SPILF update on bacterial arthritis in adults and children.

In 2020 the French Society of Rhumatology (SFR) published an update of the 1990 recommendations for management of bacterial arthritis in adults. While we (French ID Society, SPILF) totally endorse this update, we wished to provide further information about specific antibiotic treatments. The present update focuses on antibiotics with good distribution in bone and joint. It is important to monitor their dosage, which should be maximized according to PK/PD parameters. Dosages proposed in this update are high, with the optimized mode of administration for intravenous betalactams (continuous or intermittent infusion). We give tools for the best dosage adaptation to conditions such as obesity or renal insufficiency. In case of enterobacter infection, with an antibiogram result "susceptible for high dosage", we recommend the requesting of specialized advice from an ID physician. More often than not, it is possible to prescribe antibiotics via the oral route as soon as blood cultures are sterile and clinical have symptoms shown improvement. Duration of antibiotic treatment is 6 weeks for Staphylococcus aureus, and 4 weeks for the other bacteria (except for Neisseria: 7 days).

Long term NIV in an infant with Hallermann-Streiff syndrome: A case report and overview of respiratory morbidity.

Hallermann-Streiff syndrome (HSS) is a rare congenital syndrome with different anomalies including midface hypoplasia, beak nose and micrognathia. The upper airways narrowness can lead to severe respiratory complications such as obstructive sleep apnoea syndrome (OSAS), particularly in infancy. The management of these severe OSAS is difficult and poorly documented in literature. We report the case of an infant with HSS complicated by severe and early OSAS successfully managed with non-invasive ventilation (NIV), provide an overview of respiratory morbidities and discuss treatment options for HSS-related OSAS.

Personalized bacteriophage therapy to treat pandrug-resistant spinal Pseudomonas aeruginosa infection.

Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.

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.

Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with a debridement, antibiotics and implant retention (DAIR): a retrospective multicenter study in France.

Introduction: In patients undergoing a « debridement, antibiotics, and implant retention ¼ (DAIR) procedure for acute staphylococcal prosthetic joint infection (PJI), post-operative treatment with rifampin has been associated with a higher probability of success.(1,2) However, it is not known whether it is the total dose, delay of introduction or length of therapy with rifampin that is most strongly associated with the observed improved outcomes. Methods: A multicentric, retrospective cohort study of patients with acute staphylococcal hip and knee PJI treated with DAIR between January 2011 and December 2016. Failure of the DAIR procedure was defined as persistent infection, need for another surgery or death. We fitted logistic and Cox regression multivariate models to identify predictors of DAIR failure. We compared Kaplan-Meier estimates of failure probability in different levels of the 3 variables of interest - total dose, delay of introduction or length of therapy with rifampin - with the log-rank test. Results: 79 patients included (median age 71 years [63.5-81]; 55 men [70%]), including 54 (68%) DAIR successes and 25 (32%) DAIR failures. Patients observed for a median of 435 days [IQR 107.5-834]. Median ASA score significantly lower in DAIR successes than in DAIR failures (2 vs. 3, respectively p = 0.011). Bacterial cultures revealed 65 (82.3%) S. aureus and 16 (20.3%) coagulase negative staphylococci, with 2 patients being infected simultaneously with S. aureus and CNS. Among S. aureus isolates, 7 (10.8%) resistant to methicillin; 2 (3.1 %) resistant to rifampin. Median duration of antimicrobial therapy was 85 days [IQR 28.5-97.8]. Fifty-eight patients (73.4%) received rifampin at a median dose of 14.6 mg/kg/day |IQR 13-16.7], started at a median delay of 8.5 days [IQR, 4-7.5] after debridement surgery. Twenty-one patients (26.6%) developed a drug-related adverse event, leading to rifampin interruption in 6 of them (7.6% of total cohort). Determinants of DAIR failure were rifampin use (HR 0.17, IC [0.06, 0.45], p-value <0.001), association of rifampin with a fluoroquinolone (HR 0.19, IC [0.07, 0.53], p-value = 0.002) and duration of rifampin therapy (HR 0.97, IC [0.95, 1], p-value = 0.022). We did not observe a significant difference between DAIR successes and failures in rifampin use, dose and delay of introduction. In a multivariate Cox model, only duration of rifampin therapy was significantly associated with DAIR failure. Kaplan Meier estimate of DAIR failure probability was significantly higher in patients receiving less than 14 days of rifampin in comparison with those receiving more than 14 days of rifampin (p = 0.0017). Conclusion: Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with DAIR.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

Cerebral empyema and abscesses due to Cutibacterium acnes.

