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.

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.

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.

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.

Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study.

During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.

Actinomycosis after allogeneic hematopoietic stem cell transplantation despite penicillin prophylaxis.

Actinomycosis is a rare chronic and multifaceted disease caused by Actinomyces species frequently mimicking malignancy or other chronic granulomatous lung diseases. We report 4 original presentations of actinomycosis arising under supposed penicillin prophylaxis in allogeneic stem cell transplantation recipients.

Combined medico-surgical strategy for invasive sino-orbito-cerebral breakthrough fungal infection with Hormographiella aspergillata in an acute leukaemia patient.

Hormographiella aspergillata is a rare causative agent of invasive filamentous breakthrough infection, mostly arising after echinocandin exposure. We report a neutropenic patient who developed a severe sino-orbito-cerebral H. aspergillata infection while receiving empirical caspofungin, successfully controlled by an aggressive strategy associating surgical debridement and combined high-dose regimen of antifungal drugs.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort.

The challenge of infection prevention in spine surgery: an update.

Prevention is particularly challenging in implant-associated bone and joint infection, as it could reduce the following: (1) the risk of infection in particular patient populations; (2) the risk associated with particular surgical procedures; and/or (3) the risk of infection with particular pathogen that has the ability to produce biofilm, such as staphylococci. As a consequence, it is crucial to identify: (1) host-related risk factors that may be involved in the acquisition of infection; (2) surgical procedures particularly at risk of infection; and (3) the different ways to target the most frequent pathogens involved in implant-associated spinal infection. In this article, we reviewed the data of the literature on the infection prevention in spine surgery.

The follow-up of patients with postoperative infection of the spine.

The follow-up of patients with postoperative infection of the spine required a multidisciplinary teamwork under the guidance of the spine surgeon and the infectious disease (ID) specialist. During follow-up, the spine surgeon has to ensure the absence of neurological, mechanical and implant-related complications using clinical parameters and different imaging modalities. The ID physician has to give particular attention to antimicrobial efficacy and toxicity, especially during the first weeks when patients necessitate high-dose intravenous treatment.

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).

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

OBJECTIVE: HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. METHODS: In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

Prevalence of isolates with reduced glycopeptide susceptibility in orthopedic device-related infections due to methicillin-resistant Staphylococcus aureus.

We evaluated, by an improved susceptibility testing method, the prevalence and significance of low-level glycopeptide resistance in methicillin-resistant Staphylococcus aureus (MRSA) isolates, which belonged to a previously described, retrospective cohort of patients treated for orthopedic device-related infections (ODRI) at the Geneva University Hospital between 2000 and 2008. Fifty-seven individual or multiple isolates were retrieved from 41 ODRI patients for glycopeptide susceptibility and clonality studies, including 20 patients with prosthetic joint (PJ) and 21 with osteosynthesis (OS) MRSA infections. Low-level glycopeptide resistance was detected by elevated teicoplanin or/and vancomycin minimum inhibitory concentrations (MICs ≥ 4 mg/L), as determined by a previously validated combination of macrodilution and agar dilution assays of improved sensitivity. MRSA isolates with elevated teicoplanin MICs were detected in 20/41 (49 %) ODRI patients at the onset or during the course of glycopeptide therapy, namely, in 10 of 20 patients with PJ and 10 of 21 patients with OS infections. Only one isolate developed a concomitant increase in vancomycin MIC during therapy. 13/20 (65 %) glycopeptide-intermediate S. aureus (GISA)-infected patients, including 7/10 (70 %) with PJ and 6/10 (60 %) with OS, experienced treatment failure. In contrast, therapy failed in only 5/21 (24 %) ODRI patients with non-GISA isolates (p = 0.012), including 2/10 (20 %) with PJ and 3/11 (27 %) with OS infections. The emergence of low-level teicoplanin resistance could not be explained by teicoplanin administration, since only four patients received teicoplanin. The evaluation of low-level teicoplanin resistance may improve the detection of GISA isolates. Further studies are warranted to evaluate the impact of low-level teicoplanin resistance on the outcome of glycopeptide therapy.

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.

Clostridium sordellii brain abscess diagnosed by 16S rRNA gene sequencing.

Clostridium sordellii is usually associated with skin and soft tissue infections. We describe the first case to our knowledge of a Clostridium sordellii-associated brain abscess, diagnosed by 16S rRNA gene sequencing, expanding the microbiological spectrum of brain abscesses, with emphasis on the role of 16S rRNA gene PCR in their etiologic diagnosis.

Risk factors for treatment failure in orthopedic device-related methicillin-resistant Staphylococcus aureus infection.

The purpose of this study was to determine the clinical and microbiological risk factors for treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) orthopedic device-related infection (ODRI). A retrospective cohort study of patients with MRSA ODRI who were treated at Geneva University Hospitals between 2000 and 2008 was undertaken. Stored MRSA isolates were retrieved for genetic characterization and determination of the vancomycin minimum inhibitory concentration (MIC). Fifty-two patients were included, of whom 23 (44%) had joint arthroplasty and 29 (56%) had osteosynthesis. All 41 of the retrieved MRSA isolates were susceptible to vancomycin (MIC