Effectiveness and safety of daptomycin in patients with infective endocarditis undergoing heart valve replacement: a subgroup analysis from real-world data.

BACKGROUND: European Cubicin® Outcomes Registry and Experience (EU-CORE) was a retrospective, non-interventional, multicenter registry that collected real-world clinical outcomes following daptomycin use for the treatment of Gram-positive infections. EU-CORE data from patients with infective endocarditis (IE) who underwent heart valve replacement were analysed. METHODS: Clinical outcomes were assessed as success (cured or improved), failure, or non-evaluable. Adverse events (AEs) were recorded for up to 30 days after daptomycin treatment. RESULTS: Of 610 patients with IE, 198 [32.5%; left-sided IE (LIE), 166 (83.8%); right-sided IE (RIE), 21 (10.6%); both LIE and RIE, 11 (5.6%)] underwent heart valve replacement. Other than cardiovascular disease, renal disease (18.2%), sepsis (16.2%), and diabetes mellitus (15.2%) were the most significant underlying diseases. Major pathogens in patients with positive culture results (68.0%) were Staphylococcus aureus [36.8%; methicillin-resistant S. aureus (MRSA), 12.8%] and coagulase-negative staphylococci (CoNS; 31.6%). Daptomycin treatment [median duration (range), 21 days (1-112)] resulted in high clinical success in patients with S. aureus (88.4%; MRSA, 80.0%) and CoNS (81.1%) infections, with an overall success rate of 83.3%. Clinical success rate was high (90.0%) in patients who received daptomycin dose >6 mg/kg/day. Overall clinical success rate in patients followed for up to 2 years was 90.7%. AEs and serious AEs possibly related to daptomycin were reported in 6 (3.0%) and 4 (2.0%) patients, respectively. CONCLUSIONS: Daptomycin treatment was effective and well tolerated with a sustained response in patients with IE who underwent heart valve surgery. A trend towards better clinical outcomes was observed with higher daptomycin doses.

Clinical Experience with Daptomycin for the Treatment of Gram-positive Infections in Children and Adolescents.

BACKGROUND: This subgroup analysis of the European Cubicin Outcomes Registry Experience evaluated the safety and effectiveness of daptomycin in children and adolescent patients (<18 years). METHODS: Clinical outcomes at the end of therapy were assessed as success (cured or improved), failure or nonevaluable. Safety was assessed for up to 30 days post treatment. RESULTS: Eighty-one children and adolescent patients were included in this study. The most common primary infections were bacteremia (19.8%), complicated skin and soft-tissue infection (18.5%), osteomyelitis (13.6%), endocarditis (12.3%), foreign body/prosthetic infection (12.3%), uncomplicated skin and soft-tissue infection (9.9%) and other (13.6%). Daptomycin doses ranged from 4 to >10 mg/kg/day. Median duration of therapy was 12.5 (interquartile range, 7-25; mean, 16.7; standard deviation, 12.8) days. Staphylococcus aureus (46.7%) was the most commonly isolated pathogen (23.8% methicillin-resistant S. aureus). Forty-nine (60.5%) patients completed daptomycin therapy without further antibiotics, 27 (33.3%) switched to another antibiotic, 4 (4.9%) discontinued because of adverse events (AEs) and 1 (1.2%) discontinued because of other reason. Overall, 75 (92.6%; 95% confidence interval: 95.2-100.0%) patients achieved clinical success; 39 of 41 (95.1%) patients receiving daptomycin monotherapy and 36 of 40 (90.0%) patients receiving concomitant antibiotics. Six (7.4%) patients reported AEs, including 1 patient with increased blood creatine phosphokinase. Three (3.7%) patients had serious AEs; 1 (1.2%) had a serious AE possibly related to daptomycin. CONCLUSION: Daptomycin, alone or combined with other antibiotics and/or surgery, demonstrated high clinical success rates against a wide variety of infections and was well tolerated in children and adolescents.

Current features of infective endocarditis in persons on hemodialysis: a prevalence study with case control design from the prospective multicenter SEI cohort.

PURPOSE: Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD. METHODS: This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed. RESULTS: HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p < 0.002). Cardiac surgery was performed in 38 % of HD patients and 36.5 % of no-HD patients (p = 0.856). Complications were similar and in-hospital mortality did not differ significantly (26.2 % in HD vs 15.9 % in no-HD; p = 0.168). CONCLUSIONS: IE in persons on HD is characterized by distinctive clinical features, including a higher prevalence of some important comorbidities. Inconsistent with prior studies, we could not confirm a higher rate of complications and mortality in HD patients with IE.

Clinico-pathological significance of hepatitis C virus core antigen levels in chronic infection.

Hepatitis C virus core antigen (HCVcoreAg) may be measured in serum with a sensitive, recently validated assay. Beyond its value as a marker of viral infection, there are little data on its relation with clinical, histological, and virological parameters. In this study, the significance of HCVcoreAg levels was studied in a prospective cohort of 114 patients with chronic hepatitis C. HCVcoreAg was measured by a commercial chemiluminescent microparticle immunoassay. Clinical and virological data included quantitative HCV-RNA, HCV genotype, ALT, GGT, IL28B rs12979860 polymorphism as well as liver histology parameters. HCVcoreAg levels were correlated significantly with HCV-RNA (r=0.56; P<0.0001) but also with ALT levels (r=0.258; P<0.01) and liver necroinflammatory activity (r=0.205; P<0.04). Patients harbouring HCV genotype 3 showed lower levels of HCVcoreAg than both genotype 1 and two patients. In genotype 3, a direct correlation between steatosis and HCVcoreAg was found. Levels of HCVcoreAg also varied according to the IL28B genotype. These data suggest that the evaluation of HCVcoreAg serum levels may provide relevant data for the baseline clinical evaluation of chronic hepatitis C patients. HCVcoreAg serum levels may be a useful tool to further the understanding of chronic hepatitis C pathobiology.

Adefovir treatment for chronic hepatitis B in heart transplant recipients.

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice-monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV-DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild-to-moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV-DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV-DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine-resistant chronic hepatitis B.

Daptomycin for the treatment of infective endocarditis: results from a European registry.

OBJECTIVES: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. PATIENTS AND METHODS: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. RESULTS: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. CONCLUSIONS: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.

Association between valvular surgery and mortality among patients with infective endocarditis complicated by heart failure.

CONTEXT: Heart failure (HF) is the most common complication of infective endocarditis. However, clinical characteristics of HF in patients with infective endocarditis, use of surgical therapy, and their associations with patient outcome are not well described. OBJECTIVES: To determine the clinical, echocardiographic, and microbiological variables associated with HF in patients with definite infective endocarditis and to examine variables independently associated with in-hospital and 1-year mortality for patients with infective endocarditis and HF, including the use and association of surgery with outcome. DESIGN, SETTING, AND PATIENTS: The International Collaboration on Endocarditis-Prospective Cohort Study, a prospective, multicenter study enrolling 4166 patients with definite native- or prosthetic-valve infective endocarditis from 61 centers in 28 countries between June 2000 and December 2006. MAIN OUTCOME MEASURES: In-hospital and 1-year mortality. RESULTS: Of 4075 patients with infective endocarditis and known HF status enrolled, 1359 (33.4% [95% CI, 31.9%-34.8%]) had HF, and 906 (66.7% [95% CI, 64.2%-69.2%]) were classified as having New York Heart Association class III or IV symptom status. Within the subset with HF, 839 (61.7% [95% CI, 59.2%-64.3%]) underwent valvular surgery during the index hospitalization. In-hospital mortality was 29.7% (95% CI, 27.2%-32.1%) for the entire HF cohort, with lower mortality observed in patients undergoing valvular surgery compared with medical therapy alone (20.6% [95% CI, 17.9%-23.4%] vs 44.8% [95% CI, 40.4%-49.0%], respectively; P < .001). One-year mortality was 29.1% (95% CI, 26.0%-32.2%) in patients undergoing valvular surgery vs 58.4% (95% CI, 54.1%-62.6%) in those not undergoing surgery (P < .001). Cox proportional hazards modeling with propensity score adjustment for surgery showed that advanced age, diabetes mellitus, health care-associated infection, causative microorganism (Staphylococcus aureus or fungi), severe HF (New York Heart Association class III or IV), stroke, and paravalvular complications were independently associated with 1-year mortality, whereas valvular surgery during the initial hospitalization was associated with lower mortality. CONCLUSION: In this cohort of patients with infective endocarditis complicated by HF, severity of HF was strongly associated with surgical therapy and subsequent mortality, whereas valvular surgery was associated with lower in-hospital and 1-year mortality.

