Susceptibility Data Research Articles

Bacterial etiology and antimicrobial resistance pattern of pediatric bloodstream infections: a 5-year experience in an Iranian referral hospital

BackgroundBloodstream infections (BSI) are the major cause of morbidity and mortality in children in developing countries. The purpose of the current study was to establish the antimicrobial susceptibility pattern of bacterial isolates from bloodstream infections at Children’s Medical Center Hospital (CMC), Tehran, Iran.MethodsWe retrospectively recorded all positive blood cultures and antimicrobial susceptibility of all bloodstream isolates among children admitted to CMC, during 5 years. Specimen culture, bacterial identification, and antimicrobial susceptibility testing were performed according to standard laboratory methods.ResultsFrom 3,179 pathogens isolated from the blood cultures 2,824 bacteria were cultured, with 1,312 cases being identified as Gram-positive bacteria (46%) and 1,512 cases as Gram-negative bacteria (54%). The most common Gram-negative bacteria isolated were as follows: Pseudomonas spp. (n = 266, 17.6%), Klebsiella pneumoniae (n = 242, 16%), Stenotrophomonas maltophilia (n = 204, 13.5%), Enterobacter spp. (n = 164, 10.8%), Escherichia coli (n = 159, 10.5%), Pseudomonas aeruginosa (n = 126, 8.3%), Serratia marcescens (n = 121, 8%), and Acinetobacter baumannii (n = 73, 4.8%). The most common Gram-positive bacteria isolated were coagulase-negative staphylococci (CONS) (n = 697, 53%), Streptococcus spp. (n = 237, 18%), Staphylococcus aureus (n = 202, 15%) and Enterococcus spp. (n = 167, 12.7%). 34% of bacterial strains were isolated from ICUs. The rates of methicillin resistance in S. aureus and CONS were 34% and 91%, respectively. E. coli isolates showed high resistance to cefotaxime (84%). All isolates of K. pneumoniae were susceptible to colistin and 56% were susceptible to imipenem. P. aeruginosa isolates showed high susceptibility to all antibiotics.ConclusionsOur findings emphasize the need of clinicians having access to up-to-date bacterial susceptibility data for routinely prescribed drugs. Continuous monitoring of changes in bacterial resistance will aid in the establishment of national priorities for local intervention initiatives in Iran. The increased risk of BSI caused by antibiotic-resistant organisms, emphasizes the significance of implementing appropriate antibiotic prescribing regulations and developing innovative vaccination techniques in Iran.

Investigation of possible spin frustration in isolated isosceles MnIIINiII2 Triangle: Experimental and theoretical studies

Spin frustration is a unique phenomenon in magnetic complexes, where if a spin fails to lower the total energy of the system, by orienting itself in relative to its adjacent spins, it is termed as frustrated. In this work, we discuss about the magnetic properties, and the possibility of spin frustration in our isolated [NiII2MnIII(hep)4(PhCO2)(N3)2] (Hhep = 2-(2-hydroxyethyl) pyridine) having an isosceles NiII2MnIII triangle. The triangular MnIIINiII2 core was held together by two μ3-alkoxide bridges. The magnetic properties of this complex were studied in detail. Variable temperature magnetic susceptibility data of the complex in the range of 1.8 to 300 K, indicates the presence of stronger intramolecular antiferromagnetic coupling between two NiII centres than between NiII and MnIII ions. Experimentally, the ground state of the complex was found to be a mixture of E(2,0) and E(1,1) states, suggesting our complex to be close to a spin frustrated system which was supported by ab initio calculations.

Comparison of Cefazolin and Ceftriaxone Enterobacterales Susceptibilities for Inpatient Treatment of Urinary Tract Infections and Risk of Hospital-onset Clostridioides difficile Infection

Purpose: Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost and perceived safety. However, third-generation cephalosporins increase the risk of healthcare facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins. Recent evidence comparing Enterobacterales susceptibility for first- and third-generation cephalosporins in urinary specimens in the United States does not exist. This analysis assesses comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empiric agent to manage inpatient UTI and limit ceftriaxone collateral damage.Methods: This is a retrospective single center observational study. Microbiologic susceptibility data was analyzed for E. coli, K. pneumoniae, and P. mirabilis urinary specimens taken from adult inpatients admitted January 1, 2022 to December 31, 2022. Primary outcome is incidence of E. coli, K. pneumoniae, and P. mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC < 16 mcg/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone. A larger time frame, January 1, 2016 to December 31, 2022, was used to assess HOCDI risk associated with cefazolin and ceftriaxone. HOCDI risk assessment included adults administered at least one dose of either cefazolin or ceftriaxone during a minimum of four-day hospitalization.Findings: A total of 1150 urine samples were identified as E. coli, K. pneumoniae, and P. mirabilis in 2022. Susceptibility to cefazolin was observed in 1064/1150 (92.5%) isolates using the MIC breakpoint for uncomplicated UTI, and to ceftriaxone in 1115/1150 (97.0%) isolates (p < 0.001). From 2016-2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions with an HOCDI diagnoses occurring in 89 admissions. HOCDI developed in 78 admissions (0.40%) with ceftriaxone exposure and 11 cases (0.15%) developed in cefazolin exposed admissions (p < 0.001, adjusted OR 2.44, 95% CI 1.25 – 4.76).Implications: Cefazolin demonstrates high susceptibility for uropathogens commonly implicated in uncomplicated UTI, the predominant UTI managed inpatient. While ceftriaxone demonstrates a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared to cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage like HOCDI, use of cefazolin for uncomplicated urinary tract infection may be evaluated using local susceptibility data.

Best Practice of Peritoneal Dialysis-Associated Gram-Negative Peritonitis in Children: Insights From the International Pediatric Peritoneal Dialysis Network Registry

Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations are based on limited data. Analysis of 379 GNP episodes in 308 children (median age 6.9 years, interquartile range [IQR]: 3.0-13.6) from 45 centers in 28 countries reported to the International Pediatric Peritoneal Dialysis Network registry between 2011 and2023. Overall, 74% of episodes responded well to empiric therapy and full functional recovery (FFR) was achieved in 82% of cases. Invitro bacterial susceptibility to empiric antibiotics and lack of severe abdominal pain at onset were associated with a good initial response. Risk factors for failure to achieve FFR included severe abdominal pain at onset and at 60 to 72 hours from treatment initiation (odds ratio [OR]: 3.81, 95% confidence interval [CI]: 2.01-7.2 and OR: 3.94, 95% CI: 1.06-14.67, respectively), Pseudomonas spp. etiology (OR: 1.73, 95% CI: 1.71-4.21]) and invitro bacterial resistance to empiric antibiotics (OR: 2.40, 95% CI: 1.21-4.79); the risk was lower with the use of monotherapy as definitive treatment (OR: 0.40, 95% CI: 0.21-0.77). Multivariate analysis showed no benefit of dual antibiotic therapy for treatment of Pseudomonas peritonitis after adjustment for age, presenting symptomatology, 60 to 72-hour treatment response, and treatment duration. Monotherapy with cefazolin in susceptible Enterobacterales peritonitis resulted in a similar FFR rate (91% vs. 93%) as treatment with ceftazidime or cefepime monotherapy. Detailed microbiological assessment, consisting of patient-specific and center-specific antimicrobial susceptibility data, should guide empiric treatment. Treatment "deescalation" with the use of monotherapy and narrow spectrum antibiotics according to susceptibility data is not associated with inferior outcomes and should be advocated in the context of emerging bacterial resistance.

In vitro activity, pharmacodynamic profile and dose optimization of biapenem against NDM and OXA-48-like carbapenemase-producing Klebsiella pneumoniae: A multicentre study in Thailand

Biapenem (BIPM) exhibited a less efficient substrate for various metallo-β-lactamase (MBL) than other carbapenems. We aimed to evaluate in vitro susceptibility data of BIPM and optimal dose based on Monte Carlo simulation to extend treatment options. We collected 192 carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates from unique patients among multicentres in Thailand, from June 2019 to March 2023. BIPM disk diffusion and broth-microdilution testing were performed to obtain minimum inhibitory concentration (MIC). Each BIPM regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). The most common genotypes among 192 CRKP isolates were blaOXA-48 (62.3%), blaOXA-48+blaNDM (22.6%) and blaNDM (15.1%). BIPM showed 22.4 and 28.6% susceptible rate when interpreted at clinical breakpoints of 1 and 2 mg/L. The MIC50 and MIC90 of BIPM against CRKP were 8 and 32 mg/L. The BIPM dosing regimens of 300 mg q 6 h infused 6 h and 600 mg q 8 h infused 8 h met the PTA target of %fTime >MIC at 50%, 75% and 100% against isolates MICs of ≤2 mg/L. Based on CFR ≥90%, no BIPM regimens were effective against all the studied CRKP isolates. BIPM exhibited a partially susceptible rate among the CRKP isolates in Thailand. The current suggested dose of BIPM with prolonged infusion appears appropriate regimen against CRKP MICs of ≤2 mg/L. However, the empirical use of BIPM for severe CRE infection is not recommended unless the susceptibility has been confirmed.

Metal-Ligand Exchange Coupling Alters the Open-Shell Ligand Electronic Structure in a Bis(semiquinone) Complex.

The electronic structure of the bis(dioxolene) bridging ligand -SQ2Th2- is responsive to metal-ligand magnetic exchange coupling. Comparison of the crystal structure of (NiSQ)2Th2 to that of (ZnSQ)2Th2 indicates an open-shell biradical ground state for the dinuclear Ni(II) complex compared to the closed-shell quinoidal character found in the dinuclear Zn(II) complex. Consistent with a comparison of bond lengths obtained by X-ray diffraction, the analysis of the variable-temperature magnetic susceptibility data for crystalline (NiSQ)2Th2 yields reduced SQ-SQ radical-radical magnetic exchange coupling (JSQ-SQ = -203 cm-1) compared to that of (ZnSQ)2Th2 (JSQ-SQ = -321 cm-1). The reduced SQ-SQ exchange coupling in (NiSQ)2Th2 derives from an attenuation of the SQ spin densities, which in turn is derived from the Ni-SQ antiferromagnetic exchange interactions. This reduction in SQ--SQ exchange that we observe for (NiSQ)2Th2 correlates with an effective lengthening of the bridge unit by ∼2.1 Å relative to that of (ZnSQ)2Th2. This magnitude of the effective increase in the bridge distance is consistent with the (NiSQ)2Th2 JSQ-SQ value lying between those of (ZnSQ)2Th2 and (ZnSQ)2Th3. The ability to modulate spin populations on an organic radical via pairwise Ni-SQ magnetic exchange interactions is a general way to affect electronic coupling in the Th-Th bridge. Our results suggest that metal-radical exchange coupling represents a powerful mechanism for tuning organic molecular electronic structure, with important implications for molecular electronics and molecular electron transport.

Antibiotic Resistance, Biofilm Formation, and Persistent Phenotype of Klebsiella pneumoniae in a Vietnamese Tertiary Hospital: A Focus on Amikacin.

Klebsiella pneumoniae stands out as a major opportunistic pathogen responsible for both hospital- and community-acquired bacterial infections. This study comprehensively assesses the antibiotic resistance, amikacin persistent patterns, and biofilm-forming ability of 247 isolates of K. pneumoniae obtained from an intensive care unit of a tertiary hospital in Vietnam. Microdilution assays, conducted on a 96-well plate, determined the minimum inhibitory concentrations (MICs) of amikacin. Susceptibility data for other antibiotics were gathered from the antibiogram profile. Stationary-phase bacteria were exposed to 50 × MIC, and viable bacteria counts were measured to determine amikacin persistence. Biofilm forming capacity on 96-well polystyrene surfaces was assessed by biomass and viable bacteria. The prevalence of resistance was notably high across most antibiotics, with 64.8% classified as carbapenem-resistant K. pneumoniae and 81.4% as multidrug resistant. Amikacin, however, exhibited a relatively low rate of resistance. Of the isolates, 58.2% demonstrated a moderate to strong biofilm formation capacity, and these were found to be poorly responsive to amikacin. K. pneumoniae reveals a significant inclination for amikacin persistence, with ∼45% of isolates displaying an antibiotic antibiotic-survival ratio exceeding 10%. The study sheds light on challenges in treating of K. pneumoniae infection in Vietnam, encompassing a high prevalence of antibiotic resistance, a substantial ability to form biofilm, and a notable rate of antibiotic persistence.

Corynebacterium diphtheriae and Corynebacterium ulcerans: development of EUCAST methods and generation of data on which to determine breakpoints.

