Bacteriological evaluation of netilmicin

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.     

Therapeutic effects of micronomicin on experimental infections in mice by intravenous administration

Protective effects of intravenous administration of micronomicin (MCR) on mouse experimental infections were investigated. Mice were better protected by intravenous administration in S. marcescens T-55 experimental infection than subcutaneous administration. No remarkable differences were found between the two administrations in cases of P. aeruginosa BMH No. 1 and E. coli GN 2411-5 infections. Intravenous administrations of MCR, gentamicin (GM), dibekacin (DKB), amikacin (AMK) and sisomicin (SISO) protected the infection of P. aeruginosa BMH No. 1 in a similar extent. MCR was more effective intravenously than AMK; DKB and AMK; DKB, AMK and SISO in experimental infections of E. coli GN 2411-5; S. marcescens T-55; P. aeruginosa KY-8510 harboring aminoglycoside inactivating enzyme AAC(6')-4, respectively.     

Antibacterial activities and PK/PD parameters of aminoglycosides against recent clinical isolates of gram-negative rods

We examined antibacterial activities and PK/PD parameters of six kinds of aminoglycosides against seven bacterial species of clinical isolates in 2001. Aminoglycoseides examined were gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), netilmicin (NTL), and isepamicin (ISP), and bacterial isolates used were each 50 strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus spp., Serratia marcescens and Pseudomonas aeruginosa. All aminoglycosides showed good activities with low MICs against 6 species of Enterobacteriacea except S. marcescens. Eight strains (3.2%) among them were resistant to one or more aminoglycosides. Resistance to multiple aminoglycosides were detected in 16 strains (32%) of S. marcescens, among which 13 strains were resistant to AMK but susceptible to ISP. Three (6%) strains of P. aeruginosa were resistant to multiple drugs, one of which was resistant to all six aminoglycosides, and others were moderately susceptible to AMK and ISP, and susceptible to GM, AMK and ISP. Using a ratio of peak serum concentration to MIC90 (Cmax/MIC90) or a ratio of area under the curve to MIC90 (AUC/MIC90) as a pharmacokinetic and pharmacodynamic (PK/PD) parameter, we estimated the efficacy of the drug. An excellent effect of ISP, which was injected intramuscularly or intravenously at a dose of 400 mg, was expected for strains of Enterobacteriacea except S. marcescens. The Cmax/MIC90 ratios for S. marcescens were comparably higher in GM and ISP and that for P. aeruginosa were rather high in TOB when compared to other aminoglycosides. Another PK/PD parameter, AUC/MIC90 ratio, was high enough in NTL and ISP for Enterobacteriacea, suggesting good efficacy of these drugs. The (AUC/MIC90) ratios for S. marcescens were comparably high in GM and ISP, and that for P. aeruginosa were high in TOB, DKB, and ISP.     

Sensitivity distribution of bacteria newly isolated from urinary tract infections to micronomicin

The antibacterial activity of micronomicin (MCR) was studied comparatively with that of AMK, GM, CMZ and CFX against 346 strains of E. coli, K. pneumoniae, S. marcescens, P. mirabilis, P. rettgeri, P. vulgaris, M. morganii, E. cloacae, P. aeruginosa, S. aureus and S. epidermidis isolated from patients with urinary tract infections on a nation-wide scale from January to July, 1981. MCR was as high as GM in antibacterial activity against all of strains tested, especially very potent against E. coli and P. mirabilis. On the other hand, AMK showed a tendency to be a little lower in antibacterial activity than MCR and GM, CMZ and CFX were weaker in antibacterial activity against the strains tested in this study than MCR, AMK and GM.     

Combination action of sisomicin, dibekacin and cefotetan, cefotaxime, latamoxef, and cefsulodin against Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa

The combined actions of sisomicin (SISO), dibekacin (DKB) and cefotetan (CTT), cefotaxime (CTX), latamoxef (LMOX), cefsulodin (CFS) against E coli KC-14, S. marcescens T-55 and P. aeruginosa E-2 were studied. The following results were obtained. The combination of SISO-CTT, SISO-CTX, SISO-LMOX, SISO-CFS, DKB-CTT, DKB-CTX, DKB-LMOX and DKB-CFS using the checker board dilution method on E. coli KC-14, S. marcescens T-55, P. aeruginosa E-2 were found to have a synergistic effect and the minimum FIC index values were 0.26--0.50 for SISO and 0.28--0.75 for DKB, respectively. With the killing kinetic method, all combinations tested showed a synergistic effect.     

