| 1. |
- Hanberger, Håkan, et al.
(författare)
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Pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis and Staphylococcus aureus demonstrated by studies of initial killing and postantibiotic effect and influence of Ca2+ and albumin on these drugs.
- 1991
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 35:9, s. 1710-1716
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 25923 were investigated by studying the postantibiotic effect (PAE) and initial killing. The influence of Ca2+ and albumin on these drugs was also evaluated. The PAE was studied by use of bioluminescence assay of bacterial ATP. Daptomycin at clinically achievable concentrations produced a dose-dependent PAE on E. faecalis (0.6 to 6.7 h) and S. aureus (1.0 to 6.3 h). The long PAE of daptomycin was seen simultaneously with a potent dose-dependent initial killing assayed by viable count determination. The initial change in bacterial ATP was not as extensive as the decrease in viability. Vancomycin at corresponding concentrations produced shorter PAEs on E. faecalis (0.5 to 1.0 h) and S. aureus (1.3 to 1.8 h). This coincides with a weak non-dose-dependent initial change in viability and intracellular ATP. The MICs of vancomycin were not influenced by different Ca2+ concentrations or by the addition of albumin to the broth. The MICs of daptomycin for both strains were lowered, and the PAEs were prolonged with increasing concentrations of Ca2+ in the broth. The PAE of daptomycin was Ca2+ dependent to the same extent as the MIC was. In the presence of physiological concentrations of albumin and free Ca2+, the PAEs of daptomycin on both strains were reduced and the MICs were increased in comparison with the results obtained in pure Mueller-Hinton broth with approximately the same free Ca2+ concentration. This decrease in daptomycin activity was considered to be due to the albumin binding of daptomycin. Despite the albumin binding of daptomycin, the PAE produced on E. faecalis and S. aureus in the presence of a physiological free Ca2+ concentration was still over 6 h at clinically achievable concentrations.
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| 2. |
- Hällgren, Anita, 1963-, et al.
(författare)
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Genetic relatedness among Enterococcus faecalis with transposon-mediated high-level gentamicin resistance in Swedish intensive care units
- 2003
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 52:2, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- We studied 45 isolates of Enterococcus faecalis with high-level gentamicin resistance (HLGR), all but one concomitantly resistant to ciprofloxacin, and 25 ciprofloxacin-resistant isolates without HLGR for genetic relatedness using pulsed-field gel electrophoresis (PFGE). E. faecalis were isolated from patients admitted to intensive care units at eight hospitals in southern Sweden from December 1996 through December 1998. Genomic analysis by PFGE resulted in three clusters of genetically related isolates (designated clusters I, II and III) and 23 unique clones. Cluster I was found predominantly in the eastern and central parts of southern Sweden and clusters II and III in south-western Sweden. Among the 45 isolates with HLGR, 69% belonged to cluster I, 20% to cluster II, and 11% had unique PFGE patterns, which suggests that the majority of isolates with HLGR are closely related. Among the 25 ciprofloxacin-resistant isolates without HLGR, 68% had unique PFGE patterns, 12% belonged to cluster I and 20% to cluster III, which suggests the ciprofloxacin-resistant isolates are not related. All isolates with HLGR contained the aac(6′)Ie-aph(2″)Ia gene, which was carried on a Tn5281-like transposon in all isolates except one. We conclude that HLGR in E. faecalis was mainly due to dissemination of genetically related clones during the time studied, and that HLGR in these isolates was due to the presence of the aac(6′)Ie-aph(2″)Ia gene.
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| 3. |
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| 4. |
- Hällgren, Anita, 1963-, et al.
