Antibiotic susceptibility to microorganisms isolated in blood cultures of patients an the Ignacio Chavez National Institute of Cardiology

A microdilution method was utilized for determining susceptibility to several antimicrobial agents in 142 bacterial blood culture isolates obtained during a one year period. Associated clinical features were also identified. Three cases of polymicrobial bacteriemia were found. Endocarditis was the most frequent source of bacteriemia (28.5%) and the viridans streptococci were the most frequently isolated microorganism (53%). Surprisingly, half of the bacteriemic episodes corresponded to a nosocomial infection most of which were due to staphylococci (25%) and Enterobacter sp (22%). Viridans streptococci group were 61.5% resistant to penicillin (MIC > 0.12 micrograms/mL). These strains also showed a 31% resistance to ceftriaxone (MIC > 8 micrograms/mL). The staphylococcal strains showed a 19% resistance to oxacillin; this resistance occurred for coagulase negative staphylococcis in 32% (6/19) and for S. aureus in 9% (2/22). All Gram-positive microorganisms were susceptible to vancomycin. The enterobacteria group were susceptible to most antimicrobial agents; nevertheless this group showed a 45% resistance to amikacin. In contrast, the non enterobacteria group were resistant to most of the antimicrobial agents tested except to imipenem, ceftazidime and ciprofloxacin. When comparing susceptibility longitudinally, no significative changes were identified, but a significant increase was found in MIC50-90 to amikacin and cephalothin when testing S. aureus, and cefoperazone in the non enterobacteria group.     

Inducible amp C beta-lactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE)

A surveillance study of nosocomial blood stream infections [Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)] was conducted during a 14-month period in 1995 to 1996 in approximately 50 American medical centers. Among the 4725 blood stream infections, the etiologic agent was Enterobacter spp. in 230, Citrobacter freundii in 24, and Serratia marcescens in 65. The vast majority of these isolates (89%) had been sent to the University of Iowa including 198 Enterobacter spp. (46 Enterobacter aerogenes, 141 Enterobacter cloacae, 11 other Enterobacter spp.), 23 C. freundii, and 62 S. marcescens. Because these species are capable of producing Amp C beta-lactamase, we examined their susceptibility to 12 broad-spectrum antimicrobial agents. The frequency of resistance to ceftazidime and the molecular epidemiology of ceftazidime-resistant strains was also examined. Among the Enterobacter spp. and C. freundii isolates, resistance to third generation cephalosporins (ceftazidime, ceftriaxone) and broad-spectrum semisynthetic penicillins (piperacillin), with or without an enzyme inhibitor (piperacillin/tazobactam), was high, e.g., 35 to 50%. The S. marcescens isolates were quite susceptible to all agents tested. Both imipenem and cefepime were active against virtually all isolates tested including 84 stably derepressed Amp C-producing ceftazidime-resistant strains of Enterobacter spp. and C. freundii. The overall rank order of activity for the six best agents against these Amp C-producing strains was: imipenem (100% susceptible) > amikacin = cefepime (98.6%) > ciprofloxacin = gentamicin = ofloxacin (93.6 to 94.0%). Molecular typing studies of ceftazidime-resistant E. cloacae using an automated ribotyping system, as well as pulsed-field gel electrophoresis, indicated that although clonal spread of a single strain occurred in some of the medical centers, most of the episodes of bacteremia were caused by patient-unique strains. Control of these resistant organisms will require attention to microbiologic recognition of phenotypes, to infection control practices, and to limiting the overuse of certain extended spectrum beta-lactams.     

