Practice patterns for antibiotic de-escalation in culture-negative healthcare-associated pneumonia.

BACKGROUND: Published guidelines for the treatment of healthcare-associated pneumonia (HCAP) recommend initial broad-spectrum antibiotics with appropriate de-escalation based on culture results. Guideline recommendations are based on data from intubated patients, in whom cultures are easily obtained. The approach to antibiotic de-escalation for culture-negative patients has not been addressed. Consequently, there are no published reports that describe the current standard of practice. PATIENTS AND METHODS: All patients admitted to a university hospital with a diagnosis of HCAP, as defined by use of a pneumonia orderset, were identified retrospectively over a 2-year period. Antibiotics prescribed on admission, during hospital stay, and on discharge were recorded. De-escalation was defined as a change in the initial antibiotic therapy from broad- to narrow-spectrum coverage within 14 days of the initial prescription. The Pneumonia Severity Index was used for risk-adjustment. RESULTS: A total of 102 patients were included in the analysis; of these, 72% (n = 73) were culture-negative. There were more males in the culture-negative than culture-positive group; otherwise, baseline characteristics were similar. Antibiotic therapy was de-escalated in 75% of the culture-negative group and 77% of the culture-positive group (p = 1.00). Culture-negative patients were de-escalated approximately 1 day earlier than culture-positive patients (3.93 vs. 5.04 days, p = 0.03). Culture-negative patients who were de-escalated had a shorter length of hospitalization, lower hospital costs, and lower mortality rates. In 70% of the culture-negative patients, a respiratory fluoroquinolone was chosen for de-escalation. CONCLUSION: In this single-center study, most of the patients with culture-negative HCAP were safely de-escalated to a respiratory fluoroquinolone.

Identification of the indoleamine 2,3-dioxygenase nucleotide sequence in a rat liver transplant model.

A tryptophan catabolizer, indoleamine 2,3-dioxygenase (IDO) is highly expressed in the placenta and plays an essential role in maternal tolerance. Recent data have shown that the administration of an IDO inhibitor blocked not only maternal tolerance but also liver allograft tolerance. However, little is known about the induction of IDO in liver allografts, although a gene specific for tryptophan 2,3-dioxygenase (TDO) is believed to be expressed in the liver. In the present study, we investigated whether IDO is induced in liver allografts. Synthetic oligonucleotide primers based on the mouse IDO cDNA sequence were used to amplify RNA derived from livers of donor, syngeneic or allogeneic OLT rats. RNA encoding IDO was induced in the rat allogeneic liver after orthotopic liver transplantation (OLT), but not in syngeneic OLT. The rat nucleotide sequence of the RT-PCR products obtained from OLT livers revealed identities of 89% homology to the mouse IDO and of 68% to the human IDO. This study demonstrated the presence of RNA encoding IDO in allogeneic OLT livers, which may be involved in the immune response after liver transplantation.