Clinical prediction models in hospitalized patients with COVID-19: A multicenter cohort study.

BACKGROUND: Clinical spectrum of novel coronavirus disease (COVID-19) ranges from asymptomatic infection to severe respiratory failure that may result in death. We aimed at validating and potentially improve existing clinical models to predict prognosis in hospitalized patients with acute COVID-19. METHODS: Consecutive patients with acute confirmed COVID-19 pneumonia hospitalized at 5 Italian non-intensive care unit centers during the 2020 outbreak were included in the study. Twelve validated prognostic scores for pneumonia and/or sepsis and specific COVID-19 scores were calculated for each study patient and their accuracy was compared in predicting in-hospital death at 30 days and the composite of death and orotracheal intubation. RESULTS: During hospital stay, 302 of 1044 included patients presented critical illness (28.9%), and 226 died (21.6%). Nine out of 34 items included in different prognostic scores were independent predictors of all-cause-death. The discrimination was acceptable for the majority of scores (APACHE II, COVID-GRAM, REMS, CURB-65, NEWS II, ROX-index, 4C, SOFA) to predict in-hospital death at 30 days and poor for the rest. A high negative predictive value was observed for REMS (100.0%) and 4C (98.7%) scores; the positive predictive value was poor overall, ROX-index having the best value (75.0%). CONCLUSIONS: Despite the growing interest in prognostic models, their performance in patients with COVID-19 is modest. The 4C, REMS and ROX-index may have a role to select high and low risk patients at admission. However, simple predictors as age and PaO2/FiO2 ratio can also be useful as standalone predictors to inform decision making.

Superinfections caused by carbapenem-resistant Enterobacterales in hospitalized patients with COVID-19: a multicentre observational study from Italy (CREVID Study).

Objectives: To describe clinical characteristics and outcomes of COVID-19 patients who developed secondary infections due to carbapenem-resistant Enterobacterales (CRE). Methods: Retrospective observational study including COVID-19 patients admitted to 12 Italian hospitals from March to December 2020 who developed a superinfection by CRE. Superinfection was defined as the occurrence of documented bacterial infection >48 h from admission. Patients with polymicrobial infections were excluded. Demographic, clinical characteristics and outcome were collected. Isolates were classified as KPC, metallo-ß-lactamase (MBL) and OXA-48-producing CRE. A Cox regression analysis was performed to identify factors independently associated with 30 day mortality. Results: Overall, 123 patients (median age 66 years, IQR 59-75) were included. The majority of infections occurred in the ICU (81, 65.9%), while 42 (34.1%) in medical wards. The most common types of infection were bloodstream infections (BSI) (n = 64, 52%), followed by urinary-tract infections (UTI) (n = 28, 22.8%), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) (n = 28, 22.8%), intra-abdominal infections (n = 2, 1.6%) and skin infections (n = 1, 0.8%). Sixty-three (51.2%) infections were caused by KPC-, 54 (43.9%) by MBL-, and 6 (4.8%) by OXA-48-producing CRE. Thirty-day mortality was 33.3% (41/123). On Cox regression analysis, HAP/VAP compared with UTI (HR 7.23, 95% CI 2.09-24.97, P = 0.004), BSI compared with UTI (HR 3.96, 95% CI, 1.33-11.77, P = 0.004), lymphopenia on admission (HR 3, 95% CI 1.44-6.26, P = 0.003) and age (HR 1.05, 95% CI 1.02-1.08, P = 0.002) were predictors of 30 day mortality. Conclusions: Superinfections by CRE were associated with high risk of 30 day mortality in patients with COVID-19. HAP/VAP was the strongest predictor of death in these patients.

Prosthetic joint infection diagnosis applying the three-level European Bone and Joint Infection Society (EBJIS) approach.

