Anastasia Antoniadou

Application of a Loading Dose of Colistin Methanesulfonate in Critically Ill Patients: Population Pharmacokinetics, Protein Binding, and Prediction of Bacterial Kill

ABSTRACT A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.

Tigecycline in the treatment of infections from multi-drug resistant gram-negative pathogens.

OBJECTIVEnThis observational retrospective study aims to present early experience with tigecycline (TIG) in the treatment of infections due to multi-drug resistant (MDR) microorganisms.nnnMETHODSnAdult patients included, received TIG for >5 days either as monotherapy (M group) or as presumed active monotherapy (PAM group). In the PAM group, all co-administered antimicrobial(s) were resistant in vitro against the targeted pathogen(s) or had been clinically and microbiologically failing after >or=5 days of therapy despite in vitro susceptibility.nnnRESULTSnForty-five patients (35 in ICU) were treated for 28 Acinetobacter baumannii and 23 Klebsiella pneumoniae infections [21 ventilator-associated and healthcare-acquired pneumonia (VAP/HCAP), 10 bloodstream infections (BSI) and 14 surgical infections (SI)]. Successful overall clinical outcome was 80%, i.e. 81.8% in M group, 78.3% in PAM group, 90.5% in VAP/HCAP, 80% in BSI, 64.3% in SI and 85% in the cases with septic shock. Superinfections from Enterobacteriaceae inherently resistant to tigecycline occurred in 31.8% of M and 13% of PAM group (p<0.001).nnnCONCLUSIONnTIG represents a promising option in infections from MDR pathogens, however, further clinical experience is required.

Screening for resistant gram-negative microorganisms to guide empiric therapy of subsequent infection

ObjectiveTo define the potential of resistant gram-negative colonization surveillance to predict etiology of subsequent infection and improve adequacy of empiric antimicrobial treatment.DesignRetrospective cohort study.SettingA mixed medical–surgical six-bed intensive care unit (ICU), from November 2003 to December 2006.PatientsAll patients having at least one episode of ventilator-associated pneumonia (VAP) or bloodstream infection (BSI) caused by a resistant gram-negative pathogen during the study period.InterventionsColonization surveillance of the respiratory tract and gastrointestinal tract was systematically performed in all ICU patients. Tracheal aspirates were obtained twice weekly and rectal swabs once weekly. Both tracheal and rectal samples were cultured in antibiotic-enriched media (containing ceftazidime, ciprofloxacin, imipenem or piperacillin/tazobactam), to focus on resistant gram-negative pathogen isolation.Measurements and resultsColonization concordance between resistant, gram-negative pathogens of infectious episodes and previous, recent (≤7xa0days) colonization of the respiratory and gastrointestinal tract was determined, based on species identity and antimicrobial susceptibility. Concordance was 82% in VAP and 86% in BSI cases and was further confirmed by molecular testing of 15 randomly selected cases by REP-PCR. Previous colonization had high sensitivity and specificity in VAP, but was less specific in BSI cases. Knowledge of previous colonization improved the rate of adequate empiric antimicrobial treatment (91 vs. 40% in VAP and 86 vs. 50% in BSI cases, Pxa0<xa00.05).ConclusionsColonization surveillance for resistant gram-negative microorganisms is predictive of subsequent infection etiology and can improve empiric antimicrobial treatment adequacy in a critical care setting.

Evaluation of CHROMagar™ KPC for the detection of carbapenemase-producing Enterobacteriaceae in rectal surveillance cultures.

In this study, the performance of the chromogenic medium CHROMagar™ KPC was evaluated and was compared with in-house-daily prepared McConkey agar plates supplemented with imipenem (1 mg/L) for the detection of carbapenemase-producing Enterobacteriaceae. In this surveillance study, rectal swabs were cultured on both media and polymerase chain reaction (PCR) for bla(KPC) and bla(VIM) was used to confirm the genotype of growing colonies of Enterobacteriaceae. CHROMagar KPC was also tested with 17 genotypically characterised carbapenemase-producing and non-producing Gram-negative bacteria. It was shown that CHROMagar allows rapid detection of carbapenemase-producing Enterobacteriaceae, although bla(KPC)- and bla(VIM)-harbouring isolates could not be differentiated by colour or colony morphology. The positive and negative predictive values of the tested methods for the detection of carbapenemase-producing Enterobacteriaceae were, respectively, 100% and 98.8% for CHROMagar KPC and 94.7% and 88.6% for imipenem-supplemented McConkey agar. CHROMagar KPC medium is a useful screening medium for carbapenemase-producing Enterobacteriaceae in stools in settings with a high proportion of patients colonised with a variety of carbapenemase-producers.

Colonisation with vancomycin- and linezolid-resistant Enterococcus faecium in a university hospital: molecular epidemiology and risk factor analysis

During a hospital-wide prospective point prevalence survey of faecal carriage and environmental colonisation of vancomycin-resistant enterococci in a tertiary care university hospital in Athens (Greece), five clinical and one environmental isolate from a light switch (all in the haematology ward) were identified as vancomycin- and linezolid-resistant vanA-positive Enterococcus faecium (VLRE). The studied isolates exhibited a linezolid minimum inhibitory concentration of 12microg/mL and carried at least one mutated copy of the 23S rRNA gene, as shown by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to detect the G2576T mutation. The enterococcal surface protein (esp) gene was detected by PCR in all isolates. Molecular typing with pulsed field gel electrophoresis (PFGE) showed that the environmental and four of the five clinical isolates were genetically related. None of the colonised patients were previously exposed to linezolid, although heavy linezolid use was noted in the institution. A case-control study was performed to assess risk factors for VLRE colonisation. In univariate analysis, immunodeficiency, underlying haematological malignancy, duration of any antimicrobial treatment before VLRE isolation, and hospitalisation in the haematology ward were pointed out as possible risk factors. A multidisciplinary approach including intensified hand hygiene, patient contact isolation, disinfection of the inanimate environment and antibiotic restriction resulted in early containment of the VLRE colonisation outbreak.

Risk factors for community-associated methicillin-resistant Staphylococcus aureus colonisation in a large metropolitan area in Greece: An epidemiological study using two case definitions.

The aim of this study was to evaluate the epidemiology and characteristics and to identify modifiable risk factors for community-associated (CA) MRSA colonisation in a region with high prevalence. A large patient population (n=2280) from two tertiary care centres in Athens (Greece) was evaluated. Demographics and potential risk factors for CA-MRSA colonisation were recorded prospectively. Presence of the Panton-Valentine Leukocidin (PVL) toxin and mecA gene was determined in all MRSA isolates. Two definitions for CA-MRSA were applied. Univariate and multivariate analyses to identify predictors of previously unknown CA-MRSA colonisation were performed. In total, 120 (5.3%) MRSA carriers were identified; in 67 the isolates were classified as CA-MRSA using criteria based on the CDC definition, compared with 35 based on a definition including PVL toxin positivity. Factors significantly associated with previously unknown CA-MRSA carriage (CDC definition) included being a child or adolescent (OR=3.6, 95% CI 1.5-8.6), belonging to the family of an index case (OR=2.4, 95% CI 1.2-4.8), and presence of any co-morbidity (OR=1.7, 95% CI 1.04-2.8) or chronic skin disease (OR=3.6, 95% CI=2.2-6.1). In multivariate analysis, presence of any co-morbidity was the only significant predictor (OR=4.9, 95% CI 1.07-22.5; P=0.04). No easily modifiable risk factor for previously unknown CA-MRSA colonisation was identified. The CDC-based epidemiological definition for CA-MRSA appears to be more sensitive in detection of CA-MRSA colonisation than a purely molecular definition based on presence of the PVL gene.

Reliability, Validity, and Psychometric Properties of the Greek Translation of the Cambridge Depersonalization Scale (CDS) -

Introduction: The Cambridge Depersonalisation Scale is meant to capture the frequency and duration of depersonalisation symptoms over the ‘last 6 months’. Methods: In order to develop a Greek version of CDS scale, the CDS scale was translated in Greek by 2 psychiatrists. Then, the Greek version of CDS scale was back-translated by a person who did not knew the original English version. The back-translated version was reviewed in order to establish whether is consistent with the original English version. After this procedure we administered the Greek version of CDS scale to a sample of 294 Greeks in order to assess the reliability and the validity of the Greek version of scale. Results: The five components solution accounted for 58.204% of the total variation. Initial eigenvalues of the five components were: factor 1=11.555, factor 2=1.564, factor 3=1.356, factor 4=1.247 and factor 5=1.157. Six items did not load on any factor. Correlations between factors were low ranged from 0.134 to 0.314 and no complex variables were found. Cronbach’s alpha and Guttman split-half coefficient were used to evaluate interval consistency of CDS scale in 294 individuals. The alpha coefficients and Guttman split-half coefficient of the CDS scale were 0.938 and 0.921, respectively. The test-retest reliability proved to be satisfactory. The intraclass correlation coefficients for the total CDS score was very good and equal to 0,883. The CDS scale correlated highly with the SCL-90 and all subscales (p-value<0.0001). Conclusion: The psychometric strength of CDS – Greek its reliable for its future use, particularly for screening for subjects with possible diagnosis of CDS.