Etiology, Risk Factors and Outcome of 1003 Cases of Infective Endocarditis from a 33-year National Survey in the Slovak Republic: An increasing proportion of elderly patients.

BACKGROUND: Infective endocarditis (IE) is still a significant cause of mortality in European hospitals, despite of the fact, that large nationwide studies were performed in last twenty years and pathogens are well known. The aim of the study was to assess risk factors, mortality, etiology and proportion of elderly patients within a longitudinal nation wide survey of infectious endocarditis in Slovakia. PATIENTS AND METHODS: Etiology, risk factors and outcome of 1003 cases of infective endocarditis (IE) in Slovakia over the last 33 years have been assessed. RESULTS: The majority of IE were caused by Staphylococci (28.3%), 15.6% were due to Viridans streptococci, 10% due to Enterococci, 8.2% by gram-negative bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa, 3.7% by other organisms and 31.0% of all cases were culture negative. The following risk factors were recorded: age > 65 (36.8%), rheumatic fever (15.3%), dental surgery (8.7%), previous non-cardiological surgery (8.2 %), neoplasia (8.1%), diabetes (7.8%), any endoscopy (8.5%) and dialysis (4.6%). All patients were treated with antimicrobials, 507 (51%) also with surgery. Survival rate at day 60 after diagnosis was 88.1% (n=883). Only age >65 (34.3% vs. 49.5%, p=0.045) and persistent bacteremia (with three or more positive blood cultures 15.7% vs. 34.5%, p=0,001) were significantly associated with higher attributable mortality. Concerning risk factors, etiology and therapeutic strategies, rheumatic fever and neoplasia showed decrease in tendency. Dental surgery and tonsillitis were less frequent as well (26.7% vs. 2%, p<0,001 and 16% vs. 1%, p<0.001). There was a significant shift in etiology after 1997: culture-negative endocarditis was surprisingly more frequently observed in the 2007-2017 period than before and represented 10.7% of all cases in 1984-1990 in comparison to 25.1-25.6% in 2007-2010 and 2011-2017. Staphylococci decreased from 48% to 29.6% (2007-2017), but are still major pathogens. Persistent bacteremia (3 or more positive blood cultures 5.3% vs. 24.7%, p<0,001) was less commonly observed within the 1st period (1984-1990) in comparison to 2007-2010. More patients in the 1st period (1984-1990) had embolization complications of IE than in the fifth and sixth period (2007-2017) (76 vs. 16.3% p<0.001). CNS embolization decreased from 14% to less than 5% (p<0.003). Attributable mortality was lower too (26.7% vs. 9.5%, p<0.001) because of increased proportion of cardiac surgery in the treatment of IE in 2007-2017 in comparison to 1984-1990. CONCLUSIONS: Study has showed significant shifts in etiology, risk factors and complications over the observed time periods in Slovakia.

Fungal neuroinfections and fungaemia: unexpected increase of mortality from invasive fungal infections in 2005-2011 in comparison to 1989-1998: analysis of 210 cases.

OBJECTIVE: In this short communication we compared the data of fungaemia cases in Slovak hospitals from 1989-1998 published in 1999-2000 with data from 2005-2011. METHODS: Risk factors, etiology and outcome of fungaemia between two periods (1989-1998 vs. 2005-2011) were compared and risk factors for death assessed by univariate analysis (CDC 2006 Statistical Package). RESULTS: In comparison to 1989-1998 when only amphotericin B and fluconazole has been used (55%), in 2005-2011 only 35.2% patients received FLU, but 26.4% received voriconazole, 22% caspofungin and anidulafungin and about 6.6% lipid formulations of Amphotericin B. In etiology, while in 1989-1998 only 37.1% (115/310) represented non-albicans Candida (NAC) and non-Candida yeasts in 2005-2011 already reached 63.7%. The significant increase of breakthrough fungaemia may be a sign of inappropriate empiric therapy.

Colonization of the respiratory tract by drug-resistant bacteria in HIV-infected children and prior exposure to antimicrobials.

