A suppressive antiretroviral therapy (ART) is necessary to prevent mother-to-child transmission (MTCT) of HIV during pregnancy. During this period, it is recommended to continue an ongoing safe and ...suppressive regimen, but history of multiclass drug-resistance (MDR) might need tailored, uncommon approaches posing tolerability and toxicity issues. This is the case of a 33 years of age, vertically infected woman with MDR HIV infection suppressed on a darunavir/cobicistat + atazanavir regimen switched during pregnancy to lamivudine + darunavir/ritonavir + dolutegravir 50 mg bis-in-die, maintaining complete viral suppression and delivering via caesarian section and without zidovudine (AZT) intrapartum prophylaxis a healthy HIV-negative newborn who received AZT post-exposure prophylaxis and showed regular growth patterns up to 2 years. Our case shows how archived MDR might complicate the preservation of HIV RNA suppression and highlights the importance of a tailored, multidisciplinary approach for pregnant women with MDR HIV and their newborns.
To characterize the immunogenicity of mRNA-1273 (Moderna, Cambridge, MA, USA) vaccine in HIV-positive hemophilic patients during the third COVID-19 wave in Italy and to investigate biomarkers of ...coagulation and endothelial perturbation before and after complete vaccination schedule, twenty-three consecutive adult HIV-positive patients with hemophilia were included. Blood was collected before and two weeks after vaccination. We measured anti-SARS-CoV-2 spike protein antibodies to assess immunogenicity; circulating biomarkers of coagulation (protein C and D-dimer), endothelial perturbation (von Willebrand factor (VWF)) and anti-Platelet Factor 4 (PF4) antibodies were analyzed. Flow-based analysis of thrombus formation was performed in nine patients using a flow-chamber device. Two weeks after completing the vaccination schedule, all patients had anti-spike antibodies values consistent with an effective immunization. Mean (±standard deviation) basal values of protein C and VWF (106 ± 21% and 171 ± 45%, respectively) were not significantly different from data obtained two weeks after the second dose (103 ± 20%, 162 ± 43%, respectively). D-dimer median values (interquartile range) were not significantly different at baseline (442 (603–142) ng/mL) and after the second dose (477 (654–262) ng/mL). Anti-PF4 antibodies were detected in three patients with no associated clinical manifestations. No significant differences were found in flow-based analysis of thrombus formation. Our data demonstrate that in HIV-positive patients with hemophilia, SARS-CoV-2 vaccination is effective and safe, with no effects on coagulation and endothelial perturbation.
Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high ...multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role. Keywords: COVID-19, SARS-CoV-2, Antimicrobial stewardship, Multidrug resistant organisms, Antimicrobials use
Background: Early treatment with remdesivir (RMD) or monoclonal antibodies (mAbs) could be a valuable tool in patients at risk of severe COVID-19 with unsatisfactory responses to vaccination. We aim ...to assess the safety and clinical outcomes of these treatments among immunocompromised subjects. Methods: We retrospectively reviewed all nonhospitalized patients who received an early treatment with RMD or mAbs for COVID-19, from 25 November 2021 to 25 January 2022, in a large tertiary hospital. Outcomes included frequency of adverse drug reaction (ADR), duration of symptoms and molecular swab positivity, emergency department access, hospital or intensive care unit admission, and mortality in the 14 days following treatment administration. Results: Early treatments were administered to 143 patients, 106/143 (74.1%) immunocompromised, including 41 solid organ and 6 hematopoietic stem cell transplant recipients. Overall, 23/143 (16.1%) subjects reported ADRs. Median time from treatment start to SARS-CoV-2 nasopharyngeal swab negativity and symptom resolution was 10 (IQR 6–16) and 2.5 days (IQR 1.0–6.0), respectively, without differences between immunocompromised and nonimmunocompromised patients. In the 14 days after treatment administration, 5/143 patients (3.5%) were hospitalized and one died as a result of causes related to COVID-19, all of them were immunocompromised. Conclusions: RMD and mAbs have minimal ADRs and favourable outcomes in immunocompromised patients.
Background
The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of ...data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients.
Methods
Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time).
