dibekacin and Pseudomonas-Infections

The time-lag/sequential/step by step chemotherapy by fosfomycin plus sulbactam/cefoperazone including a short time small dose of steroid was done for 27 severely infected patients suffered from various cancer or other severe basal diseases. And the staggered "intensive" chemotherapy with added arbekacin or vancomycin to the previous staggered chemotherapy was done against 13 severely infected patients having MRSAs among their infecting pathogens. 1. Bacteriological effects Pseudomonas aeruginosa 6/8, Staphylococcus epidermidis 5/5, Enterococcus faecalis 3/6, Acinetobacter calcoaceticus 2/2, Klebsiella pneumoniae 2/2, MRSA 2/2, Xanthomonas maltophilia 2/3 and other 10/10 were eradicated (84.2%) by the staggered chemotherapy and MRSA 7/13, P. aeruginosa 3/4, E. faecalis 3/5, A. calcoaceticus 2/2, X. maltophilia 1/1 and others 2/2 were eradicated (53.8% in MRSA, 78.6% in others and 66.7% in total) and 3 of MRSAs were colonized. 2. Clinical effects 1) Staggered chemotherapy: Excellent 18/27, good 8/27, fair 1/27, poor 0/27 (96.3%). 2) Staggered "intensive" chemotherapy: Excellent 6/13, good 4/13, fair 2/13, poor 1/13 (76.9%) in total: excellent 60.0%, efficacy rate 90.0%.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefoperazone; Dibekacin; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Methicillin Resistance; Middle Aged; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Sulbactam; Vancomycin

Clinical efficacies of fosfomycin (FOM) or arbekacin (ABK) plus beta-lactam combination therapies against methicillin-resistant Staphylococcus aureus (MRSA) infections were examined in 15 major hospitals in Ibaraki Prefecture. The subjects were 54 inpatients from January 1991 to April 1993, and most of them showed moderate to severe infections with underlying diseases. MRSA alone was isolated from 23 patients and the other 31 patients had polymicobes including MRSA. Pseudomonas aeruginosa was the most frequent among the co-isolated strains. The number of patients treated with FOM and cefmetazole (CMZ) was 22 (Group C) and that with FOM and flomoxef (FMOX) was 25 (Group F). CMZ or FMOX was administrated 60 minutes after FOM administration. To 8 nonresponding patients in Groups C and F and 7 nonresponders to the other therapies, ABK and ceftazidime (CAZ) or ABK and piperacillin (PIPC) were treated simultaneously (Group A). The clinical efficacies of Groups C and F were 63.6% and 64%, respectively. The bacteriological efficacies (eradication rates) of both groups including microbial substitutions were 42.9% in the former and 56.5% in the latter. No statistical differences were observed in the clinical and the bacteriological efficacies between Groups C and F. The clinical and bacteriological efficacies in Group A were 66.7% and 46.2%, respectively. No side effects were observed in any cases. Mild disturbances of hepatic functions were observed in 2 cases of Groups C and F, and there were no abnormal laboratory test results in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Child; Child, Preschool; Dibekacin; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infant; Japan; Lactams; Male; Methicillin Resistance; Middle Aged; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus

Bacteriological and clinical studies were carried out on staggered intensive chemotherapy regimen for methicillin-resistant Staphylococcus aureus (MRSA) infections combined with Gram-negative opportunistic pathogens as polymicrobial infections. The regimen consisted of administering ceftazidime (CAZ) 30 minutes after infusion of arbekacin (ABK) and a bolus injection of fosfomycin (FOM). The combination of these drugs strongly inhibited the growth of MRSA and Pseudomonas aeruginosa. By this combination treatment, both of MRSA and P. aeruginosa in mixed culture became more susceptible to killing by macrophages. We evaluated the clinical efficacy and safety of combination of ABK, FOM and CAZ in the treatment of 15 patients with MRSA infections. The total efficacy rate was 80.0% and the bacterial eradication rate of MRSA was 60.0%. It is considered that staggered intensive chemotherapy with ABK, FOM and CAZ is useful for such polymicrobial infections involving MRSA.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Ceftazidime; Dibekacin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus

Arbekacin is an aminoglycoside that shows strong antimicrobial activity against Gram-positive bacteria, including MRSA, as well as Pseudomonas aeruginosa . The therapeutic effectiveness of arbekacin is directly related to C max at the infection site. To maximize drug delivery to the respiratory tract and minimize the systemic toxicity, arbekacin optimized for inhalation, ME1100, is under development. In this study, we investigated the efficacy and pharmacokinetics of ME1100 in a murine model of ventilator-associated pneumonia caused by P. aeruginosa by using a customized investigational nebulizer system.. The mice were treated for 5 min, once daily, with placebo, 3, 10 or 30 mg/mL ME1100 or 30 mg/mL amikacin.. In the survival study, the survival rate was significantly improved in the 10 and 30 mg/mL ME1100 treatment groups compared with that in the placebo group. The number of bacteria in the lungs was significantly lower in the 30 mg/mL ME1100 treatment group at 6 h after the initial treatment, compared with all other groups. In the pharmacokinetic study, the C max in the 30 mg/mL ME1100 treatment group in the epithelial lining fluid (ELF) and plasma was 31.1 and 1.2 mg/L, respectively. Furthermore, we compared the efficacy of ME1100 with that of amikacin. Although there were no significant differences in ELF and plasma concentrations between 30 mg/mL of ME1100 and 30 mg/mL of amikacin, ME1100 significantly improved the survival rate compared with amikacin.. The results of our study demonstrated the in vivo effectiveness of ME1100 and its superiority to amikacin.

Topics: Administration, Inhalation; Amikacin; Animals; Anti-Bacterial Agents; Dibekacin; Disease Models, Animal; Drug Compounding; Lung; Mice; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa NCGM1588 has a novel chromosomal class 1 integron, In151, which includes the aac(6')-Iaj gene. The encoded protein, AAC(6')-Iaj, was found to consist of 184 amino acids, with 70% identity to AAC(6')-Ia. Escherichia coli transformed with a plasmid containing the aac(6')-Iaj gene acquired resistance to all aminoglycosides tested except gentamicin. Of note, aac(6')-Iaj contributed to the resistance to arbekacin. Thin-layer chromatography revealed that AAC(6')-Iaj acetylated all aminoglycosides tested except gentamicin. These findings indicated that AAC(6')-Iaj is a functional acetyltransferase that modifies the amino groups at the 6' positions of aminoglycosides and contributes to aminoglycoside resistance of P. aeruginosa NCGM1588, including arbekacin.

Topics: Acetylation; Acetyltransferases; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Chromatography, Thin Layer; Dibekacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gentamicins; Humans; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Pseudomonas aeruginosa; Pseudomonas Infections; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Substrate Specificity

The aim of this study was to evaluate the in vitro combination effects of aztreonam (AZT) and aminoglycosides against multidrug-resistant (MDR) Pseudomonas aeruginosa strains in Japan. We investigated 47 MDR P. aeruginosa strains collected from 8 facilities. We selected the aminoglycosides amikacin (AMK), gentamicin (GM), and arbekacin (ABK) to examine their effects when combined with AZT using the checkerboard method. Of the 47 MDR P. aeruginosa strains, 41 tested positive for metallo-β-lactamase (MBL). In all combinations, aminoglycosides decreased the minimum inhibitory concentrations of AZT in a dose-dependent manner, and there was no apparent antagonism. The combination effects were scored on a scale of 0 to 4, and statistical analysis was performed using the Wilcoxon signed-rank test. In all 47 strains, AZT + ABK (mean score, 2.02) had the highest score, followed by AZT + AMK (1.68) and AZT + GM (1.38) (ABK versus GM, P < 0.0001). In 41 MBL-positive strains, AZT + ABK (mean score, 2.05) had the highest score, followed by AZT + AMK (1.56) and AZT + GM (1.37) (ABK versus AMK, P = 0.02, and ABK versus GM, P < 0.0001). AZT + ABK was the most promising combination regimen against MDR P. aeruginosa strains; the other promising combinations were AZT + AMK and AZT + GM.

Topics: Amikacin; Anti-Bacterial Agents; Aztreonam; Dibekacin; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation, Preclinical; Drug Resistance, Multiple, Bacterial; Gentamicins; Humans; Japan; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Statistics, Nonparametric

Combined effects of arbekacin (ABK) with biapenem (BIPM) were examined on both in vitro and in vivo model of a mixture of MRSA and Pseudomonas aeruginosa. As a result, significant effect in vitro was observed in combined use of ABK (1/2 MIC) with BIPM (1/4 and 1/2 MIC) against MRSA as compared with ABK or BIPM alone. Against P. aeruginosa combined effect was also observed, showing reduction of viable cells to the limitation of detection within 2 hours. Moreover, with respect to the protective effect on mixed systemic infection of MRSA and P. aeruginosa, the combined treatment with ABK and BIPM showed more excellent efficacy as compared with the single use of each drug.

Topics: Aminoglycosides; Animals; Anti-Infective Agents; Dibekacin; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Drug Therapy, Combination; Male; Methicillin Resistance; Mice; Mice, Inbred ICR; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

We experienced successful treatment of postoperative severe pneumonia of Methicillin-resistant Staphylococcus aureus (MRSA) with combination therapy of Arbekacin (ABK) and Fosfomycin (FOM) in three lung cancer patients. Case 1 was a advanced age of seventy-nine man who had had right upper lobectomy. Case 2 was a 61-year-old man who had had left lower lobectomy and extended bilateral mediastinal lymph-node dissection through the median sternotomy. And case 3 was a 59-year-old man who had suffered from pulmonary embolism after right pneumonectomy and partial resection of left atrium and superior vena cava. All cases were immuno-compromised patients and super-infected with Gram-negative rods, and Pseudomonas aeruginosa in case 1 and case 3. Clinical symptoms were improved after the start of administration of ABK and FOM inspite of ineffectiveness of prior treatment with other antibiotics. We added staggered chemotherapy of Sulbactam/Cefoperazone (SBT/CPZ) and Ceftazidime (CAZ) for case 1 and case 3 respectively. Thus, the combination therapy of ABK and FOM might be useful for severe pneumonia of MRSA in the immunocompromised patients, and the combined staggered chemotherapy of beta-lactum agents and above would be the first choice in the treatment for the case involving Pseudomonas aeruginosa.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Immunocompromised Host; Lactams; Lung Neoplasms; Male; Methicillin Resistance; Middle Aged; Pneumonia, Bacterial; Postoperative Complications; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus

The bactericidal activities of arbekacin (ABK), vancomycin (VCM), gentamicin (GM) and netilmicin (NTL) in mixed culture with Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were examined using an in vitro computer programmed pharmacokinetic simulation system and also the protective effect of these agents on systemic infection in neutropenic mice was examined. In a mixed culture of S. aureus No. 235 (MRSA) and P. aeruginosa E7, ABK showed a strong bactericidal activity and an inhibition of regrowth against both bacteria, and GM and NTL showed similar effects. On the other hand, VCM showed a bactericidal activity against S. aureus No. 235, but not against P. aeruginosa. In the protective study, ABK was evidently more effective than GM, NTL or VCM against a systemic mixed infection of mice with S. aureus No. 235 and P. aeruginosa E7. In brief, the ED50 values of ABK, VCM, GM and NTL were 19.5, > 100, 40.5 and 45.2 mg/kg, respectively.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Computer Simulation; Dibekacin; Gentamicins; Male; Methicillin Resistance; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

We examined the clinical efficacy of a combination of arbekacin and fosfomycin in the treatment of various methicillin-resistant Staphylococcus aureus (MRSA) infections. The combination of arbekacin plus fosfomycin displayed 65.4% (17/26) clinical efficacy and 65.4% (17/26) bacteriological efficacy. This combination thus appeared to be an effective regimen for the treatment of MRSA infections. However, its bacteriological efficacy against concomitant Pseudomonas aeruginosa strains was only 16.7% (1/6). In addition, in 4 episodes of superinfection involving P. aeruginosa strains developed during the combination therapy.

Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Superinfection

In vivo synergistic effects of cefodizime (CDZM) were investigated in combination with aminoglycosides (AGs), sisomicin (SISO) or dibekacin (DKB) against Pseudomonas aeruginosa in immunocompromised tumour bearing mice. Fractional effective dose (FED) indices showed that either synergistic or additive effects were observed between CDZM and AGs. The synergistic intraperitoneal bactericidal effect of CDZM in combination with SISO or DKB was also observed in immunocompromised tumour bearing mice. The post antibiotic effect (PAE) of AGs was prolonged by the addition of CDZM. Moreover, the strong synergistic bactericidal effects of CDZM and AGs against P. aeruginosa were observed in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN). These results suggest that the strong therapeutic efficacy of CDZM in combination with AGs was caused by synergistic bactericidal effect of CDZM and AGs in the presence of PMN.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Dibekacin; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Immunocompromised Host; Male; Mice; Mice, Inbred Strains; Neutrophils; Pseudomonas aeruginosa; Pseudomonas Infections; Sisomicin

Advances and limitations in the diagnosis and treatment of respiratory tract infections were discussed in relation to the prognosis of the elderly patients. Haemophilus influenzae and Streptococcus pneumoniae are the major pathogens in the community-acquired respiratory tract infections. On the other hand, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the major pathogens in the nosocomial respiratory tract infections. Detection of MRSA-PBP genes and antibiotic sensitivity tests are important for the diagnosis of MRSA. Vancomycin or arbekacin is the first-choice antibiotic for the treatment of severe infection caused by MRSA, and a combination therapy using one of the above agents and a partner antibiotic is necessary in some cases of MRSA infections. Reports concerning the significance of anaerobic bacteria in respiratory tract infections in Japan have been rare, presumably because procedures to recover anaerobic bacteria from specimens other than sputum, for example transtrancheal aspiration (TTA), bronchoscopic procedure and transcutaneous lung biopsy, are required for the diagnosis of the anaerobic respiratory tract infections. Nowadays, identification of cytomegalovirus (CMV) is a prerequisit for the rapid diagnosis of CMV infection. Therefore attempts are being made to detect a specific substance, for example messenger RNA during the stage of reactivation of CMV. Prophylaxis as well as treatment is necessary for the control of acute exacerbation of chronic respiratory tract infections. In this regard, long-term administration of a small dose of erythromycin or new-quinolone is promising.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Cytomegalovirus Infections; Dibekacin; Erythromycin; Humans; Methicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolones; Respiratory Tract Infections; Staphylococcal Infections; Vancomycin

Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative 9,3"-di-O-acetylmidecamycin (MOM) against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals after the two kinds of antibiotics were added to the logarithmic phase of the bacterial solution. Six hours after addition of antibiotic, the viable bacterial count of the culture treated with FOM and MOM underwent 2 log reduction compared to that which treated with FOM alone. Thus synergistic effect was significant. The number of viable bacteria treated with DKB and MDM showed slight reduction at 3 hours after addition of the two antibiotics and a marked reduction was noted after 20 hours compared with the control. Synergistic action was also demonstrated in in vivo experiments using mice. Three experimental mouse infection models, intraperitoneal infection, subcutaneous infection with carrageenan solution and burn infection were used. FOM was administered subcutaneously. DKB was administered intramuscularly. MDM or MOM was administered by the oral route. In all three experiments the survival rate of infected mice treated with FOM and MOM increased significantly compared to control mice. Similar synergistic effect was also obtained with DKB and MDM.

Topics: Animals; Anti-Bacterial Agents; Cell Wall; Depression, Chemical; Dibekacin; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Kanamycin; Leucomycins; Mice; Pseudomonas aeruginosa; Pseudomonas Infections

The effects of habekacin on corneal ulceration, caused by Pseudomonas aeruginosa IFO 3455, were studied in mice, in comparison with gentamicin and tobramycin. The minimal inhibitory concentrations of the antibiotics for the organism were: habekacin 2 microgram/ml, gentamicin 2 microgram/ml, and tobramycin 1 microgram/ml. Habekacin showed protective and therapeutic effects on Pseudomonas keratitis. The 50% effective dose was approximately 1 microgram per mouse, when the drug was topically applied three hours after the infection, and about 0.2 mg per mouse, when the antibiotic was intramuscularly injected one hour after the bacterial challenge to the cornea. Significant therapeutic and protective activities of habekacin were observed even by starting the topical and/or intramuscular treatment after the corneal ulcers were formed: i.e. 15 hours after the bacterial infection. Complete cure of Pseudomonas keratitis was found within a week in a number of the infected mice by both topical and systemic administrations of the drug. The protective and therapeutic effects of habekacin were comparable to those of gentamicin and tobramycin.

