Trends of Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates Between 2012 and 2023: Results From an Open Italian Cohort.

BACKGROUND: Neisseria gonorrhoeae (Ng) is a public health priority because of the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance, and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), and ciprofloxacin (CIP) during a 10-year period. METHODS: We conducted a retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral, and pharyngeal samples at San Raffaele Scientific Institute, between September 2012 and February 2023. Minimum inhibitory concentrations of antibiotics were determined by gradient-test strips. Bivariate linear regression models were applied on logarithmic minimum inhibitory concentrations values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains. RESULTS: A total of 436 Ng isolates from 352 individuals were analyzed. Minimum inhibitory concentrations of CRO and PenG reduced over time ( P < 0.001, P = 0.030), AZM increased ( P = 0.001), and CIP and TET did not change ( P = 0.473, P = 0.272). The percentages of resistant strains were as follows: PenG, 89.9%; TET, 90.8%; CIP, 48.2%; AZM, and 4.4%. CRO-DS strains were 8.7%, and only 1 case of CRO-R was identified. The proportion of resistant strains increased over time for AZM ( P = 0.007), TET ( P = 0.001), and CIP ( P < 0.001), whereas it decreased for PenG ( P < 0.001) and CRO-DS/R strains ( P < 0.001). CONCLUSIONS: Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment was confirmed to be effective.

Real-life experience with remdesivir for treatment of COVID-19 among older adults: a multicentre retrospective study.

INTRODUCTION: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. METHODS: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. RESULTS: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities. CONCLUSIONS: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.

High-dose anakinra in addition to standard of care including corticosteroids in patients with severe COVID-19 treated with non-invasive ventilation.

Management of COVID-19 patients experiencing persisting respiratory failure despite corticosteroids remains challenging. Data on high-dose intravenous anakinra (HD-ANK) in this context are lacking. We aimed to investigate the impact of HD-ANK on mortality in COVID-19 patients progressing to non-invasive ventilation (NIV) while receiving corticosteroids. We retrospectively analyzed the impact of HD-ANK on 28-day mortality in individuals hospitalized with COVID-19 necessitating NIV after corticosteroid initiation. A total of 256 patients were identified: 146 received standard-of-care only (SOC), and 110 received HD-ANK+SOC. The groups were well-balanced at baseline. In-hospital mortality at 28 days did not differ between the two groups. HD-ANK is not beneficial in patients with severe COVID-19 deteriorating despite corticosteroids.

Post-neurosurgical Nocardia meningoventriculitis: a case report and review of the literature.

The genus Nocardia consists of a group of gram-positive environmental bacteria. They typically cause lung and brain infections in immunocompromised patients, even though one out of three infected patients have a normally functioning immune system. Being a ubiquitous microorganism, in some cases Nocardia has been associated with nosocomial acquired infections and surgical procedures. A review of the literature in this field follows the case report. A 47-year-old woman underwent an endoscopic third ventriculostomy and a left retro-sigmoid craniotomy for a schwannoma removal. Meningeal symptoms began a week later, in association with C reactive protein rise and leukocytosis. Cerebrospinal fluid (CSF) examination was clear with hypoglycorrhachia, hyperprotidorrachia and polymorphonuclear cells. Cultural exam was negative. At the brain magnetic resonance imaging (MRI) purulent material was described in the occipital ventricular horns. Empirical broad spectrum antibiotic therapy was given for 31 days until the brain MRI showed a resolution of the infection. Ten days later, the patient was admitted to the hospital because of new meningeal symptoms. Cerebrospinal fluid culture and Polymerase-chain reaction (PCR) Multiplex for the most important meningitis viruses and bacteria tested negative. A broad-spectrum antibiotic therapy was started with no benefit; thus, a broad-spectrum antifungal therapy was added with little success on clinical status. Meanwhile, a 16s and 18s rRNA PCR was executed on a previous Cerebrospinal fluid with negative results, excluding bacterial and fungal infections. For this reason, all the therapies were stopped. After a few days, high fever and meningeal signs reappeared. The brain MRI showed a meningoventriculitis. An Ommaya catheter with reservoir was inserted and the drawn CSF resulted in the growth of Nocardia farcinica. Antibiogram-based antibiotic therapy was started with intravenous imipenem and trimethoprim-sulfamethoxazole, showing clinical benefit. The patient was sent home with oral linezolid and amoxicillin/clavulanate for a total of 12 months of therapy. Nocardia rarely causes post-neurosurgical complication in a nosocomial setting. This case shows the difficulty in detecting Nocardia and the importance of the correct microbiological sample and antibiogram-based antibiotic therapy to achieve successful treatment.

