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Article

Seasonal Characterization of the Aerobiome in Hematopoietic Stem Cell Transplant Rooms: Potential Risk for Immunosuppressed Patients

by
Emilio Mariano Durán-Manuel
1,2,
Edgar Fiscal-Baxin
1,3,
Andres Emmanuel Nolasco-Rojas
1,2,
Miguel Ángel Loyola-Cruz
1,
Clemente Cruz-Cruz
1,2,
Marianela Paredes-Mendoza
3,
Adolfo López-Ornelas
1,4,
Dulce Milagros Razo Blanco-Hernández
1,
Nayeli Goreti Nieto-Velázquez
1,
Aída Verónica Rodríguez-Tovar
5,
Adrián Ramírez-Granillo
5,
Enzo Vásquez-Jiménez
1,
Verónica Fernández-Sánchez
1,6,
Erika Gómez-Zamora
1,
Mónica Alethia Cureño-Díaz
1,
Andrea Milán-Salvatierra
1,
Carlos Alberto Jiménez-Zamarripa
2,7,
Claudia Camelia Calzada-Mendoza
2,* and
Juan Manuel Bello-López
1,*
1
Hospital Juárez de México, Mexico City 07760, Mexico
2
Sección de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico
3
División de Tecnología Ambiental, Universidad Tecnológica de Nezahualcóyotl, Nezahualcóyotl 57000, Mexico
4
Hospital Nacional Homeopático, Hospitales Federales de Referencia, Mexico City 06800, Mexico
5
Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
6
Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, Mexico
7
Hospital Psiquiátrico “Dr. Samuel Ramirez Moreno”, Valle de Chalco Solidaridad 56619, Mexico
*
Authors to whom correspondence should be addressed.
Microorganisms 2024, 12(11), 2352; https://doi.org/10.3390/microorganisms12112352
Submission received: 7 October 2024 / Revised: 5 November 2024 / Accepted: 12 November 2024 / Published: 18 November 2024
(This article belongs to the Section Public Health Microbiology)
Browse Figures
Versions Notes

Abstract

:
Infections pose a risk for patients undergoing hematopoietic stem cell (HSC) transplants due to their immunosuppression, making them susceptible to opportunistic infections. Therefore, understanding the composition of the aerobiome in this area is vital. The aim of this study was to characterize the aerobiome in an HSC transplant area, evaluating the impact of infrastructure and health personnel operations on air contamination. The environmental parameters and aerobiome of the HSC transplant area at Hospital Juárez de México were quantified over one year. Finally, a double-entry Vester matrix was constructed to classify problems according to their degree of causality. The abundance and taxonomic diversity of the aerobiome were dependent on seasonality, environmental factors, and high-efficiency filtration. Gram-positive bacteria predominated, followed by fungi and Gram-negative bacteria. ANOVA revealed significant differences in the bacterial aerobiome but not in the fungal aerobiome among the transplant rooms. Clinically, fungi such as Aspergillus fumigatus, Alternaria spp., Cladosporium spp., and Penicillium spp. were identified. ESKAPE bacteria typing revealed clonal dispersion. Finally, the Vester matrix highlighted critical problems associated with contamination due to the absence of HEPA filtration and non-adherence in patient management practices. HEPA filtration and positive pressure are essential to improve the air quality and reduce the microbiological load. However, the control areas will depend on patient management and routine activities, such as entry protocols in controlled areas.

1. Introduction

Scientific and technological advances in the field of hematopoietic stem cell (HSC) transplants have revolutionized the treatment of several oncohematological diseases, with acute lymphoblastic leukemia (ALL) being one of the most important because of its high incidence in the pediatric and juvenile population in Latin America [1,2,3]. HSC transplantation is a multidisciplinary procedure that involves the participation of various healthcare professionals, including hematologists, oncologists, geneticists, immunologists, and infectologists, among others. Therefore, the success of a transplant will depend on the synergy between each one of these disciplines; however, these procedures are inherently associated with significant risks, including liver disease, cardiovascular disease, endocrine disorders, graft-versus-host reactions, and opportunistic infections [4,5,6,7]. Regarding the latter, prior to HSC transplantation, the patient undergoes ablation and, consequently, opportunistic infections can easily occur, with bacterial sepsis, mycosis, and invasive pulmonary fungemia being the most common [8,9,10].
Even when these procedures include prophylactic antimicrobial treatment before and after transplantation, the presence of resistant microorganisms can occur and becomes more clinically relevant due to antibiotic therapy failure [11,12,13]. In this context, the presence of nosocomial antibiotic-resistant bacteria on surfaces and medical devices can lead to cross-contamination events and thus increase the length of stay, morbidity, and mortality due to infectious events.
In a previous study by our working group, we identified the clonal spread of the ESKAPE bacteria in the adult intensive care unit (ICU) for COVID-19 patients [14]. In this work, we showed and discussed the problematic and negative impact of the presence of antibiotic-resistant microbiological contamination in patients with respiratory support. In contrast, regarding the microbiological control of HSC transplantation rooms, beyond surfaces and medical devices, air becomes relevant as it is the vehicle for the dispersal of microorganisms in patients who receive a transplant [15,16,17].
The aerobiome in such rooms is a critical factor, yet it has been underestimated as an “invisible” biological entity. The air surrounding a patient who has received a transplant is a complex mixture of viable and non-viable particles; within the viable particles are microorganisms, such as fungal spores and bacteria, which can play a determining role in the acquisition of post-transplant infections [18,19,20,21]. The negative impact of non-viable particulate matter (PM), specifically PM2.5 in transplant areas, has been rarely studied, and the findings that have been generated have not shown clear evidence to support its relationship with the clinical worsening of transplant patients [22]. Nevertheless, their role as drivers of chronic degenerative diseases in other settings has already been reported [23,24].
The detailed seasonal characterization of the cultivable bacterial and fungal aerobiome and PM in transplant areas has become a key priority, as it provides information for the implementation of effective infection control strategies. The strengthening of patient safety during their hospital stays to reduce morbidity and mortality highlights the need for continuous improvement in the infrastructure of such wards. The aim of this study was the seasonal characterization of the bacterial and fungal aerobiome and PM in the HSC transplantation rooms of Hospital Juárez de México (HJM), a tertiary hospital located in the north of Mexico City. Implications for the seasonal presence of bacteria, fungi, and clones of the ESKAPE bacteria in the aerobiomes of HSC transplant rooms are analyzed and discussed.

2. Materials and Methods

2.1. General Description of the HSC Transplant Area at HJM

The HSC transplant area at HJM is a controlled area that was built on a total surface area of 138 m2. This area is divided into two care areas: one for HSC donors of 34 m2 (room A), with three beds, and another area for recipients of 38 m2. The remaining area is for the reception, lock chamber, bathroom, and control site. The HSC recipient area is subdivided into three single rooms of 12.71 m2 each (rooms B, C, and D). Room D is the only room with ten pascals of positive pressure provided by the presence of an air handler unit coupled to a high-efficiency particle arresting (HEPA) filter.
The HSC transplant area has the necessary infrastructure for patient care according to the recommendations reported by Inkster et al. (2022), such as air filtration and hourly air changes (ACH) (room D only), room sealing with sanitary finishing, and epoxy-coated floors, among others [25]. Figure 1 shows the aerial-view map of the HSC transplant area at HJM, and Table 1 shows the infrastructure characteristics per room in the HSC transplant area.

2.2. Determination of Air Quality Parameters (PM, Temperature, and Relative Humidity)

The PM concentrations per m3 were measured annually (bimonthly) in the four rooms of the transplant area (A, B, C, and D). For this purpose, an ExTech VPC300 optical particle counter (OPS) (FLIR Commercial Systems Inc., Wilsonville, OR, USA), previously calibrated inside a type II laminar flow hood, was used. The device was configured to quantify airborne PM of 1.0, 2.5, and 10.0 μm during a sampling interval of 20 s according to the manufacturer’s conditions (per triplicate). The analysis conditions were implemented identically as in the quantification of the bacterial and fungal aerobiomes (in terms of floor height and time). Finally, the temperature (°C) and relative humidity (RH) (%) were simultaneously recorded (per triplicate) with a calibrated thermohygrometer.

2.3. Annual Analysis of the Aerobiome in the HSC Transplant Rooms at HJM

The quantification of the aerobiome in the HSC transplant rooms at HJM was carried out for one year, namely “January to December 2023” (bimonthly), at a fixed time (10:00 a.m.), considering the greatest influx of health personnel. For the quantification of the airborne microbiological load of fungi and Gram-negative and Gram-positive bacteria, the collision method was used with the Air Ideal 3P sampler (bioMérieux, Lyon, France), according to the manufacturer’s conditions, using a set of solid culture media for each room (A, B, C, and D). These were potato dextrose agar (PDA; plus chloramphenicol (30 μg/mL) and streptomycin (30 μg/mL)), Mannitol Salt a, and MacConkey agar, for the presumptive identification of fungi, Gram-positive bacteria, and Gram-negative bacteria, respectively.
For this purpose, the air sampler was programmed for 1000 L air sample aspiration volumes, equivalent to 1 m3, as follows. With the doors closed, the air sampler was placed 1.5 m above ground level in the central part of each room and switched on, and the operator immediately left the sampling point. After sampling, the culture media were immediately enclosed and incubated aerobically at 37 °C for 48 h and 28 °C for 72 h, as the growing conditions for bacteria and fungi, respectively. Bacterial and fungal colonies were counted and reported as CFU/m3 of air sampled; finally, all colonies were isolated on the same culture media to obtain pure cultures for identification as follows.

2.4. Bacterial Aerobiome Identification by Mass Spectrometry MALDI-TOF

Only pure bacterial isolates were identified by the direct analysis of whole bacterial cells using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). For this purpose, all bacterial strains were streaked in LB agar and incubated overnight at 37 °C, and single colonies were subjected to identification by using a Bruker MALDI Biotyper (Bruker Daltonik, Bremen, Germany), according to the manufacturer’s instructions. The criterion found to best match with the identification protocol was bacterial strains with score values above 2.0 (down to 3) for high-confidence identification. With the taxonomic assignment information of the isolates, plots of the relative abundance versus taxonomic diversity and seasonal heat maps of the taxonomic diversity (per room) versus bimonthly period of analysis were constructed.

2.5. Macro- and Microscopic Identification of the Fungal Aerobiome

Representative colonies of the aerial fungal load were chosen for axenic cultures on PDA agar. These cultures were incubated aerobically for 7 days at 28 °C for the description of the macro- and microscopic morphology using the method reported by Johnson and Borman (2010) [26]. To describe the macroscopic morphology, aspects such as the texture, colonial surface, color of the obverse/reverse, and presence of diffusible pigments were identified. The microscopic identification at 1000× total magnification of the mycelium and typical and asexual reproductive structures (hypha, conidiophore, microconidium, dicthyoconidium, vesicle, phialide, and metula) was performed using lactophenol cotton blue.

2.6. Molecular Typing of Gram-Negative Bacteria (ESKAPE) by ERIC-PCR

Gram-negative bacteria (only ESKAPE bacteria) were subjected to molecular typing by ERIC-PCR, by using the primers ERIC1R (5′-ATGTAAGCTCCTGGGGGGATTCAC-3′) and ERIC2 (5′-AAGTAAGTGACTGGGGGGTGAGC-3′), according to Versalovic et al., 1991 [27]. The total reaction volume was 50 μL and consisted of 1× PCR buffer, 20 nM MgCl2, 25 mM dNTPs, 100 pM of each primer, Taq DNA polymerase (2 U), and 300 ng of genomic DNA. The cycling conditions were as follows: pre-denaturation at 95 °C for 7 s, denaturation at 90 °C for 30 s, annealing at 58 °C for 1 min, and extension at 65 °C for 8 min, with a final extension at 68 °C for 16 min at the end for 30 cycles. Genetic profiles were run in 1 X TBE buffer, pH 8.3, and separated in horizontal electrophoresis in 1.5% agarose gels, visualized, photographed under UV illumination, and analyzed by intra-gel pattern comparison. To confirm the reproducibility of the ERIC-PCR assays, these were performed three times. The Tenover criteria were used to establish the clonal relationships between isolates with the same genus and species [28]. Finally, the graphical relationships were analyzed through a distance matrix by using a linear semilogarithmic method. The dendrograms were constructed using the UPGMA algorithm, with the Dice similarity index. Genomic similarity was confirmed with a bootstrap test of 1000 repetitions using the Past4 program (Version 4.09).

2.7. Statistical Analysis and Vester Matrix Construction

Significant differences between the variables analyzed were evaluated by using ANOVA and Tukey’s post hoc test for the concentrations of 1.0, 2.5, and 10.0 mg/m3; the temperature and relative humidity (RH); and the bacterial and fungal microbiological loads. Significant differences between the variables were established when the p-value was <0.05. Additionally, the SPSS v.27.0.1.0 and XLSTAT 2023 statistical software programs were used for the analysis and graphical representation. Finally, a Vester matrix was constructed to classify microbiological problems in the HSC transplant area according to their degree of causality. For this purpose, 24 situations were identified that could impact various outcomes of microbiological contamination. Causality was assessed individually and as a group by various health professionals, including 4 microbiologists, 4 oncologists, 4 hematologists, 4 epidemiologists, 4 nurses, and 4 cleaning assistants. With the results of causality (0, 1, 2, and 3), those that occurred most frequently were considered to have causality closest to reality and were transferred to the matrix to be categorized as active, passive, critical, or indifferent problems [29].

3. Results

3.1. HEPA Pressure and Positive Filtration Impacts the Standard Air Quality Parameters

To determine the impact of HEPA filtration and positive pressure in the transplant room, the annual quantification (mg/m3) of particulate matter (PM1.0, 2.5, and 10 μm) was performed. The results revealed that, in those rooms where HEPA filtration was not available (rooms A, B, and C), the maximum PM10, PM2.5, and PM1.0 levels of 37, 24, and 15 μg/m3, respectively, were detected. The minimum PM levels were at magnitudes of 3, 2, and 3 μg/m3 for PM10, PM2.5, and PM1.0, respectively. The ANOVA and Tukey’s post hoc analysis demonstrated significant differences for all particles analyzed between donor room A and recipient rooms B and C versus recipient room D (Figure 2).
Figure 2A–G show the results of the PM10, PM2.5, and PM1.0 μm quantification from the HSC transplant rooms at HJM and the Tukey’s post hoc analysis and ANOVA for the statistical comparison of the PM levels between the rooms. Simultaneously with these determinations, measurements of the ambient temperature and RH were performed. The results revealed average maximum temperature and RH values of 27 ± 0.4 °C and 57.2 ± 0.2%, respectively. Conversely, the minimum values of these same parameters were between 21.8 ± 0.3 °C and 44.8 ± 0.1%. Interestingly, these maximum and minimum values were directly related to the seasonality for warm months and cold months (B3 “May–June”) and (B4 “July–August”); however, regarding room D, it was the room with the lowest temperature and RH values during the study period. Figure 2H,I show the results of the temporal analysis of the temperature and RH in the HSC transplant area at HJM.

3.2. Seasonal Behavior of Aerobiome Load

The seasonal analysis of the cultivable bacterial and fungal aerobiomes of the HSC transplant rooms showed the maximum microbiological loads with peaks in the months of spring (May/June) and summer (July/August), with average viable counts of 1.0 × 102 ± 22.6, 2.2 × 102 ± 22.6, and 72.5 ± 38.9 CFU/m3 for rooms A (donors), B, and C (recipients). This seasonal behavior of the loads was not detected in room D (for recipients), which had HEPA filtration and positive pressure.
The lowest microbiological loads were identified in the two-month periods at the extremes of the year, in winter (January/April) and autumn (October/December). The highest peak bacterial loads were represented by Gram-positive bacteria, followed by fungi and Gram-negative bacteria. Figure 3 shows the seasonal analysis (bimonthly) of the aerobiome microbiological loads that were analyzed in the HSC transplant rooms at HJM from January to December 2023.

3.3. Significant Differences in Bacterial Aerobiome Load Between Rooms

Because the recipient rooms (B, C, and D) and the donor room (D) presented microbiological loads with seasonal behavior (Figure 3), an ANOVA and Tukey’s post hoc test were performed to determine the existence of significant differences in bacterial microbiological contamination between the rooms. The results revealed the presence of significant differences between rooms B and D for receivers (p = 0.0197).
No differences between rooms A, B, and C were identified. In microbiological terms, it was observed that the degree of bacterial contamination was similar between rooms without HEPA filtration and positive pressure. Figure 4A shows the results of the ANOVA and Tukey’s post hoc test for the statistical comparison of the bacterial aerobiome, and Figure 4B summarizes the findings of the bacterial identification by mass spectrometry of the culturable aerobiome in the HSC transplantation area at HJM.

3.4. Clinically Important Taxonomic Diversity of Bacterial Aerobiome

To elucidate the taxonomic diversity and relative abundance (%) of the culturable bacterial aerobiome in the HSC transplant area, the mass spectrometry identification of all isolates per m3 from the four rooms (A, B, C, and D) was performed during the study period (Figure 4B). The results revealed the significant diversity of the clinically relevant bacterial genera and species in the four rooms analyzed (A = 9 genus and 16 species, B = 9 genus and 15 species, C = 9 genus and 11 species, and D = 8 genus and 13 species).
The aerobiome was mainly represented by Gram-positive bacteria, where the genus Staphylococcus spp. showed the highest relative abundance, with S. warneri, S. haemolyticus, S. saprophyticus, and S. epidermidis species being the most prevalent. Within this bacterial group (Gram-positive), Enterococcus faecalis, a bacterium belonging to the ESKAPE group, was identified. Alternatively, four bacterial genera of Gram-negative bacteria were identified, where three of them also belonged to the ESKAPE group (Escherichia coli, Enterobacter cloacae, and E. hormaechei).
Regarding the differences in the taxonomic diversity and relative abundance of the aerobiome between areas, it was identified that S. haemolyticus was present with abundances of 0.20, 0.40, and 0.33 in rooms A, B, and C, respectively, being rooms without HEPA filtration and positive pressure. In contrast, the relative abundance of S. saprophyticus increased gradually in each of the areas (A = 0.082, B = 0.096, C = 0.291), being higher in the room with HEPA filtration and positive pressure (D = 0.345).
The rest of the bacterial genera and species present in the aerobiome showed heterogeneous relative abundances in each of the rooms analyzed. Finally, S. saprophyticus, Aerococcus viridans, and E. coli (ESKAPE bacteria) were present in all four rooms, regardless of the type of use (for donors or recipients). Figure 4B summarizes the bacterial identification findings by mass spectrometry (MALDI-TOF MS) of the culturable aerobiome in the HSC transplant area (donor and recipient rooms) at HJM.

3.5. Seasonal Transition of the Bacterial Aerobiome in the HSC Transplant Area

As part of the analysis of the bacterial aerobiome, a longitudinal follow-up study of the behavior of the bacterial aerobiome per m3 of the HSC transplant area during the study period was carried out. For this purpose, heat maps were created of each of the rooms analyzed, using the information on the relative abundance and taxonomic diversity per m3 identified by mass spectrometry. The results revealed that species of the genus Staphylococcus showed a reduction in relative abundance during the bimonthly course of the study period. Species such as S. warneri, S. haemolitycus, S. equorum, and S. saprophyticus showed this behavior in the donor (A) and recipient (B and D) rooms (Figure 5).
Regarding room C, no seasonal transition (upward or downward) of this bacterial genus was observed. In the case of Aerococcus viridans, in addition to being identified in all four rooms, only in receiving room C did it show an increase in relative abundance during the study period.
Two members of the ESKAPE group (E. faecalis and E. coli) were detected in a timely manner from the second to the fourth bimester analyzed, without any change in relative abundance; only E. coli was detected at two different times (bimesters 3 and 6) in room B for recipients. Interestingly, the ESKAPE member Enterobacter hormaechei was detected in the donor room (A), with an increase in relative abundance towards the warmer months of the year (bimesters 1, 3, and 4).
Figure 5 shows the heat maps of the seasonal behavior of the bacterial aerobiome of the HSC transplant area at HJM during January to December 2023 (distributed according to bimonthly analysis).

3.6. No Significant Difference in Fungal Aerobiome Between Rooms

Regarding the fungal aerobiome loads, the ANOVA and Tukey’s post hoc test revealed the absence of significant differences between the microbiological loads per m3 of the aerobiome between the areas analyzed (p > 0.05). In microbiological terms, the degree of fungal contamination per m3 was similar between the areas, regardless of the room type (with or without HEPA filtration and positive pressure).
Figure 6A shows the results of the ANOVA and Tukey’s post hoc test for the statistical comparison of the fungal aerobiome, and Figure 6B shows representative microphotographs of the macro- and microscopic identification findings for the filamentous fungal genera of the culturable aerobiome in the HSC transplant area at HJM.

3.7. Fungal Aerobiome Reveals Filamentous Fungi Involved in Nosocomial Fungemia

The macro- and microscopic analysis of the most frequent morphotypes of the filamentous fungi that were isolated in the rooms of the HSC transplant ward revealed the presence of clinically important genera involved in cases of fungemia and/or invasive mycosis in transplant patients, such as Aspergillus fumigatus, Alternaria spp., Cladosporium spp., and Penicillium spp. This was due to the observation of characteristic asexual reproductive structures of the isolates. The four fungal genera were homogeneously distributed in the four rooms. Figure 5B shows the morphological identification of filamentous fungi from the HSC transplant area at HJM during January to December 2023.

3.8. Molecular Typing of ESKAPE Members in the Aerobiome by ERIC-PCR

The profiles of the intergenic products obtained by end point-PCR for E. cloacae and E. hormaechei isolated from the aerobiome revealed that the sizes of the amplicons ranged from slightly more than ≈280 bp to about ≈1600 bp. The intergenic region diversity (six different amplicons) showed that the seven isolates of E. hormaechei (n = 4) and E. cloacae (n = 3) were grouped into two unique clonal groups. In the case of the seven isolates of E. coli from the aerobiome, it revealed that the sizes of the amplicons ranged from slightly more than ≈100 bp to about ≈1400 bp and were grouped into a single clonal group.
Therefore, it is concluded that three clonal groups were identified, distributed across three Gram-negative bacterial genera from the ESKAPE group. The spatial distribution of these ESKAPE group clones (by room in the HSC transplant area) is shown in the heat maps in Figure 5. In Figure 7, the clonal dispersion dendrograms for E. coli, E. hormaechei, and E. cloaceae in the HSC transplant rooms at HJM are shown.

3.9. Vester Matrix Construction for Microbiological Situations in the Transplant Area

A Vester matrix was constructed to classify different situations according to their degree of causality and determine which ones resulted in microbiological problems in the HSC transplant area at HJM. Twenty-four main controversial situations were identified (Figure 8A). Additionally, the degree of causality of the microbiological findings was analyzed by the type of pathogen, whether it was multidrug-resistant (MDR) or non-MDR, and the clonal dispersion of the microorganisms. The results revealed that, of the controversial situations (24/100%), nine critical problems (37.5%), one passive problem (4.1%), zero active problems (0%), and fourteen indifferent problems (58.3%) were identified, with contamination by external microorganisms (P1) being the most relevant critical problem, followed by the contamination of medical equipment (P9) and cross-contamination between patients (P3). In contrast, bacterial (including MDR) and fungal microbiological problems (P11-P24) were grouped as indifferent problems; however, they were closely related to the critical problems as they were the result of the indifferent problems. Figure 8A shows the Vester matrix with the 24 controversial situations that could impact the microbiological characteristics of the HSC transplant area at HJM, and Figure 8B shows the spatial distribution of the passive, critical, indifferent, and active problems.

