Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Causing Nosocomial Meningitis in the Neurological Intensive Care Unit.

Acinetobacter baumannii is one of the significant healthcare-associated meningitis agents characterized by multidrug resistance and a high mortality risk. Thirty-seven A. baumannii strains were isolated from thirty-seven patients of Moscow neuro-ICU with meningitis in 2013-2020. The death rate was 37.8%. Strain susceptibility to antimicrobials was determined on the Vitek-2 instrument. Whole-genome sequencing was conducted using Illumina technology; the sequence types (ST), capsular types (KL), lipooligosaccharide outer core locus (OCL), antimicrobial resistance genes, and virulence genes were identified. The prevalent ST was ST2, belonging to the international clone IC2, and rarer, ST1, ST19, ST45, ST78, ST106, and ST400, with prevalence of KL9 and OCL1. Twenty-nine strains belonged to multidrug-resistant (MDR) and eight extensively drug-resistant (XDR) categories. Genes conferring resistance to beta-lactams (blaPER, blaGES, blaADC, blaCARB, blaCTX-M, blaTEM, and blaOXA-types), aminoglycosides (aac, aad, ant, aph, and arm), tetracyclines (tet), macrolides (msr and mph), phenicols (cml, cat, and flo), sulfonamides (dfr and sul), rifampin (arr), and antiseptics (qac) were identified. Virulence genes of nine groups (Adherence, Biofilm formation, Enzymes, Immune evasion, Iron uptake, Regulation, Serum resistance, Stress adaptation, and Antiphagocytosis) were detected. The study highlights the heterogeneity in genetic clones, antimicrobial resistance, and virulence genes variability among the agents of A. baumannii meningitis, with the prevalence of the dominant international clone IC2.

Association of Preoperative Glycated Hemoglobin and Early Postoperative Infections After Elective Craniotomy: A Retrospective Cohort Study.

BACKGROUND: The prognostic value of preoperative glycated hemoglobin (HbA1c) testing is controversial. The available evidence on the role of preoperative HbA1c in predicting postoperative complications after different surgical procedures has been conflicting. The primary aim of our retrospective observational cohort study was to assess the association between preoperative HbA1c and postoperative infections after elective craniotomy. METHODS: We extracted and analyzed data from an internal hospital database on 4564 patients who underwent neurosurgical intervention from January 2017 to May 2022. The primary outcome measure of the present study was infections established in the first week after surgery using the Centers for Disease Control and Prevention criteria. The records were stratified by the HbA1c values and intervention types. RESULTS: For patients who had undergone brain tumor removal with a preoperative HbA1c ≥6.5%, the odds of early postoperative infections were increased (odds ratio, 2.08; 95% confidence interval, 1.16-3.72; P = 0.01). We found no association between HbA1c and early postoperative infections for patients who had undergone elective cerebrovascular intervention, cranioplasty, or a minimally invasive procedure. After adjusting for age and gender, the threshold for significant infection risk for neuro-oncological patients increased with an HbA1c ≥7.5% (adjusted odds ratio, 2.97; 95% confidence interval, 1.37-6.45; P = 0.0058). CONCLUSIONS: For patients undergoing elective intracranial surgery for brain tumor removal, a preoperative HbA1c ≥7.5% is associated with a higher infection rate within the first postoperative week. Future prospective studies are required to assess the prognostic value of this association for clinical decision-making.

High-Molecular-Weight Plasmids Carrying Carbapenemase Genes blaNDM-1, blaKPC-2, and blaOXA-48 Coexisting in Clinical Klebsiella pneumoniae Strains of ST39.

BACKGROUND: Klebsiella pneumoniae, a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids. METHODS: Four clinical K. pneumoniae isolates were collected from four patients of a neuro-intensive care unit in Moscow, Russia, during the point prevalence survey. The AMR phenotype was estimated using the Vitec-2 instrument, and whole genome sequencing (WGS) was done using Illumina and Nanopore technologies. RESULTS: All strains were resistant to beta-lactams, nitrofurans, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines. WGS analysis revealed that all strains were closely related to K. pneumoniae ST39, capsular type K-23, with 99.99% chromosome identity. The novelty of the study is the description of the strains carrying simultaneously three large plasmids of the IncHI1B, IncC, and IncFIB groups carrying the carbapenemase genes of three types, blaOXA-48, blaNDM-1, and blaKPC-2, respectively. The first of them, highly identical in all strains, was a hybrid plasmid that combined two regions of the resistance genes (blaOXA-48 and blaTEM-1 + blaCTX-M-15 + blaOXA-1 + catB + qnrS1 + int1) and a region of the virulence genes (iucABCD, iutA, terC, and rmpA2::IS110). CONCLUSION: The spread of K. pneumoniae strains carrying multiple plasmids conferring resistance even to last-resort antibiotics is of great clinical concern.