Myocardial injury in patients with SARS-CoV-2 pneumonia: Pivotal role of inflammation in COVID-19.

AIMS: Infection by SARS-CoV-2 may result in a systemic disease and a proportion of patients ranging 15%-44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID-19 in order to identify predisposing and/or protective factors of CI and the outcome. METHODS AND RESULTS: This is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID-19 and at least one high-sensitivity cardiac troponin (hs-cTnt) measurement during hospitalization. CI was defined if at least one hs-cTnt value was above the 99th percentile. The primary end-point was the occurrence of CI during hospitalization. We included 750 patients (median age 67, IQR 56-77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34-147 ng/l) were detected in 390 patients (52%) during the hospitalization. At multivariable analysis age, CKD, cancer, C-reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all-cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI. CONCLUSION: This large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID-19, highlighting the leading role of systemic inflammation for the occurrence of CI.

Disseminated Mycobacterium chimaera infection favoring the development of Kaposi's sarcoma: a case report.

BACKGROUND: Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations. CASE PRESENTATION: We report the case of a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi's sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks. CONCLUSIONS: M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi's sarcoma) cannot be excluded.

One-Year Multidisciplinary Follow-Up of Patients With COVID-19 Requiring Invasive Mechanical Ventilation.

OBJECTIVES: Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. The authors investigated 1-year survival, quality of life, and functional recovery of patients with COVID-19 ARDS requiring invasive mechanical ventilation. DESIGN: Prospective observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: All patients with COVID-19 ARDS receiving invasive mechanical ventilation and discharged alive from hospital. INTERVENTIONS: Patients were contacted by phone after 1 year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS: The study included all adult (age ≥18 years) patients with COVID-19-related ARDS admitted to an ICU of the authors' institution between February 25, 2020, and April 27, 2020, who received at least 1 day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed 1 year after discharge and 56 completed a battery of tests of cognition, activities of daily living, and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by 5 (8.9%) patients. Comparing 2-month and 1-year data, the authors observed the most significant improvements in the areas of working status and exertional dyspnea. One-year chest CT scans were available for 36 patients; fibrotic-like changes were present in 4 patients. CONCLUSIONS: All patients who survived the acute phase of COVID-19 and were discharged from the hospital were alive at the 1-year follow up, and the vast majority of them had good overall recovery and quality of life.

Frailty as a predictor of mortality in COVID-19 patients receiving CPAP for respiratory insufficiency.

OBJECTIVE: Exploring the association between frailty and mortality in a cohort of patients with COVID-19 respiratory insufficiency treated with continuous positive airway pressure. METHODS: Frailty was measured using a Frailty Index (FI) created by using the baseline assessment data on comorbidities and body mass index and baseline blood test results (including pH, lactate dehydrogenase, renal and liver function, inflammatory indexes and anemia). FI > 0.25 identified frail individuals. RESULTS: Among the 159 included individuals (81% men, median age of 68) frailty was detected in 69% of the patients (median FI score 0.3 ± 0.08). Frailty was associated to an increased mortality (adjusted HR 1.99, 95% CI 1.02-3.88, p = 0.04). CONCLUSIONS: Frailty is highly prevalent among patients with COVID-19, predicts poorer outcomes independently of age. A personalization of care balancing the risk and benefit of treatments (especially the invasive ones) in such complex patients is pivotal.

Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement.

