Nosocomial Infections: Epidemiology, Pathogenesis, and Emerging Strategies for Prevention and Management

Abstract

Nosocomial infection, which are also called healthcare- associated infections (HAIs), are a big problem for public health around the word. They lead to illness that is more serious, more deaths, longer hospital visits, and higher cost for medical care. Even with better medical tools and efforts to stop infection, healthcare-associated infection are still common in places with lots of resources and place with fewer resources. The main reasons include the heavy use of invasive devices, increasing resistance to antibiotics, more people with weakened immune system, and poor practices in preventing infections. This review gives an overview of the latest information about how healthcare-associated infections spread, the getting them, how they are diagnosed, and how they are treated. Intensive care units are especially impacted, with infection rates between 3 to 6 percent in high-income countries and much higher in low- and middle-income countries. Some bacteria and fungi that are hard to treat with many drugs, like carbapenem-resistant Enterobacterales, MRSA, VRE, and new types of fungi such as Candida auris, make it harder to cure infections and lead to worse health results. Major risk factor are having a catheter for a long time, using a ventilator, being older, having a weak immune system, and not following infection control rules properly. Good management depends on starting antibiotic treatment quickly based on real evidence, then narrowing it down to the right choice later and taking care of the source of the infection early on. It is very important to improve infection control, the responsible use of antibiotics, and quick testing methods to lower the worldwide impact of hospital-acquired infection.

Keywords

Nosocomial infections; Healthcare-associated infections (HAIs); Antimicrobial resistance (AMR); Multidrug-resistant organisms (MDRO); Intensive care unit (ICU); Antimicrobial stewardship

Introduction

Nosocomial infections, also known as healthcare-associated infections (HAIs), are infections that patients contract while receiving care in healthcare settings, such as hospitals, long-term care facilities, outpatient clinics, and other clinical settings, but which were neither present nor incubating at the time of initial admission. The definitions and surveillance criteria used by major public health agencies (e.g., WHO, CDC, NHSN) are intended to distinguish between community-acquired infections and those attributable to healthcare exposure. In practice, many surveillance systems define a HAI as an infection that manifests 48 hours or more after hospital admission, or that occurs within a specified window after a healthcare procedure or discharge.⁽¹⁾

Clinical forms and common pathways

Surgical site infections (SSIs), catheter-associated urinary tract infections (CAUTI), central line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP), and Clostridium difficile infection are among the most commonly monitored clinical syndromes that are included in HAIs. Numerous healthcare-associated infections (HAIs) are linked to equipment or procedures and occur when intrusive technologies compromise the host's natural defences or when environmental controls and aseptic technique are insufficient. Cross-transmission (healthcare worker hands, contaminated surfaces), endogenous flora (overgrowth following antibiotic exposure), and contaminated fluids or devices are examples of transmission mechanisms. ⁽²⁾

Global burden and epidemiology

HAIs are a significant worldwide public health issue with significant clinical and financial repercussions. According to surveillance and systematic studies, incidence and prevalence differ significantly by geography and healthcare context. Pooled estimates from many low- and middle-income countries are several times higher, reflecting differences in infection-prevention resources, overcrowding, infrastructure, and surveillance capacity. In contrast, point-prevalence surveys from high-income countries have estimated HAI prevalence in acute-care hospitals at roughly 3–4% of inpatients on a given day. Both the scope of the issue and the greater relative burden carried by settings with fewer resources are highlighted by the World Health Organization's global assessment (2011) and subsequent meta-analyses. ⁽²⁾

Clinical and economic significance

HAIs significantly boost direct and indirect healthcare expenses, lengthen hospital stays, and increase patient morbidity and death. Additionally, they have a significant role in the usage of antibiotics and, as a result, in antimicrobial resistance (AMR). The relationship between HAIs and the AMR epidemic has been highlighted by modelling studies and burden assessments that have documented significant numbers of deaths and disability-adjusted life years (DALYs) owing to illnesses caused by antibiotic-resistant organisms in Europe and worldwide. Beyond death, HAIs compromise patient safety, impose a burden on hospital capacity, and can result in expensive outbreak interventions and damage to an institution's image. ⁽³⁾

Trends and changing context

The risk and patterns of HAIs have changed significantly during the past ten years. Despite significant advancements in focused preventive initiatives, the risk of HAI has persisted due to increased use of invasive equipment and complicated procedures, an ageing population with more comorbidities, increased ICU utilisation, and changing microbial ecology, including the expansion of multidrug-resistant species. The COVID-19 pandemic significantly changed the epidemiology of healthcare-associated infections (HAIs) in a variety of contexts. Increased use of antibiotics, shifting patient mixes, staffing shortages, and changes in infection-control priorities all contributed to increases in various HAI rates and in resistant organisms in many studies. Worldwide estimates at the same time point to ongoing regional differences and, according to certain research, an increasing worldwide prevalence signal. ⁽⁴⁾

Types of Nosocomial (Healthcare-Associated) Infections

1. Central line-associated bloodstream infection (CLABSI)

Definition: A CLABSI is a primary bloodstream infection that occurs in a patient who had a central venous catheter (central line) in place at the time of the infection or within 48 hours prior to the infection's onset and for which there is no other known cause. CDC/NHSN (NHSN Patient Safety Component Manual) provides case-classification and surveillance definitions. ⁽⁵⁾

Epidemiology & impact. Because CLABSIs are linked to substantial morbidity, death, and costs (estimates of cost per case vary greatly by location), they are considered high-impact HAIs. Although rates are still higher in certain low-resource settings, CLABSI rates vary by hospital type, ward (ICU vs. non-ICU), and have declined in many high-income settings following bundle-based preventative initiatives. ⁽⁶⁾

Common pathogens Typical CLABSI infections include Gram-positive organisms (particularly coagulase-negative staphylococci and Staphylococcus aureus), Gram-negative bacilli (such as Enterobacterales, Pseudomonas), and Candida spp.; the proportional contribution varies depending on patient demographics, region, and device care practices. ⁽⁶⁾

Risk factors. The risk of CLABSI is increased by prolonged central line dwell time, multiluminal/epicatheters, placement resulting from non-sterile settings, aseptic technique violations during insertion or maintenance, immunosuppression, and a lack of standard insertion/maintenance protocols. ⁽⁵⁾

2. Catheter-associated urinary tract infection (CAUTI)

Definition CAUTI is defined as a urinary tract infection that occurs in a patient who had an indwelling urinary catheter in place for more than two calendar days on the date of the event, and the catheter either was in place or removed on the day of the event. The CDC/NHSN surveillance criteria include specific signs and symptoms as well as microbiologic thresholds. ⁽⁷⁾

Epidemiology & impact. Among the most prevalent HAIs are CAUTIs, particularly in long-term care and hospitalised populations. The length of an indwelling catheter increases the daily risk of bacteriuria; CAUTIs are linked to higher antibiotic use, potential subsequent bloodstream infections, longer hospitalisations, and higher expenses. Rates are closely linked to the facility's catheter-use practices and catheter prevalence. ⁽⁸⁾

Common pathogens. Escherichia coli and other Enterobacterales, Enterococcus species, Pseudomonas aeruginosa, Proteus species, and Candida species are examples of common pathogens. Antibiotic recalcitrance and persistence are influenced by biofilm growth on catheter surfaces. ⁽⁸⁾

Risk factors. Risk factors include prolonged catheterisation, indwelling time, gaps in closed drainage systems, female sex, urine retention, comorbidities (such diabetes), improper catheter insertion technique, and a lack of catheter-removal protocols. ⁽⁷⁾

3. Ventilator-associated pneumonia (VAP) / Hospital-acquired pneumonia (HAP) related to ventilation

Definition. Pneumonia that develops more than 48 hours after endotracheal intubation is known as ventilator-associated pneumonia, or VAP. Hospital-acquired pneumonia (HAP) is defined as pneumonia that does not incubate at admission and develops ≥48 hours after admission; recommendations (such as IDSA/ATS) treat HAP and VAP differently. Definitions of surveillance integrate laboratory, clinical, and radiographic standards. ⁽⁹⁾