Rectal and Tracheal Carriage of Carbapenemase Genes and Class 1 and 2 Integrons in Patients in Neurosurgery Intensive Care Unit.

The spread of multidrug-resistant Gram-negative bacteria, which is associated with the distribution of beta-lactamase genes and class 1 and 2 integrons, is a global problem. In this study, in the Moscow neurosurgery intensive care unit (neuro-ICU), the high prevalence of the above-stated genes was found to be associated with intestinal and tracheal carriage. Seven-point prevalence surveys, which included 60 patients in the neuro-ICU, were conducted weekly in the period from Oct. to Nov. 2019. A total of 293 clinical samples were analyzed, including 146 rectal and 147 tracheal swabs; 344 Gram-negative bacteria isolates were collected. Beta-lactamase genes (n = 837) were detected in the isolates, including beta-lactamase blaTEM (n = 162), blaSHV (n = 145), cephalosporinase blaCTX-M (n = 228), carbapenemase blaNDM (n = 44), blaKPC (n = 25), blaOXA-48 (n = 126), blaOXA-51-like (n = 54), blaOXA-40-like (n = 43), blaOXA-23-like (n = 8), and blaVIM (n = 2), as well as class 1 (n = 189) and class 2 (n = 12) integrons. One extensively drug-resistant Klebsiella pneumoniae strain (sequence type ST39 and capsular type K23), simultaneously carried beta-lactamase genes, blaSHV-40 and blaTEM-1B, three carbapenemase genes, blaNDM, blaKPC, and blaOXA-48, the cephalosporinase gene blaCTX-M, and two class 1 integrons. Before this study, such heavily armed strains have not been reported, suggesting the ongoing evolution of antibiotic resistance.

A Fullerene-Platinum Complex for Direct Functional Patterning of Single Metal Atom-Embedded Carbon Nanostructures.

The development of patterning materials ("resists") at the nanoscale involves two distinct trends: one is toward high sensitivity and resolution for miniaturization, the other aims at functionalization of the resists to realize bottom-up construction of distinct nanoarchitectures. Patterning of carbon nanostructures, a seemingly ideal application for organic functional resists, has been highly reliant on complicated pattern transfer processes because of a lack of patternable precursors. Herein, we present a fullerene-metal coordination complex as a fabrication material for direct functional patterning of sub-10 nm metal-containing carbon structures. The attachment of one platinum atom per fullerene molecule not only leads to significant improvement of sensitivity and resolution but also enables stable atomic dispersion of the platinum ions within the carbon matrix, which may gain fundamentally new interest in functional patterning of hierarchical carbon nanostructures.

Severe Intraoperative Hyperglycemia and Infectious Complications After Elective Brain Neurosurgical Procedures: Prospective Observational Study.

BACKGROUND: Postoperative infections after brain surgery are a serious complication potentially worsening the outcome of surgical treatment. Severe intraoperative hyperglycemia (SIH) contributes to both infectious and noninfectious postoperative complications. However, there are a lack of data on the incidence of SIH in patients undergoing elective neurosurgical brain procedures and its association with the risk of postoperative infections. METHODS: A total of 514 patients were prospectively enrolled in this single-center observational cohort clinical study to assess the incidence of SIH (blood glucose concentration [BGC] ≥180 mg/dL) in adult patients undergoing elective brain neurosurgical procedures and its association with postoperative infections. Both nondiabetic and diabetic patients were included in the study. BGC was determined by whole-blood analyses taken at the beginning and at the end of the surgery. Diagnosis of infection (wound, pulmonary, blood stream, urinary tract infection, or central nervous system infection) was established according to US Centers for Disease Control and Prevention (CDC) criteria within the first postoperative week. RESULTS: SIH was recorded in at least 1 blood sample in 23 patients (4.5%). Infectious complications within the first postoperative week were diagnosed in 40 patients (7.8%). Five of 23 patients (22%) with SIH had postoperative infections, compared with 35 of 491 patients (7%) without SIH (odds ratio [OR] = 3.71; 95% confidence interval [CI], 1.24-11.09; P = .018 after fitting a multiple logistic regression model to adjust for age, body mass index [BMI], and surgery duration). Intraoperative BGC >140 mg/dL was also associated with an increased risk of postoperative infections (OR = 3.10; 95% CI, 1.43-6.75; P = .004). Elevated preoperative glycated hemoglobin (HbA1c) concentration was also associated with postoperative infections in the study population (OR = 2.4; 95% CI, 1.02-6.00; P = .045). Age, BMI, American Society of Anesthesiologists (ASA) physical status, type of surgery, and duration of intervention had no significant association with the postoperative infection rate. CONCLUSIONS: SIH is associated with a higher risk of infections within the first postoperative week in patients undergoing elective brain neurosurgical procedures. Preoperative HbA1c is a reliable marker of the potential risk both of SIH and postoperative infections in the selected cohort. Future studies need to assess possible improvements in outcome under more precise monitoring and tighter control of perioperative hyperglycemia.

