Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory infections

We determined the susceptibility of bacteria which were isolated from the patients with respiratory infections between January and October 2005, to tosufloxacin and other fluoroquinolones. A total of 900 isolate including 300 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 100 Moraxella catarrhalis, 200 Haemophilus influenzae, 100 Klebsiella pneumoniae and 100 Pseudomonas aeruginosa were tested. Tosufloxacin, gatifloxacin, levofloxacin, moxifloxacin, ciprofloxacin and prulifloxacin were used as the test antimicrobials. Tosufloxacin, gatifloxacin and moxifloxacin were potent antibiotics tested for the antibacterial activity against Streptococcus including penicillin-resistant S. pneumoniae; the MIC90 were 0.12-0.5/ micromL. Fluoroquinolones exerted the potent antibacterial activity against M. catarrhalis and H. influenzae; the MIC90 of fluoroquinolones tested were < or =0.06 microg/mL. Tosufloxacin, ciprofloxacin and prulifloxacin showed to be more active against K. pneumoniae and P. aeruginosa, but parts of some strains were resistant. These results indicate that tosufloxacin has the potent antibacterial activity against major organisms detected from patients with respiratory infections. Since it was approved in 1990, tosufloxacin was considered to be useful as a therapeutic antimicrobial for the treatment of respiratory infections.     

In vitro susceptibility of 4903 bacterial isolates to gemifloxacin--an advanced fluoroquinolone

The in vitro activity of gemifloxacin against over 4900 bacterial isolates was determined by microbroth dilution with interpretation in accordance with NCCLS guidelines. Susceptibility results were compared with those for ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin. Gemifloxacin and the other fluoroquinolones were not affected by either beta-lactamase production or penicillin-resistance in Streptococcus pneumoniae. The MIC90 values for gemifloxacin were: S. pneumoniae 0.063 mg/l; Haemophilus influenzae 0.016 mg/l; Moraxella catarrhalis 0.008 mg/l, methicillin-susceptible Staphylococcus aureus 0.063 mg/l; methicillin-susceptible Streptococcus pyogenes 0.031 mg/l; Enterobacteriaceae 0.031-0.16 mg/l; Pseudomonas aeruginosa 4 mg/l; Neisseria meningitidis 0.008 mg/l. The MIC90 for gemifloxacin was lower than those for the other quinolones tested against S. pneumoniae (ciprofloxacin 2-4 mg/l, gatifloxacin 0.5 mg/l, levofloxacin 1-2 mg/l, moxifloxacin 0.25 mg/l). This study confirms the enhanced potent activity of gemifloxacin against Gram-positive pathogens, its broad-spectrum, Gram-negative activity and indicates that gemifloxacin is likely to have an important role in treating patients with Gram-positive and/or Gram-negative infections.     

Antibacterial activity of oral Cephems against various clinically isolated strains

