Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin

The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90 % ofEnterobacteriaceae isolates at 0.25 µg/ml, with the exception ofEnterobacter aerogenes (MIC90 1 µg/ml),Enterobacter cloacae andCitrobacter freundii (MIC90 8 µg/ml). In cefotaxime-and ceftazidime-resistantKlebsiella pneumoniae strains producing SHV-2 and SHV-6 -lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25–32 µg/ml). InEnterobacteriaceae strains hyperproducing chromosomally inducible -lactamases, FK-037 (MIC90 range, 0.25–8 µg/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime againstPseudomonas aeruginosa isolates, with MIC90 values of 16 µg/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressedPseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12–2 µg/ml) and the other -lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 µg/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible,-intermediate and -resistantStreptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 µg/ml, respectively. The corresponding values forStreptococcus viridans isolates were 0.12, 1 and 8 µg/ml, respectively. In bothStreptococcus pneumoniae andStreptococcus viridans isolates, FK-037 displayed activity similar to that of cefotaxime and cefpirome and slightly higher than that of cefepime.     

The Comparative In Vitro Activity of FK-037 (Cefoselis), a New Broad-Spectrum Cephalosporin

FK-037, a new parenteral cephalosporin, was active against clinical isolates of both gram-positive and gram-negative aerobic bacteria. The activity of FK-037 was similar to that of cefpirome and cefepime and generally superior to that of ceftazidime. Methicillin-resistant staphylococci were less susceptible than methicillin-sensitive isolates but most remained within the sensitive range. All streptococci and Enterobacteriaceae were sensitive as were the majority of isolates of Acinetobacter spp. and Pseudomonas aeruginosa. There was resistance amongst other non-fermentative gram-negative bacilli but this was species specific and most pseudomonads were sensitive, with resistance seen in Stenotrophomonas maltophilia, Alcaligenes spp. and Flavobacterium spp.     

Comparative in vitro activity of the new erythromycin derivative dirithromycin against gram-positive bacteria isolated from cancer patients

The in vitro activity of dirithromycin (LY-237216), a new macrolide erythromycin derivative, was compared to that of four other agents (clarithromycin, erythromycin, roxithromycin, clindamycin) against 334 gram-positive isolates obtained from cancer patients. Dirithromycin was similar in potency and antimicrobial spectrum to the other agents tested. It was very active against beta-haemolytic streptococci andStreptococcus pneumoniae, and moderately active against penicillin and methicillin susceptibleStaphylococcus aureus, Bacillus spp.,Listeria monocytogenes andCorynebacterium jeikeium. Erythromycin resistant organisms were also resistant to dirithromycin.     

In vitro antimicrobial activity of cefpirome against ceftazidime-resistant isolates from two multicenter studies

The in vitro activity of cefpirome against ceftazidime-resistant (MIC>16 mg/l) isolates from two multicenter studies was analyzed. The first investigation carried out in the USA, was an in vitro comparison of cefpirome and five third-generation cephalosporins in which more than 6,000 isolates were evaluated, including 97Enterobacteriaceae and 1,509 staphylococci resistant to ceftazidime. The second study was a multicenter international study (>5,000 strains total) in which 160 ceftazidime-resistant gram-negative bacilli and 509 staphylococci from five countries (Australia, France, Germany, Italy and UK) were tested against cefpirome. The results from the US trial indicated that only 0.8 % of enteric bacilli were resistant to cefpirome compared to 4.9 % and 4.7 % resistant to ceftazidime and cefoperazone, respectively. In the international trial, cefpirome was also active against ceftazidime-resistant, class I -lactamase producing enteric bacilli (75 % susceptibility, MIC50 of 4 mg/l) especially againstCitrobacter spp.,Enterobacter spp. andMorganella morganii. Cefpirome was 8- to 64-fold more active than ceftazidime against seven different staphylococcal species. The antimicrobial activity of cefpirome against routine clinical isolates and those organisms resistant to third-generation cephalosporins was highly consistent within a nation (USA) and among various developed countries.     

Comparative in vitro activity of the two new 4-quinolones S-25930 and S-25932 against gram-positive bacteria isolated from cancer patients

The in vitro activity of S-25930 and S-25932, two new quinolone antimicrobial agents, against 306 gram-positive organisms representing 12 bacterial species, was evaluated and compared with the activity of ciprofloxacin, difloxacin, enoxacin, amifloxacin and A-56620. Both agents were active against staphylococcal species (including methicillin-resistant and coagulase-negative isolates),Bacillus spp. and group JK diphtheroids. They were less active against streptococcal species andListeria monocytogenes. Their activity against most isolates was superior to that of amifloxacin, enoxacin and difloxacin and similar to that of ciprofloxacin and A-56620.     

