Infection is frequent among patients in the intensive care unit (ICU). Contemporary information about the types of infections, causative pathogens, and outcomes can aid the development of policies ...for prevention, diagnosis, treatment, and resource allocation and may assist in the design of interventional studies.
To provide information about the prevalence and outcomes of infection and the available resources in ICUs worldwide.
Observational 24-hour point prevalence study with longitudinal follow-up at 1150 centers in 88 countries. All adult patients (aged ≥18 years) treated at a participating ICU during a 24-hour period commencing at 08:00 on September 13, 2017, were included. The final follow-up date was November 13, 2017.
Infection diagnosis and receipt of antibiotics.
Prevalence of infection and antibiotic exposure (cross-sectional design) and all-cause in-hospital mortality (longitudinal design).
Among 15 202 included patients (mean age, 61.1 years SD, 17.3 years; 9181 were men 60.4%), infection data were available for 15 165 (99.8%); 8135 (54%) had suspected or proven infection, including 1760 (22%) with ICU-acquired infection. A total of 10 640 patients (70%) received at least 1 antibiotic. The proportion of patients with suspected or proven infection ranged from 43% (141/328) in Australasia to 60% (1892/3150) in Asia and the Middle East. Among the 8135 patients with suspected or proven infection, 5259 (65%) had at least 1 positive microbiological culture; gram-negative microorganisms were identified in 67% of these patients (n = 3540), gram-positive microorganisms in 37% (n = 1946), and fungal microorganisms in 16% (n = 864). The in-hospital mortality rate was 30% (2404/7936) in patients with suspected or proven infection. In a multilevel analysis, ICU-acquired infection was independently associated with higher risk of mortality compared with community-acquired infection (odds ratio OR, 1.32 95% CI, 1.10-1.60; P = .003). Among antibiotic-resistant microorganisms, infection with vancomycin-resistant Enterococcus (OR, 2.41 95% CI, 1.43-4.06; P = .001), Klebsiella resistant to β-lactam antibiotics, including third-generation cephalosporins and carbapenems (OR, 1.29 95% CI, 1.02-1.63; P = .03), or carbapenem-resistant Acinetobacter species (OR, 1.40 95% CI, 1.08-1.81; P = .01) was independently associated with a higher risk of death vs infection with another microorganism.
In a worldwide sample of patients admitted to ICUs in September 2017, the prevalence of suspected or proven infection was high, with a substantial risk of in-hospital mortality.
Matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows the identification of microorganisms directly from positive blood culture broths. Use of the ...MALDI-TOF MS for rapid identification of microorganisms from blood culture broths can reduce the turnaround time to identification and may lead to earlier appropriate treatment of bacteremia. During February and April 2010, direct MALDI-TOF MS was routinely performed on all positive blood cultures. During December 2009 and March 2010 no direct MALDI-TOF MS was used. Information on antibiotic therapy was collected from the hospital and intensive care units' information systems from all positive blood cultures during the study period. In total, 253 episodes of bacteremia were included of which 89 during the intervention period and 164 during the control period. Direct performance of MALDI-TOF MS on positive blood culture broths reduced the time till species identification by 28.8-h and was associated with an 11.3% increase in the proportion of patients receiving appropriate antibiotic treatment 24 hours after blood culture positivity (64.0% in the control period versus 75.3% in the intervention period (p0.01)). Routine implementation of this technique increased the proportion of patients on adequate antimicrobial treatment within 24 hours.
