Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

BACKGROUND: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). MATERIALS/METHODS: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). RESULTS: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. CONCLUSIONS: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

The neutrophil/lymphocyte ratio as a prognostic factor in COVID-19 patients: a case-control study.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been identified in China as responsible for viral pneumonia, now called COVID-19 (Coronavirus Disease 2019). Patients infected can develop common symptoms like cough and sore throat, and, in severe cases, acute respiratory syndrome and even death. To optimize the available resources, it is necessary to identify in advance the subjects that will develop a more serious illness, therefore requiring intensive care.The neutrophil / lymphocyte ratio (NLR) parameter, resulting from the blood count, could be a significant marker for the diagnosis and management of risk stratification. PATIENTS AND METHODS: A retrospective, single-center case-control observational study was conducted. The differential cell count of leukocytes, the NLR and the clinical course of patients hospitalized in intensive care with COVID-19 were analyzed, comparing them with other patients (COVID-19 and non-COVID-19) and healthy individuals selected among workers of the Teaching Hospital Policlinico Umberto I in Rome. RESULTS: 370 patients (145 cases and 225 controls) were included in the case-control study, 211 males (57%) and 159 females (43%). The average age of the population was 63 years (SD 16.35). In the group of cases, out of 145 patients, 57 deaths and 88 survivors were recorded, with a lethality rate of 39.3%. The group of cases has an NLR of 7.83 (SD = 8.07), a much higher value than the control group where an NLR of 2.58 was recorded (SD = 1.93) (p <0.001). The Neutrophils / Lymphocytes ratio may prove to be a diagnostic factor for COVID-19, an NLR> 3.68 revealed an OR 10.84 (95% CI = 6.47 - 18.13) (p <0.005). CONCLUSIONS: The value of NLR considered together with the age variable allows a risk stratification and allows the development of diagnostic and treatment protocols for patients affected by COVID-19. A high neutrophil to lymphocyte ratio suggests worse survival. Risk stratification and management help alleviate the shortage of medical resources and reduce the mortality of critically ill patients.

A case of chronic systemic capillary leak syndrome (SCLS) exacerbated during SARS-CoV2 infection.

Systemic capillary leak syndrome (SCLS) is a very rare and lethal disease characterized by hemoconcentration and hypoalbuminemia caused by reversible plasma extravasation. The underlying cause for SCLS remains largely unknown and acute treatment has remained mainly supportive. Prophylaxis with intravenous immunoglobulin (IVIG) has been shown to successfully prevent further episodes in affected patients. We reported a case of SCLS in a patient who presented to our hospital with COVID-19 and developed profound shock.

Knowledge, attitude, barriers, professional behaviour and possible interventions: a survey on healthcare-associated infections among the healthcare workers of an intensive care unit in a large teaching hospital in Rome.

Methods: A questionnaire of 36 questions was developed and administered to assess socio-occupational characteristics, knowledge of Healthcare-associated infections, attitudes and barriers encountered in compliance with hygiene standards, self-analysis of professional behaviour, and proposals for new interventions. Variables were evaluated by univariate analysis, and multivariable logistic regression models were constructed to identify predictors of adequate knowledge, positive attitude and appropriate professional behaviour. Background: Healthcare-associated infections are the main complications of hospitalization. A bottom-up approach, where the Healthcare workers involved play a key role, can be adopted to limit the Healthcare-associated infections burden. To this end, a survey was conducted in the main intensive care unit of Umberto I Teaching Hospital of Rome, where an active surveillance system has been in place since April 2016. Results: Overall, 79/89 Healthcare workers completed the questionnaire. Multivariate analysis showed that Healthcare workers, who participated in ward meetings to share active surveillance reports, were more likely to have adequate knowledge (aOR=4.21, 95% CI: 1.36-13.07). Only job type seemed to be a predictor of adequate behaviour, since nurses and physicians were more likely to show adequate behaviour than residents in training (aOR=0.21, 95% CI: 0.06-0.74). Direct observation of compliance with standard hygiene precautions and the identification of 'local champions' to manage Healthcare-associated infections' issues were the most requested interventions. Conclusions: Our study suggests that the training of healthcare professionals is a key factor in preventing and containing the spreading of Healthcare-associated infections. Moreover, by encouraging greater Healthcare workers' involvement, we conclude that a bottom-up approach is likely to improve Healthcare-associated infections' prevention and management.

The impact of the COVID-19 pandemic on healthcare-associated infections in intensive care unit patients: a retrospective cohort study.

BACKGROUND: During the intensive care units' (ICUs) reorganization that was forced by the COVID-19 emergency, attention to traditional infection control measures may have been reduced. Nevertheless, evidence on the effect of the COVID-19 pandemic on healthcare-associated infections (HAIs) is still limited and mixed. In this study, we estimated the pandemic impact on HAI incidence and investigated the HAI type occurring in COVID-19 patients. METHODS: Patients admitted to the main ICU of the Umberto I teaching hospital of Rome from March 1st and April 4th 2020 were compared with patients hospitalized in 2019. We assessed the association of risk factors and time-to-first event through multivariable Fine and Grey's regression models, that consider the competitive risk of death on the development of HAI (Model 1) or device related-HAI (dr-HAI, Model 2) and provide estimates of the sub-distribution hazard ratio (SHR) and its associated confidence interval (CI). A subgroup analysis was performed on the 2020 cohort. RESULTS: Data from 104 patients were retrieved. Overall, 59 HAIs were recorded, 32 of which occurred in the COVID-19 group. Patients admitted in 2020 were found to be positively associated with both HAI and dr-HAI onset (SHR: 2.66, 95% CI 1.31-5.38, and SHR: 10.0, 95% CI 1.84-54.41, respectively). Despite being not confirmed at the multivariable analysis, a greater proportion of dr-HAIs seemed to occur in COVID-19 patients, especially ventilator-associated pneumonia, and catheter-related urinary tract infections. CONCLUSIONS: We observed an increase in the incidence of patients with HAIs, especially dr-HAIs, mainly sustained by COVID-19 patients. A greater susceptibility of these patients to device-related infections was hypothesized, but further studies are needed.

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission.

BACKGROUND: Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). MATERIALS/METHODS: Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. RESULTS: Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58-76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). CONCLUSIONS: In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.

Awake fiberoptic intubation in patients with stenosis of the upper airways: Utility of the laryngeal nerve block.

Awake fiberoptic intubation (AFOI) is mandatory to manage difficult airways. Superior laryngeal nerve block (SLNB) could reduce risks and improve patient comfort. The aim of this study is to assess the procedural comfort of SLNB during AFOI in a population of patients undergoing upper airway oncological surgery. Forty patients were randomized into two groups and were treated with continuous infusion of remifentanil, topic anesthesia and intercricoid block. In the study group (=20), SLNB was performed with lidocaine (L-SLNB); in the control group (n=20) SLNB was performed using saline (S-SLNB). AFOI was more comfortable in the L-SLNB group compared to S-SLNB patients [FOICS ≤ 1 in 18 patients (90%) L-SLNB; 2 (10%) S-SLNB (P <0.001)]. Intubation was faster in L-SLNB (47.45 ±15.38 sec) than S-SLNB (80.15 ±37.91 sec) (p <0.001). The SLNB procedure during AFOI is a safe and comfortable procedure in a population of patients undergoing upper airways surgery. Time to intubation was shorter in L-SLNB than in S-SLNB.

Multimodal surveillance of healthcare associated infections in an intensive care unit of a large teaching hospital

BACKGROUND: Healthcare-associated infections (HAIs), or nosocomial infections, represent a significant burden in terms of mortality, morbidity, length of stay and costs for patients hospitalized in intensive care units (ICUs). Surveillance systems are recommended by national and international institutions to gather data on HAIs in order to develop and evaluate interventions that reduce the risk of HAIs. STUDY DESIGN: Here we describe the methodology and the results of the surveillance system implemented in the ICU of the Policlinico Umberto I, a large teaching hospital in Rome, from April 2016 to October 2018. METHODS: The multimodal infection surveillance system integrates four different approaches: i) active surveillance of inpatients; ii) environmental microbiological surveillance; iii) surveillance of isolated microorganisms; and iv) behavioral surveillance of healthcare personnel. Data were collected on catheter-related bloodstream infections, ventilation-associated pneumonia, catheter-associated urinary tract infections and primary bloodstream infections that developed in patients after 48 h in the ICU. For environmental surveillance 14 points were selected for sampling (i.e. bed edges, medication carts, PC keyboards, sink faucets). The system of active surveillance of HAIs also included surveillance of microorganisms, consisting of the molecular genotyping of bacterial isolates by pulsed-field gel electrophoresis (PFGE). From 1 November 2016, monitoring of compliance with guidelines for hand hygiene (HH) and proper glove or gown use by healthcare personnel was included in the surveillance system. After the first six months (baseline phase), a multimodal intervention to improve adherence to guidelines by healthcare personnel was conducted with the ICU staff. RESULTS: Overall, 773 patients were included in the active surveillance. The overall incidence rate of device-related HAIs was 14.1 (95% CI: 12.2-16.3) per 1000 patient-days. The monthly device-related HAI incident rate showed a decreasing trend over time, with peaks of incidence becoming progressively lower. The most common bacterial isolates were Klebsiella pneumoniae (20.7%), Acinetobacter baumannii (17.2%), Pseudomonas aeruginosa (13.4%) and Staphylococcus aureus (5.4%). Acinetobacter baumannii and Klebsiella pneumoniae showed the highest proportion of isolates with a multidrug-resistant profile. A total of 819 environmental samples were collected, from which 305 bacterial isolates were retrieved. The most frequent bacterial isolates were Acinetobacter baumannii (27.2%), Staphylococcus aureus (12.1%), Enterococcus faecalis (11.1%), Klebsiella pneumoniae (5.2%) and Pseudomonas aeruginosa (4.7%). All Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae environmental isolates were at least multidrug-resistant. Genotyping showed a limited number of major PFGE patterns for both clinical and environmental isolates of Klebsiella pneumoniae and Acinetobacter baumannii. Behavioral compliance rates significantly improved from baseline to post-intervention phase. CONCLUSIONS: By integrating information gathered from active surveillance, environmental microbiological surveillance, surveillance of bacterial isolates and behavioral surveillance of healthcare personnel, the multimodal infection surveillance system returned a precise and detailed view of the infectious risk and microbial ecology of the ICU.

Role of biomarkers in adult sepsis and their application for a good laboratory practice: a pilot study.

This study measured Procalcitonin (PCT), Presepsin (PRE-S) and pro-Adrenomedullin (pro-ADM) in intensive care unit (ICU) patient’s blood to assess their contribution to accurate diagnosis of sepsis and potential predictive impact on prognosis. The final aim was to improve the use of infection biomarkers for optimizing the impact of laboratory medicine on clinical outcomes, focusing on the good management of resources designed to produce maximum effectiveness and efficiency. Sixty-four adult patients were studied during their hospitalization in ICU; blood samples were collected and categorized according to their clinical diagnosis and illness severity, and sepsis marker levels were measured on automated immunoassay platforms. PCT, PRE-S and pro-ADM infection markers were significantly lower in controls than in sepsis or septic shock groups. The area under the curve, by ROC curve analysis, was 0.945 for PCT, 0.756 for PRE-S and 0.741 for pro-ADM. Sepsis diagnostic accuracy was not improved by combining PCT, PRE-S and pro-ADM measures. Preliminary data demonstrated that, despite PRE-S and pro-ADM being able to differentiate between septic and non-septic patients with accuracy, PCT remains the most reliable marker available. The results obtained still do not allow us to consider a combination of markers, because it would merely increase laboratory costs without improving diagnostic performance. Furthermore, the results confirm a possible prognostic role of pro-ADM in septic states, but no correlation between biomarker levels and survival at 48 h was detected. Hence PCT, PRE-S, nor pro-ADM can be used to predict short-term prognosis.

Perioperative management in patients undergoing pancreatic surgery: the anesthesiologist's point of view.

BACKGROUND: A high rate of mortality and morbidity has been associated with pancreaticoduodenectomy; the 5-year survival rate is 15% to 25% compared with 1% to 5% among those who did not have any cancer-directed treatment. Systemic rather than surgical complications cause the majority of perioperative deaths, so the anesthesiologist has a crucial role in the management of these patients. This work sought to evaluate an improved approach to perioperative pain management, postsurgical complications as well as outcomes. PATIENTS: From 2002 to 2007, 40 patients underwent pancreaticoduodenectomy for pancreatic or periampullary cancer. The anesthesia protocol was standardized for postoperative pain control. Patients were randomly divided into two groups: 16 patients received an epidural analgesia with local anesthetics combined with opioids (T(9)-T(10); group A) and 24 had IV analgesia with morphine (group B). RESULTS: Postoperative mortality was 2.5%. With regard to complications we observed 4 biliary fistulas, 2 pancreatic fistulas with spontaneous healing in one patient and death in the other as well as wound infections. Patients treated with epidural analgesia experienced better pain relief, compared with subjects receiving IV analgesia, which demonstrated a higher incidence of opioid-related adverse effects such as sedation and respiratory depression. CONCLUSION: Adequate perioperative treatment included suitable nutritional support and pain management using loco-regional techniques, which seem to improve the surgical outcomes among pancreatic cancer patients.

