Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID).

Lack of standardised Clostridium difficile testing is a potential confounder when comparing infection rates. We used an observational, systematic, prospective large-scale sampling approach to investigate variability in C. difficile sampling to understand C. difficile infection (CDI) incidence rates. In-patient and institutional data were gathered from 60 European hospitals (across three countries). Testing methodology, testing/CDI rates and case profiles were compared between countries and institution types. The mean annual CDI rate per hospital was lowest in the UK and highest in Italy (1.5 vs. 4.7 cases/10,000 patient bed days [pbds], p < 0.001). The testing rate was highest in the UK compared with Italy and France (50.7/10,000 pbds vs. 31.5 and 30.3, respectively, p < 0.001). Only 58.4 % of diarrhoeal samples were tested for CDI across all countries. Overall, only 64 % of hospitals used recommended testing algorithms for laboratory testing. Small hospitals were significantly more likely to use standalone toxin tests (SATTs). There was an inverse correlation between hospital size and CDI testing rate. Hospitals using SATT or assays not detecting toxin reported significantly higher CDI rates than those using recommended methods, despite testing similar testing frequencies. These data are consistent with higher false-positive rates in such (non-recommended) testing scenarios. Cases in Italy and those diagnosed by SATT or methods NOT detecting toxin were significantly older. Testing occurred significantly earlier in the UK. Assessment of testing practice is paramount to the accurate interpretation and comparison of CDI rates.

In vivo development of daptomycin resistance in vancomycin-susceptible methicillin-resistant Staphylococcus aureus severe infections previously treated with glycopeptides.

Our aim was to describe the clinical and microbiological features of four cases of severe vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) infections in which the vancomycin non-susceptibility development and daptomycin resistance occurred under therapy with teicoplanin (three cases) and daptomycin switched to vancomycin (one case). Clinical data were retrospectively reviewed. On nine clinical epidemiologically unrelated daptomycin-susceptible (DAP-S) and daptomycin-resistant (DAP-R) MRSA, we performed: (i) DAP-VAN-TEC-CFX-RIF minimum inhibitory concentrations (MICs); (ii) glycopeptide resistance detection (GRD) by δ-hemolysis; (iii) glycopeptide population analysis; (iv) molecular characterization by PFGE-MLST-SCCmec-agr-typing; (v) rpoB and mprF single nucleotide polymorphisms (SNPs); (vi) dltA-mprF-atl-sceD expression by real-time quantitative polymerase chain reaction (qPCR). Three out of the four patients did not survive despite salvage treatment; two died with active MRSA infection and one died because of Stenotrophomonas maltophilia sepsis. The fourth patient, in which a reversion to a DAP-S phenotype occurred, survived with daptomycin plus trimethoprim/sulfamethoxazole and oxacillin treatment, and endovascular device removal. Daptomycin resistance development was preceded by a stable heterogeneous vancomycin-intermediate S. aureus (hVISA) or VISA phenotype acquisition, while in one case, daptomycin resistance was preceded by an unstable daptomycin heteroresistance (hDAP) behavior reverting to DAP-S during vancomycin plus rifampin therapy followed by high doses of daptomycin. All DAP-R strains showed hVISA or DAP-R traits, including mutations and/or up-regulation of genes involved in cell wall turnover and cell membrane perturbation. In our study, daptomycin resistance arose during glycopeptide therapy. The emergence of DAP-R isolates was preceded by a stable VISA or hVISA phenotype or by instability reverting to a DAP-S heteroresistant phenotype. Daptomycin, as first-line therapy for the treatment of severe MRSA infections, should be used at optimal dosage combined with other agents such as beta-lactams, to prevent daptomycin resistance occurrence.

Infective endocarditis in patients with hepatic diseases.

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD- patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD- patients (p = 0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p < 0.001); embolization (43.3 % versus 26.1 %, p < 0.001) and congestive heart failure (42 % versus 34.1 %, p = 0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD- and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.

Isolation of NDM-1-producing Pseudomonas aeruginosa sequence type ST235 from a stem cell transplant patient in Italy, May 2013.

We describe the first isolation of an NDM-1-producing Pseudomonas aeruginosa in Italy. In May 2013, a patient with acute lymphoblastic leukaemia and history of prior hospitalisation in Belgrad, Serbia, underwent stem cell transplantation at a tertiary care hospital in Rome, Italy. After transplantion, sepsis by NDM-1-producing P. aeruginosa occurred, leading to septic shock and fatal outcome.

Multiple bilateral pulmonary "fungus balls" in an immunocompetent patient unsuitable for surgical treatment: efficacy of azoles treatment.

Data guiding management of pulmonary mycetomas are based on uncontrolled trials and case reports. Surgical resection represents a definitive treatment associated with high mortality and sometimes not feasible due to clinical conditions. We report a case of an immunocompetent patient with multiple pulmonary mycetomas, suggestive for probable chronic aspergillosis, in which surgery was contraindicated. The patient experienced a good response to long-term oral voriconazole therapy with remarkable clinical and radiological improvement at three-month follow-up. In cases of probable chronic aspergillomas, when surgery is contraindicated, long-term antifungal therapy with voriconazole seems to be a valid alternative option.

European survey on the current surveillance practices, management guidelines, treatment pathways and heterogeneity of testing of Clostridioides difficile, 2018-2019: results from The Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

BACKGROUND: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown. AIM: To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019. METHODS: Hospital sites and their associated community practices across 12 European countries completed an online survey in 2018-2019, to report on their practices in terms of surveillance, prevention, diagnosis, and treatment of CDI. Responses were collected from 105 hospitals and 39 community general practitioners (GPs). FINDINGS: Hospital sites of 11 countries reported participation in national surveillance schemes compared with six countries for international schemes. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID)-recommended CDI testing methodologies were used by 82% (86/105) of hospitals, however countries reporting the highest incidence of CDI used non-recommended tests. Over 75% (80/105) of hospitals were aware of the most recent European CDI treatment guidelines at the time of this survey compared with only 26% (10/39) of surveyed GPs. However, up to 15% (16/105) of hospitals reported using the non-recommended metronidazole for recurrent CDI cases, sites in countries with lower awareness of CDI treatment guidelines. Only 37% (39/105) of hospitals adopted contact isolation precautions in case of suspected CDI. CONCLUSION: Good awareness of guidelines for the management of CDI was observed across the surveyed European hospital sites. However, low compliance with diagnostic testing guidelines, infection control measures for suspected CDI, and insufficient awareness of treatment guidelines continued to be reported in some countries.

Cases of cryptosporidiosis co-infections in AIDS patients: a correlation between clinical presentation and GP60 subgenotype lineages from aged formalin-fixed stool samples.

Nine cases of cryptosporidiosis co-infections in AIDS patients were clinically categorised into severe (patients 1, 3, 8 and 9), moderate (patients 4 and 5) and mild (patients 2, 6 and 7). Formalin-fixed faecal specimens from these patients were treated to obtain high quality DNA competent for amplification and sequencing of the 60-kDa glycoprotein (GP60) gene. Sequence analysis revealed that one patient was infected with Cryptosporidium hominis whereas the remaining eight patients were infected with C. parvum. Interestingly, the patients showing severe cryptosporidiosis harboured two subtypes within the C. parvum allelic family IIc (IIcA5G3 and IIcA5G3R2), whereas patients with moderate or mild infections showed various subtypes of the C. parvum allelic family IIa (IIaA14G2R1, IIaA15G2R1, IIaA17G3R1 and IIaA18G3R1). DNA extraction and genotyping of Cryptosporidium spp. is a challenging task on formalin-fixed stool samples, whose diagnostic outcome is age-dependent. The method herein reported represents a step forward routine diagnosis and improves epidemiology of HIV-related clinical cases. Due to the need to elucidate genetic richness of Cryptosporidium human isolates, this approach represents a useful tool to correlate individual differences in symptoms to subgenotyping lineages.

Ultrasonography in lesions of the carotid vessels in HIV positive patients.

PURPOSE: This study evaluated with ultrasonography (US) the presence of epiaortic vessel lesions in HIV-positive individuals receiving highly active antiretroviral therapy (HAART) and compared them with naïve patients and healthy individuals to highlight the differences among the different vascular damage patterns. MATERIALS AND METHODS: A total of 222 HIV-infected patients receiving HAART, 64 HIV-infected patients naïve to antiretroviral therapy and 135 HIV-negative control patients underwent US of the carotid vessels. The morphological examination included grey-scale and colour and power Doppler imaging to better characterise lesions and intima media thickness. An automated computerised software package (Q LAB) was used to determine intima media thickness values. Independent risk factors for the development of carotid lesions and, in particular, cholesterolaemia and triglyceridaemia were considered. Atherosclerotic plaques and inflammatory-type lesions were reported. Statistical analysis included the chi-square test, the Fisher exact test for qualitative variables and the Kruskal-Wallis test to compare continuous variables. RESULTS: We observed a higher prevalence of carotid lesions in HIV-positive patients receiving HAART compared with HIV-positive naïve patients (p<0.0000001) and HIV-negative patients (p<0.0001). Findings consistent with inflammatory-type lesions rather than classic atheroma were depicted only in five patients receiving HAART (0.02%). CONCLUSIONS: Our study confirms a higher prevalence of carotid lesions in HAART-treated HIV patients. In agreement with other authors, we identified carotid lesions that were consistent with arteritis rather than with classic atheroma, but the percentage was too small to suggest any robust hypothesis. Further studies are warranted to define the mechanism of onset of carotid lesions in HIV-positive individuals.

Early identification and optimal management of carbapenem-resistant Gram-negative infection.

BACKGROUND: Carbapenem resistance in Gram-negative bacteria is associated with severe infections in the hospital setting. No uniform screening policy or agreed set of criteria exists within the EU to inform treatment decisions for infections caused by carbapenem-resistant Gram-negative bacteria. AIM: To develop a range of consensus statements to survey experts in carbapenem resistance, to identify potential similarities and differences across the EU and across specialties. METHODS: The survey contained 43 statements, covering six key topics relating to carbapenem-resistant organisms: microbiological screening; diagnosis; infection control implementation; antibiotic stewardship; use of resources; and influencing policy. FINDINGS: In total, 136 survey responses were received (66% infectious disease specialists, 18% microbiologists, 11% intensive care specialists, 4% other/unknown) from France, Germany, Greece, Italy, Spain, and the UK. High, or very high, levels of agreement were seen for all 43 consensus statements, indicating good alignment concerning early identification and optimal management of infection due to carbapenem-resistant organisms. CONCLUSION: We offer the following recommendations: (1) screening is required when a patient may have been exposed to the healthcare system in countries/hospitals where carbapenem-resistant organisms are endemic; (2) rapid diagnostic tools should be available in every institution; (3) all institutions should have a specific policy for the control of carbapenem-resistant organisms, which is routinely audited; (4) clear strategies are required to define both appropriate and inappropriate use of carbapenems; (5) priority funding should be allocated to the management of infections due to carbapenem-resistant organisms; and (6) international co-operation is required to reduce country-to-country transmission of carbapenem-resistant organisms.

COVID-19, SARS and MERS: are they closely related?

BACKGROUND: The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. AIMS: To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. SOURCES: The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT: COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. IMPLICATIONS: There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.

Surgical site infections in HIV-infected patients: results from an Italian prospective multicenter observational study.

BACKGROUND: The quality of life of the HIV-infected population in developed countries has substantially improved over the years. Accordingly, the clinical limitations in the surgical treatment of the HIV-infected patients are becoming fewer, and the number of HIV-infected patients undergoing surgical interventions of all types is increasing. However, available data on the incidence and risk factors for post-surgical complications, such as surgical site infections (SSI), in HIV-infected patients are still limited and often controversial. The aim of this study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients. METHODS: A 1-year observational prospective multicenter surveillance study was conducted in 11 Italian Infectious Diseases Clinical Centers from which 305 consecutive HIV-infected patients undergoing different surgical procedures were enrolled. Postdischarge surveillance was conducted within 30 days after surgery. A number of variables were included in a multivariate analysis aimed at assessing potential risk factors for SSI, including body mass index, diabetes, Hepatitis C (HCV) and hepatitis B virus infection, lipodistrophy, HIV viral load, CD4 cell count and white blood cell count, preoperative hospital stay, National Nosocomial Infection Surveillance (NNIS) risk score, and any antimicrobial prophylaxis. RESULTS: SSI occurred in 29 of 305 (9.5%) patients, of which 17 (58.6%) SSI occurred during hospital stay, and 12 (41.4%) occurred during the postdischarge period. The SSI of the 29 patients were classified as superficial (21, 72.4%), deep (four, 13.8%), organ/space (one, 3.4%), and sepsis (three, 10.3%). Nearly 50% of the superficial and 50% of the deep SSI occurred during the postdischarge period. Organ/space infection and sepsis accounted for 13.7% of all SSI and were observed during the in-hospital stay. The multivariate analysis revealed that HCV co-infection was significantly associated to SSI occurrence. Total hospital stay was longer among patients with SSI than among those without SSI (p = 0.041). CONCLUSION: Although 92.5% of our HIV-infected patients presented a NNIS score < or = 1, the SSI rate was twofold higher than that reported in Italian and European studies for the general population, with more severe clinical presentations. This is the first report of an association between HCV-HIV co-infection and SSI occurrence. Additionally, the viro-immunological status of our patients was not related to SSI occurrence, which suggests the need for further research for other potential risk factors that may be implicated in the occurrence of SSI.

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes.

OBJECTIVES: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027- Clostridium difficile infection (CDI). METHODS: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027- CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Overall, 238 patients with 027+ CDI and 267 with 027- CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549-3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906-5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051-3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281-4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437-9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155-125.000, p 0.007) were associated with recurrence in 027- CDI. CONCLUSIONS: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity.

Frequency of detection of respiratory viruses in the lower respiratory tract of hospitalized adults.

BACKGROUND: Respiratory infections are the most common infections in humans. The prevalence of respiratory viruses in adults is largely underestimated, and relevant data mostly concern infants and children. OBJECTIVES: To evaluate the prevalence of respiratory viruses in adults hospitalized in Italy. STUDY DESIGN: During April 2004--May 2005, 510 consecutive lower respiratory tract samples were prospectively collected. These were evaluated with a molecular panel that detected 12 respiratory viruses. RESULTS: Two hundred and fifteen samples were positive for at least one viral pathogen, with an overall sample prevalence of 42.2%. Human rhinoviruses (HRVs) were the most commonly detected viruses (32.9%), followed by influenza virus (FLU)-A (9.0%); the other viruses were 2% or less. Multiple agents were detected in 30 samples from 29 patients, resulting in a co-infection rate of 6.7%. CONCLUSIONS: This study shows a high prevalence of viruses in the lower respiratory tract samples of hospitalized adults, mostly HRV and FLU-A. It is not possible to establish the role of viruses detected at low frequency, but our findings suggest the necessity to consider them as potential causes or precursors of lower respiratory tract infections (LRTIs).

Early syphilitic hepatitis in an immunocompetent patient: really so uncommon?

The incidence of syphilis has increased substantially over the past years, particularly in men who have sex with men. The clinical manifestations of syphilis are variable and liver involvement is uncommon, but may occur at any stage of the disease. We report a case of early syphilitic hepatitis (ESH) in an immunocompetent patient referring multiple bisexual exposures, who presented at admission with jaundice, tiredness, an ulcerated genital lesion and an increase of liver aminotransferases. During his hospital stay, he developed a skin rash, and serology for syphilis was found positive. Our case report strengthens the need to take into consideration the diagnosis of ESH in all patients with unexplained liver enzyme increase and epidemiological data of unsafe sexual exposures. Indeed, an early recognition of the clinical manifestations of syphilis can lead to a prompt treatment, and allows the prevention of the transmission of this disease to other individuals.