Hospital Reservoirs of Multidrug Resistant Acinetobacter Species-The Elephant in the Room!

Environmental contamination is estimated to contribute to up to 20% of all hospital acquired infections. Acinetobacter baumannii is an example of one the most prevalent opportunistic pathogens causing severe and persistent infections in immunocompromised patients. It has proven ability to form biofilms, has significant associated multi-drug resistance and is able to transfer mobile genetic elements to other clinically relevant pathogens. All of these factors point to a definite utility of A. baumannii as an indicator organism for effectiveness of decontamination regimens as well as environmental screening. There is an increased cost, both financial and clinical, associated with multi drug resistant organisms, carbapenem resistant A. baumannii. With a dearth of new antimicrobials in development, now is the time to radically transform and lead the introduction of scientifically based environmental screening and microbiological verified decontamination to control the dissemination of further resistance.

Carbapenemase screening in an Irish tertiary referral hospital: Best practice, or can we do better?

BACKGROUND: Carbapenems are a family of end line antibiotics with increasing levels of resistance that are a cause for concern. AIM: To ascertain whether the CPE screening programme employed in an acute tertiary hospital is fit for purpose. METHOD: We outlined the current working algorithm employed using a universal screening programme over a 26-month screening period. Rectal swabs are cultured on arrival. Those with suspicious growth are further investigated using NG-Carba 5 lateral flow tests and Vitek 2.0 sensitivity cards. These practices were compared with NHS guidelines. FINDINGS & CONCLUSIONS: In all, 53 true positives were detected from 45 patients since the screening was implemented in early 2018 (46 OXA-48, 6 KPC, 1 NDM). As the rate of screening increased, the number of positive screens decreased over time. There were a lot of similarities between the HSE guidelines and the published NHS CPE toolkit. It was evident that there is no standard practice being employed across all hospitals. Comparing the MUH to national guidelines it appears to be quicker and more effective with universal screening in place at reducing the potential contacts and identifying carriers. Cost analysis indicates that the need to confirm all positive strains in a reference lab is costly, unnecessary and time consuming. There are adequate confirmatory tests available in-house for routine positive screens. It was concluded that infection prevention and control are key to identifying and controlling possible outbreaks in a hospital setting.

Females drive asymmetrical introgression from rare to common species in Darwin's tree finches.

The consequences of hybridization for biodiversity depend on the specific ecological and evolutionary context in which it occurs. Understanding patterns of gene flow among hybridizing species is crucial for determining the evolutionary trajectories of species assemblages. The recently discovered hybridization between two species of Darwin's tree finches (Camarhynchus parvulus and C. pauper) on Floreana Island, Galápagos, presents an exciting opportunity to investigate the mechanisms causing hybridization and its potential evolutionary consequences under conditions of recent habitat disturbance and the introduction of invasive pathogens. In this study, we combine morphological and genetic analysis with pairing observations to explore the extent, direction and drivers of hybridization and to test whether hybridization patterns are a result of asymmetrical pairing preference driven by females of the rarer species (C. pauper). We found asymmetrical introgression from the critically endangered, larger-bodied C. pauper to the common, smaller-bodied C. parvulus, which was associated with a lack of selection against heterospecific males by C. pauper females. Examination of pairing data showed that C. parvulus females paired assortatively, whereas C. pauper females showed no such pattern. This study shows how sex-specific drivers can determine the direction of gene flow in hybridizing species. Furthermore, our results suggest the existence of a hybrid swarm comprised of C. parvulus and hybrid birds. We discuss the influence of interspecific abundance differences and susceptibility to the invasive parasite Philornis downsi on the observed hybridization and recommend that the conservation of this iconic species group should be managed jointly rather than species-specific.

Mycobacterium diagnostics: from the primitive to the promising.

The field of clinical microbiology has been revolutionised by genomic and proteomic methods, which have facilitated more rapid diagnosis and characterisation of infection in many cases. In contrast, mycobacteriological evolution has tended to retain the traditional methods of smear microscopy for detection of acid-fast bacilli to indicate mycobacteria, along with culture, and in synergy with more modern molecular methods. Thus, efforts have been focused on reducing the time to diagnosis of infection, while increasing the amount of diagnostic information available, including more definitive speciation, and more rapid susceptibility test results. Although smear microscopy remains a mainstay for the laboratory-based diagnosis of mycobacterial infection, molecular testing has vastly reduced the time needed for identification of Mycobacterium tuberculosis in particular, when compared with traditional culture-based techniques. Molecular methods may also yield antimicrobial susceptibility results through testing for the most common resistance-inducing mutations to some of the antimicrobial agents of choice. However, the diversity of resistance mutations already characterised suggests that these currently-available molecular detection systems should be accompanied by culture-based susceptibility testing. This review compares the efficacy of microscopic, phenotypic, proteomic and genotypic methods available for mycobacterial diagnosis. The diversity of methods currently in use reflects the complexity of this area of diagnostic microbiology.

Failure to find association between childhood abuse and cognition in first-episode psychosis patients.

This study investigated the relationship between severe childhood abuse and cognitive functions in first-episode psychosis patients and geographically-matched controls. Reports of any abuse were associated with lower scores in the executive function domain in the control group. However, in contrast with our hypothesis, no relationships were found amongst cases.

Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety.

Levomilnacipran (LVM; F2695) is the more active enantiomer of the serotonin/norepinephrine (5-HT/NE) reuptake inhibitor (SNRI) milnacipran and is currently under development for the treatment of major depressive disorder. LVM was benchmarked against two other SNRIs, duloxetine and venlafaxine, in biochemical, neurochemical and pharmacological assays. LVM exhibited high affinity for human NE (Ki = 92.2 nM) and 5-HT (11.2 nM) transporters, and potently inhibited NE (IC50 = 10.5 nM) and 5-HT (19.0 nM) reuptake (human transporter) in vitro. LVM had 2-fold greater potency for norepinephrine relative to serotonin reuptake inhibition (i.e. NE/5-HT potency ratio: 0.6) and 17 and 27 times higher selectivity for NE reuptake inhibition compared with venlafaxine and duloxetine, respectively. LVM did not exhibit affinity for 23 off-target receptors. LVM (i.p.) increased cortical extracellular levels of 5-HT, and NE (minimal effective doses: MEDs = 20 and 10 mg/kg, respectively). In anti-depressive/anti-stress models, i.p. LVM diminished immobility time in the mouse forced swim (MED = 20 mg/kg) and tail suspension (MED = 2.5 mg/kg) tests, and reduced shock-induced ultrasonic vocalizations in rats (MED = 5 mg/kg). Duloxetine and venlafaxine were less potent (MEDs ≥ 10 mg/kg). At doses active in these three therapeutically-relevant models, LVM (i.p.) did not significantly affect spontaneous locomotor activity. In summary, LVM is a potent, selective inhibitor of NE and 5-HT transporters with preferential activity at the former. It is efficacious in models of anti-depressive/anti-stress activity, with minimal potential for locomotor side effects.

Association of Clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: results from the 2009 Nationwide Inpatient Sample database.

BACKGROUND: Diarrhea is a frequent and potentially severe complication in solid organ transplant (SOT) recipients. One of the most common infectious etiologies of diarrhea in these patients is Clostridium difficile. Our objective was to investigate the association of C. difficile infection (CDI) with the outcomes of hospitalized SOT patients. METHODS: We extracted all adult cases with discharge diagnoses of SOT or CDI from the United States Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality 2009 database. We collected outcome variables (mortality, length of hospital stay [LOS], hospitalization charges, complications of the transplanted organ, and colectomy), demographic information, and comorbidity data for each of the cases. The data were evaluated using univariate and multiple variable regression analyses. RESULTS: We identified 49,198 cases with SOT of which 2.7% had CDI. Univariate comparisons of cases with SOT + CDI to those with SOT-only revealed significant differences in the evaluated outcomes including in-hospital mortality (7.4% vs. 2.4%, P < 0.001), LOS (median 9 days vs. 4 days, P < 0.001), charges (median $53,808 vs. $31,488, P < 0.001), organ complications (38.1% vs. 33.9%, P < 0.001), and colectomy (1.1% vs. 0.3%, P < 0.001). Using multiple variable regression analyses, in the SOT cohort (SOT-only and SOT + CDI), CDI was independently associated with greater mortality (adjusted odds ratio [aOR] 2.48, 95% confidence interval [CI] = 2.22, 2.76, P < 0.001), longer LOS (difference 9.6 days, 95% CI = 9.3, 9.9, P < 0.001), higher charges (difference $69,647, 95% CI = $66,190, $73,104, P < 0.001), more complications of the transplanted organ (aOR 1.36, 95% CI = 1.28, 1.44, P < 0.001), and increased need for colectomy (aOR 3.10, 95% CI = 2.35, 4.08, P < 0.001). CONCLUSIONS: Our results demonstrate that CDI is associated with overall significantly worse outcomes in hospitalized patients with SOT.