The incidence and outcomes of healthcare-associated respiratory tract infections in non-ventilated neurocritical care patients: Results of a 10-year cohort study.

The incidence of healthcare-associated respiratory tract infections in non-ventilated patients (NVA-HARTI) in neurosurgical intensive care units (ICUs) is unknown. The impact of NVA-HARTI on patient outcomes and differences between NVA-HARTI and ventilator-associated healthcare-associated respiratory tract infections (VA-HARTI) are poorly understood. Our objectives were to report the incidence, hospital length of stay (LOS), ICU LOS, and mortality in NVA-HARTI patients and compare these characteristics to VA-HARTI in neurocritical care patients. This cohort study was conducted in a neurosurgical ICU in Moscow. From 2011 to 2020, all patients with an ICU LOS > 48 h were included. A competing risk model was used for survival and risk analysis. A total of 3,937 ICU admissions were analyzed. NVA-HARTI vs VA-HARTI results were as follows: cumulative incidence 7.2 (95%CI: 6.4-8.0) vs 15.4 (95%CI: 14.2-16.5) per 100 ICU admissions; incidence rate 4.2 ± 2.0 vs 9.5 ± 3.0 per 1000 patient-days in the ICU; median LOS 32 [Q1Q3: 21, 48.5] vs 46 [Q1Q3: 28, 76.5] days; median ICU LOS 15 [Q1Q3: 10, 28.75] vs 26 [Q1Q3: 17, 43] days; mortality 12.3% (95%CI: 7.9-16.8) vs 16.7% (95%CI: 13.6-19.7). The incidence of VA-HARTI decreased over ten years while NVA-HARTI incidence did not change. VA-HARTI was an independent risk factor of death, OR 1.54 (1.11-2.14), while NVA-HARTI was not. Our findings suggest that NVA-HARTI in neurocritical care patients represents a significant healthcare burden with relatively high incidence and associated poor outcomes. Unlike VA-HARTI, the incidence of NVA-HARTI remained constant despite preventive measures. This suggests that extrapolating VA-HARTI research findings to NVA-HARTI should be avoided.

Comparison of the Efficacy and Safety of Ketoprofen Plaster and Diclofenac Plaster for Osteoarthritis-Related Knee Pain: A Multicenter, Randomized, Active-Controlled, Open-Label, Parallel-Group, Phase III Clinical Trial.

