Clinical isolates

The -NH(CH2)3N(CH2)2 amide of teicoplanin factor A2-2, coded MPT. 62,873 [122173-74-4] was also prepared. The combined effect of a moderate basicity and a slightly increased lipophilicity at neutral pH probably led to a better penetration through the cell wall. MDL 62,873 was consistentiy more active than teicoplanin against CNS clinical isolates (119,120). No semisynthetic dalbaheptide is under clinical evaluation at this writing. 

Resistance to Lincomycin. Resistance to lincomycin is developed slowly, and is usually caused by modification of 23S ribosomal RNA, which leads to co-resistance to macroHde, lincosaminide, and streptogramin B antibiotics (25). Inactivation of lincomycin by clinical isolates of strains of Staphjlococcus aureus and Staphjlococcus haemoljticus, though retention of sensitivity to macroHdes (see Antibiotics, macrolides) and streptogramins (see Antibiotics, peptides), has been found to be the consequence of the conversion of the antibiotic into its 3-(5 -adenylate) (26). 

Cross-resistance between lincomycin and clindamycin is complete (64), and co-resistances of lincomycin also apply to clindamycin. However, the inactivation of clindamycin by clinical isolates of Staphylococcus haemolyticus and Staphylococcus aureus is caused by adenylylation at the 4-position to form clindamycin 4-(5 -adenylate) [29752-38-3] (7) in contrast to the lincomycin 3-(5 -adenylate) [117785-83-8] (8) that forms (26). 

Madurastatins A1 (119 Scheme 11.17), A2 (120), A3 (121), B1 (122), and B2 (123) were isolated in 2004 from a clinical isolate of a pathogenic actinomycete, a strain of Actinomadura madurae [189]. The stereochemistry of the N-methyl-N-hydrox-yornithine residue remains unknown, but it was determined that the serine and aziridine residues are D, and the rest are L. 

Acetyl-CoA is also utilized as a cofactor to modify chloramphenicol by O-acetyltranferases (CATs). These enzymes have been found in many different bacterial genera and are usually plasmid encoded in clinical isolates. Furthermore, streptogramin type A antibiotics are acetylatedby Vat enzymes that occur on plasmids in staphylococci and enterococci. 

Harada K, Eizuru Y, Isashiki Y, Ihara S, Minamishima Y (1997) Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both ganciclovir and cidofovir. Arch Virol 142 215-225... 

Bacterial resistance to antibiotics has been recognized since the first drugs were introduced for clinical use. The sulphonamides were introduced in 1935 and approximately 10 years later 20% of clinical isolates of Neisseria gonorrhoeae had become resistant. Similar increases in sulphonamide resistance were found in streptococci, coliforms and other bacteria. Penicillin was first used in 1941, when less than 1 % of Staphylococcus aureus strains were resistant to its action. By 1947,3 8% of hospital strains had acquired resistance and currently over 90% of Staph, aureus isolates are resistant to penicillin. Increasing resistance to antibiotics is a consequence of selective pressure, but the actual incidence of resistance varies between different bacterial species. For example, ampicillin resistance inEscherichia coli, presumably under similar selective pressure as Staph, aureus with penicillin, has remained at a level of 30-40% for mai years with a slow rate of increase. Streptococcus pyogenes, another major pathogen, has remained susceptible to penicillin since its introduction, with no reports of resistance in the scientific literature. Equally, it is well recognized that certain bacteria are unaffected by specific antibiotics. In other words, these bacteria have always been antibiotic-resistant. 

The degradation of phenylmercuric acetate to benzene, methylmercuric chloride to methane, and ethylmercuric chloride to ethane and Hg + is apparently carried out by different enzymes from the plasmid-carrying Escherichia coli strain K12 (R831) (Schottel 1978) and Pseudomonas sp. Resistance to organic mercury compounds has also been found in clinical isolates of nontuber-culous, rapidly growing mycobacteria (Steingrube et al. 1991) and can present a challenge in the clinical environment. 

Steingrube VA, RJ Wallace, LC Steele, Y Pang (1991) Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria. Antimicrob Agents Chemother 35 819-823. 

