Claire Triffault-Fillit

Population pharmacokinetics and probability of target attainment of ertapenem administered by subcutaneous or intravenous route in patients with bone and joint infection

BackgroundnErtapenem is a therapeutic option in patients with Gram-negative bone and joint infection (BJI). The subcutaneous (sc) route of administration is convenient in the outpatient setting and has shown favourable pharmacokinetics (PK), but available data on ertapenem are limited.nnnObjectivesnTo perform population PK analysis and pharmacokinetic/pharmacodynamic (PK/PD) simulation of ertapenem administered by the intravenous (iv) or sc route to patients with BJI.nnnPatients and methodsnThis was a retrospective analysis of PK data collected in patients with BJI who received iv or sc ertapenem. Measured ertapenem concentrations were analysed with a non-parametric population approach. Then, simulations were performed based on the final model to investigate the influence of ertapenem route of administration, dosage and renal function on the probability of achieving a pharmacodynamic (PD) target, defined as the percentage of time for which free plasma concentrations of ertapenem remained above the MIC (fT>MIC) of 40%.nnnResultsnForty-six PK profiles (13 with iv and 33 with sc ertapenem) with a total of 133 concentrations from 31 subjects were available for the analysis. A two-compartment model with linear sc absorption and linear elimination best fitted the data. Creatinine clearance was found to significantly influence ertapenem plasma clearance. Simulations showed that twice daily dosing, sc administration and renal impairment were associated with an increase in fT>MIC and target attainment.nnnConclusionsnOur results indicate that 1u2009g of ertapenem administered twice daily, by the iv or sc route, may optimize ertapenem exposure and achievement of PK/PD targets in patients with BJI.

Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages

found a high prevalence of ESBL producers, but no CPE. In conclusion, we report two temporally and geographically linked patients with community-onset urinary tract infection caused by the same OXA-48-producing E. coli clone. The association between OXA-48 and Cambodia in NZ suggests the Cambodian patient may have acquired the organism during recent travel and indirectly transmitted to the second patient via unknown community transmission pathways. It is possible that OXA-48-positive CPE are under-recognized in NZ due to the challenges of laboratory detection. Screening with adequate selective media for CPE is highly recommended. The forthcoming national response plan to CPE in NZ has potential to help address some of these issues.

Microbiologic epidemiology depending on time to occurrence of prosthetic joint infection: a prospective cohort study

OBJECTIVESnThe high microbiologic diversity encountered in prosthetic joint infection (PJI) makes the choice of empirical antimicrobial therapies challenging, especially in cases of implant retention or one-stage exchange. Despite the risk of dysbiosis and toxicity, the combination of vancomycin with a broad-spectrum β-lactam is currently recommended in all cases, even if Gram-negative bacilli (GNB) might be less represented in late PJI. In this context, this study aimed to describe the microbiologic epidemiology of PJI according to the chronology of infection.nnnMETHODSnThis prospective cohort study (2011-2016) evaluated the microbiologic aetiology of 567 PJI according to time of occurrence from prosthesis implantation-early (<3xa0months), delayed (3-12xa0months) and late (>12xa0months)-as well as mechanism of acquisition.nnnRESULTSnInitial microbiologic documentation (nxa0=xa0511; 90.1%) disclosed 164 (28.9%) Staphylococcus aureus (including 26 (16.1%) methicillin-resistant S.xa0aureus), 162 (28.6%) coagulase-negative staphylococci (including 81 (59.1%) methicillin-resistant coagulase-negative staphylococci), 80 (14.1%) Enterobacteriaceae, 74 (13.1%) streptococci and 60 (10.6%) Cutibacterium acnes. Considering nonhaematogenous late PJI (nxa0=xa0182), Enterobacteriaceae (nxa0=xa07; 3.8%) were less represented than in the first year after implantation (nxa0=xa056; 17.2%; p <0.001), without difference regarding nonfermenting GNB (4.6% and 2.7%, respectively). The prevalence of anaerobes (nxa0=xa040; 21.9%; including 32 (80.0%) C.xa0acnes) was higher in late PJI (p <0.001). Consequently, a broad-spectrum β-lactam might be useful in 12 patients (6.6%) with late PJI only compared to 66 patients (20.3%) with early/delayed PJI (p <0.001).nnnCONCLUSIONSnConsidering the minority amount of GNB in late postoperative PJI, the empirical use of a broad-spectrum β-lactam should be reconsidered, especially when a two-stage exchange is planned.