Antimicrobial activities of gentamicin against fresh clinical isolates

Antimicrobial activities of gentamicin (GM), compared with activities of other aminoglycosides (AGs) and beta-lactam antibiotics, were studied against clinical isolates obtained during a period of July-December 1989. 1. GM-resistant strains were noted in 24% of Staphylococcus aureus, 12% of Enterobacter spp., 24% of Serratia marcescens, 7% of Morganella morganii and 26% of Pseudomonas aeruginosa, but no GM-resistant strains were observed among isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris. 2. A majority of GM-resistant strains of S. aureus were methicillin-resistant S. aureus (MRSA) and a large number of GM-resistant strains of Enterobacter spp. was also resistant to new quinolones. GM showed, however, strong antimicrobial activities against new quinolones-resistant strains of S. marcescens, M. morganii and P. aeruginosa. 3. Among all the isolates tested of S. marcescens, 24% were GM-resistant, 72% were tobramycin (TOB)-resistant, 86% were dibekacin (DKB)-resistant and 64% were amikacin (AMK)-resistant, hence the incidence of GM-resistant strains was the lowest. This tendency was also observed with P. vulgaris. However, among P. aeruginosa, 26% were GM-resistant, 14% TOB-resistant, 18% DKB-resistant and 22% AMK-resistant, thus the incidence rate for GM-resistance was somewhat higher. These results suggest that different AGs-modification enzymes were produced by various clinical isolates under the present condition. 4. Comparing the ratio of GM-resistant strains in the present study with those in 1980 and 1983, the ratio increased among S. aureus, while decreases were observed among Enterobacter spp., S. marcescens, P. vulgaris and P. aeruginosa, indicating that a unilateral tendency of increases in GM-resistant strains did not exist among clinical isolates over the years.     

Study on the drug sensitivity of multiple drug-resistant Staphylococcus aureus

Of clinically isolated Staphylococcus aureus showing resistance to multiple drugs among penicillins (PCs), cephem antibiotics (CEPs), aminoglycosides (AGs), minocycline (MINO) and fosfomycin (FOM), 64 strains were selected for the determination of MIC. Twenty-one drugs were used for the determination of MIC, with ampicillin (ABPC), cloxacillin (MCIPC), cephalothin (CET), cefazolin (CEZ), cefotiam (CTM), cefuroxime (CXM), cefamandole (CMD), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), cefmetazole (CMZ), cefoxitin (CFX), latamoxef (LMOX), cefotetan (CTT), cefoperazone (CPZ), gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), MINO, and FOM. MIC80 of each drug at 10(6) CFU/ml were: ABPC, MCIPC, CEZ, CTM, CXM, CTX, CZX, CMX, CFX, LMOX, CTT, CPZ, GM, DKB and TOB greater than 100 micrograms/ml; CET 50 micrograms/ml; CMD and AMK 25 micrograms/ml; CMZ 12.5 micrograms/ml; FOM 6.25 micrograms/ml; and MINO 0.78 micrograms/ml. The ratio of highly resistant strains with MIC greater than 100 micrograms/ml at 10(6) CFU/ml varied according to drug, and a difference tended to be seen in the degree of influence by resistant factors reflected upon MIC, e.g. drugs for which a high resistance of more than 50% was confirmed were ABPC, CXM, CZX, LMOX and TOB, and 20 approximately 30% MCIPC, CTM, CTX, CMX and CFX. MIC on MCIPC which has a correlation of structural activity with methicillin correlated with cephems (CEPs) resistance to a high degree, but many of the so-called new CEPs showed resistance even to the strains with a low MIC on MCIPC. It was assumed that CEPs resistant strains have multiple drug resistant factors based on the fact that such strains showed multiple drug resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isepamicin与六种氨基糖苷类体外抗菌活性研究

