Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to blame?

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). AIM: To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. METHODS: This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48 h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. FINDINGS: Over ten months, 72 PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. CONCLUSION: Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.

Transvaginal rectopexy using the Flex® Colorectal Drive Robotic System: a proof-of-concept approach to rectal prolapse.

BACKGROUND: The aim of this study was to demonstrate a proof-of-concept approach to rectopexy that would provide the durability of the transabdominal procedure through use of sacral rectopexy with the decreased morbidity of a perineal procedure. This was done by utilizing a transvaginal approach and developing the rectovaginal space to accommodate sacral rectopexy placement using the Flex® Colorectal Drive Robotic System by Medrobotics (Medrobotics Corp., Raynham, MA, USA). METHODS: A fresh female cadaver was acquired and placed in the high lithotomy position. The rectovaginal space was developed to accommodate the trocar of the Flex robot using blunt and sharp dissection between the posterior vaginal wall and anterior rectum. A piece of mesh was introduced into the space and using an endoscopic tacker, which was secured to the sacral promontory. The mesh was secured to the anterior rectal wall using interrupted vicryl sutures. The purse string suture was removed and the rectovaginal orifice was closed using a running vicryl suture. At the completion of the procedure, a low midline laparotomy was conducted to verify anchoring of the mesh appropriately at the sacral promontory. RESULTS: This proof-of-concept protocol is the first description of the Flex® Colorectal Drive being used successfully to perform a transvaginal rectopexy for rectal prolapse in a cadaver. This is also the first description of the Flex® Colorectal Drive robot being used transvaginally. CONCLUSIONS: This proof-of-concept approach demonstrates that transvaginal rectopexy using the Flex® Colorectal Drive is a potential surgical option to address rectal prolapse that could provide patients the durability of a transabdominal approach with the decreased morbidity of a perineal approach. While early results are promising, additional cadaveric studies are required before this procedure can be attempted in vivo.

Decay and Fission Hindrance of Two- and Four-Quasiparticle K Isomers in

Two isomers decaying by electromagnetic transitions with half-lives of 4.7(1.1) and 247(73) µs have been discovered in the heavy ^{254}Rf nucleus. The observation of the shorter-lived isomer was made possible by a novel application of a digital data acquisition system. The isomers were interpreted as the K^{π}=8^{-}, ν^{2}(7/2^{+}[624],9/2^{-}[734]) two-quasineutron and the K^{π}=16^{+}, 8^{-}ν^{2}(7/2^{+}[624],9/2^{-}[734])⊗8^{-}π^{2}(7/2^{-}[514],9/2^{+}[624]) four-quasiparticle configurations, respectively. Surprisingly, the lifetime of the two-quasiparticle isomer is more than 4 orders of magnitude shorter than what has been observed for analogous isomers in the lighter N=150 isotones. The four-quasiparticle isomer is longer lived than the ^{254}Rf ground state that decays exclusively by spontaneous fission with a half-life of 23.2(1.1) µs. The absence of sizable fission branches from either of the isomers implies unprecedented fission hindrance relative to the ground state.

Integration and proliferation of Pseudomonas aeruginosa PA01 in multispecies biofilms.

Despite an increased awareness of biofilm formation by pathogens and the role of biofilms in human infections, the potential role of environmental biofilms as an intermediate stage in the host-to-host cycle is poorly described. To initiate infection, pathogens in biofilms on inanimate environmental surfaces must detach from the biofilm and be transmitted to a susceptible individual in numbers large enough to constitute an infectious dose. Additionally, while detachment has been recognized as a discrete event in the biofilm lifestyle, it has not been studied to the same extent as biofilm development or biofilm physiology. Successful integration of Pseudomonas aeruginosa strain PA01 expressing green fluorescent protein (PA01GFP), employed here as a surrogate pathogen, into multispecies biofilm communities isolated and enriched from sink drains in public washrooms and a hospital intensive care unit is described. Confocal laser scanning microscopy indicated that PA01GFP cells were most frequently located in the deeper layers of the biofilm, near the attachment surface, when introduced into continuous flow cells before or at the same time as the multispecies drain communities. A more random integration pattern was observed when PA01GFP was introduced into established multispecies biofilms. Significant numbers of single PA01GFP cells were continuously released from the biofilms to the bulk liquid environment, regardless of the order of introduction into the flow cell. Challenging the multispecies biofilms containing PA01GFP with sub-lethal concentrations of an antibiotic, chelating agent and shear forces that typically prevail at distances away from the point of treatment showed that environmental biofilms provide a suitable habitat where pathogens are maintained and protected, and from where they are continuously released.

Using real-time alerts for clinical trials: Identifying potential study subjects.

BACKGROUND: Clinical trials are widely accepted as a necessary step in evaluating the safety and efficacy of new pharmaceutical products. In order for a sufficiently powered study, a clinical trial depends on the effective and unbiased recruitment of eligible patients. Trials involving seasonal diseases like influenza pose additional challenges. OBJECTIVE: This is a feasibility study of a mobile real-time alerting system to systematically identify potential study subjects for a randomized controlled trial evaluating the safety and efficacy of early intervention with interferon alfacon-1 for patients hospitalized for influenza virus infection. METHODS: The alerting system was setup in a 471-bed acute care teaching hospital, enabled with computerized physician order entry (CPOE) and a rules-based alerting system. Patients were identified from the entire hospital using two alerts types: pharmacy prescription records for antiviral drugs, and positive influenza laboratory results. Email alerts were generated and sent to BlackBerry(®) devices carried by the study personnel for a 6 month period. The alerts were archived automatically on a secure server and were exported for analysis in Microsoft Access. RESULTS: Over a period of 21 weeks, 779 total alerts were received. The study team was alerted to 241 patients, of whom 85 were potential study subjects. The alert system identified all but one of the patients independently identified by infection control. CONCLUSIONS: Real-time identification of potential study subjects is possible with the integration of computerized physician order entry and BlackBerry(®) technology. It is a viable method for the systematic identification of patients throughout a hospital, particularly for trials investigating time-sensitive disease progression.

Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation.

Exposure to hypobaric hypoxia, a condition involving decreased availability of oxygen is known to be associated with oxidative stress, neurodegeneration and memory impairment. The multifactorial response of the brain and the complex signaling pathways involved therewith limits the therapeutic efficacy of several antioxidants in ameliorating hypobaric hypoxia-induced memory impairment. The present study was therefore aimed at investigating the potential of acetyl-l-carnitine (ALCAR), a known antioxidant that has been reported to augment neurotrophin-mediated survival mechanisms, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor involved in the cellular defense mechanism against oxidative stress related to brain injury and neurological disorders. The study was designed to understand the mechanisms involving Nrf2 stabilization following exposure to hypobaric hypoxia. The results displayed reference memory impairment in Sprague-Dawley rats exposed to hypobaric hypoxia (7620 m) for 14 consecutive days which however improved on administration of ALCAR during hypoxic exposure. The study also revealed Nrf2 regulated augmented antioxidant response on administration of ALCAR which was through a novel tyrosine kinase A (TrkA) receptor-mediated mechanism. A decrease in free radical generation, lipid peroxidation and protein oxidation was also observed along with a concomitant increase in thioredoxin and reduced glutathione levels on administration of ALCAR during exposure to hypobaric hypoxia. The present study therefore reveals the therapeutic potential of ALCAR under conditions of hypobaric hypoxia and elucidates a novel mechanism of action of the drug.

Surgical treatment for incessant pericarditis.

A case of chronic relapsing pericarditis is presented in which all forms of medical therapy failed. Pericardectomy was performed as a last resort, with complete resolution of symptoms. Incessant pericarditis, as distinguished from recurrent intermittent pericarditis, may respond favourably to surgical removal, especially in the presence of recurrent pericardial effusion.

Optimal phasic tracheal gas insufflation timing: an experimental and mathematical analysis.

OBJECTIVE: To investigate the modulation of CO2 clearance by changes in the duration of tracheal gas flow application during tracheal gas insufflation (TGI). DESIGN: Combination of bench studies using a commercial test lung and a commercially available intensive care ventilator and mathematical analysis using a clearance model derived from first principles. SETTING: University pulmonary research laboratory. PATIENTS: None. INTERVENTIONS: Experiments using TGI were performed on a test lung at two combinations of tidal volume and frequency. TGI was limited to part of the expiratory phase (the terminal 10-100% of expiration), and two different TGI catheter flow rates were studied. Permutations over a range of compliances, dead-space volumes, catheter flows, and TGI durations were collected. A mathematical model incorporating key ventilatory and TGI-related variables was developed to provide a first-principles theoretical foundation for interpreting the experimental results. MEASUREMENTS AND MAIN RESULTS: In the physical model, alveolar Pco2 attained a minimum value with TGI flow applied during the terminal 40-60% of the expiratory phase, a finding that was consistent over an almost eight-fold range of expiratory time constants. The mathematical model shows the same qualitative pattern as the experimental model, indicating that the observed behaviors are not an experimental artifact. CONCLUSION: The optimal duration of expiratory TGI flow application is stable over a wide range of impedance characteristics. Such stability suggests that near maximal effect of expiratory TGI could be obtained by applying TGI flow solely within the final 50% of the expiratory phase. Such uniform restriction of the application profile might both simplify technique implementation and decrease adverse consequences.

Post-translational modification of the myxoma-virus anti-inflammatory serpin SERP-1 by a virally encoded sialyltransferase.

SERP-1 is a secreted serpin (serine-proteinase inhibitor) encoded by myxoma virus, a poxvirus pathogen of rabbits. SERP-1 is required for myxoma-virus virulence, and the purified protein has been shown to possess independent anti-inflammatory activity in animal models of restenosis and antigen-induced arthritis. As an inhibitor of serine proteinases, SERP-1 acts against tissue-type plasminogen activator, urokinase-type plasminogen activator, plasmin, thrombin and Factor Xa. In the present study, examination of SERP-1 glycosylation-site mutants showed that the N-linked glycosylation of Asn(172) was essential for SERP-1 secretion, whereas mutation of Asn(99) decreased secretion efficiency, indicating that N-linked glycosylation plays an essential role in the processing and trafficking of SERP-1. Furthermore, comparison of SERP-1 from wild-type myxoma virus and a virus containing a targeted disruption of the MST3N sialyltransferase locus demonstrated that SERP-1 is specifically modified by this myxoma-virus-encoded sialyltransferase, and is thus the first reported viral protein shown to by modified by a virally encoded glycosyltransferase. Sialylation of SERP-1 by the MST3N gene product creates a uniquely charged species of secreted SERP-1 that is distinct from SERP-1 produced from other eukaryotic expression systems, though this has no apparent effect upon the kinetics of in vitro proteinase inhibition. Rather, the role of viral sialylation of SERP-1 likely relates to masking antigenicity or targeting SERP-1 to specific sites of action in vivo.