MIC

Chemioterapia, 1987 Feb, 6(1), 3 - 7
In-vitro evaluation of antifungal agents in the treatment of yeast peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD); Edwards R et al.; This study compared the static and kinetic activities of six antifungal agents, in broth and used dialysate, against six yeast strains known to have caused peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) . Minimum inhibitory concentrations (MIC) and IC50 results show a trend towards greater activity by amphotericin B, 5-fluorocytosine, tioconazole and itraconazole in comparison to miconazole and ketoconazole although there was some strain variability . Minimum fungicidal concentrations (MFCs) of amphotericin B were less than or equal to 1mg/l, while 5-fluorocytosine and the azoles showed large discrepancies between MIC and MFC values . In kinetic studies amphotericin B was the most potent fungicidal agent . 5-fluorocytosine showed modest activity and failed to achieve total killing . The azoles demonstrated variable degrees of inhibition of C . glabrata and showed minimal activity with C . albicans . Itraconazole showed good activity against C . parapsilosis in broth . All agents, with the exception of 5-fluorocytosine, showed reduced activity in used dialysate in comparison to broth.

J Pharm Sci, 1987 Feb, 76(2), 153 - 6
Determination of binding parameters of macrolides, lincosamides, and streptogramins to Legionella pneumophila; Fournet MP et al.; Parameters of {3H}erythromycin binding to Legionella pneumophila were determined in vitro using both an equilibrium and a kinetic method . Different L . pneumophila serogroups, 1-3, and a virulent strain serogroup, 1, were tested . All strains of bacteria exhibited the same binding pattern, with a dissociation constant of 0.15 microM . Other macrolides, streptogramin B-types, and lincosamides competitively displaced bound erythromycin suggesting that these compounds share common binding sites on the bacteria . Minimum inhibitory concentration (MIC) values for macrolides, streptogramin B-types, and lincosamides were determined with buffered charcoal yeast extract (BCYE) medium . A good correlation (r = 0.994) was found between the corresponding inhibition constants of these antibiotics and their MIC . It was also noted that for lincosamides the microbiological inactivity was associated with a very low bacterium affinity . Thus, it is concluded that binding parameters of these antibiotics reflect their efficacy against L . pneumophila in vitro and may serve as a useful adjunct in developing new compounds.

Br J Dermatol, 1987 Feb, 116(2), 233 - 5
Sensitivities of Pityrosporum sp . to selected commercial shampoos; Butterfield W et al.; Sensitivity of 25 strains of Pityrosporum sp . to four commercial shampoos was tested using a gel diffusion method and determination of minimum inhibitory concentrations (MICs) . All the shampoos when undiluted gave inhibition zones in the gel diffusion test with 13 of the 15 strains tested . Two strains were resistant to 'Polytar' . 'Polytar' was fungistatic, 'Selsun' 'Cetavlon P.C.' and 'Genisol' were fungicidal . MIC results showed the yeast to be most sensitive to 'Cetavlon' and 'Selsun'.

J Med Chem, 1987 Feb, 30(2), 383 - 8
Structure-activity studies of 5-{{4-(4,5-dihydro-2-oxazolyl) phenoxy}alkyl}-3-methylisoxazoles: inhibitors of picornavirus uncoating; Diana GD et al.; A series of substituted phenyl analogues of 5-{{4-(4,5-dihydro-2-oxazolyl) phenoxy}alkyl}-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes . Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound . Many of these compounds exhibited mean MICs (MIC) against five serotypes as low as 0.40 microM . The mean MIC correlated well (r = 0.83) with the MIC80 (the concentration that inhibited 80% of the serotypes tested) . A quantitative structure-activity relationship study indicated a strong dependency of MIC on lipophilicity (log P) in combination with inductive effects (sigma m) and bulk factors (MW).

Int J Radiat Oncol Biol Phys, 1987 Feb, 13(2), 243 - 9
Regional lymph node and pulmonary metastases after local hyperthermia of melanomas in C57BL/6 mice; Nathanson SD et al.; The effects of local tumor hyperthermia on regional lymph node metastases are inconclusive . We studied the effects of hyperthermia on the incidence of popliteal, femoral, and abdominal lymph node metastases in C57BL/6 mice with primary B16 melanomas (F10 variant) growing subcutaneously in the left foot . Tumors were heated to 42.3, 43.5, and 44.2 degrees C for 90 minutes either 7 days after inoculation of 5 X 10(4) viable cells (microscopic tumor = mic) or when the tumors were approximately 3 mm in diameter (macroscopic tumor = mac) . Femoral lymph node metastases occurred in 0/21 control animals and in 8/22 (36%), 11/19 (58%), and 11/17 (65%) animals whose primary tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively . For all three treatments, the increase in metastases as compared to controls was statistically significant (p less than 0.004, Fisher's exact test) . The incidence of abdominal lymph node metastasis was slightly higher in the treated groups than controls . Twenty of 21 (95%) control mice developed popliteal lymph node metastases and hyperthermia-induced increases could not be demonstrated . Fifteen of 21 control mice killed 3 weeks after amputation of tumor-containing leg had pulmonary metastases with an average of 6 +/- 4 (standard deviation) lesions per affected mouse . Pulmonary metastases occurred in 22/22 (100%), 17/19 (89%), and 13/17 (76%) of mice whose tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively . The numbers of metastases for affected mice were significantly increased compared to controls for tumors heated to 43.5 and 44.2 degrees C (28 +/- 43, 43 +/- 52, 119 +/- 121, p greater than 0.02, p less than 0.006, p less than 0.002, for two sample T-test) . While 0/8 mic tumors were cured 5/9 mac tumors heated to 44.2 degrees C disappeared (p less than 0.03, Fisher's exact test) and there was a growth delay in the remaining mice . Mic tumors, heated to 43.5 degrees C, had an accelerated onset of growth while mac tumors heated to this temperature had a slight growth delay . Growth of both mic and mac primary tumors heated to 42.3 degrees C was similar to controls . These results show that therapeutic and subtherapeutic local hyperthermia increases metastases to regional lymph nodes and to lungs even when primary tumor growth rate is partially or totally controlled.

Clin Pharm, 1987 Jan, 6(1), 59 - 68
Comparison of antibiotic dosage regimens using pharmacokinetic and microbiologic factors; Schumacher GE; A pharmacokinetic meta-analysis was performed for 33 antibiotics used in treating infections caused by microorganisms for which the antibiotics are considered to be agents of first choice or primary alternatives . The pharmacokinetic indices assessed were the following components of the steady-state blood concentration-time profile: the magnitude of the peak antibiotic serum concentration at steady state compared with the minimum inhibitory concentration (CSSmax/MIC) and the intensity index, a dimensionless term that reflects the contribution of the peak serum antibiotic concentration and the duration that this concentration is above the MIC . Substantial differences in CSSmax/MIC and intensity-index values were observed among antibiotics within an antibiotic class for individual microorganisms and for groups of microorganisms . Piperacillin, amikacin, and tetracycline showed the best mean performances of the ureido penicillins, aminoglycosides, and tetracyclines, respectively . For the cephalosporins, cefadroxil displayed the highest mean values of the first-generation cephalosporins; cefuroxime and cefotetan showed the greatest measures for the second-generation agents; and all third-generation cephalosporins demonstrated very high mean performance indices . Meta-analysis of pharmacokinetic performance factors is a useful technique for making intergroup and intragroup comparisons of antibiotics.

Environ Mutagen, 1987, 9(1), 37 - 58
Methyl isocyanate: an evaluation of in vivo cytogenetic activity; Tice RR et al.; The ability of inhaled methyl isocyanate (MIC) to induce genotoxic and cytotoxic damage in vivo was evaluated by assessing the induction of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in bone marrow metaphase cells, the induction of micronuclei in polychromatic erythrocytes (MN-PCEs), and the inhibition of bone marrow cellular proliferation and erythropoiesis . B6C3F1 mice were exposed to MIC by two exposure regiments: in two experiments, male mice only were exposed to 3, 10, and 30 ppm for 2 hr; in four experiments, male and female mice were exposed to 1 and 3 ppm (in one experiment, to 6 ppm, also), 6 hr per day for 4 consecutive days . The various cytogenetic endpoints were analyzed in bone marrow and peripheral blood (4-day exposure regimen only) samples taken from bromodeoxyuridine tablet-implanted animals killed 11 to 22 hr after cessation of the exposure to MIC . Exposure to MIC for 2 hr induced a significant delay in cellular proliferation but did not induce a significant increase in CAs, SCEs (evaluated at 3 and 10 ppm, only) or in bone marrow MN-PCEs . Also, this exposure regimen did not inhibit the rate of erythropoiesis . Following exposure to MIC for 4 days, a weak but significant increase in CAs and SCEs was observed in male (in one experiment) and in female (in two experiments) mice . The induction was especially apparent in the single experiment in which mice were exposed to 6 ppm MIC . At this concentration, a significant increase in MN-PCEs in peripheral blood was observed in male but not female mice . Delay in bone marrow cell proliferation was observed in male mice beginning at 3 ppm and in female mice at 6 ppm . The 4-day exposure regimen resulted also in a depressed rate of erythropoiesis, with male mice appearing to exhibit greater depression than female mice . The results demonstrate that exposure to MIC by inhalation results in bone marrow damage, indicating the systemic genotoxic/cytotoxic activity of MIC and/or reactive metabolites.

Environ Mutagen, 1987, 9(1), 29 - 36
Sister chromatid exchange analysis in lung and peripheral blood lymphocytes of mice exposed to methyl isocyanate by inhalation; Kligerman AD et al.; Mice were exposed to 1, 3, or 6 ppm methyl isocyanate (MIC) for 6 hr/day for four consecutive days . Lung cells and peripheral blood lymphocytes (PBLs) were removed and cultured for analysis of sister chromatid exchange (SCE) and cell cycle kinetics . MIC caused a small but significant increase in SCE frequency of cultured lung cells from mice exposed to 1, 3, or 6 ppm MIC . MIC did not significantly increase SCE levels in PBLs of mice exposed to concentrations as high as 6 ppm . In cultured PBLs, MIC had a stimulatory effect on cell cycling rates as measured by the replicative index, and it caused a significant reduction in mononuclear leucocyte counts and the mitotic indices.

Am Rev Respir Dis, 1987 Jan, 135(1), 10 - 6
Sulfonamide-containing regimens for disease caused by rifampin-resistant Mycobacterium kansasii; Ahn CH et al.; Fourteen wild strains and 14 relapse or treatment failure isolates of Mycobacterium kansasii were tested and found to be highly susceptible to sulfamethoxazole (SMX), with 26 of 28 isolates having minimal inhibitory concentrations (MIC) of less than or equal to 4 micrograms/ml), using a broth microdilution method . Treatment failure isolates frequently exhibited resistance to rifampin (RMP) (greater than 2 micrograms/ml), isoniazid (INH) (greater than 4 micrograms/ml), and ethambutol (EMB) (greater than 4 micrograms/ml) not seen among the wild strain isolates . Eight patients with cavitary disease caused by RMP-resistant M . kansasii were treated with SMX-containing regimens that also included high dose INH (900 mg), EMB (25 mg/kg), and an aminoglycoside (either streptomycin or amikacin) . Patients were treated initially in the hospital for 4 to 10 wk . In 7 of the 8 patients, sputum cultures became negative in a mean of 10 wk (range, 7 to 14 wk) . Acquired drug resistance to INH, RMP, and EMB can be demonstrated in M . kansasii, and SMX in combination with other agents chosen on the basis of MIC determinations are effective in the treatment of disease caused by RMP-resistant M . kansasii.

Chemotherapy, 1987, 33(5), 328 - 30
Ciprofloxacin concentrations in human aqueous humor following intravenous administration; Behrens-Baumann W et al.; 16 patients received an intravenous infusion of 200 mg ciprofloxacin 1, 2, 3 and 6 h, respectively, before cataract extraction . This dosage produced mean aqueous humor levels of 0.165 +/- 0.09 and 0.126 +/- 0.028 microgram/ml after 1 and 3 h, respectively . The mean serum levels were 1.760 +/- 0.873 and 0.854 +/- 0.283 microgram/ml after 1 and 3 h, respectively . These levels are above the minimum inhibitory concentration of ciprofloxacin for sensitive organisms.

Trans R Soc Trop Med Hyg, 1987, 81(2), 345 - 7
A radiometric assay for antigiardial drugs; Inge PM et al.; Susceptibility of Giardia lamblia trophozoites to 3 antigiardial drugs was determined morphologically by 24h parasite counts and radiometrically by uptake of {3H}thymidine and by rapid 4h microassays of motility and viability . Growth of Giardia trophozoites in liquid culture correlated well with uptake of {3H}thymidine during a 72h period (r = 0.91, P less than 0.01) . ED50 and MIC for metronidazole, mepacrine and sodium fusidate were similar in both morphological and radiometric growth assays and, except for mepacrine, results were similar to previously reported drug efficacies obtained with more labour intensive methods . Motility and viability 4h microassays were insensitive and time-consuming and cannot be recommended for routine screening of antigiardial drugs . The radiometric growth assay is therefore a simple, objective measure of antigiardial drug activity which could be used to determine drug sensitivity profiles of clinical isolates or for screening new antigiardial drugs.

Int Arch Allergy Appl Immunol, 1987, 83(4), 432 - 5
IgA class and subclass thyroid auto-antibodies in Graves' disease and Hashimoto's thyroiditis; Weetman AP; The reported prevalence of IgA class thyroid antibodies in Hashimoto's thyroiditis is variable and the IgA subclass distribution in unknown, despite recent reports of IgG subclass restriction in the thyroid auto-antibody response . Using an ELISA, IgA class antibodies were found against thyroglobulin (Tg) and microsomes (Mic) in 40-52% of patients with Graves' disease and Hashimoto's thyroiditis, and, against thyroglobulin, they were detected in the absence of IgG antibodies in 10% of the cases . Both IgA1 and IgA2 subclasses were detected in all patients with IgA class antibodies, although a significantly higher proportion of IgA2 relative to IgA1 was found in microsomal compared with thyroglobulin antibodies . In view of the high turnover rate and unique complement-fixing properties of IgA2 antibodies, this class of thyroid auto-antibody may play an important role in determining the response in thyroid auto-immunity.

Chemotherapy, 1987, 33(4), 255 - 8
In vitro susceptibility of Mycobacterium avium to a new macrolide (RU-28965); Casal M et al.; The in vitro susceptibility of Mycobacterium avium to RU-28965 alone and in combination with rifampin, isoniazid, and sulfametoxipiridazine was studied by the agar dilution method . The synergistic effect of the RU-28965 with rifampin has been demonstrated . At a concentration of 16 micrograms/ml or lower of RU-28965, 100% of M . avium strains were inhibited . If 2 micrograms/ml of rifampin is added the MIC of RU-28965 is lowered to 0.25 microgram/ml.

J Toxicol Environ Health, 1987, 21(3), 265 - 75
Reproductive toxicity of methyl isocyanate in mice; Varma DR et al.; The effects of methyl isocyanate (MIC) vapor on pregnancy and fertility were studied in mice in view of the reported increase in reproductive complications in Bhopal following the December 3, 1984, accident . The whole-body exposure of mice to 9 and 15 ppm MIC for 3 h on d 8 of gestation led to resorption of greater than 80% of implants . In more than 75% of MIC-exposed animals, all implants were lost . At these concentrations, MIC did not cause external malformations . However, there was evidence of an increase in visceral abnormalities and a decrease in fetal and placental weights and in fetal skeleton sizes . MIC disturbed the estrus cycle and decreased the mating and pregnancy rate of female mice . The mating performance of MIC-exposed male mice was also decreased . Exposure to MIC increased serum corticosterone levels of male and nonpregnant female mice . MIC exerted no significant effects on serum corticosterone and progesterone levels of pregnant mice if the pregnancy was retained but caused a significant decrease in the serum levels of these two hormones in animals that lost all the implants . These studies show that the effects of MIC in mice mimic many of the reproductive complications in Bhopal . The mechanism of the reproductive toxicity of MIC remains to be identified.

J Infect Dis, 1987 Jan, 155(1), 93 - 9
Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration; Moore RD et al.; In an examination of the relationships among plasma aminoglycoside concentrations, the minimal inhibitory concentration (MIC) for the infecting organism, and therapeutic outcome, data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin, tobramycin, and amikacin . Clinical response to therapy occurred in 188 (80%) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response (P less than .00001 and P less than .0001, respectively) . A graded dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy.

J Antimicrob Chemother, 1987 Jan, 19(1), 39 - 43
Susceptibility of Branhamella catarrhalis to sulphamethoxazole and trimethoprim; Riley TV et al.; Fifty strains of Branhamella catarrhalis were examined for susceptibility to sulphamethoxazole, trimethoprim and a combination of the two by determinating minimum inhibitory concentrations (MICs) and fractional inhibitory concentrations (FICs) . All strains were susceptible to sulphamethoxazole and resistant to trimethoprim . On the basis of the MIC results it was predicted that greater synergy between sulphamethoxazole and trimethoprim would be observed with approximately equal proportions of each component . The lowest FIC values were obtained with a ratio of 1:1 and the greatest synergy was observed at this ratio with 39 strains (78%) . Only seven strains were most synergistically inhibited at the ratio of 20:1 (sulphamethoxazole: trimethoprim) although this ratio was still synergic for most strains . Overall the 1:20 ratio was not synergic.

Drugs, 1987, 34 Suppl 1, 14 - 9
Interpretive criteria for the agar diffusion susceptibility test with ofloxacin; Grimm H; Regression analyses to determine the correlation of minimal inhibitory concentrations (MICs) and inhibition zones produced by ofloxacin discs were carried out with 300 freshly isolated cultures of infective organisms (20 strains from each of 15 species) . After pilot studies, 5 micrograms loaded discs were chosen . Studies were performed simultaneously by using ICS/DIN and Kirby-Bauer/NCCLS methods on Mueller-Hinton agar . It was found that the correlation becomes poorer with increasing disc loads and when the Kirby-Bauer method is used . Based on preliminary MIC breakpoints of greater than or equal to 2 mg/L and greater than or equal to 8 mg/L and by calculations from regression equations, the following zone interpretations using the NCCLS method are recommended: resistant up to 12mm, intermediate 13 to 15mm, susceptible 16mm or more . The values for the DIN method are: resistant up to 13mm, intermediate 14 to 17mm, susceptible 18mm or more . No major errors were found in zone interpretations . Minor errors were observed in 0.7% when the NCCLS method was used, and in 1.3% with the DIN method.

Acta Endocrinol Suppl (Copenh), 1987, 281, 125 - 32
The thyroid microenvironment in autoimmune thyroid disease: effects of TSH and lymphokines on thyroid lymphocytes and thyroid cells; McLachlan SM et al.; Thyroid lymphocytes synthesize thyroid autoantibodies in close proximity to thyroid cells and consequently soluble mediators such as TSH and interleukins (IL) 1 and 2 may have unforeseen effects on lymphocytes and thyrocytes, respectively . Investigations of thyroid autoantibody synthesis by thyroid lymphocytes in vitro showed that TSH did not affect microsomal (Mic) antibody production, but thyroglobulin (Tg) antibody synthesis was decreased, probably as a result of complexing between Tg antibody and Tg secreted by small numbers of thyrocytes in the cell suspension . IL-1 and IL-2 partially mimicked the inhibitory effects on spontaneous autoantibody synthesis induced by Pokeweed mitogen (PWM) in cultures of thyroid lymphocytes . This inhibition may require a number of soluble mediators released by T cells in response to the mitogen; however, depletion studies indicated that the cell type responsible for PWM inhibition is unlikely to be a suppressor T cell and may be an NK cell . IL-1 and IL-2 had little effect on the viability of thyrocyte monolayers in an 18 h assay, but antibody dependent cells cytotoxicity (ADCC) using blood lymphocytes and thyroid autoantibody positive sera was demonstrated; further, the cytotoxicity appeared to be due to Mic antibodies . It is possible that IL-1 and/or IL-2 (as well as other cytokines) may affect thyroid cells after longer periods of exposure, either by altering them functionally or by direct damage . However, assuming that NK cells are present in sufficient numbers in the gland, ADCC could play a major role in the development of hypothyroidism in Hashimoto's disease.

Arch Immunol Ther Exp (Warsz), 1987, 35(2), 109 - 15
Microbial transformation of azacarbazoles . IV . Conversion of chloro-substituted alpha-carbolines by Kitasatosporia setae strain; Peczynska-Czoch W et al.; Biotransformation of alpha-carboline derivatives substituted at positions C-5, C-6, C-7 and C-8 with chlorine, carried out with Kitasatosporia setae strain yielded corresponding 1-methyl-alpha-iso-carbolines . The formation of products is dependent on the position of chlorine in substrate molecule . When chlorine is introduced at C-6, the yield of N-1 methylation is low, about 5% . Derivatives of alpha-carboline substituted with chlorine at C-7 and C-8 form corresponding alpha-iso-carbolines with yield up to 20% and 30%, respectively, whereas 5-chloro-alpha-carboline is converted into 5-chloro-1-methyl-alpha-iso-carboline with 60% yield . Apparently, additional pathway of microbial transformation of 2-chloro-alpha-carboline has been found . Primarily formed 2-chloro-1-methyl-alpha-iso-carboline subjected to complex enzymic conversion yields quantitatively 2-methoxy-1-methyl-alpha-iso-carboline-9-N-oxide . It has been found that 2-chloro-1-methyl-alpha-iso-carboline exhibit strong cytotoxic activity, against KB cells tissue culture, ID50 = 0.01 microM/ml and inhibits growth of Kitasatosporia setae strain, MIC = 0.5 microM/ml . Toxicity of formed 2-methoxy-1-methyl-alpha-iso-carboline-N-9-oxide is markedly lower, ID50 = 0.3 microM/ml and MIC = 3.5 microM/ml . The remaining C-5, C-6, C-7 and C-8 chloroderivatives of alpha-iso-carboline occur to be less active than 2-chloro-1-methyl-alpha-iso-carboline.

Drugs Exp Clin Res, 1987, 13(9), 529 - 38
Determination of MICs of conventional and experimental drugs in liquid medium by the radiometric method against Mycobacterium avium complex; Heifets LB et al.; The aim of this study was to search for new drugs active against the Mycobacterium avium complex and to re-examine the activity of some conventional antituberculosis drugs against these species . This progress report describes the protocol and phases of in vitro experiments in a search which included 57 different compounds tested against numerous strains of M . avium clinical isolates . The preliminary screening and MIC determination of these drugs were conducted in 7H12 broth by the radiometric method (BACTEC system) . Of the total of 57 drugs, 23 were discarded after preliminary screening and 17 after MIC determination . The remaining 17 drugs were considered sufficiently promising for more detailed in vitro studies . These, now in progress, include MIC determination by two additional methods (in broth by sampling and plating and in 7H11 agar plates), MBC determination and drug combination studies . The following drugs are currently undergoing these detailed studies: isoniazid, rifampin, rifabutine (ansamycin LM427), amikacin, streptomycin, ethambutol, ethionamide, cycloserine, clofazimine (CF), CF derivative B746, CF derivative B1865, ofloxacin, ciprofloxacin, cephalosporin BMY 28142, trimethoprim-sulfamethoxazole, spectinomycin derivative U6633F(B), and dihydromycoplanecin.

Scand J Infect Dis Suppl, 1987, 52, 20 - 5
Efficacy and safety of imipenem/cilastatin in the empirical treatment of septicemia; Del Valle J et al.; The clinical efficacy and safety of imipenem/cilastatin in the empirical treatment of adult non-immunocompromised patients with severe bacterial septicemia was studied in a prospective and open trial . The dosage of imipenem/cilastatin was 500 mg q 6 h . Of 58 patients included, 41 were evaluable for efficacy . In those patients, 35 had chronic underlying diseases and the foci of bacteremia were identified in 37; the most common ones being cardiovascular, urologic or intraabdominal infections . All isolated organisms were sensitive to imipenem with an MIC for 90% of the strains of 1 mg/l . Imipenem/cilastatin treatment resulted in rapid control of the infections in 39 of the 41 evaluable patients (95.5%) . In the remaining two patients treatment had to be prematurely discontinued due to adverse effects . The causative bacterial strains were eradicated from blood in all patients who received more than one day of imipenem/cilastatin treatment but persisted sensitive to imipenem in peripheral foci in five patients (17%) . Clinical and laboratory adverse reactions were noted in seven patients . In conclusion, imipenem/cilastatin was a well tolerated and effective empirical drug for treatment of septicemia.

Microbiol Immunol, 1987, 31(7), 615 - 23
Two groups of Mycobacterium avium complex strains determined according to the susceptibility to rifampicin and ansamycin; Tsukamura M; Mycobacterium avium complex strains previously not exposed to any antituberculosis agents could be divided into two groups according to their susceptibility to rifampicin and ansamycin; one group susceptible to 80 micrograms/ml rifampicin and to 1.25 micrograms/ml ansamycin, and another resistant to these concentrations . In each group, the ratio of the minimal inhibitory concentration of ansamycin against that of rifampicin was greatly different depending on the strain . This naturally occurring resistance to rifampicin and ansamycin was frequently correlated to naturally occurring resistance to ethambutol, kanamycin, enviomycin, kitasamycin, and minocycline, but not correlated to that to isoniazid and sulfadimethoxine . Ansamycin was more active than rifampicin against M . bovis, M . kansasii, M . marinum, M . xenopi, and M . haemophilum.

Acta Microbiol Hung, 1987, 34(2), 121 - 4
Diffusion of metronidazole through the dentinal tubules of extracted teeth; Csukas Z et al.; Passing of metronidazole from the root canal of extracted gangrenous teeth through the dentinal tubules was proved by agar diffusion and minimum inhibitory concentration assay . The findings explain the excellent clinical experience with metronidazole in root treatment.

Chemotherapy, 1987, 33(4), 250 - 4
Susceptibility of Bordetella pertussis and Bordetella parapertussis to 24 antibiotics; Hoppe JE et al.; The susceptibility of Bordetella pertussis (28 strains) and Bordetella parapertussis (6 strains) to 24 antibiotics (penicillin and cephalosporin derivatives, erythromycin, josamycin, cotrimoxazole, imipenem, aztreonam and fosfomycin) was studied by means of the agar dilution method using charcoal horse blood agar . Piperacillin and mezlocillin showed the highest activity (MIC 0.0039-0.00781 micrograms/ml) against B . pertussis while B . parapertussis was most susceptible to piperacillin (0.03125-0.0625 microgram/ml), mezlocillin and latamoxef (0.125-0.25 microgram/ml).

Eur J Clin Microbiol, 1986 Dec, 5(6), 629 - 33
Pharmacokinetics of intravenous antibiotics in acutely ill elderly patients; Jonsson M et al.; In a study of 20 acutely ill elderly patients treated with cefotaxime (1 g, 2 X daily) the pharmacokinetics in serum and tissue fluid were examined . Patients with impaired renal function showed increased values for the area under the curve and half-life in both serum and tissue fluid . Patients with pathological peripheral circulation manifested delayed peak concentrations in tissue fluid . Although the passage of cefotaxime into tissue fluid was slow in the elderly, its concentration was higher than the minimal inhibitory concentration for most bacterial species of clinical importance and lasted for 5.5-7h in tissue fluid and for more than 10h in serum . Thus, this study clearly illustrates that the twice-daily dosage regimen used was quite adequate in elderly patients.

J Am Diet Assoc, 1986 Dec, 86(12), 1679 - 83
Prenatal weight gains related to the birth of healthy-sized infants to low-income women; Brown JE et al.; Prepregnancy weight status and weight gain during pregnancy are major independent variables associated with infant birth weight . This study quantitated the influence of weight gain on birth weight and identified rates and total amounts of weight gain related to the birth of healthy-sized infants to healthy low-income women who entered pregnancy underweight, at normal weight, overweight, or obese . Data used in the study were obtained from randomly sampled prenatal health records from Maternal and Infant Care (MIC) projects in Cleveland and Minneapolis . Subsamples of healthy mothers who delivered healthy-sized infants were identified from each sample, and rates and total amounts of weight gain by prepregnancy weight status group were calculated . There were 384 healthy mother and healthy-sized infant pairs in the Cleveland subsample and 75 such pairs in the Minneapolis sample . Multiple regression analysis revealed that the influence of prenatal weight gain and birth weight varied depending on prepregnancy weight status . Prenatal weight gains related to the birth of healthy-sized infants (newborns with birth weights of 3,000 to 4,500 gm) to healthy mothers in the Cleveland MIC sample averaged 33 lb for underweight, 32 lb for normal weight, 29 lb for overweight, and 19 lb for obese women . Except for obese women, rates and total amount of weight gain associated with the birth of healthy-sized infants were equivalent for the two samples.

Arch Pathol Lab Med, 1986 Dec, 110(12), 1183 - 5
Granulomatous encephalitis caused by Bipolaris hawaiiensis; Morton SJ et al.; We describe a case of granulomatous encephalitis caused by Bipolaris (Drechslera) hawaiiensis in an immunocompetent patient . An 18-year-old man with a seven-month history of seizures and right leg weakness was found by computed tomographic scan to have a left frontoparietal enhancing lesion . Biopsy of the lesion revealed granulomatous inflammation and numerous septate hyphae . Culture of the biopsy specimen yielded a pure culture of B hawaiiensis in four days . Susceptibility studies revealed the organism to be sensitive to amphotericin B (minimal inhibitory concentration {MIC} equals 0.25 mg/L) and miconazole lactate (MIC equals 0.064 mg/L), but resistant to flucytosine (MIC greater than 100 mg/L) . No synergy was demonstrated with amphotericin B and flucytosine in vitro . The patient was successfully treated with surgery and systemic and intrathecal amphotericin B therapy, and a negative culture was obtained from a repeated brain biopsy six weeks later.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Dec, 263(1-2), 112 - 8
European Borrelia burgdorferi isolated from humans and ticks culture conditions and antibiotic susceptibility; Preac-Mursic V et al.; Growth of Borrelia burgdorferi in a modified Kelly-medium is described . Borrelia strains were isolated from patients (n = 11) and ticks I . ricinus (n = 19) . The modified medium which contained Co-trimoxazole is a very effective medium for isolating and culturing of Borrelia sp . The susceptibility of 7 strains of B . burgdorferi to antibiotics was studied by the macrodilution and microdilution test . After preliminary testing for optimal conditions, we determined MICs in modified Kelly medium . The MIC concentration of each antibiotic was determined as the lowest concentration which completely inhibited growth of the tested organism . The B . burgdorferi was most susceptible to Erythromycin with MIC of less than or equal to 0.15 microgram/ml . Of the Penicillins tested, Ampicillin and Mezlocillin were more active than Penicillin G . The use of Tetracycline-HCl is recommended because of its low MIC in vitro its extra- and intracellular efficiency.

Antimicrob Agents Chemother, 1986 Dec, 30(6), 906 - 12
Involvement of penicillin-binding protein 2 with other penicillin-binding proteins in lysis of Escherichia coli by some beta-lactam antibiotics alone and in synergistic lytic effect of amdinocillin (mecillinam); Gutmann L et al.; Compared with cefotaxime, ceftazidime, moxalactam, and aztreonam, ceftriaxone produced the best lytic and bactericidal effects when each was added at about 10 times the MIC to Escherichia coli W7 . When each of these antibiotics was added at its MIC, only bacteriostasis occurred, but the simultaneous addition of amdinocillin (mecillinam) was synergistic in causing rapid lysis and bactericidal effects . Induction of lysis of two E . coli mutants containing either a thermosensitive penicillin-binding protein (PBP) 2 or 3 by relatively PBP 3-specific (aztreonam) and PBP 2-specific (amdinocillin) antibiotics indicated that inhibition of only PBPs 2 and 3 can cause lysis . Examination of the interactions of cefotaxime, aztreonam, and cefsulodin, with or without amdinocillin, with their targets suggested that other combinations of PBPs could be involved in the onset of lysis . However, inhibition of both PBPs 2 and 3 may explain the better lysis-inducing activity of ceftriaxone (which binds well to both of these PBPs), as well as the synergistic effect of amdinocillin when added together with low concentrations of other beta-lactam antibiotics that interact with PBP 3.

Am Rev Respir Dis, 1986 Dec, 134(6), 1276 - 82
Characterization of beta-lactamases in Mycobacterium fortuitum including a role in beta-lactam resistance and evidence of partial inducibility; Nash DR et al.; The beta-lactamases from the 3 biovariants of M . fortuitum were compared on the basis of substrate profiles, susceptibility to enzyme inhibitors, and inducibility in the presence of selected beta-lactams . Despite differences in the distribution of beta-lactamase bands observed when enzymes from different isolates were subjected to isoelectric focusing, substrate profiles for the 3 biovariants were similar . All demonstrated a comparable broad spectrum hydrolytic activity for both cephalosporins and penicillins . The MIC for amoxicillin were reduced 4- to 16-fold when combined with the beta-lactamase inhibitor clavulanic acid, but not to a clinically susceptible range . The degree of reduction in MIC for amoxicillin correlated well with the susceptibility of enzyme to inhibition by clavulanic acid as determined in an in vitro assay . Although all M . fortuitum strains produce beta-lactamase under routine growth conditions, 90% of strains demonstrated an increase in the amount of this enzyme when cultured in the presence of selected beta-lactams as potential inducers . Quantitative assays and isoelectric focusing further indicated that this apparent induction of beta-lactamase is a simple enhancement of the same enzyme(s) produced in the absence of a known inducer . This is the first demonstration of any inducibility among mycobacterial beta-lactamases and suggests that synthesis of these enzymes in M . fortuitum is under some form of regulatory control . These results indicate that the beta-lactamases have a role in resistance of M . fortuitum to the beta-lactams . Other factors, such as permeability and penicillin-binding proteins, were not evaluated.