Epidemiology & impact. One of the most common and dangerous infections acquired in the intensive care unit, ventilator-associated pneumonia (VAP) is linked to higher ventilator days, ICU stays, and death (although estimated attributable mortality differs). ICU patient mix, sedation and movement techniques, ventilator-bundle adherence, and local pathogen prevalence all have an impact on VAP incidence. ⁽⁹⁾

Common pathogens While multidrug-resistant organisms (Pseudomonas, Acinetobacter, MRSA, resistant Enterobacterales) are frequently involved in late-onset VAP and VAP in patients who have previously been exposed to antibiotics, early-onset VAP frequently involves community-type organisms (e.g., Streptococcus pneumoniae, susceptible Enterobacterales). ⁽⁹⁾

Risk factors. Prolonged mechanical breathing, supine positioning, poor oral hygiene, aspiration risk, previous antibiotic exposure, high illness severity, and absence of ventilator care bundles increase the risk of ventilator-associated pneumonia (VAP). ⁽⁹⁾

4. Surgical site infection (SSI)

Definition Surgical site infections include those in the incision or in deep tissue, organs, or spaces after an operative procedure. Infections must occur within 30 days after the operative procedure (or within 90 days if an implanted device was used). SSIs are classified as superficial incisional, deep incisional, or organ/space infections. ⁽¹⁰⁾

 

Epidemiology & impact. A significant amount of surgical morbidity and readmissions globally are caused by SSIs, which are frequent postoperative consequences. Procedure type, wound class, patient comorbidities, and perioperative management all affect incidence; worldwide pooled data indicate that SSI rates are greater in LMICs than in high-income settings. SSIs can increase surgical mortality, extend hospital stays, and raise healthcare expenses. ⁽¹¹⁾

Common pathogens Common SSI infections include Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, Enterobacterales, and anaerobes; the combination varies depending on the surgical location and degree of contamination. ⁽¹⁰⁾

Risk factors. SSI risk is influenced by system variables (operating room sterility, preoperative hair removal, scheduling of antibiotic prophylaxis), procedure-related factors (prolonged surgery, implant usage, emergency surgery), and patient-level factors (diabetes, smoking, obesity, malnutrition). ⁽¹⁰⁾

Nosocomial pathogens

1. Bacteria parasites

• Enterococcus faecalis / Enterococcus faecium- Vancomycin-resistant enterococci (VRE) are a major source of wound infections, bloodstream infections, and catheter-associated urinary tract infections (CAUTI) in hospitals. ⁽¹²⁾
• Klebsiella pneumonia- common sources of bloodstream and urinary tract infections, ventilator-associated pneumonia (VAP), and carbapenem-resistant and ESBL-producing strains are significant nosocomial risks. ⁽¹³⁾
• Escherichia coli- prevalent cause of intra-abdominal sepsis and catheter-associated UTIs in hospitals; both drug-sensitive and multidrug-resistant strains can be found in HAI settings. ⁽¹⁴⁾
• Pseudomonas aeruginosa- known for its inherent resilience and capacity to endure in hospital water and ventilation systems; linked to VAP, bloodstream infections, urine infections, and wound infections. ⁽¹²⁾
• Clostridioides (Clostridium) difficile- major cause of pseudomembranous colitis and infectious diarrhoea linked to healthcare; closely linked to previous antibiotic exposure and hospital visits. ⁽¹⁵⁾

2. Viruses’ parasites

• SARS-CoV-2 (hospital-acquired COVID-19)- respiratory transmission in wards or rooms; linked to patient and healthcare worker outbreaks and higher death rates in certain cohorts. ⁽¹⁶⁾
• Influenza A and B- significant source of respiratory infections acquired in hospitals (including ward and long-term care outbreaks), particularly during peak seasons. ⁽¹⁷⁾
• Rhinovirus / Enteroviruses- associated with clusters of hospital-acquired respiratory or feverish illnesses, especially in paediatric settings. ⁽¹⁷⁾
• Rotavirus- causes nosocomial diarrhoea in paediatric wards (more common in the pre-vaccine period; remains important in populations not immunised). ⁽¹⁸⁾
• Hepatitis B virus (HBV)- Transfusions, dialysis, contaminated equipment, and dangerous injections are among known ways that healthcare-associated transmission can occur. ⁽¹⁹⁾
• Hepatitis C virus (HCV)- Unsafe injection, transfusion, and dialysis procedures, as well as outbreaks in medical facilities, are associated with nosocomial transmission. ⁽¹⁹⁾
• Human immunodeficiency virus (HIV)- uncommon as a hospital-acquired infection, but it has been linked to industrial exposures, tainted blood supplies, and infection control violations. ⁽²⁰⁾

3. Fungal parasites

• Candida spp. (especially C. albicans, C. parapsilosis, C. tropicalis, C. glabrata)- Intra-abdominal infections, device-related infections, and catheter-associated bloodstream infections (candidemia) are frequently caused in intensive care units and surgical wards. There is a substantial correlation between C. parapsilosis and healthcare professionals' hands and indwelling lines.  ⁽²¹⁾
• Candida auris- An major global infection-control concern is a developing, frequently multidrug-resistant yeast that easily colonises skin and surfaces and causes protracted hospital epidemics. ⁽²²⁾
• Aspergillus spp. (especially A. fumigatus)- causes invasive pulmonary aspergillosis in individuals with impaired immune systems; nosocomial clusters frequently accompany sources of polluted air or dust or building or remodelling. ⁽²³⁾
• Fusarium spp. and other opportunistic moulds (e.g., Scedosporium, Lomentospora)- cause invasive diseases (skin, bloodstream, lung) in patients who are neutropenic or severely immunocompromised; tainted solutions, flowers, or gadgets have occasionally been linked to hospital epidemics. ⁽²⁴⁾
• Cryptococcus spp. (primarily C. neoformans)- Community-acquired in HIV or immunocompromised hosts is the norm, however uncommon reports of hospital-acquired/cluster cases and device-associated presentations have been made, particularly in transplant units and extended hospital stays. ⁽²⁵⁾

Epidemiology of Nosocomial (Healthcare-Associated) Infections

Overview: prevalence versus incidence

Both incidence (new infections per patient-time or per operation) and prevalence (point prevalence surveys, PPS) metrics are used in epidemiologic descriptions of HAIs. While incidence data are required to estimate risk over time and to compute attributable outcomes (e.g., increased length of stay, mortality), prevalence surveys offer a snapshot of how many inpatients have ≥1 HAI on a particular day and are valuable for international comparisons and trend tracking. For modern HAI epidemiology, large multi-center PPSs and national surveillance networks continue to be the key sources. ⁽²⁾

Global burden and pooled estimates

It is difficult to quantify a single "global" prevalence since healthcare environments, monitoring standards, and study methodologies differ greatly. However, systematic reviews and meta-analyses offer unambiguous evidence of significant regional variations and helpful pooled estimates. A 2023 systematic review and meta-analysis of nosocomial infection studies revealed significant regional variation, with comparatively low reported prevalences in Western Europe and parts of North America and significantly higher reported prevalences in several studies from Asia, Latin America, and Africa (study-level estimates in some settings reported prevalences many times higher than high-income settings). The hidden yet significant burden of HAIs in low- and middle-income countries was also emphasised in previous WHO-sponsored syntheses. When combined, the data show a global prevalence spectrum that ranges from about 3% to 6% in various high-income settings to significantly higher and far more variable rates in many LMIC studies (sometimes reported as double-digit percentages in smaller or resource-constrained institutions). ⁽⁴⁾

High-income regions

According to multi-state point-prevalence surveys conducted in the United States, around 3.2% of inpatients experienced at least one HAI on the day of the survey (Multistate PPS, 2014 with follow-up in 2018 indicating generally comparable findings). This data serves as a baseline for temporal monitoring and national burden assessment. Pooled hospital prevalence estimates in Europe were reported by ECDC-coordinated PPSs to be in the ~5–6% range (country ranges typically 2.9%–10.0percentage across EU/EEA countries in the 2016–2017 survey), with significant inter-country variation and higher prevalence in certain countries and high-risk settings (e.g., ICUs). These surveys demonstrate that HAIs are still prevalent and vary by nation, ward type, and technique even in well-resourced institutions. ⁽²⁶⁾

Low- and middle-income countries (LMICs)