4. Discussion

Opportunistic infections in oncology patients are a challenge in hospital settings, as they pose significant risks to the patients who suffer from them, with the depletion of the immune system being the main factor of susceptibility. Even when the HSC transplantation procedure is successful, poor air quality and microbiological control can exacerbate the inherent risk of this medical procedure, allowing the spread of opportunistic pathogens of bacterial and/or fungal origin and consequently the development of infections. These microorganisms, which, under normal conditions, would not cause disease, can cause life-threatening infections in immunocompromised patients.
Therefore, it is crucial to implement strict airborne microbiological surveillance and control measures in the areas where patients are kept in order to minimize exposure to airborne contamination and consequently reduce the incidence of opportunistic infections and thus increase the chances of recovery.
Subsequently, the objective of the present study was the seasonal characterization of the aerobiome in the HSC transplant area at HJM, to relate the microbiological findings to the infrastructure of this area and to possible weaknesses in the operability of the health personnel, which could have an impact on the characteristics of the aerobiome. As observed in Figure 1 and Table 1, the area coded as “room D” was the only room with HEPA filtration and positive pressure infrastructure. These features showed a positive impact in this area, with the lowest levels of PM > 1.0, 2.5, and 10 μm (Figure 2A–G). High-efficiency HEPA filtration has been recognized as one of the best alternatives in reducing PM, including infectious bioaerosols, in various environments, such as domestic environments and areas in and around schools [30,31,32]. Concerns about the negative impact of PM and the development of chronic degenerative diseases and the need for its reduction in the hospital environment have already been described [33,34].
An important aspect to consider is that HEPA filtration systems are designed to reduce the PM load (including bacteria, spores, etc.); however, it is not a system that promotes zero microbiological contamination rates. A relevant finding is shown in Figure 3, where the seasonal influence on the fluctuations in the microbial load can be identified; this may indicate that certain periods have the most favorable conditions for microbial growth, such as the temperature and RH, which showed upward behavior in the hot months (Figure 2H,I). These results provide insights into the dynamics of microbial loads, highlighting the importance of more rigorous monitoring and control, such as the immediate implementation of improved hygiene practices and environmental control in those months where the conditions are most favorable for microbial growth.
This information can be crucial as it confirms that filtration systems act as barriers to microbiological contamination. This can be seen in Figure 4A, where it is shown that, even though significantly different rates (p = 0.0197) of airborne contamination were detected in the controlled room (D) compared to uncontrolled areas, it could be detected and quantified during the study period. In contrast, the findings for the fungal load showed no significant differences between these same areas, even with the presence of HEPA filtration and positive pressure in room D (Figure 6A), suggesting the homogeneous distribution of these microorganisms in the hospital environment, regardless of seasonality and the influence that the temperature and RH may have on their presence and abundance, as fungal spores are known to be resistant to factors such as the temperature, humidity, water availability, and others. The influence of seasonality on the behavior of the bacterial and fungal loads (Figure 3 and Figure 5) has already been reported in a previous work investigating the aerobiome in hospital environments. Nuñez and García (2023) characterized the hospital aerobiome to determine seasonal trends and the impact on window opening [35]. This work highlighted the complex taxonomic composition and relative abundance of the bacterial load in the autumn and summer months, where it is speculated that factors such as the ambient temperature may influence the changes in the taxonomic diversity and relative abundance of the aerobiome.
Regarding aerobiome characterization, while the taxonomic diversity analysis revealed bacteria predominantly from the coagulase-negative staphylococci (Figure 4B), which are considered to be environmental bacteria, seven of the ten species identified have been reported as opportunistic pathogens in patients with HSC transplants (Table 2).
We speculate that the heterogeneity in the presence and absence of species such as S. warneri, S. equorum, and S. epidermidis in the analyzed areas arises from multifactorial contamination events that could be influenced by various causes; however, the predominance of S. epidermidis in “room D” provides indications of contamination by bacteria from entirely biological (skin) sources. In contrast, the ESKAPE group of bacteria has been recognized as one of the main microbiological problems in hospital centers, mainly where critical patients are cared for.
During the COVID-19 pandemic, the ESKAPE group was identified as the group of microorganisms that led to the worsening of patients, as they generated co-infections with the SARS-CoV-2 virus and formed some of the bacterial contaminants on surfaces and/or medical devices [14,21,36]. In a worldwide report by the Antimicrobial Resistance Collaborators, a systematic analysis was provided for the 2019 Global Burden of Disease Study, where global mortality was associated with 33 bacterial pathogens, with the ESKAPE group being the main one, ranking among the top ten infectious bacterial agents causing death in susceptible patients. In particular, E. coli, the genus Enterobacter, and E. faecalis were ranked second, seventh, and ninth, respectively [37]. The microbiological findings of these three members of the ESKAPE bacteria, together with the clonal spread of Gram-negative bacilli in the rooms of HSC recipients, could reflect one of the most important exogenous contamination health problems in transplant areas in this work (Figure 7 and Table 2).
Table 2. Summary of opportunistic infections in patients with HSC transplantation reported in the scientific literature and compared with the findings of the present work.
Table 2. Summary of opportunistic infections in patients with HSC transplantation reported in the scientific literature and compared with the findings of the present work.
PathogenGenusSpeciesInfections in HSC Transplant PatientsReferences
Gram-PositiveStaphylococcusS. warneriBacteremia, oral disbiosis, oral mucositis[38,39,40]
S. haemolyticusBacteremia, meningitis, oral mucositis[38,39,41]
S. equorumSurgical site in liver transplant patients[42]
S. saprophyticusBacteremia[43]
S. epidermidisBacteremia[18]
S. ureilyticusNon-reportedNA *
S. hominisBacteremia[44]
S. capitisBacteremia[18]
S. arlettaeNon-reportedNA *
S. borealisNon-reportedNA *
EnterococcusE. faecalisBacteremia, enteric mucositis[45,46,47]
MicrococcusM. luteusCatheter-related septic shock[48]
AerococcusA. viridansNon-reportedNA *
KocuriaK. rhizophilaCatheter-related bacteremia[49]
BacillusB. pumilusNon-reportedNA *
B. mojavensis
LactobacillusL. curvatus
LacticaseibacillusL. paracasei
CytobacillusC. oceanisediminis
MetabacillusM. halosaccharovorans
PriestiaP. endophytica
P. megaterium
Gram-NegativeEnterobacterE. hormaecheiRectal and intestinal colonization[50,51]
E. cloacaeGut and urinary tract infections, bacteremia[52,53,54,55]
EscherichiaE. coliBacteremia, gastrointestinal colonization[56,57,58]
AcinetobacterA. IwoffiiBacteremia, colitis, pneumonia[59,60,61]
ShewanellaS. putrefaciensBacteremia[62,63]
PseudomonasP. putidaBacteremia[61,64]
FungiAlternariaAlternaria spp.Cutaneous phaeohyphomycosis, cutaneous alternariosis, fungal infection (brain, sinus, and skin)[65,66,67]
CladosporiumCladosporium spp.Invasive mold infections [68,69]
AspergillusA. fumigatusRhino-cerebral, cutaneous and pulmonary aspergillosis, disseminated, and gastrointestinal[70,71]
PenicilliumPenicillium spp.Invasive fungal infection, pulmonary fungal infection[72,73]
* NA: Non-applicable.
The clonal spread of the ESKAPE group bacteria has already been reported at the HJM in other critical patient care areas, the most important being the ICU for COVID-19 patients. In this context, Loyola-Cruz et al. (2023) and Durán-Manuel et al. (2021) identified the clonal spread of Acinetobacter baumannii MDR and Pseudomonas aeruginosa MDR/XDR in patients with ventilator-associated pneumonia (VAP) and as microbiological contamination in medical devices in the ICU, and this problem was exposed with an emphasis on the importance of adopting good practices in patient management and cleaning and disinfection protocols [14,74]. As shown in Figure 4B, even though the frequency of the airborne isolation of these microorganisms in the transplant area was low, their isolation has clinical relevance due to the possibility of their clonal spread on surfaces and medical devices and in patients. Finally, the mycological findings and their clinical relevance are summarized in Table 2. In recent years, filamentous fungi such as Alternaria spp. and Cladosporium spp. have been considered as emerging pathogens in transplant patients, causing life-threatening skin and invasive infections [66,68].
The fungus A. fumigatus is particularly relevant due to its high production of enzymes with proteolytic activity, which gives it an enormous capacity to cause a variety of serious infections, such as pulmonary mycosis to disseminated infections [75]. This is why the early detection and treatment of fungal infections is critical due to the high mortality associated with them. It is important to mention that, during the study period, eleven HSC transplants were performed in room D, where two cases of post-transplant opportunistic mycoses were detected (18%). These cases were represented by two male patients aged 17 and 53 years, with mucositis and pneumonia caused by Candida spp. and Aspergillus fumigatus, respectively, with ALL and multiple myeloma being the oncohematological pathologies associated with these two cases. The above discussion highlights two needs: infrastructure to control these parameters in all areas of care and mainly changes that impact the management of critically ill patients by healthcare personnel. For this reason, a risk matrix was generated, which detected critical problems that could directly influence microbiological contamination in these areas, considering various controversial situations, such as the relaxation of entry protocols to controlled areas, the inappropriate use or reuse of personal protection equipment (PPE), failures in the ventilation system, contamination by visitors, etc. (Figure 8). This tool facilitated an understanding of the controversial situations in this area in a simple and practical way (Figure 8A). We identified that, even if an area has positive pressure infrastructure and other microbiological control features, as shown in Table 1, these will be of low impact if the active problems (P1-P6 and P8-P10) are not immediately addressed.
This is in accordance with the results shown in the problem distribution map in Figure 8B. It is important to mention that the indifferent problems may be underestimated under the definition that they are those that are not exclusively related to the critical problems, as they may be the outcomes of the situations that give rise to active problems. Therefore, the fundamental purpose of this type of research is to encourage adherence to all activities that could lead to exogenous microbiological contamination in controlled areas, rather than merely proposing that positive pressure and filtration infrastructure is the only way to ensure microbiologically “clean” critical areas. As mentioned, transplantation is a complex medical procedure; however, these medical efforts can be hampered by bacterial and fungal infections, so the air in the rooms where these procedures are performed should be subject to surveillance. Alternatively, the seasonal variability in the degree of microbiological contamination highlights the need to implement more rigorous environmental control strategies during periods of increased risk.

5. Conclusions

This study shows the importance of monitoring and controlling the aerobiome in HSC transplant rooms to minimize the risk of nosocomial infections, where the implementation of measures such as HEPA filtration and the maintenance of positive pressure in critical areas is essential to improve clinical outcomes and reduce the morbidity and mortality associated with infections in immunocompromised patients.

Author Contributions

Conceptualization, J.M.B.-L. and C.C.C.-M.; methodology, E.M.D.-M., E.F.-B., M.Á.L.-C., C.C.-C., M.P.-M., A.V.R.-T., D.M.R.B.-H., V.F.-S., N.G.N.-V. and A.R.-G.; software, A.E.N.-R., M.P.-M., E.G.-Z., M.A.C.-D., V.F.-S., A.M.-S. and A.L.-O.; validation, J.M.B.-L. and C.C.C.-M.; formal analysis, E.M.D.-M., E.F.-B., J.M.B.-L. and C.C.C.-M.; investigation, E.M.D.-M., E.F.-B., M.Á.L.-C., C.C.-C., D.M.R.B.-H., C.A.J.-Z., A.M.-S. and E.V.-J.; resources, J.M.B.-L. and C.C.C.-M.; data curation, A.E.N.-R., N.G.N.-V., E.V.-J. and A.L.-O.; writing—original draft preparation, J.M.B.-L. and C.C.C.-M.; writing—review and editing, J.M.B.-L., C.C.C.-M. and E.M.D.-M.; visualization, A.E.N.-R. and J.M.B.-L.; supervision, J.M.B.-L. and C.C.C.-M.; project administration, J.M.B.-L. and C.C.C.-M.; funding acquisition, J.M.B.-L. and C.C.C.-M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The institutional Committee of Research, Ethics, and Biosafety from HJM approved the protocol under the registration number HJM 035/23-I, in accordance with the Regulation of the General Health Law on Research for Health (https://www.diputados.gob.mx/LeyesBiblio/regley/Reg_LGS_MIS.pdf (accessed on 12 November 2024)).

Data Availability Statement

Bello-López, Juan Manuel (2024), “Seasonal Characterization of the Aerobiome in Hematopoietic Stem Cells Transplant Rooms: Potential Risk for Immunosuppressed Patients”, Mendeley Data, V1, http://doi.org/10.17632/58vc8fcyd9.1.

