Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.

Diagnostic role of internal mammary lymph node involvement in tuberculous pleurisy: a multicenter study.

BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Vascular Complications following Isolated Limb Perfusion for Local Recurrence of Extremity Melanoma: A Case Report and Literature Review.

Introduction. To evaluate the role of hyperthermic isolated limb perfusion (HILP) in arterial thrombosis following melanoma-soft tissue sarcoma chemotherapy. Report. Here is presented one case of iliac-common femoral artery subacute thrombosis and a review of the appropriate literature performed using a MEDLINE search. Acute/subacute arterial occlusion is one of the most feared vascular complications of HILP, located nearly always in the external iliac-femoral artery axis, being those vessels cannulated for perfusion. Conclusions. The small number of reported cases indicates either the rarity of this complication or unawareness of its existence. The true incidence of this complication is probably underreported.

Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: predictors of virological response and drug resistance evolution in a multi-cohort study.

BACKGROUND: In treatment-naïve patients, a combination antiretroviral therapy (cART) containing tenofovir (TDF) and abacavir (ABC) with lamivudine leads to unacceptably high virological failure rates with frequent selection of reverse transcriptase mutations M184V and K65R. We explored the efficacy of at least 16 weeks of ABC + TDF-containing cART regimens in 307 antiretroviral-experienced HIV-1-infected individuals included in observational databases. METHODS: Virological failure was defined as an HIV RNA > 400 copies/ml after at least 16 weeks of treatment. Patients had received a median of three prior cART regimens. Of these, 76% concomitantly received a potent or high genetic barrier regimen (with at least one protease inhibitor [PI]) or non-nucleoside reverse transcriptase inhibitor or thymidine analogue) while a third non-thymidine nucleoside analogue was used in the remaining patients. RESULTS: The 1-year estimated probability of virological failure was 34% in 165 patients with HIV RNA > 400 copies/ ml at ABC + TDF regimen initiation. Independent predictors of virological failure were the absence of a potent or high genetic barrier cART, the higher number of cART regimens experienced, and the use of a new drug class. In the subset of 136 patients for whom there were genotypic resistance test results prior to ABC + TDF initiation, the virological failure (1-year estimated probability 46%) was independently predicted by the higher baseline viral load, the concomitant use of boosted PI, and the presence of reverse transcriptase mutation M41L. In 142 patients starting ABC + TDF therapy with HIV RNA pound < or =400 copies/ml, virological failure (1-year estimated probability 17%) was associated only with the transmission category. In a small subset of subjects for whom there were an available paired baseline and follow-up genotype (n = 28), the prevalence of most nucleoside analogue reverse transcriptase inhibitor resistance mutations decreased, suggesting a possible low adherence to treatment. No selection of K65R was detected. CONCLUSION: The virological response to ABC + TDF-containing regimens in this moderately-to-heavily treatment experienced cohort was good. Higher viral load and the presence of M41L at baseline were associated with worse virological responses, while the concomitant prescription of drugs enhancing the genetic barrier of the regimen conveyed a reduced risk of virological failure. The Appendix provides the names of other members of the MASTER cohort.

Prevalence of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy: evolution over 12 years and predictors.

OBJECTIVES: Transmitted HIV-1 drug resistance (TDR) can reduce the efficacy of first-line antiretroviral therapy. PATIENTS AND METHODS: A retrospective analysis was performed to assess the prevalence and correlates of TDR in Italy over time. TDR was defined as the presence of at least one of the mutations present in the surveillance drug resistance mutation (SDRM) list. RESULTS: Among 1690 antiretroviral therapy-naive patients, the most frequent HIV subtypes were B (78.8%), CRF02_AG (5.6%) and C (3.6%). Overall, TDR was 15%. TDR was 17.3% in subtype B and 7.0% in non-B carriers (P < 0.001). TDR showed a slight, although not significant, decline (from 16.3% in 1996-2001 to 13.4% in 2006-07, P = 0.15); TDR declined for nucleoside reverse transcriptase inhibitors (from 13.1% to 8.2%, P = 0.003) but remained stable for protease inhibitors (from 3.7% to 2.5%, P = 0.12) and non-nucleoside reverse transcriptase inhibitors (from 3.7% to 5.8%). TDR to any drug was stable in B subtype and showed a decline trend in non-B. In multivariable analysis, F1 subtype or any non-B subtype, compared with B subtype, and higher HIV RNA were independent predictors of reduced odds of TDR. CONCLUSIONS: Prevalence of TDR to nucleoside reverse transcriptase inhibitors seems to have declined in Italy over time. Increased prevalence of non-B subtypes partially justifies this phenomenon.

Cerebral abscess caused by Capnocytophaga spp in an immunocompetent subject: case report.

Capnocytophaga spp are Gram-negative bacteria commonly identified as oral saprophytes of humans, dogs and cats; they rarely cause invasive infections in immunocompetent subjects. This case report is about a rare case of cerebral abscess caused by Capnocytophaga spp in an immunocompetent subject who had no risk factors for Capnocytophaga invasive infections (oral alterations, traumatic or iatrogenic lesions of pharynx and/or oesophagus, recent dog bite). We also report Capnocytophaga spp naturally resistant to metronidazole, this being the cause of inefficacy of this drug usually included in empiric chemotherapy of cerebral abscess.

[Bacterial meningitis in adults: a retrospective multicentric study in Tuscany (Italy)]. / Le meningiti batteriche dell'adulto: studio retrospettivo multicentrico della Toscana.

The Infectious Diseases Unit of Lucca Hospital conducted a multicentric retrospective study to evaluate the epidemiological and clinical features of adult patients affected by bacterial meningitis attending all the Infectious Diseases Units of Tuscany (Italy) from July 1999 to June 2004. A specific questionnaire was sent to all the units to collect information about each case of bacterial meningitis occurring in patients older than sixteen. Patients with meningitis by Mycobacterium tuberculosis were excluded from the analysis. Nine out of 12 Infectious Diseases Units of Tuscany took part in the study and 197 cases were identified. Most cases of meningitis occurred during 2002 with a slight reduction in cases in subsequent years. Streptococcus pneumoniae and Neisseria meningitidis were the most frequently isolated pathogens with an increase in diagnosis from 1999 to 2004; in 23.8% of patients no pathogens were isolated, with a reduction in meningitis from unknown aetiology from 1999 to 2004. Most patients were treated with a combination of two antibiotics, and corticosteroid drugs were added to the therapy; in the group of patients treated with corticosteroid drugs invalidating complications occurred in 23% of cases and 5% of patients died. In all, 27 out of 197 subjects (13.7%) developed invalidating complications and 20 out of 197 patients (10.2%) died.

Sorptive behavior of sorgoleone in ultisol in two solvent systems and determination of its lipophilicity.

Sorgoleone (SGL) exuded by sorghum roots inhibits the development of some weeds. Due to its high hydrophobicity, it is expected that SGL presents low soil mobility and limited allelopathic activity in the field. This work aims to evaluate the sorptivity of sorgoleone in octanol-water and in soil under two solvent systems. The two solvent systems were methanol:water (60:40) (MeOH:H2O) and pure methanol (MeOH). These two solvent systems promote different conditions for SGL solubility. Treatments were arranged in a 2 x 6 factorial (solvent systems x equilibrium concentrations in the solution (EC)). For each solvent, the sorption was achieved by shaking 500 mg of soil with 10 ml of 0, 5, 10, 15, 25, 40, and 60 mg L-1 of SGL solution, during 24 h. After centrifugation, the supernatant was filtered and the SGL concentration was determined by high performance liquid chromatography (HPLC). Data of sorbed amount of SGL were submitted to variance analysis, using a hierarchic factorial model. The data of sorbed amount (x/m) and equilibrium concentration (C) were fitted to the linear (x/m = a + KdC) and to the Freundlich (x/m = KfC1/n) models. The isotherm obtained for the MeOH:H2O system presented linear shape, whereas for the MeOH system a two subsequent linear isotherm was fitted. Sorgoleone is a highly hydrophobic compound, presenting a log Kow of 6.1. The sorption of sorgoleone to the soil was very high. The organic environment stimulated the sorgoleone sorption to the soil.

Abdominal aortic aneurysm repair in octogenarians: outcomes and predictors.

OBJECTIVES: This study was undertaken to evaluate predictors and outcomes of octogenarians who underwent abdominal aortic aneurysm repair. DESIGN: A prospective observational study. MATERIALS AND METHODS: Between January 1st, 1997 and April 15th, 2005, 31 octogenarians were admitted to our Department with the diagnosis of abdominal aortic aneurysm. Mean follow-up time was 53.7+/-27.2 months. All patients were in good clinical condition and represented a selected healthy group of octogenarians. RESULTS: The overall perioperative (30-days) mortality rate was 3.1%. The total in-hospital morbidity rate was 22.6%. Overall survival estimates at 48 and 96 months were 81+/-8% and 46+/-21%, respectively. The actuarial freedom from aneurysm-related death at 48 and 96 months was 96+/-4% and 96+/-4%, respectively. The actuarial freedom from aneurysm-unrelated death at 48 and 96 months was 84+/-7% and 48+/-21%. Only coronary artery disease was a significant predictor of survival using multivariate stepwise logistic regression analysis. CONCLUSIONS: In this series, AAA surgery was carried out in selected octogenarians without affecting long-term survival.

Prevalence of tuberculosis infection among teen-agers in Tuscany.

INTRODUCTION: In Tuscany, Tuberculosis incidence is more than triplicate from 1982 to the beginning of the third millennium. The impact of this trend on open population is not known, as updated studies on Tuberculosis prevalence are not available. Tuberculin skin test provides the currently most widely used tool for assessing Tuberculosis transmission in a community and the prevalence of infection as well. The objective of this investigation was the evaluation of tuberculin index by means of the Mantoux test in adolescents eighteen-years old. RESULTS: The study was carried out in 21 secondary schools of Siena and its Province; 1,138 students participated to this survey. The overall prevalence of subjects with a skin reaction size > 5 mm was 1.6%; if the standard cut-off of 10 mm was used, the overall prevalence of a positive skin reaction was 0.4%. Risk factors for a doubtful or positive reaction were previous immunization with BCG and migration from high-endemicity countries. DISCUSSION: In Italy, studies on tuberculin index in young adults are scanty and controversial: our results show a very low Tuberculosis prevalence and an epidemiological pattern typical of countries with low Tuberculosis endemicity. CONCLUSIONS: The slightly increase in Tuberculosis incidence has no impact on the prevalence of latent Tuberculosis infection on our geographical area. We conclude that skin-test screening for Tuberculosis should be addressed to high risk population as migrants from Countries reporting high transmission rate, those recently exposed to an infectious case and health-workers.

HIV infection in dialysis centers in Italy: a nationwide multicenter study.

The prevalence of HIV infection in dialysis populations varies according to different countries and geographic areas. We performed a nationwide epidemiological study by means of a questionnaire in the period from January 1990 to December 1995. Questions were about whether and which HIV tests were performed and which preventive measures were adopted. A separate survey evaluated the data the HIV-positive patients. Only 62% of the centers responded to the questionnaire, corresponding to 21,500 dialysis patients in 1990 and 27,000 in 1995. The prevalence of HIV-positive subjects was 0,13% for 1995. A total of 48 patients with HIV infection were identified: risk factors were drug abuse in 16 cases, homosexuality in 9, heterosexual contact in 8, transfusion in 7, renal transplant in 3 and unknown cause in 5. Forty-five patients were on hemodialysis, and 3 were receiving peritoneal dialysis. At follow-up, 19 patients died: infection and malnutrition were the most frequent causes of death. The death rate of patients who were already HIV positive when dialysis was started (group 1, 29 cases) was 19.36 deaths/1,000 patient/month. The correlations, performed only for group 1, showed a significantly worse prognosis for patients with CD4 < 200/mm3 and for those with AIDS. In conclusion, in Italy the prevalence of HIV infection in the dialysis population is low, and the outcome of HIV-positive patients in dialysis was found to be better than earlier literature reports. The use of chronic dialysis for HIV patients with uremia should not be discouraged.

Reduced blood levels of coagulation inhibitors in chronic hemodialysis compared with CAPD.

The aim of this study was to measure the coagulation inhibitors in two groups of uremic patients treated with hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) to evaluate the differences in anticoagulant activity. In 20 patients on HD and 20 on CAPD, mean age 66 +/- 8 and 58 +/- 14 years, respectively, the following parameters were determined between dialysis exchanges: protein C (PC), protein S (PS), antithrombin III (AT III), electrophoresis, prothrombin activation fragment (F1+2), alpha 1 antitripsin (alpha 1 AT), prothrombin time (PT), and activated partial thromboplastin time (PTT). The mean values of PC, PS, and AT III were respectively, 95.7 +/- 16 on HD and 92 +/- 23 on CAPD; 82.2 +/- 13.6 on HD and 90.5 +/- 13.6 on CAPD; the mean value F1+2 was 1.2 +/- 0.5 on HD and 1.04 +/- 0.5 on CAPD (p < 0.05). A good correlation between PS and AT III% functional activity (p < 0.03, r = 0.5) in both groups was found. More-over, PS functional activity was inversely correlated with duration of dialysis (p < 0.05, r = -0.3). HD patients showed a reduction of coagulation inhibitors compared with CAPD patients. Such a phenomenon could justify the increased thrombotic risk in HD patients. Since 80% of those on HD and only 20% of those on CAPD received erythropoietin (EPO), the prothrombotic state in HD could be due to reduced PS activity secondary to EPO treatment.

[Varices of the external saphenous vein]. / Les varices de la saphène externe.

The author indicates the importance in varicose veins of involvement of the external saphenous, making clear the distinction between sapheno-popliteal ostial insufficiency without varices and venous insufficiency with varices. He recommends a surgical approach determined on the basis of good clinical examination and appropriate supplementary examinations: such surgery should always be followed by sclerotherapy.

[Prevention and treatment of edema due to arterial revascularization]. / Prevenzione e trattamento dell'edema da rivascolarizzazione arteriosa

Mean daily doses of 4-800,000 units iant. Cal. Trasylol administered i.v. for about 7 days prevented oedema and improved circulation after revascularisation surgery of the lower extremities involving the femoropopliteal axis in a large number of clinical cases.