Posaconazole serum concentrations among cardiothoracic transplant recipients: factors impacting trough levels and correlation with clinical response to therapy.

Fifty-six serum posaconazole trough levels were measured in 17 cardiothoracic transplant recipients. Initial levels were ≤ 0.5, 0.51 to 0.99, and ≥ 1 µg/ml for 47, 29, and 24% of patients, respectively. Median trough levels associated with therapeutic success were higher than those associated with failure (1.55 versus 0.34 µg/ml; P = 0.006). Patients with levels consistently >0.5 µg/ml were more likely to have successful outcome (P = 0.055). Age ≥ 65 years, oral administration, and absence of proton pump inhibitors were associated with higher levels of posaconazole (P = 0.006, 0.006, and 0.001, respectively).

Epidemiology, clinical characteristics and outcomes of extensively drug-resistant Acinetobacter baumannii infections among solid organ transplant recipients.

BACKGROUND: Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients are particularly susceptible to XDR-Ab infections, studies in this population are limited. Our objectives were to determine the epidemiology, clinical characteristics and outcomes of XDR-Ab infections among SOT patients. METHODS: A retrospective study of SOT recipients at our center who were colonized or infected with XDR-Ab between November 2006 and December 2011 was conducted. Among infected patients, the primary outcome was survival at 28 days. Secondary outcomes included survival at 90 days and clinical success at 28 days, and XDR-Ab infection recurrence. RESULTS: XDR-Ab was isolated from 69 SOT patients, of whom 41% (28) and 59% (41) were colonized and infected, respectively. Infections were significantly more common among cardiothoracic than abdominal transplant recipients (p=0.0004). Ninety-eight percent (40/41) of patients had respiratory tract infections, most commonly ventilator-associated pneumonia (VAP; 88% [36/41]). Survival rates at 28 and 90 days were 54% (22/41) and 46% (19/41), respectively. Treatment with a colistin-carbapenem regimen was an independent predictor of 28-day survival (p=0.01; odds ratio=7.88 [95% CI: 1.60-38.76]). Clinical success at 28 days was achieved in 49% (18/37) of patients who received antimicrobial therapy, but 44% (8/18) of successes were associated with infection recurrence within 3 months. Colistin resistance emerged in 18% (2/11) and 100% (3/3) of patients treated with colistin-carbapenem and colistin-tigecycline, respectively (p=0.03). CONCLUSIONS: XDR-Ab causes VAP and other respiratory infections following SOT that are associated with significant recurrence and mortality rates. Cardiothoracic transplant recipients are at greatest risk. Results from this retrospective study suggest that colistin-carbapenem combinations may result in improved clinical responses and survival compared to other regimens and may also limit the emergence of colistin resistance.