Healthcare-Associated Infection Causes and Mitigation Strategies: A Systematic Review

Summary

Objective:

To describe the landscape of healthcare-associated infections (HAI) and, in particular, to pay attention to the types of infection that are usually seen, the most common infectious agents involved and the effective prevention strategies.

Methods:

A detailed search was performed using Google and PubMed, and studies that exclusively addressed healthcare associated infections or their mitigation. Studies published since 2000 were included. Data from individual articles were extracted and categorized by study focus, type of infection, causes and contributing factors, and documented mitigation strategies. Editorials, reviews, case studies, meta-analyses, and systematic reviews were excluded.

Results:

The analysis showed that infections related to healthcare, particularly bloodstream infections, infections that occur in intensive care units, and surgical site infections, significantly burden healthcare systems. Bacterial pathogens, including drug-resistant strains, such as Staphylococcus aureus, were identified as the most prominent etiologic agents, as well as several viral pathogens. The findings also underlined the importance of strong surveillance systems and especially systems that take advantage of digital platforms to effectively monitor the trends of infection and antibiotic resistance.

Conclusions:

The review highlighted the serious need for effective monitoring systems, especially those that use digital platforms, to monitor trends of infection and antibiotic resistance. The study highlighted the importance of a multifaceted preventive approach that involves prophylactic and therapeutic measures, as well as strict adherence to the sterile technique in healthcare institutions.

Introduction

Healthcare-associated infections (HAIs) are infections acquire by patients while receiving care in healthcare settings [1]. These infections often result from inadequate medical practice, poor hygiene, or lapses in adherence to proper care protocols by patients and healthcare professionals, including blood donors. Common examples include urinary tract infections, pneumonia, bloodstream infections, skin infections, gastroenteritis, and meningitis. Many HAIs associated with medical devices such as ventilators and catheters, which, if inadequately sterilized, can serve as reservoirs for pathogens and this represent a major route of transmission [2,3]. Globally, HAI occurs in approximately 3.2% of patients in the United States, 6.5% in the European Union, and up to 40% in certain parts of Asia, Latin America, and Africa. The European Centre for Disease Prevention and Control (ECDC) estimates that nearly 3.2 million individuals develop HAI every year, with 37,000 associated deaths [4]. Such infections not only result in injury to patients but also put a very heavy burden on health systems [5]. The most common modes of transmission of HAI are airborne transmission, direct and indirect contact, respiratory droplets, invasive medical devices, and vector-borne pathways. Predominant pathogens identified in healthcare settings include Pseudomonas aeruginosa, multidrug-resistant Enterobacter cloacae and Klebsiella pneumoniae, coagulase-positive Staphylococcus aureus, vancomycin-resistant Enterococcus, Acinetobacter species, and Serratia marcescens [6].

Reducing infection risk requires effective decontamination of medical devices and equipment, installation of advanced air filtration systems in intensive care units (ICUs), and strict monitoring of air and water quality standards [7]. Proper disposal of medical waste is equally critical. Improving equipment sterilization procedures, applying aseptic techniques during interventions, ensuring safe handling of surgical instruments, and enforcing strict compliance with safety measures by healthcare workers, particularly when managing infected patients, can significantly reduce transmission [8]. This systematic review collects worldwide evidence regarding HAIs, identifying their major causes and discussing various prevention strategies adopted across healthcare systems.

Methods

A comprehensive search was performed using Google and PubMed. Only studies published from 2000 onward were included. To manage the extensive, relevance-ranked output of Google Scholar, the initial screening was capped at the first 200 results, a standard practice in systematic reviews to maintain feasibility without sacrificing rigor [9]. Both authors unanimously agreed on the final search. The selection of studies for inclusion in this review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [10].

The literature search employed keywords and medical subject headings (MeSH) related to 2 core concepts: i) hospital-acquired infections, ii) prevention and control. The search strategy combined these concept blocks using the Boolean operator AND. Within each block, synonymous terms (such as “nosocomial infection”, “healthcare-associated infection”) were connected with OR to broaden the results. Keywords were searched in both MeSH terms and title/abstract fields.

