Cost analysis of dalbavancin versus standard of care for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in two Italian hospitals

The study was presented at the 21st Conference of the National Society of Infectious Diseases and Tropical Medicine ‘Congresso Nazionale Società Italiana Malattie Infettive e Tropicali’, 20–23 November 2022, Rome, Italy (Poster PP259).OBJECTIVES: Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC). PATIENTS AND METHODS: Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC). RESULTS: One hundred and twenty-six of 228 (55.3%) patients received SoC, while 102/228 (44.7%) received dalbavancin. Twenty-seven of the 102 (26.5%) patients received dalbavancin as first-line treatment, 46 (45.1%) as second-line, and 29 (28.4%) as third- or higher-line treatment. Most patients received dalbavancin as monotherapy (62/102; 60.8%). Compared with SoC, dalbavancin was associated with a significant reduction of LOS (5 ± 7.47 days for dalbavancin, 9.2 ± 5.59 days for SoC; P < 0.00001) and with lower mean direct medical costs (3470 ± 2768€ for dalbavancin; 3493 ± 1901€ for SoC; P = 0.9401). LOS was also reduced for first-line dalbavancin, in comparison with second-, third- or higher-line groups, and for dalbavancin monotherapy versus combination therapy. Mean direct medical costs were significantly lower in first-line dalbavancin compared with higher lines, but no cost difference was observed between monotherapy and combination therapy. CONCLUSIONS: Monotherapy with first-line dalbavancin was confirmed as a promising strategy for ABSSSIs in real-life settings, thanks to its property in reducing LOS and saving direct medical costs.https://www.ncbi.nlm.nih.gov/pmc/journals/4039School of Health Systems and Public Health (SHSPH

Reasons why HIV-positive women do not want to have a child: the questionnaire-based DIDI study

Given that the majority of HIV‐positive women are of reproductive age, it is necessary to understand the interaction between HIV and family planning, especially as antiretroviral medications allow to live longer, healthier lives. Aim of this analysis form the DIDI study was to assess prevalence of motherhood desire in current years and to identify variables associated pregnancy decision‐making in HIV‐infected women. DIDI is an Italian, 16‐center, questionnaire‐based survey performed in 585 HIV‐positive women between Nov. 2010 and Feb. 2011. The items covered in the self‐administered questionnaire included: socio‐demographic characteristics, sexual and gynecological health, motherhood desire, strategies adopted to become pregnant, reasons for not wanting a child, partnership, HIV disclosure, physical and mental health, ART adherence, drug use. For the present analysis only women aged<45 years and engaged in a partnership were included. Absence of motherhood desire was defined by a negative answer at the question whether the women at present would like to have a child. 178 women were included: mean age 39 (IQR, 33–42), HIV transmission heterosexual 75%, IVDU 11%, heterosexual/IVDU 2.5%, not known 7.5%; mean CD4 and HIV‐RNA were 552/mmc (+252) and 3.85 c/ml (+4.7), respectively. Absence of motherhood desire was found in 61% of women; 50% of women declared that HIV negatively affected motherhood desire, and 22% declared a decrease in desire after start of ART. The probability of vertical transmission was estimated higher than 50% by 19% of women, even when adopting all preventive measures. Not wanting a child was associated with: fear of vertical transmission (p<0.001), fear of not being able to raise the child (p<0.001), decline in motherhood desire after HIV (p=0.007), unstable partnership (p=0.02). At multivariable analysis, variables found to be significantly associated with negative pregnancy decision‐making were: fear of vertical transmission (AOR 3.75; 95%CI 1.18–11.89), economic restrictions (AOR 0.28; 95% CI 0.10–0.76 In conclusion, absent motherhood desire in HIV‐positive women with child‐bearing potential is frequent and essential information on vertical HIV transmission is lacking. HIV‐positive women of childbearing age may benefit from counseling interventions sensitive to factors that influence infected women's pregnancy decisions

Antiretroviral therapy in HIV/HCV co-infection Italian consensus workshop

About 50% of people living with the HIV infection in Italy are co-infected with HCV. In this group of patients, the primary cause of mortality is liver disease, which accounts for up to 14% of deaths. HIV/HCV co-infection also exposes patients to a higher risk of progression to AIDS, a faster evolution towards cirrhosis, more frequent drug toxicity, and lower tolerance for antiretroviral therapy. Moreover, HCV infection can play a part in increasing immune system depression; neurological, cognitive and renal damage; and bone fragility. Hence an optimal antiretroviral regimen needs to be chosen for co-administration with anti-HCV therapy and timed appropriately to improve the prognosis of co-infected HIV/HCV patients. Unfortunately, however, data on the safety and efficacy of antiretroviral drugs in these patients is scarce, as are studies of pharmacokinetics in patients with advanced liver impairment. Furthermore, restoring adequate immune constitution seems not to slow the progression of liver disease, and the metabolic and hepatic toxicity of some antiretroviral drugs can even contribute to inflammatory and fibrogenic processes. It is therefore essential that HIV/HCV co-infected patients receive only medications capable of ensuring the best immune recovery but possessing the lowest potential to trigger immune reconstitution syndrome or hepatic and metabolic damage

Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study

Background Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.Methods We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least &gt;= 24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.Results The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index &gt;= 3, dialysis, concomitant COVID-19, and INCREMENT score &gt;= 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.Conclusions Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy

Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia

Introduction Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.Methods This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and beta-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.Results A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.Conclusion The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index &gt;4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P &lt; .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P &lt; .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P &lt; .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

Cost analysis of dalbavancin versus standard of care for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in two Italian hospitals

Objectives Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC). Patients and methods We conducted a multicentre retrospective study, including all hospitalized or outpatients diagnosed with ABSSSIs at Padua University Hospital, Padua and San Paolo Hospital, Milan (1 January 2016 to 31 July 2020). We compared patients according to antibiotic treatment (dalbavancin versus SoC), the number of lines of dalbavancin treatment, and monotherapy or combination (dalbavancin in association with other antibiotics). Primary endpoints were direct medical costs and length of hospital stay (LOS) associated with ABSSSI management; Student's t-test, chi-squared test and one-way ANOVA were used. Results One hundred and twenty-six of 228 (55.3%) patients received SoC, while 102/228 (44.7%) received dalbavancin. Twenty-seven of the 102 (26.5%) patients received dalbavancin as first-line treatment, 46 (45.1%) as second-line, and 29 (28.4%) as third- or higher-line treatment. Most patients received dalbavancin as monotherapy (62/102; 60.8%). Compared with SoC, dalbavancin was associated with a significant reduction of LOS (5 +/- 7.47 days for dalbavancin, 9.2 +/- 5.59 days for SoC; P < 0.00001) and with lower mean direct medical costs (3470 +/- 2768euro for dalbavancin; 3493 +/- 1901euro for SoC; P = 0.9401). LOS was also reduced for first-line dalbavancin, in comparison with second-, third- or higher-line groups, and for dalbavancin monotherapy versus combination therapy. Mean direct medical costs were significantly lower in first-line dalbavancin compared with higher lines, but no cost difference was observed between monotherapy and combination therapy. Conclusions Monotherapy with first-line dalbavancin was confirmed as a promising strategy for ABSSSIs in real-life settings, thanks to its property in reducing LOS and saving direct medical costs

Geotrichum capitatum Invasive Infection Early After Liver Transplant

Geotrichum capitatum is a rare fungal pathogen that has infrequently affected immunocompromised patients with onco-hematologic diseases. Geotrichum capitatum invasive infection has been associated with poor prognosis, with a mortality rate ranging from 50% to 90%. Here, we report the first case of Geotrichum capitatum invasive fungal infection in a liver transplant recipient from an unrelated deceased donor, who was effectively treated with amphotericin B and voriconazole. We also reviewed the available literature in the field