Sensitive and specific tests for the diagnosis of prosthetic joint infection (PJI) are lacking. The aim of this study was to report clinical and microbiological findings of consecutive patients diagnosed with PJI at the University Hospital of Perugia, Perugia, Italy, and to validate these diagnoses utilizing the European Bone and Joint Infection Society (EBJIS) three-level diagnostic approach from 2021. Patients with a PJI diagnosis were included in this study and examined retrospectively. Overall, 133 patients were diagnosed with PJI: mean age 72 years, 54.9% female, and 55.6% with more than one comorbidity. The most frequent involved joints were hip 47% and knee 42%. Aetiology was identified in 88/133 (66.2%): staphylococci resulted the most frequent microorganisms and over 80% (45/54) resulted rifampin susceptible. Applying the EBJIS approach, PJI diagnosis resulted: confirmed in 101 (75.9%), likely in 25 (18.8%), and unlikely in 7 (5.3%). Likely PJIs aetiology was Staphylococcus aureus 11/25, coagulase-negative staphylococci 8/25, Streptococcus agalactiae 3/25, viridans group streptococci 2/25, and Pseudomonas aeruginosa 1/25. No statistically significant differences were detected among the three diagnosis groups with regard to clinical characteristics with the exception of a higher number of confirmed PJIs occurring < 3 months after implantation. The logistic regression analysis did not disclose any independent predictor of confirmed PJIs. We recommend using all the diagnostic tests available to approach PJI diagnosis, and suggest caution before rejecting PJI diagnosis in the presence of highly virulent microorganisms from a single sample, in patients without sinus tract, and in those receiving antimicrobial at the time microbiologic samples are collected. Study approved by Umbrian Regional Ethical Committee, Perugia, Italy, Prot. N. 23,124/21/ON of 10.27.2021.

QuantiFERON-TB and tuberculin skin test in patients with active tuberculosis: the experience of a single medium-sized Italian University Hospital.

Interferon-γ releasing assays (IGRAs) are currently widely employed in the initial work up of Mycobacterium tuberculosis infection, as well as in suspected tuberculosis (TB). These assays are commonly utilized over the Tuberculin Skin Test (TST) in high resource and low TB burden settings, despite the unclear benefits shown in such contexts. The debate on the use of TST and IGRAs is of current interest also in Italy due to the increasing presence of immigrants from countries with a high incidence of TB and the rising attention of health care institutions to economic costs. The aim of this study was to compare QuantiFERON-TB (QFT) and TST results in active TB. We evaluated QFT results and TST reactions from 245 consecutive patients having both tests, registered among 411 patients admitted for TB at the Infectious Disease Clinic, Department of Medicine of the University of Perugia (Italy). We compared the rates of positive QFT and TST tests and noted no statistically significant differences overall or in relation to age, gender, HIV status and TB localization. Among foreign-born patients with confirmed TB, we observed a lower rate of positive TST results. The results of our study indicated that both QFT and TST can be used in the work up of TB having special attention when evaluating foreign-born patients.

Transgender people living with HIV: characteristics and comparison to homosexual and heterosexual cisgender patients in two Italian teaching hospitals.

Regarding people living with HIV (PLHIV), little is known about the epidemiological characteristics and management decisions for transgender individuals. This retrospective study compared transgender and cisgender (homosexual and heterosexual) PLHIV at both the S. Maria della Misericordia of Perugia and Careggi of Firenze Teaching Hospitals from 2000 to 2018. Multivariate logistic regression was performed to analyse possible relationships between viral suppression (dependent variable) and age, sexually transmitted infections (STIs), and hepatitis diagnosis (independent variables). After analysing and comparing epidemiological and clinical data for 124 transgender, 180 homosexual cisgender and 188 heterosexual cisgender PLHIV, we found that transgender PLHIV, mostly Latin American sex workers, were more likely to have other STIs. Likewise, this subgroup, on average, was younger at the time of HIV diagnosis and more likely to be less adherent to care, consequently jeopardizing the achievement of viral suppression. Finally, the use of hormone therapy and gender confirmation surgery in transgender PLHIV contributed to specific management issues. To date, major attention has focused on studying the epidemiological characteristics of homosexual and heterosexual PLHIV. Our analysis found that transgender PLHIV were the least likely group to be adequately retained in the continuum of care and presented specific issues in part due to social and behavioural realities.

In vitro antibacterial activity of ceftazidime/avibactam in combination against planktonic and biofilm carbapenemase-producing Klebsiella pneumoniae isolated from blood.

OBJECTIVES: The aim of this study was to report on in vitro tests of antibacterial activity of ceftazidime/avibactam in combination against planktonic or biofilm KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), the rate of KPC-Kp blood isolates in University of Perugia Hospital over a 5-year period, and their antimicrobial susceptibility patterns. METHODS: The antibacterial activity of ceftazidime/avibactam in combination with other antimicrobials was assessed against planktonic and biofilm bacteria by Etest and checkerboard assay. A retrospective review of laboratory data was performed to evaluate the rate of KPC-Kp from blood samples and their antimicrobial susceptibility patterns. RESULTS: Between 2014 and 2019, 130/4241 (3.1%) KPC-Kp were identified from blood cultures. Their rate increased from 2.3% in 2014-2015 to 4.5% over the last 3 years. Overall, 4.6% (6/130) of KPC-Kp isolates were susceptible to meropenem, 65.4% (85/130) to colistin, 65.1% (84/129) to tigecycline, 34.6% (45/130) to amikacin, 36.2% (42/116) to gentamicin, 40.2% (39/97) to fosfomycin and 91.5% (65/71) to ceftazidime/avibactam. Five of six ceftazidime/avibactam-resistant KPC-Kp were isolated from patients not treated with ceftazidime/avibactam. Synergism was detected both by Etest and checkerboard assay for the combination of ceftazidime/avibactam plus meropenem against planktonic isolates, whilst lower bactericidal activity was observed in biofilm KPC-Kp isolates. CONCLUSIONS: Our in vitro data suggest that the combination of ceftazidime/avibactam plus meropenem has a synergistic antibacterial activity against planktonic bacteria, whilst a lower activity was detected against biofilm, suggesting worse clinical outcomes whenever biofilm infections are present. Further analyses are required to confirm these results before extending them to clinical practice.

Partial Achievement of the 90-90-90 UNAIDS Target in a Cohort of HIV Infected Patients from Central Italy.

BACKGROUND: Despite progress in the prevention and treatment of HIV, persistent issues concerning the evaluation of continuum in care from the serological diagnosis to virologic success remains. Considering the 2020 UNAIDS target 90-90-90 for diagnosis, treatment, and viral suppression of people living with HIV (PLWH), our purpose was to verify if, starting from new diagnoses, the viral suppression rate of our cohort of new PLWH satisfied the second and the third steps. METHODS: This retrospective study regards all patients aged ≥15 undergoing HIV test at our clinic between January 2005 and December 2017. We evaluated the second and the third '90 UNAIDS targets and the unclaimed tests, linkage to care, retention in ART, and the viral suppression at 1 and 2 years. Logistic regression (odds ratio, 95% confidence interval) was performed. RESULTS: We observed 592 new diagnoses for HIV infection: 61.4% on Italians, 38.5% on foreigners. An antiretroviral treatment was started on 78.8% of the new diagnoses (467/592) (second UNAIDS target), and a viral suppression was obtained at 2 years on 82% of PLWH who had started ART (383/467) (third UNAIDS target), namely only 64.7% of the new diagnoses instead of the hoped-for 81% of the UNAIDS target. Logistic regressions demonstrated that second and third '90 UNAIDS targets were unrelated to sex, nationality, CD4 cells count, HIV-RNA and CDC stage (p>0.05). The age class 25-50 years (OR=2.24; 95% CI = 1.06-4.37; p=0.04) achieves more likely viral suppression when compared with patients <25 years. Considering the continuum of care, 88 (15%) PLWH were lost to engagement in care (55 unclaimed tests and 33 unlinked to care), 37 didn't start ART, 51 were LFTU at 2 years. CONCLUSIONS: UNAIDS goal was far to be reached. The main challenges were unreturned tests as well as the retention in ART. Rapid tests for a test-treat strategy and frequent phone communications in the first ART years could facilitate UNAIDS target achievement.

An Italian Case of Disseminated Histoplasmosis Associated with HIV.

