Susceptibility Spectrum Research Articles

Features of the pathogen and efficacy of drug-resistant tuberculosis treatment

According to the World Health Organization (WHO), nearly 10.6 million new cases of tuberculosis were detected in 2022, indicating an increase of 3.5 % from the reported 10.3 million in 2021. After the COVID-19 pandemic, the incidence of tuberculosis increased by 3.9 % from 2020 to 2022. According to the latest regulatory documents, multidrug-resistant pathogen is diagnosed when any bacteriologic or molecular genetic methods reveal drug resistance of M. Tuberculosis complex at least to isoniazid and rifampicin regardless of resistance to other antituberculosis drugs.With a wide range of virulence genes, the tuberculosis pathogen expresses genes in different phases of infection. Some genes are “switched on” in the early phases and are important for overcoming immune defenses and spreading the pathogen in the host, while others are important for survival in the latent phase. These characteristics of Mycobacterium tuberculosis determine the need for correct and adequate selection of therapy. The problem of diagnostics and treatment of drug-resistant tuberculosis remains extremely urgent. Despite the introduction of new tests for rapid determination of drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy regimen remains. When selecting therapy, the problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains. The need to assess the patient’s comorbid status, which affects the effectiveness of treatment and the occurrence of relapses, remains relevant.Despite the introduction of new tests for rapid determination of the drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy remains relevant. The problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains in the selection of therapy. Currently, the introduction of bedaquiline in therapy regimens is important for improving the effectiveness of tuberculosis treatment. In addition, studies are underway to shorten the duration of therapy for MDR-TB and XDR-TB, which is particularly important for maintaining patient adherence to treatment.

Therapeutic Phage Candidates for Targeting Prevalent Sequence Types of Carbapenem-Resistant Escherichia coli.

Carbapenem-resistant Escherichia coli (CREC) is a global threat to public health; therefore, alternative treatment options are urgently needed. Bacteriophages have emerged as promising candidates for combating CREC infections. This study aimed to investigate the genetic basis of phage sensitivity in CREC by evaluating carbapenem resistance among multidrug-resistant (MDR) E. coli isolated in Daegu, South Korea and analyzing their sequence types (STs) with phage susceptibility spectra. Among the 60 MDR E. coli isolates, 80.4% were identified as CREC, with 77.0% demonstrating resistance to imipenem and 66.6% to meropenem. Moreover, 70 lytic E. coli bacteriophages were isolated from hospital sewage water and evaluated against those 60 E. coli isolates. The phages exhibited lytic activity of 33%-60%, with average titers ranging from 5.6 × 1012 to 2.4 × 1013 PFU/mL (Plaque-Forming Unit). Furthermore, multilocus sequence typing (MLST) analysis of the bacterial isolates revealed 14 distinct STs, mostly belonging to ST131, ST410, and ST648. Notably, the phage susceptibility spectra of ST73, ST13003, ST648, ST2311, ST167, ST405, ST607, ST7962, and ST131 were significantly different. Thus, the isolated phages can effectively lyse CREC isolates, particularly those with clinically dominant STs. Conversely, ST410 exhibited a 14.2%-87.14% susceptibility spectrum, whereas ST1139, ST1487, ST10, and ST206 did not lyse, suggesting the presence of more resistant STs. Future studies are warranted to identify the reasons behind this resistance and address it. Ultimately, this study will aid in developing focused treatments to address these pressing global health issues.

