. pneumoniae strains is through the acrAB efflux system. The high prevalence of the acrAB, tolC, ompk35, and ompK36 genes were increases the ability of these isolates combat antimicrobial treatments.

Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

Extended-spectrum β-lactamase-producing bacteria and their resistance determinants in different wastewaters and rivers in Nepal

Wastewaters serve as significant reservoirs of antibiotic resistant bacteria. Despite the evidence of antimicrobial resistance in wastewaters and river water in Kathmandu, direct linkage between them is not discussed yet. This study investigated the prevalence of extended-spectrum β-lactamase (ESBL)-producing bacteria and associated resistance genes in wastewaters and river water. Out of 246 bacteria from wastewaters, 57.72% were ESBL producers and 77.64% of them were multidrug resistant (MDR). ESBL producing E. coli was dominant in municipal and hospital wastewaters (HWW) as well as in river water while K. pneumoniae was common in pharmaceutical wastewater. The blaSHV and blaTEM genes were prevalent and commonly co-occurred with aac(6')-Ib-cr in K. pneumoniae isolated pharmaceutical wastewater. blaCTX-M carrying E. coli from hospital co-harbored aac(6')-Ib-cr while that from municipal influent and river water co-harbored qnrS. Whole genome sequencing data revealed the presence of diverse ARGs in bacterial isolates against multiple antibiotics. In average, an E. coli and a K. pneumoniae isolate contained 55.75 ± 0.96 and 40.2 ± 5.36 ARGs, respectively. Multi-locus sequence typing showed the presence of globally high-risk clones with wider host range such as E. coli ST10, and K. pneumoniae ST15 and ST307 in HWW and river indicating frequent dissemination of antimicrobial resistance in wastewater of Kathmandu. Whole genome sequence data aligned with phenotypic antibiograms and resistance genes detected by PCR in selected isolates. The presence of significant plasmid replicons (IncF, IncY) and mobile genetic elements (IS903, IS26) indicate high frequency of spreading antibiotic resistance. These findings indicate burden and dissemination of antimicrobial resistance in the environment and highlight the need for effective strategies to mitigate the antibiotic resistance.

Bullet-related bacterial wound infections among injured personnel at emergency site hospitals in Bahir Dar: prevalence, antimicrobial susceptibility and associated factors.

Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause severe wound infections, persistent systemic infections and may lead to amputation and mortality. The magnitude, antimicrobial susceptibility profiles, and factors associated with bacterial wound infections among patients with bullet-related injuries are not yet studied particularly at health facilities in Bahir Dar, Northwest Ethiopia. Therefore, this study was aimed to determine the prevalence, bacterial profiles, antimicrobial susceptibility profiles, and factors associated with bacterial infections among patients with bullet-related injuries at referral health facilities in Bahir Dar, Northwest Ethiopia. A Hospital-based cross-sectional study was conducted among patients with bullet-related injuries at three referral health facilities in Bahir Dar from May 25 to July 27, 2022. A total of 384 patients with bullet-related injuries were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Wound swabs were collected aseptically and cultured on Blood and MacConkey agar following bacteriological standards. Biochemical tests were performed to differentiate bacteria for positive cultivation and antimicrobial susceptibility profiles of the isolates were done on Muller Hinton agar using the Kirby-Bauer disk diffusion technique according to the 2021 Clinical Laboratory Standard Institute (CLSI) guideline. The data were entered using Epi-Info version 7.3 and analyzed using SPSS version 25. Descriptive data were presented using frequency, percentages, figures, and charts. Logistic regression was carried out to identify factors associated with bacterial wound infections. P-value < 0.05 was considered statistically significant. The prevalence of bullet-related bacterial wound infection among three referral hospitals in Bahir Dar city was 54.7%. The most commonly isolated Gram-negative organism was Klebsiella spps 49 (23.3%) while among Gram-positive organism, Staphylococcus aureus 58 (27.6%) and coagulase-negative staphylococci (CONS) 18 (8.6%). Contamination, hospitalization and smoking habit were significantly associated with the presence of bullet-related bacterial wound infections. Over 97% multidrug resistant (MDR) bacterial isolates were identified and of theses, E. coli, Proteus species, Citrobactor, and Staphylococcus aureus were highly drug resistant. Increased prevalence of bullet-related bacterial wound infection was noticed in this study. S. aureus followed by Klebsiella species were most commonly isolated bacteria. High frequency of resistance to Ampicillin, Oxacillin, Cefepime, Ceftriaxone, Ceftazidime, Vancomycin, and Norfloxacin was observed. Therefore, proper handling of bullet injuries, prompt investigation of bacterial infections, monitoring of drug sensitivity patterns and antibiotic usage are critical.

