Identifying the drivers of multidrug-resistant Klebsiella pneumoniae at a European level.

Beta-lactam- and in particular carbapenem-resistant Enterobacteriaceae represent a major public health threat. Despite strong variation of resistance across geographical settings, there is limited understanding of the underlying drivers. To assess these drivers, we developed a transmission model of cephalosporin- and carbapenem-resistant Klebsiella pneumoniae. The model is parameterized using antibiotic consumption and demographic data from eleven European countries and fitted to the resistance rates for Klebsiella pneumoniae for these settings. The impact of potential drivers of resistance is then assessed in counterfactual analyses. Based on reported consumption data, the model could simultaneously fit the prevalence of extended-spectrum beta-lactamase-producing and carbapenem-resistant Klebsiella pneumoniae (ESBL and CRK) across eleven European countries over eleven years. The fit could explain the large between-country variability of resistance in terms of consumption patterns and fitted differences in hospital transmission rates. Based on this fit, a counterfactual analysis found that reducing nosocomial transmission and antibiotic consumption in the hospital had the strongest impact on ESBL and CRK prevalence. Antibiotic consumption in the community also affected ESBL prevalence but its relative impact was weaker than inpatient consumption. Finally, we used the model to estimate a moderate fitness cost of CRK and ESBL at the population level. This work highlights the disproportionate role of antibiotic consumption in the hospital and of nosocomial transmission for resistance in gram-negative bacteria at a European level. This indicates that infection control and antibiotic stewardship measures should play a major role in limiting resistance even at the national or regional level

Identifying the drivers of multidrug-resistant Klebsiella pneumoniae at a European level

Beta-lactam- and in particular carbapenem-resistant Enterobacteriaceae represent a major public health threat. Despite strong variation of resistance across geographical settings, there is limited understanding of the underlying drivers. To assess these drivers, we developed a transmission model of cephalosporin- and carbapenem-resistant Klebsiella pneumoniae. The model is parameterized using antibiotic consumption and demographic data from eleven European countries and fitted to the resistance rates for Klebsiella pneumoniae for these settings. The impact of potential drivers of resistance is then assessed in counterfactual analyses. Based on reported consumption data, the model could simultaneously fit the prevalence of extended-spectrum beta-lactamase-producing and carbapenem-resistant Klebsiella pneumoniae (ESBL and CRK) across eleven European countries over eleven years. The fit could explain the large between-country variability of resistance in terms of consumption patterns and fitted differences in hospital transmission rates. Based on this fit, a counterfactual analysis found that reducing nosocomial transmission and antibiotic consumption in the hospital had the strongest impact on ESBL and CRK prevalence. Antibiotic consumption in the community also affected ESBL prevalence but its relative impact was weaker than inpatient consumption. Finally, we used the model to estimate a moderate fitness cost of CRK and ESBL at the population level. This work highlights the disproportionate role of antibiotic consumption in the hospital and of nosocomial transmission for resistance in gram-negative bacteria at a European level. This indicates that infection control and antibiotic stewardship measures should play a major role in limiting resistance even at the national or regional level

Modifiable and non-modifiable risk factors for non-ventilator-associated hospital-acquired pneumonia (nvHAP) identified in a retrospective cohort study.

OBJECTIVES Hospital-acquired pneumonia in non-ventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on modifiable risk factors. METHODS All inpatients admitted to an academic teaching hospital in Switzerland between 2017 and 2018 were included. NvHAP was defined according to European Centre for Disease Prevention and Control criteria. Patient days during and after ICU stay were excluded. Candidate risk factors - both constant and time-varying - were included in uni- and multivariable Cox proportional hazards models. The decay ratio and the characteristic time of influence of HRs was estimated by adopting a linear decay in the Cox model. RESULTS A total of 66,001 hospitalizations with 314 (0.48%) nvHAP and 471,401 patient days were included. Median age was 57 years (interquartile range: 38-71 years) and 32,253 (48.9%) patients were male. Among non-modifiable risk factors, age (adjusted-HR 2.66 for age ≥60 years, 95%CI 1.59-4.45) and male sex (aHR 1.71, 95%CI 1.34-2.18) were independently associated with nvHAP. Time-varying exposures showing strongest independent association with nvHAP were tube feeding (aHR 3.24, 95%CI 2.17-4.83), impaired consciousness (aHR 2.32, 95%CI 1.63-3.31), and severely impaired activity and mobility (aHR 2.06, 95%CI 1.50-2.84). The association with nvHAP decayed within 7.1 - 13.2 days after these exposures ended. CONCLUSIONS The risk for nvHAP varies with time, depending on the patient's medical condition and medical interventions. Several risk factors for nvHAP represent potential targets for specific prevention measures