本文比较fsepamicin(ISP)、庆大霉素(GM)、地贝卡星(DKB)、乙基西索米星(NTL)、妥布霉素(TOB)、西索米星(SISO)与阿米卡星(AMK)的体外抗菌活性。金葡菌产酶株对上述抗生素的敏感性显较不产酶株为差,以ISP、NTL对金葡菌产酶株的作用最强。其平均MIC值分别为1.85和2.12mg/L;对革兰氏阴性杆菌的作用则以ISP和AMK为强。以ISP对各种细菌的MIC值最低0.32～3.39mg/L。TOB、GM、SISO、NTL与DKB对多数革兰氏阴性杆菌的作用相似,五者之间有很大程度交叉耐药。所测611株革兰氏阴性杆菌中对一种以上药物耐药者312株,占51％;其中对ISP和AMK仍敏感者分别为90.4％和91.7％,而对NTl、GM、TOB、DKB敏感者仅15～18％,本文讨论了细菌对氨基糖苷类的耐药机理及其临床意义。     

Studies on sub-MIC activities of beta-lactam antibiotics and aminoglycoside antibiotics against clinically isolated strain

Sub-MIC range of 8 kinds of beta-lactam antibiotics and 3 kinds of aminoglycoside antibiotics against strain of Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa isolated from clinical source were determined by nephlometic method, and following results were obtained. When 10 strains of S. aureus tested to ampicillin (ABPC), hetacillin (IPABPC), mecillinam (MPC), cephalexin (CEX), cefotaxime (CTX), latamoxef (LMOX), cefatrizine (CFT), cephapirin (CEPR), gentamicin (GM), dibekacin (DKB) and amikacin (AMK), ratio of MIC to MAC were 36.8, 53.6, 156.8, 29.6, 61.6, 34.4, 50.0, 111.2, 9.2, 20.0 and 13.6, respectively. When 10 strains of K. pneumoniae tested to MPC, CEX, CTX, LMOX, CFT, CEPR, GM, DKB and AMK, ratio of MIC to MAC were 409.6, 10.4, 34.4, 123.2, 39.2, 167.2, 5.2, 5.6 and 13.2, respectively. When 10 strains of P. aeruginosa tested against CTX, LMOX, GM, DKB and AMK, ratio of MIC to MAC were 16.8, 38.4, 6.8, 3.2 and 10.4, respectively.     

Studies on the combination action of sisomicin, gentamicin and cefmenoxime, ceftizoxime, cefoperazone, cefotetan against Serratia marcescens and Pseudomonas aeruginosa

The combined actions of sisomicin (SISO), gentamicin (GM) and cefmenoxime (CMX), ceftizoxime (CZX), cefoperazone (CPZ), cefotetan (CTT) against S. marcescens IFO-3735 and P. aeruginosa IFO-12689 were investigated. The results were summarized as follows. The synergistic effect of the combinations of SISO-CMX, SISO-CZX, SISO-CPZ, SISO-CTT, GM-CMX, GM-CZX, GM-CPZ and GM-CTT using the checker board dilution method on S. marcescens IFO-3735 and P. aeruginosa IFO-12689 were found. Especially the minimum FIC index value of combination of SISO-CTT and GM-CTT were rather low as 0.14 and 0.13, respectively and these synergistic effect was remarkably strong on S. marcescens IFO-3735. With the killing kinetic method, all combinations tested showed the synergistic effect in both bacteria.     