The aim of this short communication is to assess colonization by MRSA, penicillin-resistant pneumococci (PRP), fluconazole-resistant (FLU-R) Candida albicans (CA) and non-albicans Candida (NAC), and ciprofloxacin-resistant E. coli with regard to immune recovery due to CD4 T-cell increase depending on the duration of highly active antiretroviral therapy (HAART). Prior exposure to oral cephalosporins (P<0.01) was significantly related to MRSA colonization. Penicillin-resistant pneumococci were more frequently (40% vs. 12.5%, NS) related to prior cephalosporins, but not to penicillins or macrolides use. However, this association was not statistically significant. Prior receiving of fluconazole was also not associated with increased colonization by FLU-R Candida spp. (30% vs. 16.7%, NS). Cotrimoxazole (P<0.01) and amoxicillin/amoxicillin clavulanate (P<0.01) were surprisingly protective against colonization by fluconazole-resistant Candida spp. Exposure to quinolones was not a risk factor for colonization by ciprofloxacin-resistant E. coli, but receiving of rifampin was (P<0.01). Colonization by cefotaxime-resistant Klebsiella spp. and Enterobacter spp. was not significantly associated with cephalosporins, but it was with cotrimoxazole use (P<0.05). In addition, HIV-infected children on HAART who received any antibiotic were significantly more colonized by cotrimoxazole-resistant E. coli (P<0.01) than those not receiving any antibiotic prior to colonization. Exposure to cephalosporins and macrolides was significantly related to cotrimoxazole-resistant E. coli (100% vs. 20%, 75% vs. 10%; P<0.01 for both), but exposure to cotrimoxazole itself was not.

Hospital antibiotic management in Slovakia--results of the ABS maturity survey of the ABS International group.

BACKGROUND: Antibiotic stewardship (ABS) is one of the important indicators in a healthcare system. Slovakia is participating in the project "Implementing antibiotic strategies for appropriate use of antibiotics in hospitals in member states of the European Union--ABS International", the objectives of which are identification of strengths and weaknesses of antibiotic policy in participating countries. This paper summarizes the results for Slovakia. METHODS: The questionnaire survey was conducted in May 2007. The questionnaire "ABS hospital mature" analyzed the ABS-related maturities of nine hospitals in Slovakia. The mean scores (on a scale of 1-5) for the various topics were calculated and presented in the form of an "ABS hospital maturity" pentagon. The mean total score for all antibiotic-related items was also calculated. RESULTS: The mean total score for all items in nine evaluated hospitals in Slovakia was 3.93. Overall the grades for the diagnostic level in Slovak hospitals (3.94) scored lower in comparison with partner countries. Control of antibiotic consumption is implemented in Slovakia and therefore scored 4.07. Antibiotic-related organization and personnel development also scored high (4.08 and 4.26, respectively) in comparison with partner countries, but antibiotic-related roles and communication and antibiotic-related relationships to relevant environments were graded as not satisfactory (3.54 and 3.28, respectively). CONCLUSIONS: In general, our results are similar to those found by other countries. Antibiotic-related organization and personnel development appears better developed in Slovakia than in other countries. The better scores for antibiotic organization could be explained by the existence of a centralized healthcare system for 40 years. The existence of 'antibiotic resistance laboratories' in the Slovak republic since 1971 and a national computerized reporting system for antibiotic resistance since 1984 reflect this high standard.

Antifungal drug discovery, six new molecules patented after 10 years of feast: why do we need new patented drugs apart from new strategies?

After 10 years absence (between 1990-1999) of new antifungal agents and intensive research being introduced into clinical practice, 3 new azoles (Voriconazole - Pfizer, Posaconazole - Schering-Plough, Ravuconazole - Bristol-Myers Squibb) and 3 new echinocandins (Caspofungin - MSD, Anidulafungin - Astellas-Pfizer, Micafungin - Fujisawa) were patented. The question raises if we really need 6 new antifungal agents in such a short time? Perhaps, they are not here because we need them all, but because of at least fifteen years effort of many groups of investigators who successfully discovered, proved and introduced these agents to the drug market. Voriconazole (2000), Posaconazole (2005), Ravuconazole (2007) from the group of azoles; and Caspofungin (2002), Anidulafungin (2004) and Micafungin (2006) from the group of echinocandins, with unique mode(s) of action (cell wall synthesis inhibition) different from polyens, azoles, antimetabolites and new monoclonal antifungal antibody (Mycograb), were approved and introduced to the clinical practice. This paper contains some useful information regarding the recent patents on antifungal drug discovery, their current position in the strategy of treatment of invasive fungal infections is briefly reviewed.