Acknowledgments

A.L.-O., D.M.R.B.-H., N.G.N.-V, A.V.R.-T., E.V.-J., V.F.-S., M.A.C.-D., C.C.C.-M., and J.M.B.-L. received support from “Sistema Nacional de Investigadoras e Investigadores (SNII)” from Consejo Nacional de Ciencias Humanidades y Tecnologías (CONAHCyT). E.M.D.-M., A.E.N.-R. and C.C.-C. were supported by a fellowship from CONAHCyT México. C.C.C.-M. received support from Secretaría de Investigación y Posgrado and Comisión y Fomento de Actividades Académicas (C.O.F.A.A.) from the Instituto Politécnico Nacional (IPN), Secretaría de Investigación y Posgrado (Project 20241248) and the Plan de Mejora “Apoyo a las Secciones de Estudios de Posgrado e Investigación, SEPI” del Instituto Politécnico Nacional.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Meaker, G.A.; Wilkinson, A.C. Ex vivo hematopoietic stem cell expansion technologies: Recent progress, applications, and open questions. Exp. Hematol. 2024, 130, 104136. [Google Scholar] [CrossRef] [PubMed]
  2. Du, Y.; Han, B. Advances in Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria. Transplant. Cell Ther. 2021, 27, 301–307. [Google Scholar] [CrossRef]
  3. Rivera-Luna, R.; Perez-Vera, P.; Galvan-Diaz, C.; Velasco-Hidalgo, L.; Olaya-Vargas, A.; Cardenas-Cardos, R.; Aguilar-Ortiz, M.; Ponce-Cruz, J. Triple-hit explanation for the worse prognosis of pediatric acute lymphoblastic leukemia among Mexican and Hispanic children. Front. Oncol. 2022, 12, 1072811. [Google Scholar] [CrossRef] [PubMed]
  4. Penack, O.; Marchetti, M.; Aljurf, M.; Arat, M.; Bonifazi, F.; Duarte, R.F.; Giebel, S.; Greinix, H.; Hazenberg, M.D.; Kröger, N.; et al. Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: Updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2024, 11, e147–e159. [Google Scholar] [CrossRef] [PubMed]
  5. Busmail, A.; Penumetcha, S.S.; Ahluwalia, S.; Irfan, R.; Khan, S.A.; Rohit Reddy, S.; Vasquez Lopez, M.E.; Zahid, M.; Mohammed, L.A. Systematic Review on Pulmonary Complications Secondary to Hematopoietic Stem Cell Transplantation. Cureus 2022, 14, e24807. [Google Scholar] [CrossRef] [PubMed]
  6. Hayek, S.S.; Zaha, V.G.; Bogle, C.; Deswal, A.; Langston, A.; Rotz, S.; Vasbinder, A.; Yang, E.; Okwuosa, T.; American Heart Association Cardio-Oncology Committee of the Council on Clinical Cardiology and Council on Genomic and Precision Medicine, and the Council on Cardiovascular and Stroke Nursing. Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association. Circulation 2024, 149, e1113–e1127. [Google Scholar] [CrossRef]
  7. Cho, S.Y.; Lee, H.J.; Lee, D.G. Infectious complications after hematopoietic stem cell transplantation: Current status and future perspectives in Korea. Korean J. Intern. Med. 2018, 33, 256–276. [Google Scholar] [CrossRef]
  8. Pereira, M.R.; Pouch, S.M.; Scully, B. Infections in Allogeneic Stem Cell Transplantation. In Principles and Practice of Transplant Infectious Diseases; Springer: New York, NY, USA, 2018; pp. 209–226. [Google Scholar]
  9. Ferdjallah, A.; Young, J.H.; MacMillan, M.L. A Review of Infections After Hematopoietic Cell Transplantation Requiring PICU Care: Transplant Timeline Is Key. Front. Pediatr. 2021, 9, 634449. [Google Scholar] [CrossRef]
  10. Vargas-Espíndola, L.A.; Cuervo-Maldonado, S.I.; Enciso-Olivera, J.L.; Gómez-Rincón, J.C.; Jiménez-Cetina, L.; Sánchez-Pedraza, R.; García-Guzmán, K.; López-Mora, M.J.; Álvarez-Moreno, C.A.; Cortés, J.A. Fungemia in Hospitalized Adult Patients with Hematological Malignancies: Epidemiology and Risk Factors. J. Fungi 2023, 9, 400. [Google Scholar] [CrossRef]
  11. Alp, S.; Akova, M. Antibacterial Resistance in Patients with Hematopoietic Stem Cell Transplantation. Mediterr. J. Hematol. Infect. Dis. 2017, 9, e2017002. [Google Scholar]
  12. Krüger, W.H.; Bohlius, J.; Cornely, O.A.; Einsele, H.; Hebart, H.; Massenkeil, G.; Schüttrumpf, S.; Silling, G.; Ullmann, A.J.; Waldschmidt, D.T.; et al. Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology. Ann. Oncol. 2005, 16, 1381–1390. [Google Scholar] [CrossRef] [PubMed]
  13. Zając-Spychała, O.; Wachowiak, J.; Pieczonka, A.; Siewiera, K.; Frączkiewicz, J.; Kałwak, K.; Gorczyńska, E.; Chybicka, A.; Czyżewski, K.; Jachna-Sawicka, K.; et al. Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: Incidence, epidemiology, and spectrum of pathogens: Report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation. Transpl. Infect. Dis. 2016, 18, 690–698. [Google Scholar] [CrossRef] [PubMed]
  14. Durán-Manuel, E.M.; Cruz-Cruz, C.; Ibáñez-Cervantes, G.; Bravata-Alcantará, J.C.; Sosa-Hernández, O.; Delgado-Balbuena, L.; León-García, G.; Cortés-Ortíz, I.A.; Cureño-Díaz, M.A.; Castro-Escarpulli, G.; et al. Clonal dispersion of Acinetobacter baumannii in an intensive care unit designed to patients COVID-19. J. Infect. Dev. Ctries. 2021, 15, 58–68. [Google Scholar] [CrossRef]
  15. Mousavi, E.S.; Kananizadeh, N.; Martinello, R.A.; Sherman, J.D. COVID-19 outbreak and hospital air quality: A systematic review of evidence on air filtration and recirculation. Environ. Sci. Tech. 2020, 55, 4134–4147. [Google Scholar] [CrossRef] [PubMed]
  16. Ling, S.; Hui, L. Evaluation of the complexity of indoor air in hospital wards based on PM2.5, real-time PCR, adenosine triphosphate bioluminescence assay, microbial culture and mass spectrometry. BMC Infect. Dis. 2019, 19, 646. [Google Scholar] [CrossRef] [PubMed]
  17. Matoušková, I.; Holy, O. Monitoring of the environment at the transplant unit-hemato-oncology clinic. Int. J. Environ. Res. Public Health 2014, 11, 9480–9490. [Google Scholar] [CrossRef]
  18. Gill, J.; Busca, A.; Cinatti, N.; Passera, R.; Dellacasa, C.M.; Giaccone, L.; Dogliotti, I.; Manetta, S.; Corcione, S.; De Rosa, F.G. Bacterial Bloodstream Infections after Allogeneic Hematopoietic Stem Cell Transplantation: Etiology, Risk Factors and Outcome in a Single-Center Study. Microorganisms 2023, 11, 742. [Google Scholar] [CrossRef]
  19. Brun, C.P.; Miron, D.; Silla, L.M.; Pasqualotto, A.C. Fungal spore concentrations in two haematopoietic stem cell transplantation (HSCT) units containing distinct air control systems. Epidemiol. Infect. 2013, 141, 875–879. [Google Scholar] [CrossRef]
  20. Krüger, W.H.; Zöllner, B.; Kaulfers, P.M.; Zander, A.R. Effective protection of allogeneic stem cell recipients against Aspergillosis by HEPA air filtration during a period of construction--a prospective survey. J. Hematother. Stem Cell Res. 2003, 12, 301–307. [Google Scholar] [CrossRef]
  21. Holý, O.; Matoušková, I. The importance of cleanrooms for the treatment of haemato-oncological patients. Contemp. Oncol. 2012, 16, 266–272. [Google Scholar] [CrossRef]
  22. Tsai, C.K.; Yeh, C.M.; Hong, Y.C.; Chen, P.M.; Liu, J.H.; Gau, J.P.; Liu, C.J. The influence of high-efficiency particulate air filtration on mortality among multiple myeloma patients receiving autologous stem cell transplantation. Sci. Rep. 2021, 11, 11789. [Google Scholar] [CrossRef] [PubMed]
  23. Xing, Y.F.; Xu, Y.H.; Shi, M.H.; Lian, Y.X. The impact of PM2.5 on the human respiratory system. J. Thorac. Dis. 2016, 8, E69–E74. [Google Scholar] [PubMed]
  24. Brunekreef, B.; Beelen, R.; Hoek, G.; Schouten, L.; Bausch-Goldbohm, S.; Fischer, P.; Armstrong, B.; Hughes, E.; Jerrett, M.; van den Brandt, P. Effects of long-term exposure to traffic-related air pollution on respiratory and cardiovascular mortality in the Netherlands: The NLCS-AIR study. Res. Rep. Health Eff. Inst. 2009, 139, 5–71. [Google Scholar]
  25. Inkster, T.; Peters, C.; Dancer, S. Safe design and maintenance of bone marrow transplant units: A narrative review. Clin. Microbiol. Infect. 2022, 28, 1091–1096. [Google Scholar] [CrossRef]
  26. Johnson, E.M.; Borman, A.M. The importance of conventional methods: Microscopy and culture. In Aspergeukaryotic Cellillosis: From Diagnosis to Prevention; Pascualotto, A., Ed.; Springer: New York, NY, USA, 2010; pp. 55–73. [Google Scholar]
  27. Versalovic, J.; Koeuth, T.; Lupski, J.R. Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res. 1991, 19, 6823–6831. [Google Scholar] [CrossRef]
  28. Tenover, F.C.; Arbeit, R.D.; Goering, R.V.; Mickelsen, P.A.; Murray, B.E.; Persing, D.H.; Swaminathan, B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: Criteria for bacterial strain typing. J. Clin. Microbiol. 1995, 33, 2233–2239. [Google Scholar] [CrossRef]
  29. Cole, A. The Influence Matrix Methodology: A Technical Report. Landcare Research Contract Report No. LC0506/175. 2006. Available online: https://icm.landcareresearch.co.nz/knowledgebase/publications/public/imatrix_tech_report.pdf (accessed on 11 November 2024).
  30. Bluyssen, P.M.; Ortiz, M.; Zhang, D. The effect of a mobile HEPA filter system on ‘infectious’ aerosols, sound and air velocity in the SenseLab. Build Environ. 2021, 188, 107475. [Google Scholar] [CrossRef]
  31. Rawat, N.; Kumar, P. Interventions for improving indoor and outdoor air quality in and around schools. Sci. Total Environ. 2023, 858, 159813. [Google Scholar] [CrossRef]
  32. Chen, C.F.; Hsu, C.H.; Chang, Y.J.; Lee, C.H.; Lee, D.L. Efficacy of HEPA Air Cleaner on Improving Indoor Particulate Matter 2.5 Concentration. Int. J. Environ. Res. Public Health 2022, 19, 11517. [Google Scholar] [CrossRef]
