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.     

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.     

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.     

Synergistic action of cefodizime with other antimicrobial agents on clinically isolated microorganisms. II. Synergistic action with sisomicin]

Cefodizime (CDZM) possesses a broad antimicrobial spectrum and a relatively long half life in the blood. In addition, it shows excellent therapeutic efficacies in the treatment of infections in leukopenic animal models, hence it is expected that CDZM may have good efficacies against various infections in immunocompromised hosts. In the meantime, sisomicin (SISO) not only has strong antibacterial activities against Gram-negative rods (GNR), but has relatively low nephrotoxicity and ototoxicity. Thus, we examined antibacterial effectiveness of the combination of CDZM and SISO against clinical isolates in vitro. 1. Antibacterial effects of CDZM+SISO combination were examined using SISO susceptible strains of Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa. Observations that the combination of the 2 drugs showed FIC indices between less than 0.5-less than 1.0 against most of these strains at SISO concentrations of 1 MIC or sub MIC levels strongly suggested the presence of a synergistic action between the 2 drugs against SISO susceptible strains of GNR. 2. Of the strains tested, 10% of C. freundii, 6.7% of E. cloacae, 63.3% of S. marcescens, 23.3% of P. vulgaris and 18.0% of P. aeruginosa were found to be resistant to SISO, and little synergistic effect of the 2 drugs was observed against these strains. 3. As the synergistic effect of the 2 drugs against GNR was observed against SISO susceptible strains including those which were resistant to CDZM, but not against those strains which were resistant to SISO, it seems reasonable to conclude that the appearance of the synergistic effect between the 2 drugs depends on the activity of SISO.     

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.     

Effect of combination of cefsulodin and mecillinam

The effect of cefsulodin in combination with mecillinam was examined against a wide range of bacterial species. The antibacterial spectrum was widened by the combination of cefsulodin and mecillinam in the ratio of 5:1 and 10:1. In overall observations, in the in vitro test, a synergistic effect against clinical isolates was found on Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, proteus mirabilis and Proteus vulgaris, and an additive effect was found on Staphylococcus aureus, Escherichia coli, Proteus morganii, Proteus rettgeri, Proteus inconstans and Pseudomonas aeruginosa. In in vivo tests, a synergistic effect was observed on S. marcescens TN 66 and K. pneumoniae DT infections and an additive effect was observed on S. aureus 308 A-1, E. coli O-111 and T-7, C. freundii TN 518, E. cloacae TN 603, P. vulgaris GN 4712, P. morganii Tn 373 and P. aeruginosa U 31 infections.     

Combined action of cephamycin and aminoglycoside antibiotics

The combined actions of cefoxitin (CFX) with amikacin (AMK), gentamicin (GM) and dibekacin (DKB) were studied against Gram-positive and Gram-negative bacteria. The following results were obtained. The synergistic actions of CFX with AMK, GM and DKB were observed on S. aureus, S. epidermidis, E. coli, S. marcescens, K. pneumoniae, Proteus spp. and Acinetobacter by checker board titration method. The combination of CFX with AMK was most effective. In case of the combination of CFX with AMK, the simultaneous administration showed the highest bactericidal effect, followed by the case of addition of AMK after adding CFX. The phase-contrast microscopic observation on S. marcescens revealed that the bacterial cell prolonged with CFX showed a filament-like form and with AMK almost a normal form. In the combination, lysed cells were observed. The therapeutic experiment of S. marcescens infection in mice demonstrated that the combination of CFX with AMK showed superior effect than that of each drug alone.     

In vitro study on the combined effect of mezlocillin and sisomicin on clinically pathogenic P. aeruginosa and E. coli

Clinically pathogenic Pseudomonas aeruginosa and Escherichia coli were subjected to test in vitro combination effect of mezlocillin (MZPC) and sisomicin (SISO). The chequer board titration method, using brain heart infusion broth (BHIB, Difco), demonstrated the combination effect of MZPC and SISO on the both isolates. The bactericidal combination effects (MBCs) were clearly higher than the bacteriostatic combination effects (MICs). The bactericidal activities of combination with MZPC and SISO were tested on both P. aeruginosa and E. coli. The MZPC plus SISO of low concentrations showed the synergistic effects on both isolates.     

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.     

Bactericial activity of chlorhexidine gluconate against recent clinical isolates of various bacterial species in Japan

The minimum inhibitory concentration (MIC) and bactericidal activity of chlorhexidine gluconate (CHG) were determined for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Escherichia coli, Serratia marcescens, Eterobacter cloacae, Pseudomonas aeruginosa and Burkholderia cepacia, isolated from patients in medical institutions all over Japan between 2000 and 2002. The following findings were obtained. 1. The MICs of CHG against MSSA, MRSA, E. coli and B. cepacia were 0.002% or less, and those against S. marcescens, E. cloacae and P. aeruginosa were 0.008% or less. 2. Rapid and strong bactericidal effects of CHG were observed against all clinical isolates of E. coli, E. cloacae and P. aeruginosa tested even at relatively low concentrations (0.02 to 0.05%). 3. Relatively high concentration or prolonged treatment time was required to achieve sufficient bactericidal effect of CHG against some isolates of S. aureus, S. marcescens and B. cepacia. These results suggest that CHG is useful antiseptic agent or disinfectant for recent clinical isolates of various bacterial pathogens. In addition, the selection of treatment concentration and treatment time for each organism and purpose was important to obtain sufficient bactericidal effect.     

