Genomic Insights Into the Mechanism of Carbapenem Resistance Dissemination in Enterobacterales From a Tertiary Public Heath Setting in South Asia.

SUMMARY: 10.6% patients were CRE positive. Only 27% patients were prescribed at least 1 antibiotic to which infecting pathogen was susceptible. Burn and ICU admission and antibiotics exposures facilitate CRE acquisition. Escherichia coli ST167 was the dominant CRE clone. BACKGROUND: Given the high prevalence of multidrug resistance (MDR) across South Asian (SA) hospitals, we documented the epidemiology of carbapenem-resistant Enterobacterales (CRE) infections at Dhaka Medical College Hospital between October 2016 and September 2017. METHODS: We enrolled patients and collected epidemiology and outcome data. All Enterobacterales were characterized phenotypically and by whole-genome sequencing. Risk assessment for the patients with CRE was performed compared with patients with carbapenem-susceptible Enterobacterales (CSE). RESULTS: 10.6% of all 1831 patients with a clinical specimen collected had CRE. In-hospital 30-day mortality was significantly higher with CRE [50/180 (27.8%)] than CSE [42/312 (13.5%)] (P = .001); however, for bloodstream infections, this was nonsignificant. Of 643 Enterobacterales isolated, 210 were CRE; blaNDM was present in 180 isolates, blaOXA-232 in 26, blaOXA-181 in 24, and blaKPC-2 in 5. Despite this, ceftriaxone was the most commonly prescribed empirical antibiotic and only 27% of patients were prescribed at least 1 antibiotic to which their infecting pathogen was susceptible. Significant risk factors for CRE isolation included burns unit and intensive care unit admission, and prior exposure to levofloxacin, amikacin, clindamycin, and meropenem. Escherichia coli ST167 was the dominant CRE clone. Clustering suggested clonal transmission of Klebsiella pneumoniae ST15 and the MDR hypervirulent clone, ST23. The major trajectories involved in horizontal gene transfer were IncFII and IncX3, IS26, and Tn3. CONCLUSIONS: This is the largest study from an SA public hospital combining outcome, microbiology, and genomics. The findings indicate the urgent implementation of targeted diagnostics, appropriate antibiotic use, and infection-control interventions in SA public institutions.

Acceleration of the GAMESS-UK electronic structure package on graphical processing units.

The approach used to calculate the two-electron integral by many electronic structure packages including generalized atomic and molecular electronic structure system-UK has been designed for CPU-based compute units. We redesigned the two-electron compute algorithm for acceleration on a graphical processing unit (GPU). We report the acceleration strategy and illustrate it on the (ss|ss) type integrals. This strategy is general for Fortran-based codes and uses the Accelerator compiler from Portland Group International and GPU-based accelerators from Nvidia. The evaluation of (ss|ss) type integrals within calculations using Hartree Fock ab initio methods and density functional theory are accelerated by single and quad GPU hardware systems by factors of 43 and 153, respectively. The overall speedup for a single self consistent field cycle is at least a factor of eight times faster on a single GPU compared with that of a single CPU.

Long bonds and short barriers: ionization and isomerization of alkyl nitriles.

Ab initio molecular orbital calculations demonstrate that ionizing alkyl nitriles produces a dramatic geometry change involving lengthening of a C-CH(2)CN bond. The experimental determination of the adiabatic ionization energy of these species is thus very difficult. In addition, there are generally low barriers for 1,2-H shift reactions in the molecular ions leading to RCHCHN(+*) and RCHCNH(+*) isomers, which makes generating pure ionized alkyl nitrile in a mass spectrometer a challenge. Threshold photoelectron spectroscopy and threshold photoelecton photoion coincidence spectroscopy were employed to study the ionization and dissociation of two alkyl nitriles, in particular, pentanenitrile and 2,2-dimethylpropanenitrile. Threshold ionization is shown to result not in the respective molecular ions, but rather in isomeric forms, resulting in dissociation thresholds that lie below the calculated adiabatic ionization energies of the two molecules. Appearance energies for all observed fragment ions are reported and compared to available literature values. Charge separation in the dissociation of doubly ionized 2,2-dimethylpropanenitrile is observed as fragment-ion time-of-flight peak broadening at high photon energies.

Does tetrahydrofuran ring open upon ionization and dissociation? A TPES and TPEPICO investigation.

