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Patrice Nordmann - One of the best experts on this subject based on the ideXlab platform.
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characterization of a naturally occurring class d β lactamase from achromobacter xylosoxidans
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Laurent Poirel, David L Paterson, Patrice NordmannAbstract:Achromobacter xylosoxidans (previously Alcaligenes xylosoxidans) is a non-glucose-fermenting gram-negative species that is increasingly recognized as a clinically significant nosocomial pathogen. With its tendency to contaminate fluid, many outbreaks have been reported, mostly in immunocompromised hosts, causing serious infections, including bacteremia (4, 9). The organism has variable susceptibility to β-lactams (8). It is mostly resistant to narrow-spectrum penicillins and to several cephalosporins, including cefotaxime, whereas susceptibility to Ureidopenicillins and carbapenems varies (8). However, acquisition of metallo-β-lactamases, such as IMP-1, VIM-1, or VIM-2, has been reported for A. xylosoxidans, therefore leading to high-level resistance to carbapenems (12, 17-20). The intrinsic β-lactamases produced by A. xylosoxidans have been characterized only biochemically. Levesque et al. reported three types of cephalosporinases, with isoelectric points (pIs) of 7.4, 9.3, and 8.1 and molecular masses of 32.3 kDa, 22.800 kDa, and 36.200 kDa, respectively (13). Fujii et al. characterized a penicillinase with an unusually high pI of 9.8 and a molecular mass of 18 kDa (5). Philippon et al. reported a penicillinase with a pI of 5.7 and an oxacillinase with a pI of 7.7 (3, 15). None of the β-lactamase genes have been identified so far. The present study was designed to identify and to characterize, at the genetic and biochemical levels, the naturally occurring β-lactamase(s) of A. xylosoxidans.
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resistance to cefepime and cefpirome due to a 4 amino acid deletion in the chromosome encoded ampc β lactamase of a serratia marcescens clinical isolate
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Hedi Mammeri, Laurent Poirel, Pascal Bemer, H Drugeon, Patrice NordmannAbstract:A multiresistant Serratia marcescens strain, HD, isolated from a patient with a urinary tract infection, was resistant to amino-, carboxy-, and Ureidopenicillins, ceftazidime, and cefepime and was susceptible to cefotaxime and ceftriaxone, according to the guidelines of the NCCLS. No synergy was found between expanded-spectrum cephalosporins and clavulanic acid, according to the double-disk synergy test. The blaAmpC gene of the strain was amplified by PCR and cloned into Escherichia coli DH10B, giving rise to high-level resistance to ceftazidime, cefepime, and cefpirome. Sequencing analysis revealed that the blaAmpC gene from S. marcescens HD had a 12-nucleotide deletion compared to the blaAmpC gene from reference strain S. marcescens S3, leading to a 4-amino-acid deletion located in the H-10 helix of the β-lactamase. Kinetic analysis showed that this enzyme significantly hydrolyzed ceftazidime, cefepime, and cefpirome. This work underlined that resistance to the latest expanded-spectrum cephalosporins may be mediated by structurally modified AmpC-type β-lactamases.
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biochemical genetic analysis and distribution of des 1 an ambler class a extended spectrum β lactamase from desulfovibrio desulfuricans
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: Annesophie Morin, Laurent Poirel, Francine Mory, Roger Labia, Patrice NordmannAbstract:Desulfovibrio spp. are gram-negative anaerobes phylogenetically related to Bacteroides spp., which are rarely isolated and which are mostly isolated from intra-abdominal abscesses. Desulfovibrio desulfuricans clinical isolate D3 had a clavulanic acid-inhibited beta-lactam resistance profile and was resistant to some expanded-spectrum cephalosporins. A beta-lactamase gene, bla(DES-1), was cloned from whole-cell DNA of isolate D3 and expressed in Escherichia coli. Purified beta-lactamase DES-1, with a pI value of 9.1, had a relative molecular mass of ca. 31 kDa and a mature protein of 288 amino acids. DES-1 was distantly related to Ambler class A beta-lactamases and most closely related to PenA from Burkholderia pseudomallei (48% amino acid identity). It was weakly related to class A beta-lactamases CblA, CepA, CfxA, and CfxA2 from other anaerobic species, Bacteroides spp. and Prevotella intermedia. Its hydrolysis spectrum included amino- and Ureidopenicillins, narrow-spectrum cephalosporins, ceftriaxone, and cefoperazone. bla(DES-1)-like genes were not identified in phylogenetically related Desulfovibrio fairfieldensis isolates. However, they were found in some but not all D. desulfuricans strains, thus suggesting that these genes may be present in a given D. desulfuricans subspecies.
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molecular and biochemical characterization of ambler class a extended spectrum β lactamase cga 1 from chryseobacterium gleum
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: Samuel Bellais, Thierry Naas, Patrice NordmannAbstract:Antibiotic susceptibility testing by disk diffusion of a Chryseobacterium gleum isolate, strain CIP 103039, showed a typical synergy image between clavulanic acid and expanded-spectrum cephalosporins. Shotgun cloning gave a recombinant plasmid in Escherichia coli that produced a β-lactamase, CGA-1, with a pI value of 8.9 that conferred resistance to most penicillins (except Ureidopenicillins) and narrow-spectrum cephalosporins and an intermediate susceptibility to expanded-spectrum cephalosporins and aztreonam. The CGA-1 amino acid sequence shared only 60% amino acid identity with CME-1 and CME-2 from Chryseobacterium meningosepticum, the most closely related β-lactamases. CGA-1 was very likely chromosome encoded. It is a novel member of the PER subgroup of Ambler class A β-lactamases (Bush functional group 2be).
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molecular and biochemical heterogeneity of class b carbapenem hydrolyzing β lactamases in chryseobacterium meningosepticum
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Samuel Bellais, Thierry Naas, Daniel Aubert, Patrice NordmannAbstract:Although the carbapenem-hydrolyzing beta-lactamase (CHbetaL) BlaB-1 is known to be in Chryseobacterium meningosepticum NCTC 10585, a second CHbetaL gene, bla(GOB-1), was cloned from another C. meningosepticum clinical isolate (PINT). The G+C content of bla(GOB-1) (36%) indicated the likely chromosomal origin of this gene. Its expression in Escherichia coli DH10B yields a mature CHbetaL with a pI of 8.7 and a relative molecular mass of 28.2 kDa. In E. coli, GOB-1 conferred resistance to narrow-spectrum cephalosporins and reduced susceptibility to Ureidopenicillins, broad-spectrum cephalosporins, and carbapenems. GOB-1 had a broad-spectrum hydrolysis profile including penicillins and cephalosporins (but not aztreonam). The catalytic efficiency for meropenem was higher than for imipenem. GOB-1 had low amino acid identity with the class B CHbetaLs, sharing 18% with the closest, L-1 from Stenotrophomonas maltophilia, and only 11% with BlaB-1. Most of the conserved amino acids that may be involved in the active site of CHbetaLs (His-101, Asp-103, His-162, and His-225) were identified in GOB-1. Sequence heterogeneity was found for GOB-1-like and BlaB-1-like beta-lactamases, having 90 to 100% and 86 to 100% amino acid identity, respectively, among 10 unrelated C. meningosepticum isolates. Each isolate had a GOB-1-like and a BlaB-1-like gene. The same combination of GOB-1-like and BlaB-1-like beta-lactamases was not found in two different isolates. C. meningosepticum is a bacterial species with two types of unrelated chromosome-borne class B CHbetaLs that can be expressed in E. coli and, thus, may represent a clinical threat if spread in gram-negative aerobes.
Laurent Poirel - One of the best experts on this subject based on the ideXlab platform.
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characterization of a naturally occurring class d β lactamase from achromobacter xylosoxidans
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Laurent Poirel, David L Paterson, Patrice NordmannAbstract:Achromobacter xylosoxidans (previously Alcaligenes xylosoxidans) is a non-glucose-fermenting gram-negative species that is increasingly recognized as a clinically significant nosocomial pathogen. With its tendency to contaminate fluid, many outbreaks have been reported, mostly in immunocompromised hosts, causing serious infections, including bacteremia (4, 9). The organism has variable susceptibility to β-lactams (8). It is mostly resistant to narrow-spectrum penicillins and to several cephalosporins, including cefotaxime, whereas susceptibility to Ureidopenicillins and carbapenems varies (8). However, acquisition of metallo-β-lactamases, such as IMP-1, VIM-1, or VIM-2, has been reported for A. xylosoxidans, therefore leading to high-level resistance to carbapenems (12, 17-20). The intrinsic β-lactamases produced by A. xylosoxidans have been characterized only biochemically. Levesque et al. reported three types of cephalosporinases, with isoelectric points (pIs) of 7.4, 9.3, and 8.1 and molecular masses of 32.3 kDa, 22.800 kDa, and 36.200 kDa, respectively (13). Fujii et al. characterized a penicillinase with an unusually high pI of 9.8 and a molecular mass of 18 kDa (5). Philippon et al. reported a penicillinase with a pI of 5.7 and an oxacillinase with a pI of 7.7 (3, 15). None of the β-lactamase genes have been identified so far. The present study was designed to identify and to characterize, at the genetic and biochemical levels, the naturally occurring β-lactamase(s) of A. xylosoxidans.
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resistance to cefepime and cefpirome due to a 4 amino acid deletion in the chromosome encoded ampc β lactamase of a serratia marcescens clinical isolate
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Hedi Mammeri, Laurent Poirel, Pascal Bemer, H Drugeon, Patrice NordmannAbstract:A multiresistant Serratia marcescens strain, HD, isolated from a patient with a urinary tract infection, was resistant to amino-, carboxy-, and Ureidopenicillins, ceftazidime, and cefepime and was susceptible to cefotaxime and ceftriaxone, according to the guidelines of the NCCLS. No synergy was found between expanded-spectrum cephalosporins and clavulanic acid, according to the double-disk synergy test. The blaAmpC gene of the strain was amplified by PCR and cloned into Escherichia coli DH10B, giving rise to high-level resistance to ceftazidime, cefepime, and cefpirome. Sequencing analysis revealed that the blaAmpC gene from S. marcescens HD had a 12-nucleotide deletion compared to the blaAmpC gene from reference strain S. marcescens S3, leading to a 4-amino-acid deletion located in the H-10 helix of the β-lactamase. Kinetic analysis showed that this enzyme significantly hydrolyzed ceftazidime, cefepime, and cefpirome. This work underlined that resistance to the latest expanded-spectrum cephalosporins may be mediated by structurally modified AmpC-type β-lactamases.
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biochemical genetic analysis and distribution of des 1 an ambler class a extended spectrum β lactamase from desulfovibrio desulfuricans
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: Annesophie Morin, Laurent Poirel, Francine Mory, Roger Labia, Patrice NordmannAbstract:Desulfovibrio spp. are gram-negative anaerobes phylogenetically related to Bacteroides spp., which are rarely isolated and which are mostly isolated from intra-abdominal abscesses. Desulfovibrio desulfuricans clinical isolate D3 had a clavulanic acid-inhibited beta-lactam resistance profile and was resistant to some expanded-spectrum cephalosporins. A beta-lactamase gene, bla(DES-1), was cloned from whole-cell DNA of isolate D3 and expressed in Escherichia coli. Purified beta-lactamase DES-1, with a pI value of 9.1, had a relative molecular mass of ca. 31 kDa and a mature protein of 288 amino acids. DES-1 was distantly related to Ambler class A beta-lactamases and most closely related to PenA from Burkholderia pseudomallei (48% amino acid identity). It was weakly related to class A beta-lactamases CblA, CepA, CfxA, and CfxA2 from other anaerobic species, Bacteroides spp. and Prevotella intermedia. Its hydrolysis spectrum included amino- and Ureidopenicillins, narrow-spectrum cephalosporins, ceftriaxone, and cefoperazone. bla(DES-1)-like genes were not identified in phylogenetically related Desulfovibrio fairfieldensis isolates. However, they were found in some but not all D. desulfuricans strains, thus suggesting that these genes may be present in a given D. desulfuricans subspecies.
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characterization of vim 2 a carbapenem hydrolyzing metallo β lactamase and its plasmid and integron borne gene from a pseudomonas aeruginosa clinical isolate in france
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Laurent Poirel, Samuel Bellais, Thierry Naas, Delphine Nicolas, Louis Collet, Jeandidier Cavallo, Patrice NordmannAbstract:Pseudomonas aeruginosa COL-1 was identified in a blood culture of a 39-year-old-woman treated with imipenem in Marseilles, France, in 1996. This strain was resistant to b-lactams, including Ureidopenicillins, ticarcillin-clavulanic acid, cefepime, ceftazidime, imipenem, and meropenem, but remained susceptible to the monobactam aztreonam. The carbapenem-hydrolyzing b-lactamase gene of P. aeruginosa COL-1 was cloned, sequenced, and expressed in Escherichia coli DH10B. The deduced 266-amino-acid protein was an Ambler class B b-lactamase, with amino acid identities of 32% with B-II from Bacillus cereus; 31% with IMP-1 from several gram-negative rods in Japan, including P. aeruginosa; 27% with CcrA from Bacteroides fragilis; 24% with BlaB from Chryseobacterium meningosepticum; 24% with IND-1 from Chryseobacterium indologenes; 21% with CphA-1 from Aeromonas hydrophila; and 11% with L-1 from Stenotrophomonas maltophilia. It was most closely related to VIM-1 b-lactamase recently reported from Italian P. aeruginosa clinical isolates (90% amino acid identity). Purified VIM-2 b-lactamase had a pI of 5.6, a relative molecular mass of 29.7 kDa, and a broad substrate hydrolysis range, including penicillins, cephalosporins, cephamycins, oxacephamycins, and carbapenems, but not monobactams. As a metallo-b-lactamase, its activity was zinc dependent and inhibited by EDTA (50% inhibitory concentration, 50 mM). VIM-2 conferred a resistance pattern to b-lactams in E. coli DH10B that paralleled its in vitro hydrolytic properties, except for susceptibility to Ureidopenicillins, carbapenems, and cefepime. blaVIM-2 was located on a ca. 45-kb plasmid that in addition conferred resistance to sulfamides and that was not self-transmissible either from P. aeruginosa to E. coli or from E. coli to E. coli. blaVIM-2 was the only gene cassette located within the variable region of a novel class 1 integron, In56, that was weakly related to the blaVIM-1-containing integron. VIM-2 is the second carbapenem-hydrolyzing metalloenzyme characterized from a P. aeruginosa isolate outside Japan.
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integron and carbenicillinase mediated reduced susceptibility to amoxicillin clavulanic acid in isolates of multidrug resistant salmonella enterica serotype typhimurium dt104 from french patients
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Laurent Poirel, Michele Guibert, Samuel Bellais, Thierry Naas, Patrice NordmannAbstract:Fifty-seven Salmonella enterica serotype Typhimurium (S. typhimurium) isolates were collected from human patients in two French hospitals, Hopital Antoine Beclere (Clamart, France) and Hopital Bicetre (Le Kremlin-Bicetre, France), between 1996 and 1997. Thirty of them (52 percent) were resistant to amino-, carbeni-, and Ureidopenicillins, had reduced susceptibility to amoxicillin-clavulanic acid, were susceptible to cephalothin, and were resistant to sulfonamides, streptomycin, chloramphenicol, and tetracyclines. All these strains possessed a blaPSE-1-like gene and were of phage type DT104. Ten of them were studied in more detail, which revealed that blaPSE-1 is located on the variable region of a class 1 integron. This integron was found to be chromosomally located, as was another class 1 integron containing aadA2, a streptomycin-spectinomycin resistance gene. The reduced susceptibility to amoxicillin-clavulanic acid (and to ticarcillin-clavulanic acid) may result from the high level of hydrolysis of the β-lactam rather than to the clavulanic acid resistance properties of PSE-1 in these clonally related S. typhimurium isolates.
