The impact of fluoroquinolone-resistant enterobacterales colonization on fluoroquinolone prophylaxis efficacy in hematopoietic cell transplant recipients.

Introduction

Hematopoietic cell transplantation (HCT) offers survival benefits for leukemia and lymphoma patients but carries significant infection risks, especially during the pre-engraftment phase due to profound immunosuppression [ 1 , 2 ]. Complications like neutropenic fever, bacteremia, pneumonia, and C. difficile infections impair quality of life and survival [ 2 ].

Fluoroquinolone (FQ) prophylaxis has been widely adopted to reduce febrile neutropenia, bacteremia, and related infections, with trials and meta-analyses confirming its efficacy across high-risk cancer patients, though mortality benefits remain unclear [ 3 – 7 ]. However, rising FQ resistance, particularly among Enterobacterales, including extended-spectrum beta-lactamase (ESBL) producers, threatens its efficacy and drives further resistance [ 8 – 13 ].

Studies reveal variable prophylaxis practices: 57.1% of European centers (higher in Southeast Europe/Asia vs. Northwest Europe) and 87% of U.S. cancer centers use FQ prophylaxis, predominantly ciprofloxacin and levofloxacin, yet only 29% of U.S. clinicians believe benefits outweigh resistance risks [ 14 , 15 ]. Variability in FQ resistance rates, evolving infection epidemiology, and C. difficile risks complicate its routine use [ 16 – 20 ].

This retrospective cohort study evaluated FQ prophylaxis in autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) recipients, assessing neutropenic fever and pre-engraftment bacteremia (primary outcomes) in prophylaxis versus non-prophylaxis groups, further stratified by FQ-resistant Enterobacterales (FQRE) colonization (those colonized with FQ-resistant Enterobacterales (FQRE) and those who were FQRE-free). Secondary outcomes included pre-engraftment pneumonia, C. difficile infection, and in-hospital mortality among patients receiving FQ prophylaxis compared to those who did not. We also examined baseline FQRE colonization prevalence and conversion rates from negative to positive perianal surveillance cultures for FQRE during transplant admission. These findings aim to guide future prophylactic and therapeutic strategies in this vulnerable patient population.

Patients and methods

Setting, study design, and study participants

This retrospective chart review included adult patients admitted for auto-HCT or allo-HCT at the Middle East Institute of Health (MEIH), a 160-bed university-affiliated tertiary care referral center in Lebanon, between 2017 and 2022. MEIH has a 9-bed HCT unit and is affiliated with the HCT unit at Makassed General Hospital, another tertiary care hospital in Beirut. Both centers perform autologous and allogeneic HCTs, with this study specifically focused on transplant admissions to MEIH. The study adhered to the Declaration of Helsinki guidelines and received ethical approval from the Institutional Clinical Research Ethics Committee at Makassed General Hospital (approval number: 892021). Due to the retrospective design, patient consent was waived.

Data collection

Clinical and microbiological data were retrieved from electronic medical records, the HCT registry, and medical microbiology laboratory logbooks for all patients (Supplementary file 1 ).

Transplantation procedure and other definitions

Conditioning regimens, immunosuppressive therapies, and supportive treatments were administered according to internationally accepted standards [ 20 ]. Day 0 was defined as the date of auto-HCT or allo-HCT graft infusion. Refer to Supplementary File 1 for further details.

Antimicrobial prophylaxis and supportive standard of care

Infection control and patient care practices in the HCT unit were adapted from the American Society for Blood and Marrow Transplantation (ASBMT) guidelines for preventing infectious complications among HCT recipients [ 21 ] (Supplementary file 1 ).

The institutional microbiological surveillance program included weekly perianal swab cultures to detect colonization by 3rd generation cephalosporin resistant Enterobacterales (3GCRE) and FQRE starting at admission (baseline screening culture) and continuing until discharge.

Anti-infective prophylaxis followed institutional protocols based on international recommendations [ 22 , 23 ]. For antibacterial prophylaxis, auto-HCT recipients received FQ prophylaxis (levofloxacin 500 mg–750 mg PO once daily) at the start of conditioning chemotherapy, continuing until neutropenia recovery or the onset of neutropenic fever, as per the treating oncologist’s discretion. Allo-HCT recipients also received FQ prophylaxis (levofloxacin 500 mg–750 mg PO once daily) starting with conditioning chemotherapy and continuing until the first febrile episode or neutrophil engraftment, as per the treating oncologist’s discretion.

See Supplementary File 1 for details on antimicrobial prophylaxis, neutropenic fever management, infectious diseases workup, and diagnosis and management of pre-engraftment bacteremia and pneumonia in auto- and allo-HCT recipients.

Microbiological studies and antibiotic susceptibility

The microbiological data included all positive blood cultures linked to pre-engraftment bacteremia, along with their antibiotic susceptibility profiles. Perianal swab culture results detecting 3GCRE and FQRE colonization during the transplant admission were also retrieved from electronic medical records. Bacterial cultures were requested based on each patient’s clinical condition. See Supplementary File 1 for details on microbiological studies and antibiotic susceptibility testing.

Study endpoints

Primary

First Fever Post-HCT : This primary outcome focused on comparing the timing and occurrence of the first febrile episode post-HCT between recipients who received FQ prophylaxis and those who did not. All HCT recipients were included and further stratified by the baseline perianal surveillance cultures for FQRE, categorized as positive or negative. The time to febrile neutropenia was defined as the duration from Day 0 (the day of HCT graft infusion) to the first febrile episode post-HCT. Patients who developed fever after receiving broad-spectrum antimicrobials (BSA) were excluded from this analysis. Separate analyses were conducted for auto-HCT and allo-HCT recipients.

Pre-engraftment Bacteremia : This endpoint focused on comparing the timing and occurrence of the first episode of pre-engraftment bacteremia between recipients who received FQ prophylaxis and those who did not. HCT recipients were stratified by the baseline perianal surveillance cultures for FQRE, categorized as positive or negative. The time to febrile neutropenia was defined as the duration from Day 0 to the date of the first episode of pre-engraftment bacteremia. Patients who developed bacteremia after receiving BSA, or who received BSA within the first 7 days post-HCT without developing bacteremia, were excluded from the bacteremia analysis only. Separate analyses were performed for Gram-negative pre-engraftment bacteremia. Subgroup analyses were conducted for auto-HCT and allo-HCT recipients.

Secondary

Other Post-HCT Complications : We evaluated the timing and occurrence of pre-engraftment pneumonia, C. difficile infection (CDI), and all-cause in-hospital mortality in HCT recipients with and without FQ prophylaxis. Time to event was defined as the duration from Day 0 to the date of the occurrence of the respective complication. Subgroup analyses were conducted for auto-HCT and allo-HCT recipients.

Conversion from Baseline Negative to Positive FQRE/3GCRE Peri-Anal Cultures : Secondary outcomes also included examining the baseline prevalence of positive perianal surveillance cultures for FQRE and 3GCRE, and the rate of conversion from negative to positive cultures during the transplant admission. Analyses encompassed all HCT recipients, with subgroup evaluations for auto-HCT and allo-HCT patients.

Statistical analysis

Data were analyzed using SPSS Statistics (Version 23.0, IBM Corp., Armonk, NY, USA) and GraphPad Prism 10.2.1 (GraphPad Software, San Diego, CA, USA). Baseline characteristics and outcomes were summarized with descriptive statistics: medians (IQR) for continuous variables and frequencies (%) for categorical variables. Bivariate comparisons between FQ prophylaxis and non-prophylaxis HCT recipients used Pearson’s Chi-square or Fisher’s exact test for categorical variables, and Mann–Whitney U test for continuous variables, with unadjusted odds ratios (OR) and 95% CI reported ( p < 0.05 for significance). Kaplan-Meier curves estimated time-to-first febrile episode and pre-engraftment bacteremia in all HCT, auto-HCT, and allo-HCT groups, compared via log-rank test. Censoring occurred at event, BSA initiation, engraftment, or death. Unadjusted hazard ratios (HR) and 95% CI were calculated using univariate Cox regression in GraphPad Prism ( p < 0.05). Small sample sizes or event numbers limited some Kaplan-Meier analyses.

