Marta Di Pasquale

Stratifying Risk Factors for Multidrug-Resistant Pathogens in Hospitalized Patients Coming From the Community With Pneumonia

BACKGROUND  Not all risk factors for acquiring multidrug-resistant (MDR) organisms are equivalent in predicting pneumonia caused by resistant pathogens in the community. We evaluated risk factors for acquiring MDR bacteria in patients coming from the community who were hospitalized with pneumonia. Our evaluation was based on actual infection with a resistant pathogen and clinical outcome during hospitalization. METHODS  An observational, prospective study was conducted on consecutive patients coming from the community who were hospitalized with pneumonia. Data on admission and during hospitalization were collected. Logistic regression models were used to evaluate risk factors for acquiring MDR bacteria independently associated with the actual presence of a resistant pathogen and in-hospital mortality. RESULTS  Among the 935 patients enrolled in the study, 473 (51%) had at least 1 risk factor for acquiring MDR bacteria on admission. Of all risk factors, hospitalization in the preceding 90 days (odds ratio [OR], 4.87 95% confidence interval {CI}, 1.90-12.4]; P = .001) and residency in a nursing home (OR, 3.55 [95% CI, 1.12-11.24]; P = .031) were independent predictors for an actual infection with a resistant pathogen. A score able to predict pneumonia caused by a resistant pathogen was computed, including comorbidities and risk factors for MDR. Hospitalization in the preceding 90 days and residency in a nursing home were also independent predictors for in-hospital mortality. CONCLUSIONS  Risk factors for acquiring MDR bacteria should be weighted differently, and a probabilistic approach to identifying resistant pathogens among patients coming from the community with pneumonia should be embraced.

Assessment of severity of ICU-acquired pneumonia and association with etiology.

Objectives:We evaluated the association between severity of illness and microbial etiology of ICU-acquired pneumonia to define if severity should be used to guide empiric antibiotic choices. Design:Prospective observational study. Setting:ICUs of a university hospital. Patients:Three hundredy forty-three consecutive patients with ICU-acquired pneumonia clustered, according to the presence of multidrug resistant pathogens. Interventions:None. Measurements and Main Results:Two hundred eight patients had ventilator-associated pneumonia and 135 had nonventilator ICU-acquired pneumonia. We determined etiology in 217 patients (63%). The most frequent pathogens were Pseudomonas aeruginosa, Enterobacteriaceae, and methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Fifty-eight patients (17%) had a multidrug-resistant causative agent. Except for a longer ICU stay and a higher rate of microbial persistence at the end of the treatment in the multidrug-resistant group, no differences were found in clinical and inflammatory characteristics, severity criteria, and mortality or survival between patients with and without multidrug-resistant pathogens, even after adjusting for potential confounders. Patients with higher severity scores (Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment) and septic shock at onset of pneumonia had significantly lower 28- and 90-day survival and higher systemic inflammatory response. The results were similar when only patients with microbial diagnosis were considered, as well as when stratified into ventilator-associated pneumonia and nonventilator ICU-acquired pneumonia. Conclusions:In patients with ICU-acquired pneumonia, severity of illness seems not to affect etiology. Risk factors for multidrug resistant, but not severity of illness, should be taken into account in selecting empiric antimicrobial treatment.

Endotracheal Tubes for Critically Ill Patients: An In Vivo Analysis of Associated Tracheal Injury, Mucociliary Clearance, and Sealing Efficacy

BACKGROUND Improvements in the design of the endotracheal tube (ETT) have been achieved in recent years. We evaluated tracheal injury associated with ETTs with novel high-volume low-pressure (HVLP) cuffs and subglottic secretions aspiration (SSA) and the effects on mucociliary clearance (MCC). METHODS Twenty-nine pigs were intubated with ETTs comprising cylindrical or tapered cuffs and made of polyvinylchloride (PVC) or polyurethane. In specific ETTs, SSA was performed every 2 h. Following 76 h of mechanical ventilation, pigs were weaned and extubated. Images of the tracheal wall were recorded before intubation, at extubation, and 24 and 96 h thereafter through a fluorescence bronchoscope. We calculated the red-to-green intensity ratio (R/G), an index of tracheal injury, and the green-plus-blue (G+B) intensity, an index of normalcy, of the most injured tracheal regions. MCC was assessed through fluoroscopic tracking of radiopaque markers. After 96 h from extubation, pigs were killed, and a pathologist scored injury. RESULTS Cylindrical cuffs presented a smaller increase in R/G vs tapered cuffs (P = .011). Additionally, cuffs made of polyurethane produced a minor increase in R/G (P = .012) and less G+B intensity decline (P = .022) vs PVC cuffs. Particularly, a cuff made of polyurethane and with a smaller outer diameter outperformed all cuffs. SSA-related histologic injury ranged from cilia loss to subepithelial inflammation. MCC was 0.9 ± 1.8 and 0.4 ± 0.9 mm/min for polyurethane and PVC cuffs, respectively (P < .001). CONCLUSIONS HVLP cuffs and SSA produce tracheal injury, and the recovery is incomplete up to 96 h following extubation. Small, cylindrical-shaped cuffs made of polyurethane cause less injury. MCC decline is reduced with polyurethane cuffs.

Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.

Role of Streptococcus pneumoniae infection in chronic obstructive pulmonary disease patients in Italy

Background: The aim of this study was to determine the incidence of exacerbations due to Streptococcus pneumoniae in chronic obstructive pulmonary disease (COPD) patients during stable state. Methods: We conducted a prospective, observational, cohort study including stable COPD patients, who were evaluated at least every 4 months over a 24-month period at the Respiratory Unit of the IRCCS Policlinico Hospital in Milan, Italy, from 2012 to 2015. Sputum samples were collected at enrollment during stable state to evaluate the frequency of S. pneumoniae colonization and in case of an acute exacerbation to evaluate the incidence of pneumococcal infection. Results: A total of 79 stable patients with moderate to very severe COPD were enrolled. A total of 217 samples were collected, and 27% (n = 59) of those were positive for S. pneumoniae. A total of four exacerbations due to S. pneumoniae occurred during follow up (0.31 per 100 person/month). Among positive samples of S. pneumoniae, 109 serotypes were identified. The most frequent serotypes in moderate-to-severe COPD patients during both stable state and exacerbation were 19F (12%), 18 (10%), 19A and 9V (9%) and 35 F (7%). Only 32% of COPD patients were effectively vaccinated for S. pneumoniae with PPV23 vaccine. Conclusion: The most frequent S. pneumoniae serotypes in COPD patients are 19F, 18, 19A, 9V and 35 F, and that almost 50% of S. pneumoniae strains could be covered by PCV13 in adult COPD patients.

Antibiotic therapy, supportive treatment and management of immunomodulation-inflammation response in community acquired pneumonia: review of recommendations

Community-acquired pneumonia is a common and serious disease, with high rates of morbidity and mortality. Management and treatment of community-acquired pneumonia are described in three main documents: the 2007 American Thoracic Society guidelines, the 2011 European Respiratory Society guidelines, and the 2009 British Thoracic Society guidelines, updated by the NICE in 2015. Despite the validity of current guidelines in improving prognosis and management of patients with community-acquired pneumonia, not all recommendations have high levels of evidence and there are still some controversial issues. In particular, there are some areas of low evidence such as the efficacy of an antibiotic molecule or scheme in patients with same risk factors; duration of antibiotic treatment, supportive therapy for acute respiratory failure and immunomodulation molecules.This review will summarize the main recommendations with high level of evidence and discuss the recommendations with lower evidence, analyzing the studies published after the guidelines’ release.

Acute exacerbations of COPD: risk factors for failure and relapse

Acute exacerbations are a leading cause of worsening COPD in terms of lung function decline, quality of life, and survival. They also have a relevant economic burden on the health care system. Determining the risk factors for acute exacerbation and early relapse could be a crucial element for a better management of COPD patients. This review analyzes the current knowledge and underlines the main risk factors for recurrent acute exacerbations. Comprehensive evaluation of COPD patients during stable phase and exacerbation could contribute to prevent treatment failure and relapses.

Efficacy and effectiveness of Ceftaroline Fosamil in patients with pneumonia: a systematic review and meta-analysis

BackgroundPneumonia is a relevant clinical and public health issue worldwide frequently associated with infections caused by Multi-Drug Resistant (MDR) pathogens. Ceftaroline fosamil is a promising new antibiotics with broad-spectrum bacterial activity. The aim of this systematic review and meta-analysis is to assess the efficacy and the effectiveness of ceftaroline fosamil in community-acquired (CAP), hospital-acquired (HAP), healthcare-associated (HCAP) and ventilator-associated (VAP) pneumonia.MethodsA systematic review and meta-analysis was carried out retrieving both experimental and observational studies.ResultsA total of 2364 records was found and 14 manuscripts were finally considered eligible. The pooled efficacy/effectiveness was 81.2% (I2: 1.2%) in all types of pneumonia. The pooled relative risk of clinical cure was 1.1 (I2: 0.0%). The success rate was higher than 70% for infections caused by S. pneumoniae and S. aureus, including MDR pathogens.ConclusionsCeftaroline fosamil showed a high efficacy/effectiveness in patients with any type of pneumonia with a good safety profile.

Emerging antibacterial and antiviral drugs for treating respiratory tract infections

ABSTRACT Introduction: Management of LRTI is becoming more frequently challenging since the emergence of multidrug resistance bacteria and the increase of severe viral infection, reducing the number of available effective drugs. The clinical evaluation of new therapeutic associations is mandatory to cope with the increases in resistance, in association with better infection control and antimicrobial policies. Areas covered: We searched Pubmed in English language of phase I, II, III clinical trials and approved treatments for LRTI, between 2006 and 2016. Expert opinion:Development of new molecules or new combinations regimens are very important for patients with severe infections and in specific subgroups of patients like CF and bronchiectatic patients. Standardized protocols for antibiotic stewardship in difficult-to-treat infections are the next step. Moreover, non-antibiotic treatments and preventive strategies as vaccination need to be part of clinical practice.

Prevalence and etiology of community-acquired pneumonia in immunocompromised patients

Of patients with pneumonia coming from the community, 18% are immunocompromised. Specific immunocompromised states are associated with specific microbiology, which has to be taken into consideration when choosing empirical therapy.