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Daptomycin activity against Gram-Positive Cocci isolated in United Kingdom medical centers
e86 exhibiting high-level gentamicin resistance are often assumed to be resistant to other aminoglycosides, but due the presence of different aminoglycoside resistance genes this may not always be true. Methods: From the Northern General Hospital Microbiology Department database, all enterococci cultured from clinical specimens from June 2004 onwards were identified. Strains originally found to be high level gentamicin resistant, and which had been stored on beads at -80 c, were recovered on blood agar at 30 c. Suitable specimens were then prepared for disc sensitivity testing using BSAC (British Society for Antimicrobial Chemotherapy) guidelines and cultured on isotest media (6% CO2, 30 c) in the presence of gentamicin (200 mg) and streptomycin (500 mg) discs. Diameters were examined at 24 hours. Results: A total of 64 specimens were identified. 58 isolates were successfully cultured and confirmed to be high level gentamicin resistant. Duplicate patients samples were discarded resulting in 51 isolates tested. Of those speciated, almost 70% were Enterococcus faecalis and the remainder E. faecium and galinarum. Sample sites were as follows: blood culture 29% (n ¼ 15), hip tissue 26% (n ¼ 13), hip joint aspirate 6% (n ¼ 3), knee tissue 20% (n ¼ 10), knee joint aspirate 8% (n ¼ 4), line tips 6% (n ¼ 3), spine tissue 2% (n ¼ 1), unknown joint fluid 2% (n ¼ 1), unknown joint tissue 2% (n ¼ 1). 80% (n ¼ 39) of samples were resistant to streptomycin and 20% (n ¼ 12) were sensitive. Conclusion and discussion: Streptomycin may be an alternative aminoglycoside in the treatment of enterococci with high level resistance to gentamicin. We discuss further the mechanisms for aminoglycoside resistance and the implications on therapy.
P 091 THE PREVALENCE OF ANTIBIOTIC RESISTANCE IN ENTEROCOCCUS SPECIES ISOLATED IN KUWAIT HOSPITALS Udo EE, Al-Sweih N, Aravindakshan S Dept of Microbiology, Faculty of Medicine, Kuwait University, Kuwait Background and objective: A previous study (19992001) revealed that the prevalence of vancomycin resistance was low (2.6%) in Enterococcus species isolated in Kuwait hospitals. However, 19% of the isolates expressed high-level gentamicin resistance. The aim of the present study was to compare the prevalence of antibiotic resistance in current enterococcal isolates to those in the previous study to determine any changes in resistance patterns. Methods: Between 1 March and 31 July, 2006, 294 enterococcus isolates were identified using the Vitek GP card and tested for susceptibilities to antibiotics by disk diffusion and by measuring their MICs by agar dilution or Etest strips. Results: The 294 consisted of 257 (87.4%) E. faecalis, 18 (6.1%) E. faecium, 6 (2.0%) E. gallinarum, 3 (1.0%) E. avium
Abstracts and 10 (3.4) unspeciated isolates. They were isolated from urines (94, 32%), blood (19, 6.5%), high vaginal swabs (50, 17.0%), catheter tips (4, 1.3%) and other sources (127, 43.2%). Two hundred (68.0%), 127 (43.2%) and 125 (42.5%) of the isolates were resistant to high level kanamycin (MIC >2000 mg/L), streptomycin (MIC >1000 mg/L) and gentamicin (MIC >500 mg/L) respectively. They were also resistant to tetracycline (84.7%), chloramphenicol (31.2%), erythromycin (67.0%) and rifampicin (25.2%). Twenty five isolates (8.5%) were resistant to ampicillin but only four (1.3%) of them produced beta-lactamase. Only two (0.7%) E . faecalis isolates were vancomycin resistant (MIC > 32 mg/L). Conclusions: The study revealed that E. faecalis remained the most common Enterococcus species isolated in Kuwait hospitals. Although the prevalence of vancomycin resistance remained low, the proportion of isolates that were resistant to high level gentamicin (from 19% to 42.5%), kanamycin (from 20% to 68%), streptomycin (from 20% to 43.2%), and tetracycline (from 60.5% to 84.7%) had increased significantly since the last study. Beta-lactamase production was detected for the first time in enterococcus isolated in Kuwait.
P 092 DAPTOMYCIN ACTIVITY AGAINST GRAM-POSITIVE COCCI ISOLATED IN UNITED KINGDOM MEDICAL CENTERS Bowker KE 1, MacGowan A 1, French G 2, Lindsay G 2, Sader HS 4, Jones RN 4 1
Southmead Hospital, Bristol Guy’s and St Thomas’ Hospital, London 3 Southern General Hospital, Glasgow 4 JMI Laboratories, North Liberty, IA, USA 2
Background: Daptomycin is a cyclic lipopeptide with broad spectrum and potent antimicrobial activity against Gram-positive pathogens. Daptomycin has been recently approved by the European Medicines Agency (EMA) for treatment of complicated skin and soft tissue infections (cSSTI). Methods: Bacterial isolates were consecutively collected in hospitals located in Bristol, Glasgow and London in 2002-2005 from various types of infections, mainly cSSTI, bacteremia and pneumonia. The isolates were tested for susceptibility by reference broth microdilution methods against daptomycin (50 mg/L calcium) and many comparators according to CLSI methods. The isolates tested include S. aureus (SA; 684); coagulase-negative staphylococci (CoNS; 92), Enterococcus spp. (147), b-haemolytic streptococci (bHS; 133) and viridans group streptococci (VGS; 46). Results: All 1,101 isolates tested were considered susceptible to daptomycin. Daptomycin was the most potent (lowest MIC90) among selected antimicrobials commonly used to treat Gram-positive infections, including vancomycin, teicoplanin, linezolid, and b-lactam and fluoroquinolone compounds. Daptomycin activity is summarized in the table.
Abstracts
e87
Cumulative % inhibited at MIC (mg/L): Organism (no tested) Oxacillin-susceptible S. aureus (396) Oxacillin-resistant S. aureus (288) Oxacillin-susceptible CoNS (30) Oxacillin-resistant CoNS (62) Vancomycin-susceptible enterococci (114) Vancomycin-resistant enterococci (VRE; 33) b-haemolytic streptococci (133) Viridans group streptococci (45)
0.12 1.5 4.2 23.3 3.2 1.8 0.0 78.9 31.1
Oxacillin-resistant rates were elevated among SA (42.1%) and CoNS (67.4%) isolates collected during the study and daptomycin demonstrated excellent activity against both oxacillin-susceptible and -resistant staphylococci (MIC90, 0.5 mg/L). Vancomycin resistance (VRE) was detected among 14.6% of E. faecalis and 42.5% of E. faecium, but daptomycin remained highly active against these VRE strains (MIC90, 2 mg/L). Conclusions: Resistance to oxacillin or vancomycin did not adversely influence daptomycin activity against staphylococci or enterococci. Daptomycin demonstrated significant potency and spectrum against contemporary Grampositive bacteria isolated in the UK, including methicillinresistant SA and VRE.
