Biomedical subjects

P C Appelbaum

Publications and source records attributed to P C Appelbaum.

At least 73 records · Page 4Linked to original sources

PubMed1999

Activity of HMR 3647 compared to those of six compounds against 235 strains of Enterococcus faecalis.

Agar dilution was used to test the activities of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, and quinupristin-dalfopristin against 235 strains of Enterococcus faecalis. HMR 3647 was the most active compound (MICs at which 50 and 90% of the isolates are inhibited [MIC50 and MIC90, respectively] of 0.06 and 4.0 microg/ml, respectively). The MIC50 and MIC90 (with the MIC50 given first and the MIC90 given second; both in micrograms per milliliter) for other compounds were as follows: 4.0 and >32.0 for erythromycin A, 16.0 and >32.0 for azithromycin, 2.0 and >32 for clarithromycin, 32.0 and >32.0 for roxithromycin, 32.0 and >32.0 for clindamycin, and 8.0 and 16.0 for quinupristin-dalfopristin. All compounds were only bacteriostatic.

Anti-Bacterial Agents↗

PubMed1999

Postantibiotic effects of gatifloxacin against gram-positive and -negative organisms.

Gatifloxacin pneumococcal, staphylococcal and enterococcal postantibiotic effects (PAEs) were 0.5 to 4.0 h, respectively. For Escherichia coli and Pseudomonas aeruginosa, PAEs were 2.2 to 4.8 h. Pneumococcal, staphylococcal, and enterococcal postantibiotic sub-MIC effects (PA-SMEs) (four times the MICs) were 3.7 to 8.6, 2.3 to 3.8, and 1.6 h, respectively, and E. coli and P. aeruginosa PA-SMEs were >/=9.6 and 4.4 h, respectively.

Anti-Infective Agents↗

PubMed1999

In vitro development of resistance to five quinolones and amoxicillin-clavulanate in Streptococcus pneumoniae.

The ability of 50 sequential subcultures in subinhibitory concentrations of ciprofloxacin, levofloxacin, grepafloxacin, sparfloxacin, trovafloxacin, and amoxicillin-clavulanate to select for resistance was studied for six penicillin-susceptible and four penicillin-intermediate pneumococci. Subculturing in ciprofloxacin, grepafloxacin, levofloxacin, and sparfloxacin led to selection of mutants requiring increased MICs for all 10 strains, with MICs rising from (i) 0.5 to 4.0 to (ii) 4.0 to 32.0 microgram/ml after 7 to 12 passages for ciprofloxacin, from (i) 0.06 to 0.25 to (ii) 0.5 to 8.0 microgram/ml after 5 to 23 passages for grepafloxacin, from (i) 0.5 to 1.0 to (ii) 4.0 to 64 microgram/ml after 14 to 49 passages for levofloxacin, and from (i) 0.125 to 0.25 to (ii) 1.0 to 16.0 microgram/ml after 8 to 26 passages for sparfloxacin. Subculturing in trovafloxacin led to increased MICs for eight strains, with MICs rising from (i) 0.06 to 0.125 to (ii) 0.5 to 8.0 microgram/ml after 6 to 28 passages. Subculturing in amoxicillin-clavulanate led to raised MICs for only one strain, with the MIC rising from 0.015 to 0. 125 microgram/ml after 24 passages. Double mutations in both ParC and GyrA led to high-level quinolone resistance when ParC mutations were at S79. Trovafloxacin MICs were 1 to 2 microgram/ml in double mutants with ParC mutations at positions other than S79 (e.g., D83). Mutations in ParE (at D435, R447, and E474) and GyrB (at S405, D406, and D435) were found in four and six mutants, respectively. In the presence of reserpine, 29 mutants had lower ciprofloxacin MICs (2 to 16 times lower), 8 mutants had lower levofloxacin MICs (2 times), and one mutant had a lower trovafloxacin MIC (2 times), suggesting the involvement of an efflux mechanism. In contrast to the case for quinolones, subculturing in the presence of amoxicillin-clavulanate did not select for resistance to this drug.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed1999

Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 U.S. Surveillance study.

The susceptibilities of Streptococcus pneumoniae (1,476 strains) and untypeable Haemophilus influenzae (1,676 strains) to various oral beta-lactam, macrolide-azalide, and fluoroquinolone antimicrobial agents were determined by broth microdilution. Organisms were isolated from specimens obtained from outpatients in six geographic regions of the United States. MIC data were interpreted according to pharmacodynamically derived breakpoints applicable to the oral agents tested. Among H. influenzae strains, 41.6% were beta-lactamase positive. Virtually all H. influenzae strains were susceptible to amoxicillin-clavulanate (98%), cefixime (100%), and ciprofloxacin (100%), while 78% were susceptible to cefuroxime, 57% were susceptible to amoxicillin, 14% were susceptible to cefprozil, 9% were susceptible to loracarbef, 2% were susceptible to cefaclor, and 0% were susceptible to azithromycin and clarithromycin. Among S. pneumoniae isolates, 49.6% were penicillin susceptible, 17.9% were intermediate, and 32.5% were penicillin resistant, with penicillin MICs for 50 and 90% of the isolates tested of 0.12 and 4 microg/ml, respectively. Overall, 94% of S. pneumoniae isolates were susceptible to amoxicillin and amoxicillin-clavulanate, 69% were susceptible to azithromycin and clarithromycin, 63% were susceptible to cefprozil and cefuroxime, 52% were susceptible to cefixime, 22% were susceptible to cefaclor, and 11% were susceptible to loracarbef. Although ciprofloxacin has marginal activity against S. pneumoniae, no high-level fluoroquinolone-resistant strains were found. Significant cross-resistance was found between penicillin and macrolides-azalides among S. pneumoniae isolates, with 5% of the penicillin-susceptible strains being macrolide-azalide resistant, compared with 37% of the intermediate isolates and 66% of the resistant isolates. Resistance was highest in S. pneumoniae isolates from patients younger than 10 years of age, middle ear and paranasal sinus specimens, and the southern half of the United States. With the continuing rise in resistance, judicious use of oral antimicrobial agents is necessary in all age groups.

Administration, Oral↗

PubMed1999

Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology.

Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2). Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC </= 2.0 microg/ml) against all anaerobes except Peptostreptococcus magnus and Bacteroides thetaiotaomicron, while pristinamycin MICs were 0.06 to 4.0 microg/ml. Amoxicillin-clavulanate had MICs of </=1.0 microg/ml, while metronidazole was active (MICs, 0.03 to 2.0 microg/ml) against all except Propionibacterium acnes. After 48 h at twice the MIC, telithromycin was bactericidal (>/=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed1999

Activities of clinafloxacin, alone and in combination with other compounds, against 45 gram-positive and -negative organisms for which clinafloxacin MICs are high.

Time-kill studies indicated that clinafloxacin showed synergy after 24 h with ceftazidime, amikacin, and imipenem against 12, 8, and 10 of 33 gram-negative rods, respectively; with vancomycin, teicoplanin, cefotaxime, and amikacin against 3, 3, 1, and 1 of 9 staphylococci and enterococci, respectively; and with vancomycin, penicillin, and cefotaxime against 0, 2, and 2 of 3 pneumococci, respectively. The MICs of clinafloxacin alone for most strains were >/=1 microg/ml.

Anti-Bacterial Agents↗

PubMed1999

Comparison of agar dilution, microdilution, E-test, and disk diffusion methods for testing activity of cefditoren against Streptococcus pneumoniae.

This study evaluated the susceptibility of pneumococci to cefditoren by agar dilution and microdilution methods (both in air) and by E-test (AB Biodisk, Solna, Sweden) and disk diffusion methods (both in CO(2)). By the three MIC tests, the MICs at which 50 and 90% of isolates were inhibited (MIC(50)s and MIC(90)s) were, respectively, as follows (in micrograms per milliliter): for the 65 penicillin-susceptible strains tested, 0.016 and 0.03 (by agar dilution), 0.016 and 0.03 (by microdilution), and 0.016 and 0.03 (by E test); for the 68 penicillin-intermediate strains tested, 0.125 and 0.5 (by agar dilution), 0.125 and 0.5 (by microdilution), and 0. 25 and 0.5 (by E test); and for the 67 penicillin-resistant strains tested, 1.0 and 1.0 (by agar dilution), 0.5 and 1.0 (by microdilution), and 1.0 and 1.0 (by E test). With tentative cefditoren breakpoints (in micrograms per milliliter) of </=2.0 (susceptible), 4.0 (intermediate), and >/=8.0 (resistant), all strains were susceptible to cefditoren by agar, microdilution, and E-test results; with breakpoints of </=1.0, 2.0, and >/=4.0 microg/ml, 97% of strains were cefditoren susceptible by agar dilution results, 98% were susceptible by microdilution results, and 99% were susceptible by E-test results. When microdilution and E-test results were compared to those from the reference agar dilution method, 191 (95.5%) and 183 (91.5%) of strains gave essential agreement (+/-1 log(2) dilution); 8 (2.7%) minor discrepancies were found for both methods with a breakpoint of </=1. 0 microg/ml, and no discrepancies were found with a breakpoint of </=2.0 microg/ml. Disk test results (breakpoint, </=1.0 microg/ml) produced 2 major and 30 minor errors, with corresponding zone diameters (in millimeters) of >/=20 (susceptible), 17 to 19 (intermediate), and </=16 (resistant); a </=2.0-microg/ml breakpoint yielded zone diameters of >/=16 mm (susceptible). All three methods for testing the MIC of cefditoren showed excellent correlation.

Cephalosporins↗

PubMed1999

Quinolone activity against anaerobes.

The first generation of fluoroquinolones such as ciprofloxacin and ofloxacin are inactive against most anaerobic bacteria. However, some broad-spectrum quinolones, which have recently become clinically available or are under active development, have significant antianaerobic activity. This review summarises the in vitro activity of currently available, as well as experimental, quinolones against clinically significant anaerobic bacteria. Quinolones with low activity against anaerobes include ciprofloxacin, ofloxacin, levofloxacin, fleroxacin, pefloxacin, enoxacin and lomefloxacin. Compounds with intermediate antianaerobic activity include sparfloxacin and grepafloxacin. Trovafloxacin, gatifloxacin and moxifloxacin yield low MICs against most groups of anaerobes. Quinolones with the greatest in vitro activity against anaerobes include clinafloxacin and sitafloxacin (DU-6859a).

4-Quinolones↗

PubMed1998

Synergistic activity of trovafloxacin with other agents against gram-positive and -negative organisms.

The synergistic activity of trovafloxacin with other agents against 55 Gram-positive and -negative bacteria was determined by checkerboard titration. Synergistic fractional inhibitory concentration (FIC) indices (< or = 0.5) were seen in two methicillin-susceptible and one methicillin-resistant Staphyloccocus aureus with teicoplanin, one of each of the latter two with vancomycin; one methicillin-resistant coagulase-negative Staphylococcus with rifampin and one with fusidic acid; five Stenotrophomonas maltophilia with cefoperazone; three Pseudomonas aeruginosa with ticarcillin/clavulanate, four with aztreonam, two with ceftazidime, one with tobramycin, one with cefoperazone, and one with ceftriaxone; one pneumococcus with ceftriaxone; one Enterococcus faecalis with ceftriaxone, and one with vancomycin; two Bacteroides fragilis with metronidazole, two with clindamycin, and one with cefoxitin; and one Clostridium perfringens with metronidazole and one with clindamycin. All other FIC indices were additive/indifferent (0.51-2.0), and no antagonistic FIC indices (> 4.0) were observed.

Anti-Infective Agents↗

PubMed1998

Anti-anaerobic activity of erythromycin, azithromycin and clarithromycin: effect of pH adjustment of media to compensate for pH shift caused by incubation in CO2.

The activity of erythromycin, azithromycin and clarithromycin against 112 anaerobes was tested by the Oxyrase agar dilution MIC method at pH 7.2 without supplemental CO2 and by an agar dilution MIC method in CO2 with media adjusted to pH 8.0. MICs (mg/L) of erythromycin, azithromycin and clarithomycin against Bacteroides fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741 were similar by the two methods. MICs for 94 clinical isolates tested by the two methods were within two dilutions of each other. Eighteen additional isolates required CO2, and did not grow in Oxyrase. With the exception of fusobacteria, with which azithromycin yielded the lowest MICs, clarithromycin had the lowest MICs with both methods. These results show that the pH effect of incubation in CO2 can be avoided by using the Oxyrase method, or by incubating in CO2 with pH adjusted to 8.0. The latter method has the advantage of allowing testing of strains requiring CO2.

Anti-Bacterial Agents↗

PubMed1998

In vitro selection of resistance to four beta-lactams and azithromycin in Streptococcus pneumoniae.

Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 microg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 microg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin MICs (0.5 to >256.0 microg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 microg/ml) for three of the six strains, with MICs of other beta-lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 microg/ml to 0.125 to 0.5 microg/ml) for all six strains without significantly altering the MICs of other beta-lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin did not affect beta-lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for beta-lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 microg/ml after 19 passages. In contrast to strains that were initially azithromycin susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin MICs of 0.125 to 4.0 microg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 microg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin contained ermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.

Anti-Bacterial Agents↗

PubMed1998

Postantibiotic effect and postantibiotic sub-MIC effect of quinupristin-dalfopristin against gram-positive and -negative organisms.

Quinupristin-dalfopristin produced postantibiotic effects (PAEs) and postantibiotic sub-MIC effects of >2 h against 18 gram-positive cocci. Mean pneumococcal and staphylococcal PAEs were 2.8 and 4.7 h, respectively, with shorter PAEs for constitutively than inducibly macrolide-resistant staphylococci. Mean PAEs for vancomycin-susceptible and -resistant Enterococcus faecium were 8.5 and 2.6 h, respectively.

