Crescentic glomerulonephritis with anti-PR3 ANCA associated with Bartonella henselae infective endocarditis

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Pubic osteomyelitis: Epidemiology and factors associated with treatment failure

International audienceObjective: To describe the epidemiology of pubic osteomyelitis (PO) and to look for factors associated with treatment failure.Method: Retrospective study describing PO according to outcome: success or failure of initial management. Factors associated with failure determined by univariate Cox analysis. Kaplan-Meier curve compared between groups by log-rank test.Results: Twenty-five patients were included over a 13-year period; 24% of PO had blood-borne infection. Failure (44%) was always observed in chronic postoperative presentations (76%). Fistula (32%) was only observed in postoperative presentations and was significantly associated with failure (HR 5.1; P=0.011). Other risk factors were pelvic malignant tumor history, abscess, infection due to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and polymicrobial infection.Conclusion: PO is most often a chronic postoperative polymicrobial infection in patients with comorbidities at high risk of relapse. Studies in larger cohorts could assess the efficacy of more aggressive surgical strategies in patients at high risk of failure

Antibiothérapie parentérale ambulatoire : évaluation des pratiques et limites en milieu rural

International audienceOBJECTIVES: To evaluate outpatient parenteral antibiotic therapy (OPAT) practices in a French rural area. MATERIAL AND METHODS: Descriptive study assessing knowledge, practices, and limitations of OPAT use among hospital practitioners (HP), family physicians (FP), and private nurses (PN). RESULTS: OPAT (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 patient's geographic isolation (HPs), the availability of a venous catheter, the lack of training (FPs), and the expected OPAT-associated overwork (PNs). CONCLUSION: OPAT practice is weak in rural areas. Declared obstacles constitute fields of improvement for its essential expansion.Objectif Évaluer les pratiques d’antibiothérapie parentérale ambulatoire (APA) en milieu rural.Matériel et méthodesÉtude descriptive interrogeant les médecins hospitaliers (MH), libéraux (ML) et infirmiers libéraux (IDE) sur les connaissances, pratiques et freins concernant l’APA.RésultatsL’APA (ceftriaxone et pénicillines majoritairement) était utilisée par 69,6 %, 73,3 % et 97,7 % des 23 MH, 45 ML et 46 IDE pour infections respiratoires ou urinaires, bactériémies et/ou infections à germes multirésistants, en lien avec un médecin référent pour l’antibiothérapie pour 65,2 % des MH et 37,8 % des ML. Les risques/bénéfices de l’APA étaient moins connus des ML que des MH. Les principaux freins étaient l’isolement géographique du patient (MH), l’accessibilité à une voie veineuse/le manque de formation (ML) et la surcharge de travail pressentie (IDE).ConclusionLes freins à l’APA, peu utilisée en milieu rural, dégagent des axes d’amélioration au développement indispensable de cette pratique

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

International audienceOBJECTIVES: The 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. METHODS: This prospective cohort study (2011-2016) evaluated the microbiologic aetiology of 567 PJI according to time of occurrence from prosthesis implantation-early (\textless3~months), delayed (3-12~months) and late (\textgreater12~months)-as well as mechanism of acquisition. RESULTS: Initial microbiologic documentation (n~=~511; 90.1%) disclosed 164 (28.9%) Staphylococcus aureus (including 26 (16.1%) methicillin-resistant S.~aureus), 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 (n~=~182), Enterobacteriaceae (n~=~7; 3.8%) were less represented than in the first year after implantation (n~=~56; 17.2%; p \textless0.001), without difference regarding nonfermenting GNB (4.6% and 2.7%, respectively). The prevalence of anaerobes (n~=~40; 21.9%; including 32 (80.0%) C.~acnes) was higher in late PJI (p \textless0.001). 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 \textless0.001). CONCLUSIONS: Considering 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

Correction of linezolid-induced myelotoxicity after switch to tedizolid in a patient requiring suppressive antimicrobial therapy for multidrug-resistant staphylococcus epidermidis prosthetic-joint infection

