In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe

Objective   To assess the activities of levofloxacin and the comparator agents erythromycin, clarithromycin, azithromycin and doxycycline against atypical respiratory pathogens.
Methods   One hundred and forty-six Legionella pneumophila , 41 Mycoplasma pneumoniae and nine Chlamydia pneumoniae isolates were procured from various culture collections in North America and Europe and tested for susceptibility to the above agents by broth microdilution. The isolates came primarily from clinical sources and were collected from patients between 1995 and 1999.
Results   Against L. pneumophila , levofloxacin was the most active agent, with an MIC₉₀ of 0.03 mg/L, twofold more active than clarithromycin (0.06 mg/L), 16-fold more active than erythromycin and azithromycin (0.5 mg/L) and 64-fold more active than doxycycline. Against M. pneumoniae , azithromycin (MIC₉₀ ≤ 0.0005 mg/L) was the most active agent. However, two isolates of M. pneumoniae , one from the USA and one from Finland, were macrolide resistant (MIC ≥ 4 mg/L), but levofloxacin susceptible (MIC 0.25 mg/L). The geographic origin of L. pneumophila and M. pneumoniae did not affect the MIC range for any antimicrobial agent tested. Against C. pneumoniae , clarithromycin was the most active agent, with an MIC range of ≤0.008–0.03 mg/L.
Conclusions   Levofloxacin had comparable activity to the other agents tested against the atypical respiratory pathogens, confirming its potential as an alternative for empirical therapy of community-acquired pneumonia.     

Kinetic bactericidal activity of telithromycin, azithromycin and clarithromycin against respiratory pathogens

The present study assessed the comparative in vitro killing kinetics of telithromycin, azithromycin and clarithromycin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined against Streptococcus pneumoniae, beta-haemolytic streptococci, Haemophilus influenzae and Moraxella catarrhalis strains characterized by different susceptibilities to beta-lactams and macrolides. For each bacterial species, representative strains were chosen for time-kill studies. Telithromycin showed high activity against all the tested strains with MIC ranging from < or = 0.004 to 0.5 mg/L for streptococci, from 0.008 to 8 mg/L for H. influenzae, and from 0.008 to 0.5 mg/L for M. catarrhalis. In time-kill studies, telithromycin showed an overall superior bactericidal activity in respect to macrolides, particularly against resistant strains. In conclusion, telithromycin proved to possess bactericidal activity against a wide range of respiratory pathogens, including strains resistant to common macrolides.     

In vitro activity of tigecycline and occurrence of tetracycline resistance determinants in isolates from patients enrolled in phase 3 clinical trials for community-acquired pneumonia

The in vitro activity of tigecycline was evaluated against baseline pathogens isolated from patients enrolled in phase 3 clinical trials for community-acquired pneumonia conducted in 29 countries worldwide. Tigecycline was active against the most prevalent pathogens, including Streptococcus pneumoniae (MIC₉₀ 0.06 mg/L), Staphylococcus aureus (MIC₉₀ 0.25 mg/L), Haemophilus influenzae (MIC₉₀ 0.5 mg/L) and Klebsiella pneumoniae (MIC₉₀ 1 mg/L). Twelve isolates of S. pneumoniae expressing tet (M) and two isolates of K. pneumoniae producing extended-spectrum β-lactamases isolated during the study were susceptible to tigecycline. The excellent in vitro activity of tigecycline against these clinical isolates confirmed its potential utility against pathogens associated with community-acquired pneumonia.     