The presence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) in food animals is a public health concern. This study aimed to determine prevalence of ESBL-E. coli on pig ...farms and to assess the effect of reducing veterinary antimicrobial use (AMU) and farm management practices on ESBL-E. coli occurrence on pig farms. During 2011-2013, 36 Dutch conventional pig farms participated in a longitudinal study (4 sampling times in 18 months). Rectal swabs were taken from 60 pigs per farm and pooled per 6 pigs within the same age category. Presence of ESBL-E. coli was determined by selective plating and ESBL genes were characterized by microarray, PCR and gene sequencing. An extensive questionnaire on farm characteristics and AMU as Defined Daily Dosages per Animal Year (DDDA/Y) was available for the 6-month periods before each sampling moment. Associations between the presence of ESBL-E. coli-positive pigs and farm management practices were modelled with logistic regression. The number of farms with ESBL-E. coli carrying pigs decreased from 16 to 10 and the prevalence of ESBL-E. coli-positive pooled pig samples halved from 27% to 13%. Overall, the most detected ESBL genes were blaCTX-M-1, blaTEM-52 and blaCTX-M-14. The presence of ESBL-E. coli carrying pigs was not related to total AMU, but it was strongly determined by the presence or absence of cephalosporin use at the farm (OR = 46.4, p = 0.006). Other farm management factors, related with improved biosecurity, were also plausibly related to lower probabilities for ESBL-E. coli-positive farms (e.g. presence of a hygiene lock, pest control delivered by a professional). In conclusion, ESBL-E. coli prevalence decreased in pigs during 2011 and 2013 in the Netherlands. On pig farms, the use of cephalosporins was associated with the presence of ESBL-E. coli carrying pigs.
Sepsis is considered to induce immune suppression, leading to increased susceptibility to secondary infections with associated late mortality.
To determine the clinical and host genomic ...characteristics, incidence, and attributable mortality of intensive care unit (ICU)-acquired infections in patients admitted to the ICU with or without sepsis.
Prospective observational study comprising consecutive admissions of more than 48 hours in 2 ICUs in the Netherlands from January 2011 to July 2013 stratified according to admission diagnosis (sepsis or noninfectious).
The primary outcome was ICU-acquired infection (onset >48 hours). Attributable mortality risk (fraction of mortality that can be prevented by elimination of the risk factor, acquired infection) was determined using time-to-event models accounting for competing risk. In a subset of sepsis admissions (n = 461), blood gene expression (whole-genome transcriptome in leukocytes) was analyzed at baseline and at onset of ICU-acquired infectious (n = 19) and noninfectious (n = 9) events.
The primary cohort included 1719 sepsis admissions (1504 patients; median age, 62 years; interquartile range IQR, 51-71 years; 924 men 61.4%). A comparative cohort included 1921 admissions (1825 patients, median age, 62 years; IQR, 49-71 years; 1128 men 61.8% in whom infection was not present in the first 48 hours. Intensive care unit-acquired infections occurred in 13.5% of sepsis ICU admissions (n = 232) and 15.1% of nonsepsis ICU admissions (n = 291). Patients with sepsis who developed an ICU-acquired infection had higher disease severity scores on admission than patients with sepsis who did not develop an ICU-acquired infection (Acute Physiology and Chronic Health Evaluation IV APACHE IV median score, 90 IQR, 72-107 vs 79 IQR, 62-98; P < .001) and throughout their ICU stay but did not have differences in baseline gene expression. The population attributable mortality fraction of ICU-acquired infections in patients with sepsis was 10.9% (95% CI, 0.9%-20.6%) by day 60; the estimated difference between mortality in all patients with a sepsis admission diagnosis and mortality in those without ICU-acquired infection was 2.0% (95% CI, 0.2%-3.8%; P = .03) by day 60. Among nonsepsis ICU admissions, ICU-acquired infections had a population attributable mortality fraction of 21.1% (95% CI, 0.6%-41.7%) by day 60. Compared with baseline, blood gene expression at the onset of ICU-acquired infections showed reduced expression of genes involved in gluconeogenesis and glycolysis.
Intensive care unit-acquired infections occurred more commonly in patients with sepsis with higher disease severity, but such infections contributed only modestly to overall mortality. The genomic response of patients with sepsis was consistent with immune suppression at the onset of secondary infection.
Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. ...Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids.
The choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated ...by the limited availability of evidence. We compared strategies of empirical treatment (allowing deviations for medical reasons) with beta-lactam monotherapy, beta-lactam-macrolide combination therapy, or fluoroquinolone monotherapy.
In a cluster-randomized, crossover trial with strategies rotated in 4-month periods, we tested the noninferiority of the beta-lactam strategy to the beta-lactam-macrolide and fluoroquinolone strategies with respect to 90-day mortality, in an intention-to-treat analysis, using a noninferiority margin of 3 percentage points and a two-sided 90% confidence interval.