Growth of L asparagine monohydrate doped potassium dihydrogen phosphate semiorganic crystals and its structural, thermal and optical properties

A novel semiorganic crystal is harvested by doping organic amino acid L asparagine monohydrate (LAM) with inorganic compound Potassium dihydrogen phosphate (KDP) by adopting slow evaporation method. Rietveld refinement of the XRD data was performed and the structural study exhibits single phase nature of the LAM doped KDP (LAM-KDP) crystals with a slight decrease in c-axis of the unit cell parameters. Other crystallographic parameters such as crystallite size and strain were also evaluated. The interaction of LAM with KDP was studied from FT-IR analysis by detecting functional groups. The constituting elements of the crystal were identified by energy dispersive X-ray (EDX) analysis. Etching study has been employed to study surface morphology of these crystals. From UV–vis transmittance data, optical band gap and different optical constants like Urbach energy, dielectric constants, electrical and optical conductivities were evaluated. Optical transparency of the LAM-KDP crystals is observed to increase. The third order nonlinear susceptibility χ(3) and nonlinear refractive index n2 of the grown crystals have been predicted using empirical Miller's rule. The value of χ(3) has increased from 1.87 × 10−13 esu to 4.29 × 10−13 esu due to LAM doping. Change in enthalpy (ΔH), change in Gibb's free energy (ΔG) and activation energy Ea during chemical reaction were calculated by thermogravimetric analysis (TGA). Thermal decomposition characteristics of the crystals were analyzed by differential scanning calorimetry (DSC). The high transparency of LAM-KDP crystals in the entire visible spectrum and larger values of nonlinear susceptibility χ(3) and nonlinear refractive index n2 make the synthesized crystal applicable for NLO and optoelectronic devices applications.

On the origin of time-aging-time superposition.

Time-aging-time superposition and the concept of single-parameter aging refer to the experimentally verified scenario in which the relaxation profile is shifted as a whole along the logarithmic time or frequency scale during physical aging, i.e., without changing the shape of the susceptibility spectrum or decay function. This homogeneous aspect of aging and structural recovery appears to contrast the heterogeneous nature of structural relaxation in equilibrium. A picture is proposed in which both structural recovery and relaxation are heterogeneous, but lacking a local correlation of time constants. This scenario is consistent with time-aging-time superposition and single-parameter aging, as well as with recovery and relaxation processes being subject to practically the same time constant dispersion.

Dynamic susceptibility of dipolar coupled magnetic vortices

We report a calculation of the dynamic susceptibility of a pair of ferromagnetic circular nanocylinders stacked along the common axis, one on the other, and separated by a thin nonmagnetic spacer. Our theoretical model considers the dipolar energy without restrictions on dipolar sums, along with the anisotropy and exchange energies. Our results indicate that the nanocylinders dipolar interaction may affect the susceptibility spectrum. We have found, for instance, that a 30nm thick, 70nm diameter Fe nanocylinder holds a single magnetic vortex, and the planar susceptibility (χxx) spectrum displays two low-frequency peaks (at 0.37 and 1.00 GHz). We have also found that the χxx susceptibility spectrum of dipolar-coupled vortices in a pair of Fe nanocylinders with a 5 nm spacer exhibits peaks at 0.3, 0.7, 1.2, and 1.4 GHz. Furthermore, the relative weight of the peaks is controlled by the degree of spatial localization of these excitations.

The role of R-plasmids in hospital strains of Proteus

The antibiotic sensitivity of Proteus strains isolated between 2017 and 2021 was investigated. A total of 85 Proteus strains were analyzed, revealing the widespread presence of poly-resistant forms of this pathogen. The examination of the antibiotic susceptibility spectrum in these strains demonstrated that those isolated from 2017 to 2021 exhibited similarities in their resistance profiles, with an expanding range of resistance observed towards gentamycin, kanamycin, carbenicillin, and others. The study identified that hospital-derived Proteus strains possess both conjugative and non-conjugative plasmids, distributed across different compatibility groups. It was shown that 55% of Proteus strains have conjugative R-plasmids, determining stability to streptomycin, gentamycin, carbenicillin, tetracycline, chloramphenicol, refer to T, J, M, N groups of incompatibility and have molecular masses 53.0; 33.0; 38.0; 49.0 MDa, respectively. In Proteus strains plasmids belonging to Inc-PI group of incompatibility were found. Furthermore, non-conjugative R-plasmids were identified in Proteus strains, conferring stability to tetracycline and streptomycin, with molecular masses of 7.2 and 5.8 MDa, respectively. Thus, the investigation of Proteus strains isolated in two clinics highlighted the participation of both conjugative and non-conjugative resistance plasmids in the development of hospital-associated Proteus strains.

