International study of the prevalence and outcomes of infection in intensive care units

Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

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Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.

442 Antimicrobials have enabled medical advancements over several decades. However, the continuous emergence of resistance to antimicrobials restricts our ability to treat diseases and curbs efforts to achieve universal health coverage and the health-related sustainable development goal. Antimicrobial resistance is a neglected global crisis that requires urgent attention and action.1 Appropriate prescription and optimized use of antimicrobials guide the principles of antimicrobial stewardship activities, together with quality diagnosis and treatment, and reduction and prevention of infections.2 During the current coronavirus disease 2019 (COVID-19) pandemic there are potential threats that could affect antimicrobial stewardship activities and drive antimicrobial resistance. For instance, many individuals presenting with mild disease without pneumonia or moderate disease with pneumonia receive antibiotics.3 A review of studies published on hospitalized COVID-19 patients identified that while 72% (1450/2010) of patients received antibiotics, only 8% (62/806) demonstrated superimposed bacterial or fungal co-infections.4 WHO also reports that azithromycin is being widely used with hydroxychloroquine although it is not yet recommended outside of COVID-19 clinical trials.3 Furthermore, hospital admissions increase the risk of health-care-associated infections and the transmission of multidrug-resistant organisms, which in turn lead to increased antimicrobial use.5 A recent study conducted in intensive care units in 88 countries showed that although only 54% (8135/15 165) of patients had suspected or proven bacterial infection, 70% (10 640/15 165) of them had received at least one antibiotic either for prophylaxis or treatment purposes.6 Disruptions to health services during the pandemic are causing interruptions to treatments, such as for tuberculosis and human immunodeficiency virus, which can also lead to selection for drug resistance. Similarly, disruption to vaccination services can increase risk of infection, potentially leading to an overuse of antimicrobials. Another potential threat is the wide use of biocidal agents for environmental and personal disinfection, including in non-health-care settings. Low level exposure to biocidal agents can select for drug-resistant strains and enhance the risk of cross resistance to antibiotics,7 particularly those that treat Gramnegative bacteria.8 The latest update of WHO’s interim guidance on the clinical management of COVID-19 incorporates antibiotic stewardship principles with specific recommendations.3 The guidance does not recommend antibiotic therapy or prophylaxis for patients with mild or moderate COVID-19 unless signs and symptoms of a bacterial infection exist. The use of empiric antibiotic treatment for patients with suspected or confirmed severe COVID-19, based on clinical judgement considering patient host factors and local epidemiology, along with daily assessments for de-escalation, is recommended.3 The guidance further states that empiric antibiotic bacterial pneumonia treatment can be considered in older people residing in long-term care facilities and in children younger than five years with moderate COVID-19. As these are non-hospitalized patients, antibiotics within WHO’s AWaRe (access, watch, reserve) classification of antibiotics categorized as access, such as co-amoxicillin, should preferably be administered.9 We argue that antimicrobial stewardship activities should be integrated into the pandemic response across the broader health system through five measures. First, increase clinical competence among health workers treating COVID-19 patients through targeted training. Key competencies include ability to identify signs and symptoms of severe COVID-19 and that of a superimposed bacterial or fungal disease; eliminate unnecessary antibiotic use including daily de-escalation; evaluate the need for medical devices and others that increase the chances of health-careassociated infections and antibiotic use; and implement strict infection prevention and control measures. Second, ensure the continuity of essential health services and regular supply of quality assured and affordable antimicrobials including antiretroviral and tuberculosis drugs, and vaccines. Third, reduce the turnaround time of COVID-19 testing by improving testing methods and expanding testing facilities, especially for presumed patients, to reduce the urge to initiate antibiotics. Fourth, exercise maximum caution in the use of biocides for environmental and personal disinfection and prioritize biocidal agents without or with a low selection pressure for antibiotic resistance. Fifth, address gaps in research to ensure that antimicrobial stewardship activities become an integral part of the pandemic response and beyond. The research agenda includes: rapid and affordable diagnostic tests that differentiate between bacterial and viral respiratory tract infections; the shortand long-term impact of wide use of biocides for environmental and personal disinfection including cross resistance to antimicrobials; and potential alternatives for sustainable environmental and personal disinfection. These measures would stem the emergence of untreatable drug-resistant infections and diseases that could potentially lead to another public health emergency. ■ Tackling antimicrobial resistance in the COVID-19 pandemic Haileyesus Getahun, Ingrid Smith, Kavita Trivedi, Sarah Paulin & Hanan H Balkhy

Tackling antimicrobial resistance in the COVID-19 pandemic.

Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP). To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.
 In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020. COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14–3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19. COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.

/pdf/ventilator-associated-pneumonia-in-critically-ill-patients-48s51ddq25.pdf

Ventilator-associated pneumonia in critically ill patients with COVID-19.

Importance 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. Objective To provide information about the prevalence and outcomes of infection and the available resources in ICUs worldwide. Design, Setting, and Participants 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. Exposures Infection diagnosis and receipt of antibiotics. Main Outcomes and Measures Prevalence of infection and antibiotic exposure (cross-sectional design) and all-cause in-hospital mortality (longitudinal design). Results 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-resistantEnterococcus(OR, 2.41 [95% CI, 1.43-4.06];P = .001),Klebsiellaresistant to β-lactam antibiotics, including third-generation cephalosporins and carbapenems (OR, 1.29 [95% CI, 1.02-1.63];P = .03), or carbapenem-resistantAcinetobacterspecies (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. Conclusions and Relevance 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.

https://jamanetwork.com/journals/jama/articlepdf/2763669/jama_vincent_2020_oi_200024.pdf

Santhana Kannan

Papers

Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017.