The DUEL study: a multi-center in vitro evaluation of linezolid compared with other antibiotics in the Netherlands

Objective   To evaluate bacterial susceptibility to linezolid in the Netherlands in comparison with other antibiotics.
Methods   Bacterial strains were isolated between September 1999 and January 2000 from patients presumed to require antibiotic treatment. The in vitro activity of 1226 strains from 34 participating laboratories was tested against linezolid, vancomycin, teicoplanin, oxacillin, penicillin, erythromycin, ampicillin and other antibiotics against enterococci, coagulase-negative staphylococci, Staphylococcus aureus and Streptococcus pneumoniae . Minimal inhibitory concentrations (MIC) were obtained with the E test on Mueller-Hinton agar: every laboratory included control strains. For vancomycin and teicoplanin only, brain–heart infusion agar and an inoculum of 2.0 McFarland was used for Staphylococcus aureus , coagulase-negative staphylococci and enterococci to support a better growth and clear recognition of hetero-resistant colonies.
Results   The values of MIC₉₀ for linezolid were 1.5, 0.75, 0.75 and 1 mg/L for Staphylococcus aureus , coagulase-negative staphylococci, Streptococcus pneumoniae and enterococci, respectively. Six enterococcal strains with decreased susceptibility against vancomycin or teicoplanin were identified as Enterococcus faecium , E. gallinarum and E. casseliflavus (two strains each) and they were found to harbor vanA , vanC1 and vanC2/3 genes, respectively. Nine per cent of Streptococcus pneumoniae (an increase from 1% 4 years ago) showed decreased susceptibility to erythromycin, of both the ermB and mefE type; there was no cross-resistance with linezolid. Twelve coagulase-negative staphylococcal strains were resistant to teicoplanin.
Conclusion   Linezolid is a promising drug in the treatment of infections caused by Gram-positive cocci. Cross-resistance with other antibiotics tested was not found.     

In vitro activity of new quinolones against Mycoplasma pathogenic to humans

The in vitro activity of new quinolones was evaluated against Mycoplasma pneumoniae (10 strains) and Mycoplasma hominis (approximately equal to 70 strains) by agar dilution, and against Ureaplasma urealyticum (approximately equal to 115 strains) by broth dilution. The static effect of pefloxacin, ofloxacin, ciprofloxacin, enoxacin was investigated for all the strains. Rosoxacin was included in the tests for U. urealyticum and M. hominis. Pefloxacin, ofloxacin, ciprofloxacin and enoxacin were within the same range of sensitivity for M. pneumoniae; the minimal inhibitory concentrations (MICs) of the 10 strains were 1 mg/l for ciprofloxacin, 2 mg/l for pefloxacin, MICs range was (0.05-1 mg/l) for ofloxacin and (0.5-4 mg/l) for enoxacin. Ciprofloxacin was the most active compound against M. hominis; MICs range and mode MICs were respectively in mg/l: (0.1-1) 0.5 for ciprofloxacin, (0.2-2) 0.5 for ofloxacin, (0.5-2) 1 for pefloxacin, (0.5-8) 2 for enoxacin, (2-16) 2 for rosoxacin. Ofloxacin was the most active compound against U. urealyticum; MICs range and mode MICs were respectively in mg/l: (0.2-2) 1 for ofloxacin, (0.1-8) 2 for rosoxacin, (0.5-8) 4 for pefloxacin, (1-16) 4 for ciprofloxacin, (2-32) 8 for enoxacin. No difference could be observed between tetracycline sensitive or resistant strains.     

Activity of telithromycin and seven other agents against 1034 pediatric Streptococcus pneumoniae isolates from ten central and eastern European centers

Objective  To test the activity of telithromycin against 1034 Streptococcus pneumoniae isolates from pediatric patients in ten centers from ten central and eastern European countries during 2000–2001, and to compare it with the activities of erythromycin A, azithromycin, clarithromycin, clindamycin, and quinupristin–dalfopristin.
Methods  The minimum inhibitory concentrations (MICs) of telithromycin, erythromycin A, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin–dalfopristin and penicillin G were tested by the agar dilution method with incubation in air, and mechanisms of resistance to macrolides and quinolones were investigated.
Results  Strains were isolated from sputum, tracheal aspirates, ear, eye, blood, and cerebrospinal fluid. Among S. pneumoniae strains tested, 36% had raised penicillin G MICs (≥ 0.12 mg/L). Susceptibilities were as follows: telithromycin, quinupristin–dalfopristin and levofloxacin, ≥ 99%; clindamycin, 83%; and erythromycin A, azithromycin and clarithromycin, 78%. Of 230 (22.3%) erythromycin A-resistant S. pneumoniae strains, 176 (79.6%) had erm(B) , 38 (16.1%) had mef(A) , and 10 (4.3%) had mutations in 23S ribosomal RNA or in ribosomal protein L4. The rates of drug-resistant S. pneumoniae are high in all centers except Kaunas, Riga, and Prague.
Conclusion  Telithromycin had low MICs against all strains, irrespective of macrolide, azalide or clindamycin resistance. Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher.     

Comparison of the in vitro activity of pristinamycin and quinupristin/dalfopristin against Streptococcus pneumoniae

The in vitro activity of quinupristin/dalfopristin, a new injectable streptogramin, and pristinamycin was evaluated against 200 recently isolated clinical Streptococcus pneumoniae strains expressing various degrees of susceptibility to penicillin G and erythromycin. MICs were determined by the agar dilution method. All strains were susceptible to pristinamycin irrespective of their susceptibility to penicillin G or erythromycin (MIC90: 0.25 mg/L for each phenotype). The activity of quinupristin/dalfopristin was slightly lower than that of pristinamycin against 42 penicillin G-susceptible/erythromycin-susceptible strains (MIC90: 0.5 mg/L), 13 penicillin G-susceptible/erythromycin-resistant strains (MIC90: 1 mg/L), 25 penicillin G-intermediate or -resistant/erythromycin-susceptible strains (MIC90: 0.5 mg/L) and 120 penicillin G-intermediate or -resistant/erythromycin-resistant strains (MIC90: 0.5 mg/L). The activity of both streptogramins was not significantly altered in case of erythromycin resistance. Thus, both streptogramins might be useful for the treatment of penumococcal infections, especially in cases of multiresistant strains.     

Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)

The spectrum of activity and potency of doripenem, a broad-spectrum parenteral carbapenem currently in clinical development, was evaluated using 16 008 clinical bacterial isolates collected as part of an international surveillance project during 2003. Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics. Against enterococci (1474 isolates), with the exception of Enterococcus faecium, doripenem displayed modest activity (MIC50 4). Doripenem was among the most potent agents tested against Streptococcus pneumoniae, viridans group streptococci and beta-haemolytic streptococci (885, 140 and 397 isolates; MIC(90)s 0.5, 0.5 and 0.03 mg/L, respectively). For Enterobacteriaceae (> 6200 isolates), doripenem was four- to 32-fold more active than imipenem against wild-type isolates (MIC90s 0.03-0.5 mg/L). MIC90s for confirmed extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (121 and 155 isolates; 0.06 and 0.12 mg/L, respectively) were two-fold higher than for wild-type isolates. Doripenem was also active against Citrobacter spp., Enterobacter spp. and Serratia spp. (MIC90s 0.06-0.25 mg/L), including ceftazidime-resistant isolates. Doripenem and meropenem were the most active agents among all beta-lactams against Pseudomonas aeruginosa (829 isolates; MIC50/90s 0.5/8 and 0.5/16 mg/L, respectively), whereas doripenem and imipenem were the most active agents against Acinetobacter spp. (155 isolates; MIC50/90s 0.5/4 and 相似文献   

In vitro activity of quinupristin/dalfopristin in comparison with five antibiotics against worldwide clinical isolates of staphylococci

