Ceftezole, a new cephalosporin C derivative II. Distribution and excretion in parenteral administration

The distribution of ceftezole in blood and tissues and its excretion after intramuscular or intravenous administration of single doses of 10 and 20 mg/kg were compared with those of cefazolin, cephaloridine and cephalothin. Blood levels of ceftezole in rats and rabbits were lower than those of cefazolin, and higher than those of cephaloridine and cephalothin. Retention time of ceftezole in the blood was somewhat shorter than that of cefazolin. However, blood levels of ceftezole in dogs were nearly the same as those of cefazolin and cephaloridine. The rate of urinary excretion of ceftezole in 24-hour urine after administration in rats and rabbits was found to be higher than those of the other antibiotics tested. In dogs, however, the rate of urinary excretion of ceftezole was nearly the same as that of cefazolin and higher than those of cephaloridine and cephalothin. The biliary excretion of ceftezole in rats and dogs was much higher than those of cephaloridine and cephalothin, but lower than that of cefazolin. Tissue distribution of ceftezole in rats was compared with that of the other antibiotics by intramuscular and intravenous administration. The initial level of ceftezole in the kidneys was found to be substantially higher than those of the other antibiotics. The initial level of ceftezole in the liver and lungs was also slightly higher than those of the other drugs when administered intramuscularly. Tissue levels of ceftezole were somewhat lower than those of cefazolin in rabbits after intravenous administration. Ceftezole attained a higher maximum level in rat lymph by intramuscular administration than the other antibiotics tested. The maximum concentration of ceftezole present in the exudate in the rat inflammatory pouch was higher than that of cefazolin. In rabbits with cerebrospinal meningitis induced by infection of Streptococcus pyogenes, the level of ceftezole in the cerebrospinal fluid was several times higher than that in normal rabbits. The serum level and urinary excretion of ceftezole was examined in 6 healthy male volunteers after intramuscular administration of a single dose of 500 mg. Ceftezole attained a mean maximum serum level of 22.9 mug/ml 30 minutes after administration and disappeared from the blood in about 6 hours. It was excreted rapidly in the urine. The concentration in 1-hour urine was the highest (mean level: 2,667 mug/ml) and the total excretion rate was 92.6%. No metabolites with antimicrobial activity were observed in the urine. No changes in the pattern of plasma level and urinary excretion and no accumulation in the tissues were observed after repeated intramuscular administration of 20 mg/kg of ceftezole in rabbits, 26 times, for 14 days.     

Activity of cefamandole and other cephalosporins against aerobic and anaerobic bacteria

The activity of cefamandole was comparable to that of cephalothin, cefazolin, and cephaloridine against Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. In contrast, cefamandole was considerably more active than cephalothin, cefazolin, or cephaloridine against gram-negative facultative bacilli, including Haemophilus influenzae, the most striking disparities being noted with indole-positive Proteus and Enterobacter. Bacteroides fragilis was more susceptible to cefoxitin than to cefamandole or cefazolin (median minimal inhibitory concentration, approximately 8, 32, and 32 mug/ml, respectively); cephalothin exhibited still less activity against this species. The majority of other anaerobes were inhibited by relatively low concentrations of all four cephalosporins. The results indicate a potentially valuable role for cefamandole against facultative gram-negative bacilli, including H. influenzae, but no exceptional activity against anaerobes.     