Results
Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively,
p
-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (
Prevotella
7,
Fusobacterium
,
Neisseria
,
Escherichia–Shigella
and
Haemophilus
) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP.
Conclusions
In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP.
Multidrug resistance has become a serious threat for health, particularly in hospital-acquired infections. To improve patients’ safety and outcomes while maintaining the efficacy of antimicrobials, ...complex interventions are needed involving infection control and appropriate pharmacological treatments in antibiotic stewardship programs. We conducted a multicenter pre-post study to assess the impact of a stewardship program in seven Italian intensive care units (ICUs). Each ICU was visited by a multidisciplinary team involving clinicians, microbiologists, pharmacologists, infectious disease specialists, and data scientists. Interventions were targeted according to the characteristics of each unit. The effect of the program was measured with a panel of indicators computed with data from the MargheritaTre electronic health record. The median duration of empirical therapy decreased from 5.6 to 4.6 days and the use of quinolones dropped from 15.3% to 6%, both p < 0.001. The proportion of multi-drug-resistant bacteria (MDR) in ICU-acquired infections fell from 57.7% to 48.8%. ICU mortality and length of stay remained unchanged, indicating that reducing antibiotic administration did not harm patients’ safety. This study shows that our stewardship program successfully improved the management of infections. This suggests that policy makers should tackle multidrug resistance with a multidisciplinary approach based on continuous monitoring and personalised interventions.
The occurrence of pulmonary fungal superinfection due to Aspergillus spp. in patients with COVID-19 is a well-described complication associated with significant morbidity and mortality. This can be ...related to a directed effect of the virus and to the immunosuppressive role of the therapies administered for the disease. Here, we describe the first case of pulmonary infection due to Mucorales occurring in a patient with a concomitant diagnosis of COVID-19-associated pulmonary aspergillosis.
Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a ...combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment.
Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab) were compared in terms of clinical outcomes (hospitalisation and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson's chi-square or Fisher's exact test for categorical variables, whereas the Wilcoxon rank-sum test was employed for continuous ones. Kaplan-Meier curves were produced to compare the time to nasopharyngeal swab negativity.
Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups regarding clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (
= 0.088) emerged.
Early treatment of SARS-CoV-2 infection with TIX/CIL showed favourable outcomes in a small group of immunocompromised patients, reporting no significant difference compared to similar patients treated with other mAbs.
Since the start of the COVID-19 outbreak, more than four million people have died of this disease. Given its ability to provide a precise response, mass spectrometry-based proteomics could represent ...a useful tool to study this pathology. To this end, an untargeted nLC-ESI-MS/MS-based method to characterise SARS-CoV-2 proteins, including possible variants, and investigate human saliva and plasma proteome in a single analysis was developed for further application in patients. Four SARS-CoV-2 recombinant proteins, three (S1–S2–RBD) belonging to the spike glycoprotein (S) and one corresponding to the nucleoprotein (N), were prepared and analysed with nLC-UHRTOF by injecting decreasing amounts to establish the limit of detection (LOD) of the method. This was determined as 10 pg for all the components of the S protein and for N (71 amol and 213 amol, respectively). Various viral inactivation strategies plus deglycosylation and digestion approaches were then tested in saliva and plasma spiked with different quantities of SARS-CoV-2 recombinant proteins. The limit of characterisation (LOC) in saliva for the N and S proteins was observed at 100 pg (coverage of 20% and 3%, respectively); instead, in plasma, it was 33 pg for N and 330 pg for the S protein, with a coverage of 4% for both. About 300 and 800 human proteins were identified in plasma and saliva, respectively, including several key effectors and pathways that are known to be altered in COVID-19 patients. In conclusion, this approach allows SARS-CoV-2 proteins and the human proteome to be simultaneously explored, both for plasma and saliva, showing a high relevant potential for retrospective studies aimed at investigating possible virus variants and for patient stratification.
Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during ...AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.
Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.
This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥500/µL, CD4 ≥30%, and CD4/CD8 ≥1), and first-line ART regimen discontinuation by Cox regression analysis.
There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log
copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs.
In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.
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