Chronic and severe prosthetic joint infection complicated by amyloid A amyloidosis with renal and bladder impairment

A 66-year-old woman presented with renal failure and purulent discharge associated with a chronic prosthetic joint infection (PJI) of the left knee. Her medical history consisted of an untreated chronic hepatitis B and recurrent giant-cell tumour of bone revealed by spontaneous fractures 20 years previously. Multiple tumour resections led to knee prosthesis implantation in 1992 with no tumour relapse thereafter. The patient experienced a methicillin-susceptible Staphylococcus aureus chronic PJI in the following months that required two-stage prosthesis replacement and a prolonged antibiotherapy. A clinical suspicion of superinfection was confirmed in 2002 by a puncture of the synovial fluid that found a methicillin-resistant Staphylococcus epidermidis . The patient declined both surgical and medical treatment and was lost to follow-up.nnShe subsequently presented in 2015 with partial impotence, no flexion of the left knee and multiple fistulae with purulent discharge (figure 1A) that had evolved for years and that had been treated with a self-made bandage. X-ray (figure 1B) and CTxa0scan (figure 1C) found extensive periostea reaction of the femur, bone destruction and prosthesis loosening. Lab results found …

Tolerability of prosthetic joint infection empirical antimicrobial therapy: a prospective cohort study

The empirical use of vancomycin in combination with a broad-spectrum beta-lactam is currently recommended after the initial surgery of prosthetic joint infection (PJI). However, the tolerability of such high-dose intravenous regimens is poorly known. ABSTRACT The empirical use of vancomycin in combination with a broad-spectrum beta-lactam is currently recommended after the initial surgery of prosthetic joint infection (PJI). However, the tolerability of such high-dose intravenous regimens is poorly known. Adult patients receiving an empirical antimicrobial therapy (EAT) for a PJI were enrolled in a prospective cohort study (2011 to 2016). EAT-related adverse events (AE) were described according to the common terminology criteria for AE (CTCAE), and their determinants were assessed by logistic regression and Kaplan-Meier curve analysis. The EAT of the 333 included patients (median age, 69.8 years; interquartile range [IQR], 59.3 to 79.1 years) mostly relies on vancomycin (n = 229, 68.8%), piperacillin-tazobactam (n = 131, 39.3%), and/or third-generation cephalosporins (n = 50, 15%). Forty-two patients (12.6%) experienced an EAT-related AE. Ten (20.4%) AE were severe (CTCAE grade ≥ 3). The use of vancomycin (odds ratio [OR], 6.9; 95% confidence interval [95%CI], 2.1 to 22.9), piperacillin-tazobactam (OR, 3.7; 95%CI, 1.8 to 7.2), or the combination of both (OR, 4.1; 95%CI, 2.1 to 8.2) were the only AE predictors. Acute kidney injury (AKI) was the most common AE (n = 25; 51.0% of AE) and was also associated with the use of the vancomycin and piperacillin-tazobactam combination (OR, 6.7; 95%CI, 2.6 to 17.3). A vancomycin plasma overexposure was noted in nine (37.5%) of the vancomycin-related AKIs only. Other vancomycin-based therapies were significantly less at risk for AE and AKI. The EAT of PJI is associated with an important rate of AE, linked with the use of the vancomycin and the piperacillin-tazobactam combination. These results corroborate recent findings suggesting a synergic toxicity of these drugs in comparison to vancomycin-cefepime, which remains to be evaluated in PJI. (This study has been registered at ClinicalTrials.gov under identifier NCT03010293.)

Outpatient parenteral antibiotic therapy: Evaluation of practices and limits of use in rural areas in France

OBJECTIVESnTo evaluate outpatient parenteral antibiotic therapy (OPAT) practices in a French rural area.nnnMATERIAL AND METHODSnDescriptive study assessing knowledge, practices, and limitations of OPAT use among hospital practitioners (HP), family physicians (FP), and private nurses (PN).nnnRESULTSnOPAT (mainly ceftriaxone and penicillins) was used by 69.6%, 73.3%, and 97.7% of the 23 HPs, 45 FPs, and 46 PNs mostly for respiratory or urinary tract infections, bacteremia, and/or multidrug-resistant bacterial infections. Overall, 65.2% of HPs and 37.8% of FPs were in contact with an infectious disease specialist. Knowledge of OPAT benefits and risks was lower for FPs than HPs. The main obstacles were the patients geographic isolation (HPs), the availability of a venous catheter, the lack of training (FPs), and the expected OPAT-associated overwork (PNs).nnnCONCLUSIONnOPAT practice is weak in rural areas. Declared obstacles constitute fields of improvement for its essential expansion.