Tigecycline Use in Cancer Patients With Serious Infections

Abstract

Tigecycline, the first in a new class of glycylcyclines, has been approved for the treatment of complicated skin and skin structure and intraabdominal infections in adults. However, clinical data on its safety and effectiveness in cancer patients are lacking. We reviewed the records of all cancer patients treated with tigecycline for more than 48 hours between June 2005 and September 2006 at our institution and identified 110 consecutive cases (median age, 58 yr; range, 18-81 yr). We collected data on demographics, cancer type, tigecycline indication, microbiologic characteristics, side effects, and outcome. Sixty-four (58%) patients had hematologic malignancies; 27 patients had undergone hematopoietic stem cell transplantation. Thirty-one (28%) patients had neutropenia, and 62 (56%) were in the intensive care unit at the start of therapy. Most patients (106 [96%]) received tigecycline as a second-line agent (after not responding to other broad-spectrum antibiotics), and 101 (92%) received it in combination with an antipseudomonal drug. The mean duration of therapy was 11 days (range, 3-35 d). Sixty-six (60%) patients received tigecycline for refractory pneumonia, 19 (17%) had bacteremia, 9 (8%) had intraabdominal infections, and 7 (6%) had complicated skin and soft tissue infections. Fifty (45%) patients had microbiologically documented infections, and the remaining patients had negative cultures at the start of therapy.An overall clinical response was noted in 70 (64%) patients. More clinical responses were seen in patients with bacteremia than in those with pneumonia (79% vs. 51%; p = 0.029). Patients with microbiologically documented infections had significantly higher clinical response rates than patients with non-microbiologically documented infections (73% vs. 55%; p = 0.047). Forty (36%) patients did not respond to treatment; 36 of these patients died of active infection during tigecycline therapy. Patients with pneumonia had a significantly higher mortality rate than patients with bacteremia (44% vs. 16%; p = 0.026). During the 60 days of follow-up from the date of clinical response, patients with pneumonia had significantly shorter survival durations than patients with other infections. Of the 42 patients who were not on antiemetics or ventilator support at the start of tigecycline therapy, 2 (5%) experienced mild nausea, and 1 (2%) experienced nausea and vomiting. Only 4 (4%) patients overall experienced diarrhea during tigecycline therapy, all of whose stools were negative for Clostridium difficile toxin. No serious adverse events related to tigecycline use were identified. The combination of tigecycline and an antipseudomonal drug may be appropriate for treating refractory infections and multidrug-resistant organisms in cancer patients, including hematopoietic stem cell transplant recipients. Patients with refractory pneumonia had a relatively low clinical response rate in our study.

Meta-analysis of Randomized Controlled Trials of Vancomycin for the Treatment of Patients With Gram-Positive Infections: Focus on the Study Design

“…However, data from nonrandomized studies indicate that these newer antibiotics might be useful for the treatment of such patients. [88][89][90] Limited data are also available for the effectiveness of individual comparator antibiotics for the treatment of bacteremic patients. It is noteworthy that 850 CE patients were studied in 19 trials that reported the outcomes of patients with bacteremia.…”

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

“…Patients with pneumonia had lower response and higher mortality rates than those with bacteremia (51% vs. 79%, 44% vs. 16% respectively, both P<0.05). 57 In another study, tigecycline was used at standard dosages for the treatment of serious hospital-acquired infections caused by MDR bacteria, including 50 patients (24%) with hematological malignancies. Alone or combined with other antibiotics, it showed efficacy in 16/23 (70%) of bacteremia cases and in 7/12 (58%) in whom it was used for empirical treatment of febrile neutropenia.…”

“…57 Not all isolates were susceptible, or were tested to the antibiotics administered, concurrently with the tigecycline. Clinical response was achieved in 56% of transplant recipients, being higher in non-pseudomonas than pseudomonas infections (80% vs. 50%, P=0.06).…”

“…95,128,129 Tigecycline shows in vitro activity against glycopeptidenon-susceptible Gram-positive bacteria; studies that considered its activity were outlined above in the section on Gram-negative pathogens. 57,58 Other new agents active against some resistant Grampositive bacteria include lipoglycopeptides (e.g., telavancin) and anti-MRSA β-lactams (e.g. ceftaroline), whilst fosfomycin -an old agent -is active against many MRSA and VRE, especially E. faecalis, at least in vitro.…”

“…32,56 Nevertheless, tigecycline was used at standard dosage, in combination with an anti-pseudomonal drug (β-lactams, quinolones, aminoglycosides) in 110 adult cancer patients (58% with hematological malignancies and 24% post-HSCT) as salvage therapy, for the treatment of refractory pneumonia (60%), bacteremia (17%) or other infections, which were microbiologically documented in 45% of the patients. 57 Not all isolates were susceptible, or were tested to the antibiotics administered, concurrently with the tigecycline. Clinical response was achieved in 56% of transplant recipients, being higher in non-pseudomonas than pseudomonas infections (80% vs. 50%, P=0.06).…”