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
