Tolerance and microbiological efficacy of cefepime or piperacillin/tazobactam in combination with vancomycin as empirical antimicrobial therapy of prosthetic joint infection: a propensity-matched cohort study.

BACKGROUND: The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading us to propose cefepime as an alternative since 2017 in our reference centre. OBJECTIVES: To compare microbiological efficacy and tolerance of these two EAT strategies. METHODS: All adult patients with PJI empirically treated with vancomycin+cefepime (n = 89) were enrolled in a prospective observational study and matched with vancomycin+piperacillin/tazobactam-treated historical controls (n = 89) according to a propensity score including age, baseline renal function and concomitant use of other nephrotoxic agents. The two groups were compared using Kaplan-Meier curve analysis, and non-parametric tests regarding the proportion of efficacious empirical regimen and the incidence of empirical therapy-related adverse events (AE). RESULTS: Among 146 (82.0%) documented infections, the EAT was considered efficacious in 77 (98.7%) and 65 (98.5%) of the piperacillin/tazobactam- and cefepime-treated patients, respectively (P = 1.000). The rate of AE, particularly AKI, was significantly higher in the vancomycin+piperacillin/tazobactam group [n = 27 (30.3%) for all AE and 23 (25.8%) for AKI] compared with the vancomycin+cefepime [n = 13 (14.6%) and 6 (6.7%)] group (P = 0.019 and <0.001, respectively), leading to premature EAT discontinuation in 20 (22.5%) and 5 (5.6%) patients (P = 0.002). The two groups were not significantly different regarding their comorbidities, and AKI incidence was not related to vancomycin plasma overexposure. CONCLUSIONS: Based on the susceptibility profile of bacterial isolates from included patients, microbiological efficacy of both strategies was expected to be similar, but vancomycin + cefepime was associated with a significantly lower incidence of AKI.

Pubic osteomyelitis: Epidemiology and factors associated with treatment failure.

OBJECTIVE: 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.

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

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 ß-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 ß-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 ß-lactam should be reconsidered, especially when a two-stage exchange is planned.

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

OBJECTIVES: 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.