Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies

INTRODUCTION: There has been a continuing controversy about whether infection with Acinetobacter baumannii increases morbidity and mortality independently of the effect of other confounding factors. METHODS: We performed a systematic review of matched case-control and cohort studies examining the mortality attributable to infection with or acquisition of A. baumannii (infection or colonization). We included in our review studies that compared mortality and/or morbidity of patients with acquisition of or infection with A. baumannii (cases) with the outcomes of matched patients without A. baumannii isolation from clinical specimens (controls). The relevant studies were identified from searches of the PubMed and the Cochrane Library databases. Two independent reviewers performed the literature search, study selection, and data extraction from nine identified relevant studies. RESULTS: The attributable mortalities, in the hospital and in the intensive care unit, of patients with A. baumannii infection in six matched case-control studies included in our review ranged from 7.8% to 23% and from 10% to 43%, respectively. In addition, a statistically significantly higher mortality was reported for patients with A. baumannii acquisition; that is, colonization or infection (cases) compared with controls without such an acquisition in all four reviewed studies that reported data on this comparison. CONCLUSION: Although definitive statements about the mortality attributable to the acquisition of A. baumannii cannot be made from the available studies because of their methodological heterogeneity, the reviewed data suggest that infection with or acquisition of A. baumannii seems to be associated with increased mortality

Worldwide research productivity in critical care medicine

INTRODUCTION: The number of publications and the impact factor of journals are accepted estimates of the quantity and quality of research productivity. The objective of the present study was to assess the worldwide scientific contribution in the field of critical care medicine. METHOD: All research studies published between 1995 and 2003 in medical journals that were listed in the 2003 Science Citation Index (SCI(®)) of Journal Citation Reports under the subheading 'critical care' and also indexed in the PubMed database were reviewed in order to identify their geographical origin. RESULTS: Of 22,976 critical care publications in 14 medical journals, 17,630 originated from Western Europe and the USA (76.7%). A significant increase in the number of publications originated from Western European countries during the last 5 years of the study period was noticed. Scientific publications in critical care medicine increased significantly (25%) from 1995 to 2003, which was accompanied by an increase in the impact factor of the corresponding journals (47.4%). Canada and Japan had the better performance, based on the impact factor of journals. CONCLUSION: Significant scientific progress in critical care research took place during the period of study (1995–2003). Leaders of research productivity (in terms of absolute numbers) were Western Europe and the USA. Publications originating from Western European countries increased significantly in quantity and quality over the study period. Articles originating from Canada, Japan, and the USA had the highest mean impact factor.. Canada was the leader in productivity when adjustments for gross domestic product and population were made

Impact of Definitive Therapy with Beta-Lactam Monotherapy or Combination with an Aminoglycoside or a Quinolone for Pseudomonas aeruginosa Bacteremia

BACKGROUND: Bacteremia by Pseudomonas aeruginosa represents one severe infection. 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. METHODS: 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. 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, mortality, and toxicity. RESULTS: Out of 92 bacteremias there were 54 evaluable episodes 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). CONCLUSION: Our study, in accordance with previous ones, indicates that the choice between monotherapy and combination therapy may not affect treatment success significantly. However, our study does not have statistical power to identify small or moderate differences. A large randomized controlled trial evaluating this issue is justified

Toxicity after prolonged (more than four weeks) administration of intravenous colistin

BACKGROUND: The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E). METHODS: An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken. Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied. RESULTS: We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (± SD) 43.4 (± 14.6) days, mean daily dosage (± SD) 4.4 (± 2.1) million IU, mean cumulative dosage (± SD) 190.4 (± 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin. CONCLUSIONS: No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria

A bibliometric analysis of research productivity in Parasitology by different world regions during a 9-year period (1995–2003)

