ABSTRACT
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; Pâ<â0.001), and antimicrobial mismatch was significantly associated with reduced success rate of PJI treatment (OR: 0.20; 95% CI: 0.05â ±â 0.82; Pâ=â0.026). There was no difference in successful outcome between PJI caused by Gram-negative bacilli (61%) and Gram-positive bacteria (69%, Pâ=â0.516). 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).
ABSTRACT
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.
Subject(s)
Antimalarials/therapeutic use , Human Experimentation , Malaria, Falciparum/physiopathology , Plasmodium falciparum/pathogenicity , Adolescent , Adult , Animals , Blood Chemical Analysis , Culicidae , Dose-Response Relationship, Drug , Drug Administration Schedule , Humans , Malaria, Falciparum/drug therapy , Male , Middle Aged , Patient Compliance , Probability , Research Design , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Statistics, NonparametricSubject(s)
DNA, Protozoan/blood , Malaria, Falciparum/parasitology , Parasitemia/parasitology , Plasmodium falciparum/isolation & purification , Polymerase Chain Reaction/methods , Animals , Culicidae/parasitology , Culicidae/physiology , Feeding Behavior , Humans , Plasmodium falciparum/genetics , Sensitivity and SpecificityABSTRACT
Three men aged 53, 25 and 34 years and 2 women aged 39 and 34 years with HIV infection had different courses with and without highly active antiretroviral therapy (HAART). Medication regimes were often complicated and adverse events occurred frequently, which led to adjustment of treatment. Since the introduction of HAART for treatment of HIV infection, a tremendous progress has been achieved, resulting in reduction of HIV related events and in reduction of fatality due to AIDS. However, besides the positive effects of this therapy, there is also a negative side of HAART. In addition to the complexity and adverse events, the medication has to be taken lifelong while non-compliance might result in resistance-mutation. If HAART might be indicated, it is necessary to weigh the pros and contras before starting with medication.
Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , Patient Compliance/psychology , Reverse Transcriptase Inhibitors/administration & dosage , Adult , Antiretroviral Therapy, Highly Active/methods , CD4 Lymphocyte Count , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , HIV Infections/complications , HIV Infections/mortality , HIV Infections/psychology , HIV Protease Inhibitors/adverse effects , HIV-1/isolation & purification , Humans , Male , Middle Aged , Reverse Transcriptase Inhibitors/adverse effects , Treatment OutcomeABSTRACT
Two patients, a 25-year-old woman and a 62-year-old man, with Plasmodium vivax infection, suffered repeated attacks of malaria despite standard treatment with chloroquine and subsequently primaquine. The relapses were due to a combination of decreased primaquine sensitivity and incorrect prescription of primaquine. Primaquine is administered as diphosphate (salt), but the required amount has to be prescribed as base (26.3 mg diphosphate corresponds to 15 mg base).
Subject(s)
Antimalarials/therapeutic use , Malaria, Vivax/drug therapy , Primaquine/therapeutic use , Adult , Drug Tolerance , Female , Humans , Male , Middle Aged , RecurrenceABSTRACT
Clinical trials have recently begun using high concentrations of activated recombinant factor VII (rFVIIa) for the treatment of hemophilic patients with inhibitors. Unexpectedly, the activated partial thromboplastin time (aPTT) was observed to be significantly shortened during infusion of the rFVIIa. To determine the mechanism for this shortening, the effect of rFVIIa on both the prothrombin time (PT) and the aPTT of normal and various factor-deficient plasmas was examined. rFVIIa shortened the PT of all plasmas tested except FX and FV deficient plasmas. rFVIIa also shortened the aPTT of all plasmas tested except FX and FV deficient plasmas. Since there is no added tissue factor (TF) in aPTT reagents, rFVIIa appeared to shorten the aPTT in the absence of TF. To investigate this possibility, the activity of rFVIIa in a purified system containing only FX, phospholipid vesicles (1:1 PS:PC), and calcium was examined. In this system, rFVIIa activated factor X in the absence of TF. If any component of the purified system was omitted, there was no detectable activation of FX. Thus it appears that calcium and phospholipids are required for the activation of FX by rFVIIa in the absence of TF. Increasing the concentration of rFVIIa increased the rate of FX activation, but the rate of activation was always much lower than that observed with even trace amounts of tissue factor. We conclude that high concentrations of rFVIIa, in the presence of calcium and phospholipid, can directly activate FX in the absence of TF and hence account for the shortening of the aPTT in inhibitor patients treated with rFVIIa.