P 093 DAPTOMYCIN IN A COMPLICATED CASE OF PNEUMOCOCCAL INFECTION MacConnachie Alisdair A, Andrew Seaton R The Infection, Tropical Medicine and Counselling Service, Brownlee Centre, Gartnavel General Hospital, Glasgow, Scotland Background: Daptomycin is a novel lipopeptide antibiotic with broad gram positive cover. It is known to be highly bactericidal and its use in endocarditis has recently been validated. We describe the use of Daptomycin in a patient with complicated pneumococcal infection, who failed to settle on conventional antimicrobials. Case History: A 49 year old man, with a known history of alcohol excess was admitted to acute medical receiving following a collapse. Subsequent assessment revealed sepsis with meningismus, pneumonia and aortic valve endocarditis. Fully sensitive S. pneumoniae was isolated from blood cultures. Despite initial appropriate antibiotic therapy, he deteriorated with and required urgent aortic valve replacement with a porcine valve. Although stable post operatively, inflammatory markers were slow to settle. Repeated blood cultures revealed no growth and the addition of vancomycin did not significantly improve these. Repeat echocardiography revealed the presence of an aortic root abscess with fistulation through to the right ventricle. A second aortic valve replacement with aortic root remodelling was carried out. Antibiotics were continued as pre operatively, however the
0.25 70.7 74.0 66.7 62.9 7.0 3.0 97.0 71.1
0.5 99.7 99.0 96.7 90.3 51.8 33.3 100.0 97.8
1 100.0 100.0 100.0 100.0 81.6 72.7 e 100.0
2 e e e e 92.1 93.9 e e
4 e e e e 100.0 100.0 e e
>4 e e e e e e e e
patient remained intermittently pyrexial with climbing inflammatory markers (CRP 186 mg/l; white cell count 19.17). Broadening of antimicrobial cover and the addition of antifungal agents did not resolve matters and eventually all antimicrobials were stopped and Daptomycin at a dose of 6 mg/kg commenced. The patient improved rapidly with defervescence within 3 days and decreasing inflammatory markers (CRP 81 mg/l; white cell count 13.07). Following 3 months of treatment with Daptomycin he remained well with resolution of vegetations and improvement in abscess size on echocardiogram. He now continues on oral amoxicillin. Conclusions: Recent reports show the effectiveness of Daptomycin in the management of endocarditis. Our patient failed to settle despite multiple antimicrobial agents. The commencement of Daptomycin was associated with significant improvement both clinically and echocardiographically. This may be due to the high tissue penetration of Daptomycin and its high cidality.
P 094 USE OF VITEK FOR SURVEILLANCE OF ANTIBIOTIC RESISTANCE IN ESCHERICHIA COLI IN THE SCOTTISH HIGHLANDS: RESULTS OVER 15 YEARS Hay A, Macdonald E, Evans R, Davidson M Dept of Microbiology, Raigmore Hospital, Old Perth Road, Inverness IV2 3UJ Background: Automated antimicrobial susceptibility testing systems can assist good antimicrobial practice by rapidly and consistently testing a panel of antibiotics against individual bacterial isolates according to internationally agreed breakpoints. Such systems usually incorporate databases that allow the user to collect and analyse susceptibility patterns over time. Methods: Since April 1991 the microbiology service at Raigmore Hospital has used the VITEK automated identification and susceptibility testing system (bioMerieux, UK) to prospectively collect susceptibility data from over 49,000 clinically significant isolates of E. coli, the majority (>75%) from urinary tract. In July 2005 the original system was upgraded to VITEK 2. In the time period five different susceptibility cards were used. However, throughout CLSI (NCCLS) breakpoints have been used by the expert system.
