Addressing current challenges in antibiotic treatment of community acquired pneumonia

[eng] Community-acquired pneumonia (CAP) is the leading infectious cause of death and the fourth most common cause of global mortality in the world. The high incidence of CAP and the high burden of morbidity, mortality and their related costs have meant that research into CAP is among the most popular areas of investigation. Nowadays, although there has been important progress in CAP management, there are still controversial points and a great deal of room for improvement. Our investigation attempted to focus on some of the current challenges in CAP research. HYPOTHESIS 1. Mortality in community-acquired pneumonia might have decreased in recent years, and there could be certain factors related with this change. 2. Pre-hospital antibiotic treatments could have an impact on the etiology, clinical features and outcomes of patients hospitalized for community-acquired pneumonia. 3. Timing from admission to first dose of antibiotic administration could have an impact on 30-day mortality in patients with pneumonia. 4. Antibiotic de-escalation could be a safe and effective strategy in patients hospitalized with pneumococcal community-acquired pneumonia. 5. Hospitalized patients with community-acquired Legionella pneumonia would have different outcomes depending on the antibiotic treatment administered. 6. There could be differences in response to antibiotic treatment in community-acquired pneumonia based on multiple patient factors. In the first study: “Declining mortality among hospitalized patients with community-acquired pneumonia”, we found that: • Thirty-day mortality significantly decreased over time in hospitalized community-acquired pneumonia patients, despite an upward trend in patient age and other factors associated with poor outcomes. • Several changes in the management of community-acquired pneumonia and a general improvement in global care over time may have caused the observed outcomes. In the second study: “Impact of pre-hospital antibiotic use on community-acquired pneumonia”, we found that: • In our cohort, 17.3% of patients received pre-hospital antibiotic treatment. These patients were younger, with fewer comorbidities, and less frequently presented bacteraemia than those patients who had not received antibiotic before hospitalisation. • The prevalence of Legionella pneumophila was nearly three times higher in patients who received pre-hospital antibiotics, mainly those who received β-lactams. • Pre-hospital antibiotic use should be considered when choosing aetiological diagnostic tests and empirical antibiotic therapy in patients with community-acquired pneumonia. In the third study: “Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia”, we found that: • Patients receiving early treatment had significantly greater illness severity at admission. • Antibiotic administration within 4 or 8 hours of arrival at the emergency department did not improve rates of 30-day survival in hospitalized adults for community-acquired pneumonia or healthcare-associated pneumonia. In the fourth study: “Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia”, we found that: • Antibiotic de-escalation appears to be safe and effective in reducing the duration of hospital stay. • Antibiotic de-escalation did not adversely affect outcomes of patients with community-acquired pneumococcal penumonia, even those with bacteraemia and severe disease, and those who were clinically unstable at time of de-escalation. • De-escalation strategies should be more widely implemented in the management of hospitalized adults with community-acquired pneumococcal penumonia. In the fifth study: “Levofloxacin versus azithromycin for treating Legionella pneumonia: a propensity score analysis”, we found that: • No significant differences in relevant outcomes were found between patients with Legionella pneumonia treated with levofloxacin and those receiving azithromycin. In the sixth study: “Predictors for individual patient antibiotic treatment effect in hospitalised community-acquired pneumonia patients”, we found that: • Older age and smoking could influence the response to specific antibiotic regimens. • The effect modification of age and smoking should be considered as a hypothesis to be evaluated in future trials.[spa] La neumonía adquirida en la comunidad (NAC) es la principal causa infecciosa de mortalidad en el mundo. Existen todavía puntos controvertidos en el abordaje terapéutico de la NAC. En este contexto se desarrolla la presente tesis doctoral. El primer estudio, encontró una disminución sustancial en la mortalidad a 30 días durante un período de 20 años, a pesar de una tendencia al alza en varios factores con influencia pronóstica negativa. Se observaron importantes cambios en el abordaje de los pacientes de la NAC, como el aumento de uso de ventilación mecánica, ingresos en la Unidad de Cuidados Intensivos, y el uso de fluoroquinolonas. Estos cambios pudieron ser la causa de la disminución de mortalidad observada. En el segundo estudio sobre el impacto del tratamiento antibiótico previo al ingreso, los pacientes con tratamiento antibiótico previo eran más jóvenes, con menor comorbilidad, fueron menos propensos a tener fiebre, leucocitosis y bacteriemia, y en ellos la prevalencia de Legionella pneumophila fue casi tres veces mayor. En el tercer estudio se encontró que la administración de antibióticos dentro de las primeras 4-8 horas de la llegada a Urgencias no mejoró la supervivencia a los 30 días en los adultos hospitalizados para NAC o neumonía relacionada con el ámbito sanitario. En el cuarto estudio sobre la desescalada de antibióticos en pacientes con neumonía neumocócica, la desescalada no se asoció a aumento de mortalidad y fue eficaz para reducir la duración de la estancia hospitalaria, incluso en los pacientes con bacteriemia, enfermedad grave, o los que estaban clínicamente inestables al momento de desescalar. En un estudio multicéntrico que valoró el tratamiento antibiótico en la neumonía por Legionella, los pacientes tratados con azitromicina tuvieron resultados similares a los tratados con levofloxacino, mientras los pacientes tratados con claritromicina tuvieron una estancia hospitalaria más prolongada. No se encontraron diferencias entre los tratamientos en cuanto a la mortalidad a los 30 días. En el sexto estudio, se analizaron predictores clínicos de respuesta a tratamiento antibiótico empírico. La edad avanzada y el tabaquismo se asocian con una mayor mortalidad a los 30 días en pacientes que recibieron fluoroquinolonas; la edad avanzada se relacionó también con una mayor estancia hospitalaria en los pacientes que recibieron beta-lactamicos + macrolidos