We determined the antibacterial activities of oral Cephems against isolated from the patients with the respiratory infections, the urinary tract infections, and infections in the obstetrics field of an adult and a child, during the period from 2002 to 2003; Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae and Escherichia coli of 40 strains of each, and Peptostreptococcus spp. 22 strains. S. pneumoniae and H. influenzae strains that resistant is regarded were collected mainly, penicillin-intermediate S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase negative ampicillin-resistant H. influenzae (BLNAR) strains. The MICs of Cephems except cefaclor (CCL) were < or = 0.03 microgram/mL against all strains of S. pyogenes. The MICs of cefteram (CFTM) and cefditoren (CDTR) were < or = 0.0125 microgram/mL activity against 7 strains penicillin-susceptible S. pneumoniae (PSSP). However the MIC90s of cefditoren (CDTR) was 1 microgram/mL, cefteram (CFTM), and cefcapene (CFPN) were 2 micrograms/mL against PISP and PRSP, were higher than those of other drugs, but showed slightly higher than PSSP. The MIC90s of Cephems. were 0.5-4 micrograms/mL against strains of E. coli. The MIC90s of CFTM was 0.5 microgram/mL, and CDTR, CFPN were 1 microgram/mL against E. coli were higher than those of other drugs. The four strains of E. coli however were highly-resistant which MIC90s of CCL were more than 32 micrograms/mL were obtains. Furthermore it is necessary to pay much attention to the trend of resistant such as E. coli of Cephems. Although all strains showed resistant to AMPC, MIC90 of Cephems were 0.25-1 microgram/mL, good activities against K. pneumoniae. Against beta-lactamase negative ampicillin-susceptible H. influenzae (BLNAS) 23 strains the MIC90s of CCL and other Cephems were 64 micrograms/mL and 0.25-8 micrograms/mL. The MIC90s of CDTR and CFTM were < or = 1 microgram/mL of BLNAR (15 strains). However there of CFDN and CPDX were 8 micrograms/mL and CCL were > or = 16 micrograms/mL. Two strains which were produced beta-lactamase were highly--ABPC resistant. Although B. catarrhalis all strains were produced beta-lactamase and Cephems except for CCL showed better susceptibility than AMPC. The MIC90s of Cephems were 0.25-2 micrograms/mL against Peptostreptococcus spp.     

In vitro activity of telithromycin compared with macrolides and fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis

The in vitro activity of telithromycin was compared with erythromycin A, azithromycin, clarithromycin, moxifloxacin, gemifloxacin, levofloxacin, ciprofloxacin, penicillin G, ampicillin, cefuroxime and ceftriaxone against 336 consecutive strains (83 Streptococcus pneumoniae, 168 Haemophilus influenzae and 85 Moraxella catarrhalis) isolated from patients with community-acquired respiratory tract infections. Telithromycin (MIC(90), 0.008 mg/l) was the most active drug against S. pneumoniae. Telithromycin was also highly active against M. catarrhalis (MIC(90), 0.06 mg/l), but less active against H. influenzae (MIC(90), 4 mg/l).     

Moxifloxacin activity against clinical isolates compared with the activity of ciprofloxacin

The activity of moxifloxacin, a new 8-methoxyquinolone, was compared in vitro with the activity of ciprofloxacin against clinical strains isolated from various sites of infection. The mode MIC values of moxifloxacin were superior to those of ciprofloxacin against Streptococcus pneumoniae, methicillin-susceptible and -resistant Staphylococcus aureus, Enterococcus spp., Escherichia coli and Acinetobacter spp., while ciprofloxacin was more active against Klebsiella pneumoniae and Pseudomonas spp. Both antibiotics had similar activity against Haemophilus influenzae, Moraxella catarrhalis and Enterobacter spp.     

Comparative antimicrobial activity and post-antibiotic effect of azithromycin, clarithromycin and roxithromycin against some respiratory pathogens

Recent macrolide derivatives, roxithromycin, azithromycin and clarithromycin show more favourable pharmacokinetic characteristics in comparison to old ones and some differences in antibacterial activity. With the aim of improving our understanding of some aspects of their action against respiratory pathogens, we determined the MICs and MBCs of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Moraxella catarrhalis and Haemophilus influenzae. Azithromycin was the most active agent against Haemophilus influenzae and Moraxella catarrhalis, while clarithromycin was more active against Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus with MICs similar to those of erythromycin. The bactericidal activity of all tested derivatives was weak against Staphylococcus aureus (MBC/MIC ratio approximately 16) and against Moraxella catarrhalis (MBC/MIC ratio, 8-16), but good against Staphylococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae (MBC/MIC ratio, 2-4). The determination of killing curves in the presence of 2 MIC and 10 MIC of azithromycin, clarithromycin and roxithromycin confirmed their weak bactericidal activity against Staphylococcus aureus and Moraxella catarrhalis as well as their effective activity against Streptococcus pyogenes and Streptococcus pneumoniae. Azithromycin showed the highest bactericidal activity against Haemophilus influenzae. As expected, the three derivatives produced a quite prolonged PAE when exposed to 5 MIC for 1 h, ranging between 2-4 h. The bactericidal activity and the prolonged PAE of new macrolides for the most common respiratory pathogens should assure a good clinical activity in respiratory infections including those sustained by Haemophilus influenzae, which is less susceptible to erythromycin and other old macrolides.     

Susceptibility to moxifloxacin and other antimicrobial agents of major pathogens responsible for community acquired respiratory tract infection in Poland

The in vitro activity of moxifloxacin was compared with that of other antimicrobial agents against 470 bacterial strains isolated from patients with respiratory tract infection. Bacteria studied included 110 penicillin susceptible and 110 penicillin non-susceptible Streptococcus pneumoniae, 50 strains of S. pyogenes, 120 strains of Haemophilus influenzae and 80 strains of Moraxella catarrhalis. Moxifloxacin was the most active of the antimicrobials tested.     

Activity of JNJ-Q2, a new fluoroquinolone, tested against contemporary pathogens isolated from patients with community-acquired bacterial pneumonia

JNJ-Q2 is a broad-spectrum fluoroquinolone with bactericidal activity against Gram-positive and Gram-negative pathogens and is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin-structure infections. This study determined the activity of JNJ-Q2 against a worldwide year 2010 collection (89 centres in 27 countries) of three common respiratory pathogens (3757 isolates) from patients with CABP. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were tested by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and susceptibility rates for comparators were assessed using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria. JNJ-Q2 had activity against all three species, with 96.9% of strains inhibited at ≤0.015 mg/L. JNJ-Q2 [minimum inhibitory concentration for 50% and 90% of the organisms, respectively (MIC(50/90))=0.008/0.015 mg/L] demonstrated a 16-fold greater potency compared with moxifloxacin (MIC(50/90)=0.12/0.25 mg/L) and at least 128-fold greater activity compared with levofloxacin (MIC(50/90)=1/ 1 mg/L) and ciprofloxacin (MIC(50/90)=1/2 mg/L) against S. pneumoniae. Haemophilus influenzae isolates were 21.9-23.3% resistant to ampicillin, but JNJ-Q2 (MIC(50/90)≤0.004/0.015 mg/L) was at least two-fold more active than moxifloxacin (MIC(50/90)=0.015/0.03 mg/L) as well as being potent against M. catarrhalis (MIC(90)=0.015/0.015 mg/L). In conclusion, JNJ-Q2 demonstrated increased potency compared with other marketed fluoroquinolones that have been used to treat CABP pathogens, thus favouring further clinical development.     

In vitro activity of moxifloxacin against recent community-acquired respiratory tract pathogens isolated in France: a national survey

Between February and June 2000, 2345 consecutive strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae were isolated from 2088 adult patients suffering from community-acquired respiratory tract infections, in 97 hospital laboratories. Of the 1037 S. pneumoniae isolates, 48.3% were intermediately or highly penicillin resistant. For invasive isolates, the MIC90s of penicillin G, amoxycillin, cefuroxime, ceftriaxone, erythromycin, ofloxacin, ciprofloxacin and moxifloxacin were 2, 2, 4, 0.5, 1024, 2, 2 and 0.25 mg/l, respectively. All but one invasive strain were susceptible to moxifloxacin whereas 97.5% were susceptible to levofloxacin. The MIC90s of clinical isolates with intermediate susceptibility or high resistance to penicillin G, were 2, 2, 4, 1, 1024, 2, 2 and 0.25 mg/l. About 98.1, 97.0, and 83.1% of strains were inhibited by concentrations < or = 1 mg/l of moxifloxacin, levofloxacin and ciprofloxacin, respectively (E-test). Eight of the 1037 S. pneumoniae strains were not susceptible to moxifloxacin and had mutations in gyrA (eight strains), parC (four strains) or parE (three strains). Against H. influenzae (32.7% were beta-lactamase producers) and M. catarrhalis (96.3% were beta-lactamase producers), the MIC90s of moxifloxacin, amoxycillin and co-amoxiclav were 0.094 and 0.125 mg/l, 64 and 8 mg/l, and 1.5 and 0.25 mg/l, respectively. Against oxacillin-susceptible S. aureus and K. pneumoniae, the MIC90s of moxifloxacin were 0.125 and 0.84 mg/l respectively. Moxifloxacin had the highest in vitro activity of all antibiotics tested.     

Susceptibility of major pathogens of acute pharyngitis and tonsillitis to levofloxacin and other oral antimicrobial drugs

A total of 2865 strains of the causative organisms isolated from the patients with acute pharyngitis and tonsillitis at the primary medical institutions were used in this study. The MICs of levofloxacin (LVFX) and other oral antimicrobial drugs were determined and evaluated by the NCCLS guideline. LVFX, cefditoren (CDTR) and cefcapene (CFPN) were potently active against 773 isolates of Hemophilus influenzae, the MIC50S of LVFX being < or = 0.06 microgram/mL and also the same as the MIC90S of LVFX. LVFX was the most active against 496 isolates of Enterobacteriaceae. The MIC50S of LVFX were < or = 0.06 microgram/mL and were lower than those of CDTR, cefdinir (CFDN) and cefpodoxime (CPDX) (MIC50S: 0.5 microgram/mL). The MIC90S of these cephems were markedly higher than the respective MIC50S, whereas MIC50 of LVFX was 0.12 microgram/mL, only twice the MIC50. Against the majority of Streptococcus pyogenes (555 isolates) and Streptococcus spp. (495 isolates), CDTR, CFDN, CPDX and CFPN were highly active (MICs: < or = 0.06 microgram/mL), and clarithromycin (CAM) and azithromycin (AZM) were also active against these organisms (MICs: 0.12 to 0.25 microgram/mL). Against S. pneumoniae (92 isolates), CDTR and CFDN were active (MIC50S: 0.12 and 0.25 microgram/mL, respectively). However, the MIC90S of these drugs were 4-8 times the MIC50S. Against Moraxella (Branhamella) catarrhalis (454 isolates), LVFX was potently active, the MIC90 of LVFX being < or = 0.06 microgram/mL and MIC90S of the other cephems being 0.5 microgram/mL or more. When the susceptibility of these strains to LVFX was evaluated by the NCCLS guideline, about 3% of other Streptococcus spp. were resistant to the drug but no test strains resistant to LVFX were detected in H. influenzae, S. pyogenes or Enterobacteriaceae. On the other hand, the percentages of strains susceptible to the cephems tested were 60-90%, which were quite different according to kinds of drugs and species used. Furthermore, the strains of S. pneumoniae resistant to CFDN and CPDX, and those to CAM and AZM were 21-25% and 50% or more, respectively, whereas no LVFX-resistant strains were detected. The major pathogens isolated from patients with pharyngitis and tonsillitis in the primary institutions were highly susceptible to LVFX. These results suggest that LVFX is a useful drug which is potently active against the strains resistant to oral cephem and macrolide antibiotics.     

Antibacterial activity of oral cephems against various clinically isolated strains and evaluation of efficacy based on the pharmacokinetics/pharmacodynamics theory

