Главная / Архив / 2024 год / MEDICUS № 9 (63), September / HEALTH CARE-ASSOCIATED INFECTION IN IRAN

HEALTH CARE-ASSOCIATED INFECTION IN IRAN

Дата публикации: 25.09.2024

Hygieology

Гигиена

UDC 314.35:315.33

HEALTH CARE-ASSOCIATED INFECTION IN IRAN

L.V. Maksimenko,Candidate of Biological Sciences,

Associate Professor at the Department of Public Health, Healthcare Service and Hygiene

Medical Institution, Peoples' Friendship University of Russia named after Patrice Lumumba

(117198, Russia, Moscow, Miklouho-Maklaya St., 6)

E-mail: maximenko_lv@pfur.ru

Sattar Zahadat,Student of the Medical Faculty

Medical Institution, Peoples' Friendship University of Russia named after Patrice Lumumba

(117198, Russia, Moscow, Miklouho-Maklaya St., 6)

E-mail: 1032228126@pfur.ru

Abstract. The problem of mortality of hospitalised patients due to infection with antibiotic-resistant hospital strains is a global one. Iran participates in the international programme GLASS, TrSCSS and implements the national surveillance programme INISS. In this article, the results of INISS and GBD IHME-WHO database survey are presented. In Iran, the problem of antibiotic resistance is as urgent as it is for the whole world, as 51 thousand people die every year due to sepsis associated with antibiotic resistance.

Keywords: Iran, hospital infections, antibiotic resistance, GLASS, TrSCSS, GBD IHME-WHO.

The most important issue in the evaluation of the risk of infection in the hospital or while receiving medical care is the definition of this urgent and formidable phenomenon. As it is defined, “Hospital-acquired infections (HAIs) refer to infections that are not present at admission and occur within 48-72 hours after admission or up to 6 weeks after discharge, not during the incubation period” [17]. In 2010, WHO expands the concept of hospital-acquired infections to healthcare-associated infections (HCAI) to include all out-of-hospital care, e.g., on the street, at school, in an ambulance. "Health care-associated infection, also referred to as “nosocomial” or “hospital” infection, is an infection occurring in a patient during the process of care in a hospital or other health care facility that was not present or incubating at the time of admission. HCAI can affect patients in any type of setting where they receive care and can also appear after discharge. Furthermore, they include occupational infections among staff [6]. Today, out of every 100 patients in acute-care hospitals, seven patients in high-income countries and 15 patients in low- and middle-income countries will acquire at least one HAI during their hospital stay. On average, 1 in every 10 affected patients will die from their HAI (WHO) [17]. However the overall prevalence of HAI in high-quality studies is significantly higher. Allegranzi et al. wrote (2011): “The total density of care-related infections in adult intensive care units was 47.9 per 1,000 patient days (95 % CI: 36.7-59.1), which is at least three times higher than reported in the United States. Infection at the surgical site was the leading infection in hospitals (the total incidence was 5.6 per 100 surgical interventions), which is significantly higher than recorded in developed countries” [6].

There were 13.7 million (95 % CI: 10.9-17.1) infection-related deaths worldwide in 2019. More than half of the deaths, namely 7.7 million (95 % CI: 5.7-10.2) were associated with 33 pathogens of bacterial nature, both resistant and susceptible to antimicrobials within 11 infectious syndromes. Deaths associated with 33 bacterial pathogens were found to comprise 13.6 % (95% CI: 10.2-18.1) of all global deaths and 56.2 % (95 % CI: 52.1-60.1) of all sepsis-related deaths. Five leading bacterial pathogens (Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa) were responsible for 54.9 % (95 % CI: 52.9-56.9) of deaths among these 33 investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardized mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. Staphylococcus aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, Streptococcus pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths [9].

In the Gulf countries, S. aureus predominates among infections affecting inpatients, and the mortality rate does not exceed 25 cases per 100,000 population. Antimicrobial resistance (AMR) is one of the top global public health and development threats. It is estimated that bacterial AMR was directly responsible for 1.27 million global deaths and contributed to 4.95 million deaths in 2019 [8].

The aim of this study is to determine the prevalence rate of hospital-acquired infections in Iran.