The burden and variability of HAIs are consistently higher in LMICs, according to systematic research and WHO evaluations. The pooled prevalence or incidence in many LMIC studies is significantly greater than in high-income settings, according to the classic Lancet systematic review (endorsed by the WHO) and more subsequent meta-analyses. Insufficient infection-prevention resources (personnel, water/sanitation, and supplies), overcrowding, insufficient antimicrobial stewardship, and gaps in routine monitoring that can both underreport and underdetect outbreaks are contributing reasons. These results are supported by other regional systematic studies conducted in Africa, South Asia, and Latin America, which show a wide range of HAI incidence in healthcare institutions as well as frequent reports of surgical-site infections and device-associated illnesses. ⁽²⁷⁾

ICU and device-associated infections

The incidence of HAIs per patient-day is significantly greater in high-risk settings like intensive care units (ICUs) than in ordinary wards. Ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLABSI), and catheter-associated urinary tract infection (CAUTI) are device-associated infections that continue to be major global contributors to the incidence of healthcare-associated infections (HAIs) in intensive care units (ICUs) and are responsible for a disproportionate amount of morbidity, mortality, and antibiotic exposure. ICU incidence and prevalence are important factors influencing hospital HAI burden, according to a number of national monitoring systems and PPSs. ⁽²⁸⁾

Antimicrobial resistance (AMR) and HAI epidemiology

The large and increasing percentage of infections brought on by microbes resistant to antibiotics is an important epidemiologic aspect of HAIs. Studies using burden-of-disease modelling have connected AMR to millions of deaths and many DALYs worldwide; these models indicate that sub-Saharan Africa and South Asia have especially significant burdens. Multidrug-resistant Gram-negative bacilli, MRSA, and resistant Enterobacterales are common HAI infections in healthcare settings that complicate treatment, raise mortality, and extend hospital stays. Therefore, HAI and AMR epidemiology are treated as related issues in surveillance and modelling studies. ⁽²⁹⁾

Temporal trends and the effect of the COVID-19 pandemic

Longer-term trends show mixed progress: new technology, more sophisticated treatment, and more ICU capacity have perpetuated risk, although some high-income systems observed consistent drops in particular HAI types (e.g., CLABSI reductions following bundle installation). The COVID-19 pandemic disrupted standard infection-prevention practices (staffing shortages, overcrowded intensive care units, changes in patient mix and device use), and various analyses report varying effects. Several studies and meta-analyses found that during pandemic surges in many hospitals, CLABSIs and some device-associated infections increased, while trends for other HAIs varied by setting. Overall, the pandemic brought to light the brittleness of preventative gains and the necessity of robust surveillance and IPC (infection prevention and control) systems. ⁽³⁰⁾

Regional summary

• Europe (EU/EEA): According to ECDC PPSs (2016–2017; 2022–2023 surveillance updates), pooled hospital prevalence typically varies from ~2.9% to ~10%, with greater incidence in some long-term and acute-care facilities. ⁽²⁸⁾
• North America (USA): In extensive surveys, multistate PPS data show a frequency of around 3% in acute care hospitals; national surveillance also shows a significant burden in intensive care units and device-associated infections. ⁽²⁶⁾
• Asia, Africa, and Latin America: Pooled LMIC estimates are consistently higher than similar high-income pooled estimates; systematic reviews and numerous PPS reports reveal significantly higher and more varied prevalence, with some facility-level studies indicating prevalence in double digits. ⁽²⁷⁾

Interpretation and limitations of the data

Heterogeneity in case definitions, sampling frames, diagnostic capabilities, and research design (surveys vs. continuous monitoring) restricts cross-study comparisons. Pooled meta-analytic statistics must be viewed with caution since small hospital studies in LMICs may reveal relatively high incidence due to epidemic settings or inadequate resources. However, the persistent pattern across decades and approaches is that AMR exacerbates the clinical and public health effect of HAIs, which are widespread worldwide, have a higher absolute burden, and frequently result in worse outcomes in settings with limited resources. Epidemiologic goals include combating AMR, investing in IPC systems, and enhancing standardised surveillance.⁽¹⁾

Risk Factors for Nosocomial (Healthcare-Associated) Infections

1. Host / Patient-related Risk Factors-

• Reduced immune response and higher sensitivity due to advanced age (elderly) or extreme age (neonates). ⁽²⁰⁾
• Underlying comorbidities, such as immunosuppression, diabetes mellitus, chronic lung or renal illness, and cancer. ⁽²⁰⁾
• Low functional status, poor nutritional status, or malnutrition. ⁽³¹⁾
• Higher risk due to the severity of the disease and critical care status (e.g., ICU hospitalisation). ⁽³²⁾
• In certain instances, blood transfusions have been linked to immunological modulation risk in paediatric populations. ⁽³¹⁾

 

2. Hospital / Environment / Care?related Risk Factors

• Prolonged hospital stays and frequent ward transfers result in increased exposure to nosocomial infections. ⁽³³⁾
• High device use and admission to high-risk environments (such as ventilator wards and intensive care units). ⁽³²⁾
• Use of invasive devices / procedures:

• Multiple lumens and central venous catheters (CVCs)
• Urinary catheters that are implanted
• Mechanical ventilation and endotracheal tubes
• Tracheostomy
• Prosthetic implants and drains ⁽²⁰⁾

• Surgical variables include infected wounds, recent surgery, emergency surgery, extended surgical duration, and prosthetic implants. ⁽²⁰⁾
• Inadequate hand hygiene, poor equipment and room cleaning, colonised personnel, or contaminated gadgets are examples of poor adherence to infection prevention methods. ⁽³⁴⁾
• The high frequency of multidrug-resistant organisms in hospital settings and the inappropriate use of antimicrobial drugs, which results in resistant organisms. ⁽³⁵⁾
• The danger of exposure is increased by intrahospital patient transfers, or travelling between wards. ⁽³³⁾

3. Procedure / Device Specific Risk Factors

• The length of time the device is used (longer indwelling duration = higher risk). ⁽²⁰⁾
• The quantity of device manipulations (such as catheter hub entries). ⁽³⁶⁾
• Mechanical ventilation variables include re-intubation, sedation, supine posture, and poor oral hygiene. ⁽²⁰⁾
• Urinary catheterisation: extended usage, inadequate insertion and upkeep methods. ⁽³⁶⁾

4. Specific Populations / Contextual Risk Factors

• Children and newborns: identical risk factors plus transfusions, gadgets, and malnutrition. ⁽³¹⁾
• Patients undergoing neurosurgical or critical surgery, such as those following a craniotomy, have been proven to be at higher risk due to ICU hospitalisation, hypertension, and antibiotic exposure. ⁽³²⁾

Transmission routes in healthcare settings

1. Contact transmission (direct & indirect) — the most important route for many HAIs.

• Direct: individual-to-individual (e.g., staff members' infected hands touching patient wounds).
• Indirect: through-contaminated surfaces or intermediary items (such as infusion pumps, bed rails, and stethoscopes). On fomites, several infections endure long enough to spread. Hand hygiene and contact precautions focus on this path. ⁽³⁷⁾

2. Droplet transmission —Large respiratory droplets from a cough or sneeze that land on mucous membranes in the mouth, nose, and eyes after travelling a short distance (often less than one to two meters). Masks and patient location lower risk; influenza and some respiratory infections in hospital epidemics are two examples. ⁽³⁸⁾
3. Airborne transmission- tiny aerosols that may travel longer and stay suspended, such as varicella, measles, and TB. Airborne precautions and suitable ventilation/filtration are necessary because some operations (such as suctioning, bronchoscopy, and aerosol-generating procedures) can produce aerosols and raise the risk of airborne illness. ⁽³⁸⁾
4. Common-vehicle transmission — when numerous patients are infected by a single contaminated source (such as tainted food, water, drugs, or intravenous fluids), outbreak investigation and source management are necessary. ⁽¹⁴⁾
5. Vectorborne transmission — Insects are uncommon in the majority of acute care facilities, but they can occur in certain and are mostly avoidable through environmental management. ⁽¹⁴⁾

Key Diagnostic Components & Approaches

1. Defining infection onset/context
   • Differentiating between an infection acquired in the community and one linked to healthcare is an important first step. For instance, in acute care settings, an infection that develops more than 48 hours after hospital admission is frequently classified as HAI. ⁽³⁹⁾
   • The establishment of certain criteria (e.g., procedure type, device use, ward/ICU exposure) aids identifying probable HAIs. ⁽²⁰⁾
2. Clinical evaluation
   • Identify symptoms that are indicative of an infection, such as fever, elevated white-cell count, local indications of inflammation (such as wound redness for SSI), problems at the catheter site, new respiratory symptoms in ventilated patients, etc. ⁽²⁰⁾
   • Check for infections connected to devices (such as ventilators, urine catheters, and central lines) by evaluating the insertion site, maintenance problems, length of use, and potential contamination pathways. ⁽²⁰⁾
3. Microbiological and laboratory diagnostics
   • Blood cultures, urine cultures, wound swabs, catheter tip cultures, and respiratory secretions are examples of culture-based techniques that are still fundamental. ⁽³⁹⁾
   • Acknowledge the limits of conventional cultures: they are comparatively slower and may overlook infections that are fastidious or encased in biofilms. ⁽³⁹⁾
   • Advanced diagnostics: next-generation sequencing (NGS) for pathogen identification and resistance gene detection, mass spectrometry (e.g., MALDI-TOF), and molecular tests (PCR). ⁽⁴⁰⁾
   • As an illustration, a recent study discussed how microbiological data combined with artificial intelligence (AI) and machine learning is becoming a diagnostic assistance tool. ⁽⁴⁰⁾
4. Syndrome-specific diagnostic approach

• Bloodstream infections / CLABSI

Gold standard: blood cultures (where a line infection is suspected, paired peripheral + line cultures). For CLABSI surveillance, NHSN/CDC offer specific criteria (organism recovery + time, exclusion restrictions). Applying MALDI-TOF and rapid molecular panels to positive blood cultures improves early treatment and reduces ID time. In some situations, remove or culture the catheter tips. ⁽⁴¹⁾

• Catheter-associated urinary tract infection (CAUTI)

A substantial quantitative urine culture from a correctly obtained specimen is used in conjunction with symptoms (fever, suprapubic discomfort, urgency) to make the diagnosis.⁽⁴²⁾

• Ventilator-associated / hospital-acquired pneumonia (VAP/HAP)

In addition to microbiology from lower respiratory samples (endotracheal aspirate, BAL), the diagnosis is clinical (new/progressive infiltration on chest imaging + new purulent discharges or oxygenation deterioration). Molecular PCR panels can identify viral or bacterial causes more quickly, but they need to be interpreted carefully (colonisation vs. infection), according to NHSN surveillance regulations. ⁽⁴³⁾

• Surgical-site infection (SSI)

Clinical indicators (redness, swelling, purulent drainage) during specified post-operative periods, together with wound culture if drainage is present. ⁽⁴⁴⁾

Treatment of nosocomial infection

1. General Principles of Treating Nosocomial Infections

Recent evaluations emphasise a bundle strategy for all HAIs, including early source management, quick suitable empiric treatment, prompt diagnosis, and antibiotic stewardship, particularly given the rise in MDR Gram-negative infections. ⁽⁴⁵⁾

• Assess severity & risk of MDR pathogens

Take into account recent broad-spectrum antibiotic use, ICU stays, mechanical ventilation, indwelling devices, previous colonisation or infection with MDR organisms, and local resistance data (unit-specific antibiogram). ⁽⁴⁶⁾

• Start empiric therapy promptly, then de-escalate

Start wide empirical coverage for septic or critically sick patients based on the local antibiogram; once culture results and clinical response are known, narrow or cease. MDR-focused evaluations consistently show that although needless broad treatment causes resistance, delaying active therapy harms results. ⁽⁴⁶⁾

• Use short, evidence-based durations

According to more recent evaluations on MDR Gram-negative infections, where there is effective source control and clinical response, many HAP/VAP, complex UTIs, and intra-abdominal infections should be treated within 7 days. ⁽⁴⁷⁾

• Source control

Almost all contemporary HAI evaluations emphasise the need to remove or replace infected catheters, drain abscesses, debride infected surgical sites, and optimise device management (CAUTI, CLABSI, and SSI). ⁽⁴⁸⁾

• Combine with infection prevention & stewardship

2025 MDRO-HAI assessments emphasise that in order to prevent recurrence and the establishment of resistance, proper treatment must be combined with antimicrobial stewardship initiatives and infection prevention bundles. ⁽⁴⁵⁾

2. Syndrome-Specific Treatment

1. Hospital-Acquired & Ventilator-Associated Pneumonia (HAP/VAP)

5. Empiric therapy

• Cover S. aureus (MRSA risk?), Pseudomonas, and other Gram-negative bacteria.

• No major MDR risk factors / low local resistance:

• MRSA coverage with anti-pseudomonal β-lactam (such as piperacillin-tazobactam, cefepime, and meropenem).

• High MDR risk or high local resistance:

• For suspected MDR Gram-negatives, take into account newer drugs (such as ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, and cefiderocol) depending on patient characteristics and local susceptibility. ⁽⁴⁶⁾

5. De-escalation

• If the cultures are negative, reduce the coverage of MRSA to just the highest active agent.
• When an absorbable oral medication is available and the patient is clinically stable, switch to oral treatment.

5. Duration

• If the patient recovers and there is sufficient source control (e.g., secretions clearing, afebrile, increasing oxygenation), the majority of current guidelines allow 5–7 days for HAP/VAP.

2. Catheter-Associated Urinary Tract Infection (CAUTI)

1. Remove or replace the catheter

If a Foley is still required, replace it prior to urine culture collection; if not, remove it entirely. This lowers recurrence and increases cure rates. ⁽⁸⁾

2. Distinguish asymptomatic bacteriuria from CAUTI

To prevent needless antibiotic exposure, treat only symptomatic individuals (fever, suprapubic discomfort, flank pain, delirium with no apparent explanation, haemodynamic instability), particularly in older persons. ⁽⁸⁾

3. Empiric antibiotics

• Base on local resistance pattern; options include:

• Ceftriaxone, piperacillin-tazobactam, or fluoroquinolone (if local resistance is minimal) are recommended for stable patients with low MDR risk.
• If ESBL/CRE or other MDR infections are common, consider carbapenem or newer β-lactam/β-lactamase inhibitor combos for high MDR risk/ICU patients. ⁽⁸⁾

4. Duration

• For simple CAUTI with quick catheter removal, it usually takes 5–7 days; if there is a sluggish clinical response or bacteremia, it may take up to 10–14 days. ⁽⁸⁾

3. Central Line–Associated Bloodstream Infection (CLABSI) / Catheter-Related BSI

1. Immediate management

• In high-risk situations, start comprehensive IV empiric treatment for sepsis, which usually consists of broad anti-pseudomonal β-lactam ± MRSA coverage (vancomycin/linezolid) ± antifungals.
• Prior to beginning antibiotics, take peripheral and line blood cultures.

2. Catheter management

• Remove the catheter if:

• Haemodynamic instability or severe sepsis
• Pseudomonas, mycobacterial, fungal, or S. aureus BSI

• Only low-risk organisms should be considered for catheter salvage, and if vascular access is restricted, systemic antibiotics + antibiotic lock treatment should be used.

3. Targeted therapy & duration

• Adapt according to the organism, susceptibility, and existence of metastatic infection:

• For simple Gram-negative BSI after catheter removal, effective IV/IV-to-oral treatment is often administered for seven days. ⁽⁴⁷⁾
• S. aureus BSI: typically at least 14 days; if endocarditis or deep infection is present, 4-6 weeks (mostly based on long-standing data but nonetheless current practice).
• Candida BSI: remove the catheter and provide echinocandin or fluconazole (if susceptible) for at least 14 days following the last positive culture and symptom remission.

4. Surgical Site Infections (SSI)

1. Superficial SSI (skin/subcutaneous)

• Perform local wound care, drain pus, and open the incision.
• Systemic antibiotics should only be used if systemic symptoms or surrounding cellulitis are present.
• If necessary, use narrow-spectrum anti-staphylococcal medications (such as cefazolin, cloxacillin, or vancomycin/linezolid when MRSA risk is high).