BL-S786, a new parenteral cephalosporin. II. In vitro antimicrobial activity comparison with six related cephalosporins

BL-S786 was compared by in vitro studies with 6 other parenteral cephalosporins (cefamandole, cefazolin, cefoxitin, cephaloridine, cephalothin and cephradine). The following parameters were assessed: Comparative MICs against a wide variety of bacterial isolates, MIC/MBC comparisons and the effect of inoculum size on the MIC. BL-S786 showed the greatest antimicrobial activity against K. pneumoniae, C. diversus and Salmonella species; was equal to cefamandole against E. coli, E. agglomerans and P. mirabilis; and was second to cefamandole against Shigella, E. tarda, C. freundii, E. cloacae, E. aerogenes and the pathogenic Neisseriae. Essentially no activity against Serratia and Pseudomonas species was observed. Compared to the other cephalosporins tested BL-S786 showed poor activity against staphylococci and streptococci. For most species tested, the MBC of the various cephalosporins was the same or within one dilution of their respective MICs. However, for Enterobacter and indole-positive Proteus species, the MBC of BL-S786 and cefamandole was usually larger than or equal to 8-fold higher than the MICs. Cefoxitin, on the other hand, showed little MIC/MBC variations against indole-positive Proteus species. Inoculum size had only a small effect on the MICs against most gram-negative species--in some instances greater than 64-fold increases in MIC resulted by increasing inoculum size from 10(5) to 10(7) organisms per ml.     

Comparison of the antibacterial activity of nine cephalosporins against Enterobacteriaceae and nonfermentative gram-negative bacilli

The in vitro antibacterial activity of nine cephalosporins (cephalothin, cephaloridine, cephalexin, cefazolin, cefamandole, cefuroxime, cefatrizine, cefoxitin, and cefazaflur) was determined against 344 strains of Enterobacteriaceae and 99 nonfermentative gram-negative bacilli. Cefamandole, cefazaflur, and cefuroxime were the most active cephalosporins against the Enterobacteriaceae (with the exception of Serratia marcescens). However, cefoxitin was the only cephalosporin that inhibited all 30 S. marcescens strains in a concentration of 16 mug/ml and was by far the most active compound against selected cephalothin-resistant strains of Escherichia coli, Klebsiella, and Proteus mirabilis. Acinetobacter spp. were inhibited best by cefuroxime, but none of the cephalosporins had appreciable activity against the Pseudomonas spp.     

In vitro comparative activity (E test) of sparfloxacin and other 8 antimicrobial agents against bacteria isolated from patients with respiratory infections acquired in the community

Sparfloxacin is a new antimicrobial that, while maintaining a good activity against gram negative bacilli, has a better in vitro activity against gram positive bacteria such as S pneumoniae, intracellular pathogens and anaerobic bacteria. The aim of this work was to study the in vitro activity of sparfloxacin against bacteria isolated from patients with community acquired respiratory infections between October 1994 and January 1995. Using the E-test technique, we studied the susceptibility to sparfloxacin, ciprofloxacin, ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefotaxime, erythromycin, methicillin and nalidixic acid of 50 strains of S pneumoniae, 50 strains of H. influenzae, 50 strains of S aureus and 50 strains of S pyogenes. Sparfloxacin was active against 100% of S pneumoniae, H influenzae and S pyogenes strains. Twenty two percent of S aureus strains were resistant and the MIC 90 was 12 micrograms/ml. Sparfloxacin showed the best in vitro activity against H influenzae and S aureus, a similar activity with ampicillin and cefotaxime against S pneumoniae and a similar activity with ampicillin but superior to all other studied antimicrobial against S pyogenes. It is concluded that sparfloxacin is a good antimicrobial for bacteria isolated from patients with respiratory infections.     

Comparison of the in vitro activity of several cephalosporin antibiotics against gram-negative and gram-positive bacteria resistant to cephaloridine

The in vitro activity of each of two oral [cefatrizine (BL-S640), cephalexin] and three parenteral (cefamandole, cefazolin, cephapirin) cephalosporin antibiotics was compared with that of cephalothin against 168 clinical isolates of gram-negative and gram-positive bacteria selected as resistant to 20 mug of cephaloridine per ml on the basis of agar dilution susceptibility test data. Each of the five other cephalosporins inhibited a greater percentage of gram-negative bacillary isolates than did cephalothin or cephaloridine, with minimal inhibitory concentration values ranging 2- to 50-fold lower. Significant differences between minimal inhibitory concentrations of the compounds tested were also observed in tests against strains of Streptococcus faecalis and of methicillin-resistant Staphylococcus aureus. Potential advantages of including more than a single cephalosporin antibiotic in the panel of antibiotics used for routine susceptibility testing, suggested by these observations, are discussed.     

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). I. Susceptibility distribution]

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 704 bacterial strains isolated from patients with urinary tract infections (UTIs) in 11 hospitals during the period of June 1995 to May 1996. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.2% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with UTIs. The MIC90S of them were 1 microgram/ml. Vancomycin (VCM) and piperacillin (PIPC) were also active with the MIC90S of 2 micrograms/ml and 4 micrograms/ml, respectively. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with UTIs. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The other except minocycline (MINO) had very low activities with the MIC90S of 64 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and MINO showed the strongest activities against S. epidermidis isolated from patients with UTIs. The MIC90S of them were 0.25 microgram/ml. VCM was also active with the MIC90 of 1 microgram/ml. The MIC90S of cephems ranged from 2 micrograms/ml to 16 micrograms/ml in 1994, but they ranged from 8 micrograms/ml to 128 micrograms/ml in 1995. These results indicated that some resistances existed among S. epidermidis to cephems. 4. Streptococcus agalactiae All drugs except gentamicin (GM) were active against S. agalactiae. ABPC, cefmenoxime (CMX), IPM, erythromycin (EM), clindamycin (CLDM) and clarithromycin (CAM) showed the highest activities. The MICs for all strains were lower than 0.125 microgram/ml. The MIC90S of the others were 2 micrograms/ml or below. 5. Citrobacter freundii IPM showed the highest activity against C. freundii isolated from patients UTIs. Its MIC90 was 1 microgram/ml. GM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR), cefozopran (CZOP) and amikacin (AMK) were also active with the MIC90S of 4 micrograms/ml. Penicillins and cephems except CMX, CPR and CZOP showed low activities with MIC90S of 256 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. MINO and tosufloxacin (TFLX) were also active with the MIC90S of 8 micrograms/ml. Penicillins and cephems except CPR and CZOP showed lower activities with the MIC90S of 256 micrograms/ml or above. 7. Escherichia coli. Most of the antimicrobial agents were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MICs for all strains were equal to or lower than 0.5 microgram/ml. CMX and TFLX were also active with the MIC90S of 0.125 microgram/ml or below. Penicillins were slightly active with MIC90S of 128 micrograms/ml or above. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with MIC90S of 2 micrograms/ml or below. Carumonam (CRMN) had the strongest activity against K. pneumoniae, the MICs for all strains were equal to or lower than 0.125 microgram/ml. Comparing with the result of 1994, the sensitivities of K. pneumoniae against all drugs had obviously changed into a better state. For example, the MIC90S of cephems ranged from 0.25 microgram/ml to 16 micrograms/ml in 1994, but they were all lower than 2 micrograms/ml in 1995. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, ceftazidime (CAZ), cefixime (CFIX), and CRMN showed the highest activities against P. mirabilis isolated from patients with UTIs. MICs of CRMN for all     

In vitro antimicrobial activity of fluoroquinolones against clinical isolates obtained in 1989 and 1990