Materials and Methods. This study included a review of publications since 2020 on the prevalence of hospital-acquired infections in the Islamic Republic of Iran according to PubMed and the Oxford University GBD IHME database.

Nosocomial infections in Iran.

Iran participates in the Global Antimicrobial Resistance and Use Surveillance System (GLASS), a WHO project designed to enhance worldwide antimicrobial resistance (AMR) surveillance and knowledge. The GLASS, the first worldwide cooperative attempt to standardize AMR surveillance, was introduced by the World Health Organization on October 22, 2015. GLASS was established to support the second goal of the GAP-AMR program, which is to “strengthen knowledge through surveillance and research.” Its purpose is to continue filling information gaps and provide guidance for initiatives at all levels. The Sixty-eighth World Health Assembly endorsed this goal in resolution WHA68.7 [12].

Iran participates in the tripartite AMR nation self-assessment survey known as TrACSS. The Food and Agriculture Organisation of the United Nations (FAO), the World Health Organisation (WHO), and the World Organisation for Animal Health (OIE) use the TrACSS program to monitor the global status of antibiotic resistance [11]. Multi-sectoral working group(s) or coordination mechanism committee on AMR established with Iranian Government leadership.

The Iranian Hospital-Acquired Infection Surveillance System (INISS) was established in 2005. Currently, INISS has been integrated with the national health care program under the Iranian Ministry of Health. Data collecting, epidemiological monitoring, infection control, public health impact, and healthcare professional education and training to increase knowledge of infection prevention and control techniques are among the functions of INISS.

Antibiotic consumption in Iran (Islamic Republic of), for the period 2016 to 2021 by GLASS. In Iran, in 2021, the structure of antimicrobial drug consumption is represented by antibiotics (60.68 DDD/ 1000 inh./day), antimycotics and antifungals for systemic use (1.23 DDD/ 1000 inh./day), antimalarials (1.0 DDD/ 1000 inh./day), antivirals for systemic use (0.94 DDD/ 1000 inh./day), drugs for the treatment of tuberculosis (0.47 DDD/ 1000 inh./day), where DDD/ 1000 inh./day means Defined Daily Doses per 1000 inhabitants in a day [7].

Almost half of them 49.2% are access, 50.6% – watch, 0.1% – reserve, 0.1% – not classified or recommended [18].

Among antibiotics, the highest consumption was found for macrolides, lincosamides and streptogramins (J01F) – 17.55 DDD/ 1000 inh./ day, beta-lactam antibacterials, penicillins (J01C) – 17.51 DDD/ 1000 inh./day), other beta-lactam antibacterials (J01D) – 11.83 DDD/ 1000 inh./ day. Moreover, 96.8% of antibiotics are administered orally and only 3.2% parenterally. Azithromycin and amoxicillin absolutely prevailed among antibiotics. In 2021, they accounted for half (50.4%) of all antibiotics consumed. Moreover, azithromycin (AWaRe – Watch, J01F A10) accounted for 27.4%, amoxicillin (AWaRe – Access, J01C A04) – 23% of all consumed antibiotics [7].

So, understanding the structure of consumption of antibiotics and other antimicrobial drugs and their accessibility to the population allows researchers to link these data with antibiotic resistance and those negative consequences for the population such as mortality due to the inability to choose an effective antibiotic and cure infected patients.

Composition of infection-related deaths in Islamic Republic of Iran by GBD IHME. The Global Burden of Disease (GBD) of Institution for health metrics and evaluation (IHME) approach endeavors to measure disability and death from a multitude of causes worldwide. It has grown over the past two decades into an international consortium of over 12,000 researchers, and its estimates are being updated annually. GBD work was institutionalized at the WHO, and the organization continued to update GBD findings. The most negative consequence of patients’ infection in a medical institution is sepsis. Sepsis causes death or disability. A life-threatening bodily response to infection characterized by organ dysfunction. The classification of the type of infection (and in severe cases, sepsis) is based on the classification of the affected organ system. In accordance with the GBD in 2019, 51,340 people died in Islamic Republic of Iran for whom sepsis was an immediate cause of death or was in the chain of events leading to their death (intermediate cause). This means that sepsis affects 60.90 people (from 42.33 to 85.58) per 100 thousand. Bacterial infection caused 36,515 deaths. Bacterial infections absolutely prevailed as a cause of sepsis. Bacterial infection accounted for 71% of all deaths due to sepsis [10].

