Antimicrobial resistance among Escherichia coli that cause childhood community-acquired urinary tract infections in Northern Italy

<p>Abstracts</p> <p>Background</p> <p>Resistance rate of <it>Escherichia coli </it>against antimicrobials that are commonly prescribed in pediatric urinary tract infections is currently a matter of concern.</p> <p>Methods</p> <p>The antimicrobial susceptibility patterns of uropathogenic <it>Escherichia coli </it>strains to the common antibimcrobials ampicillin, cotrimoxazole, coamoxyclav, ceftazidime, ceftriaxone, nitrofurantoin, and gentamycin were determined in 177 children aged from 2 to 36 months. They presented with their first symptomatic community acquired urinary tract infection at the Department of Pediatrics, San Leopoldo Mandic Hospital, Merate-Lecco.</p> <p>Results</p> <p>High rates of ampicillin (inpatients: 50%; outpatients: 52%) resistance were identified. The resistance for cotrimoxazole (inpatients: 22%; outpatients: 15%) and especially coamoxyclav (inpatients: 6%; outpatients: 10%) was less pronounced than that to ampicillin. No resistance or less than 1% of resistance was identified for ceftazidime, ceftriaxone, nitrofurantoin, and gentamycin both in inpatients and in outpatients.</p> <p>Conclusions</p> <p>Italian children affected with a community acquired urinary tract infection are initially managed orally with coamoxyclav or parenterally with ceftriaxone. The results of the present retrospective analysis support this attitude. Parenteral ceftriaxone or an aminoglycoside should be considered for patients on antimicrobial prophylaxis or recently prescribed antimicrobials.</p

Flow cytometric immunobead assay for detection of BCR-ABL1 fusion proteins in chronic myleoid leukemia: Comparison with FISH and PCR techniques

Chronic Myeloid Leukemia (CML) is characterized by a balanced translocation juxtaposing the Abelson (ABL) and breakpoint cluster region (BCR) genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response. Currently, measurement of BCR-ABL1 mRNA transcript levels by real-time quantitative PCR (RQ-PCR) defines critical response endpoints. An antibody-based technique for BCR-ABL1 protein recognition could be an attractive alternative to RQ-PCR. To date, there have been no studies evaluating whether flow-cytometry based assays could be of clinical utility in evaluating residual disease in CML patients. Here we describe a flow-cytometry assay that detects the presence of BCR-ABL1 fusion proteins in CML lysates to determine the applicability, reliability, and specificity of this method for both diagnosis and monitoring of CML patients for initial response to therapy. We show that: i) CML can be properly diagnosed at onset, (ii) follow-up assessments show detectable fusion protein (i.e. relative mean fluorescent intensity, rMFI%&gt;1) when BCR-ABL1IS transcripts are between 1-10%, and (iii) rMFI% levels predict CCyR as defined by FISH analysis. Overall, the FCBA assay is a rapid technique, fully translatable to the routine management of CML patients

Correlation between leukocytosis and thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms

International audienceThe evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates. We found that white blood cells (WBC) count above 9.5 × 10/L at diagnosis (baseline analysis) was associated with thrombosis during the follow-up (Hazard Ratio [HR] of 1.8, 0.03). At the time-dependent analysis, therapy with hydroxyurea (HU), lowering by 35% the baseline WBC level, reduced such strength of association giving a HR of 1.3 ( value non significant). We found a trend between WBC level and thrombosis in untreated low-risk patients (RR of 1.9, 95% CI 0.9 to 3.1); in high-risk patients treated with HU this correlation was clearly lost (RR 1.1, 95% CI 0.2 to 2.7). Finally, we could not identify the presence of as a risk factor for thrombosis. Properly designed prospective studies should corroborate such results

Gimema Registry of Conception/Pregnancy in Adult Patients Diagnosed with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs)

The management of patients with chronic myeloid leukemia (CML) during pregnancy is a matter of continuous debate. The introduction of the tyrosin kinase inhibitors (TKIs) in clinical practice has dramatically changed the prognosis of CML patients. Patients diagnosed in chronic phase can expect an excellent disease control and a normal lifespan. Issues relating to fertility and pregnancy must be introduced at diagnosis. Different reports were published in patients conceving/getting pregnant during Imatinib treatment, while there are only sporadic data about other TKIs. The GIMEMA CML working party has started a retrospective and prospective study to describe all female pregnancies/male conception outcome in the CML population from January 2013 until 2015. Inclusion criteria were age>18, CML in any phase of the disease, conception/pregnancy while diagnosed with CML, treatment with TKIs (before, during or after pregnancy), and signed written informed consent IRB approved. Sixty-three patients have been enrolled so far in the study. Male to female ratio was 43/20, mother age at pregnancy (female patients or female partners of male patients) varies from 22 to 37 years. CML was diagnosed when patients were aged between 17 and 55 years old, all patients were in chronic phase at time of conception, but one. This patient was a male patient with accelerated phase aged 31 treated with Nilotinib whose conception outcome was unremarkable. Data on 71 pregnancies have been harvested. The majority of pregnancies were spontaneous, with 3 PMA (pregnancy medically assisted). All pregnancies were carried on, 2 are ongoing, and 6 ended up in an abortion within the 3rdmonth, 2 of which non induced (miscarriages). At pregnancy/conception 8 patients were treated with Nilotinib, 4 with Dasatinib, 3 with Bosutinib, the remaining patients were treated with Imatinib or were at onset with no treatment. All carried pregnancies were unremarkable, except two placental detachment, one at 5 months and one at 12 weeks pregnancy, 1 abortion threat requiring rest, 1 gestational diabetes with intra-uterine growth retard, 1 oligohydramnios, 1 congenital hip dysplasia, and 1 speech retard in a 36 months old baby girl. Data on female patients population, regarding the status of CML at pregnancy, the CML therapy since conception and throughout pregnancy, particularly regarding the organogenesis period (between 5-12 weeks), the status of the illness during pregnancy (any MR4.5, MR4 and major molecular response, complete cytogenetic response, hematologic response losses, and progressions), the outcome of pregnancy, breast feeding, baby growth and development (walk, speech, behaviour), will be detailed. The same will be for female partners of male patients treated with TKIs other than Imatinib. Acquiring detailed information about how a pregnancy/conception is managed will increase our knowledge in order to establish a consensus on patients with CML receiving TKIs who wants to father a child or become/are pregnant

Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia

The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials in which imatinib was given as first-line treatment. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow- up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to diagnosis of the second primary malignancies was 34 months. We did not find a higher incidence of second primary malignancies compared to that in the ageand sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% CI: 0.57-1.54) and 1.61 (95% CI: 0.92-2.31) in males and females, respectively. Overall, 3.1% patients died of second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to that expected in the age- and sex-matched Italian population, with a standardized mortality ratio of 2.41 (95% CI: 1.26 - 3.56). In conclusion, our analysis of patients with imatinib-treated chronic myeloid leukemia did not reveal a higher incidence of second primary malignancies; however, the outcome of second primary malignancies in such patients was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926

Comparison of FISH analysis and BCR-ABL1 Flow-cytometry Bead Assay on CML samples (N = 105 serial samples in 37 patients).

<p>* FCBA = Flow-cytometry Bead Assay; rMFI% range, 0.968–8.89; %BCR-ABL1^IS range 0.313–10.258, with 5/6 patients with %BCR-ABL1^IS ≥1%.</p><p>Comparison of FISH analysis and BCR-ABL1 Flow-cytometry Bead Assay on CML samples (N = 105 serial samples in 37 patients).</p