The in vitro activity of nine fluoroquinolones, enoxacin, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, fleroxacin and levofloxacin, and two earlier quinolones, nalidixic acid and pipemidic acid, against 1,346 bacterial strains isolated clinically between 1989 and 1990, was evaluated by agar dilution method. The bacteria studied were Staphylococcus aureus (including methicillin-susceptible and -resistant strains), Staphylococcus epidermidis, Enterococcus species (including high-level gentamicin-resistant strains), Escherichia coli, Salmonella species, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Citrobacter spp., Pseudomonas aeruginosa, Pseudomonas cepacia, Acinetobacter baumannii, and Bacteroides fragilis. In contrast to the moderate to poor activity of two earlier quinolones, the fluoroquinolones acted well against most Enterobacteriaceae and A. baumannii. The minimum inhibitory concentrations for 90% of the drug strains (MIC90s) were < 1 microgram/mL against most tested species. Ciprofloxacin, tosufloxacin, sparfloxacin, and levofloxacin were more effective against multi-drug-resistant nosocomial pathogens. All fluoroquinolones assayed were very active against methicillin-susceptible S. aureus, with MIC90s < or = 1 microgram/mL. For methicillin-resistant strains, on the other hand, the MIC90s were > or = 4 micrograms/mL. There was no significant difference in fluoroquinolone susceptibility between methicillin-susceptible and -resistant S. epidermidis. Sparfloxacin, tosufloxacin, ciprofloxacin and levofloxacin were more active against enterococci. Most fluoroquinolones were relatively inactive against B. fragilis, with the exception of tosufloxacin, sparfloxacin and levofloxacin. The MIC90s of most quinolones assayed against K. pneumoniae, Citrobacter spp., E. cloacae, S. aureus and S. epidermidis were at least four-fold higher in our study. Therefore, it is important for physicians to use fluoroquinolones carefully so as to prevent or delay the emergence of resistant strains.     

An inexpensive infrared growth sensor array for detection of bacterial antibiotic susceptibility

An inexpensive infrared sensor was constructed and used for the rapid testing of bacterial antibiotic susceptibility by detection of changes in absorbance at 950 nm. By comparing cultures of clinical isolates together with control strains (Escherichia coli NCTC 10418, Staphylococcus aureus NCTC 6571 or Pseudomonas aeruginosa NCTC 10662) after addition of an antibiotic, results on susceptibility were obtained within 3-5 h from the original plate culture. Representative strains of E. coli, P. aeruginosa, and S. aureus were tested successfully against ampicillin, penicillin, gentamicin or ciprofloxacin.     

Joining forces to improve point-of-care testing

Possible increasing of resistance to difuracil or N-(5-nitrofurfuryliden)-5-nitrofuran-2-(N'-acetyl) carboxamidohydrazon (PAP-49) in Staphylococcus sp., Streptococcus sp. and Escherichia coli was studied and the level of the resistance increasing was determined by the method of 30-fold passage of the cultures in subbacteriostatic concentrations of the drug. It was shown in vitro that the increase of the resistance to the new nitrofuran was insignificant. The most intensive adaptation was observed during the first 10 passages. During the following 10-15 passages the susceptibility level remained unchanged (E.coli) or was even somewhat higher (S. aureus and Streptococcus sp.). After that a new increase of the resistance was observed. The most marked changes in the susceptibility were detected in Streptococcus sp. and the least marked in Staphylococcus sp. and E.coli. Combinations of difuracil in subbacteriostatic concentrations with various antibacterial drugs provided both additive and synergistic effects with respect to S.epidermidis, S. pneumonase, E.coli and P.mirabilis. The most active combinations were those of difuracil with aminoglycoside antibiotics, penicillins or chloramphenicol.     

Is resistance to antibiotics changing? Development of resistance of Enterobactericeae from specimens 1977-1980

The results of sensitivity testing from the last 4 years of the enterobacteria isolates have been evaluated for ampicillin, cephalothin, gentamicin, and trimethoprim-sulfamethoxazole. There was a remarkable decrease of cephalothin resistant E. coli, proteus mirabilis, and klebsiella strains. The number of strains resistant to ampicillin was only decreased in the case of proteins mirabilis. The resistance frequency to gentamicin was unchanged. In contrast, an increasing number of resistant strains of E. coli and proteins mirabilis was observed with regard to trimethoprim-sulfamethoxazole.     