The most common infectious syndromes leading to sepsis and death were bloodstream infections (34.0 %), lower respiratory infections and all related infections in the thorax (LRI and thorax) (33.7 %), as well as peritoneal and intra-abdominal infections (12.3 %) (Table 1).

Table 1

Numbers of total infectious syndrome deaths in Islamic Republic of Iran, All Ages, 2019 [GBD IHME - WHO]

Deaths	Sex	Bloodstream infections (95% CL)	Lower respiratory infections and all related infections in the thorax	Peritoneal and intra-abdominal infections
Share among all causes of death, %	Both sexes	34.0	33.7	12.3
Number causes of death	Both sexes	17,657.65 (9,438.01-29,760.85)	17,308.96 (13,490.96-22,571.86)	6,357.01 (3,971.08-9,936.15)
Rate (per 100k)	Both sexes	20.95 (11.20-35.30)	20.53 (16.00-26.78)	7.54 (4.71-11.79)
Rate (per 100k) standardized by age	Both sexes	26.44 (14.17-44.79)	27.53 (21.51-35.72)	9.49 (5.95-14.75)
	Males	28.71 (15.26 – 48.24)	30.72 (23.72 – 40.10)	10.52 (6.47 – 16.22)
	Females	24.21 (13.15-41.20)	24.33 (19.16 – 31.52)	8.49 (6.47 – 16.22)

As you can see, the 3 forms of infections were implicated in the most sepsis deaths in Iran – in sum there is 80% of all sepsis deaths. Age-standardized analysis showed that lower respiratory infections and all related infections in the thorax were the most common in both sexes and in males and in females taking separately. Lower respiratory infections and all related infections in the thorax are more common than bloodstream infections in the age groups 1 to 4 years and 75 years and older. 4 542 deaths due to sepsis were in children under 5 which amounted to 8 %.

The Index Disability-adjusted life years (DALYs) shows the impact of disease and conditions of medical care on health and quality of life in the studied population group. The DALY is used to evaluate the «burden of disease» in different populations. To calculate DALYs, experts use two other health metrics: mortality or years of life lost (YLLS) and morbidity or years lived with disability (YLDS) relative to life expectancy in a given population.

In the ranking of Iran's neighboring countries by the average age-standardized DALY per 100k for the leading mortal nosocomial infection in Iran, Acinetobacter baumannii, Iran ranks 3rd place (162.68) after Afghanistan (388.32) and Pakistan (235.81). The lowest DALY caused by AMR Acinetobacter baumannii in the region is found in Turkey (78.61) and Armenia (86.86).

Years of life lost DALYs due to total infectious syndrome in Iran are demonstrated in Fig. 1.

Fig. 1. Total infectious syndrome DALYs per 100k in Islamic Republic of Iran, All Ages, 2019

[GBD IHME - WHO]

As can be seen, blood infections are the main cause of DALYs, regardless of gender at age standardization conditions. Diarrhea came in third place here.

Deaths associated and attributed to antibiotic resistance of the pathogen (Iran, 2019). Experts classify deaths into 2 groups, namely, associated and attributed to antibiotic resistance of pathogens. Associated deaths measure people with a drug-resistant infection that contributed to their death. The infection was implicated in their death, but resistance may or may not have been a factor. Attributable deaths measures people who would not have died of infection if it was treatable (i.e., if there was no AMR) for whom resistance can be said to have caused their death. Thus, during 2019, there were 24,908 deaths associated and 6,896 deaths attributed with bacterial AMR of pathogens with the ratio of deaths associated and attributed to AMR 3.6 : 1.

