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Biomedical subjects

E H Gerlach

Publications and source records attributed to E H Gerlach.

At least 55 records · Page 3Linked to original sources

RO 23-6240 (AM-833), a new fluoroquinolone: in vitro antimicrobial activity and tentative disk diffusion interpretive criteria.

The susceptibility of over 7000 recent clinical bacterial isolates to RO 23-6240, a new trifluorinated quinolone, was determined at four medical centers. Over 99% of Enterobacteriaceae and 97% of staphylococci were inhibited by less than or equal to 2.0 micrograms/ml of RO 23-6240. Only 71% of Pseudomonas spp. were inhibited by this concentration. Streptococci and enterococci were resistant to RO 23-6240. Clinical isolates of Haemophilus spp., pathogenic Neisseria spp., and Branhamella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of RO 23-6240. This drug's antibacterial activity was comparable with that of enoxacin and norfloxacin, but was less than that of ciprofloxacin against most species. Using less than or equal to 2.0 micrograms/ml and greater than or equal to 8.0 micrograms/ml as the susceptible and resistant MIC breakpoints for RO 23-6240, the regression analysis-derived disk diffusion zone diameter breakpoints for the 5 micrograms disk are: Susceptible greater than or equal to 19 mm intermediate 16-18 mm, and resistant less than or equal to 15 mm.

Anti-Bacterial Agents↗

Quality control limits for microdilution susceptibility tests with aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid.

A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid). Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

Anti-Bacterial Agents↗

Comparative antimicrobial activity of aminothiazolyl methoxyimino cephalosporins against anaerobic bacteria, including 100 cefoxitin-resistant isolates.

Three aminothiazolyl methoxyimino cephalosporins (ceftizoxime, ceftriaxone, and cefotaxime with and without its metabolite) were tested against 500 strains of anaerobic bacteria using the NCCLS reference agar dilution procedure. Eighty-seven percent of all strains tested were from the Bacteroides fragilis group. When tested against a collection of 100 cefoxitin-resistant isolates, ceftizoxime and the cefotaxime/desacetyl-cefotaxime combination were the most active in vitro, inhibiting 32-38% of strains. Ceftriaxone inhibited the greatest number (87%) of cefoxitin-susceptible anaerobes at less than or equal to 32 micrograms/ml. A regional variation in the activity of these drugs was confirmed when an additional 300 isolates were examined from three medical centers. Cefotaxime, ceftizoxime, and ceftriaxone were essentially equal in overall antimicrobial activity, although each drug was judged the best at one of the three locations. Cefoxitin resistance (MIC greater than or equal to 32 micrograms/ml) was consistent among the institutions at a 25% incidence for all organisms tested, and 28% cefoxitin resistance among the B. fragilis group strains. Cefoxitin resistance was not determined to be associated with a beta-lactamase mechanism, but ceftriaxone and other aminothiazolyl cephems were hydrolyzed, thus elevating their MICs. Regional variation in anaerobic organism susceptibility to cephamycins and cephalosporins in company with the variable beta-lactam resistance mechanisms seems to require periodic, epidemiologic monitoring of in vitro drug activity by appropriate methods to assure continued antimicrobial efficacy.

Bacteria, Anaerobic↗

Quality control limits for microdilution susceptibility tests with norfloxacin.

A multilaboratory study was designed to define quality control limits for microdilution susceptibility tests with norfloxacin. The following limits were proposed: for Escherichia coli ATCC 25922, 0.03 to 0.125 micrograms/ml; for Pseudomonas aeruginosa ATCC 27853, 1.0 to 4.0 micrograms/ml; for Staphylococcus aureus ATCC 29213, 0.5 to 2.0 micrograms/ml; and for Streptococcus faecalis ATCC 29212, 2.0 to 8.0 micrograms/ml. The latter represents a change in the previously recommended control limits.

Enterococcus faecalis↗

In vitro activity of the aryl-fluoroquinolones A-56619 and A-56620 and evaluation of disk susceptibility tests.

The activity of two new quinolones, A-56619 and A-56620, was compared in vitro to that of norfloxacin and ciprofloxacin against 6,699 bacterial isolates in four separate clinical laboratories. The overall percentage of strains susceptible to designated concentrations were as follows: 99.1% for norfloxacin (MIC less than or equal to 4.0 micrograms/ml), 96.1% for ciprofloxacin (MIC less than or equal to 1.0 micrograms/ml), 96.8% for A-56620 (MIC less than or equal to 2.0 micrograms/ml) and 96.1% for A-56619 (MIC less than or equal to 4.0 micrograms/ml). For disk diffusion susceptibility tests 10 micrograms A-56619 disks are tentatively recommended with interpretive standards of greater than or equal to 18 mm for susceptibility and less than or equal to 13 mm for resistance; 5 micrograms A-56620 disks may be used with tentative standards of greater than or equal to 19 mm for susceptibility and less than or equal to 14 mm for resistance.

Anti-Infective Agents↗

In vitro activity of carumonam (RO 17-2301), BMY-28142, aztreonam, and ceftazidime against 7,620 consecutive clinical bacterial isolates.

For 45-60 days four geographically separate clinical laboratories tested routine clinical bacterial isolates for susceptibility to carumonam, aztreonam, BMY-28142, and ceftazidime by the broth microdilution method. All four drugs were highly active against Enterobacteriaceae, inhibiting greater than 96% of the 4887 strains tested at less than or equal to 8.0 microgram/ml. The minimal inhibitory concentration at which 50% of the isolates were inhibited for each drug was less than or equal to 0.125 micrograms/ml. Ceftazidime was the most active against nonenteric gram-negative bacilli (86% inhibited at less than or equal to 8.0 micrograms/ml), followed by BMY 28142 (82%), carumonam (75%), and aztreonam (68%). The two monobactams exhibited no activity against gram-positive cocci at the concentrations tested, whereas BMY-28142 had excellent activity against nonenterococcal streptococci and good activity against staphylococci.

Anti-Bacterial Agents↗

In vitro activity of DJ-6783 (a keto carboxylic acid) compared with six other orally administered antimicrobial agents.

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.

Anti-Bacterial Agents↗

In vitro evaluation of cefixime (FK027, FR17027, CL284635): spectrum against recent clinical isolates, comparative antimicrobial activity, beta-lactamase stability, and preliminary susceptibility testing criteria.

Cefixime, a new orally absorbed cephalosporin, was compared by in vitro testing with other oral beta-lactams, including cephalexin, cefaclor, cefuroxime, amoxicillin, and amoxicillin + clavulanate. Enterobacteriaceae were inhibited by lower concentrations of cefixime than any of the reference drugs; 90% and 95% were inhibited by less than or equal to 1.0 and less than or equal to 8.0 micrograms/ml, respectively. Cefixime was the least active among these drugs against staphylococci, with only 31% of 1106 strains inhibited by less than or equal to 8.0 micrograms/ml and less than 1% by less than or equal to 1.0 microgram/ml. Enterococci and pseudomonads were not susceptible to any of the drugs tested. Penicillin-resistant pneumococci were relatively resistant to cefixime, but penicillin-susceptible pneumococci were very susceptible to cefixime. Other streptococci were generally susceptible to all compounds tested, with relative activities of amoxicillin greater than cefaclor and cefuroxime greater than cefixime greater than cephalexin. Cefixime was inactive against Bacteroides species. A slight inoculum effect occurred with cefixime with inocolum concentrations varying from 10(5) to 10(6) colony forming units per milliliter, but this was more marked at 10(7) colony forming units per milliliter. Cefixime was resistant to hydrolysis by seven common beta-lactamases. It inhibited the hydrolysis of nitrocefin only by type 1 cephalosporinases. The disk diffusion zone diameter breakpoints for the 30-micrograms cefixime disk were determined by regression analysis to be greater than or equal to 27 mm (susceptible) and less than or equal to 23 mm (resistant), respectively corresponding to minimal inhibitory concentration breakpoints of less than or equal to 1.0 and greater than or equal to 4.0 micrograms/ml. Because of the high interpretive error rate (13.8%) and the occurrence of these breakpoints on the parabolic portion of the regression curve, we recommend further evaluation of cefixime disks with lower potencies.

Amoxicillin↗

Antimicrobial activity of Ro 15-8074, active metabolite of a new oral cephalosporin (Ro 15-8075), against 7,775 recent clinical isolates.

Susceptibility testing of 7,775 recent clinical isolates from four medical centers showed Ro 15-8074 to be 2-to greater than 8-fold more active than either cefaclor or cefuroxime against the Enterobacteriaceae. Ro 15-8074 MICs for 50% of the strains tested were greater than or equal to 32 micrograms/ml for Staphylococcus spp., enterococci, Pseudomonas aeruginosa, and Pseudomonas maltophilia. beta-Lactamase hydrolysis experiments failed to demonstrate significant Ro 15-8074 inactivation by commonly encountered chromosomal or plasmid-mediated enzymes (P99, K1, K14, TEM, and CARB).

Anti-Bacterial Agents↗

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↗

Antimicrobial activity of HR810 against 419 strict anaerobic bacteria.

HR810 and four other new beta-lactams were tested against 419 recent clinical anaerobic bacterial isolates. HR810 was found to have an antimicrobial spectrum most similar to that of cefotaxime, inhibiting 52.6% of Bacteroides fragilis group strains and 97.2% of all other anaerobic strains at an MIC of less than or equal to 16 micrograms/ml. Cefoxitin was found to have a narrower antimicrobial spectrum against the gram-positive anaerobic bacteria (8.4 to 10.1% less) than HR810 and cefotaxime, respectively.

Anti-Bacterial Agents↗

In vitro comparative antimicrobial activity of cefpimizole against clinical isolates from five medical centers.

Cefpimizole was compared with cefoperazone and cefotaxime against 6,599 clinical bacterial isolates from five medical centers. Cefoperazone and cefotaxime were both more active and provided a greater spectrum of antimicrobial coverage than cefpimizole. Some of the cefpimizole minimum concentrations inhibiting 50% of tested strains were as follows: Citrobacter freundii and Enterobacter cloacae, 16 micrograms/ml; Escherichia coli and Klebsiella pneumoniae, 2.0 micrograms/ml; Proteus mirabilis, 1.0 microgram/ml; Pseudomonas aeruginosa, 16 micrograms/ml; Staphylococcus spp., 32 micrograms/ml; and the enterococci, greater than 32 micrograms/ml.

Bacteria↗

3-0-demethyl fortimicin A: in vitro activity and interpretive zone standards for disk diffusion susceptibility tests.

The in vitro activity of 3-0-demethyl fortimicin A was compared to that of amikacin and tobramycin against 5,230 clinical isolates in four institutions. Amikacin and tobramycin were more active than 3-0-demethyl fortimicin A against Pseudomonas aeruginosa and Acinetobacter spp., but all three drugs had similar activity against the Enterobacteriaceae and Staphylococcus aureus. Additional tests with 335 representative gram-negative bacilli compared five different aminoglycosides, demonstrating differences with some isolates. Standardized disk diffusion tests were also performed with 30 micrograms 3-0-demethyl fortimicin A disks, according to the National Committee for Clinical Laboratory Standards. The following interpretive breakpoints are proposed: less than or equal to 11 mm for resistant (MIC greater than or equal to 32 micrograms/ml) and greater than or equal to 15 mm for susceptible (MIC less than or equal to 16 micrograms/ml).

Acinetobacter↗

In vitro activity of ticarcillin plus clavulanic acid against bacteria isolated in three centers.

Over 10,000 bacterial isolates were tested against ticarcillin alone or combined with clavulanic acid (2.0 micrograms/ml). Of 5,295 Enterobacteriaceae, 72% were susceptible to ticarcillin alone, whereas 91% were susceptible to the combination. Bacteroides fragilis and Bacteroides melaninogenicus isolates were more susceptible to the combination. The activity of ticarcillin against other microorganisms was not profoundly influenced.

Anti-Bacterial Agents↗

Antibacterial activities of ciprofloxacin, norfloxacin, oxolinic acid, cinoxacin, and nalidixic acid.

In vitro studies were performed comparing ciprofloxacin (Bay o 9867) and norfloxacin with three related organic acids. Ciprofloxacin was two to eight times more active than norfloxacin against 658 bacterial isolates representing 30 species. For all species tested, ciprofloxacin MICs for 90% inhibition were less than or equal to 2.0 micrograms ml. Additional tests with 5,994 isolates detected only 37 (0.6%) strains resistant to 2.0 micrograms of ciprofloxacin per ml and 106 (1.8%) resistant to 1.0 micrograms/ml. Only 6 (0.1%) of the 5,994 strains were resistant to 16 micrograms of norfloxacin per ml, and 129 (2.1%) were resistant to 4.0 micrograms/ml. The majority of resistant strains were streptococci or Pseudomonas spp. Resistance among the Enterobacteriaceae was extremely rare (i.e., greater than 99.8% susceptible to both drugs.

Anti-Bacterial Agents↗

In vitro activity of apalcillin compared with those of piperacillin and carbenicillin against 6,797 bacterial isolates from four separate medical centers.

Quantitative susceptibility tests were performed in four separate medical centers, in which apalcillin was compared with piperacillin and carbenicillin. Data from tests of 6,797 isolates confirmed that apalcillin and piperacillin had nearly identical spectra of activity but that apalcillin was significantly more active against Pseudomonas aeruginosa (MIC required to inhibit 90% of strains, 2.0 versus 64 micrograms/ml) and Acinetobacter calcoaceticus subsp. anitratus (MIC required to inhibit 90% of strains, 2.0 versus 16 micrograms/ml). Against 166 anaerobic bacterial isolates, apalcillin demonstrated in vitro activity.

Ampicillin↗

Disk diffusion testing, quality control guidelines, and antimicrobial spectrum of HR810, a fourth-generation cephalosporin, in clinical microbiology laboratories.

HR810 is a new, very broad-spectrum cephalosporin with significant activity against members of the family Enterobacteriaceae, pseudomonads, gram-positive cocci, and anaerobes that is generally greater than the third-generation cephalosporins (99.6% of 4,128 clinical facultative enteric isolates were inhibited by less than or equal to 8.0 micrograms of HR810 per ml). Tests and statistical methods to establish in vitro antimicrobial susceptibility test criteria favor tentative breakpoints of greater than or equal to 18 mm (less than or equal to 8.0 micrograms/ml) as susceptible and less than or equal to 14 mm (greater than or equal to 32 micrograms/ml) as resistant. This provides a 93.7 to 98.3% absolute interpretive accuracy. Several preliminary ranges for zone sizes obtained with quality control organisms are proposed for the 30-micrograms HR810 disk diffusion test used during the clinical trials.

Bacteria↗