BACKGROUND: The objective of this study was to estimate the research productivity of different world regions in the field of Parasitology. METHODS: Using the PubMed database we retrieved articles from journals included in the "Parasitology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995–2003. Research productivity was evaluated based on a methodology we developed and used in other bibliometric studies by analysing: (1) the total number of publications, (2) the mean impact factor of all papers, and (3) the product of the above two parameters, (4) the research productivity in relation to gross domestic product of each region, and (5) the research productivity in relation to gross national income per capita and population of each region. RESULTS: Data on the country of origin of the research was available for 18,110 out of 18,377 articles (98.6% of all articles from the included journals). Western Europe exceeds all world regions in research production for the period studied (34.8% of total articles), with USA ranking second (19.9%), and Latin America & the Caribbean ranking third (17.2%). The mean impact factor in articles published in Parasitology journals was highest for the USA (1.88). Oceania ranked first in research productivity when adjustments for both the gross national income per capita (GNIPC) and population were made. Eastern Europe almost tripled the production of articles from only 1.9% of total production in 1995 to 4.3% in 2003. Similarly, Latin America and the Caribbean and Asia doubled their production. However, the absolute and relative production by some developing areas, including Africa, is still very low, despite the fact that parasitic diseases are major public health problems in these areas. CONCLUSION: Our data suggest that more help should be provided by the developed nations to developing areas for improvement of the infrastructure of research

Worldwide trends in quantity and quality of published articles in the field of infectious diseases

BACKGROUND: Trying to confront with the widespread burden of infectious diseases, the society worldwide invests considerably on research. We evaluated the contribution of different world regions in research production in Infectious Diseases. METHODS: Using the online Pubmed database we retrieved articles from 38 journals included in the "Infectious Diseases" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995–2002. The world was divided into 9 regions based on geographic, economic and scientific criteria. Using an elaborate retrieval system we obtained data on published articles from different world regions. In our evaluation we introduced an estimate of both quantity and quality of research produced from each world region per year using: (1) the total number of publications, (2) the mean impact factor of publications, and (3) the product of the above two parameters. RESULTS: Data on the country of origin of the research was available for 45,232 out of 45,922 retrieved articles (98.5 %). USA and Western Europe are by far the most productive regions concerning publications of research articles. However, the rate of increase in the production of articles was higher in Eastern Europe, Africa, Latin America and the Caribbean, and Asia during the study period. The mean impact factor is highest for articles originating in the USA (3.42), while it was 2.82 for Western Europe and 2.73 for the rest of the world (7 regions combined). CONCLUSION: USA and Western Europe make up a striking 80% of the world's research production in Infectious Diseases in terms of both quantity and quality. However, all world regions achieved a gradual increase in the production of Infectious Diseases articles, with the regions ranking lower at present displaying the highest rate of increase

Impact of combined beta-lactam - aminoglycoside therapy in hospitalized patients with serious infections