Tissue water content in rats measured by desiccation

The in vitro activity of cefepime was compared to that of ceftazidime, ceftriaxone, and cefotaxime in a multicenter study involving 10 clinical microbiology laboratories and clinical isolates from 18 Brazilian hospitals from 7 cities (4 states). A total of 982 isolates consecutively collected between December 1995 and March 1996 were susceptibility tested by using Etest and following the NCCLS procedures for agar diffusion tests. The cefepime spectrum was broader than that of the other broad-spectrum cephalosporins against both Gram-negative rods and Gram-positive cocci. Cefepime was particularly more active against Enterobacter sp. (MIC90, 2 micrograms/ml), Serratia sp. (MIC90, 2 micrograms/ml) and oxacillin-susceptible Staphylococcus aureus (MIC90, 3 micrograms/ml). Against Pseudomonas aeruginosa, cefepime (MIC90, 16 micrograms/ml) was slightly more active than ceftazidime (MIC90, 32 micrograms/ml) and 8- to 16-fold more active than ceftriaxone of cefotaxime (MIC90, > 256 micrograms/ml). Our results show that nosocomial bacteria, especially Gram-negative rods, have a high rate of cephalosporin resistance in Brazil. However, part of these resistant bacteria remains susceptible to cefepime. The Etest was shown to be an excellent method for multicenter studies of the in vitro evaluation of new antimicrobial agents.     

Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada

A total of 200 medical center laboratories in the USA and Canada contributed results of testing quinupristin-dalfopristin, a streptogramin combination (formerly RP 59500 or Synercid), against 28,029 Gram-positive cocci. Standardized tests [disk diffusion, broth microdilution, Etest (AB BIODISK, Solna, Sweden)] were utilized and validated by concurrent quality control tests. Remarkable agreement was obtained between test method results for characterizing the collection by the important emerging resistances: 1) oxacillin resistance among Staphylococcus aureus (41.0 to 43.7%); 2) vancomycin resistance among Enterococcus faecium (50.0 to 52.0%); and 3) the penicillin nonsusceptible rate for pneumococci (31.1% overall, with 10.6% at MICs of > or = 2 micrograms/mL). The quinupristin-dalfopristin MIC90 for oxacillin-susceptible and -resistant S. aureus was 0.5 microgram/mL and 1 microgram/mL, respectively. The quinupristin-dalfopristin MIC90 for vancomycin-resistant E. faecium was 1 microgram/mL, and only 0.2% of isolates were resistant. Other Enterococcus species were generally not susceptible to the streptogramin combination but were usually inhibited by ampicillin (86 to 97% susceptible; MIC50, 1.0 microgram/mL) or vancomycin (86 to 95%; MIC50, 1.0 microgram/mL). Among all tested enterococci, the rate of vancomycin resistance was 16.2%. The quinupristin-dalfopristin MIC90 (0.75 microgram/mL) for 4,626 tested Streptococcus pneumoniae strains was not influenced by the penicillin or macrolide susceptibility patterns. When five regions in the USA and Canada were analyzed for significant streptogramin and other antimicrobial spectrum differences, only the Farwest region had lower numbers of streptogramin-susceptible E. faecium. Canadian strains were generally more susceptible to all drugs except chloramphenicol and doxycycline when tested against E. faecalis (73% and 89% susceptible, respectively). The U.S. Southeast region had S. pneumoniae strains less susceptible to macrolides (73%) but had more susceptibility among E. faecium isolates tested against vancomycin and ampicillin. The Northeast region of the USA had the greatest rate of vancomycin resistance among enterococci. Strains retested by the monitor because of quinupristin-dalfopristin resistance (MICs, > or = 4 micrograms/mL) were generally not confirmed (2.2% validation), and only 0.2% of E. faecium isolates were identified as truly resistant. The most common errors were: 1) species misidentification (28.0%); 2) incorrect susceptibility results (65.6%); and 3) mixed cultures (4.3%) tested by participants. Overall, quinupristin-dalfopristin was consistently active (> or = 90% susceptible) against major Gram-positive pathogens in North America, regardless of resistance patterns to other drug classes and geographic location of their isolation.     

