Thomas L. Gavan

Unusual Serum Lipoprotein Abnormality Induced by the Vehicle of Miconazole

Miconazole, a phenethylimidazole,1 is effective in vitro against several pathogenic fungi,1 , 2 and has cured systemic mycoses in man.3 , 5 In contrast to amphotericin B, miconazole does not appear...

Antibiotic concentrations in human bone. A preliminary report.

Fifty patients who underwent total hip arthroplasty were given oxacillin preoperatively and intraoperatively. Simultaneous specimens of bone and serum were obtained during the operation and assayed for oxacillin content. The different doses and modes of administration were compared with respect to antibiotic concentration in bone and in serum. Significant oxacillin bone levels were attainable when oxacillin was appropriately administered.

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 (2.0μg/ml). Of 5,295Enterobacteraceae, 72% were susceptible to ticarcillin alone, whereas 91% were susceptible to the combination.Bacteroides fragilis andBacteroides melaninogenicus isolates were more susceptible to the combination. The activity of ticarcillin against other microorganisms was not profoundly influenced.

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 drugs 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.

In vitro evaluation of cefixime (FK027, FR17027, CL284635): Spectrum against recent clinical isolates, comparative antimicrobial activity, β-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.

Interpretation of the Disk Diffusion Susceptibility Test for Amikacin: Report of a Collaborative Study

Because excessively high rates of false resistance have been encountered with the 10-μg 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-μg 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-μg disk (resistant, ≤9 mm; indeterminate, 10 to 11 mm; susceptible, ≥12 mm) or, preferably, by replacing the 10-μg disk with a 30-μg 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.

Interpretive criteria, quality control guidelines, and drug stability studies for susceptibility testing of cefotaxime, cefoxitin, ceftazidime, and cefuroxime against Neisseria gonorrhoeae

Cefotaxime, cefoxitin, ceftazidime, and cefuroxime were tested in a multicenter study to establish susceptibility testing criteria and quality control guidelines for Neisseria gonorrhoeae. Interpretive criteria were established by using triplicate testing of at least 100 gonococcal strains having various susceptibility patterns to currently utilized drug regimens. Only a susceptible category was proposed for cefotaxime and ceftazidime (greater than or equal to 31 mm and less than or equal to 0.5 micrograms/ml) because of rare resistant isolates. The other interpretive crtieria were cefoxitin susceptible, greater than or equal to 28 mm (less than or equal to 2 micrograms/ml); intermediate, 24-27 mm (4 micrograms/ml), and resistant, less than or equal to 23 mm (greater than or equal to 8 micrograms/ml); cefuroxime-susceptible, greater than or equal to 31 mm (less than or equal to 1 micrograms/ml); moderately susceptible, 26-30 mm (2 micrograms/ml); and resistant, less than or equal to 25 mm (greater than or equal to 4 micrograms/ml). Quality control criteria were established by using multiple agar lots, three disk lots, and a number of replicates consistent with National Committee for Clinical Laboratory Standards M23-T guidelines.

Pharmacokinetics of gentamicin during exchange transfusions in neonates

6. Steinherz P, Rosen G, Ghavimi F, Wollner N, Wang Y, and Miller D: Improved leukocyte counts after chemotherapy with lithium carbonate, Proc Am Soc Clin Onc 20:439, 1979. 7. Ghavimi F, Exelby P, Jereb B, Scott BF, Lieberman PH, and Kosloff C: The multidisciplinary treatment for advanced stages of embryonal rhabdomyosarcoma in children, JNCI (in press). 8. Snedecor GW, and Cochran WG: Statistical methods, Ames, Iowa, 1976, Iowa State University Press, p 128. 9. Tisman, G, Herbert V, and Rosenblatt S: Evidence that lithium induces human granulocyte proliferation: Elevated Serum vitamin BI~ binding capacity in vivo and granulocyte colony proliferation in vitro, Br J Haematol 24:767, 1973. 10. MaUoy NL, Zauber NP, and Chervenick PA: The effect of lithium on blood and marrow neutrophils, Blood 52:228, 1978. 11. Rothstein G, Clarkson DR, Larsen W, Grosset BI, and Athens JW: Effect of lithium on neutrophil mass and production, N Engl J Med 298:178, 1978. 12. Rossof AH, and Coltman CA: The effect of lithium carbonate on the granulocyte phagocytic index, Experimentia 32:238, 1976. 13. Shenkman L, Borkowsky W, Holzman RS, and Shopsin B: Enhancement of lymphocyte and macrophage function in vitro by lithium carbonate, Clin Immunol Immunopathol 10:187, 1978. 14. Cohen MS, Zakhireh G, Metcalf JA, and Root RK: Granulocyte function during lithium treatment, Blood 53:913, 1979. 15. Harker WG, Rothstein G, Clarkson D, Athens JW, and Macfarlane JL: Enhancement of colony-stimulating activity production by lithium, Blood 49:263, 1977. 16. Morley DC, and Galbraith PR: Effect of lithium on granulopoiesis in culture, Can Med Assoc J 118:288, 1978. 17. Tisman G: Lithium carbonate protection against druginduced leukopenia in lymphosarcoma patients, J Int Res Commun 2:1509, 1974. 18. Catone R, Kaufman J, Mittelman A, and Murphy GP: Attenuation of myelosuppression with lithium, N Engl J Med 297:452, I977. 19. Charron D, Barrett AJ, Faille A, Alby N, Schmitt T, and Degos L: Lithium in myeloid leukemia, Lancet 1:1307, 1977. 20. Greco FA, and Brereton HD: Effect of lithium carbonate on the neutropenia caused by chemothearpy: A preliminary clinical trial, Oncology 34:153, 1977. 21. Lyman GH, Williams CG, and Preston D: A prospective randomized study of the effect of lithium carbonate on the granulocytopenia and incidence of infection associated with intensive chemotherapy and radiation therapy for undifferentiated small cell bronchogenic carcinoma, Blood 52:228, 1978. 22. Stein RS, Hanson G, Koethe S, and Hanson R: Lithiuminduced granulotosis, Ann Intern Meal 88:809, 1978. 23. Stein RS, Flexner JM, and Graber S: Lithium and granulocytopenia during induction therapy for acute myelogenous leukemia, Blood 52:277, 1978. 24. Tiefenbach A, Konja J, Potkonjak-Sesko M, and Mestrovic B: Effect of Li~CO3 on leukopenia in children during treatment of acute leukemia, Lijec Vjesm 99:163, 1977.

In vitro activity of carumonam (RO 17-2301), BMY-28142, aztreonam, and ceftazidime against 7620 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.

Quality control parameters and interpretive criteria for in vitro susceptibility tests with the macrolide azithromycin

Quality control parameters for broth microdilution and disk diffusion susceptibility tests were defined and the interpretive criteria for disk diffusion tests reviewed. For interpretation of tests with 15 µg azithromycin disks, the following criteria are recommended: ⩾19 mm for the susceptible category (MIC⩽2.0 µg/ml) and ⩽15 mm for the resistant category (MIC⩾8.0 µg/ml). Using these criteria, there was 97 % overall agreement between broth dilution and disk diffusion tests;Haemophilus influenzae isolates were susceptible to azithromycin by both methods. The quality control strainStaphylococcus aureus ATCC 25923 gave zones of 21 to 26 mm in diameter in a six-laboratory collaborative study. In azithromycin broth microdilution tests the following MIC control limits are recommended:Escherichia coli ATCC 25922, 2.0–8.0 µg/ml;Staphylococcus aureus ATCC 29213, 0.25–1.0 µg/ml; andEnterococcus faecalis ATCC 29212, 1.0–4.0 µg/ml.