Investigating Dirofilaria immitis isolates infecting domestic canines and their susceptibility/resistance patterns to macrocyclic lactones in the northern region of the Mississippi Delta area (southeast Missouri)

Previous reports of macrocyclic lactone (ML) resistance in Dirofilaria immitis, the parasitic nematode which causes heartworm disease, have mainly been from the southern Mississippi Delta region. Southeast Missouri (SEMO), forming the northern boundary of this region, has not previously been well studied. The area is an ideal propagation region for heartworm infection and possibly for the spread of ML resistance. To assess whether D. immitis isolates infecting domestic canines in SEMO exhibit evidence of resistance to MLs, domestic canines, presented to veterinary facilities testing positive for heartworms through antigen and microfilariae (MF) examination, were utilized in the study. Using a descriptive epidemiological cross-sectional study, from March 2021 through February 2022, blood sample collection from 96 canines living in SEMO testing positive for heartworms were analyzed. MiSeq technology was utilized to sequence specific genetic markers associated with susceptibility/resistance for MLs in D. immitis isolates. Genomic data revealed most D. immitis isolates had genotypic profiles consistent with resistance to MLs. Of the 96 samples tested, 91 (94.8%) had a resistant genotype, 4 (4.2%) had a mixed genotype, and 1 sample (1%) genotyped as susceptible. While detailed and reliable medical histories were not available for most canines, detailed medical history from 2 canines indicated evidence of phenotypic resistance that was consistent with their genotypes. However, in vivo preventive tests are needed to confirm a high frequency of phenotypic ML resistance in D. immitis from this region. Increasing resistance patterns to MLs indicate the approach to heartworm prevention/treatment protocol should be reconsidered. New measures may be required to stop heartworm disease.

Carbapenemases Produced by Multidrug-Resistant Strains of &lt;i&gt;Klebsiella Pneumoniae&lt;/i&gt; Isolated from Intensive Care Patients

Relevance Klebsiella pneumoniae is one of the main pathogens of nosocomial infections. Hospital strains of this pathogen are characterized by a high frequency of resistance to many antibiotics, including carbapenems. The main mechanism for the formation of resistance to carbapenems is the production of carbapenemases by bacteria. To date, K. pneumoniae is considered one of the main “distributors” of clinically important antibiotic resistance genes.Aim of the study To study the frequency of occurrence of the most common carbapenemase genes in multiresistant K.pneumoniae strains isolated from patients of intensive care units in an emergency hospital.Material and methods 4708 samples of various types of clinical material from patients of 5 intensive care units of the N.V. Sklifosovsky Research Institute for Emergency Medicine were analyzed. Microbiological studies were carried out using standard generally accepted methods. For the purposes of this study, unique sequential K.pneumoniae strains resistant to imipenem and/or meropenem were selected. DNA isolation was carried out using the RIBO-prep kit (Russia). Carbapenemase genes were detected by real-time PCR using the kits of reagents “AmpliSens MDR-MBL-FL” and “AmpliSens MDR-KPC/OXA-48-FL” on a “Rotor Gene” device (Corbett Research, Australia).Results Etiologically significant microorganisms were detected in 64.7% of the studied samples. K. pneumoniae was isolated in a quarter of the samples. 194 unique carbapenem-resistant strains of K.pneumoniae were selected. Of these, 11.3% of the genes of the studied carbapenemases were not detected. In 38.1% of strains, 1 carbapenemase was detected, in 29.9% — two and in 20.6% — three or more. Among the strains with one carbapenemase gene, OXA-48 (19.1%) and CATTLE (13.4%) producers prevailed. Strains producing only NDM betalactamase were found in 5.7% of cases. Isolated allocation of VIM and IMP was not detected. In 34%, metallobectalamases were isolated in combination with serine carbapenemases. The production of serine carbapenemases alone was detected in 48.5% of the strains. Depending on the specialization of the intensive care unit, there are differences in the frequency of detection of serine and metallobetalactamases in strains of carbapenem-resistant Klebsiella.Conclusion K. pneumoniae is the causative agent of nosocomial infections in 25% of cases. In 11.3% of carbapenem-resistant strains, the production of KPC, OXA-48, NDM, VIM and IMP genes was not detected. When developing algorithms for antibacterial therapy, it is necessary to take into account that from 25.7% to 60.6% of K. pneumoniae strains in different intensive care units are the producers of metallobetalactamases.