Rat survival to anthrax lethal toxin is likely controlled by a single gene.

We examined whether survival of different rat strains administered anthrax lethal toxin is genetically determined. A reproducible test population of first filial generation hybrid rats was bred based on the susceptibility of progenitors to anthrax lethal toxin and to maximize genetic diversity across the strains. These rats were then tested with varying doses of anthrax lethal toxin. We found that all 'sensitive' strains died within 2 h following systemic administration of 240 mug/kg lethal toxin, while one strain survived following a five times higher dose (1.4 mg/kg). The ability of lethal toxin to lyse macrophage cultures derived from the bone marrow of these strains corresponded with in vivo results. We conclude that a rat test population can detect strain differences in response to anthrax lethal toxin. Survival is influenced by the host genome background and is likely due to a single gene with a recessive mode of inheritance.

Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia.

The functional integrity of the dorsolateral prefrontal cortex (DLPFC) is altered in schizophrenia leading to profound deficits in working memory and cognition. Growing evidence indicates that dysregulation of glutamate signaling may be a significant contributor to the pathophysiology mediating these effects; however, the contribution of NMDA and AMPA receptors in the mediation of this deficit remains unclear. The equivocality of data regarding ionotropic glutamate receptor alterations of subunit expression in the DLPFC of schizophrenics is likely reflective of subtle alterations in the cellular and molecular composition of specific neuronal populations within the region. Given previous evidence of Layer II/III and V pyramidal cell alterations in schizophrenia and the significant influence of subunit composition on NMDA and AMPA receptor function, laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC. Comparisons were made between individuals diagnosed with schizophrenia, bipolar disorder, major depressive disorder and controls (n=15/group). All subunits were expressed at detectable levels in both cell populations for all diseases as well as for the control group. Interestingly, GRIA1 mRNA was significantly increased in both cell types in the schizophrenia group compare to controls, while similar trends were observed in major depressive disorder (Layers II/III and V) and bipolar disorder (Layer V). These data suggest that increased GRIA1 subunit expression may contribute to schizophrenia pathology.

AMPA receptor subunit and splice variant expression in the DLPFC of schizophrenic subjects and rhesus monkeys chronically administered antipsychotic drugs.

Disturbances in glutamate neurotransmission are thought to be one of the major contributing factors to the pathophysiology of schizophrenia. In the dorsolateral prefrontal cortex (DLPFC), glutamate neurotransmission is largely mediated by AMPA receptors. Data regarding alterations of subunit expression in the brains of patients with schizophrenia remain equivocal. This may be due to differences in technique sensitivity, endogenous control selection for normalization of data, or effect of antipsychotic drug treatment in different cohorts of schizophrenia. This study attempted to address these issues by examining the expression of AMPA receptor subunits and splice variants in the DLPFC of two schizophrenia cohorts using quantitative PCR (qPCR) with normalization to the geometric mean of multiple endogenous controls. In addition, a non-human primate model of chronic antipsychotic drug administration was used to determine the extent to which the transcript expression may be altered by antipsychotic drug treatment in the primate DLPFC. AMPA receptor subunits and flip and/or flop splice variants were not significantly different in the DLPFC of schizophrenia subjects versus controls in either of the two cohorts. However, in rhesus monkeys chronically treated with antipsychotic drugs, clozapine treatment significantly decreased GRIA1 and increased GRIA3 mRNA expression, while both clozapine and haloperidol increased the expression of GRIA2 subunit mRNA. Expression of AMPA receptor splice variants was not significantly altered by antipsychotic drug administration. This is the first study to show that AMPA receptor subunit mRNAs in the primate DLPFC are altered by antipsychotic drug administration. Antipsychotic drug-induced alterations may help explain differences in human post-mortem studies regarding AMPA receptor subunit expression and provide some insight into the mechanism of action of antipsychotic drugs.

