Recommendations for the management of pulmonary fungal infections in patients with rheumatoid arthritis.

Often life-threatening pulmonary fungal infections (PFIs) can occur in patients with rheumatoid arthritis (RA) receiving disease-modifying anti-rheumatic drugs (DMARDs). Most of the data concerning PFIs in RA patients come from case reports and retrospective case series. Of the ve most widely described PFIs, Pneumocystis jirovecii pneumonia (PJP) has rarely been seen outside Japan, pulmonary cryptococcosis has been diagnosed in only a small number of patients worldwide, pulmonary coccidioidomycosis has almost only been observed in endemic areas, the limited number of cases of pulmonary histoplasmosis have mainly occurred in the USA, and the rare cases of invasive pulmonary aspergillosis have only been encountered in leukopenic patients. Many aspects of the prophylaxis, diagnosis and treatment of PFIs in RA patients remain to be defined, as does the role of each DMARD in increasing the risk of infection, and the possibility of resuming biological and non-biological DMARD treatment after the infection has been cured. The recommendations for the management of PFIs described in this paper are the product of a consensus procedure promoted by the Italian group for the Study and Management of Infections in Patients with Rheumatic Diseases (the ISMIR group).

Listeria monocytogenes meningitis in an immunocompromised patient.

This report describes a case of meningitis caused by Listeria monocytogenes in a stem cell transplant recipient on immunosuppressive therapy for cutaneous chronic graft-versus host disease. A 59-year-old woman had undergone allogeneic stem cell transplantation (from a matched unrelated donor) 13 months previously for chronic lymphocytic leukemia. She was on regular hematologic follow-up. Though her previous malignancy has been in remission, she was immunosuppressed due to the pharmacological treatment. We describe a meningitis caused by a typical food-borne pathogen, dangerous in patients with impaired cell-mediated immunity. Moreover the bacterium had a multidrug resistance, a rare characteristic in clinical listeriosis. Rapid diagnosis and treatment are key factors in these cases. We chose ampicillin and rifampicin that allowed a complete resolution of the clinical manifestations.

A real time PCR platform for the simultaneous quantification of total and extrachromosomal HIV DNA forms in blood of HIV-1 infected patients.

BACKGROUND: The quantitative measurement of various HIV-1 DNA forms including total, unintegrated and integrated provirus play an increasingly important role in HIV-1 infection monitoring and treatment-related research. We report the development and validation of a SYBR Green real time PCR (TotUFsys platform) for the simultaneous quantification of total and extrachromosomal HIV-1 DNA forms in patients. This innovative technique makes it possible to obtain both measurements in a single PCR run starting from frozen blood employing the same primers and standard curve. Moreover, due to identical amplification efficiency, it allows indirect estimation of integrated level. To specifically detect 2-LTR a qPCR method was also developed. METHODOLOGY/FINDINGS: Primers used for total HIV-1 DNA quantification spanning a highly conserved region were selected and found to detect all HIV-1 clades of group M and the unintegrated forms of the same. A total of 195 samples from HIV-1 patients in a wide range of clinical conditions were analyzed with a 100% success rate, even in patients with suppressed plasma viremia, regardless of CD4+ or therapy. No significant correlation was observed between the two current prognostic markers, CD4+ and plasma viremia, while a moderate or high inverse correlation was found between CD4+ and total HIV DNA, with strong values for unintegrated HIV DNA. CONCLUSIONS/SIGNIFICANCE: Taken together, the results support the use of HIV DNA as another tool, in addition to traditional assays, which can be used to estimate the state of viral infection, the risk of disease progression and to monitor the effects of ART. The TotUFsys platform allowed us to obtain a final result, expressed as the total and unintegrated HIV DNA copy number per microgram of DNA or 10(4) CD4+, for 12 patients within two working days.

Daptomycin use in patients with osteomyelitis: a preliminary report from the EU-CORE(SM) database.

BACKGROUND: Osteomyelitis is a complex and heterogeneous group of infections that require surgical and antimicrobial interventions. Because treatment failure or intolerance is common, new treatment options are needed. Daptomycin has broad Gram-positive activity, penetrates bone effectively and has bactericidal activity within biofilms. This is the first report on clinical outcomes in patients with osteomyelitis from the multicentre, retrospective, non-interventional European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a large database on real-world daptomycin use. PATIENTS AND METHODS: In total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases. RESULTS: Most patients (76%) received prior antibiotic treatment, and first-line treatment failure was the most frequent reason to start daptomycin. Common sites of infection were the knee (22%) or hip (21%), and the most frequently isolated pathogens were Staphylococcus aureus (33%) and coagulase-negative staphylococci (32%). Overall, 52% of patients had surgery, 55% received concomitant antibiotics and 29% received a proportion of daptomycin therapy as outpatients. Clinical success was achieved in 75% of patients. Among patients with prosthetic device-related osteomyelitis, there was a trend towards higher success rates if the device was removed. Daptomycin was generally well tolerated. CONCLUSIONS: This analysis suggests that daptomycin is an effective and well-tolerated treatment option for osteomyelitis and highlights the importance of optimal surgical intervention and appropriate microbiological diagnosis for clinical outcomes.

Clinical experience with daptomycin in Italy: results from a registry study of the treatment of Gram-positive infections between 2006 and 2009.

The purpose of this study was to evaluate post-marketing efficacy and safety data for therapy with daptomycin (DAP) in Italy. Data from patients treated with DAP at 30 centres between January 2006 and July 2009 were analysed according to the protocol of the EU-CORE(SM). In 359 patients, DAP was most commonly prescribed for skin and skin-structure infections (55%), infective endocarditis (13%), and bacteraemia (12.5%). DAP was associated with rapid improvement, and clinical success rates ranging from 77 to 91%, despite almost half of the patient population being ≥65 years of age, 86% having significant underlying disease, and many being affected by drug-resistant pathogens. Staphylococcus aureus represented 35% of all pathogens isolated. Success rates for all staphylococcal and enterococcal infections were >80%, including methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Clinical outcomes were similar for DAP whether used as first- or second-line therapy. DAP was well tolerated even with prolonged treatment.

Interaction of alcohol intake and cofactors on the risk of cirrhosis.

OBJECTIVE: Evaluation of the interaction between alcohol intake and cofactors [hepatitis B virus (HBV), hepatitis C virus (HCV), body mass index] and coffee consumption on the risk of cirrhosis. DESIGN: Seven hundred and forty-nine consecutive patients with chronic liver disease referring to units for liver or alcohol diseases in Italy during a 6-months period. Teetotalers were excluded. The odds ratios (OR) for cirrhosis were evaluated using chronic hepatitis cases as the control group. RESULTS: An alcohol intake of more than 3 units/day resulted associated with the likelihood of cirrhosis both in males (OR 4.3; 95% CI=2.5-7.3) and in females (OR 5.7; 95% CI=2.3-14.5). A multiplicative interaction on the risk of cirrhosis between risky alcohol intake and HBsAg or HCV-Ab/HCV-RNA positivity was observed. A reduction of cirrhosis risk was observed in subjects consuming more than 3 alcohol units/day with increasing coffee intake. The OR for the association with cirrhosis decreased from 2.3 (95% CI=1.2-4.4) in subjects drinking 0-2 cups of coffee/day to 1.4 (95% CI=0.6-3.6) in those drinking more than 2 cups/day. CONCLUSIONS: In subjects with an alcohol intake >3 units/day the coexistence of HBV or HCV multiplies the risk of cirrhosis. Coffee represents a modulator of alcoholic cirrhosis risk.

The prophylaxis of infective endocarditis: a joint position study of the Italian Federation of Cardiologists and the Italian Society of Infectious and Tropical Diseases.

BACKGROUND: Antibiotic prophylaxis of patients believed to be at a risk of developing infective endocarditis has been recently revisited with limited indications compared with the previous body of knowledge in use by the medical community. As a consequence, most of the healthcare specialists in cardiology and infectious diseases have doubts related to the enormous change that has been proposed. In this study, we report the results of an Italian consensus of experts in cardiology and infectious diseases, with the aim to offer a national document that illustrates the reasons for such a change through the review of the basis of infective endocarditis prophylaxis, the historical background, and the reasons for the change, providing practical conclusions and illustrating grey areas. METHODS: The main guidelines published on the topic of antibiotic prophylaxis for infective endocarditis were discussed as well as the risk of anaphylaxis. Overall, the group agreed that the evidence for prophylaxis is weak and limited to few case-control studies, expert opinion, clinical experience, and descriptive studies. RESULTS: The 'downgrading' of the indications for prophylaxis is mainly due to a cultural change and a more critical attitude towards available published data. Although the group acknowledge the critical view of the previously published guidelines, it seems to be more practical to consider the issue of prophylaxis without the evidence required by guidelines but rather as a consensus document based on the available data. CONCLUSION: Contemporary guidelines on infective endocarditis prophylaxis challenge previous recommendations based on a low level of evidence. The main recommendation of the study group is to underline that prophylaxis may often be based on adequate education without the administration of antibiotics, which only remains suggested, following the usual practice, in patients with heart diseases, when the risk of a complicated prognosis following infective endocarditis may be anticipated.

Role of hepatitis C virus (HCV) viremia and HCV genotype in the immune recovery from highly active antiretroviral therapy in a cohort of antiretroviral-naive HIV-infected individuals.

BACKGROUND: The roles of hepatitis C virus (HCV) viremia and HCV genotype in the immune response to highly active antiretroviral therapy (HAART) are poorly understood. Our aim was to assess the CD4+ cell count recovery after HAART in human immunodeficiency virus (HIV)-infected patients with HCV viremia and HIV-infected patients who tested negative for HCV antibody (HCV-Ab). We also aimed to assess whether the response to HAART in these patients varied according to HCV genotype. METHODS: The analysis focused on 1219 HCV-Ab-negative patients and 284 HCV-viremic patients from a cohort of HIV-infected subjects that includes persons who were antiretroviral naive before initiating HAART after cohort enrollment. HCV RNA load and HCV genotype were determined in plasma specimens obtained and stored during the 6-month period preceding the initiation of HAART. RESULTS: The chance of achieving a CD4+ cell count increase of > or = 100 cells/microL from the pre-HAART level tended to be poorer in HCV-viremic patients than in patients who tested negative for HCV-Ab (adjusted relative hazard [RH], 0.82; 95% confidence interval [CI], 0.66-1.01; P = .06). In contrast, a comparison of patients who had a HCV RNA load >1 x 10(6) IU/mL with patients who had a HCV RNA load of 5-1 x 10(6) IU/mL revealed no significant association between HCV RNA load and achievement of an increased CD4+ cell count (adjusted RH, 0.97; 95% CI, 0.75-1.27; P = .83). There was no clear association between HCV genotype and the probability of achieving a CD4+ cell count increase. CONCLUSIONS: An association between the presence of HCV-Ab and immune reconstitution after HAART has been shown elsewhere. Results of our large, prospective study support a direct role of HCV viremia in the CD4+ cell count response to HAART. Moreover, our results underline the fact that, in individuals coinfected with HIV and HCV, the goal of treating HCV infection is to eradicate HCV, to both slow the rate of HCV progression and limit potential interference with the response to HAART.

Access to antiretroviral treatment, incidence of sustained therapy interruptions, and risk of clinical events according to sex: evidence from the I.Co.N.A. Study.

Objectives of the study were to assess the differences between sexes in the likelihood of starting antiretroviral therapy (ART), in rates of sustained discontinuation from highly active antiretroviral therapy (HAART), and in clinical progression. In a multicenter cohort study (I.Co.N.A. Study), 2323 men and 1335 women previously naive to antiretrovirals were enrolled. As of September 2002, 807 women and 1480 men started ART. The median time to starting ART was 28 weeks for women and 17 weeks for men (P = 0.0003 by log-rank test). This difference was no longer significant after adjusting for either HIV RNA (P = 0.21) or CD4 count (P = 0.28) at enrollment. Women tend to start HAART less frequently than mono/dual ART after adjusting for potential confounders (odds ratio = 0.78, 95% confidence interval [CI]: 0.60-1.01; P = 0.06). Women who started HAART were 1.4 times more likely than men (95% CI: 1.00-1.99; P = 0.05) to interrupt at least 1 drug because of toxicity. Twenty-one percent of women and 19% of men interrupted HAART altogether for more than 3 months (P = 0.3). Clinical progression was observed in 53 women (22.6%) and 137 men (23.4%; P = 0.56). Risk of developing a clinical event was found to be no different between women and men (relative hazard = 0.84, 95% CI: 0.56-1.26; P = 0.40).