Predicted rates of merging neutron stars in galaxies

In this work, we compute rates of merging neutron stars (MNS) in galaxies of different morphological type, as well as the cosmic MNS rate in a unitary volume of the Universe adopting different cosmological scenarios. Our aim is to provide predictions of kilonova rates for future observations both at low and high redshift. In the adopted galaxy models, we take into account the production of r-process elements either by MNS or core-collapse supernovae. In computing the MNS rates we adopt either a constant total time delay for merging (10 Myr) or a distribution function of such delays. Our main conclusions are: i) the observed present time MNS rate in our Galaxy is well reproduced either with a constant time delay or a distribution function $\propto t^{-1}$. The [Eu/Fe] vs. [Fe/H] relation in the Milky Way can be well reproduced with only MNS, if the time delay is short and constant. If the distribution function of delays is adopted, core-collapse supernovae as are also required. ii) The present time cosmic MNS rate can be well reproduced in any cosmological scenario, either pure luminosity evolution or a typical hierarchical one, and spirals are the main contributors to it. iii) The spirals are the major contributors to the cosmic MNS at all redshifts in hierarchical scenarios. In the pure luminosity evolution scenario, the spirals are the major contributors locally, whereas at high redshift ellipticals dominate. iv) The predicted cosmic MNS rate well agrees with the cosmic rate of short Gamma Ray Bursts if the distribution function of delays is adopted, in a cosmological hierarchical scenario observationally derived. v) Future observations of Kilonovae in ellipticals will allow to disentangle among constant or a distribution of time delays as well as among different cosmological scenarios

Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild–moderate disease to prevent hospital admission and death, complementing COVID-19 vaccines. However, the evidence on the efficacy of COVID-19 antivirals during the Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated the efficacy of Molnupiravir or Nirmatrelvir/Ritonavir (Paxlovid®) or Sotrovimab against standard of care (controls) on three different endpoints among 386 high-risk COVID-19 outpatients: hospital admission at 30 days; death at 30 days; and time between COVID-19 diagnosis and first negative swab test result. Multinomial logistic regression was employed to investigate the determinants of hospitalization due to COVID-19-associated pneumonia, whereas time to first negative swab test result was investigated by means of multinomial logistic analysis as well as Cox regression analysis. Results. Only 11 patients (overall rate of 2.8%) developed severe COVID-19-associated pneumonia requiring admission to hospital: 8 controls (7.2%); 2 patients on Nirmatrelvir/Ritonavir (2.0%); and 1 on Sotrovimab (1.8%). No patient on Molnupiravir was institutionalized. Compared to controls, hospitalization was less likely for patients on Nirmatrelvir/Ritonavir (aOR = 0.16; 95% CI: 0.03; 0.89) or Molnupiravir (omitted estimate); drug efficacy was 84% for Nirmatrelvir/Ritonavir against 100% for Molnupiravir. Only two patients died of COVID-19 (rate of 0.5%), both were controls, one (aged 96 years) was unvaccinated and the other (aged 72 years) had adequate vaccination status. At Cox regression analysis, the negativization rate was significantly higher in patients treated with both antivirals—Nirmatrelvir/Ritonavir (aHR = 1.68; 95% CI: 1.25; 2.26) and Molnupiravir (aHR = 1.45; 95% CI: 1.08; 1.94). However, COVID-19 vaccination with three (aHR = 2.03; 95% CI: 1.51; 2.73) or four (aHR = 2.48; 95% CI: 1.32; 4.68) doses had a stronger effect size on viral clearance. In contrast, the negativization rate reduced significantly in patients who were immune-depressed (aHR = 0.70; 95% CI: 0.52; 0.93) or those with a Charlson index ≥ 3 (aHR = 0.63; 0.41; 0.95) or those who had started the respective treatment course 3+ days after COVID-19 diagnosis (aOR = 0.56; 95% CI: 0.38; 0.82). Likewise, at internal analysis (excluding patients on standard of care), patients on Molnupiravir (aHR = 1.74; 95% CI: 1.21; 2.50) or Nirmatrelvir/Ritonavir (aHR = 1.96; 95% CI: 1.32; 2.93) were more likely to turn negative earlier than those on Sotrovimab (reference category). Nonetheless, three (aHR = 1.91; 95% CI: 1.33; 2.74) or four (aHR = 2.20; 95% CI: 1.06; 4.59) doses of COVID-19 vaccine were again associated with a faster negativization rate. Only 64.7% of patients were immunized with 3+ doses of COVID-19 vaccines in the present study. Again, the negativization rate was significantly lower if treatment started 3+ days after COVID-19 diagnosis (aHR = 0.54; 95% CI: 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, and Sotrovimab were all effective in preventing hospital admission and/or mortality attributable to COVID-19. However, hospitalizations also decreased with higher number of doses of COVID-19 vaccines. Although they are effective against severe disease and mortality, the prescription of antivirals should be carefully scrutinized by double opinion, not only to contain health care costs but also to reduce the risk of generating resistant SARS-CoV-2 strains. Only 64.7% of patients were in fact immunized with 3+ doses of COVID-19 vaccines in the present study. High-risk patients should prioritize COVID-19 vaccination, which is a more cost-effective approach than antivirals against severe SARS-CoV-2 pneumonia. Likewise, although both antivirals, especially Nirmatrelvir/Ritonavir, were more likely than standard of care and Sotrovimab to reduce viral shedding time (VST) in high-risk SARS-CoV-2 patients, vaccination had an independent and stronger effect on viral clearance. However, the effect of antivirals or COVID-19 vaccination on VST should be considered a secondary benefit. Indeed, recommending Nirmatrelvir/Ritonavir in order to control VST in high-risk COVID-19 patients is rather questionable since other cheap, large spectrum and harmless nasal disinfectants such as hypertonic saline solutions are available on the market with proven efficacy in containing VST

Presenteeism levels among Italian nurses. A multicentric survey [Livelli di presenteismo fra gli infermieri italiani. Uno studio multicentrico]

INTRODUZIONE: Il presenteismo rappresenta la necessità di "mettersi al lavoro anche se ci si sente male"; influenzando così la qualità del lavoro, portando a errori o omissioni, riducendo la produttività e aumentando i costi. Gli infermieri sono annoverati tra i professionisti con il più alto grado di presenteismo, con potenziali effetti negativi sulla qualità del lavoro. OBIETTIVI: Accertare la prevalenza del Presenteismo tra gli infermieri italiani. METODI: E’ stato condotto uno studio trasversale, multicentrico da gennaio a dicembre 2015 su un campione di infermieri italiani. 652 infermieri hanno completato il questionario. Il punteggio totale medio alla Stanford Presenteeism Scale (SPS-6) era 21.6 (± 4.0). Gli infermieri hanno mostrato elevati livelli di Presenteismo nelle sezioni: "Evitare distrazioni" e "Completare il lavoro" della Scala. RISULTATI: Gli infermieri maschi hanno mostrato livell inferiori di Presenteismo rispetto alle donne, che tendevano anche ad essere minori con l'aumentare dell'età. La presenza di ≥1 problema di salute auto-riferito è stata associata ad un aumento del punteggio. CONCLUSIONI: In linea con studi precedenti effettuati nel contesto internazionale, il Presenteismo sembra essere una condizione diffusa anche tra gli infermieri italiani, che dovrebbe essere adeguatamente riconosciuta da parte dei manager sanitari. I risultati di questa indagine potrebbero essere utilizzati come spunto di riflessione, per implementare mirate strategie di politica sanitaria.BACKGROUND: Presenteeism represents the need to "get to work although we feel sick"; thus, affecting the quality of work, leading to errors or omissions, reducing productivity and increasing costs. Nurses are among the job categories with the highest degree of Presenteeism, which may negatively affect work quality. AIMS AND OBJECTIVES: To assess the prevalence of Presenteeism among Italian nurses. METHODS: A cross-sectional, multicentric study was carried out from January to December 2015 in a sample of Italian nurses. A total of 652 nurses completed the questionnaire. The mean Stanford Presenteeism Scale (SPS-6) total score was 21.6 (±4.0). Nurses showed high Presenteeism levels when considering the "Avoiding distractions" and "Completing work" sections of the Scale. RESULTS: Male nurses showed a lower degree of Presenteeism than women, which also tended to be less severe with increasing age. The presence of ≥1 self-reported health problem was associated with an increase in the score. CONCLUSIONS: In line with previous studies performed outside Italy, Presenteeism appear to be a widespread condition also among Italian nurses, requiring appropriate treatment and recognition by healthcare providers. The results of this survey might be used as a minimum, most likely underestimated basis for targeted public health policies