Comparative in vitro activity of A-56268

The comparative in vitro activity of A-56268 was studied using 1,006 clinical isolates including streptococci, enterococci, staphylocci,Neisseria gonorrhoeae, Haemophilus influenzae and anaerobes. A-56268 showed activity comparable to that of erythromycin and was more active than josamycin and roxithromycin against erythromycin-sensitive aerobic and facultatively anaerobic gram-positive cocci. A-56268 was the most active macrolide againstClostridium spp. andNeisseria gonorrhoeae. Josamycin was more active than either A-56268 or erythromycin against the anaerobic gram-positive cocci and theBacteroides fragilis group. Staphylococci moderately resistant or resistant to erythromycin (MIC 3.12–50 mg/l) remained susceptible to josamycin but not the other macrolides.     

In vitro activity of Ro 09-1428 compared to other cephalosporins

The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gramnegative organisms. Ro 09-1428 inhibited group A streptococci at 0.12 µg/ml, and group B, C and G streptococci andStreptococcus pneumoniae at 0.5 µg/ml, whereas forStaphylococcus aureus Ro 09-1428 had MICs of 8–16 µg/ml similar to ceftazidime and E-1040. AgainstPseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at 0.12–2 µg/ml, and inhibited ceftazidime-resistant isolates. The majority ofEscherichia coli, Klebsiella spp.,Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella andShigella were inhibited by 0.5 µg/ml as with the other cephalosporins. For mostCitrobacter freundii andEnterobacter cloacae Ro 09-1428 had higher MICs of 4–16 µg/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci andListeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2,Staphylococcus aureus PC-1,Moraxella catarrhalis Bro-1,Enterobacter P-99,Pseudomonas aeruginosa Sabath-Abraham orKlebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH.     

In vitro activity of the novel cephalosporin GR69153

The in vitro activity of GR69153 was compared to that of ceftazidime, ceftriaxone, imipenem and gentamicin against a total of 702 recent clinical isolates. MICs were determined by a standard agar dilution procedure and two inocula (10⁴ and 10⁸ cfu) were used throughout. GR69153 inhibited 90 % of isolates ofEscherichia coli, Klebsiella pneumonia andProteus mirabilis at 0.25 mg/l and 90 % of isolates ofPseudomonas aeruginosa at 1 mg/l.Citrobacter freundii (MIC90 16 mg/l),Morganella morganii (MIC90 128 mg/l) andEnterobacter spp. (MIC90>128 mg/l) were considerably more resistant to GR69153. GR69153 was four-fold more active than ceftazidime against methicillin-sensitiveStaphylococcus aureus but was inactive against methicillin-resistantStaphylococcus aureus, Enterococcus faecalis andBacteroides fragilis group.     

In vitro activity of PD 117596-2, a broad-spectrum difluoroquinolone

The activity of PD 117596-2, a novel quinolone, was compared to that of other quinolones, ceftazidime, imipenem and gentamicin. PD 117596-2 inhibited mostEnterobacteriaceae at concentrations <0.25 µg/ml, being equal or superior in activity to ciprofloxacin and 2- to 4-fold more active than ofloxacin. It inhibited ceftazidime-resistantEnterobacter spp.,Citrobacter spp. andSerratia marcescens. The MIC90 forPseudomonas aeruginosa, including strains with imipenem MICs of 8 µg/ml and gentamicin MICs > 16 µg/ml, was 0.25 µg/ml. PD 117596-2 was more active than ciprofloxacin againstPseudomonas cepacia andPseudomonas maltophilia, and it inhibitedNeisseria gonorrhoeae andHaemophilus influenzae at < 0.03 µg/ml. PD 117596-2 inhibited staphylococci at 0.5 µg/ml, being 2-fold superior to other quinolones, and with an MIC of 0.25 µg/ml was more active against group A, B, C and G streptococci andStreptococcus pneumoniae. MICs forBacteroides spp. were 2 µg/ml compared to 8–32 µg/ml for other agents. The frequency of spontaneous resistance was low (< 10^–10). Differences in MICs and MBCs were within one dilution, and there was a minimal effect of inoculum size. Although PD 117596-2 was less active at pH 5.5, MICs were < 0.5 µg/ml.     

Comparative in vitro activity of the new oral penem ALP-201 against aerobic and anaerobic bacteria

The in vitro activity of the new penem derivative ALP-201 against 226 aerobic and 350 anaerobic clinical bacterial isolates was determined using agar dilution techniques. For comparison amoxicillin, cefaclor, ceftazidime, doxycycline, erythromycin, imipenem and trimethoprim/sulfamethoxazole were also tested with aerobic bacteria, and cefoxitin, chloramphenicol, clindamycin, imipenem, metronidazole and piperacillin with anaerobic bacteria. ALP-201 was found to be highly active againstEscherichia coli, Klebsiella spp.,Enterobacter spp.,Haemophilus influenzae, Branhamella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, anaerobic cocci,Propionibacterium acnes, Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria.Pseudomonas aeruginosa andClostridium difficile were resistant to ALP-201. When tested against aerobic bacteria using a high inoculum or using the broth dilution technique, the activity of ALP-201 showed little dependence on inoculum size and the bactericidal activity was similar to the inhibitory activity. Further investigations are warranted with ALP-201, which is absorbed from the gastrointestinal tract after oral administration.     

Antimicrobial activity of the new carbapenem biapenem compared to imipenem,meropenem and other broad-spectrum beta-lactam drugs

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90 % of strains (MIC90) ofEnterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of theEnterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs againstPseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (includingBacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated forXanthomonas maltophilia, oxacillin-resistantStaphylococcus spp. andEnterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.     

Comparative in vitro activity of biapenem,a new carbapenem antibiotic

Biapenem is a new carbapenem antibiotic with high stability to human renal dehydropeptidase I. Its in vitro activity was compared with that of imipenem, meropenem, ceftazidime, ceftriaxone, piperacillin and gentamicin against a total of 650 recent clinical isolates. MICs were determined by a standard agar dilution procedure and all isolates were tested at two inocula (10⁴ and 10⁶ cfu). Biapenem inhibited 90 % of isolates ofEscherichia coli, Klebsiella spp.,Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia stuartii, Enterobacter spp.,Citrobacter freundii, Serratia marcescens, Salmonella typhi, Shigella sonnei andYersinia enterocolitica at 2 mg/l and was as active as or two- to four-fold more active than imipenem against all these species, with the exception ofSerratia marcescens, against which imipenem was two-fold more active. Biapenem was two-fold more active than imipenem againstPseudomonas aeruginosa (MIC90 4 mg/l) and had activity similar to that of imipenem against theBacteroides fragilis group (MIC90 0.5 mg/l) but was two-fold less active than imipenem against methicillin-susceptibleStaphylococcus aureus (MIC90 0.06 mg/l) and was, like imipenem, inactive against methicillin-resistantStaphylococcus aureus.     

Antibacterial activity of the investigational oral and parenteral cephalosporin BK-218

BK-218 is a novel cephalosporin with a dual route of administration and spectrum of activity most similar to that of second-generation cephalosporins. BK-218 was active againstStreptococcus pneumoniae, Haemophilus influenzae andMoraxella catarrhalis but strains resistant to penicillins had higher MICs. BK-218 had greater activity (8-fold) than cefuroxime or cefaclor against oxacillin-susceptibleStaphylococcus spp. Moderate BK-218 activity was observed againstNeisseria gonorrhoeae and commonly isolatedEnterobacteriaceae such asEscherichia coli (MIC90, 1 mg/l),Klebsiella spp. (MIC90, 2 mg/l), andProteus mirabilis (MIC90, 2 mg/l). The following organisms were generally BK-218-resistant (MIC90, >16 mg/l):Bacteroides fragilis, Pseudomonas spp.,Acinetobacter spp.,Xanthomonas maltophilia, Citrobacter spp.,Enterobacter spp., indole-positiveProteus, Serratia spp., enterococci and oxacillin-resistant staphylococci.     

In vitro activity of trovafloxacin versus ciprofloxacin against clinical isolates

The comparative in vitro activity of trovafloxacin (CP 99,219), a new fluoroquinolone, was evaluated against 511 clinical isolates. MICs of trovafloxacin were fourfold higher than those of ciprofloxacin for 184Enterobacteriaceae and 110 non-fermentative gram-negative bacilli. However, trovafloxacin was 16-fold more active than ciprofloxacin against 162 gram-positive staphylococci, pneumococci, streptococci, and enterococci, and two- to fourfold more active againstHaemophilus influenzae andMoraxella catarrhalis. MICs of trovafloxacin were correspondingly higher for strains with acquired resistance to ciprofloxacin.     

