Infective endocarditis in patients with hepatic diseases.

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD- patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD- patients (p = 0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p < 0.001); embolization (43.3 % versus 26.1 %, p < 0.001) and congestive heart failure (42 % versus 34.1 %, p = 0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD- and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.

Efficacy and safety of tenofovir, entecavir, and telbivudine for chronic hepatitis B in heart transplant recipients.

BACKGROUND: Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. METHODS: In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. RESULTS: Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate (GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF (n = 9) or LdT (n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed. CONCLUSIONS: This study indicates that newer antivirals are effective and safe in HTR with CHB.

Management of immunosuppression and antiviral treatment before and after heart transplant for HIV-associated dilated cardiomyopathy.

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.

Primary sclerosing cholangitis in patient with celiac disease complicated by cholecystic empyema and acute pancreatitis.

BACKGROUND: The association of celiac disease and sclerosing cholangitis is a well known, although unusual, pathologic feature of autoimmunity. METHODS: A 64 year old patient presenting with sub-acute cholangitis and pancreatitis, treated with cholecystectomy and endoscopic sphincterotomy. The post-operative course, complicated by cholestatic jaundice, and subsequent clinical complications are described, showing how the diagnosis of sclerosing cholangitis was outlined after the Endoscopic Retrograde Cholangio-Pancreatography (ERCP) and confirmed by liver biopsy. Long term treatment with Ursodeoxycholic acid has gradually normalized bilirubin values, while cholestasis enzymes are gradually decreasing. After 18 months bleeding from oesophageal varices ensued, which was controlled through endoscopic ligation. CONCLUSIONS: The diagnosis of primary sclerosing cholangitis should be taken into account when cholangitis is associated with other immunity derangements and segmentary dilatations of the intra-hepatic bile ducts, but no dilatation of the main bile duct is noticed at imaging or endoscopy. Recovery of hepatic function should be always attempted before bringing the patient to surgery, in order to avoid postoperative hepatic decompensation.

Epidemiology, characteristics, and outcome of infective endocarditis in Italy: the Italian Study on Endocarditis.

BACKGROUND: The characteristics of patients with infective endocarditis (IE) vary significantly by region of the world. The aim of this study was to evaluate the contemporary epidemiology, characteristics, and outcome of IE in a large, nationwide cohort of Italian patients. METHODS: We conducted a prospective, observational study at 24 medical centers in Italy, including all the consecutive patients with a definite or possible diagnosis of IE (modified Duke criteria) admitted from January 2004 through December 2009. A number of clinical variables were collected through an electronic case report form and analyzed to comprehensively delineate the features of IE. We report the data on patients with definite IE. RESULTS: A total of 1,082 patients with definite IE were included. Of these, 753 (69.6%) patients had infection on a native valve, 277 (25.6%) on a prosthetic valve, and 52 (4.8%) on an implantable electronic device. Overall, community-acquired (69.2%) was more common than nosocomial (6.2%) or non-nosocomial (24.6%) health care-associated IE. Staphylococcus aureus was the most common pathogen (22.0%). In-hospital mortality was 15.1%. From the multivariate analysis, congestive heart failure (CHF), stroke, prosthetic valve infection, S. aureus, and health care-associated acquisition were independently associated with increased in-hospital mortality, while surgery was associated with decreased mortality. CONCLUSIONS: The current mortality of IE remains high, and is mainly due to its complications, such as CHF and stroke.

In vitro activity of multiple antibiotic combinations against Nocardia: relationship with a short-term treatment strategy in heart transplant recipients with pulmonary nocardiosis.

BACKGROUND/OBJECTIVES: Pulmonary nocardiosis (PN) chiefly affects immunocompromised patients, particularly transplant recipients. Cotrimoxazole is still the mainstay of treatment, but it is associated with nephro- and myelo-toxicity, and can show unpredictable activity against Nocardia isolates. METHODS: Over a 20-year period, Nocardia isolates were identified from 12 heart transplant (HTx) recipients with PN. The in vitro activity of various antibacterials, alone or in combination, was assessed using disk-diffusion, minimal inhibitory concentration (MIC), and time-kill methodology. The in vitro results were compared with the clinical outcome of the patients. RESULTS: Seven different Nocardia strains were identified. Disk diffusion and MIC determinations showed that all isolates were susceptible to amikacin, netilmicin, and linezolid, and that moxifloxacin was the most active of the fluoroquinolones. All but 1 of the isolates were susceptible to imipenem. Time-kill studies showed that imipenem/amikacin and imipenem/moxifloxacin combinations were bactericidal for most isolates. Of 12 patients who received 3-4 weeks' intravenous (IV) treatment with amikacin or ciprofloxacin in combination with a beta-lactam, followed by 1-3 months' oral cotrimoxazole, moxifloxacin, or linezolid, 11 were cured; 1 patient died, but not related to Nocardia. CONCLUSION: Initial PN treatment in HTx recipients can be successfully carried out with bactericidal combinations such as imipenem plus amikacin or moxifloxacin, administered IV for 3-4 weeks. Within 1 month, a significant clinical and radiological improvement may be observed. In our experience, a <3 month oral regimen with cotrimoxazole, moxifloxacin, or doxycycline may then be used. This may allow a reduction of side effects and treatment-related burden, without any recurrence.

