Challenges and success stories of the implementation of infection control and antimicrobial stewardship strategies: proceedings of the 5th Global Ministerial Summit on Patient Safety, 2023.

The 5th edition of the Global Ministerial Summit on Patient Safety was held in Montreux, Switzerland, in February 2023, delayed by three years due to the COVID-19 pandemic. The overarching theme of the summit was "Less Harm, Better Care - from Resolution to Implementation", focusing on the challenges of implementation of infection prevention and control (IPC) strategies as well as antimicrobial stewardship programs (ASP) around the world. IPC strategies and ASP are of increasing importance due to the substantial burden of healthcare-associated infections and antimicrobial resistance threatening patient safety. Here, we summarize countries' and regional experiences and activities related to the implementation of IPC strategies and ASP shared at the meeting. Full implementation of effective programs remains a major challenge in all settings due to limited support by political and healthcare leaders, and human and financial constraints. In addition, the COVID-19 pandemic challenged already well-established programs. By enforcing sustained implementation by dedicated, cross-disciplinary healthcare personnel with a broad skill set, a reduction in healthcare-associated infections and multidrug-resistant pathogens can be achieved, leading ultimately to improved patient safety.

Antimicrobial Multidrug Resistance: Clinical Implications for Infection Management in Critically Ill Patients.

The increasing incidence of antimicrobial resistance (AMR) worldwide represents a serious threat in the management of sepsis. Due to resistance to the most common antimicrobials prescribed, multidrug-resistant (MDR) pathogens have been associated with delays in adequate antimicrobial therapy leading to significant increases in mortality, along with prolonged hospital length of stay (LOS) and increases in healthcare costs. In response to MDR infections and the delay of microbiological results, broad-spectrum antibiotics are frequently used in empirical antimicrobial therapy. This can contribute to the overuse and misuse of antibiotics, further promoting the development of resistance. Multiple measures have been suggested to combat AMR. This review will focus on describing the epidemiology and trends concerning MDR pathogens. Additionally, it will explore the crucial aspects of identifying patients susceptible to MDR infections and optimizing antimicrobial drug dosing, which are both pivotal considerations in the fight against AMR. Expert commentary: The increasing AMR in ICUs worldwide makes the empirical antibiotic therapy challenging in septic patients. An AMR surveillance program together with improvements in MDR identification based on patient risk stratification and molecular rapid diagnostic tools may further help tailoring antimicrobial therapies and avoid unnecessary broad-spectrum antibiotics. Continuous infusions of antibiotics, therapeutic drug monitoring (TDM)-based dosing regimens and combination therapy may contribute to optimizing antimicrobial therapy and limiting the emergence of resistance.

Impact of wars and natural disasters on emerging and re-emerging infectious diseases.

Emerging Infectious Diseases (EIDs) and Re-Emerging Infectious Diseases (REIDs) constitute significant health problems and are becoming of major importance. Up to 75% of EIDs and REIDs have zoonotic origin. Several factors such as the destruction of natural habitats leading humans and animals to live in close proximity, ecological changes due to natural disasters, population migration resulting from war or conflict, interruption or decrease in disease prevention programs, and insufficient vector control applications and sanitation are involved in disease emergence and distribution. War and natural disasters have a great impact on the emergence/re-emergence of diseases in the population. According to a World Bank estimation, two billion people are living in poverty and fragility situations. Wars destroy health systems and infrastructure, curtail existing disease control programs, and cause population movement leading to an increase in exposure to health risks and favor the emergence of infectious diseases. A total of 432 catastrophic cases associated with natural disasters were recorded globally in 2021. Natural disasters increase the risk of EID and REID outbreaks by damaging infrastructure and leading to displacement of populations. A Generic National Action Plan covering risk assessment, mechanism for action, determination of roles and responsibilities of each sector, the establishment of a coordination mechanism, etc. should be developed.

Antimicrobial stewardship in the intensive care unit.

High resistance rates to antimicrobials continue to be a global health threat. The incidence of multidrug-resistant (MDR) microorganisms in intensive care units (ICUs) is quite high compared to in the community and other units in the hospital because ICU patients are generally older, have higher numbers of co-morbidities and immune-suppressed; moreover, the typically high rates of invasive procedures performed in the ICU increase the risk of infection by MDR microorganisms. Antimicrobial stewardship (AMS) refers to the implementation of coordinated interventions to improve and track the appropriate use of antibiotics while offering the best possible antibiotic prescription (according to dose, duration, and route of administration). Broad-spectrum antibiotics are frequently preferred in ICUs because of greater infection severity and colonization and infection by MDR microorganisms. For this reason, a number of studies on AMS in ICUs have increased in recent years. Reducing the use of broad-spectrum antibiotics forms the basis of AMS. For this purpose, parameters such as establishing an AMS team, limiting the use of broad-spectrum antimicrobials, terminating treatments early, using early warning systems, pursuing infection control, and providing education and feedback are used. In this review, current AMS practices in ICUs are discussed.

Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms.

The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing antibiotic use, decreasing adverse effects, and improving patient outcomes. There is a limited number of published studies assessing the impact of AMS programs on patients with neutropenia, where early appropriate antibiotic choice can be the difference between life and death. This narrative review updates the current advances in strategies of AMS for bacterial infections among high-risk patients with neutropenia. Diagnosis, drug, dose, duration, and de-escalation (5D) are the core variables among AMS strategies. Altered volumes of distribution can make standard dose regimens inadequate, and developing skills towards a personalized approach represents a major advance in therapy. Intensivists should partner antibiotic stewardship programs to improve patient care. Assembling multidisciplinary teams with trained and dedicated professionals for AMS is a priority.

Evaluation of the implementation of WHO infection prevention and control core components in Turkish health care facilities: results from a WHO infection prevention and control assessment framework (IPCAF)-based survey.

BACKGROUND: The core components (CCs) of infection prevention and control (IPC) from World Health Organization (WHO) are crucial for the safety and quality of health care. Our objective was to examine the level of implementation of WHO infection prevention and control core components (IPC CC) in a developing country. We also aimed to evaluate health care-associated infections (HAIs) and antimicrobial resistance (AMR) in intensive care units (ICUs) in association with implemented IPC CCs. METHODS: Members of the Turkish Infectious Diseases and Clinical Microbiology Specialization Association (EKMUD) were invited to the study via e-mail. Volunteer members of any healt care facilities (HCFs) participated in the study. The investigating doctor of each HCF filled out a questionnaire to collect data on IPC implementations, including the Infection Prevention and Control Assessment Framework (IPCAF) and HAIs/AMR in ICUs in 2021. RESULTS: A total of 68 HCFs from seven regions in Türkiye and the Turkish Republic of Northern Cyprus participated while 85% of these were tertiary care hospitals. Fifty (73.5%) HCFs had advanced IPC level, whereas 16 (23.5%) of the 68 hospitals had intermediate IPC levels. The hospitals' median (IQR) IPCAF score was 668.8 (125.0) points. Workload, staffing and occupancy (CC7; median 70 points) and multimodal strategies (CC5; median 75 points) had the lowest scores. The limited number of nurses were the most important problems. Hospitals with a bed capacity of > 1000 beds had higher rates of HAIs. Certified IPC specialists, frequent feedback, and enough nurses reduced HAIs. The most common HAIs were central line-associated blood stream infections. Most HAIs were caused by gram negative bacteria, which have a high AMR. CONCLUSIONS: Most HCFs had an advanced level of IPC implementation, for which staffing was an important driver. To further improve care quality and ensure everyone has access to safe care, it is a key element to have enough staff, the availability of certified IPC specialists, and frequent feedback. Although there is a significant decrease in HAI rates compared to previous years, HAI rates are still high and AMR is an important problem. Increasing nurses and reducing workload can prevent HAIs and AMR. Nationwide "Antibiotic Stewardship Programme" should be initiated.

Infection prevention and control policies in hospitals and prevalence of highly resistant microorganisms: an international comparative study.

