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(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate–severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate–severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate–severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate–severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate–severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p 1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p

Objectives: No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC).Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included.Primary endpoint: time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used.Results: A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51–76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups.Conclusion: In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.

Salmonella enterica subspecies enterica serotype Hessarek (Salmonella Hessarek) is considered a serovar with high host specificity and is an uncommon cause of disease in humans; no cases of S. Hessarek bacteremia have been reported in humans to date. On 16 July 2019, a young male presented abdominal pain, vomit, diarrhea, and fever up to 41 °C, a few hours after a kebab meal containing goat meat; he went to the Emergency Room, where a Film Array® GI Panel (BioFire, Biomerieux Company, Marcy-L´Étoile, France) was performed on his feces and results were positive for Salmonella. The culture of the feces was negative, but the blood culture was positive for Salmonella spp., which was identified as Salmonella Hessarek by seroagglutination assays. The patient was treated with ceftriaxone 2 g intravenously qd for 8 days; he was discharged in good general conditions, and ciprofloxacin 500 mg per os bid for 7 more days was prescribed, after exclusion of endocarditis and of clinical signs of complicated bacteremia. This case of Salmonella Hessarek gastroenteritis with bacteremia is probably the first case of bloodstream human infection due to this agent ever described. Further studies are needed to ascertain the global burden of S. Hessarek disease in humans.

We think that thalassemia is not necessarily a cause of aggravation of the clinical course in COVID‐19; however, certain key factors must be considered, such as the anemic condition, the likely pathogenic role of the virus on hemoglobin, and the hypercoagulable state to prevent any complications.

In an era of increasing drug resistance and limited numbers of antimicrobials in the drug production pipeline, healthcare-associated infections represent a growing public health threat. When therapeutic options are limited, clinicians often resort to using antimicrobial combinations that produce a synergistic effect on the target pathogen. Novel antibiotics are therefore welcome in the daily practice of medicine. For example, ceftaroline is a broad-spectrum cephalosporin active against a variety of bacteria, including methicillin-resistant Staphylococcus aureus, but with limited activity against enterococci, particularly Enterococcus faecium. In this study, we tested the efficacy of ceftaroline against clinical isolates of gram-positive bacteria (S. aureus, Enterococcus faecalis, and E. faecium) by the broth microdilution and E-test assays, and then evaluated the synergistic effect of ceftaroline and ampicillin using the E-test method. The time-kill assay was used to confirm the data on selected strains. This drug combination has been recently shown to be effective against E. faecalis and could offer the advantage of cost-effectiveness (compared to other synergistic associations) as well as good tolerability. The E-test was chosen because of its relative simplicity of use that makes it suitable for routine clinical laboratories as a quick tool to guide clinicians when confronted with difficult-to-treat infections that may require an empirical approach. Our results indicate the presence of a synergistic effect of ceftaroline and ampicillin on most of the strains used, especially E. faecium and E. faecalis. The fact that two of those Enterococcus strains were vancomycin resistant suggests that the possible use of this combination for combating the spread of vancomycin-resistant enterococci should be explored.

Background During the 2013–2016 West Africa Ebola virus disease (EVD) epidemic, some EVD patients, mostly health care workers, were evacuated to Europe and the USA. Case presentation In May 2015, a 37-year old male nurse contracted Ebola virus disease in Sierra Leone. After Ebola virus detection in plasma, he was medically-evacuated to Italy. At admission, rhabdomyolysis was clinically and laboratory-diagnosed and was treated with aggressive hydration, oral favipiravir and intravenous investigational monoclonal antibodies against Ebola virus. The recovery clinical phase was complicated by a febrile thrombocytopenic syndrome with pericardial effusion treated with corticosteroids for 10 days and indomethacin for 2 months. No evidence of recurrence is reported. Conclusions A febrile thrombocytopenic syndrome with pericardial effusion during the recovery phase of EVD appears to be uncommon. Clinical improvement with corticosteroid treatment suggests that an immune-mediated mechanism contributed to the pericardial effusion.

Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.

We report the case of a kidney-transplant patient, suffering an intra-abdominal abscess at the surgical site caused by a carbapenem-resistant ST258 Klebsiella pneumoniae clone, producing the KPC-3 carbapenemase. Under tigecycline treatment, the patient developed a sepsis caused by a carbapenem-susceptible ST258 K. pneumoniae strain. Complete DNA sequences of the plasmids carried by the resistant and susceptible strains from this patient were determined.The complete DNA sequences of plasmids were obtained by applying the 454 Genome Sequencer FLX-PLUS procedure on a library constructed of total plasmid DNA purified from the carbapenem-resistant and -susceptible strains.In the carbapenem-resistant strain, four plasmids encoding 24 resistance genes, including blaKPC-3, and two putative virulence clusters were detected. In the susceptible strain, large rearrangements occurred in the KPC-carrying plasmid, causing the deletion of the entire Tn4401::blaKPC-3 transposon, with the consequent reversion of the strain to carbapenem susceptibility. The patient was successfully treated with carbapenems and fully recovered.The description of the plasmid content in these two strains gives interesting insights into the plasticity of KPC-carrying plasmids in K. pneumoniae.

CMV infection is highly prevalent in general population and its clinical picture generally ranges from asymptomatic disease to mononucleosis-like syndrome. While severe life-threatening CMV disease is well documented in certain immunocompromised risk groups, severe infection with symptomatic pneumonia in immunocompetent hosts has been rarely documented. In this paper we describe a case of primary CMV infection, complicated by severe CMV pneumonia in an immunocompetent host, successfully treated with oral valganciclovir. Moreover, we reviewed CMV pneumonia cases in immunocompetent adults reported in the literature.

Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common causes of infections, has been traditionally recognized as a nosocomial pathogen. However, in recent years, its epidemiology has radically changed, being now observed even more frequently in the community, and accounting for50% of staphylococcal infections in the US outpatient setting. Community-acquired (CA)-MRSA strains typically cause infections among otherwise healthy individuals, with risk factors differing from those of nosocomial MRSA. The clinical manifestations may range from a furuncle to life-threatening infections, such as necrotizing fasciitis and pneumonia. The antibiotic treatment of these infections may also differ because CA-MRSA strains often retain susceptibility to antimicrobials other than glycopeptides and newer agents. Moreover, the production of toxins, such as the Panton-Valentine leukocidin (PVL), should influence the antibiotic choice because in these cases the use of a combination therapy with antimicrobial agents able to decrease toxin production is suggested. There are still many unanswered key questions regarding the epidemiology, prevention, and treatment of CA-MRSA infections. This article reviews current knowledge of CA-MRSA.

During the recent epidemic of Ebola virus disease (EVD) in west Africa,1 several health-care and aid workers infected with EVD were evacuated to Europe and the USA, where local transmission occurred in occupationally exposed health-care workers. Preparation for discharge requires an organised and evidence-based approach to ensure that the patient, health-care workers, family, and community are protected at all times. The risk of infection to others after discharge in the community and of unexpected late clinical events for the patient make discharge policies difficult to formulate.

Background In the current Ebola epidemic in Western Africa, many healthcare workers have become infected. Some of these have been medically evacuated to hospitals in Europe and the USA. These clinical experiences provide unique insights into the course of Ebola virus disease under optimized condition within high level isolation units. Case presentation A 50-year-old Caucasian male physician contracted Ebola virus diseases in Sierra Leone and was medically evacuated to Italy. Few days after the admission the course of the illness was characterized by severe gastro-intestinal symptoms followed by respiratory failure, accompanied by pulmonary infiltration and high Ebola viral load in the bronchial aspirate and Plasmodium vivax co-infection. The patient received experimental antiviral therapy with favipiravir, convalescent plasma and ZMAb. Ebola viral load started to steadily decrease in the blood after ZMAb administration and became undetectable by day 19 after admission, while it persisted longer in urine samples. No temporal association was observed between viral load decay in plasma and administration of favipiravir. The patient completely recovered and was discharged 39 days after admission. Conclusions This is the first case of Ebola-related interstitial pneumonia documented by molecular testing of lung fluid specimens. This reports underlines the pivotal role of fluid replacement and advanced life support with mechanical ventilation in the management of patients with Ebola virus diseases respiratory failure. Beside our finding indicates a close temporal association between administration of cZMAb and Ebola virus clearance from blood. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1169-4) contains supplementary material, which is available to authorized users.

Background: HIV infection is a risk factor for Clostridium difficile infection (CDI) yet the immune deficiency predisposing to CDI is not well understood, despite an increasing incidence of CDI among such individuals. We aimed to estimate the incidence and to evaluate the risk factors of CDI among an HIV cohort in Italy. Methods: We conducted a retrospective case-control (1:2) study. Clinical records of HIV inpatients admitted to the National Institute for Infectious Disease L. Spallanzani, Rome, were reviewed (2002-2013). Cases: HIV inpatients with HO-HCFA CDI, and controls: HIV inpatients without CDI, were matched by gender and age. Logistic regression was used to identify risk factors associated with CDI. Results: We found 79 CDI episodes (5.1 per 1000 HIV hospital admissions, 3.4 per 10000 HIV patient-days). The mean age of cases was 46 years. At univariate analysis factors associated with CDI included: antimycobacterial drug exposure, treatment for Pneumocystis pneumonia, acid suppressant exposure, previous hospitalization, antibiotic exposure, low CD4 cell count, high Charlson score, low creatinine, low albumin and low gammaglobulin level. Using multivariate analysis, lower gammaglobulin level and low serum albumin at admission were independently associated with CDI among HIV-infected patients. Conclusions: Low gammaglobulin and low albumin levels at admission are associated with an increased risk of developing CDI. A deficiency in humoral immunity appears to play a major role in the development of CDI. The potential protective role of albumin warrants further investigation., Funded by Grant RF 2011-02347608, Ministry of Health.

As of April 2016, the WHO reported a total of 28 616 Ebola virus disease (EVD) cases worldwide.1 This epidemic has the highest record of survivors who are now facing their challenges, including long-term sequelae. We present two patients with EVD2 with a complete neurocognitive recovery after impairment. Two EVD cases were admitted to the National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ in Rome. The first patient, a 50-year-old male physician, experienced EVD symptoms on 20 November 2014 and was medically evacuated from Sierra Leone, where he contracted the infection. At diagnosis, Ebola virus (EBOV) load was 6.8 log10 copies/mL. He had severe gastrointestinal symptoms, followed by an altered level of consciousness since day 10 of EVD for 5 days. An adult respiratory distress syndrome, which required mechanical ventilation, and a Plasmodium vivax coinfection were also diagnosed a few days later. At intensive care unit discharge, a clinically evident mild neurocognitive impairment, also reported by the patient, was observed for a further 5 days. He was discharged from the hospital on day 38.2 The second case, a 36-year-old male nurse, was admitted to the hospital on day 2 of EVD symptoms onset. EBOV load was 7.70 log10 copies/mL. His clinical history was complicated by an acute pericarditis and mild cognitive deficits were reported by physicians on day 3 for the next 48 hours. He was discharged on day 28. No bacterial infections or bleeding disorders were observed. Both patients were treated with fluids, empiric antibiotic therapy and antivirals (favipiravir and a mixture of EBOV monoclonal antibodies). A neuropsychological examination was performed to deeply investigate the clinical suspicion of neurocognitive impairment. The evaluation was repeated at follow-up. Neurological examination of both patients was normal at baseline and follow-up neurocognitive assessment. Tests …

When an Infection Prompts Removal of an Unnecessary DeviceAuthor(s): Nicola Petrosillo, MD; Stefano Di Bella, MD; Fabrizio Taglietti, MDReviewed work(s):Source: Infection Control and Hospital Epidemiology, Vol. 33, No. 8 (August 2012), pp. 858-859Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology ofAmericaStable URL: http://www.jstor.org/stable/10.1086/666636 .Accessed: 07/07/2012 02:48

Predisposing factors, clinical characteristics, and antimicrobial treatment of 37 hematology patients with Stenotrophomonas maltophilia bacteremia who were seen at the department of hematology of the University La Sapienza (Rome) from 1987 to 1996 were evaluated. The results were compared with a control group of patients with Pseudomonas aeruginosa bacteremia. Profound neutropenia was more prolonged in the S. maltophilia group (P=.025), severe cellulitis occurred only in S. maltophilia-infected patients (11 [30%]; P=.0002), and the bacteremia presented as breakthrough infection in 56% of the cases due to S. maltophilia (vs. only 24% of those due to P. aeruginosa; P=.002). Acute mortality rates associated with S. maltophilia and P. aeruginosa bacteremia were 24% and 21%, respectively. In both groups, profound neutropenia and hypotension at the onset of bacteremia, duration of profound neutropenia during bacteremia, severity-of-illness score > or =4, and inappropriate antibacterial treatment were factors significantly associated with death. Most S. maltophilia isolates were resistant to aminoglycosides, beta-lactams, and ciprofloxacin. Cotrimoxazole and ticarcillin-clavulanic acid showed borderline activity. Prompt administration of in vitro-active antibiotics may improve the prognosis of S. maltophilia bacteremia, especially for immunocompromised patients, and novel drug combinations are needed for the treatment of severe infections.

Anti-tumor necrosis factor alpha (anti-TNF-α) is used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure that occurred after etanercept initiation and influenza vaccination in an HIV-infected woman with rheumatoid arthritis.

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Introduction Staphylococcus aureus has emerged as a major nosocomial pathogen in the last decades and also represents the second most common pathogen isolated from patients in outpatient settings. Although methicillin-resistant S.aureus infections were traditionally limited to hospitals, community-associated cases of methicillin-resistant S.aureus infections have been reported. In our case, we observed an unexpected event during treatment. Case presentation A 60-year-old Caucasian man developed fever and multiple muscle and brain abscesses caused by Panton-Valentine leukocidin-negative community-associated methicillin-resistant S. aureus. Conclusion Although our patient was given antimicrobials active against the isolated methicillin-resistant S. aureus strain, it was only after the introduction of daptomycin that his skin, soft tissue and muscle lesions and also brain manifestations improved.

Introduction Hydrochlorothiazide and thiazide-like diuretics are considered first-line drugs for initial therapy in uncomplicated arterial hypertension. Acute cholecystitis is a well-known complication during treatment with thiazide, and these drugs are also reported to be followed by pronounced insulin resistance. Case presentation We describe a case of acute cholestatic hepatitis in a 68-year-old Caucasian man who was receiving olmesartan and hydrochlorothiazide for arterial hypertension. From the clinical and histologic findings, we diagnosed him as having hepatocellular-cholestatic injury and a disorder of glucose metabolism in the liver. To the best of our knowledge, no histopathologic description of hydrochlorothiazide hepatotoxicity has previously been documented in the literature. Conclusion In the differential diagnosis of cholestatic hepatitis, clinicians should be aware of the possibility of liver damage in patients receiving hydrochlorothiazide therapy.

Introduction Cytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear. We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008. Case presentation We describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection. Conclusion Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.

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A46-year-old Italianman seropositiveforhumanimmunodefi-ciency virus (HIV) type 1 was admitted to our department witha 3-month history of nonproductive cough and progressivelyworsening dyspnea. The patient was a former heroin addictwith liver cirrhosis caused by hepatitis C virus and previouslytreated visceral leishmaniasis and latent syphilis. He was on an-tiretroviral treatment consisting of emtricitabine, tenofovir, andfosamprenavir with an undetectable HIV load and a CD4 T-lymphocyte count of 180 cells/µL. On hospital admission, thepatient was afebrile but short of breath at rest, with a heart rateof 110 beats per minute, respiratory rate of 35 breaths perminute, and oxygen saturation of 80% on room air. Physical ex-amination revealed holoinspiratory wheezing. His oral cavitywas unremarkable. Arterial blood gas showed an arterial pH of7.48, an oxygen partial pressure of 56 mm Hg, and a carbondioxide partial pressure of 28 mm Hg while breathing ambientair. A computed tomographic scan of the chest was performedshowing multiple bilateral pulmonary lesions,somewith acavi-tary appearance (Figure 1). Bronchoscopy demonstrated tra-cheal subocclusion caused by irregular, friable rosy vegetationsextending over 4 cartilaginous rings (Figure 1C). Biopsies wereobtained (Figure 2).What isyour diagnosis?

In a recent meta-analysis, Brown et al. investigated the association between antibiotic class and the risk of community-associated Clostridium difficile infection (CDI). The results demonstrated that the risk of CDI in patients treated with macrolides was more than twice that in patients with no