Increased prevalence of penicillin-resistant viridans group streptococci in Japanese children with upper respiratory infection treated by beta-lactam agents and in those with oncohematologic diseases

BACKGROUND: Viridans group streptococci, especially penicillin-resistant strains, have been emerging as pathogens of bacteremia in neutropenic patients with hematologic malignancies. OBJECTIVES: To survey the penicillin susceptibilities of viridans group streptococci in Japanese children with and without oncohematologic diseases and to evaluate the effect of the short term administration of beta-lactam agents on the antibiotic susceptibility. METHODS: We tested 113 isolates of viridans group streptococci by the microdilution method for the minimal inhibitory concentrations (MICs) to 10 antibiotics. We isolated 40 isolates from the throats of children with an upper respiratory infection (URI) before beta-lactam antibiotic treatment, 32 isolates after the treatment, 33 isolates in hospitalized children with oncohematologic diseases and 8 isolates from blood. RESULTS: Twenty-five isolates (62.5%) from the children with URI before treatment were penicillin-intermediate or -high level resistant (MIC > or = 0.25 microg/ml). The prevalence of those isolates after antibiotic treatment (87.5%) was significantly increased compared with that before treatment (P = 0.03). The prevalences of the penicillin-high level resistant isolates (MIC > or = 4 microg/ml) in the children with oncohematologic diseases (39.4%) and in the isolates from blood (62.5%) were significantly higher than that in the children with URI before treatment (12.5%) (P < 0.01). Decreased susceptibilities to other beta-lactam agents were observed in the penicillin-high level resistant strains. CONCLUSIONS: The high prevalence of penicillin-intermediate or -high level resistant viridans group streptococci in healthy Japanese children was documented. The administration of beta-lactam agents decreased the prevalence of penicillin-susceptible isolates in the children with URI. High prevalences of penicillin-high level resistant isolates were observed in the oncohematologic patients and in the isolates from blood.     

Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein

The in vitro activity of trovafloxacin, a new fluoroquinolone, was compared with that of ciprofloxacin, ofloxacin, fleroxacin, ceftazidime, piperacillin/tazobactam, and meropenem against 613 consecutively recovered blood isolates from recently hospitalized patients. Susceptibility testing was performed by agar dilution according to NCCLS guidelines. Test strains included Acinetobacter species (n = 26), Escherichia coli (n = 137), Enterobacter species (n = 27), Klebsiella species (n = 42), Proteus species (n = 16), Pseudomonas aeruginosa (n = 28), Serratia marcescens (n = 13), Stenotrophomonas maltophilia (n = 7), enterococci (n = 54), coagulase-negative staphylococci (n = 38), Staphylococcus aureus (n = 137), Streptococcus pneumoniae (n = 27), beta-haemolytic streptococci (n = 13), and viridans group streptococci (n = 48). The overall respective MICs at which 50% and 90% of isolates were inhibited (MIC50s and MIC90s) were as follows: trovafloxacin, 0.06 and 1 mg/l; ciprofloxacin, 0.25 and 4 mg/l; ofloxacin, 0.5 and 4 mg/l; fleroxacin, 0.5 and 16 mg/l; ceftazidime, 2 and 128 mg/l; piperacillin/tazobactam, 2 and 8 mg/l; meropenem, 0.06 and 4 mg/l. For the quinolones, the rank order of activity against gram-negative microorganisms was ciprofloxacin > trovafloxacin > ofloxacin = fleroxacin, against gram-positive organisms, trovafloxacin > ciprofloxacin = ofloxacin > fleroxacin. Data obtained showed the similar activity of trovafloxacin and ciprofloxacin against gram-negative pathogens and the superior activity of trovafloxacin against gram-positive bacteria thus making it a potential candidate for the empiric treatment of patients with suspected bacteremia and sepsis.     

