Minimum Inhibitory Concentration Levels Research Articles

Unveiling environmental transmission risks: comparative analysis of azole resistance in Aspergillus fumigatus clinical and environmental isolates from Yunnan, China.

Azole resistance in Aspergillus fumigatus poses a significant clinical challenge globally. Our previous epidemiological analysis revealed a remarkably high frequency (~80%) of azole-resistant A. fumigatus in Yunnan's greenhouse environments, prompting increased local and regional research for targeted control strategies. In this study, we analyzed 94 clinical A. fumigatus isolates from Yunnan, comparing their susceptibility profiles and genotypic characteristics with environmental strains previously isolated. While the overall frequency of azole resistance in clinical isolates was lower than that in environmental samples, a significant prevalence of cross-resistance, with varying resistance patterns based on minimum inhibitory concentration (MIC) levels was observed, which exceeded rates in other regions of China. Specific mutation combinations in the cyp51A gene were linked to elevated MIC values in clinical and/or environmental samples, while some resistant strains with wild-type cyp51A remain unexplained, indicating a need for further investigation into their resistance mechanisms. The differences in unique genetic elements and the distinct genetic differentiation observed between clinical and environmental isolates can be attributed to Yunnan's unique geomorphology and potential genotype importation from other provinces and abroad. Extensive allele exchanges and sharing contributed to the selection of azole-resistant clinical isolates, suggesting a common environmental origin, and the transmission routes of local drug-resistant strains cannot be excluded. These findings emphasize the imperative for regional and targeted surveillance to monitor resistance trends and guide effective antifungal therapy, and management strategies to mitigate invasive aspergillosis risk in this region.IMPORTANCEAzole resistance in Aspergillus fumigatus is a major global health concern, with particularly high rates (~80%) observed in Yunnan's greenhouse environments. This study compares azole resistance in 94 clinical isolates from Yunnan with environmental strains, revealing lower clinical resistance but significant cross-resistance and distinct resistance patterns. Specific mutations in the cyp51A gene were associated with elevated minimum inhibitory concentration values, though some resistant strains had wild-type cyp51A, highlighting the need for further research. The unique genetic profiles and potential external genotype influences in Yunnan emphasize the need for targeted regional surveillance. Effective monitoring and control strategies are essential to manage and mitigate the risk of invasive aspergillosis.

Resistance Genes and Mortality in Carbapenem-resistant Klebsiella pneumoniae Bacteremias: Effects of the COVID-19 Pandemic

Emerging carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) (CRKP) bacteremias are presenting significant public health risks due to limited treatment options and increased mortality. K. pneumoniae isolates exhibit carbapenem resistance rates that vary from 25% to 50% throughout the European continent, including our country. To assess the characteristics of CRKP bacteremia, a condition that has recently demonstrated an increasing prevalence in our center. We sought to ascertain the resistance rates of isolated strains to antibiotics other than carbapenems, identify the responsible carbapenemase genes, evaluate the efficacy of antibiotics, determine mortality rates, explore clonality among strains, and investigate the influence of the COVID-19 pandemic on all these factors. Retrospective observational study. This study included patients aged 18 and older who had experienced meropenem-resistant K. pneumoniae bacteremia. Meropenem resistance was confirmed by employing the Kirby-Bauer disk diffusion method. Meropenem minimum inhibitory concentration (MIC) levels were determined using the gradient test, while colistin MIC levels were ascertained using the disk elution technique. Carbapenemase genes were evaluated via colony polymerase chain reaction (PCR), and clonality analysis was performed using the arbitrarily primed PCR technique. The study comprised 230 patients, with a mean age of 63.1 ± 15.9 years, of whom 58.7% were male. Oxacillinase-48 (OXA-48) was detected in 74.8% of the patients, New Delhi metallo-beta-lactamase (NDM) in 12.6%, OXA-48 + NDM in 7.8%, and KPC in 4.8%. The 14-day and 30-day mortality rates were 57% and 69.6%, respectively. Multivariate analysis of the 30-day mortality revealed several crucial factors, including bacteremia development in the intensive care unit, the occurrence of bacteremia during the COVID-19 pandemic, polymicrobial bacteremia, the use of indwelling intravenous catheters, a platelet count of ≤ 140,000/μl, procalcitonin levels of ≥ 6 μg/l, and a Charlson comorbidity score ≥ 3. Notably, the OXA-48 and KPC genes were upregulated significantly during the COVID-19 pandemic, while the NDM gene groups were downregulated. Additionally, both 14-day and 30-day mortality rates increased significantly. In this study, the most prevalent carbapenemase gene was OXA-48; however, there has been a recent increase in KPC genes. No dominant epidemic strain was identified through clonality analysis. The clustering rate was 68% before the pandemic, increasing to 85.7% during the pandemic. The significance of infection control measures is underscored by the rise in both clustering and mortality rates during the COVID-19 pandemic.

