Population characteristics

In total, 387 patients were affected by the outbreaks included in the study. Of the studies included, 25 described outbreaks occurring in adult HSCT units including 231 patients, 8 in pediatric units including 69 patients, and 6 in both adult and pediatric units, including 77 patients. Of note, a study describing an outbreak involving ten patients did not specify if the population included adult or pediatric patients. ^{Reference Mikulska, Durando and Pia Molinari35} The median outbreak duration was 109 days (interquartile range (IQR) 58.3–177).

Pathogens and outcomes

Among the 40 identified outbreaks, 19 were viral, 17 were bacterial, and four were fungal. Regarding outcomes, 185 (47.8%) patients received antimicrobial treatment, and 91 (23.5%) patients died due to the outbreak. Viral outbreaks affected 182 patients (47%), with a median duration of 91 days (IQR 30–120), resulting in 28 deaths and a mortality rate of 15.4%. Bacterial outbreaks involved 167 patients (43.2%), with a median duration of 150 days (IQR 78–266), leading to 38 deaths and a mortality rate of 22.8%. Fungal outbreaks affected 38 patients (9.8%), with a median duration of 191 days (IQR 131–217), and resulted in 26 deaths, corresponding to a mortality rate of 65.8%.

Adenovirus was the most frequently identified pathogen, implicated in 6 outbreaks (15%), ^{Reference Venard, Carret, Corsaro, Bordigoni and Faou25,Reference Jalal, Bibby and Tang32,Reference Mattner, Sykora, Meissner and Heim34,Reference Swartling, Allard, Törlen, Ljungman, Mattsson and Sparrelid39,Reference Lefeuvre, Salmona and Feghoul48,Reference Fattouh, Stapleton and Eshaghi49} followed by Pseudomonas aeruginosa ^{Reference Lyytikäinen and Golovanov26,Reference Fanci, Pecile and Casalone33,Reference Chaves, Tomich and Salomão43,Reference Gbaguidi-Haore, Varin, Cholley, Thouverez, Hocquet and Bertrand50} and RSV, ^{Reference Harrington, Hooton and Hackman15,Reference McColl, Corser, Bremner and Chopra19,Reference Kassis, Champlin and Hachem36,Reference Kelly, Metzger and Bolon40} each responsible for four outbreaks (10%). The pathogens with the highest mortality rates were Aspergillus spp. and P. aeruginosa. Of the 26 patients infected with Aspergillus spp., 24 died, yielding a mortality rate of 92.3%, while 27 out of 61 patients with a P. aeruginosa infection expired, corresponding to a mortality rate of 44.3%.

Associations between pathogens and sources of contamination were identified. Notably, 75% of P. aeruginosa outbreaks were associated with contaminated sanitary fixtures (P = .007) and water (P = .039). Similarly, all outbreaks caused by NTM were traced back to water as the contamination source (P = .009). Outbreaks involving Aspergillus spp. were exclusively associated with construction activities (P < .001), with 33% also linked to air-conditioning; however, the latter association did not reach statistical significance (P = .073). For viral infections, an index case was identified in 36.8% of outbreaks (P = .016). This included the sole influenza outbreak and 50% of adenovirus outbreaks, although the association was not statistically significant for each virus. Conversely, in 75% of outbreaks related to RSV, the source remained unidentified (P = .039).

