Assessment of antimicrobial mismatches in empirical treatment in early PJI after aseptic revision arthroplasty.

Background: In early periprosthetic joint infection (PJI), 'debridement, antibiotics and implant retention' (DAIR) is a widely accepted form of treatment. Empirical antimicrobial treatment is started while culture results of tissue samples taken during debridement are pending. Objectives: In this retrospective study we assessed the antimicrobial mismatch rate between empirical treatment and the susceptibility of the causative microorganisms of PJI after aseptic revision arthroplasty. We analysed risk factors for antimicrobial mismatches and the impact of mismatches on the outcome of PJI treatment. Results: A total of 119 patients were included in the analysis. In 72% (86/119) of the cases there was an antimicrobial mismatch in empirical treatment. Most of the antimicrobial mismatches were caused by multidrug-resistant (MDR) Staphylococcus spp. (77%, 66/86). In multivariable analysis, polymicrobial PJI was significantly associated with antimicrobial mismatch (OR: 6.89; 95% CI: 2.38-19.53; P < 0.001), and antimicrobial mismatch was significantly associated with reduced success rate of PJI treatment (OR: 0.20; 95% CI: 0.05 ±â€…0.82; P = 0.026). There was no difference in successful outcome between PJI caused by Gram-negative bacilli (61%) and Gram-positive bacteria (69%, P = 0.516). Conclusions: Mismatching empirical antimicrobial treatment after DAIR following aseptic revision arthroplasty was significantly associated with failure of PJI treatment. Polymicrobial PJI is a risk factor for antimicrobial mismatch of the empirical treatment of PJI. Antimicrobial mismatch and delay in targeted treatment should be integrated in the approach to optimize antibiotic treatment to improve clinical outcomes, while minimizing unintended side effects of antimicrobial use (antimicrobial stewardship).

Clinical outcome of experimental human malaria induced by Plasmodium falciparum-infected mosquitoes.

BACKGROUND: Human experimental malaria infections have been safely carried out previously. The objective of this study was to evaluate infection rates and clinical safety of different protocols for human experimental malaria induced by Plasmodium falciparum-infected mosquitoes. METHODS: Thirty nonimmune volunteers were infected by bites of 1-2 or 4-7 Anopheles stephensi mosquitoes infected with the NF54 strain of P. falciparum. RESULTS: A 100 or 50% infection rate was obtained after bites of 4-7 and 1-2 infected mosquitoes, respectively. Median prepatent period was 8.8 days. The most common symptoms after a median incubation time of eight days were headache, malaise/fatigue and fever. There was no significant difference in clinical and parasitological presentation between groups infected by 4-7 or 1-2 mosquitoes. Delay of treatment by maximally 48 hours after the first positive thick smear was generally well tolerated but fever was higher and more frequently observed. The most prominent laboratory abnormality was uncomplicated thrombocytopenia. Two volunteers with parasitaemia developed psychiatric side effects after chloroquine treatment. CONCLUSION: With stringent inclusion criteria, close monitoring and immediate administration of treatment upon detection of parasitaemia, experimental human malaria challenges can be considered safe and generally well tolerated.