Precision Dosing of Meropenem in Adults with Normal Renal Function: Insights from a Population Pharmacokinetic and Monte Carlo Simulation Study.

This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free (f) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions (fT>MIC). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40%fT>MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100%fT>MIC or a 90%PTA for 100%fT>4MIC, higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets.

Effect of low concentrations of lactic acid and temperature on the expression of adhesion, invasion, and toxin-encoding genes of Campylobacter jejuni from poultry.

The consumption of contaminated poultry meat is considered as a significant route of campylobacteriosis transmission. Lactic acid is a disinfectant agent with bactericidal effects on Campylobacter spp. The purpose of this study was to assess the low concentrations of lactic acid effect and different temperatures on the transcriptomic responses of Campylobacter jejuni (C. jejuni) adhesion and virulence-associated genes including peb4, ciaB, cdtA, cdtB, and cdtC. The samples were incubated at 10°C and 22°C for 48 h upon exposure to 30% and 60% lactic acid. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of lactic acid was also determined. Then, gene expression was assessed using real-time polymerase chain reaction (RT-PCR). Lactic acid had lower MIC and MBC levels at lower temperature. The utilization of both levels of lactic acid significantly reduced the expression of peb4, ciaB, cdtB, and cdtC genes over 48 h of incubation at 22°C. However, no significant difference was found in the expression of the cdtA gene between 10 and 22°C at 30% lactic acid. These results highlight the potential of low-concentration lactic acid in the downregulation of adhesion and virulence-associated genes as well as reduction of C. jejuni pathogenicity.

Identification of vancomycin resistance in enterococcus &amp; determination of minimal inhibitory concentration of vancomycin by E-test

Infections due to Enterococcal species is 2 prevalent cause of Nosocomial Infections in health care settings. They are crucial because to their inherent resistance to penicillins, cephalosporins, and low level aminoglycosides &amp; their tendency to develop higher level of aminoglycoside and vancomycin resistance, which leaves few therapeutic alternatives for therapy. Isolation and identification of Enterococci with their Antibiogram &amp; determination of Minimal Inhibitory Concentration (MIC) of Vancomycin by E-test. The antibiogram generated by Kirby Baur disc diffusion method and standard microbiological procedures were used to identify enterococcal isolates from distinct clinical samples. MIC level for Vancomycin was tested for all the isolates using E-test from BIOMERIEUX. Total of 108 isolates (62 E.faecalis and 46 E. faecium) were tested by E-test for MIC of Vancomycin, of which 40 (37.03%) (22 E.faecalis &amp; 18 E. faecium) were Vancomycin Resistant (VRE) strains, having MIC level &amp;#62;32 μg/ml. Nine strains out of 40 (45%) were found to have MIC &amp;#62;256 μg/ml. The enterococcal isolates were observed to be sensitive to Linezolid (80%), Ofloxacin (74%), Amoxyclav (74%) and Cefaperazone (70%). For the Indian medical community, the rise of antibiotic resistance among Enterococcal species has been a significant concern. So this is need of present era that our laboratories must be well-equipped to report the resistance patterns displayed by enterococci in order to practise evidence-based medicine and reduce hospital acquired infections.

