Prospective intervention study with a microarray-based, multiplexed, automated molecular diagnosis instrument (Verigene system) for the rapid diagnosis of bloodstream infections, and its impact on the clinical outcomes

The Verigene Gram-positive blood culture test (BC-GP) and the Verigene Gram-negative blood culture test (BC-GN) identify representative Gram-positive bacteria, Gram-negative bacteria and their antimicrobial resistance by detecting resistance genes within 3 h. Significant benefits are anticipated due to their rapidity and accuracy, however, their clinical utility is unproven in clinical studies. We performed a clinical trial between July 2014 and December 2014 for hospitalized bacteremia patients. During the intervention period (N = 88), Verigene BC-GP and BC-GN was used along with conventional microbiological diagnostic methods, while comparing the clinical data and outcomes with those during the control period (N = 147) (UMIN registration ID: UMIN000014399). The median duration between the initiation of blood culture incubation and the reporting time of the Verigene system results was 21.7 h (IQR 18.2-26.8) and the results were found in 88% of the cases by the next day after blood cultures were obtained without discordance. The hospital-onset infection rate was higher in the control period (24% vs. 44%, p = 0.002), however, no differences were seen in co-morbidities and severity between the control and intervention periods. During the intervention period, the time of appropriate antimicrobial agents\u27 initiation was significantly earlier than that in the control period (p = 0.001) and most cases (90%; 79/88) were treated with antimicrobial agents with in-vitro susceptibility for causative bacteria the day after the blood culture was obtained. The costs for antimicrobial agents were lower in the intervention period (3618 yen vs. 8505 yen, p = 0.001). The 30-day mortality was lower in the intervention period (3% vs. 13%, p = 0.019)

Colistin resistance in carbapenemase-producing Klebsiella pneumoniae bloodstream isolates: evolution over 15 years and temporal association with colistin use by time series analysis

Bacteremia caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) is associated with increased mortality and often, colistin is the only available antibiotic against these infections. In the present study, we i) tested last-resort antibiotics against CP-Kp blood isolates from patients who were hospitalized in Laiko hospital, a 500-bed tertiary care hospital in Athens, Greece, between 2002 and 2016, ii) investigated the trends of antimicrobial resistance to colistin over time as well as its temporal association of colistin use during the study period. In total, 313 blood isolates were tested positive for carbapenemase production with multiplex PCR during the study period. Of them, 197 (62.9%) were resistant to meropenem (MIC >8 mg/L), 79 (25.2%) exhibited meropenem MICs of 4-8 mg/L and 37 (11.8%) displayed MICs in the susceptible range (MIC ≤2 mg/L). Resistance frequencies to colistin, fosfomycin and tigecycline were 35.1% (110/313), 30.0% (94/313) and 5.4% (17/313), respectively. Polymyxin B displayed the same susceptibility pattern as colistin, with the MICs of the two antibiotics differing by one or two dilutions without difference in interpretation. Among 313 isolates containing carbapenemase-encoding gene(s), blaKPC was detected in 198 isolates (63.3%), blaVIM in 89 (28.4%), blaNDM-1 in 17 (5.4%) and blaOXA-48 in 4 (1.3%). Five isolates carried more than one carbapenemase gene (three carried blaKPC + blaVIM, one carried blaKPC + blaNDM-1 and one carried blaVIM + blaΝDM-1). Then, we studied the trends of antimicrobial resistance to colistin in our hospital during 2002-2016 using the linear regression analysis. The analysis revealed a statistically significant increasing trend in colistin resistance over time from 0% in 2002 to 26.9% in 2016 [R2= 0.5, p8 mg/L), τα 79 (25,2%) είχαν ΕΑΠ στη μεροπενέμη που κυμαινόταν στο εύρος 4–8 mg/L και τα 37 (11,8%) ήταν ευαίσθητα (ΕΑΠ ≤2 mg/L). Όσον αφορά τα υπόλοιπα αντιβιοτικά που ελέγχθηκαν, 35,1% (110/313) ήταν ανθεκτικά στην κολιμυκίνη, 30% (94/313) στη φωσφομυκίνη και 5,4% (17/313) στην τιγκεκυκλίνη. Η πολυμυξίνη Β παρουσίασε το ίδιο προφίλ ευαισθησίας με την κολιμυκίνη και οι τιμές ΕΑΠ διέφεραν κατά μία ή δύο αραιώσεις, χωρίς διαφορά στην κατηγοριοποίηση των αποτελεσμάτων ως ευαίσθητα ή ανθεκτικά. Από τα 313 στελέχη που περιείχαν γονίδια που κωδικοποιούσαν καρβαπενεμάσες, 198 (63,3%) ήταν KPC, 89 (28,4%) ήταν VIM, 17 (5,4%) ήταν NDM-1 και 4 (1,3%) ήταν OXA-48. Πέντε στελέχη έφεραν περισσότερα από ένα γονίδια αντοχής (3 στελέχη είχαν KPC και VIM, 1 KPC και NDM-1 και 1 VIM και NDM-1). Στη συνέχεια, μελετήσαμε την τάση της αντοχής της κολιμυκίνης στο νοσοκομείο μας κατά τη χρονική περίοδο 2002-2016 εφαρμόζοντας την στατιστική ανάλυση γραμμικής παλινδρόμησης (linear regression analysis). Βρήκαμε ότι η αντοχή στην κολιμυκίνη παρουσίασε στατιστικώς σημαντική αυξητική τάση στον χρόνο, από 0% το 2002 σε 26,9% το 2016 [R2 = 0,5, p< 0,01; point estimate of coefficient, 2,97, 95% confidence interval (CI) 1,20–4,75; standard error of the slope coefficient, 0,82]. Επιπλέον, παρατηρήθηκε αυξητική τάση στον χρόνο στην χρήση της κολιμυκίνης, από 0,2 DDDs/100 ασθενο-ημέρες το πρώτο τρίμηνο του 2002 σε 7,10 DDDs/100 ασθενο-ημέρες το δεύτερο τρίμηνο του 2016 (R2 = 0,54, p< 0,01; point estimate of coefficient, 0,66, 95% CI 0,49–0,82; standard error of the slope coefficient, 0,08). Τέλος, για να διερευνήσουμε την πιθανή συσχέτιση μεταξύ της αντοχής στην κολιμυκίνη και χρήσης του αντιβιοτικού στο νοσοκομείο μας εφαρμόσαμε την στατιστική μέθοδος ανάλυσης χρονοσειρών (time series analysis). Η συνολική επίπτωση της ανθεκτικής στην κολιμυκίνη K. pneumoniae υπολογίστηκε ότι ήταν 0,37 στελέχη ανά 10.000 ασθενο-ημέρες και η μέση χρήση κολιμυκίνης ανά τρίμηνο ήταν 5,14 DDDs/100 ασθενο-ημέρες. Αφού δημιουργήσαμε τις επιμέρους χρονοσειρές της αντοχής και της χρήσης της κολιμυκίνης χρησιμοποιώντας τη μέθοδο των Box και Jenkins, στη συνέχεια κατασκευάσαμε το μοντέλο γραμμικής συνάρτησης μεταφοράς (linear transfer function model) το οποίο μας έδωσε τη δυνατότητα να ποσοτικοποιήσουμε τη δυναμική συσχέτιση μεταξύ χρήσης κολιμυκίνης και αντοχής στο φάρμακο. Το μοντέλο ανέδειξε την ύπαρξη αυτής της δυναμικής συσχέτισης και συγκεκριμένα, ότι η αύξηση της χρήσης κολιμυκίνης κατά 1 DDD/100 ασθενο-ημέρες οδηγεί σε +0.05 αύξηση της επίπτωσης αντοχής στην κολιμυκίνη. Μάλιστα, η επίδραση της κολιμυκίνης στην αύξηση της αντοχής εμφανίζεται μετά από διάστημα 3 μηνών. Σύμφωνα με το μοντέλο, η χρήση κολιμυκίνης και η προηγούμενη αντοχή στην κολιμυκίνη μπορούν να εξηγήσουν το 69% της αντοχής στην κολιμυκίνη. Άλλοι παράγοντες συμβάλλουν στην ανάπτυξη του υπόλοιπου 31% της αντοχής. Συνοψίζοντας, τα ευρήματά μας μπορούν και πρέπει να αποτελέσουν το σημείο εκκίνησης για την εφαρμογή αυστηρών μέτρων με σκοπό την ελάττωση της αντοχής στην κολιμυκίνη στο νοσοκομείο μας

Evaluation of Antimicrobial Susceptibility of Enterobacteriaceae Causing Urinary Tract Infections in Africa