Combined effects of micronomicin and latamoxefi in vitro synergistic activities

In vitro synergistic activities of new aminoglycoside antibiotic micronomicin (MCR, Sagamicin) combined with oxacephem antibiotic latamoxef (LMOX, Siomarin) were investigated. These antibiotics exhibited synergistic activities at FIC index lower than 0.5 against 20.8%, 32.7% and 1.9% of clinical isolates of Pseudomonas aeruginosa (48 strains), Serratia marcescens (52 strains) and Escherichia coli (54 strains), respectively. Partial synergism (0.5 less than FIC index less than 1) was observed in 79.2%, 55.8% and 31.5% of the same microorganisms, too. Each bacteriostatic concentrations of MCR and LMOX showed synergistically bactericidal effects when the drugs were administered at the same time against P. aeruginosa BMH No. 1, S. marcescens F-3283 and E. coli GN2411-5.     

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.     

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.     

Combination antibacterial effects between aztreonam and eight other antibiotics

In vitro interactions between aztreonam (AZT) 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 AZT with 8 other antibiotics were generally additive or indifferent. Synergism was occasionally seen against S. marcescens or P. aeruginosa with AZT plus isepamicin (ISP). Antagonism was observed only between AZT and latamoxef against P. vulgaris. In a phase-contrast microscopic study, synergistic effects between AZT and aspoxicillin or ISP were confirmed against E. coli 177 and P. aeruginosa 15846. AZT in combination with ISP demonstrated a synergy against experimental urinary tract infection in mice caused by P. aeruginosa 15846. We believe that combinations of several antibiotics with AZT should be considered for initial therapy of infections because synergism and additive action were observed and antagonism was rarely found in our study.     

Laboratory and clinical studies of sulbactam/cefoperazone in the pediatric field

The authors have carried out the laboratory and clinical studies of sulbactam/cefoperazone (SBT/CPZ) and obtained the following results. The antibacterial activities of SBT/CPZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, P. aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to SBT/CPZ ranged from 0.39 to 6.25 micrograms/ml, and the peak of distribution was 1.56 micrograms/ml. The peak of susceptibility distribution of K. pneumoniae was 0.20 microgram/ml, and the distribution of E. coli and E. aerogenes ranged from 0.10 to 12.5 micrograms/ml and that of S. marcescens, from 0.2 to 25 micrograms/ml. The growth of 80.8% of P. aeruginosa was inhibited at the concentration of 12.5 micrograms/ml. The distribution of E. cloacae ranged from 0.1 to 50 micrograms/ml. For pharmacokinetic study, SBT/CPZ was given in a single dose of 20 mg/kg by drip infusion for 1 hour in 2 children and 40 mg/kg by drip infusion for 1 hour in 1 children. With drip infusion of SBT/CPZ, the peak serum level were 17.8/43.9 micrograms/ml, 21.8/75.5 micrograms/ml on completion of the infusion, respectively. SBT/CPZ was effective in 14 cases out of 16 cases with clinical effect. No side effect was observed except for eosinophilia in 1 case.     

Antibacterial activities of sisomicin against fresh clinical isolates]

To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.     

Cefpodoxime proxetil, its in vitro antibacterial activity, affinity to bacterial penicillin-binding proteins, and synergy of bactericidal activity with serum complement and mouse-cultured macrophages

Cefpodoxime proxetil (CS-807) is an orally active prodrug of an oxime-type cephem antibiotic. The MIC60 values of cefpodoxime (R-3746) the active form of CS-807, were 3.13, 6.25, 0.05, 0.38, 0.2, 0.1, 3.13, 3.13, 6.25, 6.25, 0.1 and 12.5 micrograms/ml against S. aureus, coagulase-negative staphylococci, S. pneumoniae, E. coli carrying R plasmids, P. vulgaris, P. rettgeri, C. freundii, S. marcescens, A. calcoaceticus, P. cepacia, ampicillin-resistant H. influenzae and B. fragilis, respectively. Its activity was stronger than that of cefaclor and ampicillin. R-3746 manifested little activity against P. aeruginosa, methicillin-resistant S. aureus, and Enterococcus spp. R-3746 showed stronger binding affinity than cefaclor with the PBP2 of S. aureus, PBPs 1a, 1bs, 2 and 3 of E. coli, PBPs 1b, 1c and 3 of P. rettgeri, and the PBP3 of P. aeruginosa than cefaclor. Synergy of the bactericidal effect between R-3746 and serum complement was moderate, although the cells of E. coli NIHJ-JC2 and S. aureus 209P were well engulfed and rapidly digested by mouse-cultured macrophages in the presence of greater than 1/8 MIC of R-3746. Good clinical efficacy can be expected of CS-807 provided its pharmacokinetics prove to be good.     