Results

Baseline Characteristics of HCT Recipients

A total of 156 patients underwent HCT during the study period (2017–2022). Of these, 42.9% (67/156) were under the age of 50 (Table 1 ). The most common underlying condition necessitating HCT was multiple myeloma, affecting 34.6% (54/156) of recipients, followed by acute leukemias at 32.7% (51/156) and lymphomas at 28.8% (45/156). Regarding the type of transplant, 60.9% (95/156) of patients underwent auto-HCT, while 39.1% (61/156) received allo-HCT (Table 1 ).

Additional baseline peri-transplant clinical characteristics and non-infectious post-transplant complications for the entire study cohort are detailed in Table 1 . Data for auto-HCT and allo-HCT recipients are in Supplementary Tables S1 and S1 , respectively.

Receipt of fluoroquinolone prophylaxis, and baseline FQRE and 3GCRE carriage

Fluoroquinolone prophylaxis was administered to 73.1% (114/156) of all HCT recipients (Table 1 ). At baseline, 39.1% of the cohort (61/156) tested positive for FQRE, and 50.0% (78/156) tested positive for 3GCRE on peri-anal surveillance cultures (Table 1 ). Data specific to auto-HCT and allo-HCT recipients are provided in Supplementary Tables S1 and S2 , respectively.

First episode of neutropenic fever post-HCT

The frequency and timing of post-HCT neutropenic fever were analyzed by FQ prophylaxis use and baseline FQRE peri-anal carriage (Table 2 ; Fig. 1 ). Overall, 85.9% (134/156) of recipients developed fever post-HCT, with a median onset of 3 days (IQR: 1–7) (Table 2 ). FQ prophylaxis was associated with a reduced frequency of fever during neutropenia (80.7%, 92/114 vs. 100%, 42/42 without prophylaxis) and with delayed onset (median: 3 days, IQR: 1–7 vs. 1.5 days, IQR: 1–4) (Table 2 ). Kaplan-Meier analysis confirmed a lower likelihood of fever within 10 days post-HCT in patients receiving prophylaxis (HR: 0.47, 95% CI: 0.27–0.81, p < 0.001) (Fig. 1 a).

Among the FQ prophylaxis group, FQRE-positive patients had a higher fever frequency (83.7%, 36/43 vs. 78.6%, 55/70) and earlier onset (median: 2 days, IQR: 1–4 vs. 5 days, IQR: 2–8) compared to FQRE-negative patients. Kaplan-Meier analysis showed a trend toward earlier fever in FQRE-positive patients (HR: 1.59, 95% CI: 0.98–2.59, p = 0.06) (Fig. 1 b).

Without prophylaxis, all patients developed fever, with FQRE-positive patients experiencing earlier onset (median: 1 day, IQR: 1–2 vs. 4 days, IQR: 1–7 in FQRE-negative patients) (Table 2 ). Kaplan-Meier analysis revealed a significantly higher likelihood of fever in FQRE-positive patients without prophylaxis (HR: 2.31, 95% CI: 1.16–6.56, p = 0.02) (Fig. 1 c).

FQ prophylaxis was associated with a lower risk of febrile neutropenia regardless of FQRE status, with comparable hazard ratios in FQRE-positive (HR: 0.35, 95% CI: 0.18–0.73, p = 0.003) and FQRE-negative patients (HR: 0.42, 95% CI: 0.24–0.77, p = 0.003) (Fig. 1 d and e).

Subgroup analysis results for auto-HCT and allo-HCT recipients are presented in Supplementary Table S3 and Figures S1 a–e, S2 a–e.

Pre-engraftment bacteremia

The frequency and timing of pre-engraftment bacteremia were analyzed in 64 patients based on the administration of FQ prophylaxis and baseline FQRE peri-anal carriage (Table 3 ; Fig. 2 ). All patients either developed bacteremia without prior BSA or did not receive BSA within the first 7 days post-HCT. Overall, bacteremia occurred in 39.1% (25/64) of patients, with a median onset of 5 days (IQR: 2.5–8).

