Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study)

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and ‘other sites’ infections’ (OTA). Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016–2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting. Results: 206 patients enrolled (males 50%, median age 62 [IQR 50–76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI vs 90.7% OTA (p = 0.003) and 46.3% ABSSSI vs 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure. Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5–22 vs 3, 0–11.7; p<0.0001) and received longer previous (18 days, 9–30 vs 11, 7–19; p = 0.007)/concomitant antibiotic treatments (21 days, 14–52 vs 11, 8–14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% vs 75%, p = 0.459) and safety (no AE: 81.5% vs 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies. Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use

Nephrolithiasis and hydronephrosis in an HIV-infected man receiving tenofovir

The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-patients because of its favourable resistance profile. Tenofovir is mainly eliminated by the kidneys and renal toxicity should be carefully monitored. We describe here the case of an HIV-infected patient, without a prior history of renal failure who developed nephrolithiasis and hydronephrosis after starting a tenofovir-containing HAART regimen

Long-term immunologic outcome in HAART-experienced subjects receiving lopinavir/ritonavir

The long-term immunological efficacy of regimens including lopinavir/ritonavir (LPV/r) has not been assessed in HIV-infected HAART-experienced subjects. The present study included 452 consecutive HIV-infected outpatients starting LPV/r before May 2003 after failing (HIV-RNA > 1000 copies/ml) HAART. Four groups were considered according to CD4 cell counts at LPV/r initiation: group 1 (G1, n = 115) /= 350 cells/mm(3). The majority of patients were males (n = 320, 70.8%), the median age was 38 years, and 180 (39.6%) were on CDC stage C. The median time of previous HAART was 51.1 months (12-81.7) and a median of 7 antiretroviral regimens and of 3 protease inhibitors was changed before LPV/r. The mean CD4 cell count increase was 105, 113, 128, and 144 cells/mm(3) after 12 months (p 1000 copies/ml. A mean increase of 64 and 65 cells/mm(3) and of 88 and 56 cells/mm(3) at month 12 and 48 was observed in G1 and G2, respectively. The use of LPV/r-based regimens also provided a durable immunologic recovery in highly pretreated HIV-infected subjects

Subclinical hypothyroidism in HIV-infected subjects

Objectives: The correlation between subclin. hypothyroidism [TSH (TSH) &rt;4 mIU/L with normal free triiodothyroxine and free thyroxine levels], HIV infection and HAART is still unclear. Patients and methods: To evaluate the predictive factors of subclin. hypothyroidism in an HIV-infected population, we identified three groups of subjects: G1, subjects on stable highly active antiretroviral therapy (HAART) (for at least 1 yr) at baseline and at month 24 (n= 97); G2, subjects naive at both baseline and month 24 (n= 47); G3, subjects starting HAART at baseline (n= 46). Results: The three groups were comparable with respect to age, gender, body wt. and prevalence of HCV infection. At baseline, subclin. hypothyroidism was detected in 14 subjects in G1 (14.4%), 5 in G2 (10.6%) and 4 in G3 (8.7%) (P= 0.18) and these were excluded from the anal. At month 24, 15 subjects had developed subclin. hypothyroidism: 4 in G1 (4.8%), 3 in G2 (7.1%) and 8 in G3 (19.0%). In the multivariable anal., the higher increase in total cholesterol was predictive of subclin. hypothyroidism (RR: 1.53 for each addnl. 10 mg/dL, 95% Cl 1.23-1.90; P < 0.01); other variables, which were statistically significant in the univariate anal., such as G3 group, body wt. and higher increase in CD4+ cell count and in triglyceride serum levels were not confirmed to be assocd. with TSH alterations. Conclusions: The occurrence of subclin. hypothyroidism in HIV-pos. patients seems to be related to the increase in total cholesterol serum levels occurring after HAART initiation. Thyroid function should be monitored in all HIV-infected subjects, esp. in those starting HAART

Monitoring of human cytomegalovirus (HCMV)-specific CD4+ T cell frequency by cytokine flow cytometry as a possible indicator for discontinuation of HCMV secondary prophylaxis in HAART-treated AIDS patients.

Objective: Absolute CD4+ T cell count and human cytomegalovirus (HCMV)-specific CD4+ T cell frequency (as determined by cytokine flow cytometry, CFC) were compared for their ability to predict HCMV disease and safe discontinuation of HCMV secondary prophylaxis. Study design: Three groups of AIDS patients with previous nadir CD4+ T cell count <100/μl were studied. Group A included 48 HAART-treated patients with no HCMV disease. Group B included 11 HAART-treated patients with previous HCMV disease who discontinued HCMV prophylaxis. Group C included 23 HAART-treated (n=16) or -naive (n=7) patients with previous HCMV disease either continuing or starting HCMV prophylaxis. Patients underwent follow-up for detection of HCMV viremia or disease (groups A and B) and for discontinuation of HCMV secondary prophylaxis on the basis of either HCMV-specific or absolute CD4+ T cell count (group C). Results: During follow-up, while some patients showed a stable HCMV-specific CD4+ T cell response, others had a fluctuating response (unstable responders) or showed no response at all. In detail, 13/48 group A patients were either HCMV non-responders or unstable responders and 2 of them developed HCMV viremia; 3/11 group B patients were unstable responders, none developing either HCMV viremia or disease; finally, 9 group C patients discontinued HCMV prophylaxis based on absolute CD4+ T cell count >150cells/μl, but in 2 of them lacking HCMV-specific response HCMV retinitis relapsed. None of the seven group C patients discontinuing HCMV prophylaxis on the basis of CFC showed HCMV disease relapse. Conclusions: CFC may support absolute CD4+ T cell count for both guiding HCMV prophylaxis discontinuation and better monitoring HCMV infection in AIDS patients with no previous HCMV disease or having discontinued HCMV prophylaxis

Efficacy of intraventricular amikacin treatment in pan-resistant Pseudomonas aeruginosa postsurgical meningitis

Mariadelfina Molinaro,1 Paola Morelli,2 Manuela De Gregori,1,3,4 Simona De Gregori,1 Ilaria Giardini,1 Federica Tordato,2 Vincenzina Monzillo,5,6 Daria Pocaterra,2 Erminia Casari7 1Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, 2Infectious Diseases Unit, Hospital Health Direction, Humanitas Clinical and Research Center, Milan, 3Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 4Study in Multidisciplinary Pain Research Group, Parma, 5Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 6Infectious Diseases Unit, Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, 7Microbiology Unit, Analysis Laboratory, Humanitas Clinical and Research Center, Milan, Italy Background: We describe a case of pan-resistant Pseudomonas aeruginosa postsurgical meningitis associated with the presence of an external ventricular device. We changed therapy twice; finally, by using amikacin and a continuous infusion of cefepime, we obtained clinical improvement. Case presentation: A female patient, who underwent surgery for a cavernous angioma, presented with meningitis. Cerebrospinal fluid culture revealed a multidrug-resistant Pseudomonas aeruginosa, initially sensitive only to colistin. We successfully used intrathecal amikacin and intravenous cefepime continuous infusion plus intravenous amikacin after two previous ineffective therapeutic approaches. Conclusion: The evaluation of the antibiotic concentration and the bactericidal activity in cerebrospinal fluid may contribute to the choice of the drug in cases of multidrug-resistant meningitis. Keywords: pan-resistant meningitis, Pseudomonas aeruginosa, amikaci