PURPOSE: To compare the efficacy and safety of ketoprofen plasters and diclofenac plasters after 3 weeks of administration in patients with osteoarthritis-related knee pain. METHODS: This multicenter, randomized, active-controlled, open-label, parallel-group, noninferiority phase III study randomized 236 adults with osteoarthritis-related knee pain for 3 weeks with ketoprofen plaster 30 mg twice daily (n = 118) or diclofenac plaster 15 mg once daily (n = 118). The primary efficacy end point was the mean change from baseline to week 3 in the mean knee pain intensity score during walking, as measured by a 100-mm visual analog scale with a predefined noninferiority margin of 10.0 mm. Secondary end points included changes in knee pain intensity score during walking (weeks 1 and 2) and at rest (weeks 1, 2, and 3), Knee Injury and Osteoarthritis Outcome Score, Patient Global Impression of Improvement scale assessments, and frequency of rescue medication use after 2 and 3 weeks of treatment. FINDINGS: A total of 223 patients (115 in the ketoprofen group and 108 in the diclofenac group) were included in the per-protocol analysis. After 3 weeks of treatment, the least squares mean change from baseline in knee pain intensity scores during walking was -35.9 (95% CI, -39.7 to -32.2) in the ketoprofen group and -31.7 (95% CI, -35.5 to -27.9) in the diclofenac group, with noninferiority found (least squares mean difference, -4.2; 95% CI, -9.6 to 1.1). Ketoprofen significantly (P < 0.05) reduced the pain intensity score at rest after 2 and 3 weeks of treatment compared with diclofenac. No statistically significant difference was found between the groups in terms of changes in pain intensity score during walking at weeks 1, 2, and 3. The mean Patient Global Impression of Improvement score was statistically significant (P < 0.001) in favor of ketoprofen after 2 and 3 weeks of treatment. In addition, the Knee Injury and Osteoarthritis Outcome Score improved in both groups, and no statistically significant difference was found between the groups in terms of frequency of rescue medication use. The overall adverse event profile of the groups was similar, and no difference was found in skin reaction rates between the 2 groups. IMPLICATIONS: Ketoprofen plasters can be effectively and safely administered to patients with osteoarthritis-related knee pain.

Multidrug-Resistant Klebsiella pneumoniae Causing Severe Infections in the Neuro-ICU.

The purpose of this study was the identification of genetic lineages and antimicrobial resistance (AMR) and virulence genes in Klebsiella pneumoniae isolates associated with severe infections in the neuro-ICU. Susceptibility to antimicrobials was determined using the Vitek-2 instrument. AMR and virulence genes, sequence types (STs), and capsular types were identified by PCR. Whole-genome sequencing was conducted on the Illumina MiSeq platform. It was shown that K. pneumoniae isolates of ST14K2, ST23K57, ST39K23, ST76K23, ST86K2, ST218K57, ST219KL125/114, ST268K20, and ST2674K47 caused severe systemic infections, including ST14K2, ST39K23, and ST268K20 that were associated with fatal incomes. Moreover, eight isolates of ST395K2 and ST307KL102/149/155 were associated with manifestations of vasculitis and microcirculation disorders. Another 12 K. pneumoniae isolates of ST395K2,KL39, ST307KL102/149/155, and ST147K14/64 were collected from patients without severe systemic infections. Major isolates (n = 38) were XDR and MDR. Beta-lactamase genes were identified: blaSHV (n = 41), blaCTX-M (n = 28), blaTEM (n = 21), blaOXA-48 (n = 21), blaNDM (n = 1), and blaKPC (n = 1). The prevalent virulence genes were wabG (n = 41), fimH (n = 41), allS (n = 41), and uge (n = 34), and rarer, detected only in the genomes of the isolates causing severe systemic infections-rmpA (n = 8), kfu (n = 6), iroN (n = 5), and iroD (n = 5) indicating high potential of the isolates for hypervirulence.

External Ventricular Drainage in Patients With Acute Aneurysmal Subarachnoid Hemorrhage After Microsurgical Clipping: Our 2006-2018 Experience and a Literature Review.