2. Deep/organ-space SSI

• Surgical source management, which includes debridement, drainage, and re-exploration, is essential.
• For abdominal surgery, enteric Gram-negative bacteria and anaerobes, or pathogens common to the process, should be covered with empirical antibiotics.
• According to recent research on antibiotic duration for intra-abdominal and deep infections, the duration is usually 4–7 days following sufficient source management.⁽⁴⁷⁾

Management of MDR & XDR Pathogens in Nosocomial Infections

1. General MDR principles

• When available, use fast diagnostics (PCR panels, MALDI-TOF, carbapenemase detection) to optimise treatment early. ⁽⁴⁶⁾
• Whenever feasible, use new medicines or β-lactam/β-lactamase inhibitor combos over polymyxins, as recent research indicates better results and lower toxicity. ⁽⁴⁶⁾
• If source control is sufficient and clinical response is satisfactory, use short, customised periods (typically ~7 days). ⁽⁴⁷⁾

2. Examples of agent selection

• ESBL-producing Enterobacterales

• For serious infections, carbapenems (such meropenem) continue to be the gold standard.
• If the isolate is susceptible and local statistics support it, piperacillin-tazobactam may be utilised for some low-risk, non-severe infections.
• In certain areas, newer cefepime/zidebactam or other developing drugs are being researched or used in early stages.

• Carbapenem-resistant Enterobacterales (CRE)

• Depending on the kind and susceptibility of carbapenemase, cefiderocol, imipenem–relebactam, meropenem–vaborbactam, or ceftazidime–avibactam. ⁽⁴⁶⁾

• MDR Pseudomonas aeruginosa

• There is still a dearth of high-quality data; regimens frequently use sulbactam-based therapy (such as high-dose ampicillin/sulbactam or sulbactam–durlobactam when available) +/- additional drugs; polymyxin B is still used as salvage but with close toxicity monitoring. ⁽⁴⁶⁾

• MRSA and VRE

• MRSA: Depending on the infection location and susceptibility, linezolid, daptomycin, and ceftaroline are utilised; vancomycin is still the norm.
• VRE: daptomycin or linezolid (typically high-dose for severe infections).

Recent advances & research trends in preventing and treating nosocomial (healthcare-associated) infections

1. Artificial intelligence (AI) & data-driven surveillance

       AI models (deep learning, machine learning) are being used to prioritise infection-prevention measures (hand hygiene compliance, device removal reminders), automate HAI surveillance, forecast individual patient risk, and identify outbreaks earlier. Research indicates that when AI is linked with EHRs and IPC processes, it can lessen human labour and perhaps reduce the incidence of local HAIs. ⁽⁴⁹⁾

Practical uses & examples

• Automated EHR-based surveillance that detects possible VAP, CAUTI, or CLABSI before manual review. ⁽⁵⁰⁾
• Early-warning systems that forecast deterioration/infection risk and initiate preventive review by combining vital signs, test results, and device data. ⁽⁵¹⁾

Limitations & next steps

• Prospective trials and transparent/validated methods are required; model generalisability, data quality, physician trust, and interaction with IPC procedures continue to be obstacles. ⁽⁵²⁾

2. Phage therapy (bacteriophages) for MDR nosocomial pathogens

What is new include early trials aimed at MDR Gram-negatives and challenging device-associated infections (Pseudomonas, Klebsiella, Acinetobacter, Enterococcus), as well as more compassionate-use cases and revived clinical interest. Many patients have shown clinical benefits, according to recent systematic reviews; nonetheless, the evidence is inconsistent and the data from controlled trials is still few. ⁽⁵³⁾

Practical uses & examples

• Inhaled/instilled phages or IV usage for severe pulmonary or bloodstream infections in compassionate use or early-phase studies; topical/locoregional phage formulations for infections related to wounds and devices. ⁽⁵⁴⁾

Challenges

• Limited host range (requires phage screening or cocktails), possible immunological neutralisation, bacterial resistance to phages, problems with biofilm delivery, and obstacles related to regulation and standardisation. Manufacturing/regulatory frameworks and larger, controlled RCTs are still needed. ⁽⁵⁵⁾

 

3. Nanotechnology & antimicrobial nanomaterials/surfaces

       New developments include the development of engineered nano-coatings and nanomaterials (such as silver, copper, metal oxides, photodynamic nanoparticles, and nanostructured surfaces) for high-touch surfaces, medical device coatings, and wound dressings that can inactivate viruses, disrupt membranes, and reduce microbial adhesion. Reviews highlight environmental applications, prototype device coatings, and encouraging in-lab antimicrobial and anti-biofilm effects. ⁽⁵⁶⁾

Practical uses & examples

• Coatings based on copper or silver for high-touch surfaces, endotracheal tubes, and catheters; nanostructured surfaces intended to physically rip bacterial membranes or lessen adhesion. ⁽⁵⁷⁾

Challenges & safety

• Long-term biocompatibility, environmental/toxicity assessment, and proof of decreased clinical HAI rates (not simply in vitro kill) are necessary to translate lab effectiveness into robust, secure, and regulatory-approved clinical devices. Ecological effects and resistance should be tracked. ⁽⁵⁸⁾

4. Rapid diagnostics & point-of-care pathogen/resistance testing

        What is new: next-generation sequencing (NGS) techniques, MALDI-TOF, quick phenotypic AST platforms, and rapid molecular syndromic panels are reducing the time to resistance discovery and diagnosis. Rapid testing have been linked to lower mortality and improved antibiotic optimisation in bloodstream infections when used in conjunction with antimicrobial-stewardship programs (ASP). For respiratory and bloodstream diseases, new quick phenotypic susceptibility tests (hours) and multiplex panels are becoming more popular. ⁽⁵⁹⁾

Practical uses & examples

• Multiplex PCR panels for respiratory and bloodstream infections; MALDI-TOF + rapid resistance indicators for quicker organism identification; and point-of-care AST to direct early targeted therapy (e.g., rapid UTI AST) ⁽⁵⁹⁾

Limitations

• Cost, the possibility of panel-restricted false negatives, the necessity for stewardship integration to convert quicker results into better outcomes, and the difficulties of adoption in settings with limited resources. ⁽⁶⁰⁾

Challenges & Future Directions for Nosocomial (Healthcare-Associated) Infections

Major current challenges

1. Rising antimicrobial resistance (AMR) and limited new antibiotics

       AMR is making HAIs more severe and expensive (more treatment failures, longer hospital stays, greater mortality). Global assessments indicate significant and increasing AMR-attributable loads and predict catastrophic future mortality in the absence of intervention. ⁽⁶¹⁾

2. Diagnostic delays and limited access to rapid testing

      Targeted treatment and IPC response are delayed by the slowness of conventional cultures, which may overlook biofilm-embedded or picky organisms. Additionally, the absence of quick point-of-care AST and molecular diagnostics (or their integration with stewardship) causes delays. The deployment of improved fast diagnostics is still inconsistent because of implementation and cost issues. ⁽⁶²⁾

3. Environmental reservoirs & complex device-associated infections

       Hardy organisms (including C. difficile, C. auris, and MDR Acinetobacter) endure in environments and biofilms on devices; outbreaks associated with tainted goods or improperly reprocessed equipment still happen. Advanced identification and focused remediation are required for these situations. ⁽⁶³⁾

4. Surveillance, data fragmentation and limited genomic capacity

       Outbreak identification and precision therapies are delayed because routine surveillance is frequently uneven and many institutions lack real-time dashboards or genetic typing capabilities to quickly map transmission. It is still a technological and governance problem to integrate lab, genomic, and EHR data. ⁽⁵⁰⁾

5. Workforce, behavioural and organisational barriers

       Adherence to bundles and protocols is decreased by understaffing, heavy workloads, insufficient IPC training, and issues with safety culture. Without consistent leadership, audit/feedback, and incentives, behavioural change at scale is challenging. ⁽⁶⁴⁾

High-priority future directions & research / implementation themes

1. Scale up rapid diagnostics + actionable stewardship

       Increased use of quick ID and rapid phenotypic AST (including multiplex panels and point-of-care testing) in conjunction with antimicrobial stewardship programs (ASP) is a proven, high-impact strategy that shortens the time to successful therapy and decreases needless broad-spectrum usage. Cost-effectiveness, implementation science, and methods for converting quicker outcomes into clinical action should be the main areas of research. ⁽⁶⁵⁾