Antimicrob Agents Chemother, 1986 Dec, 30(6), 927 - 32
Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis; Heifets LB et al.; We determined the MICs of ethambutol for both Mycobacterium avium and Mycobacterium tuberculosis strains by using broth dilution (7H12 broth, radiometric method) and agar dilution (7H11 agar) methods . We found the MICs to be much lower in liquid than in solid medium . The broth-determined MICs for susceptible M . tuberculosis and most of the M . avium strains were comparable to the levels in blood of patients, being lower than the peak levels . We propose that the MICs, determined radiometrically in in 7H12 broth, be considered as tentative criteria for susceptibility testing of M . avium isolates in future clinical trials . The use of these values instead of critical concentrations should also be considered as an alternative to the conventional susceptibility testing method in chemotherapy of tuberculosis . Ethambutol produced bactericidal effects against both M . tuberculosis and M . avium, and the MIC/MBC ratios were in the same range for both species when MICs and MBCs were tested in 7H12 broth by conventional sampling and plating.

J Dent Res, 1986 Dec, 65(12), 1420 - 3
Metronidazole concentrations in human plasma, saliva, and gingival crevice fluid after a single dose; Van Oosten MA et al.; Metronidazole concentrations were estimated in four human volunteers after a single dose of 750 mg taken orally . Samples of blood, saliva, and gingival crevice fluid were collected before intake and during the following 24 hours . The concentrations of metronidazole in plasma and saliva were measured by high-performance liquid chromatography (HPLC) . The concentrations in gingival fluid were estimated by a capillary agar-diffusion assay . The results of the metronidazole measurements as obtained by both methods were significantly correlated . The peak concentrations of metronidazole in plasma and saliva were in the same range, 8.7-13.8 micrograms/mL, and similar concentrations were found in the gingival fluid samples . It is concluded that metronidazole taken orally has similar pharmacokinetics in both saliva and plasma, and that a single oral dose of 750 mg metronidazole leads to a concentration of the drug in the gingival crevice fluid that exceeds the minimal inhibitory concentration for most anaerobic oral micro-organisms.

J Clin Microbiol, 1986 Dec, 24(6), 976 - 81
Susceptibility testing of slowly growing mycobacteria by a microdilution MIC method with 7H9 broth; Wallace RJ Jr et al.; Based on previous success with rapidly growing mycobacteria, a microdilution MIC system was devised for slowly growing mycobacterial species using 7H9 broth . Test drugs included isoniazid, rifampin, ethambutol, streptomycin, clofazamine, and sulfamethoxazole . Sixty isolates of four mycobacterial species, including Mycobacterium tuberculosis, from patients who had never received drug therapy were evaluated in the system, as well as 25 drug-resistant isolates and 11 control strains . MICs were read when good macroscopic control growth was evident, a period which varied with each species . Most species exhibited a narrow range of MICs with easily discernible growth endpoints . The aminoglycosides, ethambutol, clofazamine, and sulfamethoxazole were the only drugs with activity against all species at clinically achievable levels in serum . Correlation between susceptibilities by the proportion method in agar with single drug concentrations and the broth method were excellent for M . tuberculosis, M . kansasii, and M . marinum for isoniazid, rifampin, and ethambutol . Isolates of the M . avium complex were much more susceptible in broth than in agar for rifampin, ethambutol, and streptomycin . Given the successful transition of most microbiology laboratories to MIC plates for other bacterial species, this method would allow for testing of multiple drugs at multiple concentrations and has good potential for evaluation of drug combinations and drug-resistant isolates.

Southeast Asian J Trop Med Public Health, 1986 Dec, 17(4), 591 - 4
In vitro studies on the sensitivity of local Entamoeba histolytica to anti-amoebic drugs; Chintana T et al.; The in vitro activity of drugs, namely dehydroemetine, ornidazole, metronidazole and tinidazole were determined against the locally isolated strains of E . histolytica in Thailand . The test was performed in liquid monophasic medium, i.e . liver marmite serum medium . In all, locally isolated strains from thirty hosts studied, the minimal inhibitory concentration (MIC) for dehydroemetine ranged from 0.125 to 1 microgram/ml, ornidazole ranged from 0.0625 to 0.25 microgram/ml, metronidazole ranged from 0.0625 to 0.125 microgram/ml, and tinidazole ranged from 0.0625 microgram/ml to 0.25 microgram/ml . The MIC of dehydroemetine was significantly different from ornidazole, metronidazole and tinidazole . Metronidazole was superior to that of dehydroemetine but was not significantly different among ornidazole, metronidazole and tinidazole.

Hinyokika Kiyo, 1986 Nov, 32(11), 1747 - 61
{Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of norfloxacin}; Sakai S et al.; We studied the basic and clinical effects of norfloxacin (NFLX) in 120 patients with gonococcal infections (110 men with urethritis and 10 women with cervicitis)--all residents at Sapporo City; and epidemiologically analyzed the sources of their infections . The male patients were between 16 and 67 years old and the female patients were between 20 and 61 years old, with a peak in the early 20s both for sexes . 70.6% of the male patients in their 10s were infected from their girl friends or so-called pick-up friends and 50% of the female patients from their husbands . The other half of the female were workers serving at so-called special massage parlors . The minimum inhibitory concentration (MIC) of NFLX against N . gonorrhoeae distributed was 0.0125 approximately 3.13 micrograms/ml, with a peak at 0.025 micrograms/ml . NFLX inhibited 93.3% of the clinical strains of this species at less than 0.1 microgram/ml and 96.2% at less than 1 microgram/ml, where the inoculation was 10(6) CFU/ml . Twenty one (20.2%) of the 104 N . gonorrhoeae strains were penicillinase-producing one (PPNG) . NFLX inhibited 18 of these PPNG (85.7%) at less than 0.1 microgram/ml and the other 3 strains at 1.56 approximately 3.13 micrograms/ml . Oral administration of 200 mg NFLX showed the average peak serum level of 0.72 micrograms/microliter in 2 hours and the average peak level in the urethral secretions of 0.5 micrograms/ml in one hour . These two concentrations of NFLX covered 95.2% of the MIC distribution against N . gonorrhoeae . The clinical efficacy of 600 mg NFLX (peros) was 97.4 and 93.1% for a 3-and 7-day treatment for male urethritis; and 100% for both 3-and 7-day treatment for female cervicitis . Complicated urethritis with C . trachomatis was noticed in 32.7% of the male urethritis and in 20% of the female cervicitis cases . Urethral secretions among about half of these patients were observed even after treatment with NFLX . As a subsequent treatment, another effective chemotherapeutic is required against C . trachomatis . No adverse reactions were detected with NFLX . All the above results demonstrate that NFLX is a highly effective and safe chemotherapeutic agent for treatment of gonorrhoea.

Antimicrob Agents Chemother, 1986 Nov, 30(5), 675 - 8
Comparative pharmacokinetics of two multiple-dose mezlocillin regimens in normal volunteers; Colaizzi PA et al.; Mezlocillin was previously reported to exhibit dose-dependent pharmacokinetics . These reports suggest that it may be possible to administer a relatively large dose at a longer interval than is usual and still achieve therapeutic concentrations in serum . In a randomized, crossover study, we compared concentrations of mezlocillin in serum after a single dose and at steady state in 12 healthy volunteers who received 4 g every 6 h and 5 g every 8 h . A slight, but statistically significant, dose-dependent effect was observed upon the area under the concentration-time curve and total body clearance . No accumulation was observed with either schedule . Although concentrations in serum were higher after the 5-g dose, the more frequent administration of the 4-g dose schedule produced serum concentrations above the MIC for susceptible bacteria for a greater portion of the day . In the absence of clear guidelines from human studies which relate serum concentrations to clinical response, the available data indicate that the more frequent dosage schedule is appropriate for severe infections.

Am J Vet Res, 1986 Nov, 47(11), 2325 - 8
3-Acetyl-4''-isovaleryl tylosin for prevention of swine dysentery; Jacks TM et al.; The 21 field isolates of Treponema hyodysenteriae which were tested were sensitive to 3-acetyl-4''-isovaleryl tylosin (AIV); the minimal inhibitory concentration was 0.25 to 16 micrograms/ml . 3-Acetyl-4''-isovaleryl tylosin administered prophylactically to pigs at concentrations of 5 to 100 mg/kg of feed and tylosin at 110 mg/kg of feed for 28 or 31 days prevented swine dysentery induced by tylosin-sensitive T hyodysenteriae strain SQ2; 15 nonmedicated, inoculated control pigs had bloody diarrhea, and 9 pigs died . In 2 additional trials, AIV administered prophylactically for 28 days at 55 or 110 mg/kg of feed prevented swine dysentery induced by tylosin-insensitive T hyodysenteriae strain B204 . All of the inoculated principal pigs medicated with AIV at 55 or 110 mg/kg of feed or carbadox at 55 mg/kg of feed and the noninoculated sentinel pigs for each group had solid feces throughout the 56-day trial . In the nonmedicated, inoculated control groups, bloody diarrhea began at 4 to 5 days after inoculation was done, and 9 of 10 principal pigs and 6 of 9 sentinel pigs had dysentery; 2 pigs died . In the groups medicated with AIV at 27.5 or 5.5 mg/kg of feed, all 5 principal pigs and 3 or 4 sentinel pigs in each group had dysentery; 3 or 4 pigs in each group died . In the group medicated with tylosin at 110 mg/kg of feed, 7 of 10 principal pigs and all 9 sentinel pigs had dysentery; 1 pig died.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1986 Nov, 18 Suppl D, 31 - 41
Morphological and biochemical changes in Escherichia coli after exposure to ciprofloxacin; Diver JM et al.; Examination of morphological and biochemical changes in Escherichia coli KL-16 after exposure to ciprofloxacin revealed distinct concentration-dependent responses . At levels close to the MIC extensive filamentation was seen, whereas at the most bactericidal concentration cells were elongated but not filamented . At higher concentrations ovoid cells were seen . Some cells showed surface vacuoles, but no significant leakage of cell contents was detected . Filamentation and vacuolation were shown to make only a minor contribution to ciprofloxacin-induced cell death, and the data indicate that there are two or more mechanisms involved in the lethal action of ciprofloxacin.

J Antimicrob Chemother, 1986 Nov, 18(5), 575 - 83
Elimination of plasmids by enoxacin and ofloxacin at near inhibitory concentrations; Weisser J et al.; The abilities of the 4-quinolones enoxacin and ofloxacin, inhibitors of DNA gyrase subunit A, to eliminate plasmids from Escherichia coli have been studied in a narrow concentration range just below the MIC . These compounds cured most efficiently at the highest concentration which still allows cell growth and produced 20% to 100% plasmid-free cells, depending upon the plasmid tested . Higher concentrations were required to eliminate plasmids from a gyrANalr strain, consistent with their higher MICs, but maximal curing frequencies were similar to those obtained with the Nals strain . Kinetics of plasmid elimination indicated that plasmid loss occurred by inhibition of plasmid replication, which seems to be somewhat more sensitive to the action of 4-quinolones than chromosome replication . Low or high curing frequencies with a given curing agent seem to be a property of the plasmid tested.

Cancer Genet Cytogenet, 1986 Nov, 23(3), 189 - 97
Morphologic, immunologic, and cytogenetic (MIC) working classification of acute lymphoblastic leukemias . Report of the workshop held in Leuven, Belgium, April 22-23, 1985 . First MIC Cooperative Study Group; {In vitro activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis et al.; Thomas L, Naumann P, Crea A.

The in vitro activity of ciprofloxacin and ofloxacin against 33 strains of mycobacteria was investigated in a comparative study . The resulting MIC values were compared with serum levels, measured in a cross-over study . Possible therapeutic application of these substances in mycobacterial infections are being discussed . We found the antimycobacterial activity of ciprofloxacin to be insufficient for its clinical application, whereas the corresponding MIC values for ofloxacin could be achieved in vivo . Further animal and clinical studies appear justified.

Antimicrob Agents Chemother, 1986 Nov, 30(5), 777 - 80
Purification and properties of DNA gyrase from a fluoroquinolone-resistant strain of Escherichia coli; Sato K et al.; Subunit A and B proteins of DNA gyrase were separately purified from fluoroquinolone-resistant Escherichia coli GN14181 (MIC of ofloxacin, 100 micrograms/ml) and susceptible strain KL-16 . The supercoiling activities of reconstituted Ar+Br (r, resistant) and Ar+Bs (s, susceptible) were 250-fold more resistant to new fluoroquinolones than those of As+Bs and As+Br.

Fundam Appl Toxicol, 1986 Oct, 7(3), 502 - 22
Methyl isocyanate subchronic vapor inhalation studies with Fischer 344 rats; Dodd DE et al.; Groups of Fischer 344 rats were exposed to 3.1, 0.6, 0.15, or 0.0 (control) ppm of methyl isocyanate (MIC) vapor 6 hr per day for two 4-day sessions separated by a 2-day rest . There were no deaths during the study . The rats were killed the morning following the last exposure day . The 3.1-ppm-exposed rats had decreased body weight, food consumption, and blood oxygen saturation (males only) . Increased hemoglobin concentration (males only) and lung weights were also observed in this group of rats . Multiple histologic lesions, limited to the respiratory tract, were observed in rats of the 3.1-ppm group only . The lesions consisted of necrosis, suppurative inflammation, squamous metaplasia, and intraluminal and submucosal fibroplasia (bronchi and bronchioles only) which extended from the anterior nasal cavity to the terminal bronchioles . In a second study, rats were exposed to 3.0 ppm MIC, 6 hr per day, for either one or two 4-day sessions and sacrificed on postexposure Days 1, 15, 43, and 85 . All rats survived the 4- or 8-day exposure regimen, although significant decreases in body weight and encrustation of the eyes, nose, or mouth area were observed . During the first 15 days postexposure, male mortality was 63%; only 6% of the MIC-exposed females died . The cause of death was interpreted to be a combination of pulmonary vascular and inflammatory changes coupled with anorexia . For survivors, recovery from the necrotizing and irritating effects of MIC vapor was observed . Squamous metaplasia of respiratory epithelium, observed in rats sacrificed at the end of the exposure period, was replaced by tall pseudostratified columnar (regenerative) epithelium beginning in the bronchi and bronchioles as well as the distal trachea . Collagen maturation and condensation of the intraluminal and submucosal fibroplasia occurred during the postexposure period . The results of these investigations support the current threshold limit value for MIC of 0.02 ppm.

J Clin Microbiol, 1986 Oct, 24(4), 647 - 9
Cefixime disk susceptibility test criteria; Fuchs PC et al.; A total of 583 bacterial isolates was tested for susceptibility to cefixime by broth microdilution and by disk agar diffusion with 5-, 10-, and 30-microgram disks . At MIC breakpoints of less than or equal to 1.0 and greater than or equal to 4 micrograms/ml for susceptible and resistant, respectively, the 5-microgram disk showed slightly better discrimination . The 5-microgram cefixime disk is recommended with proposed interpretive breakpoint criteria of: less than or equal to 17 mm, resistant; 18 to 20 mm, intermediate; and greater than or equal to 21 mm, susceptible.

Kidney Int, 1986 Oct, 30(4), 481 - 7
Benefit from high intrarenal levels of gentamicin in the treatment of E . coli pyelonephritis; Bergeron MG et al.; The importance of high intrarenal levels of gentamicin on the outcome of experimental pyelonephritis was studied in rats receiving either a short course (three days) of gentamicin (G) alone or combined with a longer course (14 days) of ampicillin (A), cephalothin (C), or trimethoprim (T), or two weeks of therapy with ampicillin, cephalothin, trimethoprim and gentamicin given alone . While ampicillin, cephalothin and trimethoprim were undetectable in the medulla within six hours of cessation of therapy, gentamicin was still detectable in levels six folds above the MIC up to six months after treatment had ceased . Six months after the end of treatment, the percentage of sterile left kidneys in animals treated with ampicillin (50%), cephalothin (15%), trimethoprim (20%) was lower than the percentage of animals receiving 14 days of gentamicin (100%), or the combinations AG:89%, CG:67% and TG:60%, P less than 0.01 . Following three days of gentamicin, 50% of the left kidneys were sterilized . When compared to ampicillin, cephalothin or trimethoprim alone, combined therapies significantly reduced the number of CFU in the kidneys P less than 0.01 . These combinations were almost as effective as two weeks of therapy with gentamicin . Short-term therapy (three days) with an aminoglycoside which concentrates in the renal parenchyma, combined with an antibiotic which will accumulate in other parts of the nephron, may result in "pharmacological synergy" . This new approach to therapy of pyelonephritis may be promising.

J Antimicrob Chemother, 1986 Oct, 18(4), 441 - 51
Inhibition of K88-mediated adhesion of Escherichia coli to mammalian receptors by antibiotics that affect bacterial protein synthesis; Chopra I et al.; The ability of ten inhibitors of bacterial protein synthesis to decrease adhesion of Escherichia coli bearing K88ac fimbriae was examined . In the presence of the antibiotics at concentrations below the MIC values neomycin was the least effective inhibitor of adhesion and minocycline the most active . The effect of minocycline on the synthesis of individual polypeptides encoded by the K88ac determinant was examined in detail . The rate of synthesis of K88ac pilus protein in the presence of minocycline 0.75 mg/l (0.5 MIC) was less than that of total cell protein synthesis, suggesting that pilus protein becomes progressively 'diluted' in the outer membrane during exposure to this antibiotic concentration . Furthermore, the synthesis of two 'helper' polypeptides (molecular weights of 27.5 K and 27 K) which are probably involved in secretion of K88ac pilus protein through the cell envelope, was particularly sensitive to minocycline . Our observations suggest that the ability of translational inhibitors to decrease K88ac mediated adhesion probably results from direct inhibition of synthesis of fimbrial protein itself, together with inhibition of 'helper' polypeptide synthesis.

Hinyokika Kiyo, 1986 Oct, 32(10), 1551 - 72
{Epidemiological and therapeutic studies on gonorrheal infections--clinical efficacy of T-2588 . (Sapporo Clinical Research Group for STD)}; Kumamoto Y et al.; T-2588, a new oral cephalosporin antibiotic, for gonorrheal infections, was administered to 146 patients with gonorrheal infection cases (140 urethritis cases in males, 6 cervicitis cases in females) . Twenty three strains (20.9%) out of 110 clinically isolated gonococci were PPNG . The MICs of T-2588 for the clinically isolated gonococci strains showed a distribution peak at 0.025 microgram/ml and ranged between 0.0125 microgram/ml to 0.1 microgram/ml when an inoculum size of 10(6)/CFU/ml was used . The distribution of MICs of PPNG also showed a peak at 0.025 microgram/ml and the maximum MIC was 0.2 microgram/ml, which is one dilution tube higher than the maximum MIC of non-PPNG . The rate of complication by Chlamydia trachomatis was 20.9% in male and 33.3% in female . At the dose of 400 mg given 2 times a day, the efficacy rate for the males on the 3rd and 7th day was 90.5% (efficacy rate against PPNG, 73.3%) and 95.3% (80.0%), respectively . At the dose of 300 mg given 3 times a day, it was 93.3% and 100%, respectively, and at the dose of 600 mg given 3 times a day, it was 100% and 100%, respectively . Therefore, the administration of T-2588 3 times a day resulted in a higher efficacy rate than that given 2 times a day . This effect was extremely marked in the case of patients with PPNG . The best clinical results were obtained at a daily dose of 600 mg t.i.d . Although the female patients were few, in number and no conclusion can be drawn, the best results were obtained with a daily dose of 600 mg t.i.d . (100%) . There were three mild side effects (1.7%), which could not be attributed to the administration of T-2588 in the present study . In conclusion, T-2588 can be to be expected sufficiently clinically effective against gonorrheal infections, including PPNG, at a daily dose of 600 mg t.i.d . for 3 days.

J Clin Hosp Pharm, 1986 Oct, 11(5), 335 - 42
Determination of in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations; Cottrell WN et al.; The in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations were determined by utilizing high-performance liquid chromatography techniques following a once daily irrigation . A total of 14 chlorhexidine irrigations established a mean concentration of 0.006% w/v, 2-3 h post irrigation . A total of 12 noxythiolin irrigations established a mean concentration of 0.266% w/v, 2-3 h post irrigation, which correlated to a mean formaldehyde concentration of 0.0119% w/v at 2-3 h, as estimated from N-methylthiourea . For both solutions the minimum inhibitory concentration was exceeded for up to 5 h post irrigation, which is sufficient contact time to establish a total kill, thus indicating the possibility that a once daily irrigation may be appropriate in asymptomatic bacteriuria which utilizes either chlorhexidine or noxythiolin.

Gan To Kagaku Ryoho, 1986 Oct, 13(10), 3046 - 55
{Serum and tissue concentrations of UFT in patients with lung cancer}; Aota M et al.; Postoperative serum and tissue concentrations of 5-FU, FT-207 and uracil were measured in 36 patients with lung cancer who were administered UFT for seven days preoperatively . The concentration of 5-FU was high in tumor tissue and lymph nodes, but very low in serum . Such differences were not observed in the FT-207 levels . Tumor concentration of 5-FU in patients administered daily doses of 600 mg was 0.151 +/- 0.099 microgram/g which was three times higher than the minimum inhibitory concentration, and higher than that seen with other doses . The histological type and T factor were not related to the tissue concentration of 5-FU . Lymph node metastasis was not related to the concentration of 5-FU in the lymph nodes . The optimal daily dose of UFT for patients with lung cancer was considered to be 600 mg.

Life Sci, 1986 Sep 15, 39(11), 993 - 1001
Effect of atriopeptin III on renin release in vitro; Henrich WL et al.; The ability of atriopeptin III (AP) to directly inhibit renal renin release has not been resolved . This issue was examined in a series of experiments performed in a system of rat renal cortical slices (dry weight 1.91 mg) in which the goal was to explore the effects of AP on renin release induced by cyclic AMP (cAMP)-coupled stimuli or by agents which are believed to decrease intracellular calcium (Cai) . Concentration response relationships were initially established for all test agents . The cAMP stimuli utilized were isoproterenol (10(-5) M), forskolin (10(-5) M), and dibutyryl cAMP (3 X 10(-4) M); each of these agents produced a significant increase in renin release in the system (with isoproterenol a 59% increase, with forskolin 37%, and with dibutyryl cAMP 52%) . The addition of AP (2.09 X 10(-8) M, a minimum inhibitory concentration derived from preliminary studies) significantly blunted these increases; in the case of the dibutyryl cAMP-stimulated renin release, the inhibition was partial as a significant 25% increase in renin occurred in the presence of AP . The addition of the calcium channel blocking agent diltiazem (10(-4) M) resulted in a significant increase in renin release (364 to 567 ng X mg-1, p less than .05) which was not blocked by the addition of AP . Similarly, TMB-8 (0.6 X 10(-4) M), another agent thought to lower Cai, also resulted in increased renin release (455 to 810 ng X mg-1), p less than .01) which was also unaffected by the addition of the AP . In summary, these results show that AP is capable of partially inhibiting renin release in vitro, particularly renin release coupled to cAMP action . In contrast, renin release induced by a decline in Cai appears to be unaffected by the addition of AP.

Hum Genet, 1986 Sep, 74(1), 81 - 4
Cytogenetic effects of methyl isocyanate exposure in Bhopal; Goswami HK; Among human survivors following the methyl isocyanate (MIC) gas tragedy the major complaints have been related to deep-seated suffocation, terrible pain in breathing, and severe ocular irritations . In order to assess the possible genetic effects we have used lymphocyte cultures and screened chromosomes by two techniques; one by looking for chromosomal aberrations and the other by estimating sister-chromatid exchange (SCE) frequencies . Both these parameters are good indicators of genetic damage in chromosomal DNA . SCE frequencies in lymphocytes have been increased more than three times in MIC-exposed persons . The results were compared to two groups of controls (one group comprising persons present in the same house; the second group of persons were chosen from distant places, 20-50 km away from the incident) . Chromosomal breaks have been observed in 10 out of 14 MIC-affected people (71.4%) studied while only 6 out of 28 (21.4%) controls had chromosomal breaks . Some MIC-exposed persons had chromatin bodies in addition to the normal 46 chromosomes . These observations suggest that chromosomal DNA has been damaged.

J Clin Microbiol, 1986 Sep, 24(3), 448 - 50
Tentative disk diffusion susceptibility interpretive criteria for pefloxacin; Fuchs PC et al.; Standardized broth microdilution and disk diffusion susceptibility tests for pefloxacin were performed on 585 clinical isolates . The 5-micrograms pefloxacin disk is recommended, and the following breakpoints are proposed: susceptible, greater than or equal to 19 mm (MIC, less than or equal to 2.0 micrograms/ml); resistant, less than or equal to 15 mm (MIC, greater than 4.0 micrograms/ml); and intermediate, 16 to 18 mm.

Antimicrob Agents Chemother, 1986 Sep, 30(3), 468 - 74
Inhibition of DNA replication initiation by aminoglycoside antibiotics; Matsunaga K et al.; The reinitiation of DNA replication induced by a temperature shift in a dnaC(Ts) mutant of Escherichia coli was markedly inhibited by aminoglycoside antibiotics around the MIC in a short period . Protein synthesis continued for several minutes after the addition of aminoglycosides but was immediately blocked by chloramphenicol, suggesting that the inhibition of initiation of replication by aminoglycosides is not a secondary effect due to the interruption of protein synthesis . Aminoglycosides did not significantly affect RNA synthesis, suggesting that primer RNA synthesis for DNA initiation is not blocked by the agents . The lethal action of habekacin was observed simultaneously with the inhibition of DNA reinitiation . DNA elongation demonstrated with a dnaE(Ts) mutant or toluene-treated cells of a polA mutant was not significantly affected by aminoglycosides . The oriC-membrane complex formation was markedly interrupted by habekacin in the dnaC(Ts) mutant, and the in vitro reconstitution of the oriC-membrane complex was completely blocked by aminoglycosides . The present studies show that aminoglycosides block initiation of DNA replication and suggest that the inhibition is caused by the interruption of oriC-membrane attachment.

Clin Exp Immunol, 1986 Aug, 65(2), 319 - 28
Subpopulations of thyroid autoantibody secreting lymphocytes in Graves' and Hashimoto thyroid glands; McLachlan SM et al.; Lymphocytes isolated from Graves' and Hashimoto thyroid tissue by enzymatic (dispase) digestion or mechanical disaggregation were markedly different in terms of their ability to synthesize thyroid autoantibodies in culture . Dispase digestion, followed by removal of thyroid follicular cells, gave a lymphocyte population with a high T:B cell ratio (6:1) . However, the ability of these cell suspensions to synthesize microsomal (Mic) and thyroglobulin (Tg) antibodies spontaneously was significantly increased compared with lymphoid suspensions isolated by mechanical means . Spontaneous synthesis of thyroid autoantibodies was not markedly enhanced in cell suspensions prepared from patients' lymph node tissue by digestion compared with mechanical disaggregation . Further, Mic and Tg antibody production by thyroid lymphocytes prepared using dispase was inhibited by pokeweed mitogen (PWM) whereas in most cases suspensions prepared from the same tissues by mechanical dispersion synthesized low or undetectable levels of autoantibodies whether PWM was present or absent . Digestion of tissue debris remaining after mechanical removal of lymphocytes gave suspensions which had an increased proportion of suppressor/cytotoxic T cells compared with suspensions produced mechanically or by digestion alone; however, in terms of spontaneous autoantibody synthesis and PWM induced inhibition, these suspensions were similar to these obtained by digestion alone . It would therefore seem that enzymatic digestion of thyroid tissue resulted in the isolation of a lymphoid population which was different from that extracted by mechanical disaggregation . The digestion process appears to permit the recovery of lymphocytes closely associated with thyroid follicular cells and our studies suggest that it is this population which makes the major contribution to autoantibody synthesis.

Mutat Res, 1986 Aug, 174(4), 285 - 93
Mutagenicity of methylisocyanate and its reaction products to cultured mammalian cells; Caspary WJ et al.; Methylisocyanate (MIC) induced mutagenic responses in the absence of exogenous activation in the mouse lymphoma cell forward mutation assay at concentrations as low as 8-24 microM . MIC produced predominantly small mutant colonies, suggesting the possibility of clastogenic activity . The intermediate hydrolysis product, methylamine, was also mutagenic without exogenous activation but required several hundred-fold higher concentrations (ca . 3 mM) . N,N'-Dimethylurea, the final product in the reaction of methylisocyanate and water, was totally refractory in either the presence or absence of S9 for concentrations up to 57 mM (5 mg/ml) . The ethyl ester of N-methylcarbamic acid was also tested since it was the only available analogue to the highly reactive N-methylcarbamic acid intermediate . This compound was mutagenic only in the presence of S9 at doses exceeding 5-40 microM, which suggested the possibility that the free acid, produced by enzymatic hydrolysis, is also mutagenic . The mutagenic activity of the ester resulted solely in the production of small mutant colonies.

J Immunol Methods, 1986 Jul 11, 91(1), 129 - 38
Measurement of spontaneous and stimulated anti-microsomal antibody synthesis in vitro by avidin-biotin enzyme immunoassay; Harigai M et al.; The spontaneous and stimulated anti-microsomal (anti-Mic) antibody synthesis in vitro by peripheral blood lymphocytes (PBL) from patients with Hashimoto's thyroiditis (HT) was studied by a highly sensitive and thyroid microsome-specific enzyme immunoassay using an avidin-biotin system (A-B EIA) . Since the amount of the synthesized anti-Mic antibody by PBL in vitro is very small, it is difficult to study its kinetics and response to mitogens or the specific antigen by conventional assay systems . We applied the avidin-biotin system to conventional indirect EIA and established an assay system which was about four times as sensitive as indirect EIA . PBL from patients with HT synthesized significant amount of IgG anti-Mic antibody spontaneously but those from normal individuals and patients with rheumatoid arthritis did not . IgG anti-Mic antibody synthesis with pokeweed mitogen stimulation was increased in all HT patients and that with thyroid microsome stimulation was increased in three out of five patients . These results indicate that A-B EIA is a useful system to study the mechanism of anti-Mic antibody synthesis in vitro.

Br Med J (Clin Res Ed), 1986 Jul 5, 293(6538), 11 - 3
Intramuscular loading dose of quinine for falciparum malaria: pharmacokinetics and toxicity; Wattanagoon Y et al.; In a study of intramuscular injection of quinine eight adults with moderately severe falciparum malaria resistant to chloroquine were treated with quinine dihydrochloride, being given a loading dose of 20 mg salt (16.7 mg base)/kg followed by three or four eight hourly maintenance doses of 10 mg salt (8.3 mg base)/kg injected into the anterior thigh . All patients responded to treatment . Fever and parasite clearance times (mean (SD) 60 (23) h and 53 (22) h respectively) were comparable with those obtained with intravenous quinine . The mean peak plasma quinine concentration of 11.0 mg/l (34.4 mu mol/l) {corrected} was reached a median of five hours after administration of the loading dose . In all patients plasma quinine concentrations exceeded the high minimum inhibitory concentration for Plasmodium falciparum malaria prevalent in Thailand within four hours of the start of treatment but did not cause toxicity other than mild cinchonism . When intravenous infusion is not possible an intramuscular quinine loading dose is an effective means of starting treatment in patients with moderately severe falciparum malaria who cannot swallow tablets.

Indian J Lepr, 1986 Jul-Sep, 58(3), 401 - 6
Blood dapsone levels in leprosy patients treated with acedapsone; George J et al.; The metabolism of the repository drug acedapsone (DADDS,4,4'-diacetyldiaminodiphenyl sulfone) was studied in 15 individuals receiving 225 mg of DADDS, intramuscularly for a period of 75 days . Plasma levels of DDS were determined on the 2nd, 7th, 15th, 30th, 60th and 75th day after administration of the drug by spectrophoto-fluorometric technique . The mean peak levels of DDS (85.36 ng/ml) were noticed on 7th day followed by a gradual decrease in DDS concentration . The mean half-life level (44.53 ng/ml) of DDS were observed around the 15th day . The mean DDS level for the entire period of observation after one dose was 41.95 ng/ml . On the 75th day, the DDS level reached the minimum value of 14.76 ng/ml which was still about 5 times more than the minimal inhibitory concentration (MIC) level of DDS against M . leprae (3 ng/ml) . The results are discussed.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Jul, 261(4), 425 - 31
The susceptibility of a strain of Leptospira interrogans serogroup icterohaemorrhagiae to amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline; Broughton ES et al.; The failure of prophylactic penicillin to prevent a laboratory acquired case of Icterohaemorrhagiae leptospirosis prompted determination of the MIC and MBC of amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline for the infecting strain . Amoxycillin followed by erythromycin were the most effective, with MBCs of 0.5 mg/l after 7 days exposure and 0.1 mg/l after 21 days exposure respectively . Leptospires grew in the presence of high concentrations of tetracycline hydrochloride and oxytetracycline after prolonged incubation . This effect was less pronounced with minocycline, with MIC's of 0.025, 0.05 and 0.1 mg/l after 7, 14 and 21 days exposure respectively . The MIC of lincomycin was 0.25 mg/l at each time interval . These results support the high dose, long duration antibiotic regimens recommended in the literature.

Antimicrob Agents Chemother, 1986 Jul, 30(1), 15 - 9
Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis; Heim KL et al.; The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis . Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX . Multiple blood and dialysate samples were collected during the 72-h period after drug administration . The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v . administration were 2.2 +/- 1.0 h (mean +/- standard deviation), 0.17 +/- 0.03 liters/kg, and 81.0 +/- 31.0 ml/min, respectively . No significant differences were observed in these parameters after i.p . administration . The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 +/- 0.43 and 2.84 +/- 0.70 ml/min, respectively, after i.v . administration . The bioavailability of CTX after i.p . instillation was 74.6 +/- 21.3% . Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i.p . dosing . Administration (i.v.) of 2 g every 12 h or i.p . instillation of 2 g every 24 h may be used for the treatment of i.p . infections with highly susceptible organisms (MIC less than 1.0 microgram/ml).