Susceptibility of clinical isolates to cefotaxime

Susceptibilities of 737 strains of 19 species of bacteria to cefotaxime (CTX) were determined based on the inhibition zone diameter obtained by the single-disc method. Four categories were assessed. 1. Susceptibility of clinical isolates to CTX and 6 other antibiotics Against most strains, CTX showed higher antibacterial activity than other drugs (CET, ABPC, SBPC, CMZ, GM, AMK), especially for S. pneumoniae, S. pyogenes and S. agalactiae. Furthermore, CTX was more active than the other antibiotics against E. coli, Indole (+) Proteus, P. mirabilis, Klebsiella sp., S. marcescens, H. influenzae and E. cloacae. 2. Susceptibility of strains isolated from different clinical materials CTX showed the highest antibacterial activity against most strains isolated from sputum, urine, pus, blood and cerebrospinal fluid. However, CTX was occasionally less than potent AMK and GM against strains isolated from bile. Against P. aeruginosa strains derived from clinical materials, the following results were obtained: AMK greater than CFS, FOM greater than CTX greater than GM greater than SBPC 3. Susceptibility of clinical isolates in 7 different fields CTX was the most active antibiotic tested in the fields of internal medicine, pediatrics, urology, obstetrics & gynecology, dermatology and otorhinolaryngology. But in surgery, CTX was less potent than GM and AMK. 4. Susceptibility of clinical isolates of inpatients and outpatients CTX showed excellent activity against many beta-lactamase resistant strains isolated from patients.     

Studies on the combination action of sisomicin, gentamicin and piperacillin, cefmetazole against Pseudomonas aeruginosa and Serratia marcescens

The combined actions of sisomicin (SISO), gentamicin (GM) and piperacillin (PIPC), cefmetazole (CMZ) against Pseudomonas aeruginosa E-2 and Serratia marcescens T-55 were studied. The following results were obtained. 1. The combinations of SISO-PIPC, SISO-CMZ, GM-PIPC and GM-CMZ using the checker board dilution method on P. aeruginosa E-2 and S. marcescens T-55 were found to have a synergistic effect and the minimum FIC index values were 0.38 in all combinations. 2. With the killing kinetic method, all combinations tested showed a synergistic effect. 3. A synergistic effect of the combinations of SISO-PIPC, SISO-CMZ, GM-PIPC and GM-CMZ was observed in the protective effect on experimental P. aeruginosa E-2 and S. marcescens T-55 infections in mice.     

Antibacterial activities of various aminoglycosides against clinically isolated methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from samples collected from various patients during 1986, and antibacterial activities of 6 aminoglycosides (AGs) (netilmicin (NTL), gentamicin (GM), sisomicin (SISO), dibekacin (DKB), tobramycin (TOB) and amikacin (AMK] and 4 beta-lactam antibiotics (cefazolin (CEZ), cefmetazole (CMZ), cloxacillin (MCIPC) and methicillin (DMPPC) against these MRSA were evaluated. Among these 6 AGs, NTL was the most potent, and its MIC50 and MIC80 were 1.56 and 3.13 micrograms/ml, respectively. Antibacterial activities of GM, SISO, DKB and TOB were weak, and MIC50's of GM and DKB were both 100 micrograms/ml, while those of SISO and TOB were 50 and greater than 100 micrograms/ml, respectively. Frequency of highly resistant specimens to AMK was rather low and its MIC50 and MIC80 were 12.5 and 25 micrograms/ml, respectively. As for antibacterial activities of the above 4 beta-lactam antibiotics, the MIC50 and MIC80 of CMZ were 6.25 and 12.5 micrograms/ml, respectively, and therefore, its antibacterial activity to MRSA is relatively good. However, MIC50's of CEZ, MCIPC and DMPPC were all greater than 100 micrograms/ml, showing poor antibacterial activities. Recently, MRSA became a problem in various fields of clinical practice, and a number of literatures reporting refractory infections caused by MRSA have been published. Since MRSA is featured as multiply resistant bacteria, it is known that MRSA is resistant to the majority of existing antibiotics (penicillins, cephems, macrolides, AGs, etc.). In 1985, we reported results of our study concerning the antibacterial activities of a number of CEPs and some of AGs against multiply resistant S. aureus including MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. IV. Synergistic action with dibekacin]

Antimicrobial activities of cefodizime (CDZM) in combination with dibekacin (DKB) were studied in vitro against clinically isolated Gram-negative rods. The results obtained are summarized as follows. 1. Similarly to combinations of CDZM+sisomicin (SISO) and CDZM+gentamicin (GM), combined activities of CDZM and DKB were dependent on antimicrobial activities of DKB, and the combined activities were more strongly dependent on DKB concentrations than on CDZM concentrations. The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when DKB concentrations in blood are at or somewhat lower than 1 MIC, and that clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+GM combination. 2. As we have suggested previously, it seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams.     

Antibacterial activity and ototoxicity in guinea pigs, and nephrotoxicity in rats of arbekacin

Arbekacin (HBK), 1-N[(S)-4-amino-2-hydroxybutyl]-3',4'-dideoxykanamycin B, showed broad antibacterial spectra against gram-positive and gram-negative bacteria including Pseudomonas aeruginosa. It was also effective against gentamycin- or tobramycin-resistant bacteria. HBK was resistant to various aminoglycoside-inactivating enzymes except for AAC (2') and AAC (6')-IV, both of which slowly inactivated it. Even at higher dosages (150 mg/kg i.m. or greater, which resulted in some deaths), HBK never decreased the pinna reflex in guinea pigs, while 150 mg/kg or more of dibekacin (DKB) or amikacin (AMK) caused loss of this reflex. HBK has less ototoxicity than do DKB and AMK. This was confirmed by histopathological examination of the inner ear. The degree of nephrotoxicity of HBK was suggested to be similar to that of DKB as judged from serum biochemical tests, urinalysis, and histopathological findings.     

The antimicrobial activity of sisomicin against fresh clinical isolates

Antimicrobial activities of sisomicin (SISO) against clinical isolates obtained in the second half of 1986 were investigated together with other 4 aminoglycosides (AGs) (gentamicin (GM), tobramycin (TOB), dibekacin (DKB), amikacin (AMK] and 2 cephems (cefotiam, cefotaxime), and were compared to the results reported in the period of late 1970's through early 1980's in Japan. 1. The incidence of SISO-resistant Staphylococcus aureus in the present study was 18% and is comparable to that of the other studies suggesting that the incidence of SISO resistant strains remains on the stable level. The incidence of SISO-resistant Pseudomonas aeruginosa showed the tendency of slight increase. 2. SISO-resistant strains of Enterobacter spp., Serratia marcescens and Citrobacter freundii did not show increase from the 1970/1980 levels. 3. Isolation rates of SISO-resistant indole(+) Proteus varied depending on strains. Isolation rates of SISO-resistant P. vulgaris and Morganella morganii were both as low as 4%, but that of Providencia rettgeri was as high as 60%. Refering to an American study reporting that the Genus Providencia including P. rettgeri showed high incidence of resistance to SISO as well as to GM or TOB, we pointed out that the antimicrobial activity of AGs against Genus Providencia should be evaluated separately from those of other indole(+) Proteus strains. 4. No SISO-resistant strains of Escherichia coli, Klebsiella pneumoniae or P. mirabilis were found. 5. SISO had good antimicrobial activity against most of the investigated species and SISO may still be regarded as one of the clinically useful AGs.     

Clinical evaluation of amikacin by intravenous drip infusion for infections in the field of internal medicine

Amikacin (AMK) by intravenous drip infusion was given to patients with infections in the field of internal medicine and the results were followings: AMK was administered to 19 patients. Diagnosis included sepsis or suspected sepsis (11 cases), pneumonia (2 cases), chronic respiratory tract infections (3 cases) and urinary tract infections (3 cases). Underlying disease included hematologic disease (13 cases), lung fibrosis (1 case), chronic respiratory insufficiency (1 case), diabetes mellitus (1 case), hepatic coma and bronchial asthma (1 case) and prostatic hypertrophy (1 case). Nineteen episodes responded to single therapy (2 cases) or combined therapy with other antibiotics (17 cases). AMK by intravenous drip infusion (dissolved in not less than 100 ml of saline or glucose) was administered at the dose of 200 mg/day to 600 mg/day divided into 2 or 3 times, over 1 hour to 2 hours. The mean duration of therapy was 10 days and the mean total dose was 4.3 g. Clinical effects: Excellent in 7 cases, good in 7 cases, fair in 3 cases and poor in 2 cases, and efficacy rate was 74%. Bacteriological effects: Disappeared in 3 cases, partly disappeared and unchanged in 3 cases, superinfection in 1 case and newly appeared in 1 case. Four strains out of 7 cases of which were detected the causative bacteria were disappeared. GM resistant bacteria (S. marcescens in 2 strains and C. diversus in 1 strain) were disappeared by the administration of AMK, also some clinical symptoms and signs were improved. No side effects and no abnormalities in laboratory findings were noted in any cases attributed to AMK. In conclusion, high efficacy rate was obtained without any side effects, intravenous drip infusion of AMK seemed to be useful for infections in patients with bleeding tendency (e.g. leukemia) or malignant disease.     

