Biomedical subjects

C Thornsberry

Publications and source records attributed to C Thornsberry.

At least 127 records · Page 7Linked to original sources

PubMed1985

Disk diffusion antimicrobial susceptibility testing for clinical and epidemiologic purposes.

Antimicrobial susceptibility testing is one of the most important and useful tests performed by the clinical microbiology laboratory. The value of disk susceptibility testing in epidemiology is enhanced by its simplicity of performance, reproducibility of results, and ability to indicate whether a single strain is likely to be the cause of many infections. By using a specific set of antimicrobials for either gram-positive or gram-negative bacterial susceptibility testing and by following recommended testing procedures, laboratories can reliably identify similarities and differences in strains. We propose a list of antimicrobial agents chosen specifically for their value in disk susceptibility testing for clinical and epidemiologic purposes and describe the recommended methods of testing.

Anti-Bacterial Agents↗

PubMed1985

Imipenem (N-formimidoyl thienamycin): in vitro antimicrobial activity and beta-lactamase stability.

In vitro studies with imipenem (N-formimidoyl thienamycin or MK0787) were performed with 8481 clinical isolates in three separate medical centers. More extensive comparative studies were also performed with 605 representative isolates, comparing imipenem to six other beta-lactams. Although the newer beta-lactams were often more active against susceptible species, imipenem demonstrated the broadest spectrum of antibacterial activity, with MIC 90s less than or equal to 4.0 micrograms/ml for all species tested except Pseudomonas maltophilia and P. cepacia. Imipenem was very active against all streptococci and staphylococci, in contrast to the third-generation cephalosporins. There was no evidence of cross-resistance between imipenem and the cephalosporins or penicillins. Resistance to hydrolysis by seven beta-lactamase preparations was documented for imipenem, cefotaxime, and moxalactam. Like many other beta-lactams, imipenem inhibited the Type I beta-lactamase produced by Enterobacter cloacae. Other beta-lactamases from gram-negative bacilli were also inhibited by high concentrations of imipenem.

Enterobacteriaceae↗

PubMed1985

The in vitro activity of sulphones alone and in combination with ampicillin or amoxicillin against Legionella pneumophila and other Legionella spp. including beta-lactamase studies.

Penicillinate sulphone beta-lactamase inhibitors, sulbactam, and BL-P2013, were very effective alone and in combination with ampicillin-like penicillins against 34 strains of Legionellae. The minimum concentrations inhibiting 50% of tested isolates (MIC50) results were as follows: sulbactam, BL-P2013, and amoxicillin = 2.0 micrograms/ml; ampicillin = 1.0 microgram/ml; erythromycin = 0.5 microgram/ml; and rifampin = 0.03 microgram/ml. Synergy was commonly observed when the sulphones were combined with ampicillin or amoxicillin, generally reducing the drug minimum inhibitory concentrations (MICs) fourfold to eightfold (synergy rates 85-91%). BL-P2013 was a slightly more active inhibitor of Legionella spp. beta-lactamase than dicloxacillin or sulbactam.

Amoxicillin↗

PubMed1985

Evaluation of in vitro antibacterial activity of enoxacin: comparison with other orally absorbed antimicrobial agents, proposed disk diffusion test interpretive criteria, and quality control limits.

The antibacterial activity of enoxacin was assessed by a standard microdilution susceptibility test method against 6,096 consecutive clinical isolates at four clinical laboratories and compared with that of norfloxacin and cefaclor. Its activity was comparable to that of norfloxacin; both inhibited over 90% of Enterobacteriaceae at 0.5 micrograms/ml. Resistance to enoxacin [minimum inhibitory concentration (MIC) greater than 4 micrograms/ml] was observed in only 18 of 4,076 Enterobacteriaceae (0.5%, 36 of 650 nonfermentative gram-negative bacilli (5.5%), and 6 of 836 staphylococci (0.7%). Relatively poor activity was observed against streptococci. An additional 618 selected clinical isolates were tested with enoxacin and were compared with nine other orally absorbed antimicrobial agents. The greatest activity was observed with enoxacin, norfloxacin, and cotrimoxazole, but some difference were noted with individual species. Results of enoxacin disk diffusion susceptibility testing of 487 isolates were correlated with the MICs, analyzed, and interpretive criteria were determined. With MIC breakpoints of: susceptible = less than or equal to 2.0 micrograms/ml, intermediate = 4.0 micrograms/ml, and resistant = greater than 4.0 micrograms/ml, the corresponding preliminary disk diffusion zone diameter breakpoints for the 10-micrograms enoxacin disk are: susceptible greater than or equal to 18 mm, intermediate 15-17 mm, and resistant less than or equal to 14 mm. Quality control zone diameter limits were determined for three standard QC organisms.

Anti-Bacterial Agents↗

PubMed1985

Apalcillin [PC-904]: spectrum of activity and beta-lactamase hydrolysis/inhibition.

Apalcillin is a Pseudomonas-active penicillin with a broad spectrum of antibacterial activity similar to that of piperacillin, except for the greater potency of apalcillin against Acinetobacter spp. and Pseudomonas aeruginosa. Studies with 846 isolates representative of the common bacterial pathogens compared apalcillin to piperacillin, azlocillin, mezlocillin, carbenicillin, ticarcillin, cefotaxime, and cefoperazone. Apalcillin and piperacillin were both active against all 13 species of the Enterobacteriaceae that were tested (MIC 50s less than or equal to 8.0 micrograms/ml) but some strains were resistant to both penicillins. Apalcillin was active against Pseudomonas aeruginosa and Acinetobacter spp. (MIC 50 less than 2.0 micrograms/ml). Like other penicillins, apalcillin was not effective against beta-lactamase-producing Staphylococcus spp., Haemophilus spp. or Neisseria gonorrhoeae. Rates of hydrolysis by six beta-lactamase preparations from gram-negative bacilli were determined, comparing apalcillin, piperacillin, azlocillin, ticarcillin, ampicillin and dicloxacillin to benzyl penicillin. Apalcillin and ticarcillin were more resistant than piperacillin and azlocillin to hydrolysis by the PSE-2 enzyme from P. aeruginosa. As did many other penicillins, apalcillin inhibited the Type 1 beta-lactamase that is produced by Enterobacter cloacae. The other enzymes were inhibitory only in very high concentrations.

Ampicillin↗

PubMed1985

In vitro antimicrobial susceptibility testing using 30 microG and 75 microG U63196-E (cefpimizole AC-1370) disks.

U63196-E, a new cephalosporin, was evaluated for its antimicrobial spectrum and its application to standardized in vitro susceptibility test methods. The proposed criteria for the 75-micrograms U63196-E disk are greater than or equal to 18 mm (less than or equal to 16 micrograms/ml) = susceptible and less than or equal to 14 mm (greater than 32 micrograms/ml) = resistant. These limits are preferred to the 30 micrograms disk and produce only 4.2% major and very major interpretive errors. Previously published interpretive criteria for the 75 micrograms cefoperazone disk were confirmed.

Cephalosporins↗

PubMed1985

In vitro antimicrobial activity of cefoperazone-sulbactam combinations against 554 clinical isolates including a review and beta-lactamase studies.

Cefoperazone was tested against 554 clinical isolates alone and with sulbactam in three combinations. The addition of sulbactam in low concentrations (less than or equal to 4 micrograms/ml) improved the spectrum of cefoperazone principally against gram-negative bacilli such as Acinetobacter species, some Pseudomonas species, and beta-lactamase-positive Enterobacteriaceae. Nearly all of the spectrum increase was achieved at a sulbactam level of less than or equal to 2 micrograms/ml. Sulbactam was found to be an effective antimicrobial agent against Acinetobacter species (MIC50, 1.0 microgram/ml), Pseudomonas acidovorans (MIC50, 2.0 micrograms/ml), Neisseria gonorrhoeae (MIC50, less than or equal to 0.5 microgram/ml), and N. meningitidis (MIC50, less than or equal to 0.5 microgram/ml). Sulbactam had a higher affinity and binding constant for the plasmid-mediated beta-lactamases such as TEM-1 and TEM-2 compared to cefoperazone (greater than or equal to 10-fold difference). This finding was important as cefoperazone can be hydrolyzed at a moderate rate by the highly efficient TEM enzymes (less than 2% of clinical Escherichia coli isolates). Sulbactam increased the susceptibility (less than or equal to 16 micrograms/ml) of 220 isolates of Enterobacteriaceae to cefoperazone from 88.6 to 96.3% when 4.0 micrograms/ml of sulbactam was added. The cefoperazone antimicrobial activity was also increased against the nonenteric bacilli from a 69.5 to a 87.4% total inhibition. MICs among cefoperazone-susceptible gram-negative and gram-positive strains were routinely decreased 2- to 32-fold, as calculated from MIC90 results. Therefore, sulbactam should predictably increase the antimicrobial spectrum and clinical effectiveness of cefoperazone against nosocomial and other pathogens such as the plasmid-containing enteric bacilli, Bacteroides species and Acinetobacter species, and possibly provide the opportunity to reduce dosage schedules for infecting species already susceptible to cefoperazone alone.