Long-term outcome of hepatitis B and hepatitis C virus co-infection and single HBV infection acquired in youth.

Co-infection with HBV and HCV seems to be associated with more severe liver disease in retrospective and cross-sectional studies in adults, but no data are available when co-infection is acquired in youth. The long-term outcome of infection acquired in youth was assessed in patients co-infected with HBV and HCV and in patients with HBV infection only. Twenty-seven patients with HBV and HCV co-infection and 27 patients infected with HBV only were enrolled. Seventy-six per cent of the patients were treated with alpha-interferon for 1 year. After a median follow-up of 23 years, the annual progression rate of fibrosis was 0.07 in patients co-infected with HBV and HCV, and in those infected with HBV it was 0.07 and 0.11 (P < 0.004) for HBe and anti-HBe-positive patients, respectively. In co-infected patients, the development of cirrhosis was observed in 2 (7.4%) and of hepatocellular carcinoma (HCC) in 1 (3.7%), while in those with HBV, cirrhosis appeared in one patient (3.7%). Alcohol intake (OR = 9.5 +/- 1.2; 95% CI = 6.6-13.9; P < 0.0001) was independently associated with cirrhosis and HCC. alpha-interferon showed no efficacy during treatment, but the treated group showed higher HCV RNA clearance during post-treatment follow-up. Co-infection with HBV and HCV and single HBV infection acquired in youth showed a low rate of progression to liver fibrosis, no liver failure, and low development of HCC during a median follow-up of 23 years (range 17-40).

[Novel clinical and epidemiologic trends in elderly infective endocarditis]. / Endocardite infettiva nell'anziano: nuovi aspetti epidemiologici e clinici.

The age of peak incidence of infective endocarditis (IE) has shifted from 45 years in the 50's to 70 years at the present time. Elderly persons carry a five times higher risk of IE than the general adult population. Factors accounting for this phenomenon include increased use of invasive procedures and implanted medical devices as well as a higher prevalence of degenerative valve disease. In the elderly, IE onset may be insidious, often masked by one or more underlying conditions such as cancer, diabetes and chronic organ failure, hence the diagnosis may be delayed. The leading pathogen is Staphylococcus aureus, more frequently methicillin-resistant, although Streptococcus bovis and enterococci are gaining prevalence. Vascular phenomena and embolic events are less common in the elderly, probably due to a lessened acute phase response and a larger use of antiplatelet and anticoagulant drugs. Because of diminished renal clearance, antibiotics should be carefully titrated in aged IE patients. Cardiac surgery is performed less often in elderly IE due to poor preoperative conditions. Indeed, both these factors may account for the higher mortality rate, that is twice that of younger IE patients. Notwithstanding, age > or = 65 years has been found to be an independent predictor of mortality. Prophylactic measures residing mostly on the prevention of health-care associated acquisition need to be more widely implemented in this growing subgroup of IE patients.

Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study.

BACKGROUND: We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. METHODS: Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. RESULTS: The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. CONCLUSIONS: In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study.

BACKGROUND: Elderly patients are emerging as a population at high risk for infective endocarditis (IE). However, adequately sized prospective studies on the features of IE in elderly patients are lacking. METHODS: In this multinational, prospective, observational cohort study within the International Collaboration on Endocarditis, 2759 consecutive patients were enrolled from June 15, 2000, to December 1, 2005; 1056 patients with IE 65 years or older were compared with 1703 patients younger than 65 years. Risk factors, predisposing conditions, origin, clinical features, course, and outcome of IE were comprehensively analyzed. RESULTS: Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance. Streptococcus bovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P < .001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P < .001), and age older than 65 years was an independent predictor of mortality. CONCLUSIONS: In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care-associated acquisition and improve outcomes in this major subgroup of patients with IE.

Infection of intravascular prostheses: how to treat other than surgery.

Long-term antimicrobial therapy may be effective in some patients with intravascular prosthesis infection. However, this approach does not represent an alternative to surgery when this is feasible, but is merely the best opportunity for patients too ill to tolerate a re-intervention. Prosthetic valve endocarditis may be treated with antibiotic therapy alone in selected patients who are haemodynamically stable with non-staphylococcal infections and no para-valvular complications. In contrast, infections of pacemaker leads or other implantable cardiac devices require complete hardware removal, as infection recurrence always occurs, even after a seemingly effective initial treatment. Attempts to treat conservatively infections of abdominal aortic grafts can be successful in a few cases, provided the patient is stable, the pathogen has been identified, and antibiotic susceptibility has been demonstrated. Treatment requires at least 4-6 weeks and may be followed by a sequential oral regimen once the acute phase of the infection has subsided. The correct duration of this treatment is often unknown and relapses are common after treatment withdrawal. The availability of novel antibacterial and antifungal agents - showing fast microbicidal activity that includes biofilm micro-organisms - such as daptomycin and caspofungin, or having a wide antimicrobial spectrum, such as tigecycline, may increase the probability of long-standing suppression or even eradication of the infection in these particular subsets of inoperable patients. However, so far, very little experience is available on the efficacy and tolerability of these drugs in intravascular prosthesis infections. Controlled studies are lacking and difficult to plan. Well-designed prospective studies may help to establish guidelines and reach a multidisciplinary consensus on the optimal therapeutic approach, and are therefore awaited.

Efficacy of caspofungin addition to trimethoprim-sulfamethoxazole treatment for severe pneumocystis pneumonia in solid organ transplant recipients.

BACKGROUND: Pneumocystis jiroveci pneumonia may be a life-threatening opportunistic infection in immunosuppressed solid organ transplant recipients. Despite effective treatment with high-dose trimethoprim-sulfamethoxazole and steroids, morbidity is often severe and lethality remains high. New therapeutic approaches are therefore warranted. Caspofungin, a beta-1,3-glucan synthesis inhibitor, has shown activity against the cyst forms of P. jiroveci in experimental animal models. We here report our preliminary clinical experience with caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen. METHODS: Four solid organ transplant patients with severe hypoxemic P. jiroveci pneumonia were treated with the combination of trimethoprim-sulfametoxazole and caspofungin. In two cases, caspofungin was added as salvage treatment due to failure of trimethoprim-sulfametoxazole monotherapy. RESULTS: In these four patients, the use of caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen led to a rapid improvement and a complete cure of pneumonia. No side effects or drug interactions were observed. DISCUSSION: This preliminary clinical experience suggests that the addition of caspofungin to trimethoprim-sulfamethoxazole, which is active against trophic forms, may provide a synergistic activity against P. jiroveci by fully inhibiting the organism life cycle.

Anti-envelope 1 and 2 immune response in chronic hepatitis C patients: effects of hepatitis B virus co-infection and interferon treatment.

Antibodies against envelope glycoprotein 1 and 2 (anti-E1/E2) have been suggested to influence HCV replication levels. Hepatitis B virus (HBV) may interfere with hepatitis C virus (HCV) replication. At present there are no data on anti-E1/E2 antibody responses or on the effect of interferon (IFN) treatment in HBV-HCV co-infection. Accordingly, we evaluated serum anti-E1/E2 antibodies in 50 patients (median age, 26.5; males, 30) with chronic hepatitis, 38 with HCV and 12 with HBV-HCV co-infection, who had undergone alpha-IFN treatment. Before starting IFN, the HCV group showed higher HCV-RNA levels (bDNA assay) than the HBV-HCV group (median 3.75 vs. 0.64 x 10(6) Eq/ml, respectively; P < 0.05). Similarly, the anti-E2 levels (EIA assay) were higher in the HCV group than in the HBV-HCV (mean +/- SD, 53.8 +/- 54.58 vs. 24.5 +/- 41.50 U/ml, respectively; P < 0.02), and the prevalence of anti-E2 was also higher in the HCV group (94 vs. 58%, respectively; P < 0.007). No correlation was found between anti-E1/E2 antibodies and the HCV-RNA levels. The prevalence of E1/E2 antibodies was similar in the different HCV genotypes. Higher baseline levels of anti-E2 antibodies and a decrease or disappearance of anti-E2 antibodies during IFN were associated with IFN sustained response in both groups, whereas no reduction in the anti-E1/E2 levels was observed in non-responders. The data show that HBV co-infection influences both HCV replication and the anti-E1/E2 antibody production. High pre-treatment levels of anti-E2 antibodies and their decrease or disappearance during interferon treatment are often associated with HCV clearance in sustained responders, irrespective of the HCV genotype.

Endocarditis abscess of the aortic annulus involving the left ventricular inferior wall and causing a moderate aortic systolic obstruction: diagnosis by transthoracic and transesophageal echocardiography.

Abscesses are an important and potentially devastating complication of aortic valve endocarditis. The extension of the infectious process from the aortic valve to surrounding tissue can occur in different directions. This case report describes a 28-year-old man in whom the abscess of the aortic annulus was very large, causing a moderate aortic systolic obstruction, and also involved the left ventricular inferior wall. The diagnosis was provided by a combination of TTE and TEE examination and was confirmed by cardiac surgery.

Treatment of recurrent staphylococcal mediastinitis: still a controversial issue.

BACKGROUND: Although surgical management with early debridement and closed mediastinal irrigation has proved successful in reducing early mortality following poststernotomy deep sternal wound infection, recurrence rates are still up to 20%. This study compared the effectiveness and safety of wound dressing with granulated sugar versus early muscle flap surgery in the management of recurrent postoperative Staphylococcal mediastinitis. METHODS: Between January 1995 and January 2002, 25 patients with severe recurrent staphylococcal mediastinitis were treated with granulated sugar wound dressing (group A) or with wound debridement, v-shape sternectomy and associated muscle flap surgery (group B). Clinical outcomes and perioperative data were analyzed. Outcomes were compared between the groups evaluating the length of time for normalization of white blood cell (WBC) count and of body temperature and length of hospital stay. Patient characteristics determining best treatment option were identified. Survival and incidence of recurrence at follow-up were also analyzed. RESULTS: Study groups proved homogenous as to preoperative characteristics. Complete cure was achieved earlier in group A than in group B (defervescence: p = 0.0005; WBC normalization: p = 0.0001, respectively). Hospital stay was shorter in group A. A statistically significant difference was found in hospital mortality (16% overall) between the two groups with better outcomes in group A (p = 0.039). In the patient subset with the most severe preoperative profile (hemodialysis, tracheostomy, inotropic support) surgical treatment produced worse results than the sugar dressing method (p 0.048). No case of recurrence was observed. CONCLUSIONS: Both treatments proved effective in recurrent type IV A Staphylococcal mediastinitis. Granulated sugar proved a safer option in severely compromised patients.

Core promoter mutations 3 years after anti-hepatitis B e seroconversion in patients with chronic hepatitis B or hepatitis B and C infection and cancer remission.

OBJECTIVES: In this study, we aimed to evaluate the persistence of hepatitis B virus (HBV) DNA and the role of HBV core promoter and precore region mutations in 28 young cancer survivor patients with HBV or HBV and hepatitis C virus (HCV) infections, and persistently normal ALT levels, after spontaneous or interferon (IFN)-induced anti-hepatitis B e (HBe) seroconversion. METHODS: Sera from 15 patients with HBV and 13 with dual HBV-HCV infection were analyzed for the presence of HBV-DNA and HCV-RNA by polymerase chain reaction 3 yr after anti-HBe seroconversion. A total of 21 patients had seroconverted spontaneously and seven did so after IFN treatment. The core promoter and the precore regions were amplified sequenced directly. RESULTS: Among patients with HBV infection, HBV-DNA was detected in five of nine (55%) with spontaneous anti-HBe and in all six treated patients (p = 0.092). In the coinfected patients, four had cleared both HBV-DNA and HCV-RNA, five were HBV-DNA negative/HCV-RNA positive and four had the reverse viral pattern. Among the 15 patients with persistence of HBV-DNA, a 7-base pair nucleotide deletion in the core promoter (1757-1763) was present in seven of 10 patients with spontaneous and in one of five patients with IFN-induced seroconversion (p = 0.033). The G1896A precore stop codon mutation was never observed. HBV-DNA levels were significantly lower in patients with the core promoter deletion (p = 0.011). The 7-base pair deletion generated a truncated X protein at amino-acid position 132. CONCLUSIONS: A core promoter deletion after anti-HBe seroconversion was associated with low HBV-DNA levels, probably because of downregulation of pregenomic RNA production and truncation of the X protein. HBV-DNA persistence was a frequent event, even in the absence of active liver disease.