Introduction The placement of an external ventricular drain (EVD) is widely practiced in neurosurgery for various diseases and conditions accompanied by impaired cerebrospinal fluid (CSF) circulation, intracranial hypertension (ICHyp), intraventricular hemorrhage (IVH), and hydrocephalus. Specialists have been using this method in patients with acute aneurysmal subarachnoid hemorrhage (aSAH) for more than 50 years. Extensive experience gained at the Burdenko Neurosurgical Center (BNC) in Moscow, the Russian Federation, in the surgical treatment of patients with acute aSAH enabled us to describe the results of using an EVD in patients after microsurgery. The objective of the research was to assess the effectiveness and safety of the EVD and clarify the indications for the microsurgical treatment of aneurysms in patients with acute SAH. Materials and methods From 2006 until the end of 2018, 645 patients registered in the BNC database underwent microsurgery for acute (0-21 days) aSAH. During the case study, we assessed the severity of hemorrhage according to the Fisher scale, the condition of patients on the Hunt-Hess (H-H) scale during surgery, the time of placement of EVD (before, during, and after surgery), and the duration of EVD. The number of patients with parenchymal intracranial pressure (ICP) transducers was assessed by the degree of correlation of ICP data through the EVD and parenchymal ICP transducer. One of the aims of the research was to compare the frequency of using EVD and decompressive craniectomy (DCH). The incidence of EVD-associated meningitis was analyzed. The need for a ventriculoperitoneal shunt (VPS) in patients after using EVD was also assessed. Overall outcomes were assessed using a modified Rankin scale (mRS) at the time of patient discharge. Exclusion criteria were as follows: patients aged less than 18 years and the lack of assessed data. Patients undergoing endovascular and conservative treatments also were excluded. Results Among the patients enrolled in the study, 22% (n=142) had EVD. Among these, 99 cases (69.7%) had EVD installed in the operating room just before the start of the surgical intervention. In some cases, ventriculostomy was performed on a delayed basis (16.3%). A satisfactory outcome (mRS scores of 1 and 2) was observed in 24.7% (n=35). Moderate and profound disability at the time of discharge was noted in 55.7% (n=79). Vegetative outcome at discharge was noted in 8.4% (n=12), and mortality occurred in 12.3% (n=15). Conclusion EVD ensures effective monitoring and reduction of ICP. EVD is associated with a relatively low risk of infectious, liquorodynamic, and hemorrhagic complications and does not worsen outcomes when used in patients with aSAH. We propose that all patients in the acute stage of SAH with H-H severity of III-V should receive EVD immediately before surgery.

Early Response of Antimicrobial Resistance and Virulence Genes Expression in Classical, Hypervirulent, and Hybrid hvKp-MDR Klebsiella pneumoniae on Antimicrobial Stress.

Klebsiella pneumoniae is an increasingly important hospital pathogen. Classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp) are two distinct evolutionary genetic lines. The recently ongoing evolution of K. pneumoniae resulted in the generation of hybrid hvKP-MDR strains. K. pneumoniae distinct isolates (n = 70) belonged to 20 sequence types with the prevalence of ST395 (27.1%), ST23 (18.6%), ST147 (15.7%), and ST86 (7.1%), and 17 capsular types with the predominance of K2 (31.4%), K57 (18.6%), K64 (10.0%), K1 (5.7%) were isolated from patients of the Moscow neurosurgery ICU in 2014-2019. The rate of multi-drug resistant (MDR) and carbapenem-resistant phenotypes were 84.3% and 45.7%, respectively. Whole-genome sequencing of five selected strains belonging to cKp (ST395K47 and ST147K64), hvKp (ST86K2), and hvKp-MDR (ST23K1 and ST23K57) revealed blaSHV, blaTEM, blaCTX, blaOXA-48, and blaNDM beta-lactamase genes; acr, oqx, kpn, kde, and kex efflux genes; and K. pneumoniae virulence genes. Selective pressure of 100 mg/L ampicillin or 10 mg/L ceftriaxone induced changes of expression levels for named genes in the strains belonging to cKp, hvKp, and hybrid hvKp-MDR. Obtained results seem to be important for epidemiologists and clinicians for enhancing knowledge about hospital pathogens.

Antimicrobial Resistance and Genomic Characterization of OXA-48- and CTX-M-15-Co-Producing Hypervirulent Klebsiella pneumoniae ST23 Recovered from Nosocomial Outbreak.

Multidrug resistance (MDR) and hypervirulence (hv) have been long considered distinct evolutionary traits for Klebsiella pneumoniae (Kp), a versatile human pathogen. The recent emergence of Kp strains combining these traits poses a serious global threat. In this article, we describe the phenotypic and genomic characteristics of an MDR hvKp isolate, MAR14-456, representative of a nosocomial outbreak in Moscow, Russia, that was recovered from a postoperative wound in a patient who later developed multiple abscesses, fatal sepsis, and septic shock. Broth microdilution testing revealed decreased susceptibility of MAR14-456 to carbapenems (MICs 0.5-2 mg/L) and a high-level resistance to most ß-lactams, ß-lactam-ß-lactamase-inhibitor combinations, and non-ß-lactam antibiotics, except ceftazidime-avibactam, amikacin, tigecycline, and colistin. Whole-genome sequencing using Illumina MiSeq and ONT MinION systems allowed to identify and completely assemble two conjugative resistance plasmids, a typical 'European' epidemic IncL/M plasmid that carries the gene of OXA-48 carbapenemase, and an IncFIIK plasmid that carries the gene of CTX-M-15 ESBL and other resistance genes. MLST profile, capsular, lipopolysaccharide, virulence genes encoded on chromosome and IncHI1B/FIB plasmid, and the presence of apparently functional type I-E* CRISPR-Cas system were all characteristic of hvKp ST23, serotype K1-O1v2. Phylogenetic analysis showed the closest relatedness of MAR14-456 to ST23 isolates from China. This report highlights the threat of multiple resistance acquisition by hvKp strain and its spread as a nosocomial pathogen.

Treatment of high fracture risk patients in routine clinical practice.

A retrospective cohort study determined the high incidence of recurrent fractures in osteoporotic patients with high fracture risk during the observation. The strategy of starting treatment with more potent regimens (zoledronic acid, denosumab and/or teriparatide) seems to have the best secondary fracture prevention efficacy. OBJECTIVE: This paper describes the various medical therapy regimens prescribed to osteoporotic patients with high fracture risk and the result of treatment. METHODS: We carried out a retrospective cohort study in selected Osteoporosis Centers. Patients were considered to have high fracture risk in case of a history of a low-energy hip fracture or two or more vertebral or other site fractures. A total of 812 subjects (768 women and 44 men) aged 36-95 years were included. The observation period was 2285.1 patient-years. Demographic data, clinical findings, and BMD data obtained by DXA, as well as a history of fractures that had occurred during the follow-up, were included in the analysis. RESULTS: Overall, at baseline, there were 637 non-vertebral fractures including 104 hip fractures. A total of 590 patients had vertebral fractures; of these, 69% suffered multiple fractures. Being on treatment, 119 (14.7%) patients developed new vertebral and non-vertebral fractures. The incidence of new non-vertebral fractures and hip fractures was 39.4 and 13.1 per 1000 patient-years. The total number of vertebral fractures increased by 24.8% from 1353 to 1689. The best results of the treatment were achieved in patients who were started on zoledronic acid, denosumab, or teriparatide and had an adequate duration of treatment. Although these patients had significantly lower BMD values at the time of diagnosis compared with other patients, they showed a lower incidence of new vertebral and hip fractures, during the follow-up. CONCLUSION: Therapy of patients at high risk of fractures started with more potent treatment regimens (zoledronic acid, denosumab and/or teriparatide) of adequate duration was more effective in terms of prevention of new vertebral and hip fractures as compared with other treatment options. However, treatment appears to be challenging given the number of recurrent fractures in patients on treatment and the frequency of drug withdrawal or replacement.

Quality of life after fragility fracture in the Russian Federation: results from the Russian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (ICUROS).

Changes in health-related quality of life (QoL) due to hip, humeral, ankle, spine, and distal forearm fracture were measured in Russian adults age 50 years or more over the first 18 months after fracture. The accumulated mean QoL loss after hip fracture was 0.5 and significantly greater than after fracture of the distal forearm (0.13), spine (0.21), proximal humerus (0.26), and ankle (0.27). INTRODUCTION: Data on QoL following osteoporotic fractures in Russia are scarce. The present study evaluated the impact of hip, vertebral, proximal humerus, distal forearm, and ankle fracture up to 18 months after fracture from the Russian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study. METHODS: Individuals age ≥ 50 years with low-energy-induced humeral, hip, clinical vertebral, ankle, or distal forearm fracture were enrolled. After a recall of pre-fracture status, HRQoL was prospectively collected over 18 months of follow-up using EQ-5D-3L. Multivariate regression analysis was used to identify determinants of QALYs loss. RESULTS: At 2 weeks, patients with hip fracture (n = 223) reported the lowest mean health state utility value (HSUV) compared with other fracture sites. Thereafter, utility values increased but remained significantly lower than before fracture. For spine (n = 183), humerus (n = 166), and ankle fractures (n = 214), there was a similar pattern of disutility with a nadir within 2 weeks and a progressive recovery thereafter. The accumulated mean QoL loss after hip fracture was 0.5 and significantly greater than after fracture of the distal forearm (0.13), spine (0.21), proximal humerus (0.26), and ankle (0.27). Substantial impairment in self-care and usual activities immediately after fracture were important predictors of recovery across at all fracture sites. CONCLUSIONS: Fractures of the hip, vertebral, distal forearm, ankle, and proximal humerus incur substantial loss of QoL in Russia. The utility values derived from this study can be used in future economic evaluations.

Implementing an infection control and prevention program decreases the incidence of healthcare-associated infections and antibiotic resistance in a Russian neuro-ICU.