Mark H Wilcox - One of the best experts on this subject based on the ideXlab platform.
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effects of piperacillin tazobactam on clostridium difficile growth and toxin production in a human gut model
Journal of Antimicrobial Chemotherapy, 2005Co-Authors: Simon D Baines, Jane Freeman, Mark H WilcoxAbstract:Objectives: Clostridium difficile infection (CDI) is a major cause of morbidity in the nosocomial environment. Antimicrobial agents such as the third-generation cephalosporins, lincosamides and aminopenicillins are well known for their propensity to induce CDI, but the definitive reasons why remain to be elucidated. Despite their broad spectrum of activity against both aerobic and anaerobic bacteria, the Ureidopenicillins remain a class of antimicrobials infrequently associated with the development of CDI. Methods: We used a triple-stage chemostat model that simulates the human gut to study the effects of the Ureidopenicillin/b-lactamase inhibitor combination piperacillin/tazobactam on gut bacterial populations and C. difficile. Results: Piperacillin/tazobactam rapidly reduced all enumerated gut bacterial populations (including bacteroides, bifidobacteria and lactobacilli) below the limits of detection by the end of the piperacillin/ tazobactam instillation period. Despite such widespread disruption of gut bacterial populations, C. difficile populations remained principally as spores, with no sustained proliferation or high-level cytotoxin production observed. Conclusions: Factors other than reduced colonization resistance must be responsible for determining whether CDI develops following antimicrobial administration. We believe the gut model is a promising approach for the study of C. difficile pathogenesis reflecting in vivo events likely to occur in CDI.
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long term surveillance of cefotaxime and piperacillin tazobactam prescribing and incidence of clostridium difficile diarrhoea
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Mark H Wilcox, Jane Freeman, Warren Fawley, Sarah Mackinlay, Alex Brown, Katrina Donaldson, Oliver CorradoAbstract:Objectives: We followed the effects of changes to a new antibiotic policy favouring a Ureidopenicillin as opposed to a third-generation cephalosporin on the long-term incidence of Clostridium difficile diarrhoea (CDD) and antibiotic utilization in a large Elderly Medicine Unit. Patients and methods: In 1999, piperacillin–tazobactam was added to the formulary in Elderly Medicine and its use promoted in preference to cefotaxime. Following review and feedback to clinicians of surveillance data, cefotaxime prescribing was actively restricted during 2000–2001. An audit of prescriber adherence to antibiotic policy was carried out by reviewing the records of 159 patients during February–April 2001. In December 2001, due to manufacturer production problems, supply of piperacillin–tazobactam was stopped. We performed standardized period prevalence surveillance (February– April) allowing comparisons of antibiotic utilization and CDD incidence during the 5 year study period (1998–2002). Results: CDD incidence did not change significantly (P > 0.1) during 1998–1999 despite a marked increase in piperacillin–tazobactam prescribing. However, when cefotaxime prescribing was curtailed in 2001, CDD rates decreased (in four of five wards) and overall by 52% (P 5 0.008). When piperacillin– tazobactam became unavailable in 2002, despite advice to the contrary cefotaxime prescribing rose five-fold, and CDD rates increased in four of five wards and by 232% (P < 0.01) overall. Adherence to antibiotic policy introduced in 2000 was good (81% accordance); 94%, 88% and 73% of patients with cellulitis, urinary tract and respiratory tract infection, respectively, received appropriate antibiotics. Conclusions: Long-term prescribing of piperacillin–tazobactam in Elderly Medicine in preference to cefotaxime is associated with reduced rates of CDD. However, unless cephalosporin prescribing is curtailed, the beneficial effects on CDD rates may be missed. This is one of few studies to document adverse effects due to loss of antibiotic supply.
