Economic Control of Quality of Manufactured Product.

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

Before 1985 at the Pitie-Salpetriere Hospital in Paris (2,400 beds), resistance to cefotaxime in clinical isolates of Enterobacteriaceae involved only species producing inducible class 1 beta-lactamase. Between November 1985 and April 1987, however, 62 isolates (57 of Klebsiella pneumoniae and five of Escherichia coli) showed decreased susceptibility to cefotaxime (mean MIC, 8-16 micrograms/mL). The transferability of cefotaxime resistance in E. coli K12 was demonstrated for 15 of 16 selected isolates. By isoelectric focusing using iodometric detection with 20 mg of ceftriaxone/100 mL and determination of substrate and inhibition profiles, three beta-lactamases mediating cefotaxime resistance were identified as SHV-2 (isoelectric point [pI] 7.6), CTX-1 (pI 6.3), and "SHV-2-type" or SHV-3 (pI 6.98). The three beta-lactamases hydrolyzed penicillins and cephalosporins (including cefotaxime and ceftriaxone) and were therefore designated "extended broad-spectrum beta-lactamases" (EBS-Bla). The enzymes conferred to derivatives a high level of resistance to amoxicillin, ticarcillin, piperacillin, and cephalothin and a decreased degree of susceptibility (i.e., MICs increased by 10- to 800-fold) to cefotaxime, ceftriaxone, ceftazidime, and aztreonam. These beta-lactamases did not affect the activity of cephamycins (cefoxitin, cefotetan, moxalactam) or imipenem. Synergy between clavulanate or sulbactam (2 micrograms/mL) and amoxicillin was greater against derivatives producing EBS-Bla than against those producing TEM-1, TEM-2, or SHV-1; this synergy was greater with clavulanate than with sulbactam against derivatives producing SHV-2 and the SHV-2-type enzyme but was similar with clavulanate and sulbactam against those producing CTX-1. A double-disk synergy test performed with cefotaxime and Augmentin disks (placed 30 mm apart, center to center) seemed a useful and specific test for the detection of strains producing EBS-Bla.

https://www.jstor.org/stable/info/4454571

Extended Broad-Spectrum β-Lactamases Conferring Transferable Resistance to Newer β-Lactam Agents in Enterobacteriaceae: Hospital Prevalence and Susceptibility Patterns

https://www.sld.cu/galerias/pdf/sitios/mednat/antibacterial_activity_of_plant_extracts_and_phytochemicals_on_antibioticresistant_bacteria.pdf?origin=publication_detail

Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria

An important task of the clinical microbiology laboratory is the performance of antimicrobial susceptibility testing of significant bacterial isolates. The goals of testing are to detect possible drug resistance in common pathogens and to assure susceptibility to drugs of choice for particular infections. The most widely used testing methods include broth microdilution or rapid automated instrument methods that use commercially marketed materials and devices. Manual methods that provide flexibility and possible cost savings include the disk diffusion and gradient diffusion methods. Each method has strengths and weaknesses, including organisms that may be accurately tested by the method. Some methods provide quantitative results (eg, minimum inhibitory concentration), and all provide qualitative assessments using the categories susceptible, intermediate, or resistant. In general, current testing methods provide accurate detection of common antimicrobial resistance mechanisms. However, newer or emerging mechanisms of resistance require constant vigilance regarding the ability of each test method to accurately detect resistance.

Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices

In the words of the authors, the paper by A. W. Bauer et al., from the University of Washington in Seattle, on a standardized single-disk method for antibiotic susceptibility testing “. . . consolidate(s) and update(s) previous descriptions of the method and provide(s) a concise outline for its performance and interpretation.” Clinical microbiologists were relieved that finally a disk diffusion method had been standardized, could be used with ease, and provided reliable results as compared with minimum inhibitory concentration tests. The pivotal role of Hans Ericsson’s theoretical and practical studies (H. Ericsson and G. Svartz-Malmberg, Antibiot. Chemother. 6:41–74, 1959), as well as earlier reports by some of the authors of the publications cited, must be mentioned as a matter of fairness. Most of the recommendations given are still valid today even though some of the antimicrobial agents are obsolete, new ones have been added, some zone sizes had to be modified, and new media were designed for Haemophilus influenzae and Neisseria gonorrhoeae. Recommendations of the National Committee for Clinical Laboratory Standards continue to be based on this publication; the “Kirby-Bauer” method is, among the many disk methods used in other countries, still the one that has been researched most thoroughly and updated continuously. ALEXANDER VON GRAEVENITZ

Antibiotic susceptibility testing by a standardized single disk method.

Antimicrobial susceptibility testing

The bacterial cell biology viruses host parasite interactions, spread and control of infection, laboratory diagnosis of infection pathogenic bacteria pathogenic viruses pathogenic fungi parasites local and systemic infections advancing fronts in medical microbiology. Appendix: additional pathogenic organisms.

Sherris medical microbiology : an introduction to infectious diseases

The resistance of Staphylococcus aureus to methicillin and related drugs can be reliably determined by using the Kirby-Bauer method of susceptibility testing if the incubation temperature is 35 C or below, but resistance may be missed at 37 C. The 1-mug discs of oxacillin and nafcillin or the 5-mug discs of methicillin may be used for this purpose but not the 1-mug discs of cloxacillin. The latter fail to discriminate between sensitive and resistant staphylococci by zone measurement; some resistant strains of staphylococci may show larger zones of inhibition than sensitive strains. Stability of these antibiotic-containing discs was studied under conditions of temperature and humidity variation that might be encountered in a clinical laboratory refrigerator. Oxacillin discs were the most stable and are to be preferred for susceptibility testing. Nafcillin discs were less stable, and methicillin discs lose their potency rapidly unless carefully stored in a refrigerator with a desiccant.

Reliability of the Kirby-Bauer disc diffusion method for detecting methicillin-resistant strains of Staphylococcus aureus.

Seven laboratories participated in a collaborative study to evaluate the Autobac 1 system. Results obtained with this assay system were compared to those obtained by the standardized Bauer-Kirby disk diffusion test, and each of these two methods was compared to the agar dilution technique. Comparison of the Autobac 1 and the disk diffusion results from the seven laboratories showed an overall average of 91.5% interpretive agreement with the 17 antimicrobial agents tested. The distribution in the levels of Autobac 1/disk diffusion agreement was such that with 13 antimicrobial drugs agreement was 90% or higher; with three, between 85 and 90%; and with one, 77% (nitrofurantoin). Comparison of the Autobac 1 and disk diffusion tests with the International Collaborative Study agar dilution test showed that both methods gave levels of agreement with the International Collaborative Study agar dilution technique that were generally high and equivalent. The average overall agreement between the agar dilution test and each of the other two methods was approximately 90%. Disagreements that did occur tended to involve organisms that were drug susceptible by the Autobac 1 system but intermediate or resistant by the other two methods. This was in part due to the narrow intermediate interpretive zone of the Autobac 1 test. In reproducibility studies with the Autobac 1 and disk diffusion methods, no significant differences were observed between the interpretive reproducibility of the two methods. Images

John C. Sherris

Papers

Antibiotic susceptibility testing by a standardized single disk method.

Antimicrobial susceptibility testing

Sherris medical microbiology : an introduction to infectious diseases

Reliability of the Kirby-Bauer disc diffusion method for detecting methicillin-resistant strains of Staphylococcus aureus.

Laboratory Evaluation of a Rapid, Automated Susceptibility Testing System: Report of a Collaborative Study