OBJECTIVE: Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. METHODS: We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. RESULTS: We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P < .016), sludge flow (P = .001), and pericapillary edema (P < .001), while recovered patients showed a higher prevalence of enlarged capillaries (P < .001), loss of capillaries (P = .002), meandering capillaries (P < .001), and empty dermal papillae (P = .006). CONCLUSION: COVID-19 patients present microvascular abnormalities at NVC. Currently ill and recovered subjects are characterized by a different distribution of elementary capillaroscopic alterations, resembling acute and post-acute microvascular damage. Further studies are needed to assess the clinical relevance of NVC in COVID-19.

Impact of surgical timing on survival in patients with infective endocarditis: a time-dependent analysis.

The purpose of this study was to evaluate the impact of surgical timing on survival in patients with left-sided infective endocarditis (IE). This was a retrospective study including 313 patients with left-sided IE between 2009 and 2017. Surgery was defined as urgent (US) or early (ES) if performed within 7 or 28 days, respectively. A multivariable Cox regression analysis including US and ES as time-dependent variables was performed to assess the impact on 1-year mortality. ES was associated with a better survival (aHR 0.349, 95% CI 0.135-0.902), as US (aHR 0.262, 95% CI 0.075-0.915). ES and US were associated with a better prognosis in patients with left-sided IE.

Subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.

Pulmonary Vascular Thrombosis in COVID-19 Pneumonia.

OBJECTIVES: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. DESIGN: Observational study. SETTING: Medical and intensive care unit wards of a teaching hospital. PARTICIPANTS: The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. INTERVENTIONS: Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. CONCLUSIONS: The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia.

Invasive fungal infections in patients with COVID-19: a review on pathogenesis, epidemiology, clinical features, treatment, and outcomes.

COVID-19 is frequently associated with the onset of secondary infections, especially in severe cases treated in the intensive care unit. While bacterial pathogens are the most frequently encountered causative agents, several factors put SARS-CoV-2 infected patients at a heightened risk of invasive fungal infections, which have been recognized as a substantial cause of morbidity and mortality in this population. Moreover, the frequent occurrence of these complications in severely ill subjects and the absence of pathognomonic features, together with the emergence of fungal species with reduced susceptibility to first-line treatments and the difficult to manage safety profile of several antifungal drugs, demand an additional focus on these rare but challenging complications. In this review, we will summarize the currently available literature on fungal superinfections in COVID-19 patients, exploring the pathogenesis, epidemiology, clinical features, treatment, and outcomes.

Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching.

Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis are largely unknown. Study aims were to estimate the incidence of pre-engraftment bloodstream infections (PE-BSIs) and viral infections (VIs; cytomegalovirus [CMV], adenovirus [ADV], human herpes virus 6 [HHV6], and BK-polyomavirus hemorrhagic-cystitis [BKPyV-HC]), their predictive factors, and infection-related mortality (IRM) after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21%, and 17% received haploidentical (haplo), matched-unrelated donor (MUD), and matched-related donor, respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13 days after HSCT: cumulative incidence function (CIF) at 28 days was 32%, without differences among donor types (P = .988). By multivariate analysis, CIF of PE-BSI was higher in patients with severe neutropenia before HSCT (adjusted hazard ratio [AHR] = 2.90) and in multidrug-resistant Gram-negative bacteria rectal carriers (AHR = 2.68). IRM at 30 days was 5%, without differences by donor type (P = .106). Overall, 208 patients experienced ≥1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at a median time of 20 days after HSCT: CIF at 90 days was 91%, significantly higher in MUD and haplo (P = .0089). By multivariate analysis, also acute GVHD grade ≥2 (AHR = 1.32) and host/donor CMV-serology mismatch (positive/positive versus negative/negative: AHR = 2.95, positive/negative versus negative/negative: AHR = 2.41, negative/positive versus negative/negative: AHR = 2.35) affected VIs occurrence. IRM at 180 days was 8%, without differences among donor types (P = .106). In conclusion, study results did not show a significant impact of donor type on PE-BSI incidence; conversely, MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT.

Bowel perforation in a Covid-19 patient: case report.

INTRODUCTION: Since the outbreak of novel coronavirus (2019-nCoV), it became evident that a proportion of patients may present with gastrointestinal symptoms. CASE: We report the case of a Covid-19-infected patient who, during recovery from the pulmonary pneumonia, had gastrointestinal symptoms followed by a diastasic right colon perforation due to acute over distension of the bowel. CONCLUSION: This case highlights the importance of paying attention to initial gastrointestinal symptoms in order to prevent possible complications.

