As outlined above, the endogenous flora of a patient cannot be eliminated, but the flora changes over time during hospitalization. Therefore, infection control aims at preventing exposure to nosocomial multiresistant bacteria rather than controlling any bacteria. The IDSA included among the top five methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) or multiresistant Pseudomonas aeruginosa, Acinetobacter baumannii, and gram-negative bacteria expressing extended broad-spectrum betalactamases (ESBL). In addition, other pathogens expressing plasmid-mediated AmpC betalactamases are of importance [38]. These pathogens – if untreated – have the potential to abrogate a successful hematological treatment by inducing a potentially lethal sepsis. On the other hand, infection with resident bacteria is almost unavoidable when prolonged and severe neutropenia persists over weeks and months. Severe mucositis leads to translocation of bacteria in the gut and ultimately entry into the bloodstream. The commonly required central venous catheter disrupts the skin as a natural barrier and can lead to catheter-related bloodstream infections.

Many viruses reside in the body and require treatment only under severe immunosuppression leading to increased replication and symptomatic disease. Endogenous viruses increasing morbidity and mortality in HCT patients are mainly cytomegalovirus (CMV) and other herpesviruses and polyomavirus [4, 36].

The most common viruses transmitted in hospitals are respiratory viruses such as influenza [25], parainfluenza, respiratory syncytial virus (RSV), metapneumovirus, and adenoviruses. Several studies indicate that RSV infection early after HCT has a mortality rate between 30 and 60 % [41]. Less frequent, but highly contagious are varicella zoster and measles. Infections with these viruses are preventable by definition and require a source that comes directly or indirectly into contact with the susceptible patient. Visitors, especially children, and HCWs are common vectors for transmission of viruses. These individuals may not feel sick, but carry viruses in the respiratory secretions for prolonged times. Therefore, vaccination of HCWs and family members is a basic infection control procedure and wearing masks and hand hygiene are essential to prevent transmission (see below).

The intestinal and respiratory tracts are colonized with bacteria and fungi. Not surprisingly, yeast infections are usually originating from the endogenous gut flora. Prevention of candidiasis with an antifungal prophylaxis has shown to reduce invasive candida infections [40]. Few studies indicate that Pneumocystis jirovecii pneumonia (PCP) might be transmitted by the airborne route [46]. Animal studies demonstrated that P. jirovecii could be spread through the air, and air samples from areas frequented or occupied by P. jirovecii-infected patients were positive for PCP: However, the introduction of routine prophylaxis with TMP/SMX basically eliminated the risk of PCP, independent of the mode of acquisition. Molds and many dimorphic fungi in endemic areas are airborne. High densities of fungal spores occur during construction work in close proximity of the patient [55]. Special air filtration is a mandatory precaution during construction works as are outlined below. More recently, the hospital water supply has also been described as a possible source of molds [1]. Opportunistic molds (e.g., Aspergillus and Fusarium species) can be cultured from water and on water-related surfaces of hematology units. Studies by Anaissie and colleagues indicated the potential relatedness of environmental and clinical strains among patients with aspergillosis and fusariosis by epidemiological typing [1]. A relative humidity >60 %, especially over 80 %, promotes growth of any molds in any environment. Therefore, air conditioners are frequently set at a humidity of 30–50 %. An extremely humid climate may limit the capacity of the air condition to lower the humidity below 60 %.

Transmission of protozoa and helminths in the hospital setting is a rare event. Standard air conditioning prevents exposure to mosquitoes that may transmit malaria in southern countries. Similarly, simple water treatment, required, e.g., by regulatory agencies in Europe as well as in the USA, prevents contamination of the water with helminths. Hospitals in a highly exposed area are referred to special literature in this field.

Numerous reports in healthcare facilities report airborne transmission of Aspergillus spp., Mucorales, Mycobacterium tuberculosis, measles (rubeola) virus, and varicella-zoster virus [63]. The current recommendations of the CDC to prevent airborne transmission [32] include protective care in single rooms ventilated with ≥12 air exchanges/hour with appropriate fraction of fresh air and central or point-of-use HEPA filters with 99.97 % efficiency for removing particles ≥0.3 μm in diameter, regular replacement of filters, and directed airflow [63, 69]. Twelve air exchanges per hour require a high air volume, which is generated by powerful ventilators. In new construction, noise of ventilators and uncomfortable airflow to the patient should be considered.

Consistent positive air pressure differential between the patient’s room and the hallway ≥2.5 Pa (i.e., 0.01 in. by water gauge) [63] and well-sealed rooms prevent the inflow of spore-containing air from outside. Continuous monitoring and self-closing doors prevent drops in positive pressure. Portable HEPA filters in case of shortage of protective environment have been shown to remove airborne fungal spores and mycobacteria [26, 62] and may be useful during constructions. Data to compare central versus portable filters are lacking.

As laminar airflow (LAF) – consisting of HEPA-filtered air moving in a parallel, unidirectional flow – has not improved survival in HCT recipients, it is not generally recommended, but might protect patients from infection during mold outbreaks related to hospital construction [19]. Anterooms to ensure air balance between rooms and hallways are not generally mandatory and are recommended only for certain airborne infections such as tuberculosis, measles, and varicella.

Dust control is a central issue, as dust contains spores causing mold infections. Despite the proven association of surface contamination with nosocomial infections, only little data support the value of routine surface disinfection in general hospital wards [22]. However, lack of appropriate disinfection of the surfaces is a risk factor for VRE and Clostridium difficile [37]. In addition, patients colonized or infected with methicillin-resistant S. aureus (MRSA) spread their germs all over the room: In fact, more than 50 % of the environment of such patients is contaminated with MRSA [8]. Studies demonstrate that enterococci survive in the environment of hematology units despite vigorous highly active disinfection of the surfaces [21], probably due to rapid recontamination by patients and HCWs.

CDC recommends daily wet-dusting to avoid aerosolization of dust and cleaning of horizontal surfaces with an approved hospital disinfectant [63]. Dust levels can be further reduced by avoiding carpeting and by floor and furniture surfaces with a smooth, nonporous, and washable finish, which has to be compatible with commonly used disinfectants [64]. As vacuum cleaners could aerosolize fungal spores, they should be fitted with HEPA filters. Boyce and colleagues published a new approach with hydrogen vapor to completely disinfect a room using a commercial equipment and reducing contamination and transmission of C. difficile[9].

Contamination of floor and surfaces occurs within hours after disinfection of the environment. Therefore, at least once daily disinfection of the environment is recommended in transplant units [63, 77].

Water leaks and moisture of walls lead to mold proliferation. This can easily be detected by a moisture meter. Plants, plant soil, and flower water might contain gram-negative bacteria, especially Pseudomonas spp. or molds. Pots can be visibly overgrown with molds. Therefore, most centers do not allow plants and flowers in patient rooms [69]. In addition, HCW handling plants might transmit pathogens from plants to patients, unless meticulous hand hygiene is performed. With the exception of water-retaining bath toys which have been associated with Pseudomonas aeruginosa outbreaks [13], toys should not generally be forbidden in pediatric wards but should be washed and disinfected regularly, following guidelines.

As mold outbreaks have been reported repeatedly during hospital construction/renovation [74], measures to reduce the content of molds in the air should be specially addressed during these high-risk periods and planned in advance [52]. In moderate climates with four seasons, fungal spores are detected in ambient air from spring to late fall. Therefore, constructions should be planned in a low fungal spore season unless LAF with 12 air changes are in place. Dust-proof barriers with airtight seals [63] and a positive pressure difference between patient care and construction or renovation areas prevent dust – and mold spores – from entering patient care areas. Patients/healthcare personnel and medical equipment should not cross construction area; paths for construction workers should be separate. If patients have to cross construction area, they should wear face masks, preferably N95 or FFP2. Air monitoring and infection surveillance should be intensified during construction.