We compared the antimicrobial activity of commercially available oral cephem agents, cefaclor (CCL), cefroxadine (CXD), cefdinir (CFDN), cefixime (CFIX), cefpodoxime (CPDX), cefteram (CFTM), cefcapene (CFPN), and cefditoren (CDTR), against Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, and ESBL-producing bacteria isolated from clinical materials in Kansai Medical University Hospital between 2002 and 2003. Based on the Pharmacokinetics/Pharmacodynamics (PK/PD) theory, we determined the concentration of each agent at which the time above MIC (TAM) value was 40% or more, and calculated the rate of efficacy against each type of bacteria. In S. pneumoniae strains, the MIC(50,80,90) values of CDTR were 0.25, 0.5, and 0.5 microg/ml, respectively, lower than those of the other agents, demonstrating the most potent antimicrobial activity. However, the efficacy rate for CDTR calculated based on the PK/PD theory was 58.5%. CFTM showed the highest efficacy rate (66.1%). In H. influenzae strains, the antimicrobial activity of CDTR was most potent, followed by that of CFTM and that of CFPN/CFIX. The MIC90 value of CDTR was lowest (0.25 microg/ml), followed by that of CFTM (0.5 microg/ml). The efficacy rate for CDTR was 100%. This result supports that CDTR frequently eradicates H. influenzae. In E. coli strains, the MIC90 values of the above agents, excluding CCL and CXD, ranged from 0.5 to 1 microg/ml. The antimicrobial activity of CFIX against K. pneumoniae was most potent, followed by that of CFDN/CPDX and that of CFTM. In ESBL-producing bacteria, most agents showed an MIC90 value of more than 4 microg/ml. In S. agalactiae and S. pyogenes strains, all of the agents showed satisfactory MIC values. In methi- cillin-sensitive Staphylococcus aureus (MSSA) strains, CFDN and CXD showed a high efficacy rate, whereas the efficacy rates for the other agents were low. The frequent use of oral agents has increased the number of cephem-resistant bacteria. ESBL-producing bacteria become highly resistant, and the presence or absence of response can be readily evaluated. However, when a mutation of penicillin-binding protein (PBP) occurs, drug resistance is less marked. Therefore, it is difficult to evaluate the treatment response in many cases. In S. pneumoniae strains, the efficacy rates for all of the agents were low in the evaluation using the PK/PD theory, suggesting that a dose higher than the standard dose should be established. Thus, in the future, the efficacy should be evaluated based on the PK/PD theory, appropriate antimicrobial treatment should be administered, and the administration method that does not increase the number of resistant bacteria must be established.     

Antimicrobial susceptibility surveillance of Streptococcus pneumoniae and Haemophilus influenzae isolates to cefteram and other antimicrobial drugs during January 2003 to July 2004

The antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates during January 2003 to July 2004 was determined to seven various antimicrobial drugs including cefteram (CFTM). The in vitro activities of these drugs against the fresh isolates were compared. The oral cephalosporins including CFTM were potently active against penicillin susceptible S. pneumoniae. The activity of CFTM and cefditoren was the most active among four oral cephalosporins. The susceptibilities of penicillin intermediate S. pneumoniae and penicillin resistant S. pneumoniae to antimicrobial agents were decreased. The MIC of CFTM was not beyond 4 microg/mL for any isolate of S. pneumoniae. The activity of CFTM was very high to beta-lactamase-negative and ampicillin-susceptible H. influenzae isolates. These MIC against all isolates were 0.03 microg/mL or less. The MIC of CFTM was not beyond 1 microg/mL for any isolate of beta-lactamase-positive H. influenzae or beta-lactamase-negative-ampicillin resistant H. influenzae. In conclusion, CFTM exhibits a potent activity against fresh isolates of S. pneumoniae and H. influenzae, and has a potential of effectiveness in the infections.     

