[Enhanced susceptibility of diabetic mice to gram-negative organisms].
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Biomedical subjects
Publications and source records attributed to Y Obana.
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The phenomenon that mixed infection with certain species of bacteria and Acinetobacter calcoaceticus is more virulent than single infection was analyzed experimentally. In mixed infections with A. calcoaceticus paired with either Escherichia coli, Serratia marcescens, or Pseudomonas aeruginosa, the virulence of the latter three organisms was markedly increased over that of single infections only by slime-producing strains of A. calcoaceticus. Of the 100 strains of A. calcoaceticus tested, 14 had slime-producing ability. There was scarcely any difference in the chemical components of the slimes of the two strains tested, but the components of the slime of P. aeruginosa were different from those of these strains. The slime of these two strains exhibited lethal activity in mice, but no correlation was found between the amount of slime produced and the virulence. The slime enhanced the virulence of E. coli, S. marcescens, and P. aeruginosa when it was inoculated along with their viable cells. Furthermore, the slime exhibited potent cell-impairing activity against mouse neutrophils both in vitro and in vivo. This activity was considered to be mainly responsible for the enhancement of virulence in mixed infections.
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The virulence of clinical isolates of Acinetobacter calcoaceticus subsp. anitratus was studied in mice, and in-vitro and in-vivo activities of several antimicrobial agents were evaluated. In in-vitro susceptibility testings, tetracyclines, aminoglycosides, and peptide were highly sensitive, and minocycline and doxycycline were the most active of 21 antibiotics tested against 84 clinical isolates of Acin. calcoaceticus. Virulence tests for mice revealed that some strains exhibited high virulence with LD50 values between 10(3) and 10(4) viable cells/mouse. Against lethal and urinary tract infections produced by Acin. calcoaceticus Ac-54 strain in mice, minocycline, doxycycline, gentamicin, and dibekacin, which were highly active in vitro, were effective.
The therapeutic efficacy of AC-1370, a new cephalosporin, was compared with that of cefoperazone in experimental infections in mice. For intraperitoneal infections caused by Escherichia coli and Klebsiella pneumoniae, the efficacy of AC-1370 was inferior to that of cefoperazone. On the other hand, AC-1370 was more potent than cefoperazone against pseudomonal infections. The MICs of AC-1370 against the test strains, however, were inferior or equivalent to those of cefoperazone. Serum and peritoneal exudate levels of AC-1370 in infected mice were more durable than those of cefoperazone. The relationship between AC-1370 and neutrophils was investigated. The efficacy of AC-1370 was more dependent on neutrophils than that of cefoperazone. AC-1370 did not enhance the neutrophil functions of migration and phagocytosis to any significant extent.
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The therapeutic efficacy of six beta-lactam and aminoglycoside antibiotics were compared in diabetic mice with experimentally induced Klebsiella pneumoniae pneumonia. beta-Lactams caused a reduction in the numbers of bacteria, with clearance of bacteria from the lungs of diabetic and normal mice. The effect in diabetic mice, however, was very poor. In contrast thereto, no remarkable difference was seen between diabetic and normal mice when treated with aminoglycosides. The concentration of the test antibiotics to the lungs in diabetic mice was lower than in normal mice. The aminoglycosides were more effective than the beta-lactams. These data suggest that in treating acute and more chronic forms of pulmonary infection caused by K. pneumoniae in diabetic mice aminoglycoside antibiotics are particularly valuable, whereas beta-lactams must be given in large quantities using multiple administrations.
In experimental infections in mice, the therapeutic efficacies of rectal administration of ceftizoxime (CZX) were compared with those of subcutaneous administration. The efficacies of rectal administration were equivalent to those of subcutaneous administration against intraperitoneal infections due to Streptococcus pneumoniae and Escherichia coli. Against Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Morganella morganii and Serratia marcescens, the efficacies of rectal administration were inferior to those of subcutaneous administration. Against urinary tract and respiratory tract infections, the efficacies of rectal administration were slightly inferior to those of subcutaneous administration. Serum concentrations of CZX for rectal administration were less than those of subcutaneous administration.