Comparison of antimicrobial susceptibilities of Corynebacterium species by broth microdilution and disk diffusion methods

Corynebacterium species are increasingly being implicated in foreign-body infections and in immunocompromised-host infections. However, there are no specific recommendations on the method or the criteria to use in order to determine the in vitro activities of the antibiotics commonly used to treat Corynebacterium infections. The first aim of our study was to compare the susceptibilities of various species of Corynebacterium to vancomycin, erythromycin, and penicillin by using a broth microdilution method and a disk diffusion method. Second, the activity of penicillin against our isolates was assessed by using the interpretative criteria recommended by the National Committee for Clinical Laboratory Standards for the determination of the susceptibility of streptococci and Listeria monocytogenes to penicillin. Overall, 100% of the isolates were susceptible to vancomycin, while considerable variations in the activities of erythromycin and penicillin were noted for the different species tested, including the non-Corynebacterium jeikeium species. A good correlation in the susceptibilities of vancomycin and erythromycin between the disk diffusion and the microdilution methods was observed. However, a 5% rate of major or very major errors was detected with the Listeria criteria, while a high rate of minor errors (18%) was noted when the streptococcus criteria were used. Our findings indicate considerable variations in the activities of erythromycin and penicillin against the various species of Corynebacterium. Because of the absence of definite recommendations, important discrepancies were observed between the methods and the interpretations of the penicillin activity.     

Antibiotic sensitivity of important pathogens of bacterial respiratory tract infections in Northeast Germany

BACKGROUND: There is still a lack of comprehensive study results about resistance of bacterial respiratory pathogens from the east of the Federal Republic of Germany. METHODS: In Greifswald we isolated in 1995 and 1996 320 strains of typical pathogens and tested their susceptibility to 14 antibiotics, using the microbouillon dilution method. RESULTS: Pneumococci and beta-haemolytic streptococci were completely susceptible to penicillin and all other beta-lactam-antibiotics, clindamycin and vancomycin. 4.8% of pneumococci and 10.0% of Streptococcus pyogenes isolates were resistant to erythromycin. This should lead to a more differentiated use of macrolides as concerns these pathogens, especially as penicillin still has high efficacy in these cases. Pneumococci had resistance rates of 4.8%, 9.5% and 6.7% to cotrimoxazole, tetracycline and ofloxacin, respectively. No strain of Haemophilus influenzae produced a beta-lactamase, 2.6% of strains were relatively resistant to ampicillin, even in combination with sulbactam. Cefaclor, erythromycin and tetracycline had restricted efficacy of 16.7%, 14.1% and 53.8%, respectively. Cefuroxime, cefixime, cefepime, imipenem and ofloxacin all had complete efficacy. 77.8% of Moraxella catarrhalis isolates were beta-lactamase positive. Strains were susceptible to erythromycin, ofloxacin and all tested beta-lactam-antibiotics except ampicillin and cefaclor. There was a relative resistance to clindamycin and tetracyclin of 22.2% and 2.2%, respectively. DISCUSSION: We present our results in national and international comparison, describe tendencies of resistance, give reasons for the low incidence of penicillin resistance in pneumococci in Germany and draw conclusions for empirical chemotherapy.     

Antipneumococcal activities of RP 59500 (quinupristin-dalfopristin), penicillin G, erythromycin, and sparfloxacin determined by MIC and rapid time-kill methodologies

Previous time-kill studies have shown that RP 59500 is rapidly bactericidal against pneumococci. To extend these findings, the activities of RP 59500, its two components RP 57669 RP 54476, penicillin G, erythromycin and sparfloxacin against 26 penicillin-susceptible, 25 penicillin-intermediate, and 25 penicillin-intermediate, and 25 penicillin-resistant pneumococci were determined by the agar dilution MIC and the time-kill testing methodologies within 10 min (ca. 0.2 h) and at 1 and 2 h. Respective agar dilution MICs at which 90% of isolates are inhibited for penicillin-susceptible, -intermediate, and -resistant strains were as follows: penicillin G, 0.03, 1, and 4 micrograms/ml;RP 59500, 1, 1, and 1 microgram/ml; RP 57669, 8, 32, and 16 micrograms/ml; RP 54476, > 128, > 128, and > 128 micrograms/ml; erythromycin, 0.06, 2, and > 128 micrograms/ml; and sparfloxacin, 1, 0.5, and 0.5 microgram/ml. RP 59500 was equally active (MIC at which 90% of isolates are inhibited, 1.0 microgram/ml) against erythromycin-susceptible and -resistant strains. Time-kill testing results showed that only RP 59500 at one to four times the MIC killed pneumococci at 0.2 h; RP 59500 was also the most active compound at 1 and 2 h. By comparison, penicillin and sparfloxacin at one, two, and four times the MICs reduced the original inoculum by > or = 1 log at 2 h for 46, 80, and 95% and for 50, 72, and 86% of strains, respectively. The killing activity of RP 59500 was the same against erythromycin-susceptible and -resistant strains. RP 57669, RP 54479, and erythromycin were either inactive or bacteriostatic at 2 h. Of all drugs tested, RP 59500 yielded the most rapid killing.     

From outcomes research to disease management: a guide for the perplexed

Dirithromycin is a new macrolide antibiotic that is effective against group A beta-hemolytic streptococcal pharyngotonsillitis. This prospective, multicenter, randomized study compared the serum and tonsil tissue concentrations of erythromycylamine (to which dirithromycin is rapidly converted by nonenzymatic hydrolysis during absorption) and erythromycin after 5- and 10-day regimens of dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive dirithromycin 500 mg orally once daily (n = 22) or erythromycin base 250 mg orally four times daily (n = 17). Data from 12 patients receiving dirithromycin and 10 receiving erythromycin were eligible for analysis. Mean serum concentrations (+/-standard deviation) of erythromycylamine and erythromycin were 0.20 +/- 0.07 microgram/mL and 0.12 +/- 0.25 microgram/mL, respectively, after the 5-day regimen and 0.17 +/- 0.10 microgram/mL and 1.57 +/- 3.16 micrograms/mL, respectively, after the 10-day regimen. The mean serum concentration of erythromycin after 10 days was skewed by the data for one of the six patients in the group (concentration of > 8 micrograms/mL). Mean concentrations of erythromycylamine in tonsil tissue were 4.62 +/- 0.97 micrograms/ g after 5 days and 3.47 +/- 2.84 micrograms/g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patients given erythromycin for 10 days. The high concentrations of erythromycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis with dirithromycin.     

Interpretation of Mini-Mental State Examination scores in community-dwelling elderly and geriatric neuropsychiatry patients

Detection of Klebsiella pneumoniae strains with extended-spectrum beta-lactamase (ESBL)-related resistance phenotypes is becoming important in clinical microbiology laboratories. In this study, we investigated the usefulness of three screening methods, the Etest ESBL screen, the double-disk synergy test, and the ceftazidime disk test, for identifying ESBL-producing K. pneumoniae strains. The agar dilution method was used as the standard. We also determined the in vitro activity of several new antimicrobial agents against these organisms. Strains that exhibited an increase in the minimum inhibitory concentration (MIC) to the third-generation cephalosporins or aztreonam of 2 micrograms/mL or more, but were susceptible to the three cephamycins tested, were considered to have ESBL-related resistance phenotypes. The frequency of ESBL-producing K. pneumoniae isolates (according to the disk-diffusion method) has increased markedly in recent years, from 3.4% in 1993 to 10.3% in 1997. A total of 93 preserved isolates of K. pneumoniae collected from December 1995 through March 1997 were found to be resistant to at least one of the third-generation cephalosporins (cefotaxime and ceftazidime) or aztreonam using the routine disk diffusion method. Among these isolates, 35 were classified as having an ESBL phenotype using the agar dilution method. The remaining 58 isolates were classified as cephamycin resistant, which indicated resistance to both cephamycins and third-generation cephalosporins or aztreonam. The susceptibility rates of the ESBL-producing isolates were 11% for cefotaxime, 14% for ceftazidime, and 6% for aztreonam. The susceptibility rates of these 35 isolates to imipenem, ciprofloxacin, and ofloxacin were 100%, 80%, and 86%, respectively. Both the MIC50 and MIC90 of meropenem were 0.06 microgram/mL, while the MIC50 and MIC90 of BAY 12-8039 were 0.125 and 2 micrograms/mL, respectively. Thirty-two (91%) of the 35 isolates of K. pneumoniae with the ESBL-related resistance phenotype were detected by the Etest ESBL screen, while the ceftazidime disk screen test detected 77% of these isolates, and the double-disk synergy test detected 74%. The Etest ESBL screen appears to be an acceptable, convenient, and sensitive method for the detection of ESBL-producing isolates in the clinical microbiology laboratory.     

Resistance to antibiotics of Streptococcus pneumoniae strains

Streptococcus pneumoniae strains are exhibiting increasing rates of antibiotics resistance. A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents and therefore this paper describes the study of resistance and multiresistance of pneumococci to 7 antibiotics: penicillin (P), erythromycin (E), clindamycin (CC), tetracycline (T), co-trimoxazole (SXT), cefotaxime (CTX) and vancomycin (Va), using the disk-diffusion technique according to NCCLS procedure. We tested a total of 218 S. pneumoniae strains isolated from various materials: from sputum (54), noses (117), throats (28) and different swabs specimens (19). The overall percentage of resistant isolates to penicillin was 3.7%, to erythromycin--4.1%, to clindamycin--10.6%, to tetracycline--17.4%, to co-trimoxazole--15.6%, to cefotaxime--2.3%. In the sputum was most the monoresistant strains (66.7%). The multiresistance was highest in the penicillin resistant pneumococci. With the exception of vancomycin, the number of resistant strains to non-beta-lactam antibiotics (erythromycin, clindamycin, tetracycline, co-trimoxazole) was higher in penicillin-resistant strains compared with penicillin susceptible isolates. All isolates were susceptible to vancomycin.     

Decreased nitrogen rates and irrigation effect on celery yield and internal quality

Sparfloxacin, a new orally administered fluoroquinolone, was tested against 14,182 clinical strains isolated (generally blood stream and respiratory tract cultures) at nearly 200 hospitals in the United States (USA) and Canada. Sparfloxacin activity was compared with 13 other compounds by Etest (AB BIODISK, Solna, Sweden), broth microdilution, or a standardized disk diffusion method. Using the Food and Drug Administration/product package insert MIC breakpoint for sparfloxacin susceptibility (< or = 0.5 microgram/ml), 94% of Streptococcus pneumoniae (2666 isolates) and 89% of the other streptococci (554 isolates) were susceptible. However, at < or = 1 microgram/ml (the breakpoint for all nonstreptococcal species) sparfloxacin susceptibility rates increased to 100% and 98%, respectively, for the two groups of streptococci. Only 50% and 65% of pneumococci were susceptible to ciprofloxacin (MIC90, 3 micrograms/ml) and penicillin (MIC90, 1.5 micrograms/ml), respectively. Although there were significant differences between regions in the USA in the frequency of penicillin-resistant pneumococcal strains, results indicate that the overall sparfloxacin MIC90 was uniformly at 0.5 microgram/ml. Nearly all (> or = 99%) Haemophilus species and Moraxella catarrhalis, including those harboring beta-lactamases, were susceptible to sparfloxacin, ciprofloxacin, and amoxicillin/clavulanic acid. Only cefprozil and macrolides demonstrated lower potency and spectrum against these two species. Sparfloxacin was active against oxacillin-susceptible Staphylococcus aureus (96 to 97%), Klebsiella spp. (95%), and other tested enteric bacilli (93%). Comparison between broth microdilution MIC and disk diffusion interpretive results for M. catarrhalis, Staphylococcus aureus, and the Enterobacteriaceae showed an absolute intermethod categorical agreement of > 95% using current sparfloxacin breakpoints, in contrast to those of cefpodoxime for S. aureus where a conspicuous discord (98% versus 59%) between methods was discovered. These results demonstrate that sparfloxacin possesses sufficient in vitro activity and spectrum versus pathogens that cause respiratory tract infections (indications), especially strains resistant to other drug classes such as the earlier fluoroquinolones, oral cephalosporins, macrolides, and amoxicillin/clavulanic acid. The sparfloxacin susceptibility breakpoint for streptococci may require modification (< or = 1 microgram/ml) based on the MIC population analysis presented here. A modal MIC (0.38 to 0.5 microgram/ml) was observed at the current breakpoint. Regardless, sparfloxacin inhibited 89% (nonpneumococcal Streptococcus spp.) to 100% (Haemophilus spp., M. catarrhalis) of the isolates tested with a median activity of 97% against indicated species.     

