Introduction

Nosocomial infections can be defined as an infection developed within a person during a stay in a hospital or any other healthcare facility.

To be precise, any infection developed in a person while receiving medical support in a health care setting, which was not present or was not in the incubation period prior to the admission of the person in the health care setting, is called nosocomial infection. To be a nosocomial infection, the disease must be developed only after at least 48 of admission to/visiting a healthcare facility.

It is also called ‘Hospital Acquired Infection (HAI)’ or ‘Healthcare Associated Infection (HCAI).’

The pathogens causing such infections are acquired during the process of receiving healthcare facilities in facilities like hospitals, nursing homes, clinics, diagnostic centers, rehabilitation centers, or any other clinical centers. The infection can develop and be noticed during the period of stay within such centers or may also be developed after discharge. 

The pathogens can be transmitted from any factors of the hospital environment (like air, water, bedding, building, wastes, etc.), hospital staff, medical devices, other patients, or any other objects. The pathogen may be the normal flora of the patient itself. During a hospital stay, if the immune system is compromised, the normal flora (opportunistic pathogens within or on the patient’s body) develops the infection. Such infections are also called nosocomial infections. If the incubation periods of such pathogens are shorter than the duration of hospital stay, the disease is observed during the period of stay within the hospital. However, if the incubation period is longer than the duration of the patient’s stay in the hospital, the disease is developed after the discharge of the patient. 

Types of Nosocomial Infections

The US Center for Disease Control and Prevention (CDC) categorizes nosocomial infections, broadly into the following 4 most frequent types:

Central Line-associated Bloodstream  Infection (CLABSI)

These are the bloodstream infections developed in patients with central venous catheters (catheters inserted in veins for administration of intravenous medications). It is common in patients in ICUs and is one of the major causes of HAI-associated morbidity and mortality globally; with about 12 to 25% mortality rate in the USA in 2020. 

Catheter-associated Urinary Tract Infection (CAUTI)

These are urinary tract infections (infections developed in the urinary tract) in persons with indwelling urinary catheters. It is the most common form of HAIs and is the prime cause of secondary bloodstream infections. A major case of complicated UTI cases is associated with urinary catheterization. 

Surgical Site Infections (SSI)

These are the infections developed in or around the site where surgery was done within 30 days of surgery. The infection can be superficial or limited to the epidermal layer (Superficial SSI), deep beneath the incision area in muscle (Deep Incisional SSI), or infecting inner organs (Space SSI).   

Ventilator-associated Pneumonia (VAP)

Pneumonia is the second most common nosocomial infection after UTI seen in patients with critical illness and the associated mortality rate may be up to 50%. If a patient receiving mechanical ventilator support develops pneumonia after 48 hours of being incubated, then pneumonia can be defined as ventilator-associated pneumonia. 

Besides, there are other types of nosocomial infections, viz.:

Gastroenteritis/Gastrointestinal Infections

Gastrointestinal infections seen in patients after at least 48 hours of admission, during their stay in the healthcare facility, or within 3 days of being discharged from the healthcare facility can be defined as nosocomial gastroenteritis. 

Nosocomial Skin Infection

Infection of the skin due to exposure to pathogenic microorganisms in a healthcare facility is called nosocomial skin infection.  After a long hospital stay or use of antimicrobials and/or other medications making the immune system weak, the normal skin flora of the patients begins to develop several forms of skin infections like rashes, ulcers, cellulitis, folliculitis, pyogenic and non-pyogenic wounds, etc. The most common causative is Staphylococcus spp.; either normal flora or Staph transmitted from other patients or most commonly healthcare workers.  

Non-catheter-associated Bloodstream Infections and Urinary Tract Infections

These are bloodstream infections and urinary tract infections seen in hospitalized (including recently discharged) patients without any catheterization. 

Non-ventilator-associated Pneumonia (NVAP)and other Respiratory Tract Infections

In hospitalized patients without ventilator support, several forms of respiratory tract infections are seen; all these RTIs fall under this category. While VAP is associated primarily with aerobes, the non-ventilator-associated RTIs are caused by aerobes, anaerobes, as well as respiratory viruses.

Nosocomial infections can also be classified on the basis of associated pathogenic microorganisms into bacterial, fungal, and viral nosocomial infections. 

Risk Factors

The common risk factors associated with the development of nosocomial infections are listed below: 

1. Immunocompromisation 

Patients with immune-compromised conditions due to any disease or administration of medical products are likely to develop nosocomial infections more often than patients with healthy/functional immune systems. 

