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C Thornsberry

Publications and source records attributed to C Thornsberry.

At least 37 records · Page 2Linked to original sources

Resistance in respiratory tract pathogens: an international study 1997-1998.

Multiple antibiotic resistance threatens current treatment for community-acquired pneumonia (CAP). This paper presents a summary of resistance data for Streptococcus pneumoniae (6,223 isolates), Haemophilus influenzae (4,016) and Moraxella catarrhalis (1,263) collected from 153 centers throughout Japan, China, UK, Germany, Spain, France, Italy, Brazil and USA. Antiobiotics tested were: beta-lactams (penicillin, ampicillin, co-amoxiclav, cefuroxime, and ceftriaxone), macrolides (azithromycin and clarithromycin), sulphonamide (trimethoprim-sulfamethoxazole), glycopeptide (vancomycin) and fluoroquinolone (levofloxacin). S. pneumoniae with reduced susceptibility to penicillin were predominant in France, Spain and Japan (54-65%), ,beta-lactamase-producing H. influenzae most common in the USA, France and Spain (>25%) and most M. catarrhalis produced beta-lactamase irrespective of origin. S. pneumoniae susceptibility to azithromycin and clarithromycin varied widely. Levofloxacin was active against almost all isolates in all countries and none was resistant to vancomycin. Because of increasing resistance to older drugs, the newer fluoroquinolones have a role in the therapy of CAP and other respiratory infections, although surveillance studies must continue.

Bacterial Proteins↗

Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in Asia and Europe, 1997-1998.

A multicentre, collaborative study was performed in Asia and Europe during the winter of 1997-1998 to determine the in vitro activity of selected antimicrobial agents against common respiratory pathogens. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates were collected from 48 sites in China, France, Germany, Italy, Japan, Spain and the UK and tested in a central laboratory in the USA. Broth microdilution MICs were determined for beta-lactams (penicillin, amoxycillin/clavulanate, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), sulphonamides (co-trimoxazole), glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). The percentage of isolates susceptible to each antimicrobial class varied substantially by country. Penicillin susceptibility amongst pneumococci ranged from 34% in France and Spain to 92% in Germany, and macrolide susceptibility varied between 26% in China and 91% in the UK. In most countries beta-lactam, macrolide and cotrimoxazole resistance was more prevalent amongst penicillin-intermediate and -resistant S. pneumoniae isolates. However, little or no resistance was detected to levofloxacin (0.3% intermediate and resistant) or vancomycin (0% intermediate and resistant). For H. influenzae the prevalence of beta-lactamase production varied from 6% in China and Germany to 32% in Spain, and for M. catarrhalis, from 79% in Germany to 98% in Japan. With the exception of ampicillin, beta-lactamase production had a minimal effect on beta-lactam activity against H. influenzae or M. catarrhalis. Our findings demonstrate that antimicrobial resistance profiles of common respiratory isolates differ dramatically between countries in Asia and Europe.

Asia↗

Benchmarking the in vitro activities of moxifloxacin and comparator agents against recent respiratory isolates from 377 medical centers throughout the United States.

To benchmark the activity of moxifloxacin (a newer fluoroquinolone), a U.S. study comprising 16,141 contemporary isolates of Streptococcus pneumoniae (5,640), Haemophilus influenzae (6,583), and Moraxella catarrhalis (3,648) referred from 377 institutions during 1998 is described. For S. pneumoniae the modal MIC and MIC at which 90% of the isolates were inhibited (MIC(90)) for moxifloxacin were 0.12 and 0.25 microg/ml, respectively, independent of susceptibility to other drug classes, geography, or site of infection. Eleven isolates were intermediate or resistant to levofloxacin and grepafloxacin; of these isolates, 1 remained susceptible to sparfloxacin, 2 remained susceptible to moxifloxacin, and 4 remained susceptible to trovafloxacin. All 11 isolates possessed classic mutations in gyrA and/or parC known to confer reduced susceptibility to fluoroquinolones. Four isolates (originating from four separate states) belonging to a multidrug-resistant, fluoroquinolone-resistant clone were identified by pulsed-field gel electrophoresis. For moxifloxacin and trovafloxacin, at least 87% of isolates demonstrated MICs > or =3 twofold concentrations below the susceptibility breakpoints, in contrast to no more than 15% for levofloxacin, grepafloxacin, and sparfloxacin. Of the isolates that were multidrug resistant (7.4%), >98% remained susceptible to moxifloxacin. The modal MIC and MIC(90) for M. catarrhalis (both 0.06 microg/ml) and for H. influenzae (both 0.03 microg/ml) were independent of beta-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future studies.

Anti-Infective Agents↗

Prevalence of gyrA, gyrB, parC, and parE mutations in clinical isolates of Streptococcus pneumoniae with decreased susceptibilities to different fluoroquinolones and originating from Worldwide Surveillance Studies during the 1997-1998 respiratory season.

From 8,419 worldwide clinical isolates of Streptococcus pneumoniae obtained during 1997-1998, 69 isolates with reduced susceptibility or resistance to fluoroquinolones (FQs) were molecularly characterized. For the isolates in this prevalence study, only parC (Ser-79-->Tyr) and gyrA (Ser-81-->Phe or Tyr) mutations, especially in combination, were found to contribute significantly to resistance. These mutations influenced the FQ MICs to varying degrees, although the rank order of activity remains independent of mutation type, with ciprofloxacin the least active, followed by levofloxacin, gatifloxacin/grepafloxacin/moxifloxacin/sparfloxaci n/trovafloxacin, and clinafloxacin/sitafloxacin. Efflux likely plays a crucial role in reduced susceptibility for new hydrophilic FQs.

Anti-Infective Agents↗

Analysis of ciprofloxacin activity against Streptococcus pneumoniae after 10 years of use in the United States.

As the most commonly used fluoroquinolone in the United States since 1987, ciprofloxacin has exerted the greatest selective pressure on S. pneumoniae and provides a valuable marker to evaluate the actual and potential emergence of fluoroquinolone resistance in this species. Analysis of susceptibility results obtained with 5,640 strains collected from throughout the United States showed that only 16 (0.3%) of the isolates demonstrated MICs of > or =4 microg/ml. The prevalence of this phenotype was significantly higher (P < 0.05) among penicillin-resistant populations, among isolates from patients >64 years old, and among respiratory isolates. However, >99% of strains had MICs of <4 microg/ml regardless of the risk group examined, and the MIC population distributions were the same for each risk group. These findings demonstrate that the phenotype of a MIC of > or =4 microg/ml remains uncommon after 10 years of ciprofloxacin use; however, these findings are no reason to become complacent with regard to appropriate use of fluoroquinolones and the need to carefully track resistance trends. Equally important is careful analysis of data that result from surveillance in terms of risk factors and other associated trends so that resistance and susceptibility, and their consequences, are neither over- nor underestimated.

Adolescent↗

Antimicrobial resistance in respiratory tract pathogens: results of an international surveillance study.

An international surveillance study was performed to assess the resistance patterns among respiratory tract pathogens during the winter of 1997-1998. The pathogens studied included Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The antibiotics tested included five beta-lactams (penicillin, ampicillin, amoxicillin, amoxicillin-clavulanic acid, cefuroxime axetil and ceftriaxone), two macrolides (azithromycin and clarithromycin), one sulfonamide (trimethoprim-sulfamethoxazole), one glycopeptide (vancomycin) and one fluoroquinolone (levofloxacin). A total of 11,502 isolates were tested from nine countries, using microdilution susceptibility tests as recommended by National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The susceptibility rates varied greatly around the world. Ninety percent of M. catarrhalis isolates produced beta-lactamase, making them resistant to ampicillin. beta-Lactamase production by H. influenzae ranged from 5% in Germany to 34% in the USA (mean 17.5%). Of the S. pneumoniae isolates, 32.8% had some resistance to penicillin, but this ranged greatly from 7.8% in Germany to 66.5% in France. Penicillin resistance in S. pneumoniae was associated with resistance to other beta-lactams, macrolides and sulfonamides, but not to levofloxacin or vancomycin. All isolates of H. influenzae and M. catarrhalis were susceptible to levofloxacin. Results of this study support the conclusion that these three respiratory tract pathogens are becoming more resistant to selected antimicrobials, and that the level of resistance in these isolates to the antimicrobials varies greatly from one country to another.

Drug Resistance, Microbial↗

Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in the United States, 1997-1998.

A national antimicrobial resistance surveillance study was conducted from December 1997 to May 1998 to determine the prevalence of antimicrobial resistance in 6620 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In this centralized study, which involved 163 institutions located in 43 states, we determined MICs for representatives of five antimicrobial classes: beta-lactams (penicillin, co-amoxiclav, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), co-trimoxazole, glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). In most S. pneumoniae isolates, all antimicrobials were to be found active, but amongst penicillin-resistant isolates (MICs > or = 2 mg/L), resistance to other beta-lactams, macrolides and co-trimoxazole was common. For vancomycin and levofloxacin, however, activity was not associated with penicillin resistance. The prevalence of penicillin-nonsusceptible (intermediate and resistant) pneumococci was highest in the South Atlantic (44%) and East South Central (43%) regions and lowest in the Mid-Atlantic (28%) and New England (28%) regions. Resistance to beta-lactams, macrolides and co-trimoxazole was more commonly found amongst respiratory isolates than blood isolates and in strains from patients < or = 12 years old than from older patients. beta-lactamase, which was detected in 33% of H. influenzae and 92% of M. catarrhalis strains, did not affect the activity of the beta-lactams under study other than ampicillin. Certain agents, such as vancomycin and the fluoroquinolones, remain highly active, and well-designed surveillance systems that monitor MIC distributions would be needed to detect a potential for reduced susceptibility. In addition, surveillance programmes should be designed to collect information about associated resistance as well as differences in prevalence associated with region, specimen source and patient age.

Adolescent↗

Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates to 26 antimicrobial agents: a prospective U.S. study.

An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates was performed during the winter of 1996-1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2, 752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate, and 19% were highly resistant to penicillin. On the basis of the MICs at which 90% of isolates are inhibited and modal MICs, the hierarchy of the five fluoroquinolones from most to least active was grepafloxacin > sparfloxacin > levofloxacin = ciprofloxacin > ofloxacin. For S. pneumoniae isolates for which penicillin MICs were elevated, the MICs of the cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole were also elevated, but the MICs of the fluoroquinolones, vancomycin, and rifampin were not. The prevalence of penicillin-susceptible pneumococci varied by U.S. Bureau of the Census region (range, 44% in the East South Central region to 75% in the Pacific region). In addition, S. pneumoniae isolates from blood were significantly more susceptible to penicillin than those from respiratory, ear, or eye specimens, and pneumococci from patients </=2 years old were significantly more resistant to penicillin than those from older patients (by chi-square analysis, P < 0.05). beta-Lactamase was produced by 35% of H. influenzae isolates and 93% of M. catarrhalis isolates, resulting in increased MICs of amoxicillin and certain cephalosporins. We noted that the antimicrobial resistance patterns of S. pneumoniae isolates, which correlate with the penicillin susceptibility phenotype, vary by site of infection, age group of the patient, and geographic source of the isolate.

Adolescent↗

In vitro antibacterial properties of pexiganan, an analog of magainin.

Pexiganan, a 22-amino-acid antimicrobial peptide, is an analog of the magainin peptides isolated from the skin of the African clawed frog. Pexiganan exhibited in vitro broad-spectrum antibacterial activity when it was tested against 3,109 clinical isolates of gram-positive and gram-negative, anaerobic and aerobic bacteria. The pexiganan MIC at which 90% of isolates are inhibited (MIC90) was 32 micrograms/ml or less for Staphylococcus spp., Streptococcus spp., Enterococcus faecium, Corynebacterium spp., Pseudomonas spp., Acinetobacter spp., Stenotrophomonas spp., certain species of the family Enterobacteriaceae, Bacteroides spp., Peptostreptococcus spp., and Propionibacterium spp. Comparison of the MICs and minimum bactericidal concentrations (MBCs) of pexiganan for 143 isolates representing 32 species demonstrated that for 92% of the isolates tested, MBCs were the same or within 1 twofold difference of the MICs, consistent with a bactericidal mechanism of action. Killing curve analysis showed that pexiganan killed Pseudomonas aeruginosa rapidly, with 10(6) organisms/ml eliminated within 20 min of treatment with 16 micrograms of pexiganan per ml. No evidence of cross-resistance to a number of other antibiotic classes was observed, as determined by the equivalence of the MIC50s and the MIC90s of pexiganan for strains resistant to oxacillin, cefazolin, cefoxitin, imipenem, ofloxacin, ciprofloxacin, gentamicin, and clindamicin versus those for strains susceptible to these antimicrobial agents. Attempts to generate resistance in several bacterial species through repeated passage with subinhibitory concentrations of pexiganan were unsuccessful. In conclusion, pexiganan exhibits properties in vitro which make it an attractive candidate for development as a topical antimicrobial agent.

Anti-Bacterial Agents↗

Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996-1997 respiratory season. The Laboratory Investigator Group.

A U.S. surveillance study of antimicrobial resistance in respiratory tract pathogens in the respiratory season (1996-1997) is reported that included 11,368 isolates from 434 institutions in 45 states and the District of Columbia. beta-lactamase was produced by 33.4% of Haemophilus influenzae and 92.7% of Moraxella catarrhalis. Of the 9,190 Streptococcus pneumoniae isolates tested, 33.5% were not susceptible to penicillin (MIC > or = 0.12 microgram/mL), with 13.6% having high-level resistance (MICs > 1 microgram/mL). For H. influenzae, the most active antimicrobials (based on percent of strains susceptible) were levofloxacin (100%) and ceftriaxone (99.9%); the least active were ampicillin (67.2%) and clarithromycin (58.1%). For M. catarrhalis, the most active drugs were amoxicillin-clavulanate, ceftriaxone, and levofloxacin (100%); the least active was ampicillin. The order of the activity of the drugs against S. pneumoniae were levofloxacin (97.3%) > ceftriaxone (87.1%) > amoxicillin-clavulanate (81.7%) = clarithromycin (80.9%) > cefuroxime (74.5%) > penicillin (66.5%). The activity of the beta-lactams and clarithromycin against isolates of S. pneumoniae was closely associated with the resistance to penicillin. Levofloxacin was more active against S. pneumoniae overall, because it exhibited no cross-resistance. These data indicate that the incidence of beta-lactamase production in H. influenzae (33.4%) and M. catarrhalis (92.7%) is similar to other recent studies, and that the incidence of penicillin-intermediate and -resistant S. pneumoniae is increasing, particularly the high-level penicillin-resistant (MICs > 1 microgram/mL) strains, which were often multi-resistant.

Amoxicillin-Potassium Clavulanate Combination↗

The activity of a combination of penicillin and novobiocin against bovine mastitis pathogens: development of a disk diffusion test.

The combination of penicillin and novobiocin is currently available for the treatment of bovine mastitis, but methods are not available for susceptibility testing of the combination by veterinary diagnostic laboratories. The minimum inhibitory concentration (MIC) and disk diffusion data were determined for penicillin, novobiocin, and a combination of the two in a 1:2 ratio for 225 staphylococcal, streptococcal, and Gram-negative isolates from bovine intramammary infections. Based on the drug concentrations in milk following infusion, linear regression analysis, and error rate bounding, the interpretive zone diameters selected were < or = 16 mm for resistant isolates and > or 17 mm for susceptible isolates with a disk containing 10 U of penicillin and 30 micrograms of novobiocin. Additionally, MIC breakpoints of < or = 2 micrograms/ml of penicillin and 4 micrograms/ml of novobiocin were selected to categorize isolates as susceptible and > or = 4 micrograms/ml of penicillin and 8 micrograms/ml of novobiocin were selected to categorize isolates as resistant. The MIC and disk diffusion results, as well as studies to monitor bacterial killing by antimicrobial agents over time, indicated that the combination of penicillin and novobiocin in a 1:2 ratio was more active than were the individual drugs. Kinetics of the kill curves with the penicillin and novobiocin combination (1:2 ratio) showed that the combination was bactericidal for Staphylococcus aureus and Staphylococcus xylosus.

Animals↗

Comparative activity of eight antimicrobial agents against clinical bacterial isolates from the United States, measured by two methods.

In a surveillance study conducted during 1992-1993 at 83 medical institutions of different types and sizes (e.g., laboratories, community hospitals, teaching hospitals) and from different geographical areas of the United States, clinical bacterial isolates were tested for their susceptibility to eight comparative antimicrobial agents (cefepime, ceftazidime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, and piperacillin). A total of 12,574 isolates were tested by either the Etest method (AB Biodisk) or a microdilution method (MicroScan) in the participating laboratories; 11.8% of these isolates were subsequently retested for quality assurance purposes by both methods in a central laboratory. The results obtained in the central laboratory were essentially the same as the results obtained in the participating laboratories. This article presents data for gram-negative and gram-positive isolates other than Streptococcus pneumoniae, the results of which have been previously published. Antimicrobial susceptibility results obtained with the two different minimum inhibitory concentration (MIC) methods--MicroScan and Etest--showed that most isolates of Enterobacteriaceae were susceptible to cefepime, exceeding the activity of ceftazidime, ceftriaxone, and cefotaxime, principally because of the greater activity of cefepime against the species that produce Bush group 1 beta-lactamases (predominantly Enterobacter cloacae, Enterobacter aerogenes, and Citrobacter freundii). In addition, the activity of cefepime against Pseudomonas aeruginosa isolates was essentially equivalent to that of ceftazidime and greater than that of third-generation cephalosporins. Most methicillin-susceptible Staphylococcus aureus were susceptible to all the cephalosporins, whereas methicillin-resistant S. aureus and enterococci were resistant. Overall, the most active antimicrobials in this study were imipenem, ciprofloxacin, and cefepime, but the activity of all the antimicrobials varied with different species. Categorically, the results from the microdilution and Etest methods were equivalent.

Anti-Bacterial Agents↗

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin, including quality control parameters.

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 < = or 2.0 micrograms/ml).

Anti-Infective Agents↗

Activity of penicillin and three third-generation cephalosporins against US isolates of Streptococcus pneumoniae: a 1995 surveillance study.

In a surveillance study of Streptococcus pneumoniae from the United States the incidence of resistance (including both resistant and relatively resistant strains) to penicillin was 37.2% when tested by the oxacillin disk-diffusion test, or 27.2% when tested by microdilution minimum inhibitory concentrations. Strains that were susceptible to penicillin by the oxacillin test were also susceptible to the third-generation cephalosporins cefotaxime, ceftriaxone, and ceftizoxime. The overall resistance (without regard to penicillin resistance) to cefotaxime was 8.8%, to ceftriaxone was 7.9%, and to ceftizoxime was 17.2%; the rates of resistance among penicillin-resistant and relatively resistant strains (combined), however, were 23.6% for cefotaxime, 21.4% for ceftriaxone, and 43.2% for ceftizoxime. The incidence of penicillin resistance and relative resistance in these pneumococcal isolates varied from one institution to another, but all institutions had these strains and the incidence varied from 4.3% to 60.9%. Having ceftizoxime, the least active of the third-generation cephalosporins, tested on the formulary did not appear to increase selection of beta-lactam-resistant strains. The increased resistance to penicillin with the concomitant increase in resistance to third-generation cephalosporins may greatly increase the difficulty of selecting optimal therapy of patients with life-threatening infections due to S. pneumoniae.

Cefotaxime↗

Interpretive criteria for antimicrobial susceptibility testing of ceftiofur against bacteria associated with swine respiratory disease.

Ceftiofur, an extended-spectrum cephalosporin, is active against a variety of animal pathogens, including organisms associated with swine respiratory disease. However, minimum inhibitory concentration (MIC) breakpoint and disk diffusion interpretive criteria have not been established for swine pathogens. Susceptibility tests were performed by broth microdilution MIC and disk diffusion methods on 246 bacterial species that cause swine respiratory disease. Ceftiofur was active against Salmonella sp., Pasteurella multocida, Actinobacillus pleuropneumoniae, Streptococcus suis, and Escherichia coli but was not active against Bordetella bronchiseptica measured by MIC. Based on pharmacokinetic studies of ceftiofur in swine after a single intramuscular injection of 3 or 5 mg/kg body weight of ceftiofur and on the MIC and disk diffusion data, we recommend MIC breakpoints and disk diffusion distances, respectively, of < or = 2 micrograms/ml and > or = 21 mm for susceptible, 4 micrograms/ml and 18-20 mm for intermediate, and > or = 8 micrograms/ml and > or = 17 mm for resistant classification for swine pathogens. When these breakpoints were applied to data from a previous study using bovine pathogens, only 1 minor interpretive error occurred.

Actinobacillus pleuropneumoniae↗