Purpose
Sepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear. We aimed to summarize the epidemiological evidence related to ...the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis.
Methods
We searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018. We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin. We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed.
Results
Of the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries. Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide. The proportion of HA sepsis among all hospital-treated sepsis cases was 23.6% (95% CI 17–31.8%, range 16–36.4%). In the ICU, 24.4% (95% CI 16.7–34.2%, range 10.3–42.5%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 48.7% (95% CI 38.3–59.3%, range 18.7–69.4%) had a hospital origin. The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 9.3 (95% CI 7.3–11.9, range 2–20.6)). In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 56.5 (95% CI 35–90.2, range 9.2–254.4) and it was particularly high in NICUs. Mortality of ICU patients with HA sepsis with organ dysfunction was 52.3% (95% CI 43.4–61.1%, range 30.1–64.6%). There was a significant inter-study heterogeneity. Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies.
Conclusion
HA sepsis is of major public health importance, and the burden is particularly high in ICUs. There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients.
Antimicrobial resistance (AMR) and hospital-acquired infections (HAIs) are global health challenges. The burden of antibiotic resistance in HAIs is still unclear in low- and lower-middle-income ...countries (L-LMICs). This study summarizes recent data on antibiotic resistance in priority HAIs (ESKAPE-E) in L-LMICs and compares them with data from high-income countries (HICs). EMBASE, Web of Science, and Global Index Medicus were searched for studies on AMR patterns in HAIs published from 01/2010 to 10/2020. Random-effects meta-analyses were performed to obtain pooled estimates. In total, 163 eligible studies were included in the review and meta-analysis. The pooled methicillin resistance proportion in Staphylococcus aureus was 48.4% (95% confidence interval 95%CI 41·7-55·2, n = 80). Pooled carbapenem resistance proportions were high in Gram-negative pathogens: Escherichia coli: 16·6% (95%CI 10·7-23·4, n = 60); Klebsiella pneumoniae: 34·9% (95%CI 24·6-45·9, n = 50); Pseudomonas aeruginosa: 37.1% (95%CI 24·6-45·9, n = 56); Enterobacter spp.: 51·2% (95%CI 27·5-74·7, n = 7); and Acinetobacter baumannii (complex): 72·4% (95%CI 62·1-81·7%, n = 36). A higher resistance proportions were observed for third-generation cephalosporins: Klebsiella pneumoniae: 78·7% (95%CI 71·5-85·2, n = 46); Escherichia coli: 78·5% (95%CI 72·1-84·2%, n = 58); and Enterobacter spp.: 83·5% (95%CI 71·9-92·8, n = 8). We observed a high between-study heterogeneity (I
2
> 80%), which could not be explained by our set of moderators. Pooled resistance proportions for Gram-negative pathogens were higher in L-LMICs than regional and national estimates from HICs. Patients in resource-constrained regions are particularly affected by AMR. To combat the high resistance to critical antibiotics in L-LMICs, and bridge disparities in health, it is crucial to strengthen local surveillance and the health systems in general.
BackgroundNeonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide.MethodsWe performed a ...systematic review and meta-analysis. 13 databases were searched for the period January 1979–May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level.ResultsThe search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009–2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias.ConclusionNeonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide.
Vancomycin-resistant enterococci infections are of great public health significance due to limited therapeutic options. We investigated epidemiological trends and risk factors of vancomycin ...resistance in enterococci isolates from patients with bloodstream infections in the EU/EEA from 2012 to 2018. Routine vancomycin susceptibility data of clinical E. faecium (n = 67,022) and E. faecalis (n = 103,112) blood isolates from the European Antimicrobial Resistance Surveillance Network were analysed using descriptive statistics and multivariable regression analyses. In Europe, proportions of vancomycin-resistant E. faecium (VREFm) increased from 8.1% (95%CI 6.7-9.7%) in 2012 to 19.0% (95%CI 16.8-21.5%) in 2018. Rising VREFm proportions were observed across all European regions, both genders and all age groups except children and adolescents (1-19 years). Adults (20-59 years) and elderly (≥60 years) had an increased likelihood of VREFm compared to children and adolescents (1-19 years) (OR: 1.99 95%CI 1.42-2.79, p < 0.001 and OR: 1.56 95%CI 1.09-2.23, p = 0.014, respectively). Inpatients hospital units, including internal medicine and ICUs, were associated with an increased likelihood of VREFm (OR: 2.29 (95%CI 1.58-3.32, p < 0.001) compared to the emergency department which reflects patients with community origin of E. faecium infections. The mean proportion of vancomycin-resistant E. faecalis in Europe was found to be low (1.1% 95%CI 0.9-1.4%). Local and regional authorities should intensify efforts directed at diagnostic and antimicrobial stewardship for vancomycin and all last resort drugs for the management of VREFm, particularly for hospitalized elderly patients.
Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these ...infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011-2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs.
The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009-2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models' case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data.
We estimated the EU/EEA burden of HAIs in DALYs in 2011-2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.
Vancomycin-resistant
Enterococcus faecium
(VREF) and methicillin-resistant
Staphylococcus aureus
(MRSA) are associated with significant health burden. We investigated linezolid and daptomycin ...resistance among VREF and MRSA in the EU/EEA between 2014 and 2018. Descriptive statistics and multivariable logistic regression were used to analyze 6,949 VREF and 35,131 MRSA blood isolates from patients with bloodstream infection. The population-weighted mean proportion of linezolid resistance in VREF and MRSA between 2014 and 2018 was 1.6% (95% CI 1.33–2.03%) and 0.28% (95% CI 0.32–0.38%), respectively. Daptomycin resistance in MRSA isolates was similarly low 1.1% (95% CI 0.75–1.6%). On the European level, there was no temporal change of daptomycin and linezolid resistance in MRSA and VREF. Multivariable regression analyses showed that there was a higher likelihood of linezolid and daptomycin resistance in MRSA (aOR: 2.74,
p
< 0.001; aOR: 2.25,
p
< 0.001) and linezolid in VREF (aOR: 1.99,
p
< 0.001) compared to their sensitive isolates. The low proportion of linezolid and daptomycin resistance in VREF and MRSA suggests that these last-resort antibiotics remain effective and will continue to play an important role in the clinical management of these infections in Europe. However, regional and national efforts to contain antimicrobial resistance should continue to monitor the trend through strengthened surveillance that includes genomic surveillance for early warning and action.
Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many ...European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.
Due to limited therapeutic options, vancomycin-resistant
(VREF) is of great clinical significance. Recently, rising proportions of vancomycin resistance in enterococcal infections have been reported ...worldwide. This study aims to describe current epidemiological trends of VREF in German hospitals and to identify factors that are associated with an increased likelihood of vancomycin resistance in clinical
isolates.
2012 to 2017 data from routine vancomycin susceptibility testing of 35,906 clinical
isolates from 148 hospitals were analysed using data from the German
System. Descriptive statistical analyses and uni- and multivariable regression analyses were performed to investigate the impact of variables, such as year of sampling, age and region, on vancomycin resistance in clinical
isolates.
From 2014 onwards the proportions of clinical
isolates exhibiting resistance to vancomycin increased from 11.2% (95% confidence interval CI 9.4-13.3%) to 26.1% (95% CI 23.1-29.4%) in 2017. The rise of VREF proportions is primarily observed in the southern regions of Germany, whereas northern regions do not show a major increase. In the Southwest and Southeast, VREF proportions increased from 10.8% (95% CI 6.9-16.5%) and 3.8% (95% CI 3.0-11.5%) in 2014 to 36.7% (95% CI 32.9-40.8%) and 36.8% (95% CI 29.2-44.7%) in 2017, respectively. VREF proportions were considerably higher in isolates from patients aged 40-59 years compared to younger patients. Further regression analyses show that in relation to secondary care hospitals,
samples collected in specialist care hospitals and prevention and rehabilitation care centres are more likely to be vancomycin-resistant (odds ratios: 2.4 95% CI 1.2-4.6 and 2.4 95% CI 1.9-3.0, respectively). No differences in VREF proportions were found between female and male patients as well as between different clinical specimens.