Evidence-based clinical susceptibility breakpoints have been lacking for antimicrobial agents used for diphtheria. We aimed to evaluate broth microdilution and disc diffusion methods and create a dataset of MIC values and inhibition zone diameters (ZDs) from which breakpoints could be determined. We included 400 recent clinical isolates equally distributed by species (Corynebacterium diphtheriae and Corynebacterium ulcerans) and by national surveillance programmes (France and Germany). Non-duplicate toxigenic and non-toxigenic isolates were chosen to enable the inclusion of a diversity of susceptibility levels for the 13 agents tested. Broth microdilution and disc diffusion, using EUCAST methodology for fastidious organisms, were used. The distributions of MIC and ZD values were largely in agreement among methods and countries. Breakpoints to allow categorization of WT isolates as susceptible, i.e. susceptible (S) or susceptible, increased exposure (I) were determined for 12 agents. The data supported a breakpoint for benzylpenicillin and amoxicillin of resistant (R) > 1 mg/L since WT isolates were inhibited by 1 mg/L or less. WT isolates were categorized as I (S ≤ 0.001 mg/L) for benzylpenicillin, emphasizing the need for increased exposure, and S (S ≤ 1 mg/L) for amoxicillin. Erythromycin breakpoints were set at S ≤ 0.06 mg/L and R > 0.06 mg/L. The corresponding ZD breakpoints were determined for all agents except amoxicillin, for which categorization was based on benzylpenicillin results. This work provided a large set of antimicrobial susceptibility data for C. diphtheriae and C. ulcerans, using a harmonized methodology. The dataset allowed EUCAST and experts in the diphtheria field to develop evidence-based breakpoints in January 2023.

Utilizing Machine Learning Models for Predicting Diamagnetic Susceptibility of Organic Compounds.

This research is centered on examining the magnetic characteristics of organic molecules, with a particular emphasis on magnetic susceptibility, an essential physical property that provides insights into molecular microstructures and reaction processes. Traditional approaches for determining and calculating magnetic susceptibility are generally inefficient and demanding. To overcome these challenges, we have introduced a novel approach using quantitative structure-property relationships, which efficiently elucidates the relationship between the structural properties of molecules and their molar magnetic susceptibility. In our study, we utilized a comprehensive database comprising molar magnetic susceptibility data for 382 organic molecules. We applied six distinct molecular fingerprinting methods-RDKit Fingerprint, Morgan Fingerprint, MACCS Keys, atom pair fingerprint, Avalon Fingerprint, and topology fingerprint-as feature inputs for training seven different machine learning models, namely random forest, AdaBoost, gradient boosting, extra trees, elastic net, support vector machine, and multilayer perceptron (MLP). Our findings revealed that the integration of the atom pair fingerprint with the MLP model yielded R2 values of 0.88 and 0.90 in the validation and test sets, respectively, showcasing exceptional predictive accuracy. This advancement significantly expedites research and development processes related to the magnetic properties of organic molecules. Moreover, by employing this effective predictive method, it is expected to considerably reduce both experimental and computational expenses while maintaining high accuracy. This development represents a breakthrough in the rapid screening and prediction of properties for various compounds, offering a new and efficient pathway in this field of study.

Rifampicin Resistant Tuberculosis Among Presumptive Pulmonary Tuberculosis in Province Referral Hospital, Indonesia: Dynamic Cases of a 7-Year Report.

Indonesia has the second highest tuberculosis (TB) cases globally. This study aimed to determine the sociodemographic factors associated with TB and rifampicin-resistant tuberculosis (RR-TB) cases among presumptive pulmonary TB patients in Aceh Referral Hospital. Study Design: A retrospective cross-sectional study. A retrospective cross-sectional review of presumptive pulmonary TB patients having a sputum test at the clinical microbiology laboratory was conducted from January 2015 to December 2021. Patient characteristics and drug susceptibility data were abstracted from the hospital information system of TB (SITB) and analyzed by univariate and bivariate analysis. The Mycobacterium tuberculosis (MTB) was detected in 32.8% sample (1,521/4,637). Of the TB-confirmed cases, 14.1% (215/1,521) were resistant to rifampicin (RR-TB). Most of them were male patients (71.63%), were in the age range of 35-54 years (48.7%), lived in rural areas of the country (56.3%), and were previously TB-treated cases (65.5%). Overall, 35-44-year-old patients (adjusted odds ratio [AOR]=2.11, 95% CI=1.25, 3.5, P<0.05) were more likely to have RR-TB compared to>65-year-old patients. Gender and residence were not associated with RR-TB (P>0.05). Case detection decreased in pandemic conditions (19.5% in 2019 to 13.9% and 7.91% in 2020 and 2021, respectively). The findings revealed the dynamic cases and sociodemographic factors of TB and RR-TB in a province referral hospital in Indonesia for 7 years. The cases of TB and RR-TB among presumptive TB patients were 32.8% and 14.1%, respectively. The cases were found to be more noticeable in males, adults (45-54 years old), and patients residing in rural areas.