Livelli di presenteismo fra gli infermieri italiani. Uno studio multicentrico

BACKGROUND: Presenteeism represents the need to "get to work although we feel sick"; thus, affecting the quality of work, leading to errors or omissions, reducing productivity and increasing costs. Nurses are among the job categories with the highest degree of Presenteeism, which may negatively affect work quality. Aims and objectives: To assess the prevalence of Presenteeism among Italian nurses. METHODS: A cross-sectional, multicentric study was carried out from January to December 2015 in a sample of Italian nurses. A total of 652 nurses completed the questionnaire. The mean Stanford Presenteeism Scale (SPS-6) total score was 21.6 (±4.0). Nurses showed high Presenteeism levels when considering the “Avoiding distractions” and “Completing work” sections of the Scale. RESULTS: Male nurses showed a lower degree of Presenteeism than women, which also tended to be less severe with increasing age (both p<0.05). The presence of ≥1 self-reported health problem was associated with an increase in the score (p<0.05). CONCLUSIONS: In line with previous studies performed outside Italy, Presenteeism appear to be a widespread condition also among Italian nurses, requiring appropriate treatment and recognition by healthcare providers. The results of this survey might be used as a minimum, most likely underestimated basis for targeted public health policies.INTRODUZIONE: Il presenteismo rappresenta la necessità di "mettersi al lavoro anche se ci si sente male"; influenzando così la qualità del lavoro, portando a errori o omissioni, riducendo la produttività e aumentando i costi. Gli infermieri sono annoverati tra i professionisti con il più alto grado di presenteismo, con potenziali effetti negativi sulla qualità del lavoro. OBIETTIVI: Accertare la prevalenza del Presenteismo tra gli infermieri italiani. METODI: E’ stato condotto uno studio trasversale, multicentrico da gennaio a dicembre 2015 su un campione di infermieri italiani. 652 infermieri hanno completato il questionario. Il punteggio totale medio alla Stanford Presenteeism Scale (SPS-6) era 21.6 (± 4.0). Gli infermieri hanno mostrato elevati livelli di Presenteismo nelle sezioni: "Evitare distrazioni" e "Completare il lavoro" della Scala. RISULTATI: Gli infermieri maschi hanno mostrato livell inferiori di Presenteismo rispetto alle donne, che tendevano anche ad essere minori con l'aumentare dell'età (entrambi p <0,05). La presenza di ≥1 problema di salute auto-riferito è stata associata ad un aumento del punteggio (p <0,05). CONCLUSIONI: In linea con studi precedenti effettuati nel contesto internazionale, il Presenteismo sembra essere una condizione diffusa anche tra gli infermieri italiani, che dovrebbe essere adeguatamente riconosciuta da parte dei manager sanitari. I risultati di questa indagine potrebbero essere utilizzati come spunto di riflessione, per implementare mirate strategie di politica sanitaria

Determination of the main bioaerosol components using chemical markers by liquid chromatography–tandem mass spectrometry

This work is part of an extensive research project aimed at the determination and characterization of bioaerosol with a multidisciplinary approach. In this context, one of the main objectives of the project has been the development of a comprehensive analytical method for the determination of different chemical biomarkers of the bioaerosol, by liquid chromatography coupled with tandem mass spectrometry. The following biomarkers have been considered, and correlated to specific components of bioaerosol as unambiguous indicators: • ergosterol fungal components • chlorophylls, phytosterols (stigmasterol and b-sitosterol), -tocoferol vegetable cells and algae • cholesterol animal cells, vegetable cells and algae. • dipicolinic acid bacterial spores • muramic and meso-2,6-diaminopimelic acid bacterial cells To verify the method, to find diagnostic ratios and to calculate the appropriate conversion factors, fungal spores, bacterial cells and spores, and algae of known species, commonly airborne, were analysed. The material was subjected to freezing and de-freezing cycles, followed by extraction, hydrolysis and purification of the biomarkers. The chromatographic separation of the bacterial biomarkers was achieved by using a polymeric column, based on Hydrophilic Liquid Interaction with the electrospray ionization mass spectrometric detection, whereas sterols and chlorophylls were separated by a reversed phase column, coupled to atmospheric pressure chemical ionization – tandem mass spectrometer. The optimized method was applied to environmental particulate matter sampled in an outdoor site. Bacterial and fungal content was compared to the results obtained from the classical direct viable counting method in the sampled particulate matte