Unsuccessful therapy with adefovir and entecavir-tenofovir in a patient with chronic hepatitis B infection with previous resistance to lamivudine: a fourteen-year evolution of hepatitis B virus mutations

<p>Abstract</p> <p>Background</p> <p>Complex mutants can be selected under sequential selective pressure by HBV therapy. To determine hepatitis B virus genomic evolution during antiviral therapy we characterized the HBV quasi-species in a patient who did no respond to therapy following lamivudine breakthrough for a period of 14 years.</p> <p>Case Presentation</p> <p>The polymerase and precore/core genes were amplified and sequenced at determined intervals in a period of 14 years. HBV viral load and HBeAg/Anti-HBe serological profiles as well as amino transferase levels were also measured. A mixture of lamivudine-resistant genotype A2 HBV strains harboring the rtM204V mutation coexisted in the patient following viral breakthrough to lamivudine. The L180M+M204V dominant mutant displayed strong lamivudine-resistance. As therapy was changed to adefovir, then to entecavir, and finally to entecavir-tenofovir the viral load showed fluctuations but lamivudine-resistant strains continued to be selected, with minor contributions to the HBV quasi-species composition of additional resistance-associated mutations. At the end of the 14-year follow up period, high viral loads were predominant, with viral strains harboring the lamivudine-resistance signature rtL180M+M204V. The precore/core frame A1762T and G1764A double mutation was detected before treatment and remaining in this condition during the entire follow-up. Specific entecavir and tenofovir primary resistance-associated mutations were not detected at any time. Plasma concentrations of tenofovir indicated adequate metabolism of the drug.</p> <p>Conclusions</p> <p>We report the selection of HBV mutants carrying well-defined primary resistance mutations that escaped lamivudine in a fourteen-year follow-up period. With the exception of tenofovir resistance mutations, subsequent unselected primary resistance mutations were detected as minor populations into the HBV quasispecies composition during adefovir or entecavir monotherapies. Although tenofovir is considered an appropriate therapeutic alternative for the treatment of entecavir-unresponsive patients, its use was not effective in the case reported here.</p

Disappearance of FDG uptake on PET scan after antimicrobial therapy could help for the diagnosis of Coxiella burnetii spondylodiscitis.

A 55 year-old man was admitted for worsening of a chronic low back pain associated with L4-L5 anterolisthesis, despite taking non-steroidal anti-inflammatory drugs for several months. He had a medical history of high blood pressure and obesity (body mass index, 37 kg/m2). He lived in the countryside but had no direct contact with animals except his dog. There were no fever, chills, sweats or weight loss. C reactive protein (CRP) was &lt;2.9 mg/L. Radiographs showed L4-L5 anterolisthesis with endplate erosions and bony sclerosis (figure 1A). On MRI (figure 1B), there was a significant enhancement of L4-L5 vertebral endplates and paravertebral soft tissues. Positron emission tomography (PET) CT scan showed an intense uptake of the L4-L5 space (figure 1C). Blood and CT-guided discovertebral cultures remained sterile (including for mycobacteria) and 16s PCR and in-house specific Coxiella burnetii PCR were negative. C. burnetii serology (Focus diagnostics Q fever immunofluorescent antibody IgG and IgM test kits) was positive and in favour of a chronic Q fever (phase I, IgG 2048; phase II, IgG 4096; IgM were negative). Brucella and Bartonella were negative. An echocardiogram was performed to exclude vegetations caused by bacterial endocarditis. The patient was treated with doxycycline (200 mg/day) and hydroxychloroquine (400 mg/day) for 10 months. A significant improvement with reduction of the back pain was noticed and the CRP remained &lt;2.9 mg/L. The antibody titres decreased and the pathological uptake of the L4-L5 space on PET scan disappeared when antibiotics were stopped (figure 1D)

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 (&lt;3 months), delayed (3-12 months) and late (&gt;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 &lt;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 &lt;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 &lt;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