A structural study on lipid A and the O-specific polysaccharide of the lipopoly-saccharide from a clinical isolate of Bacteroides vulgatus from a patient with Crohn s disease was conducted by Hashimoto and coworkers [39]. They separated two potent virulence factors, capsular polysaccharide (CPS) and lipopolysaccharide (LPS), from a clinical isolate of B. vulgatus and characterized the structure of CPS. Next, they elucidated the strucmres of O-antigen polysaccharide (OPS) and lipid A in the LPS. LPS was subjected to weak acid hydrolysis to produce the lipid A fraction and polysaccharide fraction. Lipid A was isolated by PLC, and its structure was determined by MS and NMR. 

Gavin, P. J. Warren, J. R. Obias, A. A. Collins, S. M. Peterson, L. R. Evaluation of the Vitek 2 system for rapid identification of clinical isolates of Gram-negative bacilli and members of the family Streptococcaceae. Eur. J. Clin. Microbiol. Infect. Dis. 2002,21,869-874. 

Figure 6.4 Expanded portion of the MALDI-TOF mass spectra of two different clinical isolates (by region) of Vibrio parahaemolyticus obtained on a reflectron TOF/MS, showing a single change in mass of a protein from m/z 9479 to mtz 9587 giving rise to the strain and geography-related differences observed in Figure 6.3 and reported in Wilkes et al.54...

Original strains provided by J.M. Farber, Health Canada isolated from dried infant formula by S.Edelson-Mammel, FDA Environmental samples obtained from M. Kotewicz, FDA Clinical isolate obtained from F. Khambaty, FDA... 

Jones, M. E. Blosser-Middleton, R. S. Thornsberry, C. Karlowsky, J. A. Sahm, D. F. The activity of levofloxacin and other antimicrobials against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999-2002. Diagn. Microbiol. Infect. Dis. 2003,47,579-586. 

O Neill, G. L. Brazier, J. S. Magee, J. T. Duerden, B. I. A comparison of PCR ribotyping and pyrolysis mass spectrometry for typing clinical isolates of Clostridium difficile. Anaerobe 1996, 2, 211-215. 

Carter, D.A., Burt, A., Taylor, J.W., Koenig, G.L. and White, T.J. (1996) Clinical isolates of Histoplasma capsulatum from Indianapolis have a recombining population structure. Journal of Clinical Microbiology 34, 2577-2584. 

Betts JC et al. Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551. Microbiology 2000 146 3205-3216. 

The preceding protocol can be successfully applied, essentially without modifications, to prepare active cell-free extracts from bacteria other than Escherichia coli (e.g., Bacillus stearothermophilus and clinical isolates of Pseudomonas aeruginosa bearing multiple antibiotic resistance). 

Finally, the clusters were tested as inhibitors of hemagglutination of pig and rabbit erythrocytes by type-1 piliated UTI89 clinical isolate E. coli. The inhibition titer (IT), that is, the lowest concentration of the inhibitor at which no agglutination occurs, showed tetramer 51 to be the best inhibitor of hemagglutination, with an IT of about 3 fiM, or a factor of 6000 as compared to its affinity, and corresponding to 1000-fold better inhibition than that induced by D-mannose. Overall, tetravalent cluster 51 was the best noncovalent cross-linker of Con A and the best ligand known to E. coli K12 FimH. 

Table 1. MICs (ug/ml) of rifaximin and other antimicrobials against 40 strains (39 clinical isolates and the NCTC 11638 strain) of H. pylori at pH 7.0 (from Holton et al. [53])... 

Swiss mice were infected by intraperitoneal injection of 0.25 ml of S. aureus Colliva (clinical isolate). The bacterial suspension contained a sufficient number of organisms to kill all the animals within 72 h. Antibiotics were given orally or subcutaneously 1 h after bacterial inoculation. ND = Not determined. 

Table 8. Activity of rifaximin, vancomycin and metronidazole against 93 clinical isolates of C. difficile (from Marchese et al. [48])... 

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