A total of 656 patients were included during the beta-lactam strategy periods, 739 during the beta-lactam-macrolide strategy periods, and 888 during the fluoroquinolone strategy periods, with rates of adherence to the strategy of 93.0%, 88.0%, and 92.7%, respectively. The median age of the patients was 70 years. The crude 90-day mortality was 9.0% (59 patients), 11.1% (82 patients), and 8.8% (78 patients), respectively, during these strategy periods. In the intention-to-treat analysis, the risk of death was higher by 1.9 percentage points (90% confidence interval CI, -0.6 to 4.4) with the beta-lactam-macrolide strategy than with the beta-lactam strategy and lower by 0.6 percentage points (90% CI, -2.8 to 1.9) with the fluoroquinolone strategy than with the beta-lactam strategy. These results indicated noninferiority of the beta-lactam strategy. The median length of hospital stay was 6 days for all strategies, and the median time to starting oral treatment was 3 days (interquartile range, 0 to 4) with the fluoroquinolone strategy and 4 days (interquartile range, 3 to 5) with the other strategies.
Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality. (Funded by the Netherlands Organization for Health Research and Development; CAP-START ClinicalTrials.gov number, NCT01660204.).
Selective decontamination of the digestive tract (SDD) is an infection prevention measure for intensive care unit (ICU) patients that was proposed more than 30 years ago, and that is currently ...considered standard of care in the Netherlands, but only used sporadically in ICUs in other countries. In this narrative review, we first describe the rationale of the individual components of SDD and then review the evidence base for patient-centered outcomes, where we distinguish ICUs with low prevalence of antibiotic resistance from ICUs with moderate–high prevalence of resistance. In settings with low prevalence of antibiotic resistance, SDD has been associated with improved patient outcome in three cluster-randomized studies. These benefits were not confirmed in a large international cluster-randomized study in settings with moderate-to-high prevalence of antibiotic resistance. There is no evidence that SDD increases antibiotic resistance. We end with future directions for research.
AbstractBackgroundWe conducted a post-hoc analysis of a double blind, randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged 65 years or older to ...assess public health impact. MethodsFor all outcomes, we included all randomized subjects, using a modified intention-to-treat (mITT) approach to determine vaccine efficacy (VE), vaccine preventable disease incidence (VPDI) defined as control minus vaccinated group incidence, and numbers needed to vaccinate (NNV) (based on a five-year duration of protection). ResultsResults are reported for, in order, clinical, adjudicated (clinical plus radiologic infiltrate determined by committee), pneumococcal, and vaccine-type pneumococcal (VT-Sp) community-acquired pneumonia; invasive pneumococcal disease (IPD) and VT-IPD. VEs (95% CI) for all hospital episodes were 8.1% (−0.6%, 16.1%), 6.7% (−4.1%, 16.3%), 22.2% (2.0%, 38.3%), 37.5% (14.3%, 54.5%), 49.3% (23.2%, 66.5%), and 75.8% (47.6%, 88.8%). VPDIs per 100,000 person-years of observation (PYOs) were 72, 37, 25, 25, 20, and 15 with NNVs of 277, 535, 816, 798, 1016, and 1342. For clinical CAP, PCV13 was associated with a reduction of 909 (−115, 2013) hospital days per 100,000 PYOs translating to a reduction over 5 years of one hospital day for every 22 people vaccinated. When comparing at-risk persons (defined by self-report of diabetes, chronic lung disease, or other underlying conditions) to not at-risk persons, VEs were similar or lower, but because baseline incidences were higher the VPDIs were approximately 2–10 times higher and NNVs 50–90% lower. ConclusionA public health analysis of pneumonia and IPD outcomes in a randomized controlled trial found substantial burden reduction following adult PCV13 immunization implemented in a setting with an ongoing infant PCV7-PCV10 program. VPDIs were higher among at-risk adults. FundingThe original study and the current analysis were funded by Pfizer.