  33. Tecer, L.H.; Alagha, O.; Karaca, F.; Tuncel, G.; Eldes, N. Particulate matter (PM(2.5), PM(10-2.5), and PM(10)) and children’s hospital admissions for asthma and respiratory diseases: A bidirectional case-crossover study. J. Toxicol. Environ. Health A 2008, 71, 512–520. [Google Scholar] [CrossRef]
  34. Ren, Z.; Liu, X.; Liu, T.; Chen, D.; Jiao, K.; Wang, X.; Suo, J.; Yang, H.; Liao, J.; Ma, L. Effect of ambient fine particulates (PM2.5) on hospital admissions for respiratory and cardiovascular diseases in Wuhan, China. Respir. Res. 2021, 22, 128. [Google Scholar] [CrossRef] [PubMed]
  35. Núñez, A.; García, A.M. The aerobiome in a hospital environment: Characterization, seasonal tendencies and the effect of window opening ventilation. Build. Environ. 2023, 230, 110024. [Google Scholar] [CrossRef]
  36. Cureño-Díaz, M.A.; Durán-Manuel, E.M.; Cruz-Cruz, C.; Ibáñez-Cervantes, G.; Rojo-Gutiérrez, M.I.; Moncayo-Coello, C.V.; Loyola-Cruz, M.Á.; Castro-Escarpulli, G.; Razo-Blanco Hernández, D.M.; Bello-López, J.M. Impact of the modification of a cleaning and disinfection method of mechanical ventilators of COVID-19 patients and ventilator-associated pneumonia: One year of experience. Am. J. Infect. Control 2021, 49, 1474–1480. [Google Scholar] [CrossRef] [PubMed]
  37. GBD 2019 Antimicrobial Resistance Collaborators. Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet 2022, 400, 2221–2248. [Google Scholar] [CrossRef]
  38. Chebbi, Y.; Frigui, S.; Raddaoui, A.; Belloumi, D.; Lakhal, A.; Torjemane, L.; Abeljelil, N.B.; Ladeb, S.; Othmen, T.B.; Fatmi, R.E.; et al. Coagulase negative Staphylococcus bacteremia in hematopoietic stem cell transplant recipients: Clinical features and molecular characterization. Acta Microbiol. Immunol. Hung. 2021, 68, 73–79. [Google Scholar] [CrossRef]
  39. Osakabe, L.; Utsumi, A.; Saito, B.; Okamatsu, Y.; Kinouchi, H.; Nakamaki, T.; Hironaka, S. Influence of Oral Anaerobic Bacteria on Hematopoietic Stem Cell Transplantation Patients: Oral Mucositis and General Condition. Transplant. Proc. 2017, 49, 2176–2182. [Google Scholar] [CrossRef]
  40. Laheij, A.M.G.A.; Raber-Durlacher, J.E.; Koppelmans, R.G.A.; Marie-Charlotte, D.N.; Huysmans, J.M.; Potting, C.; van Leeuwen, S.J.M.; Hazenberg, M.D.; Brennan, M.T.; von Bültzingslöwen, I.; et al. Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients. Sci. Rep. 2019, 9, 16929. [Google Scholar] [CrossRef]
  41. Oyama, T.; Kageyama, K.; Araoka, H.; Mitsuki, T.; Yamaguchi, K.; Kaji, D.; Taya, Y.; Nishida, A.; Ishiwata, K.; Takagi, S.; et al. Clinical and microbiological characteristics of bacterial meningitis in umbilical cord blood transplantation recipients. Int. J. Hematol. 2022, 116, 966–972. [Google Scholar] [CrossRef]
  42. Kawecki, D.; Chmura, A.; Pacholczyk, M.; Lagiewska, B.; Adadynski, L.; Wasiak, D.; Malkowski, P.; Sawicka-Grzelak, A.; Rokosz, A.; Szymanowska, A.; et al. Surgical site infections in liver recipients in the early posttransplantation period: Etiological agents and susceptibility profiles. Transplant. Proc. 2007, 39, 2800–2806. [Google Scholar] [CrossRef]
  43. Ali, N.; Adil, S.N.; Shaikh, M.U. Bloodstream and central line isolates from hematopoietic stem cell transplant recipients: Data from a developing country. Transpl. Infect. Dis. 2014, 16, 98–105. [Google Scholar] [CrossRef]
  44. Song, W.; Song, X.; Zhu, Y.; Ren, Y.; Xu, J.; Zhu, Q. Microbiology and Clinical Outcome of Bloodstream Infections in Patients After Hematopoietic Stem Cell Transplantation. Infect. Drug. Resist. 2023, 17, 5375–5386. [Google Scholar] [CrossRef] [PubMed]
  45. Benamu, E.; Deresinski, S. Vancomycin-resistant enterococcus infection in the hematopoietic stem cell transplant recipient: An overview of epidemiology, management, and prevention. F1000Research 2018, 7, 3. [Google Scholar] [CrossRef] [PubMed]
  46. Balletto, E.; Mikulska, M. Bacterial Infections in Hematopoietic Stem Cell Transplant Recipients. Mediterr. J. Hematol. Infect. Dis. 2015, 7, e2015045. [Google Scholar] [CrossRef] [PubMed]
  47. Mikulska, M.; Del Bono, V.; Raiola, A.M.; Bruno, B.; Gualandi, F.; Occhini, D.; di Grazia, C.; Frassoni, F.; Bacigalupo, A.; Viscoli, C. Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: Reemergence of Gram-negative rods and increasing antibiotic resistance. Biol. Blood Marrow Transplant. 2009, 15, 47–53. [Google Scholar] [CrossRef]
  48. Kogure, Y.; Nakamura, F.; Nukina, A.; Kamikubo, Y.; Ichikawa, M.; Kurokawa, M.; Kamikubo, Y.; Kurokawa, M. Catheter-related septic shock by Micrococcus in an autologous hematopoietic stem cell transplantation recipient. Am. J. Infect. Control 2014, 42, 87. [Google Scholar] [CrossRef]
  49. Altuntas, F.; Yildiz, O.; Eser, B.; Gündogan, K.; Sumerkan, B.; Çetin, M. Catheter-related bacteremia due to Kocuria rosea in a patient undergoing peripheral blood stem cell transplantation. BMC Infect. Dis. 2004, 4, 62. [Google Scholar] [CrossRef]
  50. Cao, W.; Zhang, J.; Bian, Z.; Li, L.; Zhang, S.; Qin, Y.; Wan, D.; Jiang, Z.; Zhang, R. Active screening of intestinal colonization of carbapenem-resistant Enterobacteriaceae for subsequent bloodstream infection in allogeneic hematopoietic stem cell transplantation. Infect. Drug Resist. 2022, 15, 5993–6006. [Google Scholar] [CrossRef]
  51. Yan, L.; Sun, J.; Xu, X.; Huang, S. Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital. Antimicrob. Resist. Infect. Control 2020, 9, 155. [Google Scholar] [CrossRef]
  52. Zając-Spychała, O.; Wachowiak, J.; Frączkiewicz, J.; Salamonowicz, M.; Kałwak, K.; Gorczyńska, E.; Chybicka, A.; Czyżewski, K.; Dziedzic, M.; Wysocki, M.; et al. Multidrug-resistant bacterial infections in children undergoing haematopoietic stem cell transplantation over a 6-year period: Analysis of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation. J. Appl. Microbiol. 2020, 128, 292–300. [Google Scholar] [CrossRef]
  53. Liu, D.Y.; Xiong, M.; Zhang, J.P.; Lu, Y.; Wei, Z.J.; Zhao, Y.L.; Cao, X.Y.; Sun, R.J.; Zhou, J.R.; Yuan, L.L. Incidence and predisposing risk factors of blood stream infections occurred pre-engraftment in 757 patients with allogeneic hematopoietic stem cell transplantation. J. Clin. Hematol. 2021, 34, 24–30. [Google Scholar]
  54. Yan, C.H.; Wang, Y.; Mo, X.D.; Sun, Y.Q.; Wang, F.R.; Fu, H.X.; Chen, Y.; Han, T.T.; Kong, J.; Cheng, Y.F.; et al. Incidence, Risk Factors, Microbiology and Outcomes of Pre-engraftment Bloodstream Infection After Haploidentical Hematopoietic Stem Cell Transplantation and Comparison With HLA-identical Sibling Transplantation. Clin. Infect. Dis. 2018, 67, S162–S173. [Google Scholar] [CrossRef] [PubMed]
  55. Heston, S.M.; Young, R.R.; Hong, H.; Akinboyo, I.C.; Tanaka, J.S.; Martin, P.L.; Vinesett, R.; Jenkins, K.; McGill, L.E.; Hazen, K.C.; et al. Microbiology of bloodstream infections in children after hematopoietic stem cell transplantation: A single-center experience over two decades (1997–2017). Open Forum Infect. Dis. 2020, 7, ofaa465. [Google Scholar] [CrossRef] [PubMed]
  56. Blennow, O.; Ljungman, P.; Sparrelid, E.; Mattsson, J.; Remberger, M. Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl. Infect. Dis. 2014, 16, 106–114. [Google Scholar] [CrossRef] [PubMed]
  57. Malagola, M.; Rambaldi, B.; Ravizzola, G.; Cattaneo, C.; Borlenghi, E.; Polverelli, N.; Turra, A.; Morello, E.; Skert, C.; Cancelli, V.; et al. Bacterial Blood Stream Infections Negatively Impact on Outcome of Patients Treated with Allogeneic Stem Cell Transplantation: 6 Years Single-Centre Experience. Mediterr. J. Hematol. Infect. Dis. 2017, 9, e2017036. [Google Scholar] [CrossRef] [PubMed]
  58. Kubiak, J.; Davidson, E.; Soave, R.; Kodiyanplakkal, R.P.; Robertson, A.; Besien, K.V.; Shore, T.B.; Lee, J.R.; Westblade, L.F.; Satlin, M.J. Colonization with Gastrointestinal Pathogens Prior to Hematopoietic Cell Transplantation and Associated Clinical Implications. Transplant. Cell. Ther. 2021, 27, 499.e1–499.e6. [Google Scholar] [CrossRef]
  59. Amer, R.; Salameh, H.; Mosleh, S.; Abu-Taha, A.; Hamayel, H.; Enaya, A.; Adas, A.; Khursani, A.; Wild-Ali, M.; Mousa, T.; et al. Epidemiology of early infections and predictors of mortality after autologous hematopoietic stem-cell transplantation among multiple myeloma, Hodgkin, and non-Hodgkin lymphoma: The first experience from Palestine. BMC Infect. Dis. 2022, 22, 725. [Google Scholar] [CrossRef]
  60. Averbuch, D.; Engelhard, D. Gram-Negative Bacterial Infections After Hematopoietic Stem Cell or Solid Organ Transplantation. In Transplant Infections, 4th ed.; Springer: Cham, Switzerland, 2016; pp. 357–380. [Google Scholar]
  61. Mikulska, M.; Raiola, A.M.; Galaverna, F.; Balletto, E.; Borghesi, M.L.; Varaldo, R.; Gualandi, F.; Giannoni, L.; Pastori, G.; Giacobbe, D.R.; et al. Pre-Engraftment Bloodstream Infections after Allogeneic Hematopoietic Cell Transplantation: Impact of T Cell-Replete Transplantation from a Haploidentical Donor. Biol. Blood Marrow Transplant. 2018, 24, 109–118. [Google Scholar] [CrossRef]
  62. Averbuch, D.; Tridello, G.; Hoek, J.; Mikulska, M.; Akan, H.; Yanez San Segundo, L.; Pabst, T.; Özçelik, T.; Klyasova, G.; Donnini, I.; et al. Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group. Clin. Infect. Dis. 2017, 65, 1819–1828. [Google Scholar] [CrossRef]
  63. Rajendra, A.; Jain, H.; Bonda, V.A.; Nayak, L.; Tembhare, P.; Shetty, D.; Thorat, J.; Jain, H.; Subramanian, P.G.; Patkar, N.; et al. Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol. Blood Adv. 2021, 5, 1178–1193. [Google Scholar] [CrossRef]