Among the deaths associated with AMR, the following bacteria lead: Acinetobacter baumannii (4,480.72 deaths), Staphylococcus aureus (3,612.60 deaths) and Escherichia coli (3,378.32 deaths). Among the deaths attributed with AMR, the following bacteria lead: Acinetobacter baumannii (1,428.19 deaths), Escherichia coli (1,004.53 deaths), Staphylococcus aureus (997.80 deaths). As you can see, the leading place is occupied by the same 3 pathogens of bacterial nature (Table 2).

Table 2

Deaths attributable to bacterial antimicrobial resistance by pathogen-drug combination

in Islamic Republic of Iran, All ages, both sexes, 2019 [GBD IHME - WHO]

Bacteria - pathogen	An antibiotic to which the pathogen is resistant	Number of deaths
Acinetobacter baumannii	Fluoroquinolones	555
	Carbapenems	540
	Aminoglycosides	162
	Anti-pseudomonal penicillin/ Beta-lactamase inhibitors	145
	Third-generation cephalosporins	14
	Fourth-generation cephalosporins	8
	Beta lactam/ Beta-lactamase inhibitors	3
Escherichia coli	Carbapenems	286
	Third-generation cephalosporins	259
	Fluoroquinolones	205
	Trimethoprim-Sulfamethoxazole	129
	Aminoglycosides	54
	Beta lactam/ Beta-lactamase inhibitors	41
	Aminopenicillin	30
Staphylococcus aureus	Methicillin	787
	Macrolides	103
	Trimethoprim-Sulfamethoxazole	59
	Fluoroquinolones	37
	Vancomycin	12

“Acinetobacter is common in the environment, on human skin and is often the causative agent of nosocomial infection. It should be noted that the pathogen is a conditional pathogen that causes an infectious process only in immunocompromised patients. The analysis of the accumulated information about Acinetobacter allows to draw not only pessimistic conclusions predicting the further spread of resistant strains and the associated increase in morbidity and mortality” [5]. Intensive care units (ICU) differ from other hospital wards due to the constant contact of patients with medical staff, the large number of invasive procedures performed, and the constant use of antimicrobials, which creates conditions for the selection of antibiotic-resistant strains. A review of multicentre epidemiological studies has shown that E. coli often leads as a causative agent of bloodstream infections, nosocomial pneumonia, skin and soft tissue infections [4]. Staphylococcus aureus causes severe infectious diseases such as soft tissue infections, endocarditis, sepsis, toxic shock syndrome and food poisoning. Coagulase-positive Staphylococcus aureus is the main causative agent of hospital infections. It has a large number of pathogenicity factors that are well studied [3]. Preliminary data suggest the need to vaccinate the population to establish protective immunity targeting multiple pathogenicity factors of S. aureus [2]. Toxins and pathogenicity factors produced by S. aureus are determined by genes located not only in the core genome but also in mobile genetic elements. These elements also ensure resistance of Staphylococcus aureus to antibiotics, including vancomycin, methicillin and daptomycin [1]. As shown in Table 2, methicillin and azithromycin (macrolide), frequently used in Iran, are absolutely leading among all antibiotics to which S. aureus shows resistance.

Correspondent to Izadi et al. (2020) “The overall rate of HAIs was 26.57 per 1000 patients and 7.41 per 1000 patient-days. HAIs are common in ICU wards, while Urinary Tract Infection (UTI) and device-related infections are more prevalent in Iran. A multicenter study (n=107 669 patients) of Izadi et al. (2020) found that “the most common HAIs were UTIs (26.83%; 1.99 per 1000 patient-days), ventilator-associated events (20.28%; 1.5 per 1000 patient-days), surgical-site infections (19.73%; 1.45 per 1000 patient-days) and bloodstream infections (13.51%; 1 per 1000 patient-days), respectively. The highest rate of HAIs was observed in intensive care units. Device, catheter and ventilator-associated infections accounted for 38.72%, 18.79% and 16% of all HAIs, respectively [14].

