Serum posaconazole levels during acute myeloid leukaemia induction therapy: correlations with breakthrough invasive fungal infections.

The usefulness of posaconazole therapeutic drug monitoring (TDM) is still a matter of debate. A correlation between posaconazole serum levels and breakthrough invasive fungal infections (IFI) has not been clearly demonstrated so far. We analysed posaconazole serum levels in patients with acute myeloid leukaemia (AML) during induction therapy and correlated them with the incidence of breakthrough IFI and the need of systemic antifungal therapy. Overall, 77 AML patients receiving posaconazole were evaluated for serum levels; breakthrough IFI were observed in five with at least one posaconazole TDM (6.5%). Median serum level was 534 ng ml(-1) (IQ range: 298.5-750.5 ng ml(-1) ) and did not change significantly over time. Four of the 40 patients with median posaconazole levels <500 ng ml(-1) developed IFI, as compared with only 1 of the 37 patients with median levels ≥500 (10% vs. 2.7%, P = 0.19). Median posaconazole levels on day 7 were 384.5 ng ml(-1) (IQ range: 207-659 ng ml(-1) ) and 560.5 ng ml(-1) (IQ range: 395-756 ng ml(-1) ) in patients requiring or not systemic antifungal treatment respectively (P = 0.067). These results seem to confirm that higher median serum levels of posaconazole correlate with higher prophylactic efficacy against proven/probable IFI and with lesser need of systemic antifungal therapy.

Relapsing bloodstream infections during treatment of acute leukemia.

Acute leukemia (AL) patients may experience more than one episode of bloodstream infection (BSI) caused by the same pathogen during the entire chemotherapy program. In order to identify factors influencing BSI recurrence (R-BSI) during subsequent phases of treatment, we analyzed all BSIs occurring to consecutively treated AL patients during a period of active epidemiologic surveillance at our institution between 2004 and 2011. Two hundred and fifty BSIs were observed in 138 patients receiving more than 1 cycle of chemotherapy. BSI due to the same pathogen recurred in 39/138 (28.3 %) patients. Gram-negative rods (GNRs) accounted for 59.6 % and Gram-positive cocci (GPCs) for 34.4 % of BSI. Four pathogens were involved in R-BSI: Escherichia coli, Pseudomonas aeruginosa, coagulase-negative staphylococci, and Streptococcus viridans. GNRs were significantly more frequent among R-BSI compared to non-relapsing BSI (nR-BSI) [69/94 (73.4 %) vs 70/156 (50.6 %), p < 0.0001]; in particular, E. coli accounted for 67 % of R-BSI vs 32.1 % of nR-BSI (p < 0.0001). Receiving more than four chemotherapy courses and having an extended spectrum ß-lactamase (ESBL)-producing E. coli BSI at any time of treatment were significantly associated to R-BSI. A trend toward a higher mortality among R-BSI patients in comparison with nR-BSI was observed (17.9 and 7.1 %, respectively, p = 0.12). Among AL patients, R-BSI is a frequent phenomenon, which may contribute to the shift of epidemiology toward GNR and to a higher mortality. This should significantly impact the strategies of antibiotic prophylaxis and treatment in patients with AL.