piperacillin--tazobactam-drug-combination and Hematologic-Diseases

Background Piperacillin/tazobactam, a semisynthetic antibiotic, is widely used to treat polymicrobial infections. Its hematologic adverse reactions are rare and the severity can be mild to life-threatening. To our knowledge, there has not been a publication reviewing hematologic abnormalities attributable to piperacillin/tazobactam. Aim of the review To evaluate the characteristic, clinical identification, mechanism and treatment of the hematologic toxicity caused by piperacillin/tazobactam. Method A search of Medline and Embase electronic databases was performed for case reports of adverse reactions of hematologic system related to piperacillin/tazobactam from inception to December 2018. Statistical analysis of demographic, clinical features, laboratory Indexes and treatments was performed using Microsoft EXCEL 2007. Results Fifty-nine references were obtained involving 62 patients. The adverse drug reactions were mainly hemolytic anemia (25, 40.3%), thrombocytopenia (23, 37.1%), and neutropenia (12, 19.4%), which might be accompanied by some typical symptoms. Hemolytic anemia or thrombocytopenia was generally believed to be immune-mediated and often appeared within 10 days, and neutropenia was thought to be related to bone marrow suppression and usually occurred 2 weeks after the initiation of piperacillin/tazobactam. Most patients improved or recovered within a week with treatment or not, and fewer high-quality evidence-based treatments were identified. Conclusion Although part of the patients have clinical symptom, the hematologic adverse drug reactions of piperacillin/tazobactam are easily overlooked or misdiagnosed. Take special caution for patients with prolonged piperacillin/tazobactam treatment or specific disease, and prompt recognition and treatment of the adverse drug reactions are essential and can hasten recovery regardless of the type of side reactions.

Topics: Anti-Bacterial Agents; Hematologic Diseases; Humans; Piperacillin, Tazobactam Drug Combination

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Infections; Ceftazidime; Drug Resistance, Bacterial; Escherichia coli; Fever; Gram-Positive Bacteria; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hospitalization; Humans; Israel; Meropenem; Middle Aged; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].

Topics: Amoxicillin; Antibiotic Prophylaxis; Antigens, Fungal; Artifacts; Aspergillosis; Aspergillus; False Positive Reactions; Galactose; Hematologic Diseases; Hematologic Neoplasms; Humans; Immunoglobulin G; Mannans; Multiple Myeloma; Myeloma Proteins; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sensitivity and Specificity

Piperacillin/tazobactam (P/T) was used in the treatment of 14 patients at the age of 5 to 15 years: 5 patients with acute lymphoblastic leukemia, 3 with acute nonlymphoblastic leukemia, 4 with severe aplastic anemia, 1 with lymphoma and 1 with neuroblastoma. P/T was administered as intravenous infusions in a daily dose of 200-300/25-37.5 mg/kg body weight divided into 3 or 4 portions. All the patients were subjected to intestine selective antimicrobial decontamination. In 7 patients the afebrile condition was recorded before elimination of agranulocytosis without correction of the therapy i.e. without combination of P/T with some other antibiotics such as amphotericin B, vancomycin or aminoglycosides. In 5 patients the effect was stated after correction of the regimen by its supplementing with amphotericin B. 2 patients died. No side effects of P/T was observed. The afebrile condition was provided in 1 to 7 days. P/T is recommended for the treatment of fever of obscure etiology in patients with agranulocytosis and for effective control of infection in such patients.

Topics: Adolescent; Agranulocytosis; Child; Child, Preschool; Drug Therapy, Combination; Fever of Unknown Origin; Hematologic Diseases; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome