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P2094 Association between antibiotic use and incidence of methicillin-resistant Staphylococcus aureus in general intensive care unit
Relationship between antibiotic use and resistance respectively, based on multiple species animal data using allometric scaling (R2 > 0.97). A long t1/2 of ~16 hours is predicted in humans. Conclusions: EDP-420 is well absorbed and has optimal pre-clinical PK properties across multiple species. The excellent correlation of allometric plots of PK parameters in four preclinical species suggests that EDP-420 PK behaviour in humans can be well predicted. P2093 Tissue distribution of [14C]-EDP-420 in the rat by quantitative whole-body autoradiography L.J. Jiang, M. Takeuchi, R. Lewsley, A. Sonderfan, T. Baba, Y.S. Or (Watertown, US; Osaka, JP; Harrogate, UK) Objectives: EDP-420 (EP-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections (RTI). This study shows the tissue distribution of radioactivity in the male and female albino rat and the male pigmented rat following a single oral gavage administration of 10 mg/kg of [14 C]EDP-420 using QWBA. Methods: Rats were euthanised by cold shock following deep anaesthesia under isoflurane at specific times after dosing. The carcasses were frozen in a mixture of hexane and solid carbon dioxide and were subjected to quantitative whole-body autoradiography (QWBA) procedures. Radioactivity concentrations in tissues were quantified from the whole body autoradiograms using a validated image analysis system. Results: Radioactivity was widely distributed at 2 hours after administration to male albino rats with Tmax = 8−10 hours in most tissues. Cmax in most tissues was greater than plasma Cmax of 0.871 mg equiv/g. Highest concentrations of radioactivity in tissues were generally associated with the Harderian gland (unique to rodents), lung, pituitary and spleen, with Cmax = 20−60 mg equiv/g, and AUC0−∞ = 671–1940 mg equiv-h/g. Plasma AUC0−∞ was 14.5 mg equiv-h/g. The ratios of Cmax and AUC0−∞ in lung over the corresponding values in plasma were 32.3 and 46.3, respectively. The majority of tissues had terminal half-lives of radioactivity in the range of 10 to 20 hours. Plasma had the shortest terminal half-life of 6.15 hours. There was little evidence for any gender difference in the distribution of radioactivity. Absorbed radioactivity was eliminated by both the biliary and renal routes. Quantifiable radioactivity was present in melanin-containing tissues (uveal tract and pigmented skin) of pigmented animals and declined at late sampling times. Conclusion: EDP-420 has demonstrated good tissue distribution (especially lung penetration) in rats, suggesting that EDP-420 may be an effective compound for the treatment of RTI.
Relationship between antibiotic use and resistance P2094 Association between antibiotic use and incidence of methicillin-resistant Staphylococcus aureus in general intensive care unit
S605 Results: Three hundred sixty five new MRSA cases were registered in the hospital by September, 2006. 34.3% (CI: 29.6; 39.3) of cases were detected in general ICU. 88.8% (CI: 82.1; 93.2) of them received antibiotics before the cultures were taken of whom 36.0% (CI: 24.5; 40.6) received ciprofloxacin, 31.5% (CI: 23.6; 40.07) ceftriaxone, and 8.1% (CI: 4.3; 14.7) ceftazidime. In contrast, for the study time period the proportion in total antibiotic consumption in DDD/bed days for ciprofloxacin was 11.1% (CI: 6.8; 1.8), ceftriaxone 11.7% (CI: 7.3; 18.2), and ceftazidime 0.83% (CI: 0.2; 4.2). Ciprofloxacin was the only fluoroquinolone used. Average monthly antibiotic consumption in ICU was 134.37 (CI: 122.2; 146.6) DDD per 100 bed days or 230.1 (CI: 221.54; 252.3) PAD. There was no correlation or association between monthly variations in total consumption and MRSA incidence. Time trend analysis showed association of number of new MRSA cases and PAD for ciprofloxacin. We observed the peak of ciprofloxacin consumption measured in PAD before increase in MRSA cases with the time delay of 2−3 months. There was no such association with consumption of third generation cephalosporins and other antibiotics except vancomycin that was used for treatment. Conclusions: Use of ciprofloxacin and 3rd generation cephalosporins was identified as a risk factor for acquisition of MRSA infection and did not reflect the general pattern of antibiotic use in our ICU. Measurement of antibiotic consumption by using PAD could have advantage for evaluation of the impact of antibiotic resistance selection pressure. P2095 Carbapenem consumption and resistance of P. aeruginosa and K. pneumoniae to carbapenems: results from a 7-year study in a general hospital M. Lelekis, C. Loupa, A. Karaitianou, H. Papadaki, I. Tzannou, E. Katsiki-Divari, K. Papaefstathiou, G. Kouppari (Athens, GR) Objective: The aim of the present study was to record on one hand carbapenem consumption and on the other hand carbapenem resistance of P. aeruginosa and K. pneumoniae strains isolated in our 300-bed general hospital over a 7 year period. Methods: Antibiotic consumption for the period 1999 to 2005 was studied retrospectively using data from the pharmacy computer. Antibiotic use was calculated in DDDs per 1000 patient days (ABC Calc 3.0). On the other hand data concerning imipenem resistance of P. aeruginosa and K. pneumoniae strains isolated in our hospital during the same time period were taken from the microbiology department. Results: Antibiotic consumption was 572, 647, 678, 675, 710, 785 and 892 DDDs/1000 patient days (years 1999, 2000, 2001, 2002, 2003, 2004, 2005 respectively). Carbapenem consumption was 3.8, 6.7, 6.2, 3.9, 7.1, 9.8, 15.2 DDDs/1000 patient days for the above mentioned years (figure). During the same time period P. aeruginosa resistance to imipenem was 14.5%, 7.8%, 14%, 17.5%, 15.4%, 15.5%, 15.5% and that of K. pneumonia to imipenem 0, 2.1%, 0, 0, 2%, 2.3%, 7.3% (figure).