Geriatric falls: injury severity is high and disproportionate to mechanism.

OBJECTIVE: Falls are a well-known source of morbidity and mortality in the elderly. Fall-related injury severity in this group, however, is less clear, particularly as it relates to type of fall. Our purpose is to explore the relationship between mechanism of fall and both pattern and severity of injury in geriatric patients as compared with a younger cohort. METHODS: Our trauma registry was queried for all patients evaluated by the trauma service over a 412-year period (1994-1998). Two cohorts were formed on the basis of age greater than 65 or less than or equal to 65 years and compared as to mechanism, Injury Severity Score (ISS), Abbreviated Injury Scale score, and mortality. RESULTS: Over the study period, 1,512 patients were evaluated, 333 greater than 65 years and 1,179 less than or equal to 65 years of age. Falls were the injury mechanism in 48% of the older group and 7% of the younger group (p < 0.05). Falls in the older group constituted 65% of patients with ISS >15, with 32% of all falls resulting in serious injury (ISS >15). In contrast, falls in the younger group constituted only 11% of ISS >15 patients, with falls causing serious injury only 15% of the time (both p < 0.05). Notably, same-level falls resulted in serious injury 30% of the time in the older group versus 4% in the younger group (p < 0.05), and were responsible for an ISS >15 30-fold more in the older group (31% vs. <1%; p < 0.05). Abbreviated Injury Scale evaluation revealed more frequent head/neck (47% vs. 22%), chest (23% vs. 9%), and pelvic/extremity (27% vs. 15%) injuries in the older group for all falls (all p < 0.05). The mean ISS for same-level falls in the older group was twice that for the younger group (9.28 vs. 4.64, p < 0.05), whereas there was no difference in mean ISS between multilevel and same-level falls within the older group itself (10.12 vs. 9.28, p > 0.05). The fall-related death rate was higher in the older group (7% vs. 4%), with falls seven times more likely to be the cause of death compared with the younger group (55% vs. 7.5%) (both p < 0.05). Same-level falls as a cause of death was 10 times more common in the elderly (25% vs. 2.5%, p < 0.05). CONCLUSION: Falls among the elderly, including same-level falls, are a common source of both high injury severity and mortality, much more so than in younger patients. A different pattern of injury between older and younger fall patients also exists.

Posttransplantation lymphoproliferative disorder: endoscopic findings.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) may manifest a variety of nonspecific symptoms and must be suspected in the patient who undergoes solid organ transplantation. Common sites of occurrence include the gastrointestinal tract, the central nervous system, and lymphoid tissue of the oral pharynx, mediastinum, and mesentery. The large incidence of gastrointestinal involvement provides an opportunity for endoscopic diagnosis. This is the description of a characteristic endoscopic finding in patients who have undergone liver transplantation who are under evaluation for suspected PTLD. METHODS: During a 2-year period, 27 liver transplantations were performed in 24 pediatric patients. Fourteen patients underwent endoscopic evaluation. Indications for endoscopy included abdominal pain, vomiting, hematemesis, irritability, growth failure, anemia, occult blood loss, and suspected PTLD. Biopsy specimens were obtained from any endoscopically detected abnormality and from the duodenum, gastric antrum, esophagus, terminal ileum, cecum, and rectum. Specimens with suspected PTLD were evaluated with Epstein-Barr virus latent membrane stain. RESULTS: Six patients were found to have a characteristic lesion, which was raised, rubbery, and erythematous, with a central ulceration. Lesions were singular or multiple and ranged from 5 to 15 mm in diameter. Microscopic evaluation revealed a monotonous proliferation of lymphocytes. All specimens were positive for Epstein-Barr virus latent membrane protein stain. Stains for cytomegalovirus were negative. Biopsy specimens from the eight patients without identified characteristic lesions were negative for PTLD. CONCLUSIONS: Panendoscopy is a useful tool for the diagnosis and treatment of gastrointestinal PTLD. Endoscopy is easily accomplished, may provide an instantaneous result if the characteristic lesion is identified, and provides tissue for disease classification. Patients with unexplained gastrointestinal signs or symptoms should undergo panendoscopy for suspected PTLD.