Evaluating the Expression of Efflux Pumps in Pseudomonas aeruginosa in Exposure to Sodium Dodecyl Sulfate, Didecyldimethylammonium Chloride, and Octenidine Dihydrochloride.

Emerging resistance of Gram-negative bacteria, including Pseudomonas aeruginosa, to commonly used detergents and disinfectant is encountering us with hazard. Inappropriate use of disinfectants has forced bacteria to gain resistance. The ability of bacteria to extrude substrates from the cellular interior to the external environment has enabled them to persist in exposure to toxic compounds, which is due to existence of transport proteins. Efflux pumps, in Gram-negative bacteria, are proteins responsible for exporting molecules outside of the cell, by crossing the two membranes. In this study, 40 P. aeruginosa strains from hospitals, clinics, and burn center laundries and 40 P. aeruginosa strains from urban laundries were collected. This study evaluated the minimum inhibitory concentration (MIC) level of sodium dodecyl sulfate (SDS), didecyldimethylammonium chloride (DDAC), and octenidine dihydrochloride (Od) in P. aeruginosa strains. The real-time PCR was carried out to evaluate the expression of MexAB-OprM, MexCD-OprJ, and MexXY-OprM efflux system. The obtained results indicated a higher MIC level for SDS, DDAC, and Od in medical laundries. The sub-MIC level of DDAC and Od increased the expression level of MexAB-OprM, MexCD-OprJ, and MexXY-OprM in P. aeruginosa strains, suggesting that efflux pumps contribute to disinfectant resistance in P. aeruginosa.

Occurrence and characterization of plasmid-encoded qnr genes in quinolone-resistant bacteria across diverse aquatic environments in southern Ontario.

Antimicrobial resistance is an ever-increasing threat. The widespread usage of ciprofloxacin has led to the manifestation of resistance due to chromosomal mutations or the acquisition of plasmid-mediated quinolone resistance (PMQR) traits. Some particular PMQR traits, qnr genes, have been identified globally in clinical and environmental isolates. This study aimed to determine the prevalence of ciprofloxacin-resistant bacteria in aquatic environments in southern Ontario and investigate the extent of dissemination of ciprofloxacin resistance traits among the bacterial communities. We surveyed the prevalence of plasmid encoding qnr genes using a multiplex PCR assay of associated PMQR genes, qnrA, qnrB, and qnrS, on 202 isolates. Despite the absence of significant impacts on minimum inhibitory concentration levels, the presence of qnr genes correlates with heightened resistance to quinolones and nalidixic acid in some isolates. Taxonomic analysis highlights distinct differences in the composition and diversity of ciprofloxacin-sensitive (CipS) and ciprofloxacin-resistant (CipR) populations, with Proteobacteria dominating both groups. Importantly, CipR populations exhibit lower genetic diversity but higher prevalence of multiple antibiotic resistances, suggesting co-selection mechanisms. Co-occurrence analysis highlights significant associations between ciprofloxacin resistance and other antibiotic resistances, implicating complex genetic linkages. The results of our study signified the critical role of environmental monitoring in public health.

Ceftazidime-avibactam resistance determination in carbapenem-resistant Klebsiella pneumoniae infections before its use in practice.