Bactericidal activity of trovafloxacin (CP-99,219)

Trovafloxacin was found to be a typical quinolone producing a biphasic dose response against Escherichia coli, Staphylococcus aureus or Streptococcus pneumoniae. A reduced rate of kill was seen against Enterococcus faecalis, which is also typical of the quinolones. However, the bactericidal activity of trovafloxacin against S. aureus and S. pneumoniae was greater than most other quinolones previously tested. The enhanced bactericidal activity of trovafloxacin against S. aureus may be explained by the possession of a very strong bactericidal mechanism B. Trovafloxacin may prove to be a quinolone of choice against S. aureus infections.     

Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases

We determined the inhibitory activities of gatifloxacin against Staphylococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase II and compared them with those of several quinolones. The inhibitory activities of quinolones against these type II topoisomerases significantly correlated with their antibacterial activities or cytotoxicities (correlation coefficient [r] = 0.926 for S. aureus, r = 0.972 for E. coli, and r = 0.648 for HeLa cells). Gatifloxacin possessed potent inhibitory activities against bacterial type II topoisomerases (50% inhibitory concentration [IC50] = 13.8 microg/ml for S. aureus topoisomerase IV; IC50 = 0.109 microg/ml for E. coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC50 = 265 microg/ml) among the quinolones tested. There was also a significant correlation between the inhibitory activities of quinolones against S. aureus topoisomerase IV and those against E. coli DNA gyrase (r = 0.969). However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme. The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S. aureus topoisomerase IV and that for E. coli DNA gyrase. These ratios were higher than those for other quinolones, indicating that gatifloxacin possesses a higher selectivity for bacterial type II topoisomerases.     

Antimicrobial potentiality of a new beta-lactum antibiotic fosfomycin

Antimicrobial action of penicillin and some of its derivatives including fosfomycin was studied with respect to 225 strains of Gram-positive and Gram negative bacteria. Fosfomycin was found to possess somewhat less activity against Staphylococcus aureus compared with other penicillins; however, it showed powerful activity towards Escherichia coli, Klebsiella spp. and Proteus mirabilis.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1993). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 657 bacterial strains isolated from patients with urinary tract infections in 10 hospitals during the period of June 1993 to May 1994. Of the above total bacterial isolates, Gram-positive bacteria accounted for 28.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 71.7% and most of them were Escherichia coli. 1. Enterococcus faecalis Ampicillin (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest activities against E. faecalis isolated from patients with urinary tract infections. The MIC90s of them were 2 micrograms/ml. Piperacillin (PIPC) was also active with the MIC90 of 8 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 3. Staphylococcus epidermidis VCM showed the strongest activity against S. epidermidis isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml. ABK was also active with the MIC90 of 4 micrograms/ml. The others except ABPC were not so active with the MIC90s of 32 micrograms/ml or above. 4. Streptococcus agalactiae Most of the agents were active against S. agalactiae isolated from patients with urinary tract infections. Penicillins, cephems, erythromycin (EM), and clindamycin (CLDM) showed the highest activities. The MIC90s of them were 0.25 microgram/ml or below. Amikacin (AMK) and minocycline (MINO) showed somewhat low activities with the MIC90s of 16 micrograms/ml. 5. Citrobacter freundii IPM showed the highest activities against C. freundii isolated from patients with urinary tract infections. Its MIC90 was 2 micrograms/ml. Cefozopran (CZOP) and gentamicin (GM) were also active with the MIC90s of 8 micrograms/ml. Penicillins and cephems generally were not so active. 6. Enterobacter cloacae IPM and GM showed the highest activities against E. cloacae. The MIC90s of them were 1 microgram/ml. CZOP and tosufloxacin (TFLX) were also active with the MIC90s of 8 micrograms/ml. Penicillins and cephems except CZOP showed lower activities with the MIC90s of 64 micrograms/ml or above. 7. Escherichia coli Most of antimicrobial agents were active against E. coli. Flomoxef (FMOX), CZOP, IPM, CPFX and TFLX showed the highest activities against E. coli. The MIC90s of them were 0.125 microgram/ml or below. Cefmenoxime (CMX), ceftazidime (CAZ), cefuzonam (CZON), latamoxef (LMOX), carumonam (CRMN), norfloxacin (NFLX) and ofloxacin (OFLX) were also active with the MIC90s of 0.25 microgram/ml. Penicillins and MINO were not so active with the MIC90s of 32 micrograms/ml or above. 8. Klebsiella pneumoniae CZOP, IPM and CRMN showed the highest activities against K. pneumoniae. The MIC90s of them were 0.125 microgram/ml or below. CAZ, CZON, CFIX, CPFX and TFLX were also active the MIC90s of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128 micrograms/ml or above. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, CAZ, CZON, LMOX, CFIX, CRMN and CPFX showed the highest activities against P. mirabilis isolated from patients with urinary tract infections. The MIC90s of them were 0.125 microgram/ml or below. MINO was not so active with the MIC90 of 256 micrograms/ml or above. 10. Pseudomonas aeruginosa Most of the agents were not so active against P. aeruginosa. IPM showed MIC90 of 8 micrograms/ml.     

