Factors Related to ICU-Acquired Infections Incidence in Iran: Analysis of National Nosocomial Infections Registry Data

Background: Patients admitted to intensive care units (ICUs) are particularly susceptible to hospital-acquired infections (HAIs) and the HAIs are higher in the ICUs than other wards of the hospital. This study aimed at investigating factors associated with ICU-acquired infections incidence in Iran. Methods: In this multi-center study, Iranian nosocomial infections surveillance (INIS) and hospital statistics and information system (AVAB) were used to collect data on patients with HAIs in 2018. The data was expanded based on 12 months of the year (13,632 records in terms of "hospital-ward-month") and then, the last observation carried forward method was used to replace the missing data. The generalized negative binomial regression with “patient-days” as an offset variable was used to identify the factors affecting ICU-acquired infections incidence. Results: The median age of patients was 57.5 (IQR=55.09) years. Of the 22.92%, 5.76%, 13.62%, 43.41%, and 14.29% of patients were in NICU, PICU, internal ICU, general ICU, and surgical ICU, respectively. Only 13.73% of hospitals were in ecient zone (zone III). Based on multivariable regression, the number of death (IRR=1.02), the number of infections due to the device (catheters and ventilators) (IRR=1.1), ward type (PICU (IRR=1.58), internal ICU (IRR=1.63), general ICU (IRR=1.53) and surgical ICU (IRR=1.47)), hospital's expertise, hospital's accreditation, bed occupancy rate indicator (IRR=1.17 for moderate conditions) were associated with an increase of ICU-acquired infections incidence. Infection due to ventilator, infection due to catheter, and the number of surgery in hospitals reduced 5%, 7%, and 1% incidence of infections, respectively. Conclusions: Based on the results, the most common ICU-acquired infections VAE UTI.


Background
Hospital-acquired infections (HAIs) are a major health concern worldwide and are regarded as the most common complications in any health-care facility [1]. According to the European Center for Disease Prevention and Control estimates, more than 2.5 million cases of HAIs occur annually in Europe and the United States, HAIs account for 100,000 deaths annually [2].
Patients admitted to intensive care units (ICUs) are particularly susceptible to HAIs and the morbidity of HAIs is higher in the ICUs than other wards of the hospital, which are often severe [2,3]. ICU-acquired infections affect patient's safety in developing and developed countries and are considered responsible for a substantial proportion of disability, increased length of stay (LOS) and mortality, delays in the recovery process, and impose additional costs and nancial burden on the healthcare system of countries [4,5].
Studies on infection in intensive care in Europe demonstrated the prevalence of ICU-acquired infections to be signi cantly higher (20.6%) [6]. The important ICU-acquired infections are ventilator-associated pneumonia (VAP), urinary catheter-related infection (UTI), central line-associated bloodstream infection (CLABSI), and surgical site infection (SSI) [6,7]. In addition, a meta-analysis study by Ling et al. in Southeast Asia showed that the pooled incidence of HAI was 20 patient per 1000 ICU-days [8].
The majority of these infections are associated with the aging, severity of the disease, and healthcare factors including increase the use of invasive devices (endotracheal tubes, tracheostomy, central venous and urinary catheterization, and mechanical ventilation), type of providing health services, and inappropriate use of antimicrobial drugs [6,7,9].
Hence, HAIs prevention is now the most successful intervention and the recognition of the magnitude of related factors to the incidence of ICU-acquired infections has become essential for adopting proper infection control measures and reducing the incidence of infection in hospitals especially in ICU wards.
Therefore, this study aimed at investigating factors associated with ICU-acquired infections incidence in Iran.

Data sources
In this multi-center study, Iranian nosocomial infections surveillance (INIS) and hospital statistics and information system (AVAB) were used to collect data on patients with HAIs from 662 hospitals in 2018.
The national infectious control committee registers the HAIs including the following: bone and joint, central nervous system, chorionic villus sampling, eye, ear, nose, throat or mouth, urinary tract infections, ventilator-associated events, surgical site infections, central line-associated bloodstream infections, gastrointestinal system, reproductive tract infection, and skin and soft tissue infections. The data is collected to reduce mortality, morbidity, and complications of HAIs.
Iranian nosocomial infections surveillance collects data from about 863 hospitals and records different types of information in different units of each hospital including age, gender, type of HAIs, number of hospitalizations, patient-day, number of deaths, number of surgeries, date of infection, province, university, a liated organization, devices used, and outcome of infection. In addition, we extracted performance indicators including the average LOS, occupancy rate, and bed turnover from AVAB that is a web-based system for each hospital.
Expanded data and missing data imputation The data including 12,586 records in terms of "hospital-ward-month" for ICU-acquired infections was expanded based on 12 months of the year (13,632 records in terms of "hospital-ward-month") and then, the last observation carried forward (LOCF) method was used to replace the missing data. In LOCF imputation, rst, the data on each variable in each hospital ward was sorted in terms of months, and the last observation was replaced through the forward method; then, the data on the same variable was sorted in terms of the reversed order of months and the last observation was replaced for the missing values through the backward method. Finally, the average values obtained in the two steps of forward and backward methods were used as the value of the missing data. In addition, the hospitals with no data on the number of infections and hospitalizations (in none of the months under the study) were excluded. Final ICU-acquired infections were 10,836 records obtained from 579 hospitals.

National standard for hospital performance indicators
Hospital performance indicators were categorized on the basis of the standards of Ministry of Health and Medical Education (MOHME) of Iran as follows: Average LOS (day): <3.5 (desirable), 3.5-4 (moderate) and > 4 (undesirable) Bed occupancy rate (%): >70 (desirable), 60-70 (moderate) and < 60 (undesirable) Bed turnover rate: >24 (desirable), 17-24 (moderate) and < 17 (undesirable) Death to bedridden ratio (%): <2 (desirable), 2-3 (moderate) and > 3 (undesirable) In addition, the national average rate of bed turnover (134.24) and bed occupancy (62.73) was used to plot the Pabon Lasso graphical chart. The plotted Pabon Lasso graph indicates four zones, where zone I is the ine cient area, zone II, zone III are the e cient area of the model, and zone IV.

Data Analysis
Mean (standard deviation), median (interquartile range) and count (percentage) were used to describe quantitative and qualitative variables, respectively.
To identify the factors affecting ICU-acquired infections incidence, we used generalized negative binomial regression with "patient-days" as an offset variable. All the variables with a p-value of less than 0.2 at the univariable model entered into the multivariable regression model. Data were analyzed by the Stata (version 12) and p < 0.05 was considered statistically signi cant for all statistical tests.

Results
The median age of patients was 57.5 (IQR = 55.09) years. The median hospitalization-infection length and hospital LOS in the patients were 8.28 (IQR = 12.8) days and 21 (IQR = 21.75) days, respectively. The highest median of the number of death was observed in internal ICU (7, IQR = 10). The distribution of different variables by type of ICU in Iran hospitals was shown in Table 1. general hospitals and medium hospitals (bed size = 100-320). In addition, based on the Pabon Lasso model, only 13.73% of hospitals were in e cient zone (zone III) ( Table 2). Considering performance indicators including average LOS, bed occupancy and bed turnover, the frequency of desirable conditions was higher in hospitals ( Fig. 1). The risk of ICU-acquired infections incidence In investigating the relationship between ICU-acquired infections incidence and hospital variables and indicators, the number of death (death in HAIs patients) was associated with an increase of ICU-acquired infections incidence (IRR = 1.02; 95% CI: 1.01-1.02). Based on multivariable generalized negative binomial regression, the number of infections due to the device (catheters and ventilators) was associated with a 10% increase in ICU-acquired infections incidence rate (IRR = 1.1; 95% CI: 1.08-1.13). Also, PICU, internal ICU, general ICU, and surgical ICU were associated with a 58%, 63%, 53%, and 47% increase in ICU-acquired infections incidence rate compared to the NICU, respectively. Considering the hospital's expertise, the largest increase in the incidence of ICU-acquired infections was related to the heart hospitals (IRR = 2.91; 95% CI: 2.37-3.57), accidents (IRR = 2.08; 95% CI: 1.6-2.71), and pediatric hospitals (IRR = 1.95; 95% CI: 1.67-2.27). In addition, the risk of an increase in the incidence of the ICUacquired infections was 23% (IRR = 1.23; 95% CI: 1.12-1.35) and 73% (IRR = 1.73; 95% CI: 1.52-1.97) higher in hospitals with accreditation 1 and 2, respectively. In hospitals with moderate conditions in terms of bed occupancy rate indicator, the incidence of ICU-acquired infections was 1.17 times higher than the desirable conditions (IRR = 1.17; 95% CI: 1.09-1.25) ( Table 3). Based on univariable regression, infection due to the ventilator, infection due to catheter, and the number of surgery in hospitals were associated with an increase in ICU-acquired infections incidence, but in multivariable regression, these variables were not statistically signi cant. As the hospital bed surgery turnover increases, the incidence rate of infections decreases by one percent (IRR = 0.99; 95% CI: 0.99-0.99) ( Table 3).