Background: The impact of infection prevention and control (IPC) programs in limited resource countries such as Russia are largely unknown due to a lack of reliable data. The aim of this study is to evaluate the effect of an IPC program with respect to healthcare associated infection (HAI) prevention and to define the incidence of HAIs in a Russian ICU. Methods: A pioneering IPC program was implemented in a neuro-ICU at Burdenko Neurosurgery Institute in 2010 and included hand hygiene, surveillance, contact precautions, patient isolation, and environmental cleaning measures. This prospective observational cohort study lasted from 2011 to 2016, included high-risk ICU patients, and evaluated the dynamics of incidence, etiological spectrum, and resistance profile of four types of HAIs, including subgroup analysis of device-associated infections. Survival analysis compared patients with and without HAIs. Results: We included 2038 high-risk patients. By 2016, HAI cumulative incidence decreased significantly for respiratory HAIs (36.1% vs. 24.5%, p-value = 0.0003), urinary-tract HAIs (29.1% vs. 21.3%, p-value = 0.0006), and healthcare-associated ventriculitis and meningitis (HAVM) (16% vs. 7.8%, p-value = 0.004). The incidence rate of EVD-related HAVM dropped from 22.2 to 13.5 cases per 1000 EVD-days. The proportion of invasive isolates of Klebsiella pneumoniae and Acinetobacter baumannii resistant to carbapenems decreased 1.7 and 2 fold, respectively. HAVM significantly impaired survival and independently increasing the probability of death by 1.43. Conclusions: The implementation of an evidence-based IPC program in a middle-income country (Russia) was highly effective in HAI prevention with meaningful reductions in antibiotic resistance.

Comparative analysis of Klebsiella pneumoniae strains isolated in 2012-2016 that differ by antibiotic resistance genes and virulence genes profiles.

The antibacterial resistance and virulence genotypes and phenotypes of 148 non-duplicate Klebsiella pneumoniae strains collected from 112 patients in Moscow hospitals in 2012-2016 including isolates from the respiratory system (57%), urine (30%), wounds (5%), cerebrospinal fluid (4%), blood (3%), and rectal swab (1%) were determined. The majority (98%) were multidrug resistant (MDR) strains carrying blaSHV (91%), blaCTX-M (74%), blaTEM (51%), blaOXA (38%), and blaNDM (1%) beta-lactamase genes, class 1 integrons (38%), and the porin protein gene ompK36 (96%). The beta-lactamase genes blaTEM-1, blaSHV-1, blaSHV-11, blaSHV-110, blaSHV-190, blaCTX-M-15, blaCTX-M-3, blaCTX-M-55, blaOXA-48, blaOXA-244, and blaNDM-1 were detected; class 1 integron gene cassette arrays (aadA1), (dfrA7), (dfrA1-orfC), (aadB-aadA1), (dfrA17-aadA5), and (dfrA12-orfF-aadA2) were identified. Twenty-two (15%) of clinical K. pneumoniae strains had hypermucoviscous (HV) phenotype defined as string test positive. The rmpA gene associated with HV phenotype was detected in 24% of strains. The intrapersonal mutation of rmpA gene (deletion of one nucleotide at the polyG tract) was a reason for negative hypermucoviscosity phenotype and low virulence of rmpA-positive K. pneumoniae strain KPB584. Eighteen virulent for mice strains with LD50 ≤ 104 CFU were attributed to sequence types ST23, ST86, ST218, ST65, ST2174, and ST2280 and to capsular types K1, K2, and K57. This study is the first report about hypervirulent K. pneumoniae strain KPB2580-14 of ST23K1 harboring extended-spectrum beta-lactamase CTX-M-15 and carbapenemase OXA-48 genes located on pCTX-M-15-like and pOXA-48-like plasmids correspondingly.

Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease.

