MD Conference Express ICAAC 2011 - (Page 9)
Table 2. Antibiotic Duration.
Days of use ProHosp PCT intervention group ProReal study ProHosp control group (standard care) 5.0 6.2 7.9 p value 0.001; 1 vs 2 <0.001; 2 vs 3
Dr. Day and his colleagues were interested in whether combining antifungal therapies in the induction phase of treatment would offer a survival advantage when compared with amphotericin monotherapy, the standard practice in Vietnam. Enrolled patients presented with a syndrome that was consistent with cryptococcal meningitis and microbiological evidence of Cryptococcus in the CSF and/or blood. All patients were >14 years of age and HIV-positive. Patients with prior history of cryptococcal infection or prior antifungal treatment (>3 days) were excluded. Patients were randomly assigned to receive one of three possible induction treatments: amphotericin B 1 mg/kg/day monotherapy for 4 weeks (Arm I, the standard of care in Vietnam); amphotericin B 1 mg/kg/day plus flucytosine 100 mg/kg/day for 2 weeks (Arm II); or amphotericin B 1 mg/kg/day plus fluconazole 400 mg twice daily for 2 weeks (Arm III; Table 1). The coprimary endpoint was mortality at 2 and 10 weeks. Secondary endpoints included survival to 6 months and disability at 70 days and 6 months. Table 1. Study Design.
Treatment Arm I II Week 1 2 3 4 5 6 7 8 9 10 26 FLCZ 200 mg/day FLCZ 200 mg/day APT B 1 mg/kg/day APT B 1 mg/kg/day + FLTS 200 mg/day APT B 1 mg/kg/day + FLCZ 200 mg/day FLCZ 400 mg daily FLCZ 400 mg daily
PCT affected the decision to withhold or initiate antibiotics. Its greatest effect in patients with COPD exacerbation or bronchitis was to reduce initial prescription of antibiotic therapy, whereas for patients with pneumonia, it was most effective in shortening antibiotic duration. No significant increases in adverse medical outcome were detected. Published evidence on PCT-guided antibiotic therapy to date has been obtained in trials in which physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance.
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
Written by Noelle Lake, MD
III
FLCZ 400 mg daily
FLCZ 200 mg/day
The first randomized, controlled trial to show a survival benefit of an antifungal treatment in HIV-infected patients with cryptococcal meningitis was completed this year in Vietnam [ISRCTN 95123928]. Results were presented by Jeremy N. Day, MD, Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam, in collaboration with colleagues from the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The study compared three induction-phase treatment strategies that are currently recommended by the Infectious Disease Society of America [Perfect JR et al. Clin Infect Dis 2010]. Although combination therapy with flucytosine is considered first-line therapy, a mortality benefit over other regimens has not been shown in a randomized, controlled trial. Also, there are distinct disadvantages to flucytosine use—namely expense, toxicity, and poor availability in areas with high cryptococcal disease rates.
APT=amphotericin; FLCZ=fluconazole; FLTS=flucytosine. Reproduced with permission from J. Day, MD.
The intent-to-treat (ITT) population comprised 298 patients, predominantly male, with a median age of 28 years. Approximately 30% had some level of impaired consciousness, reflected by a Glasgow coma score of <15. All patients underwent lumbar puncture, which revealed elevated CSF opening pressure (>18 cm/CSF) in over twothirds of patients and high yeast burdens (median 5.9 log 10 CFU/mL). Compared with amphotericin monotherapy, the amphotericin+flucytosine combination was associated with a significantly reduced hazard of death by both Day 70 [HR, 0.61; 95% CI, 0.39 to 0.97; p=0.04] and Day 182 [HR, 0.56; 95% CI, 0.36 to 0.89; p=0.01] (Figure 1). Amphotericin B, combined with fluconazole, offered
Official Peer-Reviewed Highlights from the 51st ICAAC
9
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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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