Bagheri Pejman et al (2021) used INISS to investigate the prevalence of nosocomial infections in a teaching hospital. According to their data within 1 year from 2018 to 2019, the prevalence rate of HAIs (number of the cases per 100 hospitalizations) was 2.95%. The highest rate of HAIs was reported from ICUs which «is the part of a hospital provides continuous treatment for patients who are seriously ill, very badly injured, or who have just had an operation» [13]. Of the infected patients, 45.61% were female, 98.95% had underlying diseases, and 30.88% died due to nosocomial infections. The median (interquartile range) of the duration of hospital stay among infected patients was 13 (7-18) days. The most common site of infection was ventilator-associated events (39.40%) and the most common isolated agent, irrespective of the organ involved, was Acinetobacter (spp.) (22.75%). So “ICU and Acinetobacter (spp.) as the most affected ward and most common agent involved in recorded HAIs respectively. The rate of HAI in the study hospital was exceptionally low when compared to its counterparts in a few other developed countries. The INISS needs to be further evaluated with regard to the completeness and representativeness of the surveillance system» [16].

Mohammadi et al. (2022) note: “Despite decreasing the number of admissions during the COVID era (hospitalizations showed a reduction of 43.79%), the total hospital nosocomial infections remained unchanged; 4.73% in the pre-COVID period versus 4.78% during the COVID-19 period. During the COVID period the infection percentages statistically significant (p<0.05) increased in the cardiovascular care unit and intensive care units, but declined in cardiology and neurology wards” [15].

Thus, Health care-associated infection, aggravated by antimicrobial resistance of pathogens, annually causes the deaths of an average of 13.7 million people worldwide, more often due to pneumonia or sepsis. At the same time, the use of antibiotics greatly simplifies the use of other antibacterial drugs (antibiotics, antifungal, antimalarial, antiviral), while 96.8% of antibiotics are administered orally in Iran. The most negative consequence of infection of patients in Iranian medical institutions is sepsis. Every year in Iran, more than 51 thousand people die due to sepsis (61 deaths per 100,000), and bacterial infections are responsible for 71% of them. Three forms of infections were the cause of the majority of sepsis deaths in Iran – together they account for 80% of all sepsis deaths – bloodstream infections, lower respiratory tract infections and all related chest infections, as well as peritoneal and intra-abdominal infections. 8% of deaths due to sepsis occur in children under 5 years of age. Lower respiratory tract infections and all related chest infections are more common than bloodstream infections in the age groups from 1 to 4 years and from 75 years and older. Blood infections are also the main cause of DALYs. In 2019, almost 25 thousand deaths were associated with the AMR. Among the deaths associated with antimicrobial resistance of the pathogen, Acinetobacter baumannii, Staphylococcus aureus and E. coli are leading. Russian scientists warned about the threat of Acinetobacter (Chebotar et al.) 10 years ago. In total, more than 26 per 1000 people were identified. The greatest risk of nosocomial injection was found in intensive care units.

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Материал поступил в редакцию 11.09.24

ИНФЕКЦИИ, СВЯЗАННЫЕ С ОКАЗАНИЕМ

МЕДИЦИНСКОЙ ПОМОЩИ, В ИРАНЕ

Л.В. Максименко,кандидат биологических наук,

доцент кафедры общественного здоровья, здравоохранения и гигиены

Медицинский институт, ФГАОУ ВО Российский университет

дружбы народов имени Патриса Лумумбы

(117198, Россия, Москва, ул. Миклухо-Маклая, 6)

E-mail: maximenko_lv@pfur.ru

Саттар Захадат, студент медицинского факультета

Медицинский институт, ФГАОУ ВО Российский университет

дружбы народов имени Патриса Лумумбы

(117198, Россия, Москва, ул. Миклухо-Маклая, 6)

E-mail: 1032228126@pfur.ru

Аннотация. Проблема смертности госпитализированных пациентов вследствие инфицирования госпитальными штаммами, проявляющими антибиотикорезистентность, носит глобальный характер. Иран участвует в международной программе GLASS, TrSCSS и реализует программу национального надзора INISS. В статье приведены результаты исследования базы данных INISS и GBD IHME-WHO. В Иране проблема антибиотикорезистентности столь же актуальна, как и для всего мира, поскольку ежегодно 51 тысяча чел. гибнет по причине сепсиса, связанного с антибиотикорезистентностью возбудителя.

Ключевые слова: Иран, госпитальные инфекции, устойчивость к антибиотикам, GLASS, TrSCSS, GBD IHME-WHO.