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Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea
2004Co-Authors: Mark H Wilcox, Jane Freeman, Warren Fawley, Sarah Mackinlay, Alex Brown, Katrina Donaldson, Oliver CorradoAbstract:Objectives: We followed the effects of changes to a new antibiotic policy favouring a Ureidopenicillin as opposed to a third-generation cephalosporin on the long-term incidence of Clostridium difficile diarrhoea (CDD) and antibiotic utilization in a large Elderly Medicine Unit. Patients and methods: In 1999, piperacillin–tazobactam was added to the formulary in Elderly Medicine and its use promoted in preference to cefotaxime. Following review and feedback to clinicians of sur-veillance data, cefotaxime prescribing was actively restricted during 2000–2001. An audit of prescri-ber adherence to antibiotic policy was carried out by reviewing the records of 159 patients during February–April 2001. In December 2001, due to manufacturer production problems, supply of piperacil-lin–tazobactam was stopped. We performed standardized period prevalence surveillance (February– April) allowing comparisons of antibiotic utilization and CDD incidence during the 5 year study period (1998–2002). Results: CDD incidence did not change significantly (P> 0.1) during 1998–1999 despite a marked increase in piperacillin–tazobactam prescribing. However, when cefotaxime prescribing was curtailed in 2001, CDD rates decreased (in four of five wards) and overall by 52 % (P 5 0.008). When piperacillin– tazobactam became unavailable in 2002, despite advice to the contrary cefotaxime prescribing ros
Reuben Ramphal - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of cephalosporin monotherapy and aminoglycoside Ureidopenicillin combination therapy for the treatment of febrile episodes in neutropenic patients
PharmacoEconomics, 2000Co-Authors: Joseph A. Paladino, Debra A. Fong, Alan Forrest, Reuben RamphalAbstract:Objective: To assess the relative cost effectiveness of cephalosporin monotherapy options and aminoglycoside/Ureidopenicillin combination therapy for the treatment of febrile episodes in adult patients with neutropenia.
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Cost Effectiveness of Cephalosporin Monotherapy and Aminoglycoside/ Ureidopenicillin Combination Therapy: For the Treatment of Febrile Episodes in Neutropenic Patients
2024Co-Authors: Joseph A. Paladino, Debra A. Fong, Alan Forrest, Reuben RamphalAbstract:Objective: To assess the relative cost effectiveness of cephalosporin monotherapy options and aminoglycoside/Ureidopenicillin combination therapy for the treatment of febrile episodes in adult patients with neutropenia. Design and setting: This was a retrospective cost-effectiveness analysis conducted from the institutional perspective. Methods: The analysis was based on 741 febrile episodes in adult patients with neutropenia enrolled in 5 randomised trials: 3 comparing monotherapy with ceftazidime or cefepime, and 2 comparing cefepime monotherapy versus aminoglycoside/Ureidopenicillin combination therapy. Resource utilisation included costs for study antibacterials, treatment of adverse effects and failures, and hospitalisation. The primary end-point was the overall cost of treatment per patient. Cost-effectiveness ratios were also analysed. Results: No significant differences in clinical success rates were detected. Median per-patient costs in the monotherapy comparisons were $US7849 for cefepime and $US7788 for ceftazidime [1997 values; not significantly different (NS)]. Corresponding costs for the monotherapy versus combination therapy comparisons were $US9780 for cefepime and $US10 159 for gentamicin/Ureidopenicillin (NS). Despite a higher acquisition cost for cefepime, there were no statistically significant differences in cost effectiveness compared with either ceftazidime monotherapy or gentamicin/Ureidopenicillin combination therapy. Sensitivity analyses revealed that monotherapy can be cost effective compared with combination therapy in many situations. Conclusion: There were no economic differences between the 3 regimens tested. Therefore, drug cost should not be a deciding factor when choosing antibacterial therapy for the treatment of febrile episodes in adult patients with neutropenia.Aminoglycosides, Antibacterials, Cefalosporins, Cefepime, Ceftazidime, Cost analysis, Fever, Gentamicin, Immunocompromised infections, Penicillins, Pharmacoeconomics
Oliver Corrado - One of the best experts on this subject based on the ideXlab platform.