Studies were considered suitable for inclusion if they fulfilled the following criteria: “Population (P): Patients receiving care in healthcare settings (hospitals, intensive care units, surgical units, long-term care facilities, outpatient clinics), of all ages and genders, with or without invasive devices. Intervention (I): Infection prevention and control strategies, including hand hygiene, PPE use, device sterilization, aseptic techniques, environmental measures, and antibiotic stewardship programs. Comparator (C): Standard care/usual infection control, alternative preventive strategies, or no intervention. Outcomes (O): Primary outcomes: HAI incidence/prevalence; effectiveness of interventions in reducing HAIs. Secondary outcomes: Predominant pathogens, antibiotic resistance patterns, adverse events related to interventions.” In Addition, only clinical studies providing data on HAI and their prevention strategies were considered. Editorials, reviews, case studies, meta-analysis, and systematic reviews were excluded. Studies focusing exclusively on HAI or their mitigation, published from 2000 onward, were included.

Data from each article were extracted and categorized according to study focus, type of HAIs, causes and contributing factors, and documented mitigation strategies. Interpretations were then made regarding year-to-year incidence trends, risk evaluation, root causes of insufficient preventive measures, and advocacy for antibiotic regimens, with attention to risks of developing antibiotic-resistant HAIs. The outcome of this review provides 2-decade assessment of HAI risks and evaluates progress in prevention and antibiotic resistance mitigation.

Results

Fig. 1 presents the literature screening process and outcomes. Based on predefined exclusion criteria, duplicates, reviews, meta-analyses, reports, and systematic reviews were removed, leaving 70 articles for inclusion. Articles were further categorized into 2 groups: those addressing HAI characterization and those focusing on prevention and mitigation strategies (Fig. 2).

Fig. 1.

Literature search strategy (PRISMA flow diagram), PRISMA: preferred reporting items for systematic reviews and meta-analyses, RCT: randomized controlled trial.

Fig. 2.

Prevalence of healthcare-associated infections (2000–2025): (A) Percentage of HAI studies; (B) Distribution of HAI types. HAI: healthcare-associated infections.

The HAIs represent a substantial burden to healthcare systems and economies. These infections can originate from multiple sources (Fig. 3), including transmission within hospital settings, direct patient-to-patient contact, contamination from medical devices, and exposure to polluted environmental media such as water and air. In our systematic review, we compiled research focused on the diverse origins of HAI. Our analysis revealed that 40.6% of HAIs were bloodborne infections, 25% were linked to infections acquired during hospitalization, 15.6% originated in ICUs. Operating room infections accounted for 12.5%, while contaminated medical equipment was implicated in 6.3% of cases.

Fig. 3.

Sources of HAIs. HAI: healthcare-associated infections.

The main infectious agents identified include gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus) and gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii). Many of these bacteria are drug-resistant strains, which place significant strain on healthcare resources and the economy. In addition to bacterial pathogens, a substantial number of viral and fungal pathogens also contribute to HAIs. significantly. Of the studies reviewed, 21% reported bacterial pathogens as the source of infection, while 18% highlighted drug-resistant strains, 34% focused on viral agents, 11% examined both bacterial and viral pathogens, another 11% studied fungal pathogens, and 5% investigated a combination of bacterial and fungal agents. Fig. 4 displays the causative pathogens reported in these studies.

Fig. 4.

Pathogens associated with HAI. ESBL-EC: extended-spectrum β-lactamase–producing Escherichia coli, MRSA: methicillin-resistant Staphylococcus aureus, SFTSV: severe fever with thrombocytopenia syndrome virus, HAI: healthcare-associated infections, MRSA: methicillin-resistant Staphylococcus aureus.

Our findings indicate Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) as the most frequently implicated bacterium worldwide, followed by Escherichia coli and Pseudomonas aeruginosa. Viral pathogens constituted the second most dominant group, with agents such as rotavirus, hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency viruses (HIV) being common causes of HAIs. Fungal pathogens were the least prevalent, with Candida, Aspergillus and Mucor among those identified (Fig. 4).

To reduce the global impact of HAI, various organizations have developed diverse mitigation strategies, including promotion of hygiene, sterilization of medical devices, use of personal protective equipment (PPE), effective disinfectants, and controlling the misuse of antibiotics. In addition, numerous research groups have experimented with different approaches to address the challenges in managing HAIs. In this review, we specifically focused on the preventive measures adopted to control these infections, revealing that 40% of the studies concentrated on preventive measures. We further categorized these measures into several subgroups based on their focus, such as prophylaxis, antibiotic and other therapeutic interventions, risk assessment and management strategies, and improvements in medical procedures. Notably, 45% of the studies were categorized under risk management and strategies, followed by prophylaxis (23%) and therapeutic measures (19%), while improvements in medical procedures accounted for only 13% of the mitigation strategies (Fig. 5).