Sources of contamination

Ten major sources of contamination were identified: inadequate disinfection protocols or deviation from protocol (18 studies), ^{Reference Orth16–Reference Zambon, Bull, Sadler, Goldman and Ward18,Reference Klausner, Zukerman, Limaye and Corey21,Reference Knowles, Herra and Devitt24,Reference Lyytikäinen and Golovanov26,Reference Silini, Locasciulli and Santoleri29,Reference Hirji, Saragosa and Dedier30,Reference Jalal, Bibby and Tang32–Reference Mattner, Sykora, Meissner and Heim34,Reference Kampmeier, Pillukat, Pettke, Kossow, Idelevich and Mellmann42,Reference Nakamura, Azuma and Sato44–Reference Prescott, Billam and Yates46,Reference Lefeuvre, Salmona and Feghoul48–Reference Gbaguidi-Haore, Varin, Cholley, Thouverez, Hocquet and Bertrand50} hospital environment (11 studies), ^{Reference Nakamura, Azuma and Sato4,Reference Labarca, Leber and Kern23,Reference Knowles, Herra and Devitt24,Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28,Reference Hirji, Saragosa and Dedier30,Reference Fanci, Pecile and Casalone33,Reference Mattner, Sykora, Meissner and Heim34,Reference Iroh Tam, Kline and Wagner38,Reference Kampmeier, Pillukat, Pettke, Kossow, Idelevich and Mellmann42,Reference Prescott, Billam and Yates46,Reference Fattouh, Stapleton and Eshaghi49} hospital water supply (9 studies), ^{Reference Lyytikäinen and Golovanov26,Reference Oren, Zuckerman, Avivi, Finkelstein, Yigla and Rowe27,Reference Kline, Cameron and Streifel31,Reference Fanci, Pecile and Casalone33,Reference Iroh Tam, Kline and Wagner38,Reference Kampmeier, Pillukat, Pettke, Kossow, Idelevich and Mellmann42,Reference Nakamura, Azuma and Sato44,Reference Prescott, Billam and Yates46,Reference Gbaguidi-Haore, Varin, Cholley, Thouverez, Hocquet and Bertrand50} index cases (eight studies), ^{Reference Zambon, Bull, Sadler, Goldman and Ward18,Reference Kirkpatrick, Harrington and Smith20,Reference Weinstock, Eagan and Malak22,Reference Silini, Locasciulli and Santoleri29,Reference Jalal, Bibby and Tang32,Reference Mattner, Sykora, Meissner and Heim34,Reference Branch-Elliman, Araujo-Castillo, Snyder, Sullivan, Alonso and Wright45,Reference Lefeuvre, Salmona and Feghoul48} transmission from healthcare workers (seven studies), ^{Reference Harrington, Hooton and Hackman15,Reference Zambon, Bull, Sadler, Goldman and Ward18–Reference Klausner, Zukerman, Limaye and Corey21,Reference Van Der Doef, Bathoorn and Van Der Linden41,Reference Ouederni, Rekaya and Bouabdallah47} sanitary fixtures (six studies), ^{Reference Lyytikäinen and Golovanov26,Reference Fanci, Pecile and Casalone33,Reference Iroh Tam, Kline and Wagner38,Reference Kampmeier, Pillukat, Pettke, Kossow, Idelevich and Mellmann42,Reference Prescott, Billam and Yates46,Reference Gbaguidi-Haore, Varin, Cholley, Thouverez, Hocquet and Bertrand50} transmission from visitors (five studies), ^{Reference Harrington, Hooton and Hackman15,Reference Zambon, Bull, Sadler, Goldman and Ward18,Reference Weinstock, Eagan and Malak22,Reference Mattner, Sykora, Meissner and Heim34,Reference Swartling, Allard, Törlen, Ljungman, Mattsson and Sparrelid39} construction (three studies), ^{Reference Rotstein, Cummings and Tidings13,Reference Barnes and Rogers14,Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28} contaminated supplies/products (one study), ^{Reference Orth16} and air conditioning (one study). ^{Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28} The contamination source was not identified in 10 of the studies reviewed. ^{Reference Townsend, Yolken and Bishop12,Reference McColl, Corser, Bremner and Chopra19,Reference Venard, Carret, Corsaro, Bordigoni and Faou25,Reference Mikulska, Durando and Pia Molinari35–Reference Doshi, Woodwell, Kelleher, Mangan and Axelrod37,Reference Swartling, Allard, Törlen, Ljungman, Mattsson and Sparrelid39,Reference Kelly, Metzger and Bolon40,Reference Chaves, Tomich and Salomão43,Reference Ouederni, Rekaya and Bouabdallah47}

Inadequate disinfection protocols or deviation from protocols was observed in 19 outbreaks. Examples of inadequate protocols included lapses in hand hygiene and surface disinfection policies, ^{Reference Zambon, Bull, Sadler, Goldman and Ward18,Reference Branch-Elliman, Araujo-Castillo, Snyder, Sullivan, Alonso and Wright45} use of multiuse medication vials, or a failure to routinely screen patients for a particular pathogen. ^{Reference Silini, Locasciulli and Santoleri29} Deviations from established protocols included a unit’s failure to comply with its own Carbapenemase-producing Enterobacterales (CPE) screening algorithm. ^{Reference Prescott, Billam and Yates46} In response, some groups modified their hand hygiene protocols, such as soap and water followed by alcohol hand rub ^{Reference Branch-Elliman, Araujo-Castillo, Snyder, Sullivan, Alonso and Wright45} or changing hand disinfectant solution to 95% ethanol. ^{Reference Mattner, Sykora, Meissner and Heim34} Another group reporting an outbreak of carbapenemase-producing E. cloacae and E. coli increased ward cleaning and room decontamination after discharge, limited kitchen access to hospital staff, and introduced weekly kitchen decontamination. ^{Reference Prescott, Billam and Yates46} An Actinomycetales spp. outbreak was traced to the reinfusion of contaminated cell products from the unit’s cell manipulation lab, where control was achieved through repairing the facility’s laminar hood, removing plants from the lab, and retraining staff. ^{Reference Hirji, Saragosa and Dedier30} In an S. maltophilia outbreak, mislabeled hand-moisturizing cream had been mistakenly used as soap for hand sanitation, and one healthcare worker was linked to all affected patients. ^{Reference Klausner, Zukerman, Limaye and Corey21}

Infection control measures in studies involving a contaminated hospital environment often focused on disposing or replacing equipment. An adenovirus outbreak in a pediatric unit was controlled by introducing single-use pacifiers and bottle nipples, improving diaper disposal, disinfecting all surfaces, and changing to a new disinfectant. ^{Reference Mattner, Sykora, Meissner and Heim34} An NTM outbreak was traced to the development of biofilms on special handwashing machines in patient rooms and was controlled through improved maintenance and scheduled replacement of parts. ^{Reference Nakamura, Azuma and Sato44} Another group reporting an outbreak found hospital-provided hand lotion was contaminated with P. lilacinus, ^{Reference Orth16} which was eliminated after disposal of the lotion.