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long term surveillance of cefotaxime and piperacillin tazobactam prescribing and incidence of clostridium difficile diarrhoea
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Mark H Wilcox, Jane Freeman, Warren Fawley, Sarah Mackinlay, Alex Brown, Katrina Donaldson, Oliver CorradoAbstract:Objectives: We followed the effects of changes to a new antibiotic policy favouring a Ureidopenicillin as opposed to a third-generation cephalosporin on the long-term incidence of Clostridium difficile diarrhoea (CDD) and antibiotic utilization in a large Elderly Medicine Unit. Patients and methods: In 1999, piperacillin–tazobactam was added to the formulary in Elderly Medicine and its use promoted in preference to cefotaxime. Following review and feedback to clinicians of surveillance data, cefotaxime prescribing was actively restricted during 2000–2001. An audit of prescriber adherence to antibiotic policy was carried out by reviewing the records of 159 patients during February–April 2001. In December 2001, due to manufacturer production problems, supply of piperacillin–tazobactam was stopped. We performed standardized period prevalence surveillance (February– April) allowing comparisons of antibiotic utilization and CDD incidence during the 5 year study period (1998–2002). Results: CDD incidence did not change significantly (P > 0.1) during 1998–1999 despite a marked increase in piperacillin–tazobactam prescribing. However, when cefotaxime prescribing was curtailed in 2001, CDD rates decreased (in four of five wards) and overall by 52% (P 5 0.008). When piperacillin– tazobactam became unavailable in 2002, despite advice to the contrary cefotaxime prescribing rose five-fold, and CDD rates increased in four of five wards and by 232% (P < 0.01) overall. Adherence to antibiotic policy introduced in 2000 was good (81% accordance); 94%, 88% and 73% of patients with cellulitis, urinary tract and respiratory tract infection, respectively, received appropriate antibiotics. Conclusions: Long-term prescribing of piperacillin–tazobactam in Elderly Medicine in preference to cefotaxime is associated with reduced rates of CDD. However, unless cephalosporin prescribing is curtailed, the beneficial effects on CDD rates may be missed. This is one of few studies to document adverse effects due to loss of antibiotic supply.
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Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea
2004Co-Authors: Mark H Wilcox, Jane Freeman, Warren Fawley, Sarah Mackinlay, Alex Brown, Katrina Donaldson, Oliver CorradoAbstract:Objectives: We followed the effects of changes to a new antibiotic policy favouring a Ureidopenicillin as opposed to a third-generation cephalosporin on the long-term incidence of Clostridium difficile diarrhoea (CDD) and antibiotic utilization in a large Elderly Medicine Unit. Patients and methods: In 1999, piperacillin–tazobactam was added to the formulary in Elderly Medicine and its use promoted in preference to cefotaxime. Following review and feedback to clinicians of sur-veillance data, cefotaxime prescribing was actively restricted during 2000–2001. An audit of prescri-ber adherence to antibiotic policy was carried out by reviewing the records of 159 patients during February–April 2001. In December 2001, due to manufacturer production problems, supply of piperacil-lin–tazobactam was stopped. We performed standardized period prevalence surveillance (February– April) allowing comparisons of antibiotic utilization and CDD incidence during the 5 year study period (1998–2002). Results: CDD incidence did not change significantly (P> 0.1) during 1998–1999 despite a marked increase in piperacillin–tazobactam prescribing. However, when cefotaxime prescribing was curtailed in 2001, CDD rates decreased (in four of five wards) and overall by 52 % (P 5 0.008). When piperacillin– tazobactam became unavailable in 2002, despite advice to the contrary cefotaxime prescribing ros