The threshold photoelectron spectrum (TPES) of tetrahydrofuran (THF) is compared to that of the unsaturated furan molecule. In general, there is a similarity in the orbital ionization profile for the two species, though unlike furan, THF exhibits (modest) vibrational detail only in the (9b)(-1) X (2)B band. An adiabatic ionization energy of 9.445 +/- 0.010 eV has been derived from the onset of the TPES spectrum. Threshold photoelectron photoion coincidence spectroscopy was used to explore the loss of a hydrogen atom from ionized THF over the photon energy range of 9.9-10.4 eV. RRKM fitting of the resulting breakdown curves yields an E(0) of 0.85 +/- 0.03 eV (82 +/- 3 kJ mol(-1)) (AE = 10.30 +/- 0.04 eV). If the G3 IE of 9.48 eV is used to convert the experimental data from photon energy to THF ion internal energy, E(0) = 0.81 +/- 0.01 eV (78 +/- 1 kJ mol(-1)). The latter value is closer to the G3 E(0) of 72 kJ mol(-1) for the formation of the cyclic ion 1. A variety of ring-opening reactions were also probed at the B3-LYP/6-31+G(d) and G3 levels of theory. The distonic isomer (*)CH(2)CH(2)CH(2)OCH(2)(+) lies 70 kJ mol(-1) higher than ionized THF, which places it within 1 kJ mol(-1) of the threshold for the dissociation to 1. All of the probed H-loss products from the distonic isomer (which includes singlet and triplet species) lie significantly higher in energy than ion 1, eliminating the possibility that ionized THF dissociates to m/z 71 via a ring-opening reaction in the present experiment. The derived Delta(double dagger)S value for the dissociation, 8 +/- 5 J K(-1) mol(-1), is also consistent with the formation of 1. The experimentally derived E(0) values can be used to derive the Delta(f)H(o)(0) for ion 1. Together with the Delta(f)H(o)(0) values for the THF ion (752.0 +/- 2 kJ mol(-1), derived from the neutral Delta(f)H(o)(0) of -154.9 +/- 0.7 kJ mol(-1) and experimental IE of 9.445 +/- 0.010 eV) and H atom (218.5 kJ mol(-1)) our E(0) of 82 +/- 3 kJ mol(-1) yields a Delta(f)H(o)(0) for ion 1 of 620 +/- 4 kJ mol(-1) (Delta(f)H(o)(298) = 594 +/- 4 kJ mol(-1)), in good agreement with the G3 Delta(f)H(o)(0) of 621 kJ mol(-1). Appearance energies for all fragment ions up to photon energies of 34 eV are also reported and discussed in comparison with the available literature.

Methyl t-butyl ether and methyl trimethylsilyl ether ions dissociate near their ionization thresholds: a TPES, TPEPICO, RRKM, and G3 investigation.

The threshold photoelectron spectra and threshold photoelectron photoion coincidence (TPEPICO) mass spectra of methyl t-butyl ether, (CH(3))(3)COCH(3) (MTBE), and methyl trimethylsilyl ether, (CH(3))(3)SiOCH(3) (MTMSE), have been measured using synchrotron radiation. The effect of silicon substitution on the unimolecular dissociation processes and the threshold photoelectron spectrum has been investigated. Both molecular ions dissociate at low internal energies. For ionized MTBE, the parent ion is no longer observed at an internal energy of only 0.2 eV. For this reason, it was not possible to fit the TPEPICO data to extract reliable thermochemical information. G3 level calculations place the molecular ion 5 kJ mol(-1) above the lowest-energy dissociation products, (CH(3))(2)COCH(3)(+) + (*)CH(3), suggesting the participation of an isomer, potentially the distonic ion (*)CH(2)(CH(3))(2)CO(+)(H)CH(3), in the dissociation. However, the calculations are not considered accurate enough to reliably determine the role this isomer plays, if any. RRKM modeling of the threshold region of the TPEPICO breakdown curves for ionized MTMSE leads to an E(0) for methyl loss of 63 +/- 2 kJ mol(-1), in good agreement with the G3 value of 66 kJ mol(-1). The resulting Delta(f)H(0) for (CH(3))(2)SiOCH(3)(+) of 384 +/- 10 kJ mol(-1) (Delta(f)H(298) = 361 +/- 10 kJ mol(-1)) is 28 kJ mol(-1) lower than the G3 value of 412 kJ mol(-1) due to the G3 Delta(f)H(0) for neutral MTMSE being 16 kJ mol(-1) higher than the previously reported value and the fact that the experimental IE(a) is 6 kJ mol(-1) lower than the G3 estimate. Appearance energy values for higher-energy fragmentation channels up to 36 (for MTBE) and 32 eV (for MTMSE) are reported and compared to literature values. An investigation of fragment ion peak broadening at high internal energy indicated that the two doubly charged molecular ions are not stable on the microsecond time scale. Each was found to dissociate into two singly charged ions along one or more neutral species.

The rotational spectrum and theoretical study of a dinuclear complex, MnRe(CO)(10).

The first rotational spectrum of a dinuclear complex, MnRe(CO)(10), has been obtained using a high-resolution pulsed beam microwave spectrometer. Sixty-four hyperfine components of the J=11-->J(')=12 and J=12-->J(')=13 rotational transitions were measured for two rhenium isotopomers. The B values obtained from the experiment are B=200.36871(18) MHz for the (187)Re isotopomer and B=200.5561(10) MHz for the (185)Re isotopomer. The measured rotational constants are in reasonably good agreement with the B values calculated from the x-ray diffraction structural data, and from theoretical calculations. The gas-phase Mn-Re bond distance is approximately 2.99 A, and the calculated value is only slightly longer. The experimental quadrupole coupling constant for the manganese atom is eQq(aa) ((55)Mn)=-16.52(5) MHz, and the corresponding quadrupole coupling constants for the two rhenium isotopomers are eQq(aa) ((187)Re)=370.4(4) MHz and eQq(aa) ((185)Re)=390.9(6) MHz. The quadrupole coupling constants were also determined from a variety of theoretical calculations, with very large Gaussian orbital bases. The best estimates, at a nonrelativistic level, are eQq(aa) ((55)Mn)=0.68 MHz and eQq(aa) ((187)Re)=327.6 MHz with a 874 GTO basis set, but the results are very basis set dependent, especially the sign of the Mn quadrupole coupling. Very slight bending of angles MnC(eq)O(eq) and ReC(eq)O(eq) angles is found in the calculations.