Design, synthesis, anti-infective potency and mechanism study of novel Ru-based complexes containing substituted adamantane as antibacterial agents

Infections caused by Staphylococcus aureus (S. aureus) are increasing difficult to treat because this pathogen is easily resistant to antibiotics. However, the development of novel antibacterial agents with high antimicrobial activity and low frequency of resistance remains a huge challenge. Here, building on the coupling strategy, an adamantane moiety was linked to the membrane-active Ru-based structure and then developed three novel metalloantibiotics: [Ru(bpy)2(L)](PF6)2 (Ru1) (bpy = 2,2-bipyridine, L = amantadine modified ligand), [Ru(dmb)2(L)](PF6)2 (Ru2) (dmb = 4,4′-dimethyl-2,2′-bipyridine) and [Ru(dpa)2(L)](PF6)2 (Ru3), (dpa = 2,2′-dipyridylamine). Notably, complex Ru1 was identified to be the best candidate agent, showing greater efficacy against S. aureus than most of clinical antibiotics and low resistance frequencies. Mechanism studies demonstrated that Ru1 could not only increase the permeability of bacterial cell membrane and then caused the leakage of bacterial contents, but also promoted the production of reactive oxygen species (ROS) in bacteria. Importantly, complex Ru1 inhibited the biofilm formation, exotoxin secretion and increased the potency of some clinical used antibiotics. In addition, Ru1 showed low toxic in vivo and excellent anti-infective efficacy in two animal infection model. Thus, Ru-based metalloantibiotic bearing adamantane moiety are promising antibacterial agents, providing a certain research basis for the future antibiotics research.

Investigating Phenotypic and Genotypic Resistance to Pyrazinamide Antibiotic in Multidrug-resistant (MDR) Mycobacterium Tuberculosis Isolates in Khuzestan Province from 2017 to 2022

Background and Objectives Pyrazinamide is one of the effective drugs for treating tuberculosis. Inclusion of this drug in the treatment regimen shortens the duration of tuberculosis treatment. The mutation in pncA gene causes loss of pyrazinamidase activity, the most important resistance mechanism in Mycobacterium tuberculosis isolates. Therefore, the purpose of this study is to investigate the phenotypic and genotypic resistance to pyrazinamide antibiotic in multidrug-resistant (MDR) Mycobacterium tuberculosis isolates in Khuzestan province between 2017 and 2022. Subjects and Methods This study was conducted on 40 isolates of Mycobacterium tuberculosis in Ahvaz TB Regional Laboratory. Drug sensitivity of the isolates was determined by the relative method in the antibiotic pyrazinamide in the isolates. Then, the frequency of pncA gene mutations related to pyrazinamide resistance in MDR isolates was determined using sequencing. Results According to the results of the drug sensitivity to rifampin and isoniazid antibiotics, there were 25 isolates, of which 16 strains were resistant to two drugs, namely isoniazid and rifampin (MDR-TB), and 9 were single-drug resistant isolates (8 isolates resistant to rifampin and 1 isolate resistant to Isoniazid). Of the 17 samples that had the pncA gene and were resistant to pyrazinamide, 13 had mutations in the pncA gene while 4 did not have any mutations. The most common mutation was a non-synonymous mutation in which the amino acid Val had changed to Phe. Conclusion According to the results of this study, there is a high frequency of resistance to pyrazinamide in MDR strains. Also, there is a high percentage of single-resistance mutations in the pncA gene, while there is lower prevalence of mutations in the panD and rpsA genes, which provide quick and accurate information about the sensitivity to pyrazinamide for MDR-TB and mono-resistant isolates. Therefore, the best method for detecting resistance to pyrazinamide is sequencing and whole pncA DNA sequence to confirm pyrazinamide resistance instead of the usual methods covering mutated hotspots.

Phylogenomic and phenotypic analyses highlight the diversity of antibiotic resistance and virulence in both human and non-human Acinetobacter baumannii.

