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Biomedical subjects

J Turnidge

Publications and source records attributed to J Turnidge.

At least 19 recordsLinked to original sources
PubMed2006

Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values.

MIC distribution data were obtained from a variety of international sources, and pooled after selection by a defined criterion. Sixty-seven of these datasets were subjected to a range of statistical goodness-of-fit tests. The log-normal distribution was selected for subsequent modelling. Cumulative counts of MIC distribution data were fitted to the cumulative log-normal distribution using non-linear least squares regression for a range of data subsets from each antibiotic-bacterium combination. Estimated parameters in the regression were the number of isolates in the subset, and (the log(2) values of) the mean and standard deviation. Optimum fits for the cumulative log-normal curve were then used to determine the wild-type MIC range, determined by calculating the MICs associated with the lower and upper 0.1% of the distribution, rounding to the nearest two-fold dilution, and calculating the probabilities of values higher and lower than these values. When plotted logarithmically, histograms of MIC frequencies appeared normal (Gaussian), but standard goodness-of-fit tests showed that the two-fold dilution grouping of MICs fits poorly to a log-normal distribution, whereas non-linear regression gave good fits to population (histogram) log-normal distributions of log(2) MIC frequencies, and even better fits to log-normal cumulative distributions. Optimum fits were found when the difference between the estimated and true number of isolates in the fitted subset was minimal. Sixteen antibiotic-bacterium datasets were fitted using this technique, and the log(2) values of the means and standard deviations were used to determine the 0.1% and 99.9% wild-type cut-off values. When rounded to the nearest two-fold dilution, > or = 98.5% of MIC values fall within the cut-off value range. Non-linear regression fitting to a cumulative log-normal distribution is a novel and effective method for modelling MIC distributions and quantifying wild-type MIC ranges.

Anti-Infective Agents↗
PubMed2001

Characterization of Pseudomonas aeruginosa isolates: occurrence rates, antimicrobial susceptibility patterns, and molecular typing in the global SENTRY Antimicrobial Surveillance Program, 1997-1999.

During 1997-1999, a total of 70,067 isolates (6631 Pseudomonas aeruginosa isolates) were analyzed in the SENTRY program by geographic region and body site of infection. The respiratory tract was the most common source of P. aeruginosa. P. aeruginosa isolation rates increased during the study interval. Europe was the only region to show a significant decline in beta-lactam and aminoglycoside susceptibility rates. There was a reduction in the rates of susceptibility of Canadian isolates to imipenem and of Latin American isolates to meropenem. A total of 218 multidrug-resistant P. aeruginosa isolates (MDR-PSA; resistant to piperacillin, ceftazidime, imipenem, and gentamicin) were observed; MDR-PSA occurrence rates (percentages of all isolates) ranged from 8.2% (Latin America) to 0.9% (Canada). No antimicrobial inhibited >50% of MDR-PSA strains. Molecular characterization of selected, generally resistant strains was performed. Isolates showing unique ribogroups were found in Europe, Latin America, and the United States, but clonal spread was documented in several medical centers.

Anti-Bacterial Agents↗
PubMed2001

Integration of molecular characterization of microorganisms in a global antimicrobial resistance surveillance program.

The SENTRY Antimicrobial Surveillance Program has incorporated molecular strain typing and resistance genotyping as a means of providing additional information that may be useful for understanding pathogenic microorganisms worldwide. Resistance phenotypes of interest include multidrug-resistant pathogens, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and fluoroquinolone-resistant (FQR) strains of gram-negative bacilli and Streptococcus pneumoniae. Clusters of > or =2 isolates within a given resistance profile that are linked temporally and by hospital location are flagged for DNA fingerprinting. Further characterization of organisms with respect to resistance genotype is accomplished with use of polymerase chain reaction and DNA sequencing. This process has been highly successful in identifying clonal spread within clusters of multiresistant pathogens. Between 50% and 90% of MRSA clusters identified by phenotypic screening contained evidence of clonal spread. Among the Enterobacteriaceae, ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing clusters of infection, and approximately 50% of recognized clusters demonstrate clonal spread. Clusters of Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia have been noted with clonal spread among patients with urinary tract, respiratory, and bloodstream infections. Characterization of mutations in the FQR-determining region of phenotypically susceptible isolates of E. coli and S. pneumoniae has identified first-stage mutants among as many as 40% of isolates. The ability to characterize organisms phenotypically and genotypically is extremely powerful and provides unique information that is important in a global antimicrobial surveillance program.

Bacterial Infections↗
PubMed2001

In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis.

The in vitro pharmacodynamic properties of colistin and colistin methanesulfonate were investigated by studying the MICs, time-kill kinetics, and postantibiotic effect (PAE) against mucoid and nonmucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. Twenty-three clinical strains, including multiresistant strains, and one type strain were selected for MIC determination. Eleven strains were resistant; MICs for these strains were >128 mg/liter. For the susceptible strains, MICs of colistin ranged from 1 to 4 mg/liter, while the MICs of colistin methanesulfonate were significantly higher and ranged from 4 to 16 mg/liter. The time-kill kinetics were investigated with three strains at drug concentrations ranging from 0.5 to 64 times the MIC. Colistin showed extremely rapid killing, resulting in complete elimination at the highest concentrations within 5 min, while colistin methanesulfonate killed more slowly, requiring a concentration of 16 times the MIC to achieve complete killing within 24 h. Colistin exhibited a significant PAE of 2 to 3 h at 16 times the MIC against the three strains after 15 min of exposure. For colistin methanesulfonate, PAEs were shorter at the concentrations tested. Colistin methanesulfonate had lower overall bactericidal and postantibiotic activities than colistin, even when adjusted for differences in MICs. Our data suggest that doses of colistin methanesulfonate higher than the recommended 2 to 3 mg/kg of body weight every 12 h may be required for the effective treatment of P. aeruginosa infections in cystic fibrosis patients.

Anti-Bacterial Agents↗
PubMed2001

In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.

Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.

Anti-Bacterial Agents↗
PubMed2001

Responsible prescribing for upper respiratory tract infections.

Upper respiratory tract infections (URTIs) are responsible for a large amount of community antibacterial use worldwide. Recent systematic reviews have demonstrated that most URTIs resolve naturally, even when bacteria are the cause. The high consumer expectation for antibacterials in URTIs requires intervention by the general practitioner and a number of useful strategies have been developed. Generic strategies, including eliciting patient expectations, avoiding the term 'just a virus', providing a value-for-money consultation, providing verbal and written information, empowering patients, conditional prescribing, directed education campaigns, and emphasis on symptomatic treatments, should be used as well as discussion of alternative medicines when relevant. The various conditions have differing rates of bacterial infection and require different approaches. For acute rhinitis, laryngitis and tracheitis, viruses are the only cause and, therefore, antibacterials are never required. In acute sore throat (pharyngitis) Streptococcus pyogenes is the only important bacterial cause. A scoring system can help to increase the likelihood of distinguishing a streptococcal as opposed to viral infection, or alternatively patients should be given antibacterials only if certain conditions are fulfilled. Strategies for treating acute otitis media vary in different countries. Most favour the strategy of prescribing antibacterials only when certain criteria are fulfilled, delaying antibacterial prescribing for at least 24 hours. In otitis media with effusion, on the other hand, there is no primary role for antibacterials, as the condition resolves naturally in almost all patients aged >3 months. Detailed strategies for acute sinusitis have not been worked out but restricting antibacterial prescribing to certain clinical complexes is currently recommended by several authorities because of the high natural resolution rate.

Anti-Bacterial Agents↗
PubMed2000

Genetic relatedness of multidrug-resistant, methicillin (oxacillin)-resistant Staphylococcus aureus bloodstream isolates from SENTRY Antimicrobial Resistance Surveillance Centers worldwide, 1998.

We reviewed Staphylococcus aureus bloodstream infection isolates from SENTRY centers worldwide during 1998 to evaluate the molecular epidemiology of multiply drug-resistant methicillin (oxacillin)-resistant S. aureus (MDR-MRSA). MDR-MRSA was defined as a S. aureus isolate with a MIC for oxacillin at >2 microg/ml and with four or more additional resistances. A total of 325 unique patient isolates of MDR-MRSA from five continents were analyzed using ribotyping and pulsed-field gel electrophoresis (PFGE). The frequency of MDR-MRSA among all S. aureus BSI isolates ranged from only 2.2% in Canada to 35.6% in the Asia-Pacific region. Forty-eight ribotypes (RT) were distinguished, but over 80% of the isolates were contained within the 10 most prevalent RTs. The most common RT, RT 184.5, which included 30% of all MDR-MRSA, was found on four of five continents. PFGE provided superior discrimination and identified numerous clusters of possible clonal dissemination of MDR-MRSA within individual medical centers and between institutions that are in geographic proximity. In four instances, strains with indistinguishable PFGE patterns were found on more than one continent. The predominant PFGE subtype in South America (RT 893.5/Ia) was isolated from patients at centers in Brazil, Argentina, and Portugal, and closely related subtypes were isolated in Chile and Italy. There is great geographic variation in rates of methicillin- and multidrug-resistance among S. aureus bloodstream isolates worldwide. Although many MDR-MRSA strains group geographically, a few closely related epidemic strains have wide regional and even global range.

Anti-Bacterial Agents↗
PubMed1999

Fusidic acid pharmacology, pharmacokinetics and pharmacodynamics.

Fusidic acid comes in a variety of formulations for oral, intravenous and topical use. After oral administration of 500 mg Cmax values range from 14.5-3.3 mg/l and an elimination half-life of 8.9-11.0 h. Similar values are obtained with intravenous administration of the sodium salt, although peaks tend to be higher. Bioavailability for the new film-coated tablet is approximately 91% while that of the suspension formulation appears to be much lower. Repeated dosing results in substantial drug accumulation when given 8-hourly, and to a variable extent depending on dose when administered 12-hourly. One study has demonstrated a modest dose-dependency for pharmacokinetics, with decreased clearance at higher doses. Fusidic acid is primarily eliminated by non-renal mechanisms, and a proportion of the drug is metabolised to seven or more breakdown products that can be detected in bile. Hypoalbuminaemia increases fusidic acid clearance, while clearance is decreased in the presence of severe cholestasis, and essentially unchanged in renal failure. Fusidic acid is highly protein-bound (91-98S), but has good penetration to a number of tissues including skin blisters, burns, infected bone and joints. Topical application of fusidic acid results in poor penetration through skin but good penetration into aqueous and vitreous humour. Little is known about the pharmacodynamics of fusidic acid, apart from the fact that it is slowly bactericidal against Staphylococcus aureus, and produces moderate post-antibiotic effects in vitro.

Administration, Oral↗
PubMed1999

Resistance to fusidic acid.

Resistance to fusidic acid is determined by a number of mechanisms. The best described are alterations in elongation factor G, which appear in natural mutants that are harboured at low rates in normal populations of staphylococci (10(6) to 10(8)). Altered drug permeability has also been described, and appears to be plasmid-borne. Binding by chloramphenicol acetyltransferase type I and efflux are other described mechanisms of resistance whose prevalence is unclear. A large number of studies have examined rates of fusidic acid resistance in staphylococci. Most show low levels of resistance. Studies where high levels of resistance have been seen are from areas of the hospital where cross infection is common. Rates of resistance have tended to be slightly higher in methicillin-resistant strains of Staphylococcus aureus. Studies on the evolution of resistance have shown no major trends to the emergence of resistance. In one case this is despite increasing use of both systemic and topical fusidic acid over more than 24 years. Selection for resistant variants during treatment was recognised early in vitro and in vivo. However, evidence suggests that it does not occur at high frequency in clinical practice. Nevertheless, accumulated experience is that fusidic acid in combination with other agents results in less resistance emergence.

Animals↗
PubMed1999

Fusidic acid in vitro activity.