Two-dimensional realization of electromagnetically induced phase grating in a quantum dot nanostructure

In this paper a novel method for electromagnetically induced phase grating in a quantum dot nanostructure is proposed. The four-level quantum dot nanostructure which is designed by solving the Schrödinger and Poisson equations. By size control of quantum dot and external voltage, one can obtain appropriate energy levels which can be interacted by four-optical fields. In this case, a probe, a two-dimensional standing wave and a driving field simultaneously interact by quantum dot for creation of coherent population trapping. A terahertz (THz) signal can influence the electron population in dark and bright levels, therefore optical susceptibility and transmission spectrum of probe field in the medium can be altered. In the presence of the THz field, the medium becomes phase dependent and this makes more of probe energy transfer to the higher order of the diffraction.

Detection of Extended-spectrum β-lactamase-producing Escherichia coli isolates by isothermal amplification and association of their virulence genes and phylogroups with extraintestinal infection

Extraintestinal pathogenic Escherichia coli (ExPEC) producing extended-spectrum β-lactamases (ESBL) cause serious human infections due to their virulence and multidrug resistance (MDR) profiles. We characterized 144 ExPEC strains (collected from a tertiary cancer institute) in terms of antimicrobial susceptibility spectrum, ESBL variants, virulence factors (VF) patterns, and Clermont’s phylogroup classification. The developed multiplex recombinase polymerase amplification and thermophilic helicase-dependent amplification (tHDA) assays for blaCTX-M, blaOXA, blaSHV, and blaTEM detection, respectively, were validated using PCR-sequencing results. All ESBL-ExPEC isolates carried blaCTX-M genes with following prevalence frequency of variants: blaCTX-M-15 (50.5%) > blaCTX-M-55 (17.9%) > blaCTX-M-27 (16.8%) > blaCTX-M-14 (14.7%). The multiplex recombinase polymerase amplification assay had 100% sensitivity, and specificity for blaCTX-M, blaOXA, blaSHV, while tHDA had 86.89% sensitivity, and 100% specificity for blaTEM. The VF genes showed the following prevalence frequency: traT (67.4%) > ompT (52.6%) > iutA (50.5%) > fimH (47.4%) > iha (33.7%) > hlyA (26.3%) > papC (12.6%) > cvaC (3.2%), in ESBL-ExPEC isolates which belonged to phylogroups A (28.4%), B2 (28.4%), and F (22.1%). The distribution of traT, ompT, and hlyA and phylogroup B2 were significantly different (P < 0.05) between ESBL-ExPEC and non-ESBL-ExPEC isolates. Thus, these equipment-free isothermal resistance gene amplification assays contribute to effective treatment and control of virulent ExPEC, especially antimicrobial resistance strains.

Emerging insights into ethnic-specific TP53 germline variants.

The recent expansion of human genomics repositories has facilitated the discovery of novel TP53 variants in populations of different ethnic origins. Interpreting TP53 variants is a major clinical challenge because they are functionally diverse, confer highly variable predisposition to cancer (including elusive low-penetrance alleles), and interact with genetic modifiers that alter tumor susceptibility. Here, we discuss how a cancer risk continuum may relate to germline TP53 mutations on the basis of our current review of genotype-phenotype studies and an integrative analysis combining functional and sequencing datasets. Our study reveals that each ancestry contains a distinct TP53 variant landscape defined by enriched ethnic-specific alleles. In particular, the discovery and characterization of suspected low-penetrance ethnic-specific variants with unique functional consequences, including P47S (African), G334R (Ashkenazi Jewish), and rs78378222 (Icelandic), may provide new insights in terms of managing cancer risk and the efficacy of therapy. Additionally, our analysis highlights infrequent variants linked to milder cancer phenotypes in various published reports that may be underdiagnosed and require further investigation, including D49H in East Asians and R181H in Europeans. Overall, the sequencing and projected functions of TP53 variants arising within ethnic populations and their interplay with modifiers, as well as the emergence of CRISPR screens and AI tools, are now rapidly improving our understanding of the cancer susceptibility spectrum, leading toward more accurate and personalized cancer risk assessments.

Primary cilia TRP channel regulates hippocampal excitability

Polycystins (PKD2, PKD2L1, and PKD2L2) are members of the transient receptor potential family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney nephron cilia is associated with polycystic kidney disease, but the function of PKD2L1 in neurons is undefined. In this report, we develop animal models to track the expression and subcellular localization of PKD2L1 in the brain. We discover that PKD2L1 localizes and functions as a Ca2+ channel in the primary cilia of hippocampal neurons that apically radiate from the soma. Loss of PKD2L1 expression ablates primary ciliary maturation and attenuates neuronal high-frequency excitability, which precipitates seizure susceptibility and autism spectrum disorder-like behavior in mice. The disproportionate impairment of interneuron excitability suggests that circuit disinhibition underlies the neurophenotypic features of these mice. Our results identify PKD2L1 channels as regulators of hippocampal excitability and the neuronal primary cilia as organelle mediators of brain electrical signaling.

Strong adaptive immunity in humans with inherited CD4 deficiency

Abstract Since the early 1970s when the T cell receptor was first characterized, the role of human CD4 in adaptative immunity has been extensively studied, especially in the context of HIV infection and inborn error of immunity (e.g. HLA class II deficiency). Nonetheless, it was only recently (2019, 2021) that patients with inactivating germline mutations in CD4has been described. Herein, we present five novel patients from three unrelated kindred with bi-allelic rare variants in CD4. Consistent with previous studies, patients showed a broad spectrum of clinical infectious susceptibility which was rather mild given their lack of detectable CD4 +T cells in peripheral blood mononuclear cells (PBMCs). Despite an almost unremarkable immunophenotype, patient’s PBMCs were characterized by the expansion of an enigmatic CD4 −CD8 −(DN) TCRαβ +T cells population which retained some functional characteristic of typical CD4 +T cells. We observed that the patient’s DN cells transcriptionally (Sc-RNAseq) and functionally (cytokine production/secretion) were comparable to that of healthy donor CD8 −T cells. Interestingly, using cutting-edge long-read sc-RNAseq technology we revealed that patient’s DN cells expressed normal TCR repertoires, and paired TCRαβ sequences comparable to healthy donor CD4 +T cells. Furthermore, via biochemical studies we identified a CD4alternative transcript expressed in patient’s PBMCs (also detected in healthy donor cells) leading to the surface expression of an unreported CD4 shorter isoform which is not detectable with conventional CD4 antibodies. To conclude, our study not only characterizes novel CD4-deficient patients, but also reveals alternative CD4 isoform expression and its compensatory role in immunity. AAI Careers in Immunology Fellowship 2022 (RG222573)

Electron-phonon correlations inducing excitonic excitations in semimetal and semiconducting materials

The influence of phonons on the low-energy excitonic excitations at zero temperature in the extended Falicov-Kimball model has been investigated. In the framework of the unrestricted Hartree-Fock approximation, a set of self-consistent equations for the excitonic condensate order parameter and a lattice distortion is derived when both electron-phonon coupling and electron-hole Coulomb interaction are treated on an equal footing. The low-energy excitation properties of the excitonic condensate are addressed in signatures of the optical conductivity and the dynamical excitonic susceptibility function. The real part of the optical conductivity is evaluated by the Kubo linear response theory and the imaginary part of the dynamical excitonic susceptibility is found by adapting the random phase approximation. In the semimetal state, one always finds a sharp peak in the optical conductivity spectrum indicating the stability of the excitonic condensation in the BCS type if the correlation between electrons and phonons becomes significant. In contrast, the peak is smeared out on the semiconducting side indicating the stability of the BEC-type excitonic condensate. In this semiconducting side, the sharp peak signature appears and the system turns to the BCS-type excitonic condensation state by increasing the electron-phonon correlations. In either the semimetal or the semiconducting normal state, increasing the electron-phonon correlations always reinforces a low-energy sharp peak in the dynamical excitonic susceptibility spectrum, indicating the existence of the tightly bound excitonic excitations before the condensation state. Specifically, on the semiconducting side, the ``halo'' phase with the preformed excitons exiting outside of the BEC-excitonic condensation state has been specified. The halo phase becomes more recognizable by raising the electron-phonon correlations.