Myocardial ischemic tolerance following heat stress is abolished by ATP-sensitive potassium channel blockade

The purpose of this study was to compare the effect, both in vitro and in vivo, of cefepime with those of four other cephalosporins, namely ceftriaxone, cefotaxime, cefuroxime and cephalothin, against penicillin-resistant pneumococci. One hundred pneumococcal strains, 31 penicillin-susceptible, 30 penicillin-intermediate-resistant and 39 penicillin-resistant pneumococci, were used in MIC studies. Time-kill experiments were carried out for four strains. In the mouse peritonitis model, the dose that gave protection to 50% of mice challenged with a lethal dose of pneumococci (ED50) was determined for three pneumococci and five cephalosporins. The MICs of all five cephalosporins and penicillin correlated significantly with each other. In vitro, the most potent cephalosporins against pneumococci were cefotaxime, ceftriaxone and cefepime, followed by cefuroxime and cephalothin. In time-kill experiments, carried out for four pneumococci, no differences were found in the killing effect of these five cephalosporins in relation to MICs. In the mouse peritonitis model, there was no significant correlation between log(MIC) and log(ED50) for the five cephalosporins against three pneumococci (Spearman's rho = 0.39, P = 0.16). However, if the values for cefepime against the three pneumococci were excluded, there was a significant correlation for the remaining four cephalosporins (Spearman's rho = 0.62, P = 0.04). For all three pneumococci, the ED50s of cefepime were lower than expected from the MICs. It was not possible to explain this beneficial difference in the effect of cefepime in terms of in-vitro bactericidal activities, serum protein binding or pharmacodynamic parameters.     

Stenotrophomonas (Xanthomonas) maltophilia: in vitro susceptibility to selected antimicrobial drugs, single and combined, with and without defibrinated human blood

Sixteen selected isolates of Stenotrophomonas maltophilia varied in susceptibility to the combined phagocytic/serum bactericidal activity of fresh defibrinated human blood (65 vol%). Four representative isolates (X1, X11, X25, and X50), which differed in susceptibility to cefepime, ceftazidime, rifampin, and timentin, were subjected to checkerboard microtiter broth dilution tests involving combinations of cefepime plus timentin, ceftazidime plus ofloxacin, cotrimoxazole plus timentin, rifampin plus polymyxin B, and rifampin plus polymyxin B nonapeptide; all combinations yielded additive or synergistic effects against all four strains. Unexpectedly, the combination of cefepime plus timentin was bactericidally active against the two cefepime-resistant isolates. This finding was substantiated by blood/broth plus combined antimicrobial drug assays. Cefepime plus timentin effectively killed all four test strains. Ofloxacin combined with ceftazidime was bactericidally active against the test strains, including two isolates (X11, X50) with intermediate ofloxacin sensitivity. Cotrimoxazole plus timentin in blood, but not in broth, was bactericidal for the timentin-resistant isolate X25. As expected, various triple combinations of chemotherapeutic agents in blood and broth revealed polymyxin B plus rifampin, regardless of the third combination partner, to exert bactericidal activity against all test strains. Similarly, rifampin combined with ofloxacin and ceftazidime was bactericidally active in blood and broth. The observation that timentin combined with cefepime was effective against cefepime-resistant strains of S. maltophilia might prove of clinical relevance with regard to chemotherapy of nosocomial infections due to multiple-antibiotic resistant strains of this opportunistic pathogen.     

Pneumococcal resistance to antimicrobial agents in the province of Québec, Canada

The serogroup/serotypes (SGTs) and antimicrobial susceptibilities to 10 antimicrobial agents of 110 clinical strains of Streptococcus pneumoniae were determined. Strains intermediately resistant or highly resistant to penicillin G (80 of 110) belonged predominantly to SGTs 23 (45.0%), 19 (13.7%), 6 (10.0%), 9 (6.2%), and 14 (3.7%). The MICs of all cephalosporins, tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol increased along with the MICs of penicillin G. However, erythromycin resistance and clindamycin resistance were observed more frequently among the intermediately penicillin-resistant strains. Multiple resistance was observed for 32 strains, of which 25 were highly resistant to penicillin G and belong to SGT 23F. All strains were susceptible to vancomycin.     

Rapid increase of pneumococcal resistance to beta-lactam and other antibiotics in isolates from the respiratory tract (Nagasaki, Japan: 1975-1994)

The susceptibility of 101 pneumococcal isolates from the respiratory tract during 1991-1994 was examined and compared with the susceptibility of isolates over the period of 1975-1990. A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents. During 1991-1994, 38% of all the isolates were resistant to penicillin. The rates of resistance during this period were 16-23% for three newer cephalosporins, 18% for imipenem, 69% for tetracycline, 31% for erythromycin, 20% for chloramphenicol and 9% for clindamycin. The use of antibiotics within one month prior to pneumococcal isolation was correlated with penicillin resistance (P < 0.05). Serotyping of the isolates by antiserum revealed differences in predominant types between penicillin-resistant (19F, 23F,4) and -susceptible isolates (15, 4, 11A). Our data suggests that anti-pneumococcal antibiotics should be carefully chosen on the basis of susceptibility tests.     

Minimum inhibitory concentrations for selected antimicrobial agents against organisms isolated from the mammary glands of dairy heifers in New Zealand and Denmark

Minimum inhibitory concentrations were determined for selected antimicrobial agents against 872 bacteria isolated from intramammary infections in heifers in New Zealand (n = 401) and Denmark (n = 471). These values were reported in micrograms per milliliters. Antimicrobial agents tested against isolates from New Zealand were penicillin, cloxacillin, cephapirin, ceftiofur, novobiocin, enrofloxacin, erythromycin, and pirlimycin. The minimum inhibitory concentrations that inhibit 90% of the strains tested for these antimicrobial agents with Staphylococcus aureus were 4.0, 0.5, 0.5, 2.0, 1.0, 0.25, 0.5, and 1.0, respectively. The minimum inhibitory concentration values that inhibit 90% of the strains tested against the Staphylococcus spp. ranged from 0.5 to 1.0 for all antimicrobics. The minimum inhibitory concentrations against streptococci were < or = 0.06, 0.5, 0.13, 0.13, 4.0, 1.0, 0.13, and < or = 0.06, respectively. Antimicrobial agents tested against isolates from Denmark included penicillin, ampicillin, oxacillin, cephalothin, ceftiofur, penicillin plus novobiocin, erythromycin, and pirlimycin. Against S. aureus, the minimum inhibitory concentrations were 0.13, 0.5, 0.5, 0.5, 1.0, 0.25, 0.5, and 0.5, respectively. The minimum inhibitory concentrations against Staphylococcus spp. were 0.25, 0.25, 0.5, 0.5, 1.0, < or = 0.06, 0.13, 1.0, and 0.5, respectively. The minimum inhibitory concentrations against the streptococci were < or = 0.06, 0.13, 0.5, 0.5, 1.0, < or = 0.06, 0.13, 0.5, and 0.5, respectively. Minimum inhibitory concentration values for staphylococci from New Zealand and Denmark were similar to values reported for US isolates. Streptococci from New Zealand and Denmark had lower minimum inhibitory concentration values than did US isolates. Only ceftiofur and enrofloxacin were active against the Gram-negative bacilli.     

In vitro activity of the new ketolide HMR3647 in comparison with those of macrolides and pristinamycins against Enterococcus spp

Ninety-four erythromycin-susceptible and 107 erythromycin-resistant enterococcal strains (MIC of >/=512 microgram/ml) were inhibited by the ketolide HMR3647 at MICs of 相似文献   

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.