Clinical and laboratory evaluation of aspoxicillin in the pediatric field

The authors have carried out the clinical and laboratory evaluation of aspoxicillin (ASPC, TA-058). The results were as follows: Antibacterial activities The susceptibility to ASPC was estimated by plate dilution method on 26 strains each of S. aureus, E. coli, Salmonella and P. aeruginosa and 19 strains of S. marcescens isolated from clinical specimens. Minimum inhibitory concentration (MIC) of ASPC against E. coli and Salmonella was about twice active to compare with ampicillin (ABPC), but MIC of ASPC against S. aureus was two-fold less active than that of ABPC. Antimicrobial activities of ASPC against S. marcescens were similar to that of ABPC, while against P. aeruginosa its activities were two-fold higher than that of carbenicillin. Serum levels and urinary excretions When ASPC was administered at 20 mg/kg by one shot intravenous injection, serum concentration was 75 micrograms/ml after 15 minutes and half-life (T 1/2 beta) was 1.65 hours. Urinary excretion within 6 hours after ASPC injection reached to 245.6 mg (26.1%). The reason of this law urinary excretion rate was due to the underlying disease (hydronephrosis). In case of 20 mg/kg administration of ASPC by intravenous drip infusion, peak serum level reached to 88 micrograms/ml at the end of injection, and half-life (T 1/2 beta) was 0.77 hour. Since ASPC degradation by beta-lactamase was proceeded, urinary excretion of this case was not measured by microbiological method. Penicillonic acid and its epimer were detected by HPLC method. It was found that beta-lactamase producing strain was S. marcescens which was isolated by urine culture.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antimicrobial activity of sulbactam/cefoperazone. Comparison with other new cephems

Antimicrobial activities of sulbactam/cefoperazone (SBT/CPZ) against 50 fresh clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were compared to those of CPZ, Cefotiam (CTM), Cefotaxime (CTX) and Latamoxef (LMOX). Minimal inhibitory concentrations (MIC's) of SBT and CPZ mixed in a ratio of 1:1 were determined by the dilution method using Mueller-Hinton agar and expressed by absolute concentrations of CPZ. Antimicrobial activities of SBT/CPZ against principally penicillinase (PCase) producing bacteria, i.e., S. aureus, E. coli, K. pneumoniae, P. mirabilis, were superior to those of CPZ alone. The presence of SBT in concentrations around 0.39 approximately 1.56 micrograms/ml clearly enhanced CPZ's antimicrobial activities against these PCase producing strains. The synergistic antimicrobial effects of SBT in combination with CPZ were less pronounced against principally cephalosporinase (CEPase) producing bacteria, i.e., C. freundii, Enterobacter spp., S. marcescens, P. vulgaris, and P. aeruginosa, and exerted with SBT at concentrations around 3.13 approximately 12.5 micrograms/ml. Comparative antimicrobial activities indicated by MIC80's of tested agents showed that SBT/CPZ had more stable activities against bacteria ranging from Gram-positive to Gram-negative bacteria than CTM, CTX and LMOX. MIC's of SBT/CPZ were higher than 25 micrograms/ml against 8% of S. aureus, 18% of C. freundii, 10% of Enterobacter spp., 26% of S. marcescens, 2% of P. vulgaris, and 18% of P. aeruginosa. These resistant strains against which the addition of SBT showed no synergism, may possess other mechanism of resistance than beta-lactamase production. It is concluded that the presence of CPZ resistant strains is an actual current problem and not an imaginary future problem, and that the number of resistant strains against other new cephems which have different chemical structure from CPZ is increasing. When these present bacteriological environments are considered, the appearance of SBT/CPZ in the clinical practice is timely and meaningful.     

In vitro activity of aztreonam against gram negative bacteria from clinical specimens and its comparison with other commonly used antibiotics

A total of 755 gram negative bacteria isolated from clinical specimens were tested against aztreonam by the disc agar diffusion test. The strains of bacteria used in this study consisted of Escherichia coli (314), Enterobacter aerogenes (30), E. agglomerans (7), E. cloacae, (39), Citrobacter diversus (9), C. freundii (13), Hafnia alvei (3), Acinetobacter calcoaceticus (10), Klebsiella oxytoca (6), K. ozaenae (5), K. pneumoniae (107), Morganella morganii (3), Moraxella sp. (10), Pasteurella multocida (1), Proteus mirabilis (66), P. vulgaris (4), Providencia rettgeri (12), P. stuartii (5), Pseudomonas aeruginosa (85), P. fluorescens (2), P. maltophila (7), Salmonella sp. (1) and Serratia marcescens (17). In vitro activity against aztreonam was compared with amikacin, ampicillin, carbenicillin, cephalosporin, cefoxitin, chloramphenicol, gentamicin, nitrofurantoin, piperacillin, tetracycline, sulfamethoxazole-trimethoprim and tobramycin. Over 99% of E. coli and Enterobacter species were susceptible to aztreonam. All the 118 strains of Klebsiella, 87 strains of Proteus-Providencia and 17 strains of S. marcescens were also susceptible. Aztreonam also showed good activity against P. aeruginosa, inhibiting 90% of the 85 isolates tested.