MD Conference Express ICAAC 2011 - (Page 11)
range of 68% (Acinetobacter spp.) to 100% (Haemophilus influenzae). When CXA-201 potency was analyzed by site of infection, approximately 95% of all isolates had an MIC ≤8 μg/mL, with a range of 94% (blood) to 96.9% (urine). Whether sorted by site or source, approximately 95% of isolates had an MIC value <8 μg/mL. All pathogens had an MIC90 ≤8 μg/mL except Enterobacter cloacae (88% inhibited at ≤8 μg/mL) and Acinetobacter spp. (68.5% inhibited at ≤8 μg/mL). Thus, CXA-201 is predicted to achieve excellent target attainment of 40% T>MIC against common ICU pathogens and multidrug-resistant gramnegative pathogens, including P. aeruginosa (99.3% inhibited at ≤8 μg/mL).
Successful treatment was defined as resolution of fever (maintained for at least 4 days) or any clinical sign of infection whenever present and eradication of the infecting microorganism whenever isolated, without change in the initial allocated treatment. Failure was defined as one of the following: death from primary infection, persistence of bacteremia beyond the first 24 hours of therapy, breakthrough bacteremia, documented pathogen resistant to assigned antibiotic(s), lack of response that required antibacterial therapy modification, development of shock or acute respiratory distress syndrome or disseminated intravascular coagulation or multiple organ failure, relapse of infection within 7 days of treatment discontinuation, or toxicity requiring treatment discontinuation. Overall response to therapy was significantly (p<0.01) more effective following piperacillin/tazobactam plus tigecycline (72%) compared with monotherapy (47%; Table 1). Piperacillin/tazobactam plus tigecycline treatment success rates were significantly (p≤0.01) greater for microbiologically (with bacteremia) and clinically documented infections compared with monotherapy. Single gram-positive and -negative (E. coli) bacteremias and coagulase-negative Staphylococcus species were more successfully treated with combination therapy than monotherapy (Table 2). Table 1. Classification of Febrile Episodes and Response To Therapy.
Type of infection Piperacillin/ tazobactam + tigecycline* 174 54/88 (61%) 52/86 (60%) 2/2 (62%) 16/19 (84%) 56/67 (83%) 126/174 (72%) Piperacillin/ tazobactam* 190 27/96 (28%) 26/94 (27%) 1/2 (25%) 9/19 (47%) 54/75 (72%) 90/190 (47%) <0.01 <0.01 0.5 0.01 0.07 <0.01 p value
Tigecycline Plus Standard Therapy Is More Effective Than Standard Therapy Alone For Treating Infections in Febrile Neutropenic Cancer Patients
Written by Eric Butterman
Tigecycline, first in a new class of glycylcyclines, in combination with piperacillin/tazobactam, is effective, safe, and well tolerated in high-risk febrile neutropenic oncohematologic patients. Giampaolo Bucaneve, MD, University of Perugia, Perugia, Italy, believes that tigecycline in combination should be considered one of the “first-line” empiric antibiotic therapies (particularly in a specific epidemiological setting (eg, high rate of extended-spectrum β-lactamase-producing gramnegatives and/or methicillin-resistant Staphylococci). This combination therapy may aid in reducing the increase and extensive use of carbapenems, which have been associated with an increase in multidrug-resistant bacteria. This prospective, randomized, multicenter study included 364 cancer patients from 28 Italian oncohematological departments with profound (<500 neutrophils/mmc) chemotherapy-induced neutropenia and fever (>38.5°C once or >38°C on at least two occasions during a period of 12 hours) due to presumed infection. Patients were randomized centrally and stratified according to center and underlying disease (acute leukemia vs lymphoma and solid tumors). Patients received either IV (n=174) piperacillin/tazobactam (4.5 g 3x daily) plus tigecycline (50 mg twice daily) or IV (n=190) piperacillin/tazobactam (4.5 g 3x daily) as monotherapy. All other antibiotic therapy was stopped at randomization.
Total febrile episodes Microbiologically documented infections with bacteremia without bacteremia Clinically documented infections Unexplained fever Total *success/total
Table 2. Agents of Bacteremias and Antibiotic Susceptibility.
Organism Total Gram-positives Total Gram-negatives Coagulase-negative Staphylococcus Tigecycline* 80/89 (90%) 53/66 (80%) 54/58 (93%) Piperacillin/ tazobactam* 23/94 (24%) 45/71 (63%) 4/62 (6.5%)
Official Peer-Reviewed Highlights from the 51st ICAAC
11
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Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011
MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten
MD Conference Express ICAAC 2011
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