First report of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae) resistance to spirotetramat in Florida

One of the most destructive invasive pests worldwide is the whitefly, Bemisia tabaci MEAM1. The Florida vegetable crop market, worth millions of dollars annually, suffers major losses because of whitefly injury. Spirotetramat is frequently used by Florida vegetable crop growers to control whitefly nymphs. A previous study based on maximum dose bioassays indicated that MEAM1 populations in Florida may be developing resistance to spirotetramat. Thus, the long-term efficacy of this active ingredient depends on the development of baseline susceptibility data and the continued monitoring of MEAM1 populations' susceptibility. In the present study, 16 populations of whiteflies collected in south Florida were tested for resistance to spirotetramat through serial dilution bioassays designed to test whitefly nymphs. The field populations’ responses were compared with a susceptible MEAM1 laboratory colony. Median lethal concentrations (LC50) and resistance ratios (RRs) were quantified to determine MEAM1 resistance levels. Among the populations tested, 12.5% remained relatively susceptible (3–4 RR) to spirotetramat. Low to moderate resistance was found in 56% of the populations (16–58 RR). Over 30% of the populations tested were highly or extremely resistant (126–795 RR). Overall, the variable susceptibility of spirotetramat in some field populations indicates that resistance to this insecticide has developed in certain regions of south Florida. This is the first report of spirotetramat resistance in the United States. These results will directly refine management recommendations for spirotetramat use in areas where MEAM1 populations exhibit resistance.

Unraveling Multicopper [Cu3] and [Cu6] Clusters with Rare μ3-Sulfato and Linear μ2-Oxido-Bridges as Potent Antibiofilm Agents against Multidrug-Resistant Staphylococcus aureus.

In this research article, two multicopper [Cu3] and [Cu6] clusters, [Cu3(cpdp)(μ3-SO4)(Cl)(H2O)2]·3H2O (1) and [Cu6(cpdp)2(μ2-O)(Cl)2(H2O)4]·2Cl (2) (H3cpdp = N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol), have been explored as potent antibacterial and antibiofilm agents. Their molecular structures have been determined by a single-crystal X-ray diffraction study, and the compositions have been established by thermal and elemental analyses, including electrospray ionization mass spectrometry. Structural analysis shows that the metallic core of 1 is composed of a trinuclear [Cu3] assembly encapsulating a μ3-SO42- group, whereas the structure of 2 represents a hexanuclear [Cu6] assembly in which two trinuclear [Cu3] motifs are exclusively bridged by a linear μ2-O2- group. The most striking feature of the structure of 2 is the occurrence of an unusual linear oxido-bridge, with the Cu3-O6-Cu3' bridging angle being 180.00°. Whereas 1 can be viewed as an example of a copper(II)-based compound displaying a rare μ3:η1:η1:η1 bridging mode of the SO42- group, 2 is the first example of any copper(II)-based compound showing an unsupported linear Cu-O-Cu oxido-bridge. Employing variable-temperature SQUID magnetometry, the magnetic susceptibility data were measured and analyzed exemplarily for 1 in the temperature range of 2-300 K, revealing the occurrence of antiferromagnetic interactions among the paramagnetic copper centers. Both 1 and 2 exhibited potent antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA BAA1717) and the clinically isolated culture of methicillin-resistant S. aureus (MRSA CI1). The mechanism of antibacterial and antibiofilm activities of these multicopper clusters was investigated by analyzing and determining the intracellular reactive oxygen species (ROS) generation, lipid peroxidation, microscopic observation of cell membrane disruption, membrane potential, and leakage of cellular components. Additionally, 1 and 2 showed a synergistic effect with commercially available antibiotics such as vancomycin with enhanced antibacterial activity. However, 1 possesses higher antibacterial, antibiofilm, and antivirulence actions, making it a potent therapeutic agent against both MRSA BAA1717 and MRSA CI1 strains.