Infection, 1986 Jul-Aug, 14(4), 186 - 9
Activity of the trometamol salt of fosfomycin in an in vitro model of the treatment of bacterial cystitis; Greenwood D; The response to trometamol fosfomycin of four strains of Escherichia coli was studied in an in vitro model in which the hydrokinetic aspects of the treatment of bacterial cystitis can be stimulated . Two strains of E . coli that were fully susceptible to fosfomycin, and a strain of intermediate susceptibility responded well to relatively low concentrations of the trometamol salt: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for at least 18 h; however, the emergence of resistance was completely suppressed only when a peak concentration of 2500 mg/l was achieved in the bladder model . A strain of E . coli that was fully resistant to fosfomycin in conventional minimum inhibitory concentration titrations responded to the highest dosage used, but this did not prevent further resistance from emerging . These results were obtained in the absence of the potentiating agent, glucose-6-phosphate, which is commonly used in susceptibility tests of fosfomycin . The implications of the results for fosfomycin dosage in bacterial cystitis and for the interpretation of susceptibility tests is discussed.

Z Lebensm Unters Forsch, 1986 Jul, 183(1), 1 - 7
{In vitro toxicity tests of diethyleneglycol with cell cultures and an automated bacterial test system}; Lindl T et al.; Diethyleneglycol was tested for its general cytotoxic effects in three cell culture test systems and in a novel, automated bacterial test system . The first cytotoxic effects were detected in the cell culture test systems at DEG-concentrations of 1 g/1 and 3g/1 . The bacterial test system showed a minimal inhibitory concentration of 5 g/1 DEG (20% growth reduction) . Morphological observations showed evidence of membrane damage to the cultured cells by DEG . With the bacterial test system one could determine the amount of DEG semiquantitatively in wines to which this material had been added.

Antimicrob Agents Chemother, 1986 Jul, 30(1), 127 - 31
Tellurite susceptibility and non-plasmid-mediated resistance in Escherichia coli; Tomas JM et al.; Tellurite (TeO3(2-)) is highly toxic toward Escherichia coli (MIC, approximately 1 microgram ml-1) . Mutants (Tel) that were resistant to low levels of TeO3(2-) (MIC, approximately 10 micrograms ml-1) and collaterally resistant to arsenate were isolated . These Tel mutants were unable to grow on media containing low levels of Pi, which supported growth of the parent strain . When grown at much higher Pi levels they exhibited depressed levels of the outer membrane phoE protein and the periplasmic phoS protein, as well as several other proteins indicative of Pi starvation . Tel mutants were markedly defective in 32Pi transport, and TeO3(2-) was shown to be a potent competitive inhibitor of 32Pi transport in the parent strain . The Tel phenotype could be complemented by an F' plasmid harboring the phoR, phoB, and phoA loci, and curing of the F' plasmid completely restored TeO3(2-) resistance . Of a variety of well-characterized Pi transport mutants, only phoB mutants were equally resistant to TeO3(2-), and susceptibility could also be restored in strains carrying an F' plasmid for the phoB region and lost once more after F' curing . The tel and phoB loci were equally cotransducible with lac . Tel mutants still synthesized alkaline phosphatase, the phoA gene product, after Pi starvation, suggesting that the phoB locus per se was not involved because phoB is a positive regulatory gene for phoA expression . The results indicate that TeO3(2-) is transported into E . coli by a phosphate transport system and that resistance to TeO3(2-) specifically selects for as yet uncharacterized mutants in the phoB-phoA region of the chromosome.

Pathol Biol (Paris), 1986 Jun, 34(5 Pt 2), 684 - 7
{Comparative study of the fungistatic activity in vitro of omoconazole and 6 other imidazoles against yeasts}; Mosse M et al.; Omoconazole (CM 8282) is a new synthetic antifungal agent with a spectrum of activity quite similar to that of the imidazole family . Fungistatic activity of this product was compared to that of the six following reference products: clotrimazole, econazole, isoconazole, ketoconazole, miconazole, and tioconazole . MICs against 55 recent clinical yeast isolates were determined by agar dilution on pH 5.5-adjusted Sabouraud and casitone media . MIC 90% values showed that tioconazole was the most active product, followed by omoconazole and econazole, whereas ketoconazole was the least active compound under our experimental conditions.

Methods Find Exp Clin Pharmacol, 1986 Jun, 8(6), 367 - 72
Activities of cefoxitin in vitro and in vivo: a study in patients with biliary tract infection undergoing percutaneous transhepatic biliary drainage; Masuda G et al.; Activities of cefoxitin and the effect on killing of bacteria in bile from six patients undergoing percutaneous transhepatic biliary drainage were analyzed in relation to in vitro activities of the drug, with particular reference to the incubation time . The bacteriostatic and bactericidal activities of cefoxitin with short term (6 hr) incubation correlated well with the duration of the effective cefoxitin concentration and the decrease of viable bacteria in bile juice from the patients . These timed in vitro activities can be used as well as the conventional MIC and MBC with the prolonged incubation of 24 hr, in the deductive analysis of bacterial response in vivo.

Jpn J Antibiot, 1986 May, 39(5), 1273 - 8
{Penetration of cefotaxime into human bone marrow blood}; Endo F et al.; Concentrations of cefotaxime (CTX) in bone marrow blood and venous blood were examined with the passage of time in 21 cases which received operations of bone and joint . Concentrations of CTX in bone marrow blood at 30 minutes of a single intravenous administration 2 g each of CTX were found to be 85.2 +/- 24.5 micrograms/ml . Concentration ratio of CTX in bone marrow blood to that in venous blood was reached the peak at 120 minutes after administration . Concentrations of CTX observed were higher than the MIC of CTX against major pathogens responsible for the postoperative infections in orthopaedic field . The CTX, therefore, is expected to have an effective antibiotic in prophylaxis.

Fundam Appl Toxicol, 1986 May, 6(4), 756 - 71
Acute inhalation studies with methyl isocyanate vapor . II . Respiratory tract changes in guinea pigs, rats, and mice; Fowler EH et al.; Hartley guinea pigs, Fischer-344 rats, and B6C3F1 mice of both sexes were exposed to varying concentrations of methyl isocyanate (MIC) vapor with the highest concentration being 20.4 ppm for rats and mice and 10.5 ppm for guinea pigs . A control group for each species was exposed to air only . All animals were exposed for a duration of 6 hr, and survivors were sacrificed 14 days following exposure . The respiratory tract was removed and examined microscopically from all animals . Guinea pigs were more sensitive to the MIC vapor than were rats which were in turn more sensitive than mice . Gross lesions encountered in many of the animals that died consisted of nasal discharge, often blood tinged, and discoloration of the lungs . Microscopic lesions included acute necrosis of epithelial lining throughout the respiratory tract in animals that died shortly after exposure coupled with congestion, edema, and inflammation . A microscopic lesion which appeared unique to guinea pigs was bronchiolitis obliterans where the necrosis and inflammation had completely closed the bronchioles . Additional microscopic lesions observed in some animals that died or were sacrificed at the end of the study (postexposure Day 14) consisted of squamous metaplasia of respiratory epithelium in the nasal cavity, which extended into the larynx, trachea, and, in some cases, the bronchi . In addition, epithelial regeneration throughout the tract and submucosal fibroplasia in the trachea, bronchi, and bronchioles were observed, the latter lesion being primarily confined to rodents . No animals exposed to 2.4 or 1.0 ppm of MIC vapor died following exposure . There were minimal microscopic lesions at sacrifice in the 2.4 ppm-exposed animals from all three species . Only in guinea pigs were there lesions in the 1.0-ppm group attributed to MIC vapor exposure.

Fundam Appl Toxicol, 1986 May, 6(4), 747 - 55
Acute inhalation studies with methyl isocyanate vapor . I . Methodology and LC50 determinations in guinea pigs, rats, and mice; Dodd DE et al.; Groups of male and female Fischer 344 rats, B6C3F1 mice, and Hartley guinea pigs were exposed once for 6 hr to mean concentrations of 10.5, 5.4, 2.4, 1.0, or 0 (control) ppm of methyl isocyanate (MIC) vapor . Rats and mice were also exposed to 20.4 ppm of MIC . No deaths occurred in animals exposed to 2.4 or 1.0 ppm . The majority of deaths for the 20.4- and 10.5-ppm groups occurred during postexposure Days 1 through 3, while at 5.4 ppm deaths were observed throughout the 14-day postexposure period . The 6-hr LC50 values (with 95% confidence limits) were 6.1 (4.6 to 8.2) ppm for rats, 12.2 (8.4 to 17.5) ppm for mice, and 5.4 (4.4 to 6.7) ppm for guinea pigs . Notable clinical observations during and immediately following MIC exposure were lacrimation, perinasal/perioral wetness, respiratory difficulty (e.g., mouth breathing), decreased activity, ataxia, and hypothermia . The frequency of clinical signs decreased during the second postexposure week . Body weight losses were common in all species following MIC exposures of 2.4 ppm or greater . At 1.0 ppm, only female mice had body weight depression . Recovery of body weight loss was observed in the 5.4- (guinea pigs only), 2.4- and 1.0-ppm concentration groups . The lungs of all animals that died were discolored . Following microscopic examination of the respiratory tract, deaths were attributed to pulmonary edema and congestion . In a separate study, Fischer 344 rats and Hartley guinea pigs were exposed once for 4 hr to mean concentrations of 36.1, 25.6, 15.2, or 5.2 ppm of MIC vapor . In general, the results were similar to those of the single 6-hr exposure study.

Pathol Biol (Paris), 1986 May, 34(5), 445 - 7
{Comparative in vitro activity of a new macrolide RU 28965 and of erythromycin against Chlamydia trachomatis}; Dutilh B et al.; Activity of a new macrolide, RU 28965, and erythromycin against 8 Chlamydia trachomatis strains isolated from the human genital tract was studied . Minimal inhibitory concentrations were determined using cycloheximide-treated McCoy cells . Giemsa and immunofluorescence staining with monoclonal antibodies were used to detect Chlamydial inclusions . Immunofluorescence proved more sensitive and easier to read . All the strains were highly susceptible to RU 28965 (MIC = 0.05 mg/l - 0.1 mg/l) and erythromycin (MIC = 0.02 mg/l - 0.2 mg/l).

Jpn J Antibiot, 1986 May, 39(5), 1359 - 71
{Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology}; Cho N et al.; A combination of imipenem (MK-0787), a new carbapenem antibiotic, plus cilastatin sodium (MK-0791), a dehydropeptidase inhibitor (MK-0787/MK-0791 = 1:1) was studied in the field of obstetrics and gynecology and the following results were obtained . Absorption and penetration into genital organ tissues were good . Following a 0.5 g/0.5 g intravenous drip infusion, the maximum plasma concentration in uterine arterial blood was 20.8 micrograms/ml, and the maximum concentrations of the drug in tissues were 9.9 approximately 16.8 micrograms/g, and these levels of MK-0787 exceeded the MIC values against main causative organisms . Rates of elimination of the drug from the tissue and from the plasma were similar . Against gynecological and obstetrical infections, a dose of 0.5 g/0.5 g twice daily for an average duration of 6.3 days produced a clinical efficacy ratio of 94.4% (17/18) and a bacteriological effects rating of 76.9% (10/13) . As side effects, one patient showed an eruption and another had an elevated GOT and GPT . Based on the above results, MK-0787/MK-0791 appears to be effective against gynecological and obstetrical infections.

Jpn J Antibiot, 1986 May, 39(5), 1259 - 72
{Concentrations of cefmenoxime and cefotiam in the bile and gallbladder tissue following intravenous administration in patients with biliary tract diseases}; Shoda Y et al.; To test the effectiveness of cefmenoxime (CMX) and cefotiam (CTM) in patients with biliary tract diseases, concentrations of either antibiotic were measured after an intravenous bolus injection of 1.0 g of CMX or CTM, or simultaneous injection of both (1.0 g each) . CMX or CTM was injected in 76 patients with biliary tract diseases (mostly cholelithiasis) prior to a cholecystectomy and concentrations of CMX or CTM were measured by the bioassay (agar well) method at 30 to 60 minutes after the injection . Average concentrations of both CMX and CTM in gallbladder bile and gallbladder tissue sufficiently exceeded the minimal inhibitory concentration (MIC) against main causative organisms of biliary tract infections . Concentrations of both antibiotics in gallbladder bile were significantly higher in patients with patent cystic ducts than with obstructed cystic ducts . Concentrations of both antibiotics in the gallbladder tissue reached at a similar high level regardless of the patency of the cystic ducts, but concentrations were lower in severely inflamed gallbladders . CMX and CTM were administered alternatively (cross-over fashion), or simultaneously (combined) to 13 patients with T-tube drainage or percutaneous transhepatic cholangio-drainage, and concentrations of both antibiotics in bile from the drainage tube were measured by high performance liquid chromatography at hourly intervals after the injection . Concentrations of both antibiotics were far greater than MICs against main attributable microorganisms in biliary tract infections . The concentration of CMX slightly exceeded that of CTM . Concentrations of both antibiotics were lower in bile of patients showing abnormally high serum GTP, A1-P, and total bilirubin levels than in bile of patients with normal values of these variables . It is speculated that the secretion of both antibiotics in the bile may decrease in cases with severe hepatic failure, but effective concentrations of both antibiotics in the gallbladder tissue should be maintained as long as the blood circulation in the gallbladder was maintained.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1986 May, 182(3), 299 - 309
On the influence of different growth conditions to the resistance of some methylotrophic bacteria to aldehydes; Heinzel M; The resistance to formaldehyde of several facultatively methylotrophic bacteria has been investigated . The MIC-values were in the range of formaldehyde concentrations used for preservation purposes . The resistance could be explained partly by the action of aldehyde dehydrogenase found in two of the strains and by the development of a penetration barrier by the cell envelopes described formerly.

Antimicrob Agents Chemother, 1986 May, 29(5), 797 - 802
Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat; Cozens RM et al.; The bactericidal activity of 23 beta-lactam antibiotics was compared in slowly growing bacteria cultured in a chemostat . In an attempt to mimic possible in vivo conditions, slowly growing cultures were produced by limitation of iron, glucose, phosphate, or magnesium . Only select antibiotics remained effectively bactericidal against slowly growing cells . For these compounds, the rate of antibiotic-induced loss of viability was a constant when killing was expressed per generation (in contrast to absolute time) in that slowly growing bacteria were killed proportionately more slowly . Individual antibiotics differed greatly, however, in their specific bactericidal activities against slowly growing cells, i.e., in the absolute degree of killing elicited during exposure of the bacteria to MIC equivalents of the drugs . Specific bactericidal activities varied not only with drug structure but also with the bacterial strains and, to a lesser extent, with the nature of the growth-limiting nutrient . In slowly growing cultures exposure to the low drug concentrations studied here (near MIC) caused killing without detectable lysis . Antibiotics with high specific bactericidal activities were capable of rapidly killing cultures of slowly growing pathogens despite extremely long generation times approaching those reported for in vivo growth rates.

Pathol Biol (Paris), 1986 May, 34(5), 360 - 3
{Sensitivity to various antibiotics of spiroplasmas isolated from mosquitoes in France}; Abalain-Colloc ML et al.; Spiroplasmas are helical mycoplasmas that play a significant role in plant diseases . They are also found in arthropods that are likely to bite humans, such as ticks and mosquitoes . These arthropods can act as vectors and therefore may be of epidemiologic significance . Furthermore, mainly on the grounds of morphologic evidence, spiroplasmas have been incriminated in the genesis of human Creutzfeld-Jacob disease . We recovered six strains of Spiroplasma sp . from 1927 female mosquitoes . In vitro susceptibility of each strain to the following antibiotics was studied: tetracycline, oxytetracycline, doxycycline, erythromycin, chloramphenicol, rifampin, kanamycin, gentamicin and pefloxacin . Minimal inhibitory concentrations (MICs) were determined by dilution in liquid SP4 medium using microtiter plates . Plates were incubated for 24 to 48 hours at 30 degrees C . The inoculum contained approximately 5 X 10(5) CFU/ml . Each of the six strains was found to be highly susceptible to tetracycline, oxytetracycline, doxycycline, erythromycin, chloramphenicol and pefloxacin (MICs less than or equal to 0.16 microgram/ml, 0.63 microgram/ml, 0.08 microgram/ml, 0.16 microgram/ml and 0.32 microgram/ml respectively) . On the opposite, the strains exhibited resistance to rifampin and variable degrees of susceptibility to kanamycin (12.5 micrograms/ml less than MIC less than 50 micrograms/ml) and gentamicin (3.12 micrograms/ml less than MIC less than 50 micrograms/ml) . From our results, spiroplasmas seem to have more or less the same susceptibility to antibiotics as mycoplasmas.

J Hosp Infect, 1986 May, 7(3), 269 - 76
A comparative trial between cefotetan and cephazolin for wound sepsis prophylaxis during elective upper gastrointestinal surgery with an investigation of cefotetan penetration into the obstructed biliary tree; Leaper DJ et al.; Cefotetan is a cephamycin antibiotic theoretically suited to prophylaxis of wound infection during upper elective gastrointestinal surgery . In a prophylaxis trial 100 patients undergoing this type of surgery were randomly allocated to receive 1g cefotetan or cephazolin iv at induction of anaesthesia . Cefotetan-treated patients had significantly fewer postoperative infections overall (P less than 0.05) and there were no wound infections recorded in this group . In a separate pharmacokinetic study the penetration of cefotetan into common bile duct bile and gallbladder wall was measured in a further six patients, all of whom had been jaundiced preoperatively . At the time of maximum risk concentrations of cefotetan in bile and biliary tissue as well as blood and wound fat were in excess of the minimum inhibitory concentration for the majority of relevant pathogens . Cefotetan appears to be equally or more effective than cephazolin and is a suitable alternative prophylactic agent in elective upper gastrointestinal surgery.

J Med Chem, 1986 Apr, 29(4), 494 - 9
Synthesis and antitumor and antiviral properties of 5-alkyl-2'-deoxyuridines, 3',5'-cyclic monophosphates, and neutral cyclic triesters; Beres J et al.; A series of 5-alkyl-2'-deoxyuridine 3',5'-cyclic monophosphates (5-R-cdUMP's, R = Et, i-Pr, n-Pr, n-Bu, n-Pent, n-Hex, n-Oct) was prepared and tested in culture systems as antitumor and antiviral agents in comparison to the 5-alkyl-2'-deoxyuridines (5-R-dUrd's) themselves . Only the 5-Et- and 5-n-Bu-cdUMP showed appreciable cytostatic activities against murine L1210 and human lymphoblast Raji cells (ID50 range: 28-82 micrograms/mL) . 5-Et-dUrd itself was much more active (ID50 = 1.6 and 2.9 micrograms/mL) . The 5-i-Pr-, and 5-n-Bu-dUrd's were inactive, but activity increased again for groups with chain lengths of five carbons or greater . 5-Et-cdUMP and 5-Et-dUrd had greatly reduced activities against deoxythymidine kinase deficient (TK-) L1210 and Raji cells . 5-Et-cdUMP evidently is not an efficient prodrug source of the corresponding 5'-monophosphate where the TK- cells are concerned . Of the 5-R-cdUMP's, 5-Et-cdUMP displayed reasonably good antiviral potency against herpes simplex types 1 and 2 (MIC50, mostly 7-70 micrograms/mL) and vaccinia virus (MIC, 70 micrograms/mL) . The activity was nonetheless 10- to 100-fold less than that for 5-Et-dUrd . The other 5-R-dUrd's generally showed decreasing antiviral activity with increasing 5-R chain length . Methyl and/or benzyl neutral triesters of certain 5-R-cdUMP's were inactive as antivirals and largely inactive against tumor cells in culture . In contrast to the 5'-monophosphates, the 5-R-cdUMP's failed to inhibit thymidylate synthetase from L1210 cells.

Clin Pharm, 1986 Apr, 5(4), 319 - 24
Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides; Deziel-Evans LM et al.; The influence of five pharmacokinetic indices on therapeutic response was retrospectively studied in 45 adult patients treated with aminoglycosides for bacterial infections . Subjects were treated for a minimum of five days, had culture and sensitivity reports, and had at least one set of steady-state peak and trough serum aminoglycoside concentrations . Serum drug concentrations were determined by enzyme-multiplied immunoassay or by fluorescence polarization assay . Minimum inhibitory concentrations (MICs) for the drugs were determined by microdilution assays . Cure was determined by negative cultures or absence of clinical evidence of infection . Values for five pharmacokinetic indices were determined for each patient: ratio of steady-state peak serum concentration to MIC (Cssmax/MIC); time that the serum concentration remained above the MIC during a 72-hour period (tsupra-MIC(72)); the intensity index for a 72-hour period (II(72)), which is related but not identical to the area under the curve (AUC), reflecting the contributions of Cssmax/MIC and tsupra-MIC(72); time that the serum concentration was greater than four times the MIC during a 72-hour period (tsupra-(4 X MIC)(72)), and the intensity index related but not identical to AUC greater than four times the MIC (II4 X MIC(72)), which reflects the contribution of Cssmax/(4 X MIC) and tsupra-(4 X MIC)(72) . Statistical analysis revealed significant correlations between each of the five indices and the patients' therapeutic responses . The following index values were associated with cures: Cssmax/MIC greater than 4 (and ideally greater than 8); tsupra-MIC(72) of at least 40 hours; tsupra-(4 X MIC)(72) of at least 10 hours; (4) II(72) greater than 400; and II4 X MIC(72) greater than 50 . All five pharmacokinetic indices were good predictors of patient outcome . The ratio of maximum steady-state serum aminoglycoside concentration to minimum inhibitory concentration is the index most easily monitored and interpreted.

J Clin Hosp Pharm, 1986 Apr, 11(2), 95 - 100
An investigation of the in vitro anti-bacterial activity of noxythiolin against 1,000 pathogenic bacterial isolates; Ashley KC et al.; The susceptibility of 1,000 recent bacterial isolates to noxythiolin was determined by the disc susceptibility method . No Gram-positive strains were resistant to this method but 56 (5.6%) of Gram-negative strains gave zones of inhibition of 12 mm diameter or less . The minimum inhibitory concentration (MIC) of the latter were determined by the agar incorporation method . No strains had MIC values greater than 4096 mg/litre . Since concentrations of 50,000 mg/litre can be used for topical treatment, these organisms may be considered susceptible.

Presse Med, 1986 Mar 8, 15(10), 471 - 4
{Treatment of septicemia and endocarditis with pefloxacine . 15 cases}; Wolff M et al.; The therapeutic effectiveness of pefloxacin was evaluated in 15 patients admitted to an intensive care unit and suffering from septicaemia or endocarditis . Seven of these patients had a focal infection (acute anterior mediastinitis or epiduritis) . Pefloxacin was combined with an aminoglycoside in 13 cases and with rifampicin in 1 case . Blood cultures became or remained negative in all patients . The associated focus of infection was sterilized in 5 patients; a pefloxacin-resistant pathogen was subsequently isolated in 2 other patients . Three patients died some time after the infectious episode . The minimum inhibitory concentration of pefloxacin ranged from 0.25 to 2 mg/l . The bactericidal activity of the serum at peak concentration was greater than or equal to 1/8 in all cases and greater than or equal to 1/32 in 10 cases . No resistant mutants were selected during treatment . However, 8 strains of a species different from that of the initial pathogen were isolated from a site other than the primary focus . Pefloxacin can therefore be used successfully in the treatment of systemic infections, but close monitoring of bacterial ecology is required.

J Clin Microbiol, 1986 Mar, 23(3), 634 - 6
Tentative disk diffusion susceptibility interpretive criteria for BMY-28142, a new cephalosporin; Fuchs PC et al.; A total of 750 bacterial isolates, including 37 different species, were tested for susceptibility to BMY-28142 by standardized broth microdilution and disk diffusion tests . The zone diameter interpretive criteria tentatively suggested for the 30-micrograms BMY-28142 disk are as follows: susceptible = greater than or equal to 18 mm (MIC less than or equal to 8.0 micrograms/ml), resistant = less than or equal to 14 mm (MIC greater than or equal to 32 micrograms/ml), and indeterminate = 15 to 17 mm.

Jpn J Antibiot, 1986 Mar, 39(3), 721 - 5
{Clinical study on the tissue distribution of cefmenoxime in the field of otolaryngology}; Fujita K et al.; Concentrations of cefmenoxime (CMX) in serum and tissue were determined in surgical patients with chronic sinusitis, maxillary cyst or chronic tonsillitis . CMX was intravenously administered in a dose of 1 gram . Thirty minutes after the administration, patients were operated under local anesthesia . Concentrations of CMX in tissues were determined 1 hour after administration, and were 15.8 micrograms/g and 20.3 micrograms/g in mucous membrane of maxillary sinus and maxillary cyst . CMX was not detectable in tonsils of 8 patients out of 11 examined . An examination of MIC against various bacteria isolated from sinus pus and pharyngeal swab indicated that CMX was effective enough to produce a prophylactic effect against otolaryngo-infections.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 482 - 7
Antirhinovirus activity of purine nucleoside analogs; De Clercq E et al.; A wide variety of purine nucleoside (mainly tubercidin and adenosine) analogs, which had previously been shown to inhibit the replication of a broad spectrum of RNA viruses, were evaluated for their antirhinovirus activity in human diploid (WI-38) fibroblasts . Tubercidin, 5-(1-hydroxyethyl)tubercidin, 5-(2-buten-1-yl)tubercidin, toyocamycin, and sangivamycin emerged as the most potent inhibitors . These compounds inhibited the replication of rhinovirus types 1A, 1B, and 9 at an MIC well below 1 microgram/ml . However, these compounds proved cytotoxic for the uninfected host cells at concentrations which were only slightly higher (3- to 10-fold, on the average) than those required for inhibition of rhinovirus replication . The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50 . None of the carbocyclic and acyclic analogs of adenosine tested exhibited a potent or selective antirhinovirus activity.

J Antimicrob Chemother, 1986 Mar, 17(3), 389 - 96
A non-comparative study of parenteral ampicillin and sulbactam in intra-thoracic and intra-abdominal infections; Mehtar S et al.; Fifty-four patients were treated with intravenous ampicillin and sulbactam in an open study of intra-thoracic and intra-abdominal infection . Thirty-one were treated with 500 mg each of the combination 6-hourly while 23 patients were given 1 g of ampicillin and 500 mg of sulbactam, 6-hourly . Thirteen of fourteen (93%) patients with severe respiratory tract infection and 22/26 (85%) patients in the intra-abdominal infection group responded clinically and bacteriologically . Seven patients with clinical sepsis (but not confirmed bacteriologically) improved on therapy . 50/55 (91%) clinical isolates from this study were eliminated . An increase in MIC was found in two cases . There were minimal side effects, pain at site of injection being the commonest complaint.

Chemioterapia, 1986 Feb, 5(1), 23 - 5
Ciclopiroxolamine: clinical and microbiological considerations . Preliminary data; Oliveri S et al.; Ciclopiroxolamine's action has been evaluated in 20 cases of dermatophytosis . The minimum inhibitory concentrations (MIC) for the strains was determined in vitro before treatment (To), after the 4th day (T4), and after the 7th day (T7) of treatment, in relation with the drug's fungicide effect . No significant variation was observed among the MIC values . By comparing the MIC of T4 versus the MIC of To a 0.93 coefficient of linear correlation was obtained while in comparing T7 versus T4 the coefficient was equivalent to 1.0 . After 7 days of treatment 5 patients clinically recovered, 11 improved and 4 showed no improvement . Drug tolerance was excellent except for one case.

J Clin Pharmacol, 1986 Feb, 26(2), 79 - 86
Factors associated with nephrotoxicity and clinical outcome in patients receiving amikacin; Williams PJ et al.; Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity . In 42 of these patients, data were examined for factors associated with clinical outcome . Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total dose, mean daily dose, organism minimum inhibitory concentration (MIC), mean peak levels, mean trough levels, mean area under the serum concentration-time curve (AUC), total AUC, mean AUC greater than MIC, total AUC greater than MIC, mean Schumacher's intensity factor (IF), total IF, In (mean maximum concentration {Cmax}/MIC) . Model-dependent pharmacokinetic parameters were calculated by computer based on a one-compartment model . When the parameters were examined individually, duration of therapy and total AUC correlated significantly (P less than .05) with nephrotoxicity . In contrast, a stepwise discriminant function analysis identified only duration of therapy (P less than .001) as an important factor . Based on this model and on Bayes' theorem, the predictive accuracy of identifying "nephrotoxic" patients increased from 0.17 to 0.39 . When examined individually, mean IF, MIC, total dose, mean daily dose, and ln (mean Cmax/MIC) correlated significantly (P less than .05) with cure . In contrast, a simultaneous multivariable analysis identified IF, MIC, and total dose according to one model and ln (mean Cmax/MIC) according to a second statistical model of parameters selected to have the greatest prospective value . Based on Bayes' theorem and the first model, the predictive accuracy of identifying patients not cured increased from 0.19 to 0.83 . For the second model, the predictive accuracy increased from 0.19 to 0.50.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicol Appl Pharmacol, 1986 Feb, 82(2), 329 - 35
Sensory and pulmonary irritation with exposure to methyl isocyanate; Ferguson JS et al.; Methyl isocyanate (MIC) was tested for its potency as a sensory irritant and as a pulmonary irritant in mice . To evaluate sensory irritation, animals were exposed to MIC at concentrations between 0.5 and 7.6 ppm for a period of 90 min . A characteristic reflex decrease in respiratory rate indicating sensory irritation was observed . The concentration evoking a 50% decrease in respiratory rate (RD50) was found to be 1.3 ppm . To evaluate pulmonary irritation, animals were first anesthetized and fitted with a tracheal cannula . Following recovery from anesthesia, they were exposed to MIC at concentrations between 0.4 and 7.3 ppm for a period of 90 min . A characteristic decrease in respiratory rate indicating pulmonary irritation in tracheally cannulated (TC) mice was observed . The concentration evoking a 50% decrease in respiratory rate (RD50TC) was found to be 1.9 ppm . Thus, MIC was found to be a potent sensory and pulmonary irritant.

J Antimicrob Chemother, 1986 Feb, 17(2), 165 - 71
Antigiardial activity of the bile salt-like antibiotic sodium fusidate; Farthing MJ et al.; Possible antigiardial activity of the bile salt-like antibiotic, sodium fusidate has been investigated during 24 h liquid culture of Giardia lamblia trophozoites and in 4 h microassays for parasite motility inhibition and viability . Sodium fusidate inhibited Giardia growth (ED50 0.2 mM; MIC 0.3 mM) but was considerably less potent than metronidazole (ED50 0.002 mM; MIC 0.05 mM) . Sodium fusidate and metronidazole were active inhibitors of parasite motility (ED50 0.9 and 0.3 mM respectively) but were largely without effect in the 4 h viability assay . Sodium fusidate was active at concentrations well below its critical micellar concentration (2.7 mM) suggesting that its effect was not merely related to its membranolytic detergent properties . Its taurine and glycine conjugates were markedly less potent and paradoxically stimulated growth at low concentration . The studies suggest that sodium fusidate does have antigiardial activity and in view of its relative freedom from teratogenic and other toxic effects may be useful in pregnancy when other antigiardial agents are contra-indicated or as an adjunct in combination therapy when other single agents have failed to eradicate infection.

Hinyokika Kiyo, 1986 Feb, 32(2), 293 - 6
{Clinical study of cinoxacin in acute simple cystitis}; Inaba T et al.; Cinoxacin (CINX) was administered twice a day for 7 consecutive days (400 mg X 2/day) to 34 female patients suffering from acute simple cystitis . The overall clinical efficacy was excellent in 15 cases (94%) and moderate in one case (6%) according to the criteria for clinical evaluation by the UTI committee . The efficacy was not determined in 18 cases . Bacteriological examination revealed 11 cases of single infection by E . coli, 2 cases of single infection by P . cepacia and S . epidermidis and one case of single infection by S . sunguis . MIC of E . coli ranged from 3.13 to 6.25 micrograms/ml . MIC of P . cepacia was 3.13 micrograms/ml and MIC of S . epidermidis more than 100 micrograms/ml . All the strains were eradicated with the efficacy of 100% . There was no relapse of acute simple cystitis in 16 cases after 7 days treatment of CINX . No serious side effects were recognized except for slight general fatigue and heart burn in 2 cases . It was thus concluded that CINX is clinically effective and safe for acute simple cystitis caused by E . coli and P . cepacia.

J Antimicrob Chemother, 1986 Feb, 17(2), 139 - 46
Behaviour of TEM-1 beta-lactamase as a resistance mechanism to ampicillin, mezlocillin and azlocillin in Escherichia coli; Livermore DM et al.; Escherichia coli isolates which synthesised the extremely common 'TEM-1' plasmid mediated beta-lactamase were more resistant to the alpha-aminopenicillins, ampicillin, mezlocillin and azlocillin, than were strains which lacked this enzyme . However, many TEM-1+ isolates remained sensitive to therapeutic concentrations of mezlocillin (less than 64 mg/l), whereas virtually none was susceptible to such levels of ampicillin or azlocillin . Transconjugants of E . coli K12 into which we introduced various TEM-1 coding plasmids similarly acquired lower levels of resistance to mezlocillin than to ampicillin and azlocillin . Those which expressed relatively small amounts of enzyme remained sensitive to 64 mg/l of mezlocillin, whereas they were substantially resistant (MIC greater than 64 mg/l) to the other alpha-aminopenicillins . These data suggested that the enzyme afforded weaker protection against mezlocillin than against azlocillin and ampicillin and we attempted to relate this finding to its hydrolytic activity . Extracted TEM-1 beta-lactamase hydrolysed high concentrations of mezlocillin more rapidly than ampicillin and azlocillin; however, mezlocillin was calculated to be the weakest substrate at the low concentrations which are likely to be obtainable in the bacterial cell . These data may partly account for the residual activity of mezlocillin against enzyme producers, but target and permeability factors probably also contribute.