Yellow nail syndrome as a cause of unexplained edema.

Yellow nail syndrome is a rare cause of edema due to a disordered lymphatic drainage. We recently observed two cases of long-standing, chronic edema, whose nature could not be understood despite innumerable diagnostic procedures. The diagnosis was suspected based on an attentive clinical exam and confirmed by radionuclide lymph scan. Yellow nail syndrome has to be considered in the differential diagnosis in cases of systemic edema, as well as long standing pleural effusions, particularly in patients with bronchiectasis or sinusitis. Clues to diagnosis are the presence of dystrophic, yellowish nails, peripheral lymphedema and relapsing pleural effusions and/or ascites. Long-term control of symptoms is difficult to achieve and may benefit from the judicious use of diuretics and intravenous albumin and by topical alpha-tocopherol. Pleurodesis may be needed. Other pathologic conditions are often associated to yellow nail syndrome and should be ruled out.

[Treatment of multiresistant Gram positive endocarditis]. / La terapia delle endocarditi da Gram positivi multiresistenti.

Epidemiology of infectious endocarditis has changed in last decades, endocarditis associated to hospital practices, sustained by multiresistant pathogens being highly increased. In particular, methicillin-resistant staphylococci (MRSA), almost resistant to a number of other antimicrobial classes, often exhibit a reduced susceptibility to vancomycin (h-VISA) with MICs' values more e than 1 mg/l, leading to suppose a reduced therapeutic efficacy of this drug. Thirty-one percent of MRSA strains in the ICE study, which prospectively collected more than 5000 endocarditis, were h-VISA. Daptomycin shows a rapid bactericidal activity against both methicillin-susceptible staphylococcci (MSSA) and MRSA, included those strains with reduced susceptibility to vancomycin. Daptomycin shows a good therapeutic efficacy in staphylococcal endocarditis: MRSA 71%, MSSA 75%. These data suggest the use of daptomycin as initial therapy for treatment of staphylococcal endocarditis, independently from methcillin susceptibility. Some experimental data showed that daptomycin efficacy can diminish, if it is used as a rescue therapy after vancomycin failure. The thickness of bacterial cell-wall recognized in h-VISA strains can represent a physical and electrical barrier to reach both the vancomycin and daptomycin target site. However, the reduced efficacy of daptomycin following vancomycin exposure is an extremely rare event in the clinical practice. It is preferrable to use daptomycin as first line therapy, at a proper dosage. As far as endocarditis is concerned, recent data proved the excellent daptomycin tolerability, with dosages up to 8-10 mg/kg/die. During the treatment, CPK values must be always monitored. For endocarditis sustained by vancomycin-resistant enterococci, therapeutic choices are based on linezolid or ampicillin-ceftriaxone combination therapy. Daptomycin alone, or in association with gentamycin and rifampin, can represent a promising therapeutic alternative.

Molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter baumannii in a university hospital in Italy.

This study investigated the molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter baumannii that occurred between June 2003 and June 2004 in a tertiary-care hospital in Naples, Italy. A. baumannii was isolated from 74 patients, of whom 38 were infected and 36 were colonised. Thirty-three patients had ventilator-associated pneumonia, three had hospital-acquired pneumonia, and two had sepsis. Genotypic analysis of 45 available A. baumannii isolates revealed two distinct pulsed-field gel electrophoresis (PFGE) patterns. Of these, PFGE pattern 1 was represented by isolates from 44 patients and was identical to that of an epidemic A. baumannii clone isolated in another hospital of Naples during 2002. All A. baumannii isolates of PFGE type 1 showed identical multiresistant antibiotypes, characterised by resistance to all antimicrobial agents tested, including carbapenems, with the exception of colistin. In these isolates, inhibition of OXA enzymes by 200 mM NaCl reduced the imipenem MIC by up to four-fold. Molecular analysis of antimicrobial resistance genes showed that all A. baumannii isolates of PFGE type 1 harboured a class 1 integron containing the aacA4, orfX and bla(OXA-20) gene cassettes, an ampC gene and a bla(OXA-51)-like allele. Moreover, a bla(OXA-58)-like gene surrounded by the regulatory elements ISAba2 and ISAba3 was identified in a 30-kb plasmid from A. baumannii isolates of PFGE type 1, but not PFGE type 2. Thus, selection of a single A. baumannii clone producing an OXA-58-type carbapenem-hydrolysing oxacillinase was responsible for the increase in the number of A. baumannii infections that occurred in this hospital.

Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition.

OBJECTIVES: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). METHODS: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. RESULTS: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. CONCLUSIONS: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.

International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

OBJECTIVE: The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. METHODS: Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. RESULTS: The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. CONCLUSION: Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.

Inhaled tobramycin in children with acute bacterial rhinopharyngitis.

Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria. As topical drugs might reduce this phenomenon, the aims of our study were to evaluate inhaled tobramycin in children with acute bacterial rhinopharyngitis and to compare it with oral amoxicillin/clavulanate. The trial was conducted as randomized, parallel group and double blind. Children, aged 3-6 years, with acute bacterial rhinopharyngitis were treated with 15 mg of aerosolized tobramycin (Group A) or 50 mg/Kg of amoxicillin/clavulanate (Group B) twice daily for 10 days. The following parameters were assessed: nasal obstruction, mucopurulent rhinorrhea, post-nasal drip, adenoidal hypertrophy, tympanic inflammation, tympanogram, rhinomanometry and cultures. Of 416 patients screened, 311 children (178 females and 133 males), median age 4.5 years, completed the study: 156 in Group A and 155 in Group B. Both treatments improved all parameters (p<0.01 for all). Intergroup analysis showed that inhaled tobramycin induced a better improvement versus amoxicillin/clavulanate concerning nasal obstruction (p<0.05), adenoidal hypertrophy (p<0.01), tympanic inflammation (p<0.01), rhinomanometry (p<0.01) and cultures (p<0.05). In conclusion, inhaled tobramycin may represent a valid treatment for acute bacterial rhinopharyngitis in children, as it is effective, safe, economic and simple to use.

Superior vena cava thrombosis after intravascular AICD lead extraction: a case report.

Pacemaker lead extraction has been shown to be an effective and safe treatment in the case of infected per-manent pacemaker leads. However, it can lead to potentially serious complications, usually occurring during the ex-traction procedure. This report describes a case of a 74-year-old male with a persistent superior vena cava thrombo-sis related to an infected permanent pacemaker lead transvenous extraction. Clinical and surgical management are discussed.

Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections.

The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.

Influence of tauroursodeoxycholic and taurodeoxycholic acids on hepatic metabolism and biliary secretion of phosphatidylcholine in the isolated rat liver.

Studies were carried out using an isolated rat liver system to define: the contribution of exogenous phosphatidylcholine (PC) to biliary phospholipid secretion; and its hepatic metabolism during perfusion of the livers with conjugated bile salts with different hydrophilic/hydrophobic properties. A tracer dose of sn-1-palmitoyl-sn-2-[14C]linoleoylPC was injected as a bolus into the recirculating liver perfusate, under constant infusion of 0.75 mumol/min of tauroursodeoxycholate or taurodeoxycholate. The effects on bile flow, biliary lipid secretion, 14C disappearance from the perfusate and its appearance in bile, as well as hepatic and biliary biotransformation were determined. With both the bile salts, about 40% of the [14C]PC was taken up by the liver from the perfusate over 100 min. During the same period less than 2% of the given radioactivity was secreted into bile. More than 95% of the 14C recovered in bile was located within the identical injected PC molecular species. The biliary secretion of labeled as well as unlabeled PC, however, was significantly higher in livers perfused with taurodeoxycholate than tauroursodeoxycholate, while the reverse was observed with respect to bile flow and total bile salt secretion. The exogenous PC underwent extensive hepatic metabolization which appeared to be influenced by the type of bile salt perfusing the liver. After 2 h perfusion, the liver radioactivity was found, in decreasing order, in PC, triacylglycerol, phosphatidylethanolamine and diacylglycerol. In addition, the specific activity of triacylglycerol was significantly higher in tauroursodeoxycholate than in taurodeoxycholate-perfused livers (P less than 0.025), while the reverse was true for the specific activity of hepatic PC (P less than 0.01). Because taurodeoxycholate and tauroursodeoxycholate showed opposite effects on both biliary lipid secretion and hepatic PC biotransformations, we conclude that the hepatic metabolism of glycerolipids is influenced by the physiochemical properties of bile salts.

Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis.

BACKGROUND: Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. AIM: To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. METHODS: Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. RESULTS: 'Polymerase region': M204V/I variants were found in all group A patients, but in none of group B1 (P=0.0007) and in four of nine of group B2 (44%; P=0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. 'Core promoter': the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P=0.03) of group B1 and one of nine (11%; P=0.002) of group B2 patients. 'Precore': the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P=0.004) of group B1 and one of nine (11%; P=0.002) of group B2. CONCLUSIONS: Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation.

