Re: "Comparison of antipseudomonal betalactams for febrile neutropenia empiric therapy: systematic review and network metaanalysis" by Horita et al

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Current treatment options for infections caused by carbapenem-resistant Enterobacteriaceae in patients with hematological malignancies

Infections are a common complication in patients with hematological malignancies, especially during neutropenia. Recently, an increase in multidrug-resistant gram-negative pathogens has been observed in the etiology of infectious complications, including carbapenem-resistant Enterobacteriaceae. However, therapeutic options for treatment of these infections are limited. The review represents treatment options for infections caused by carbapenem-resistant Enterobacteriaceae, including the use of reserve drugs such as polymyxin, carbapenems, tigecycline, as well as a new antibiotic – ceftazidime-avibactam, which contains a new β-lactamase inhibitor with unique properties

Infectious complications caused by carbapenemase-producing Enterobacterales in patients with hematological disorders

Mortality rates approaching 60 % have been reported in hematological patients with infections caused by carbapenemase-producing Enterobacterales. The incidence of these infections is rapidly increasing, whereas the therapeutic options are limited. This review represents characteristics of infections caused by carbapenemase-producing Enterobacterales in patients with hematological disorders, highlights risk factors and management options of these infections

Molecular characterization of extended-spectrum β-lactamase-producing <i>Escherichia coli</i> collected from patients with hematological malignancies during chemotherapy cycles

Objective: to evaluate the genetic relatedness of extended-spectrum β-lactamase (ESBL) producing Escherichia coli isolated from the gut in patients with acute myeloid leukemia and lymphoma at admission and during chemotherapy cycles. Materials and methods. The prospective study (2013–2014) included 73 patients (median age 39 years) with acute myeloid leukemia (n = 25) and lymphoma (n = 48). The follow-up period lasted for 96 days. ESBL-producing E. coli isolated from the gut were included in this study. ESBL-production was confirmed by phenotypic tests, blaCTX-M and blaTEM genes were detected by polymerase chain reaction, and genotyping was performed by ERIC (Enterobacterial Repetitive Intergenic Consensus) polymerase chain reaction. Results. ESBL-producing E. coli were detected in 39 (53 %) of 73 patients: of them 12 (16 %) patients were colonized at admission and 27 (37 %) patients – during chemotherapy cycles. Gene blaCTX-M was detected in 67 % of E. coli, blaTEM – in 41 %, both genes – in 26 %. There was no genetically related ESBL-producing E. coli among 12 isolates detected at admission. Genetic relatedness was detected in 16 (59 %) of 27 isolates obtained during a hospital stay. Genetically related ESBL-producing E. coli were isolated from patients hospitalized in the same and different departments, these isolates were characterized by the presence of both identical and various determinants of resistance. Conclusion. Our data demonstrated the possibility of patient-to-patient transmission of ESBL-producing E. coli isolated from the gut during a hospital stay

Genotyping by Random Amplified Polymorphic DNA Assay of Acinetobacter baumannii Isolated from Blood Culture of Patients with Hematological Malignancies

Relevance. Acinetobacter baumannii is a significant nosocomial pathogen that can cause severe infections, especially in immunocompromised patients. Aims. This study aimed to investigate clonal diversity of A. baumannii isolated from blood culture in hematological patients by random amplified polymorphic DNA assay (RAPD). Materials &amp; Methods. Genotyping of A.baumannii isolated from blood culture in hematological patients in 7 Russian hospitals (2003–2017) was assessed by RAPD-PCR with primer OPA-2 (5’-TGCCGAGCTG-3’). The computer-assisted analysis was performed by using GelJ software by UPGMA method and Dice similarity coefficient for banding patterns comparison. Using a similarity coefficient (SC) of ≥ 65%, the strains were grouped. Based on the similarity coefficient, the strains were determined as genetically related (≥ 80%). Strains had identical RAPD-patterns if the similarity coefficient was 100%. Results. A total of 96 A. baumannii strains were examined, of those 77 (80.2%) were nonsusceptible to carbapenems. Acquired OXA-carbapenemase genes were detected among 79.2% carbapenem non-susceptible strains. RAPD-PCR genotyping revealed 84 RAPD patterns. The four groups (A-D) including 98% strains were defined by similarity coefficient ≥65%. The predominant group A included 58 (60.4%) strains, the C and B groups – had 15 strains (15.6%) each, and the group D – 6 strains (6.3%). A total of 82 (85.4%) genetically related A. baumannii with a similarity coefficient ≥ of 80% were allocated into 20 clusters. Identical RAPD-patterns were defined for 22 strains that belonged to 6 clusters within the group A and 1 cluster within the group B. Strains with identical RAPD-patterns were detected in a single hospital as well as in several hospitals located in different cities. Conclusions. The current study has demonstrated genetic diversity and clonal dissemination of A. baumannii in hematological departments

THE EFFICACY OF POSACONAZOLE FOR PROPHYLAXIS OF INVASIVE MYCOSES IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

Efficacy of posaconazole for prophylaxis was evaluated in 77 chemotherapy cycles in 59 patients with acute myeloid leukemia (AML) aged 39 (17–62) years from 2012  till 2017. Posaconazole was given in oral suspension 200 mg three times a day after meal during chemotherapy cycle or on 1st  day after the cycle. Administration of posaconazole predominated in patients with de novo AML (84.5%) on 1st induction cycles (66.3%). Neutropenia was present in all patients with median duration of 22 days. Median duration of prophylaxis was 21  (2–57)  days. Posaconazole prophylaxis was interrupted in 28  (36.4%) of 77 cases, mainly due to diarrhea (28.6%). In 17 (61%) of 28 cases prophylaxis was resumed within a median of 3 days. In 72 (93.5%) of cases duration of posaconazole prophylaxis was ≥ 7 days, in 5 (6.5%) cases &lt; 7 days. Efficacy of prophylaxis was evaluated in cases of posaconazole duration ≥ 7 days. Invasive pulmonary aspergillosis (probable) was in 2 (2.7%) of 72 cases. Administration of posaconazole with duration ≥ 7 days was in 46 cases on chemotherapy cycle, in 26 cases – on first day after the cycle. Patients using Posaconazole after a course of chemotherapy in comparison with patients receiving the drug in the first days of the course had significantly less interruptions of prophylaxis (11,5% vs 41,3%, p=0.009) and a reduction in duration of Posaconazole using (19 days vs 27 days, p=0.007).One case of invasive aspergillosis was registered in each group.We confirmed the  efficacy of posaconazole  for prophylaxis of invasive mycoses  in patients  with AML. Administration of posaconazole prophylaxis on first day after the end of chemotherapy cycle results in saving of drug by reducing duration of posaconazole using by 8 days and does not increase the incidence of invasive mycoses

Infectious complications in patients with multiple myeloma on first chemotherapy cycle

The aim of the study was to evaluate the profile and risk factors for acquisition of infections in patients with de novo multiple myeloma (MM) on the 1st chemotherapy cycle (CC).Materials and methods. Study included patients with de novo MM undergoing chemotherapy from January 2013 till November 2017 in National Research Center for Hematology, Russia.Results. A total of 156 patients with de novo MM (median age 61 years) were included in the study. Follow-up period was 21–82 days (median 26 days), first CC contained bоrtezomib. Infections occurred in 77 (49.4 %) of patients with MM, from them 29 (37.7 %) – on admission, 48 (62.3 %) – throughout treatment. Solitary infections were in 47 (61%) of patients, multiple infections – in 30 (39 %) of patients. The most prevalent type of infection was pneumonia (62.3 %), followed by urinary tract infections (27.3 %) and herpesvirus infections (24.7 %). 30% of patients with infections were afebrile. Significant risk factors associated with infections at admission and during CC were ECOG score 4, anemia, hypercalcemia, humoral immunodeficiency, admission from other hospital, use of antibiotics prior to first CC. Additional risk factors for infections at admission were Durie–Salmon stage III MM, paresis, lower extremity paraplegia and dysfunction of the pelvic organs, whereas during treatment – ISS stage III MM and renal failure. Infections were uncommon in patients with ISS stage I MM (7.8 %). Mortality after 1st CC was 1.9 % caused by pneumonia and acute respiratory failure.Conclusions. Patients with de novo MM undergoing 1st CC had high incidence of infections with a prevalence of pneumonia. Factors associated with infections were stage III MM, serious illness, admission from other hospital, humoral immunodeficiency, and renal failure

Allergic bronchopulmonary mycosis in a child caused by <i>Paecilomyces lilacinus</i>

The article discusses the problem of allergic bronchopulmonary mycoses, which occur in children much more often than they are diagnosed. Their treatment is a challenge, and the prognosis is very problematic. In addition to the most frequent cause of Aspergillus, allergic bronchopulmonary mycoses can be caused by various fungi. The clinical example demonstrates the difficulty of diagnosing and treating a child with allergic bronchopulmonary mycosis caused by a rare type of filamentous fungi Paecilomyces lilacinus

Infectious complications in patients with acute leukemia according to the duration of neutropenia

Introduction. Patients with hematological malignancies undergoing chemotherapy (CT) have high incidence of infections which profile is affected by various factors including neutropenia.Objective was to evaluate incidence and type of infections in patients with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) according to neutropenia duration.Materials and methods. Prospective study (2013–2015) included 110 patients (66 AML, 44 ALL) that received 480 CT cycles throughout 6 month.Results. Neutropenia with median duration of 15 (2–55) days was in 288 (60 %) of CT cycles. Infections occurred in 242 (50 %) of CT cycles and predominated in neutropenic compared to non-neutropenic patients (80 % vs 6 %, p &lt;0.0001). Infections prevailed in patients with AML compared to ALL patients (93 % vs 18 %, p &lt;0.0001) as in patients with neutropenia (96 % vs 45 %, p &lt;0.0001) and without neutropenia (27 % vs 4 %, p = 0.02). Prolongation of neutropenia from 1–7 days to ≥22 days was associated with increase of infections rate from 52 to 96 % (p &lt;0.0001). Incidence of infections in AML patients was high (92–100 %) regardless of neutropenia duration, whereas in ALL patients it increased from 25–33 to 91 % if neutropenia lengthened from 2 weeks to ≥22 days. During neutropenia the probability of fever of unknown origin was 33.9 %, clinically documented infection – 31.3 %, bacteremia – 17.2 %. They predominated in the first 2 weeks of neutropenia. Probability of invasive aspergillosis (IA) increased after 28 days of neutropenia and reached 66 % on the 55th day. First case of IA in patients with ALL was on 28th day of neutropenia whilst in AML patients – 4 (44 %) of 9 occurred more early (6–16 days of neutropenia). Nine (6 %) of 110 patients died, 4 (4 %) of them due to infection.Conclusions. Neutropenia was a predictor of infectious complications in patients with AML and ALL. Correlation between duration of neutropenia and incidence of infections was in patients with ALL, whereas in AML patients the rate of infections was high regardless of neutropenia duration. In patients with neutropenia for 2 weeks the most common types of infection were fever of unknown origin, clinically documented infection and bacteremia whilst IA predominated if neutropenia duration was ≥28 days