E. Pujate, A. Balode, P. Oss, U. Dumpis (Riga, LV) Objectives: The use of 3rd generation cephalosporins and fluoroquinolones has been previously associated with increased risk for acquisition of MRSA. Active surveillance of all MRSA cases and infection control programme was started in March, 2003 when the first cases were identified in our hospital. Most of the outbreaks were associated with the ICU. Aim of this study was to examine possible correlation between aggregated antibiotic consumption data and MRSA incidence in the general ICU. Method: Retrospective study on antibiotic usage and MRSA incidence was performed in ICU. Data on MRSA cases were taken from MRSA surveillance database. Number of new MRSA cases in ICU was calculated monthly. Antibiotic consumption was measured in DDD per 100 bed days and patient on antibiotic days (PAD) recorded every day for each antibiotic by the nurse. Statistical analysis was performed with SPSS 13 software package.
Conclusions: During the study period, total consumption increased significantly in our hospital and this was the case for carbapenem consumption as well. At the same time while P. aeruginosa resistance to carbapenems seems to have stabilised around 15%, it is worrisome that
Relationship between antibiotic use and resistance P2094 Association between antibiotic use and incidence of methicillin-resistant Staphylococcus aureus in general intensive care unit
S605 Results: Three hundred sixty five new MRSA cases were registered in the hospital by September, 2006. 34.3% (CI: 29.6; 39.3) of cases were detected in general ICU. 88.8% (CI: 82.1; 93.2) of them received antibiotics before the cultures were taken of whom 36.0% (CI: 24.5; 40.6) received ciprofloxacin, 31.5% (CI: 23.6; 40.07) ceftriaxone, and 8.1% (CI: 4.3; 14.7) ceftazidime. In contrast, for the study time period the proportion in total antibiotic consumption in DDD/bed days for ciprofloxacin was 11.1% (CI: 6.8; 1.8), ceftriaxone 11.7% (CI: 7.3; 18.2), and ceftazidime 0.83% (CI: 0.2; 4.2). Ciprofloxacin was the only fluoroquinolone used. Average monthly antibiotic consumption in ICU was 134.37 (CI: 122.2; 146.6) DDD per 100 bed days or 230.1 (CI: 221.54; 252.3) PAD. There was no correlation or association between monthly variations in total consumption and MRSA incidence. Time trend analysis showed association of number of new MRSA cases and PAD for ciprofloxacin. We observed the peak of ciprofloxacin consumption measured in PAD before increase in MRSA cases with the time delay of 2−3 months. There was no such association with consumption of third generation cephalosporins and other antibiotics except vancomycin that was used for treatment. Conclusions: Use of ciprofloxacin and 3rd generation cephalosporins was identified as a risk factor for acquisition of MRSA infection and did not reflect the general pattern of antibiotic use in our ICU. Measurement of antibiotic consumption by using PAD could have advantage for evaluation of the impact of antibiotic resistance selection pressure. P2095 Carbapenem consumption and resistance of P. aeruginosa and K. pneumoniae to carbapenems: results from a 7-year study in a general hospital M. Lelekis, C. Loupa, A. Karaitianou, H. Papadaki, I. Tzannou, E. Katsiki-Divari, K. Papaefstathiou, G. Kouppari (Athens, GR) Objective: The aim of the present study was to record on one hand carbapenem consumption and on the other hand carbapenem resistance of P. aeruginosa and K. pneumoniae strains isolated in our 300-bed general hospital over a 7 year period. Methods: Antibiotic consumption for the period 1999 to 2005 was studied retrospectively using data from the pharmacy computer. Antibiotic use was calculated in DDDs per 1000 patient days (ABC Calc 3.0). On the other hand data concerning imipenem resistance of P. aeruginosa and K. pneumoniae strains isolated in our hospital during the same time period were taken from the microbiology department. Results: Antibiotic consumption was 572, 647, 678, 675, 710, 785 and 892 DDDs/1000 patient days (years 1999, 2000, 2001, 2002, 2003, 2004, 2005 respectively). Carbapenem consumption was 3.8, 6.7, 6.2, 3.9, 7.1, 9.8, 15.2 DDDs/1000 patient days for the above mentioned years (figure). During the same time period P. aeruginosa resistance to imipenem was 14.5%, 7.8%, 14%, 17.5%, 15.4%, 15.5%, 15.5% and that of K. pneumonia to imipenem 0, 2.1%, 0, 0, 2%, 2.3%, 7.3% (figure).
E. Pujate, A. Balode, P. Oss, U. Dumpis (Riga, LV) Objectives: The use of 3rd generation cephalosporins and fluoroquinolones has been previously associated with increased risk for acquisition of MRSA. Active surveillance of all MRSA cases and infection control programme was started in March, 2003 when the first cases were identified in our hospital. Most of the outbreaks were associated with the ICU. Aim of this study was to examine possible correlation between aggregated antibiotic consumption data and MRSA incidence in the general ICU. Method: Retrospective study on antibiotic usage and MRSA incidence was performed in ICU. Data on MRSA cases were taken from MRSA surveillance database. Number of new MRSA cases in ICU was calculated monthly. Antibiotic consumption was measured in DDD per 100 bed days and patient on antibiotic days (PAD) recorded every day for each antibiotic by the nurse. Statistical analysis was performed with SPSS 13 software package.
Conclusions: During the study period, total consumption increased significantly in our hospital and this was the case for carbapenem consumption as well. At the same time while P. aeruginosa resistance to carbapenems seems to have stabilised around 15%, it is worrisome that