  64. Mussetti, A.; Kernan, N.A.; Prockop, S.E.; Scaradavou, A.; Lehrman, R.; Ruggiero, J.M.; Curran, K.; Kobos, R.; O’Reilly, R.; Boulad, F. Allogeneic hematopoietic stem cell transplantation for nonmalignant hematologic disorders using chemotherapy-only cytoreductive regimens and T-cell-depleted grafts from human leukocyte antigen-matched or -mismatched donors. Pediatr. Hematol. Oncol. 2016, 33, 347–358. [Google Scholar] [CrossRef]
  65. Liu, A.W.; Bateman, A.C.; Greenbaum, A.; Garvin, K.; Clarridge, J.; Grim, J. Cutaneous phaeohyphomycosis in a hematopoietic stem cell transplant patient caused by Alternaria rosae: First case report. Transpl. Infect. Dis. 2017, 19, e12698. [Google Scholar] [CrossRef] [PubMed]
  66. Rotte, L.G.; Loeffen, Y.G.; Bierings, M.B.; Wolfs, T.F.; Lindemans, C.A. Allogenic Hematopoietic Stem Cell Transplantation Is Feasible in Pediatric Patients with an Active or Recently Diagnosed Invasive Fungal Infection. Transplant. Cell. Ther. 2021, 27, e1–e781. [Google Scholar] [CrossRef] [PubMed]
  67. Ferreira, I.D.S.; Teixeira, G.; Abecasis, M. Alternaria alternata Invasive Fungal Infection in a Patient with Fanconi’s Anemia after an Unrelated Bone Marrow Transplant. Clin. Drug Investig. 2013, 33, 33–36. [Google Scholar] [CrossRef] [PubMed]
  68. Chien, S.H.; Liu, Y.C.; Liu, C.J.; Ko, P.S.; Wang, H.Y.; Hsiao, L.T.; Chiou, T.J.; Liu, J.H.; Gau, J.P. Invasive mold infections in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation. J. Microbiol. Immunol. Infect. 2019, 52, 973–982. [Google Scholar] [CrossRef] [PubMed]
  69. Corzo-León, D.E.; Satlin, M.J.; Soave, R.; Shore, T.B.; Schuetz, A.N.; Jacobs, S.E.; Walsh, T.J. Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: A single-centre study with focus on emerging pathogens. Mycoses 2015, 58, 325–536. [Google Scholar] [CrossRef]
  70. Al-Bader, N.; Sheppard, D.C. Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies. Virulence 2016, 7, 950–966. [Google Scholar] [CrossRef]
  71. Abad, A.; Fernandez-Molina, J.V.; Bikandi, J.; Ramírez, A.; Margareto, J.; Sendino, J.; Hernando, F.L.; Pontón, J.; Garaizar, J.; Rementeria, A. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev. Iberoam. Micol. 2010, 27, 155–182. [Google Scholar] [CrossRef]
  72. Vazquez, J.A.; Miceli, M.H.; Alangaden, G. Invasive fungal infections in transplant recipients. Ther. Adv. Infect. Dis. 2013, 1, 85–105. [Google Scholar] [CrossRef]
  73. Ramírez, I.; Hidrón, A.; Cardona, R. Successful treatment of pulmonary invasive fungal infection by Penicillium non-marneffei in lymphoblastic lymphoma: Case report and literature review. Clin. Case Rep. 2018, 6, 1153–1157. [Google Scholar] [CrossRef]
  74. Loyola-Cruz, M.Á.; Durán-Manuel, E.M.; Cruz-Cruz, C.; Márquez-Valdelamar, L.M.; Bravata-Alcántara, J.C.; Cortés-Ortíz, I.A.; Cureño-Díaz, M.A.; Ibáñez-Cervantes, G.; Fernández-Sánchez, V.; Castor-Escarpulli, G.; et al. ESKAPE bacteria characterization reveals the presence of Acinetobacter baumannii and Pseudomonas aeruginosa outbreaks in COVID-19/VAP patients. Am. J. Infect. Control 2023, 51, 729–737. [Google Scholar] [CrossRef]
  75. Earle, K.; Valero, C.; Conn, D.P.; Vere, G.; Cook, P.C.; Bromley, M.J.; Bowyer, P.; Gago, S. Pathogenicity and virulence of Aspergillus fumigatus. Virulence 2023, 14, 2172264. [Google Scholar] [CrossRef] [PubMed]
Microorganisms 12 02352 g001
Figure 1. Aerial map of the HSC transplant area at HJM. (A) Donor room. (B–D) Recipient rooms.
Figure 1. Aerial map of the HSC transplant area at HJM. (A) Donor room. (B–D) Recipient rooms.
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Microorganisms 12 02352 g002
Figure 2. Standard air quality parameters of the HSC transplant rooms. PM10, PM2.5, and PM1.0 μm quantification (A–D) and Tukey’s post hoc and ANOVA tests for the comparison of the PM levels between rooms (E–G). Temperature (°C) and relative humidity (RH%) in the HSC transplant rooms (H,I). * Statistically significant (p ≤ 0.05).
Figure 2. Standard air quality parameters of the HSC transplant rooms. PM10, PM2.5, and PM1.0 μm quantification (A–D) and Tukey’s post hoc and ANOVA tests for the comparison of the PM levels between rooms (E–G). Temperature (°C) and relative humidity (RH%) in the HSC transplant rooms (H,I). * Statistically significant (p ≤ 0.05).
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Microorganisms 12 02352 g003
Figure 3. Seasonal analysis (bimonthly) of bacterial (Gram-positive/-negative) and fungal aerobiome microbiological loads analyzed in the HSC transplant area at HJM from January to December 2023. White bar: Gram-negative bacteria, gray bar: Gram-positive bacteria, and black bar: fungi.
Figure 3. Seasonal analysis (bimonthly) of bacterial (Gram-positive/-negative) and fungal aerobiome microbiological loads analyzed in the HSC transplant area at HJM from January to December 2023. White bar: Gram-negative bacteria, gray bar: Gram-positive bacteria, and black bar: fungi.
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Microorganisms 12 02352 g004
Figure 4. (A) ANOVA and Tukey’s post hoc test for the statistical comparison of the culturable bacterial aerobiome between transplant area rooms. (B) Bacterial identification findings (relative abundance and taxonomic diversity) by mass spectrometry MALDI-TOF of the culturable bacterial aerobiome (per room) of the HSC transplant area at HJM.
Figure 4. (A) ANOVA and Tukey’s post hoc test for the statistical comparison of the culturable bacterial aerobiome between transplant area rooms. (B) Bacterial identification findings (relative abundance and taxonomic diversity) by mass spectrometry MALDI-TOF of the culturable bacterial aerobiome (per room) of the HSC transplant area at HJM.
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Microorganisms 12 02352 g005
Figure 5. Heat maps of the seasonal behavior of the culturable bacterial aerobiome of the HSC transplant area at HJM during January to December 2023 (distributed according to bimonthly analysis). (A) Donor room, (B–D) recipient rooms.
Figure 5. Heat maps of the seasonal behavior of the culturable bacterial aerobiome of the HSC transplant area at HJM during January to December 2023 (distributed according to bimonthly analysis). (A) Donor room, (B–D) recipient rooms.
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Microorganisms 12 02352 g006
Figure 6. Fungal aerobiome of the HSC transplant rooms. (A) ANOVA and Tukey’s post hoc test for fungal aerobiome. (B) Macro- and microscopic identification of fungi in the aerobiome of the HSC transplant area at HJM. The colonial morphology (front and back): Alternaria sp., Cladosporium sp., Aspergillus fumigatus, and Penicillium spp. Sexual reproductive structures at 1000× total magnification. H = Hypha, Co = Conidiophore, Mc = Microconidium, Dc = Dicthyoconidium, V = Vesicle, Ph = Phialide, M = Metula.
Figure 6. Fungal aerobiome of the HSC transplant rooms. (A) ANOVA and Tukey’s post hoc test for fungal aerobiome. (B) Macro- and microscopic identification of fungi in the aerobiome of the HSC transplant area at HJM. The colonial morphology (front and back): Alternaria sp., Cladosporium sp., Aspergillus fumigatus, and Penicillium spp. Sexual reproductive structures at 1000× total magnification. H = Hypha, Co = Conidiophore, Mc = Microconidium, Dc = Dicthyoconidium, V = Vesicle, Ph = Phialide, M = Metula.
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Microorganisms 12 02352 g007
Figure 7. Genomic diversity (clonal dispersion) by dendrogram construction of ESKAPE bacteria detected in aerobiome in HSC transplant rooms of the Hospital Juárez de México. Escherichia coli (A), Enterobacter hormaechei (B), and E. cloaceae (C). PA (Pseudomonas aeruginosa as internal control).
Figure 7. Genomic diversity (clonal dispersion) by dendrogram construction of ESKAPE bacteria detected in aerobiome in HSC transplant rooms of the Hospital Juárez de México. Escherichia coli (A), Enterobacter hormaechei (B), and E. cloaceae (C). PA (Pseudomonas aeruginosa as internal control).
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Microorganisms 12 02352 g008
Figure 8. Microbiological risk analysis in the HSC transplant area at HJM. (A) Vester matrix of 24 controversial situations of potential microbiological contamination. (B) Identification and classification of problems according to the influence and dependency on the identified problems.
Figure 8. Microbiological risk analysis in the HSC transplant area at HJM. (A) Vester matrix of 24 controversial situations of potential microbiological contamination. (B) Identification and classification of problems according to the influence and dependency on the identified problems.
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Table 1. Infrastructure by room (donors and recipients) in the HSC transplant rooms at HJM.
Table 1. Infrastructure by room (donors and recipients) in the HSC transplant rooms at HJM.
CharacteristicUnitDonor RoomRecipient Rooms
ABCD
Dimensionsm23412.712.712.7
Positive pressurePaNoNoNoYes
HEPA filtration0.3 mmNoNoNoYes
Air changesAC/h00010
Sanitary sealingNon applicableNoYes YesYes
Epoxy floor coatingYesYes YesYes
Shared bathroom between patientsNoYesYesYes
Single washbasinYesYes YesYes
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MDPI and ACS Style

