•Low prevalence of ESBL-E infections in hematopoietic stem cell transplant recipients with non-negligible mortality rate.•Increasing ESBL production rate in E. coli strains and predominance of ...CTX-M-1 enzyme.•High genetic diversity and limited clonal spread of ESBL-E strains.
Extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) create a therapeutic challenge and have high potential for dissemination. The purpose of our study was to investigate the epidemiology of these infections in hematopoietic stem cell transplant (HSCT) recipients and to determine the genes encoding ESBL.
This retrospective study comprised adult patients hospitalized at the National Bone Marrow Transplant Center (NBMTC) and infected with ESBL-E post-HSCT between January 2006 and December 2016. The search for the ESBL and carbapenemase genes was performed by polymerase chain reaction (PCR) amplification. Molecular typing was performed by pulsed field gel electrophoresis (PFGE) after digestion with XbaI.
Forty ESBL-E were responsible for infections in 34 HSCT recipients (3.3% of total HSCT recipients). Prior hospital stay, prior antibiotic therapy and prior colonization with ESBL-E were reported in 62.5%, 70% and 50% of the infectious episodes, respectively. The initial antibiotic treatment was appropriate in 67.7% of cases. Imipenem was the most prescribed antibiotic (64.5%). The mortality rate due to ESBL-E infection was 8.8%.
The ESBL-E, isolated mainly from blood cultures (40%), belonged mostly to K. pneumoniae (n=19) and E. coli (n=17). Associated antibiotic resistance rates were 17.5% for ertapenem, 85% for ciprofloxacin and 30% for amikacin. The predominant gene encoding ESBL was blaCTX-M (55%). Among the seven carbapenem-resistant strains, four had the blaOXA-48 gene and two the blaKPC gene. There was no clonal relationship between the strains.
There was low prevalence of ESBL-E infections in HSCT recipients in our center, with no epidemic distribution but non-negligible mortality rate.
The purpose of our study was to investigate the epidemiology of coagulase negative staphylococci (CoNS) responsible for bacteremia in hematopoietic stem cell transplant (HSCT) recipients and to ...determine the prevalence and the genetic background of methicillin resistance. The prevalence of CoNS bacteremia was 7.4% (54/728), higher in allograft (10.7%) than in autograft (4.7%) recipients. A sepsis or a septic shock were observed in 9% of cases. No deaths were attributable to CoNS bacteremia. The methicillin resistance rate was 81%. All MR-CoNS, harbored mecA gene and 90% were typeable with SCCmec typing using PCR amplification. The SCCmec type IV was the most frequent (44%). Clonal dissemination of MR- Staphylococcus epidermidis strains was limited. Our study showed a low prevalence and favorable outcome of CoNS bacteremia in HSCT recipients with limited clonal diffusion. However, they were associated with a significant rate of severe infections and a high rate of methicillin resistance, mediated by SCCmec IV element in most cases.
Abstract Escherchia coli is the most common etiological agent of urinary tract infections. In this study we had two goals: First of all, to find out if urine stains isolated from our patients – ...having the particularity of being immunocompromised – would have a virulence genes distribution different from the one observed in strains isolated from ordinary patients. Second, we wanted to identify a common virulence profile associated to these particular strains. The prevalence of virulence factors (VF)-encoding genes was analyzed by PCR. Of the tested VF-encoding genes, malX (80%), ompT (79%), fyuA (74%), usp (67%), chuA (66%), iroN (59%), iutA (56%), papC (36%), pap AH (30%), papEF (28%) , hlyA (28%), papG allele II (25%), cnf1 (21%), focG (20%), cvaC (20%) and papG allele III (7%) were significantly associated to urinary strains. Virulence genes distribution of urinary strains isolated from onco-hematology patients and the one observed in strains isolated from ordinary patients are almost the same. The virulence profiles containing adhesins type 1, S and F1C fimbriae, siderophore genes and three individual genes ompT, usp and malX were present in half of the urinary strains and were significantly associated to them. Two virulence signatures occurred significantly in UTI-causing strains (12%). These findings provide first insight into the virulence of UTI-causing E. coli strains isolated in onco-hematology patients.
Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is ...to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib’s efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome—overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)—were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3–85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3–51), 18 months (3–72), and 24 months (3–100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.
Background :
Healthcare-associated infections (HAIs) are with high rates of mortality and an additional cost, in onco-hematology patients.
Aim
:
The study aims to assess the prevalence trends of ...HAIs in the onco-hematology ward of the Tunisian National Bone Marrow Transplant Center (NBMTC), and to determine the principal associated risk factors.
Methods:
Six repeated point prevalence surveys were conducted, from May 2018 to March 2019, using a two months interval. All patients hospitalized in the day of the survey were included. Risk factors of HAIs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). They were assessed using a logistic regression model.
Results:
Nineteen patients out of a total of 74 patients have been diagnosed with 19 HAIs, representing a prevalence of 25.7%. No significant downward or upward trend of prevalence was revealed over time (p=0.3). The most common HAI was respiratory tract infection (57.9%) with a prevalence of 14.9%. Multiple logistic regression analysis revealed that HAI was significantly associated with neutropenia (Adjusted OR: 14; 95% CI: 1.5-127; p=0.01) and duration of central venous catheter (Adjusted OR: 1.1; 95% CI: 1-1.2; p=0.005).
Conclusion:
High prevalence of HAIs in our center with a high rate of mortality, requiring identifying potential problems in infection control practices.
Carbapenem resistant Enterobacteriaceae (CRE) are major human pathogens because, these cause high number of difficult-to-treat infections. Allogeneic hematopoietic stem cell transplant (AHSCT) ...recipients are highly exposed to these type of bacteria. The aim of our study was to investigate prevalence of CRE colonization in AHSCT patients and to determine genes encoding carbapenem resistance. A retrospective study conducted between January 2015 and December 2019, involved 55 patients colonized with CRE strains. We determined the rate of antibiotic resistance according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the carbapenem resistance genes by PCR assays for genes encoding most frequent β-lactamases namely, blaGES, blaKPC, blaIMI, blaNDM, blaVIM, blaIMP and blaOXA-48. Eighty-one episodes of CRE colonization were recorded in 55 patients, mainly suffering from acute leukaemia (30%) and aplastic anemia (26%). History of hospitalization was noted in 80 episodes. Prior antibiotic treatment, severe neutropenia and corticosteroid therapy were respectively found in 94%, 76% and 58% of cases. Among the 55 patients, six patients (11%) developed a CRE infection. The CRE responsible for colonization were carbapenemase producers in 90% of cases. They belonged mostly to Klebsiella pneumoniae (61/81) and Escherichia coli species (10/81). Antibiotic resistance rates were 100% for ertapenem, 53% for imipenem, 42% for amikacin, 88% for ciprofloxacin and 27% for fosfomycin. Molecular study showed that blaOXA-48 gene was the most frequent (60.5%), followed by blaNDM (58%). Thirty-five (43%) strains were co-producers of carbapenemases. In our study, we report a high rate of CRE intestinal colonization in AHSCT recipients of our center.
Background: High dose Melphalan (HDM) and autologous stem cell transplantation (ASCT) is a standard care for Myeloma ≤ 65 years. Studies have demonstrated that depth of response prior to ASCT does ...not impact outcome post ASCT, e.g. solely depth of response post ASCT matters. However, with improving induction regimens, the questions remains whether patients achieving a deeper response at completion of induction would not perform better post ASCT.
ASCT can only be performed in Tunisia if newly diagnosed Multiple Myeloma (NDMM) achieves at least PR; we therefore sought to report the national Tunisian experience.
Patients and Methods: NDMM aged ≤65 years received three cycles of Thalidomide (200mg daily) and Dexamethasone, followed by HDM and ASCT.52% received maintenance therapy for 12 months with Thalidomide, from 3 months post transplantation. Non responders to TD induction were salvaged with Lenalidomide or Bortezomib-based regimen. The response was assessed based on IMWG response criteria. The study is performed in ITT.
Results: 202 consecutive pts were included between April 2012 and December 2014. The median age was 56 yrs (range, 25-65), sex ratio was 1.R-ISS stage was 3 in 27.5%. 21% had high risk cytogenetic (by Conventional karyotyping and FISH). Renal failure was observed in 17%. ORR after induction was 71% with 12% CR, 17% VGPR. 22% failed to obtain PR following TD induction, and 51% of whom received salvage induction therapy (ST) with 72% that further reached ≥PR after ST. Overall, 141 pts (70%) underwent ASCT, 121 of whom had evidence of chemo-sensitive MM at completion of induction. 16% were transplanted in CR, 22% in VGPR and 62% in PR.
At 3 months post-ASCT, the ORR in induction chemo-sensitive MM was 89%: 36% CR, 20% VGPR, and 33% PR. With a median follow-up post-ASCT of 27 months, the OS, PFS and EFS at 27 months were 82%, 60.5% and 56%, respectively. Maintenance treatment was significantly associated with longer PFS only in MM who did not achieve CR (29 versus 9 months, p=0.004). MM with improved response post-ASCT had a significantly longer PFS (39 versus 21 months, p=0.003) and EFS (39 versus 20 months, p=0.002). Importantly, achieving CR before (p=0.03) and after ASCT (p<0.0001) was also predictive for prolonged EFS. Early relapses/progressions (less than 18 months) was the sole predictive factor of adverse OS in our study (p=0.01).
In multivariate analysis, ISS stage 3 was the sole independent predictor of induction failure (p=0.003). Importantly, predictive factors of achievement of CR post-ASCT comprised absence of delay farther to 4 months from completion of induction (p=0.006; OR = 4.54) and achievement of at least VGPR status before transplant (p=0,001; OR = 4.09).
Conclusion: Achievement of at least VGPR at completion of induction improved response after ASCT and consequently influenced the post-ASCT outcome. Therefore, depth of response matters before and after ASCT, and validates in some extent the concept of induction salvage therapy prior to ASCT for patient not reaching response.
Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria.
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