C-reactive protein interacts with amphotericin B liposomes and its potential clinical consequences.

OBJECTIVES: Amphotericin B (AmB) is the gold standard for treating invasive fungal infections. New liposomal-containing AmB formulations have been developed to improve efficacy and tolerability. Serum/plasma C-reactive protein (CRP) values are widely used for monitoring infections and inflammation. CRP shows a high affinity to phosphocholine and it aggregates structures bearing this ligand, e.g. phosphocholine-containing liposomes. Therefore, we studied the interaction between CRP and phosphocholine-containing liposomal AmB preparations in vivo and in vitro. METHODS: CRP was prepared by affinity chromatography. Liposomal AmB (L-AmB, AmBisome®) was spiked (final concentrations of L-AmB: 150 mg/L) to CRP-containing serum (final CRP concentration: 300 mg/L). Following the addition of L-AmB, complex formation was monitored turbidimetrically. The size of CRP-L-AmB complexes was assessed using gel filtration. CRP was monitored in patients receiving either L-Amb or AmB lipid complex (ABLC). RESULTS: Following addition of L-AmB to CRP-containing plasma, turbidimetry showed an increase in absorbance. These results were confirmed by gel permeation chromatography. Similarly, in vivo effects were observed following intravenous administration of AmBisome®: a decline in CRP values was observed. In patients receiving L-Amb, decline of CRP concentration was faster than in patients receiving ABLC. CONCLUSIONS: In vitro experiments are suggestive of a complexation between CRP and liposomes in plasma. Interpretation of CRP values following administration of AmBisome® might be impaired due to this complexation. In vivo formation of complexes between liposomes and CRP might contribute, or even lead, to intravascular microembolisation. Similar effects have been described following the administration of Intralipid® and other phosphocholine-containing liposomes.

Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial.

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, Setting, and Participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main Outcomes and Measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and Relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT02208154.

The evaluation of the transport medium for extracted premolars prior to cryopreservation: an in vitro study.

Autotransplantation is a versatile technique for the replacement of a missing tooth and cryopreservation can expand its scope. The aim of this in vitro study is to compare the antimicrobial effect of different transport protocols on procured teeth prior to cryopreservation. Streptococcus oralis biofilms were grown on ten sterile premolars, incubated for 48 h and subjected to the following transport procedures: an untreated (contaminated) control group, a group rinsed with phosphate buffered saline (PBS), a group transported in PBS, a group transported in Dulbecco's Modified Eagle's medium (DMEM) supplemented with fetal calf serum (FCS), and a group transported in DMEM supplemented with FCS and antibiotics (AB). The effect of cryopreservation as such, as well as the combination with a transport medium (DMEM + FCS + AB) on the contamination was also tested. The surviving bacteria were harvested, and determined by plate counting. There was no significant reduction in contamination after rinsing the tooth, after transport in PBS or after transport in DMEM with FCS. Significant reductions were observed for transport in DMEM with AB when compared to the control group (p = 0.003). Cryopreservation as such reduced the biofilm significantly (p < 0.001). No cumulative effect could be found when transport in DMEM + FCS + AB was followed by cryopreservation. Within the limitations of this laboratory set-up, DMEM + FCS + AB was the most effective transport medium in S. oralis biofilm elimination. It could not be concluded that rinsing of the tooth gives an additional reduction. Cryopreservation as such decontaminated the teeth more effectively than any tested transport procedure.