1. Introduction

According to the European Center for Disease Prevention and Control (ECDC), 8.9 million healthcare-associated infections (HAIs) are estimated to occur every year in European hospitals and long-term care facilities [1]. Studies summarizing the results of 15 participating countries in Europe revealed that the most frequently isolated microorganisms from patients suffering from a nosocomial infection (NI) are bacteria such as Pseudomonas aeruginosa, coagulase-negative Staphylococcus spp., and Escherichia coli [1]. These results are quite similar to those found in other regions of the world, with the next most common microorganism being viruses [2]. However, parasites also contribute to HAIs. In a worldwide study conducted in 2007, it was shown, that parasitic infections account for 0.6 to 1% of infections acquired during a stay in hospital, depending on the geographic region (0.7% in Western Europe) [3]. These infections represent an increasing threat to patients and an increasing challenge to health care workers, especially in intensive care units (ICUs). In 2017, 11,788 (8.3%) patients staying in an ICU for more than two days faced at least one HAI [1]. NIs or HAIs mostly affect patients with impaired immunity and effectuate complications in addition to their original disease. Impaired immunity might be due to age (very young, very old), pre- and postsurgical status, disturbances in metabolism (e.g., diabetes), and of course, defects in immunity (innate, caused by immunosuppressive agents, or diseases, with AIDS being a prominent example).

The most important source of NIs is the patients themselves, who represent reservoirs for pathogens. Other sources can be health care personnel and visitors and even non-hospital personnel ^[4][5][4,5]. Moreover, food, water, blood transfusion, organ transplantation, and arthropods (themselves or as vectors) are further possible sources of NIs.^{[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]}

This article gives an overview of parasites as causative agents of NIs, grouped by the main routes of infection. The main routes discussed are transfusion-mediated/solid organ transplantation (SOT)-mediated, during birth, contact with health care workers/other patients (person-to-person), water/food, and arthropods. Parasites, routes of infection, estimated frequency of infection, and selected references are summed up in Table 1. Moreover, short reference is given to the most common bacterial, fungal, and viral NIs in Table 2.

Table 1. Nosocomial parasites, listed according to their route of infection, with their infective stages, routes of infection, reported frequencies, and selected references.

2. Selected Most Common Bacterial, Fungal, and Viral NIs

The majority of nosocomial infections are caused by bacteria, fungi, and viruses. Table 2 gives an overview of common nosocomial infections.

In the most recent ECDC report on nosocomial bacterial infections [1], including data from 14 European countries, the most frequently observed disease was pneumonia, followed by blood stream infections and urinary tract infections. Pneumonia was associated with the use of intubates in 97.3%, and the most commonly isolated pathogens were Pseudomonas aeruginosa, followed by Staphylococcus aureus. P. aeruginosa is a Gram-negative, multidrug-resistant opportunistic pathogen that can be isolated from soil, water, skin flora, and most man-made environments throughout the world. This bacterium also has the potential to form biofilms, making it even harder to treat. S. aureus is a Gram-positive coccoid commensal bacterium of the microbiota of the human body; however, some strains of S. aureus are associated with severe infections in humans ^[52][190]. Bloodstream infections in HAI are associated with catheter usage in 37% of all cases. The most frequently isolated pathogens include coagulase-negative staphylococci and Enterococcus spp. [1]. S. epidermidis and S. saprophyticus, coagulase-negative Staphylococcus species, are commensals of the skin and/or urinary tract but can cause severe infections in immunosuppressed patients. Enterococci are Gram-positive cocci and normally intestinal commensals, even belonging to the obligate gut flora. However, they can cause life-threatening infections in immunocompromised persons. Urinary tract infections in ICUs are mostly associated with the use of urinary catheters (97.9%), and the most frequently isolated pathogens are Escherichia coli and species of the already mentioned genus Enterococcus. E. coli also belongs to the obligate intestinal flora; however, in the wrong habitat (e.g., the urinary tract), it may cause severe infections ^[53][191]. Hand hygiene is of major importance for the prevention of nosocomial infections, particularly in settings with immunosuppressed patients. Involved are, most frequently, Gram-negative bacteria and Bacillus spp. ^[54][192]; however, anaerobic bacteria, such as Fusobacterium sp. and Clostridium spp., are also isolated from nosocomial infection-sites of cancer patients ^[55][193]. As all the described bacteria can be found in/on healthy human bodies, the most likely source of infection and contamination of catheters/tubi is either the patient himself/herself or health care personnel.

Members of the genus Aspergillus can cause a variety of diseases, subsumed as Aspergillosis. Aspergillosis is assumed to affect more than 14 million people worldwide. Invasive aspergillosis occurs infrequently in SOT recipients but with a high mortality rate of 40% ^[56][194]. However, it is not entirely clear as to whether these infections are due to a (re-)activation of already present Aspergillus spp. or whether they are acquired during transplantation through contaminated air, ventilation systems, or air filters, or if they are derived from the organ itself if the donor is infected ^[57][195]. Certain Candida species, especially Candida albicans, are part of the human microbial flora, but in critically ill patients, they are a source of candidemia. Between 2009 and 2010, Candida spp. were the fifth most common pathogen identified in HAIs reported to the CDC. Nosocomial fungal infections are most likely due to intravascular catheters colonized by Candida spp. from the patient’s endogenous microflora or Candida spp. acquired from the healthcare environment ^[58][196].

Viruses account for 1–5% of nosocomial infections ^[59][197]. Nosocomial spread of viruses often parallels outbreaks in the community. Many viruses are spread via aerosols, and thus visiting relatives and health care personnel are the most important sources of infection. Respiratory viruses (e.g., respiratory syncytial virus (RSV), influenza viruses, rhinoviruses, coronaviruses, and adenoviruses) are increasingly being recognized as significant pathogens associated with seasonal nosocomial outbreaks. RSV is a major cause of morbidity in infants and young children; influenza mostly commonly affects elderly persons and has an associated mortality rate of 50%. Rhinoviruses and coronaviruses (exclusive of SARS-CoV-2) are responsible for up to 40% and 15% of cases of the common cold, respectively. Other aerosol-spread viruses, like measles, mumps, and rubella viruses, do not play huge roles in nosocomial infections anymore, thanks to vaccination programs. Neither rubella nor mumps infections have more severe etiopathologies in immunocompromised individuals, but such patients can develop severe progressive measles infection associated with giant cell pneumonia, with an associated mortality rate of 70%. Gastrointestinal viruses can be spread via the feco–oral route, the most prominent example being rotaviruses. Rotaviruses have been identified as the cause of diarrhea outbreaks in the elderly as well as in children, of whom up to 70% shed the virus in their stools. Blood-borne viruses, such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 (HIV-1) have all been associated with nosocomial infections. While the risk of an infection with hepatitis B upon percutaneous contact with an infected individual is up to 30% (in unvaccinated persons), the average risk of transmission of HIV was calculated to be 0.32% ^[60][198].

All infection scenarios described involved highly immunocompromised individuals in intensive care units, cancer units, or pediatric clinics. However, one has to keep in mind that many of the described bacterial, fungal, and viral nosocomial infections can also occur in e.g., outpatient clinics ^[61][199] or dental clinics ^[62][200].

Table 2. Common agents of nosocomial infections (bacteria, fungi, viruses).