Fig. 5.

HAI management strategies, HAI: Healthcare-associated infections.

We classified mitigation strategies under the following categories of Risk Management and Strategies (RMS): Surveillance-based strategies. Our review highlights that studies in this group focus on monitoring various aspects such as medical procedures, healthcare worker practices, personal hygiene, decontamination protocols, and advanced nursing procedures, with a strong emphasis on surveillance systems, particularly the development of online tools to track HAI; additionally, monitoring antibiotic regimens and resistance patterns improves prevention and control efforts, while disinfection of the hospital environment and medical equipment is crucial for mitigating infection risks (Table 1).

Table 1.

Mitigation strategies implemented for HAI.

Countries	Procedure/Reference
UK	Selective decontamination of the digestive tract [11].
South Africa	Post-HIV exposure prophylaxis [12].
Spain	Continuous infusion of meropenem (pharmacokinetics study) [13].
Sweden	Catheterizations: Micro-hole drainage zone and conventional eyelet catheter [14].
Canada	Probiotic treatment: for patients receiving systemic antibiotics [15].
USA	Multi-component intervention-“reverse Trendelenburg position, dysphagia screening, oral care and vaccinations” [16].
China	High-quality nursing procedures [17].
Sweden	Probiotics: Lactiplantibacillus plantarum 299 and 299v on oropharyngeal pathogens [18].
Japan	Hospital-acquired bacterial pneumonia /treated with tedizolid and linezolid [19].
China	JUC spray dressing (catheter pretreatment) [20].
Germany	Octenidine bathing reduced the ICU acquired bacteremia (17%) [21].
USA	Direct-gloving strategy (87% adherence); usual care of hand hygiene before donning gloves (41%) [22].
USA	Daily disinfection approach resulted in lowered CFU in the intervention group compared to the control group [23].
Greece	Probiotics reduced the incidence of VAP (11.9%) sepsis (6.8%) [24].
Thailand	Comparison of periurethral cleaning solutions: normal saline solution and Savlon solution [25].
Brazil	Chlorhexidine gluconate 2% ideal for low cost HAI prevention in ICU [26].
Multinational	Use of ceftolozane/tazobactam resulted in clinical cure rates 50.5% and 44.4% [27].
China	Online nosocomial infection surveillance systems (RT-NISSs) [28].
US	Antifungal prophylaxis [29].
China	Establishment of a comprehensive training and monitoring system for hospital logistic staff to address nosocomial infection during covid 19 pandemic [30].
USA	Surgical Care Improvement Project (SCIP) [31].
Germany/Spain	Surveillance systems for nosocomial infection in the neonatal unit [32].
China	Nosocomial infection surveillance system [33].
Spain	New automated HAI surveillance method [34].
Germany	Statutory surveillance system for MRSA [35].
USA	HCV; HBV risk management in HCW [36].
India	Infection control strategies in HCW [37].
Pakistan	Infection control activities [38].

HAI: healthcare-associated infections, ICU: intensive care unit, COVID19: corona virus disease of 2019, MRSA: methicillin-resistant staphylococcus aureus, HCV: hepatitis C virus, HBV: hepatitis B virus, HCW: healthcare worker, CFU: colony-forming units, VAP: ventilator-associated pneumonia, USA: United States of America, UK: United Kingdom.

Prophylactic approaches

This strategy focuses on measures used to prevent HAI before they occur. It encompasses prophylactic treatments, such as the use of probiotics during antibiotic therapy, and occupational health measures to reduce the spread of bloodborne infections among healthcare workers. The enforcement of regulations on PPE is also integral to this approach (Table 1).

Treatment-based strategies

Treatment focus involves antibiotic therapies, ongoing surveillance of therapeutic interventions, and systematic follow-up on patient outcomes. This approach aims to ensure that treatment protocols are effective and that any therapeutic shortcomings are promptly identified and addressed (Table 1).

Medical procedure protocols

Proper execution of medical procedures, such as gloving, catheterization, and maintaining aseptic techniques during surgical or invasive procedures, is crucial to significantly reducing the risk of HA (Table 1). Every category is crucial in a solid strategy to stop and manage hospital-acquired infections.

Discussion

This study emphasizes the significant impact of HAIs on healthcare systems and global economies. These infections originate from various sources, including transmission within hospital environments, direct patient-to-patient spread, contaminated medical devices, and exposure to polluted air and water, all of which complicate infection control efforts. The first objective of this systematic review was to screen articles on HAI published between 2000 and 2025. The review identified the potential sources of infection, with particular focus on blood-borne transmission.