(författare)
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Rectal colonization and frequency of enterococcal cross-transmission among prolonged-stay patients in two Swedish intensive care units
- 2005
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 37:8, s. 561-571
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to gain insight into the dynamics of the rectal flora during prolonged ICU stay, with a particular focus on colonization and cross-transmission with resistant pathogens, and to evaluate methods for the rapid isolation of relevant bacteria from rectal swabs. Patients admitted to a general intensive care unit (GICU) or a cardiothoracic ICU (TICU) at the University Hospital of Linköping, Sweden, between 1 November 2001 and January 2002 with a length of stay > 5 d were included (n = 20). Chromogenic UTI agar medium was used for discrimination of different species, and appropriate antibiotics were added to detect resistance. Direct plating was compared to enrichment broth for a subset of specimens. The study showed an early alteration in rectal flora, with a dramatic decrease in Gram-negative rods in favour of Gram-positive bacteria. An ampicillin- and high-level gentamicin resistant clone of Enterococcus faecium was found in 6 of 10 patients in the GICU and 2 of 11 patients in the TICU. Enrichment broth did not enhance the detection of Gram-negative bacteria compared to direct plating on Chromogenic UTI medium, but enrichment broths were needed for optimal detection of resistant Gram-positive bacteria.
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| 5. |
- Isaksson, Barbro, et al.
(författare)
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Postantibiotic effect of aminoglycosides on gram-negative bacteria evaluated by a new method.
- 1988
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 22:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- The in-vitro postantibiotic effect (PAE) of amikacin, gentamicin, netilmicin and tobramycin was investigated by a bioluminescent assay of bacterial ATP. Two strains each of Escherichia coli and Pseudomonas aeruginosa were exposed for 1 h to different concentrations of the aminoglycosides. The aminoglycoside was removed by a 10(-3) dilution, and regrowth of bacteria was followed at hourly intervals by monitoring bacterial ATP. This method simplified the PAE studies and made such studies possible at high aminoglycoside concentrations. The length of the PAE was dose-dependent for all the aminoglycosides studied. The PAEs ranged between three and seven hours for all four strains at the aminoglycoside concentrations normally reached in serum during standard dosing. The long PAE of aminoglycosides, especially after exposure to high drug concentrations, constitutes an argument in favour of administering aminoglycosides in higher-than-usual doses with longer intervals between doses. This proposal is also supported by recent pharmacokinetic, bacteriological and toxicity data.
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| 6. |
- Isaksson, Barbro, et al.
(författare)
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Postantibiotic effect of aminoglycosides on staphylococci.
- 1993
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 32:2, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- The postantibiotic effects (PAEs) of amikacin, gentamicin, netilmicin and tobramycin on Staphylococcus aureus and S. epidermidis were determined in vitro by a bioluminescence assay of bacterial ATP. Five strains of S. aureus and two strains of S. epidermidis were exposed for 1 h to varying concentrations of these aminoglycosides. Following removal of the antibiotics by dilution, bacterial regrowth was monitored at hourly intervals. The duration of the PAE increased with increasing aminoglycoside concentration. The mean PAEs for the five S. aureus strains ranged from 5-10 h at clinically achievable aminoglycoside concentrations (16-32 mg/L of amikacin and 4-8 mg/L of gentamicin, netilmicin and tobramycin). The results for one of the strains of S. epidermidis were similar to those observed for the S. aureus strains, while the PAEs on the other less susceptible S. epidermidis strain were shorter (0.5-2.5 h). For comparison, two of the S. aureus strains were exposed for 1 and 2 h to a range of concentrations of dicloxacillin (0.25-32 mg/L); this agent induced a much shorter PAE (0-2.3 h). It may be important to take account of the PAE when designing dosing regimens.
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| 7. |
- Isaksson, Barbro, et al.
(författare)
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Synergic post-antibiotic effect of amikacin in combination with beta-lactam antibiotics on gram-negative bacteria.