Multicenter study of isolated micro-organisms resistant to antimicrobials in 10 Portuguese hospitals in 1994

In 1994, Microbiology Laboratories of ten Portuguese hospitals analysed isolated microorganisms found in blood and urine samples and studied antimicrobial susceptibilities of the most frequent bacterial pathogens. From 63780 blood samples, the most frequent were Staphylococcus spp. and from 69189 urine samples significant numbers of Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa and Candida spp. were isolated. Escherichia coli strains (c.7000) revealed a low percentage of resistance to antibiotics with the exceptions of ampicillin (48%) and co-trimoxazol (25%). Klebsiella pneumoniae isolates (c.2000) revealed important resistance to ampicillin (98%), cephalotin (31%), co-trimoxazol (38%) and gentamicin (28%), while values for 3rd generation cephalosporins varied among hospitals, with several strains showing phenotype of extended-spectrum beta-lactamase. A great variation in resistance values of P. aeruginosa (c.4000) was found in relation to the antibiotics as well as to the hospitals. Resistance to methicillin in S. aureus (c.6000) was high, reaching an average of 47%, and it was even higher with S. epidermidis (c.3000) and S. haemolyticus (c.650). Only vancomycin was always active against these strains. In E. faecalis (c.2500) resistance was of 2% to ampicillin, 35% to gentamicin, 45% to streptomycin and 1% to vancomycin. E. faecium isolates (c.300) showed the most worrying results with 70% resistance to ampicillin, 42% to gentamicin, 59% to streptomycin and 9% (30 strains isolated in 5 hospitals) to vancomycin. Vancomycin resistant strains were also resistant to all other antibiotics.     

In vitro antimicrobial activities of lactoferrin, its concomitant use with cefpodoxime proxetil and clinical effect of cefpodoxime proxetil

As one of the biodefense mechanisms, lactoferrin (LFN) in the secreta of female genital organ may be an interesting biological material in view of its antimicrobial activity. In the present study, we investigated antimicrobial activities of LFN and its combination with cefpodoxime proxetil (CPDX-PR), we also as evaluated clinical effect of CPDX-PR. The following results were obtained. 1. Antimicrobial activities of LFN were tested against 15 strains of 10 species of bacteria, and potent activities against Staphylococcus aureus 209P, Escherichia coli, Klebsiella pneumoniae and Proteus spp. were found. 2. In a concomitant use of LFN with CPDX-PR (a checkerboard method), synergistic actions were observed against S. aureus 209P, E. coli STf, K. pneumoniae 602 and Pseudomonas aeruginosa 1046, and additive actions against E. coli NIHJ and Providencia rettgeri 1603. In 3 strains, the MICs of CPDX-PR in the presence of LFN were reduced to < 1/64. 3. In the evaluation of clinical effect of CPDX-PR, efficacy rates were 53/57 (92.9%) in a patient group with infections. The incidence of adverse reaction was 0/57.     