2. Invasive Medical Procedures including Catheterization 

Invasive medical procedures like surgery, catheterization, angioplasty, medical device insertion, thrombectomy, coronary stenting, etc. increase the risk of the introduction of pathogens directly into the dermal or muscular region escaping the primary layer of defense, the skin. This will make the patent more prone to the development of infections. Similarly, medical devices allow the route of administration of pathogens and also allow for biofilm formation; hence, increasing the chance of infection.

3. Prolonged Use of Antimicrobials 

Prolonged use of antimicrobials will inhibit normal flora, allowing colonization of other pathogenic organisms from the environment. Similarly, some antimicrobials also tend to weaken the immune system increasing the chance of infection. 

4. Prolonged Hospitalization 

Prolonged hospitalization increases the risk of exposure to pathogens increasing the chance of acquiring nosocomial infection. 

5. Use of Contaminated Medical Devices 

Medical devices like thermometers, pulse-oximeter, sphygmomanometers, etc. are used for multiple patients without sterilization. This will also increase the risk of transmission of pathogens. 

6. Contact with other Patients and Career Medical Personals 

Pathogens from other patients and medical personnel can be transmitted to susceptible patients visiting healthcare settings. 

7. Chronic Diseases 

Chronic diseases like HIV, COPD, cancer, etc. make a person more susceptible to nosocomial infection. 

8. Age

Age is also a major factor influencing the chance of acquiring HCAIs. Elderly people and neonates are more susceptible than children and adults. 

Epidemiology of Nosocomial Infections

These types of infections are reported globally and can occur in any healthcare setting. In general, about 10% of admitted persons are reported to be infected with a type of hospital-acquired infection. Among the hospital-admitted patients, patients in intensive care units (ICU), burn units, and surgical or post-surgical wards suffer from HAIs. 

The prevalence rate is a little higher in developing countries than in developed countries. In high-income (developed) countries about 7 in 100 i.e. 7% and 15 in 100 i.e. 15% of patients admitted to acute health care services are infected with at least one nosocomial infection. Among HAI-acquired patients, about 10% will die from the infection; hence, it is one of the major causes of mortality and morbidity in healthcare settings. The date is, however, different in different regions/countries. There is no regular study done on this topic in every country, so the exact rate of prevalence is difficult to determine.  The US CDC reports that about 3.2% of hospitalized patients in the USA develop at least one nosocomial infection. 

Common Pathogens Responsible for Nosocomial Infections

Bacterial infections are the most common types of nosocomial infections followed by fungal and viral infections. Parasitic infections are rarely encountered; hence they contribute a negligible portion of nosocomial infections. 

Bacterial Pathogens 

They are the most common types of microorganisms causing HCAIs. Both opportunistic and true pathogenic bacteria cause HCAIs. Some common bacterial pathogens associated with nosocomial infections are:

Gram-Positive Bacteria	Gram-Negative Bacteria
Staphylococcus aureus (Methicillin Resistant Staphylococcus aureus (MRSA), Vancomycin Resistant Staphylococcus aureus (VRSA)) Coagulase Negative Staphylococcus (CONS) Enterococcus spp. (Vancomycin Resistant Enterococci (VRE)) Streptococcus spp.  Clostridium difficile	Enterobacterales (E. coli, Klebsiella spp., Proteus mirabilis, Enterobacter spp., Salmonella spp., etc.) Pseudomonas aeruginosa  Acinetobacter baumannii Haemophilus influenza

Fungal Pathogens

Fungi account for most of the HCAIs after bacteria. They mainly infect severely immunocompromised patients, patients with severe granulocytopenia, and ventilated patients. Some common fungal pathogens associated with nosocomial infections are:

1. Candida spp. (Candida albicans, fluconazole resistant C. krusei, C. glabrata) 
2. Aspergillus spp. (A. fumigatus, A. flavus) 
3. Mucorales (Mucor spp.)
4. Fusarium spp. 
5. Pneumocystis jirovecii
6. Scedosporium spp. 
7. Malassezia spp. 
8. Acremonium spp. 

Viral Pathogens

Several viruses are responsible for a minor portion of nosocomial infections. Some common viruses causing nosocomial infections are:

1. Noroviruses
2. Rotaviruses
3. Influenza viruses
4. Respiratory syncytial virus
5. Herpes Simplex Virus
6. Hepatitis B and C virus

Common Nosocomial Infections and Associated Risk Factors and Pathogens

Common Source/Reservoir of Pathogens Associated with Nosocomial Infections

1. Healthcare setting staff (including both clinical and non-clinical personnel) 
2. Environmental aspects like surface, water, food, air, patient room, bathroom, basin, bedding, door knobs, medical devices, etc.
3. Patients (normal flora of patients themselves or microbiome from other patients) 
4. Visiting members of patients 
5. Hospital wastes   
6. Animals like pests, insects, and others in the healthcare facility 

Transmission of Nosocomial Infections

1. Contact transmission: Direct contact with patients or healthcare workers or contact with contaminated surfaces and equipment. 
2. Droplet transmission: From infectious respiratory droplets produced during coughing, sneezing, speaking, etc., or during medical procedures.
3. Airborne transmission: Infectious agents can transmit over long distances via contaminated air. 
4. Fecal-oral transmission: Fecal-contaminated food and water ingestion can also transmit nosocomial infections. 
5. Vector transmission: Vectors such as insects and rodents can spread pathogens in healthcare settings. 
6. Vehicle Transmission: The vehicle includes food, water, medical devices, syringes, PPEs, body fluid-contaminated materials, etc. 

Impact of Nosocomial Infection on Patients

• Increased morbidity and mortality rate

HCAIs make the case worse and/or cause secondary infections and increase the morbidity and mortality rate of patients. 

• Prolonged hospital stay

The nosocomial infections will increase the severity of the case demanding prolonged hospital stays and more medicines for treatment. 

• Chance of antimicrobial-resistant infections

Nosocomial infections are often caused by antimicrobial-resistant species transmitted from hospital settings. Hospitalized patients are often administered antibiotics which can induce the development of antimicrobial resistance in patient-associated microorganisms.  

• The increased cost of treatment 

Increased case morbidity and antimicrobial-resistant infections demand prolonged hospital stays and more medicines for treatment which will increase the cost of treatment. 

Antibiotic Resistance and Nosocomial Infections 

Healthcare settings are the primary source of origin and dissemination of antimicrobial-resistant species because they are the place where antimicrobials are mainly used and pathogens from different sources are accumulated. Many pathogens causing HCAIs are found to be antimicrobial-resistant strains and the cases of antimicrobial-resistant associated HCAIs are increasing rapidly across the globe.  

ESKAPE is a group of multi-drug resistant pathogenic bacteria, mostly responsible for nosocomial infections. This group includes 6 pathogens, viz. Enterococcus faecium (Vancomycin Resistant Enterococcus faecium), Staphylococcus aureus (MRSA and VRSA), Klebsiella pneumoniae (Carbapenem resistant Klebsiella pneumoniae (CRKP)), Acinetobacter baumannii (Carbapenem resistant Acinetobacter baumannii (CRAB)), Pseudomonas aeruginosa (Carbapenem resistant Pseudomonas aeruginosa (CRPA)), and Enterobacter spp. (Pan-drug resistant Enterobacter spp.).  Besides, Beta-lactamase producing Enterobacterales, drug-resistant Candida spp., and other fungal pathogens, drug-resistant Streptococcus spp. are also serious threats to nosocomial infections. 

These AMR pathogens increase the chance of HCAIs, case severity, prolonged hospital stay, increased cost of treatment, and higher mortality. 

Prevention, Control, and Management of Nosocomial Infections 

For the prevention, control, and management of nosocomial infections, the following measures should be adopted.

The practice of good hand hygiene– Healthcare workers should practice good hand hygiene like washing with soap and water, use of gloves, or use of hand sanitizers before and after visiting a patient. Similarly, the family person visiting or taking care of the patients must follow hand hygiene. This will reduce the transmission of pathogens from healthcare workers to patients. 

Proper and regular sanitization of hospital setting– Healthcare settings including patient rooms, beddings, equipment, surfaces, etc. must be regularly disinfected and cleaned. 

Regular monitoring and surveillance of the hospital environment for any potential pathogens is necessary. The data from such a program will allow the infection control department to make effective plans to prevent and control nosocomial infections.

Patient isolation– Patients with infectious diseases and patients with higher susceptibility to infections must be isolated.

Antimicrobial stewardship can help to reduce the probability of emergence/development and spread of AMR pathogens. 

Use of PPE (personal protective equipment)– PPE like globes, masks, goggles, aprons, body suits, etc. is very important to prevent the transmission of pathogens in healthcare facilities. Healthcare workers must use PPE so that they can prevent acquiring and transmitting pathogens from one patient to another. Patients must also use general PPE like masks and gloves during their stay and visit to healthcare facilities.

Immunization can play a very important role in developing immunity against possible HCAIs. 

Educating healthcare workers/staff regarding HCAIs, their mode of transmission, and methods to prevent such diseases can be a very effective method to prevent and control the spread of HCAIs in a healthcare facility.   

Minimize the hospital visit and hospital stay duration if possible, because prolonged hospital stay will increase the risk of being infected with HCAIs.    

Proper management of hospital wastes and proper pest control is also very important to prevent the emergence and spread of infection in hospitals. 

Ensuring proper implication of strategies and plans to prevent and control HCAIs is also very important.