A study of the antibacterial action of cefoperazone (CPZ) and piperacillin (PIPC) against E. coli demonstrated clear differences between these 2 drugs. CPZ showed higher bactericidal and lytic activity which was dose dependent and not greatly influenced by inoculum size. In contrast, the activity of PIPC was strongly influenced by inoculum size and showed high bactericidal activity only against a low inoculum size. The activity of CPZ was not related to the pH of the culture medium, whereas PIPC showed increased activity in an acid medium. In a study of the drug sensitive phase of a synchronous culture, CPZ was highly effective during the period of cell division showing strong bactericidal activity at that time. The bactericidal action of CPZ was inhibited by the addition of chloramphenicol. In contrast, PIPC which by itself demonstrated only weak bactericidal activity was not effective during the period of cell division. Although CPZ and PIPC both activate autolysin activity, CPZ was more active in this regard.
In experimental infections induced with S. aureus, S. pneumoniae, E. coli, K. pneumoniae, P. mirabilis and H. influenzae in mice, the therapeutic efficacies of ampicillin (ABPC) after its rectal administration were compared with those obtained after its oral and subcutaneous administration, and the following results were obtained. Generally, in experimental intraperitoneal infections of mice, the effects of ABPC after rectal administration were inferior to those after subcutaneous administration and superior to those after oral administration. In experimentally induced intraperitoneal and urinary tract infection of E. coli KC-14, similar results were obtained. The plasma levels were reflected as the difference between various administration in the therapeutic efficacies observed with ABPC.
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The following results were obtained from the bacteriological evaluations of netilmicin (NTL), a newly developed antibiotic agent, with gentamicin (GM), dibekacin (DKB) and amikacin (AMK) as the controls. (1) NTL demonstrated broad antibacterial spectra against both Gram-positive and Gram-negative bacteria, but its antibacterial potency against streptococci was not very strong among other Gram-positive bacteria. (2) In terms of distribution of sensitivity of clinically isolated bacterial strains, NTL proved to have antibacterial potency comparable to that of GM and higher potency than that of DKB of AMK against E. coli K. pneumonia, Enterobacter sp., or H. influenzae. However, its efficacy was inferior to GM against Proteus sp., S. marcescens and P. aeruginosa. (3) In conjunction with the influences of pH of culture media or of addition of horse sera upon the antibacterial efficacy, NTL showed an inclination similar to that of GM, DKB and AKM. Its antibacterial efficacy was fortified on the alkaline side or by addition of sera. In connection with the influences of the amounts of inoculated bacteria upon antibacterial efficacy, there were hardly any appreciable influences on it by any of the tested bacterial strains. (4) The interactions of NTL with carbenicillin were evaluated with the chequerboard titration method to find remarkable cooperative actions in any of E. coli, K. pneumoniae, S. marcescens, A. calcoaceticus and P. aeruginosa. (5) The results of evaluation on the patterns of its antibacterial effects revealed that it acted bactericidal in any tested bacterial strains. (6) As to the therapeutic effects against experimental infections in mice, it was found out that NTL = GM greater than DKB and AMK against E. coli, GM greater than NTL = DKB and AMK against K. pneumoniae and GM and DKB greater than NTL greater than or equal to AMK against A. calcoaceticus and P. aeruginosa in the decreasing order of efficacy.
The most effective administration method of polymyxin B (PL-B), a peptide antibiotic, has been studied in the experimental mice infection with Pseudomonas aeruginosa. 1) Pseudomonas aeruginosa damaged by PL-B, when the drug was free, immediately began to regrow in vitro. 2) the therapeutic efficacy of PL-B on multiple administration was less effective than its single administration. 3) An important factor to decide the therapeutic efficacy of PL-B was the high drug concentration in plasma and peritoneal fluid.
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