Role of Rehabilitation Department for Adult Individuals With COVID-19: The Experience of the San Raffaele Hospital of Milan.

The rapid evolution of the health emergency linked to the spread of severe acute respiratory syndrome coronavirus 2 requires specifications for the rehabilitative management of patients with coronavirus disease 2019 (COVID-19). The symptomatic evolution of patients with COVID-19 is characterized by 2 phases: an acute phase in which respiratory symptoms prevail and a postacute phase in which patients can show symptoms related to prolonged immobilization, to previous and current respiratory dysfunctions, and to cognitive and emotional disorders. Thus, there is the need for specialized rehabilitative care for these patients. This communication reports the experience of the San Raffaele Hospital of Milan and recommends the setup of specialized clinical pathways for the rehabilitation of patients with COVID-19. In this hospital, between February 1 and March 2, 2020, about 50 patients were admitted every day with COVID-19 symptoms. In those days, about 400 acute care beds were created (intensive care/infectious diseases). In the following 30 days, from March 2 to mid-April, despite the presence of 60 daily arrivals to the emergency department, the organization of patient flow between different wards was modified, and several different units were created based on a more accurate integration of patients' needs. According to this new organization, patients were admitted first to acute care COVID-19 units and then to COVID-19 rehabilitation units, post-COVID-19 rehabilitation units, and/or quarantine/observation units. After hospital discharge, telemedicine was used to follow-up with patients at home. Such clinical pathways should each involve dedicated multidisciplinary teams composed of pulmonologists, physiatrists, neurologists, cardiologists, physiotherapists, neuropsychologists, occupational therapists, speech therapists, and nutritionists.

Homeostatic model assessment for insulin resistance index trajectories in HIV-infected patients treated with different first-line antiretroviral regimens.

OBJECTIVE: To describe the trajectories of the homeostatic model assessment for insulin resistance (HOMA-IR) index in a cohort of HIV-1 infected patients during their first-line antiretroviral (ART) regimen. METHODS: Retrospective analysis of naïve patients who started ART from 2007 at the Infectious Diseases Unit of the San Raffaele Hospital, Milan. We included patients treated with two nucleoside reverse transcriptase inhibitors (NRTIs, tenofovir, abacavir, lamivudine or emtricitabine), and one anchor drug (ritonavir-boosted protease inhibitor [PI/r], non-NRTI [NNRTI], or integrase strand transfer inhibitor [InSTI]), and with HOMA-IR assessed both before and after the start of ART. Univariate and multivariate mixed linear models estimated HOMA-IR changes during ART. RESULTS: Among 618 patients included in the study, 218 received InSTI-, 210 PI/r-, and 190 NNRTI-based regimens. Median follow-up was 27.4 (16.3-41.2) months. Adjusted mean change in HOMA-IR index was significantly higher (P = .041) in patients treated with InSTI-based regimens [0.160 (95% CI: 0.003-0.321) units per year] compared with NNRTI-based regimens [-0.005 (95% CI: -0.184-0.074) units per year]; no difference was observed between patients treated with NNRTI- and PI/r-based regimens or between INSTI-based and PI/r-based regimens. CONCLUSION: InSTI-based first-line ARTs were independently associated with greater increases in HOMA-IR index.

Invasive Pulmonary Aspergillosis Complicated by Carbapenem-Resistant Pseudomonas aeruginosa Infection During Pembrolizumab Immunotherapy for Metastatic Lung Adenocarcinoma: Case Report and Review of the Literature.

The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs. These observations lead experts' opinion to suggest primary anti-Pneumocystis prophylaxis in patients undergoing CTLA-4 and PD-1/PDL1 agents who will receive prednisone 20 mg daily for ≥ 4 weeks. Few data on invasive fungal infections in this context are available. We report here a case of probable invasive pulmonary aspergillosis (p-IPA) complicating first-line immunotherapy with pembrolizumab for metastatic lung cancer that was further aggravated by multidrug-resistant Pseudomonas aeruginosa superinfection of fungal cavities; the patient received concurrent systemic corticosteroid therapy as anti-edema treatment for cerebral metastases. Reviewing literature about Aspergillus diseases in subjects receiving CTLA-4 and PD-1 and PDL1-targeted agents, we found three cases of invasive aspergillosis and one case of exacerbation of chronic progressive pulmonary aspergillosis after nivolumab treatment; to the best of our knowledge, this is the first report of p-IPA complicating pembrolizumab immunotherapy. Briefly, in this new setting of biological/targeted drugs, waiting for growing clinical experience, we recommend a high level of alertness in diagnosing any infectious complications.

Short-Term Peripheral Venous Catheter-Related Bloodstream Infections: Evidence for Increasing Prevalence of Gram-Negative Microorganisms from a 25-Year Prospective Observational Study.

The aim of this study was to describe the etiology and outcome of short-term peripheral venous catheter (PVC)-related bloodstream infections (PVCRBSI) in a 25-year period (1992 to 2016) and to identify predictive factors of Gram-negative PVCRBSI. This was a prospective observational study including all episodes of PVCRBSI. A multivariate logistic regression model adjusted for calendar year was built to explore factors associated with a Gram-negative bacterial etiology. Over the study period, 711 episodes of PVCRBSI were identified. Incidence rate of PVCRBSI increased from 0.06 to 0.13 episodes/1,000 patient-days. A Gram-negative bacterial etiology was demonstrated in 162 (22.8%) episodes. There was a significant increase in the proportion of Gram-negative infections (22.6% in 1992 to 1996 versus 33.2% in 2012 to 2016). Independent predictive factors of Gram-negative PVCRBSI were the following: being in the hospital for more than 7 days with a catheter in situ for more than 3 days (adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI], 1.20 to 2.69), surgery in the previous month (aOR, 2.39; 95% CI, 1.40 to 4.09), and antimicrobial treatment with beta-lactams (aOR, 1.80; 95% CI, 1.16 to 2.78). In conclusion, we reported an increase in the prevalence of Gram-negative PVCRBSI over the last 25 years. Factors associated with a Gram-negative bacterial etiology were being in the hospital for more than 7 days with a catheter in situ for more than 3 days, having undergone surgery, and having received antimicrobial treatment with beta-lactams.

Influence of empirical double-active combination antimicrobial therapy compared with active monotherapy on mortality in patients with septic shock: a propensity score-adjusted and matched analysis.

OBJECTIVES: To evaluate the influence on mortality of empirical double-active combination antimicrobial therapy (DACT) compared with active monotherapy (AM) in septic shock patients. METHODS: A retrospective study was performed of monomicrobial septic shock patients admitted to a university centre during 2010-15. A propensity score (PS) was calculated using a logistic regression model taking the assigned therapy as the dependent variable, and used as a covariate in multivariate analysis predicting 7, 15 and 30 day mortality and for matching patients who received DACT or AM. Multivariate models comprising the assigned therapy group and the PS were built for specific patient subgroups. RESULTS: Five-hundred and seventy-six patients with monomicrobial septic shock who received active empirical antimicrobial therapy were included. Of these, 340 received AM and 236 DACT. No difference in 7, 15 and 30 day all-cause mortality was found between groups either in the PS-adjusted multivariate logistic regression analysis or in the PS-matched cohorts. However, in patients with neutropenia, DACT was independently associated with a better outcome at 15 (OR 0.29, 95% CI 0.09-0.92) and 30 (OR 0.25, 95% CI 0.08-0.79) days, while in patients with Pseudomonas aeruginosa infection DACT was associated with lower 7 (OR 0.12, 95% CI 0.02-0.7) and 30 day (OR 0.26, 95% CI 0.08-0.92) mortality. CONCLUSIONS: All-cause mortality at 7, 15 and 30 days was similar in patients with monomicrobial septic shock receiving empirical double-active combination therapy and active monotherapy. However, a beneficial influence of empirical double-active combination on mortality in patients with neutropenia and those with P. aeruginosa infection is worthy of further study.