Antibacterial activity of cefpodoxime against clinical isolates in 2000 and 2001

As the post-marketing surveillance of cefpodoxime proxetil (Banan), MICs of cefpodoxime (CPDX, an active form of Banan) against 1090 clinical isolates of 22 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of oral cephem antibacterials, cefaclor, cefdinir, cefditoren, and cefcapene. In this study, remarkable change in the activity of CPDX was observed in Streptococcus pneumoniae and Haemophilus influenzae compared with the susceptibility in the studies before Banan was launched. This cause is considered to be the increase in the incidence of the following resistant strains: penicillin-intermediate S. pneumoniae (47.3%), penicillin-resistant S. pneumoniae (PRSP, 15.1%), and beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae (24.0%), which were scarcely isolated in 1989 when Banan was launched. Other tested drugs also exhibited low activity against these resistant strains. However, CPDX showed comparatively good activity with MIC90 of 2 micrograms/mL against PRSP. Against methicillin-susceptible Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, and Moraxella catarrhalis, CPDX also showed comparatively good activity with MIC90 of < or = 4 micrograms/mL, which was almost equal to that in the studies before its marketing. Against quinolones-resistant Neisseria gonorrhoeae, CPDX showed excellent activity with MIC90 of 0.5 microgram/mL. Against members of the family Enterobacteriaceae except for Citrobacter freundii, Enterobacter spp., Proteus vulgaris, and Morganella morganii, CPDX showed good activity. However, in Escherichia coli, Klebsiella spp. Proteus spp., and Providencia spp., there are some high-resistant strains to all tested drugs including CPDX. Against Peptostreptococcus spp., MIC90 of CPDX was 8 micrograms/mL and its MIC range was widely distributed from 0.03 to 32 micrograms/mL, which were similar to those in the studies before its marketing. In this study, CPDX showed the decrease in the activity against several species as did other drugs tested, but against most of species tested, CPDX maintained good activity. Furthermore, it is necessary to pay much attention to the trend of resistant strains.     

Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms

Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.     

Minimal inhibitory concentrations and time-kill determination of moxifloxacin against aerobic and anaerobic isolates

Moxifloxacin is a new oral 8-methoxy-quinolone with a wide spectrum of activity against Gram-negative and anaerobic bacteria, atypical micro-organisms and multi-resistant Gram-positive bacteria. This study was designed to assess the in vitro activity of moxifloxacin against Gram-positive bacteria with different resistance patterns, anaerobes and atypical micro-organisms such as Chlamydia and Mycoplasma. Moxifloxacin had good activity against Streptococcus pneumoniae with all strains inhibited by < or =0.12 mg/l. The minimal inhibitory concentrations (MICs) of moxifloxacin for Streptococcus pyogenes and Streptococcus agalactiae ranged from 0.03 to 0.5 mg/l while those of ciprofloxacin were about two- to four-fold higher (MICs=0.12-1 mg/l). Moxifloxacin was poorly active against enterococci but its activity against Clostridium and Bacteroides spp. was in the same range as that of metronidazole and superior to that of clindamycin. Moxifloxacin was substantially more active than both ciprofloxacin and sparfloxacin against Chlamydia.     

Studies on susceptibility of isolated organisms from pediatric infections against various antimicrobial agents

Twelve oral antimicrobial agents were tested for their antimicrobial activities against causative organisms isolated from pediatric infections. Activities of these antimicrobial agents against Streptococcus pyogenes were also examined in relation to T-antigen typing of the species. The results of the investigation are summarized as follows. 1. Against Staphylococcus aureus, rokitamycin (RKM), josamycin, ofloxacin, minocycline exhibited strong antimicrobial activities, and few strains of S. aureus showed resistance to these antimicrobial agents. More strains exhibited resistance to erythromycin (EM) than to other macrolide antibiotics (MLs) examined. Amoxicillin (AMPC)-resistance was often observed also. 2. Against S. pyogenes, beta-lactam antibiotics (beta-lactams) and RKM had MIC80 of 0.20 microgram/ml or below, and no resistant strains of this organism were observed against these antibiotics. Only 2 resistant strains (2.0%) of S. pyogenes to MLs were detected, but resistance to tetracyclines (TCs) was observed at a high frequency, with 71.4% or more strains among T-4, T-6, T-12 and T-28 antigen types exhibited resistance to TCs. Among the 21 strains of T-12 antigen type examined, only one strain (4.8%) was found resistant to MLs. These observations suggested that the reduction in the frequency of ML-resistant strains was not due to the reduction in the number of T-12 antigen type strains but due to losses of resistance factors against MLs of plasmids. 3. Antibacterial activities of beta-lactams and MLs against Streptococcus pneumoniae strains were good, similarly to activities against S. pyogenes. But many strains of S. pneumoniae were resistant to TCs. 4. New quinolone antimicrobial agents (quinolones) showed excellent activities against Branhamella catarrhalis strains with EM and RKM showing the next best activities. The number of resistant strains against quinolones, however, seemed to be on an increase. 5. Quinolones had strong antimicrobial activities against Haemophilus influenzae, few strains of which showed resistance to quinolones. AMPC had the next best activity, but approximately 10% of H. influenzae exhibited resistance to this antibiotic. 6. Against Campylobacter spp., quinolones and MLs showed the best activities with MIC80 values at or below 0.25 microgram/ml, and no resistant strains of the species against these antimicrobial agents were observed. Fosfomycin and TCs showed somewhat inferior activities to quinolones and MLs, with beta-lactams showing still lower activities. 7. Only few strains of Mycoplasma pneumoniae and Chlamydia trachomatis were examined, but MLs and TCs appeared to be effective against these organisms.(ABSTRACT TRUNCATED AT 400 WORDS)     

