Rosamicin: in vitro activity comparison with erythromycin and other antibiotics against clinical isolates from the genito-urinary tract and Neisseria meningitidis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Thornsberry.
Explore the source record for details and available documents.
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.
The inability of sulfamethoxazole-trimethoprim (SXT) to eradicate Haemophilus influenzae nasopharyngeal carriage in all asymptomatic patients in closed populations was examined in vitro. A broth medium was adapted for susceptibility testing of H. influenzae which permitted us to determine minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs). The minimum inhibitory concentrations were all low, but the MBCs were bimodally distributed. Trimethoprim alone or the combination SXT either was bactericidal for H. influenzae isolates at low concentrations (i.e., low MBCs) similar to minimum inhibitory concentrations or showed no bactericidal activity (i.e., high MBCs). If trimethoprim was bactericidal when tested alone against H. influenzae, then the combination SXT was also bactericidal. H. influenzae carriage could not be eradicated from asymptomatic patients with SXT therapy when that combination was not bactericidal for these isolates in vitro. H. influenzae carriage was eradicated from patients when the activity of SXT was bactericidal in vitro. H. influenzae strains that are not killed by trimethoprim or SXT seem to occur at random.
Sodium clavulanate at subinhibitory concentrations affected the activity of penicillin G, ampicillin, or amoxicillin on beta-lactamase-positive strains of Neisseria gonorrhoeae as demonstrated by marked reduction in the minimal inhibitory concentrations of the drugs for the organisms. The compound did not affect the activity of these penicillins on beta-lactamase-negative strains of N. gonorrhoeae. It also had no effect on the activity of cefoxitin against either beta-lactamase-negative or -positive strains. The reduction in minimal inhibitory concentrations of the penicillins for the beta-lactamase-positive organisms brought about by sodium clavulanate is probably due to inhibition of the beta-lactamase by the compound.
The emergence of beta-lactamase-producing strains of Neisseria gonorrhoeae has led to a reexamination of the role of the disc agar diffusion method in susceptibility testing of gonococci. Our data show that the disc agar diffusion test can be used to screen for beta-lactamase production by these organisms. The disc tests were done on GC Agar Base supplemented with 1% IsoVitaleX. An inoculum of 10(8) colony forming units/ml and either a 10-unit-penicillin or a 10-microgram-ampicillin disc were used. A zone diameter of less than or equal to 19 mm was indicative of beta-lactamase production. These results were compared with results of chemical tests for beta-lactamase and with minimal inhibitory concentrations. Recommondations were also made for a disc test with tetracycline and spectinomycin, but these methods must remain tentative because of the lack of resistant strains.
Since their recognition early in 1976, penicillinase (beta-lactamase)-producing Neisseria gonorrhoeae (P.P.N.G.) have been isolated in more than 15 countries. Most strains isolated in or epidemiologically linked with the Far East are relatively resistant to tetracycline in vitro, are phenotypically wild-type or proline-dependent auxotypes, and carry a plasmid with a molecular weight of 5800 000 (5-8 X 10(6)) daltons coding for beta-lactamase production. In contrast, P.P.N.G. epidemiologically linked with West Africa are more susceptible to tetracycline, require arginine for growth, and their gene coding for beta-lactamase synthesis is contained in a smaller 3-2 X 10(6) dalton plasmid. Moreover, 43% of the Far Eastern strains, but none of those from West Africa, have an additional 24-5 X 10(6) dalton conjugative plasmid which transfers the beta-lactamase R factor(s) to other gonococci. The presence of this conjugative plasmid may explain the relatively high prevalence of P.P.N.G. in certain areas of the Far East.
Neisseria gonorrhoeae resistant to high levels of spectinomycin (more than 2,048 microng/ml), were isolated from specimens obtained from a patient with urethritis. The bacterial resistance to spectinomycin is probably due to ribosomal changes that are a result of a chromosomal mutation. If spectinomycin fails to cure gonorrhea, spectinomycin resistance should be considered.
In 1972 and 1973 a nationwide outbreak of typhoid fever occurred in Mexico. The responsible strain of Salmonella typhi had a characteristic pattern of phage lysis, resembling the type A pattern, referred to as degraded Vi(A), and was resistant to chloramphenicol and other antimicrobial agents in vitro and in vivo. Eighty cases of infection with strains of S. typhi that were related to the Mexican epidemic strain were reported in the United States. The epidemic in Mexico subsided in mid-1973, and no further cases of typhoid fever due to chloramphenicol-resistant organisms were reported in the United States. Infections with chloramphenicol-sensitive strains of S. typhi with the phage lysis pattern of degraded (Vi(A) occurred in association with travel in Mexico before and after the height of the epidemic in Mexico. Although typhoid fever due to chloramphenicol-resistant organisms has not been reported in the United States since the subsidence of the Mexican epidemic, testing of isolates of S. typhi for antibiotic sensitivity is recommended because of the continued existence of resistant strains elsewhere.
The following regimens were randomly administered to 271 men with gonococcal urethritis: 4.8 X 10(6) units of aqueous procaine penicillin G intramuscularly plus 1 g of probenecid orally (APPG); nine tablets of trimethoprim-sulfamethoxazole (TMP-SMZ; 720 mg of TMP and 3,600 mg of SMZ), orally as a single dose (TMP-SMZ-9); and 12 tablets of TMP-SMZ (960 mg of TMP and 4,800 mg of SMZ) orally as two doses of six tablets taken at a 6-hr interval (TMP-SMZ-12). The failure rates of the APPG, TMP-SMZ-9, and TMP-SMZ-12 regimens were 4%, 23%, and 19%, respectively. APPG was significantly more effective (P less than 0.05) than TMP-SMZ-9 or TMP-SMZ-12. Isolates of Neisseria gonorrhoeae from treatment failures as compared to those from treatment successes were significantly more resistant to SMZ (P less than 0.01) and to the TMP-SMZ combination in a ratio of 19 parts SMZ to one part TMP (P less than 0.05). Minimal inhibitory concentrations of SMZ, TMP, TMP-SMZ, and penicillin G showed positive correlation coefficients.
Minimal inhibitory concentrations (MICs) of antimicrobial agents for anaerobic bacteria can be determined by agar dilution and broth dilution (including microdilution) techniques. If MICs are not determined routinely, the disk broth or category methods are recommended for routine use. The Bauer-Kirby disk diffusion method and its interpretative standards should not be used for anaerobes.
Over 8,400 pretreatment isolates of Neisseria gonorrhoeae collected in the United States between November 1972 and April 1975 were tested for their in vitro resistance to penicillin, ampicillin, tetracycline, and spectinomycin. Trends and seasonality of resistance were examined by use of a harmonic regression technique. During the study period, there was a significant difference among years in the mean minimal inhibitory concentrations (MICs) for each antibiotic (P less than 0.001 for penicillin, ampicillin, and tetracycline; P less 0.05 for spectinomycin), and the mean MIC for each antibiotic decreased. Resistance to tetracycline and penicillin was highest in the winter months. Seasonality of resistance, alone or as an interaction with year, approached significance (P less than 0.10) or was significant (P less than 0.05) for all four antibiotics.
Recent isolates of Neisseria gonorrhoeae have been shown to be resistant to penicillin because they produce beta-lactamase. In this study, conjugal transfer of the beta-lactamase gene to a recipient N. gonorrhoeae strain occurred in one of the two strains studied but not in the other. The transconjugant could also conjugally transfer the beta-lactamase gene to an Escherichia coli strain.
Cefuroxime, a new parenteral cephalosporin was compared with cephalothin by broth microdilution susceptibility testing against 5,887 routine clinical bacterial isolates in four large clinical laboratories. The minimal inhibitory concentrations (MICs) of cefuroxime against the Enterobacteriaceae were consistently lower than those of cephalothin. This was most striking among the Enterobacter species, which were generally susceptible to cefuroxime (MIC </= 8 mug/ml), but resistant to cephalothin. Similar results occurred with Haemophilus species, Acinetobacter anitratus, meningococci, and Aeromonas hydrophilia, but Pseudomonas species and enterococci were resistant to high concentrations of both drugs. Streptococci showed slightly greater susceptibility to cefuroxime than to cephalothin. By contrast, staphylococci were more susceptible to cephalothin. Bacteroides fragilis was resistant to cefuroxime, but other anaerobes were generally susceptible.