BACKGROUND: There are differences in infection prevention and control (IPC) policies to prevent transmission of highly resistant microorganisms (HRMO). The aim of this study is to give an overview of the IPC policy of six European hospitals and their HRMO prevalence, to compare the IPC policies of these hospitals with international guidelines, and to investigate the hospitals' adherence to their own IPC policy. METHODS: The participating hospitals were located in Salzburg (Austria), Vienna (Austria), Kayseri (Turkey), Piraeus (Greece), Rome (Italy) and Rotterdam (The Netherlands). Data were collected via an online survey. Questions were aimed at prevalence rates in the years 2014, 2015, 2016 of carbapenemase-producing Klebsiella pneumoniae (CPK), carbapenemase-producing Pseudomonas aeruginosa (CPPA), vancomycin-resistant Enterococcus faecium (VRE) and hospitals' IPC policies of 2017. Implemented IPC measures (i.e. with a self-reported adherence of > 90%) were counted (26 points maximal). RESULTS: The self-reported prevalence of CPK per year was low in the Austrian and Dutch hospitals and high in the Turkish and Greek hospitals. CPPA was highly prevalent in the Turkish hospital only, while the prevalence of VRE in four hospitals, except the Austrian hospitals which reported lower prevalence numbers, was more evenly distributed. The Dutch hospital had implemented the most IPC measures (n = 21), the Turkish and Greek hospitals the least (n = 14 and 7, respectively). CONCLUSION: Hospitals with the highest self-reported prevalence of CPK and CPPA reported the least implemented IPC measures. Also, hospitals with a higher prevalence often reported a lower adherence to own IPC policy.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

The Effect of Mesenchymal Stromal Cells on the Mortality of Patients with Sepsis and Septic Shock: A Promising Therapy.

Purpose: Sepsis and septic shock are the major causes of death in intensive care units. This study aimed to evaluate the clinical safety and efficacy of mesenchymal stem cells (MSCs) in sepsis and septic shock patients. Methods: Ten patients were enrolled in the study. Adipose-derived MSC infusions were given (1 × 106/kg, on the 1st, 3rd, 5th, 7th, and 9th days of therapy) together with standard therapy. Before the MSC applications, blood samples were collected for cytokine assessment (TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10). The clinical and laboratory improvements were recorded and compared with control groups selected retrospectively. The clinical trial was registered on 16.03.2022 with the registration number NCT05283317. Results: In the study group, the ages of patients ranged from 22 to 68 years, and APACHE II scores ranged from 14 to 42. In the control group, ages ranged from 22 to 80 years and their APACHE II scores were between 14-35. The survival rate in the study group was 100% on the 14th day whereas it was 70% on the 28th day. A significant decrease in the SOFA score (adjusted), clinical, and laboratory improvements were observed during the MSC administration. However, no significant cytokine level changes were observed. In the control group, the survival rate of 20 patients was 70% on the 14th day, whereas 60% was on the 28th day. While deaths were observed in the control group in the first week of treatment, deaths in the MSCs group were observed between the 15th and 28th days. Conclusion: MSCs treatment may have a positive impact on the survival rates of sepsis during the early phase. However, further randomized controlled studies with a large group of patients are needed. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier: NCT05283317.

Antiseptic barrier caps in central line-associated bloodstream infections: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the evidence concerning the effectiveness of antiseptic barrier caps vs. manual disinfection in preventing central line-associated bloodstream infection (CLABSI). METHODS: The protocol of this systematic review and meta-analysis was pre-registered in PROSPERO (CRD42021259582). PubMed, Cochrane Library and Web of Science databases were searched from 2011 to 2021. Randomized-controlled trials (RCT) and observational studies on hospitalized patients of any age were included. RESULTS: Fourteen studies were included. Compared with manual disinfection, antiseptic barrier caps significantly reduced CLABSI rate per 1000 line-days (Standardized Mean Difference [SMD]: -0.02; 95%CI: -0.03 to -0.01) and number of CLABSI per patient (RR: 0.60; 95%CI: 0.41-0.89). Subgroup analysis showed that antiseptic barrier caps were more effective in reducing CLABSI rate per 1000 line-days in ICU (SMD: -0.02; 95%CI: -0.03 to -0.01) and non-ICU patients (SMD: -0.03; 95%CI: -0.05 to -0.01), adults (SMD: -0.02; 95%CI: -0.04 to -0.01), as in observational studies (SMD: -0.02; 95%CI: -0.02 to -0.01). Antiseptic barrier caps also significantly reduce CLABSI risk in ICU patients (RR: 0.65, 95%CI: 0.42-1.00), adults (RR: 0.50, 95%CI: 0.29-0.86), and observational studies (RR: 0.54; 95%CI: 0.32-0.91). No differences were found when only children or RCTs were taken into account. Median cost savings amongst studies were $21,890 [IQR 16,350-45,000] per CLABSI. CONCLUSIONS: Antiseptic barrier caps appear to be effective in reducing CLABSI. The real-world impact needs to be confirmed by RCTs.

