Molecular Typing and Resistance Profile of Acinetobacter baumannii Isolates during the COVID-19 Pandemic: Findings from the "EPIRADIOCLINF" Project.

Due to the COVID-19 pandemic, there has been a shift in focus towards controlling the spread of SARS-CoV-2, which has resulted in the neglect of traditional programs aimed at preventing healthcare-associated infections and combating antimicrobial resistance. The present work aims to characterize the colonization or infection with Acinetobacter baumannii of COVID-19 patients and to identify any clonality between different isolates. Specifically, data and resistance profiles of A. baumannii isolates were prospectively collected from patients recruited by the EPIRADIOCLINF project. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular typing. Overall, we analyzed 64 isolates of A. baumannii from 48 COVID-19 patients. According to our analysis, we have identified the spread of a clonally related isolate, referred to as B. The PFGE pattern B includes four subtypes: B1 (consisting of 37 strains), B2 (11), B3 (5), and B4 (2). Furthermore, in the isolates that were examined using MLST, the most observed sequence type was ST/281. In terms of resistance profiles, 59 out of the total isolates (92.2%) were found to be resistant to gentamicin, carbapenems, ciprofloxacin, and tobramycin. The isolation and identification of A. baumannii from COVID-19 patients, along with the high levels of transmission observed within the hospital setting, highlight the urgent need for the implementation of effective prevention and containment strategies.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial).

INTRODUCTION: In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose. METHODS AND ANALYSIS: The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell'Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences. TRIAL REGISTRATION DETAILS: The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.

[Giant parathyroid adenoma: a rare cause of severe hypercalcemia].

We report the case of a 37-year-old woman that developed severe hypercalcemia due to a parathyroid gland mass. After the initial medical treatment, only a minimal reduction of calcemia was observed and her clinical condition worsened; thus, she required continuous renal replacement therapy (CRRT) that resulted in the normalization of calcium serum level. She then underwent a left thyroid lobectomy with exeresis of the associated parathyroid glands; the histological diagnosis revealed a giant parathyroid adenoma (GPA). CRRT, initially recommended only in case of severe refractory hypercalcemia poorly responsive to pharmacological approaches, is now being evaluated in the first line treatment of life-threatening cases, with or without associated acute kidney injury (AKI).

Diagnostic surveillance by Candida albicans germ tube antibody in intensive care unit patients.

BACKGROUND: The diagnosis of Invasive Candidiasis (IC) presents serious problems, mainly associated with the absence of pathognomonic symptoms of the disease and the difficulty of isolating the fungus in blood culture. Candida albicans germ tube antibody (CAGTA) provides a rapid and simple test for diagnosis of IC. The aim of this study was to evaluate the diagnostic role of the CAGTA in the monitoring of critically-ill patients at risk of developing IC. METHODS: During diagnostic surveillance in the intensive care units (ICU) CAGTA was performed twice a week if predetermined risk factors were present and a positive result was considered when a serum titer ≥1/160 was detected in at least one sample. RESULTS: Seventy critically ill patients were included in the study. Twenty-three patients with proven/probable IC were identified. The sensitivity, specificity, PPV, and NPV of CAGTA for the diagnosis of proven/probable IC in all 70 patients were 91.3%, 68.1%, 58.3%, and 94.1%, respectively. Statistically significant highest titers were found in patients with proven/probable IC as well as increasing titers more than 1/160. CONCLUSIONS: Our results suggest that detection of CAGTA could be a useful biomarker for the diagnosis of proven and probable IC in critical patients during prolonged ICU stay. During the monitoring it is opportune to evaluate the titers kinetics since the clinical diagnosis of proven/probable IC coincided with increase titer from negative (<1/160) to more than 1/160.

Renal resistive index: a new reversible tool for the early diagnosis and evaluation of organ perfusion in critically ill patients: a case report.

BACKGROUND: We reported a case of early detection of peripheral hypoperfusion trough the evaluation of a new index in intensive care: Renal Doppler Resistive Index (RRI). CASE PRESENTATION: We admitted a 76-year-old man who underwent ileostomy and hernioplasty because of an intestinal occlusion due to obstructive strangulated right inguinal hernia. The post-operative period was characterised by hemodynamic instability and he needed an invasive hemodynamic monitoring, administration of vasopressors and continuous renal replacement therapy (CRRT). Then, hemodynamic stability was obtained and vasopressors interrupted. RRI was lower than 0.7. In the eleventh post-operative day, despite stable macrocirculatory parameters, we found increased values of RRI. An abdomen ultrasound first and then a CT scan revealed the presence of bleeding from the previous ileostomy. Hence, the patient immediately underwent another surgical operation. CONCLUSIONS: RRI modification appears to be more precocious than any other hemodynamic, microcirculatory and metabolic parameter routinely used. RRI has been widely used to assess renal function in critically ill patients; now, we presume that RRI could represent a common and useful tool to manage target therapy in critical condition.

A simplified lung ultrasound approach to detect increased extravascular lung water in critically ill patients.

BACKGROUND: The quantification of B-lines at lung ultrasonography is a valid tool to estimate the extravascular lung water (EVLW) in patients after major cardiac surgery. However, there is still uncertainty about the correlation between B-lines and EVLW in a general population of critically ill. AIM: To evaluate a simplified lung ultrasonographic assessment as a tool to estimate the EVLW in critically ill patients admitted to a polyvalent intensive care unit (ICU). METHODS: Nineteen consecutive critically ill patients requiring mechanical ventilation and hemodynamic monitoring were enrolled. Lung ultrasonography and the thermodilution methodology (PiCCO system) were performed by two independent operators. The positive scan at lung ultrasound was defined by visualization of at least 3 B-lines. We then compared the number of chest areas positive for B-lines with the EVLW index obtained by the invasive procedure. RESULTS: A significant correlation was found between the number of lung quadrants positive for B-lines and EVLW indexed using both actual body weight (rho = 0.612 p = 0.0053) and predicted body weight (rho = 0.493 p = 0.032). Presence of more than 3 positive lung quadrants showed a good performance in identifying an EVLW index value >10 ml/kg of actual body weight(area under the ROC 0.894; 95% CI 0.668-0.987 p < 0.0001). Presence of of more than 4 positive lung quadrants indentified an EVLW index value >10 ml/kg of predicted body weight (area under the ROC 0.8; 95% CI 0.556-0.945 p = 0.0048). CONCLUSION: A simplified lung ultrasound approach can by used as a reliable noninvasive bedside tool to predict EVLW in emergency and critically ill patients.

Focal epilepsy as a long term sequela of Parvovirus B19 encephalitis.

Human Parvovirus B19 (PVB19), the etiological agent of the fifth disease, is associated with a large spectrum of pathologies, among which is encephalitis. Since it has been detected from the central nervous system in children or in immunocompromised patients, its causative role in serious neurological manifestations is still unclear. Here we report the case of an 18-year-old healthy boy who developed encephalitis complicated by prolonged status epilepticus. The detection of PVB19 DNA in his serum and, subsequently, in his cerebrospinal fluid supports the hypothesis that this virus could potentially play a role in the pathogenesis of neurological complications. In addition, the detection of viral DNA and the presence of specific IgM and IgG antibodies in serum, together with clinical findings such as skin rash, support the presence of a disseminated viral infection. In the presence of neurological disorders, especially when there are no specific signs, but seizures and rash are present, it is important to search for PVB19 both in immunocompromised and immunocompetent patients. Moreover, the introduction of the PVB19 DNA test into diagnostic protocols of neuropathies, especially those undiagnosed, could clarify the etiological agent that otherwise could remain unrecognized.

Rapidly fatal hemorrhagic pneumonia and group A Streptococcus serotype M1.

We report 3 cases of fulminant hemorrhagic pneumonia in previously health patients. Sudden-onset hemoptysis and dyspnea developed; all 3 patients and died <12 h later of massive pulmonary bleeding, despite aggressive supportive care. Postmortem analysis showed that the illnesses were caused by group A Streptococcus emm1/sequence type 28 strains.

Acquisition and cross-transmission of Staphylococcus aureus in European intensive care units.

OBJECTIVE: To study the acquisition and cross-transmission of Staphylococcus aureus in different intensive care units (ICUs). METHODS: We performed a multicenter cohort study. Six ICUs in 6 countries participated. During a 3-month period at each ICU, all patients had nasal and perineal swab specimens obtained at ICU admission and during their stay. All S. aureus isolates that were collected were genotyped by spa typing and multilocus variable-number tandem-repeat analysis typing for cross-transmission analysis. A total of 629 patients were admitted to ICUs, and 224 of these patients were found to be colonized with S. aureus at least once during ICU stay (22% were found to be colonized with methicillin-resistant S. aureus [MRSA]). A total of 316 patients who had test results negative for S. aureus at ICU admission and had at least 1 follow-up swab sample obtained for culture were eligible for acquisition analysis. RESULTS: A total of 45 patients acquired S. aureus during ICU stay (31 acquired methicillin-susceptible S. aureus [MSSA], and 14 acquired MRSA). Several factors that were believed to affect the rate of acquisition of S. aureus were analyzed in univariate and multivariate analyses, including the amount of hand disinfectant used, colonization pressure, number of beds per nurse, antibiotic use, length of stay, and ICU setting (private room versus open ICU treatment). Greater colonization pressure and a greater number of beds per nurse correlated with a higher rate of acquisition for both MSSA and MRSA. The type of ICU setting was related to MRSA acquisition only, and the amount of hand disinfectant used was related to MSSA acquisition only. In 18 (40%) of the cases of S. aureus acquisition, cross-transmission from another patient was possible. CONCLUSIONS: Colonization pressure, the number of beds per nurse, and the treatment of all patients in private rooms correlated with the number of S. aureus acquisitions on an ICU. The amount of hand disinfectant used was correlated with the number of cases of MSSA acquisition but not with the number of cases of MRSA acquisition. The number of cases of patient-to-patient cross-transmission was comparable for MSSA and MRSA.