Standard precautions include hand hygiene and wearing of appropriate personal protective equipment (i.e., gloves, surgical masks or eye and face protection, and gowns) during interventions/situations in which emission of blood, body fluids, secretions, or excretions is possible [73]. The WHO has set important guidelines (http://​whqlibdoc.​who.​int/​publications/​2009/​9789241597906_​eng.​pdf) for hand hygiene that should be followed by all persons entering the patient room before and after each patient contact. Use of alcohol-based hand rubs is superior to hand washing, the latter should be performed in case of soiled hands [11, 76]. Gloves should be worn during all interventions, leading to contact with blood, secretions, and body fluids, but are not recommended as a routine protective precaution, if hand hygiene guidelines are strictly followed. Unfortunately, compliance with hand hygiene rarely exceeds 40 % during daily care. Higher compliance is achieved in clinical studies with reported rates of >60 %, but as soon as observation is suspended, rates drop again. Certain centers use face masks either during winter seasons or even year-round to further reduce the risk of transmission of respiratory viruses. Surgical masks equally prevented transmission of influenza compared to N95 respirator [44]. This approach has not been shown to improve outcome or to reduce nosocomial infection in a randomized controlled clinical trial, but should be considered in severely immunosuppressed patients. On transports in the hospital, CDC recommends patients in the preengraftment period to wear masks. Masks are likely to prevent transmission of viruses and bacteria while in contact with visitors and other patients during transport, especially in elevators. However, a recent randomized study could not show a beneficial effect of well-fitting masks for the risk of invasive aspergillosis in high-risk patients [47]. Patients after HCT but also other immunosuppressed patients should avoid crowded areas and daycare centers for children to prevent exposure to persons with respiratory infections [32].

Airborne, droplet, or contact precautions should be applied only in case of an indication such as M. tuberculosis and MRSA colonization [64].

Besides routine hospital hygiene measures as described above, HCW suffering from possibly transmissible infections should abstain from patient contact according to published recommendations [7]. The application of this recommendation is difficult in winter seasons, as many HCWs are coughing. A reasonable approach is to recommend routine wearing of surgical mask when entering patient rooms. Vaccination against transmissible diseases is recommended in most countries and is discussed elsewhere in this textbook. Reported outbreaks with gram-negative bacteria and Candida infections lead to the recommendation not to wear artificial fingernails while working in direct patient contact on a transplant unit [33].

Visitors must be instructed to follow the general hospital hygiene rules when visiting patients. Hand hygiene should be performed before and after each patient visit. Written policies should be handed out to HCT recipients and candidates, their household contacts, and visitors. Nursing staff should screen visitors for the presence of transmissible diseases. During a symptomatic transmissible infection, after a known recent exposure to a communicable disease (e.g., chickenpox, mumps, measles, pertussis) or after receipt of a live vaccine, visitors should not see immunocompromised patients. The number of visitors should be kept low: in our center, visitors are restricted to three persons at a time.

Bundle approaches to reduce the incidence of catheter-related infections should be strictly implied [54]. Non-tunneled central venous catheters used most frequently due to the need of multiple lumina in HCT patients should be disinfected daily with either chlorhexidine [59] or octenidine hydrochloride [70], which is available only in Europe. Coated catheters may be a reasonable choice for high-risk patients. Importantly, both the intraluminal surface and the extraluminal surface must be coated, e.g., by chlorhexidine [45] or minocycline/rifampin [27]. The exit site should not come into contact with tap water [30].

Water of hematological units should provide water free of Legionella spp., Pseudomonas spp. and fungi [2]. Commonly used systems are point-of-use filters at the faucet or a centralized system to ensure germ-free water. The sinks of toilets are almost always contaminated with fecal pathogens. Our own studies clearly demonstrate that aerosolization occurs during flushing (data not shown). Therefore, closing the toilet lid is a reasonable approach to avoid contact with frequently multiresistant P. aeruginosa. Shower drains have been shown to cause outbreaks with P. aeruginosa. Frequent disinfection of the sinks may reduce the rate of nosocomial P. aeruginosa infection [5]. A standard operating procedure should be implemented to decontaminate shower heads before biofilm becomes established, e.g., weekly decontamination with a washer-disinfector cleared by the European agency (EN DIN ISO 15883-1-2006) [23]. Manual reprocessing is also considered safe.