2. Expand genomic surveillance & real-time outbreak analytics

       Precise transmission mapping and quicker, targeted outbreak control are made possible by routine access to whole-genome sequencing (WGS) or tailored sequencing for high-risk diseases; investment in lab networks and analytical processes is a top goal. ⁽⁶⁶⁾

3. Harness AI and data science for early detection & decision support

       Prioritising IPC activities, predicting high-risk patients, and automating HAI surveillance are all possible using machine-learning models based on EHR, device, and lab data. Prospective validation, clinical integration, fairness, and generalisability must all be addressed in research. ⁽⁶⁷⁾

4. Develop and rigorously test alternative therapeutics (phage, endolysins, microbiome approaches)

      Although they require high-quality RCTs, standardised manufacturing, and regulatory frameworks, bacteriophage treatment, modified phages/endolysins, and microbiome restoration techniques offer promise against MDR, biofilm-associated illnesses. ⁽⁶⁸⁾

5. Translate nanotechnology & antimicrobial surfaces into safe clinical products In vitro, surface and medical device contamination can be decreased by nanocoatings and antimicrobial compounds; however, future research must demonstrate long-term biocompatibility, environmental safety, durability, and clinical efficacy (lower HAI rates) through carefully planned studies. ⁽⁶⁹⁾
6. Strengthen IPC implementation, workforce & health systems (global equity focus)

       It is crucial to invest in basic IPC programs, supply chains (PPE, disinfectants), training, regular audits, and sustainable financing, particularly in LMICs. Scalable, affordable IPC packages should be found through policy and implementation research. ⁽⁷⁰⁾

7. Integrate One-Health approaches & AMR policy actions

Reducing AMR drivers that feed nosocomial dangers will need coordinated effort across human health, animal/agriculture, and the environment (vaccines, stewardship, and surveillance). Vaccines that stop infections that frequently cause healthcare-associated infections (HAIs) and policy studies aimed at reducing the overuse of antibiotics are among the top research objectives. ⁽⁷¹⁾

8. Build implementation science & behavioural interventions into IPC research

Studies on maintaining compliance (rather than just short-term benefits) and extensive trials of behavioural interventions (audit/feedback, incentives, workflow redesign) are required. Policymakers will be able to prioritise investments with the aid of economic research. ⁽⁶⁶⁾

CONCLUSION

One of the biggest problems in contemporary healthcare is nosocomial or healthcare-associated infections, which significantly increase morbidity, mortality, length of hospital stays, and financial burden worldwide. Because of changing pathogen resistance, greater use of invasive equipment, diverse patient populations, and ongoing gaps in infection-control policies, healthcare-associated infections (HAIs) remain despite advancements in medical technology, antimicrobial treatment, and infection-prevention frameworks.A multifaceted, system-wide strategy that incorporates strict infection-prevention and control (IPC) procedures, robust antimicrobial stewardship, quick diagnoses, environmental and device-related safety, and ongoing staff training is necessary for effective prevention. Multidrug-resistant organisms, biofilms on medical equipment, and environmental persistence of infections, highlight the necessity for coordinated monitoring, early diagnosis, and prompt response.

AI-driven surveillance, phage treatment, nanotechnology, and quick molecular diagnostics are examples of recent advancements that present potential answers but call for validation that is more extensive, implementation research, and fair access across healthcare systems. To lower avoidable infections and enhance patient safety, IPC capability must be strengthened, particularly in environments with limited resources.

In the end, lowering the burden of HAIs necessitates cooperation between administrators, researchers, legislators, and healthcare practitioners. Nosocomial infections can be considerably decreased with the constant use of evidence-based procedures and the responsible integration of developing technology, resulting in safer healthcare settings and improved patient outcomes.

