piperacillin--tazobactam-drug-combination and Graft-vs-Host-Disease

The utility of weekly rectal swab surveillance cultures (RSSCs) as a resource to identify gut colonization with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and guide empirical antibiotic therapy in hematopoietic stem cell transplantation (HSCT) recipients continues to be a subject of interest. There is an urgent need to assess and justify modifications to empirical antibiotics based on regional epidemiology and patient groups. This study aimed to study the utility of weekly rectal swab surveillance cultures (RSSCs) to guide empirical antibiotic therapy and to examine the impact of gut colonization on transplantation outcomes. This retrospective analysis of 317 successive first HSCTs performed mainly for hemoglobinopathies was conducted in 3 pediatric bone marrow transplantation centers in the Indian subcontinent between April 2016 and April 2021. Transplantation, infection control, and febrile neutropenia management protocols were identical in the 3 centers. First-line antibiotics were chosen based on RCCS reports, with meropenem used for ESBL and high-dose meropenem with colistin used for carbapenemase-resistant colonization for first half of the study, with no adjustment made in the second half. Clinical response to antibiotics, long-term outcomes, antibiotic-resistant bacteremia, and acute graft-versus-host disease (GVHD) were analyzed. The log-rank test, chi-square, and Wilcoxon rank-sum tests were used to compare data using R Statistical software. Of the 871 weekly RSSCs done, 162 were positive for ESBL- or KPC-resistant organism. RCCSs were ESBL-positive in 106 patients (33%) and KPC-positive in 10 patients (3%). Among the 97 ESBL-positive patients for whom a antimicrobial susceptibility testing report was available, only 22 (25%) demonstrated clinical resistance to piperacillin-tazobactam (Pip-Taz). Among the 10 KPC-positive patients, only 4 (40%) demonstrated clinical resistance to Pip-Taz and 3 (30%) had clinical resistance to meropenem. Two-thirds of patients with ESBL-positive RSSC in whom first-line empirical antibiotics were used responded clinically. Even among the 15 patients who were resistant to first-line empirical antibiotics (Pip-Taz) on RSSC reports, 67% responded clinically to Pip-Taz. Twenty-seven of these patients (56%) never needed carbapenem therapy. Empirical Pip-Taz therapy in ESBL-positive patients did not prolong meropenem use within 100 d

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Child; Escherichia coli; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infection Control; Klebsiella pneumoniae; Meropenem; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; United States

Changes in fecal microbiota affect the incidence and extent of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Most patients with hematological malignancies receive antibiotics for the treatment of febrile neutropenia prior to allogeneic HSCT, and pre-transplant use of antibiotics may influence the fecal microbiota and GVHD.. We retrospectively analysed consecutive adult patients with hematological malignancies who received allogeneic HSCT at Chungnam National University Hospital between 2007 and 2018. Pre-transplant use of antibiotics was defined as the use of antibiotics before conditioning chemotherapy.. Pre-transplant use of glycopeptide tends to increase the incidence of extensive cGVHD.

Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenems; Cefepime; Disease-Free Survival; Female; Glycopeptides; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Transplantation, Homologous; Treatment Outcome; Young Adult

Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P < 0.01 and P < 0.05, respectively). We found pathological evidence for increased GVHD in the colon of imipenem-cilastatin-treated mice (P < 0.05), but no difference in the concentration of short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P < 0.01) and the compromising of intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon.

Topics: Animals; Anti-Bacterial Agents; CD4-Positive T-Lymphocytes; Cilastatin; Cilastatin, Imipenem Drug Combination; Colon; Drug Combinations; Feces; Female; Flow Cytometry; Gastrointestinal Microbiome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Imipenem; Interleukin-23; Mice; Mice, Inbred C57BL; Penicillanic Acid; Phylogeny; Piperacillin; Piperacillin, Tazobactam Drug Combination; Transplantation, Homologous; Verrucomicrobia

In this prospective study including 78 adult patients with haematological malignancy (90 episodes) we performed galactomannan (GM) (Platelia Aspergillus) screening twice weekly for the diagnosis of invasive aspergillosis. There were five proven and four probable invasive aspergillosis cases. The sensitivity, specificity and positive and negative predictive values were 100, 88, 47 and 100%, respectively. There were eight patients with false positive GM (10.2%). In six patients the false GM reactivity was due to the administration of piperacillin-tazobactam (P-T). A significant association was found between false positive GM (= or > 0.5) and the administration of P-T (p < 0.01). Two other patients with no invasive aspergillosis (2.5%) and false GM reactivity had graft versus host disease (GVHD) and one of them had also mucositis grade IV. The kinetic patterns of false positive GM due to P-T is discussed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Artifacts; Aspergillosis; Biomarkers; Combined Modality Therapy; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Fungemia; Galactose; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Mucositis; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity