Meropenem-Vaborbactam for the Treatment of Post-Neurosurgical Meningitis Caused by KPC Producer Klebsiella Pneumoniae: A Case Report and Review of the Literature.

Meningitis and ventriculitis, due to carbapenem-resistant Enterobacterales, are frequently associated with significant morbidity and mortality. In the case of multi-drug-resistant pathogens, it is necessary to consider the limited susceptibility profile as well as the penetration of the antimicrobials into the brain. Limited data are available regarding the treatment of central nervous system infections caused by carbapenem-resistant Enterobacterales. We report a study of a patient treated with meropenem-vaborbactam in the case of post-neurosurgical meningitis due to carbapenemase-producing Klebsiella pneumoniae (CPKP).

Durability of doravirine with dolutegravir dual regimen compared with other dolutegravir-based dual combinations.

OBJECTIVES: The availability of doravirine (DOR) allowed clinicians to prescribe a dolutegravir (DTG)-based two-drug regimen (2DR) in individuals not eligible to receive lamivudine (3TC) or rilpivirine (RPV). The aims of this study were to describe the durability of DTG + DOR compared with DTG/3TC and DTG/RPV and the rate of virological failure and target not-detected maintenance over time. METHODS: This retrospective, monocentric analysis included all subjects who started a DTG-based 2DR from 2018 to 2022 as a simplification. Descriptive statistics and non-parametric tests to describe and compare the groups were applied. Kaplan-Meier probability curves and Cox regression models for regimens durability were used. RESULTS: The study enrolled 710 individuals: 499 treated with DTG/3TC, 140 with DTG/RPV, and 71 with DTG + DOR. A 2DR with DOR was prescribed to older subjects who had a longer infection, greater exposure to different antiretroviral regimens, a higher proportion of resistance-associated mutations, and a worse immune-virologic status. Over a cumulative follow-up of 68 152 weeks, 42 discontinuations were registered (5.9%). DTG + DOR had a risk of treatment interruption of 7.8% at 48 weeks and 9.8% at 96 weeks, significantly higher than the other 2DRs. In the multivariate Cox model, DTG + DOR and DTG/RPV were significantly associated with discontinuation. The maintenance of target not detected during follow-up was similar among groups. The rate of virological failure was higher for DTG + DOR through different event definitions. CONCLUSIONS: DTG + DOR durability was high over a long follow-up albeit lower than for other 2DRs. This combination might be an effective option in people with HIV that has proven difficult to treat.

Impact of treatment with direct-acting antivirals on inflammatory markers and autoantibodies in HIV/HCV co-infected individuals.

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0-F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p = .099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks.

Early remdesivir to prevent severe COVID-19 in recipients of solid organ transplant: a real-life study from Northern Italy.

OBJECTIVES: The effectiveness of a 3-day course of remdesivir to prevent severe disease in patients with COVID-19 who received solid organ transplant (SOT) is unknown. We wanted to study the efficacy of this therapeutic option in patients with COVID-19 who received SOT in preventing both hospitalizations for outpatients and clinical worsening due to COVID-19 for those already hospitalized for other reasons. METHODS: This is a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted all the data of patients with COVID-19 receiving SOT who received and did not receive pre-emptive remdesivir between December 23, 2021, and February 26, 2022. We used a Cox proportional hazard model to assess whether receiving pre-emptive remdesivir was associated with lower rates of hospitalization. RESULTS: A total of 24 patients who received SOT were identified. Among these, seven patients (29, 1%) received pre-emptive remdesivir, whereas 17 (70, 9%) patients did not. Receiving remdesivir significantly reduced the hospitalization rate in outpatients who received SOT and the clinical worsening of the condition of already hospitalized patients who received SOT (hazard ratio 0.05; confidence interval [0.00-0.65], P-value = 0.01). CONCLUSION: In our cohort of patients infected with SARS-CoV-2 who received SOT, pre-emptive remdesivir was effective in reducing the hospitalization rate due to COVID-19 and in preventing the clinical worsening of the condition of patients who received SOT who were hospitalized for reasons other than COVID-19.

COVID-19 Infection Among Incarcerated Individuals and Prison Staff in Lombardy, Italy, March 2020 to February 2021.

Importance: Owing to infrastructural and population characteristics, the prison setting is at increased risk for transmission of SARS-CoV-2 and for severe clinical outcomes. Because of structural and operational reasons, research in prison settings is challenging and available studies are often monocentric and have limited temporal coverage; broader-based research is necessary. Objectives: To assess the extent and dynamics of the COVID-19 pandemic within the prison system of a large Italian region, Lombardy, and report the infection prevention and control measures implemented. Design, Setting, and Participants: This repeated cross-sectional study was carried out from March 1, 2020, through February 28, 2021 (first wave, March-June 2020; second wave, October 2020-February 2021) in the prison system of Lombardy, which includes 18 detention facilities for adults. All incarcerated persons and the prison staff of the penitentiary system of the Lombardy region participated in the study. Exposures: The main exposures of interest were the weekly average number of incarcerated individuals placed in quarantine in single or shared isolation rooms, the rate of sick leave by symptomatic and asymptomatic prison staff reported to the prison occupational medicine department on a weekly basis, and the level of overcrowding. Main Outcomes and Measures: The primary outcome measures were weekly COVID-19 crude case rates, weekly test positivity rate, and the relative risk of acquiring the infection for prison staff, incarcerated persons, and the general population. Results: The study population comprised a mean of 7599 incarcerated individuals and 4591 prison staff. Approximately 5.1% of the prison population were women; demographic characteristics of the prison staff were not available. During the study, COVID-19 occurred in 1564 incarcerated individuals and 661 prison staff. Most of these cases were reported during the second wave (1474 in incarcerated individuals, 529 in prison staff), when stringent measures previously enforced were relaxed. During both epidemic waves, incarcerated individuals and prison staff had a higher relative risk for COVID-19 infection than the general population during both the first wave (incarcerated individuals: 1.30; 95% CI, 1.06-1.58; prison staff: 3.23; 95% CI, 2.74-3.84) and the second wave (incarcerated individuals: 3.91; 95% CI, 3.73-4.09; prison staff: 2.61; 95% CI, 2.41-2.82). Conclusions and Relevance: The findings of this study suggest that the prison setting was an element of fragility during COVID-19 pandemic, with a high burden of COVID-19 cases among both the incarcerated individuals and prison staff. The prison setting and prison population need to be included and possibly prioritized in the response during epidemic events.