Evaluation of the mutagenicity of aminoglycoside antibiotics in Salmonella typhimurium and Saccharomyces cerevisiae.

The mutagenicity of aminoglycoside antibiotics (KM, AKM, DKB, RSM, AMK, GM, TOB) has been studied in cells of the bacteria Salmonella typhimurium and in the yeast Saccharomyces cerevisiae. The bacterial strains (Ames') monitor reverse mutation (point mutation) and the yeast strain D5 monitors mitotic crossing-over, mitotic gene conversion and point mutation. None of these antibiotics demonstrated any mutagenic activities in either the bacteria or the yeast.     

Bacterial combination effect between carumonam and eight other antibiotics

In vitro interactions between carumonam (CRMN) and 8 other antibiotics were studied using the agar dilution checkerboard technique against 88 clinical isolates of Escherichia coli, Proteus vulgaris, Serratia marcescens and Pseudomonas aeruginosa. Combinations of CRMN with 8 other antibiotics were generally additive or indifferent. Synergism was found against S. marcescens or P. aeruginosa with CRMN plus fosfomycin, gentamicin (GM) or dibekacin. Antagonism was not observed with CRMN plus any of the 8 other antibiotics tested. In a phase-contrast microscopic study, the synergism of CRMN in combination with GM were confirmed against P. aeruginosa 15846. CRMN in combination with GM demonstrated a in vivo synergy against experimental urinary tract infection caused by P. aeruginosa 15846 in mice. We think that combinations of several antibiotics with CRMN should be appropriate for initial therapy of infections because no antagonism appeared to occur with other antibiotic agents.     

The combined effects of aspoxicillin with aminoglycoside antibiotics on Pseudomonas aeruginosa

Combined actions of aspoxicillin (ASPC) with several aminoglycosides (AGs) against various Pseudomonas aeruginosa strains were examined using the checker board method and experimental infection of mice, and the actions were compared with those of piperacillin (PIPC) and mezlocillin (MZPC). 1. The combination of ASPC with gentamicin, amikacin (AMK) or tobramycin showed synergistic activities against 81.9-95.5% of the test strains. These frequencies were higher than those of reference penicillins (PCs). Mean values of FIC index for combinations between ASPC and AGs were smaller than 0.5, thus, the combinations showed the strongest synergism among the PCs tested. 2. ASPC combined with AGs showed synergistic actions on experimental mouse infections caused by strains of P. aeruginosa. The potency of ASPC was the same as that of PIPC, but MZPC had a weaker activity than ASPC or PIPC. 3. Schedule of administration of ASPC and AMK was examined using experimental infection in mice caused by P. aeruginosa. When AMK was administered first, a synergism was clearly observed when ASPC was administered within 1 hour of the AMK administration. When ASPC was administered first, a synergism was observed when AMK was administered within 4 hours of the ASPC administration. 4. Influences of AMK and ASPC or reference PCs on growth of P. aeruginosa 22 were examined at lower concentrations than MIC. AMK showed a bacteriostatic action on the test strain at 1/4 MIC. But no influence was observed at lower concentrations than 1/4 MIC of AMK. ASPC and reference PCs showed slight effects on growth of the test strain at concentrations of 1/32 MIC of PIPC, 1/128 MIC of MZPC and 1/256 MIC of ASPC. The PCs showed bactericidal action against the test strain at these concentrations when combined with 1/4 MIC of AMK.