To ensure the appropriate usage of ceftazidime-avibactam (CAZ-AVI), recently introduced in our hospital, we aimed to determine susceptibility rates, enzyme analysis, and clonal relationship among strains, together with clinical data. Between June 1 and September 30, 2021, demographic and microbiological data of the patients were recorded. In the obtained samples, meropenem and colistin minimal inhibitory concentration (MIC) levels, carbapenem resistance genes, and the clonal relationship were studied by molecular methods. CAZ-AVI was not used in any of the patients. 140 carbapenem-resistant Klebsiella pneumoniae were isolated from 57 patients. Resistance to CAZ-AVI was found in 76 (54.3%) strains. Out of 57 patients, 31 (54.4%) isolates could be reached. Meropenem MIC level was ≥ 32 µg/mL in 26 (83.9%), and colistin MIC level was ≥ 4 µg/mL in 17 (54.8%) isolates. Enzyme analysis revealed NDM in 20 (64.5%), OXA-48 in 17 (54.8%), and KPC in seven (22.6%). NDM + OXA-48 was determined in 10 (32.2%) strains. NDM was determined in all CAZ-AVI resistant strains, OXA-48 in 16.1% (2/5) strains. Seven genotypes were detected. The largest cluster was genotype 3 clusters (11 isolates). Of 31 patients, 22 (71.0%) died. CAZ-AVI was susceptible in one of the patients who survived and four who died. Before using a new antibiotic, each center should determine the basal data and phenotypic/genotypic resistance ratios specific to that antibiotic. While a high NDM rate and low CAZ-AVI sensitivity limit the use of the drug in our center, it is clear that CAZ-AVI use in sensitive strains will decrease mortality.

In Vivo Intra-Articular Antibiotic Concentrations at 24 Hours After TKA Fall Below the Minimum Inhibitory Concentration for Most Bacteria: A Randomized Study of Commercially Available Bone Cement.

The use of antibiotic-loaded bone cement (ALBC) to help reduce the risk of infection after primary total knee arthroplasty (TKA) is controversial. There is a paucity of in vivo data on the elution characteristics of ALBC. We aimed to determine whether the antibiotic concentrations of 2 commercially available ALBCs met the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) for common infecting organisms. Forty-five patients undergoing TKA were randomized to receive 1 of the following: bone cement without antibiotic (the negative control; n = 5), a commercially available formulation containing 1 g of tobramycin (n = 20), or a commercially available formulation containing 0.5 g of gentamicin (n = 20). Intra-articular drains were placed, and fluid was collected at 4 and 24 hours postoperatively. An automated immunoassay measuring antibiotic concentration was performed, and the results were compared against published MIC and MBEC thresholds. The ALBC treatment groups were predominantly of White (65%) or Black (32.5%) race and were 57.5% female and 42.4% male. The mean age (and standard deviation) was 72.6 ± 7.2 years in the gentamicin group and 67.6 ± 7.4 years in the tobramycin group. The mean antibiotic concentration in the tobramycin group was 55.1 ± 37.7 μg/mL at 4 hours and 19.5 ± 13.0 μg/mL at 24 hours, and the mean concentration in the gentamicin group was 38.4 ± 25.4 μg/mL at 4 hours and 17.7 ± 15.4 μg/mL at 24 hours. Time and antibiotic concentration had a negative linear correlation coefficient (r = -0.501). Most of the reference MIC levels were reached at 4 hours. However, at 24 hours, a considerable percentage of patients had concentrations below the MIC for many common pathogens, including Staphylococcus epidermidis (gentamicin: 65% to 100% of patients; tobramycin: 50% to 85%), methicillin-sensitive Staphylococcus aureus (gentamicin: 5% to 90%; tobramycin: 5% to 50%), methicillin-resistant S . aureus (gentamicin: 5% to 65%; tobramycin: 50%), Streptococcus species (gentamicin: 10% to 100%), and Cutibacterium acnes (gentamicin: 10% to 65%; tobramycin: 100%). The aforementioned ranges reflect variation in the MIC among different strains of each organism. Gentamicin concentrations reached MBEC threshold values at 4 hours only for the least virulent strains of S . aureus and Escherichia coli. Tobramycin concentrations did not reach the MBEC threshold for any of the bacteria at either time point. The elution of antibiotics from commercially available ALBC decreased rapidly following TKA, and only at 4 hours postoperatively did the mean antibiotic concentrations exceed the MIC for most of the pathogens. Use of commercially available ALBC may not provide substantial antimicrobial coverage following TKA. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Mutations in the pmrB gene constitute the major mechanism underlying chromosomally encoded colistin resistance in clinical Escherichia coli