- 1991
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 28:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- The post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains each of Pseudomonas aeruginosa and Serratia marcescens using a bioluminescent assay of bacterial ATP. Two models were used for combining beta-lactam antibiotics and amikacin: in one model the cultures were incubated with 32 mg/L of ceftazidime, 128 mg/L of ceftriaxone or 32 mg/L of piperacillin for 1 h. Different concentrations of amikacin (0.5-64 mg/L) were then added. Incubation of the combinations continued for one more hour. The antibiotics were eliminated by dilution. In the second model tested, one strain of S. marcescens was simultaneously exposed to amikacin and a beta-lactam antibiotic for 2 h. The PAEs produced by the drugs in combination were longer than the sum of the individual effects of the drugs when they were used alone. Results were equally good with both models. A synergic PAE was also found with amikacin concentrations close to the MIC in combination with low concentrations of ceftazidime, ceftriaxone and piperacillin.
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| 8. |
- Isaksson, Barbro, et al.
(författare)
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Synergistic post-antibiotic effect of amikacin and beta-lactam antibiotics on Enterococcus faecalis.
- 1991
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 27, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- The in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains of Enterococcus faecalis using a bioluminescent assay of bacterial ATP. The two strains of E. faecalis were resistant to amikacin, ceftazidime and ceftriaxone but sensitive to piperacillin. The bacterial cultures were incubated with the beta-lactam antibiotics for 1 h and concentrations of amikacin between 2-64 mg/l were then added. Thereafter, incubation continued with the combinations for one more hour. After dilution, regrowth was monitored by measuring bacterial ATP every hour. Increasing concentrations of amikacin (2-64 mg/l), ceftazidime (8-32 mg/l) and ceftriaxone (32-128 mg/l) resulted in little or no PAE (0-0.3 h) on these strains. PAEs of 0.5 to 1.6 h resulted from exposure to piperacillin (4-32 mg/l). In combination amikacin and piperacillin increased the PAE to 5.5 h. A synergistic PAE was also seen when the enterococci were exposed to amikacin combined with ceftazidime or ceftriaxone in concentrations close to the MICs of the latter antibiotics.
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| 9. |
- Lindqvist, Maria, et al.
(författare)
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A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county
- 2009
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Ingår i: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 41:5, s. 324-333
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.
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| 10. |
- Lindqvist, Maria, 1983-
(författare)
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Epidemiological and molecular biological studies of multi-resistant methicillin-susceptible Staphylococcus aureus
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance is increasingly recognised as a major problem and threat. During the last decades Gram-positive bacteria in general, and methicillin-resistant Staphylococcus aureus (MRSA) in particular, have been in focus both concerning matters of antibiotic resistance and as pathogens causing health care-associated (nosocomial) infections. In contrast to MRSA, studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. However, interest in MSSA has increased since it was shown that MRSA emerges from susceptible backgrounds by acquisition of a staphylococcal cassette chromosome element, carrying the mecA gene encoding methicillin-resistance (SCCmec).In an outbreak investigation of MRSA in Östergötland County, Sweden, in 2005, a high incidence of MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin (ECT-R) was detected. Analysis showed that 91 % of the investigated isolates were genetically related (clonal). The ECT-R clone was divided into four different but closely related patterns with pulsed-field gel electrophoresis (PFGE), and was designated spa type t002. Whole genome sequencing revealed that the ECT-R clone carried a pseudo-SCC element estimated to be 12 kb in size, showing a resemblance of more than 99 % with the SCCmec type II element of MRSA strain N315 (New York/Japan clone). This suggested a probable derivation from a highly successful MRSA strain, which had partially excised its SCCmec. The clonal outbreak was concentrated in eight hospital departments and two primary care centres, all located in the city of Linköping. Despite a high exchange of patients with the hospitals in the neighbouring counties in southeast Sweden (Jönköping- and Kalmar County), the ECT-R clone seemed to be limited to Östergötland County. However, a tobramycin-resistant clone predominated by isolates of spa type t084 was found in all three counties in southeast Sweden, and in particular among newborns, suggesting inter-hospital transmission.The ECT-R clone has survived as an abundant MSSA clone for a decade in Östergötland County, which indicates an insufficiency in the maintenance of basic hygiene guidelines, and that the clone probably possesses mechanisms of virulence and transmission that are yet to be discovered.
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