A 71-year-old man (85 kg) has a past history of vitiligo, ischemic myocardiopathy, and bilateral knee arthroplasties. A 1-stage exchange of the right prosthetic-joint infection (PJI) was done in 2016 for a mechanical prosthetic loosening. A massive constrained prosthetic joint was used to compensate for the bone loss (Supplementary Figure S1A). Iterative postoperative dislocations were followed by occurrence of a fistula in January 2017 and prosthetic loosening (Supplementary Figure S1B) without any pain. Because it was impossible to imagine a 2-stage exchange, a debridement and implant retention (DAIR) procedure followed by suppressive antimicrobial therapy was proposed. Daptomycin (700 mg/day) and ceftaroline (1200 mg/ day) were prescribed after the surgery. A multidrug-resistant Staphylococcus epidermidis, which is only susceptible to dap-tomycin, vancomycin, fosfomycin, and linezolid, was found in culture from all operative samples. After 6 weeks of intravenous antimicrobial therapy, 600 mg of linezolid bid was prescribed in August 2017. Concomitant medications were ramipril, bisopr-olol, furosemide, and aspirin. Under therapy, the patient experienced a progressive decrease of hemoglobin and hematocrit (without decrease of white blood cells or platelets). Five months after linezolid introduction, the patient developed asthenia related to anemia, with a decrease of hemoglobin to 65 mg/dL, and without leucopenia or thrombocytopenia (Figure 1). The patient did not take any treatment with potential bone marrow toxicity, except linezolid. The patient has no other adverse drug reactions. A blood transfusion (2 bags) was performed, which led to an immediate increase of the hemoglobin level to 84 mg/ dL, and linezolid was switched to 200 mg of tedizolid once a day. In May 2018, 9 months after the DAIR surgery and 4 months after the switch, the patient was perfectly fine, walked despite rupture of the right knee extensor apparatus (video S2), without any pain, without any local signs of relapse (Supplementary Figure S1C), without clinical signs of neuropathy, and he experienced a continuous increase of the hemoglobin to 14 mg/dL under tedizolid therapy. No other treatment was changed or introduced

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

OBJECTIVES: The 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. METHODS: This prospective cohort study (2011-2016) evaluated the microbiologic aetiology of 567 PJI according to time of occurrence from prosthesis implantation-early (<3 months), delayed (3-12 months) and late (>12 months)-as well as mechanism of acquisition. RESULTS: Initial microbiologic documentation (n = 511; 90.1%) disclosed 164 (28.9%) Staphylococcus aureus (including 26 (16.1%) methicillin-resistant S. aureus), 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 (n = 182), Enterobacteriaceae (n = 7; 3.8%) were less represented than in the first year after implantation (n = 56; 17.2%; p <0.001), without difference regarding nonfermenting GNB (4.6% and 2.7%, respectively). The prevalence of anaerobes (n = 40; 21.9%; including 32 (80.0%) C. acnes) 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). CONCLUSIONS: Considering 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

Genetic polymorphisms of ABCB1 (P-glycoprotein) as a covariate influencing daptomycin pharmacokinetics: a population analysis in patients with bone and joint infection

International audienceBackground Daptomycin has been recognized as a therapeutic option for the treatment of bone and joint infection (BJI). Gene polymorphism of ABCB1, the gene encoding P-glycoprotein (P-gp), may influence daptomycin pharmacokinetics (PK). Objectives We aimed to examine population PK of daptomycin and its determinants, including genetic factors, in patients with BJI. Patients and methods We analysed data from patients who received daptomycin for BJI between 2012 and 2016 in our regional reference centre and who had measured daptomycin concentrations and P-gp genotyping. A population approach was used to analyse PK data. In covariate analysis, we examined the influence of three single nucleotide variations (SNVs) of ABCB1 (3435C\textgreaterT, 2677G\textgreaterT/A and 1236C\textgreaterT) and that of the corresponding haplotype on daptomycin PK parameters. Simulations performed with the final model examined the influence of covariates on the probability to achieve pharmacodynamic (PD) targets. Results Data from 81 patients were analysed. Daptomycin body CL (CLDAP) correlated with CLCR and was 23% greater in males than in females. Daptomycin central V (V1) was allometrically scaled to body weight and was 25% lower in patients with homozygous CGC ABCB1 haplotype than in patients with any other genotype. Simulations performed with the model showed that sex and P-gp haplotype may influence the PTA for high MIC values and that a dosage of 10mg/kg/24h would optimize efficacy. Conclusions Daptomycin dosages higher than currently recommended should be evaluated in patients with BJI. Gender and P-gp gene polymorphism should be further examined as determinants of dosage requirements

