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.

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.

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.

[Disseminated actinomycosis treated with clindamycin]. / Actinomycose disséminée traitée par clindamycine.

Actinomycosis is a rare bacterial disease caused by Actinomyces spp., an anaerobic bacteria from the oropharynx, digestive, and female genital tracts. Initial clinical presentation often mimics malignancy, which can lead to a delay in diagnosis. Cervico-facial, genitourinary, digestive, and respiratory features are the most frequent. Few cases are reported in children and risk factors are not well known in this population. We report on the case of an 8-year-old boy with disseminated actinomycosis with cervico-facial, pulmonary, and bone involvement caused by Actinomyces israelii. The infiltrative appearance initially suggested malignancy and the patient was started on chemotherapy for presumed histiocytosis. Evaluation of subsequent tissue samples demonstrated the presence of filamentous structures consistent with fungal or filamentous bacterial infection. Prolonged culture yielded the correct diagnosis. The patient had a severe allergic reaction to piperacillin/tazobactam and was therefore transitioned to clindamycin to complete a 9-month course. This treatment, which has not been reported in children, led to a favorable clinical, biological, and radiological response, with a good clinical tolerance.

[Children exposed to multidrug-resistant tuberculosis: How should we manage? Analysis of 46 child contacts and review of the literature]. / Enfants au contact d'individus atteints d'une tuberculose multi-résistante : quelles stratégies adopter ? Analyse de 46 enfants contacts et revue de la littérature.

INTRODUCTION: Tuberculosis-related morbidity and mortality remain important. Emergence and diffusion of multidrug-resistance tuberculosis (MDR-TB) is a global public health concern. Cases of MDR-TB in children are a sentinel event indicating the spread of a mycobacterial strain within a community. Latent TB precedes MDR-TB and screening and follow-up of contact individuals are key points of TB infection control. METHODS: We performed the case-investigation of 20 adult cases of MDR-TB managed in our institution. RESULTS: Forty-six pediatric contact individuals were identified. A high proportion of these children were lost to follow-up (80% at 12 months), showing that monitoring this reservoir population with migrant history is challenging. Five (11%) children presented a secondary infection: one child was diagnosed with active TB infection (positive tuberculin skin test associated with abnormalities on chest computer tomography [CT] scan). Four children were diagnosed with latent TB infection (isolated positive tuberculin skin test with normal CT scan). Two of these children received a treatment adjusted to the strain of the index case. DISCUSSION: In the setting of emerging MDR-TB, tuberculin skin test may be likely replaced by specific interferon-gamma release assays (IGRA), independent of prior BCG vaccination. In addition, chest CT scan is preferred to chest X-ray to detect TB lesions. The management of latent TB infection is controversial: immediate treatment with second-line anti-TB drugs adapted to the index case strain or, consistently with WHO guidelines, a simple follow-up with subsequent treatment in case of active TB.

[Tumor-bronchial actinomycosis simulating a recurrence of lung cancer 14 years after initial treatment: A case report]. / Actinomycose bronchique pseudo-tumorale simulant une ré-évolution d'un cancer bronchique 14ans après la prise en charge thérapeutique initiale : à propos d'un cas.

A patient with a history of squamous cell carcinoma of the right upper lung lobe treated 14 years before by concomitant chemo-radiotherapy was referred on account of dyspnea. Bronchial endoscopy revealed complete obstruction of the right main bronchus highly suggestive of a tumor recurrence. However, biopsy samples only showed inflammatory and necrotic tissue with no evidence of malignancy. Despite complete tissue resection by rigid bronchoscopy, a rapid and complete recurrence occurred requiring the placement of a Y-shaped bronchial prosthesis. Repeat histological, bacteriological and mycological analyses were negative. The patient was soon readmitted to hospital for a lung infection due to recurrence of obstruction inside and around the prosthesis. Bacterial examination of biopsy samples identified Actinomyces meyeri. Appropriate antibiotic therapy led to a complete regression of the bronchial obstruction. Unfortunately, the patient died a few months later due to massive hemoptysis after the removal of the prosthesis. Autopsy examination showed a fistula between the right main bronchus and pulmonary artery, with no evidence of neoplastic recurrence nor the persistence of lesions associated with actinomycosis.

Management of emerging multidrug-resistant tuberculosis in a low-prevalence setting.

Multidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies.

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.

[Influenza A H1N1 in neonatal intensive care unit: analysis and lessons]. / Grippe A H1N1 en unité de néonatologie : analyse et enseignements.

Since WHO announced the flu-like pandemic H1N1v in autumn 2009, data on clinical presentation and treatment of H1N1v infection in preterm infants with oseltamivir remain scarce. We cared for four infected preterm infants and ordered prophylactic treatment with oseltamivir in 13 additional contact preterm infants. A number of lessons can be drawn from this experience. The first two cases in twins were revealed by an increase in the number of apnea and one infant required mechanical ventilation. Cough was the major symptom in the two other infected infants. No digestive intolerance was observed among the 17 preterm infants during oseltamivir treatment. Polymerase chain reaction (PCR) quickly determined whether an infant was infected, making it helpful in deciding on initial containment. PCR remained positive, whereas culture became negative. Therefore, culture appeared to be more relevant in deciding on the end of containment. Follow-up of the four infected infants showed their ability to develop immunity against H1N1v.

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.

In vivo and in vitro detection of a superantigenic toxin Vbeta signature in two forms of streptococcal toxic shock syndrome.

The aim of this study was to examine the production of superantigenic toxins in vivo and in vitro in two patients with streptococcal toxic shock syndrome (TSS). In the first patient, a woman with puerperal fever and Streptococcus pyogenes peritonitis, flow cytometry of blood cells and in vitro studies of the isolate showed massive expansion of Vbeta 2-positive T cells corresponding to SpeC production. In the second case, involving a patient with streptococcal TSS and purpura fulminans following non-steroidal anti-inflammatory drug (NSAID) therapy, no Vbeta expansion of T cells was observed in vivo, but the SpeC Vbeta signature was also detected in vitro. In this latter patient, NSAID administration and/or severe disseminated infection might partly explain the absence of Vbeta T cell expansion in vivo. Combined in vivo and in vitro detection of a superantigenic toxin Vbeta signature may be useful to determine which superantigenic toxin is involved in individual cases of streptococcal TSS.

Analysis of superantigenic toxin Vbeta T-cell signatures produced during cases of staphylococcal toxic shock syndrome and septic shock.

Most clinical isolates of Staphylococcus aureus harbour genes encoding superantigenic toxins that bind the Vbeta domain of T-cells, but little information is available concerning superantigenic toxin production during staphylococcal toxic shock syndrome (TSS) and septic shock. This prospective study investigated 14 patients with staphylococcal TSS or septic shock; the toxin gene profile of each isolate was determined and flow-cytometry was used to identify the discriminant Vbeta signature (DVbetaS) of each superantigenic toxin in vitro. Attempts were also made to identify in-vivo production of superantigenic toxin DVbetaS in patients' blood. The DVbetaS identified in vitro were: toxic shock syndrome toxin (TSST)-1, Vbeta 2; staphylococcal enterotoxin (SE), Vbeta 9, Vbeta 22; SEB, Vbeta 3, Vbeta 14, Vbeta 17; SED, Vbeta 1, Vbeta 8; egc, Vbeta 5.3, Vbeta 7.1, Vbeta 9, Vbeta 23; and SElK, Vbeta 5.1. The DVbetaS of TSST-1 and SEB were detected in patients with menstrual and non-menstrual TSS, respectively, whereas no Vbeta signature was detected during septic shock. All patients with septic shock (but only one patient with TSS) had lymphopenia and/or impaired cellular immunity. Detection of a superantigenic toxin DVbetaS may help to show which toxin is produced during staphylococcal TSS, thus confirming the diagnosis and hastening the administration of anti-toxin therapy. In contrast, this approach failed to demonstrate superantigenic toxin involvement in cases of septic shock. In this latter condition, a superantigenic toxin may not be produced by S. aureus, or its production may occur without expansion of targeted T-cells because of T-cell apoptosis and/or anergy.

One in five mortality in non-menstrual toxic shock syndrome versus no mortality in menstrual cases in a balanced French series of 55 cases.

Staphylococcus aureus superantigenic toxins are responsible for menstrual and non-menstrual toxic shock syndrome (TSS). We compared the clinical and biological characteristics of 21 cases of menstrual TSS (MTSS) with 34 cases of non-menstrual TSS (NMTSS) diagnosed in France from December 2003 to June 2006. All 55 S. aureus isolates had been spontaneously referred to the French National Staphylococcal Reference Center, where they were screened for superantigenic toxin gene sequences. Most of the patients had previously been in good health. The most striking differences between MTSS and NMTSS were the higher frequency in NMTSS of neurological disorders (p=0.028), of S. aureus isolation by blood culture (50% versus 0% in MTSS), and the higher mortality rate in NMTSS (22% versus 0% in MTSS). The tst and sea genes were less frequent in isolates causing NMTSS than in those causing MTSS (p<0.001 and 0.051, respectively). Higher mortality was significantly associated with the presence of the sed gene (p=0.041), but when considering NMTSS survivors and non-survivors, no clinical or bacteriological factors predictive of vital outcome were identified. Specific antitoxinic therapy was rarely prescribed, and never in fatal cases. Higher mortality was observed in NMTSS than in MTSS, and no definite factors could explain the higher severity of NMTSS. NMTSS would require more aggressive therapy, comprising systematic rapid wound debridement, antistaphylococcal agents, including an antitoxin antibiotics, and intravenous immunoglobulin.

[Vaccination against influenza: results of a study on vaccination coverage among health care workers in the Croix-Rousse Hospital (Hospitals of Lyon)]. / Vaccination contre la grippe: résultats d'une enquête sur la couverture vaccinale du personnel hospitalier à l'hôpital de la Croix-Rousse (hôpitaux de Lyon).

INTRODUCTION: The aim of this study was to evaluate the vaccinal status among Croix-Rousse Hospital workers, attitude towards this vaccination, and the information delivered in order to promote this vaccination. METHODS: Questionnaires were delivered by electronic mailing. RESULTS: Six hundred (and) twenty-nine questionnaires were analyzed (26.7% of hospital workers); 30.7% of responders were vaccinated against influenza, 89.2% of responders were aware of influenza and vaccine. Vaccine coverage was lower in younger workers, non health-care workers, non physician health-care workers, and surgeons who responded. Motivation and reserve varied according to the status, position, and age, with some discrepancies. CONCLUSION: These results suggest implementing a better targeted vaccination campaign, according to the various categories of personnel.

[Multi-recurrent cardiac arrest: when to discontinue cardiopulmonary resuscitation?]. / Arrêt cardiaque multirécidivant: quand arrêter la réanimation cardiopulmonaire?

A 52-year-old man developed an out-of-hospital cardiac arrest complicating a myocardial infarction. After prolonged cardiopulmonary resuscitation, he was admitted to an intensive care unit, where 25 episodes of cardiac arrests occurred within a few hours. Finally the outcome was favourable. This case raises the question of the duration a cardiopulmonary resuscitation in case of out-of-hospital and in-hospital cardiac arrest. The question is to determine how long resuscitation efforts must be prolonged after recurrent cardiac arrests.