The risk of blood-borne infections extends beyond donors; occupational exposure among ambulance operators was reported at 63.4%,and accidental exposures accounted for 54.8% of infections among healthcare workers in Bosnia and Herzegovina, although the rates in Germany were significantly lower [39–41]. Multiple studies have similarly identified blood-borne infections as a major risk factor in the spread of HAIs [40–48].

Our review also identified hospitalization itself as an important context for these infections. For example, a study in Lombardy, Italy, reported a 4.9% prevalence of HAIs among hospitalized patients. Multiple studies have similarly identified hospitalization as a major risk factor for the spread of HAIs [49–56].

Neonatal infections accounted for 11.9% of cases, highlighting the heightened vulnerability of neonates and children under 5 years to diarrheagenic pathogens; studies have shown that rotavirus is responsible for 69% of diarrheal cases in pediatric wards, with Salmonella also contributing significantly [49,55,57]. Other studies also support the occurrence of HAIs in children [58–62].

In ICUs, 11.9% of infections were reported, and a global study by Vincent et al. [63] noted that 54% of confirmed infections originated in the ICU. During pandemic situations, ICU-acquired bacterial infections—such as those caused by carbapenem-non-susceptible Klebsiella pneumoniae—have been observed at 9.4%, while fungal infections due to Candida have also been documented [54,59,64]. Operating room–related infections and those linked to contaminated medical equipment represent 9.5% and 4.8% of cases, respectively. Surgical site infections (SSIs) were reported in at least 19.4% of patients, as reported by in previous studies [65–68]. In contrast, infections from contaminated medical devices are less common; one study found an 80% prevalence of Staphylococcus species on stethoscopes, while another reported a 52.6% prevalence of Bacillus species on contaminated equipment [3,69].

Our review also emphasizes mitigation strategies for HAIs, structured according to identified categories. Research by Zafar et al. [38], Beltrami et al. [36], and Bari et al. [37]. has primarily focused on infection control strategies. Among these, surveillance-based interventions have proven particularly effective. Various forms of surveillance, including targeted, active, passive, environmental, and point prevalence surveillance, play crucial roles in mitigating HAI.

We observed that previous studies focused heavily on surveillance approaches. In addition to surveillance, prophylactic strategies demonstrated high effectiveness in preventing HAIs. The importance of prophylaxis in infection prevention has also been reported. Several studies also examined the role of antibiotics and other therapeutic measures in combating HAIs, while some specifically addressed therapeutic interventions. Finally, the promotion of proper medical procedures remains essential for preventing HAIs. Some studies have provided detailed insights into how adherence to appropriate procedures can significantly reduce infection risk.

One of the main challenges we faced was the inability to dig deeper into specific patient or treatment subgroups. The original studies we analyzed varied widely in their methods, what they measured, and how they reported their data. More importantly, many simply did not provide the detailed breakdown needed to create fair comparisons. This means we couldn't pinpoint what might be driving the differences in results or whether certain approaches consistently worked better. Moving forward, we need studies that report their findings more consistently and completely. Only then can we truly understand for whom and under what conditions these treatments are most effective.

In conclusion, this study provides a comprehensive overview of infections associated with healthcare settings, highlighting the substantial contribution of bloodstream infections, ICU-acquired infections, and surgical site infections. Findings indicate that the primary agents since 2000 have been Gram-positive bacteria, particularly Staphylococcus aureus (including resistant strains), alongside viral pathogens. The review underscores the urgent need for improved surveillance systems, particularly through emerging technologies, to enable real-time monitoring of infection and antimicrobial resistance patterns. The evidence also supports the adoption of diversified prevention strategies, including enhanced hygiene practices, thorough sterilization of medical units and equipment, and proactive risk reduction measures. A combination of targeted therapy and strict adherence to clinical protocols provides a comprehensive framework for minimizing the incidence and impact of these infections in hospital settings.

Acknowledgement

The authors would like to thank the Deanship of Scientific Research at Shaqra University for supporting this work. The author would also like to acknowledge ContentConcepts (www.contentconcepts.com) for the English language editing.

Disclosure statement

No artificial intelligence (AI) tools were used in the writing of this article, the creation of images, or the collection and analysis of data presented herein. This work has not been presented at any conference, and no related abstracts have been published in proceedings or supplements.

Disclosure

Authors have no conflict of interests, and the work was not supported or funded by any drug company.