Elena Nicco

Epidemiology, species distribution, antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy.

Candida is an important cause of bloodstream infections (BSI), causing significant mortality and morbidity in health care settings. From January 2008 to December 2010 all consecutive patients who developed candidemia at San Martino University Hospital, Italy were enrolled in the study. A total of 348 episodes of candidaemia were identified during the study period (January 2008–December 2010), with an incidence of 1,73 episodes/1000 admissions. Globally, albicans and non-albicans species caused around 50% of the cases each. Non-albicans included Candida parapsilosis (28.4%), Candida glabrata (9.5%), Candida tropicalis (6.6%), and Candida krusei (2.6%). Out of 324 evaluable patients, 141 (43.5%) died within 30 days from the onset of candidemia. C. parapsilosis candidemia was associated with the lowest mortality rate (36.2%). In contrast, patients with C. krusei BSI had the highest mortality rate (55.5%) in this cohort. Regarding the crude mortality in the different units, patients in Internal Medicine wards had the highest mortality rate (54.1%), followed by patients in ICU and Hemato-Oncology wards (47.6%). This report shows that candidemia is a significant source of morbidity in Italy, with a substantial burden of disease, mortality, and likely high associated costs. Although our high rates of candidemia may be related to high rates of BSI in general in Italian public hospitals, reasons for these high rates are not clear and warrant further study. Determining factors associated with these high rates may lead to identifying measures that can help to prevent disease.

Why is community-associated MRSA spreading across the world and how will it change clinical practice?

Meticillin-resistant Staphylococcus aureus (MRSA) emerged in 1960 and over the following 40 years was a problem confined largely to the healthcare setting. In the late 1990s the first US reports of so-called community-associated MRSA (CA-MRSA) infections appeared. CA-MRSA infections were defined as MRSA infections occurring in patients who had no identifiable predisposing risk factors, such as healthy children and young adults. CA-MRSA is associated with a novel genetic profile and phenotype; it is remarkably fit and capable of spreading within communities, it is virulent and is often susceptible to multiple narrow-spectrum antimicrobials other than beta-lactams. CA-MRSA infections involve predominantly skin and soft tissue; however, necrotizing pneumonia and necrotizing fasciitis have been described. At present, several reports suggest that CA-MRSA may be replacing the hospital-acquired MRSA strains (HA-MRSA), with potentially catastrophic consequences. Given the rapid spread and the high virulence of CA-MRSA, global strategies are needed. Prompt, appropriate treatment, guided by the site and type of infection and risk factors for HA-MRSA or CA-MRSA, increases the chances of a successful outcome and is urgently needed.

High-dose daptomycin in documented Staphylococcus aureus infections

Daptomycin is approved at a dose of 4-6 mg/kg/day for the treatment of complicated skin and soft-tissue infection and Staphylococcus aureus bloodstream infection. Clinical experience with doses >6 mg/kg/day is limited, but data reported to date suggest that daptomycin can be safe and effective at higher doses. We describe our experience with daptomycin at doses >6 mg/kg/day and ≤6 mg/kg/day for S. aureus infections. A retrospective chart review of all patients treated with daptomycin from January 2008 to 28 February 2010 was performed. During the study period, 53 patients received daptomycin, including 22 patients receiving daptomycin at a standard dose (SD) (mean 5 mg/kg/day, range 4-6 mg/kg/day) and 31 patients receiving a higher dose (HD) (mean 8 mg/kg/day, range 7-9 mg/kg). The median treatment duration was 13.5 days and 19 days for the SD and HD groups, respectively. Clinical success was observed in 16/22 patients (73%) in the SD group and 29/31 patients (94%) in the HD group (P=0.05). Microbiological success was observed in 13/19 patients (68%) and 27/29 patients (93%) in the SD and HD groups, respectively (P<0.05). Of the 53 patients, 2/22 treated with SD daptomycin and 3/31 treated with HD daptomycin experienced a grade 1 adverse event while receiving therapy (i.e. anaemia, diarrhoea, nausea, hypokalaemia and arthralgia) but did not require discontinuation of daptomycin treatment. These results suggest that daptomycin may be used at doses higher than 6 mg/kg/day without toxicity and possibly with better outcome than conventional doses. We recommend further randomised controlled prospective studies with higher doses of daptomycin.

Clinical Performance of the (1,3)-β-d-Glucan Assay in Early Diagnosis of Nosocomial Candida Bloodstream Infections

ABSTRACT Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-β-d-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first Candida-positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.

Natural killer cells in HIV controller patients express an activated effector phenotype and do not up-regulate NKp44 on IL-2 stimulation

Control of HIV replication in elite controller (EC) and long-term nonprogressor (LTNP) patients has been associated with efficient CD8+cytotoxic T-lymphocyte function. However, innate immunity may play a role in HIV control. We studied the expression of natural cytotoxicity receptors (NKp46, NKp30, and NKp44) and their induction over a short time frame (2–4 d) on activation of natural killer (NK) cells in 31 HIV controller patients (15 ECs, 16 LTNPs). In EC/LTNP, induction of NKp46 expression was normal but short (2 d), and NKp30 was induced to lower levels vs. healthy donors. Notably, in antiretroviral-treated aviremic progressor patients (TAPPs), no induction of NKp46 or NKp30 expression occurred. More importantly, EC/LTNP failed to induce expression of NKp44, a receptor efficiently induced in activated NK cells in TAPPs. The specific lack of NKp44 expression resulted in sharply decreased capability of killing target cells by NKp44, whereas TAPPs had conserved NKp44-mediated lysis. Importantly, conserved NK cell responses, accompanied by a selective defect in the NKp44-activating pathway, may result in lack of killing of uninfected CD4+NKp44Ligand+ cells when induced by HIVgp41 peptide-S3, representing a relevant mechanism of CD4+ depletion. In addition, peripheral NK cells from EC/LTNP had increased NKG2D expression, significant HLA-DR up-regulation, and a mature (NKG2A−CD57+killer cell Ig-like receptor+CD85j+) phenotype, with cytolytic function also against immature dendritic cells. Thus, NK cells in EC/LTNP can maintain substantially unchanged functional capabilities, whereas the lack of NKp44 induction may be related to CD4 maintenance, representing a hallmark of these patients.

Disseminated Salmonella paratyphi infection in a rheumatoid arthritis patient treated with infliximab.

Anti-tumour necrosis factor (TNF)-alpha treatments are immunosuppressant and represent an important risk factor for developing infections. We report a case of Salmonella paratyphi bacteraemia associated with soft tissue infection in a patient who used infliximab and had recently travelled to India. This case report provides supporting evidence, essentially based only on case reports, that patients receiving anti-TNF-alpha treatments have an increased susceptibility to Salmonella infections, which may develop at unusual and disseminated sites. We emphasize the importance of appropriate counselling of patients undergoing anti-TNF treatment and travelling to areas in which Salmonellae are endemic, as well as the importance of advice to these patients concerning food hygiene.

Effectiveness of a project to prevent HIV vertical transmission in the Republic of Congo

OBJECTIVES To evaluate the effectiveness of a prevention programme against the vertical transmission of HIV in a resource-limited setting and to investigate variables associated with compliance. PATIENTS AND METHODS The Kento-Mwana project (2005-2008) provided counselling, serological and biomolecular testing and prophylaxis/therapy to HIV-positive pregnant women and their children attending four antenatal clinics in Pointe Noire, Republic of Congo. Expected and actual rates of vertical transmission of HIV were compared. Univariate and multivariate analyses were performed in order to identify variables associated with non-compliance. RESULTS The observed transmission rate in the group who completed follow-up was 5/290 (1.7%, 95% CI 0.6%-4.1%). The overall estimated transmission rate in the target population, computed taking into account the expected vertical transmission of HIV among drop-outs, was 67-115/638 (10.5%-18.0%). A comparison between this rate and the expected transmission rate in the absence of intervention (25%-40%) showed that the programme was able to prevent approximately 50% of vertical transmissions. Older age (OR 0.33, 95% CI 0.16-0.66, P = 0.002), telephone availability (OR 0.42, 95% CI 0.24-0.72, P = 0.002) and occupation (OR 0.57, 95% CI 0.29-1.10, P = 0.092) were associated with better compliance. CONCLUSIONS Despite the vast majority of women accepting counselling and testing, many of them refused prophylaxis or dropped out, thus reducing the effectiveness of the intervention from an ideal 2% to a still important but less impressive median transmission rate of 15% (range 10.5%-18%). Promoting participation and compliance, rather than increasing the potency of antiretroviral regimens, is crucial for preventing the vertical transmission of HIV in Africa.

Bordetella holmesii endocarditis in a patient with systemic lupus erythematous treated with immunosuppressive agents

Sir, Bordetella holmesii, formerly designated as CDC non-oxidizer group 2, was recently classified as a member of the genus Bordetella. This pathogen has been reported as a rare cause of bactaeremia, respiratory tract infection, and endocarditis, particularly in younger patients. Anatomic or functional asplenia, renal transplantation, HIV infection, long-term steroid therapy, Hodgkin’s lymphoma, and chronic obstructive pulmonary disease are all predisposing conditions for invasive disease. Bordetella spp. represents one of the non-HACEK (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) Gram-negative rods that can cause endocarditis. Infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli is a rare and poorly understood disease; only few cases have been described so far and all present a high mortality rate (24%). From 1972 to 2011, only two cases of Bordetella holmesii endocarditis have been found in a review of the English literature. The diagnosis of B. holmesii IE was confirmed by the presence of a valvular vegetation in only one of these two cases, and was documented through the use of the echocardiography; in the other case, the diagnosis was only clinically suspected. Here we report a case of IE caused by Bordetella holmesii in a patient affected by systemic lupus erythematous (SLE) and receiving an immunosuppressive treatment with azathioprine and prednisone. On March 2011, a 48-year-old male patient was admitted to the Infectious Diseases Department of the San Martino University Hospital of Genoa, Italy, due to a long history of fever and fatigue. His medical history included an autoimmune thyroiditis and a recent diagnosis of SLE, which had been based on physical examination and laboratory test results (positivity of antinuclear antibody test). Before this hospitalization, no organ involvement of SLE had been described and no new sign was diagnosed on this matter at the Infectious Diseases Department. In his medical history, the patient had received remittent courses of prednisone therapy (25 mg/die) for his rheumatic conditions. On 1 February 2011, due to a persistent febrile state, azathioprine was introduced to his therapeutic scheme. During this period, a positron emission tomography/computed tomography scan was performed and it documented no evidence of metabolically active disease. However, due to the presence of a diastolic murmur on auscultation, a transthoracic echocardiography (TTE) was performed, which documented the presence of mobile vegetation on a bicuspid aortic valve, with moderate–severe aortic regurgitation and left ventricle overload. No lesions compatible with Libman–Sacks endocarditis existed prior to this episode. The immunosuppressive therapy was then discontinued and the patient was hospitalized at the Infectious Diseases Department with the diagnosis of suspected IE. His temperature was 36.3uC, heart rate was 90 bpm, and blood pressure was 125/65 mmHg. Physical examination revealed normal S1 and S2 sounds, but a 2/6 diastolic murmur on the aortic auscultation site was detected. Laboratory test results showed elevated C-reactive protein (90.9 mg/l, normal range: 0–5 mg/l) and no leukocytosis. Serial sets of blood cultures were performed and colonies of Gramnegative rods grew from five of them. The isolated pathogen grew on blood and chocolate agar plates after 2 days of incubation, but showed a very limited growth on MacConkey agar. The strain produced a diffusible brown pigment on blood agar plate and was catalase negative. Initially, it was not possible to identify the isolate neither through routine laboratory procedure by using VITEK 2 AES (BioMérieux, Durham, NC, USA) nor by the API NE and NH strips (BioMérieux). The strain was subsequently identified as Bordetella holmesii by sequence analysis of the hypervariable regions V3 and V6 of the 16S rRNA gene; by insertion elements (IS1001, IS1002, and IS481) analysis; by using previously described primers and conditions, and by differential biochemical tests (oxidase, nitrate reduction, and urease production) used to differentiate Bordetella

Inflammation Markers Correlate With Common Carotid Intima-Media Thickness in Patients Perinatally Infected With Human Immunodeficiency Virus 1

OBJECTIVES To investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV-1). METHODS We conducted a cross-sectional observational study. Human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. Common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. Metabolic parameters and markers of inflammation were measured only in HIV-1-infected patients. Statistical analysis was performed by multiple regression and by a matrix of Pearson correlation coefficients. The Student t test was used to compare mean common carotid intima-media thickness values between groups. RESULTS Forty patients (21 female) with HIV-1 infection acquired from birth with a mean age ± SD of 16.3 ± 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 ± 4.6 years were included in the study. Mean common carotid intima-media thickness in the HIV-1-infected group (0.450 ± 0.088 mm) was significantly higher (P < .05) than in the control group (0.407 ± 0.079 mm). No significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and HIV status. In multiple regression analyses, higher levels of insulin (P= .007) and elevated levels of glycated hemoglobin (P= .01) were associated with intima-media thickness changes. CONCLUSIONS Patients perinatally infected with HIV have increased common carotid intima-media thickness compared with healthy individuals. These changes were more pronounced with increasing age and inflammation markers. Interventions that improve cardiovascular risk profiles should be considered in HIV-infected young adults.

Safety and efficacy of pegylated interferon and ribavirin in adolescents with human immunodeficiency virus and hepatitis C virus acquired perinatally.

Limited evidence is available currently regarding the efficacy and safety of pegylated interferon (PEG‐IFN) and ribavirin in patients co‐infected perinatally with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). No information is available on whether or not these patients should be treated earlier for infection with HCV. This report describes four patients with HIV and HCV co‐infection acquired perinatally, who were treated with PEG‐IFN and ribavirin for chronic viral hepatitis caused by HCV. J. Med. Virol. 82: 1110–1114, 2010.