Discussion
The incidence of HAIs depends on many factors, including medical interventions, hospital factors, and personal characteristics. In addition, it varies in hospital wards and shows that although the intensive care units have increased the recovery rate and reduced mortality, on the other hand, the length of hospital stay of these patients and the use of invasive devices and catheters have increased HAIs in these wards [10].
Based on the results, the number of death (death in HAIs patients), type of ICU, hospital's expertise, and bed occupancy rate indicator were associated with an increase in ICU-acquired infections incidence rate.
Knowing the causes, type, and frequency of HAIs can be very effective in optimal management and improving the quality of services. Therefore, organizing the nosocomial infection control committee, designing and implementing educational programs, paying attention to the basic design of the physical structure of hospital wards, creating motivational and attitudinal mechanisms in infection control are important factors that can reduce HAIs [11].
Device-related infections are a leading cause of HAIs, particularly in ICUs. Also, catheter-related infections are the most frequent cause of hospital-acquired bacteremia and mechanical complications and are mostly accessible to prevention if establishing standard disinfection and sterilization mechanisms and rigorous policies are implemented [12,13]. Furthermore, mechanical ventilation is a commonly used mode of support in the ICU [11,14]. In this study, the number of infections due to the device (catheters and ventilators) was associated with a 10% increase in ICU-acquired infections incidence rate. In addition, the most common ICU-acquired infections were VAE (38.6%) and UTI (19.76%), which are mostly related to the device used. Other studies show that the important infections in the ICU include UTI, pneumonia, bloodstream infections [7,15,16]. In Ohannessian et al.'s study, the HAIs incidence rate was 14.9 per 1,000 patients-days. Furthermore, pneumonia and UTI rates were 9.7 and 6.1 per 1,000 patients-days [5]. Furthermore, in Choudhuri et al.'s study, pneumonia accounted for more than a third of HAIs observed in ICUs. The duration of mechanical ventilation, duration of endotracheal intubation, duration of urinary catheterization, and ICU length of stay were signi cantly related to ICU-acquired infections [17].
Present ndings imply that device-related infections are associated with increased complications and costs. Therefore, the speci c preventive strategies of device-related infections, establishing a system of reporting and follow-up, healthcare workers' education and training about the use of invasive devices are necessary to reduce the ICU-acquired infections.
However, our study had some limitations. One, this study was a retrospective study, so there is a possibility of some biases. Second, the impact of pathogens, antimicrobial resistance, and other factors on ICU-acquired infections incidence rate was not considered in our study and may limit our interpretation. But, this study was a multicenter study and conducted using registered data, so it can be claimed that the results are generalizable. In addition, this study was the rst large sample size, comprehensive and national study that was conducted the investigating factors associated with ICUacquired infections incidence and will be better clarify the factors affecting the occurrence of infections.

Conclusions
Based on the results, internal ICU had the largest increase in ICU-acquired infections incidence compared to the NICU and the most common ICU-acquired infections were VAE and UTI. The occurrence of HAIs in medical centers is inevitable and its control is one of the most important health goals of medical centers. Therefore due to the high sensitivity of intensive care units, full hygiene should be taught to the medical staff, especially the ICU wards. Ventilators and catheters should be used in special circumstances and minimum duration. Regular hand washing, the use of antimicrobial gels, and the use of disposable gloves and masks in the face of patients are very reasonable and necessary. Availability of data and materials

Abbreviations
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.