Biomedical subjects
Publications and source records attributed to C Thornsberry.
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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.
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A multi-center study of 1,838 clinical isolates established the accuracy of diffusion susceptibility tests with 30-mug cephalothin disks and 30-mug cefamandole disks. The same interpretive zone standards can be applied to tests with either disk but the two drugs cannot be tested interchangeably.
Randomly selected strains of beta-lactamase-negative and beta-lactamase-positive Neisseria gonorrhoeae were tested by an agar dilution method for susceptibility to rosamicin, josamycin, erythromycin, clindamycin, and penicillin G. Rosamicin was more active than erythromycin, which was more active than josamycin or clindamycin; the latter two were similar in their activity. The susceptibility to the macrolide antibiotics and clindamycin was independent of beta-lactamase production, but the penicillin minimal inhibitory concentrations were higher in the beta-lactamase-positive group because of the enzyme.
Because excessively high rates of false resistance have been encountered with the 10-mug amikacin disk in diffusion susceptibility tests, a study was performed to examine existing zone diameter interpretative criteria and to compare the accuracy of 10- and 30-mug amikacin disks by the error rate-bounded classification scheme. Although current zone diameter interpretative criteria eliminate false susceptibles, there is an unacceptably high rate of false resistants. This problem can be resolved in most instances by revising the zone diameter interpretative criteria for the 10-mug disk (resistant, </=9 mm; indeterminate, 10 to 11 mm; susceptible, >/=12 mm) or, preferably, by replacing the 10-mug disk with a 30-mug disk and adopting new interpretative criteria (resistant, </=14 mm; indeterminate, 15 to 16 mm; susceptible, >/=17 mm). Because of significant differences in performance among media, it is necessary to include Pseudomonas aeruginosa ATCC 27853 among controls routinely tested and to exclude from use lots of Mueller-Hinton agar yielding results outside the 75% tolerance (90% confidence) limits for amikacin.
Strains of Streptococcus pneumoniae resistant to penicillin have been reported from several countries around the world. Many South African isolates, in addition, exhibit resistance to tetracycline, chloramphenicol, erythromycin, clindamycin, and cotrimoxazole in varying patterns. A qualitative test of the ability of antibiotic-resistant pneumococci to inactivate penicillin, oxacillin, cephalothin, cefoxitin, chloramphenicol, tetracycline, minocycline, erythromycin, clindamycin, streptomycin, gentamicin, and cotrimoxazole revealed that only chloramphenicol was degraded. This finding was confirmed in a quantitative test in which the residual antimicrobial activity of broth containing chloramphenicol in subinhibitory concentrations was determined after incubation with antibiotic-resistant bacteria. Chloramphenicol resistance was shown to be associated with the production of inducible chloramphenicol acetyltransferase. No beta-lactamase activity was demonstrated. Plasmid deoxyribonucleic acid was not demonstrable in partially purified lysates of antibiotic-resistant strains of S. pneumoniae.
Piperacillin is a new semisynthetic penicillin with a spectrum of activity broader than that of carbenicillin or ticarcillin. Studies were performed to establish standards for agar diffusion susceptibility tests with piperacillin disks. Tests with 100-, 150-, and 200-micrograms piperacillin disks and with 100-micrograms carbenicillin disks were evaluated. With both penicillins, 100-micrograms disks were satisfactory, in spite of the fact that piperacillin is a larger molecule and diffuses at a slower rate. With both carbenicillin and piperacillin disks, resistant strains of Staphylococcus aureus produced zones less than or equal to 28 mm and susceptible strains gave zones greater than or equal to 29 mm in diameter. When testing other microorganisms, zone standards of less than or equal to 13 mm for resistant (minimal inhibitory concentration, greater than or equal to 256 micrograms/ml) and greater than or equal to 17 mm for susceptible (minimal inhibitory concentration, less than or equal to 64 micrograms/ml) are recommended for tests with 100-micrograms piperacillin disks. Similar zone standards are currently recommended for carbenicillin and ticarcillin disk tests.
Standard Bauer-Kirby disk tests were performed with 85 selected isolates, each tested in triplicate by four different investigators. Each disk test was observed, and zone diameters were measured, under two lighting conditions (transmitted light and reflected light). The two lighting systems produced similar zone measurements (+/-2 mm) with 96% of the tests. When there were greater differences, zones appeared to be larger when observed with reflected light. Interlaboratory reproducibility was much greater when using reflected light rather than transmitted light. We concluded that zone diameters should be measured from the back of the plate while it is resting on, or held 2 to 3 inches [ca. 5.1 to 7.6 cm] above, a black, nonreflecting, flat surface, illuminated by a reflected light source.
A collaborative study was undertaken to evaluate a simple, convenient device which expedites inoculum standardization for antimicrobial disk susceptibility tests. The Inocupac system (Minnesota Mining & Manufacturing [3M] Co., St. Paul, Minn.) was used to perform disk tests in parallel with the standard Bauer-Kirby method. Five investigators tested 100 selected isolates, each in triplicate. Inter- and intralaboratory precision of both disk procedures was essentially comparable. The Inocupac system failed to consistently provide satisfactory growth with some streptococci, but when testing common gram-negative bacilli, staphylococci, and most enterococci, the Inocupac system gave zones about the same size (+/-2 mm) as the Bauer-Kirby procedure. Interpretive agreement between the two test systems varied from 90 to 99% with different antimicrobial agents, and repeated tests with the Bauer-Kirby method demonstrated the same degree of interpretive agreement. The Inocupac system is a valid alternative method for inoculating disk susceptibility tests.
