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Central Nervous System (CNS) infections related to external ventricular derivation are a major complication of patients undergoing neurosurgical procedures. Antimicrobial treatment of CNS infections should be based not only on the susceptibility of the isolated microorganism, but also on the treatment's pharmacokinetic properties demonstrating the passage of the molecule through the blood-brain barrier. When CNS infections are caused by multi-drug resistant Gram-negative bacteria, intrathecal colistin is considered an effective and safe option. We review the literature of intrathecal/intraventricular use of colistin, comprehensive of both pharmacokinetic data and clinical experiences.

Background Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. Methods We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. Results In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. Conclusions PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the “statin effect” of TDF.

Direct-acting antivirals (DAAs) demonstrated high efficacy and safety even in the post-liver transplant (LT) setting and in HIV-infected patients, but data are very limited in the early post-LT period with the most recently available DAA. Two HIV/HCV-coinfected LT recipients (both grafts from HIV/HCV-negative donors) experienced early HCV recurrence with severe hepatitis and were treated with sofosbuvir/velpatasvir for 12 weeks. Unfortunately, both patients failed: one (genotype 4d) showed virological breakthrough at week 3 with resistance-associated substitutions (RASs) for both NS5A and NS5B, while the other (genotype 1a) experienced virological relapse without RAS. Both progressed to fibrosing cholestatic hepatitis and were successfully retreated with glecaprevir/pibrentasvir for 16 weeks achieving sustained virological response. The higher prevalence of RAS in experienced genotype 4 patients and the long time to viral suppression observed in subjects with fibrosing cholestatic hepatitis should be taken into account, considering longer treatment duration to increase the chances of achieving sustained virological response.

This study reports the results of a one-day point prevalence study of infections performed in 2001 (SPIR01) and 2002 (SPIR02) in a Regional network of ICUs in Piedmont, Italy. The study aims were to illustrate the overall proportion of infected patients and the rate of ICU-acquired infections. Mortality rate was evaluated three weeks after the study days. Resistance pattern of Staphylococcus aureus, coagulase negative Staphylococci and Pseudomonas aeruginosa were recorded. The primary end-point of the study was to document the prevalence and associated risk factors of the ICU-acquired infections, and the impact of infections on mortality. The prevalence of ICU-acquired infection was 30% in SPIR01, and 38.3% in SPIR02. The rate of methicillin-resistance was high among isolates of Staphylococcus aureus and coagulase-negative Staphylococci. The prevalence of ICU-acquired infections was lower than that reported in the EPIC study. In our experience, this Regional survey stimulated further research and collaboration to improve the prophylaxis, diagnosis and treatment of ICU-acquired infections.