Primary cilia TRP channels regulate hippocampal excitability.

Polycystins (PKD2, PKD2L1 and PKD2L2) are members of transient receptor potential (TRP) family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney is associated with polycystic kidney disease but the physiological role of PKD2L1 is largely undefined. In this report, we develop animal models to track the expression and subcellular localization of these channels in the brain. We discover PKD2L1 localizes and functions as a Ca2+ channel in the primary cilia of hippocampal neurons, which apically radiate from the axon hillock. Loss of PKD2L1 expression ablates primary cilia maturation, and attenuates neuronal high frequency excitability, and precipitates seizure susceptibility and autism spectrum disorder-like behavior in mice. The disproportionate impairment of interneuron excitability suggests circuit disinhibition underlies the neurophenotypic features of these mice. Our results identify PKD2L1 channels as regulators of hippocampal excitability and the neuronal primary cilia as organelle mediators of brain electrical signaling.

Method of the assessment of the degree of immune disturbances in patients with pulmonary tuber- culosis depending on the spectrum of drug resistance of the etiological agent

The aim of the study was to evaluate the disturbances of cell-mediated immunity, natural resistance and humoral immunity in patients diagnosed with pulmonary tuberculosis depending on the drug susceptibility spectrum of the etiological agent in order to develop a procedure to identify the degree of severity and pathogenetic types. Material and methodology: a prospective, selective, case-control study was performed, which included 129 new cases of tuberculosis diagnosed during 2017-2018, distributed in groups depending on the spectrum of the drug resistance. Results: immune defficiencies were more evident in patients with MDR-TB, especially in those who acquired the resistance, and cell-mediated immunity was more suppressed, followed by natural resistance. Hyperfunction of the humoral immunity was confirmed in two thirds of all groups. The proposed method can be applied in the evaluation of the immune state in TB patients.

The Mystery of Cancer Resistance: A Revelation Within Nature.

Cancer, a disease due to uncontrolled cell proliferation is as ancient as multicellular organisms. A 255-million-years-old fossilized forerunner mammal gorgonopsian is probably the oldest evidence of cancer, to date. Cancer seems to have evolved by adapting to the microenvironment occupied by immune sentinel, modulating the cellular behavior from cytotoxic to regulatory, acquiring resistance to chemotherapy and surviving hypoxia. The interaction of genes with environmental carcinogens is central to cancer onset, seen as a spectrum of cancer susceptibility among human population. Cancer occurs in life forms other than human also, although their exposure to environmental carcinogens can be different. Role of genetic etiology in cancer in multiple species can be interesting with regard to not only cancer susceptibility, but also genetic conservation and adaptation in speciation. The widely used model organisms for cancer research are mouse and rat which are short-lived and reproduce rapidly. Research in these cancer prone animal models has been valuable as these have led to cancer therapy. However, another rewarding area of cancer research can be the cancer-resistant animal species. The Peto's paradox and G-value paradox are evident when natural cancer resistance is observed in large mammals, like elephant and whale, small rodents viz. Naked Mole Rat and Blind Mole Rat, and Bat. The cancer resistance remains to be explored in other small or large and long-living animals like giraffe, camel, rhinoceros, water buffalo, Indian bison, Shire horse, polar bear, manatee, elephant seal, walrus, hippopotamus, turtle and tortoise, sloth, and squirrel. Indeed, understanding the molecular mechanisms of avoiding neoplastic transformation across various life forms can be potentially having translational value for human cancer management. Adapted and Modified from (Hanahan and Weinberg 2011).

Nonlinear optical response of a strongly-driven quantum dot exciton-biexciton system

We examine the effective linear and the third-order nonlinear optical susceptibilities of an InAs/GaAs semiconductor quantum dot with a cascade exciton-biexciton configuration that is strongly driven by a nearly resonant pump electromagnetic field, while, at the same time, it interacts with a weak electromagnetic field. We assume that the applied fields are linearly polarized, which permits us to simplify the relative energy level diagram by using a three-level ladder-type scheme. We derive the equations of motion, in the dipole approximation, in a rotating frame, and follow an expansion approach to calculate the components of the density matrix which are associated to the effective linear and the self-Kerr third-order nonlinear optical susceptibilities. We present the spectra of the first-order susceptibility and the self-Kerr susceptibility and investigate the dependence of their profiles on the Rabi frequency and the detuning of the pump field, in the one-photon and the two-photon resonance regimes. The role of the biexciton energy shift on the susceptibilities is also studied. In addition, we present a dressed state analysis which appears to be crucial for obtaining a better understanding of several spectral properties of the susceptibilities.

ANTIBIOTIC RESISTANCE PROFILES IN ACINETOBACTER BAUMANNII STRAINS ISOLATED FROM WASTEWATER IN SOUTHERN ROMANIA

Introduction: Given the high mobility of antibiotic resistance genes and their propensity for transmission among human, animal, and environmental reservoirs, managing the risks associated with antibiotic resistance is a challenging goal. The Acinetobacter species are among the most relevant bacteria with clinical significance and special abilities to acquire resistance mechanisms and to survive in diverse environmental conditions. A particular interest in A. baumannii strains is their association with chronic nosocomial infections, such as pneumonia, urinary tract infections, soft tissue infections, or nosocomial meningitis. Objectives: This study aimed to compare the antibiotic resistance profiles of 48 A. baumannii strains collected in 2020 and 2021 from a wastewater treatment plant (WWTP) in the southern region of Romania and evaluate the role of WWTP in disseminating antibiotic resistance in the aquatic environment. Methods: The detection and quantification of resistant bacteria were achieved using the filter membrane technique and chromogenic media supplemented with antibiotics. The analysis and identification of the bacterial species present in the collected samples were carried out using Bruker MALDI-TOF spectrometry. The antibiotic susceptibility spectrum was tested by the standardized disc diffusion method. Results: Among the analyzed strains, 47 presented resistance phenotypes of clinical and epidemiological importance, 15 of them being MDR, 9 XDR, and 23 PDR. Conclusion: Our results demonstrate the role of the WWTP in the accumulation and dissemination of antimicrobial resistance from the clinical and other anthropic sources into the aquatic environment, as well as the potential impact of the COVID-19 pandemic on the evolution of this phenomenon.

2051. Relebactam enhances Imipenem activity across the Imipenem susceptibility spectrum among Pseudomonas aeruginosa isolates collected in the United States--SMART 2018-2020