Histoplasma capsulatum is a dimorphic fungus, endemic in the Americas, Africa (var. duboisii), India, and Southeast Asia. H. capsulatum infection is rarely diagnosed in Italy, while in Latin America, progressive disseminated histoplasmosis (PDH) is one of the most frequent AIDS-defining illnesses and causes of AIDS-related deaths. We report a case of PDH and new HIV infection diagnosis in a Cuban patient, who has been living in Italy for the past 10 years. Bone marrow aspirate and peripheral blood smear microscopy suggested H. capsulatum infection. The diagnosis was confirmed with the culture method identifying its thermal dimorphism. Liposomal amphotericin B was administered alone for 10 days and then for another 2 days, accompanied with voriconazole; the former was stopped for probable side effects (persistent fever and worsening thrombocytopenia), and voriconazole was continued to complete 4 weeks. PDH maintenance treatment consisted of itraconazole for one year. Antiretroviral therapy (ART) was started on the third week of antifungal treatment. At the 3-year follow-up, the patient is adherent on ART, the virus was suppressed, and she has an optimal immune recovery. This case highlights the need to suspect histoplasmosis in the differential diagnosis of opportunistic infections in immunocompromised persons, native to or who have traveled to endemic countries.

Two-stage revision and systemic antifungal therapy of Candida glabrata primary prosthetic hip infection successfully treated: a case report.

BACKGROUND: Overall, fungi are estimated to cause approximately 1% of prosthetic joint infections, Candida glabrata account for less than 10% of these cases. No well-defined treatment strategy is available. CASE PRESENTATION: A 71-year-old Caucasian man with non-insulin-dependent diabetes was admitted for hip prosthesis revision. For the past 17 years he suffered from recurrent infection of a perianal fistula, the last episode being 1 week before admission, and was prescribed amoxicillin/clavulanate 1 g twice a day. At surgery, the synovial fluid tested positive for infection with the Synovasure® Alpha Defensin Test, and the orthopedic surgeon reported intraoperative evidence of infection. While the synovial fluid failed to grow microorganisms, seven different samples including periprosthetic tissue and the prosthesis grew Candida glabrata. Imipenem 2 g and teicoplanin 600 mg daily were administered during surgery. Also an antibiotic loaded spacer was positioned. A week later micafungin 100 mg a day was added, and after another week imipenem was replaced with ertapenem 1 g once a day. The combination of antibiotics and antifungal was administered for a total of 7 weeks, while he also underwent treatment of the perianal fistula. The reimplantation was performed after an 8-week antibiotic-free interval. Before reimplantation, his erythrocyte sedimentation rate and C-reactive protein level were normal. At reimplant surgery, several samples were collected for microbiology, before administering ertapenem 1 g, teicoplanin 600 mg and micafungin 100 mg once a day. This antimicrobial combination was continued for 15 days until the microbiologic investigations, including culture and molecular testing after sonication technique of the spacer, were reported negative for bacteria and fungi. In this patient, systemic antifungal and extensive debridement allowed for clinical and microbiologic cure. CONCLUSIONS: Although Candida glabrata prosthetic joint infection is a rare event, the incidence could increase in the future, and there is need for more definitive treatment protocols. Diagnosis depends on culture. Fungal etiology must always be included in the differential diagnosis of prosthetic joint infection.

Treating Primary Arthroprosthesis Infection Caused by Mycobacterium abscessus subsp. abscessus.

Prosthetic joint infections (PJI) caused by nontuberculous mycobacteria are very rare, and results of treatment can be unpredictable. A 72-year-old female underwent hip replacement after an accidental fall in a local hospital in Santo Domingo. The postoperative period was uneventful except for a traumatic wound near the surgical scar. PJI caused by Mycobacterium abscessus subsp. abscessus was diagnosed 6 months later. A two-stage reimplantation was performed after a 3-month period of aetiology-directed therapy, including amikacin, imipenem, and clarithromycin. M. abscessus isolate was reported to be resistant to clarithromycin when incubation was protracted for 14 days and to harbour the gene erm(41). The patient manifested major side effects to tigecycline. At reimplant, microbiologic investigations resulted negative. Overall, medical treatment was continued for a 7-month period. When discontinued and at 6-month follow-up, the patient was clinically well, inflammatory markers were normal, and the radiography showed well-positioned prosthesis. Mycobacterium abscessus subsp. abscessus is a very rare cause of PJI, yet it must be included in the differential diagnosis, especially when routine bacteria cultures are reported being negative. Further investigations are needed to determine any correlations between clinical results and in vitro susceptibility tests, as well as the clinical implications of M. abscessus subsp. abscessus harbouring the functional gene erm(41). Moreover, investigations are needed for determine optimal timings of surgery and lengths of medical therapy to improve patient outcome.