Comparative in vitro antibacterial activity of the new carbapenem meropenem (SM-7338)

The in vitro antimicrobial activity of the new carbapenem meropenem (SM-7338) was determined by an agar dilution method in comparison with imipenem, ticarcillin/calvulanic acid, ceftazidime and the fourth-generation cephalosporin cefepime (BMY 28142). Meropenem showed superior activity againstEnterobacteriaceae (MIC900.06 mg/l) and against non-fermentative gram-negative rods, with the exception ofXanthomonas maltophilia. Meropenem had excellent activity against beta-lactamase-producingHaemophilus influenzae andNeisseria gonorrhoeae, and against theBacteroides fragilis group. Imipenem was slightly more active then meropenem against gram-positive cocci especiallyEnterococcus faecalis.     

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.     

Inoculum effect and bactericidal activity of cefditoren and other antibiotics againstStreptococcus pneumoniae,Haemophilus influenzae,andNeisseria meningitidis

The inoculum effect on minimum inhibitory and minimum bactericidal concentrations of cefditoren, benzylpenicillin, ampicillin, cefotaxime, ceftriaxone, and meropenem against six clinical isolates each ofStreptococcus pneumoniae, Haemophilus influenzae, andNeisseria meningitidis was studied using inocula of approximately 10⁴ to 10⁵ and 10⁷ to 10⁸ cfu/ml. Vancomycin was also studied againstStreptococcus pneumoniae. The inoculum effect was observed only with benzylpenicillin and ampicillin against five of six strains ofHaemophilus influenzae. All antibiotics tested were bactericidal.     

In vitro activity of florphenicol

Florphenicol was active at a lower concentration than chloramphenicol against over half of 234 recent clinical bacterial isolates. The majority (98 %) of the isolates were inhibited by florphenicol at a concentration of 8 mg/l or less. Florphenicol was particularly effective against chloramphenicol resistant strains ofHaemophilus influenzae, Klebsiella aerogenes andBacteroides spp. Florphenicol was bacteristatic for salmonellae andEscherichia coli but bactericidal forHaemophilus influenzae. Florphenicol was slightly more active than chloramphenicol againstChlamydia trachomatis, Mycoplasma hominis andMycoplasma pneumoniae but less active againstUreaplasma urealyticum.     

In vitro activity of tosufloxacin (A-60969) and clarithromycin (A-56268, TE-031) against resistantHaemophilus influenzae,Streptococcus pneumoniae andBranhamella catarrhalis isolates

The activity of tosufloxacin (A-60969), a new oral quinolone, and clarithromycin (A-56268, TE-031), a new oral macrolide, was compared in vitro to that of other oral quinolones and beta-lactam antimicrobial agents against clinical isolates of ampicillin and/or chloramphenicol resistantHaemophilus influenzae, penicillin resistantStreptococcus pneumoniae and beta-lactamase producingBranhamella catarrhalis. Results were compared to those for sensitive isolates. Tosufloxacin was the most active compound againstHaemophilus influenzae and was more active than ciprofloxacin or ofloxacin against all strains ofStreptococcus pneumoniae. Tosufloxacin was also more active than any of the beta-lactam drugs tested against penicillin resistant or relatively penicillin resistant isolates. Clarithromycin was the most active compound tested against both penicillin sensitive and penicillin resistantStreptococcus pneumoniae, and was as active as ciprofloxacin againstBranhamella catarrhalis. In view of the favourable in vitro activity against common bacterial respiratory pathogens, tosufloxacin should be considered for clinical trials in adults with respiratory tract infections, while clarithromycin might be useful in treatment of infection with these organisms in all age groups.     

Spectrum of activity of azithromycin

In recent years, a number of newer macrolides have been developed. One such antibiotic is azithromycin, which has a 15-membered ring structure and is classed as an azalide. The limitations of erythromycin and the discovery of pathogenic bacteria such asCampylobacter, Legionella andChlamydia species provide incentives to study the usefulness of newer antibiotics of this class. Azithromycin has good activity against staphylococci, streptococci,Moraxella catarrhalis and other rapidly growing pyogenic bacteria. The good activity of azithromycin againstHaemophilus influenzae (MIC90 0.5 mg/l) is particularly important as erythromycin has only marginal activity against this organism. Azithromycin has also been shown to be more potent than the macrolides againstEnterobacteriaceae. In common with erythromycin and tetracycline, the agent has good activity againstLegionella, Chlamydia andCampylobacter. Opportunistic infections involvingToxoplasma gondii andPneumocystis carinii are an increasing problem and azithromycin is particularly interesting in view of its activity against these difficult-to-treat organisms.     

Antibacterial activity of the new carbapenem meropenem (SM-7338) against clinical isolates

The in vitro antibacterial activity of the new carbapenem antibiotic meropenem (SM-7338) against 567 clinical isolates was evaluated. SM-7338 exhibited activity against a broad spectrum of organisms, including aerobes and anaerobes, and was superior to the other beta-lactam drugs tested (piperacillin, cefotaxime, ceftazidime, ceftriaxone, cefoxitin). SM-7338 was more active than imipenem, gentamicin and amikacin againstEnterobacter cloacae andPseudomonas aeruginosa. SM-7338 was less potent than imipenem against staphylococci and enterococci, but the activity of the two antibiotics against anaerobes was similar. SM-7338 and imipenem showed a high bactericidal activity at a concentration of 2–4 x MIC.     

In vitro activity of RO 15-8074 and RO 19-5247

The in vitro activity of RO 15-8074 (cefetamet) and RO 19-5247, new oral cephalosporins, was compared with that of amoxicillin, cephalexin, cefaclor, cefuroxime and erythromycin against 292 clinical isolates using the agar dilution method. Both RO 15-8074 and RO 19-5247 were very active against Proteus mirabilis, Neisseria gonorrhoeae, Haemophilus influenzae and Streptococcus pyogenes,but less active against Staphylococcus saprophyticus and Enterobacter cloacae.RO 19-5247 was more active than RO 15-8074 against Haemophilus influenzae and Streptococcus viridans.     

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.     

Susceptibility of European respiratory tract isolates to trovafloxacin, ciprofloxacin, clarithromycin, azithromycin and ampicillin

As part of the Artemis project, 11 500 isolates (3000 from patients with respiratory tract infections) were collected throughout six European countries between 1994 and 1996. Twenty-seven hospitals or laboratories participated in this first phase of the study. The activities of three classes of antimicrobial agents (fluor-oquinolones,-lactam agents, macrolides) are presented for the six most frequently isolated pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae). Overall, trovafloxacin and ciprofloxacin activities were similar forHaemophilus influenzae, Moraxella catarrhalis andKlebsiella pneumoniae isolates. Of theStreptococcus pneumoniae isolates, 6% were resistant to penicillin. Trovafloxacin had the highest activity against theStreptococcus pneumoniae isolates, with a minimum inhibitory concentration of 0.25 mg/l for 90% of isolates (MIC₉₀); all strains tested were susceptible to trovafloxacin. The MIC₉₀ of ciprofloxacin forStreptococcus pneumoniae was 3 mg/l, and overall 52% of the strains were susceptible; 9% were resistant. Azithromycin and clarithromycin exhibited similar activity against all collected pathogens, exceptHaemophilus influenzae. All strains ofHaemophilus influenzae were susceptible to azithromycin compared with 79% for clarithromycin, with respective MIC₉₀s of 2 and 16 mg/l. The data presented demonstrate differences in the susceptibility patterns of six major respiratory tract pathogens in Europe.     

Antimicrobial activity of doripenem and other carbapenems against gram-negative pathogens from Korea

A total of 950 gram-negative bacterial isolates from patients with bacteremia and urinary tract infections were collected from tertiary-care hospitals in Korea. In vitro antimicrobial susceptibility testing was performed using broth microdilution test according to Clinical and Laboratory Standards Institute protocol. In general, carbapenems such as doripenem, imipenem, and meropenem were very active against Enterobacteriaceae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Acinetobacter sp. isolates. Doripenem was more potent than imipenem against most Enterobacteriaceae species except Proteus spp. based on minimum inhibitory concentration (MIC)(50) and MIC(90). In addition, doripenem displayed similar activity to meropenem but was superior to imipenem against ceftazidime-resistant Enterobacteriaceae isolates. For P. aeruginosa and Acinetobacter spp. isolates, MIC(50)s of doripenem were 1 and 0.5 mg/L, respectively, which were the same with those of meropenem but two- to fourfold lower than those of imipenem (both 2 mg/L). On the basis of the in vitro data, we conclude that doripenem has equivalent or more activity than other carbapenems such as imipenem and meropenem against most gram-negative pathogens from Korea. Thus, doripenem may be a promising new antimicrobial agent for the treatment of infections caused by gram-negative pathogens in Korea.     

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.     

Comparative antimicrobial activity of the new macrolide flurithromycin against respiratory pathogens

The activity of flurithromycin againstHaemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis andStaphylococcus aureus was determined by the agar dilution method. Flurithromycin showed high activity againstStreptococcus pneumoniae, Streptococcus pyogenes andBranhamella catarrhalis (MIC90=0.032–0.25 mg/l). Its MIC90 value againstHaemophilus influenzae strains was 4.0 mg/l and 16 mg/l againstStaphylococcus aureus strains. Flurithromycin has promising antibacterial activity which warrants clinical trials.     

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.     

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.     

