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.

Recipient-born bloodstream infection due to extensively drug-resistant Acinetobacter baumannii after emergency heart transplant: report of a case and review of the literature.

Infections due to drug-resistant Gram-negative rods are an emerging risk factor for increased mortality after solid organ transplant. Extensively drug-resistant (XDR) Acinetobacter baumannii (Acb) is a major threat in several critical care settings. The limited available data on the outcome of XDR Acb infections in organ transplant recipients mostly comes from cases of donor-derived infections. However, recipients of life-saving organs are often critically ill patients, staying long term in intensive care units, and therefore at high risk for nosocomial infections. In this report, we describe our experience with the exceedingly complex management of a recipient-born XDR Acb bloodstream infection clinically ensued shortly after heart transplant. We also review the current literature on this mounting issue relevant for intensive care, transplant medicine and infectious diseases.

Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.

BACKGROUND: Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. METHODS: This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. RESULTS: Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. CONCLUSIONS: In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. CLINICAL TRIALS REGISTRATION: NCT01577862.

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.

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.

High-dose daptomycin for cardiac implantable electronic device-related infective endocarditis.

BACKGROUND: Cardiac implantable electronic device (CIED)-related endocarditis is a growing challenge because of increasing incidence and significant mortality. Current treatment is based on complete hardware removal coupled with long-term administration of effective and safe antimicrobials. Daptomycin at the dose of 6 mg/kg/day has been found to be effective in staphylococcal endocarditis, but limited data exist on CIED endocarditis. Moreover, whether higher doses could be more effective but equally safe in this setting is currently unknown. METHODS: We report here our experience with high-dose daptomycin in the treatment of 25 cases of CIED endocarditis due to staphylococci. RESULTS: Patients were mostly elderly and male, with large lead vegetations and severe comorbidities. Pathogens were Staphylococcus epidermidis (56%), Staphylococcus aureus (28%), and other coagulase-negative staphylococci (16%). Only 4 patients (16%) had a normal pretreatment renal function. The median daptomycin daily dose was 8.3 mg/kg (range, 6.4-10.7). Daptomycin was administered for a median of 20 days (range, 8-52). Percutaneous lead extraction was performed in 88% of patients. Two patients (8%) failed to clear bacteremia. The overall clinical success of treatment was 80%, whereas a complete microbiological success was observed in 92% of patients. Creatine phosphokinase values were monitored and increased above normal in 5 cases (20%). No serious adverse event related to high-dose daptomycin was observed and no patient required discontinuation because of muscle toxicity. CONCLUSIONS: Our experience suggests that high-dose daptomycin may be a safe therapeutic option in staphylococcal CIED endocarditis and may be associated with high microbiological responses and clinical success.

Inherited hyper-homocysteinemia as a cause of nonbacterial thrombotic endocarditis.

BACKGROUND AND AIM OF THE STUDY: Despite high rates of valve disease, non-bacterial thrombotic endocarditis remains an uncommon condition, the individual susceptibility to which might be influenced by an inherited thrombophilic state. METHODS: A comprehensive hemostasis study was conducted in a 17-year-old patient with definite nonbacterial thrombotic endocarditis, including a genetic screening for all major inherited thrombophilias. RESULTS: Non-bacterial thrombotic endocarditis was detected on a bicuspid aortic valve. A hemostasis work-up showed that the patient had severe hyperhomocysteinemia, and was homozygous for the C677T mutation of the methylenetetrahydrofolate reductase gene. CONCLUSION: Based on the present clinical case, a novel hypothesis was proposed that the pathophysiology of non-bacterial thrombotic endocarditis might be affected by a genetic predisposition, such as an inherited thrombophilic state.

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.

Molecular epidemiology of multidrug-resistant Acinetobacter baumannii in a tertiary care hospital in Naples, Italy, shows the emergence of a novel epidemic clone.

The molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in two intensive care units of the V. Monaldi university hospital in Naples, Italy, from May 2006 to December 2007. Genotype analysis by pulsed-field gel electrophoresis (PFGE), trilocus sequence-based typing (3LST), and multilocus sequence typing (MLST) of A. baumannii isolates from 71 patients identified two distinct genotypes, one assigned to PFGE group A, 3LST group 1, and ST2 in 14 patients and the other to PFGE group B, 3LST group 6, and ST78 in 71 patients, that we named ST2/A and ST78/B, respectively. Of these, ST2/A corresponded to European clone II identified in the same hospital during 2003 and 2004; ST78/B was a novel genotype that was isolated for the first time in May 2006 but became prevalent during 2007. The ST78/B profile was also identified in five patients from two additional hospitals in Naples during 2007. The ST2/A and ST78/B isolates were resistant to all antimicrobials tested, including carbapenems, but were susceptible to colistin. Both ST2/A and ST78/B isolates possessed a plasmid-borne carbapenem-hydrolyzing oxacillinase gene, bla(OXA-58), flanked by ISAba2 and ISAba3 elements at the 5' and 3' ends, respectively. The selection of the novel ST78/B A. baumannii clone might have been favored by the acquisition of the bla(OXA-58) gene.

Correlates and prognostic value of the first-phase hepatitis C virus RNA kinetics during treatment.