INTRODUCTION: Cutibacterium acnes is a commensal bacterium of the skin, frequently reported in prosthetic shoulder or spinal implant infections, but rarely in cranial and intracranial infections. METHODS: We retrospectively reviewed patients with intracranial samples positive to Cutibacterium acnes managed in the neurosurgical units of our hospital of Lyon, France, between 2008-2016. RESULTS: We included 29 patients, of whom 23 had empyema (with or without abscess), 17 had cranial osteomyelitis, and six only had abscess. Prior neurosurgery was reported in 28 patients, and the remaining patient had four spontaneous abscesses. Twelve patients had polymicrobial infections, including methicillin-susceptible Staphylococcus in 11 cases. The clinical diagnosis was difficult because of indolent and delayed symptoms: a CT scan or MRI was required. Thirteen patients (52%) had material at the infection site. All patients with bone flap implant or bones from biological banks had a bone flap-associated infection. Drainage was surgically performed in 25 cases or by CT scan-guided aspiration in four cases. All patients received an adapted antibiotic therapy (from three weeks to six months). The outcome was favorable in 28 patients. Three patients relapsed during the antibiotic therapy, requiring further surgery. CONCLUSION: Cutibacterium acnes can be responsible for postoperative empyema and cerebral abscesses, with particular indolent forms, which make their diagnosis difficult. They are often polymicrobial and associated with bone flap osteomyelitis. Their outcome is favorable after drainage and adapted antibiotic therapy.

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.

Subcutaneous teicoplanin in staphylococcal bone and joint infections.

OBJECTIVE: We aimed to describe the use of subcutaneous teicoplanin as an alternative for the treatment of staphylococcal bone and joint infections. METHODS: A retrospective multicentric cohort (2002-2015) was conducted with patients receiving subcutaneous teicoplanin for a staphylococcal bone and joint infection. RESULTS: Forty patients were assessed. A median loading dose of 9.4 mg/kg/12h (IQR, 6.1-13.1) was administered to 35 patients, subcutaneously for 18 of them. Thirteen of these patients received three injections per week. No excess risk of failure was identified. The trough level was not significantly different between the various routes (p=0.462), and was significantly higher if the loading dose was≥9 mg/kg/injection (p<10-3). CONCLUSION: The use of subcutaneous teicoplanin seems to be acceptable as an alternative to other routes of administration for antibiotics.

Efficacy of Bacteriophages in a Staphylococcus aureus Nondiabetic or Diabetic Foot Infection Murine Model.

This study investigated the in vivo efficacy of three bacteriophages combined compared with linezolid in two mouse models (nondiabetic and diabetic) of Staphylococcus aureus foot infection. In both models, a single injection of bacteriophages in the hindpaw showed significant antibacterial efficacy. Linezolid was as effective as bacteriophages in nondiabetic animals but ineffective in diabetic animals. These findings further support preclinical and clinical studies for the development of phage therapy.

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.

A practical approach to tuberculosis diagnosis and treatment in liver transplant recipients in a low-prevalence area.

Solid organ transplant candidates/recipients are at risk of mycobacterial infections. Although guidelines on the management of latent tuberculosis infection and active tuberculosis are available for solid organ transplant recipients, limited guidance focuses on end-stage liver disease or liver transplant recipients who require management in a referral center. Therapeutic challenges arise from direct antituberculosis drug-related hepatotoxicity, and substantial metabolic interactions between immunosuppressive and antituberculosis drugs. Another issue is the optimal timing of therapy with regards to the time of transplantation. This review focuses on the importance of tuberculosis screening with immunological tests, challenges in the diagnosis, management, and treatment of latent tuberculosis infection and active tuberculosis, as well as risk assessment for active tuberculosis in the critical peri-liver transplantation period. We detail therapeutic adjustments required for the management of antituberculosis drugs in latent tuberculosis infection and active tuberculosis, particularly when concomitantly using rifampicin and immunosuppressive drugs.

Should we expand the indications for the DAIR (debridement, antibiotic therapy, and implant retention) procedure for Staphylococcus aureus prosthetic joint infections? A multicenter retrospective study.