J Periodontol, 1986 Feb, 57(2), 104 - 7
Serum and crevicular fluid concentrations after a single oral dose of metronidazole; Britt MR et al.; Previous studies have shown that metronidazole is an effective chemotherapeutic agent in the treatment of certain types of periodontal disease . The purpose of this study was to assess, over 18 hours, the concentration of the drug in serum and gingival crevicular fluid after a single oral dose . Six female volunteers with gingivitis created by cessation of brushing for 2 weeks, took 250 mg of metronidazole orally . Micropipettes were used to collect 20 microliters of serum and 4 to 5 microliters of gingival fluid hourly for 8 hours, and at the 12th and 18th hours . Samples were assayed with a high pressure liquid chromatograph . Mean drug levels in serum closely matched those reported by Stephen et al . (Br Dent J 7: 313, 1966) with polography . Mean serum drug levels peaked at 6.09 micrograms/ml at the 2nd hour, and mean gingival crevicular fluid drug levels peaked at 3.62 micrograms/ml at the 2nd and 7th hours . The drug was detectable in both fluids for up to 18 hours . Mean serum concentrations remained greater than mean gingival fluid concentrations at all time intervals, though the differences were not significant (P less than 0.05) as determined by a Hoteling's T2 test . Using reported minimal inhibitory concentration values of metronidazole for various periodontopathogens, it was concluded that a single oral dose of metronidazole will deliver potentially inhibitory levels of the drug to the periodontium in serum and in gingival crevicular fluid.

Eur J Clin Microbiol, 1986 Feb, 5(1), 18 - 22
In vitro activity of the aryl-fluoroquinolones A-56619 and A-56620 and evaluation of disk susceptibility tests; Barry AL et al.; 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.

Antimicrob Agents Chemother, 1986 Feb, 29(2), 216 - 24
High-level amikacin resistance in Escherichia coli due to phosphorylation and impaired aminoglycoside uptake; Perlin MH et al.; Plasmid pMP1-1 in Escherichia coli L-0 encodes aminoglycoside (AG) 3'-phosphotransferase II {APH(3')-II} . This enzyme modifies and confers high-level resistance to kanamycin . Although amikacin is a substrate for APH(3')-II, strain L-0(pMP1-1) is susceptible to amikacin . Plasmid pMP1-2 is a spontaneous mutant of pMP1-1 which determines increased APH(3')-II activity for amikacin, apparently as a result of an increase in the copy number of the plasmid . From amikacin-susceptible, gentamicin-susceptible transformants and transconjugants that bear the APH(3')-II gene on plasmid pMP1-1 or pMP1-2 or cloned into multicopy plasmid pBR322, we selected spontaneous mutants at concentrations of amikacin or gentamicin that were two to four times higher than the MICs of these antibiotics . In each case, whether they were selected by using amikacin or gentamicin, the mutants exhibited modest (two- to eightfold) increases in the MIC of gentamicin and major (64- to 128-fold) increases in the MIC of amikacin . Using these laboratory strains of E . coli, we examined the effects on AG susceptibility of the interaction of AG-modifying enzyme activity and generalized AG uptake . Increasing the level of activity of an AG phosphotransferase in these strains lowered their susceptibility to AGs which were substrates for which the enzyme had low Kms . However, an increase in AG-modifying activity alone did not result in large increases in the MICs for poor substrates of the enzyme . In strains which lacked AG-modifying enzymes, a decrease in the rate of AG uptake increased the MICs modestly for a broad spectrum of AGs . When a strain bore the phosphotransferase, a decrease in generalized AG uptake could raise the MIC further, not only for low-Km substrates, but even for AG substrates for which the enzyme had high Kms . Thus, increased modifying activity, together with a diminished rate of uptake, could produce even higher MICs for poor AG substrates.

Eur J Clin Pharmacol, 1986, 31(4), 479 - 83
Pharmacokinetics of intravenous and intraperitoneal ceftriaxone in chronic ambulatory peritoneal dialysis; Albin H et al.; The kinetics of ceftriaxone was investigated in 8 patients without infection, who were receiving continuous ambulatory peritoneal dialysis (CAPD) . Ceftriaxone 1 g was injected i.v . and 1 g was given intraperitoneally in the CAPD fluid during a 4-h dwell time . Ceftriaxone was assayed by HPLC . After intravenous administration, the kinetic parameters of ceftriaxone were: plasma t1/2, 12.3 h, total plasma clearance, 14.0 ml/min, volume of distribution at steady state 0.18 l/kg, and peritoneal clearance 0.59 ml/min . Over 72 hours only 5.5% of the dose was eliminated by the peritoneal route . After intraperitoneal administration, ceftriaxone rapidly appeared in serum; the absorption t1/2 was 1.1 h and the mean peak concentration was 38.8 micrograms/ml . The absorption of ceftriaxone from the peritoneal space was 39% . A single 1.0 g IP dose led to serum and dialysate concentrations of ceftriaxone above the minimum inhibitory concentration for susceptible pathogens for 24 hours.

J Emerg Med, 1986, 4(4), 311 - 6
The Bhopal tragedy--what has Swedish disaster medicine planning learned from it?
Lorin HG, Kulling PE.
On December 3, 1984, a leak of methylisocyanate (MIC) from a chemical plant in Bhopal, India, affected 150,000 to 200,000 people . More than 10,000 people were severely injured and approximately 2,500 died . In this article a survey of symptoms, treatment, and rescue work is given . On the basis of this, we discuss ways to help reduce the effects of a major release of an irritant gas . People living in the vicinity of potential health hazards need information on how to behave in case of accidents . Rescue workers and medical personnel must be trained to operate under "toxic conditions." There must be planning for treatment of thousands of patients at the same time, a circumstance that will often require temporary "satellite hospitals" to be opened . As symptoms and injuries are of the same kind, even if the magnitude and the effect may differ, treatment can, in many ways, be standardized . Therefore members of the health care team, irrespective of their daily different specialty fields, can work with the most urgent missions.

Eur J Clin Pharmacol, 1986, 31(1), 79 - 83
Pharmacokinetics of amikacin in cystic fibrosis: a study of bronchial diffusion; Autret E et al.; 36 pharmacokinetic studies of amikacin were performed to evaluate the bronchial diffusion of amikacin in 9 children with cystic fibrosis, 3 to 15 years old . Amikacin was administered i.v . according to a variable dosage regimen . Four children without cystic fibrosis were enrolled as controls . The mean half life was 1.1, the volume of distribution averaged 0.26 l/kg, and the mean plasma clearance was 131 ml/min/1.73 m2, which no differed from that of the controls . The mean peak plasma concentration was always above the MIC but its level depended on the unit dose: 18.5 mg/l, 25,95 mg/l and 31,46 mg/l for doses of 5, 7.5 and 12.5 mg/kg, respectively . Between consecutive amikacin infusions, the plasma level was above the MIC for 21% and 46% of the time after the 5 and 7.5 mg/kg doses . The maximum concentration in sputum between H1 and H2 was always below the MIC, except after 15 mg/kg . The ratio AUC sputum/AUC plasma was between 0.028 and 0.61, and it increased from the beginning to the end of the course of treatment . No side effects were observed on hearing, or vestibular and renal function . The results are used to suggest more appropriate dosing regimens.

Clin Exp Immunol, 1986 Jan, 63(1), 80 - 6
Association between thyroid microsomal antibodies of subclass IgG-1 and hypothyroidism in autoimmune postpartum thyroiditis; Jansson R et al.; The potential role of thyroid microsomal (Mic) antibodies in the development of postpartum hypothyroidism was investigated in 34 euthyroid women, whose sera were found to contain Mic antibodies in pregnancy . Additional serum samples were obtained 2 . 5 and 10-12 months after delivery and analysed for IgG class and IgG subclass levels of Mic antibodies by ELISA techniques . Characteristically, Mic antibodies decreased from early pregnancy to 2 months postpartum, increased two-fold 5 months postpartum and had returned 10-12 months postpartum to the early pregnancy level . Mic antibodies were predominantly subclass IgG-1 or IgG-4 with only minor contributions from IgG-2 and IgG-3 . In each individual the percentage contribution made by each IgG subclass to Mic antibody was essentially similar in early pregnancy and the postpartum period despite changes in total IgG class Mic antibody . During the year following delivery, thyrotoxicosis alone (Graves' disease) developed in 5 women . In the remaining 29 patients the absolute levels of Mic antibodies of IgG-4 subclass were similar 5 months postpartum in women with maximal serum thyrotropin (TSH) greater than 20 mU/1 (mean optical density in ELISA +/- s.d.; 0.84 +/- 0.538; n = 13) and in women with maximal TSH less than 10 mU/l (0.69 +/- 0.457; n = 16) . In contrast, significantly higher values were observed for Mic antibody of IgG-1 subclass in patients with TSH greater than 20 mU/l (1.14 +/- 0.440) compared with women with maximal TSH less than 10 mU/l (0.65 +/- 0.289) (P less than 0.001 by t-test for groups) . These results imply that the magnitude of Mic antibody levels of subclass IgG-1 but not IgG-4 is associated with the development of postpartum hypothyroidism and possibly with tissue destruction in autoimmune thyroid disease in general.

Indian J Lepr, 1986 Jan-Mar, 58(1), 19 - 28
Armadillo as a model for studying chemotherapy of leprosy: preliminary studies; Dhople AM; In order to determine the suitability of the armadillos as a model of human leprosy for chemotherapeutic studies, especially in evaluating newer anti-leprosy drugs, uninfected Armadillos were used to study the metabolic disposition of DDS . Serum DDS levels ranged from 500 ng/ml at 3 hours to 13 ng/ml at 96 hours after intravenous administration of DDS (1 mg/kg) . In an ad libitum feeding trial of DDS it was found that the level of serum DDS varied according to the dose of DDS, and even at a dose of 0.0001%, the animals maintained MIC of DDS against M . leprae . Finally, it was demonstrated that armadillos acetylate DDS to MADDS and 7-9% of DDS is acetylated by armadillos.

Antimicrob Agents Chemother, 1986 Jan, 29(1), 179 - 81
In vitro activity of antibiotics alone and in combination against Actinobacillus actinomycetemcomitans; Yogev R et al.; The MICs for 90% of the organisms tested (MIC90S) of 11 antibiotics against 24 clinical isolates of Actinobacillus actinomycetemcomitans were determined by the MIC 2000 system . The lowest MIC90S (16 micrograms/ml) were observed with ceftriaxone and rifampin . The next lowest MIC90S were found with cephapirin, tetracycline, and chloramphenicol (3.12 micrograms/ml) . The MIC90S of penicillin, ampicillin, ticarcillin, piperacillin, and amikacin were each greater than or equal to 12.5 micrograms/ml . Antibiotic synergy was studied by the killing curve method and was defined as a greater than or equal to 2 log10 reduction in CFU when two antibiotics were used in combination at one-fourth the MBC for each compared with the effect of each antibiotic alone at one-half the MBC . Synergism between rifampin and penicillin, cephapirin, or ceftriaxone was tested for with 12 A . actinomycetemcomitans strains . In 7 of 37 instances, synergism was demonstrated for the combinations rifampin plus ceftriaxone (n = 3) or rifampin plus penicillin (n = 4); in 9 instances, an additive effect was noted, and impaired killing with drug combinations compared with the effect of a single antibiotic was suggested in 4 strains . The majority of strains were indifferent to the combinations . Similarly, variable results were observed when the combination of trimethoprim and cephapirin was tested against eight A . actinomycetemcomitans strains . Our data suggest that rifampin and cephapirin are the most active of the 11 antibiotics studied against A . actinomycetemcomitans . In addition, in vitro synergism between rifampin and other antibiotics or between trimethoprim and cephapirin was not consistently demonstrable.

Trans R Soc Trop Med Hyg, 1986, 80(2), 201 - 3
Response of Plasmodium falciparum to dihydrofolate reductase inhibitors in Malindi, Kenya; Spencer HC et al.; The response of Plasmodium falciparum isolates to dihydrofolate reductase inhibitors (DHFRI) was examined in Malindi, Kenya . All 20 infected children treated with pyrimethamine/sulphadoxine responded . In contrast, after treatment with pyrimethamine, parasitaemia in 9 of 14 infections failed to clear or recrudesced during the seven-day follow-up . In a 48-hour in vitro test, five of six isolates resistant to pyrimethamine in vivo had a minimal inhibitory concentration (MIC) to pyrimethamine greater than or equal to 300 nmoles/1 compared with less than or equal to 100 nmoles/1 for the four sensitive isolates; four isolates did not grow . MIC to M-B 35769, an experimental DHFRI structurally similar to pyrimethamine were the same (six isolates) or 10-fold lower (three isolates) . In the laboratory four of five isolates adapted to in vitro culture had the same MICs as in the field while one isolate became less responsive to both drugs . Cycloguanil (the active metabolite of proguanil) was more active in vitro in the laboratory than pyrimethamine or M-B 35769.

Microbios, 1986, 47(191), 117 - 26
A nystatin-resistant mutant of Saccharomyces cerevisiae: isolation and characterization by electron microscopy and chemical analysis of whole cells, cell-walls and protoplasts; Beezer AE et al.; A mutant of Saccharomyces cerevisiae NCYC 239 with a high minimum inhibitory concentration (35 micrograms ml-1) for nystatin, compared to that of the parent strain (2 micrograms ml-1), was derived by a series of subcultures in media containing increasing antibiotic concentrations . In the absence of nystatin, the growth rate of the mutant was significantly lower than the parent strain, although mean cell-size and size-distribution were similar . No differences between strains were detectable by electron microscopy . Analysis of whole cells showed the total sterol present and the ratio of ergosterol:24(28)dehydroergosterol was similar . However, there were marked differences in amino acid content and chain-length of fatty acids in the cell wall, and protoplasts from resistant cells had decreased amounts of unsaturated fatty acids . It is suggested that alterations in cell wall components in the mutant may be directly linked to the mechanism of nystatin resistance.

Scand J Infect Dis, 1986, 18(5), 439 - 45
Effect of mecillinam on Escherichia coli growth curves when given alone and associated with ampicillin; Yourassowsky E et al.; The effects on growth curves of strains of Escherichia coli by mecillinam, ampicillin, and combinations of the two antibiotics were investigated using the Abbott-MS-2 system . Maximal increase in optical density in the residual growth phase was found to be concentration dependent for ampicillin and nearly concentration independent for mecillinam . The addition of ampicillin potentiated the effect on mecillinam . However, when mecillinam concentrations were more than 100 times the MIC or when ampicillin was added with a lag time, the growth curves for combinations of mecillinam plus ampicillin showed a mecillinam profile . Killing curves confirmed that the combination of ampicillin and mecillinam acts strongly synergistic and exerts a much faster bactericidal effect.

Boll Ist Sieroter Milan, 1986, 65(1), 22 - 31
{Evaluation of the in vitro activity of aztreonam on 1990 gram-negative bacterial strains recently isolated in Campania hospitals}; Covelli I et al.; The in vitro activity of aztreonam, leader of a new class of antibiotics, the monobactams, has been investigated . The effectiveness of the new molecule on 1990 strains of Gram-negative clinical isolates has been compared to that of some other drugs widely utilized for the treatment of nosocomial infections . Aztreonam has shown the highest activity against all the tested strains, with a geometrical mean of MICs (MG) of 0.37 and a MIC 90 of 8 micrograms/ml.

Biol Res Pregnancy Perinatol, 1986, 7(1), 20 - 2
Mycotic vaginitis in pregnancy: a double evaluation of the susceptibility to the main antimycotic drugs of isolated species; Guaschino S et al.; The authors examined 160 non-selected patients between the 28th and 40th weeks of gestational age with mycotic vaginitis . The chemosusceptibility of the isolated yeast to the main antimycotic drugs was evaluated through the Kirby-Bauer method as well as the determination of MIC . The antimycotic drugs tested were Nystatin, Miconazole, Ketoconazole, Clotrimazole, Amphotericin B, Econazole and 5-Fluorocytosine . The obtained data indicate a lacking effectiveness of Clotrimazole in contrast with the high percentage of therapeutical success reported in the literature . Better results were found with Econazole and the other antimycotic drugs tested . Nystatin is the most effective drug "in vitro" . The authors furthermore highlight the utility of MIC determination, above all in the cases of recurrent vaginitis and when systemic therapy is undertaken.

J Fr Ophtalmol, 1986, 9(4), 317 - 21
{Intracameral penetration of pefloxacine in man}; Bron A et al.; Authors have studied the intraocular penetration of a new antibiotic, pefloxacin in 35 patients (35 eyes) . This study emphasizes the three main qualities of this recent quinolone in ophthalmology: wide spectrum adequate for the most pathogens commonly found in endophthalmitis . Very large penetration in the aqueous humour flow with an average level of 0.95 mu/ml, which is over the minimal inhibitory concentration for many bacterial infections and is equal to 25% of average serum level.

Drugs, 1986, 31 Suppl 3, 23 - 7
Analysis of the relationship between ampicillin resistance and beta-lactamase production in Branhamella catarrhalis; Stobberingh EE et al.; 23 strains of Branhamella catarrhalis, mainly isolated from patients with acute exacerbations of chronic bronchitis, were studied . The strains were selected on the basis of a positive beta-lactamase reaction using the cefinase disc or the nitrocefin method . No bands were visible by isoelectric focusing of the crude enzyme extracts of strains showing a weak positive reaction with the cefinase method . In the 15 remaining strains, at least 6 different isoelectric focusing patterns could be detected . Four strains showed a pattern similar to that of the Ravasio strain, the most common type in a previous study . The most prevalent type in this study, present in 5 strains, demonstrated an isoelectric focusing pattern quite different from those described so far: a main band at pI 5.28 and 2 minor bands at pI 5.71 and 6.37 . Two beta-lactamase-positive, but ampicillin-sensitive strains (MIC = 0.064 mg/L) showed different isoelectric focusing patterns, pI = 4.93 and 5.43, respectively, but similar substrate profiles.

Acta Derm Venereol Suppl (Stockh), 1986, 121, 131 - 8
In vitro assessment of antifungal drug resistance; Holmberg K; Several studies have documented the variability in the susceptibility pattern of fungi to antifungal drugs, and fungi possess resistance determinants to negate the effects of antifungal agents . In vitro assessment of both resistance and susceptibility are measured by suitable concentration endpoints of the antifungal drug, the minimal inhibitory concentration (MIC) . MICs serve as the main parameter to define the fungistatic action on fungi growing in culture . For the antifungals used for treatment of local mycoses, the limit between a MIC value indicating susceptibility and one indicating resistance is usually determined empirically on the basis of the correlation between MIC values, and either positive or negative response to chemotherapy . The principles of susceptibility testing of fungi are essentially the same as those for bacteria . However, testing with fungi must deal with the fact that interpretation of the results is complicated by inherent differences in fungal morphology, growth rate, and optimal culture conditions . Several factors could adversely affect the test results and must be considered in the design of susceptibility testing of fungi . It is obvious when the present data on fungal susceptibility testing are reviewed that much more work on standardization of techniques and interpretation of results is necessary . This presentation will focus on the in vitro susceptibility testing for determining primary and secondary drug resistance of griseofulvin and azole antifungal agents, and the correlation between the activities of these antifungals in vitro and in vivo.

Jpn J Antibiot, 1986 Jan, 39(1), 79 - 86
{A study on the disc sensitivity for ceftizoxime}; Kanazawa Y et al.; Susceptibilities of 175 strains of 27 bacterial species to ceftizoxime (CZX) were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zones by the single-disc method under the experimental conditions established by Kanazawa . The experiments demonstrated a significant correlation between MIC by the dilution method and diameter of inhibition zone in each of the conventional assay of over-night (about 16 hours) incubation, the delayed assay (about 24 hours incubation), and the rapid assay (about 3 approximately 4 or 5 approximately 6 hours incubation), thus confirming the applicability of the single-disc assay for CZX . Analysis of the data obtained by using CZX disc containing 30 micrograms revealed the primary regression equation to be: D (diameter, mm) = 27.3-9.7 log MIC (micrograms/ml) in conventional assay, D = 32.5-12.3 log MIC (micrograms/ml) in delayed assay, D = 22.8-7.5 log MIC (micrograms/ml) in 5 approximately 6 hours rapid assay, and D = 17.9-5.1 log MIC (micrograms/ml) in 3 approximately 4 hours rapid assay, respectively . The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution test, as a reference for the experimental errors which may be involved in the estimation of MIC of CZX by the single-disc assay.

Infection, 1986, 14 Suppl 1, S16 - 9
{Criteria for the interpretation of sensitivity testing of ofloxacin with the agar diffusion test}; Grimm H; Regression analyses to determine the correlation of MIC and inhibition zone produced by ofloxacin disks were carried out using 300 freshly isolated cultures of infective organisms (20 strains each from 15 species) . It was found in pilot studies that the correlation becomes poorer with increasing disk loads . Disks containing 5 micrograms of ofloxacin were chosen for comparative studies using Mueller-Hinton agar and Kirby-Bauer, as well as DIN-58940 methods . Based on preliminary MIC breakpoints of 1 and 4 mg/l and on calculations from regression equations, the following zone interpretations using the Kirby-Bauer method are recommended: resistant = up to 12 mm, intermediate = 13 to 19 mm, susceptible = 20 mm or more . The respective values for the DIN method are: resistant = up to 14 mm, intermediate = 15 to 21 mm, susceptible = 22 mm or more . The results are similar to those obtained by us in previous studies with norfloxacin, enoxacin and ciprofloxacin.

Czech Med, 1986, 9(4), 191 - 5
Ceftriaxon in treatment of bacterial meningitis; Duniewicz M et al.; The authors tested cephalosporin antibiotic of the 3rd generation--Ceftriaxon--in treatment of bacterial meningitis . After studying the infiltration of the antibiotic into the cerebrospinal fluid in 13 patients with parotitic meningoencephalitis, the authors treated 15 patients with bacterial meningitis . Ceftriaxon has been applied in 100 mg/kg in two doses i.v . The research antibiotic levels in cerebrospinal fluid varied from 10 to 30% of sera levels and were much higher than MIC for pathogens isolated from liquor . The treatment effects were very good the dropping of temperature followed on the 3-4 day, the 5-6, day under 100/3 . The side effects showed a short time increasing of transaminases and diarrhoea . After completing the treatment normalisation occurred quickly . Other side effects have not occurred . The authors can state, Ceftriaxon in treatment of bacterial meningitis is a highly effective antibiotic.

Drugs, 1986, 31 Suppl 3, 64 - 9
Detection, distribution and inhibition of Branhamella catarrhalis beta-lactamases; Philippon A et al.; Beta-lactamase-producing isolates of Branhamella catarrhalis were first detected in France in 1977 . The frequency of beta-lactamase producers has increased, especially since 1980 . An agar iodometric test, a fast chromogenic test and an acidimetric test were used to assess the beta-lactamase-producing capabilities of 188 isolates of B . catarrhalis obtained mainly from sputum and the pharynx . Data from the first 2 procedures indicated positive beta-lactamase activity for all 49 strains of B . catarrhalis identified, but there were some discrepancies in the acidimetric test results . Evidence from a diffusion technique showed significant increases in the inhibition diameters surrounding filter discs impregnated with amoxycillin in the presence of clavulanic acid, or with ampicillin in the presence of sulbactam, compared with discs of the penicillins used alone . Two types of enzyme activity emerged from examination of isoelectric focusing patterns . Type I, having pI values of 5.35, 5.55 and 5.85, accounted for 87.2% of the enzyme-producing isolates . Type II, with pIs of 5.5, 5.9 and 6.25, occurred in 12.8% of isolates and appeared to be less widely distributed . The beta-lactamase inhibitors clavulanic acid and sulbactam in combination with benzylpenicillin produced potentiated effects, as demonstrated by significant reductions in MIC (33- and 44-fold decreases, respectively) . Higher concentrations of each inhibitor similarly affected the MICs of amoxycillin . A weak synergy occurred with cefoxitin, a beta-lactamase-resistant beta-lactam antibiotic, and the 2 beta-lactamase inhibitors . Because B . catarrhalis has been shown to be a beta-lactamase-producing pathogenic organism, the addition of enzyme inhibitors, such as clavulanic acid and sulbactam, to standard therapy may be beneficial.

Antiviral Res, 1986 Jan, 6(1), 57 - 65
Comparative efficacy of broad-spectrum antiviral agents as inhibitors of rotavirus replication in vitro; Kitaoka S et al.; Several nucleoside analogues which have previously been established as broad-spectrum antiviral agents, i.e . ribavirin, vidarabine, pyrazofurin, tubercidin, carbodine, (S)-9-(2,3-dihydroxypropyl)adenine {(S)-DHPA}, carbocyclic 3-deazaadenosine (C-c3 Ado), (RS)-3-adenine-9-yl-2-hydroxypropanoic acid {(RS)-AHPA} isobutyl ester and neplanocin A were compared for their potency and selectivity as inhibitors of human rotavirus (strains Wa, KUN and MO) replication in vitro . As the most efficacious inhibitors emerged (S)-DHPA, C-c3 Ado, (RS)-AHPA isobutyl ester and neplanocin A, with a minimum inhibitory concentration of 60, 1.4, 1.2 and 0.2 micrograms/ml, and a selectivity index of greater than 3, 70, 80 and greater than 20, respectively . As has been postulated for their antiviral action in general, these adenosine analogues probably owe their anti-rotavirus activity to inhibition of S-adenosylhomocysteine hydrolase, a key enzyme in regulating methylations including those that are required for the maturation of viral mRNA.

Hinyokika Kiyo, 1986 Jan, 32(1), 151 - 61
{Epidemiological and therapeutic studies of gonorrheal infection--clinical efficacy of sultamicillin}; Kumamoto Y et al.; We conducted an epidemiological study including analyses of background factors of 192 male and 13 female patients with gonorrheal infection in the Sapporo area and at the same time, investigated the therapeutic efficacy of sultamicillin, an ester linked prodrug of ampicillin and beta-lactamase inhibitor sulbactam in the treatment of these patients . The percentage of infections in Sapporo was rather high in the young generation, being as high as 13.5% in teen-age boys and 30.8% in teen-age girls, which were higher than the 6.1% and 6.3% of corresponding groups in Honshu island . The source of infections was so-called special public bath-ouse which accounted for about 31.8% of all cases which however, was lower than the 50% in Honshu island . By contrast, the percentage of their friends or so-called pick-up friends as a source of infection in Sapporo was as high as 46.9% which was significantly higher than the 19.9% in Honshu . Juveniles who had nonprostitutes of the other sex as a source of infection are a characteristic of the patients in Sapporo . The isolation rate of PPNG was 13.8% . The MIC (10(6) CFU/ml) of sultamicillin ranged from 0.05 to 0.39 micrograms/ml in beta-lactamase non-producing strains and from 0.20 to 1.56 micrograms/ml in beta-lactamase producing strains showing no trend of higher MIC against beta-lactamase producing strains . There was almost no difference in the efficacy of sultamicillin between a daily dose of 750 mg (2 tablets) and 1125 mg (3 tablets) nor in side effects . The eradication rate (efficacy rate) of gonococcus following a 3-day therapy was 96.2% (38.9% excellent cure rate) in male patients and 83.3% (8.3%) in female patients . In 31% of the male patients who underwent a 7-day therapy, residual serous secretion was found though some inaccuracy is involved in this data since dropouts were not counted . This suggests the need of concurrent therapy with other appropriate drugs in consideration of possible mixed infection involving Chlamydia trachomatis or other microorganisms.

Comp Biochem Physiol A, 1986, 85(1), 161 - 9
Characterization of insulin binding to bovine liver and mammary microsomes; Smith DH et al.; Bovine liver and mammary gland (MG) appear metabolically independent of insulin, yet the specificity and kinetics of 125I-insulin (125I-INS) binding to bovine liver and MG microsomes (MIC) indicate the presence of insulin receptors in MIC from both tissues . The insulin receptors from bovine liver (Kd = 7.6 X 10(-10) M) and MG (Kd = 9.6 X 10(-11) M) were similar to each other and to other insulin receptors in their binding affinities and pH optima . Perturbation of rat liver and bovine MG MIC by phospholipase or NaCl treatment increased 125I-INS binding to the membranes, suggesting exposure of cryptic insulin receptors . Different responses in 125I-INS binding to membrane perturbation suggest differences between rat and bovine membranes.

Jpn J Antibiot, 1985 Dec, 38(12), 3674 - 82
{Fundamental and clinical studies on aztreonam}; Hirabayashi K et al.; Aztreonam (AZT), a new monocyclic beta-lactam antibiotic, was studied on the transfer into intrapelvic tissues and on the clinical efficacy in the treatment of 19 cases of obstetrical and gynecological infections . The AZT levels were examined in the pelvic dead space exudate in 6 patients who received radical hysterectomy due to uterocervical cancer . The simulation curves for AZT were well performed after the decision of the pharmacokinetic parameters using the two-compartment model . Following 1-hour intravenous drip infusion of 1 g of AZT, the peak concentration of AZT in cubital venous blood was estimated 73.3 micrograms/ml at the end of infusion . The peak concentration of AZT in the pelvic dead exudate was estimated 18.6 micrograms/ml at 2.31 hours after infusion . Following intravenous 1-hour drip infusion of 1 g, the transferred level of AZT into uterine tissues was maintained at the effective concentration which means the excess level of the MIC against clinical isolates often observed in the field of obstetrics and gynecology . AZT was administered 2-4 g/day in 2 times a day by intravenous drip infusion for 60-90 minutes . The subjects were 19 patients with the following infections; pyometra (1), puerperal intrauterine infection (4), postoperative parametritis (4), pelvioperitonitis (2), purulent lymphocyst (1), acute salpingoophoritis (1), vaginal stump abscess (1), Douglas abscess (2), pelvioperitonitis + pyosalpinx (2), vulval abscess (1) . Clinical efficacy was; excellent in 2 cases, good in 11 cases and poor in 6 cases . No notable side effect or abnormal laboratory finding was noted.

Jpn J Antibiot, 1985 Dec, 38(12), 3660 - 5
{Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology}; Horii T et al.; Fundamental and clinical studies were performed on aztreonam (AZT), a new antibiotic with single beta-lactam ring, with the following results . Following intravenous drip infusion of 1 g, transfer of AZT to the internal genital organs was found to be good . Transfer of AZT to exudate of pelvic dead space was also good . AZT was given to 6 cases, who had gynecological or obstetrical infectious disease . AZT was effective in the 5 cases out of 6, although it showed high MIC against bacteria isolated from the effective cases . The above results demonstrated that AZT was a safe and effective drug.

Jpn J Antibiot, 1985 Dec, 38(12), 3591 - 8
{Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology}; Kamiishi H et al.; The following results were obtained through the fundamental and clinical studies of aztreonam (AZT), a new monobactam antibiotic, in obstetrics and gynecology . Satisfactory tissue penetration was not recognized in 3-5 hours after intravenous injection of 1 g . However, the concentration was more than MIC for the majority of aerobic Gram-negative bacteria in intravenous drip infusion of AZT 1 g and in intravenous injection and intravenous drip infusion of 2 g . There was no difference of serum concentration of AZT between uterine arterial blood and cubital venous blood . AZT was administered by intravenous drip infusion to 2 cases of puerperal endometritis, 2 cases (the same patient) of vaginal wall abscess, 1 case of postoperative lymphocele infection and 1 case of infected ovarian cyst suspected, and it was effective for all of them . Neither subjective/objective side effects nor abnormal laboratory findings were noted in any case.

Jpn J Antibiot, 1985 Dec, 38(12), 3471 - 6
{Clinical study on the penetration of latamoxef into the pulmonary tissue in surgery of the chest}; Seno N et al.; In the surgery of the chest, we are often experienced pulmonary infections, so it is considered that the grasping antibiotic levels in pulmonary tissue is very important because of the decision of antibiotic dose schedule against pulmonary infections . For this purpose, latamoxef (LMOX) at a dose of 2 g was intravenously administered to 14 cases with pulmonary cancer, 3 cases with pulmonary tuberculosis, 2 cases with pulmonary abscess and 1 case with bronchiectasis, totally 20 cases and the concentrations in serum, pulmonary tissue, bronchia and sputum were measured up to 6 hours and the results obtained were as follows; The average serum concentration of LMOX was 137.2 micrograms/ml at 1/2 hour and decreased gradually, fell to 20.3 micrograms/ml at 6 hours . The average levels of LMOX in normal alveolus of pulmonary tissue and in bronchia were 63% and 48% of the serum level, respectively . The average level of LMOX in inflammatory alveolus of pulmonary tissue was approximately 20% lower than the normal alveolus . The average level of LMOX in sputum increased gradually and appeared 4.6 micrograms/ml at 6 hours . LMOX was shown a good results on the penetration into the pulmonary tissue and its level almost exceeded the minimal inhibitory concentration against clinical isolates from sputum of respiratory tract infections.

Chemioterapia, 1985 Dec, 4(6), 431 - 3
Siccanin: a new antifungal antibiotic with antidermatophytic properties . In vitro studies; Bellotti MG et al.; The in vitro antifungal properties of the antibiotic siccanin were determined by the minimal inhibitory concentrations (MIC) values against 51 fungal strains (yeasts and filamentous fungi) . The comparison was made with econazole, clotrimazole, 5-fluorocytosine and griseofulvin . The results show the useful antidermatophytic activity of siccanin.

Ann Allergy, 1985 Dec, 55(6), 835 - 9
Effect of ipratropium bromide on repeated methacholine challenges; Giulekas D et al.; The purpose of this study was to trace the protective effect of ipratropium bromide (IB) during methacholine inhalation challenge (MIC) at the first and fourth hour after its administration . IB-inhaler contains 0.02 mg IB in each puff and it was used in the usual dosage of two puffs (0.04 mg) . In 20 asthmatic patients, the dose of methacholine caused a drop in FEV1 of 20% (PD20-FEV1) . It was concluded that IB protected patients significantly one hour after its administration and showed a significant bronchodilating effect in comparison to placebo . IB protected 19 of the 20 patients one hour after administration during MIC while placebo protected none . IB protected 13 of the 20 patients, after the second PD20-FEV1 with methacholine, four hours after its administration.

Br J Oral Maxillofac Surg, 1985 Dec, 23(6), 428 - 34
Antibiotic treatment of cervicofacial actinomycosis for patients allergic to penicillin: a clinical and in vitro study; Martin MV; The minimum inhibitory concentrations for erythromycin, clindamycin, lincomycin, tetracycline and minocycline have been determined for 92 clinical and three culture collection isolates of Actinomyces . From a consideration of MIC values and expected serum levels from oral therapy, minocycline was the drug of choice for the treatment of actinomycosis in patients allergic to penicillin . The serum levels of six patients allergic to penicillin, treated with oral minocycline 1 g/day were monitored and found to exceed the MIC for the Actinomyces species responsible for the condition . In all six Actinomycosis cases resolution was achieved in 8-16 weeks of oral minocycline therapy with no recrudescence for 1 year.