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen that causes infections in the immunocompromised. With a high incidence of muti-drug resistance, carbapenem-resistant A. baumannii is designated as a priority 1 pathogen by the WHO. The current literature has expertly characterized clinical isolates of A. baumannii. As the challenge of these infections has recently been classified as a One Health issue, we set out to explore the diversity of isolates from human and non-clinical sources, such as agricultural surface water, urban streams, various effluents from wastewater treatment plants, and food (tank milk); and, importantly, these isolates came from a wide geographic distribution. Phylogenomic analysis considering almost 200 isolates showed that our diverse set is well-differentiated from the main international clones of A. baumannii. We discovered novel sequence types in both hospital and non-clinical settings and five strains that overexpress the resistance-nodulation-division efflux pump adeIJK without changes in susceptibility reflected by this overexpression. Furthermore, we detected a bla ADC-79 in a non-human isolate despite its sensitivity to all antibiotics. There was no significant differentiation between the virulence profiles of clinical and non-clinical isolates in the Galleria mellonella insect model of virulence, suggesting that virulence is neither dependent on geographic origin nor isolation source. The detection of antibiotic resistance and virulence genes in non-human strains suggests that these isolates may act as a genetic reservoir for clinical strains. This endorses the notion that in order to combat multi-drug-resistant infection caused by A. baumannii, a One Health approach is required, and a deeper understanding of non-clinical strains must be achieved.IMPORTANCEThe global crisis of antibiotic resistance is a silent one. More and more bacteria are becoming resistant to all antibiotics available for treatment, leaving no options remaining. This includes Acinetobacter baumannii. This Gram-negative, opportunistic pathogen shows a high frequency of multi-drug resistance, and many strains are resistant to the last-resort drugs carbapenem and colistin. Research has focused on strains of clinical origin, but there is a knowledge gap regarding virulence traits, particularly how A. baumannii became the notorious pathogen of today. Antibiotic resistance and virulence genes have been detected in strains from animals and environmental locations such as grass and soil. As such, A. baumannii is a One Health concern, which includes the health of humans, animals, and the environment. Thus, in order to truly combat the antibiotic resistance crisis, we need to understand the antibiotic resistance and virulence gene reservoirs of this pathogen under the One Health continuum.

Exceptions to the rule: When does resistance evolution not undermine antibiotic therapy in human bacterial infections?

The use of antibiotics to treat bacterial infections often imposes strong selection for antibiotic resistance. However, the prevalence of antibiotic resistance varies greatly across different combinations of pathogens and drugs. What underlies this variation? Systematic reviews, meta-analyses, and literature surveys capable of integrating data across many studies have tried to answer this question, but the vast majority of these studies have focused only on cases where resistance is common or problematic. Yet much could presumably be learned from the cases where resistance is infrequent or absent. Here we conducted a literature survey and a systematic review to study the evolution of antibiotic resistance across a wide range of pathogen-by-drug combinations (57 pathogens and 53 antibiotics from 15 drug classes). Using Akaike information criterion-based model selection and model-averaged parameter estimation we explored 14 different factors posited to be associated with resistance evolution. We find that the most robust predictors of high resistance are nosocomial transmission (i.e., hospital-acquired pathogens) and indirect transmission (e.g., vector-, water-, air-, or vehicle-borne pathogens). While the former was to be expected based on prior studies, the positive correlation between high resistance frequencies and indirect transmission is, to our knowledge, a novel insight. The most robust predictor of low resistance is zoonosis from wild animal reservoirs. We also found partial support that resistance was associated with pathogen type, horizontal gene transfer, commensalism, and human-to-human transmission. We did not find support for correlations between resistance and environmental reservoirs, mechanisms of drug action, and global drug use. This work explores the relative explanatory power of various pathogen and drug factors on resistance evolution, which is necessary to identify priority targets of stewardship efforts to slow the spread of drug-resistant pathogens.

Antimicrobial Resistance and Molecular Characterization of Salmonella Rissen Isolated in China During 2008-2019.