Background: Pseudomonas aeruginosa bacteremia represents a severe infection. The use of antibiotic combinations represents a common therapeutic approach for decades. Several recent original papers and systematic reviews questioned the benefit of using beta-lactams in combination with other antimicrobials for various serious bacterial infections. 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: 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. 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, 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 all-cause mortality. 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.Conclusion: Our study, in accordance with previous studies, indicates that the choice between appropriate definitive monotherapy with a beta lactam may not alter treatment success and other outcomes significantly compared to appropriate definitive combination therapy with a beta-lactam plus an aminoglycoside or a quinolone in patients with Pseudomonas aeruginosa bacteremia. However, our study does not have the statistical power to identify small differences regarding in outcomew between treatment groups. Recent guidelines on the management of patients with sepsis suggest broad spectrum empirical antimicrobial coverage. However, at the same time they suggest narrow definitive therapy (de-escalation) based on susceptibility testing results, in agreement with our results. A large multicentre randomized controlled trial can offer good quality evidence and further insights regarding the optimal therapy for Pseudomonas aeruginosa bacteremia.Υπάρχουσα γνώση - Σκοπός της μελέτης. Η βακτηριαιμία από Pseudomonas aeruginosa είναι μια σοβαρή λοίμωξη συνδεδεμένη με σημαντικά ποσοστά νοσηρότητας και θνησιμότητας. Η χρήση συνδυασμών αντιμικροβιακών αποτελεί συχνή θεραπευτική προσέγγιση για αυτή τη λοίμωξη. Πρόσφατες πρωτότυπες μελέτες και συστηματικές ανασκοπήσεις αμφισβήτησαν το κλινικό όφελος της χρήσης συνδυασμών βήτα λακταμικών με αμινογλυκοσίδες ή κινολόνες σε σοβαρές λοιμώξεις. Μελετήσαμε αν η μονοθεραπεία με ένα βήτα-λακταμικό οδηγεί σε παρόμοια αποτελέσματα με τη χρήση των προαναφερθέντων συνδυασμών σε ασθενείς με ψευδομοναδική βακτηριαιμία.Μέθοδοι. Πολυκεντρική αναδρομική μελέτη κοόρτης σε 3 τριτοβάθμια νοσοκομεία (2 στην Ελλάδα και 1 στην Ιταλία). Συμπεριλήφθηκαν ασθενείς με στελέχη Pseudomonas aeruginosa ευαίσθητα στη δράση ενός βήτα λακταμικού και τουλάχιστον μιας αμινογλυκοσίδης ή μιας κινολόνης . Τα περιστατικά έλαβαν κατάλληλη αντιμικροβιακή αγωγή για τουλάχιστον 48 ώρες. Η κύρια έκβαση που μελετήθηκε ήταν η θεραπευτική επιτυχία. Δευτερεύουσες εκβάσεις ήταν η θεραπευτική επιτυχία σε ασθενείς που έλαβαν την ίδια εμπειρική και στοχευμένη αντιμικροβιακή αγωγή, η θνησιμότητα από όλα τα αίτια, η αποδοτέα θνησιμότητα στη λοίμωξη και η τοξικότητα. Αποτελέσματα. Ανευρέθηκαν 92 επεισόδια βακτηριαιμίας από τις βάσεις δεδομένων των νοσοκομείων. Από αυτά, 54 πληρούσαν τα κριτήρια εισαγωγής στη μελέτη. Η θεραπευτική επιτυχία ήταν μεν υψηλότερη στους ασθενείς που έλαβαν συνδυασμένη αγωγή (85%) σε σύγκριση με αυτούς που έλαβαν μονοθεραπεία με ένα βήτα λακταμικό (65%), όμως η διαφορά δεν ήταν στατιστικώς σημαντική [Λόγος συμπληρωματικών πιθανοτήτων (OR) 3,1, 95% Διάστημα Εμπιστοσύνης (CI) 0,69–14,7, p = 0,1]. Μόνο η πολύ μακρά νοσηλεία (>2 μήνες) πριν την βακτηριαιμία συσχετίστηκε με μειωμένη κλινική επιτυχία σε πολυπαραγοντικές αναλύσεις (OR 0,73, 95% CI 0,01–0,95, p = 0,046). Η θνησιμότητα από όλα τα αίτια δεν διέφερε σημαντικά μεταξύ της ομάδας που έλαβε συνδυασμένη αγωγή [6/31 (19%)] και της μονοθεραπείας [8/19 (42%)], p = 0,11. Η θνησιμότητα αποδοτέα σε λοίμωξη ήταν 3/31 (10%) με συνδυασμένη αγωγή έναντι 5/19 (26%) με μονοθεραπεία, p = 0,23. O δείκτης συνοσηρότητας Charlson συσχετίστηκε με αυξημένη συνολική θνησιμότητα ενώ η πολύ μακρά νοσηλεία με θνησιμότητα αποδοτέα στη λοίμωξη. Συμπεράσματα: Η μελέτη μας, σε συμφωνία με προηγούμενες μελέτες, έδειξε πως σε ασθενείς με βακτηριαιμία από Pseudomonas aeruginosa η επιλογή κατάλληλης στοχευμένης μονοθεραπείας με ένα βήτα λακταμικό σε σύγκριση με κατάλληλη συνδυασμένη αγωγή αμινογλυκοσίδης ή κινολόνης με ένα βήτα λακταμικό δεν επηρεάζει σημαντικά τη θεραπευτική επιτυχία και άλλες εκβάσεις. Πρέπει να τονιστεί πως η παρούσα μελέτη δεν έχει την στατιστική ισχύ να αναδείξει μικρές διαφορές στις εκβάσεις ανάμεσα στις δύο θεραπευτικές ομάδες. Πρόσφατες κατευθυντήριες οδηγίες για την αντιμετώπιση σηπτικών ασθενών συνιστούν ευρέος φάσματος εμπειρική αντιμικροβιακή κάλυψη. Συγχρόνως όμως συστήνουν αποκλιμάκωση με στενού φάσματος στοχευμένη αντιμικροβιακή αγωγή, σε συμφωνία με τα ευρήματα της μελέτης μας. Μια μεγάλη τυχαιοποιημένη κλινική δοκιμή που θα συγκρίνει στοχευμένη μονοθεραπεία με συνδυασμένη θεραπεία σε ασθενείς με ψευδομοναδική βακτηριαιμία θα απαντήσει περαιτέρω στα σχετικά ερωτηματικά