BACKGROUND: The effect of oral and/or parenteral ademetionine (500 mg intravenous [IV] and tablet formulation) on clinical symptoms and biochemical markers of intrahepatic cholestasis (IHC) was investigated in subjects with alcoholic liver disease (ALD) and compensated liver function. METHODS: Prospective, multicenter, open-label study consisting of a screening period and an 8-week treatment period and performed in subjects (18-75 years) with compensated ALD and confirmed IHC. Subjects with a baseline serum conjugated bilirubin value above normal range were initially treated with IV ademetionine for two weeks (500-800 mg daily) and continued with oral ademetionine 1500 mg daily for a further six weeks. Subjects with a baseline serum conjugated bilirubin value within normal range were treated with oral ademetionine for eight weeks. RESULTS: A total of 72 subjects were treated; 41 initially with IV ademetionine and 31 with oral ademetionine. Clinical symptoms status improved from baseline to end of treatment with an increase in the proportion of subjects with no symptoms. Ademetionine showed significant improvements in primary efficacy parameters alkaline phosphatase (ALP) and γ-glutamyltransferase (γGT) (P<0.0001). Although decreases of ALP were higher for subjects initially treated with IV ademetionine, these subjects also had higher baseline values. No safety concerns with ademetionine arose with respect to the severity or frequency of adverse events (AEs) during the treatment period, laboratory parameters, and vital signs. CONCLUSIONS: Administration of oral or IV/oral ademetionine step-therapy for 8 weeks to subjects with IHC due to ALD was safe and provided a significant improvement of disease burden.

Healthcare-associated ventriculitis and meningitis in a neuro-ICU: Incidence and risk factors selected by machine learning approach.

PURPOSE: To define the incidence of healthcare-associated ventriculitis and meningitis (HAVM) in the neuro-ICU and to identify HAVM risk factors using tree-based machine learning (ML) algorithms. METHODS: An observational cohort study was conducted in Russia from 2010 to 2017, and included high-risk neuro-ICU patients. We utilized relative risk analysis, regressions, and ML to identify factors associated with HAVM development. RESULTS: 2286 patients of all ages were included, 216 of them had HAVM. The cumulative incidence of HAVM was 9.45% [95% CI 8.25-10.65]. The incidence of EVD-associated HAVM was 17.2 per 1000 EVD-days or 4.3% [95% CI 3.47-5.13] per 100 patients. Combining all three methods, we selected four important factors contributing to HAVM development: EVD, craniotomy, superficial surgical site infections after neurosurgery, and CSF leakage. The ML models performed better than regressions. CONCLUSION: We first reported HAVM incidence in a neuro-ICU in Russia. We showed that tree-based ML is an effective approach to study risk factors because it enables the identification of nonlinear interaction across factors. We suggest that the number of found risk factors and the duration of their presence in patients should be reduced to prevent HAVM.

Quality of life after hip, vertebral, and distal forearm fragility fractures measured using the EQ-5D-3L, EQ-VAS, and time-trade-off: results from the ICUROS.

INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study is a multinational observational study set up to describe the costs and quality of life (QoL) consequences of fragility fracture. This paper aims to estimate and compare QoL after hip, vertebral, and distal forearm fracture using time-trade-off (TTO), the EuroQol (EQ) Visual Analogue Scale (EQ-VAS), and the EQ-5D-3L valued using the hypothetical UK value set. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months after fracture. Health state utility values (HSUVs) were derived for each fracture type and time-point using the three approaches (TTO, EQ-VAS, EQ-5D-3L). HSUV were used to estimate accumulated QoL loss and QoL multipliers. RESULTS: In total, 1410 patients (505 with hip, 316 with vertebral, and 589 with distal forearm fracture) were eligible for analysis. Across all time-points for the three fracture types, TTO provided the highest HSUVs, whereas EQ-5D-3L consistently provided the lowest HSUVs directly after fracture. Except for 13-18 months after distal forearm fracture, EQ-5D-3L generated lower QoL multipliers than the other two methods, whereas no equally clear pattern was observed between EQ-VAS and TTO. On average, the most marked differences between the three approaches were observed immediately after the fracture. CONCLUSIONS: The approach to derive QoL markedly influences the estimated QoL impact of fracture. Therefore the choice of approach may be important for the outcome and interpretation of cost-effectiveness analysis of fracture prevention.

Genome Sequences of Two NDM-1 Metallo-ß-Lactamase-Producing Multidrug-Resistant Strains of Klebsiella pneumoniae with a High Degree of Similarity, One of Which Contains Prophage.

We report genome sequences of two NDM-1 metallo-ß-lactamase-producing multidrug-resistant Klebsiella pneumoniae isolates of sequence type 147 (ST147) from one hospital. The genomes are highly similar and differ in prophage located in the chromosome of K. pneumoniae KPB-1470/16 and in the additional plasmid-carrying blaOXA-48 gene in K. pneumoniae KPB-417/16.