Bacteria↗

PubMed1985

The cefoperazone-sulbactam combination. In vitro qualities including beta-lactamase stability, antimicrobial activity, and interpretive criteria for disk diffusion tests.

Three concentrations of the penicillanic acid sulfone, sulbactam were tested in combination with cefoperazone against 632 recent clinical bacterial isolates. Cefoperazone was effective alone (less than or equal to 16 micrograms/mL) against 95% of Enterobacteriaceae and combined with 4 micrograms/mL sulbactam inhibited 99.5% of strains. This coverage of enteric bacilli was superior to timentin (99.1%), ceftazidime (98.2%), and tobramycin (90.9%). The minimum inhibitory concentrations (MICs) of cefoperazone-susceptible strains also were markedly decreased by sulbactam (overall MIC90s, 8.0 micrograms/mL for cefoperazone and 1.0 microgram/mL for cefoperazone and 4.0 micrograms/mL for sulbactam). Sulbactam also expanded the spectrum of cefoperazone against Acinetobacter species, some rare Pseudomonas species, and Bacteroides fragilis group species. Sulbactam had direct antimicrobial activity against the acinetobacters and Pseudomonas acidovorans, but the increased activity of cefoperazone-sulbactam against some other Pseudomonas species and anaerobes was attributed to beta-lactamase inhibition. The cefoperazone MICs against beta-lactamase producing Staphylococcus species also were lowered to the level of enzyme-deficient strains. Cefoperazone bactericidal activity was improved by 4.0 micrograms/mL sulbactam, and no antagonism was observed. beta-lactamase hydrolysis studies confirmed a slow hydrolysis of cefoperazone only by TEM beta-lactamases and a high-grade resistance to enzyme breakdown by sulbactam. Differential beta-lactamase affinity studies for cefoperazone and sulbactam showed potential efficacy and applications to plasmid-mediated TEM and OXA enzymes and only marginal effective sulbactam inhibition of Pseudomonas and Klebsiella species enzymes. Disk diffusion studies on 556 strains confirmed the applicability of the cefoperazone 75-micrograms disk to testing routine isolates other than enterococci and methicillin-resistant Staphylococcus aureus. The addition of 4.0 micrograms sulbactam/mL in a fixed concentration to dilution test systems and 15 micrograms sulbactam to the 75 micrograms cefoperazone disk were recommended for in vitro tests. Susceptibility and resistant interpretive criteria for the disk and dilution tests can be applied with confidence. Only 0.4% false-susceptibility errors and a 97.5% absolute interpretive agreement were achieved using the 75 micrograms cefoperazone/15 micrograms sulbactam disk.

Anti-Bacterial Agents↗

PubMed1985

Reliability of cefaclor, cefazolin, cefamandole, and cephalothin disks to predict susceptibility of Enterobacteriaceae, Staphylococcus species, and Haemophilus influenzae.

Interpretive zone-size standards currently used for cephalothin and cefamandole disk tests also may be applied to tests with disks containing 30 micrograms of cefaclor or cefazolin. Against 627 representative isolates, susceptibility to cefaclor and cefazolin could be predicted by testing cephalothin. However, cefazolin is more active than cephalothin against isolates of Escherichia coli with a TEM beta-lactamase plasmid. The expanded spectrum of cefamandole continues to necessitate separate testing. Against methicillin-resistant staphylococci, cefaclor disks were more reliable than cephalothin or cefamandole, but false-susceptible results were seen with all four disks. For testing Haemophilus influenzae, the cefazolin disks were not reliable; cephalothin or cefaclor disks could predict susceptibility to either drug.

Cefaclor↗

PubMed1985

In-vitro evaluation of Sch 34343: antimicrobial activity, beta-lactamase stability and inhibition.

Sch 34343 was compared with representative parenteral beta-lactams including monobactams (aztreonam), 1-oxa-beta-lactams (latamoxef), carbapenems (imipenem) and cephalosporins (cefamandole, cefoperazone, cefotaxime, cefsulodin and ceftazidime). Sch 34343 was active against the Enterobacteriaceae (MIC50 range, 0.12-4.0 mg/l) and the facultative Gram-positive cocci (MIC50 range, 0.03-4.0 mg/l), and was comparable to the third-generation cephalosporins and imipenem. Pseudomonas aeruginosa and other Pseudomonas spp. were not susceptible to Sch 34343. Haemophilus influenzae and Neisseria spp. were all susceptible to less than or equal to 2.0 mg/l of Sch 34343. Methicillin-resistant staphylococci (MIC90, 32 mg/l) appear to be insusceptible to Sch 34343. Sch 34343 inhibited the majority of cefotaxime- and gentamicin-resistant bacteria (MICs less than or equal to 8.0 mg/l). The new penem was stable to hydrolysis by 11 beta-lactamase preparations (both plasmid- and chromosomally-mediated types). Sch 34343 inhibited beta-lactamases as did other newer cephalosporins.

Anti-Bacterial Agents↗

PubMed1985

Cefpiramide: comparative in-vitro activity and beta-lactamase stability.

Cefpiramide is a new Pseudomonas-active cephalosporin with a broad spectrum of antibacterial activity. Like cefoperazone, cefpiramide was moderately susceptible to hydrolysis by a variety of beta-lactamases from Gram-negative bacilli. Tests with 6552 bacterial isolates in five separate medical centres documented cefpiramide's effectiveness against the more commonly encountered bacterial pathogens. Additional studies with 761 selected isolates, representing 35 species, demonstrated similarities between cefpiramide and cefoperazone; cefpiramide was more active against Acinetobacter spp. and Pseudomonas spp. Like most other cephalosporins, cefpiramide inhibited methicillin-susceptible staphylococci, non-enterococcal streptococci, Neisseria gonorrhoeae, N. meningitidis and beta-lactamase-negative Haemophilus influenzae. Cefpiramide was marginally active against Streptococcus faecalis (MIC 50, 8.0 mg/l).

Bacteria↗

PubMed1985

Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin.

The in vitro activity of BMY-28142, a new cephalosporin, was tested by a broth microdilution system and compared with those of cefotaxime, ceftazidime, cefoperazone, moxalactam, and HR 810 against 747 bacterial isolates, one-third of which were resistant to one or more third-generation cephalosporins. BMY-28142 was the most active drug tested against 326 Enterobacteriaceae with an MIC for 90% of the organisms tested (MIC90) of 1.0 micrograms/ml. Against these Enterobacteriaceae the relative activities were: BMY-28142 greater than HR 810 greater than moxalactam and ceftazidime greater than cefotaxime greater than cefoperazone. For cefotaxime- and cefoperazone-resistant strains, the MIC90 of BMY-28142 was 4.0 micrograms/ml (compared with 0.13 micrograms/ml for susceptible strains). BMY-28142, with an MIC90 of 8.0 micrograms/ml for Pseudomonas aeruginosa, was about half as active as ceftazidime. The relative activities against P. aeruginosa were: ceftazidime greater than BMY-28142 greater than HR 810 greater than cefoperazone greater than moxalactam and cefotaxime. The MIC90 of BMY-28142 against staphylococci was 2.0 micrograms/ml, which was fourfold less active than HR 810, slightly less active than cefotaxime and cefoperazone, and fourfold more active than ceftazidime and moxalactam. BMY-28142 was very active against beta-lactamase-positive and -negative Haemophilus influenzae (MIC90, 0.06 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.015 micrograms/ml),aand nonenterococcal streptococci. Its activity against Streptococcus faecalis was poor (MIC90, 64 micrograms/ml). BMY-28142 was stable against the several beta-lactamases tested but exhibited little beta-lactamase inhibitory effect.

Bacteria↗

PubMed1985

A gene probe for TEM type beta-lactamases.

A restriction fragment of plasmid pBR322 bearing the TEM-1 beta-lactamase structural gene was electroeluted from agarose gels after digestion with EcoRI and HinfI. The 1-kilobase fragment was 32P-labeled and used to examine genetic relationships with nucleic acids encoding seven other beta-lactamase classes. The probe hybridized only with TEM-2 and OXA-2 class plasmids.

DNA, Bacterial↗

PubMed1985

Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae.

Broth microdilution MICs were determined for 258 clinical isolates of Mycobacterium fortuitum (3 biovariants) and M. chelonae (2 subspecies) with amikacin, tobramycin, cefoxitin, doxycycline, erythromycin, and sulfamethoxazole-trimethoprim and with several new beta-lactams and aminoglycosides and ciprofloxacin. Variations in susceptibility by and within species subgroups confirm the need for susceptibility testing against clinically important strains.

