Impact of EUCAST rapid antimicrobial susceptibility testing (RAST) on management of Gram-negative bloodstream infection.

OBJECTIVES: During bloodstream infections, reducing the time to antimicrobial susceptibility testing is crucial to initiation of early appropriate antibiotic therapy. For Gram-negative infections, a phenotypic approach remains necessary. Rapid antimicrobial testing (RAST) is a recently developed phenotypic EUCAST method. The goal of this study was to evaluate the accuracy and clinical impact of RAST. PATIENTS AND METHODS: From September 2020 to August 2021, Gram-negative episodes with positive blood culture detected in the morning were included in the RAST group. Categorical agreement of RAST with conventional antimicrobial testing on strains was determined. To assess antibiotic management and patient outcomes, the RAST group was compared with a control group (CG) with positive blood culture detected in the afternoon for which overnight antimicrobial testing was performed. RESULTS: The RAST group included 61 episodes from 61 patients, while the CG group included 49 episodes from 48 patients. While RAST performed on 41 E. coli, 11 K. pneumoniae and 9 P. aeruginosa strains highlighted 99.3 % of categorical agreement, 7.4 % of unreadable zones and 9.4 % of technical uncertainty area at 4 h incubation were also reported. For the RAST group, effective antibiotic therapy was prescribed in 100 % of patients on the day of positive blood culture (day 1) vs 88 % in CG (p = 0,007). As for beta-lactams on day 1, RAST led to 9 escalations and 6 de-escalations. Mortality and length of hospital stay did not significantly differ between the two groups. CONCLUSION: RAST improves management of antibiotic therapy in patients with Gram-negative sepsis.

Arthritis Caused by Nannizziopsis obscura, France.

Nannizziopsis spp., fungi responsible for emerging diseases, are rarely involved in human bone and joint infections. We present a rare case of septic arthritis with necrotizing cellulitis caused by N. obscura in a patient in France who had undergone kidney transplant. Rapid, aggressive medical and surgical management led to a favorable outcome.

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

BACKGROUND: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. METHODS: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. RESULTS: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group. CONCLUSION: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.

Doravirine: a review.

PURPOSE OF REVIEW: The current review addresses the role of doravirine (DOR), a novel once-daily nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line therapy at a time in which multiple options are available, and issues of antiviral efficacy, safety, simplicity and cost are critical to make informed decisions. RECENT FINDINGS: DOR combination regimens have been tested in two large randomized double-blinded clinical trials in treatment-naïve patients, showing noninferiority to ritonavir-boosted darunavir-based and efavirenz (EFV)-based regimens. The main features of DOR are reviewed in this report including its antiviral activity, genetic barrier to resistance, safety, once-daily dosing and coformulation in a single tablet with tenofovir disoproxil fumarate and lamivudine. DOR pharmacokinetics and drug-drug interactions are also reviewed as DOR can be given without food restriction and has no interaction with proton pump inhibitors. DOR has shown a superior safety profile than EFV regarding neuropsychiatric and cutaneous adverse events. DOR is currently being investigated in treatment-experienced patients and in those with transmitted NNRTI drug resistance. SUMMARY: DOR is a promising new NNRTI that could become the preferred drug in its class for treatment initiation. DOR has shown excellent antiviral activity in treatment-naïve patients, a better safety profile than EFV and a low potential for drug-drug interactions.

Hepatitis A infections in men who have sex with men using HIV PrEP in Paris.

The current hepatitis A outbreak in Europe is largely involving men having sex with multiple male partners. The objective of the present report was to warn teams dealing against the persistent risk of viral and bacterial sexually transmitted infection (STIs) in patients receiving HIV pre-exposure prophylaxis (PrEP). We have notified and investigated three cases of acute hepatitis A virus (HAV) infection in people receiving HIV PrEP in our clinic between December 2016 and March 2017. The patients were not epidemiologically related, had no recent travel history to HAV endemic areas, reported multiple STIs during this period and had not been vaccinated against HAV. They were all identified as genotype A, strain VRD_521_2016 virus.Large-scale vaccination against viral hepatitis is recommended in men having sex with men, especially in those using PrEP, as PrEP is used by people who have high-risk sexual behaviour.

Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis.

Despite increasing reports of human infection, data about the optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides, initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation (n = 17), diabetes or glucose intolerance (n = 10), rheumatoid arthritis or Still's disease (n = 4), chronic hematological diseases (n = 3), or chronic granulomatous disease (n = 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n = 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections (n = 6). The main antifungal drugs used were azoles (n = 41) and amphotericin B (n = 16). Surgical excision or drainage was performed in 64% of cases (n = 27). The cure rate was 67% (n = 28). There were 10% cases of treatment failure or partial response (n = 4), 19% relapses (n = 8), and 7% losses to follow-up (n = 3). The death rate was 19% (n = 8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy.