We report a case of resistance development towards cefiderocol in a patient with intra-abdominal and bloodstream infections caued by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.

Background: There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries.

Abdominal surgery may affect intestinal absorption and the resulting levels of posaconazole in the blood. We measured plasma posaconazole levels in surgical intensive care unit (SICU) patients and tried to develop a predictive population pharmacokinetics model. A total of 270 samples from 15 patients receiving posaconazole via nasogastric tube were measured by high-performance liquid chromatography (HPLC). SICU patients showed lower plasma drug concentrations, a higher apparent clearance, and a higher volume of distribution than those in hematology patients, possibly due to poor absorption.T he use of posaconazole in patients with hematological malignancies has been published extensively (4,6,19,20). Although recipients of solid organs and patients undergoing major abdominal surgery are also at risk for developing invasive fungal infections, and case reports show the suitability of posaconazole for this population (14,15), no pharmacokinetic data on posaconazole are yet available for patients of a surgical intensive care unit (SICU). Application of posaconazole via nasogastric tube in healthy volunteers resulted in up to 20% decreased plasma drug concentrations (5), but this has not yet been studied in seriously ill patients with high APACHE II and SOAP II scores. It is not clear whether and to what extent posaconazole pharmacokinetics is affected in these patients.The aims of the prospective POLICE trial (posaconazole via gastric tube) were to determine posaconazole concentrations in SICU patients in order to control if sufficient concentrations are achieved and to develop a population pharmacokinetics (PopPK) model. Posaconazole concentrations were determined by reversedphase high-performance liquid chromatography with UV detection as previously published (16). PopPK modeling was performed using nonlinear mixed-effects modeling (NONMEM version VI) with the first-order conditional estimation (FOCE) method and INTERACTION option (3). The influence of the following candidate covariates was examined consecutively: body weight, body height, body mass index, sex, age, albumin, ␥-glutamyltransferase, glutamine-oxalacetic transaminase, glutamatepyruvate transaminase, and bilirubin.Two hundred seventy samples from 15 SICU patients who underwent extensive abdominal surgery were eligible for evaluation. They received posaconazole for prophylactic or therapeutic purposes, regardless of participation in the study. Demographic parameters are shown in Table 1.All patients received 200 mg posaconazole every 6 h (q6h) as absorption was considered saturable. Daily posaconazole doses were administered via nasogastric tube: only twice was a jejunal or duodenal tube used. Other medication was not restricted during posaconazole treatment. Each patient received pantoprazole intravenously (40 mg/day) to prevent development of stress ulcers.In transplant patients (n ϭ 6), immunosuppressive therapy was mostly performed with tacrolimus or cyclosporine. Enteral nutrition was either normocaloric or high energy (3.0 to 5.8 g fat/100 ml) an...