Topics: Administration, Topical; Aminoglycosides; Animals; Anti-Bacterial Agents; Corneal Ulcer; Dibekacin; Injections, Intramuscular; Keratitis; Male; Mice; Pseudomonas Infections

Dibekacin was used for the treatment of 5 patients with bacterial respiratory tract infections (4 cases of Ps. aeruginosa and 1 case of S. marcescens) intravenously. Serum levels of DKB was observed by the method of enzyme immunoassay (EIA) and bioassay and no differentiation was observed between EIA and bioassay. Four cases of Ps. aeruginosa and 1 case of S. marcescens were all disappeared in 5 or 7 days of administration. No side effects were observed. The results obtained in this study indicate that DKB intravenous challenge might become one of the important method on respiratory tract infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Dibekacin; Drug Evaluation; Female; Humans; Infusions, Parenteral; Kanamycin; Male; Middle Aged; Pseudomonas Infections; Respiratory Tract Infections; Sputum

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Conjunctivitis; Dibekacin; Female; Humans; Infant; Kanamycin; Male; Middle Aged; Ophthalmic Solutions; Pseudomonas Infections

Topics: Adult; Aged; Anti-Bacterial Agents; Dibekacin; Female; Humans; Infusions, Parenteral; Kanamycin; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Surgical Wound Infection

I) The author has successfully produced a model of experimental osteomyelitis caused by pseudomonas aeruginosa using the following procedure though such a demonstration has been said to be very difficult. After impregnation in a solution containing about 10(5) pseudomonas aeruginosa, 3 mm silk thread of No. 5 was dried under low-pressure atmosphere and then inserted into the metaphysis of right tibia of a mouse. This method can be produced experimental osteomyelitis in 100% of the animals. In the experimental osteomyelitis generated pathologically by this method, inoculated organisms do not transmigrate into blood, the kidney and the contralateral tibia. This may therefore be regarded as a local infection causing no death, making a long period of observation possible. In view of the X-ray and patho-histological findings, it is similar to human osteomyelitis. Furthermore, its host is a pure-bred mouse with constant elements making a league-scale experiment possible. II) This is an experimental model of osteomyelitis proved quite useful for the quantitative analysis of the effects of antibiotics, and would be a good method for evaluation of antibiotics to be developed in the future.

Topics: Animals; Bacteriological Techniques; Dibekacin; Gentamicins; Mice; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Sisomicin; Tibia

The aminoglycoside dibekacin, developed in Japan and now on the market in Germany, has been tested for its clinical and microbiological effectiveness on 45 patients with highly resistant germs. 41 of the 55 primary sensitive germs could be thus eliminated from the urine, 6 of the 11 being pseudomonas germs. The clinical results of 33 of the 45 patients were very good, only 4 of them were not convincing. The nephrotoxic side effects were noticeably slight. No evidence of damage to the VIIIth brain nerve was observed in these patients. The results were satisfactory considering the selection of problem patients in the test group. Dibekacin can be regarded with gentamicin as a first choice aminoglycoside.

Topics: Adult; Aged; Dibekacin; Drug Evaluation; Drug Resistance, Microbial; Female; Humans; Kanamycin; Male; Middle Aged; Pseudomonas Infections; Urinary Tract Infections

Topics: Administration, Topical; Animals; Dibekacin; Guinea Pigs; Kanamycin; Keratitis; Ophthalmic Solutions; Pseudomonas Infections

The effectiveness of immunizing mice with protease toxoid (PT) or elastase toxoid (ET) on the corneal ulcerization due to either protease or elastase were investigated. Consequently, mice immunized with either PT or ET were protected from corneal ulcers experimentally induced by the homologous enzyme, either protease or elastase. Similarly, two kinds of rabbit immune sera, anti-PT and anti-ET, were found to prevent corneal ulcers by the homologous enzyme. Then, the therapeutic effects of vaccination with a single or mixed vaccine consisting of one, two or three components, i.e., PT, ET and/or the common antigen (OEP) of Pseudomonas aeruginosa, were examined on corneal ulcers in mice produced by live cultures of the bacteria. For the same purpose, administration of a single or combined rabbit immune sera against PT, ET and OEP was conducted. As a result, vaccination with the three-component-mixed vaccine or administration with rabbit immune sera combined with anti-PT and anti-ET sera in addition to anti-OEP serum, were found to be the most effective in preventing corneal ulceration as well as in treating corneal ulcers in mice.

Topics: Animals; Antigens, Bacterial; Bacterial Vaccines; Corneal Ulcer; Dibekacin; Pancreatic Elastase; Peptide Hydrolases; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Toxoids

Majority of Pseudomonas aeruginosa strains were inhibited at 25 approximately 50 microng/ml of carbenicillin. There was no difference in MIC'S determined using either MUELLER-HINTON agar or Heart Infusion agar. All strains which showed one plus or more sensitivity in either of mono- or tri-disc test showed MIC of 100 microng/ml or less. In view of the high serum concentrations obtainable with 20 approximately 30 g per day dose of carbenicillin, the disc sensitivity test for this antibiotic should reasonably be interpreted as sensitive when it is one plus or more. The combination of carbenicillin with gentamicin or dibekacin showed marked synergism in vitro against Pseudomonas aeruginosa.

Topics: Carbenicillin; Dibekacin; Drug Combinations; Drug Synergism; Gentamicins; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections

Synergistic effects of immune gamma-globulin fraction containing antibodies of OPE, protease and elastase of Pseudomonas aeruginosa on the activities of antibiotic, dibekacin (DKB), in the cornea of mice were examined for the purpose of studying therapy for corneal ulcers due to Pseudomonal infection. In the case of the intramuscular injection, a medium effective dose (ED50) of DKB alone against corneal ulcers caused by strain IID 1210 of P. aeruginosa in experimental mice was 620 mug per mouse. When 15.6 to 18.7 mg of gamma-globulin fraction was subcutaneously given to each mouse prior to the infection with strain IID 1210, opacity instead of severe ulcers was observed only in the central area of cornea. The immune gamma-globulin fraction was far more effective in the protection of cornea from the infection than the calf serum that showed no antibody titer against OEP, protease and elastase. The ED50 values of DKB's combined with the immune gamma-globulin, Fr. 1 and Fr. 2, and the calf serum were 34 and 73, and 480 mug per mouse respectively. There was found no statistical difference in ED50 value between DKB combined with the calf serum and one without it. There was, however, significant difference in ED50 value between DKB's combined with Fr. 1 and Fr. 2, and one with the calf serum. When DKB alone is dropped in the eye of mouse for the protection, the ED50 value was 15 mug per mouse. When 1.56 to 1.87 mg of the immune gamma-globulin fraction was dropped in the eye after the infection with P. aeruginosa, there was observed no protection against corneal ulcers. the ED50 values of DKB's combined with Fr. 1, Fr. 2 and the calf serum were 0.96, 0.94 and 13 mug per mouse, respectively. There was no significant difference between the ED50 values of 0.96 and 0.94 mug, and between 15 and 18 mug. There was, however, significant difference between the former ED50 values (0.96 and 0.94 mug) and the latter ones (15 and 18 mug). The combination of DKB and the immune gamma-globulin fraction was found to be superior to the combination of DKB and the calf serum in the therapeutic effect on corneal ulcers caused by strain IID 1210 of P. aeruginosa.

Topics: Abscess; Animals; Antibodies, Bacterial; Antigens, Bacterial; Corneal Opacity; Corneal Ulcer; Dibekacin; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Immune Sera; Immunoglobulin G; Kanamycin; Mice; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Animals; Dibekacin; Eye; Eye Diseases; Kanamycin; Pseudomonas Infections; Rabbits; Retinal Degeneration