Fusidic acid is a narrow spectrum agent that acts to inhibit protein synthesis by inhibition of elongation factor G at the level of the ribosome. Because of high protein binding susceptibility testing in vitro is affected by the presence of blood or serum. In addition, there is a modest inoculum effect in vitro. A breakpoint of 1 or 2 mg/l is most widely used for defining resistance to systemic treatment with fusidic acid. Fusidic acid activity is principally directed at staphylococci, both Staphylococcus aureus and coagulate-negative species which are highly susceptible. It is also active against Gram-positive anaerobic activity, and shows in vitro activity against Neisseria spp., Bordetella pertussis and Moraxella catarrhalis. It has no activity against other aerobic Gram-negative species. Modest activity (MICs just above breakpoint values) is seen with Streptococcus and Enterococcus spp. as well as Gram-negative anaerobic bacteria. Fusidic acid is defined as bacteriostatic. For staphylococci MBC values are generally 8--32-fold that of the MIC. Interaction studies with other antibiotics give varying results depending on methodology. However, interaction with beta-lactams is generally indifferent, as it is with rifampicin, while aminoglycosides and macrolides appear to be synergistic and fluoroquinolones antagonistic. Fusidic acid appears to inhibit the function of neutrophils and T-lymphocytes at clinically achieved concentrations.

Anti-Bacterial Agents↗
PubMed1999

Pharmacokinetics and pharmacodynamics of fluoroquinolones.

The fluoroquinolones have moderate to excellent bioavailability, moderate to long elimination half-lives (50 to 98%) and volumes of distribution >1.5 L/kg. There is considerable variation in elimination pattern between fluoroquinolone agents, ranging from predominant renal excretion to extensive hepatic metabolism. Protein binding also varies between agents. Tissue concentrations often exceed plasma concentrations, while concentrations in CSF are modest in the presence of inflammation. Fluoroquinolones show concentration-dependent killing in vitro, and animal models have demonstrated the 24-hour AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) ratio to be the best predictor of bacterial killing in vivo, with the peak plasma concentration (Cmax)/MIC ratio being important for some bacteria, to prevent the emergence of resistance during treatment. Animal models and human studies with ciprofloxacin, grepafloxacin and levofloxacin show that a 24-hour AUC/MIC ratio of about 100, or a Cmax/MIC ratio of about 10 gives maximum clinical and bacteriological efficacy. These values can be used to predict the efficacy of different agents against different pathogens, and to define pharmacodynamic 'breakpoints'.

Animals↗
PubMed1998

Emergence and epidemiology of vancomycin-resistant enterococci in Australia.

Enterococci with acquired resistance to vancomycin and other glycopeptides (VRE) have emerged and spread rapidly through Europe and the United States since 1988. The first isolate of VRE in Australia occurred in 1994. Only one case was noted in 1995. Since March 1996 there has been a steady increase in the number of reports of VRE throughout the country. To August 1998 there have been 69 documented strains or clusters of strains detected in patients with documented infection, and about 3 times as many strains have been detected through screening procedures of contacts or in risk groups. 19% of strains whose source was known were blood isolates, while 34% came from urine and 47% came from other specimens. The strains have been found in 26 institutions in 10 widely separated cities or regions of the country (in 6/8 states or territories), without any obvious temporal associations in their appearance. All strains appear to have arisen locally except for one strain imported from the United Kingdom. Furthermore there was no direct evidence of interhospital transfer of strains. All clinical strains were examined by PCR to confirm species and to test for the presence of known vancomycin-resistance genes. Of the 69 strains, 42 were vanB E. faecium, 12 were vanA E. faecium, 9 were vanB E. faecalis, 3 were vanA E. faecalis. Three were negative for vanA, vanB, vanC1, vanC2/C3 and vanD. PGFE profiles on 38 strains have revealed at least 8 types of vanB E. faecium, 6 of vanA E. faecium, 4 of vanB E. faecalis and 2 of vanA E. faecalis. Isolates containing vanA always had different profiles from those containing vanB. Clinical clustering was confirmed by PFGE, and supported by extended antibiogram. 14 of 15 E. faecalis were ampicillin susceptible compared to only 2 of 54 E. faecium. One E. faecalis strain was beta-lactamase positive. The epidemiology of VRE in Australia appears to be different from that of Europe or the United States, since vanB E. faecium predominates and strains have appeared in diverse locations independently and are highly polyclonal.

Anti-Bacterial Agents↗
PubMed1998

Emergence of vancomycin-resistant enterococci in Australia: phenotypic and genotypic characteristics of isolates.

Enterococci with resistance to glycopeptides have recently emerged in Australia. We developed multiplex PCR assays for vanA, vanB, vanC1, and vanC2 or vanC3 in order to examine the genetic basis for vancomycin resistance in Australian isolates of vancomycin-resistant Enterococcus faecium and E. faecalis (VRE). The predominant genotype from human clinical E. faecium isolates was vanB. The PCR van genotype was consistent with the resistance phenotype in all but six cases. One vanA E. faecalis isolate had a VanB phenotype, one vanB E. faecium isolate had a VanA phenotype, and four E. faecalis isolates were consistently negative for vanA, vanB, vanC1, and vanC2 or vanC3, even though they exhibited a VanB phenotype. These four isolates were subsequently examined for the presence of vanD by published methods and were found to be negative. No vancomycin-susceptible strains produced a PCR product. On the basis of our findings the epidemiology of VRE in Australia appears to be different from that in either the United States or Europe. Our multiplex PCR assays gave a rapid and accurate method for determining the genotype and confirming the identification of glycopeptide-resistant enterococci. Rapid and accurate methods are essential, because laboratory-based surveillance is critical in programs for the detection, control, and prevention of the transmission of glycopeptide-resistant enterococci.

Anti-Bacterial Agents↗
PubMed1996

Metronidazole resistance: a predictor of failure of Helicobacter pylori eradication by triple therapy.

Triple therapy (bismuth and two antibiotics) will eradicate Helicobacter pylori infection in 70-90% of subjects. Treatment failure has been attributed to patient compliance and antimicrobial drug resistance. The aim of this study was to examine factors influencing the eradication of H. pylori following triple therapy. Thirty seven subjects with H. pylori cultured from antral biopsies were treated with colloidal bismuth subcitrate (120 mg qid for 2 weeks), metronidazole (400 mg tid for 1 week) and amoxycillin (500 mg tid for 1 week). Pretreatment isolates of H. pylori were tested for metronidazole susceptibility by agar dilution according to the National Committee for Clinical Laboratory Standards guidelines. Factors including age, sex, clinical diagnosis and metronidazole resistance were evaluated in relation to H. pylori. The overall metronidazole resistance was 32%. Metronidazole resistant strains were more frequent in females, with a resistance rate of 54%. Helicobacter pylori eradication occurred in 68% of patients with a metronidazole susceptible stain and only 17% of patients with a metronidazole resistant strain (P < 0.03). Helicobacter pylori eradication is dependent upon susceptibility to metronidazole. This data would support the role for routine metronidazole susceptibility testing using appropriate standardized methods when triple therapy is to be considered.

Amoxicillin↗
PubMed1995

Home intravenous antibiotic therapy. A safe and effective alternative to inpatient care.

OBJECTIVE: To assess the practicality, safety, cost effectiveness and outcome of receiving intravenous antibiotics at home. METHODS: Patients with serious bacterial infections requiring parenteral antibiotic therapy were enrolled in a pilot program to receive treatment at home. Antibiotics were premixed in the hospital pharmacy and administered by the Royal District Nursing Service, and medical back-up was provided. RESULTS: Twenty patients (mean age, 58 years; range, 19-84 years) received 21 courses of intravenous antibiotics at home (mean duration +/- SD, 26 +/- 9 days; range, 11-44 days). Conditions treated included osteomyelitis (10 patients), endocarditis (5), vascular graft and pacemaker sepsis (4), and chronic cellulitis (1). Treatment at home was well tolerated with no significant complications, and cure was achieved in 18 of the 20 patients. It was both efficient and cost effective, with a mean benefit in treatment costs between home and the equivalent inpatient therapy of at least $112 per day for the 538 days that home therapy was provided. Moreover, the reduced bed use could allow an additional hospital throughput of between 86 and 107 patients annually. CONCLUSIONS: Home intravenous antibiotic therapy is safe, effective and well tolerated. It allows more efficient inpatient care and reduces total treatment costs in an important subpopulation of patients.

Adult↗