This study aimed to provide epidemiological features of Salmonella enterica serovar Rissen, determine antimicrobial susceptibility, virulence gene profiles, and describe the potential association of S. Rissen from different sources in China. During 2008-2019, a total of non-repetitive 228 S. Rissen isolates were collected from human, animals and environment in China. The antimicrobial susceptibility test, screening of antimicrobial and virulence genes by PCR, and pulsed-field gel electrophoresis (PFGE) were performed. Among the 154 isolates from human, the majority of the cases (80.5%) occurred in summer, and S. Rissen was mainly detected in people aged 21-40 (37.7%) and 41-60 (28.6%) years old, and 74 non-human source S. Rissen strains were identified, with pork being the most common source. About 93.4% isolates were resistant to at least one of the 12 tested antimicrobial agents, and high frequencies of resistance were observed for tetracyclines (91.2%), trimethoprim-sulfamethoxazole (74.1%) and ampicillin (67.5%). A total of 171 (75%) isolates were resistant to at least three categories of antimicrobials, and the most common resistance profile was Tetracycline(s)-β-Lactams-Sulfonamides. The resistance rates to chloramphenicol, quinolones and sulfafurazole were significantly higher in strains isolated from human compared to non-human source strains. Among these isolates, the β-Lactams resistance was mainly associated with gene blaTEM (54.7%), sulfonamide resistance with sul2 (45.7%) and sul3 (54.3%), tetracycline resistance with tetA (81.3%). All the isolates harbored virulence genes hilA, sopB, sciN, stn and ssrB, and most of them harbored ssaQ (98.7%), mgtC (98.7%) and invA (98.2%). The majority (91.7%) of S. Rissen isolates showed high similarity (>80%) with each other in PFGE patterns and came from human, animals and environment. The high frequencies of multidrug resistance and probable clonal dissemination in this serovar call for the necessity of systematic surveillance on S. Rissen in China.

Antibiotic Resistance in Seawater Samples from East Coast of Spain

Seawater has been proposed as a reservoir for antibiotic-resistant bacteria and antibiotic resistance genes, thus representing a risk to public health. In this study, we evaluated the presence of antibiotic resistance determinants (bacteria and genes) in 77 seawater samples collected at different points along the coast of the Gulf of Valencia (Spain). Specifically, indicators of fecal contamination bacteria, Escherichia coli and Enterococcus sp., were isolated, and their antibiotic resistance profiles were analyzed through the use of the Sensititre® system, followed by the detection of the main antibiotic resistance genes (blaTEM, qnrS, tetW, sulI, and ermB). The highest frequencies of resistance in the E. coli isolates were detected for ampicillin (35.1%) and ciprofloxacin (17.5%), followed by sulfamethoxazole and trimethoprim (15.7%), while 23% of enterococci isolates showed resistance to a single antibiotic, 20% against tetracycline and 3% against daptomycin. Through PCR analysis, 93% of the E. coli strains showed the blaTEM and sulI resistance genes. Among the enterococci, the presence of the blaTEM gene was detected in 40% of the isolates, while the rest of the genes were present at very low rates. Among the water samples, 57% were positive for at least one of the tested genes, italic format with blaTEM being the most commonly found gene (47%), followed by the qnrS (33%) and sulI (23%) genes. These results show that seawater, in addition to being subjected to a high rate of fecal contamination, can contribute to the spread of antibiotic resistance.

The Role of miR-29a and miR-143 on the Anti-apoptotic MCL-1/cIAP-2 Genes Expression in EGFR Mutated Non-small Cell Lung Carcinoma Patients.

The survival rate of lung cancer is low due to the high frequency of drug resistance in patients with mutations in the driver genes. Overexpression of anti-apoptotic genes is one of the most prominent features of tumor drug resistance. EGFR signaling induces the expression of anti-apoptotic genes. Also, microRNAs (miRNAs) have a critical role in regulating biological functions such as apoptosis; a process mostly eluded in cancer progression. The mutation screening was performed on one thousand non-small cell lung carcinoma patients to enroll clinical samples in this study. Bioinformatics analysis predicted that miRNAs (miR-29a, miR-143) might regulate MCL-1 and cIAP-2 expression. We investigated the expression of MCL-1, cIAP-2, miR-29a, and miR-143 encoding genes in adenocarcinoma patients with or without EGFR mutations before treatment. The potential role of miR-29a and miR-143 on gene expression was evaluated by overexpression and luciferase assays in HEK-293T cells. EGFR mutations were found in 262 patients (26.2%) with a greater incidence in females (36.23% vs. 20.37%, P = 0.001). The expression levels of MCL-1 and cIAP-2 genes in patients with mutated EGFR were higher than those of wild-type EGFR. In contrast, compared to those of patients with wild-type EGFR, the expression levels of miR-29a and miR-143 were lower in the patients carrying EGFR mutations. In cell culture, overexpression of miR-29a and miR-143 significantly downregulated the expression of MCL-1 and cIAP-2. Dual-luciferase reporter experiments confirmed that miR-29a and miR-143 target MCL-1 and cIAP-2 mRNAs, respectively. Our results suggest that upregulation of EGFR signaling in lung cancer cells may increase anti-apoptotic MCL-1 and cIAP-2 gene expression, possibly through downregulation of miR-29a-3p and miR-143-3p.