Molecular epidemiology of Streptococcus bovis causing endocarditis and bacteraemia in Italian patients.

Streptococcus bovis is being recognised increasingly as a cause of infective endocarditis, and has also been associated with underlying gastrointestinal malignancy. This study evaluated the molecular epidemiology of S. bovis isolates responsible for endocarditis or bacteraemia in Italian patients between January 1990 and August 2003. S. bovis isolates were classified on the basis of their biochemical profiles, antimicrobial susceptibilities and genotypes. Of 25 isolates studied, 20 were S. bovis I and five were S. bovis II. Seven biochemical profiles were identified. Pulsed-field gel electrophoresis (PFGE) analysis identified 22 profiles that differed by at least two DNA fragments and showed a similarity of < 87%. Most PFGE patterns represented single isolates that differed in antimicrobial susceptibility, but three PFGE types were observed, with identical profiles and antibiotypes, in isolates from two different patients. S. bovis I and II isolates grouped into two distinct genetic clusters (I and II) with a similarity coefficient of 38%. Two sub-clusters (Ia and Ib), with a similarity coefficient of 47%, included 17 S. bovis I isolates with similar biochemical profiles (15 with biotype A, and two with biotype B), but different resistance phenotypes. Based on the phenotypic and genotypic heterogeneity of the isolates, it is postulated that the increase in S. bovis endocarditis in this geographical area might have been caused by the selection of sporadic endemic clones from the endogenous intestinal flora.

Role of immunosuppressive regimen on the incidence and characteristics of cytomegalovirus infection in heart transplantation: a single-center experience with preemptive therapy.

OBJECTIVE: This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. PATIENTS AND METHODS: Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. RESULTS: The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). CONCLUSIONS: The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

Streptococcus bovis endocarditis and its association with chronic liver disease: an underestimated risk factor.

Clinical and epidemiological characteristics of Streptococcus bovis endocarditis were prospectively studied among 199 patients with definite endocarditis. Thirty patients (15.1%) had S. bovis endocarditis. Compared with patients with non-S. bovis endocarditis, these 30 patients were older (mean age, 58.6+/-12.4 years vs. 46.0+/-17.0 years; P<.001) and had higher rates of bivalvular involvement (43.3% vs. 7.7%; P<.001), embolism (73.3% vs. 40.2%; P=.002), and diskitis (23.3% vs. 0.6% P<.001). In patients with S. bovis biotype I (S. bovis I) endocarditis, advanced liver disease was present in 56.7%, compared with 15.3% of patients with non-S. bovis endocarditis (P<.001), and colonic adenoma was present in 46.7%. The in-hospital mortality rate (16.7%) was correlated with delayed diagnosis and advanced liver diseases. In our city, S. bovis I endocarditis is frequently correlated with liver diseases; diskitis may be the first sign of the disease.

Prognostic determinants of six-month morbidity and mortality in heart transplant recipients. The Italian Study Group on Infection in Heart Transplantation.

BACKGROUND: Knowledge of time course and risk factors for morbidity and mortality may allow better cardiac graft allocation, surveillance timing, and planning of immunosuppressive strategies. METHODS: Six-month morbidity and mortality were retrospectively analyzed in a multiinstitutional series of 645 heart transplant recipients. RESULTS: During a 3432 patient-months follow-up, 87 patients died of infection (n = 11), rejection (n = 11), multiorgan failure (n = 9) and other transplant-related causes (n = 56); six-month survival rate was 86%. Three hundred thirty-seven recipients had 967 treated rejection episodes (2.87 episodes/patient with rejection, lethality 3.2%); 223 major infectious episodes occurred in 162 patients (1.38 episodes/infected patient, lethality 7%). Six-month rejection and infection-free survival rates were 44% and 73%. Total mortality and cause-specific morbidity sharply declined after the first month; 160 patients (25%) had no events during follow-up. At multivariable analysis, significant risk factors for mortality were postoperative acute kidney failure, prolonged cardiopulmonary bypass time, and previous cardiac surgery. Rejection was associated with steroid-free and globulin-free immunosuppression and infection was associated with steroid immunosuppression, cytolytic treatment, venous lines placement greater than 7 days, and mechanical ventilation time. No single or combination of variables was able to discriminate patients with an event-free course. CONCLUSIONS: Morbidity and mortality have the highest incidence during the early posttransplantation phase. Preoperative variables are of limited value with respect to immunosuppressive treatment in predicting outcome. Infection is far less frequent than rejection but, in view of the higher lethality rate, deserves a vigorous effort for prevention, which is best addressed by appropriate modulation of immunosuppressive strategies.