Respiratory infections caused by Klebsiella pneumoniae are characterized by high rates of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. In the present study, we investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor, both derived from the virulent strain 52145R. We demonstrated that the AcrB knockout was more susceptible, not only to quinolones, but also to other antimicrobial agents, including ␤-lactams, than the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model, in contrast to the wild-type strain. The results of this study suggest that, in addition to contributing to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for K. pneumoniae to resist innate immune defense mechanisms of the lung, thus facilitating the onset of pneumonia.

The objective of this study is to evaluate the clinical and microbiological characteristics of bacteremia associated with pressure ulcers (BAPU) and factors associated with mortality. This study was a prospective observational cohort study of patients with BAPU at a teaching hospital between January 1984 and December 2015. Fifty-six episodes were included. The incidence of BAPU decreased from 2.78 cases per 10,000 hospital discharges in the period from 1984 to 1999 to 1.05 cases per 10,000 hospital discharges in the period from 2000 to 2015 (p < 0.001). In 20 cases (35.7%), the bacteremia was hospital-acquired, since it occurred more than 48 h after the hospital admission. The most frequent microorganisms isolated in blood culture were Staphylococcus aureus, Proteus spp., and Bacteroides spp. The bacteremia was polymicrobial in 14 cases (25.0%). Overall mortality was observed in 23 episodes (41.1%). The risk factors independently associated with mortality were hospital-acquired bacteremia (odds ratio [OR] 5.51, 95% confidence interval [95%CI] 1.24–24.40), polymicrobial bacteremia (OR 6.88, 95%CI 1.22–38.89), and serum albumin <23 g/L (OR 8.00, 95%CI 1.73–37.01). BAPU is an uncommon complication of pressure ulcers and is mainly caused by S. aureus, Proteus spp., and Bacteroides spp. In our hospital, the incidence of BAPU has declined in recent years, coinciding with the implementation of a multidisciplinary team aimed at preventing and treating chronic ulcers. Mortality rate is high, and hospital-acquired bacteremia, polymicrobial bacteremia, and serum albumin < 23 g/L are associated with increased mortality.

The aim of the study was to evaluate the impact of a multifaceted antimicrobial stewardship intervention on antibiotic consumption in a primary health care (PHC) area in Spain. Quasi-experimental study conducted in a PHC area with nine PHC centers, a 400-bed acute care teaching hospital, and 18 nursing homes serving a population of 260,561. The intervention was based on the 2016 CDC Core Elements of Outpatient Antibiotic Stewardship publication and targeted 130 PHC physicians, 41 PHC pediatricians, 19 emergency physicians, and 18 nursing home physicians. The components were commitment, actions for improving antibiotic prescribing, tracking and feedback, and education and experience. The primary outcome was overall antibiotic consumption. Secondary outcomes were consumption of antibiotics to treat pharyngotonsillitis, acute otitis media, acute sinusitis, acute bronchitis, and urinary tract infection (UTI), percentage of patients treated with specific antibiotics, and dispensing costs. Consumption was measured in defined daily doses per 1,000 inhabitants per day (DID) and compared pre-and postintervention (2016 vs. 2018). Overall antibiotic consumption decreased from 16.01 to 13.31 DID (−16.85%). Consumption of amoxicillin/clavulanic acid and quinolones decreased from 6.04 to 4.72 DID (−21.88%) and 1.64 to 1.23 DID (−25.06%), respectively. The percentage of patients treated with antibiotics decreased from 26.99 to 22.41%. The intervention resulted in cost savings of €72,673. Use of antibiotics to treat pharyngotonsillitis, UTI, and acute otitis media, sinusitis, and bronchitis decreased significantly. Our antimicrobial stewardship program led to a decrease in antibiotic consumption and significantly improved the use of antibiotics for the most prevalent PHC infections.

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