Electronic structure of CeCu4In from band structure calculations and X-ray photoelectron spectroscopy

We present a combined new experimental and theoretical study of the electronic structure for the heavy fermion CeCu4In based on X-ray photoelectron spectroscopy (XPS) data and ab-initio band structure calculations. The compound crystallizes in the orthorhombic CeCu4.38In1.62 type of structure (space group Pnnm). Below the Fermi energy the total density of states contains mainly 3d–states of Cu atoms that hybridized with the Ce 4f electronic states. The Ce core-level XPS spectra point to a stable trivalent configuration of Ce atoms in CeCu4In, consistently with the magnetic susceptibility data. For more detailed information about electronic states the fully relativistic band structure was calculated within the density functional theory (DFT) for the first time. Based on these calculations we present calculated photoemission spectra, which very well reproduce the experimental ones. The Fermi level is located at a deep decrease in the density of electronic states and reaches a value of 3.69 states/(eV f.u.). This value is much smaller than the one obtained experimentally, which indicates the importance of many-body effects, which are not properly taken into account in ab-initio calculations. The valence band is formed mainly by Cu(3d) electrons with a small contribution of Ce(4f) electrons in the immediate vicinity of the Fermi level.

Antibiotic prescribing patterns and carriage of antibiotic-resistant Escherichia coli and Enterococcus species in healthy individuals from selected communities in Lusaka and Ndola districts, Zambia.

This study assessed antibiotic prescribing patterns in primary healthcare facilities and antimicrobial resistance (AMR) profiles of commensal Escherichia coli and enterococci isolated from pregnant women and children under 5 years of age. This cross-sectional study was conducted in Lusaka and Ndola districts of Zambia. Prescription pattern data were obtained from hospital pharmacies. Identification and antimicrobial susceptibility profiles of E. coli and enterococci were determined by conventional methods, while confirmation of both pathogens and AMR genes were determined by PCR. Data were analysed using WHONET and SPSS version 25.0. Most prescribed antibiotics at the primary healthcare facilities belonged to the Access group of the WHO Access, Watch and Reserve (AWaRe) classification. All the primary healthcare facilities adhered to the AWaRe framework of ≥60% prescribed antibiotics belonging to the Access group. However, resistance was highest in the Access group of antibiotics. E. coli resistance to ampicillin ranged from 71% to 77% and to co-trimoxazole from 74% to 80%, while enterococcal resistance to tetracycline was 59%-64%. MDR was highest in E. coli (75%) isolates, while XDR was highest in enterococcal isolates (97%). The identified AMR genes in E. coli included blaCTX-M, sul2 and qnrA, while those of enterococci included erm(B), erm(C) and erm(A). Resistance was highest in the prescribed WHO Access group of antibiotics. These findings highlight the need to use local susceptibility data to formulate country-specific treatment guidelines in line with WHO AWaRe classification and enforce regulations that prohibit easy access to antibiotics.

Predictive Modeling of Phenotypic Antimicrobial Susceptibility of Selected Beta-Lactam Antimicrobials from Beta-Lactamase Resistance Genes.

The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34-3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81-0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06-5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39-67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae.

Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis.

The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier). The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy.

Microbiological Survey and Evaluation of Antimicrobial Susceptibility Patterns of Microorganisms Obtained from Suspect Cases of Canine Otitis Externa in Gran Canaria, Spain.

A retrospective study of microbiological laboratory results from 2020 to 2022, obtained from a veterinary diagnostic laboratory of the island of Gran Canaria, Spain, focused on canine otitis cases, was performed. The objective of this study was to analyze the pathogen distribution, antimicrobial susceptibility, prevalence of multidrug resistant phenotypes and the role of coinfections in otitis cases in order to provide up-to-date evidence that could support effective control strategies for this prevalent pathology. A total of 604 submissions were processed for the diagnosis of canine external otitis. Of the samples analyzed, 472 were positive for bacterial or fungal growth (78.1%; 95% CI: 74.8-81.4%). A total of 558 microbiological diagnoses were obtained, divided in 421 bacterial (75.4%; 95% CI: 71.8-79.0%) and 137 fungal (24.6%; 95% CI: 20.9-28.1%) identifications. Staphylococcus pseudintermedius, Malassezia pachydermatis and Pseudomonas aeruginosa were the most prevalent microorganisms detected in clinical cases of otitis. High level antimicrobial resistance was found for Pseudomonas aeruginosa (30.7%), Proteus mirabilis (29.4%), Staphylococcus pseudintermedius (25.1%) and Escherichia coli (19%). Multidrug-resistant phenotypes were observed in 47% of the bacteria isolated. In addition, a 26.4% prevalence of methicillin-resistant Staphylococcus pseudintermedius was detected. The high prevalence of antimicrobial resistant phenotypes in these bacteria highlights the current necessity for constant up-to-date prevalence and antimicrobial susceptibility data that can support evidence-based strategies to effectively tackle this animal and public health concern.