J Pharm Pharmacol, 1985 Dec, 37(12), 878 - 83
The sustained release of pyrimethamine base or pyrimethamine pamoate from a biodegradable injectable depot preparation in mice; Coleman MD et al.; The pharmacokinetics and mass fate in mice, of pyrimethamine (425 mg kg-1 s.o.) administered subcutaneously either as the base (BASE) or the pamoate salt (PAM) in an injectable oil mixture (benzyl benzoate-peanut oil 50:50 v/v) have been evaluated . Maximum measured plasma pyrimethamine levels after BASE were attained within 24 h, and were twice as high as after PAM . 25% of animals dosed with BASE died; among the survivors plasma drug levels fell rapidly below the minimum inhibitory concentration (MIC) for Plasmodium berghei (100-200 ng ml-1) by 5 weeks . In contrast, no mice dosed with PAM died and plasma levels were sustained above the MIC for 13 weeks, drugs still being detectable in plasma after four months . Overall, there was no significant difference between areas under the curve from zero time to the time of the final sampling of pyrimethamine following PAM or BASE . The rapid initial elimination of 14C-radioactivity (2.64 +/- 0.47% dose day-1 over 4 weeks) seen after dosage with {14C}BASE reflected the plasma disposition of pyrimethamine in the mice dosed with BASE . 90% of the excreted 14C was eliminated by one month by which time less than 1% (0.03 +/- 0.02%) of the {14C}BASE was recovered from the injection site . Both BASE and {14C}BASE studies suggest that exhaustion of this preparation occurred by 7 weeks . Excretion of 14C-radioactivity after {14C}PAM was gradual and sustained with a low mean daily rate, that was maintained throughout the study i.e . 1.21 +/- 0.17% day-1 (4 weeks), 0.88 +/- 0.28% day-1 (8 weeks), 0.5 +/- 0.31% day-1 (12 weeks), 0.42 +/- 0.27% day-1 (16 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1985 Dec, 28(6), 745 - 50
In vitro and in vivo antipicornavirus activity of some phenoxypyridinecarbonitriles; Kenny MT et al.; Nineteen phenoxypyridinecarbonitriles were initially evaluated for their in vitro activity against rhinoviruses (RV) 1A, 2, and 64 and coxsackievirus (Cox) A21 and for their oral prophylactic and therapeutic activity in Swiss albino mice challenged with Cox A21 . On the basis of the results of these studies, one compound, 6-(3,4-dichlorophenoxy)-3-(ethylthio)-2-pyridinecarbonitrile, was selected for further evaluation . Expanded in vitro spectrum of activity studies showed that the MIC causing a 50% reduction in viral cytopathic effect in infected cultures (MIC50) was 3.0 micrograms/ml or less against 11 of 20 RV serotypes tested . The compound was only moderately active (MIC50, 5 to 7 micrograms/ml) against four of the RV serotypes evaluated, while RV 4, 5, 8, 13 and Hank's were relatively resistant to compound inhibition . Of the nine enteroviruses studied, only Cox A21, echovirus 12, poliovirus 2, and enterovirus 70 were inhibited at compound concentrations of less than 2.0 micrograms/ml . The compound provided significant protection to mice infected with a normally lethal dose of Cox A21 when administered in a single oral dose of 150 mg/kg (P less than 0.01) and during a regimen of continuous oral doses of 37.5 mg/kg per day (P less than 0.001) . Mechanism of action studies indicated that the compound inhibited picornavirus uncoating or some earlier virus-host cell-associated event.

Jpn J Antibiot, 1985 Nov, 38(11), 3285 - 93
{Clinical evaluation of aztreonam in children}; Ito S et al.; Clinical usage of aztreonam (AZT), a newly synthesized antibiotic which belongs to monobactam, was evaluated for its efficacy and safety in 22 patients aged from 1 month-old to 13 year-5 month-old with bacterial infections and the following results were obtained . AZT was administered to 4 patients with pyelonephritis and 10 patients with tonsillitis at a daily dosage of 40.4-120.9 mg/kg and to 5 patients with clinical sepsis associated with agranulocytosis caused by intensive antileukemic therapy at a daily dosage of 142.4-171.4 mg/kg, divided into 3 or 4, by intravenous injection or by 30 minutes drip infusion . The clinical results of these 19 evaluable patients were as follows: excellent; 10 cases, good; 5 cases, fair; 2 cases, poor; 2 cases . The over all efficacy rate was 78.9% and that of pyelonephritis and tonsillitis was 100.0% . No clinical side effects were observed in any 23 patients, including a patient who proved to be suffering from Mycoplasma pneumoniae infection, and no abnormal laboratory findings caused by AZT was noticed . The MICs of AZT against 9 strains isolated from patients with pyelonephritis and those with tonsillitis were as follows: MICs against all of 3 strains of K . pneumoniae were less than 0.05 microgram/ml . MICs against 2 out of 4 strains of H . influenzae were less than 0.05 microgram/ml and those of the remaining 2 strains were 0.10 microgram/ml . MIC against 1 strain of S . aureus was 1.56 microgram/ml . MIC against 1 strain of S . epidermidis was more than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Int Ophthalmol, 1985 Nov, 8(4), 193 - 8
Effects of selected repeated intravitreal chemotherapeutic agents; Vernot J et al.; The toxic effects of repeated intravitreal injections of selected chemotherapeutic agents were studied in female albino rabbits . Three groups of eyes participated in each therapeutic regimen . Agents studied were doxorubicin (dox), 3 and 5 micrograms; 5-fluorouracil (5-FU), 0.375 and 1.0 mg; bleomycin (bleo), 15 micrograms; thiotepa (thio), 12 micrograms; etoposide (VP-16), 150 micrograms; and methotrexate (MTX), 600 mic . Toxicity was evaluated using electroretinography (ERG) in 66% and histopathology in 100% of eyes 5 weeks following the initial injection and at least 2 weeks after the final injection of each series . Eyes receiving 2 doses of dox 3 micrograms showed no toxicity . Eyes receiving 3 or more doses of dox 3 micrograms and those treated with 2 or more doses of dox 5 demonstrated toxicity proportional to the number of doses received . Eyes treated with 5-FU 0.375 or 1.0 mg showed no toxic reaction . Successive intravitreal injections of 5-FU, 0.375 mg and dox 5 micrograms, and 5-FU, dox, and bleo produced no toxicity . Eyes treated with successive intravitreal injections of 5-FU, dox, bleo, and thio displayed decreased ERG response . The addition of VP-16 and MTX resulted in further loss of ERG response and more severe histologic retinal changes.

Hinyokika Kiyo, 1985 Nov, 31(11), 2090 - 104
{Epidemiologic and therapeutic study on gonorrheal infections--one shot therapy by aztreonam}; Kumamoto Y et al.; A clinical study of a new monocyclic beta-lactam antibiotic, AZTREONAM (hereafter referred to as AZT) for gonorrheal infections as well as epidemiologic study of gonorrheal infections were made Epidemiology: There was a reflection of the increasing sexual activity of the younger generation; both male and female patients in their twenties were most frequent (male 49.5%, female 43.7%) and the percent of teen age patients was 15.1% (male) and 34.4% (female) . Forty two strains (17.2%) out of 244 clinically isolated gonococci were PPNG . Residue of serious secretion was observed in a little less than 20% suggesting a complication by Chlamydia trachomatis . Clinical Result: One shot (1-2 g) therapy by AZT was given to 244 gonorrheal infection cases (212 urethritis cases of males . 32 cervicitis cases of females) with the following highly effective rate . Although beta-lactamase producing MIC of AZT at 10(6) CFU/ml showed a peak of 0.025 microgram/ml and ranged between less than 0.0125 microgram/ml to 0.2 microgram/ml . The time required for the elimination of gonococci was studied by the administration of 1 g and 2 g AZT . Gonococci became extinct in 1-8 hours or 4-4.5 hours on average . The difference between n 1 g and 2 g was scarcely observed . Clinical effect of 1 g one shot and 2 g one shot AZT was examined on the 3rd treatment day for 244 male and females cases . The effective rate was high; 90.7% by 1 g, 97.1% by 2 g for male urethritis, 100% by 1 g also by 2 g for female cervicitis . This therapeutic efficacy was kept even in PPNG, isolated cases . There were two side effects (0.8%), one case each of numbness and, redness and swelling of both hands, out of 244 cases, but both of them were minor ones without clinical complication.

J Clin Microbiol, 1985 Nov, 22(5), 735 - 9
Clinical laboratory studies of disinfection with Sporicidin; Isenberg HD; The clinical microbiology laboratory evaluation of disinfectants can serve as a guide for their application to reduce hospital-acquired infections . The use of Sporicidin, a glutaraldehyde-phenol formulation, was evaluated by the application of modified MIC and MBC determinations for standard organisms . In addition, the effect of this formulation on bacteria that may proliferate in water at ambient temperatures was studied . This investigation indicated that such studies can help the clinical microbiologist to guide the use of disinfectants and sterilants for the maintenance of a safe hospital environment.

Antimicrob Agents Chemother, 1985 Nov, 28(5), 700 - 2
Elimination of plasmids by new 4-quinolones; Weisser J et al.; Nalidixic acid and six of the new 4-quinolones eliminated F'lac and various native R plasmids from Escherichia coli at one half or one quarter the MIC . Four of eight plasmids tested were cured by all derivatives, with frequencies from 10 to 98% . Quinolones did not eliminate all plasmids that were cured by novobiocin, and vice versa.

Rev Infect Dis, 1985 Nov-Dec, 7 Suppl 4, S716 - 23
Pharmacokinetics and extravascular penetration of aztreonam in patients with abdominal sepsis; Winslade NE et al.; Patients with abdominal sepsis were enrolled in a clinical trial of aztreonam vs . tobramycin . All were given clindamycin concomitantly . The pharmacokinetics of aztreonam in 21 patients randomly assigned to receive treatment with aztreonam are reported . The mean age of these patients was 68 years; most had underlying disorders such as malnutrition and cardiac or pulmonary disease . Creatinine clearance (Clcr) ranged from 11.2 to 133.1 ml/min . The usual dose of aztreonam was 2.0 g every 8-12 hr . A single pharmacokinetic study was performed over one dosing interval after steady-state conditions were achieved . In approximately one-half of the patients, peritoneal fluid was collected during the interval between doses . Penetration of aztreonam, as expressed as the ratio of concentration in the peritoneal fluid to that in serum, was higher for aztreonam (0.95:1) than for tobramycin (0.46:1) . The ratio of the concentration in peritoneal fluid to the minimum inhibitory concentration (MIC) of the infecting bacteria was also higher for aztreonam . Serum pharmacokinetic data were analyzed by both two-compartment and moment analysis . For both the steady-state volume of distribution (Vdss) and total body clearance (TBC), the values determined by both methods were highly correlated (r = .96, .99, respectively) . Average values for Vdss and TBC were 0.28 liters/kg and 80 ml/min . TBC for aztreonam correlated strongly with CLcr and was described by the regression equation TBC = 1.1 (Clcr) + 1.6, r = .87, P less than .01.

J Infect Dis, 1985 Nov, 152(5), 1032 - 6
Effect of tetracycline on the attachment of K88+ enterotoxigenic Escherichia coli to porcine small-intestinal cells; Deneke CF et al.; The attachment of six strains of K88+, porcine pathogenic, enterotoxigenic Escherichia coli to isolated porcine intestinal mucosal cells was decreased following growth in the presence of concentrations of oxytetracycline below the minimal inhibitory concentration (MIC) . The decrease in binding by the wild-type strains was detected at concentrations of drug as low as 0.001 microgram/ml, which was greater than four orders of magnitude below the MIC . When drug resistance was induced in these six strains, there was still a decrease in binding when the bacteria were grown in the presence of tetracycline . This decrease was comparable to the decrease in binding capacity of the wild-type strains caused by growth in the presence of tetracycline . In contrast, when one strain (G1108E) was made tetracycline resistant by the introduction of the R16 plasmid, the antibiotic had less effect on the binding of this strain than on the wild-type strain; however, growth in the presence of antibiotic still decreased adhesion . Overall, oxytetracycline decreased the adhesion of wild-type, induced-resistant, and genetically resistant K88+ enterotoxigenic E . coli to porcine small-intestinal cells, and this effect occurred at antibiotic concentrations several orders of magnitude below the MIC.

J Clin Microbiol, 1985 Nov, 22(5), 786 - 8
Disk susceptibility of ofloxacin, a new carboxyquinolone; Mandell W et al.; Ofloxacin, a fluorinated carboxyquinolone, was tested against 485 clinical isolates, and the MICs and disk inhibitory zones were correlated . A critical zone of greater than or equal to 19 mm and an MIC of less than or equal to 2 micrograms/ml indicate susceptibility . An MIC of 4 micrograms/ml and a zone size of 16 to 18 mm is intermediate, and an MIC of greater than or equal to 8 micrograms/ml with a zone size of less than 15 mm indicates resistance . Alternatively, organisms inhibited by an MIC of less than or equal to 4 micrograms/ml with a critical zone diameter of greater than or equal to 15 mm could be considered susceptible . By either of these criteria, major errors in judging susceptibility or resistance are less than 1%.

J Clin Microbiol, 1985 Oct, 22(4), 688 - 90
Interpretive standards and quality control guidelines for cefpiramide disk susceptibility tests; Barry AL et al.; Disk susceptibility tests with 30- and 75-micrograms cefpiramide disks were evaluated with 614 bacterial isolates . Quality control parameters were also evaluated, and control limits for disk tests are recommended . Tests with 75-micrograms disks are recommended, with zone size standards of greater than or equal to 19 mm for susceptible (MIC, less than or equal to 32 micrograms/ml) and less than or equal to 15 mm for resistant (MIC, greater than or equal to 128 micrograms/ml).

Antimicrob Agents Chemother, 1985 Oct, 28(4), 570 - 5
Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods; Heifets LB et al.; A radiometric method to determine the MIC of ansamycin (LM427) for Mycobacterium avium complex clinical isolates has been developed . It is based on a comparison of the conventional growth curve determination and the radiometric detection of growth (growth index) in the same liquid medium (7H12 broth) . This new method requires less time and labor than does a conventional determination of MIC in liquid medium (CFU) . Other advantages of this method include relatively short periods of exposure of the drug to 37 degrees C and the composition of 7H12 broth, which has practically no substrates which could absorb or bind the drug . Thus, a more accurate estimation of the MIC in this medium can be expected than by the conventional agar dilution (proportion) method . The MICs of ansamycin appeared to be higher in agar plates than in 7H12 broth . More than 70% of the isolates had a broth-determined MIC one to three times lower than the average peak concentration of ansamycin achieved in sera of patients . The wide range of MICs suggests the importance of testing susceptibility in broth with many concentrations in addition to, or rather than in, agar plates with concentrations of 2.0 or 1.0 micrograms/ml only . Taking into account relatively low levels of ansamycin in sera of patients, it would be appropriate to compare the MICs with the levels in serum to make the outcome of chemotherapy more predictable.

Antibiot Med Biotekhnol, 1985 Oct, 30(10), 751 - 4
{Antibiotic sensitivity of an Escherichia coli strain used for preparing colibacterin}; Astanina LN et al.; Sensitivity of a E . coli strain and commercial colibacterins prepared with its use to 18 antibiotics was tested . The MIC was determined by the method of serial dilutions . It was shown that the strain and colibacterins were sensitive to 9 antibiotics and resistant to the others.

Jpn J Antibiot, 1985 Oct, 38(10), 2797 - 808
{In vitro susceptibilities of causative organisms isolated from patients with primary respiratory tract infections to BRL 25000 (clavulanic acid/amoxicillin)}; Deguchi K et al.; The in vitro susceptibilities of various causative organisms recently isolated from patients with primary respiratory tract infections to BRL 25000 (a formulation of amoxicillin, 2 parts, and potassium clavulanate, 1 part), amoxicillin (AMPC), cefaclor (CCL), cephalexin (CEX), cefadroxil (CDX) and cefroxadine (CXD) were determined . beta-Lactamase producing strains were detected by nitrocefin chromogenic method and PCG acidometric method . The frequency of isolation of beta-lactamase production in strains of S . aureus, H . influenzae, B . catarrhalis and K . pneumoniae was 92%, 18%, 36% and 98%, respectively . Against S . aureus strains with MIC values to AMPC of less than or equal to 100 micrograms/ml and CEX of less than or equal to 25 micrograms/ml BRL 25000 showed MIC values in the range 0.39-6.25 micrograms/ml with inocula of 10(6) CFU/ml, while BRL 25000 required 12.5-100 micrograms/ml of concentrations for inhibition of the strains with MIC values to AMPC of greater than 100 micrograms/ml and CEX of greater than or equal to 25 micrograms/ml . Against S . pyogenes and S . pneumoniae BRL 25000 showed MIC values in the range less than 0.024-0.10 micrograms/ml with inocula of 10(6) CFU/ml, which is much more active than CCL, CEX, CDX and CXD and slight less active than AMPC . Against H . influenzae and B . catarrhalis BRL 25000 showed MIC values in the range 0.20-6.25 micrograms/ml with inocula of 10(6) CFU/ml, which showed most potent activity among the agents tested . The activity of BRL 25000 against K . pneumoniae was approximately equal to that of CCL and superior to that of AMPC, CEX, CDX and CXD.

J Antibiot (Tokyo), 1985 Oct, 38(10), 1337 - 43
Potent antitumor antibiotic complex: PD 114,759, PD 115,028, PD 119,707, and PD 119,193; Tunac JB et al.; Four novel antitumor antibiotics (PD 114,759, PD 115,028, PD 119,707 and PD 119,193) are produced as a complex by a new species of Actinomadura . The proposed name for the culture is Actinomadura verrucosospora subsp . veractimyces ATCC 39363 . The antibiotics are extremely bioactive, with MIC values of less than 0.006 ng/ml against several bacteria and ID50 values of 0.003 approximately 0.107 ng/ml against L1210 leukemia cells in vitro . Antitumor activities vs . P388 leukemia in vivo were observed at doses of 0.313, 0.40, and 0.5 micrograms/kg (daily X 5) for PD 119,707, PD 115,028, and PD 114,759, respectively.

Antimicrob Agents Chemother, 1985 Oct, 28(4), 524 - 7
Evaluation of the in vitro bactericidal action of ciprofloxacin on cells of Escherichia coli in the logarithmic and stationary phases of growth; Zeiler HJ; Cells of Escherichia coli Neumann and E . coli KL16 were suspended in phosphate-buffered saline pH 7.4 and allowed to reach stationary growth conditions . Ciprofloxacin was added at different concentrations, and time-kill curves were constructed . It could be demonstrated that the number of viable cells was reduced quickly by several logs for E . coli Neumann, whereas a weak and slow killing effect was observed with E . coli KL16 . When ciprofloxacin or norfloxacin was added to logarithmically growing cultures of E . coli Neumann or E . coli KL16, no principal differences in the killing rate for the two strains could be observed . Ciprofloxacin, however, was more bactericidal than norfloxacin . It was also demonstrated that the bactericidal action of ciprofloxacin on cells in the stationary growth phase was better at pH 7.4 than at pH 8.6 . This dependence is different from that observed in MIC studies, in which the MIC were lower at pH 8.0 than at pH 7.2 . It was also found that the bactericidal action of ciprofloxacin or norfloxacin on cells of E . coli Neumann in the stationary phase of growth could not be reduced by the addition of chloramphenicol, whereas under conditions of logarithmic growth the rapid killing effect of ciprofloxacin was reduced in the presence of chloramphenicol.

J Antimicrob Chemother, 1985 Oct, 16(4), 527 - 30
In-vitro activity of ciprofloxacin against clinical isolates of mycobacteria resistant to antimycobacterial drugs; Marinis E et al.; The activity of ciprofloxacin against 42 clinical isolates of mycobacteria was studied in vitro by the 1% standard proportion method on Lowenstein-Jensen medium . Ciprofloxacin was found active against all strains of Mycobacterium tuberculosis sensitive to streptomycin, isoniazid, ethambutol and rifampicin . The MIC of ciprofloxacin was 3.2 mg/l . This concentration of ciprofloxacin was sufficient to inhibit almost all strains showing intermediate sensitivity or resistance to one or more of the above agents . The same phenomenon was also observed with the atypical isolates.

J Pharmacobiodyn, 1985 Sep, 8(9), 695 - 700
Kinetics of bactericidal activity of aminoglycosides during dynamic dilution; Nakamura Y et al.; The time courses for viable microorganism count after addition of aminoglycosides were investigated in exponentially decreasing concentrations in in vitro using a continuous flow culture system . When aminoglycosides were added to the incubation medium containing Escherichia coli, the growth rate began to decrease after a lag phase and recovered gradually after the concentration fell below its effective level . To simulate this time course, the following equation including the retardation function was proposed; (Formula: see text) where N is the number of viables, ko is the generation rate constant, kd is the dilution rate constant, Pc is the bactericidal coefficient per unit concentration characteristic to the individual antibiotic, kr is the reciprocal of the retardation time and Co is the initial concentration of the antibiotic . Pc and kr were calculated using the nonlinear least square method and the calculated time course agreed with the observed experimental data indicating the appropriateness of this equation . Pc has a negative relationship to the minimum inhibitory concentration for six aminoglycosides studied, kanamycin, amikacin, kanamycin B, tobramycin, dibekacin and habekacin . The values of kr ranged between 3.12 X 10(-2) to 6.40 X 10(-2) min-1 and are thought to correlate with the mechanism of antibiotic actions.

No To Shinkei, 1985 Aug, 37(8), 759 - 65
{The activating effect of MCI-2016 (bifemelane hydrochloride) on EEG in cats}; Egawa M et al.; In order to make clear the activating effect of MCI-2016 on EEG, power spectrum analysis was performed and the interaction in EEG between MCI-2016 and some drugs were studied in succinylcholine-immobilized cats . MCI-2016 at doses of 5 and 10 mg/kg iv produced apparent arousal pattern in cortical EEG characterized by low amplitude fast wave, and evoked the right-shift in power spectrum . In the case of meclofenoxate at doses of 20 and 40 mg/kg iv, the shifts in power spectra were similar to that of MCI-2016, very slight changes were observed by Ca-hopantenate at a dose of 200 mg/kg iv and typical left-shift was introduced by imipramine at a dose of 2 mg/kg iv . MCI-2016 tended to suppress the SWS state induced by alpha-methyl-p-tyrosine and scopolamine at a dose of 350 mg/kg ip and 0.015 mg/kg iv, respectively . Subsequently, the duration of arousal state in EEG induced by physostigmine at a dose of 0.01 mg/kg iv was enhanced by MCI-2016 at a dose of 1.5 mg/kg iv whose injection does not produce any arousal pattern in EEG . The activating effect of MIC-2016 on EEG was indicated quantitatively and it is suggested that the cholinergic mechanism and the catecholaminergic mechanism would be involved in the EEG activating effect of MCI-2016.

J Antimicrob Chemother, 1985 Aug, 16(2), 199 - 204
Effects of tetracyclines on experimental Legionella pneumophila infection in guinea-pigs; Yoshida S et al.; The activities of tetracycline, doxycycline and minocycline against Legionella pneumophila strain Philadelphia-1 were compared in vitro, in peritoneal macrophages and in-vivo experiments in guinea-pigs . Minocycline was the most effective in in-vitro minimum inhibitory concentration assays . In the assay measuring inhibitory effects of drugs on intracellular bacterial multiplication, minocycline and doxycycline were equally effective and tetracycline was the least effective of the three . In-vivo experiments were carried out using guinea-pigs infected intraperitoneally . From the analysis of cumulative survival rates, only minocycline had statistically significant effects . Doxycycline, however, did significantly prolong the infected animals' survival days . These data lend some support to the case reports showing that tetracycline derivatives are effective in the treatment of Legionnaires' disease.

Clin Pharmacol Ther, 1985 Aug, 38(2), 150 - 6
Moxalactam epimer disposition in patients undergoing continuous ambulatory peritoneal dialysis; Morse G et al.; The kinetics of the epimers of moxalactam (R-MOX, S-MOX) were investigated in patients without infections who were receiving continuous ambulatory peritoneal dialysis after both intravenous and intraperitoneal injections of moxalactam . R-MOX and S-MOX were well absorbed from the peritoneal cavity, with mean systemic availability of 0.71 +/- 0.18 and 0.79 +/- 0.18, respectively . After intravenous MOX, serum clearance was 10.2 +/- 3.4 (R-MOX) and 10.9 +/- 3.2 (S-MOX) ml/hr/kg . Net time-averaged peritoneal dialysis clearance of both epimers was minimal, about 10% of serum clearance . Serum and dialysate MOX concentrations were above the minimum inhibitory concentrations for susceptible bacteria for 24 hours after a 2.0 or 1.0 gm intravenous or intraperitoneal dose . Gastrointestinal side effects occurred after a 2.0 gm dose (both intravenous and intraperitoneal) but not after a 1.0 gm dose . There were no significant differences in the kinetics of R-MOX and S-MOX . A single 1.0 gm ip dose leads to serum and dialysate MOX concentrations above the minimum inhibitory concentration for susceptible pathogens for 24 hours.

Antibiot Med Biotekhnol, 1985 Aug, 30(8), 592 - 5
{Action of biologically active compounds on kanamycin inactivation by resistant microorganisms}; Kutsenko NN et al.; Products of kanamycin inactivation were identified chromatographically and radiometrically in E . coli 154, K . aerogenes 600 and P . vulgaris 7470 . It was shown that the efficiency of kanamycin inactivation in the membrane fraction was 2 times higher than that in cytosol . A decrease in the culture resistance to kanamycin was observed, when the antibiotic was used in combination with the main proteins or phosphonites: a 16-64-fold decrease in the kanamycin MIC . Comparison of the data on the efficiency of the inactivation inhibition by intact cells and in acellular extracts suggests that the effect of protamine on this process is mediated by the cell membrane, whereas phosphonites can also directly interact with the enzymes inactivating the antibiotic.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Aug, 93(4), 289 - 96
Determination of interpretive breakpoints for ceftazidime disc-diffusion susceptibility testing using single-strain regression analysis; Petersson AC et al.; Interpretive breakpoints for ceftazidime disc-diffusion susceptibility testing were determined using single-strain regression analysis (SRA) . Regression lines were determined for a total of 58 strains representing 15 species, from inhibition zone diameters obtained for discs containing six different ceftazidime concentrations . Statistical analysis for excluding non-linearity of test-results was performed . A minimum of five tests on consecutive days was required for maximal precision of regression analysis according to the SRA-method . Calculated regression lines showed similarities within individual and groups of bacterial species . A minimum of five strains could be used to represent these groups . Interpretive breakpoints according to recommended MIC-limits were determined for each species taking into consideration confidence limits for zone correlates of MIC-values . Single-strain regression analysis for the determination of interpretive breakpoints for ceftazidime disc-diffusion susceptibility testing in individual laboratories.

J Clin Microbiol, 1985 Aug, 22(2), 310 - 1
Proposed disk diffusion susceptibility criteria for ofloxacin; Fuchs PC et al.; Disk diffusion zone diameter breakpoint criteria for ofloxacin were tentatively established by correlating MICs with 1-, 3-, and 5-micrograms disk inhibitory zone diameters for 638 bacterial isolates representing 36 species . We recommend use of 5-micrograms disks with the following breakpoints: susceptible (MIC, less than or equal to 2.0 micrograms/ml), greater than or equal to 16 mm; intermediate (MIC, 4.0 micrograms/ml), 13 to 15 mm; and resistant (MIC, greater than or equal to 8.0 micrograms/ml), less than or equal to 12 mm.

Jpn J Antibiot, 1985 Jul, 38(7), 1898 - 904
{Clinical studies of aspoxicillin in pediatrics}; Haruta T et al.; A clinical and laboratory evaluation and a blood level studied on aspoxicillin (ASPC), a new injectable penicillin derivative; the following results were obtained . ASPC was intravenously administered in 3 or 4 divided doses at a daily dosage ranging from 83.3 to 111.9 mg/kg to 5 patients (1 case of lacunar tonsillitis caused by H . influenzae, 3 cases of pneumonia caused by H . influenzae, 1 case of pneumonia caused by E . coli) . As the results, a global effect were excellent in 3 cases and good in 2 cases . The overall efficacy ratio was 100% . All isolated organisms were eradicated, excluding the only case of pneumonia due to H . influenzae infection . No side effects were found in any of the 7 patients including 2 patients who were dropped out the efficacy evaluation because of Mycoplasma pneumonia . Laboratory findings showed a slight elevation of GOT and GPT in 2 cases and temporary eosinophilia in 1 case . Blood level of ASPC in 2 cases after 10 mg/kg administration by intravenous injection was 28.5 or 35.5 micrograms/ml at 30 minutes, 14.3 or 20.7 micrograms/ml at 1 hour, 6.1 or 8.8 micrograms/ml at 2 hours, 1.3 or 3.02 micrograms/ml at 4 hours . The half-life was 0.81 or 1.01 hours, respectively . Judging from the results of this blood level and the MIC of ASPC against clinically isolated organisms, good efficacy will be obtained to pediatric infections by the sensitive strains, if it is given 10 mg/kg to mild patients or 20 mg/kg to moderate or severe patients in 3 or 4 divided dose at a daily dosage.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 123 - 7
Difference in blister fluid penetration after single and multiple doses of ceftriaxone; LeBel M et al.; Plasma and suction skin blister fluid concentrations of ceftriaxone were studied in 12 subjects after intravenous administration of 1 g of ceftriaxone every 12 h (q12h) and 2 g every 24 h (q24h) after single and multiple doses . Ceftriaxone concentrations were determined by high-pressure liquid chromatography . Mean peak plasma concentrations (at the end of the 5-min infusion) were 254.0 and 374.8 micrograms/ml after administration of 1 g q12h after single and multiple doses, respectively . Similarly, with 2 g q24h, maximum levels were 409.6 and 443.5 micrograms/ml . Forty-eight hours after the last dose of ceftriaxone, plasma concentrations were still detectable: 1.2 micrograms/ml after 1 g q12h and 3.0 micrograms/ml after 2 g q24h . Higher ceftriaxone concentrations were observed in blister fluid after multiple doses than after a single dose . Peak concentrations almost doubled in the blister fluid after multiple doses: 36.0 versus 67.0 micrograms/ml and 38.6 versus 68.9 micrograms/ml for 1 g q12h and 2 g q24h, respectively . Elimination half-life of ceftriaxone in the blister (8.3 and 11.5 h) was longer than plasma half-life (6.3 h) . With the area under the concentration-time curve ratio, a 113% increase in tissue penetration was observed after multiple doses for the 1 g q12h regimen . The free plasma and blister fluid ceftriaxone concentrations observed at the end of the dosing interval of the 2 g q24h regimen were higher than the MIC for 90% of the susceptible microorganisms and justified the once-a-day use of ceftriaxone.

Jpn J Antibiot, 1985 Jul, 38(7), 1819 - 26
{Bactericidal activity of aspoxicillin in an in vitro model simulating human serum levels}; Matsushita T et al.; Bactericidal activities of aspoxicillin (ASPC) against E . coli (2 strains) and K . pneumoniae (1 strain) were compared with those of piperacillin (PIPC) using in vitro kinetic models simulating human serum levels . In the model of intravenous injection, both drugs exhibited bactericidal action against the strains of E . coli . The activity of ASPC was found to superior to PIPC and ASPC could decrease viable cell counts from 10(7) cells/ml to 10(8) cells/ml . On the other hand, the bactericidal activity of ASPC against K . pneumoniae was weaker than that of PIPC . In the model of intravenous drip infusion, ASPC showed a high level of bactericidal activity comparable to that observed in the intravenous model against E . coli . Interestingly, the bactericidal activity of ASPC against K . pneumoniae in this model was similar to that of PIPC, though the MIC value of ASPC was higher than that of PIPC . In the intravenous model, the effects of ASPC and PIPC on the morphology of E . coli KC-14 were examined with a phase contrast microscope . Exposure to PIPC caused only an elongation of the cells, but the treatment with ASPC resulted in the formation of spheroplast-like structure of the cells, which were finally subjected to bacteriolysis.

J Antimicrob Chemother, 1985 Jul, 16 Suppl A, 1 - 11
Structure activity relationships of spiramycins; Omura S et al.; Sixty-six derivatives of spiramycin I and neospiramycin I were synthesized and evaluated by four parameters, MIC, affinity to ribosomes (ID50), therapeutic effect in mice and retention time in HPLC . Among the derivatives, 3,3'',4''-tri-O-propionyl- and 3,4''-di-O-acetyl-3''-O-butyrylspiramycin I showed the highest therapeutic effect which was superior to acetylspiramycin . Structure activity relationships of spiramycins are discussed.

G Batteriol Virol Immunol, 1985 Jul-Dec, 78(7-12), 224 - 44
{Evaluation of the in vitro activity of cefotetan on bacterial strains of recent hospital isolation}; Lembo M et al.; The in vitro activity of cefotetan, a new cephamycin antibiotic, was tested against 296 bacterial strains, recently clinically isolated, by measuring the minimum inhibitory concentrations . Comparisons were made with other drugs (cefoxitin, cefotaxime, piperacillin, rifampicin, clindamycin, tetracycline, chloramphenicol) widely utilized for the treatment of nosocomial infections . Cefotetan showed the highest activity against all the tested strains, with a geometrical mean of MICs (MG) of 0.32 and a MIC 50 and MIC 90 of 0.12 and 8 micrograms/ml, respectively.

