Pasquale Sordillo

Hepatitis E Virus Genotype 4 Outbreak, Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.

18-Fluoro-2-deoxyglucose positron emission tomography-computed tomography: an additional tool in the diagnosis of prosthetic valve endocarditis

OBJECTIVES To evaluate the role of 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET-CT) in the diagnosis of infectious endocarditis (IE). METHODS We retrospectively examined 27 consecutive patients who were admitted to the Infectious Diseases Department of Tor Vergata University Hospital between 2009 and 2013 with a suspicion of IE. The final IE diagnosis was defined according to the modified Duke criteria, and the microbiological and diagnostic results were collected for each patient. RESULTS Twenty out of 27 patients had a suspected prosthetic valve endocarditis (PVE) and seven had a suspected native valve endocarditis (NVE). Twenty-five out of 27 patients (92%) had a confirmed diagnosis of IE (18/25 PVE and 7/25 NVE); 16 had a positive echocardiography evaluation and 16 had positive (18)F-FDG-PET-CT findings. Echocardiography showed a higher sensitivity as a diagnostic tool for the detection of IE compared to (18)F-FDG-PET-CT (80% vs. 55%). However, a greater number of PVE had positive (18)F-FDG-PET-CT results compared to those with positive echocardiography findings (11/13 vs. 9/13), and overall 89% (16/18) of confirmed PVE resulted (18)F-FDG-PET-CT positive. Analyzing only the cases who underwent transoesophageal echocardiography, (18)F-FDG-PET-CT showed a sensitivity of 85% in PVE (vs. 69% for echocardiography and 77% for the Duke criteria). All seven patients with NVE had a positive echocardiography and negative (18)F-FDG-PET-CT findings (p<0.001). CONCLUSIONS The results of this study further highlight the limitations of echocardiography in the diagnosis of PVE and the potential advantages of (18)F-FDG-PET-CT in these cases.

Late hepatitis B virus reactivation after lamivudine prophylaxis interruption in an anti-HBs-positive and anti-HBc-negative patient treated with rituximab-containing therapy

We describe a case of an anti-HBs-positive patient who experienced hepatitis B reactivation 18 months after the discontinuation of rituximab and after 12 months of lamivudine prophylaxis. The patient carried a hepatitis B genotype D virus harbouring a single immune escape mutation, sT118K. No consensus guidelines regarding the optimal length of treatment or the best elective drug have been defined for antiviral prophylaxis for HBsAg-negative, anti-HBc- and/or anti-HBs-positive patients undergoing immunosuppressive treatment. Screening based on HBV serological markers and HBV DNA testing is a critical issue to recognise hepatitis B reactivation as early as possible. Furthermore, it is of outstanding importance to identify alternative markers (e.g. cccDNA, HBV core related antigen, etc.), that could be predictive of HBV reactivation.

Complication of nasal piercing by Staphylococcus aureus endocarditis: a case report and a review of literature

Body piercing, a growing trend especially in young people, is often complicated by severe infections. We present a case of acute bacterial endocarditis by Staphylococcus aureus complicated by multiple cerebral, kidney, spleen embolisms in a young girl, with no known previous cardiac abnormalities, following the piercing of nasal septum. This case highlights the importance of education of patients with and without structural heart disease to the potential dangerous and even life threatening infectious complications of piercing, and stimulate further discussion on the possibility of antibiotic prophylaxis of such procedures.Body piercing, a growing trend especially in young people, is often complicated by severe infections. We present a case of acute bacterial endocarditis by Staphylococcus aureus complicated by multiple cerebral, kidney, spleen embolisms in a young girl, with no known previous cardiac abnormalities, following the piercing of nasal septum. This case highlights the importance of education of patients with and without structural heart disease to the potential dangerous and even life threatening infectious complications of piercing, and stimulate further discussion on the possibility of antibiotic prophylaxis of such procedures.

Two-year surveillance on fluconazole susceptibility of Candida spp isolates in a general and university hospital in Rome

Fluconazole susceptibility was tested in 385 clinical yeast isolates (285 Candida albicans, 38 C. glabrata, 31 C. tropicalis, 31 other Candida subsp.) using the agar disk diffusion test. Yeasts were collected from specimens obtained from outpatients (69) and inpatients (intensive care unit: 79 isolates, major burn unit: 31 isolates, hematology ward: 45 isolates, gynecology ward: 67 isolates, other wards: 94 isolates). Three hundred and fifty-six (92%) yeast isolates showed to be susceptible, 18 (5%) were susceptible dose-dependent, and 10 (3%) were resistant to fluconazole. Of the resistant group, 3 isolates were C.albicans, while seven were Candida non-albicans (2 C. rugosa, 2 C. humicola, 1 C. tropicalis, 1 C. ciferrii, 1 C. glabrata). The disk-diffusion method was easy to perform and there were no difficulties in the interpretation of inhibition zone diameters. Fluconazole maintained a good activity against Candida spp despite its extensive use for the prophylaxis and treatment of fungal infections.