Piperacillin, a new semisynthetic penicillin, was found to have potent antimicrobial activity against nearly all (405) tested bacterial species. Piperacillin was consistently 4 approximately 16-fold more active than carbenicillin against the Enterobacteriaceae, 16 approximately 32-fold against Pseudomonas aeruginosa and Pseudomonas species, and 16-fold against Streptococcus faecalis. Carbenicillin and piperacillin were equally effective against Staphylococcus aureus, but inactivated by beta-lactamase. A 38% overall synergy rate for the piperacillin-gentamicin combination was identified, a finding similar to that for carbenicillin-gentamicin. Highest incidences of synergy were found for both antibiotic pairs tested on gentamicin-resistant isolates (Ps. aeruginosa and Providencia). In vitro findings suggest that piperacillin alone or in combination with aminoglycosides may be highly efficacious in the treatment of most serious bacterial infections.
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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.
In September 1976 the Center for Disease Control (Atlanta, Georgia) initiated surveillance for cases of infection due to penicillinase-productin Neisseria gonorrhoeae in the United States. One hundred ninety-one cases of penicillinase-producing gonococcal infection were confirmed through June 30, 1977. Of 177 cases for which histories of sexual exposure were available, 69 were traced to sexual contact in the Far East, and one was traced to sexual contact in West Africa. Of 181 cases for which clinical information was available, 174 were uncomplicated anogenital infections, but local complications, such as salpingitis, epididymitis, and a Bartholin's gland abscess, were reported. Spectinomycin is the only drug now recommended by the U.S. Public Health Service for treatment of gonorrhea that is effective against uncomplicated infections due to penicillinase-producing gonococci. For these organisms, the distribution of minimal inhibitory concentrations (MICs) of penicillin, ampicillin, tetracycline, erythromycin, and spectinomycin was higher than and significantly different from the distribution of MICs for isolates of non-penicillinase-producing gonococci collected in this country. Since surveillance began the incidence of confirmed cases of penicillinase-producing gonococcal infection has decreased from 20.8 cases per month in 1976 to 16.8 cases per month in 1977.
Previous studies from Seattle, Wash., suggested that strains of Neisseria gonorrhoeae which require arginine, hypoxanthine, and uracil (Arg-Hyx-Ura- auxotype) are unifomly highly susceptible to penicillin G, are relatively resistant to complement-dependent killing by heated, pooled human serum, and are associated with disseminated gonococcal infection. For further study of the epidemiology of these strains and for analysis of the susceptibility to penicillin, serum sensitivity, and the nutritional requirements of gonococcal isolates from other cities, a survey was made of urethral and cervical strains isolated in 1972--1974 from 50 randomly selected pateit-s with uncomplicated gonorrhea from each of nine cities. Arg-Hyx-Ura-strains represented greater than 50% of isolates from Seattle and Des Moines, Iowa, 22% of isolates from Denver, Colo., and Dayton, Ohio, and less than or equal to 12% of the isolates from Boston, Mass., Newark, N.J., Norfork, Va., Miami, Fla., and Oakland, Calif. Arg-Hyx-Ura- strains were recovered from 42% of white and 9% of black patients (P less than 0.001), and clincis with the highest incidences of these strains had the highest proportion of white patients among those with gonorrhea. Arg-Hyx-Ura- strains were all susceptible to less than or equal to 0.125 microgram of penicillin G/ml and were more resistant than strains with other auxotypes to killing by heat-inactivated human serum plus complement (P less than 0.001).
Six isolates of Legionnaires disease bacteria were tested for their susceptibility to 22 antimicrobial agents. The most active agent was rifampin (minimal inhibitory concentration, </=0.01 mug/ml). On the basis of minimal inhibitory concentration breakpoints that have been used to categorize susceptibility for most of these drugs, the organisms were susceptible to rifampin, cefoxitin, erythromycin, the aminoglycosides, minocycline and doxycycline, chloramphenicol, ampicillin, penicillin G, carbenicillin, colistin, and sulfamethoxazole-trimethoprim (19:1 ratio); sensitive to intermediate in susceptibility to tetracycline, methicillin, cefamandole, cephalothin, and clindamycin; and resistant to vancomycin. More clinical data must be obtained before an optimal therapeutic regimen can be recommended.
Fifty clinical isolates of Streptococcus pneumoniae received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests. No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin. This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin. An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance. Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms. Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade. However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy.
In an ongoing cooperative study of uncomplicated genital gonorrhea within the United States, 6,735 pretreatment gonococcal isolates were tested for their in vitro resistance to penicillin. By using a regression analysis technique, we examined 99 patient-associated variables which might be associated with penicillin resistance of the isolates. Patients were most likely to have relatively resistant isolates if they were black, had used antimicrobial agents within 2 weeks of treatment for gonorrhea, or were men with symptomatic urethritis.