P 091 THE PREVALENCE OF ANTIBIOTIC RESISTANCE IN ENTEROCOCCUS SPECIES ISOLATED IN KUWAIT HOSPITALS Udo EE, Al-Sweih N, Aravindakshan S Dept of Microbiology, Faculty of Medicine, Kuwait University, Kuwait Background and objective: A previous study (19992001) revealed that the prevalence of vancomycin resistance was low (2.6%) in Enterococcus species isolated in Kuwait hospitals. However, 19% of the isolates expressed high-level gentamicin resistance. The aim of the present study was to compare the prevalence of antibiotic resistance in current enterococcal isolates to those in the previous study to determine any changes in resistance patterns. Methods: Between 1 March and 31 July, 2006, 294 enterococcus isolates were identified using the Vitek GP card and tested for susceptibilities to antibiotics by disk diffusion and by measuring their MICs by agar dilution or Etest strips. Results: The 294 consisted of 257 (87.4%) E. faecalis, 18 (6.1%) E. faecium, 6 (2.0%) E. gallinarum, 3 (1.0%) E. avium
Abstracts and 10 (3.4) unspeciated isolates. They were isolated from urines (94, 32%), blood (19, 6.5%), high vaginal swabs (50, 17.0%), catheter tips (4, 1.3%) and other sources (127, 43.2%). Two hundred (68.0%), 127 (43.2%) and 125 (42.5%) of the isolates were resistant to high level kanamycin (MIC >2000 mg/L), streptomycin (MIC >1000 mg/L) and gentamicin (MIC >500 mg/L) respectively. They were also resistant to tetracycline (84.7%), chloramphenicol (31.2%), erythromycin (67.0%) and rifampicin (25.2%). Twenty five isolates (8.5%) were resistant to ampicillin but only four (1.3%) of them produced beta-lactamase. Only two (0.7%) E . faecalis isolates were vancomycin resistant (MIC > 32 mg/L). Conclusions: The study revealed that E. faecalis remained the most common Enterococcus species isolated in Kuwait hospitals. Although the prevalence of vancomycin resistance remained low, the proportion of isolates that were resistant to high level gentamicin (from 19% to 42.5%), kanamycin (from 20% to 68%), streptomycin (from 20% to 43.2%), and tetracycline (from 60.5% to 84.7%) had increased significantly since the last study. Beta-lactamase production was detected for the first time in enterococcus isolated in Kuwait.
P 092 DAPTOMYCIN ACTIVITY AGAINST GRAM-POSITIVE COCCI ISOLATED IN UNITED KINGDOM MEDICAL CENTERS Bowker KE 1, MacGowan A 1, French G 2, Lindsay G 2, Sader HS 4, Jones RN 4 1
Southmead Hospital, Bristol Guy’s and St Thomas’ Hospital, London 3 Southern General Hospital, Glasgow 4 JMI Laboratories, North Liberty, IA, USA 2
Background: Daptomycin is a cyclic lipopeptide with broad spectrum and potent antimicrobial activity against Gram-positive pathogens. Daptomycin has been recently approved by the European Medicines Agency (EMA) for treatment of complicated skin and soft tissue infections (cSSTI). Methods: Bacterial isolates were consecutively collected in hospitals located in Bristol, Glasgow and London in 2002-2005 from various types of infections, mainly cSSTI, bacteremia and pneumonia. The isolates were tested for susceptibility by reference broth microdilution methods against daptomycin (50 mg/L calcium) and many comparators according to CLSI methods. The isolates tested include S. aureus (SA; 684); coagulase-negative staphylococci (CoNS; 92), Enterococcus spp. (147), b-haemolytic streptococci (bHS; 133) and viridans group streptococci (VGS; 46). Results: All 1,101 isolates tested were considered susceptible to daptomycin. Daptomycin was the most potent (lowest MIC90) among selected antimicrobials commonly used to treat Gram-positive infections, including vancomycin, teicoplanin, linezolid, and b-lactam and fluoroquinolone compounds. Daptomycin activity is summarized in the table.
Abstracts
e87
Cumulative % inhibited at MIC (mg/L): Organism (no tested) Oxacillin-susceptible S. aureus (396) Oxacillin-resistant S. aureus (288) Oxacillin-susceptible CoNS (30) Oxacillin-resistant CoNS (62) Vancomycin-susceptible enterococci (114) Vancomycin-resistant enterococci (VRE; 33) b-haemolytic streptococci (133) Viridans group streptococci (45)
0.12 1.5 4.2 23.3 3.2 1.8 0.0 78.9 31.1
Oxacillin-resistant rates were elevated among SA (42.1%) and CoNS (67.4%) isolates collected during the study and daptomycin demonstrated excellent activity against both oxacillin-susceptible and -resistant staphylococci (MIC90, 0.5 mg/L). Vancomycin resistance (VRE) was detected among 14.6% of E. faecalis and 42.5% of E. faecium, but daptomycin remained highly active against these VRE strains (MIC90, 2 mg/L). Conclusions: Resistance to oxacillin or vancomycin did not adversely influence daptomycin activity against staphylococci or enterococci. Daptomycin demonstrated significant potency and spectrum against contemporary Grampositive bacteria isolated in the UK, including methicillinresistant SA and VRE.