Anti-Bacterial Agents↗

PubMed1998

Activity of HMR 3647 compared to those of five agents against Haemophilus influenzae and moraxella catarrhalis by MIC determination and time-kill assay.

The microdilution MICs of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, and pristinamycin against 50/90% of 249 Haemophilus influenzae and 50 Moraxella catarrhalis isolates were 2/4, 0.06/0.125; 8/16, 0.25/0.25; 2/4, 0.06/0.125; 16/16, 0.25/0.25; 32/>32, 1/2; and 2/4, 0.5/0.5 microg/ml. Azithromycin was bactericidal against all 10 H. influenzae and 3 of 5 M. catarrhalis isolates and HMR 3647, erythromycin A, clarithromycin, roxithromycin, and pristinamycin were bacteriostatic, against all 15 strains after 24 h at the MIC.

Anti-Bacterial Agents↗

PubMed1998

In vitro activities of cefminox against anaerobic bacteria compared with those of nine other compounds.

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.

Anti-Bacterial Agents↗

PubMed1998

Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media.

The management of acute otitis media is complicated by the emergence of resistance to beta-lactam and other antibiotics among common pathogens. We conducted a large, international study of infants and children with acute otitis media to identify pathogens and susceptibility patterns. During the winter of 1994 to 1995, middle ear fluid samples were collected from 917 patients with acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia, Israel, and the United States. A single reference laboratory performed in vitro susceptibility testing. Pathogens were isolated from 62% of the patients. For Streptococcus pneumoniae (30% of the patients), untypeable Haemophilus influenzae (17%), and Moraxella catarrhalis (4%), there was significant variation among geographic regions (P < 0.001). The composite susceptibilities of these three organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate ranged from 90% in Israel to 95% in Eastern and Central Europe. beta-Lactamase was produced by 31 and 100% of the isolates of H. influenzae and M. catarrhalis, respectively. More isolates of S. pneumoniae were susceptible to amoxicillin (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%; P = 0.002). The prevalence of resistant S. pneumoniae was highest in patients less than 12 months of age. S. pneumoniae, H. influenzae, and M. catarrhalis remain the most important bacterial pathogens in patients with acute otitis media; however, their prevalence is variable and resistance patterns are changing.

Acute Disease↗

PubMed1998

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents.

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.

Anti-Bacterial Agents↗

PubMed1998

Activities and time-kill studies of selected penicillins, beta-lactamase inhibitor combinations, and glycopeptides against Enterococcus faecalis.

The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were tested against 212 Enterococcus faecalis strains (9 beta-lactamase producers) by standard agar dilution MIC testing (10[4] CFU/spot). The MICs at which 50 and 90% of the isolates were inhibited (MIC50s and MIC90s, respectively) were as follows (microg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and 1. Agar dilution MIC testing of the nine beta-lactamase-positive strains with an inoculum of 10(6) CFU/spot revealed higher beta-lactam MICs (piperacillin, 64 to >256 microg/ml; ticarcillin, 128 to >256 microg/ml; and ampicillin, 16 to 128 microg/ml); however, MICs with the addition of inhibitors were similar to those obtained with the lower inoculum. Time-kill studies of 15 strains showed that piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24 h at four times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Ampicillin gave 99.9% killing of 14 beta-lactamase-negative strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate was slower than that observed for piperacillin-tazobactam, relative to the MIC. For the one beta-lactamase-producing strain tested by time-kill analysis with a higher inoculum, addition of the three inhibitors (including sulbactam) to each of the beta-lactams resulted in bactericidal activity at 24 h at two times the MIC. For an enzyme-negative strain, addition of inhibitors did not influence kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than those of the beta-lactams, with bactericidal activity against 6 strains after 24 h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at four times the MIC. Slower-kill kinetics by both glycopeptides were observed at earlier periods.

Anti-Bacterial Agents↗

PubMed1998

Determination of activities of levofloxacin, alone and combined with gentamicin, ceftazidime, cefpirome, and meropenem, against 124 strains of Pseudomonas aeruginosa by checkerboard and time-kill methodology.

A total of 124 Pseudomonas aeruginosa strains were tested for synergy between levofloxacin and cefpirome, ceftazidime, gentamicin, and meropenem. Checkerboards yielded synergistic fractional inhibitory concentration (FIC) indices (< or =0.5) with 25 of 496 possible combinations. All other FIC indices were >0.5 to 2 (additive or indifferent), with no antagonism. Time-kill studies with 12 strains showed that levofloxacin (0.06 to 0.5 microg/ml) was synergistic with cefpirome, ceftazidime, gentamicin, and meropenem in 10, 9, 4, and 11 strains, respectively.

Anti-Bacterial Agents↗