Arch Pathol Lab Med, 1985 Jul, 109(7), 595 - 601
Antibiotic susceptibility testing accuracy . Review of the College of American Pathologists Microbiology Survey, 1972-1983; Jones RN et al.; The antibiotic susceptibility testing results for the College of American Pathologists' Microbiology Surveys subscribers for 1981 to 1983 were compared for accuracy and problem areas with earlier data dating back to 1972 . Disk diffusion (Kirby-Bauer) test accuracy was 96.3%, 96.4%, and 95.0% for the Bacteriology, Comprehensive, and Basic Surveys participants, respectively . The overall dilution test and automated system (Autobac I) accuracy was 95.8% and 93.8%, respectively . More laboratories (more than 40% of bacteriology and comprehensive laboratories) were using dilution minimum inhibitory concentration tests, usually frozen-form commercial systems . The current test accuracy was comparable with data for previous years, but the Basic Survey subscribers have demonstrated improvement since mid-1981 . Several testing problems were identified, principally in the interpretive criteria available in national consensus publications such as the National Committee for Clinical Laboratory Standards M2-A3 . Many of these problems have recently been resolved through the cooperation of the National Committee for Clinical Laboratory Standards' subcommittees and the College of American Pathologists' surveys.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 84 - 9
Antiviral and antimetabolic activities of neplanocins; De Clercq E; Of a series of carbocyclic analogs of adenosine, in which the ribose moiety was replaced by a cyclopentenyl ring, neplanocin A, or (-)-9-{trans-2, trans-3-dihydroxy-4-(hydroxymethyl)cyclopent-4-enyl}adenine proved particularly effective in inhibiting the multiplication of DNA viruses (i.e., vaccinia), (-)RNA viruses (i.e., parainfluenza, measles, and vesicular stomatitis), and double-stranded RNA viruses (i.e., reo) in vitro in cell culture . Depending on the cells used, the MIC of neplanocin A for these viruses ranged from 0.01 to 4 micrograms/ml, and depending on the parameter used to assess toxicity for the host cell, the specificity index of neplanocin A ranged from 50 to 4,000 . As postulated before for other adenosine analogs, neplanocin A may owe its antiviral action to inhibition of S-adenosylhomocysteine hydrolase, hence perturbation of transmethylation reactions . In vivo, neplanocin A afforded only marginal protection against a lethal infection of mice with vesicular stomatitis virus.

Biochimie, 1985 Jul-Aug, 67(7-8), 763 - 7
Effect of mic gene structure on repressor activity in the OmpA system; Green PJ et al.; It has been previously established that micRNA (mRNA-interfering complementary RNA) complementary to an individual mRNA specifically represses the expression of the target mRNA . We have constructed several plasmids which produce micRNAs which are complementary to different regions of the ompA mRNA . The repressor activity of these different micRNAs has been compared to determine the role of mic gene structure in effective micRNA function . The results indicate that micRNAs complementary to regions of the ompA mRNA likely to encounter ribosomes have the highest repressor activities . A clear effect of mic gene dosage was also observed . This was demonstrated using both identical and different mic(ompA) genes.

J Immunol Methods, 1985 Jun 25, 80(2), 163 - 75
A method for analysing the clonal precursors of concanavalin A-induced suppressor cells; Good MF et al.; Spleen cells from 3 different strains of mice (C57 (H-2b), CBA (H-2k) and BALB/c (H-2d} were stimulated in vitro with different concentrations of concanavalin A (CA) for 48 h . This resulted in the production of cells capable of inhibiting the generation of alloantigen-specific cytotoxic T lymphocytes (CTL) in a mixed lymphocyte culture (MLC) . 1 microgram/ml was an effective concentration of CA to induce C57 and BALB/c suppressor cells (SC), but 5 micrograms/ml CA was required to induce CBA SC . SC precursors (SC-P) were shown to be radiosensitive and the results suggest that SC themselves may be radiosensitive . SC were effective in the presence of added interleukin-2 (IL-2) . SC were then induced at limit dilution in microwells in a volume of 25 microliter . A MIC (200 microliter) was then (after 48 h) added to each microwell . This resulted in a dilution of the concentration of CA to a level below which it was effective at inducing suppression . Cytotoxicity was then assessed 7 days later . It was thus possible to analyse SC-P at the clonal level and estimate their frequency . The frequency of C57 splenic SC-P (active against a C57 anti-BALB/c MLC) was 14.4 X 10(-6), the frequency of CBA splenic SC-P (active against a CBA anti-BALB/c MLC) was 92.3 X 10(-6), and the frequency of BALB/c splenic SC-P (active against a BALB/c anti-CBA MLC) was 15.8 X 10(-6) . It was possible to analyse SC-P at a clonal level whether or not the MLC contained added IL-2 . SC and SC-P were shown to be sensitive to anti-Thy-1 and complement.

Hinyokika Kiyo, 1985 Jun, 31(6), 1085 - 91
{A study on the levels of cefoperazone in urological organs}; Fukatsu H et al.; The concentration of Cefoperazone (CPZ) in urological organs and serum was measured after the intravenous administration of 2 g of CPZ . Serum levels on healthy adults attained a maximal value of 122.1 +/- 4.2 micrograms/ml at 30 minutes . Serum levels of patients operated under general anesthesia attained a maximal value of 159.0 +/- 13.9 micrograms/ml at 30 minutes . Serum concentration on operated cases continued to be 1.3-2.2 fold higher than that of the healthy adults . Prostate tissue levels attained a maximal value of 80.9 +/- 3.6 micrograms/g at 30 minutes, vesical tissue levels were 52.1 +/- 1.3 microgram/g at 60 minutes and renal tissue were 94.0 +/- 14.5 micrograms/g at 90 minutes . Judging from the minimal inhibitory concentration of CPZ, CPZ seemed to be clinically useful in the treatment of urological infections.

Rev Med Interne, 1985 Jun, 6(3), 272 - 9
{Bacteriologic surveillance of patients with infectious endocarditis . Value and limitations of the determination of minimal inhibitory concentration and serum bactericidal activity}; Martin T et al.; This is a retrospective study of the records of 17 patients who suffered from infectious endocarditis with positive blood cultures, and concerns the possibilities of predicting immediate infectious signs in patients:--by testing each of the antibiotics used for the minimal inhibitory concentration;--by determining the peak of the serum bactericidal activity of patients . All the patients were under observation, as outpatients, for more than a year and proved completely cured of their infectious endocarditis . A satisfactory minimal inhibitory concentration does not necessarily prevent an infectious evolution in the immediate future . The determination of the peak serum bactericidal activity does not reflect faithfully and instantaneously the anti-infectious action of the treatment; this is shown by the excellent and rapid evolution 13 times out 20 although serum bactericidal activity was considered insufficient (less than 1/8) . This level of 1/8 is not a guarantee of therapeutic efficiency . Finally the antiinfectious treatment has been, in the majority of cases, determined by clinical signs and in very few cases by serum bactericidal activity results.

Jpn J Antibiot, 1985 Jun, 38(6), 1552 - 6
Serum concentration of sisomicin by intravenous infusion and its clinical response as a single agent; Tamura K et al.; SISO in doses of 1.0 to 1.8 mg/kg was administered by a 30-minute intravenous infusion every 12 hours to 10 patients with infections, 9 of whom had underlying diseases including malignant diseases, diabetes mellitus, and diabetes insipidus with indwelling FOLEY catheter . The serum concentration of SISO was around 6.75 micrograms/ml in the end of infusion, and less than 1.0 micrograms/ml at 8 to 12 hours after infusion . SISO was given to the patients as a single agent for at least 3 to 5 days and all patients experienced an excellent to good response clinically, and causative organisms which showed a minimal inhibitory concentration of less than 1.56 micrograms/ml disappeared after the treatment associated with clinical improvement . There were no untoward effects noted in this study.

Tubercle, 1985 Jun, 66(2), 109 - 15
Activity of the combination of fludalanine and cycloserine against mycobacteria in vitro; Dickinson JM et al.; The initial steps in the incorporation of alanine into the bacterial cell wall include the conversion of natural to D-alanine by a racemase followed by the coupling of 2 D-alanine molecules by a synthetase to yield a dipeptide . A combination of fludalanine (3-fluoro-2-deutero-D-alanine), an analogue of D-alanine that irreversibly inactivates the racemase, and cycloserine, which inhibits the synthetase, has been found to be more active against a wide range of non-mycobacterial organisms than either fludalanine or cycloserine alone . When tested against 16 strains of slowly growing mycobacteria including M . tuberculosis, the combination was no more active than cycloserine alone . However the cycloserine minimal inhibitory concentration (MIC) of the combination against the rapidly growing species M . phlei and M . fortuitum was much lower than the MIC of cycloserine alone, particularly with low ratios of fludalanine to cycloserine, and was within the range attainable by therapeutic cycloserine plasma concentrations in man, suggesting its possible use in the treatment of disease due to M . fortuitum.

J Vet Pharmacol Ther, 1985 Jun, 8(2), 194 - 201
Pharmacokinetics of amikacin in the horse following intravenous and intramuscular administration; Orsini JA et al.; The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration . Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured . Doses of 4.4, 6.6 and 11.0 mg/kg were given . The concentrations at 15 min following i.v . injection were 30.3 +/- 0.3, 61.2 +/- 6.9 and 122.8 +/- 7.4 micrograms/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses . Mean peak Cs values after the intramuscular injections occurred at 1.0 h post-injection and were 13.3 +/- 1.6, 23.0 +/- 0.6 and 29.8 +/- 3.2 micrograms/ml, respectively . The t 1/2 of amikacin was 1.44, 1.57 and 1.14 h for the 4.4, 6.6 and 11.0 mg/kg doses, respectively . In this study, minimum inhibitory concentrations (MIC) of amikacin sulfate were determined for six pathogens . Based on the MIC and the pharmacokinetic parameters, it would appear that the usual therapeutic dose of amikacin would be between 4.4 and 6.6 mg/kg twice daily and, for the more serious life-threatening infections, dosing three times a day.

J Med Microbiol, 1985 Jun, 19(3), 383 - 90
Morphological response and growth characteristics of Legionella pneumophila exposed to ampicillin and erythromycin; Elliott TS et al.; The morphological response of two strains of Legionella pneumophila to ampicillin 10 micrograms/ml and erythromycin 10 micrograms/ml in vitro was studied by electronmicroscopy, MIC estimations and viable counts . In the presence of ampicillin, discrete lesions appeared in the bacterial cell walls through which cytoplasmic contents extruded and lysis occurred . A few spheroplasts, together with minicells of 0.15-micron diameter, and apparently normal cells were present after exposure to ampicillin for several hours . Conversely, erythromycin initially resulted in inhibition of division and the formation of filamentous organisms . The cell walls of these filaments were eventually disrupted with numerous small membranous vesicles appearing on their surfaces . On further erythromycin treatment, breakage of the cell wall at a restricted number of sites occurred, leading to cell lysis . In the presence of erythromycin, a few morphologically normal cells were present but no spheroplasts or minicells were observed . Viable counts demonstrated that ampicillin killed the bacteria faster than erythromycin . Regrowth did not occur in the continued presence of either antibiotic, but after their removal regrowth was observed.

Arch Surg, 1985 Jun, 120(6), 752 - 3
Cefoxitin concentration in wound fluid; Bagley DH et al.; The concentration of cefoxitin was determined in fluid obtained from human surgical wounds during the first postoperative day . Intravenous administration of cefoxitin sodium at a dosage of 1 or 2 g every six hours rapidly produced wound-fluid concentrations greater than the minimal inhibitory concentration for most susceptible organisms . After three hours, wound-fluid concentrations surpassed the serum concentrations of cefoxitin . The higher dosage resulted in higher wound-fluid levels.

Pathol Biol (Paris), 1985 Jun, 33(5 Pt 2), 577 - 80
{Comparative activity of minocycline and doxycycline on mycoplasmas pathogenic for man}; Bebear C et al.; Susceptibility of Mycoplasma pneumoniae (10 strains), Mycoplasma hominis (20 strains) and Ureaplasma urealyticum (100 strains) to minocycline and doxycycline was studied in vitro . Minimal inhibitory concentrations were determined using an agar dilution method for M . pneumoniae and M . hominis and a metabolic inhibition test for U . urealyticum . M . pneumoniae strains were highly susceptible to minocycline and doxycycline (MIC less than or equal to 0.1 mg/l) . Among M . hominis strains, 17 were susceptible (MIC less than or equal to 0.1 mg/l), whereas 3 were inhibited only by concentrations ranging from 4 to 16 mg/l . Among the 100 U . urealyticum strains, 95 were inhibited by 4 mg/l minocycline and 94 by 4 mg/l doxycycline . Both antibiotics exhibited similar activities against the three species (same ranges, same mode MICs).

Southeast Asian J Trop Med Public Health, 1985 Jun, 16(2), 214 - 8
The in vivo and in vitro sensitivity of Plasmodium falciparum to quinine; Lwin M et al.; The in vivo and in vitro sensitivity of P . falciparum to quinine were studied simultaneously on 20 isolates of P . falciparum from infected patients in Rangoon and in Tharrawaddy Township . The in vivo study showed 85% sensitive and 5% resistance at RI level . The peak plasma quinine level in all the cases were above mean MIC on days 1, 3, 5 and 7 . Schizont maturation was inhibited at 128 p.mol/well in 15% of the cases but the rest were at or below 64 p.mol/well in vitro test . However, no relationship was detected between the in vivo and in vitro sensitivity of quinine.

South Med J, 1985 Jun, 78(6), 731 - 2
Successful treatment of gram-negative bacillary meningitis with imipenem/cilastatin; Rodriguez K et al.; A patient with meningitis caused by a strain of Actinetobacter anitratus that was resistant to all commercially available antibiotics was treated with imipenem/cilastatin administered intravenously in a dose of 1 gm of imipenem every six hours . The minimal inhibitory concentration of imipenem against the isolate was less than or equal to 0.04 micrograms/ml . The patient tolerated the drug well and was cured after 12 days of therapy.

Pediatr Infect Dis, 1985 May-Jun, 4(3), 321 - 5
Advances in diagnosis and treatment of childhood meningitis; Yogev R; The seriousness of bacterial meningitis in pediatrics mandates more rapid and accurate diagnostic tests . Of the available tests to detect bacterial antigens, latex particle agglutination appears to be the best because it is simple and highly sensitive . For differentiation between bacterial and aseptic meningitis, serum C-reactive protein levels in excess of 50 mg/liter and cerebrospinal fluid lactate levels higher than 2.2 mmol/ml indicate a bacterial etiology . Available data confirm that one of the newer "third generation" cephalosporins can be used effectively and safely as a single drug for therapy of meningitis caused by the usual spectrum of bacteria, if the achievable cerebrospinal fluid drug levels exceed the minimal inhibitory concentration of the infecting bacteria by at least 10-fold . Use of these agents will obviate the potential toxicity of current antibiotics and may result in considerable cost savings.

Jpn J Antibiot, 1985 May, 38(5), 1301 - 3
{Basic study on cefminox in the field of obstetrics and gynecology}; Doko F; In patients with carcinoma of the uterine cervix, cefminox (CMNX, MT-141) was given intravenously after panhysterectomy and the pelvic dead space exudate and serum levels of the drug were determined at various periods . The pelvic dead space exudate level reached its peak of 67.21 +/- 39.81 micrograms/ml at 2 hours, which decreased gradually to 26.04 +/- 6.66 micrograms/ml at 6 hours . In the serum, the drug level attained the peak of 152.98 +/- 85.37 of 7.26 +/- 1.66 micrograms/ml was still detected . The pelvic dead space exudate level was much higher than its MIC or 3h-MBC at all periods studied . From these results it was considered that CMNX achieves levels high enough to be expected of clinical efficacy in the pelvic dead space exudate and serum.

Jpn J Antibiot, 1985 May, 38(5), 1213 - 24
{Pharmacokinetics and clinical studies on cefminox in the field of obstetrics and gynecology}; Cho N et al.; Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained . The absorption and the penetration of CMNX into pelvic dead space exudate were good . The mean peak serum level after single intravenous injection was 190.8 micrograms/ml . The level in pelvic dead space exudate reached a peak of 36.6 micrograms/ml 4 hours after an intravenous injection of 1 g and 6.5 micrograms/ml after 12 hours, thus the level over MIC against main pathogenic organisms was maintained for a long time . CMNX was administered against gyneco-obstetrical infections such as intrauterine, intrapelvic, adnexal infections and postoperative wound infections with daily dose of 2 g and was effective in 11 cases out of 12 cases (91.7%), and 81.8% of bacteriological effect was obtained . No side effect was observed . From the above results the usefulness of CMNX in the field of obstetrics and gynecology was suggested.

Infection, 1985 May-Jun, 13(3), 134 - 6
An amphotericin B-resistant case of rhinocerebral mucor mycosis; Barnert J et al.; A 51-year-old male patient with diabetes mellitus complicated by ketoacidotic imbalance developed a rhinocerebral mucor mycosis that advanced despite early amphotericin B therapy and extensive surgical intervention . The MIC of amphotericin B for the isolated mucor species was 64 mg/l, meaning that in vitro resistance also existed . Only long-term treatment with ketoconazole (600 mg/day, perorally) was successful in curing the disease.

Hinyokika Kiyo, 1985 May, 31(5), 863 - 70
{Prostatic tissue levels of ceftizoxime}; Hoshi S et al.; The concentration of Ceftizoxime (CZX) was determined in the prostatic tissue and serum of 130 patients with benign prostatic hypertrophy . Two grams of CZX was given by intravenous injection prior to TUR . The mean value of CZX levels in prostatic tissue and prostatic level/serum levels ratio (p/s ratio) after administration were 47.2 +/- 2.8 micrograms/g, 49.1% at 30 minutes, 33.3 +/- 2.2 micrograms/g, 51.4% at one hour, 22.2 +/- 2.7 micrograms/g, 60.8% at 2 hours, 13.6 +/- 3.9 micrograms/g, 64.2% at 4 hours, 3.04 +/- 0.54 micrograms/g, 74.5% at 8 hours, respectively . In conclusion, the concentration of CZX in the prostatic tissues attained the minimal inhibitory concentration of 80% for the gram-negative bacteria, the excluding P . aeruginosa . Thus clinical effectiveness of CZX could be expected on bacterial prostatitis and bacterial infection after prostatic operations.

J Appl Physiol, 1985 May, 58(5), 1485 - 8
Airway reactivity and lung function in triiodothyronine-induced thyrotoxicosis; Irwin RS et al.; To evaluate the possible relationship between asthma and hyperthyroidism, airway reactivity and lung function were prospectively compared in healthy volunteers before, during, and after liothyronine (triiodothyronine, T3)-induced hyperthyroidism . Base-line evaluation of the 10 subjects included clinical evaluation, thyroid and pulmonary function tests, and airway reactivity assessed by methacholine inhalational challenge (MIC) . All studies were normal . During T3-induced hyperthyroidism, no subject developed respiratory symptoms or changes in pulmonary function or airway reactivity . The mean percent change in forced expiratory volume at 1 s from base line (delta FEV1) of -2.4 +/- 3.0 after MIC was not significantly different from that obtained before T3 administration (-1.4 +/- 1.5, P greater than 0.2) . When all serum T3 concentrations and delta FEV1 values before, during and after T3-induced hyperthyroidism were compared, there was no significant correlation . We conclude that T3-induced hyperthyroidism of 3-wk duration has no effect on airway reactivity or lung function in normal volunteers.

J Infect, 1985 May, 10(3), 189 - 93
The effect of antibiotics on the growth of Legionella pneumophila in guinea-pig alveolar phagocytes infected in vivo by an aerosol; Fitzgeorge RB; The likely efficacy of four antibiotics of possible use in the treatment of Legionnaires' disease was assessed in terms of their capacity to inhibit the replication of Legionella pneumophila within guinea-pig alveolar macrophages and polymorphonuclear leukocytes (PMN) compared with their minimum inhibitory concentrations (MIC) in vitro . All the antibiotics used had similar MIC values with regard to L . pneumophila (0.032-0.062 mg/l), but differences of up to 100 fold in the concentration required to eliminate viable intracellular organisms were observed . The most effective antibiotics were found to be rifampicin and ciprofloxacin . These eliminated viable L . pneumophila from alveolar macrophages and PMN at concentrations of 0.005 and 0.01 mg/l respectively, whereas erythromycin and gentamicin required higher concentrations of 0.1 and 0.5 mg/l respectively . It is suggested that assays performed in cultures of relevant cells may provide useful additional means of assessing antibiotic efficacy against intracellular pathogens and help to explain discrepancies otherwise observed between in vitro and in vivo findings.

Am J Vet Res, 1985 May, 46(5), 1200 - 5
Comparison of minimal inhibitory concentration and disk-diffusion antimicrobic sensitivity testing of bacterial pathogens isolated from food animals; Libal MC; Disk-diffusion sensitivity tests were conducted with the antimicrobics sulfathiazole, gentamicin, erythromycin, kanamycin, penicillin, ampicillin, and spectinomycin on 300 to 350 bacterial isolates of food animal origin . The minimal inhibitory concentration of each antimicrobic was also determined for each bacterial isolate, using a microdilution technique . Results indicated that inhibitory zone sizes should be larger for some antimicrobics when testing animal pathogens than those zone sizes recommended for testing human pathogens . In addition, zone interpretive data are reported for spectinomycin, a drug for which such data were previously lacking.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 May, 259(3), 378 - 89
Comparative determination of minimal inhibitory and bactericidal concentrations of ciprofloxacin, cefotaxime and HR 810 for gram-negative bacteria either sensitive or resistant to ureidopenicillins and/or gentamicin; Bartmann K et al.; The minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations of ciprofloxacin were compared with those of the cephalosporins HR 810 and cefotaxime in 250 strains from 10 species of Gram-negative bacteria with sensitivity or resistance to gentamicin and/or piperacillin . Ciprofloxacin had an inhibitory activity higher than, or practically equal to the best of the two cephalosporins . The MBC of ciprofloxacin was more often less than or equal to twice the MIC than with the beta-lactam antibiotics . Parallel resistance was found with pipemidic acid as representative of DNA-gyrase inhibitors . No direct parallel resistance was observed with resistance to gentamicin, piperacillin or cefotaxime.

Hinyokika Kiyo, 1985 May, 31(5), 871 - 4
{A study of prostatic tissue levels of cefoperazone}; Yoshida H et al.; Prostatic tissue levels of Cefoperazone (CPZ) were studied after the administration of 3 g of CPZ, in 16 patients with prostatic hypertrophy who underwent retropubic prostatectomy . The CPZ concentration in the surgical capsule at 60 min . after the administration of CPZ was about 2 times higher than that in the gland . As compared with the histological type of removed gland, the levels in the glandular hyperplasia were slightly higher than that in the fibromuscular and mixed type hyperplasia, but the difference was not statistically significant . CPZ was found to be effective for the treatment of post-operative and bacterial prostatitis, since the CPZ levels of prostatic tissue were considerably high and above the minimal inhibitory concentration level for most bacteria.

Antimicrob Agents Chemother, 1985 Apr, 27(4), 605 - 7
Pharmacokinetics of ceftazidime, alone or in combination with piperacillin or tobramycin, in the sera of cancer patients; Drusano GL et al.; We administered 2 g of ceftazidime intravenously every 8 h to cancer patients for the empiric therapy of febrile episodes . Ceftazidime was administered as monotherapy for patients with granulocyte counts in excess of 1,000/microliter . Febrile, neutropenic patients were randomized to also receive either piperacillin or tobramycin . The pharmacokinetic profile of ceftazidime during a steady-state dosing interval was ascertained in 21 patients . No differences were seen between groups for any of the pharmacokinetic parameters examined . As expected, the observed half-life was longer, the serum clearance was smaller, and the volumes of distribution were larger than in previously reported studies of volunteers . Serum concentrations remained above the MIC for inhibition of 90% of strains of the most common bacteremic pathogens seen in our cancer center for the entire 8-h dosing interval.

Infect Control, 1985 Apr, 6(4), 157 - 60
A comparison of antibiotic susceptibility profiles using single and multiple isolates per patient; Bennett WP et al.; We compared the antibiogram statistics generated by including all clinical isolates to those obtained by tabulating no more than one isolate of a particular organism from a given patient . We found that 48.3% of the isolates presented multiple occurrences in individual patients but found no practical differences in the profiles obtained by the two methods . We also tabulated the occurrence of minimum inhibitory concentration (MIC)-distinct organisms among the sets of multiple isolates of E . coli and of S . aureus and found that only 20.9% of those isolates represented duplicate organisms by MIC profile . This heterogeneity of MIC sensitivity that occurs in multiple isolates from individual patients was not expected but provides an explanation for the lack of difference between the two methods of tabulating antibiotic susceptibility statistics.

Isr J Med Sci, 1985 Apr, 21(4), 340 - 5
Increasing frequency of penicillin-resistant pneumococci: epidemiological aspects and case-control study; Amitai Y et al.; At the Hadassah University Hospital, Mt . Scopus, Jerusalem, the frequency of patients with relatively penicillin-resistant pneumococci (RPRP) isolates has increased from 0.9 to 10.8% during the years 1979-82 . Infants and children were particularly involved . Significantly more RPRP isolates were found in those less than 14 years old than in those who were older (P less than 0.005) . The determination of susceptibility or relative resistance to penicillin was based on the disk sensitivity method, which remained unchanged throughout the study period . The minimal inhibitory concentration (MIC) to penicillin G was also determined for 20 RPRP isolates and was found to be in the range of relative resistance to penicillin (0.25 to 0.50 micrograms/ml) in all 20 isolates . A case-control study of 16 index patients examined antibiotic usage during the 60 days preceding pneumococcal isolation . Total antibiotic usage was high in both groups (18.8 vs . 8.8 days, P = 0.2); beta-lactam antibiotic usage was significantly higher in the RPRP group than in the control group (13.3 vs . 4.2 days, 0.01 less than P less than 0.02) . General prescribing practices, even in nonisolated areas where there is no need for public health programs to dispense prophylactic antibiotics, may produce sufficiently high antibiotic exposures to aid the emergence of RPRP strains.

Aust Vet J, 1985 Mar, 62(3), 79 - 82
Ocular inserts for application of drugs to bovine eyes--in vitro studies on gentamicin release from collagen inserts; Punch PI et al.; Soluble collagen and insoluble collagen films were impregnated with gentamicin and investigated in vitro as vehicles for the delivery drugs . Succinylated collagen released significantly higher levels of antibiotic than the insoluble films, and maintained mean inhibitory concentrations (MIC) for Moraxella bovis for 24 h.

Cancer Res, 1985 Mar, 45(3), 992 - 9
Cellular pharmacology in murine and human leukemic cell lines of diaziquone (NSC 182986); Egorin MJ et al.; We investigated the in vitro interaction with and antitumor effect on several murine and human leukemic cell lines of diaziquone (AZQ) . L1210 cells accumulated AZQ from Roswell Park Memorial Institute Medium 1640 with or without newborn calf serum by a temperature-dependent and sodium azide-resistant process . AZQ inhibited, in a dose-dependent fashion, {3H}thymidine incorporation into L1210 cells, but this inhibition was slow to develop, requiring approximately 6 hr to become apparent . The minimal inhibitory concentration of AZQ for this process was 0.05 to 0.25 nmol/ml . AZQ was a much less effective inhibitor of L1210 cell {3H}uridine and {14C}valine incorporation . In suspension cultures, AZQ inhibited growth of L1210 and HL-60 cells at minimal inhibitory concentrations of 0.5 to 1 nmol/ml . In soft agar cultures, AZQ inhibited HL-60 cell cloning at minimal inhibitory concentrations of 0.1 to 0.3 nmol/ml . AZQ provoked a dose-dependent increase in oxygen consumption when added to intact L1210, HL-60, and K562 cells and was converted to an AZQ anion free radical by these cells . When the aziridine rings of AZQ were opened by acid treatment, the resulting molecule was not accumulated by L1210 cells, did not provoke O2 consumption, did not form free radicals when added to L1210 cells, and was a much less effective inhibitor of {3H}thymidine incorporation by L1210 cells than was AZQ.

Quad Sclavo Diagn, 1985 Mar, 21(1), 10 - 22
{Polycenter evaluation of the break-point system}; Casella P et al.; Several research center have been set up to evaluate the system that deals with sensitivity to microbes under Sensititre break-point . The study has been broken down as follows: the break-point system was compared with the agar diffusion according to Bauer et al., using 1180 strains of fast-growing Gram-negative bacteria; a limited number of strains (176) have been used to compare the Sensititre break-point and the Sensititre MIC; results have been obtained testing 448 strains processed by break-point with correct inoculum and with simplified inoculum, from a colony; an investigation has been carried out on the time and cost of the break-point functioning . Having taken the Bauer system and others are compared them with the break-point, it was seen that their total agreement was 90.3% with 2% of major disagreement . The total major disagreement between Sensititre MIC and Sensititre break-point was 2.7% . The total major disagreement of the latter was largely the result of cephalotin (21%) on the Escherichia coli strains . An initial research centre has been formed to try to trow light upon the origins of such disagreements and we are now pleased to report back their initial findings . The preparation and reading of a test with the Bauer system and others takes about 18 minutes and costs 5600 Lit; a break-point test takes 10 minutes and costs 4500 Lit.

Mycopathologia, 1985 Mar, 89(3), 135 - 8
Chemotherapy of Aspergillus fumigatus keratitis: an experimental study; Garcia de Lomas J et al.; An experimental Keratitis study of Aspergillus fumigatus was performed in 130 rabbits divided into 12 groups of ten animals each . Three antifungal drugs (myconazole, amphotericin B and pimaricin) were tested using two procedures (topical drops and subconjunctival injections) and two different concentrations (500 and 10 000 times the MIC) . In each case, the drugs were applied every 3 h starting 14 h after inoculation . Miconazole was useful at 10 mg/ml concentration by topical drops and subconjunctival injections, but was less useful at 5 mg/ml . Amphotericin B was useful at 5 mg/ml concentration by topical drops and less useful at 2 mg/ml . No differences were found between the two concentrations by subconjunctival administration . Pimaricin was useful by topical drops at 50 mg/ml concentration and less useful at 10 mg/ml as well as by subconjunctival injections.

J Vet Pharmacol Ther, 1985 Mar, 8(1), 105 - 9
Apramycin: minimal inhibitory concentrations for avian Escherichia coli and serum levels after intramuscular injection in turkeys; Freidlin PJ et al.; The minimal inhibitory concentrations (MIC) of apramycin, a unique aminocyclitol antibiotic, for 100 Escherichia coli isolates recovered from clinical cases of avian colibacillosis were determined using the agar dilution method . All isolates were inhibited at apramycin concentration of 8.0 micrograms/ml; 90 and 50% of the isolates were inhibited at 6.6 and 3.4 micrograms/ml, respectively . A commercial injectable product containing 200 mg apramycin/ml was administered intramuscularly (i.m.) to groups of 6- and 12-week-old turkeys at 10, 15 and 20 mg/kg . Apramycin was quickly absorbed from the i.m . injection site . Mean peak serum drug concentrations were reached 1 h after treatment and were 19.5, 27.5 and 36.0 micrograms/ml, respectively . The serum elimination half-life (t 1/2) of the drug ranged between 1.75 h for the 10 mg/kg dose and 2.5 h for the 20 mg/kg dose . Very low concentrations of the drug were found 24 h after treatment . Duration of serum apramycin concentrations in relation to the MIC, dose, and age of birds was determined.

Quad Sclavo Diagn, 1985 Mar, 21(1), 31 - 43
{Critical evaluation of the Abbott MS-2 automatic system in the rapid determination of antibiograms}; Malfa SA et al.; The Abbott MS-2 system for rapid determinations of the bacterial growths in the kinetic mode is briefly described . Some details of the operations of the apparatus and about the experimental procedure are given by referring to a phenomenological description for the bacterial growth . A critical analysis of the antimicrobic susceptibilities and of the minimum inhibiting concentrations (MIC) provided by the apparatus is also carried out . In particular the problems arising for cephalosporins is emphasized.

Hinyokika Kiyo, 1985 Mar, 31(3), 539 - 43
{Concentration level of latamoxef sodium (LMOX) in prostatic tissue}; Takao M et al.; The concentration of latamoxef sodium (LMOX) in serum and prostatic tissue was evaluated . Thirty seven patients with benign prostatic hypertrophy were given 1 g LMOX intravenously prior to prostatectomy . Prostatic tissue and blood were sampled at 1, 2 or 3 hrs after administration of LMOX . The concentration of LMOX in prostatic tissue was 17.4 +/- 3.4 micrograms/g tissue, 11.1 +/- 1.3 microgram/g tissue and 8.9 +/- 1.3 microgram/g tissue 1, 2 and 3 hrs after injection, respectively (mean +/- S.E.) . The penetration ratio of LMOX (concentration in tissue/in serum) to prostate was 30-45% . Therefore, the 80% MIC of LMOX is lower than 8 micrograms/ml for most gram negative bacteria, the results suggest that LMOX is very effective against prostatitis caused by these organisms.

Vet Res Commun, 1985 Feb, 9(1), 25 - 34
Pharmacokinetics of chloramphenicol in cows after intramuscular application; Tanner U et al.; The concentrations of chloramphenicol and its water-soluble metabolites in the plasma of six clinically healthy heifers were measured at intervals during five days after intramuscular administration of free chloramphenicol (20 mg/kg) in a vehicle containing 40% of an organic solvent . Estimations were carried out by a colorimetric method and by high pressure liquid chromatography (for the very low values beyond the second day) . For free chloramphenicol a peak concentration of 1.7 micrograms/ml at 7.3 h after injection was found (MIC: 5 micrograms/ml) . Bioavailability was calculated to be 63% . It is shown that absorption was apparently not a uniform process but occurred rather slowly (t 1/2 (ab) = 10.2 h) for the main part of the available dose, whereas one sixth was quickly absorbed (t'1/2 (ab) = 0.7 h) . The apparent half-time of elimination was 10.2 h for the unchanged drug . At the fifth day after administration the plasma concentration was below the limit of detectability (10 ng/ml) in all animals.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Feb, 259(1), 78 - 89
The bactericidal activity of ampicillin, amoxicillin, tetracycline, and doxycycline against H . influenzae under various conditions of culture; Bartmann K et al.; The bactericidal activities of ampicillin, amoxicillin, tetracycline, and doxycycline at a concentration of 1 mg/l were compared for 13 strains of H . influenzae with a typical minimal inhibitory concentration of these drugs . Conditions of culture used were: liquid medium in shaken flasks, stationary flasks and stationary tubes, with and without the addition of 30% human serum . Ampicillin and amoxicillin exerted the same bactericidal activity . Survival rates at 5 h were on the average near 1%, however, with large variations . At 24 h survival rate was uniformly below 0.12% . The bactericidal activity of the tetracyclines depended more on the cultural conditions . A marked reduction of the bacterial population below 1% was found at 24 h between 12 of 12 and 5 of 13 strains according to the experimental circumstances . Tetracycline was more bactericidal than doxycycline, especially in the presence of serum.

Eur J Clin Microbiol, 1985 Feb, 4(1), 30 - 3
Interpretive criteria for temocillin disk diffusion susceptibility testing; Fuchs PC et al.; The susceptibility of 677 clinical bacterial isolates to temocillin was determined by broth microdilution and disk diffusion methods for the purpose of evaluating disks with three different temocillin concentrations and determining the temocillin disk diffusion interpretive criteria . The 60 microgram temocillin disk provided the highest interpretive accuracy (96.2%), although the 30 microgram disk differed by having only three (1.2%) additional minor interpretive errors . Based on available temocillin pharmacokinetics and recommended dosage schedules, the minimum inhibitory concentration breakpoints chosen were: greater than or equal to 32 micrograms/ml = resistant and less than or equal to 16 micrograms/ml = susceptible . The corresponding disk diffusion zone diameter breakpoints for the 60 microgram disk were less than or equal to 17 mm and greater than or equal to 21 mm; zone diameters of 18-20 mm were considered intermediate . For the 30 microgram disk these were less than or equal to 15 mm, greater than or equal to 19 mm and 16-18 mm respectively.

Br J Oral Maxillofac Surg, 1985 Feb, 23(1), 60 - 6
Candida glabrata (syn . Torulopsis glabrata) associated with a chronic hyperplastic lesion of the palate; Price JD et al.; A case initially presenting as chronic hyperplastic candidosis is described . After treatment with nystatin on three separate occasions over a seven-year period, a lesion similar to that diagnosed originally occurred in the same site . Further examination of this later occurrence showed it to be associated with the imperfect fungus Candida glabrata which had a high minimum inhibitory concentration for nystatin (greater than 30 micrograms/ml) . The lesion eventually resolved following treatment with miconazole gel and surgical excision of the hyperplastic tissue . The patient has remained symptomless for a two-year follow-up period.

Chemotherapy, 1985, 31(6), 451 - 5
Aztreonam: correlation between disk diffusion and agar plate dilutions susceptibility tests; Toma EC et al.; Regression lines and error rate-bounded analyses were performed for correlating inhibitory zone diameters with the 30-micrograms aztreonam disk and aztreonam minimal inhibitory concentration for gram-negative aerobic clinical isolates . A correlation coefficient of -0.81 was found for the regression line . Preliminary proposed criteria to distinguish susceptible isolates from resistant ones are: susceptible greater than or equal to 22 mm (MIC less than or equal to 8 micrograms/ml), intermediate 16-21 mm (MIC = 16 micrograms/ml) and resistant less than or equal to 15 mm (MIC greater than or equal to 32 micrograms/ml) . Using these criteria, the rates for false-susceptible and false-resistant isolates were zero.

Arzneimittelforschung, 1985, 35(3), 639 - 43
{The pharmacokinetics of josamycin}; Wildfeuer A et al.; Determination of the distribution coefficients in vitro demonstrates that josamycin (Wilprafen) is at least 15 times more lipophilic than erythromycin . On the other hand the distribution coefficients of penicillin G and of amoxicillin be in the hydrophilic range . The serum protein binding of josamycin is 15%, which is markedly less than with the other macrolides . These in vitro experiments show that small structural differences can alter the physicochemical and biological behaviour of an antibiotic, even when the molecules are closely related . A cross-over experiment with 12 volunteers and multiple application of 1 g of josamycin base or 1.175 g of erythromycin ethyl succinate showed that both macrolides are rapidly absorbed and reach their maximum within the first hour . In 21 patients the concentration of josamycin in lung tissue was 2 to 3 times that in the blood . The highest concentration of josamycin reached was 3.68 micrograms/g lung tissue (mean of 12 patients) and this was found for the group of patients from whom the tissue samples had been taken 2-3 h after the last administration of the drug . Lower mean concentrations of erythromycin were found in the serum and lung tissue of a similar group of 31 patients . The results indicate that the new macrolide antibiotic josamycin accumulates well in lung tissue and that the concentrations necessary for the treatment of infections (minimal inhibitory concentrations {MIC}) are rapidly reached also in the tissue.

Microbiol Immunol, 1985, 29(4), 309 - 15
Bioluminescent assay as a potential method of rapid susceptibility testing; Kouda M et al.; A method of rapid susceptibility testing by bioluminescent assay was developed . Correlation between the 50% inhibition dose of antimicrobics for bacterial adenosine triphosphate measured by bioluminescent assay and the minimum inhibitory concentration obtained by the broth dilution method was satisfactory . In the bioluminescent assay the incubation time required was only 90 min.

Chemotherapy, 1985, 31(3), 169 - 72
Mezlocillin concentrations in human aqueous humour after intravenous and subconjunctival administration; Behrens-Baumann W et al.; 27 patients received either 4 g intravenous infusion 1-3 h or 100 mg subconjunctival application of mezlocillin 1-12 h before cataract extraction . After intravenous administration the mean aqueous humour concentration of mezlocillin was 2.9 micrograms/ml after 2 h . The subconjunctival dose produced a mean aqueous humour concentration of 23 and 2.6 micrograms/ml after 3 and 12 h, respectively . These levels are above the minimum inhibitory concentration of mezlocillin for sensitive organisms.

Antimicrob Agents Chemother, 1985 Jan, 27(1), 132 - 4
Susceptibility of intra- and extracellular Mycobacterium avium-intracellulare to cephem antibiotics; Nozawa RT et al.; Intra- and extracellular susceptibility of 35 clinically isolated Mycobacterium avium-intracellulare strains to cefotaxime (CTX), ceftizoxime (CZX), and cefoperazone was studied . MICs for 50% of the isolates in vitro were 6.25 micrograms/ml for CTX and CZX and 25 micrograms/ml for cefoperazone . A strain susceptible to CTX (MIC, 0.78 micrograms/ml) and CZX (MIC, 1.56 micrograms/ml) infected human peripheral blood mononuclear cells in the presence of 20% autologous plasma . The mycobacteria replicated exclusively in monocytes under the above culture condition . Concentrations of CZX 1- to 16-fold higher than its in vitro MIC had little effect on intracellular replication of the strain . A concentration of CTX 16-fold higher than its in vitro MIC was bacteriostatic to the mycobacteria, but CTX of lower concentrations showed no effect on intracellular replication . Thus, ineffectiveness of the cephems on the therapy of M . avium-intracellulare infection was suggested.

Acta Anat (Basel), 1985, 121(3), 140 - 6
Possible role of endothelium in the orientation of smooth muscle cells in experimental neointima; Reimers D et al.; Myointimal cells (MIC) orientation and intimal thickening evolution, induced by grafting an autogenous venous patch onto the rat common carotid artery, were studied with light microscopy at different times until 14 months after surgery . Intimal thickenings in the venous patch were most prominent at an intermediate postoperative period, after which their mean size did not change significantly . In host artery neointima, the greatest MIC proliferation was observed at a late stage of evolution . MIC arrangement was predominantly circumferential to the blood stream in venous patch neointima, whereas it was mostly axial in the host artery . The interaction between MIC orientation and endothelial regeneration in the operated vessel is discussed.

Prostate, 1985, 6(2), 163 - 8
Amifloxacin distribution in the dog prostate; Frimodt-Moller PC et al.; Constant infusion experiments with amifloxacin, a quinoline carboxylic acid derivative, were performed in five anesthetized dogs to determine the drug concentrations in prostatic secretion (PS), prostatic interstitial fluid (PIF), prostatic tissue, and plasma (P) . The experiments were carried out under steady-state conditions . Amifloxacin concentrations in PS and PIF were lower than the corresponding P concentrations, as might be expected for an acid compound . There was no significant difference between the PS/P and PIF/P concentration ratios of the drug, and none exceeded 1.0 . The concentrations of amifloxacin in PS, PIF, and prostatic tissue were above the minimal inhibitory concentration values of most gram-positive bacteria causing chronic bacterial prostatitis . Clinical trials of amifloxacin seem justified.

Clin Ther, 1985, 7(2), 151 - 3
Comparison of Escherichia coli susceptibility to cephalothin, cefazolin, ceforanide, and cefamandole; Greenberg RN et al.; Twenty-seven Escherichia coli test strains that were not susceptible to cephalothin were tested for susceptibility to cefazolin, cefamandole, and ceforanide . By zone-size criteria (greater than or equal to 18 mm), 67% of E coli were susceptible to cefazolin and cefamandole, and 93% were susceptible to ceforanide . By microtiter assay (MIC less than or equal to 8 micrograms/ml), 88% were susceptible to cefazolin and cefamandole, and 94% were susceptible to ceforanide . The results support susceptibility testing of E coli with specific first- or second-generation cephalosporins rather than with class agents.

Drugs Exp Clin Res, 1985, 11(3), 169 - 76
Pefloxacin: evolution of in vitro activity during 18 months of use in an intensive care unit; Tigaud S et al.; The MIC of pefloxacin against all the strains (3122) isolated in an intensive care unit during 18 months was studied . The MIC of pefloxacin was estimated by standard agar diffusion method in Mueller-Hinton agar . All the strains with a MIC lower than 2 mg/l were considered as sensitive, between 2 and 4 mg/l as "intermediary" and over 4 mg/l as resistant . Geometrical means of MICs were calculated for each month and for different species . The study continued for 18 months from the introduction of the drug which was in widespread and constant use as a first-choice antibiotic . No significant increase was detected in the incidence of resistant strains during the study; on the other hand, small, limited clusters of resistant strains were observed during minor nosocomial epidemics . The general features of quinolone activity, the spectrum of this new quinolone and the slow evolution of the bacterial population are discussed.

Acta Otolaryngol Suppl, 1985, 424, 7 - 12
Penetration of cefaclor to adenoid tissue and middle ear effusion in chronic OME; Ernstson S et al.; Cefaclor given per os 20 mg/kg body weight was readily absorbed and distributed to adenoid tissue and to middle ear effusion in children with chronic OME . The levels obtained were above the MIC values of most strains of respiratory pathogens . The penetration characteristics were the same after the first and the 20th dose in a b.i.d . regimen . Elimination was completed within about 12 h . The double dose, 40 mg/kg body weight, did not give higher levels but a longer duration.

Jpn J Antibiot, 1985 Jan, 38(1), 45 - 8
{A study on transference of cefmenoxime into the cerebrospinal fluid}; Shibata Y et al.; Two grams of cefmenoxime (CMX) was administered by one-shot intravenous injection to the patients in normal pressure hydrocephalus without meningitis, and the transference of CMX into the cerebrospinal fluid (CSF) from blood was investigated . After the injection of CMX, CSF and serum were serially taken, and the concentrations of CMX were measured by agar-well method using E . coli . The conclusions drawn from this study are summarized as follows: The concentrations of CMX in CSF were more slowly decreased than those in serum . The mean ratio of transference of CMX into CSF from the serum was 1.4% . After the intravenous injection of 2 g CMX, the mean maximum concentration of CMX in CSF was 0.36 microgram/ml, which exceeded 80% MIC (minimal inhibitory concentration) against several Gram-positive cocci and Gram-negative rods, and higher concentrations than the 80% MIC were kept over 4 hours in CSF . The efficacy of CMX may be kept by its injections less than 4 times a day.

Indian J Lepr, 1985 Jan-Mar, 57(1), 149 - 58
A study of relapse in non lepromatous and intermediate groups of leprosy; Pandian TD et al.; Dapsone has been used as a monotherapy and in well organised control units, the prevalence of leprosy has come down . The relapse rates presented in this communication are quite low compared with those reported by various authors quoted in this paper . Relapse rates appear to remain steady at about 5/1000 for each following year after R.F.C . for 7 years . This relapse rate does not appear to be related to regularity of treatment . The relapse rate appears that longer the duration of treatment, the earlier relapse due to severity of the disease of those who had longer treatment . Health education for R.F.C . cases on signs of relapse is a must before they are declared R.F.C . The levels of Sulphone in the blood remain above MIC for as much as ten days after the last dose and therefore Dapsone allows self-administration . It is expected that with the introduction of bacteriocidal drugs in the treatment of paucibacillary leprosy, the relapse rates would go down . As observed from a study conducted in Jalma, maintenance treatment as advocated by the NLCP (1964) and WHO (1970) does not seem to be necessary . The necessity of such maintenance treatment may be obviated with the use of multi-drug regimen in paucibacillary leprosy . This would enable a large number of cases to be released from control thereby reducing patient load considerably and making the supervised treatment of multibacillary cases more easy.

Drugs Exp Clin Res, 1985, 11(4), 237 - 40
Sensitivity testing of bacteria to ceftriaxone using discs with different amounts of antibiotic; Borowski J et al.; Studies were performed to compare the results of sensitivity testing of bacteria to ceftriaxone using discs containing 10, 20, 30 and 40 micrograms of the antibiotic . The highest correlation between diameters of zone inhibition and MIC values was found with discs containing 30 micrograms of ceftriaxone . The lowest percentage of false results was also obtained with 30 micrograms discs.

Chemotherapy, 1985, 31(2), 151 - 9
Acyclic pyrimidine nucleoside analogues: influence on growth of L5178y mouse lymphoma cells and antiherpes activity in KB cells; Allen LB et al.; Several uracil and cytosine nucleoside analogues with 2-hydroxyethoxymethyl, 2-aminoethoxymethyl or 1,3-dihydroxypropoxymethyl side chains were synthesized and evaluated for cytostatic (L5178y mouse lymphoma cells) and antiviral (herpes simplex virus type 1 infected KB cells) activity . Two compounds exhibited antiherpesvirus activity . These were 1-(2'-hydroxyethoxymethyl)-5-aza-cytosine and 1-(1',3'-dihydroxypropoxymethyl)-5-iodouracil . The MIC values were 25.8 and 325.7 micrograms/ml, respectively.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 251 - 6
The use of bacteria producing the aminoglycoside inactivating enzyme ANT-(2") in an in-vitro model; Wiedemann B et al.; A series of transconjugants of Escherichia coli W3110 containing different plasmids coding for the aminoglycoside inactivating enzyme ANT-(2") were tested in an in-vitro model simulating the concentration time curves of aminoglycosides after intramuscular administration of 80 or 120 mg . There was good correlation of the MIC, which ranged from 2 to 32 mg/l, with the killing ability of the drugs . A second dose had no or only little effect on ANT-(2") producing strains . All strains, although of 'intermediate' sensitivity were found to be resistant in the in-vitro model . Only netilmicin could eliminate some of the strains but its activity on ANT-(2")-positive strains was not as good as on ANT-(2")-negative ones.

Int J Fertil, 1985, 30(2), 10 - 7
The effect of in vitro sperm capacitation on sperm velocity and motility as measured by an in-office, integrated, microcomputerized system for semen analysis; Burke RK et al.; The authors measured the effects of in vitro washing and capacitation on sperm velocity and motility on one hundred males, using an in-office, integrated, microcomputerized system for objective semen analysis . Sperm characteristics, including sperm velocity, percentage of motile sperm, and the motility index improved significantly following the washing procedure . Average sperm velocity increased from 19.9 microns per second in the original specimens to 26.3 mic/sec following washing (P less than 0.05), while percentage of motile sperm and the sperm motility index (MI) increased from 30% to 86% (P less than 0.01) and 6.6 to 22.5 (P less than 0.01) respectively . The most significant differences occurred in the asthenospermic subgroup, with sperm velocity increasing from 16.3 microns per second to 24.6 mic/sec (P less than .001), percentage motility increasing from 15% motility to 85% motility (P less than 0.001), and the motility index (MI) increasing from 2.4 to 21.6 (P less than 0.001) . The advantage of a widely acceptable method for quantitative evaluation of semen quality is discussed.

Presse Med, 1984 Dec 8, 13(44), 2693 - 5
{Diffusion of fosfomycin into the cerebrospinal fluid in purulent meningitis}; Stahl JP et al.; Cerebrospinal fluid levels of fosfomycin were measured in 10 patients with bacterial meningitis . Fosfomycin 200 mg/kg/day was administered in three 4-hour intravenous infusions . The antibiotic was associated with amoxicillin in 9 patients and with cefotaxime in one . Cerebrospinal fluid was obtained on the 2nd and 5th days of treatment, 2 hours after the end of the infusion . The mean CSF fosfomycin levels were 31 mg/l on the 2nd day and 37.2 mg/l on the 5th day . These levels were higher than the MIC 90 for most bacteria encountered in meningitis . Fosfomycin could be used to treat some cases of bacterial meningitis, but always in association with another antibiotic.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Dec, 258(2-3), 287 - 95
Different mechanisms of TEM-1 and Oxa-1 mediated resistance to piperacillin in E . coli; Marre R et al.; Clinical isolates of Oxa-1 and TEM-1 producing strains of E . coli were studied . Susceptibility to piperacillin was determined by the agar and broth dilution procedure, and beta-lactam hydrolysis rates measured by the iodometric method . The beta-lactamases were identified by isoelectric focusing . Our data on TEM-1 producing strains showed a statistically significant correlation between the MIC, if determined by the agar dilution test, and the specific beta-lactamase activity . The majority of Oxa-1 producing E . coli was resistant to piperacillin although the inactivation rate of piperacillin was usually low . Cell wall permeability of TEM-1 producing strains of E . coli to piperacillin was below the lower limit of detectability, but preincubation of the E . coli strains in piperacillin containing broth led to increased cell wall permeability . Bactericidal kinetics of an Oxa-1 and TEM-1 E . coli were studied . It revealed that regrowth of the Oxa-1 strain in piperacillin containing broth was associated with a 25% decrease of piperacillin concentrations without the formation of degradation products, suggesting binding of piperacillin to bacterial cells . The TEM-1 plasmid bearing strain inactivated piperacillin, and the degradation products (penicilloate) could be detected.

Drugs, 1984 Dec, 28(6), 544 - 53
Assessment of drug disposition in the lung; Rebuck AS et al.; Airway disposition of drugs is assessed with either physiological changes in lung mechanics or nuclear scanning of the tagged medication . Several methods have been described for assessment of the pulmonary disposition of drugs delivered by routes other than the airways . These methods include tissue biopsy and sputum analysis of pooled secretions and tracheal washings . More recently, bronchoalveolar lavage fluid has been analysed for a variety of pharmacological agents and comparisons drawn between blood and lavage supernatant levels . Problems in correcting for dilution have been overcome by using a naturally occurring tracer substance, such as creatinine or albumin, which has a similar molecular weight to the test chemicals and which can be assayed readily in blood and lavage fluid . It has become apparent that neither naturally occurring not exogenous chemicals enter the lung in a concentration that is predictable from their levels in the blood . While the alpha 2-macroglobulin level in lavage fluid is approximately 25 times less than that in serum, a 1:1 relationship exists for alpha 1-antitrypsin . Cortisol achieves a concentration in lung fluid equal to that of blood, but lung fluid concentrations of methylprednisolone and prednisone are one-half, or at best one-third, of the blood concentration, respectively . Knowledge regarding the penetration of antibiotics into the lung is useful in determining the potential effectiveness of a given agent and its likely acinar MIC . It appears that the alveolar-capillary unit is not freely permeable to all agents, raising the possibility that a blood-lung barrier exists which is responsible for maintaining the alveolar environment . The knowledge that there is a differential permeability among drugs makes it important for clinicians to assess this characteristic of each agent before conclusions linking dose and response are drawn.

Eur J Clin Microbiol, 1984 Dec, 3(6), 605 - 11
Beta-lactams in sexually transmitted diseases: rationale for selection and dosing regimens; Kunimoto D et al.; A review is given of the selection and rational of optimal treatment regimens for patients with sexually transmitted pathogens, e.g . in cases of gonorrhea, chlamydial infections, chancroid, syphilis, pelvic inflammatory diseases and ophthalmia neonatorum . The scientific basis for the selection of a beta-lactam agent is discussed, including dose, MIC, the critical serum level and maintenance interval, and the duration of therapy . Except in the case of penicillinase-producing Neiserria gonorrhoeae, penicillin remained until recently the most effective agent available against many sexually transmitted diseases . However, ceftriaxone, a new third-generation cephalosporin, has been shown to have a long half-life (8 h) and excellent in vitro efficacy against Neiserria gonorrhoeae (including penicillinase-producing strains) and Haemophilis ducreyi . In view of its exceptional clinical efficacy against both gonorrhea and chancroid, clinical studies of its efficacy against other sexually transmitted diseases appear warranted.

J Am Optom Assoc, 1984 Nov, 55(11), 839 - 44
An improved technique for collection of human tears; Webster HJ et al.; While pursuing a study of lysozyme levels in human tears, the authors were dissatisfied with collection systems previously used . We therefore constructed a new, improved apparatus for tear collection using a thin, flexible polyethylene tube attached to a standard 25-gauge 1.0 cc tuberculin syringe . This system is superior to previously-designed apparati in that it permits the collection of a relatively large volume of tears in a short time without risking damage to delicate ocular structures . This promises to enhance the reliability of tear chemistry research without significantly adulterating the chemical composition of the samples . Typical results for total protein, levels of IgA and lysozyme, and Minimum-Inhibitory-Concentration bioassay of tears are presented to support the authors' position that standard chemical assays are not altered . An additional bonus inherent in this technique is the potential for obtaining larger populations of experimental subjects due to the low level of irritation that subjects experience when tears are sampled . This apparatus is easily amenable to clinical and medical diagnostic studies of tear chemistry in patients suffering from various eye diseases.

Pediatr Infect Dis, 1984 Nov-Dec, 3(6), 526 - 9
Individualization of tobramycin dosage in patients with cystic fibrosis; Hsu MC et al.; Tobramycin was administered to 52 patients, ages 2 months to 27 years, with cystic fibrosis during acute exacerbation of Pseudomonas-related pulmonary infection . Elimination pharmacokinetics of tobramycin was characterized for each patient after intravenous administration using a standardized infusion technique . The minimal inhibitory concentration was determined for Pseudomonas strains isolated from 26 of the 52 patients . The pharmacokinetic parameters of individual patient were used to adjust the dose and dosing interval to maintain the serum concentration of tobramycin above the minimal inhibitory concentration for the infecting organism for at least 75% of the dosing interval without exceeding the maximum concentration of 12 micrograms/ml or a minimum concentration of 2.0 micrograms/ml . This resulted in an increase of the mean daily dose of tobramycin to 12 mg/kg from an initial mean dose of 5.5 mg/kg and a reduction of the dosing interval from 8 hours to 4 or 6 hours for patients greater than 1 year of age . Significant differences between the pharmacokinetic profiles of the infants and older patients were observed.

Antimicrob Agents Chemother, 1984 Nov, 26(5), 689 - 93
Paradox between the responses of Escherichia coli K1 to ampicillin and chloramphenicol in vitro and in vivo; Kim KS et al.; We evaluated the activity of ampicillin and chloramphenicol in vitro and in vivo against an Escherichia coli K1 strain . In vitro, the strain was relatively susceptible to both antibiotics (MIC and MBC of ampicillin, 2 and 4 micrograms/ml; MIC and MBC of chloramphenicol, 4 and 64 micrograms/ml) . Checkerboard determinations of MBCs of drug combinations were consistent with antibiotic antagonism . Killing curves with concentrations of antibiotics similar to in vivo levels in blood and cerebrospinal fluid of infected rats indicated antagonism within the first 4 h and an indifferent effect of the combination at 24 h . Paradoxically, the combination was significantly more effective than ampicillin or chloramphenicol alone in vivo in infant rats . This was shown by (i) more rapid bacterial clearance from the blood and cerebrospinal fluid, (ii) a decreased incidence of meningitis in bacteremic animals, and (iii) improved survival . These findings illustrate a divergence between the effects of ampicillin and chloramphenicol against E . coli in vitro and in vivo and suggest that this combination is an effective synergistic regimen in this experimental model of E . coli bacteremia and meningitis.

J Gen Microbiol, 1984 Nov, 130 ( Pt 11), 2883 - 91
Resistance in inhibitors of RNA polymerase in actinomycetes which produce them; Blanco MG et al.; Resistance to the endogenous antibiotic was studied in three actinomycetes that produce inhibitors of RNA polymerase . The three producers, Nocardia mediterranei (rifamycin producer), Streptomyces spectabilis (streptovaricin producer) and Streptomyces lydicus (streptolydigin producer), were each highly resistant to the antibiotic they produce (MIC greater than 200 micrograms ml-1) and in vivo RNA synthesis was also resistant . However, cross-resistance to the other RNA polymerase inhibitors was not found . Resistance to these antibiotics was due to target site modification, since the RNA polymerase enzymes of the three producing organisms were highly resistant in vitro to the corresponding antibiotic, and no antibiotic-inactivating enzymes were detected . A mutant was isolated from S . spectabilis which was sensitive to steptovaricin (its own product) and also showed an increased sensitivity to rifamycin and streptolydigin . This mutant had RNA polymerase which was extremely sensitive to the three antibiotics.

Am J Med, 1984 Oct 19, 77(4C), 12 - 6
Interpretation of susceptibility testing of ceftriaxone; Squires E et al.; Susceptibility of a variety of bacterial isolates to ceftriaxone was determined by Kirby-Bauer assays using 30 micrograms ceftriaxone disks and by microdilution (MIC) assays using standard procedures . The relation between zones of inhibition and MICs was expressed by the following regression equation: zone diameter = 22.98-2.653 In (MIC) . Using this regression line and the breakpoints estimated from ceftriaxone concentrations in plasma 12 to 24 hours after 1- and 2-g doses, the susceptibility of a pathogen to ceftriaxone was classified as follows: susceptible-zone 16 mm or greater, MIC 16 micrograms/ml or less; moderately susceptible-zone 13 to 15 mm, MIC 17 to 63 micrograms/ml; resistant-zone 12 mm or less, MIC 64 micrograms/ml or greater . These breakpoints were used to determine the susceptibility of organisms isolated during clinical studies in the United States . The correlation between the in vitro results and the bacteriologic outcomes achieved in the clinical cases was analyzed to assess the suitability of the chosen breakpoints . The results of the disk assays were correctly predictive of bacteriologic responses with 1,388 of 1,513 organisms (91.7 percent), whereas the results of dilution assays correctly predicted the response with 897 of 941 organisms (95.3 percent) . The correlation between in vitro results and bacteriologic outcome in patients treated with ceftriaxone was equivalent or superior to that achieved in patients treated with the comparative agents cefamandole and cefazolin . Thus, the chosen cutoff points for indicating susceptibility and resistance to ceftriaxone appear to be suitable and highly predictive of clinical success.

Am J Surg, 1984 Oct 19, 148(4A), 8 - 14
Comparison of ceftriaxone and cefazolin prophylaxis against infection in open heart surgery; Beam TR et al.; One hundred four patients undergoing elective open heart surgery were enrolled in a prospective, double-blind trial comparing prophylaxis against infection using a single 1 g dose of ceftriaxone and seven doses of cefazolin . Patients in both groups had similar risk factors for infection . The likelihood of achieving a tissue concentration in excess of the minimal inhibitory concentration for Staph . aureus was significantly greater with ceftriaxone in atrial appendage (p less than 0.001), muscle (p less than 0.01), and bone (p less than 0.01) than with cefazolin . The serum half-life of ceftriaxone was approximately 15.7 hours . All 49 serum samples obtained 18 to 24 hours after delivery of ceftriaxone and 26 of 33 samples obtained 40 to 48 hours after delivery had drug concentrations in excess of 3.1 micrograms/ml, the mean minimal inhibitory concentration for isolates of Staph . aureus . Early and late infectious complications were infrequent and occurred at similar rates in both groups . Neither drug was associated with significant toxicity . A single 1 g dose of ceftriaxone was as effective and safe as multiple doses of cefazolin and demonstrated superior tissue penetration.

Eur J Clin Microbiol, 1984 Oct, 3(5), 463 - 7
Susceptibility of Legionella spp . to imipenem and 27 other beta-lactam antibiotics; Ruckdeschel G et al.; With 28 beta-lactam antibiotics the susceptibilities of 60 strains of Legionella spp . (49 Legionella pneumophila and 11 ATCC type strains of other Legionella species) were determined . Agar dilution testing was used on buffered charcoal-yeast extract agar to which 0.1% alpha-ketoglutarate was added . The most active of the penicillins tested were ampicillin (MIC = 0.06-8 mg/l) and temocilin (MIC = 0.125 - 16 mg/l); the most active cephalosporins were ceftazidime (MIC = 0.03 - 0.5 mg/l), HR 810 (MIC = 0.06 - 1 mg/l) and cefoxitin (MIC = 0.125 - 2 mg/l) . Of all the drugs tested imipenem had the most pronounced activity (MIC = .0075 - 0.06 mg/l).

J Antibiot (Tokyo), 1984 Oct, 37(10), 1238 - 45
Mycoversilin, a new antifungal antibiotic . III . Mechanism of action on a filamentous fungus Trichophyton rubrum; Kole HK et al.; Mycoversilin is active against filamentous fungi, being specifically inhibitory to Trichophyton rubrum, minimum inhibitory concentration being 15 micrograms/ml . Mycoversilin inhibits sporulation to the extent of 28.5% even at the growth inhibitory concentration whereas inhibition of spore germination requires higher concentration . It has no effect on radial growth . Further it shows no action either on the release of UV absorbing materials or on the respiration of T . rubrum . However, the antibiotic inhibits in vivo synthesis of protein fairly strongly, DNA moderately and RNA slightly at the minimum inhibitory concentration . Cell-free protein synthesis is also strongly inhibited, the site of action being the inhibition of leucyl-tRNA formation by the antibiotic which has no action on leucine activation.

Am J Clin Pathol, 1984 Oct, 82(4), 455 - 8
Inability to control selected drugs on commercially obtained microdilution MIC panels; Kellogg JA; As more broad spectrum antimicrobics continue to appear, many manufacturers have added drugs to their microdilution minimal inhibitory concentration (MIC) test panels at the expense of testing each drug over a broad range of twofold dilutions . Micro Scan (Mahwah, NJ) gram-positive and gram-negative 96-well microdilution panels were tested with the suggested control organisms over a period of 60 days to determine if on-scale MIC endpoints could be achieved with at least one organism per drug . Of 13 antimicrobics in the gram-positive panel, seven (clindamycin, tetracycline, cephalothin, gentamicin, nitrofurantoin, trimethaprim-sulfa, and streptomycin) could not be controlled effectively . Of 18 drugs in the gram-negative panel, six (tobramycin, trimethaprim-sulfa, cefoperazone, mezlocillin, ticarcillin, and kanamycin) similarly could not be controlled . The accuracy of results obtained when patient isolates were tested with these 13 antimicrobics could not be substantiated by control procedures as stated in the Micro Scan instructions.

Antimicrob Agents Chemother, 1984 Oct, 26(4), 501 - 6
Regrowth of aminoglycoside-resistant variants and its possible implication for determination of MICs; Soren L et al.; Regrowth of aminoglycoside-resistant variants was seen when large inocula of two strains of Escherichia coli were incubated with gentamicin in concentrations well above their MICs (0.5 micrograms/ml) . The extent of the selection of resistant variants was proportional to the concentration of gentamicin during incubation; after incubation with gentamicin (greater than or equal to 2 micrograms/ml for 24 h), all bacteria were resistant to at least 8 micrograms/ml . Bacteria resistant to these concentrations always formed small colonies, whereas variants resistant to lower concentrations (1 to 2 micrograms/ml) could form both small and normal colonies . The regrowth of resistant variants could be monitored by luciferase assay of intracellular ATP in cultures incubated with gentamicin (less than or equal to 2 micrograms/ml) . In cultures incubated with higher concentrations, regrowth did occur, although this did not result in viability (CFU per milliliter) or ATP levels above those of the initial inocula . The implications of this regrowth for MIC determinations in broth and the possible clinical revelance of the resistant variants are discussed.

Isr J Med Sci, 1984 Oct, 20(10), 905 - 7
Laboratory diagnosis of mycoplasma infections; Senterfit LB; The relative efficiency of different media for the isolation of M . pneumoniae is discussed, with emphasis on the utility of SP-4 medium as a primary medium for isolation . Media available for isolation and identification of ureaplasmas are also described . Rapid methods of identification of isolated mycoplasmas are surveyed . The use and value of serologic procedures in the clinical laboratory are evaluated with particular reference to the complement fixation procedure and its value as compared to other methods . The possibilities for the development of direct antigen detection procedures for clinical use are discussed with particular reference to ELISA and other antigen capture methods . The problems that arise in susceptibility testing of isolates are raised, and a usable procedure is proposed both for minimal inhibitory concentration and minimal bacteriocidal concentration determination . A general procedure for the laboratory diagnosis of mycoplasmal infection that is adaptable to various laboratory circumstances and needs is proposed.

Chemioterapia, 1984 Oct, 3(5), 271 - 7
In vitro evaluation of ceftazidime (GR 20263), amikacin and sisomicin, in a model simulating serum pharmacokinetics of therapeutic doses; Xerri L et al.; The activity of ceftazidime, amikacin and sisomicin was investigated in an in vitro model using varying concentrations of antibiotic which mimic the serum levels of patients after the intramuscular administration of a 500, 250 and 70 mg dose respectively . Using this test, during the time of the agar MIC value correlation, ceftazidime, amikacin and sisomicin proved to be active against strains sensitive to 16 micrograms/ml, 8 micrograms/ml and 4 micrograms/ml respectively . Using the above concentrations as the cut-off points in defining the sensitivity of the strains, ceftazidime revealed the same level of activity as amikacin (6 and 5 resistant strains respectively out of the 185 tested) and proved much more active than sisomicin (48 resistant strains).