P 093 DAPTOMYCIN IN A COMPLICATED CASE OF PNEUMOCOCCAL INFECTION MacConnachie Alisdair A, Andrew Seaton R The Infection, Tropical Medicine and Counselling Service, Brownlee Centre, Gartnavel General Hospital, Glasgow, Scotland Background: Daptomycin is a novel lipopeptide antibiotic with broad gram positive cover. It is known to be highly bactericidal and its use in endocarditis has recently been validated. We describe the use of Daptomycin in a patient with complicated pneumococcal infection, who failed to settle on conventional antimicrobials. Case History: A 49 year old man, with a known history of alcohol excess was admitted to acute medical receiving following a collapse. Subsequent assessment revealed sepsis with meningismus, pneumonia and aortic valve endocarditis. Fully sensitive S. pneumoniae was isolated from blood cultures. Despite initial appropriate antibiotic therapy, he deteriorated with and required urgent aortic valve replacement with a porcine valve. Although stable post operatively, inflammatory markers were slow to settle. Repeated blood cultures revealed no growth and the addition of vancomycin did not significantly improve these. Repeat echocardiography revealed the presence of an aortic root abscess with fistulation through to the right ventricle. A second aortic valve replacement with aortic root remodelling was carried out. Antibiotics were continued as pre operatively, however the
0.25 70.7 74.0 66.7 62.9 7.0 3.0 97.0 71.1
0.5 99.7 99.0 96.7 90.3 51.8 33.3 100.0 97.8
1 100.0 100.0 100.0 100.0 81.6 72.7 e 100.0
2 e e e e 92.1 93.9 e e
4 e e e e 100.0 100.0 e e
>4 e e e e e e e e
patient remained intermittently pyrexial with climbing inflammatory markers (CRP 186 mg/l; white cell count 19.17). Broadening of antimicrobial cover and the addition of antifungal agents did not resolve matters and eventually all antimicrobials were stopped and Daptomycin at a dose of 6 mg/kg commenced. The patient improved rapidly with defervescence within 3 days and decreasing inflammatory markers (CRP 81 mg/l; white cell count 13.07). Following 3 months of treatment with Daptomycin he remained well with resolution of vegetations and improvement in abscess size on echocardiogram. He now continues on oral amoxicillin. Conclusions: Recent reports show the effectiveness of Daptomycin in the management of endocarditis. Our patient failed to settle despite multiple antimicrobial agents. The commencement of Daptomycin was associated with significant improvement both clinically and echocardiographically. This may be due to the high tissue penetration of Daptomycin and its high cidality.
P 094 USE OF VITEK FOR SURVEILLANCE OF ANTIBIOTIC RESISTANCE IN ESCHERICHIA COLI IN THE SCOTTISH HIGHLANDS: RESULTS OVER 15 YEARS Hay A, Macdonald E, Evans R, Davidson M Dept of Microbiology, Raigmore Hospital, Old Perth Road, Inverness IV2 3UJ Background: Automated antimicrobial susceptibility testing systems can assist good antimicrobial practice by rapidly and consistently testing a panel of antibiotics against individual bacterial isolates according to internationally agreed breakpoints. Such systems usually incorporate databases that allow the user to collect and analyse susceptibility patterns over time. Methods: Since April 1991 the microbiology service at Raigmore Hospital has used the VITEK automated identification and susceptibility testing system (bioMerieux, UK) to prospectively collect susceptibility data from over 49,000 clinically significant isolates of E. coli, the majority (>75%) from urinary tract. In July 2005 the original system was upgraded to VITEK 2. In the time period five different susceptibility cards were used. However, throughout CLSI (NCCLS) breakpoints have been used by the expert system.