ObjectivesThe mechanisms underlying chromosomally encoded colistin resistance in Escherichia coli remain insufficiently investigated. In this study, we investigated the contribution of various pmrB mutations from E. coli clinical isolates to colistin resistance. MethodsThe resistance mechanisms in eight mcr-negative colistin-resistant E. coli isolates obtained from a nationwide surveillance program in Taiwan using recombinant DNA techniques and complementary experiments were investigated. The minimal inhibitory concentrations (MICs) of colistin in the recombinant strains were compared with those in the parental strains. The expression levels of pmrA and pmrK (which are part of the pmrCAB and pmrHFIJKLM operons associated with colistin resistance) were measured using reverse transcription-quantitative real-time polymerase chain reaction. ResultsIn the complementation experiments, various mutated pmrB alleles from the eight mcr-negative colistin-resistant E. coli strains were introduced into an ATCC25922 mutant with a PmrB deletion, which resulted in colistin resistance. The MIC levels of colistin in the most complemented strains were comparable to those of the parental colistin-resistant strains. Increased expression levels of pmrA and pmrK were consistently detected in most complemented strains. The impact for colistin resistance was confirmed for various novel amino acid substitutions, P94L, G19E, L194P, L98R and R27L in PmrB from the parental clinical strains. The detected amino acid substitutions are distributed in the different functional domains of PmrB. ConclusionsColistin resistance mediated by amino acid substitutions in PmrB is a major chromosomally encoded mechanism in E. coli of clinical origin.

MIC distribution analysis identifies differences in AMR between population sub-groups.

Phenotypic data, such as the minimum inhibitory concentrations (MICs) of bacterial isolates from clinical samples, are widely available through routine surveillance. MIC distributions inform antibiotic dosing in clinical care by determining cutoffs to define isolates as susceptible or resistant. However, differences in MIC distributions between patient sub-populations could indicate strain variation and hence differences in transmission, infection, or selection. The Vivli AMR register contains a wealth of MIC and metadata for a vast range of bacteria-antibiotic combinations. Using a generalisable methodology followed by multivariate regression, we explored MIC distribution variations across 4 bacteria, covering 7,135,070 samples, by key population sub-groups such as age, sex and infection type, and over time. We found clear differences between MIC distributions across various patient sub-groups for a subset of bacteria-antibiotic pairings. For example, within Staphylococcus aureus, MIC distributions by age group and infection site displayed clear trends, especially for levofloxacin with higher resistance levels in older age groups (odds of 2.17 in those aged 85+ compared to 19-64), which appeared more often in men. This trend could reflect greater use of fluoroquinolones in adults than children but also reveals an increasing MIC level with age, suggesting either transmission differences or accumulation of resistance effects. We also observed high variations by WHO region, and over time, with the latter likely linked to changes in surveillance. We found that MIC distributions can be used to identify differences in AMR levels between population sub-groups. Our methodology could be used more widely to unveil hidden transmission sources and effects of antibiotic use in different patient sub-groups, highlighting opportunities to improve stewardship programmes and interventions, particularly at local scales.

Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy.

The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.

Role of MIC levels and 23S rRNA mutation sites to clarithromycin in 14-day clarithromycin bismuth quadruple therapy for Helicobacter pylori eradication: A prospective trial in Beijing