BACKGROUND: Analysis of hepatitis C virus (HCV) RNA kinetics during antiviral therapy may allow estimation of the probability of response. METHODS: To assess clinical and virological correlates and the predictive value of first-phase HCV RNA kinetics during pegylated interferon and ribavirin treatment, we studied 119 patients with chronic hepatitis C who were treated with pegylated interferon and ribavirin. HCV RNA level was measured 5 min before and 2, 14, and 28 days after the start of treatment. For each patient the Delta(t0-t2) log(10) HCV RNA value was calculated, which indicates the relative reduction in HCV RNA level from before treatment to day 2 after logarithmic transformation. RESULTS: A Delta(t0-t2) log(10) HCV RNA value < or =0.8 showed a 95% negative predictive value for virological response, whereas one >2.5 had a 93% positive predictive value for virological response, independent of genotype and histology. The Delta(t0-t2) log(10) HCV RNA value was strictly related to final treatment outcome and could differentiate not only patients with a sustained virological response from nonresponders but also patients who experienced relapse from the former. The Delta(t0-t2) log(10) HCV RNA value was highest among patients infected with genotypes 2 and 3 and was lowest among patients infected with genotype 1. It decreased with increasing grades of fibrosis and steatosis and was also inversely related to gamma-glutamyl transpeptidase (GGT) level and HOMA-IR (homeostasis model assessment for insulin resistance) score. In multivariate analysis, Delta(t0-t2) log(10) HCV RNA value was the strongest predictor of sustained virological response and appeared to be independently related to viral genotype and GGT level. CONCLUSION: HCV RNA kinetics has strong predictive value. It correlates with virological and clinical parameters that are known predictors of antiviral treatment outcome, including insulin resistance. The measurement of HCV load as early as 2 days after the start of pegylated interferon and ribavirin is a useful tool for the prediction of treatment outcome in individual patients and should be used in clinical practice.

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.

Emergence of coagulase-negative staphylococci as a cause of native valve endocarditis.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are an infrequent cause of native valve endocarditis (NVE), and our understanding of NVE caused by CoNS is incomplete. METHOD: The International Collaboration on Endocarditis-Prospective Cohort Study includes patients with endocarditis from 61 centers in 28 countries. Patients with definite cases of NVE caused by CoNS who were enrolled during the period June 2000-August 2006 were compared with patients with definite cases of NVE caused by Staphylococcus aureus and patients with NVE caused by viridans group streptococci. Multivariable logistic regression was used to determine factors associated with death in patients with NVE caused by CoNS. RESULTS: Of 1635 patients with definite NVE and no history of injection drug use, 128 (7.8%) had NVE due to CoNS. Health care-associated infection occurred in 63 patients (49%) with NVE caused by CoNS. Comorbidities, long-term intravascular catheter use, and history of recent invasive procedures were similar among patients with NVE caused by CoNS and among patients with NVE caused by S. aureus. Surgical treatment for endocarditis occurred more frequently in patients with NVE due to CoNS (76 patients [60%]) than in patients with NVE due to S. aureus (150 [33%]; P=.01) or in patients with NVE due to viridans group streptococci (149 [44%]; P=.01). Despite the high rate of surgical procedures among patients with NVE due to CoNS, the mortality rates among patients with NVE due to CoNS and among patients with NVE due to S. aureus were similar (32 patients [25%] and 124 patients [27%], respectively; P=.44); the mortality rate among patients with NVE due to CoNS was higher than that among patients with NVE due to viridans group streptococci (24 [7.0%]; P=.01). Persistent bacteremia (odds ratio, 2.65; 95% confidence interval, 1.08-6.51), congestive heart failure (odds ratio, 3.35; 95% confidence interval, 1.57-7.12), and chronic illness (odds ratio, 2.86; 95% confidence interval, 1.34-6.06) were independently associated with death in patients with NVE due to CoNS (c index, 0.73). CONCLUSIONS: CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes.

Phylogenetic analysis of viridans group streptococci causing endocarditis.

Identification of viridans group streptococci (VGS) to the species level is difficult because VGS exchange genetic material. We performed multilocus DNA target sequencing to assess phylogenetic concordance of VGS for a well-defined clinical syndrome. The hierarchy of sequence data was often discordant, underscoring the importance of establishing biological relevance for finer phylogenetic distinctions.

Genotypic diversity of coagulase-negative staphylococci causing endocarditis: a global perspective.

Coagulase-negative staphylococci (CNS) are important causes of infective endocarditis (IE), but their microbiological profiles are poorly described. We performed DNA target sequencing and susceptibility testing for 91 patients with definite CNS IE who were identified from the International Collaboration on Endocarditis-Microbiology, a large, multicenter, multinational consortium. A hierarchy of gene sequences demonstrated great genetic diversity within CNS from patients with definite endocarditis that represented diverse geographic regions. In particular, rpoB sequence data demonstrated unique genetic signatures with the potential to serve as an important tool for global surveillance.

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.

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.

Comparative activities of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases.

This study evaluated the activity of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against nine epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemase in Naples, Italy. The isolates were susceptible to colistin but differed in their resistance to imipenem and rifampicin. Time-kill studies showed a bactericidal effect for colistin but not for imipenem, rifampicin or sulbactam/ampicillin used as single agents. Synergism was observed with combinations of rifampicin+imipenem or sulbactam/ampicillin for all isolates and with colistin+rifampicin for isolates showing higher minimum inhibitory concentrations for rifampicin. Combined use of the antimicrobials tested may provide good therapeutic options for OXA-58 carbapenemase-producing A. baumannii infections.