Multiple spin echoes in heterogeneous systems: physical origins of the observed dips.

Dipolar interactions in liquids have recently offered a new challenge to investigate porous media by exploiting intermolecular quantum coherences, which are obtained through a simple two-pulse sequence (90 degrees -tau-120 degrees ). This sequence, in the presence of an external gradient (G), refocuses a train of echoes at multiple integer values of time tau. The first and second echo amplitudes are acquired for heterogeneous systems such as porous media at different time values (tau). In our first experiments on bovine bone samples we have observed unpredicted dips on the second echo time behavior. We argue that a strict relation occurs between the average pore dimensions and the dips time position through the correlation distance d=pi/(gamma G tau) (defined as half a cycle of the magnetization helix, which originates in the presence of an external gradient). Although the experimental results have revealed an exceptional connection between the porous structure and the correlation distance, no physical explanation was so far provided. In this paper we propose a possible physical cause of the observed phenomenon. In addition we report an accurate analysis of new experiments performed on glass beads phantoms, which confirms our conclusions.

Multiple spin echoes for the evaluation of trabecular bone quality.

We report a simple and efficient MR method for the evaluation of trabecular bone quality. This technique is based on detection and imaging of Multiple Spin-Echoes (MSE), a manifestation of the dipolar field generated by residual intermolecular dipolar couplings in liquids. In the particular implementation we have used, originally proposed by Bowtell [J. Magn. Reson. 100 (1992) 1; J. Magn. Reson. 88 (1990) 643; Phys. Rev. Lett. 76 (1996) 4971], multiple spin echoes (MSE) are refocused in a two-pulse experiment in the presence of a correlation linear magnetic field gradient G(c). This gradient generates a magnetisation helix and results in the spatial modulation of the sample magnetisation. In heterogeneous systems, the amplitude of the MSE signal depends on sample heterogeneity over a distance d=pi/(gammaG(c)tau) which is half a cycle of the magnetisation helix, thus providing a novel contrast mechanism that can be tuned to a specific length scale. We have exploited this mechanism to study young bovine trabecular bone samples ex-vivo. We show that MSE images present a different contrast from conventional MR images, and that, by varying the experimental parameters, the image contrast can be related to specific trabecular pore sizes. The potential of this technique for the early diagnosis of osteoporotic diseases is discussed.

Characterization of trabecular bone by dipolar demagnetizing field MRI.

A multiple spin-echo (MSE) sequence has been applied for the first time to study trabecular bone ex vivo. The second echo generated by the demagnetizing field presents discrete drops in signal intensity for certain values of the pitch of the magnetization helix created by the correlation gradient. These dips may reflect characteristic pore sizes in the trabecular bone specimens. This hypothesis is supported by similar experiments performed on a phantom with uniform pore size distribution. Trabecular bone images weighted in the MSE contrast mechanism are reported.

Characterization of porous media structure by non linear NMR methods.

In this paper we discuss the possibility of modifying the multiple spin echoes existing theory, developed for a homogeneous system, to describe also an inhomogeneous system such as a porous medium. We report here the first experimental application of MSE methods to materials like travertine. The ratio A(2)/A(1) from water in travertine presents minima for characteristic values of the delay time tau, like what was previously observed in the trabecular bone. By a judicious choice of the delay time tau and of the G gradient strength, the MSE sequence can be made sensitive to a specific length-scale of the sample heterogeneity. Furthermore the MSE image shows a particular new contrast that makes the non linear NMR method very attractive for the assessment of variations of the porous structure in porous systems.

Anaerobic threshold in runners and cyclists.

Two different noninvasive procedures have been used to determine the anaerobic threshold (AT) in 15 long distance runners and in 6 cyclists. The AT values obtained by ventilatory methods (on treadmill for runners and on cycloergometer for cyclists) and the AT values obtained by a field test were significantly correlated.