BackgroundRising clarithromycin resistance undermines Helicobacter pylori (H. pylori) treatment efficacy. We aimed to determine clarithromycin's minimum inhibitory concentration (MIC) levels and identify specific mutation sites in the 23S ribosomal subunit (23S rRNA) that predict treatment outcomes in a 14-day regimen of clarithromycin bismuth quadruple therapy (amoxicillin 1g, clarithromycin 500 mg, rabeprazole 10 mg, and colloidal bismuth pectin 200 mg). Materials and methodsWe included adult H. pylori patients who hadn't previously undergone clarithromycin-based treatment, either as initial or rescue therapy. Exclusions were made for penicillin allergy, recent use of related medications, severe illnesses, or inability to cooperate. Patients underwent a 14-day clarithromycin bismuth quadruple therapy. Gastric mucosa specimens were obtained during endoscopy before eradication. MIC against amoxicillin and clarithromycin was determined using the E-test method. The receiver operating characteristic (ROC) curve helped to find the optimal clarithromycin resistance MIC breakpoint. Genetic sequences of H. pylori 23S rRNA were identified through Sanger Sequencing. (ChiCTR2200061476) ResultsOut of 196 patients recruited, 92 met the inclusion criteria for the per-protocol (PP) population. The overall intention-to-treat (ITT) eradication rate was 80.00 % (84/105), while the modified intention-to-treat (MITT) and PP eradication rates were 90.32 % (84/93) and 91.30 % (84/92) respectively. No amoxicillin resistance was observed, but clarithromycin resistance rates were 36.19 % (38/105), 35.48 % (33/93), and 34.78 % (33/92) in the ITT, MITT, and PP populations respectively. Compared with the traditional clarithromycin resistance breakpoint of 0.25 μg/mL, a MIC threshold of 12 μg/mL predicted better eradication. Among 173 mutations on 152 sites in the 23S rRNA gene, only the 2143A > G mutation could predict eradication outcomes (p < 0.000). ConclusionsInterpretation of elevated MIC values is crucial in susceptibility testing, rather than a binary "susceptible" or "resistant" classification. The 2143A > G mutation has limited specificity in predicting eradication outcomes, necessitating further investigation into additional mutation sites associated with clarithromycin resistance.

Study of the sensitivity of methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; to antibiotics and bacteriophage preparations

Objective. To evaluate the sensitivity of methicillin-resistant Staphylococcus aureus strains to antibiotics and therapeutic and prophylactic preparations of bacteriophages. Materials and methods. The antibiotic sensitivity of strains of methicillin-resistant S.aureus was studied by the disco-diffusion method, the determination of the minimum inhibitory concentrations of vancomycin and linezolid by broth microdilution method, and ceftaroline by E-tests. The sensitivity of methicillin-resistant S.aureus to bacteriophage preparations was studied. Results. It has been established that linezolid and vancomycin are quite active drugs against methicillin-resistant S.aureus (MRSA), however, resistance to them begins to develop. MRSA resistance to fluoroquinolones and cefoxitin was the highest of all antibiotics tested; the results obtained with cefoxitin can be interpreted for other cephalosporins (except ceftaroline) and all penicillins. Only 67.9% of MRSA strains retained sensitivity to ceftaroline, but ceftaroline-resistant strains had low levels of minimal inhibitory concentration. The preparations of the bacteriophages “Sextaphage” and “Piobacteriophage Phagio” showed their lytic activity only in relation to 35.8% and 18.9% of MRSA isolates, respectively. Conclusion. Monitoring the development of antibiotic resistance in methicillin-resistant S.aureus is an important part of the strategy of rational antibiotic therapy for staphylococcal infections. Only taking into account the preliminary step-by-step determination of the phage sensitivity of the causative agent of the disease, bacteriophage preparations can be considered as a completely possible alternative to antibiotics for the treatment of purulent inflammatory diseases caused by MRSA.