Durán-Manuel, E.M.; Fiscal-Baxin, E.; Nolasco-Rojas, A.E.; Loyola-Cruz, M.Á.; Cruz-Cruz, C.; Paredes-Mendoza, M.; López-Ornelas, A.; Razo Blanco-Hernández, D.M.; Nieto-Velázquez, N.G.; Rodríguez-Tovar, A.V.; et al. Seasonal Characterization of the Aerobiome in Hematopoietic Stem Cell Transplant Rooms: Potential Risk for Immunosuppressed Patients. Microorganisms 2024, 12, 2352. https://doi.org/10.3390/microorganisms12112352

AMA Style

Durán-Manuel EM, Fiscal-Baxin E, Nolasco-Rojas AE, Loyola-Cruz MÁ, Cruz-Cruz C, Paredes-Mendoza M, López-Ornelas A, Razo Blanco-Hernández DM, Nieto-Velázquez NG, Rodríguez-Tovar AV, et al. Seasonal Characterization of the Aerobiome in Hematopoietic Stem Cell Transplant Rooms: Potential Risk for Immunosuppressed Patients. Microorganisms. 2024; 12(11):2352. https://doi.org/10.3390/microorganisms12112352

Chicago/Turabian Style

Durán-Manuel, Emilio Mariano, Edgar Fiscal-Baxin, Andres Emmanuel Nolasco-Rojas, Miguel Ángel Loyola-Cruz, Clemente Cruz-Cruz, Marianela Paredes-Mendoza, Adolfo López-Ornelas, Dulce Milagros Razo Blanco-Hernández, Nayeli Goreti Nieto-Velázquez, Aída Verónica Rodríguez-Tovar, and et al. 2024. "Seasonal Characterization of the Aerobiome in Hematopoietic Stem Cell Transplant Rooms: Potential Risk for Immunosuppressed Patients" Microorganisms 12, no. 11: 2352. https://doi.org/10.3390/microorganisms12112352

APA Style

Durán-Manuel, E. M., Fiscal-Baxin, E., Nolasco-Rojas, A. E., Loyola-Cruz, M. Á., Cruz-Cruz, C., Paredes-Mendoza, M., López-Ornelas, A., Razo Blanco-Hernández, D. M., Nieto-Velázquez, N. G., Rodríguez-Tovar, A. V., Ramírez-Granillo, A., Vásquez-Jiménez, E., Fernández-Sánchez, V., Gómez-Zamora, E., Cureño-Díaz, M. A., Milán-Salvatierra, A., Jiménez-Zamarripa, C. A., Calzada-Mendoza, C. C., & Bello-López, J. M. (2024). Seasonal Characterization of the Aerobiome in Hematopoietic Stem Cell Transplant Rooms: Potential Risk for Immunosuppressed Patients. Microorganisms, 12(11), 2352. https://doi.org/10.3390/microorganisms12112352

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