Comparative antimicrobial activity of RP 59,500 (quinupristin-dalfopristin), the first semisynthetic injectable streptgramin, against gram-positive cocci and other recent clinical pathogens

RP 59,500 (Quinupristin-Dalfopristin) is the first semisynthetic injectable streptogramin antimicrobial agent, which is a combination of quinupristin and dalfopristin in a 30:70 ratio. The components of RP 59,500 act synergically to provide bactericidal activity through action at different sites on bacterial ribosomes. In the present study, the antimicrobial activity of RP 59,500 was compared with those of four macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin). Susceptibility testing was carried out by microdilution method on 303 strains of 10 species, especially antibiotic-resistant Gram-positive cocci. RP 59,500 was active against a wide range of Gram-positive cocci including methicillin-resistant Staphylococci and penicillin-resistant Streptococcus pneumoniae. The MICs90 of RP 59,500 against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis were both 0.25 microgram/ml, although those of four macrolides were higher than 32 micrograms/ml. The MICs90 of RP 59,500 against penicillin-sensitive, -intermediate and -resistant S. pneumoniae were all 0.5 microgram/ml, although those of four macrolides against penicillin-resistant S. pneumoniae were higher than 32 micrograms/ml. RP 59,500 also exhibited equivalent activities to the four macrolides against strains of Streptococcus pyogenes. Streptococcus agalactiae and Moraxella catarrhalis. RP 59,500 exhibited the highest activities against Enterococcus faecalis, Enterococcus faecium and Enterococcus avium strains which are intrinsically resistant to most antimicrobial agents. No cross-resistance was observed between RP 59,500 and the four macrolides, which will merit attention in future clinical trials of the agent. The effect of human serum on the MIC of RP 59,500 was studied with strains of S. aureus, S. epidermidis and E. faecalis. The presence of 20% (V/V) serum had little or no effect on the MIC, although 50% (V/V) serum increased MICs by 4-8 folds. Laboratory-induced resistance to RP 59,500 occurred in a stepwise fashion in broth cultures of S. aureus, S. epidermidis and E. facalis strains and the induction rate was slow and no more than four fold increases were observed. Population analysis was performed on RP 59,500 and the reference macrolides against S. aureus ATCC 25,923 strain. Although low frequencies (less than 0.01%) of resistant sub-population were detected with EM, CAM, AZM and RXM, no RP 59,500-resistant sub-population was detected in this study.     

Douglas-fir root-associated microorganisms with inhibitory activity towards fungal plant pathogens and human bacterial pathogens

A microbial culture collection composed of 1820 bacterial strains, including 298 actinomycete strains, was established from the roots of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings harvested from conifer nurseries and forest sites. Two hundred and thirty-four strains inhibited the growth of Fusarium, Cylindrocarpon, and (or) Pythium spp. in in vitro assays. A significantly greater proportion of bacterial strains from actinomycete genera exhibited antifungal properties compared with bacterial strains from nonactinomycete genera. Eighty-nine percent of identified inhibitory strains were Streptomyces, Streptoverticillium, Bacillus, Pseudomonas, or Burkholderia species. The actinomycete species were isolated almost exclusively from forest seedlings. Recovery of inhibitory strains representing 29 microbial species was enhanced using a variety of methods to isolate microorganisms from the roots of seedlings from nursery and forest sites. Bacterial strains (including actinomycete strains) with antifungal activity were tested for in vitro growth inhibition of six clinical human bacterial pathogens (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa). Forty-eight percent of the tested strains inhibited one or more human pathogens, Inhibitory activity towards fungal and bacterial pathogens was strain specific, not species specific, and many inhibitory strains exhibited broad-spectrum activity. Strains with antifungal activity against several conifer root pathogens were also more likely to inhibit multiple species of clinical bacterial pathogens.