Widespread Resistance to Temephos in Aedes aegypti (Diptera: Culicidae) from Mexico.

Organic synthetic insecticides continue to be part of the arsenal for combating vector-borne diseases in Mexico. Larvicides are a fundamental part of the process in programs for mosquito control, temephos being one of the most widely used in Mexico. In the present study, we analyzed the frequency of temephos resistance in twenty-three Aedes aegypti populations using the discriminating concentration (DC) of 0.012 mg/L. We also tested 5× DC (0.6 mg/L) and 10× DC (0.12 mg/L) of temephos. The resistance distribution to temephos was interpolated to unsampled sites using the inverse distance weighting (IDW) method. The populations of Ae. aegypti showed a high frequency of resistance (1× DC) with mortality rates below 93% in 22 of the 23 populations analyzed. Moderate resistance intensity (5× DC) was found in 78% of the populations, and high intensity (10× DC) in 30%. Predicted mortality was below 60% in the populations of the Pacific Coast, along the Gulf of Mexico, and in the state of Coahuila in Northeastern Mexico in relation to 1× DC; the Pacific Coast and Northeast patterns hold for 5× and 10× DC. The results suggest the need for rotation of the larvicide to effectively control the larval populations of the vector in the country.

Epidemiology and Antibiotic Resistance of Enterobacteriaceae Isolated in Urinary Tract Infections at Oued Eddahab Military Hospital Agadir

Objective: Determine the current bacteriological profile of urinary tract infections and the antibiotic resistance of the main enterobacteria isolated in urine. Methods: Retrospective study over a period of 18 months from January 1, 2022 to June 30,2023 including all urinary cytobacteriological examinations of patients hospitalized in the various departments of the Oued Eddahab Military Hospital in Agadir, as well as outpatients. Results: Out of 4483 urine samples, 487 met the criteria for UTI (10.86% of total samples). The microorganisms were predominantly Enterobacteriaceae (421/487 86.44%). Of the infections, 75% originated from outpatients. The sex Ratio F/M was 1.35. E.Coli dominated the epidemiological profile for both inpatients and outpatients (63% vs. 77%). There was a high frequency of resistance to the main families of antibiotics, while quinolones, fosfomycin, nitrofurans, and aminoglycosides retained good activity. Resistance to third-generation cephalosporins through the production of extended-spectrum betalactamase was present in 09% of Enterobacteria. Finally, no resistance to imipenem and colistin was detected.

Resistance to Seven Site-Specific Fungicides in Botrytis cinerea from Greenhouse-Grown Ornamentals.

The fungal pathogen Botrytis cinerea is a notorious problem on many floriculture greenhouse hosts including petunia, geranium, and poinsettia; these key crops contribute to the $6.43 billion U.S. ornamental industry. While growers use cultural strategies to reduce relative humidity and free moisture to limit Botrytis blight, fungicides remain a primary component of control programs. Isolates (n = 386) of B. cinerea sampled from symptomatic petunia, geranium, and poinsettia in Michigan greenhouses from 2018 to 2021 were screened for resistance to eight fungicides belonging to seven Fungicide Resistance Action Committee (FRAC) groups. Single-spored isolates were subjected to a germination-based assay using previously defined discriminatory doses of each fungicide. Resistance was detected to thiophanate-methyl (FRAC 1; 94%), pyraclostrobin (FRAC 11; 80%), boscalid (FRAC 7; 67%), iprodione (FRAC 2; 65%), fenhexamid (FRAC 17; 38%), cyprodinil (FRAC 9; 38%), fludioxonil (FRAC 12; 21%), and fluopyram (FRAC 7; 13%). Most isolates (63.5%) were resistant to at least four FRAC groups, with 8.7% of all isolates demonstrating resistance to all seven FRAC groups tested. Resistance frequencies for each fungicide were similar among crops, production regions, and growing cycles but varied significantly for each greenhouse. Phenotypic diversity was high, as indicated by the 48 different fungicide resistance profiles observed. High frequencies of resistance to multiple fungicides in B. cinerea populations from floriculture hosts highlight the importance of sustainable and alternative disease management practices for greenhouse growers.