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Identifier 000404876
Title Η κλινική σημασία της χορήγησης συνδυασμών αμινογλυκοσιδών με βήτα λακταμικά αντιβιοτικά σε νοσοκομειακούς ασθενείς με σοβαρές λοιμώξεις
Alternative Title Impact of combined beta -lactam aminoglycoside therapy in hospitalised patients with serious infections
Author Μπληζιώτης, Ιωάννης Α.
Thesis advisor Σαμώνης, Γεώργιος
Reviewer Γκίκας, Αχχιλέας
Κογιεβίνας, Εμμανουήλ
Μαυρουδής, Δημήτριος
Γανωτάκης, Εμμανουήλ
Γαλανάκης, Εμμανουήλ
Κοφτερίδης, Διαμαντής
Abstract Background: Bacteremia by Pseudomonas aeruginosa represents a severe infection. Recent studies report overall mortality in patients with this infection between 20% and 60% and mortality attributed to the infection around 15%. The use of antibiotic combinations represents a common therapeutic approach against infections with Pseudomonas aeruginosa, used for decades. The rationale for using antibiotic combinations lies on their different mechanisms of action, their in vitro synergy and the wide antimicrobial spectrum that they offer. However, the administration of more than one antimicrobial increases toxicity as well as the chances for emergence of antimicrobial resistance. During the last 15 years several original papers and systematic reviews questioned the benefit of using beta-lactams in combination with other antimicrobials for various serious bacterial infections in immunocompetent and immunocompromised patients. It is not clear whether beta-lactam monotherapy leads to similar rates of treatment success compared to combinations of beta-lactams with aminoglycosides or quinolones for the treatment of Pseudomonas aeruginosa bacteremia. Methods: We performed a retrospective cohort study from 3 tertiary hospitals (2 in Greece and 1 in Italy). Pseudomonas aeruginosa isolates were susceptible to a beta-lactam and an aminoglycoside or a quinolone (appropriate therapy according to in vitro results). Patients received appropriate therapy for at least 48 hours. Primary outcome of interest was treatment success in patients with definitive beta-lactam combination therapy compared to monotherapy. Secondary outcomes were treatment success keeping the same empirical and definitive regimen, all-cause mortality, mortality attributed to infection, and toxicity. Results: Out of 92 Pseudomonas aeruginosa bacteremias that were retrieved in the databases of the hospitals and evaluated, there were 54 episodes fullfiling the inclusion criteria for the primary outcome (20 received monotherapy). Treatment success was higher with combination therapy (85%) compared to beta-lactam monotherapy (65%), however not statistically significantly [Odds ratio (OR) 3.1; 95% Confidence Interval (CI) 0.69–14.7, p = 0.1]. Very long (.2 months) hospitalisation before bacteremia was the only factor independently associated with treatment success (OR 0.73; 95% CI 0.01–0.95, p = 0.046), however this result entailed few episodes. All-cause mortality did not differ significantly between combination therapy [6/31 (19%)] and monotherapy [8/19 (42%)], p = 0.11. Only Charlson comorbidity index was associated with excess mortality (p = 0.03). Mortality due to infection was 3/31 (10%) in patients that received combination therapy compared to 5/19 (26%) in the monotherapy group. Only very long duration of hospitalisation was associated with mortality attributed to infection (p=0.01) Conclusion: Our study, in accordance with previous ones, indicates that the choice between appropriate definitive monotherapy with a beta lactam and appropriate definitive combination therapy with a beta-lactam plus an aminoglycoside or a quinolone may not affect treatment success significantly in patients with Pseudomonas aeruginosa bacteremia. However, our study does not have the statistical power to identify small or moderate differences regarding this outcome. Also, our results showed that the choice of definitive therapy is not associated with mortality, as long as the therapy is appropriate. Recent guidelines on the management of septic patients and patients with febrile neutropenia suggest broad spectrum empirical antimicrobial coverage by means of antimicrobial combinations in many patient populations. However, at the same time they suggest narrow definitive therapy (de-escalation) based on susceptibility testing results, in agreement with our results. The results of our study, in combination with results from published studies show that definitive monotherapy with a beta-lactam is an appropriate choice for Pseudomonas aeruginosa bacteremia. However there are fine outcomes that have not been evaluated sufficiently, such as the effect of therapy on the duration of patient hospitalization, on the emergence of antimicrobial resistance, and the effect on overall costs. A large multicentre randomized controlled trial can offer good quality evidence and further insights on this significant clinical question.
Language Greek
Issue date 2016-07-19
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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