ABSTRACT
Background
Antimicrobial management in pediatric transplantation lacks standardized international guidelines, and current practices across European transplant centers remain poorly described. This study aimed to evaluate microbiological screening and peri‐transplant antimicrobial strategies among centers participating in the European Reference Network on Transplantation in Children (ERN TransplantChild), including both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) programs.
Methods
Between December 2022 and February 2023, healthcare professionals within the network completed a structured survey addressing microbiological screening practices and peri‐transplant antimicrobial strategies in pediatric transplant recipients.
Results
Of 127 transplant programs invited, 76 (59.8%) responded, including 62 SOT and 14 HSCT programs from 36 centers across 16 European countries. Pre‐transplant screening strategies, microbiological methods, and decolonization practices varied substantially between centers. Reported prevalence of methicillin‐resistant Staphylococcus aureus and extended‐spectrum β‐lactamase–producing organisms was below 10% in most programs. In SOT, perioperative prophylaxis varied according to transplanted organ type. Cephalosporins were most commonly used in kidney and heart transplantation, whereas broader‐spectrum regimens, including piperacillin–tazobactam and vancomycin, were more frequently adopted in liver, intestinal, and lung transplantation. Postoperative prophylaxis was continued beyond 24 h in most SOT programs. Antifungal prophylaxis was more commonly adopted in liver, intestinal, and lung transplant recipients. In HSCT, antibacterial peri‐transplant use was not routinely prescribed in a substantial proportion of programs, particularly in autologous transplantation, whereas antifungals were widely used in allogeneic HSCT.
Conclusions
Marked heterogeneity in microbiological screening and peri‐transplant antimicrobial strategies across European pediatric transplant centers underscores the need for transplant‐specific, evidence‐based guidelines distinguishing between SOT and HSCT settings. These findings provide a foundation for the development of shared clinical pathways and harmonized recommendations.
This European survey revealed marked heterogeneity in microbiological screening and peri‐transplant antimicrobial strategies across pediatric transplant programs, particularly in solid organ transplantation. The findings highlight important opportunities for antimicrobial stewardship and support the development of shared, transplant‐specific evidence‐based recommendations.
Abbreviations
- CRE
carbapenem‐resistant Enterobacteriaceae
- ERN
European reference network
- ESBL
extended spectrum beta‐lactamase
- ESCMID/EUCIC
European society of clinical microbiology and infectious diseases/European committee on infection control
- HSCT
hematopoietic stem cell transplantation
- IGRA
interferon gamma release assay
- MDRO
multidrug resistant organisms
- MRSA
methicillin‐resistant Staphylococcus aureus
- SOT
solid organ transplantation
- SSI
surgical site infections
- WHO
World Health Organization
1. Background
Infections continue to represent a major cause of morbidity in pediatric transplant recipients, making peri‐transplant antimicrobial management a critical component of care. Surgical antimicrobial prophylaxis has proven effective in reducing postoperative surgical site infections (SSI) across various surgeries and is therefore recommended by the World Health Organization (WHO) and other international societies [1, 2, 3, 4].
Peri‐transplant antimicrobial strategies in pediatric transplantation encompass two distinct clinical settings. In solid organ transplantation (SOT), antimicrobial prophylaxis is primarily intended to prevent surgical site infections and early post‐operative complications [4]. In contrast, in hematopoietic stem cell transplantation (HSCT), antimicrobial approaches are mainly driven by prolonged immunosuppression and neutropenia, often extending until engraftment [5].
Candidates for transplantation frequently undergo repeated hospitalizations, including intensive care unit admissions, and are commonly exposed to broad‐spectrum antimicrobial agents before transplantation [6]. Compared with otherwise healthy individuals undergoing elective surgeries, this increases the risk of colonization with multi‐drug resistant organisms (MDRO), which is increasingly considered in preoperative preventive strategies. These strategies may include microbiological screening before transplantation to guide antimicrobial selection and, in selected cases, the implementation of decolonization measures [7]. However, approaches to MDRO screening and antimicrobial prophylaxis in colonized patients remain poorly standardized because of limited and heterogeneous evidence.
Although perioperative antimicrobial prophylaxis is widely recognized as a key component of infection prevention in SOT, the optimal timing and duration of administration remain insufficiently defined, and extending antibiotic administration beyond the immediate perioperative period has not consistently been associated with lower rates of surgical site infections [8]. In contrast, in HSCT, antimicrobial strategies are frequently guided by the duration of neutropenia and immunosuppression, with limited consensus regarding the optimal duration of administration and substantial variability across centers.
Despite the clinical relevance of these issues, little is known about current practices across European pediatric transplant programs.
The European Reference Network on Transplantation in Children (ERN TransplantChild) is a European network of healthcare providers involved in both SOT and HSCT, with the aim of promoting multidisciplinary collaboration and shared approaches to common challenges in pediatric transplantation, including infection prevention.
This study aimed to provide a comprehensive overview of current attitudes and practices regarding pre‐transplant antimicrobial screening and use in different pediatric transplant settings across Europe, and to identify areas of variability that may inform future stewardship initiatives and the development of shared evidence‐based protocols.
2. Materials and Methods
ERN TransplantChild includes 40 healthcare providers (HCPs) across 21 European countries, of which 33 are Full Members (fully validated and integrated into the ERN) and seven are Affiliated Partners (collaboration with the ERN with a more limited role). TransplantChild is organized into four Operational Areas (OAs), each grouping member HCPs by geographic region: OA1 (Northern Europe) includes Denmark, Estonia, Finland, Norway, and Sweden; OA2 (Central and Eastern Europe) includes Austria, Germany, Hungary, Ireland, Latvia, Lithuania, and Poland; OA3 (Western Europe) includes Belgium, Croatia, France, Luxembourg, and the Netherlands; OA4 (Southern Europe) includes Italy, Malta, Portugal, and Spain. Network activities are carried out through six Working Groups, each dedicated to a specific strategic domain.
The Board of ERN TransplantChild developed a cross‐sectional questionnaire to evaluate current practices and attitudes regarding microbiological screening and peri‐transplant antimicrobial strategies in pediatric transplant recipients. Consistent with the multidisciplinary nature of the network, both SOT and HSCT programs were invited to participate in the survey, which explored different aspects of antimicrobial preventive strategies across the different transplant settings.
Professionals from SOT and HSCT programs belonging to full member, affiliated partner, and supporting partner Centers of ERN TransplantChild were invited to complete the online survey between December 2022 and February 2023. Participation was voluntary, and completion of the survey was considered implicit consent to participate.
After general questions regarding local microbiological screening practices in transplant recipients, the survey included clinical scenarios addressing antimicrobial prophylaxis and management strategies in different transplant‐related settings (https://ec.europa.eu/eusurvey/runner/ProphylaxisSurvey2022).
3. Results
3.1. Survey Participation and Programs Characteristics
Overall, 76 out of 127 (59.8%) transplant programs completed the survey, including 62 SOT and 14 HSCT programs from 36 centers across 16 European countries (Table 1). Most centers reported having local protocols for peri‐transplant antimicrobial prophylaxis and infection prevention practices in place. In approximately 70% of programs, prophylaxis decisions were primarily managed by pediatric transplant physicians, whereas infectious diseases specialists were involved less frequently.
TABLE 1.
Distribution of pediatric SOT and HSCT programmes by country, experience, and number of patients in follow‐up.
| Tx program (n) | Heart (8) | Intestinal (5) | Kidney (24) | Liver (17) | Lung (8) | HSCT (14) | Total 76 (%) | |
|---|---|---|---|---|---|---|---|---|
| Country, n (%) | Belgium | 1 | 1 | 1 | 3 (3.9) | |||
| Denmark | 1 | 2 | 3 (3.9) | |||||
| Estonia | 1 | 1 | 2 (2.6) | |||||
| Finland | 1 | 1 | 1 | 1 | 1 | 1 | 6 (7.9) | |
| France | 1 | 1 | 2 (2.6) | |||||
| Germany | 2 | 1 | 3 (3.9) | |||||
| Ireland | 1 | 1 (1.3) | ||||||
| Italy | 1 | 1 | 3 | 4 | 2 | 2 | 13 (17.1) | |
| Lithuania | 1 | 1 | 2 (2.6) | |||||
| Norway | 1 | 1 (1.3) | ||||||
| Poland | 1 | 1 | 2 (2.6) | |||||
| Portugal | 2 | 1 | 3 (3.9) | |||||
| Spain | 3 | 1 | 4 | 2 | 2 | 6 | 18 (23.6) | |
| Sweden | 2 | 3 | 1 | 1 | 2 | 9 (11.8) | ||
| The Netherlands | 2 | 1 | 1 | 4 (7.9) | ||||
| Other: UK | 1 | 1 | 2 | 4 (7.9) | ||||
| Years of experience in PT, n (%) | < 5 | 1 | 1 | 1 | 3 (4) | |||
| 6–10 | 1 | 1 | 4 | 2 | 2 | 3 | 13 (17.1) | |
| 11–15 | 2 | 1 | 3 | 4 | 3 | 2 | 15 (20) | |
| > 15 | 4 | 3 | 17 | 10 | 2 | 9 | 45 (59.2) | |
| PT recipients in follow up, n (%) | < 25 | 2 | 4 | 1 | 4 | 2 | 13 (17.1) | |
| 26–50 | 1 | 1 | 9 | 1 | 4 | 16 (20.8) | ||
| 51–75 | 3 | 3 | 1 | 7 (9.1) | ||||
| 76–100 | 1 | 2 | 3 | 1 | 7 (9.1) | |||
| > 100 | 2 | 3 | 6 | 12 | 4 | 6 | 33 (43.4) |
Abbreviations: HSCT, hematopoietic stem cell transplantation; PT, pediatric transplantation; Tx, transplantation.
3.2. MDROs Prevalence and Screening Practices
Only a minority of programs reported receiving periodic institutional reports on the prevalence of multidrug‐resistant organisms (MDROs), including 25 of 62 SOT programs (40.3%) and 7 of 14 HSCT programs (50%) (Table 2). Where available, reported rates of antimicrobial resistance were generally low. Methicillin‐resistant Staphylococcus aureus (MRSA) prevalence was below 10% in most reporting centers. Similarly, extended‐spectrum β‐lactamase (ESBL)‐producing organisms were reported at rates below 10% in the majority of programs, whereas carbapenem‐resistant Enterobacterales (CRE) rates above 30% were reported by only one HSCT center (Figure 1).
TABLE 2.
SOT and HSCT general information about programmes.
| Question | Answer | Kidney, 24 n (%) | Heart,8 n (%) | Liver, 17 n (%) | Intestine, 5 n (%) | Lung, 8 n (%) | Total SOT, 62 (%) | HSCT, 14 n (%) |
|---|---|---|---|---|---|---|---|---|
| Is an official antimicrobial prophylaxis protocol for pediatric transplant patients available in your hospital? | yes | 21 (87.5%) | 6 (75%) | 15 (88.3)% | 4 (80%) | 7 (87.5%) | 53 (85.5%) | 13 (92.9%) |
| no | 3 (12.5%) | 1 (12.5%) | 2 (11.7%) | 1 (20%) | 1 (12.5%) | 8 (12.9%) | 1 (7.1%) | |
| other | 0 | 1 (12.5%) | 1 (1.6%) | |||||
| Who is in charge of antibiotic prophylaxis management? | ID specialists | 2 (8.3%) | 2 (25%) | 3 (17.6%) | 1 (20%) | 2 (25%) | 10 (16.1%) | 4 (28.6%) |
| pediatrician | 20 (83.3%) | 4 (50%) | 10 (59%) | 4 (80%) | 6 (75%) | 44 (70.9%) | 10 (71.4%) | |
| surgeon | 1 (4.2)% | 1 (5.9%) | 2 (3.2%) | |||||
| other | 1 (4.2)% | 2 (25%) | 3 (17.6%) | 6 (9.7%) | ||||
| What is the post‐transplant recipient location? | PICU | 15 (62.5%) | 4 (50%) | 14 (82.3%) | 3 (60%) | 6 (75%) | 42 (67.7%) | 1 (7.1%) |
| ward | 7 (29.1%) | 1 (12.5%) | 2 (11.7%) | 1 (20%) | 1 (12.5%) | 12 (19.3%) | 13 (92.9%) | |
| surgical PICU | 2 (8.3%) | 3 (37.5%) | 1 (5.9%) | 1 (20%) | 1 (12.5%) | 8 (12.9%) | ||
| other | ||||||||
| Do you usually perform a systematic screening with microbial tests for patients in your pre‐transplantation assessment? (the answer could be multiple): | never | 5 (20.8%) | 3 (37.5%) | 1 (5.9%) | 9 (14.5%) | |||
| rectal swab | 7 (29.1%) | 3 (37.5%) | 13 (76.5%) | 4 (80%) | 4 (50%) | 31 (50%) | 9 (64.3%) | |
| nasal swab | 7 (29.1%) | 3 (37.5%) | 12 (70.6%) | 3 (60%) | 5 (62.5%) | 30 (48.4%) | 7 (50%) | |
| IGRA | 10 (41.6%) | 2 (25%) | 5 (29.4%) | 4 (50%) | 21 (33.8%) | 4 (28.6%) | ||
| VRE | 1 (4.2)% | 1 (1.6%) | ||||||
| MRSA | 2 (8.3%) | 2 (3.2%) | ||||||
| cultures | 8 (33.3%) | 8 (12.9%) | ||||||
| other | 2 (25%) | 2 (11.7%) | 1 (20%) | 3 (37.5%) | 6 (9.7%) | 3 (21.4%) | ||
| Do you receive periodic reports about the prevalence of MDR organisms in your hospital? | yes | 11 (45.8%) | 2 (25%) | 9 (52.9%) | 1 (20%) | 2 (25%) | 25 (40.3%) | 7 (50%) |
| no | 10 (41.6%) | 3 (37.5%) | 7 (41.2%) | 4 (80%) | 6 (75%) | 30 (48.4%) | 4 (28.6%) | |
| other | 3 (12.5%) | 3 (37.5%) | 1 (5.9%) | 7 (11.3%) | 3 (21.4%) | |||
| Do you have an antimicrobial/antifungal protocol for prophylaxis? | yes | 18 (75%) | 8 (100%) | 14 (82.3%) | 4 (80%) | 7 (87.5%) | 51 (82.2%) | 14 (100%) |
| no | 6 (25%) | 3 (17.6%) | 1 (20%) | 1 (12.5%) | 11 (17.7%) | |||
| Do you have different antimicrobial/antifungal prophylaxis strategies according to the type of HSCT (allogeneic or autologous)? | yes | 13 (92.9%) | ||||||
| no | 1 (7.1%) |
FIGURE 1.
Countries participating to the survey with corresponding organ transplantation programs and reported rates of multidrug resistant organisms. Abbreviations: CRE, carbapenems resistant enterobacterales; ESBL, extended spectrum beta‐lactamase producing Enterobacterales; MRSA, methicillin resistant Staphylococcus aureus .
Pre‐transplant screening and decolonization practices varied across programs (Table 2). In SOT programs, nasal and rectal swabs were the most commonly adopted screening methods, whereas rectal swabs predominated in HSCT settings. Screening for latent tuberculosis using interferon gamma release assay (IGRA) was performed in 33.8% of SOT programs and 28.6% of HSCT programs.
3.3. Solid Organ Transplantation
Among SOT recipients without known colonization by MDROs, cephalosporins were the most frequently used agents, accounting for approximately half of all prophylactic regimens. These included first‐generation (19.3%), second‐generation (14.5%), and third‐generation (16.1%) cephalosporins (Table 3).
TABLE 3.
Antimicrobial prophylaxis in SOT patients without known colonization.
| PERIOPERATIVE antimicrobial prophylaxis | TOTAL, 62 n (%) | POSTOPERATIVE antimicrobial prophylaxis | TOTAL, 62 n (%) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Kidney, 24 n (%) | Heart, 8 n (%) | Liver, 17 n (%) | Intestine, 5 n (%) | Lung, 8 n (%) | Kidney, 24 n (%) | Heart, 8 n (%) | Liver, 17 n (%) | Intestine, 5 n (%) | Lung, 8 n (%) | |||
| NO prophylaxis | 6 (25%) | 6 (9.7%) | ||||||||||
| Ampicillin | 1 (5.9%) | 1 (1.6%) | 1 (5.9%) | 1 (1.6%) | ||||||||
| Amoxicillin + clavulanic acid | 3 (12.7%) | 1 (5.9%) | 1 (12.5%) | 5 (8.1%) | 2 (8.3%) | 2 (11.7%) | 4 (6.4%) | |||||
| Ampicillin + sulbactam | 1 (5.9%) | 1 (20%) | 1 (12.5%) | 3 (4.8%) | 1 (5.9%) | 1 (20%) | 1 (12.5%) | 3 (4.8%) | ||||
| First‐generation cephalosporin | 7 (29.1%) | 4 (50%) | 1 (5.9%) | 12 (19.3%) | 3 (12.5%) | 4 (50%) | 7 (11.3%) | |||||
| Co‐trimoxazole | 1 (4.2%) | 1 (1.6%) | 0 | |||||||||
| Second‐generation cephalosporin | 4 (16.6%) | 3 (37.5%) | 2 (11.7%) | 9 (14.5%) | 5 (20.8%) | 2 (25%) | 2 (11.7%) | 9 (14.5%) | ||||
| Third‐generation cephalosporins | 7 (29.1%) | 1 (12.5%) | 2 (25%) | 10 (16.1%) | 6 (25%) | 2 (25%) | 2 (25%) | 10 (16.1%) | ||||
| Antipseudomonal third‐generation cephalosporins | 1 (5.9%) | 1 (12.5%) | 2 (3.2%) | 1 (5.9%) | 1 (12.5%) | 2 (3.2%) | ||||||
| Amoxicillin/ampicillin; Third‐generation cephalosporins | 1 (4.2%) | 3 (17.6%) | 4 (6.4%) | 1 (4.2%) | 3 (17.6%) | 4 (6.4%) | ||||||
| Amoxicillin+clavulanic acid; antipseudomonal third generation cephalosporin | 1 (12.5%) | 1 (1.6%) | 1 (12.5%) | 1 (1.6%) | ||||||||
| Piperacillin+tazobactam | 4 (23.5%) | 2 (40%) | 1 (12.5%) | 7 (11.3%) | 4 (23.5%) | 2 (40%) | 2 (25%) | 8 (12.9%) | ||||
| Piperacillin + tazobactam, metronidazole | 1 (4.2%) | 1 (1.6%) | 1 (4.2%) | 1 (1.6%) | ||||||||
| Piperacillin + tazobactam, vancomycin | 1 (5.9%) | 1 (20%) | 2 (3.2%) | 1 (5.9%) | 1 (20%) | 2 (3.2%) | ||||||
| Vancomycin (teicoplanin), aminoglycoside, metronidazole | 1 (5.9%) | 1 (1.6%) | 1 (5.9%) | 1 (1.6%) | ||||||||
| Carbapenems† | 1 (5.9%) | 1 (20%) | 1 (12.5%)* | 3 (4.8%) | 1 (5.9%) | 1 (20%) | 1 (12.5%) | 3 (4.8%) | ||||
| DURATION | ||||||||||||
| 24 h | 7 (29.1%) | 1 (12.5%) | 1 (12.5)% | 9 (14.5%) | ||||||||
| 2–7 days | 9 (37.5%) | 6 (75%) | 11 (64.7%) | 3 (60%) | 3 (37.5%) | 32 (51.6%) | ||||||
| 8–14 days | 1 (12.5%) | 2 (11.7%) | 1 (20%) | 2 (25%) | 6 (9.7%) | |||||||
| Until indwelling drainages are removed or the patient has been extubated | 1 (4.2%) | 2 (11.7%) | 2 (25%) | 5 (8.1%) | ||||||||
| other | 3 (12.5%) | 2 (11.7%) | 1 (20%) | 6 (9.7%) | ||||||||
| No prophylaxis | 4 (16.7%) | 4 (6.4%) | ||||||||||
Note: Colors according to the AWaRe antimicrobial classification system (green: Access category; yellow: Watch category).
1 center (12.5%): CF patients tobramycin, meropenem, flucloxacillin; no CF: meropenem, flucloxacillin.
1 center: meropenem plus vancomycin.
Antibiotic selection varied according to transplanted organ. Kidney and heart transplant programs most commonly used cephalosporins, whereas liver and intestinal transplant programs more frequently adopted broader‐spectrum regimens, particularly piperacillin–tazobactam, either alone or in combination with other agents. Lung transplant programs demonstrated the greatest heterogeneity, with each center reporting a distinct prophylactic regimen (Table 3).
Postoperative prophylaxis was continued beyond surgery in 90.3% of SOT programs. Duration varied substantially: 14.5% limited prophylaxis to 24 h, 51.6% continued antibiotics for 2–7 days, and 9.7% extended treatment to 8–14 days. In most cases, postoperative antibiotics represented a continuation of the perioperative regimen.
Among SOT recipients colonized with MDROs, colonization was not considered a contraindication to transplantation in 93.4% of programs. In 74.2% of cases, prophylactic regimens were adapted according to the susceptibility profile of the colonizing organisms. Decolonization strategies were not routinely implemented in 58% of programs; 22.6% adopted decolonization exclusively for MRSA, whereas only a small minority extended this approach to ESBL‐ or CRE‐colonized patients. As in non‐colonized recipients, postoperative prophylaxis most commonly lasted 2–7 days (Table 4).
TABLE 4.
Antimicrobial prophylaxis in SOT patients with known MDROs colonization. (Abbreviations: MRSA: Methicillin‐susceptible Staphylococcus aureus ; ESBL: Extended spectrum beta‐lactamase; VRE: Vancomycin‐resistant enterococcus; SOT: Solid organ transplantation).
| SOT known colonization | Kidney, 24 n (%) | Heart, 8 n (%) | Liver, 17 n (%) | Intestine, 5 n (%) | Lung, 8 n (%) | TOTAL, 62 n (%) | |
|---|---|---|---|---|---|---|---|
| Colonization considered a contraindication for transplantation | yes | 2 (8.3%) | 2 (3.2%) | ||||
| no | 21 (87.5%) | 8 (100%) | 17 (100%) | 5 (100%) | 7 (87.5%) | 58 (93.4%) | |
| other | 1 (4.16%) | 1 (12.5%) | 2 (3.2%) | ||||
| pre‐transplant decolonization strategy | MRSA | 5 (20.8%) | 3 (37.5%) | 4 (23.6%) | 1 (20%) | 1 (12.5%) | 14 (22.6%) |
| ESBL | |||||||
| CRE | |||||||
| MRSA, ESBL, CRE | 2 (8.3%) | 1 (5.9%) | 3 (4.8%) | ||||
| MRSA, ESBL | 2 (25%) | 2 (25%) | 4 (6.4%) | ||||
| MRSA, CRE | 1 (5.9%) | 1 (1.6%) | |||||
| ESBL, CRE | 1 (4.16%) | 1 (1.6%) | |||||
| Other | 1 (4.16%) | 2 (25%) | 3 (4.8%) | ||||
| None | 15 (62.5%) | 3 (37.5%) | 11 (64.9%) | 4 (80%) | 3 (37.5%) | 36 (58%) | |
| Duration of pre‐transplant decolonization strategy | 7 days | 3 (60%) | 1 (17%) | 4 (6.4%) | |||
| 8–14 days | 3 (37.5%) | 3 (4.8%) | |||||
| until the first negative microbiological sample | 3 (37.5%) | 5 (20%) | 1 (17%) | 1 (100%) | 2 (50%) | 12 (19.3%) | |
| Other | 2 (25%) | 5 (20%) | 4 (66%) | 2 (50%) | 13 (20.9%) | ||
| Change in IV PERIOPERATIVE prophylaxis according to susceptibilities? | yes | 19 (79.2%) | 6 (75%) | 11 (64.9%) | 4 (80%) | 6 (75%) | 46 (74.2%) |
| no | 5 (20.8%) | 2 (25%) | 6 (35.4%) | 1 (20%) | 2 (25%) | 16 (25.8%) | |
| Duration of POSTOPERATIVE prophylaxis in colonized patients | No postoperative therapy | 3 (12.5%) | 3 (4.8%) | ||||
| 24 h | 3 (12.5%) | 3 (4.8%) | |||||
| 2–7 days | 5 (20.8%) | 4 (50%) | 9 (52.9%) | 2 (40%) | 1 (12.5%) | 21 (33.9%) | |
| 8–14 days | 3 (12.5%) | 3 (37.5%) | 1 (5.9%) | 1 (20%) | 3 (37.5%) | 12 (19.3%) | |
| Until indwelling drainages are removed or the patient has been extubated | 4 (16.6%) | 3 (17.7%) | 7 (11.3%) | ||||
| other | 5 (20.8%) | 1 (12.5%) | 4 (23.6%) | 2 (40%) | 4 (50%) | 16 (25.8%) | |
Antifungal prophylaxis was prescribed selectively in 53.2% of SOT programs, routinely in 22.6%, and not routinely used in 20.9% of programs. Liver, intestinal, and lung transplant programs more frequently adopted antifungal preventive strategies. Fluconazole and liposomal amphotericin B were the most commonly used agents (27.4% and 20.9%, respectively) (Table 5).
TABLE 5.
Anti‐fungal and tuberculosis prophylaxis in solid organ transplantation.
| Question | Answer | Kidney, 24 n (%) | Heart, 8 n (%) | Liver, 17 n (%) | Intestine, 5 n (%) | Lung, 8 n (%) | Total, 62 n (%) |
|---|---|---|---|---|---|---|---|
| Do you recommend antifungal PERIOPERATIVE prophylaxis? | Always | 3 (12.5%) | 3 (37.5%) | 3 (17.6%) | 2 (40%) | 3 (37.5%) | 14 (22.6%) |
| Never | 10 (41.7%) | 2 (25%) | 1 (5.9%) | 13 (20.9%) | |||
| Only in selected cases | 10 (41.7%) | 3 (37.5%) | 12 (70.6%) | 3 (60%) | 5 (62.5%) | 33 (53.2%) | |
| Other | 1 (4.2%) | 1 (5.9%) | 2 (3.2%) | ||||
| Which antifungal prophylaxis would you prescribe (relatively to those who answered yes in the first question)? | Liposomal Amphotericin B | 2 (14.3%) | 2 (33.3%) | 5 (31.2%) | 2 (40%) | 2 (25%) | 13 (20.9%) |
| Fluconazole | 6 (42.8%) | 2 (33.3%) | 5 (31.2%) | 3 (60%) | 1 (12.5%) | 17 (27.4%) | |
| Echinocandins | 1 (7.1%) | 3 (18.8%) | 1 (12.5%) | 4 (6.4%) | |||
| Echinocandins, Fluconazole | 1 (7.1%) | 1 (1.6%) | |||||
| Echinocandins, L‐Amphotericin B | 1 (6.2%) | 1 (1.6%) | |||||
| Voriconazole | 1 (6.2%) | 2 (25%) | 3 (4.8%) | ||||
| Isavuconazole | 1 (16.7%) | 1 (1.6%) | |||||
| Voriconazole, L‐Amphotericin B | 1 (12.5%) | 1 (1.6%) | |||||
| Other | 4 (28.6%–16.7%) | 1 (16.7%) | 1 (6.2%) | 1 (12.5%) | 7 (11.3%) | ||
| What is the duration of antifungal prophylaxis (relatively to those who answered yes in the first question)? | 2–7 days | 6 (42.8%) | 3 (50%) | 8 (50%) | 3 (60%) | 3 (37.5%) | 23 (37.1%) |
| 8–14 days | 2 (14.3%) | 4 (25%) | 1 (20%) | 1 (12.5%) | 8 (12.9%) | ||
| 15–21 days | 2 (14.3%) | 1 (6.2%) | 3 (4.8%) | ||||
| 22–28 days | 1 (7.1%) | 3 (18.8%) | 2 (25%) | 6 (9.7%) | |||
| Other | 3 (21.4%) | 3 (50%) | 1 (20%) | 2 (25%) | 9 (14.5%) | ||
| In the case of positive IGRA for tuberculosis before transplantation, do you treat this latent tuberculosis without previous and appropriate treatment? | Yes, before and after transplantation | 10 (41.7%) | 6 (35.3%) | 1 (20%) | 1 (12.5%) | 18 (29%) | |
| Yes, before transplantation | 6 (25%) | 2 (25%) | 3 (17.6%) | 2 (40%) | 4 (50%) | 16 (25.8%) | |
| Yes, after transplantation | 2 (25%) | 2 (3.2%) | |||||
| No | 2 (8.3%) | 1 (12.5%) | 3 (4.8%) | ||||
| Other | 5 (20.8%) | 3 (37.5%) | 8 (47.1%) | 2 (40%) | 3 (37.5%) | 21 (33.9%) |
Latent tuberculosis infection without adequate previous treatment was managed either before transplantation (25.8%) or both before and after transplantation (29%) (Table 5).
3.4. Hematopoietic Stem Cell Transplantation
In HSCT programs, peri‐transplant antibiotic strategies differed between autologous and allogeneic transplantation (Table 6). Antibiotics were not routinely used in 31% of allogeneic and 53.8% of autologous HSCT programs. When prescribed, prophylactic regimens varied substantially across centers and were most commonly continued until neutrophil engraftment.
TABLE 6.
Antimicrobial prophylaxis in HSCT programmes.
| HSCT | Allogeneic HSCT | Autologous HSCT | |
|---|---|---|---|
| Do you recommend antimicrobial prophylaxis? | Never | 31% | 53.8% |
| Always | 46% | 30.8% | |
| Only in selected cases | 23% | 15.4% | |
| Which antimicrobial prophylaxis do you prescribe? | Ampicillin/amoxicillin | 11.1% | 16.7% |
| Ampicillin/amoxicillin; levofloxacin | 11.1% | ||
| Ampicillin/amoxicillin; levofloxacin; co‐trimoxazole | 11.1% | ||
| Fenoximetylpenicillin | 11.1% | ||
| Cefazolin; ciprofloxacin | 11.1% | ||
| Levofloxacin; co‐trimoxazole | 11.1% | 16.7% | |
| Ciprofloxacin | 11.1% | 33.3% | |
| Co‐trimoxazole | 22.2% | 33.3% | |
| What is the DURATION of the antimicrobial prophylaxis? | Until engraftment § | 44.4% | 66.6% |
| If present, as long as the child is being treated for GvHD | 11.1% | ||
| Until discontinuation of immunosuppressive therapy | 22.2% | 16.7 | |
| Until day + 100 | 16.7% | ||
| Vaccine response or re‐vaccination | 22.2% | ||
| Do you recommend antifungal prophylaxis? | Always | 92.3% | 69.2% |
| Never | 15.4% | ||
| Only in selected cases | 7.7% | 15.4% | |
| Which antifungal prophylaxis would you prescribe? (the answer could be multiple): | Fluconazole | 23.1% | 70% |
| L‐AmB | 15.4% | ||
| Echinocandins | 7.6% | ||
| Posaconazole; fluconazole | 7.6% | ||
| Echinocandins; voriconazole; posaconazole; L‐AmB | 7.6% | ||
| Echinocandins; fluconazole | 15.4% | 10% | |
| Echinocandins; fluconazole; L‐AmB | 10% | ||
| L‐AmB; fluconazole | 10% | ||
| L‐AmB; voriconazole | 7.6% | ||
| L‐AmB; posaconazole | 7.6% | ||
| L‐AmB; fluconazole; voriconazole | 7.6% | ||
| What is the DURATION of the antifungal prophylaxis? | If present, as long as the child is being treated for GvHD | 38.5% | |
| Until day +100 | 15.4% | ||
| Until discontinuation of immunosuppressive therapy | 23.1% | 10% | |
| Until engraftment§ | 15.4% | 90% | |
| Other | 7.6% | ||
| Colonization with MDROs as contraindication for transplantation | No | 100% | |
| Yes | |||
| Pre‐transplant decolonization strategies | No | 90% | |
| Yes | 10% | ||
Antifungals was used in 92.3% of allogeneic HSCT programs and in 69.2% of autologous programs. Liposomal amphotericin B was the most frequently used agent, whereas fluconazole monotherapy was more commonly adopted in autologous transplantation.
4. Discussion
For the first time, this survey explored current practices regarding microbiological screening and peri‐transplant antimicrobial strategies in pediatric transplant programs across Europe, including both SOT and HSCT settings within the ERN TransplantChild network. Our findings revealed substantial heterogeneity in prophylactic and peri‐transplant antibiotic strategies, particularly regarding perioperative management in SOT recipients.
Although most centers reported having local protocols, antimicrobial strategies varied considerably according to transplant type, local epidemiology, and institutional practices.
4.1. Solid Organ Transplantation
Despite the relatively well‐defined objective of preventing surgical site infections and early postoperative complications, our survey revealed marked variability in both the choice and duration of antimicrobial prophylactic regimens across SOT programs.
Cephalosporins were the most commonly used agents in kidney and heart transplantation, ranging from first‐ to third‐generation compounds. This heterogeneity likely reflects the limited pediatric evidence currently available. In fact, in kidney transplantation, previous studies have shown no significant differences in SSI rates between first‐ and third‐generation cephalosporins, supporting the use of narrower‐spectrum agents when local epidemiology permits [9]. Similarly, in heart transplantation, the optimal choice between cephalosporins and glycopeptides remains controversial, with institutional MRSA prevalence representing an important factor guiding antibiotic selection [10, 11, 12, 13, 14]. Notably, most centers in our survey reported MRSA prevalence below 10%, a finding that may not support routine glycopeptide use in many settings.
In contrast, liver and intestinal transplant programs more frequently adopted broader‐spectrum regimens, particularly piperacillin–tazobactam with or without vancomycin. Lung transplant programs showed the greatest heterogeneity. These findings are consistent with the limited and heterogeneous literature currently available in pediatric transplant populations [15, 16, 17, 18]. Importantly, broader‐spectrum prophylaxis does not necessarily translate into improved outcomes and may increase antimicrobial exposure without clear clinical benefit.
Duration of prophylaxis emerged as another major source of variability. Although evidence from non‐transplant surgical settings consistently demonstrates no benefit from extending antimicrobial prophylaxis beyond 24–48 h, most SOT programs in our survey continued antibiotics for several days postoperatively, often until drain removal or extubation [4, 8]. Kidney transplant programs represented a partial exception, more frequently limiting prophylaxis to a single perioperative dose. Prolonged postoperative prophylaxis has also been described in pediatric surgical and intensive care settings and represents an important target for antimicrobial stewardship initiatives [19, 20]. Encouragingly, recent pediatric liver transplant studies suggest that shortening postoperative prophylaxis can reduce broad‐spectrum antibiotic exposure without increasing adverse outcomes [17].
The management of patients colonized with MDROs further illustrates the challenges faced by transplant centers. Although colonization was not considered a contraindication to transplantation in most programs, it frequently influenced perioperative antibiotic selection. Decolonization strategies were rarely applied beyond MRSA carriers, reflecting the limited evidence supporting decolonization for Gram‐negative bacteria. Current ESCMID/EUCIC guidelines provide only weak recommendations for targeted prophylaxis in ESBL‐colonized patients and no specific recommendations for carbapenem‐resistant organisms [6]. Consequently, clinical practice remains largely based on local epidemiology, observational data, and institutional experience [21, 22].
Antifungal prophylaxis also varied substantially across SOT programs, particularly among liver and lung transplant recipients. While these transplant populations are generally considered at higher risk for invasive fungal infections, interpretation of our findings is limited by the scarcity of pediatric‐specific evidence and by the heterogeneity of local preventive strategies [23, 24, 25]. Overall, these findings further emphasize the need for more standardized and evidence‐based preventive strategies across pediatric transplant centers.
4.2. Hematopoietic Stem Cell Transplantation
In HSCT programs, peri‐transplant antimicrobial use follows a different clinical rationale than in SOT, being primarily aimed at preventing infections during periods of profound immunosuppression and neutropenia, usually until engraftment [5]. Our findings indicate that most centers appropriately differentiated strategies between autologous and allogeneic transplantation.
Consistent with current guidelines, routine antibacterial use was not universally adopted, particularly in autologous HSCT programs [5]. Nevertheless, substantial heterogeneity in antimicrobial strategies was observed across centers, including frequent use of fluoroquinolones despite recommendations limiting routine administration to selected high‐risk settings.
Antifungal prophylaxis was widely adopted in allogeneic HSCT programs and less consistently used in autologous transplantation, broadly reflecting current international recommendations [5]. Overall, these findings suggest persistent heterogeneity in prophylactic strategies across HSCT programs and highlight the importance of continued antimicrobial stewardship efforts tailored to transplant type and individual risk factors.
4.3. MDRO And Tuberculosis Screening
Across both SOT and HSCT programs, pre‐transplant screening for MDRO colonization was widely implemented, typically using rectal and nasal swabs. Interestingly, nasal screening for MRSA appeared to be less commonly adopted in HSCT programs compared with SOT settings, possibly reflecting the greater emphasis on Gram‐negative surveillance in neutropenic patients. However, fewer than half of programs reported access to regular institutional surveillance data. This gap may limit the ability to tailor prophylaxis according to local resistance patterns and could contribute to unnecessary broad‐spectrum antimicrobial use [7].
Screening for latent tuberculosis infection was inconsistently applied despite the increased risk of reactivation following transplantation, particularly during the first post‐transplant year [26, 27, 28, 29, 30]. Given the limited predictive value of currently available diagnostic tests in transplant populations, the optimal screening and prevention strategy remains uncertain and warrants further investigation [31].
4.4. Strengths and Limitations
This study provides a contemporary real‐world overview of microbiological screening and peri‐transplant antimicrobial practices across pediatric transplant centers within a large and well‐established European reference network, addressing an area in which pediatric‐specific evidence remains limited. Nevertheless, the survey‐based design introduces inherent limitations, including potential reporting bias and the inability to capture within‐program variability. Furthermore, microbiological epidemiology and antimicrobial resistance data were self‐reported and not independently validated. Finally, because most participating centers were large specialized transplant programs, the findings may not be fully generalizable to smaller or non‐network institutions.
5. Conclusions
Pediatric transplant care continues to face important gaps in evidence‐based guidance, contributing to substantial heterogeneity in antimicrobial prophylaxis practices across European transplant centers, particularly in the perioperative management of SOT recipients. As the threat of MDROs continues to increase, integration of local epidemiology into clinical decision‐making becomes increasingly important.
Our findings highlight important opportunities for antimicrobial stewardship across both SOT and HSCT settings, particularly regarding optimization of antimicrobial spectrum and duration of administration. Extended postoperative antibiotic use remained common in several SOT programs despite limited supporting evidence, whereas HSCT programs showed substantial heterogeneity in antimicrobial approaches. Greater involvement of infectious diseases specialists in perioperative antimicrobial management may further support stewardship efforts and promote more standardized approaches across centers.
The development of shared, evidence‐based protocols within collaborative networks such as ERN TransplantChild, together with prospective pediatric studies, will be essential to optimize antimicrobial prophylaxis strategies, improve patient outcomes, and preserve the effectiveness of existing antimicrobial agents.
Funding
This study was supported by the European Reference Network on Paediatric Transplantation (ERN TransplantChild), funded by the EU4Health Programme (EU4H‐2023‐ERN‐IBA‐01; Specific Agreement No. 101156607). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HADEA). Neither the European Union nor HADEA can be held responsible for them.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.
Cecilia Liberati and Daniele Donà are first co‐authors.
Elisa Benetti and Francisco Hernández ‐ Oliveros are last co‐authors.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.