Drug-targeting in antimicrobial chemotherapy by means of liposomes

Bakkerwoudenberg, Iajm; Lokerse, Af; Vinkvandenberg, Jc; Roerdink, Fh; Mf, Michel

doi:10.1007/bf00404596

Cited by 8 publications

(8 citation statements)

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“…These findings suggest that liposome prepara tions act as a reservoir for amphotericin B, allowing slow release of the entrapped drug. However, in other time-kill studies [10], the growth of Listeria monocytogenes in broth at 37°C was not influenced by the addition of liposomes composed of cholesterol, sphingo Chcmothcrapy 1996;42:170-176myelin and phosphatidylserine in a molar ra tion of 5:4:1 and loaded with ampicillin. In summary, encapsulation of amikacin, netil micin and tobramycin into anionic or cationic liposomes does not enhance their activities against P. aeruginosa.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Bactericidal Action of Amikacin, Netilmicin and Tobramycin in Free and Liposomal Formulation against <i>Pseudomonas aeruginosa</i>

Omri¹,

Ravaoarinoro²

1996

Chemotherapy

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The rates at which free, cationic and anionic liposomal forms of amikacin, netilmicin and tobramycin kill Pseudomonas aeruginosa were studied in vitro. Control inocula with no antibiotic yielded 6.76, 9.53 and 9.74 log CFU/ml at 0, 6 and 24 h, respectively. Empty anionic or cationic liposomes had no effect on bacterial growth. The killing rates of free antibiotics against the bacterial strain were not enhanced by the addition of either empty anionic or cationic liposomes. After 6 and 24 h of exposure at 1, 2 and 4 times the minimum inhibitory concentrations, free amikacin, netilmicin and tobramycin demonstrated a more rapid bactericidal effect than encapsulated anionic or cationic liposomes. The killing rates of liposomal aminoglycosides were lower than those of free aminoglycosides at identical concentrations, suggesting that only fractions of the encapsulated drugs were released from liposomes.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Bactericidal Action of Amikacin, Netilmicin and Tobramycin in Free and Liposomal Formulation against <i>Pseudomonas aeruginosa</i>

Omri¹,

Ravaoarinoro²

1996

Chemotherapy

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“…The amount of human serum depends upon whether human serum or broth medium is used as the diluent. Among the variables in either human serum or broth known to affect the bactericidal activity of certain antimicrobial agents and microorganisms are proteins (4,24,52,78,79), pH (109), phosphates (51), osmolality and salt concentrations (51), and divalent cations (23). The use of human serum as the diluent in the SBT has been shown to be important for certain antimicrobial agents and microorganisms (10,48,67,91).…”

Section: Historical Review Of the Sbtmentioning

confidence: 99%

Serum bactericidal test

Stratton

1988

Clin Microbiol Rev

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The serum bactericidal test represents one of the few in vitro tests performed in the clinical microbiology laboratory that combines the interaction of the pathogen, the antimicrobial agent, and the patient. Although the use of such a test antedates the antimicrobial era, its performance, results, and interpretation have been subject to question and controversy. Much of the confusion concerning the serum bactericidal test can be avoided by an understanding of the various factors which influence bactericidal testing. In addition, the methodologic aspects of the serum bactericidal test have recently been addressed and should place this test on firmer ground. New information on the clinical utility of this test is becoming available; additional data are needed to establish more clearly the usefulness of the serum bactericidal test in specific infections. Such clinical trials from multiple centers will enable firmer recommendations for the future use of the serum bactericidal test.

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“…Some of these studies show that the penetrability is primarily dependent on the free fraction in serum (2,3,9,12,27,28,33), whereas others show the contrary (5, 7, 31). The effect of protein binding on therapeutic efficacy was also examined in various animal models (1,16,17,19,20,25), but the results were inconclusive. The clinical significance of the effect of protein binding on therapeutic efficacy is still controversial.…”

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Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics

Tawara

Matsumoto

Kamimura

et al. 1992

Antimicrob Agents Chemother

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The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia. The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated. In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum. A linear relationship was seen between V/ED.0 values and AUC of free levels in serum/MIC valaues.On the other hand, in mice with pneumonia caused by K. pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue. There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum. The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung. These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection.The significance of antibiotic protein binding has been discussed for the past 40 years. Protein binding has two direct effects on therapeutic efficacy because it affects antibacterial activity and distribution. It is accepted that only the free fraction can act against bacteria (23, 29). The effect of protein binding in serum on extravascular penetration is less clearly established. Although the effects of protein binding in serum on penetration into extravascular fluid and tissues has been studied in various animal (5,7,12,31) and human (2, 3, 9, 27, 28, 33) models, the results were contradictory. Some of these studies show that the penetrability is primarily dependent on the free fraction in serum (2,3,9,12,27,28,33), whereas others show the contrary (5, 7, 31). The effect of protein binding on therapeutic efficacy was also examined in various animal models (1,16,17,19,20,25), but the results were inconclusive. The clinical significance of the effect of protein binding on therapeutic efficacy is still controversial.In the study reported here, we investigated the effect of protein binding in serum on the therapeutic efficacy of eight cephem antibiotics which markedly differ in their extent of binding and in their in vitro activities against the test strains. The therapeutic efficacy of each compound was evaluated against intraperitoneal infections with Staphylococcus aureus or Klebsiella pneumoniae and pneumonia with K. pneumoniae, because the discrepancies of the results of studies on therapeutic efficacy may be due to differences in animal models. The relationship among the therapeutic activity, total or...

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Drug-targeting in antimicrobial chemotherapy by means of liposomes

Cited by 8 publications

References 0 publications

Comparison of the Bactericidal Action of Amikacin, Netilmicin and Tobramycin in Free and Liposomal Formulation against <i>Pseudomonas aeruginosa</i>

Comparison of the Bactericidal Action of Amikacin, Netilmicin and Tobramycin in Free and Liposomal Formulation against <i>Pseudomonas aeruginosa</i>

Serum bactericidal test

Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics

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