Abstract Background The Beta-Lactamase Inhibitors (BLIs) Relebactam (REL) and Avibactam (AVI) both inhibit class A and C beta-lactamases and are approved in combination with the beta-lactam antibiotics imipenem (IMI/REL) and ceftazidime (CAZ/AVI), respectively. Our goal was to evaluate the effect of these BLIs on susceptibility of Pseudomonas aeruginosa isolates that are either nonsusceptible (NS), Intermediate (I) or Susceptible (S) to the partner beta-lactam antibiotic. Methods In 2018-2020, ∼20 unique participating sites in the United States each collected up to 250 consecutive aerobic gram-negative isolates per year (50 each from urine, intraabdominal and blood; 100 from lower respiratory tract). Susceptibility to Imipenem (IMI) and Ceftazidime (CAZ) were determined alone as well as in combination with their cognate BLIs. MICs were determined using broth microdilution and evaluated by CLSI interpretive criteria. Results A total of 2,537 P. aeruginosa isolates were evaluated. Among IMI-NS isolates (MIC &amp;gt;2 μg/mL) REL restored IMI susceptibility to 75% and among CAZ-NS isolates (MIC &amp;gt;8 μg/mL) AVI restored CAZ susceptibility to 73%. For IMI-I isolates (MIC of 4 μg/mL), the presence of REL restored susceptibility to 98%, and 95% had MICs at least one dilution less than the susceptible breakpoint. For CAZ-I isolates (MIC of 16 μg/mL), AVI restored susceptibility to 84% of isolates, and 62% had MICs at least one dilution below the susceptible breakpoint. The addition of REL shifted the mode IMI MIC of IMI-S (MIC ≤ 2 μg/mL) isolates 4-fold, from 2 to 0.5 μg/mL, whereas there was no change in the mode CAZ MIC of CAZ-S (MIC ≤ 8 μg/mL) isolates in the presence of AVI. Conclusion Both REL and AVI restore susceptibility to P. aeruginosa isolates nonsusceptble to their cognate beta-lactam antibiotics (IMI and CAZ, respectively). However, REL had greater enhancement of IMI towards IMI-I isolates when compared to the effect of AVI on CAZ towards CAZ-I isolates. REL substantially enhances IMI activity towards IMI-S isolates whereas no such enhancement was observed for AVI upon CAZ activity towards CAZ-S isolates. REL is differentiated by its ability to enhance the activity of the cognate beta-lactam (IMI) across the susceptibility spectrum. Disclosures Charles A. DeRyke, PharmD, Merck &amp; Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck &amp; Co., Inc.: Stocks/Bonds.

Unusual non-albicans candida yeast in South India: Incidence in cancer patients and antifungal susceptibility towards first-line drugs

Unusual Ascomycetes yeasts are frequently reported in obstinate infections among the cancer population. Emergence of resistance among the non-albicans yeasts towards promising first-line azoles queries over treatment options. The present study probes on the recent trends in incidence of and emerging non- albicans yeasts in cancer patients and to determine the species-wise antifungal susceptibility towards first-line Triazoles and Echinocandin. A total of 53 isolates recovered from the clinical specimens collected from 87 cancer patients were presumptively identified on CHROMagar and speciated by sequencing internal transcribed spacer (ITS) target. The species-wise antifungal susceptibility were determined for the first-line triazoles (Fluconazole, Voriconazole, Posaconazole) and Echinocandin (Anidulafungin) following CLSI guidelines. The proportion of Candida isolates were predominantly non-albicans Candida (NAC) species (85%) and (15%). All isolates were speciated using ITS sequencing and the spectrum of NAC species isolated were dominated with (17) followed by (9), (5), C. tropicalis (4), (3), (3), (2) and one isolate of each and The unusual NAC species showed varied resistance profile towards first-line azoles and were susceptible to Anidulafungin. The changing spectrum, high prevalence and pattern of low level azoles susceptibility among unusual NAC species recovered from the cancer population are alarming.

Experimental and Theoretical Heterodyne-Detected Sum Frequency Generation Spectroscopy of Isotopically Pure and Diluted Water Surfaces.

The χ(2) (second-order nonlinear optical susceptibility) spectrum of the water surface has been a matter of debate for a few decades. Here, we report that we experimentally measured the isotopic dilution dependence of the χ(2) spectrum and theoretically reproduced it by employing the quantum/classical mixed approach with a new idea to subtract an artifact. The present theoretical framework allows for clarifying the effects of the intramolecular, intermolecular, and Fermi resonance couplings on the OH-stretch vibrational spectra of water at the surface as well as in the bulk.