Effective management of waterborne pathogens often centered on mitigating patient exposure to contaminated water sources. In response to an L. pneumophila outbreak, one unit stopped using tap water, disconnected humidifiers, and started ciprofloxacin prophylaxis for all patients on the unit. ^{Reference Oren, Zuckerman, Avivi, Finkelstein, Yigla and Rowe27} Following an NTM outbreak traced to a contaminated ice machine, one group permanently required patients to drink bottled water, in addition to their longstanding practice of running showers for two minutes before patient use. ^{Reference Iroh Tam, Kline and Wagner38}

Controlling outbreaks introduced to the unit by patients, visitors or staff often focused on isolation and strict adherence to infection control practices. For instance, a SARS-CoV-2 outbreak among healthcare personnel, initially transmitted by an HSCT patient, did not spread to other patients in the unit due to stringent protocols. These included immediate transfer of all patients to single rooms, restricted visitor access, limitations on patient movement, comprehensive use of personal protective equipment, and strict quarantine, testing, and retesting protocols. ^{Reference Greiner, Götz and Malner-Wagner51} A parainfluenza outbreak was controlled by closing the affected wards and isolating infected patients. ^{Reference Zambon, Bull, Sadler, Goldman and Ward18} However, the outbreak recurred as a patient who survived an initial outbreak remained persistently infected, constituting the index case for a second outbreak at that same institution. ^{Reference Zambon, Bull, Sadler, Goldman and Ward18} Another group controlled an outbreak of astrovirus by color-coding uniforms of staff taking care of infected patients, disinfecting common rooms, and implementing contact isolation. ^{Reference Van Der Doef, Bathoorn and Van Der Linden41} Another unit controlled an RSV outbreak by implementing cohort nursing, isolating patients, and administering ribavirin. ^{Reference McColl, Corser, Bremner and Chopra19} Various techniques were employed for control of outbreaks related to visitors, such as discontinuing floating staff ^{Reference Weinstock, Eagan and Malak22} and banning visitors from common areas, such as the ward’s kitchen. ^{Reference Swartling, Allard, Törlen, Ljungman, Mattsson and Sparrelid39}

Contaminated sanitary fixtures were implicated in six outbreaks. ^{Reference Lyytikäinen and Golovanov26,Reference Fanci, Pecile and Casalone33,Reference Iroh Tam, Kline and Wagner38,Reference Kampmeier, Pillukat, Pettke, Kossow, Idelevich and Mellmann42,Reference Prescott, Billam and Yates46,Reference Gbaguidi-Haore, Varin, Cholley, Thouverez, Hocquet and Bertrand50} An outbreak of S. maltophilia was traced to a shower outlet in the room of an affected patient. ^{Reference Kampmeier, Pillukat, Pettke, Kossow, Idelevich and Mellmann42} Shower fixtures were similarly implicated in an outbreak of P. aeruginosa, and disinfection of showerheads, pipes, and handgrips between patients, and antibiotic prophylaxis controlled that outbreak. ^{Reference Lyytikäinen and Golovanov26} Another group reporting an outbreak of P. aeruginosa traced the source to p-traps (bend pipes that connect sinks to sewer systems) in drains in patient rooms and mandated the replacement of p-traps upon discharge when a patient had been admitted for more than one week. ^{Reference Gbaguidi-Haore, Varin, Cholley, Thouverez, Hocquet and Bertrand50}

An association with construction was noted in all three outbreaks of Aspergillus spp., ^{Reference Rotstein, Cummings and Tidings13,Reference Barnes and Rogers14,Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28} two of which involved pediatric units. ^{Reference Barnes and Rogers14,Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28} One of the outbreaks occurred while the unit was undergoing construction to add additional beds with laminar air flow filtration; the construction led to a sharp increase in Aspergillus spp. spore counts in the unit, which returned to expected levels after the conclusion of the construction. ^{Reference Barnes and Rogers14} Another group noted an outbreak in a newly renovated ward, where cases of invasive aspergillosis were much higher than those in non-renovated wards. ^{Reference Rotstein, Cummings and Tidings13} The third outbreak was traced to contaminated air conditioning and contaminated insulation in the unit’s nurses’ station’s wall and construction on a different building floor. ^{Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28} The team noted high Aspergillus spp. conidia counts in the part of the unit with the highest case counts, but nearly none in the part that was employing HEPA filtration systems. To control the outbreak, the team installed HEPA filters in the affected part of the unit, decontaminated the wall insulation, sealed off construction areas to ductwork, and added itraconazole to their prophylaxis regimen. ^{Reference Hahn, Cummings, Michalek, Lipman, Segal and McCarthy28}