REFERENCES

1. 1. Prevention I, (IPC) C. Report on the Burden of Endemic Health Care-Associated Infection Worldwide. World Health Organization [Internet]. 2011 Jan 12 [cited 2025 Nov 29]; Available from: https://www.who.int/publications/i/item/report-on-the-burden-of-endemic-health-care-associated-infection-worldwide?
   2. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate Point-Prevalence Survey of Health Care–Associated Infections. N Engl J Med [Internet]. 2014 Mar 27;370(13):1198–208. Available from: http://dx.doi.org/10.1056/nejmoa1306801
   3. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. The Lancet Infectious Diseases [Internet]. 2019 Jan;19(1):56–66. Available from: http://dx.doi.org/10.1016/s1473-3099(18)30605-4
   4. Raoofi S, Pashazadeh Kan F, Rafiei S, Hosseinipalangi Z, Noorani Mejareh Z, Khani S, et al. Global prevalence of nosocomial infection: A systematic review and meta-analysis. Kuo YH, editor. PLoS ONE [Internet]. 2023 Jan 27;18(1):e0274248. Available from: http://dx.doi.org/10.1371/journal.pone.0274248
   5. Bloodstream Infection Event (Central Line-Associated Bloodstream  Infection and Non-central Line Associated Bloodstream Infection) (2025) cdc.gov. Available at: https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf
   6. Haddadin Y, Annamaraju P, Regunath H. Central Line–Associated Blood Stream Infections. [Updated 2022 Nov 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430891/
   7. Urinary Tract Infection (Catheter-Associated Urinary Tract Infection [CAUTI] and Non-Catheter-Associated Urinary Tract Infection [UTI]) Events (2025) cdc.gov. Available at: https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf
   8. Werneburg GT. Catheter-Associated Urinary Tract Infections: Current Challenges and Future Prospects. RRU [Internet]. 2022 Apr;Volume 14:109–33. Available from: http://dx.doi.org/10.2147/rru.s273663
   9. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical Infectious Diseases [Internet]. 2016 July 14;63(5):e61–111. Available from: http://dx.doi.org/10.1093/cid/ciw353
   10. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg [Internet]. 2017 Aug 1;152(8):784. Available from: http://dx.doi.org/10.1001/jamasurg.2017.0904
   11. Gillespie BM, Harbeck E, Rattray M, Liang R, Walker R, Latimer S, et al. Worldwide incidence of surgical site infections in general surgical patients: A systematic review and meta-analysis of 488,594 patients. International Journal of Surgery [Internet]. 2021 Nov;95:106136. Available from: http://dx.doi.org/10.1016/j.ijsu.2021.106136
   12. De Oliveira DMP, Forde BM, Kidd TJ, Harris PNA, Schembri MA, Beatson SA, et al. Antimicrobial Resistance in ESKAPE Pathogens. Clin Microbiol Rev [Internet]. 2020 June 17;33(3). Available from: http://dx.doi.org/10.1128/cmr.00181-19
   13. (AMR) ARD. WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. World Health Organization [Internet]. 2024 May 17 [cited 2025 Dec 20]; Available from: https://www.who.int/publications/i/item/9789240093461
   14. Haque M, Sartelli M, McKimm J, Abu Bakar MB. Health care-associated infections – an overview. IDR [Internet]. 2018 Nov;Volume 11:2321–33. Available from: http://dx.doi.org/10.2147/idr.s177247
   15. Turner NA, Anderson DJ. Hospital Infection Control: Clostridioides difficile. Clinics in Colon and Rectal Surgery [Internet]. 2020 Feb 25;33(02):098–108. Available from: http://dx.doi.org/10.1055/s-0040-1701234
   16. Dave N, Sjöholm D, Hedberg P, Ternhag A, Granath F, Verberk JDM, et al. Nosocomial SARS-CoV-2 Infections and Mortality During Unique COVID-19 Epidemic Waves. JAMA Netw Open [Internet]. 2023 Nov 10;6(11):e2341936. Available from: http://dx.doi.org/10.1001/jamanetworkopen.2023.41936
   17. Chow EJ, Mermel LA. Hospital-Acquired Respiratory Viral Infections: Incidence, Morbidity, and Mortality in Pediatric and Adult Patients. Open Forum Infectious Diseases [Internet]. 2017 Jan 1;4(1). Available from: http://dx.doi.org/10.1093/ofid/ofx006
   18. Kambhampati A, Koopmans M, Lopman BA. Burden of norovirus in healthcare facilities and strategies for outbreak control. Journal of Hospital Infection [Internet]. 2015 Apr;89(4):296–301. Available from: http://dx.doi.org/10.1016/j.jhin.2015.01.011
   19. Singh J, Stoitsova S, Zakrzewska K, Henszel L, Rosi?ska M, Duffell E. Healthcare-associated hepatitis B and C transmission to patients in the EU/EEA and UK: a systematic review of reported outbreaks between 2006 and 2021. BMC Public Health [Internet]. 2022 Dec 3;22(1). Available from: http://dx.doi.org/10.1186/s12889-022-14726-0
   20. Tobin EH, Zahra F. Nosocomial Infections. [Updated 2025 Aug 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559312/
   21. Scaglione G, Colaneri M, Offer M, Galli L, Borgonovo F, Genovese C, et al. Epidemiology and Clinical Insights of Catheter-Related Candidemia in Non-ICU Patients with Vascular Access Devices. Microorganisms [Internet]. 2024 Aug 6;12(8):1597. Available from: http://dx.doi.org/10.3390/microorganisms12081597
   22. Caliman Sato M, Izu Nakamura Pietro EC, Marques da Costa Alves L, Kramer A, da Silva Santos PS. Candida auris: a novel emerging nosocomial pathogen – properties, epidemiological situation and infection control. GMS Hygiene and Infection Control [Internet]. 2023 Aug 16;18. Available from: https://journals.publisso.de/en/journals/hic/volume18/dgkh000444
   23. R-P. Vonberg, Gastmeier P. Nosocomial aspergillosis in outbreak settings. Journal of Hospital Infection [Internet]. 2006 July;63(3):246–54. Available from: http://dx.doi.org/10.1016/j.jhin.2006.02.014
   24. Douglas AP, Stewart AG, Halliday CL, Chen SCA. Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management. JoF [Internet]. 2023 Oct 29;9(11):1059. Available from: http://dx.doi.org/10.3390/jof9111059
   25. Vallabhaneni S, Haselow D, Lloyd S, Lockhart S, Moulton-Meissner H, Lester L, et al. Cluster of Cryptococcus neoformans Infections in Intensive Care Unit, Arkansas, USA, 2013. Emerg Infect Dis [Internet]. 2015 Oct;21(10). Available from: http://dx.doi.org/10.3201/eid2110.150249
   26. Magill SS, O’Leary E, Janelle SJ, Thompson DL, Dumyati G, Nadle J, et al. Changes in Prevalence of Health Care–Associated Infections in U.S. Hospitals. N Engl J Med [Internet]. 2018 Nov;379(18):1732–44. Available from: http://dx.doi.org/10.1056/NEJMoa1801550
   27. Allegranzi B, Nejad SB, Combescure C, Graafmans W, Attar H, Donaldson L, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. The Lancet [Internet]. 2011 Jan;377(9761):228–41. Available from: http://dx.doi.org/10.1016/s0140-6736(10)61458-4
   28. Suetens C, Latour K, Kärki T, Ricchizzi E, Kinross P, Moro ML, et al. Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two European point prevalence surveys, 2016 to 2017. Eurosurveillance [Internet]. 2018 Nov 15;23(46). Available from: http://dx.doi.org/10.2807/1560-7917.es.2018.23.46.1800516
   29. Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet [Internet]. 2022 Feb;399(10325):629–55. Available from: http://dx.doi.org/10.1016/s0140-6736(21)02724-0
   30. Abubakar U, Awaisu A, Khan AH, Alam K. Impact of COVID-19 Pandemic on Healthcare-Associated Infections: A Systematic Review and Meta-Analysis. Antibiotics [Internet]. 2023 Nov 7;12(11):1600. Available from: http://dx.doi.org/10.3390/antibiotics12111600
   31. Jima SA, Gerete TB, Hailu FB, Ayane GB, Jatu MG, Hardido TG, et al. Prevalence and associated factors of nosocomial infection among children admitted at Jimma Medical Center, Southwest Ethiopia: a retrospective study. Front Pediatr [Internet]. 2025 Apr 4;13. Available from: http://dx.doi.org/10.3389/fped.2025.1485334
   32. Nuñez- Lupaca JN, Riley-Moguel AE, Marín G, Zarate-Calderon C, Ruvalcaba-Guerrero H, Wangapakul T, et al. Nosocomial infections and their associated risk factors in post-craniotomy patients: a multivariate analysis. Egypt J Neurosurg [Internet]. 2025 Mar 12;40(1). Available from: http://dx.doi.org/10.1186/s41984-025-00408-7
   33. Isigi SS, Parsa AD, Alasqah I, Mahmud I, Kabir R. Predisposing Factors of Nosocomial Infections in Hospitalized Patients in the United Kingdom: Systematic Review. JMIR Public Health Surveill [Internet]. 2023 Dec 19;9:e43743. Available from: http://dx.doi.org/10.2196/43743
   34. Cheung J. Nosocomial Infection: What Is It, Causes, Prevention, and More. Osmosis [Internet]. 2025 Mar 4 [cited 2025 Dec 28]; Available from: https://www.osmosis.org/answers/nosocomial-infection
   35. Wang L, Zhou KH, Chen W, Yu Y, Feng SF. Epidemiology and risk factors for nosocomial infection in the respiratory intensive care unit of a teaching hospital in China: A prospective surveillance during 2013 and 2015. BMC Infect Dis [Internet]. 2019 Feb 12;19(1). Available from: http://dx.doi.org/10.1186/s12879-019-3772-2
   36. Cheng K, He M, Shu Q, Wu M, Chen C, Xue Y. <p>Analysis of the Risk Factors for Nosocomial Bacterial Infection in Patients with COVID-19 in a Tertiary Hospital</p> RMHP [Internet]. 2020 Nov;Volume 13:2593–9. Available from: http://dx.doi.org/10.2147/rmhp.s277963
   37. CDC. Healthcare-Associated Infections (HAIs). 2024 [cited 2025 Dec 28]. Healthcare-Associated Infections (HAIs). Available from: https://www.cdc.gov/healthcare-associated-infections/index.html
   38. Collins AS. Preventing Health Care–Associated Infections. In: Hughes RG, editor. Patient Safety and Quality: An Evidence-Based Handbook for Nurses. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008 Apr. Chapter 41. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2683/
   39. Szabó S, Feier B, Capatina D, Tertis M, Cristea C, Popa A. An Overview of Healthcare Associated Infections and Their Detection Methods Caused by Pathogen Bacteria in Romania and Europe. JCM [Internet]. 2022 June 4;11(11):3204. Available from: http://dx.doi.org/10.3390/jcm11113204
   40. Sandu AM, Chifiriuc MC, Vrancianu CO, Cristian RE, Alistar CF, Constantin M, et al. Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control—A Narrative Review. Infect Dis Ther [Internet]. 2025 Apr 10;14(5):933–71. Available from: http://dx.doi.org/10.1007/s40121-025-01143-0
   41. Lamy B, Dargère S, Arendrup MC, Parienti JJ, Tattevin P. How to Optimize the Use of Blood Cultures for the Diagnosis of Bloodstream Infections? A State-of-the Art. Front Microbiol [Internet]. 2016 May 12;7. Available from: http://dx.doi.org/10.3389/fmicb.2016.00697
   42. Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases [Internet]. 2010 Mar 1;50(5):625–63. Available from: http://dx.doi.org/10.1086/650482
   43. Pneumonia (Ventilator-associated [VAP] and non-ventilator associated Pneumonia [PNEU]) Event (2025) cdc.gov. Available at: https://www.cdc.gov/nhsn/pdfs/pscmanual/6pscvapcurrent.pdf
   44. Keely Boyle K, Rachala S, Nodzo SR. Centers for Disease Control and Prevention 2017 Guidelines for Prevention of Surgical Site Infections: Review and Relevant Recommendations. Curr Rev Musculoskelet Med [Internet]. 2018 June 16;11(3):357–69. Available from: http://dx.doi.org/10.1007/s12178-018-9498-8
   45. Kolbe-Busch S, Djouela Djoulako PD, Stingu CS. Trends in Healthcare-Acquired Infections Due to Multidrug-Resistant Organisms at a German University Medical Center Before and During the COVID-19 Pandemic. Microorganisms [Internet]. 2025 Jan 25;13(2):274. Available from: http://dx.doi.org/10.3390/microorganisms13020274
   46. Macesic N, Uhlemann AC, Peleg AY. Multidrug-resistant Gram-negative bacterial infections. The Lancet [Internet]. 2025 Jan;405(10474):257–72. Available from: http://dx.doi.org/10.1016/s0140-6736(24)02081-6
   47. Marino A, Augello E, Bellanca CM, Cosentino F, Stracquadanio S, La Via L, et al. Antibiotic Therapy Duration for Multidrug-Resistant Gram-Negative Bacterial Infections: An Evidence-Based Review. IJMS [Internet]. 2025 July 18;26(14):6905. Available from: http://dx.doi.org/10.3390/ijms26146905
   48. Werneburg GT. Catheter-Associated Urinary Tract Infections: Current Challenges and Future Prospects. RRU [Internet]. 2022 Apr;Volume 14:109–33. Available from: http://dx.doi.org/10.2147/rru.s273663
   49. El Arab RA, Almoosa Z, Alkhunaizi M, Abuadas FH, Somerville J. Artificial intelligence in hospital infection prevention: an integrative review. Front Public Health [Internet]. 2025 Apr 2;13. Available from: http://dx.doi.org/10.3389/fpubh.2025.1547450
   50. van der Werff SD, van Rooden SM, Henriksson A, Behnke M, Aghdassi SJS, van Mourik MSM, et al. The future of healthcare?associated infection surveillance: Automated surveillance and using the potential of artificial intelligence. J Intern Med [Internet]. 2025 June 5;298(2):54–77. Available from: http://dx.doi.org/10.1111/joim.20100
   51. Villanueva-Miranda I, Xiao G, Xie Y. Artificial intelligence in early warning systems for infectious disease surveillance: a systematic review. Front Public Health [Internet]. 2025 June 23;13. Available from: http://dx.doi.org/10.3389/fpubh.2025.1609615
   52. Odone A, Barbati C, Amadasi S, Schultz T, Resnik DB. Artificial intelligence and infectious diseases: an evidence-driven conceptual framework for research, public health, and clinical practice. The Lancet Infectious Diseases [Internet]. 2025 Sept; Available from: http://dx.doi.org/10.1016/s1473-3099(25)00412-8
   53. Uchechukwu CF, Shonekan A. Current status of clinical trials for phage therapy. Journal of Medical Microbiology [Internet]. 2024 Sept 25;73(9). Available from: http://dx.doi.org/10.1099/jmm.0.001895
   54. Muñoz-Egea MC, Rodríguez A, Esteban J, García-Quintanilla M. Phage Therapy for Hospital-Acquired Respiratory Bacterial Infections: A Review. Open Respiratory Archives [Internet]. 2026 Jan;8(1):100507. Available from: http://dx.doi.org/10.1016/j.opresp.2025.100507
   55. Liu Y, Thong S, Moreira W, Yeo JH, Zhong Y, Chong ZS, et al. Clinical application of customized and non-customized bacteriophage therapy in patients with refractory/resistant bacterial infections: A systematic review and meta-analysis. International Journal of Antimicrobial Agents [Internet]. 2025 Oct;66(4):107570. Available from: http://dx.doi.org/10.1016/j.ijantimicag.2025.107570
   56. Y?lmaz GE, Göktürk I, Ovezova M, Y?lmaz F, K?l?ç S, Denizli A. Antimicrobial Nanomaterials: A Review. Hygiene [Internet]. 2023 July 19;3(3):269–90. Available from: http://dx.doi.org/10.3390/hygiene3030020
   57. Hasan J, Xu Y, Yarlagadda T, Schuetz M, Spann K, Yarlagadda PK. Antiviral and Antibacterial Nanostructured Surfaces with Excellent Mechanical Properties for Hospital Applications. ACS Biomater Sci Eng [Internet]. 2020 May 7;6(6):3608–18. Available from: http://dx.doi.org/10.1021/acsbiomaterials.0c00348
   58. Zhu X, Tang Q, Zhou X, Momeni MR. Antibiotic resistance and nanotechnology: A narrative review. Microbial Pathogenesis [Internet]. 2024 Aug;193:106741. Available from: http://dx.doi.org/10.1016/j.micpath.2024.106741
   59. Moore LSP, Villegas MV, Wenzler E, Rawson TM, Oladele RO, Doi Y, et al. Rapid Diagnostic Test Value and Implementation in Antimicrobial Stewardship Across Low-to-Middle and High-Income Countries: A Mixed-Methods Review. Infect Dis Ther [Internet]. 2023 June;12(6):1445–63. Available from: http://dx.doi.org/10.1007/s40121-023-00815-z
   60. Peri AM, Chatfield MD, Ling W, Furuya-Kanamori L, Harris PNA, Paterson DL. Rapid Diagnostic Tests and Antimicrobial Stewardship Programs for the Management of Bloodstream Infection: What Is Their Relative Contribution to Improving Clinical Outcomes? A Systematic Review and Network Meta-analysis. Clinical Infectious Diseases [Internet]. 2024 Apr 27;79(2):502–15. Available from: http://dx.doi.org/10.1093/cid/ciae234
   61. Naghavi M, Vollset SE, Ikuta KS, Swetschinski LR, Gray AP, Wool EE, et al. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. The Lancet [Internet]. 2024 Sept;404(10459):1199–226. Available from: http://dx.doi.org/10.1016/s0140-6736(24)01867-1
   62. World Health Organization: WHO. Infection prevention and control GLOBAL. World Health Organization: WHO [Internet]. 2019 Nov 25 [cited 2025 Dec 29]; Available from: https://www.who.int/health-topics/infection-prevention-and-control
   63. Sandu AM, Chifiriuc MC, Vrancianu CO, Cristian RE, Alistar CF, Constantin M, et al. Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control—A Narrative Review. Infect Dis Ther [Internet]. 2025 Apr 10;14(5):933–71. Available from: http://dx.doi.org/10.1007/s40121-025-01143-0
   64. Canciu A, Cernat A, Tertis M, Graur F, Cristea C. Tackling the issue of healthcare associated infections through point-of-care devices. TrAC Trends in Analytical Chemistry [Internet]. 2023 Apr;161:116983. Available from: http://dx.doi.org/10.1016/j.trac.2023.116983