Aminoglycosides↗

PubMed1985

Acquired ability of Staphylococcus aureus to produce toxic shock-associated protein and resulting illness in a rabbit model.

Staphylococcus aureus from patients with toxic shock syndrome (TSS) produce TSS toxin 1. We transferred, by a bacteriophage, the ability to produce TSS toxin 1 from a TSS toxin 1-positive to a TSS toxin 1-negative strain of S. aureus. This recombinant strain produced TSS toxin 1 as confirmed by isoelectric focusing, immunodiffusion, radioimmunoassay, and autoradiography. The recombinant produced TSS-like illness in rabbits, and was significantly (P less than 0.001) more lethal than the recipient strain. Both strains produced fever and diarrhea, but, in addition, rabbits challenged with the recombinant also developed lowered blood pressure (P = 0.002), conjunctival hyperemia, erythroderma, and respiratory distress. Histopathological findings in rabbits challenged with the recombinant strain were remarkably similar to those described for humans with TSS, e.g., erythrophagocytosis, liver "triaditis," and vasodilatation. This study demonstrates that this protein may contribute to the pathogenesis of the TSS.

Animals↗

PubMed1985

Ciprofloxacin disk susceptibility tests: interpretive zone size standards for 5-microgram disks.

Evaluations of 5-microgram ciprofloxacin disk diffusion susceptibility tests were performed independently by seven different investigators. The results of the separate tests were combined to increase the number of resistant strains in the challenge set of microorganisms. Based on data with 2,652 isolates, the following interpretive breakpoints are tentatively proposed for use in ongoing clinical trials of ciprofloxacin: less than or equal to 15 mm, resistant (MIC greater than 2.0 micrograms/ml); 16 to 20 mm, intermediate (1.0 less than MIC less than or equal to 2.0 micrograms/ml); and greater than or equal to 21 mm, susceptible (MIC less than or equal to 1.0 micrograms/ml). Disk tests with Streptococcus spp. and with Pseudomonas maltophilia were not reliable; other microorganisms were accurately categorized by the disk diffusion test.

Acinetobacter↗

PubMed1985

Antimicrobial susceptibility testing of Francisella tularensis with a modified Mueller-Hinton broth.

A modified Mueller-Hinton broth was developed to perform antimicrobial susceptibility tests on Francisella tularensis. Adequate growth of the organism was obtained within 24 h of inoculation, and MICs could be read at that time. We tested 15 selected strains of F. tularensis and five reference quality control strains in this medium with 36 antimicrobial agents. The MICs of the aminoglycosides and tetracycline increased 1 to 3 dilutions in this medium compared with those in the usual medium, but the other antimicrobial agents were not consistently affected by the medium. Even though the medium caused an increase in MICs, the aminoglycosides and tetracyclines remained very active in vitro against F. tularensis. Other antimicrobial agents effective in vitro were chloramphenicol, erythromycin, ceftazidime, moxalactam, cefotaxime, ceftriaxone, and Sch 29482 (a cephalosporin).

Anti-Bacterial Agents↗

PubMed1985

Colonization of human wounds by Escherichia vulneris and Escherichia hermannii.

In this report we present clinical descriptions of 12 Hawaiian patients from whom Escherichia vulneris or E. hermannii strains were isolated. All but two patients had soft-tissue infections with multiple bacteria, particularly Staphylococcus aureus. The other two had purulent conjunctivitis associated with S. aureus and infected malignant peritonitis with multiple organisms, respectively. In none of the cases were the Escherichia spp. found in abundant quantities or considered pathogenic. In preliminary animal pathogenicity studies, 12 strains each of E. vulneris and E. hermannii failed to cause serious symptoms in 4-week-old mice when 10(7) cells were injected intraperitoneally. When 10(6) cells were used, none of these bacterial strains injected into mouse soft tissue was capable of producing persistent wound infections. Susceptibility studies of 40 strains of these bacteria to 20 different antimicrobial agents showed that they were susceptible to third-generation cephalosporins as well as to most other cephalosporins, aminoglycosides, trimethoprim, and sulfamethoxazole-trimethoprim; these strains were only marginally susceptible or resistant to penicillin, tetracycline, chloramphenicol, and nitrofurantoin.

Adult↗