Polish honeys exhibit activity against Pseudomonas aeruginosa isolated from wounds

Pseudomonas aeruginosa is recognized as an opportunistic pathogen and a common contributor to wound infections. This study focused on evaluating the antibacterial activity of selected Polish honeys against P. aeruginosa. Six bacterial strains isolated from wounds and four types of honeys (multifloral, linden, buckwheat, and heather) were utilized. The minimal inhibitory concentrations (MIC) were determined through the micro-dilution method employing 96-well plates, while antibiofilm activity was assessed using fluorescence microscopy after a 4-hour incubation period with the honeys. Results indicated diverse antibacterial efficacy among honeys, with linden and heather honeys demonstrating the most potent activity. Linden honey displayed an average MIC of 20.8%, while heather honey exhibited an MIC of 25%. Both honeys significantly reduced biofilm formation, with linden honey achieving a reduction of 54-67% and heather honey of 45-58%. Buckwheat and multifloral honeys exhibited lower activity, demonstrating average MIC levels of 37.5% and 41.7%, respectively, and a biofilm reduction below 20%. Conclusively, Polish honeys exhibited promising activity against both planktonic and biofilm forms of P. aeruginosa. These findings suggest potential applications in wound healing treatments, emphasizing the need for further research in this area. The study contributes valuable insights to the limited literature on the antibacterial activity of Polish honeys.

NaClO Co-selects antibiotic and disinfectant resistance in Klebsiella pneumonia: Implications for the potential risk of extensive disinfectant use during COVID-19 pandemic

The inappropriate use of antibiotics is widely recognized as the primary driver of bacterial antibiotic resistance. However, less attention has been given to the potential induction of multidrug-resistant bacteria through exposure to disinfectants. In this study, Klebsiella pneumonia, an opportunistic pathogen commonly associated with hospital and community-acquired infection, was experimentally exposed to NaClO at both minimum inhibitory concentration (MIC) and sub-MIC levels over a period of 60 days. The result demonstrated that NaClO exposure led to enhanced resistance of K. pneumonia to both NaClO itself and five antibiotics (erythromycin, polymyxin B, gentamicin, tetracycline, and ciprofloxacin). Concurrently, the evolved resistant strains exhibited fitness costs, as evidenced by decreased growth rates. Whole population sequencing revealed that both concentrations of NaClO exposure caused genetic mutations in the genome of K. pneumonia. Some of these mutations were known to be associated with antibiotic resistance, while others had not previously been identified as such. In addition, 11 identified mutations were located in the virulence factors, demonstrating that NaClO exposure may also impact the pathogenicity of K. pneumoniae. Overall, this study highlights the potential for the widespread use of NaClO-containing disinfectants during the COVID-19 pandemic to contribute to the emergence of antibiotic-resistant bacteria. Environmental ImplicationConsidering the potential hazardous effects of disinfectant residues on environment, organisms and biodiversity, the sharp rise in use of disinfectants during COVID-19 pandemic has been considered highly likely to cause worldwide secondary disasters in ecosystems and human health. This study demonstrated that NaClO exposure enhanced the resistance of K. pneumonia to both NaClO and five antibiotics (erythromycin, polymyxin B, gentamicin, tetracycline, and ciprofloxacin), highlighting the widespread use of NaClO-containing disinfectants during the COVID-19 pandemic may increase the emergence of antibiotic-resistant bacteria in the environment.

Unusual and Unconsidered Mechanisms of Bacterial Resilience and Resistance to Quinolones.

Quinolone resistance has been largely related to the presence of specific point mutations in chromosomal targets, with an accessory role of impaired uptake and enhanced pump-out. Meanwhile the relevance of transferable mechanisms of resistance able to protect the target of pump-out or inactivate quinolones has been increasingly reported since 1998. Nevertheless, bacteria have other strategies and mechanisms allowing them to survive and even proliferate in the presence of quinolones, which might be qualified as resistance or resilience mechanisms. These include decreasing levels of quinolone target production, transient amoeba protection, benthonic lifestyle, nutrient-independent slow growth, activation of stringent response, inactivation or degradation of quinolones as well as apparently unrelated or forgotten chromosomal mutations. These mechanisms have been largely overlooked, either because of the use of classical approaches to antibiotic resistance determination or due to the low increase in final minimum inhibitory concentration levels. This article is devoted to a review of a series of these mechanisms.

Can Nanobubble Ozone Liposomes Be A New Agent In The Fight Against Foodborne Infections?