Antibiotic Susceptibilities Among Recent Clinical Isolates of Haemophilus influenzae and Moraxella catarrhalis from Fifteen Countries

 Between July 1998 and July 1999, 3,060 Haemophilus influenzae and 1,486 Moraxella catarrhalis strains were isolated in 31 centers in 15 countries in order to determine their antimicrobial susceptibilities and the presence of β-lactamase production in Haemophilus influenzae. Overall 17.1% of the Haemophilus influenzae isolates were β-lactamase positive, while more than 95% were susceptible to amoxicillin/clavulanate, cefaclor, loracarbef, cefuroxime, azithromycin and ciprofloxacin. Eleven (0.3%) isolates were β-lactamase positive and ampicillin resistant and 7 (0.2%) isolates were ciprofloxacin resistant. The minimum inhibitory concentrations for 90% of the isolates tested were lowest for ciprofloxacin (0.03) and highest for cefprozil (8) against Moraxella catarrhalis.     

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 cefpirome and cefepime,two new cephalosporins

In in vitro tests the broad-spectrum cephalosporins cefpirome and cefepime were highly active againstEnterobacteriaceae, although often less so against strains resistant to amoxicillin-clavulanate and ticarcillin-clavulanate, and against most strains ofAcinetobacter spp. andAeromonas hydrophila. They were also active againstPseudomonas aeruginosa, although strains with non-plasmid mediated beta-lactam resistance were sometimes less sensitive. OtherPseudomonas spp. varied in their sensitivity. Both agents were highly active againstHaemophilus influenzae, but beta-lactamase-producingBranhamella catarrhalis were somewhat less sensitive.Neisseria gonorrhoeae were susceptible, although non-beta-lactamase producing penicillin-resistant strains had higher MICs.Gardnerella vaginalis was also susceptible andCampylobacter coli/jejuni usually susceptible. Both antibiotics had good activity againstStaphylococcus aureus and coagulase-negative staphylococci except for methicillin-resistant strains andStaphylococcus haemolyticus which were of borderline sensitivity. All streptococci were sensitive, with the exception of highly penicillin-resistant pneumococci and enterococci against which cefpirome had greater activity than cefepime. Both antibiotics had little useful activity against theBacteroides fragilis group orBacteroides oralis group but were active against most other anaerobes.Clostridium difficile and some otherClostridium species were resistant.     

In vitro antibacterial properties of cefetamet and in vivo activity of its orally absorbable ester derivative,cefetamet pivoxil

The in vitro activity of cefetamet, the microbiologically active metabolite of the orally administered prodrug cefetamet pivoxil, was compared with that of cephalexin, cefaclor, cefuroxime and amoxicillin. Cefetamet was highly active againstEnterobacteriaceae, Neisseria spp.,Vibrio spp.,Haemophilus influenzae and streptococci other than enterococci. Cefetamet inhibited cefaclor-resistant species such asProteus vulgaris, Providencia stuartii, Providencia rettgeri andSerratia marcescens. Staphylococci,Pseudomonas aeruginosa and cephalosporinase-overproducing strains ofEnterobacter cloacae were resistant to cefetamet. The superior activity of cefetamet compared with older oral beta-lactam antibiotics against a large number of gram-negative pathogens correlated with enhanced stability towards betalactamases. In accordance with the in vitro findings, cefetamet pivoxil showed good activity in experimental infections in the mouse and rat, suggesting satisfactory bioavailability in these animals after oral administration.     

Nationwide surveillance of antimicrobial resistance among Haemophilus influenzae and Streptococcus pneumoniae in intensive care units in Taiwan

A nationwide susceptibility surveillance of Streptococcus pneumoniae and Haemophilus influenzae isolates collected from patients treated at the intensive care units (ICUs) of ten Taiwanese major teaching hospitals was conducted from September 2005 through November 2005. High rates of resistance (intermediate/resistant) of S. pneumoniae to penicillin (85% resistance), ceftriaxone (46%/20%), and cefepime (43%/15%) by meningitis criteria, and in contrast, non-susceptibilities (intermediate/resistant) to penicillin (0%/0%), ceftriaxone (20%/0%) and cefepime (15%/0%) by non-meningitis criteria were noted (p values < 0.05) by the Clinical and Laboratory Standards Institute 2008. Resistant rate of S. pneumoniae to azithromycin was also high (63%). S. pneumoniae isolates were significantly more susceptible to ertapenem (87%) than to imipenem (39%) and meropenem (44%) (p values < 0.05). Rates of non-susceptibilities of H. influenzae isolates to ampicillin and cefaclor were high (55% and 45%, respectively). No β-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae isolates were found. Imipenem has a notably higher MIC₉₀ value (8 μg/ml) for H. influenzae than that of the other two carbapenems. Tigecycline showed good in vitro activities against these two respiratory pathogens. High rates of resistance among isolates of S. pneumoniae and H. influenzae continue to exist in the ICUs of Taiwan.