 

1. 65. Bennett N, Tanamas SK, James R, Ierano C, Malloy MJ, Watson E, et al. Healthcare-associated infections in long-term care facilities: a systematic review and meta-analysis of point prevalence studies. bmjph [Internet]. 2024 May;2(1):e000504. Available from: http://dx.doi.org/10.1136/bmjph-2023-000504
   66. Kwon JH, Advani SD, Branch-Elliman W, Braun BI, Cheng VCC, Chiotos K, et al. A call to action: the SHEA research agenda to combat healthcare-associated infections. Infect Control Hosp Epidemiol [Internet]. 2024 Sept;45(9):1023–40. Available from: http://dx.doi.org/10.1017/ice.2024.125
   67. Al-Tawfiq JA. Striving for zero traditional and non-traditional healthcare-associated infections (HAI): a target, vision, or philosophy. ASHE [Internet]. 2025;5(1). Available from: http://dx.doi.org/10.1017/ash.2025.10031
   68. Strathdee SA, Hatfull GF, Mutalik VK, Schooley RT. Phage therapy: From biological mechanisms to future directions. Cell [Internet]. 2023 Jan;186(1):17–31. Available from: http://dx.doi.org/10.1016/j.cell.2022.11.017
   69. Huang Y, Guo X, Wu Y, Chen X, Feng L, Xie N, et al. Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment. Sig Transduct Target Ther [Internet]. 2024 Feb 21;9(1). Available from: http://dx.doi.org/10.1038/s41392-024-01745-z
   70. World Health Organization: WHO. WHO launches first ever global report on infection prevention and control. World Health Organization: WHO [Internet]. 2022 May 6 [cited 2025 Dec 29]; Available from: https://www.who.int/news/item/06-05-2022-who-launches-first-ever-global-report-on-infection-prevention-and-control
   71. World Health Organization: WHO. Antimicrobial resistance. World Health Organization: WHO [Internet]. 2023 Nov 21 [cited 2025 Dec 29]; Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance