scholarly journals Pediatric fever in neutropenia with bacteremia—Pathogen distribution and in vitro antibiotic susceptibility patterns over time in a retrospective single-center cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246654
Author(s):  
Melina Stergiotis ◽  
Roland A. Ammann ◽  
Sara Droz ◽  
Christa Koenig ◽  
Philipp Kwame Abayie Agyeman

Background Fever in neutropenia (FN) is a potentially life-threatening complication of chemotherapy in pediatric cancer patients. The current standard of care at most institutions is emergency hospitalization and empirical initiation of broad-spectrum antibiotic therapy. Methods We analyzed in retrospect FN episodes with bacteremia in pediatric cancer patients in a single center cohort from 1993 to 2012. We assessed the distribution of pathogens, the in vitro antibiotic susceptibility patterns, and their trends over time. Results From a total of 703 FN episodes reported, we assessed 134 FN episodes with bacteremia with 195 pathogens isolated in 102 patients. Gram-positive pathogens (124, 64%) were more common than Gram-negative (71, 36%). This proportion did not change over time (p = 0.26). Coagulase-negative staphylococci (64, 32%), viridans group streptococci (42, 22%), Escherichia coli (33, 17%), Klebsiella spp. (10, 5%) and Pseudomonas aeruginosa (nine, 5%) were the most common pathogens. Comparing the in vitro antibiotic susceptibility patterns, the antimicrobial activity of ceftriaxone plus amikacin (64%; 95%CI: 56%-72%), cefepime (64%; 95%CI 56%-72%), meropenem (64%; 95%CI 56%-72), and piperacillin/tazobactam (62%; 95%CI 54%-70%), respectively, did not differ significantly. The addition of vancomycin to those regimens would have increased significantly in vitro activity to 99% for ceftriaxone plus amikacin, cefepime, meropenem, and 96% for piperacillin/tazobactam (p < 0.001). Conclusions Over two decades, we detected a relative stable pathogen distribution and found no relevant trend in the antibiotic susceptibility patterns. Different recommended antibiotic regimens showed comparable in vitro antimicrobial activity.

2013 ◽  
Vol 21 (9) ◽  
pp. 2417-2426 ◽  
Author(s):  
Karin G. E. Miedema ◽  
Rik H. L. J. Winter ◽  
Roland A. Ammann ◽  
Sara Droz ◽  
Lodewijk Spanjaard ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Norazah Ahmad ◽  
Rohaidah Hashim ◽  
Azura Mohd Noor

Acute melioidosis may present as localised or septicaemic infections and can be fatal if left untreated.Burkholderia pseudomalleiresistant to antibiotics used for the treatment of melioidosis had been reported. The aim of this study was to determine the in vitro antibiotic susceptibility patterns ofBurkholderia pseudomalleiisolated in Malaysia to a panel of antibiotics used for the treatment of melioidosis and also to potential alternative antibiotics such as tigecycline, ampicillin/sulbactam, and piperacillin/tazobactam. A total of 170Burkholderia pseudomalleiisolates were subjected to minimum inhibitory concentration determination usingE-test method to eleven antibiotics. All isolates were sensitive to meropenem and piperacillin/tazobactam. For ceftazidime, imipenem, amoxicillin/clavulanic acid, and doxycycline resistance was observed in 1 isolate (0.6%) for each of the antibiotics. Trimethoprim/sulfamethoxazole resistance was observed in 17 (10%) isolates. For other antibiotics, ampicillin/sulbactam, chloramphenicol, tigecycline, and ciprofloxacin resistance were observed in 1 (0.6%), 6 (3.5%), 60 (35.3%) and 98 (57.7%) isolates respectively. One isolate B170/06 exhibited resistance to 4 antibiotics, namely, ciprofloxacin, chloramphenicol, trimethoprim/sulfamethoxazole, and tigecycline. In conclusion, the Malaysian isolates were highly susceptible to the current antibiotics used in the treatment of melioidosis in Malaysia. Multiple resistances to the antibiotics used in the maintenance therapy are the cause for a concern.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2154-2154
Author(s):  
Eline J.M. Bertrums ◽  
Axel Rosendahl-Huber ◽  
Jurrian de Kanter ◽  
Anais C.N. van Leeuwen ◽  
Flavia Peci ◽  
...  

Abstract Background Childhood cancer survivors are confronted with a variety of chronic health conditions as a consequence of their life saving therapy. Chemotherapy is the cornerstone of childhood cancer treatment, which consists of combinations of various drugs administered over multiple years. Most chemotherapeutic drugs act by fatally damaging the DNA or blocking the replication thereof. Although high-intensity chemotherapy efficiently eradicates tumor cells, the impact on the genomes of normal, that is noncancerous, cells remains unknown. Mutagenicity of cancer treatment on normal hematopoietic cells may contribute to the development of chronic health conditions later in life, such as therapy-related acute myeloid leukemia (t-AML). Here, we characterized the mutational consequences of chemotherapy in the genomes of hematopoietic stem and progenitor cells (HSPCs) of children treated for cancer. Methods This study was approved by the Biobank and Data Access Committee of the Princess Máxima Center for Pediatric Oncology and all samples were obtained via the in-house biobank. We performed whole-genome sequencing (WGS) on multiple single HSPCs from all patients as well as the t-AML if available. In case of t-AML patients, samples were taken before t-AML treatment. Data on mutation accumulation in HSPCs of healthy individuals from 0-63 years of age was previously acquired. To distinguish the effects of different chemotherapies, we developed an in vitro approach using cord blood HSPCs to experimentally define the mutational consequences of individual chemotherapeutic drugs in primary human cells. Results Our cohort consisted of 22 pediatric cancer patients of which we obtained bone marrow aspirates and/or peripheral blood from timepoints pre- and post-treatment for their first cancer. We included 17 t-AML patients with varying first cancer diagnoses and five acute lymphoblastic leukemia (ALL) patients who did not develop t-AML. Patient characteristics and therapy information is described in Table 1. We compared the mutational burden of pre- and post-treatment HSPCs of the childhood cancer patients to those of healthy treatment-naïve individuals. HSPCs at time of first diagnosis of childhood cancer patients displayed a mutation burden similar to HSPCs of healthy individuals. In contrast, post-treatment HSPCs showed a significantly higher increase in mutation number over time than expected by normal ageing. We used mutational signature analysis to pinpoint the causes of this increased mutation burden in post-treatment HSPCs. Surprisingly, in most of these HSPCs the additive mutational effect could be attributed to clock-like processes, active during normal aging. Only few chemotherapeutic drugs showed direct mutagenic effects, such as platinum drugs and thiopurines. Whereas cisplatin-induced mutations could be observed in all cells exposed to this drug, thiopurine-induced mutations were present in a subset of the exposed HSPCs. These differences in thiopurine-induced mutagenesis across multiple exposed HSPCs could even be observed within individual patients. In one patient, the HSPCs containing the thiopurine-signature shared the oncogenic MLL-rearrangement with the t-AML blasts and had shorter telomeres compared to the HSPCs without this signature. This finding indicates that these cells have undergone more cell divisions, suggesting that thiopurine-induced mutagenesis requires DNA replication. We also identified novel therapy-associated mutational signatures. One of these signatures was observed in multiple patients who received a hematopoietic stem cell transplantation, as part of their cancer treatment, after which they displayed a viral reactivation for which they were treated. By WGS of in vitro exposed cord blood HSPCs, we demonstrated that this signature is caused by the antiviral drug ganciclovir, which is commonly used to treat cytomegalovirus infections. The second signature was present in HSPCs of a patient who received a combination of thiotepa and treosulfan. Conclusions Enhanced mutation accumulation after pediatric cancer treatment is caused by both direct and indirect mechanisms. The variance in mutagenic effects of (chemo)therapies on healthy HSPCs may influence the risk an individual patient has to develop t-AML and could, in future, play a role in t-AML risk assessment of pediatric cancer survivors and the development of new treatment regimens. Figure 1 Figure 1. Disclosures Zwaan: Sanofi: Consultancy.


2006 ◽  
Vol 49 (8) ◽  
pp. 882 ◽  
Author(s):  
Sun Mi Park ◽  
Byung Kyu Choe ◽  
Chun Soo Kim ◽  
Joon Sik Kim ◽  
Heung Sik Kim ◽  
...  

2020 ◽  
Vol 41 (S1) ◽  
pp. s34-s35
Author(s):  
Dustin Flannery ◽  
Ibukun Akinboyo ◽  
Sagori Mukhopadhyay ◽  
Alison Tribble ◽  
Lihai Song ◽  
...  

Background:Escherichia coli (E. coli) is a leading cause of infections among term and preterm newborn infants. Continued surveillance of neonatal E. coli antibiotic susceptibility patterns is important to optimize empiric antibiotic prescription for infants at risk for infection, in light of evolving reports of multidrug-resistant gram-negative bacteria in all settings. Our objective was to determine E. coli epidemiology and antibiotic susceptibility patterns among a large sample of infants admitted to neonatal intensive care units (NICUs) across the United States from 2009 to 2017. Methods: Retrospective observational study using the Premier Database, including infants born from 2009 to 2017 and admitted to academic or community NICUs contributing microbiology data during the study period. We analyzed antibiotic susceptibilities for E. coli isolated from blood, cerebrospinal fluid, and urine. We focused on clinically relevant and priority susceptibility categories: (1) ampicillin nonsusceptible; (2) aminoglycoside nonsusceptible; (3) carbapenem nonsusceptible; and (4) extended-spectrum β-lactamase (ESBL; phenotypic definition). We determined the proportion of infants with nonsusceptible organisms in each category by year and tested for changes over time. Lastly, we assessed susceptibility patterns by specimen source, birthweight, and timing of infection. Results: Of the 117,484 included infants, 733 (0.6%) had at least 1 E. coli episode, of which 721 (98.4%) had available susceptibility results, from 69 centers. Patient and center characteristics of infants with E. coli are shown in Table 1. Most organisms were tested against ampicillin (99.9%), gentamicin (99.6%), and ceftriaxone (91.5%). Figure 1 shows nonsusceptibility rates for the categories of interest. Overall, ampicillin nonsusceptibility ranged from 63.3% to 68.6% per year (mean, 66.8%±1.5%); aminoglycoside nonsusceptibility ranged from 10.7% to 23.2% (mean, 16.8%±4.5%); carbapenem nonsusceptibility was 0% for all years; and ESBL ranged from 1.2% to 11.3% (mean, 5.1%±3.4%). We detected no statistically significant trends for any of the categories of interest over time (all P > .05), and susceptibility trends were consistent when repeated by specimen source, birthweight, and timing of infection. Conclusions: We found stable, yet concerning, patterns of E. coli antibiotic nonsusceptibility among infants admitted to NICUs across the United States from 2009 to 2017. Rates of ampicillin nonsusceptibility and aminoglycoside nonsusceptibility were higher than previous reports. ESBL E. coli rates were low but present among neonatal patients. No carbapenem nonsusceptible E. coli was identified. These findings can inform empiric antibiotic prescription for infants admitted to NICUs across the United States.Funding: NoneDisclosures: None


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