Acute and chronic viral hepatitis.

Viral hepatitis is the most common cause of acute and chronic hepatitis. The term viral hepatitis generally refers to infections resulting from one of the hepatotrophic viruses: hepatitis A, B, C, D, and E. The last 10 years have brought many important advances in understanding the epidemiology, pathogenesis, molecular biology, and immunoprophylaxis of infections caused by hepatotrophic viruses. Development of sensitive and specific immunoassays has enabled detection of specific agents. This has allowed for identification of infected patients and monitoring response to therapy. Additionally, serologic markers have allowed for isolation of contaminated blood products and a reduction in the spread of disease. The remaining challenge is the application of this knowledge to the treatment and prevention of viral hepatitis. This article explores the risk factors, epidemiology, microbiology, clinical and laboratory diagnosis, treatment, and prevention of the hepatotrophic viral infections.

Cost-effective supply use in permanent central venous catheter operations.

A prospective, randomized trial was designed to determine whether a streamlined operating room supply pack was cost-effective in the placement of permanent central venous catheters. Over a 12-month period, 139 consecutive patients were randomized and evaluated. There were no differences found between the mean ages, sex, indication for catheter placement, mean operative time, or surgeon and nurse satisfaction between treatment groups. In addition, 30-day catheter infection rate, 30-day catheter malfunction rate, and 30-day catheter removal rate were similar between groups. Supply costs were $411.32 per patient operation in the control group and only $180.34 per patient operation in the study group, resulting in an average cost-effectiveness ratio of $230.98 per catheter placed. Based on these data, a streamlined operating room supply setup is cost-effective in the operative placement of permanent central venous catheters.

Complications of gastroesophageal antireflux surgery in neurologically impaired versus neurologically normal children.

Antireflux surgery was performed in 234 children over a 5-year period; 153 were neurologically impaired (NI) and 81 were neurologically normal (NN). Initial presentation, demographic data, and type of antireflux operation were similar in the two groups. Eighty-six percent of the NI group versus 30% of the NN group had gastrostomy tubes placed. The incidence of late postoperative complications was 26% in the NI group and 12% in the NN group (P less than .01). During the late postoperative period, NI children underwent reoperation four times as frequently as NN children (19% v 5%, respectively; P less than .01). Wrap herniation accounted for 38% of complications and 59% of reoperations in the late postoperative period. Mortality due to aspiration occurred in 9% of the NI group versus 1% of the NN group. Combined failure rate (reoperation plus aspiration-induced deaths) was 28% in NI and 6% in NN (P less than .01). We conclude that neurological status is the major predictor of operative success and that wrap herniation due to crural disruption is the most common cause of operative failure.

Somatomedin-A inhibits glucagon-stimulated hepatic gluconeogenesis.

Somatomedin/insulin-like growth factors have been noted to produce insulin-like actions on the liver that include the ability to inhibit the formation of glucagon-stimulated but not basal c-AMP production. This raises the possibility that these compounds may also be able to inhibit glucagon-stimulated hepatic gluconeogenesis. The purpose of this study was to determine the effects of varying concentrations of somatomedin-A on glucagon-stimulated gluconeogenesis in isolated perfused rat liver. The infusion of glucagon increased the rate of gluconeogenesis from 0.0038 +/- 0.001 to 0.042 +/- 0.007 microM 14C-glucose made from 14C-alanine per min. This action of glucagon was reduced to 22% of its maximum by the coinfusion of 1 microU/ml of SM-A and completely eliminated by the coinfusion of 100 microU/ml of SM-A. Somatomedin alone did not alter the basal rate of gluconeogenesis. The decrease in the release of 14C glucose from livers that had been stimulated by glucagon could not be attributed to increased glycogenolysis. Thus, it appears that the reduction in 14C release represents SM-A mediated reduction in glucagon-stimulated gluconeogenesis.