In countries with declining numbers of confirmed cases of COVID-19, lockdown measures are gradually being lifted. However, even if most physical distancing measures are continued, other public health ...measures will be needed to control the epidemic. Contact tracing via conventional methods or mobile app technology is central to control strategies during de-escalation of physical distancing. We aimed to identify key factors for a contact tracing strategy to be successful.
We evaluated the impact of timeliness and completeness in various steps of a contact tracing strategy using a stochastic mathematical model with explicit time delays between time of infection and symptom onset, and between symptom onset, diagnosis by testing, and isolation (testing delay). The model also includes tracing of close contacts (eg, household members) and casual contacts, followed by testing regardless of symptoms and isolation if testing positive, with different tracing delays and coverages. We computed effective reproduction numbers of a contact tracing strategy (RCTS) for a population with physical distancing measures and various scenarios for isolation of index cases and tracing and quarantine of their contacts.
For the most optimistic scenario (testing and tracing delays of 0 days and tracing coverage of 100%), and assuming that around 40% of transmissions occur before symptom onset, the model predicts that the estimated effective reproduction number of 1·2 (with physical distancing only) will be reduced to 0·8 (95% CI 0·7–0·9) by adding contact tracing. The model also shows that a similar reduction can be achieved when testing and tracing coverage is reduced to 80% (RCTS 0·8, 95% CI 0·7–1·0). A testing delay of more than 1 day requires the tracing delay to be at most 1 day or tracing coverage to be at least 80% to keep RCTS below 1. With a testing delay of 3 days or longer, even the most efficient strategy cannot reach RCTS values below 1. The effect of minimising tracing delay (eg, with app-based technology) declines with decreasing coverage of app use, but app-based tracing alone remains more effective than conventional tracing alone even with 20% coverage, reducing the reproduction number by 17·6% compared with 2·5%. The proportion of onward transmissions per index case that can be prevented depends on testing and tracing delays, and given a 0-day tracing delay, ranges from up to 79·9% with a 0-day testing delay to 41·8% with a 3-day testing delay and 4·9% with a 7-day testing delay.
In our model, minimising testing delay had the largest impact on reducing onward transmissions. Optimising testing and tracing coverage and minimising tracing delays, for instance with app-based technology, further enhanced contact tracing effectiveness, with the potential to prevent up to 80% of all transmissions. Access to testing should therefore be optimised, and mobile app technology might reduce delays in the contact tracing process and optimise contact tracing coverage.
ZonMw, Fundação para a Ciência e a Tecnologia, and EU Horizon 2020 RECOVER.
To assess the attributable mortality of ventilator-associated pneumonia using results from randomized controlled trials on ventilator-associated pneumonia prevention.
A systematic search was ...performed in PubMed, Embase, Web of Science, and Cochrane Library from their inception until July 2010. In addition, a reference and related article search was performed.
Randomized ventilator-associated pneumonia prevention studies in which all patients were mechanically ventilated and from which ventilator-associated pneumonia and mortality rates of intervention and control group could be extracted were included.
Fifty-three papers were identified describing 58 comparisons. Statistical significant reductions in ventilator-associated pneumonia incidences were reported in 20 of the 58 comparisons, whereas none of these trials reported a significant reduction of mortality. Pooled estimates of the relative risk reductions of both ventilator-associated pneumonia and mortality were calculated and the attributable mortality was estimated as the ratio between the relative risk reductions of mortality and ventilator-associated pneumonia. Effects of study quality, diagnostic methods used, and effectiveness of preventing ventilator-associated pneumonia on the mortality rate of ventilator-associated pneumonia were assessed in subgroup analyses. The overall attributable mortality of ventilator-associated pneumonia was estimated as 9%. In subgroup analyses, the attributable mortality varied between 3% and 17%.
Based on the results of 58 randomized studies on ventilator-associated pneumonia prevention, the attributable mortality rate of ventilator-associated pneumonia was estimated to be 9% and ranged between 3% and 17% in subgroup analyses. Together with the results of other recent studies, there is cumulative evidence that the attributable mortality resulting from ventilator-associated pneumonia is approximately 10%.
PDF