Antimicrobial activities of macrolides against recent clinical isolates,and analysis of resistant mechanisms

We examined antibacterial activities of 4 kinds of macrolides, erythromycin (EM), clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM), against 6 bacterial species of clinical strains isoleted in 2002. Bacterial isolates used were each 50 strains of methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae and 43 strains of Streptococcus pneumoniae. S. agalactiae were derived from gynecological samples, and other species were isolated from respiratory specimens. Antimicrobial activities against S. aureus, S. pyogenes, S. agalactiae, M. catarrhalis and H. influenzae of 14-membered macrolides, such as EM and CAM, were higher than those of 16-membered macrolide, RKM. By contrast, against S. pneumoniae, RKM was more effective than 14-membered macrolides. Six, three and four strains of S. aureus, S. pyogenes and S. agalactiae, respectively, were resistant to macrolides. Thirty-five among 43 pneumococcal isolates were resistant, and 15 of the 35 were highly-resistant, MIC of > 128 micrograms/ml, to any one of EM, CAM or AZM. Isolation frequency of resistant strains to RKM was lower than those to 14- and 15-membered macrolides: only one strain was highly-resistant and 12 were intermediately-resistant. No resistant strain was recognized in M. catarrhalis and H. influenzae. Further, we analyzed the resistant mechanisms, methylation or efflux, of macrolide resistant strains by the double-disk method. Methylation was major mechanism in S. aureus, and in S. pyogenes, all of the resistance was caused by methylation. In S. agalactiae and S. pneumoniae, methylation and efflux shared about half and half.     

In vitro antibacterial activity of FK041, a new orally active cephalosporin.

The in vitro activity of FK041, a new orally active cephem antibiotic, against a wide variety of clinical isolates of bacteria was investigated and compared with those of cefdinir (CFDN) and cefditoren (CDTR). FK041 exhibited broad spectrum activity against reference strains of Gram-positive and Gram-negative aerobes and anaerobes. FK041 was active against clinical isolates of Gram-positive organisms except Enterococcus faecalis with MIC90s less than 1.56 microg/ml. FK041 was more active than CFDN and CDTR against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae and was comparable to CFDN and CDTR against Streptococcus pyogenes and Streptococcus pneumoniae. FK041 had no activity against methicillin-resistant staphylococci, like CFDN and CDTR. FK041 showed moderate activity against penicillin-resistant S. pneumoniae with an MIC range of 0.05 approximately 3.13 microg/ml, and was superior to CFDN but inferior to CDTR. Against clinical isolates of many Gram-negative organisms such as Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, FK041 had good activity comparable or superior to those of CFDN and CDTR. However, it was inferior to CDTR in activity against Moraxella catarrhalis, Haemophilus influenzae, Morganella morganii, and Serratia marcescens, and was inactive against Pseudomonas aeruginosa. With FK041 a small difference between MIC and MBC against S. aureus, E. coli, K. pneumoniae, and H. influenzae was found, indicating that its action is bactericidal against these species. FK041 was stable to group 2beta-lactamase hydrolysis but was unstable to group 1beta-lactamase hydrolysis. The stability of FK041 to these enzymes was similar to those of CFDN and CDTR. FK041 showed high affinity for the main penicillin-binding proteins (PBPs) of S. aureus (PBP 3, 2, and 1) and E. coli (PBP 3, 4, lbs, 2, and 1a).     

Antimicrobial activities of sultamicillin against clinical isolates from upper respiratory tract infections

Sultamicillin (SBTPC) is a mutual prodrug in which ampicillin (ABPC) and a potent beta-lactamase inhibitor sulbactam (SBT) are ester-bound in an equimolar ratio. SBTPC is hydrolyzed during absorption after oral administration to provide ABPC and SBT for systemic circulation. In the present study, the antimicrobial activities of SBTPC against 50 isolates each of 6 species (Staphylococcus aureus, Klebsiella pneumoniae subsp. pneumoniae, Branhamella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes) of bacteria freshly obtained from upper respiratory tract infections were examined in relation to their bacterial beta-lactamase producing abilities. beta-Lactamase producing strains were identified using the acidometry disc method with benzylpenicillin (PCG) of cefazolin (CEZ) as a substrate, and their frequencies of appearance were calculated as follows: S. aureus 86%; K. pneumoniae subsp. pneumoniae 100%; B. catarrhalis 68%; H. influenzae 24%. Fourteen per cent of S. aureus strains examined were beta-lactamase positive using both PCG and CEZ acidometry discs. SBTPC, however, demonstrated excellent antimicrobial activities even against these beta-lactamase producing strains. Good activities were observed especially against those bacterial strains producing penicillinase (PCase). Average MIC80 values of SBTPC were 3.13 micrograms/ml for S. aureus and K. pneumoniae subsp. pneumoniae, 0.39 micrograms/ml for B. catarrhalis and H. influenzae, 0.05 micrograms/ml for S. pneumoniae and 0.025 micrograms/ml for S. pyogenes. As SBTPC was shown to possess excellent antimicrobial activities against PCase producing strains, the enhancement in activities of SBTPC compared to ABPC alone can be attributed to the inhibition of beta-lactamase by SBT which, as noted above, is a component of SBTPC in an equimolar ratio to ABPC.     

In vitro activity of gatifloxacin compared with gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin against uropathogens cultured from patients with complicated urinary tract infections

Minimum inhibitory concentrations (MICs) of gatifloxacin were compared with those of gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin using an agar dilution method for 400 uropathogens cultured from the urine of urological patients with complicated and/or hospital-acquired urinary tract infections (UTI). The collection of strains was made up of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). The antibacterial activity of the three newer fluoroquinolones, gatifloxacin, gemifloxacin, and moxifloxacin, were similar, but showed some drug specific differences. Gemifloxacin was most active against Escherichia coli, but less so against Proteus mirabilis. In this series all isolates of E. coli were inhibited at a MIC of 0.25 mg/l gatifloxacin and moxifloxacin and by 0.125 mg/l gemifloxacin. The MIC distribution of all fluoroquinolones showed a bimodal distribution for staphylococci, enterococci and Pseudomonas aeruginosa. The two modes for P. aeruginosa were 1 and 64 mg/l for gemifloxacin and moxifloxacin and 0.5 and 64 mg/l for gatifloxacin. For staphylococci the two modes were 0.125 and 2 mg/l for gatifloxacin, 0.03 and 4 mg/l for gemifloxacin, and 0.03 and 2 mg/l for moxifloxacin; for enterococci, 0.25 and 16 mg/l for gatifloxacin, 0.06 and 2 mg/l for gemifloxacin, and 0.25 and 8 mg/l for moxifloxacin. Compared with trovafloxacin the MICs were similar, but the newer fluoroquinolones were more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. Of the newer fluoroquinolones gatifloxacin had the highest rate of renal excretion and could be considered a promising alternative fluoroquinolone agent for the treatment of UTI.