Toothpick ingestion is a medical emergency. Perforations of the intestine are common and the associated mortality is high. Adequate therapy depends on localization of the toothpick in the gastrointestinal tract. Ingested toothpicks should be kept in mind as an important differential diagnosis in patients with acute abdomen.
AIMSThe aim of the present study was to assess the pharmacokinetics of total and unbound ceftriaxone in intensive care unit (ICU) patients and its protein binding characteristics.
METHODSTwenty patients (m/f 15/5, age 25-86 years, body weight 60-121 kg, APACHE II 7-40, estimated glomerular filtration rate 19-157 ml min -1 , albumin 11.7-30.1 g l -1 , total bilirubin <0.1-36.1 mg dl -1 ) treated with intravenous ceftriaxone were recruited from two ICUs. Timed plasma samples were obtained using an opportunistic study protocol. Ceftriaxone concentrations were determined by high-performance liquid chromatography; unbound concentrations were determined after ultrafiltration using a new method which maintains physiological pH and temperature. The pharmacokinetics was described by a onecompartment model, the protein-binding characteristics by MichaelisMenten kinetics.
RESULTSFor total drug, the volume of distribution was 20.2 l (median; interquartile range 15.6-24.5 l), the half-life 14.5 h (10.0-25.5 h) and the clearance 0.96 l h -1 (0.55-1.28 l h -1 ). The clearance of unbound drug was 1.91 l h -1 (1.46-6.20 l h -1 ) and linearly correlated with estimated glomerular filtration rate (slope 0.85, y-intercept 0.24 l h -1 , r 2 = 0.70). The unbound fraction was higher in ICU patients (33.0%; 20.2-44.5%) than reported in healthy volunteers, particularly when renal impairment or severe hyperbilirubinaemia was present. In all patients, unbound concentrations during treatment with ceftriaxone 2 g once daily remained above the EUCAST susceptibility breakpoint (≤1 mg l -1 ) throughout the whole dosing interval.
Drug exposure after standard doses of linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.
Background
Secondary peritonitis requires surgical source control and adequate antimicrobial treatment. Antimicrobial regimens are usually selected according to local susceptibility data of individual pathogens against single agents, but this neglects both the polymicrobial nature of the infection and the use of combination therapy. We analysed the probability of common regimens to cover all relevant pathogens isolated in one patient (“spectrum adequacy rate”, SAR) in a real-life data set.Methods
Data from 242 patients with secondary peritonitis (88 community acquired, 154 postoperative cases) treated in our IMCU/ICU were obtained retrospectively. The relative frequency of pathogens, resistance rates and the SAR were analysed using the free software R.ResultsEnterococci were isolated in 47.1 % of all patients, followed by Escherichia coli (42.6 %), other enterobacteriaceae (33.1 %), anaerobes (29.8 %) and Candida spp. (28.9 %). Resistance patterns were consistent with general surveillance data from our hospital. The susceptibility rates and SAR were lower in postoperative than in community acquired cases. The following regimens yielded a SAR > 95 % when enterobacteriaceae only were considered: piperacillin/tazobactam + gentamicin, cefotaxim (only for community acquired cases), cefotaxim + gentamicin, meropenem, tigecycline + gentamicin or tigecycline + ciprofloxaxin. When enterococci were also considered, all betalactam based regimens required combination with vancomycin or linezolid for a SAR > 95 %, whereas TGC based regimens were not compromised. As for Candida spp., the SAR of fluconazole was 81.9–87.5 %.ConclusionsThis study demonstrates a rational approach to assess the adequacy of antimicrobial regimens in secondary peritonitis, which may help to adjust local guidelines or to select candidate regimens for clinical studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.