The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model

Background/aim: In the last years, incidence of carbapenem resistant Acinetobacter baumannii sepsis is increasing with high mortality. However, it is not clear whether this is due to inadequate antimicrobial choice or a more severe clinical course. We aimed to evaluate the inflammation and adrenal involvement in the carbapenem resistant A. baumannii by using experimental mouse model sepsis. Materials and methods: Balb/c female mice were randomly put into control and three sepsis groups ( A. baumannii susceptible to carbapenem-CSAB-, A. baumannii resistant to carbapenem-CRAB-, Escherichia coli). A total of sixty mice were included in this study with each group having 15 mice. Mice were sacrificed 72 h after bacterial inoculation, and blood was taken from each mouse for the assessment of cytokines and corticosterone. Both adrenal glands were dissected; one was used for culture and the other was used for histopathological examination. Bacterial loads of organs were calculated as CFU/g. The histopathological changes, bacterial levels in adrenal and cytokine and corticosterone levels were assessed and compared among the groups. Results: The bacterial level was higher in E. coli (108, 45 ±30, 55 log10 CFU/g) (mean±SD) than other sepsis groups. The lowest level of corticosterone was observed in the E. coli group (p < 0.001). TNF alpha level was highest in the CRAB and E. coli group and this difference was statistically significant than control group (p < 0.05). The IL-6 level in CRAB was significantly higher than the control group (10, 20 pg/mL). The adrenal gland congestion was significantly severe in all the sepsis groups compared to the control. In the group comparison, congestion was significantly more severe in the E. coli group than in CSAB and CRAB groups. Conclusion: Adrenal involvement and inflammatory reactions are seen in E. coli sepsis and in CRAB sepsis. These findings will be focused on in future clinical trials.

Current infection prevention and control strategies of COVID-19 in hospitals

Background/aim: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been appeared first in China since December 2019. Transmission of SARS-CoV-2 occurs primarily with droplets through coughing and sneezing and also occurs through inhalation of aerosolized secretions, which travel, remain suspended in the air longer. Materials and methods: Since early stages of the outbreak, COVID-19 cases have been described in healthcare workers (HCWs). However, in the early stages, the disease may be asymptomatic. This may lead to incorrect diagnosis or delayed diagnosis and may lead to the nosocomial spread of the virus. One of the most important causes of transmission among HCWs is being exposed to an aerosolized virus in a closed environment for a long time. It is possible to prevent and control the spread of COVID-19 in hospitals with outpatient treatment and triage. Results: Infection control measures, including wearing surgical masks, hand hygiene, and social distance are considered essential in preventing human-to-human transmissions of SARS-CoV-2. Immediate response and practices of infection control measures are critical for saving lives during an epidemic inside and outside the hospital. Conclusion: Analyzing current knowledge about the features of SARS-CoV-2 infection, screening, personal protection protocols, triage and psychological support practices for healthcare professionals can be promising in terms of controlling the infection.

Discrepancy between colistin and polymyxin B susceptibility results among Escherichia coli and Klebsiella pneumoniae clinical isolates.

The selection of therapeutic agent to be used for the treatment of multidrug-resistant bacteria is a major concern. Polymyxin B use has been commenced in Turkey, although its clinical breakpoint is not listed in the EUCAST. This study aimed to determine the correlation between the MIC values of polymyxin B and colistin. A total of 505 isolates, including 122 isolates of Escherichia coli and 383 isolates of Klebsiella pneumoniae were included in the present study. All the isolates were assessed for colistin and polymyxin B using the broth microdilution method. The categorical agreement in the E. coli isolates was 98.4%, and the rate of very major error was 33.3%. The categorical agreement in the K. pneumoniae isolates was 99.5%, the rate of major error was 0.36%, and the rate of very major error was 0.98%. In the evaluation of the essential agreement, 1.6% error in E. coli and 2.3% error in K. pneumoniae were observed. It was concluded that polymyxin B should never be used in the treatment of the isolates reported as colistin-resistant, and if the MIC values are above 4 mg/L in E. coli and K. pneumoniae. Our results indicate importance of reporting both polymyxin B and colistin susceptibility results of clinical isolates.

Human anthrax in Turkey: A ten years' experience (2009-2018).

Anthrax is a notifiable disease in Turkey. In order to control the human disease, animal foci are being monitored and prevention and control activities are being implemented by the Ministry of Health in coordination with the Ministry of Agriculture and Forestry. The objective of our study was to evaluate the national surveillance data and control activities in the last decade. A total of 1174 anthrax cases and 9 deaths have been reported. Anthrax was frequent in eastern provinces and in big cities where large animal movements were significant. The incidence rate was 1.5 times higher in males than in females. The disease was more common in the 30-64 age group. The number of cases increased in the summer and autumn seasons. Human anthrax is still being reported though in decreasing numbers in Turkey. A collaborative control programme continues to be needed.

The Outcome of Fungal Pneumonia with Hematological Cancer.

BACKGROUND: Fungal pneumonia is a common infectious complication of hematological cancer (HC) patients. In this retrospective study, the objective was set to identify the risk factors and outcome of fungal pneumonia in adult HC patients. MATERIALS AND METHODS: This retrospective study was conducted with adult (>16 years) HC patients from January 2017 and December 2018. RESULTS: During the study period, of 181 patients included 76 were diagnosed with fungal pneumonia. The most common HC was identified as acute myeloid leukaemia (40%). Of the participating patients, 52 (29%) were hematopoietic stem cell transplant (HSCT) recipients. The median age of patients with fungal pneumonia was significantly greater: 57 vs. 48 (odds ratio [OR]: 1.08) and they had longer hospitalization durations (OR: 1.14). Overall, 37 patients (20%) died, and 28-day mortality was significantly greater among patients with fungal pneumonia than without fungal pneumonia (33% vs. 11%). The most significant risk factors for mortality in fungal pneumonia were identified as need of intensive care unit (ICU) (OR: 191.2, P <0.001) and the need of vasopressor support (OR:81.6, P <0.012). ICU-mortality was (88%). CONCLUSION: Fungal pneumonia is a lethal complication in HC patients. Intensive care need is the most important predictive factor for mortality.

Risk prediction for candidemia in surgical intensive care unit patients.

OBJECTIVE: Patients in surgical intensive care units are thought to be at the highest risk for developing candidemia, especially patients undergoing abdominal surgery. The present study aims to investigate risk factors for candidemia in patients with abdominal surgery. METHODS: A retrospective study was undertaken that involved patients admitted to the surgical ICU between January 2016 and January 2017. All postoperative adult patients (>18 years old) who underwent abdominal surgery were included in this study. RESULTS: During the one-year study period, 49 patients developed candidemia. Thirty-five of candida isolates were non-albicans strains. Of them, 25 (51%) isolates were Candida parapsilosis, eight (16.3%) isolates were C. glabrata, one (2%) isolate was C. tropicalis and one (2%) isolate was C. kefyr. The median age of all patients enrolled in this study was 60.5±15.6 years. In univariate analysis, the duration of the hospital stays, intensive care unit stay, type of surgery, respiratory failure, total parenteral nutrition, transfusion and use of central venous catheter were significantly higher in patients with candidemia. In multivariate analysis, duration of hospital and intensive care unit stay and use of central venous catheter was associated with an increased risk of candidemia. The mortality rate of case patients was 36.7%. CONCLUSION: Patients undergoing abdominal surgery are at increased risk of candidemia, especially the patients with prolonged intensive care unit/hospital stay and the patients with a central venous catheters. Antifungal prophylaxis may be considered for patients with increased risk.

Turkish Urologists' preferences regarding antibiotic prophylaxis for transrectal prostate biopsy.

OBJECTIVE: Antibiotic prophylaxis for transrectal prostate biopsy (PB) is very important in preventing infectious complications, and in this study, we aimed to evaluate the antibiotic preferences of Turkish urologist for transrectal PB. MATERIAL AND METHODS: The survey about PB and antibiotic prophylaxis behaviors was administered to urologists working in Turkey who had previously participated in at least one international and one national congress. RESULTS: A total of 237 urologists were included in the study. Antibiotic prophylaxis prior to PB was performed by 234 (98.7%) participants. Rectal swabbing prior to PB was not performed by 227 (95.8%) participants. The most common complication associated with PB was prostatitis (63%), followed by urinary tract infection (29%). Only 25.7% of Turkish urologists reported a single dose of antibiotic prophylaxis. Our participants often administered antibiotic prophylaxis for a period of 3, 5, or 7 days (16%, 21.1%, 35.9%, respectively). The most common antibiotic agent preferred for prophylaxis was ciprofloxacin (65%). CONCLUSION: The biopsy behavior of Turkish urologists was mostly compatible with the literature, but it was revealed that Turkish urologists do not prefer single-dose antibiotic therapy, and their practice patterns regarding the administration of pre-biopsy rectal swabbing are inconsistent with the literature.