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Biomedical subjects

Jan Bell

Publications and source records attributed to Jan Bell.

7 recordsLinked to original sources
PubMed2006

Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis--caution with trough concentrations.

BACKGROUND: : Once daily intravenous aminoglycoside dosing (ODD) is widely used to treat acute Pseudomonas aeruginosa exacerbations in patients with cystic fibrosis. Controversy exists as to what is the most appropriate method of therapeutic drug monitoring (TDM) of such therapy with recommendations including trough plasma concentrations of <1 mg/L or <2 mg/L, area under curve (AUC) and various nomograms. This study aimed to compare the exposures to ODD of tobramycin in adults and children with cystic fibrosis using the AUC and trough TDM approaches. METHODS: : Using a mono-exponential software program to calculate AUC from 2 plasma concentrations, AUCs were determined in 22 adults with pre-dose tobramycin concentrations <1 mg/L. The exposure of 5 children with reduced tobramycin clearances was simulated at the usual recommended dose of 10 mg/kg/daily but retaining a trough <1 mg/L. RESULTS: : A tobramycin dose of 10 mg/kg of tobramycin in these patients with normal serum creatinine and a trough concentration <1 mg/L resulted in exposures in excess of those associated with conventional 8-hourly dosing. CONCLUSIONS: : The TDM approach of a trough <1 mg/L, as used with conventional 8-hourly tobramycin dosing, is not relevant to ODD.

Adolescent↗
PubMed2006

Contemporary antimicrobial activity of triple antibiotic ointment: a multiphased study of recent clinical isolates in the United States and Australia.

Triple antibiotic ointment (TAO) containing neomycin, polymyxin B, and bacitracin was launched in the 1950s in the United States (USA) as a prescription product and then was used over the counter (OTC) since the 1970s (USA) to prevent superficial wound infections. In Australia, TAO has been restricted to prescription use. This study 1) determined cross-resistance patterns of neomycin compared with other aminoglycosides; 2) determined the level and trend of resistance to TAO and individual components especially versus mupirocin-resistant strains (USA); and 3) established the baseline TAO activity level against pathogens from Australia. A total of 200 strains (> or =50% gentamicin-resistant) from the United States were used for the cross-resistance study including Staphylococcus aureus (110), coagulase-negative staphylococci (CoNS; 50), Pseudomonas aeruginosa (10), Escherichia coli (20), and other Enterobacteriaceae (10) tested against TAO, bacitracin, polymyxin B, neomycin, amikacin, gentamicin, streptomycin, tobramycin, and mupirocin. Fifty gentamicin-resistant isolates from each year (1997-2002) were used to determine the activity of TAO over time. Baseline resistance rates of TAO among 300 Australian isolates (AGARS Program, 2002-2003) were also studied. Reference broth microdilution methods were used in all phases of this study. At a 1:100 dilution of the ointment concentration, TAO inhibited all CoNS, Pseudomonas aeruginosa, and Enterobacteriaceae isolates, and resistance to TAO among Staphylococcus aureus at this concentration was only 5% in the cross-resistance study. Patterns of susceptibility in the United States did not significantly vary from 1997 to 2002. Australian pathogens showed that TAO was 98% active against methicillin-resistant Staphylococcus aureus and 100% for Enterobacteriaceae, methicillin-susceptible S. aureus, CoNS, and P. aeruginosa, the rates equivalent to those observed in the United States. Mupirocin-resistant S. aureus (5%) and CoNS (47%) were all TAO-susceptible. All Gram-negative species were also mupirocin-resistant, but inhibited by neomycin and/or polymyxin B components of TAO. In conclusion, aminoglycoside resistance patterns differ significantly, and none of the commonly tested agents could accurately predict neomycin resistance. TAO resistance was rare in the United States after extensive OTC use and was not adversely influenced by decades of parenteral aminoglycoside use. Australian surveillance showed high levels of TAO susceptibility in sampled isolates as a baseline for possible OTC availability. TAO maintains a wider spectrum of activity compared with mupirocin and was usable against mupirocin-resistant Gram-positive strains.

Administration, Topical↗
PubMed2004

VanD-type vancomycin-resistant Enterococcus faecium and Enterococcus faecalis.

Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 microg/ml) and susceptible to teicoplanin (0.25 microg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d-alanyl-d-lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX(D) activity, which is not required in the absence of d-Ala-d-Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY(D) activity in the membrane fractions was inhibited by penicillin G. The mutations E(13)G in the region of d-alanine:d-alanine ligase (which is implicated in d-Ala1 binding in A902) and S(319)N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d-Ala-d-Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS(D) of BM4539 and BM4540 and a 1-bp deletion in vanS(D) of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS(D), had a G(140)E mutation in VanR(D) that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS(D) or vanR(D) gene that lead to constitutive resistance to vancomycin.

Amino Acid Sequence↗
PubMed2004

VanE-type vancomycin-resistant Enterococcus faecalis clinical isolates from Australia.

Three distinct Enterococcus faecalis VanE-type isolates-BM4574, BM4575, and BM4576-obtained in Australia were studied. Expression of the resistance genes was constitutive in BM4575, probably due to a 2-bp deletion into the vanSE gene, and inducible in BM4574 and BM4576. Transcription analysis of the vanE operons suggested that the five genes were cotranscribed from an initiation site located 25 bp upstream from the ATG start codon of vanE.

Australia↗
PubMed2003

SENTRY Antimicrobial Surveillance Program Asia-Pacific region and South Africa.

The SENTRY Antimicrobial Surveillance Program was initiated in January 1997 and was designed to monitor the predominant pathogens and antimicrobial resistance for both nosocomial and community-acquired infections globally by using validated, reference-quality identification and susceptibility testing methods performed in a central laboratory. Consecutive bacterial or fungal isolates, deemed clinically significant by local criteria, are forwarded to the local reference laboratory from various study objectives. The major objectives include blood stream infections, community-acquired respiratory tract infections (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis), pneumonias in hospitalised patients, skin and soft tissue infections, and urinary tract isolates from hospitalised patients. In 2001, special objectives were introduced to examine gastroenteritis pathogens and beta-haemolytic streptococcal isolates. Over 22 nations participate in SENTRY surveillance globally. The Women's and Children's Hospital, Adelaide has been the reference centre for the Asia-Pacific region and South Africa since 1998, and three other Australian institutions, from Brisbane, Perth, and Adelaide, are part of the global network. All isolates received from our region are tested against up to 29 antimicrobial agents using custom-made broth microdilution panels. The data generated from SENTRY allows Australia to compare our antimicrobial resistance patterns and trends with our regional neighbours.

Anti-Bacterial Agents↗
PubMed2002

Pathogen occurrence and antimicrobial resistance trends among urinary tract infection isolates in the Asia-Western Pacific Region: report from the SENTRY Antimicrobial Surveillance Program, 1998-1999.

Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram-positive and -negative species. The most common causative uropathogens often have intrinsic or acquired resistance mechanisms which include ESBL production among enteric bacilli, multi-drug resistant staphylococci and non-fermentative Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter spp. and vancomycin-resistant Enterococcus spp. This study evaluates pathogen frequency and the resistance rates among urinary tract infection (UTI) pathogens in 14 medical centres in the Asia-Pacific region between 1998 and 1999. The isolates were referred to a central monitor for reference NCCLS broth microdilution testing, identification confirmation and patient demographic analysis. Over 50% of the 958 pathogens were Escherichia coli and Klebsiella spp. followed by P. aeruginosa, Enterococcus spp. and Enterobacter spp. Susceptibility for the three enteric bacilli was high for carbapenems (100%), 'fourth-generation' cephalosporins (cefepime 94.9-98.6%) and amikacin (> or = 93.0%). Beta-lactamase inhibitor compounds were more active against E. coli (piperacillin/tazobactam; > 90% susceptible) than the other two enteric species and all other tested agents had a narrower spectra of activity. The rank order of anti-pseudomonal agents was amikacin (91.5% susceptible)> imipenem > piperacillin/tazobactam > tobramycin > ceftazidime and cefepime (77.4 and 76.4% susceptible, respectively). Susceptibility to quinolones for the P. aeruginosa isolates was only 63.2-67.0%. Only one vancomycin-intermediate Enterococcus spp. (van C phenotype) was detected among the 103 strains tested. Newer fluoroquinolones (gatifloxacin; MIC(50), mg/l) were more potent against enterococci than ciprofloxacin (MIC(50), 2 mg/l) and high-level resistance to aminoglycosides was common (41.7%). The data presented are compared to studies of similar design from other areas which are part of the SENTRY surveillance network.

Anti-Bacterial Agents↗