In this study, a nanobubble ozone liposome solution containing 2% ZnCl2 was used. The aging tests were conducted according to the ASTM F 1980 [1] standards. The minimum inhibitory concentration (MIC) level of the nanobubble ozone liposome solution with 2% ZnCl2 was determined as 1.562 ppm for strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) by the CLSI M07 A9 [2] standard test method. To assess the time-dependent antibacterial effect of the nanobubble liposome solution with 2% ZnCl2, the solution's efficiency at a concentration of 2000 ppm and for different time intervals was tested on strains of Salmonella enterica subsp. enterica (ATCC® 14028™) and Listeria monocytogenes (ATCC® 7644™). The results showed that the antibacterial activity of the strains of S. enterica subsp. enterica started at the end of the 10th minute and the solution was effective after 30 minutes. For strains of L. monocytogenes, it was observed that the activity started at the end of the 2nd minute and the product was effective after the 10th minute. According to the ASTM F 1980 standards, it was found that the nanobubble ozone liposome solution retained its effectiveness in one-year stability tests. As a result, the nanoparticle liposome solution, a new product, does not lose its stability and effectiveness for a long time, contrary to what is known. Although the half-life of gaseous ozone is as short as 20 minutes, the stability in the nanoparticle liposome solution has been determined as at least one year. Since nanoparticle liposome solution is a natural and slow-release product, nanobubble ozone liposome solution with 2% ZnCl2 may be used as a newly developed agent against contaminations in food processing facilities caused by biofilm-forming microorganisms through the use in disinfections of surfaces that are in direct contact with food products.

Antibacterial and antioxidant activities in various parts of Artocarpuslacucha Buch. Ham. ethanolic extract.

Artocarpus lacucha is an endemic plant to North Sumatera, Indonesia. This plant has pharmacological activities, including acting as an antioxidant and antibacterial. The aim of the present study was to analyze the antibacterial and antioxidant activities, and determine the flavonoid compounds from four parts of A. lachuca, namely leaves, barks, twigs and fruits. Antioxidant activity was investigated using the 2,2-diphenyl 1-picrylhydrazyl (DPPH) and cupric reducing antioxidant capacity (CUPRAC) methods. Antibacterial activity was analyzed using disk diffusion and microdilution methods. Several flavonoids, such as luteolin-7-O-glucoside, rutin, quercetin, kaempferol and apigenin, were determined using high performance liquid chromatography. Based on the antioxidant activity test results using the DPPH method, the bark ethanolic extract provided the highest antioxidant capacity, while the CUPRAC method indicated that the twig ethanolic extract had the highest antioxidant capacity. The antibacterial activity test results demonstrated that at a low concentration of 750 µg/disk the bark ethanolic extract obtained the highest inhibition zone and minimum inhibitory concentration level against six of nine pathogenic bacteria. Therefore, A. lachuca bark ethanolic extract could be potentially developed as antioxidant and antibacterial agents.

Efficacy of Various Herbal Preparations Against Oral Candida: A Lab-Based Study

ABSTRACT Aim: This research was done to analyze the effectiveness related to herbal chemicals in tackling candidiasis. Materials and Methods: Grounded and ethanol-extracted residues of plants like Avicennia marina, Fagonia indica, Portulaca oleracea, Lawsania inermis, Ziziphus spina, Asphodelus tenuifolius, and Salvadora persica were used in the study. The extract was used against candida species, after which the antibacterial as well as cytotoxicity toward the former were evaluated. Results: L. inermis and P. oleracea with minimal inhibitory concentration of approx. 10 cenmL had an increased activity against candida species. The preparations of these plants acted against Candida albicans during its stages related to pathogenesis during biofilm production. Superadded infections like in case of bacterial infections along with candida can be difficult to cure. On human RBCs, these plant preparations had no toxicity at their minimum inhibitory concentration level. Conclusion: We concluded that, as far as being anti-candida and acting against MDR bacterial infections, preparations of plants were effective as an alternative to allopathic drugs.