Our objective was to evaluate the antimicrobial susceptibility of Enterobacteriaceae causing urinary tract infections (UTIs) in adults in Africa. The PubMed database was systematically searched to identify relevant studies published after 2000. Google, World Health Organization, and African Field Epidemiology networks were also searched. Twenty-eight studies, accounting for 381,899 urine isolates from 14 African countries, met the inclusion criteria. Escherichia coli, Klebsiella spp., and Proteus spp. were the most commonly encountered uropathogens. Cefotaxime, imipenem, fosfomycin, and ciprofloxacin were the antibiotics with the highest activity against E. coli isolates from outpatients, with susceptibility being 92 to 99, 100, 100, and 68 to 91%, respectively. The susceptibility among Klebsiella spp. isolates from outpatients varied from 80 to 100% for amikacin and from 53 to 100% for ciprofloxacin, while susceptibility was 74 to 78, 97, and 77% for ciprofloxacin, amikacin, and fosfomycin, respectively, among Klebsiella species isolates from inpatients or patients with hospital-acquired UTIs. With regard to Proteus spp., the highest activity was observed among fluoroquinolones; 71 to 100% of the P. mirabilis isolates were susceptible to ciprofloxacin in four studies, and 74 to 100% of the P. vulgaris isolates were susceptible to ofloxacin in two studies. The currently available evidence suggests that the antimicrobial susceptibility patterns of Enterobacteriaceae uropathogens in African countries were similar to those in countries of southeast Europe. Further original studies are warranted from African countries for which there is limited published data

Morbidity and outcomes of foreign travelers in Zakynthos island, Greece: a retrospective study.

BACKGROUND: Although there is satisfactory recording of diseases affecting travelers visiting developing countries, little is known regarding morbidity of travelers when visiting developed countries. We sought to evaluate the morbidity of foreign travelers in Zakynthos, a popular Greek island attracting large number of foreign tourists every summer. METHODS: Data from foreign travelers that accommodated in Zakynthos and sought medical services from the private offices of Zante Medical Care from May 1 to October 30 2012 were retrospectively analyzed. RESULTS: Two thousand six hundred and eighty-eight patients were included in the study. The mean age (± SD) of the patients whom the age was recorded was 29.6 (± 18.3) and 51.5% of them were from 18 to 40 years old. Disorders of the respiratory tract (32.7%), dermatologic conditions (21.1%), musculoskeletal injuries (16.4%), and gastrointestinal disorders (16.3%) were the four most prevalent clinical categories among patients. Ear disorder was the most common syndromic description (14.5%) among which 81.2% were ear infections; otitis externa and otitis media were diagnosed in 8.5% and 3.3% patients in total. The most common specific diagnosis was gastroenteritis (14.3%). Insect bite and sunburn were the most common diagnosis (6.5% and 3.8%, respectively) among patients with a dermatologic condition. Ear infection was the most common diagnosis in pediatric patients. CONCLUSION: Disorders mainly of the upper respiratory tract were the predominant causes of illness among foreign travelers in Zakynthos. Traveler's diarrhea was the most common specific diagnosis but the prevalence within the total population was not very high

Impact of vacuum-assisted closure (VAC) therapy on clinical outcomes of patients with sternal wound infections: a meta-analysis of non-randomized studies.

OBJECTIVE: To examine the impact of VAC therapy on mortality of patients with sternal wound infections after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Controversial results regarding mortality of patients with sternal wound infections were published. METHODS: We performed a systematic search in PubMed and Scopus. Mortality was the primary outcome of the meta-analysis. Recurrences, complications and length of stay were secondary outcomes. RESULTS: Twenty-two retrospective studies including 2467 patients were eligible for inclusion. Patients treated with VAC had significantly lower mortality compared to those treated without VAC [2233 patients, RR = 0.40, (95% CI 0.28, 0.57)]. This finding was consistent regardless of the study design, the exclusion of studies with positive findings, the criteria for establishment of the compared groups, the time of mortality assessment or the type of infections under study, provided that adequate data was available. VAC therapy was associated with fewer recurrences (RR = 0.34, 95% CI: 0.19-0.59). The meta-analysis did not show any difference in the length of stay (RR = -2.25, 95% CI: -7.52-3.02). CONCLUSIONS: VAC therapy was associated with lower mortality than other surgical techniques in retrospective cohorts of patients with DSWIs following cardiothoracic surgery

Prevalence and treatment of aerobic vaginitis among non-pregnant women: evaluation of the evidence for an underestimated clinical entity

We sought to evaluate the evidence on the prevalence of aerobic vaginitis (AV) among symptomatic non-pregnant women, as well as the treatment administered for this clinical entity. The PubMed and Scopus databases were systematically searched. Sixteen studies met the inclusion criteria, 11 of which reported on the prevalence of possible AV, two on the prevalence of diagnosed AV, and three on the treatment and outcomes of women with diagnosed AV. The prevalence of diagnosed AV varied from 5 to 10.5 %. Streptococcus spp., Staphylococcus aureus, and coagulase-negative staphylococci were the most commonly identified Gram-positive pathogens among women with possible AV, with prevalences of up to 58.7, 41.7, and 37.4 %, respectively, while Escherichia coli was the most common Gram-negative pathogen identified, with a prevalence of up to 23 % among symptomatic women. Regarding antibiotic treatment for AV, the antibiotic schemes administered, which mainly consisted of suppositories of aminoglycosides, showed good effectiveness without serious adverse events provided by any of the included studies. The currently available data suggest that the prevalence of AV is not negligible, while the prevalence of possible AV is considerable. Well-designed studies comparing the prevalence of aerobic pathogens between symptomatic and asymptomatic women are warranted

Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: A systematic review and meta-analysis

Objectives: The cost-effectiveness of augmenting immunization against hepatitis B infection with hepatitis B immunoglobulin (HBIG) remains controversial, particularly for the subpopulation of babies of HBsAg+/HBeAg? mothers that are considered as low-infective. We aimed to evaluate the effectiveness of vaccine alone compared with vaccine plus HBIG for the immunization of babies of HBsAg+/HBeAg- mothers. Methods: We searched PubMed, Scopus and Cochrane Central Register of Controlled Trials databases to identify studies comparing the effectiveness of combined immunization (vaccine plus HBIG) with vaccine alone in neonates of HBsAg+/HBeAg- mothers. A systematic review and meta-analysis of eligible studies was performed. Results: A total of nine eligible studies were identified (four randomized controlled trials). No difference was found regarding the primary outcome of our meta-analysis, namely occurrence of hepatitis B infection, between neonates who received vaccine only, compared with those who received both vaccine and HBIG (four studies, 3426 patients, OR=0.82, 95% CI=0.41-1.64). This finding was consistent with regards to seroprotection rate (four studies, 1323 patients, OR=1.24, 95% CI=0.97-1.58). Safety data were not reported in the included studies. Conclusions: The available limited published evidence suggests that vaccine alone seems to be equally effective to the combination of HBIG and hepatitis B vaccine for neonates of HBsAg+/HBeAg- mothers in preventing infection. Further studies are needed in order to clarify the potential benefit of combined immunization to this specific subgroup of patients. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Continuous versus Conventional Infusion of Amphotericin B Deoxycholate: A Meta-Analysis

<div><p>Background</p><p>Treatment with Amphotericin B (AmB) deoxycholate, which is still used widely, particularly in low-resource countries, has been challenged due to nephrotoxicity. We sought to study whether continuous infusion of AmB deoxycholate reduces nephrotoxicity retaining, however, the effectiveness of the drug.</p><p>Methods</p><p>PubMed and Scopus databases were systematically searched to identify studies comparing the outcomes of patients receiving 24-h infusion of AmB (“continuous group”) and those receiving 2–6-h infusion of AmB (“conventional group”). Nephrotoxicity and all-cause mortality were the primary outcomes of the review, while treatment failure was the secondary outcome.</p><p>Results</p><p>Five studies met the inclusion criteria; one randomized controlled trial, two prospective cohort studies, and two retrospective cohort studies. The majority of patients were neutropenic with an underlying hematologic malignancy. All 5 studies (392 patients) provided data regarding the development of nephrotoxicity. A non-significant trend towards lower nephrotoxicity was observed for patients receiving continuous infusion of AmB compared with those receiving conventional infusion [RR = 0.61 (95% CI 0.36, 1.02)]. Four studies (365 patients) provided data regarding mortality; no relevant difference was detected between patients receiving continuous and those receiving conventional infusion of AmB [RR = 0.81 (95% CI 0.36, 1.83)]. Data on treatment failure of the two methods of administration was insufficient for meaningful conclusions.</p><p>Conclusion</p><p>The available evidence from mainly non-randomized studies suggests that continuous infusion of AmB deoxycholate might offer an advantage over the conventional infusion regarding the development of nephrotoxicity, without compromising patient survival. Further randomized studies are needed to investigate this issue.</p></div

Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections

We evaluated the number of deaths attributable to carbapenem-resistant Enterobacteriaceae by using studies from around the world published before April 9, 2012. Attributable death was defined as the difference in all-cause deaths between patients with carbapenem-resistant infections and those with carbapenem-susceptible infections. Online databases were searched, and data were qualitatively synthesized and pooled in a metaanalysis. Nine studies met inclusion criteria: 6 retrospective case–control studies, 2 retrospective cohort studies, and 1 prospective cohort study. Klebsiella pneumoniae was the causative pathogen in 8 studies; bacteremia was the only infection in 5 studies. We calculated that 26%–44% of deaths in 7 studies were attributable to carbapenem resistance, and in 2 studies, which included bacteremia and other infections, −3% and −4% of deaths were attributable to carbapenem resistance. Pooled outcomes showed that the number of deaths was significantly higher in patients with carbapenem-resistant infections and that the number of deaths attributable to carbapenem resistance is considerable