Eur J Clin Microbiol, 1984 Oct, 3(5), 427 - 32
Effects of antibiotics on adhesion of enterotoxigenic Escherichia coli strains; Forestier C et al.; Subinhibitory concentrations of 28 antibiotics were tested for their effects on MRHA patterns of four enterotoxigenic Escherichia coli strains possessing colonization factor antigens CFA/I, CFA/II or CFA/III . Only penicillin G, oleandomycin, doxycycline and minocycline inhibited the haemagglutination pattern of three Escherichia coli strains with CFA/I and CFA/II when added to the medium culture at concentrations ranging from 1/2 to 1/50 of the MIC . At the same concentrations they also decreased the adhesion index of the four strains to human intestinal cells . However, neither the specific agglutination of bacterial cells with CFA antisera nor the production of CFAs was affected.

J Antimicrob Chemother, 1984 Sep, 14 Suppl C, 39 - 45
Interpretive criteria for the agar diffusion susceptibility test with enoxacin; Grimm H; Regression analyses to determine the correlation of MIC and inhibition zone produced by enoxacin discs were carried out using 300 freshly isolated cultures of infective organisms (20 strains each from 15 species) . For this purpose, commercially available discs containing 10 micrograms enoxacin and locally made discs containing 5 and 10 micrograms enoxacin were used . Studies were performed simultaneously with I.C.S . and Kirby-Bauer methods on Iso-Sensitest and Mueller-Hinton agars . It was found that correlation becomes poorer with increasing disc content and when the Kirby-Bauer method was used . Based on preliminary MIC breakpoints of 1 and 4 mg/l and the zone cut-off points calculated from regression equations, no major errors were found in zone interpretations . Minor errors were observed in 3.7% with our own 5 micrograms discs used in the I.C.S . method, and in 11.0% with 10 micrograms commercial discs and the Kirby-Bauer method . For 5 micrograms enoxacin discs and the Kirby-Bauer method the following zone interpretations are recommended: resistant up to 13 mm, intermediate 14-21 mm, susceptible 22 mm or more . The respective values for the I.C.S . method are: resistant up to 14 mm, intermediate 15-22 mm, susceptible 23 mm or more.

Antimicrob Agents Chemother, 1984 Sep, 26(3), 426 - 7
Treatment of typhoid fever with cefamandole; Uwaydah M et al.; Cefamandole therapy was evaluated in nine patients with typhoid fever . Six patients, including all five who received the antibiotic by continuous intravenous drip (8.0 g daily), were cured . Dosage schedules resulting in maintenance of antibiotic concentrations in serum high above the MIC seemed to correlate well with treatment success.

Pathol Res Pract, 1984 Sep, 179(1), 61 - 6
Accuracy of frozen section diagnosis in breast cancer detection . A review of 4436 biopsies and comparison with cytodiagnosis; Fessia L et al.; Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in a single pathology laboratory were checked against the final pathological report . In 4284 cases (96.57%) there was no difference between the FSD and the definitive diagnosis . There were 74 (1.66%) false negative reports and no false positive diagnoses . The diagnosis was deferred to paraffin sections in 78 cases (1.75% of biopsies) . The predictive value for positive results was 100% and for negative results 97.5%; the specificity was 100%, the sensitivity 94.6% and the accuracy 98.3% . Minimal breast cancer, in situ (CIS) especially, was the main source of false negative reports . In non minimal invasive cancers (NMIC) FSD was correct in 99.42% . In minimal invasive cancers (MIC) FSD was correct in 80.21%, false negatives and deferred diagnosis increased to 8.79% and 10.98% . In CIS false negatives increased to 76.82% and deferred diagnoses to 12.19% . The sensitivity of fine needle aspiration, performed before biopsy in a portion of the patients, was lower than FSD in NMIC (71.39% versus 99.21%) and in MIC (41.66% versus 80.55%), identical to FSD in CIS (7.40% versus 7.40%) . The value of cytodiagnosis in addressing surgery is discussed.

Am J Public Health, 1984 Sep, 74(9), 1014 - 9
Needs assessment under the Maternal and Child Health Services Block Grant: Massachusetts; Guyer B et al.; The Massachusetts maternal and child health (MCH) agency has developed a needs assessment process which includes four components: a statistical measure of need based on indirect, proxy health and social indicators; clinical standards for services to be provided; an advisory process which guides decision making and involves constituency groups; and a management system for implementing funds distribution, namely open competitive bidding in response to a Request for Proposals . In Fiscal Years 1982 and 1983, the process was applied statewide in the distribution of primary prenatal (MIC) and pediatric (C&Y) care services and lead poisoning prevention projects . Both processes resulted in clearer definitions of services to be provided under contract to the state as well as redistribution of funds to serve localities that had previously received no resources . Although the needs assessment process does not provide a direct measure of unmet need in a complex system of private and public services, it can be used to advocate for increased MCH funding and guide the distribution of new MCH service dollars.

J Med Chem, 1984 Sep, 27(9), 1111 - 8
Benzylamines: synthesis and evaluation of antimycobacterial properties; Meindl WR et al.; The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described . The most active compounds in this test, N-methyl-3-chlorobenzylamine (19, MIC 10.2 micrograms/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 micrograms/mL), and N-butyl-3,5-difluorobenzylamine (103, MIC 6.4 micrograms/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties . The combinations of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M . tuberculosis H 37 Ra.

J Antibiot (Tokyo), 1984 Sep, 37(9), 1054 - 65
In vitro and in vivo anti-Candida activity and toxicology of LY121019; Gordee RS et al.; LY121019 (N-p-octyloxybenzoylechinocandin B nucleus) is a semisynthetic antifungal antibiotic that possesses potent anti-Candida activity . The MIC50 and the MIC90 for both LY121019 and amphotericin B were 0.625 and 1.25 micrograms/ml, respectively . Only an 8-fold increase in the MIC against C . albicans occurred during 34-day exposure to subinhibitory concentrations indicating that LY121019 has a low potential for causing resistance development . Scanning electron microscopic studies revealed that LY121019 caused severe damage to the C . albicans cell . The ED50's for LY121019 and amphotericin B administered parenterally to mice were 7.4 and 2.5 mg/kg, respectively . Parenterally administered LY121019 at doses of 6.25 mg/kg significantly reduced the recovery of C . albicans from infected mouse kidneys . Orally administered 50 and 100 mg/kg doses of LY121019 were effective in eliminating C . albicans from the gastrointestinal tract of infected mice . Topical application of 5% LY121019 was as effective as 3% nystatin in the treatment of superficial C . albicans infections . Local administration of LY121019, nystatin, or miconazole was effective against rat vaginal candidiasis . LY121019 was administered intravenously to dogs at doses up to 100 mg/kg/day, 5 days a week for 3 months; all dogs survived . Compound related effects included a histamine-like reaction, increased serum alkaline phosphatase and SGPT, fatty vacuolization of the liver, and some tissue damage at the injection site . The no effect dose in dog was 10 mg/kg . LY121019 had no more than 1/20 the toxicity of amphotericin B in the dog.

Jpn J Antibiot, 1984 Sep, 37(9), 1701 - 13
{MICs and MBCs of cefotaxime, desacetylcefotaxime and ceftriaxone against four principal bacteria causing meningitis}; Deguchi K et al.; The MICs and MBCs of cefotaxime (CTX), desacetylcefotaxime (Des-CTX) and ceftriaxone (CTRX) were determined in relation to 4 of the principal bacterial species which cause meningitis, i.e., S . pneumoniae, S . agalactiae, H . influenzae and E . coli . These tests were performed using final inocula of 10(8) cells/ml and 10(6) cells/ml . Comparison was made with the MIC and MBC values of benzylpenicillin (PCG) and ampicillin (ABPC) . 1 . Against 25 strains of S . pneumoniae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.024 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml, respectively; and PCG, less than 0.012 micrograms/ml at both size . Similarly, the MBC 90 values were: CTX, 0.01 and 0.05 micrograms/ml; Des-CTX, 0.78 and 0.39 micrograms/ml; CTRX, 0.20 and 0.10 micrograms/ml; and PCG, 0.024 and 0.012 micrograms/ml, respectively . It is thus apparent that PCG showed the lowest values for both the MIC and MBC, followed by CTX, CTRX and then Des-CTX . Against 25 strains of S . agalactiae, the MIC 90 values with inocula of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and PCG, 0.39 and 0.20 micrograms/ml, respectively . Similarly, the MBC 90 values of Des-CTX were 0.78 and 0.39 micrograms/ml, while the other 3 antibiotics showed the same values with both the 10(8) and 10(6) cells/ml inocula: 0.10 micrograms/ml for CTX, 0.20 micrograms/ml for CTRX and 0.39 micrograms/ml for PCG . Accordingly, CTX showed the lowest values, followed by CTRX and then PCG being about the same as Des-CTX . Against 25 strains of H . influenzae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.10 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.39 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and ABPC, 50 and 6.25 micrograms/ml, respectively . Similarly, the MBC 90 values were: CTX, 0.20 and 0.10 micrograms/ml; Des-CTX, 1.56 and 1.56 micrograms/ml; CTRX, 0.39 and 0.20 micrograms/ml; and ABPC, greater than 100 and 50 micrograms/ml, respectively . Accordingly, in terms of the MIC 90, CTX and CTRX showed the same values, but in terms of the MBC 90 CTX was superior . (ABSTRACT TRUNCATED AT 400 WORDS)

Vet Q, 1984 Sep, 6(4), 229 - 35
Inclusion keratoconjunctivitis ('pink eye') in sheep . A proposal for a new name for chlamydial keratoconjunctivitis in sheep and comment on recent clinical trials; Bogaard AE Jr; The cytoplasmatic inclusion bodies, which, in 1931, Coles discovered in the corneal cells of sheep suffering from contagious keratoconjunctivitis are now considered to be the reticulate bodies of a chlamydia, Colesiota conjunctivae (synonym: Chlamydia psittaci ovis) . According to the postulates of Koch Colesiota conjunctivae is a primary cause of contagious keratoconjunctivitis in sheep, but the clinical picture is complex and is a result of the interaction between the infecting chlamydiae, host resistance factors, and secondary infections caused by opportunistic bacterial ocular pathogens . The clinical syndrome might also be caused by other micro-organisms, such as Mycoplasma conjunctivae or environmental factors, such as dust . However, in these cases, cytoplasmatic inclusion bodies cannot be found in the corneal cells of diseased eyes . To differentiate chlamydial keratoconjunctivitis from keratoconjunctivitis due to other causes, it is proposed to include in the name the laboratory findings typical for this disease: Sheep Inclusion Keratoconjunctivitis . Chlamydia are Gram-negative bacteria, which are obligate intracellular parasites . Prolonged treatment seems to be required to eradicate chlamydiae from a host and antibiotics must reach intracellular levels that are higher than their minimum inhibitory concentration for chlamydiae . Tetracyclines are the drugs of choice . This means that for a microbiological cure, diseased sheep must be injected several times a day for a week or more . Because the disease is usually self-limiting and economic losses are considered low, this seems unnecessary and control of the disease by local treatment of secondary infections seems sufficient . However, this will not prevent spreading of the disease in a herd and relapses may occur.

Antimicrob Agents Chemother, 1984 Aug, 26(2), 164 - 9
Growth of group IV mycobacteria on medium containing various saturated and unsaturated fatty acids; Saito H et al.; Seventy-one strains of 15 species of rapidly growing mycobacteria were studied for their susceptibilities to fatty acids with 2 to 20 carbons by the agar dilution method at pH 7.0 . Most mycobacteria other than potential pathogens (Mycobacterium fortuitum and Mycobacterium chelonei) were resistant to saturated fatty acids, except for lauric acid (C12:0) (MIC, 6.25 to 25 micrograms/ml) and capric acid (C10:0) (MIC, 50 to 100 micrograms#ml) . M . fortuitum and M . chelonei were substantially insusceptible to these fatty acids . Unsaturated fatty acids with 16 to 20 carbons, except for C20:5, were highly toxic to group IV mycobacteria other than M . fortuitum, M . chelonei, Mycobacterium smegmatis, and Mycobacterium phlei, these being highly resistant to all the unsaturated acids, except for C16:1, C18:3, and C20:5 . Introduction of double bonds to C16 to C20 fatty acids caused a marked increase in their activities that depended on the increase in the number of double bonds, at least up to three or four . M . fortuitum and M . chelonei were more resistant to the unsaturated fatty acids (particularly to C20:3 and C20:4) than the other group IV mycobacteria.

Eur J Clin Microbiol, 1984 Aug, 3(4), 344 - 6
The activity of ciprofloxacin and other 4-quinolones against Chlamydia trachomatis and Mycoplasmas in vitro; Ridgway GL et al.; Ciprofloxacin was found to be the most active of a group of 4-quinolone antibiotics tested against the SA2f strain of Chlamydia trachomatis (MBC and MIC 1.0 mg/l) . Against genital isolates of Chlamydia trachomatis, ciprofloxacin was twice as active as rosoxacin . Ciprofloxacin showed similar activity to that of oxytetracycline against clinical isolates of Mycoplasma hominis and Ureaplasma urealyticum, and was 8-fold more active than rosoxacin against the latter.

J Antimicrob Chemother, 1984 Aug, 14(2), 105 - 14
Antifungal relative inhibition factors: BAY l-9139, bifonazole, butoconazole, isoconazole, itraconazole (R 51211), oxiconazole, Ro 14-4767/002, sulconazole, terconazole and vibunazole (BAY n-7133) compared in vitro with nine established antifungal agents; Odds FC et al.; Nine new antifungal agents were tested for their activity in vitro in terms of relative inhibition factors (RIFs) against 26 isolates of Candida species, eight isolates of Aspergillus species and six isolates of dermatophyte fungi . Eight of the new compounds were azole antifungals, the ninth was a phenylmorpholine derivative . Against Candida species, all the novel compounds gave RIFs that were of a similar order to RIFs for established imidazole compounds . Two topical antifungals, butoconazole and terconazole, and two systemic antifungals, itraconazole and vibunazole, gave mean RIFs less than 60% in tests with Candida species, and therefore matched clotrimazole, ketoconazole and tioconazole in terms of RIF . However, none of the new compounds gave RIFs as low as amphotericin B against the Candida isolates . Against Aspergillus isolates, itraconazole, with a mean RIF of 25%, was even more active in vitro than amphotericin B . Vibunazole was as active as ketoconazole against Aspergillus isolates . All the new antifungals except Bay l-9139 gave very low RIFs against dermatophyte isolates, and thus matched established imidazole antifungals for inhibitory effects in vitro . In terms of RIF data, all the nine new compounds tested appear to offer reasonable potential for antifungal chemotherapy in vivo . A similar conclusion would not have been drawn from minimal inhibitory concentration data, which tended to show most of the new antifungals in a very poor light . Tests with amphotericin B, 5-fluorocytosine and ketoconazole showed that RIF can vary substantially with the pH of the test medium . For amphotericin B and ketoconazole the best activity was seen at neutral pH values; for 5-fluorocytosine the greatest inhibitory activity was found at lower pH values.

J Clin Microbiol, 1984 Aug, 20(2), 295 - 7
Failure of the disk diffusion test to detect tobramycin resistance in kanamycin-resistant Escherichia coli strains; Santanam P; Approximately 40% of Escherichia coli strains isolated from clinical specimens at the Institute of Medical Microbiology of the University of Zurich were resistant to kanamycin but susceptible to tobramycin in disk diffusion tests . Whereas 50% of these strains required a MIC of 7 micrograms of tobramycin per ml to inhibit 1 x 10(5) to 4 x 10(5) cells, 20% of them required a concentration of 8 micrograms or more of the drug per ml . The disk diffusion test, therefore, failed to detect resistance to tobramycin in kanamycin-resistant E . coli strains . Cell extracts from two representative strains phosphorylated and inactivated kanamycin, amikacin, gentamicin, tobramycin, 3',4'-dideoxykanamycin B (dibekacin), butirosin, lividomycin,and ribostamycin, which together constituted a novel spectrum of substrates for the enzymatic activity.

Hinyokika Kiyo, 1984 Aug, 30(8), 1135 - 42
{A study of prostatic tissue levels of ceftizoxime, cefoperazone and cefotaxime}; Ikeda S et al.; Prostatic tissue levels and serum levels of Ceftizoxime (CZX), Cefoperazone (CPZ) and Cefotaxime (CTX), after intravenous administration were studied in 82 patients with prostatic hypertrophy, who underwent transurethral surgery . CZX was found to be the most effective for treatment of prostatic infection, since its prostatic tissue level was considerably higher than the others, satisfactorily above the MIC level of most bacteria . The prostatic tissue levels were not correlated with prostate size . The levels in fibromuscular hyperplasia were significantly higher than in glandular hyperplasia.

Am J Ophthalmol, 1984 Jul 15, 98(1), 17 - 20
Piperacillin levels in human tears and aqueous humor; Woo FL et al.; Thirty patients scheduled to undergo elective intraocular surgery were each given 4 g of piperacillin intravenously . Specimens of serum, tears, and aqueous humor were collected from zero to nine hours after infusion and assayed for piperacillin content by high pressure liquid chromatography . In noninflamed eyes piperacillin sodium distributed into tears and aqueous humor in concentrations exceeding the minimum inhibitory concentration required for many gram-positive and gram-negative organisms . Higher levels of piperacillin were anticipated in patients with inflamed eyes who possessed an altered blood-aqueous barrier, and in patients receiving serial doses of this agent.

Am J Obstet Gynecol, 1984 Jul 1, 149(5), 477 - 80
In vitro activity of clindamycin against strains of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum isolated from pregnant women; Harrison HR et al.; Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum are genital agents that are being increasingly implicated in infectious pregnancy complications and abnormal pregnancy outcomes . We measured the in vitro activity of clindamycin against strains of these three agents which were isolated from pregnant women . For 30 strains of C . trachomatis, the median minimal inhibitory concentration was 1.0 microgram/ml (range, 0.25 to 2.0 micrograms/ml) . For 27 strains of M . hominis, the median minimal inhibitory concentration was 0.12 microgram/ml (range, 0.06 to 0.25 microgram/ml) and the median minimal bactericidal concentration was 0.5 microgram/ml (range, 0.06 to 2.0 micrograms/ml) . For 27 strains of U . urealyticum, the mean minimal inhibitory concentration was 4 micrograms/ml (range, 1.0 to 32.0 micrograms/ml) and the mean minimal bactericidal concentration was 32.0 micrograms/ml (range, 4.0 to 128 micrograms/ml) . Thus in vitro clindamycin would appear to be highly active against pregnancy-associated strains of M . hominis, less active against strains of C . trachomatis, and least active against strains of U . urealyticum . Since M . hominis has been strongly linked to postabortal fever and to postpartum fever and endometritis, our results indicate that clindamycin should be evaluated in treatment trials in pregnancy aimed at prevention of M . hominis-induced morbidity as well as in treatment of the complications themselves.

J Antibiot (Tokyo), 1984 Jul, 37(7), 760 - 72
Chemical modification of spiramycins . IV . Synthesis and in vitro and in vivo activities of 3'',4''-diacylates and 3,3'',4''-triacylates of spriamycin I; Sano H et al.; 3'',4''-Diacylates and 3,3'',4''-triacylates of spiramycin I were synthesized and evaluated by the four parameters, MIC against bacteria, affinity to ribosomes, retention time in HPLC and therapeutic effect . Among them, 3,3'',4''-tri-O-propionyl and 3,4''-di-O-acetyl-3''-O-butyryl-spiramycin I were the most active in vivo, which were superior to acetylspiramycin.

Ophthalmic Surg, 1984 Jul, 15(7), 578 - 82
Dematiaceous fungal keratitis following penetrating keratoplasty; Levenson JE et al.; A keratitis with an unusual, sessile, filamentary mass extending into the anterior chamber developed in a patient three weeks after penetrating keratoplasty . The causative organism was identified as Exophilia (Wangiella) dermatitidis, a dematiaceous fungus . The infection was cured with a combination of medical and surgical therapy . Inoculation of the isolate into rabbit corneas produced a similar keratitis from which the same organism was cultured . Miconazole levels measured in corneal tissue removed at surgery were approximately 25 times greater than the minimum inhibitory concentration for the fungal isolate.

Antimicrob Agents Chemother, 1984 Jun, 25(6), 690 - 3
Antibiotic susceptibility patterns in Rochalimaea quintana, the agent of trench fever; Myers WF et al.; Rochalimaea quintana, the etiological agent of trench fever, was tested by an agar dilution method for its susceptibility to the following 14 antibiotics: penicillin G, methicillin, ampicillin, cephalothin, vancomycin, doxycycline, tetracycline, erythromycin, chloramphenicol, streptomycin, kanamycin, rifampin, colistin, and amphotericin B . The MIC of each of these antibiotics was determined . The results showed that R . quintana is susceptible in vitro to these antibiotics, with the exception of vancomycin, kanamycin, streptomycin, colistin, and amphotericin B.

Chemioterapia, 1984 Jun, 3(3), 175 - 7
Synergic activity of beta-lactamines and aminoglycosides vs . bacterial strains treated with sub-MIC concentrations; Gismondo MR et al.; The aim of the present paper was to evaluate the interaction between beta-lactamines and aminoglycosides against Gram-positive and Gram-negative bacteria previously treated with sub-inhibitory doses of each antibiotic in the combination . Bacterial strains were: S . aureus ATTC 25923, S . mitis NCTC 3165, E . coli ATTC 25922, P . vulgaris ATTC 13315 . Antibiotics used were penicillin G and gentamicin . The most synergistic combination was the ratio of 4 (penicillin G) to 1 (gentamicin) before and after sub-MIC treatment with penicillin.

Chemioterapia, 1984 Jun, 3(3), 173 - 4
In vitro activity of ciprofloxacin against Chlamydia trachomatis and Ureaplasma urealyticum; Rumpianesi F et al.; The in vitro activity of ciprofloxacin against 5 strains of Chlamydia trachomatis and 5 strains of Ureaplasma urealyticum was tested . Both C . trachomatis and U . urealyticum showed a certain degree of variability in their susceptibility to the drug . The minimum inhibitory concentration (MIC) of ciprofloxacin against C . trachomatis was 1 micrograms/ml, whereas the minimum bactericidal concentration was greater than or equal to 10 micrograms/ml . The MIC of ciprofloxacin against U . urealyticum was 1 micrograms/ml for 3 strains and higher than 10 micrograms/ml for two strains.

Pathol Biol (Paris), 1984 Jun, 32(5 Pt 2), 654 - 7
{In vitro comparative study of the sensitivity of Aspergillus to antifungal agents}; Guinet R et al.; Minimum inhibitory concentrations (MIC) of amphotericin B, 5-fluorocytosine, miconazole, tioconazole, econazole and ketoconazole were determined for 310 Aspergillus strains belonging to four different species isolated from clinical specimens . Econazole exhibited the best in vitro activity with MIC less than or equal to 3.12 micrograms/ml for 96% of strains and less than or equal to 1.56 micrograms/ml for 68% . For amphotericin B, 69% of strains were less than or equal to 1.56 micrograms/ml and, for 5-fluorocytosine, 50% were less than or equal to 25 micrograms/ml . Miconazole and ticonazole exhibited comparable in vitro activities with MIC less than or equal to 6.25 micrograms/ml for 66% and 58% of strains respectively . Ketoconazole was the less active agent in vitro, with MIC less than or equal to 6.25 micrograms/ml for only 27% of strains . Moreover, this study demonstrated significant differences in susceptibility from species to species . A . fumigatus was susceptible to amphotericin B (75%) and 47% of strains were susceptible to 5-fluorocytosine . A . niger showed high susceptibility to amphotericin B (82%) and 5-fluorocytosine (82%) . A . flavus exhibited the highest resistance to 5-fluorocytosine (14%), the highest susceptibility to ketoconazole (72%), and average susceptibility to amphotericin B (41%) . A . nidulans was rarely susceptible to amphotericin B (21%) or 5-fluorocytosine (29%) and 46% of strains were susceptible to miconazole and ketoconazole . These results provide useful guidelines for the choice of antifungal agents in the difficult treatment of aspergillosis.

Cell, 1984 Jun, 37(2), 429 - 36
The use of RNAs complementary to specific mRNAs to regulate the expression of individual bacterial genes; Coleman J et al.; A naturally occurring small RNA molecule ( micF RNA), complementary to the region encompassing the Shine-Dalgarno sequence and initiation codon of the ompF mRNA, is known to block the expression of that mRNA in E . coli . We have constructed a plasmid that produces a complementary RNA to the E . coli lpp mRNA (mic{Ipp} RNA) . Induction of the mic(Ipp) gene efficiently blocked lipoprotein production and reduced the amount of lpp mRNA . Two mic(ompC) genes were similarly engineered and their expression was found to inhibit drastically production of OmpC . Analysis of several types of mic(ompA) genes suggests that micRNAs complementary to regions of the mRNA likely to come in contact with ribosomes were most effective . The novel capabilities of this artificial mic system provide great potential for application in both procaryotic and eucaryotic cells.

Antiviral Res, 1984 Jun, 4(3), 159 - 68
5-substituted deoxyuridines--structural requirements for antiviral activity against herpes simplex virus types 1 and 2 and possible biochemical basis for relative potency; Sim IS et al.; A number of structurally related 5-substituted pyrimidine 2'-deoxyribonucleosides were tested for antiviral activity against herpes simplex virus types 1 and 2 in cell culture . A minimum inhibitory concentration was determined for each compound and from a comparison of these values a number of conclusions were drawn with regard to those molecular features which enhance or reduce antiviral activity . Analogues in which the 5-substituent was unsaturated and conjugated with the pyrimidine ring were more potent antiviral drugs than the corresponding non-conjugated and alkyl-substituted analogues . The length of the 5-substituent and the nature of any heteroatoms contained within it also affected antiviral activity . When one pair of isomers was examined in more detail, differences in antiviral activity similar to those observed in cell culture occurred in virus-infected mice . The biochemical basis for the greater antiviral activity of the preferred isomer was related to affinity both for virus thymidine kinase and virus DNA polymerase.

Pathol Biol (Paris), 1984 Jun, 32(5 Pt 2), 488 - 91
{Nonparametric approach to the determination of critical diameters . Comparison with conventional methods}; Flandrois JP et al.; Bacteria are usually classified as susceptible (S), intermediate (l) or resistant (R) by comparison of their MICs with two reference MIC cutoff levels . Three sets Sc, Ic and Rc are thus constructed . By using agar diffusion, the same bacteria are classified as Sd, Id or Rd, by comparison of inhibition zone diameters with two reference diameter breakpoints . These Sd, Id and Rd sets are not absolutely identical with Sc, Ic and Rc respectively . Diameter breakpoints were submitted to successive adjustments until minimal differences were achieved, i.e . when the greatest possible number of elements was included in the sets: (Formula: see text) Comparison of this method with more conventional techniques emphasizes its value.

Pathol Biol (Paris), 1984 May, 32(5), 450 - 4
{Acute experimental pyelonephritis . Treatment with tobramycin . Influence of the rhythm of administration on efficacy and renal tolerability}; Herscovici L et al.; Acute experimental pyelonephritis was produced in rabbits by injecting E . coli (tobramycin MIC 1 mg/l) into the left kidney and temporarily obstructing the ureter . Animals were given 10 mg/kg tobramycin intramuscularly 48 h after surgery and subsequently every day for 7, 10 or 15 days, either in a single daily dose or in three divided doses at 8 h intervals . Animals were killed 24 h after the last injection . Comparison of results shows that kidneys were sterilized by a single daily dose but not by three divided daily doses . In rabbits given the single daily dose regimen, kidneys recovered a normal macroscopical and histological aspect, serum anti-E . coli antibodies rose more slowly and less significantly, serum creatinine increased less, and renal enzymatic activities were restored (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) . These findings suggest better efficacy and renal tolerance of the single daily dose regimen as compared to the three daily divided dose regimen in the treatment of acute experimental pyelonephritis.

Pathol Biol (Paris), 1984 May, 32(5), 351 - 4
{Determination of the minimum bactericidal concentration . Influence of various technical factors}; Thabaut A et al.; Measurement of minimal bactericidal concentrations of antibiotics is requisite to select the most appropriate drugs in severe infections . However, MBC assays are reliable only if the various technical modalities are well-standardized . We determined MBCs of ampicillin (E . coli), gentamicin (E . coli, P . aeruginosa, S . aureus), cefazolin (E . coli), ticarcillin (P . aeruginosa), and oxacillin (S . aureus), for different values of a number of parameters : inoculum from a 4 h and 18 h culture, measurement of MBC for 99.9% and 99.99% of bacteria, plate microdilution and macrodilution in plastic or glass test tubes, inoculation under a 1 ml or 0.1 ml volume, determination of MIC and subculture at the 24th hour, with or without Vortex agitation at the 20th hour . Most MBCs were identical for 99.9% and 99.99% of bacteria . Conversely, results were significantly modified by changes in other factors . Very high MBCs were consistently found in plastic tubes . MBCs were higher after inoculation under a 1 ml volume than under a 0.1 ml volume . MBC was usually similar to MIC with the microdilution technique, or with glass tubes, inoculation under a 0.1 ml volume and subculture at the 24th hour following Vortex agitation at the 20th hour.

Pathol Biol (Paris), 1984 May, 32(5), 318 - 21
{Comparative effects of 4 cephalosporins on the incorporation of tritiated diaminopimelic acid during bacterial growth}; Rolin O et al.; When comparing antibiotic activities, it might be of interest to study parameters other than minimal inhibitory concentrations (MIC's) . Specific activity of beta-lactams on bacterial cell wall makes it possible to determine radiolabelled diaminopimelic acid (DAP) incorporation in growing cultures . We have studied the effects of various concentrations of cefalotin , cefotaxime, latamoxef (moxalactam) and ceftiolene (42 980 RP) on DAP incorporation in 6 strains of E . coli, E . cloacae and S . aureus . Drug concentration which inhibits 90 % of radioactivity incorporation (CII 90) was found to vary from 0.1 X MIC to 3 X MIC . This fact suggests that beta-lactam action on cell wall synthesis and/or structure and MIC's are not always strictly correlated.

J Antibiot (Tokyo), 1984 May, 37(5), 532 - 45
Studies of 7 beta-{2-(aminoaryl)acetamido}-cephalosporin derivatives . I . Synthesis and structure-activity relationships in the aminopyridine series; Goto J et al.; The synthesis and in vitro activity of 7 beta-(2-aminopyridyl-2-alkoxyiminoacetamido)cephalosporins with various substituents at the 3-position are described . The effects of substitution pattern on the pyridine ring, oxime substituent and 3-substituent were studied as a function of the MIC values . Of these various kinds of derivatives, 7 beta-{2-(2-aminopyridin-6-yl)-2-alkoxyiminoacetamido}cephalo sporins exhibited significantly higher activity against most of micro-organisms.

J Clin Immunol, 1984 May, 4(3), 202 - 8
Mononuclear-cell subsets in human idiopathic crescentic glomerulonephritis (ICGN): analysis in tissue sections with monoclonal antibodies; Stachura I et al.; Mononuclear inflammatory cells (MIC) were analyzed in renal biopsies from 16 patients with ICGN (7 with glomerular immune complex deposits, 3 with anti-GBM disease, and 6 without immune deposits) by the avidin-biotin-immunoperoxidase technique utilizing monoclonal antibodies to cell surface antigens: T11 (total T), T4 (inducer/helper T), T8 (suppressor/cytotoxic T), B1 (B cells), M1 (monocytes/granulocytes), and Leu 7 {natural killer (NK) cells} . Total MIC were significantly increased in both glomeruli and interstitial tissues of the patients . Interstitial MIC consisted mainly of lymphocytes (80%) and monocytes (19%), with small numbers of B and NK cells present . In contrast, MIC in renal glomeruli of patients with ICGN were composed of monocytes (65%) rather than T lymphocytes (34%) . A majority of T lymphocytes found in renal tissues of patients and controls had the helper/inducer phenotype . Tissue T4/T8 ratios were not significantly different in the glomeruli and interstitium . Monocytes and T lymphocytes accumulating in renal tissues of patients with ICGN may mediate glomerular injury in all forms of human ICGN.

Pathol Biol (Paris), 1984 May, 32(5), 347 - 50
{Antibiotic sensitivity test . Comparative multicenter study of the gel diffusion and ATB methods}; Gayral JP et al.; The ATB method is a new method for antibiotic susceptibility testing . In a collaborative study, it was compared to a standard disc diffusion method . 23 strains were tested to determine reproducibility and 969 strains were used in the comparative study . Reproducibility of both methods is equivalent; differences due to strains were observed . Agreement between both methods is 87,9%, minor discrepancies are 8,7% and major discrepancies are 3,3% . Significant differences were found for carbenicillin and cefalotin and confirmed by MIC determination using the agar dilution method . Overall results show that the ATB method is reliable and comparable to disc diffusion for routine susceptibility testing.

J Antibiot (Tokyo), 1984 May, 37(5), 572 - 6
Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12; Rake JB et al.; The binding of cefonicid (SK&F 75073), a new parenteral cephalosporin, to the penicillin-binding proteins (PBPs) of Escherichia coli K-12 (strain KN-126) was determined by competitive binding studies versus benzyl{14C}penicillin . Cefonicid showed its greatest affinity for PBPs 1a greater than 3 greater than 1b, bound with low affinity to PBPs 4 greater than 2, and did not bind to PBPs 5 and 6 . Provisional affinity constants (cefonicid concentration that gave 50% inhibition of {14C}penicillin binding) were determined: PBP 1a, less than 0.25 microgram/ml; PBP 3, 0.7 microgram/ml; PBP 1b, 10 micrograms/ml; PBP 4, 26 micrograms/ml; PBP 2, 90 micrograms/ml; PBPs 5 and 6 greater than 256 micrograms/ml . Direct binding studies with {14C}-cefonicid confirmed this pattern of binding . Subinhibitory concentrations of cefonicid (MIC, broth 0.2 microgram/ml, agar 0.4 microgram/ml) induced filamentation of E . coli KN-126 . This implies that PBP 3 is the primary inhibitory site despite the higher affinity of PBP 1a for this cephalosporin.

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