The proportion of VREF is increasing in German hospitals, particularly in southern regions in Germany. Increased efforts in infection control and antibiotic stewardship activities accounting for local resistance patterns are necessary to combat the spread of VREF in Germany.
Due to limited therapeutic options and their association with high mortality and morbidity, carbapenem-non-susceptible Acinetobacter spp. (CNA) are of significant public health importance. This study ...aimed to describe current epidemiological trends of CNA proportions in Europe and to identify factors that are associated with carbapenem non-susceptibility of isolates from patients with invasive Acinetobacter spp. infections.
Data from routine carbapenem susceptibility testing of 18,412 invasive clinical Acinetobacter spp. isolates from 30 European countries in 2013-2017 were analysed using descriptive statistical analyses and uni- and multivariable regression analyses. These data were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net).
The population-weighted mean proportion of carbapenem-non-susceptible Acinetobacter spp. in Europe is 35.6% (95% confidence interval CI 29.7-42.0%). With CNA proportions of 75.5% (95% CI 71.2-79.4%) and 71.5% (95% CI 66.7-75.9%) the burden of CNA is particularly high in Southern and Eastern European regions. In contrast, Northern and Western European regions recorded CNA proportions of 2.8% (95% CI 1.2-6.0%) and 6.3% (95% CI 4.5-8.9%), respectively. Population-weighted mean CNA proportions are especially high in Acinetobacter spp. isolates from intensive care units (54.0% 95% CI 47.6-60.3%). Male gender, age above 20 years and ICU admission were identified as independent factors associated with an increased likelihood of CNA.
The burden of carbapenem-non-susceptible Acinetobacter spp. is particularly high in Southern and Eastern Europe. There is a risk that resistance could spread to other parts of Europe. Therefore, increased efforts in infection control and antibiotic stewardship, particularly in Intensive Care Units, are necessary to combat the spread of CNA in Europe.
Data on microbiological profiles in odontogenic infections are scarce. This study aimed to analyze the spectrum of pathogens and antimicrobial resistance in clinical isolates from dental and ...oral-maxillofacial clinical settings in Germany. We analyzed 20,645 clinical isolates (dental practices:
n
= 5,733; hospitals:
n
= 14,912) from patients with odontogenic infections using data (2012–2019) from the German
Antimicrobial-Resistance-Surveillance
(ARS) system. A total of 224 different species from 73 genera were found in clinical isolates from dental practices, and 329 different species from 97 genera were identified in isolates from hospital patients. In both hospitals and dental practices
Streptococcus
spp. (33 and 36%, respectively) and
Staphylococcus
spp. (21 and 12%, respectively) were the most frequently isolated microorganisms. In
Streptococcus
spp. isolates from hospitals, penicillin and aminopenicillin resistance proportions were 8.0% (95%CI 4.7–14.9%) and 6.9% (95%CI 4.7–9.9%), respectively. Substantially lower resistance proportions of penicillin and aminopenicillin were observed in dental practices 2.6% (95%CI 1.4–4.7%) and 2.1% (95%CI 1.1–4.0%), respectively. Among
Staphylococcus aureus
isolates from hospital patients methicillin resistance proportions were 12.0% (95%CI 9.7–14.8%), which was higher than in isolates from dental practices (5.8% (95%CI 4.1–8.1%). High clindamycin and macrolide resistance proportions (>17%) were observed in
Streptococcus
spp. and
Staphylococcus aureus
isolates. In
Klebsiella
spp. isolates carbapenem resistance proportions were <1%. In sum, substantial antibiotic resistance was observed in isolates from odontogenic infections, which calls for strengthened efforts in antibiotic stewardship and infection prevention and control measures in both hospitals and dental practices.
PDF