Comparative in vitro activity of lomefloxacin,a new difluoroquinolone

The in vitro activity of lomefloxacin, a new difluoroquinolone, was compared with that of norfloxacin, ciprofloxacin, gentamicin and ceftazidime against a total of 577 recent clinical isolates. MICs were determined by a standard agar dilution procedure, and two inocula (10⁴ and 10⁶ CFU) were used throughout. Lomefloxacin inhibited most species of theEnterobacteriaceae, Staphylococcus aureus (including methicillin-resistant strains) andHaemophilus influenzae at 1 mg/l.Pseudomonas aeruginosa (MIC 90, 4 mg/l) was somewhat more resistant, andPseudomonas maltophilia (MIC 90, 16 mg/l) and theBacteroides fragilis group (MIC 90, 32 mg/l) were considerably more resistant. Overall, lomefloxacin was as active as norfloxacin, but was two- to eightfold less active than ciprofloxacin against most species tested.     

Utility of Serial Rectal Swab Cultures for Detection of Ceftazidime- and Imipenem-Resistant Gram-Negative Bacilli from Patients in the Intensive Care Unit

 Forty-four patients receiving intensive care were studied prospectively to assess the utility of serial rectal swab cultures and clinical correlates of resistance for Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., Morganella morganii, and Serratia marcescens strains resistant to ceftazidime or imipenem. Strains of Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., or Morganella morganii were found in 26 of 44 (59%) patients: 17 (65%) in clinical sites (11 with concomitant rectal isolates) and nine (35%) in a rectal site only. Of 49 total isolates, 13 (26.5%) were resistant: 10 (20.4%) to ceftazidime and three (6.1%) to imipenem. Surveillance rectal swabs from 27 patients without a clinical isolate identified two patients with resistant organisms (15% of all resistant isolates). The majority of resistance to ceftazidime or imipenem among Pseudomonas or Enterobacter can be detected by the use of clinical specimens alone.     

In vitro activity of cefcanel versus other oral cephalosporins

Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against grampositive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptibleStaphylococcus aureus andStaphylococcus epidermidis, MIC90 1 µg/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC 16 µg/ml.Streptococcus pyogenes andStreptococcus pneumoniae were inhibited by 0.015–1 µg/ml, concentrations comparable to other cephalosporins.Clostridium spp. were inhibited by 0.25 µg/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were >64 µg/ml forBacteroides spp. The MIC90 forMoraxella catarrhalis was 1 µg/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime.Escherichia coli andKlebsiella pneumoniae which were high beta-lactamase producers were resistant, MICs >64 µg/ml, and 50 % ofEnterobacter cloacae andCitrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases.Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of 16 µg/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibitedHaemophilus influenzae carrying TEM-1.     

In vitro activity of trospectomycin (U-63366F), a novel spectinomycin analog,against gram-positive isolates from cancer patients

The in vitro activity of trospectomycin was compared to that of amikacin, cephalothin and vancomycin against gram-positive organisms, mostly isolated from cancer patients. Trospectomycin was considerably more active than amikacin against most isolates tested, particularly species ofStaphylococcus andStreptococcus. Overall, vancomycin was the most active agent tested.     

In vitro activity of cefpodoxime against bacterial isolates obtained from patients with cancer

The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Cefpodoxime inhibited the majority ofStreptococcus spp.,Haemophilus influenzae andProteus mirabilis at a concentration of 0.12 µg/ml. It was also active againstCitrobacter diversus, Escherichia coli, Klebsiella spp.,Proteus vulgaris, Serratia marcescens and methicillin-susceptibleStaphylococcus aureus isolates. Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients.     

In vitro activity of FCE 22101, imipenem,and ceftazidime against over 6,000 bacterial isolates and MIC quality control limits of FCE 22101

Six geographically separate laboratories within the USA tested 6,198 bacterial isolates against FCE 22101 (a penem), imipenem (a carbapenem) and ceftazidime (a third-generation cephalosporin). Ninety-three percent of 2,749Enterobacteriaceae were inhibited by FCE 22101, while 95 % were susceptible to ceftazidime and 99 % were susceptible to imipenem. FCE 22101 had little activity againstPseudomonas spp. but was active against most gram-positive pathogens, including enterococci. FCE 22101 MICs for standard quality control strains were defined as 0.5–2.0µg/ml forEscherichia coli ATCC 25922, 2–8µg/ml forEnterococcus faecalis ATCC 29212 and 0.06–0.25µg/ml forStaphylococcus aureus ATCC 29213.