Objective   To evaluate the in vitro activity of quinupristin/dalfopristin (Q/D), a streptogramin combination, in comparison with five antibiotics against worldwide clinical isolates of staphylococci.
Methods   A multicenter in vitro study was performed using the E test during a period of 3 months (April to June) in 1997 on fresh, clinically significant, non repetitive strains of staphylococci from patients hospitalized in 23 different hospitals in 18 countries tested.
Results   A total of 2132 staphylococcal isolates including methicillin resistant (MR), methicillin susceptible (MS) S. aureus (1003 MS, 462 MR), S. epidermidis (169 MS, 251 MR), S. haemolyticus (28 MS, 46 MR), S. hominis (28 MS, 16 MR), and coagulase negative staphylococci (86 MS, 43 MR) were analyzed.
Q/D was highly active against all species tested. MIC₉₀ (mg/L) ranged from 0.5 to 2 depending on the species. Strains had MIC≤1 mg/L in 97.6%. For S. aureus , S. epidermidis , S. hominis and other coagulase-negative staphylococci no differences in MIC₉₀ were observed for MS or MR. One dilution difference was observed for S. haemolyticus , which overall was the less susceptible species. Erythromycin resistance was observed among 57– 87% of MR-strains and was lower among MS-strains (18–56%). Erythromycin resistance had no or little influence on MIC of Q/D. In comparison to vancomycin, Q/D was two to four times more active.
Conclusions   The streptogramin combination Q/D showed an excellent in vitro activity against all staphylococcal species tested regardless of the resistance pattern to other drug classes, particularly resistance to methicillin. Q/D was two to four times more active than vancomycin and MIC values varied from 0.5–2 according to the species. The synergy of Q/D was well conserved in macrolide-resistant strains.     

Comparative activity of linezolid against staphylococci and enterococci isolated in Italy

The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC₉₀s for linezolid (2–4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC₉₀ 2–4 mg/L), glycopeptides and β -lactams. In E. faecium , only glycopeptides (MIC₉₀ 2 mg/L) and linezolid (MIC₉₀ 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.     

Activity of the new quinolone WCK 771 against pneumococci

The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.     

Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms

NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance ( mef and/or erm ) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8–64 compared to 1–32 (levofloxacin), 0.5 ≥ 32 (sparfloxacin) and 0.125–4 (moxifloxacin). Telithromycin MIC₅₀ and MIC₉₀ values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.     

Comparative in vitro activity of ertapenem against bacterial pathogens isolated from patients with lower respiratory tract infections

This study compared the in vitro activity of ertapenem, ceftriaxone, cefepime, ciprofloxacin and amoxicillin–clavulanate against 381 aerobic and facultative bacterial pathogens isolated from 320 patients with acute bacterial exacerbation of chronic bronchitis or community-acquired pneumonia. Streptococcus pneumoniae and Haemophilus influenzae accounted for 54.6% of the isolates. The ertapenem MIC was ≤2 mg/L for 98.4% of isolates and ≥8 mg/L for 1.0% (all methicillin-resistant Staphylococcus aureus ). Ertapenem had the most potent activity against Enterobacteriaceae, Moraxella catarrhalis , and methicillin-susceptible S. aureus , and its activity against H. influenzae and H. parainfluenzae , all strains of which were susceptible, was not altered by β -lactamase production. Only one S. pneumoniae strain, a penicillin-resistant isolate, was resistant to ertapenem. Ertapenem was highly active in vitro against pyogenic bacteria recovered from patients with community-acquired lower respiratory tract infections.     

Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci

BAL9141 has been reported to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), many enterococci, and streptococci with various resistant patterns. BAL9141 potency was assessed by time–kill curves alone or with subinhibitory concentrations of gentamicin (MIC/4). BAL9141 exhibited bactericidal activity alone against all the streptococci and staphylococci. Among ampicillin-susceptible enterococci, BAL9141 was bactericidal against some strains, but no BAL9141 inhibition was observed of ampicillin-resistant Enterococcus faecium . The activity of BAL9141 with gentamicin was slightly enhanced (not synergy) or indifferent against staphylococci. BAL9141 demonstrated bactericidal action alone against Enterococcus faecalis and some E. faecium strains (− 4.8 to −6.0 log₁₀ CFU/mL), but static effects were also noted. Drug interactions with gentamicin showed early synergy (4–8 h) for all enterococci, and indifference or synergy at 24 h (no antagonism). BAL9141 (≤8 mg/L) showed promising bactericidal activity alone and synergy with gentamicin against some of the vancomycin-resistant enterococci tested.     

Comparative in vitro activities of five quinolone antibiotics, including gemifloxacin, against clinical isolates

The in vitro activities of ciprofloxacin, ofloxacin, norfloxacin, levofloxacin and gemifloxacin against 343 clinical isolates were compared. Gemifloxacin showed the greatest activity, with MIC₉₀ values as low as 0.03–0.25 mg/L against Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , methicillin-susceptible Staphylococcus aureus and Klebsiella pneumoniae , while methicillin-resistant Staphylococcus aureus , Enterococcus spp., Pseudomonas spp., Acinetobacter spp., Escherichia coli and Enterobacter spp. strains exhibited low rates of susceptibility to all five fluoroquinolones.     

Activity of five quinolones, three macrolides and telithromycin against 12 Haemophilus influenzae strains with different resistance phenotypes

Gemifloxacin MICs for 12 Haemophilus influenzae strains with different resistance phenotypes were 0.001-0.015 mg/L. Gemifloxacin was bactericidal against all 12 strains after 24 h at 2 x MIC. Ciprofloxacin, levofloxacin, gatifloxacin and moxifloxacin had MICs of 0.008-0.03 mg/L and similar kill kinetics. Macrolides and telithromycin had unimodal MICs (1.0-8.0 mg/L), except for two strains without efflux systems (0.0125-0.5 mg/L) and two with efflux systems and ribosomal protein mutations (> 64.0 mg/L), and were bactericidal against eight to ten strains tested at 2 x MIC after 24 h.     

Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp., Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis

The activity of moxifloxacin was compared with that of other antimicrobial agents against 54 strains of Ureaplasma spp., 54 strains of Mycoplasma hominis , 14 strains of Mycoplasma genitalium , and 44 strains of Chlamydia trachomatis . Moxifloxacin inhibited 90% of all isolates at a concentration ≤1 mg/L, being the most active compound against C. trachomatis and sharing the highest activity with garenoxacin and gemifloxacin against mycoplasmas. Moxifloxacin killed the 30 mycoplasma isolates tested at a concentration ≤1 mg/L, except those resistant to fluoroquinolone. Thus, moxifloxacin has attracted interest as a potential therapy for mycoplasmal or chlamydial urogenital infections.     

In vitro activities of oral cephem and telithromycin against clinical isolates of major respiratory pathogens in Japan

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.     

Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 β-lactamase

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.     

Comparative study of the antibacterial activity of cefpodoxime against enterobacteria producing beta lactamases

Cefpodoxime proxetil (RU 51 807) is the oral prodrug of cefpodoxime (RU 51 763), a third generation cephalosporin. The antibacterial activity of cefpodoxime was compared with the activities of amoxicillin in combination with clavulanic acid (AUG), cefaclor (CCl), cefuroxime (CXM) and cefotaxime (CTX), against species of Enterobacteriaceae showing a resistance pattern against ampicillin (AMP), ticarcillin (TIC), cefalothin (CFT) and cefotaxime (CTX) respectively. For strains AMP and TIC R, CFT and CTX S, MICs 90% of cefpodoxime were 1 mg/l (E. coli), 0.5 (K. pneumoniae), 0.06 (P. mirabilis), 0.5 (Shigella sp.) and 1 (Salmonella sp.); they were 4 to 16 times as high for AUG -CCL -CXM and 4 to 16 times as low for CTX. For K. pneumoniae AMP and TIC R, CFT I/R and CTX S, similar résults were obsereved for the 5 beta-lactam antibiotics, but with an activity 10 times as low. Among the species AMP R, TIC S, CFT R and CTX S, cefpodoxime was active against P. rettgeri, P. stuartii, C. diversus, E. aerogenes and Y. enterocolitica (MICs 90% ranging from 2 to 4 mg/l; from 0.12 to 1 mg/l for CTX) and less active or inactive against P. vulgaris, E. cloacae, S. marcescens, M. morganii and E. coli (MICs 90% ranged from 16 to 32 mg/l; from 1 to 4 mg/l for CTX).(ABSTRACT TRUNCATED AT 250 WORDS)