Anti-bacterial activities of a sulfonated human immunoglobulin preparation against penicillin resistant Streptococcus pneumoniae and Pseudomonas aeruginosa

Abstract

Anti-bacterial activities of a sulfonated human immunoglobulin preparation against penicillin resistant Streptococcus pneumoniae and Pseudomonas aeruginosa were examined. Five week old CBA/J mice were challenged by 10 times of 50% lethal doses of penicillin sensitive (SP1) and resistant (SP2) strains of Streptococcus pneumniae serotype 19, and were treated with a sulfonated human immunoglobulin preparation (hIg). Fifty % protective dose (ED50) were 2-4 mg hIg/ mouse. These doses were parallel with the challenged doses despite of the challenged bacteria, and it was calculated that 6 x 10(6) bacteria were killed by one mg of hIg in both bacteria. Minimal inhibitory concentrations (MIC) of piperacillin, flomoxef, imipenem, amikacin and ofloxacin against SP1 and SP2 were estimated under the presence of various concentrations of hIg. It was found that under the presence of over 10-20 mg/ml of hIg, SP1 and SP2 were not grown even without any antibiotic. That is, MIC of hIg itself against penicillin sensitive and resistant Streptococcus pneumoniae serotype 19 were 10-20 mg/ml. Since about 10(6) bacteria/ml were used for this test, it was calculated that 5-10 x 10(4) bacteria were killed by one mg of hIg in vitro. This result suggested that in vivo anti-bacterial activities of hIg could be 100 times higher than that in vitro. Synergistic or at least additive effects between hIg and all antibiotics tested were seen by the MIC. If hIg was 100 times effective in in vivo, these results suggested that hIg could improve the effect of chemotherapy in clinical cases. Similar in vitro test were carried out for Pseudomonas aeruginosa, and synergistic or at least additive effects between hIg and all antibiotics tested were also confirmed in Pseudomonas aeruginosa. This result suggested that hIg could be effective for clinical pseudomonas infection.