Subcutaneous suppressive antibiotic therapy for bone and joint infections: safety and outcome in a cohort of 10 patients

International audienceBackground Optimal treatment of prosthetic joint infection and chronic osteomyelitis consists of surgical removal of biofilm-embedded bacteria, followed by a 6-12week course of antimicrobial therapy. However, when optimal surgery is not feasible, oral prolonged suppressive antibiotic therapy (PSAT) is recommended to prevent prosthesis loosening and/or relapse of infection. Since 2010, we have used infection salvage therapy using off-label subcutaneous (sc) injection of a beta-lactam as PSAT for patients in whom oral PSAT is not possible. Methods A single-centre prospective cohort study (2010-18) reporting treatment modalities, efficacy and safety in all patients receiving sc PSAT. NCT03403608. Results The 10 included patients (median age 79years) had polymicrobial (n=5) or MDR bacterial (n=4) prosthetic joint infection (knee, n=4; hip, n=3) or chronic osteomyelitis (n=3). After initial intensive therapy, seven patients received ertapenem, three patients received ceftriaxone and one patient received ceftazidime by sc injection (one patient received 8 days of ceftriaxone before receiving ertapenem). In one patient, sc PSAT failed with recurrent signs of infection under treatment. In three patients, sc PSAT had to be discontinued due to side effects; in only one of these was the sc route implicated (skin necrosis following direct sc injection and not gravity infusion). Median treatment duration was 433days. In six patients, sc PSAT was successful with favourable outcome at the time of writing. Interestingly, three patients with MDR bacterial carriage at baseline lost this under PSAT during follow-up. Conclusions As salvage therapy, sc PSAT delivered by gravity infusion is a safe and interesting alternative when an optimal surgical strategy is not feasible and no oral treatment is available

Pressure ulcer-related pelvic osteomyelitis: Evaluation of a two-stage surgical strategy (debridement, negative pressure therapy and flap coverage) with prolonged antimicrobial therapy

Background: A two-stage surgical strategy (debridement-negative pressure therapy (NPT) and flap coverage) with prolonged antimicrobial therapy is usually proposed in pressure ulcer-related pelvic osteomyelitis but has not been widely evaluated. Methods: Adult patients with pressure ulcer-related pelvic osteomyelitis treated by a two-stage surgical strategy were included in a retrospective cohort study. Determinants of superinfection (i.e., additional microbiological findings at reconstruction) and treatment failure were assessed using binary logistic regression and Kaplan-Meier curve analysis. Results: Sixty-four pressure ulcer-related pelvic osteomyelitis in 61 patients (age, 47 (IQR, 36-63)) were included. Osteomyelitis was mostly polymicrobial (73%), with a predominance of S. aureus (47%), Enterobacteriaceae spp. (44%) and anaerobes (44%). Flap coverage was performed after 7 (IQR, 5-10) weeks of NPT, with 43 (68%) positive bone samples among which 39 (91%) were superinfections, associated with a high ASA score (OR, 5.8; p = 0.022). An increased prevalence of coagulase negative staphylococci (p = 0.017) and Candida spp. (p = 0.003) was observed at time of flap coverage. An ESBL Enterobacteriaceae spp. was found in 5 (12%) patients, associated with fluoroquinolone consumption (OR, 32.4; p = 0.005). Treatment duration was as 20 (IQR, 14-27) weeks, including 11 (IQR, 8-15) after reconstruction. After a follow-up of 54 (IQR, 27-102) weeks, 15 (23%) failures were observed, associated with previous pressure ulcer (OR, 5.7; p = 0.025) and Actinomyces spp. infection (OR, 9.5; p = 0.027). Conclusions: Pressure ulcer-related pelvic osteomyelitis is a difficult-to-treat clinical condition, generating an important consumption of broad-spectrum antibiotics. The lack of correlation between outcome and the debridement-to-reconstruction interval argue for a short sequence to limit the total duration of treatment