Paravalvular leak of a mechanical mitral valve prosthesis associated with Burkholderia cepacia subacute endocarditis: a rare case successfully treated by multidisciplinary approach

Prosthetic valve endocarditis (PVE) represents an uncommon and very serious complication after heart valve surgery. Prosthetic valve endocarditis occurs in 1% to 6% of patients with valve prostheses and affects both mechanical and biological valves [1]. Up to 34% of all cases of infective endocarditis involve prosthetic heart valves. Prosthetic valve endocarditis represents a nosographic entity independent from native valve endocarditis (NVE) because of its specific clinical features, epidemiology, and microbiological findings; its management is complex and requires a multidisciplinary approach [2]. Anatomical signs of infective endocarditis in the mitral position include valve dysfunction, paravalvular leaks, and annular abscesses. In particular, the incidence of paravalvular leaks (PVL) is estimated at 2–17%: they can be asymptomatic conditions that do not always require treatment or can cause hemolysis and heart failure [2]. Burkholderia cepacia is a Gram-negative bacillus that represents an important nosocomial pathogen, especially in patients affected by cystic fibrosis and chronic granulomatous diseases [3]. It is rarely responsible for endocarditis in community settings, but sporadic cases have been described among intravenous heroin users and patients with prosthetic valves. According to the clinical data, most patients are treated by administration of trimethoprim-sulfamethoxazole even if the microorganism is actually characterized by multidrug resistance [4]. We present the case of a female patient who was submitted to redo cardiac surgery due to echocardiographic evidence of a paravalvular prosthetic mitral valve leak causing severe regurgitation; intraoperative evaluation revealed anatomical signs of previously undetected endocarditis, while cultures from the prosthetic valve indicated the presence of a very rare microorganism: Burkholderia cepacia. A 75-year-old woman with history of previous mitral valve replacement with a mechanical prosthesis (St. Jude 31-mm valve in 2001) was admitted to our department with the diagnosis of prosthesis dysfunction due to a paravalvular leak and critical stenosis of the left anterior descending coronary artery. The patient was in atrial fibrillation; her medical history featured a previous stroke (2 years before). In May 2016, the patient presented with fever and dyspnea and was admitted to the Internal Medicine Ward of one of our referral hospitals with the diagnosis of bronchopneumonia. After a thoracic computed tomography (CT) scan, an empiric antibiotic therapy with ceftriaxone and clarithromycin was administered. Due to a new onset of systolic murmur, the patient underwent transthoracic and transesophageal echocardiography (TTE and TEE), which demonstrated mitral valve prosthesis dysfunc-

Dapsone hypersensitivity syndrome complicated by Scedosporium apiospermum pneumonia in an immunocompetent patient.

Dapsone (4,40diaminodiphenyl sulphone) has been used since the middle of the 20th century for leprosy treatment, usually in combination with rifampin and clofazimine. Dapsone hypersensitivity syndrome (DHS) occurs in 0.5-3% of patients treated with this drug. The exact immune mechanism behind this idiosyncratic reaction with multi-organ involvement is unclear. Some genetic and environmental factors, by increasing the production of dapsone-reactive metabolites or affecting the ability of the liver to detoxificate them, may increase the risk of developing DHS. Latency before the onset of symptoms can vary from 2-6 h, in previously sensitised patients, to 6 months [1]. Typical DHS manifestations include high fever, skin rash, malaise, methemoglobinaemia, liver toxicity (jaundice, hepatitis and hepatomegaly) and generalised lymphadenopathy. Acute renal failure, hypersensitivity pneumonia, cholangitis, sensory peripheral neuropathy, pancreatitis and pleural effusion have been reported less frequently [2]. The discontinuation of dapsone and the early initiation of high-dosage systemic corticosteroid therapy are crucial to decrease mortality and morbidity. Scedosporium spp. are hyaline filamentous fungi ubiquitously present in soil, sewage and polluted waters. Although these fungi have a uniform worldwide distribution, they are more commonly found in temperate climates than in tropical climates. The most common species responsible for human disease are Scedosporium apiospermum (teleomorph: Pseudallescheria boydii) and Scedosporium prolificans, both of which are very similar to Aspergillus spp. These pathogens, once mainly known as agents of cutaneous and subcutaneous tissue infections (e.g. maduromycosis) in immunocompetent patients, have recently been reported to cause systemic life-threatening infections in immunocompromised hosts with increasing frequency. Scedosporium-related pneumonia, meningoencephalitis, brain abscesses and endocarditis have been documented in patients with advanced human immunodeficiency virus (HIV) infection and haematological malignancies, as well as in stem cell transplantation recipients. In the international medical literature, there are only a few reports of life-threatening Scedosporium spp. infections in immunocompetent patients. Rodriguez-Tudela et al. [3], in a recent review of 162 cases of scedosporiosis, reported 34 infections in patients with no underlying chronic condition; of note, 23 of these cases (82%) had suffered surgery or traumatism before the acquisition of the infection. Katragkou et al. [4] reviewed 23 cases of Scedosporium apiospermum infection after near-drowning. In this particular condition, Scedosporium apiospermum has been reported to cause severe invasive infections, with frequent central nervous system dissemination, in young and immunocompetent hosts. We report the case of a patient who died of a rapidly progressive pneumonia caused by Scedosporium apiospermum. The patient we describe did not present any typical risk factor for this opportunistic infection, except for a 10-day course of steroid therapy administered to control a DHS. A 53-year-old Indian man presented with a 10-day history of fever, generalised itchy maculopapular rash involving the palms and soles, and jaundice. His past medical history was unremarkable, and he denied taking any medication on a regular basis. He had been living in Italy for the past 26 years, but he had travelled to his L. Ceccarelli G. Calisti (&) D. Delle Rose A. Ricciardi G. Maffongelli P. Sordillo L. Sarmati M. Andreoni Infectious Diseases Unit, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy e-mail: giorgiocalisti@gmail.com

Multidrug resistance after lamivudine therapy for chronic hepatitis B.

Besides interferon, five oral nucleos(t)ide analogues are currently approved for the treatment of chronic hepatitis B (CHB): lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), tenofovir (TDF) and telbivudine (LdT). Treatment of CHB with any single nucleoside reverse transcriptase inhibitor (NRTI) generally leads to rapid suppression of viral replication in the short term; however, long-term therapy can cause the emergence of drug-resistant mutants. Lamivudine, the first NRTI approved for CHB therapy, is still commonly used as the first-choice therapy for its potency, relatively low cost and safety profile. Mutations conferring resistance to LAM have been mapped to the C domain of the viral reverse transcriptase (RT) and are often associated with compensatory mutations in the conserved B domain that partially restore the capacity of mutants in vitro. When drug resistance occurs during LAM therapy, the most appropriate management is the early combination of LAM with ADV or possibly TDF. ADV usually does not exhibit cross resistance with LAM and undetectable viremia is obtained after three months in 100% of patients who started combined therapy with viremia of <6log cp/ml. Also, ETV is effective in patients with LAM resistance. However, its efficacy is lower than in naı̈ve patients and it needs to be administered in high dose. Also, the likelihood of resistance is higher than that observed in naı̈ve patients, because two of the three mutations conferring resistance to ETVare usually present in LAMresistant hepatitis B virus (HBV). Here, we report the case of a 47-year-old male with CHB, HBeAg-negative and anti-HBe-positive, and negative for HCV (hepatitis C virus), HDV (hepatitis D virus) and HIV. He presented with advanced liver disease (Ishak grading 10 and staging 5), elevated HBV DNA (528 000 UI/ml) and increased ALT. He refused PEG-interferon and, according to the national guidelines at that time, started therapy with LAM in February 2006, without performing genotyping. After three months, HBV DNA was below 200 UI/ml and ALT was normal. HBV DNA and ALT measurements, performed every three months, were normal until November 2007, when, despite high adherence to the therapy regime, HBV DNA was 412 UI/ml with a normal ALT value. After a further month, HBV DNA had increased to 1028 UI/ml. HBV genotyping by in-house nested PCR was performed, obtaining the following results: four primary RT mutations, L180M, A181V,

Aciclovir, herpes viruses and HIV: a never-ending story

Evaluation of: Delany S, Mlaba N, Clayton T et al. Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomized placebo-controlled trial in South Africa. AIDS 23, 461–469 (2009). HIV infection continues to be among the leading causes of morbidity and mortality, especially in Africa. The prevalence of herpes simplex virus type 2 (HSV-2) has already reached high seroprevalence of up to 90% in HIV-seropositive individuals, and HSV-2 is now the leading cause of genital ulcer disease in both developing and developed countries. The role of HSV-2 as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV diffusion, also facilitating HIV spread among the low-risk population who have stable long-term sexual partnerships. To date, no vaccine to prevent HSV-2 acquisition or reactivation has been developed, although antivirals have been shown to be safe and effective in reducing HSV-2 shedding frequency and the duration of genital ulcer disease. The paper under evaluation confirms the favorable effect of therapies aimed at suppressing HSV-2 reactivation in HIV-seropositive patients on HIV plasma and vaginal load. In this study, aciclovir 400 mg twice daily was able to significantly reduce plasma and genital HIV RNA, the frequency of HIV shedding, genital HSV-2 DNA and the frequency of genital ulcerations. These results suggest that HSV-2 control with low-cost aciclovir can play an important role in reducing HIV spread, mainly in developing countries, where costs limit the use of highly active antiretroviral therapy.

In vitro Activity of a New Antibacterial Drug, Trospectomycin Sulphate (U-63,366F), against Bacteroides Strains Isolated from the Vagina

The antibacterial activity of trospectomycin, clindamycin, metronidazole, imipenem, cefoxitin, and piperacillin was tested against 72 Bacteroides spp. strains isolated from the vagina of women with vaginitis by determining the minimal inhibitory concentration using the agar dilution method. Trospectomycin shows a good activity which is comparable to that of imipenem and metronidazole. Its expanded spectrum of activity makes trospectomycin suitable for the use in single-drug therapy of pelvic infections in women.