Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Evaluating the in vitro susceptibility of bovine mastitis pathogens to a combination of kanamycin and cefalexin: Recommendations for a disk diffusion test.

Cows suffering from bovine mastitis have markedly reduced milk production because of inflammation within the udder subsequent to infection and damage from bacterial toxins. Antibiotic treatment is commonly used as a preventative and therapeutic measure for bovine mastitis. The most common pathogens include Staphylococcus aureus, various streptococci (Streptococcus dysgalactiae, Streptococcus uberis), and coliforms (Escherichia coli), which can be contracted from other infected cows or from the environment. A combination of kanamycin and cefalexin (1:1.5 wt/wt) is currently used therapeutically in Europe for the treatment of bovine mastitis, although standardized methods for the in vitro determination of the susceptibility of target pathogens have not been developed. This study evaluates the appropriate broth microdilution testing criteria for kanamycin and cefalexin administered in combination and reports the development of a disk diffusion test. At a ratio of kanamycin:cefalexin relevant to that observed in milk postadministration (10:1 wt/wt), the minimum inhibitory concentrations were determined against 307 isolates of target mastitis pathogens (staphylococci, streptococci, and E. coli). Based on achievable concentrations in milk and the resulting distribution of minimum inhibitory concentrations, preliminary broth breakpoints for kanamycin/cefalexin (10:1 fixed ratio) of or=32/3.2 microg/mL resistant were applied to evaluated staphylococci, streptococci, and E. coli. Parallel testing by disk diffusion and resulting error-rate bounded analysis using a combined disk concentration of 30 microg of kanamycin and 15 microg of cefalexin resulted in the establishment of preliminary disk interpretive breakpoints of >or=20 mm susceptible, 18 to 19 mm intermediate, and

Review of in vitro activity of third-generation cephalosporins and other newer beta-lactam antibiotics against clinically important bacteria.

The third-generation cephalosporins and some newer beta-lactam compounds such as the monobactams and carbapenems, when compared with first- and second-generation cephalosporins, have an extended spectrum of activity and generally greater activity against gram-negative bacilli of clinical importance. The increased spectrum includes the Enterobacteriaceae and Pseudomonas aeruginosa. Although the third-generation cephalosporins have some activity against P. aeruginosa, of those drugs now available in the United States, ceftazidime and cefoperazone are much more active than the others, and ceftazidime is more active than cefoperazone. The activity of the third-generation compounds against Acinetobacter species and other Pseudomonas species is limited. These compounds inhibit the growth of Hemophilus and Neisseria species (including beta-lactamase-producing isolates), nonenterococcal streptococci, and anaerobic gram-positive cocci. They also inhibit the growth of methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci but generally are not as active against these organisms as are the first-generation cephalosporins. They do not inhibit methicillin-resistant S. aureus. The activity of third-generation cephalosporins against anaerobes varies, but moxalactam and ceftizoxime are similar in activity to cefoxitin, a second-generation compound. The third-generation cephalosporins do not inhibit the growth of Listeria. A majority of organisms resistant to cephalothin and cefamandole (first- and second-generation cephalosporins) and to aminoglycosides are inhibited by third-generation cephalosporins.

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.

Epidemiologic characteristics of infections caused by ampicillin-resistant Hemophilus influenzae.

Hrom February 1974 through May 1975, 58 isolates of ampicillin-resistant Hemophilus influenzae from patients were submitted to the Center for Disease Control from 23 states and the District of Columbia. The epidemiologic characteristics of these widely scattered cases were strikingly similar to those of cases previously reported from individual communities or institutions. Because of the nationwide distribution of resistant isolates and the adverse consequences of ineffective therapy, the use of chloramphenicol is recommended for the initial management of systemic illness definitely or probably due to H. influenzae type b.

Cefoperazone: spectrum of antibacterial activity and disc diffusion testing.

Cefoperazone is a new cephalosporin with a very wide spectrum of antibacterial activity, including Enterobacteriaceae, Pseudomonas aeruginosa, staphylococci, streptococci (other than serological group D strains), Neisseria and Haemophilus species (including beta-lactamase positive strains) and some anaerobes. On testing more than 8700 clinical isolates, approximately 93% were inhibited by 16 micrograms/ml of cefoperazone, 95% by 32 micrograms/ml and 98% by 64 micrograms/ml. The drug is less active on Acinetobacter and group D streptococci. We recommend that a disc containing 75 micrograms of cefoperazone be used in the diffusion test with 'breakpoints' of less than or equal to 14 mm for resistant, 15-17 mm for intermediate, and greater than or equal to 18 mm for susceptible bacteria.

Cefuroxime, cefamandole, cefoxitin, and cephalothin in vitro susceptibility tests: reassessment of the "class representative" concept, confirmation of disk interpretive criteria, and proposed quality control guidelines.

The relationship of cefuroxime in vitro susceptibility tests to similar cephalosporins (cefamandole, cefoxitin, and cephalothin) was evaluated using 396 recent clinical isolates. The previously published interpretive criteria of greater than or equal to 18 mm (less than or equal to 8.0 micrograms/mL) = susceptible and less than or equal to 14 mm (greater than or equal to 32 micrograms/mL) = resistant for each drug were considered appropriate. The results of all study methods demonstrated cefuroxime to be slightly less active than cefamandole against most species, yet both drugs possessed nearly identical antimicrobial spectra. Cephalothin and cefoxitin were confirmed to have spectra significantly different from cefamandole and from each other, thus requiring separate testing. The application of the "class representative" concept to cefuroxime and cefamandole seems justified. Use of a 30-micrograms cefuroxime disk yielded the best predictive results and minimized the number of false-susceptible (very major) interpretive errors. Quality control guidelines are presented in a tentative form for cefuroxime, and modifications in the cephalothin and cefamandole zone limits are suggested.

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.

Gentamicin, tobramycin, and sisomicin disc susceptibility tests. Revised zone standards for interpretation.

Studies were undertaken to reevaluate interpretive zone standards for gentamicin and tobramycin disc tests. Disc tests with an investigational aminoglycoside, sisomicin, were also evaluated. The data suggest modification of zone standards for gentamicin disc tests to R (resistant) less than or equal to 12 mm and S (susceptible) greater than or equal to 16 mm. Currently recommended standards for tobramycin disc tests (R less than or equal to 12 mm and S greater than or equal to 15 mm) were found to be satisfactory. For 10-microgram sisomicin discs, zone standards of R less than or equal to 12 mm and S greater than or equal to 15 mm were also appropriate. Although gentamicin is structurally similar to sisomicin, it was less active against Pseudomonas aeruginosa. The activity spectrum of sisomicin against the collection of 470 bacterial isolates studied more nearly resembled that of tobramycin. Data analysis suggested that tobramycin disc tests might be used to predict susceptibility to sisomicin. However, these two drugs differ in their susceptibilities to aminoglycoside-inactivating enzymes produced by some resistant strains. In those institutions where such strains are endemic, the class concept of disc testing may not be applicable.

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.

The anti-microbial activity, beta-lactamase stability, and disk diffusion susceptibility testing of carumonam (RO 17-2301, AMA-1080), a new monobactam.

Carumonam, a new monobactam, was found to have an anti-microbial spectrum similar to aztreonam. Its spectrum includes Enterobacteriaceae, Haemophilus influenzae, pathogenic Neisseria species, Pseudomonas aeruginosa, and some streptococci. Staphylococcus species, enterococci, and many other nonenteric gram-negative bacilli were not inhibited. Enterobacteriaceae resistant to cefoperazone (minimum inhibitory concentrations [MICs] greater than or equal to 32 mg/L) were more likely inhibited by carumonam (52% at less than or equal to 8.0 mg/L) than aztreonam (39%) or ceftazidime (35%). Dilution test methods on agar or in Mueller-Hinton broth produced similar results. Carumonam minimum bactericidal concentrations were usually the same or one dilution above the MIC. Carumonam and aztreonam were very stable to most chromosomal (P99, K1, K14) and plasmid-mediated beta-lactamases (TEM, OXA, PSE). The Klebsiella oxytoca enzymes hydrolyzed aztreonam at rates greater than or equal to fivefold higher than carumonam but at a rate less than 1% that of cephaloridine. The aztreonam MICs for these Klebsiella stains were greater than or equal to 32 mg/L, but the hydrolysis rates do not fully explain the high-grade resistance to aztreonam. In vitro susceptibility tests with 30-micrograms carumonam disks were found to be very predictive. Similar regression statistics were observed for aztreonam and cefotaxime. Recommendations for carumonam susceptibility testing are susceptible greater than or equal to 21 mm (less than or equal to 8.0 mg/L) and resistant less than or equal to 14 mm (greater than or equal to 32 mg/L). Cross-resistance analysis favors the independent testing of carumonam or aztreonam against gram-negative species other than Enterobacteriaceae and P. aeruginosa.

In-vitro activities of cefamandole and cephalothin against 1,881 clinical isolates. A multi-center study.

By use of an agardilution technic, 1,881 clinical isolates were tested against cefamandole and cephalothin. The isolates represented 18 genera, recovered in five geographically separate centers within the United States. The majority of strains were susceptible (MICs less than or equal to 8 micrograms/ml) to both drugs. Cefamandole showed greater activity against most of the bacterial pathogens. Enterococci, Serratia spp., and Acinetobacter spp. were resistant to both drugs. Cephalothin was more active against Staphylococcus aureus, and both cephalosporins were relatively inactive against methicillin-resistant strains of S. aureus. Enterobacter spp. and indole-positive Proteus spp. were susceptible to cefamandole but resistant to cephalothin.

Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins.

Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins. Am J Clin Pathol 70: 909--913, 1978. Studies were carried out to determine whether susceptibility or resistance to 11 cephalosporins could be predicted reliably from the results of tests with a single cephalothin disk. The cephalosporins were tested with a microdilution technic and with a standardized disk test. Strains susceptible to a cephalothin disk were predictably susceptible to all other cephalosporins. However, 2--12% of the strains were resistant to cephalothin disks but were susceptible to the more active parenteral drugs cefoxitin, cephamandole, cefuroxime, and BL-S786. Because of differences in antimicrobial activities, the cephalosporins could be divided into three subgroups for purposes of susceptibility testing: one subgroup includes the majority of cephalosporins and may be represented by tests with cephalothin, the second subgroup inclues three active parenteral drugs (cephamandole, cefuroxime, and BL-S786) and may be represented by tests with cefuroxime, and the third subgroup consists of cefoxitin, a cephamycin with a unique broad spectrum of activity. Until the drugs in the second and third subgroups are released for general therapeutic use, the practice of testing only one cephalosporin disk appears to be a reasonably reliable procedure.

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.

Development of a standardized susceptibility test for campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem.

A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.

Effect of media and blood on the antimicrobial activity of cephalosporins on serogroup D streptococci: a review.

The influence of culture medium on in vitro of selected cephalosporins on on group D streptococci was investigated by agar diffusion and broth dilution methods. The activity of cephalothin, cefamandole, and cefoperazone were not substantially influenced by the type of culture medium used, but cefuroxime, ceftizoxime, cefotaxime (CTX), cefmenoxime, and ceftriaxone varied markedly with both the commercial brand and the blood content of the broth used. The differences were more likely to occur in some Mueller-Hinton media, particularly when supplemented with 5% lysed sheep blood, and resulted in susceptible results instead of the resistant results that were obtained with these same media without blood. Some strains of Streptococcus faecalis showed these discrepancies, but S. bovis did not. The influence of the media on in vitro activity suggests a complex interaction between some cephalosporins, media components, and organisms. The cephalosporins that were affected by media share an identical moiety at the 7-acyl position (cefuroxime is slightly different); this structure is not shared by those cephalosporins that were not affected, however. It is possible that this structure may play a part in the phenomenon.

Cefpirome (HR810) disk diffusion susceptibility tests: confirmation of interpretive criteria using cefotaxime and cefoperazone-resistant strains and effects of blood supplemented media.

Cefpirome (formerly HR810) is a wide-spectrum, beta-lactamase-stable cephalosporin with antimicrobial activity against Pseudomonas species, Enterobacteriaceae, and gram-positive species. Reevaluation of the 30-microgram disk diffusion tests with commercially prepared disks using strains resistant to "third generation," cephalosporins confirms the proposed susceptibility breakpoint zone of greater than or equal to 18 mm (minimal inhibitory concentration correlate, less than or equal to 8.0 micrograms/ml) and the resistance breakpoint zone of less than or equal to 14 mm (minimal inhibitory concentration correlate, greater than or equal to 32 micrograms/ml). Major and minor interpretive errors were only 3.8%, and these errors could be further reduced (2.3%) by not testing methicillin-resistant Staphylococcus species. The addition of 5% sheep blood or chocolated blood to Mueller-Hinton agar slightly increased the cefpirome zone diameters (17.7-22.2 mm) for nearly 60% of Streptococcus faecalis strains tested.

Antimicrobial activity of LY164846, a new oral cephalosporin, and recommendations for disk diffusion tests.

LY164846 is a new oral cephalosporin with a limited spectrum of antimicrobial activity that includes staphylococci (other than methicillin-resistant), streptococci (other than enterococci), Haemophilus influenzae (beta-lactamase-negative and beta-lactamase-positive), Branhamella catarrhalis (beta-lactamase-negative and beta-lactamase-positive), and Neisseria species (beta-lactamase negative and beta-lactamase-positive). The tentative recommendations for susceptibility breakpoints are less than or equal to 4 micrograms/ml and greater than or equal to 19 mm for susceptible, 8 micrograms/ml and 15-18 mm for intermediate, and greater than or equal to 16 micrograms/ml and less than or equal to 14 mm for resistant.

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.

Ceftriaxone: a summary of in vitro antibacterial qualities including recommendations for susceptibility tests with 30-micrograms disks.

The new aminothiazoyl-cephalosporin, ceftriaxone (Ro 13-9904), was found to have excellent inhibitory activity against the Enterobacteriaceae (minimum inhibitory concentration needed to inhibit 50% of isolates (MIC50) less than or equal to 0.004-0.5 microgram/ml, Haemophilus influenzae (MIC50 less than or equal to 0.004 micrograms/ml), Neisseria species (MIC50 less than or equal to 0.001 microgram/ml), pneumococci (MIC50 0.25 micrograms/ml), Staphylococcus aureus (MIC50 2.0 micrograms/ml), and Streptococcus pyogenes (MIC50 0.015 micrograms/ml). Ceftriaxone was less effective against Acinetobacter species, Pseudomonas aeruginosa, and other Pseudomonas species (MIC50 8.0-16 micrograms/ml). Methicillin-resistant S. aureus and enterococci were not significantly inhibited by ceftriaxone. Ceftriaxone was very resistant to beta-lactamase hydrolysis, although the type IV cephalosporinase minimally destroyed the compound at 16.4-19.9% of the rates for cephaloridine. Type I cephalosporinases were inhibited by ceftriaxone and related enzyme-stable cephalosporins. Based on analysis of disk-MIC regression statistics, tentative recommendations for the disk test of the National Committee for Clinical Laboratory Standards are 21 mm or more = susceptible, 14-20 mm = moderately susceptible, and 13 mm or less = resistant. These criteria produce interpretive accuracy of more than 92%, with very rare major errors. Ceftriaxone was comparable to cefotaxime in spectrum and activity, thus allowing the use of the "spectrum-class" concept (for example, cefotaxime tests in vitro to predict ceftriaxone susceptibility, and vice versa).