To evaluate factors associated with failure in patients treated with DAIR (debridement, antibiotic therapy, and implant retention) for Staphylococcus aureus prosthetic joint infections (PJIs). We retrospectively analyzed consecutive patients with stable PJI due to S. aureus treated with DAIR at six hospitals between 2010 and 2014. Cox proportional hazards regression was used to study factors associated with treatment failure at 2 years. Of 154 eligible patients, 137 were included (mean age 73 ± 13 years; male 56%). The estimated success rate according to the Kaplan-Meier method was 76.2 [95% CI 68-83] at 2 years of follow-up. In multivariate analysis, longer duration of treatment (hazard ratio (HR) 0.78 [0.69-0.88]; p < 0.001) and combination therapy including rifampin (HR 0.08 [0.018-0.36]; p = 0.001) were independently associated with success, whereas active smoking was independently associated with failure (HR 3.6 [1.09-11.84]; p = 0.036). When the analysis was restricted to patients with early infection onset (< 3 months), early acute infection was also predictive of a better prognosis (HR 0.25 [0.09-0.7]; p = 0.009). Failure was not associated with time from prosthesis insertion to debridement, nor with duration of symptoms > 3 weeks and type of prosthesis (hip or knee). These results remained unchanged when the 14 patients under immunosuppressive therapy were removed from analysis. These data suggest that DAIR can be performed even if infection and symptoms are delayed but reserved to patients who are able to follow rifampin-based combination therapy for a prolonged duration that should not be different for hip and knee PJI.

Head and neck squamous cell carcinoma in people living with HIV in France.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC), mainly due to smoking, is one of the leading causes of cancer deaths. However, an increasing number of tumors - especially oropharyngeal cancer - are reported in non-smokers in association with the human papillomavirus (HPV). As HIV-infected individuals are particularly at risk of HPV-related disease, we aimed to describe the burden of HNSCC in this population. METHODS: Retrospective chart review of patients from HIV clinics diagnosed with HNSCC between 2004 and 2014. Case patients were defined using the International Classification of Disease for Oncology (3rd edition). Age at HIV diagnosis and time from HIV diagnosis to HNSCC diagnosis were collected. Oropharyngeal cancers were considered as potentially HPV-related cancers, and their prevalence was compared with other HNSCCs over time. RESULTS: The 286 patients enrolled in the study had a median age at HNSCC diagnosis of 52 years; 84% were males and 68% had a history of smoking. The oropharynx was the most frequent site (41%), followed by cancer of the oral cavity (31%), larynx (22%), and hypopharynx (7%). The prevalence (and proportion) of potentially HPV-related cancers increased significantly over time with a mean of 0.78 additional case patient per year. CONCLUSION: The prevalence of HNSCC is modest compared with other cancers in HIV-infected individuals. The prevalence of oropharynx carcinoma, a potentially HPV-related carcinoma, seems to increase over time. Even if tobacco may be an important contributor, the role of HPV in HIV-infected individuals presenting with HNSCC should be investigated.

Non-compliance with IDSA guidelines for patients presenting with methicillin-susceptible Staphylococcus aureus prosthetic joint infection is a risk factor for treatment failure.

OBJECTIVE: The long-term impact of treatment strategies proposed by the IDSA guidelines for patients presenting with methicillin-susceptible S. aureus (MSSA) prosthetic joint infection (PJI) is not well-known. PATIENTS AND METHODS: Retrospective (2000-2010) cohort study including patients presenting with MSSA hip or knee PJI. A univariate Cox analysis was performed to determine if the non-compliance with IDSA surgical guidelines was a risk factor for treatment failure. RESULTS: Eighty-nine patients with a mean follow-up of 2.8 years were included. Non-compliance with IDSA surgical guidelines was associated with treatment failure (hazard ratio 2.157; 95% CI [1.022-4.7]). The American Society of Anesthesiologists score, inadequate antimicrobial therapy, and a rifampicin-based regimen did not significantly influence patient outcome. CONCLUSION: Based on the IDSA guidelines, if a patient presenting with MSSA PJI is not eligible for implant retention, complete implant removal is needed to limit treatment failure.

Tigecycline-based prolonged salvage therapy in patients presenting with complex bone and joint infection.

OBJECTIVES: To assess the clinical experience of tigecycline-based salvage therapy in patients presenting with Bone and Joint Infections (BJI). PATIENTS AND METHODS: Multicenter retrospective cohort study in France and Turkey (2007-2014). RESULTS: Thirty-six patients (age 58.2±17.8 years; 21 men) were included. The most frequently isolated bacteria were Enterobacteriaceae and staphylococci. Tigecycline (50mg BID, mainly in combination (69.4%), mean duration of 58 days) was indicated for multidrug resistance (90.6%) and/or previous antibiotic intolerance (36.1%), and/or as second- or third-line therapy (69.4%). Six patients (16.7%) experienced early treatment discontinuation for adverse event (4 severe vomiting, 1 pancreatitis, 1 asymptomatic lipase increase). Clinical success was observed in 23 of 30 assessable patients who completed the tigecycline therapy (mean follow-up: 54.1±57.7 weeks). CONCLUSION: Prolonged tigecycline-based therapy could be an alternative in patients presenting with BJI requiring salvage therapy, especially if multidrug-resistant Enterobacteriaceae and/or staphylococci are involved.

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.