Spectroscopic and biological studies of mixed ligand complexes of transition metal (II) ions with chloroquine and ketoprofen

To create fresh transition metal complexes of chloroquine and ketoprofen, we combined Ni(II), Co(II), Cu(II), and Zn(II). Metal analysis, IR, UV-vis, and X-ray diffraction (XRD) spectrum analyzes of the complexes were utilized to characterize them. The octahedral geometry was proposed for all compounds on the basis of the UV-vis and magnetic susceptibility data. The practical size of the ligands and complexes with crystallinity structure was in the nano range according to the XRD data. The antibacterial and antifungal activities of the ligands and their metal complexes have been examined.

Mannose-binding lectin gene polymorphism in psoriasis and vitiligo: an observational study and computational analysis.

Psoriasis and vitiligo are inflammatory autoimmune skin disorders with remarkable genetic involvement. Mannose-binding lectin (MBL) represents a significant immune molecule with one of its gene variants strongly linked to autoimmune diseases. Therefore, in this study, we investigated the role of the MBL variant, rs1800450, in psoriasis and vitiligo disease susceptibility. The study comprised performing in silico analysis, performing an observational study regarding psoriasis patients, and performing an observational study regarding vitiligo patients. Various in silico tools were used to investigate the impact of the selected mutation on the function, stability, post-translational modifications (PTMs), and secondary structures of the protein. In addition, a total of 489 subjects were enrolled in this study, including their demographic and clinicopathological data. Genotyping analysis was performed using real-time PCR for the single nucleotide polymorphism (SNP) rs1800450 on codon 54 of the MBL gene, utilizing TaqMan genotyping technology. In addition, implications of the studied variant on disease susceptibility and various clinicopathological data were analyzed. Computational analysis demonstrated the anticipated effects of the mutation on MBL protein. Furthermore, regarding the observational studies, rs1800450 SNP on codon 54 displayed comparable results in our population relative to global frequencies reported via the 1,000 Genomes Project. This SNP showed no significant association with either psoriasis or vitiligo disease risk in all genetic association models. Furthermore, rs1800450 SNP did not significantly correlate with any of the demographic or clinicopathological features of both psoriasis and vitiligo. Our findings highlighted that the rs1800450 SNP on the MBL2 gene has no role in the disease susceptibility to autoimmune skin diseases, such as psoriasis and vitiligo, among Egyptian patients. In addition, our analysis advocated the notion of the redundancy of MBL and revealed the lack of significant impact on both psoriasis and vitiligo disorders.

Effect of different strategies for excluding duplicate cultures on the correlation between hospital resistance rates and antibiotic consumption.

Studies may underestimate the impact of antibiotics on bacterial resistance when correlating hospital antibiotic use with resistance rates (RRs) that exclude duplicate cultures as duplicates usually include more resistant isolates. Comparing correlations between antibiotic consumption and RRs resulting from different strategies for excluding duplicates could help explore how their exclusion affects such correlations. We obtained antibiotics consumption and Pseudomonas aeruginosa susceptibility data from 2017 to 2021 for seven antibiotics and for carbapenems as a group in a university hospital. We calculated RRs using seven different time criteria for excluding duplicates. We assessed the correlations of antibiotic consumption to the same-year and next-year RR rates for the three most distinct rates. Duplicate cultures represented 53.45% of total cultures. RRs were higher when duplicates were included. We compared RRs resulting from excluding all duplicates, excluding duplicates monthly or admitting one culture per day. All antibiotics except meropenem showed a correlation with same-year RRs, either positive or negative, whereas all antibiotics showed a positive correlation with next-year RRs. For same-year and next-year correlations, the criteria with fewer duplicates (and therefore fewer resistant strains) found more correlations. However, the inclusion of duplicates taken at least 1 month apart found the most correlations. Admitting one culture per day found the fewest correlations. Excluding duplicates from RRs affects the correlation of antibiotics consumption with RRs in P. aeruginosa. Including at least some duplicate cultures in correlation analyses, such as those taken 1 month apart, should be considered.