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Biomedical subjects

F M MacKenzie

Publications and source records attributed to F M MacKenzie.

5 recordsLinked to original sources

An outbreak of multiply-resistant Klebsiella pneumoniae in the Grampian region of Scotland.

A predominantly hospital-based outbreak of multiply-resistant Klebsiella pneumoniae capsular type K2 (MRK) expressing expanded spectrum betalactamase (ESBL) activity and fully sensitive only to the carbapenems and amikacin is described. The organism was isolated from 283 patients between March 1992 and September 1995. The outbreak started in the intensive care unit (ICU) of a major acute hospital and spread through surgical wards, a medical ward, a geriatric unit in a separate hospital and various other local hospitals. Environmental screening revealed extensive ward contamination. The decline of the outbreak after the spring of 1995 coincided with the re-emphasis of standard infection control procedures and the launch of a works programme aimed at addressing underlying sites of environmental contamination. Of the 283 cases, 166 (59.0%) were detected through a specially instigated case finding programme. The MRK caused 11 cases of septicaemia, two postoperative intra-abdominal abscesses, one case of postoperative meningitis, 102 cases of urinary tract infection and 28 wound infections and was isolated from the respiratory tracts of five patients with ventilator associated pneumonia. The difficulty in controlling the outbreak is ascribed to heavy environmental contamination, frequent inter- and intra-hospital patient transfers and prolonged carriage of the outbreak strain.

Anti-Bacterial Agents

Comparison of methodologies used in assessing the postantibiotic effect.

The postantibiotic effect (PAE) of the carbapenem antibiotic meropenem was determined for the reference strains of Escherichia coli NCTC 4174 and E. coli NCTC 12210. Regrowth of bacteria after antibiotic exposure was determined by viable counting and bioluminescence alone and in combination with an impedance technique and a morphological technique was also employed. Different methods of calculating the PAE were also used. After exposure of E. coli to 0.1-100 x MIC of meropenem for 2 h, concentration dependent differences in counts by bioluminescence, and viable counting were observed, the latter always being lower. The unexposed control of E. coli NCTC 4174 yielded counts of 1.1 x 10(6) +/- 1.1 x 10(5) and 1.3 x 10(6) +/- 4.7 x 10(5) by viable counting and bioluminescence respectively and E. coli NCTC 12210 gave counts of 4.2 x 10(6) +/- 1.8 x 10(6) and 1.1 x 10(7) +/- 4.3 x 10(6) by the same methods. After exposure to 100 x MIC of meropenem, NCTC 4174 yielded counts of 1.28 x 10(3) +/- 5.35 x 10(2) and 2.59 x 10(5) +/- 8.61 x 10(4) and NCTC 12210 gave counts of 5.22 x 10(3) +/- 9.74 x 10(2) and 5.21 x 10(6) +/- 1.45 x 10(6) by viable counting and bioluminescence, respectively. The discrepancies were due to the inability of the viable counting procedure to detect spheroplasts. Falsely low post exposure counts led to falsely low determinations of PAE by viable counting alone and in combination with the impedance technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents

Automatic procedures for measuring post-antibiotic effect and determining random errors.

Four methods are described for determining the post-antibiotic effect (PAE) automatically using the high resolution capabilities of the conductance measurement of bacterial growth. The time resolution of each method is derived by a statistical procedure for calculating random error from the component errors involved in each determination. The procedures are illustrated using data generated from the measurements of the growth of Escherichia coli NCTC 4174 after exposure of cultures to five antibiotic concentrations. Excellent agreement was found to exist between three of the four methods. However, that based on the determination of the time of peak growth rate is shown to provide better resolution than the other methods, i.e., those based on growth to 10(7) organisms/mL, the duration of the lag phase or the mean retardation of growth averaged over the entire period of observation. The results strongly suggest that PAE may be ascribed entirely to a prolongation of lag time.

Anti-Bacterial Agents

Postantibiotic effect of meropenem on members of the family Enterobacteriaceae determined by five methods.

The postantibiotic effect (PAE) of meropenem was determined for 11 strains, both clinical isolates and reference strains of members of the family Enterobacteriaceae. The study compares PAE results obtained by five methods used to monitor bacterial regrowth, including viable counting, alone and in combination with impedance; bioluminescence, alone and in combination with impedance; and a morphological technique. After exposure of the test organisms to meropenem (0.1 x to 100 x MIC) for 2 h, concentration-dependent differences in counts by bioluminescence and viable counts were observed, the latter always being lower. The differences varied with the test organism. For example, after exposure of Providentia stuartii NCTC 10318 to 0.1 x MIC, the counts were 5.5 x 10(5) and 2.0 x 10(5) whereas after exposure of Citrobacter freundii MR76 to 0.1 x MIC of meropenem the counts were 2.3 x 10(6) and 6.8 x 10(3) by bioluminescence and viable counting, respectively. The discrepancies were probably due to the relative inability of the viable counting procedure to detect fragile aberrant morphologies and resulted in differences in the calculated PAE values. With methods which do not detect fragile morphologies, the PAE may be underestimated. A general trend was observed for the order of magnitude of the PAEs by the following methods (in order of decreasing magnitude of PAE): (i) morphological technique, (ii) bioluminescence technique alone, (iii) bioluminescence in combination with impedance, (iv) viable counting in combination with impedance, and (v) viable counting alone. It is our opinion that of the methods examined in this study, bioluminescence in combination with impedance best reflects the true values for PAEs, and these results were examined more closely.

Bacteriological Techniques

The post-antibiotic effect.

Pharmacodynamics are being applied increasingly to the design of antibiotic dosing regimens. One characteristic of pharmacodynamics is the post-antibiotic effect (PAE), the delayed regrowth of bacteria following exposure to an antibiotic. In this review the various laboratory techniques which have been used to determine the PAE are critically evaluated and compared with the standard viable counting method. The potential sources of error associated with these methods are considered and recommendations are made for the optimum testing system; on the basis of current evidence the bioluminescence and impedence techniques appear to be the most suitable in terms of being the least labour-intensive and producing the most reliable results. Whichever technique is used, the properties of the growth medium, including osmolality and pH, the size of the bacterial inoculum, the initial antibiotic concentration, the exposure time to the antibiotic and the method of antibiotic removal should be standardized. Other post-(antibiotic) exposure events and their relationships with the PAE and theories concerning the mechanism (or mechanisms) by which antibiotics produce PAEs are discussed. Finally, consideration is given to the clinical significance of the PAE and how it, in conjunction with other pharmacodynamic parameters, might be used to allow antibiotic dosing regimens to be developed on a more scientific basis.

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