The aim of this thesis was to contribute to infection preventive strategies in hematology patients with prolonged neutropenia. Invasive pulmonary aspergillosis (IPA) develops by pulmonary deposition of conidia. A placebo-controlled trial on the efficacy of prophylactic aerosolized liposomal amphotericin-B (L-AmB) was performed in hematology patients during treatment-related neutropenia. For the intent-to-treat analysis, 18 of 132 placebo patients developed IPA, versus 6 of 139 in L-AmB patients (P=.005). Short-term prophylactic nebulization of liposomal amphotericin B was not associated with decline in pulmonary function or systemic adverse effects, only coughing was significantly more reported. In a study among acute leukemia patients, the mortality rate was 26% and 16%, respectively, in patients with and without IPA (P=.08), with corrected additional IPA-related costs of €15280 (P<.001), which makes IPA prevention both efficacious and cost-effective. Current guidelines advocate administration of 7-14 days of broad-spectrum antibiotics for unexplained ferver (UF) in neutropenic hematology patients. Effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. In the Erasmus MC, broad-spectrum antibiotics are initially administered, but discontinued when after 72 hours no bacterial etiology is documented. Among 166 hematology patients on selective antibiotic prophylaxis, 317 febrile episodes were observed; 56% were due to UF. Due to the restrictive antibiotic policy, the mean treatment duration was only 3.7 days. Overall-mortality after neutrophil recovery was 3.6% (6 of 166 patients). No patient died from untreated bacterial infection, suggesting that discontinuation of broad-spectrum antibiotics in this setting is safe, provided that no infectious etiology is documented. Diagnosing catheter-related bloodstream infection (CRBSI) often involves tip culture, using the conventional semi-quantitative roll-plate method. The quantitative sonication technique could have additional value, as it may also detect endoluminal microorganisms. However, in a prospective study of 313 tunnelled catheters from 279 hematology patients, the diagnostic performance in patients with suspected CRBSI was equally limited for both methods. Finally, in a placebo-controlled trial on the efficacy of a daily prophylactic 70%-ethanol lock on the prevention of endoluminal CRBSI in tunneled devices, a 3.6-fold, non-significant, reduction was observed for ethanol-treated hematology patients. Partially, the lack of significance may reflect a lack of power. More patients receiving ethanol discontinued lock-therapy, because of non-severe adverse events.

CRBSI, IPA, acute leukemia, aerosolized liposomal amphotericin B, bacteremia, catheter-related bloodstream infection, infection prevention, invasive pulmonary aspergillosi, prolonged neutropenia
H.A. Verbrugh (Henri)
Erasmus MC: University Medical Center Rotterdam
Aktie BV, AstraZeneca BV, Boehringer Ingelheim BV, Eli Lilly Nederland BV, Gilead Sciences BV, Janssen-Cilag BV, Merck Sharp & Dohme BV, Pfizer BV, Romedic BV, Schering-Plough BV, ViiV Healthcare BV
978-90-8559-997-5
hdl.handle.net/1765/19772
Erasmus MC: University Medical Center Rotterdam

Slobbe, L. (2010, June 16). Infectious complications in hematology patients: A clinical focus on prevention. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/19772