FQ prophylaxis was associated with a lower prevalence of bacteremia in our cohort (35.7%, 20/56 vs. 62.5%, 5/8) and with delayed onset (6.5 days, IQR: 3–8 vs. 2 days, IQR: 1.5–3.5). Kaplan-Meier analysis confirmed a significantly lower likelihood of bacteremia in patients with FQ prophylaxis (HR: 0.31, 95% CI: 0.12–0.94, p = 0.02), with cumulative probabilities of ~ 63% by day 5 in those without prophylaxis and ~ 40% by day 14 in those with prophylaxis (Fig. 2 a).

Among patients receiving FQ prophylaxis, bacteremia prevalence was similar between FQRE-positive (37.5%, 6/16) and FQRE-negative (35.0%, 14/40) groups. However, FQRE-positive patients experienced earlier onset (2.5 days, IQR: 2–10 vs. 7 days, IQR: 5–8.5). Kaplan-Meier analysis showed a trend toward earlier bacteremia in FQRE-positive patients (HR: 1.14, 95% CI: 0.40–3.05, p = 0.62), with probabilities converging at ~ 23% by day 10 (Fig. 2 b).

In patients without FQ prophylaxis, all FQRE-positive patients (3/3) developed bacteremia (median onset: 3 days, IQR: 2–4), compared to 40.0% (2/5) of FQRE-negative patients (median onset: 1.5 days, IQR: 1–2). Kaplan-Meier analysis suggested a higher likelihood of bacteremia in FQRE-positive patients (HR: 2.59, 95% CI: 0.42–20.06, p = 0.31) (Fig. 2 c).

FQ prophylaxis was associated with a reduced risk of bacteremia regardless of FQRE status. In FQRE-positive patients, prophylaxis reduced bacteremia risk (HR: 0.20, 95% CI: 0.04–1.03, p = 0.05). In FQRE-negative patients, prophylaxis also lowered risk but was not statistically significant (HR: 0.58, 95% CI: 0.16–3.68, p = 0.47) (Fig. 2 d and e).

Subgroup analysis results for auto-HCT and allo-HCT recipients are in Supplementary Table S4 and Figures S3 a–b, S4 . Gram-negative bacteremia results for the entire cohort and auto-/allo-HCT recipients are in Supplementary Tables S5 and Figures S5 a–e, S6 a–b, S7 .

Bacteriological findings in pre-engraftment bacteremia

The pathogens involved in bacteremia, along with their resistance to FQ and 3GC, are summarized in Table 4 , which also details stratification by FQ prophylaxis, highlighting the relationship between prophylaxis and resistance patterns. Among the 25 patients who developed bacteremia, 60% (15/25) were due to Gram-negative bacteria, of which 48% (12/25) were FQ-resistant. Gram-positive bacteria accounted for 56% (14/25) of cases, with 52% (13/25) showing FQ resistance. Escherichia coli was the most common Gram-negative pathogen, responsible for 28% (7/25) of cases, followed by Enterobacter cloacae and Pseudomonas aeruginosa , each accounting for 8% (2/25). Among Gram-positive bacteria, coagulase-negative staphylococci predominated, causing 52% (13/25) of cases.

Patients who received FQ prophylaxis had a lower prevalence of Gram-negative organisms causing bacteremia (55%,11/20) compared to those without prophylaxis (80%,4/5) ( p = 0.62). Conversely, Gram-positive organisms were more prevalent in the FQ prophylaxis group (65%,13/20) compared to the non-prophylaxis group (20%, 1/5) ( p = 0.13).

FQ resistance among Gram-negative bacteria was higher in the prophylaxis group (50%,10/20) compared to the non-prophylaxis group (40%,2/5) ( p = 0.41). A similar trend was observed for Gram-positive bacteria, with higher FQ resistance in the prophylaxis group (60%,12/20) compared to the non-prophylaxis group (20%,1/5) ( p = 0.16). Resistance to 3GC among Gram-negative bacteria was greater in the prophylaxis group (40%,8/20) than in the non-prophylaxis group (20%,1/5) ( p = 0.38). Notably, carbapenem resistance was not detected in any Gram-negative bacteria associated with bacteremia.

Bacteremia pathogens and their FQ and 3GC resistance are summarized in Supplementary Table S6 for auto- and allo-HCT recipients.

Other post-transplant complications among HCT recipients: pre-engraftment pneumonia, c. difficile infection, and all-cause mortality

Pre-engraftment pneumonia

Pre-engraftment pneumonia occurred in 5.1% of the overall cohort (8/156), with 6 cases in the auto-HCT group and 2 cases in the allo-HCT group. The median occurrence was 7.5 days post-HCT (IQR: 6 to 9) (Table 5 ). In patients who received FQ prophylaxis, pneumonia was numerically less frequent (4.4%, 5/114) with a median occurrence of 8 days post-HCT (IQR: 4–11), compared to 7.1% (3/42) in the non-prophylaxis group with a median occurrence at 6 days (IQR: 5–8), though the difference was not statistically significant (OR = 0.596, 95% CI: 0.136–2.613; p = 0.445).

C. difficile-associated infection

CDI was observed in 3.2% of the overall cohort (5/156), with 4 cases in the auto-HCT group and 1 case in the allo-HCT group. The median occurrence was 5 days post-HCT (IQR: 1.5–13.5) (Table 5 ). Among those receiving FQ prophylaxis, the CDI prevalence was 1.8% (2/114) with a median occurrence at 3.5 days (IQR: 2–5), compared to 7.1% (3/42) in the non-prophylaxis group (median occurrence 7 days, IQR: 1–20) (OR = 0.232, 95%CI: 0.037–1.441; p = 0.121).

All-cause in-hospital mortality

The all-cause in-hospital mortality rate among HCT recipients was 3.8% (6/156), with 3 cases in both the auto-HCT and allo-HCT groups. The median time to death was 47 days post-HCT (IQR: 33 to 59 days) (Table 5 ). In patients who received FQ prophylaxis, mortality was lower at 2.6% (3/114), with a median time to death of 53 days (IQR: 33–76), compared to 7.1% (3/42) in the non-prophylaxis group with a median time to death of 44 days (IQR: 30–50) (OR = 0.351, 95% CI: 0.068–1.814; p = 0.344).

For these 3 post-transplant complications, similar trends were seen in auto- and allo-HCT recipients (Supplementary Tables S7 and S8 ).

Conversion from baseline negative to positive FQRE and 3GCRE surveillance cultures

Among 60 HCT recipients who tested negative for FQRE and were eligible for conversion analysis, 21.7% (13/60) converted to positive cultures (Table 6 ). Conversion occurred in 22.9% (11/48) of patients who received FQ prophylaxis, compared to 16.7% (2/12) in those who did not (OR = 1.486, 95% CI: 0.288–7.556; p = 0.99). The median time to conversion was 13 days (IQR: 8–24 days) (Table 6 ). Rates stratified by HCT type are in Supplementary Table S9 .

Among 50 HCT recipients who tested negative for 3GC-resistant Enterobacteriaceae (3GCRE), 26% (13/50) converted to positive cultures (Table 6 ). Conversion occurred in 25% (10/40) of patients receiving FQ prophylaxis, while 30% (3/10) in those who did not receive prophylaxis (OR = 0.778, 95% CI: 0.196–3.195; p = 0.71). The median time to conversion was 10 days (IQR: 7–14 days). Rates stratified by HCT type are in Supplementary Table S9 .

Discussion

This retrospective single-center study of HCT recipients demonstrates high baseline rates of FQRE and 3GCRE carriage. Nearly 40% of patients were FQRE-positive and 50% were 3GCRE-positive on peri-anal surveillance cultures, considerably higher than previously reported. In a single-center prospective study from the USA, Satlin et al. found that 23% of HCT recipients were colonized with FQRE prior to transplant [ 24 ], while a study from Japan reported 16% colonization among patients with hematologic malignancies [ 25 ]. Our findings suggest a higher prevalence of FQRE in the local community, consistent with the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) data from Lebanon, where 3rd generation cephalosporin resistance in E. coli BSI ranged from 50% to 58.8%, and FQ resistance increased from 50.7% in 2020 to 56.4% in 2021 [ 26 ]. These data underscore the endemic presence of 3GCRE and FQRE in Lebanon and the public health challenges posed by antimicrobial resistance. HCT recipients are particularly vulnerable due to prolonged exposure to broad-spectrum antimicrobials during immunosuppressive therapy, as well as recurrent hospitalizations and extended inpatient stays [ 27 , 28 ].

Fluoroquinolone prophylaxis is routinely recommended for neutropenic cancer patients at high risk of prolonged and severe neutropenia. Guidelines from ASCO [ 5 ], IDSA [ 22 ], and NCCN [ 23 ] support its use to reduce neutropenic fever, bacteremia, and mortality. The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) similarly recommends levofloxacin prophylaxis for patients with or expected to develop mucositis, with systematic monitoring for resistance in cases of early neutropenic fever or bacteremia [ 29 ]. These recommendations, however, are tempered by concerns about emerging FQ resistance [ 30 , 31 ], and guidelines from ESMO discourage routine prophylaxis, citing limited mortality benefit and resistance concerns [ 32 ].

In our cohort, FQ prophylaxis was associated with reduced frequency and delayed onset of neutropenic fever, with protective effects observed in both auto- and allo-HCT recipients. Patients with baseline FQRE carriage also appeared to benefit, although less markedly than FQRE-negative patients. These findings are consistent with studies in cancer populations, where prophylaxis reduced febrile neutropenia by 24–29% [ 6 , 33 ]. Caro et al. similarly reported reduced neutropenic fever in AML patients receiving prophylaxis despite high background resistance (41%-45%) (hazard ratio 0.59, p = 0.039) [ 34 ]. Taken together, these results suggest that FQ prophylaxis may retain clinical utility even in high-resistance settings, although its effect can be attenuated in colonized patients. Differences in reported effectiveness across studies likely reflect variations in local resistance patterns, patient populations, and statistical approaches [ 35 – 37 ].

Pre-engraftment bacteremia occurred in 39.1% of patients, more frequently in allo-HCT recipients. FQ prophylaxis was associated with a lower incidence and delayed onset of bacteremia, in line with prior reports. Yeshurun et al. observed lower bacteremia among auto-HCT recipients receiving prophylaxis (4.5% vs. 15.1%) [ 38 ], and Maurer et al. reported a reduction among allo-HCT recipients (14% vs. 28%) [ 39 ]. Notably, baseline FQRE colonization did not significantly increase bacteremia risk in our cohort, and prophylaxis remained protective in FQRE-positive patients (HR 0.20, p = 0.05). This contrasts with findings from Satlin et al., who reported higher gram-negative bacteremia in FQRE-colonized patients despite prophylaxis (31% vs. 1.1%) [ 24 ], and Santos et al., who found increased bloodstream infections in colonized HCT recipients [ 40 ]. Such discrepancies highlight the need for multicenter studies to clarify how colonization status interacts with prophylaxis efficacy.

Pre-engraftment pneumonia occurred in 5.1% of patients, with a lower, non-significant prevalence in those receiving prophylaxis (4.4% vs. 7.1%). Yeshurun et al. reported a significant reduction in pneumonia among auto-HCT recipients on prophylaxis (6.2% vs. 12.3%, p = 0.04) [ 38 ]. Although less frequent than fever or bacteremia, pneumonia remains a clinically relevant complication.

CDI was observed in 3.2% of patients overall, with a lower but non-significant prevalence in the prophylaxis group (1.8% vs. 7.1%). While FQ use is a recognized CDI risk factor [ 41 , 42 ], prophylaxis may reduce exposure to broad-spectrum empiric antibiotics, as previously suggested by Maurer et al. [ 39 ]. Our data are consistent with this notion, indicating that FQ prophylaxis does not appear to substantially increase CDI risk in this population.

All-cause in-hospital mortality was 3.8%, with a non-significant trend toward lower rates among patients receiving prophylaxis (2.6% vs. 7.1%). This aligns with prior reports showing no significant mortality difference [ 38 , 39 ].

Finally, conversion from FQRE-negative to positive status occurred in 21.7% of eligible patients, with a higher—but not statistically significant—conversion rate among those receiving prophylaxis. Existing studies suggest limited impact of FQ prophylaxis on gut microbiome disruption compared to broad-spectrum β-lactams [ 43 , 44 ]. Our findings are in line with this, indicating that prophylaxis may not substantially exacerbate colonization dynamics, although further research is warranted.

Limitations

This study has several limitations. First, it is a single-center, retrospective analysis, which may be subject to incomplete or inaccurate data collection and potential confounding. Prior patient information was limited, as some had received inpatient care before HCT while others were admitted solely for the transplant, restricting the analysis of prior antimicrobial exposure. Second, the decision to prescribe FQ prophylaxis was at the treating oncologist’s discretion, without protocol guidance, introducing potential selection bias. Third, levofloxacin susceptibility was not routinely tested in perianal cultures; ciprofloxacin served as a surrogate per EUCAST guidelines, with MICs often extrapolatable to levofloxacin due to shared resistance mechanisms, though pathogen-specific MICs could provide additional granularity.

The study period was restricted to 2017–2022 because baseline perianal screening for FQRE was first implemented in 2017, and data beyond 2022 were not available for logistical reasons. We acknowledge that this does not capture the most recent epidemiology and that antimicrobial resistance patterns are dynamic. Nevertheless, resistance was already highly prevalent, with baseline FQRE carriage detected in nearly 40% of HCT recipients, underscoring endemicity in our setting. These findings support the applicability of our results to regions with similar epidemiology, while recognizing that they may not fully reflect the current situation. Despite these limitations, the study provides valuable insights into the efficacy of FQ prophylaxis in preventing neutropenic fever and pre-engraftment bacteremia among HCT recipients in a high-resistance region. Larger, multicenter studies with extended follow-up are needed to validate these findings and enhance their generalizability.

Conclusion

In this cohort of auto- and allo-HCT recipients with high baseline colonization by MDR pathogens, including FQRE, fluoroquinolone prophylaxis was associated with reduced frequency and delayed onset of febrile neutropenia and bacteremia, even in the context of regional 3GCRE and FQRE endemicity. The protective effect appeared to extend to both FQRE-colonized and non-colonized patients, although the magnitude was attenuated and not always statistically significant. Importantly, FQ prophylaxis was not linked to increased CDI, new acquisition of FQRE/3GCRE colonization, or in-hospital mortality. These findings suggest that FQ prophylaxis may retain clinical utility in HCT recipients in high-MDR settings, but confirmation in larger, multicenter studies is warranted.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Supplementary Material 3

Acknowledgements

None.

Author contributions

Concept and design: Rima Moghnieho Data Acquisition: Ahmad Khalil, Antoine Khoury, Hilal W. Abdessamad, Monica Abi Abdallah, Pamela Sfeir, Mariana Mezher, Bilal Hamade, Kamal Zahran, and Edmond Abboud. Analysis or interpretation of data: Rima Moghnieh, Dania Abdallah, Aysar Fakih, Rana Attieh, Farah Hneini, Marilyne Sily, Wael Zorkot, and Shadi Eid. Drafting of the manuscript: Rima Moghnieh and Dania Abdallah. Critical revision of the manuscript for important intellectual content: Rima Moghnieh, Dania Abdallah, and Ahmad Ibrahim. Supervision: Rima Moghnieh and Ahmad Ibrahim. ll authors read and approved the final version of the manuscript.

Funding

None.

Data availability

The data that support the findings of this study will be shared on reasonable request to the corresponding author.

Declarations

Ethics approval and consent to participate

The study adhered to the Declaration of Helsinki guidelines and received ethical approval from the Institutional Clinical Research Ethics Committee at Makassed General Hospital (approval number: 892021). Due to the retrospective design, patient consent was waived. During the data collection phase, only subject case numbers were included. At a later stage, a different number was assigned to each of our cases to safeguard subject privacy. All methods used were performed in accordance with the hospital’s IRB committee guidelines and regulations. The contributing authors only performed data entry and analysis as well as the drafting of the manuscript.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

Supplementary Materials

Supplementary Material 1

Supplementary Material 2

Supplementary Material 3

Data Availability Statement

The data that support the findings of this study will be shared on reasonable request to the corresponding author.