Minimum inhibiting concentration

J Toxicol Sci, 1989 May, 14(2), 105 - 14
Non-specific cardiovascular depressant effect of methyl isocyanate (MIC) in rats; Kumar P et al.; Methyl isocyanate (MIC) either inhaled (5, 10 mg/lit) or administered by intravenous (5, 10, 28 mg/kg) or subcutaneous (1300, 1500 mg/kg) routes produced a dose dependent fall in blood pressure (BP) and heart rate (HR) in anaesthetised rats . Higher doses (10 mg/lit inhalation, 10 & 28 mg/kg i.v., 1500 mg/kg s.c.) increased the lung body weight index (LBI) and tracheobronchial resistance (TBR) concomitant with gross pulmonary damage and edema . However, lower doses (5 mg/lit inhalation, 5 mg/kg i.v., 1300 mg/kg s.c.) produced the cardiovascular depressant effect without affecting LBI, lung morphology and TBR . The effects of MIC on BP, HR and TBR were not counteracted by muscarinic, histaminic and 5-HT receptor blockers and by vagotomy . Studies with hydrolysis products of MIC showed that relatively large doses of methylamine (MA) and dimethylurea (DMU) (i.v.) produced cardiovascular depressant effects, without affecting the LBI & TBR . The results indicate that the cardiovascular depressant effect of MIC may not be entirely a sequel to its effect on respiratory organs, release of vasoactive substances or its hydrolysis products . A non-specific cardiovascular depressant effect of MIC is suggested.

Chest, 1989 May, 95(5), 1051 - 5
Combination of ofloxacin and amikacin in the treatment of sternotomy wound infection; Yew WW et al.; Mycobacterium fortuitum infection of soft tissue and wound (postoperative or otherwise) has been well reported in medical literature . In 1987, ten patients in our hospital with various cardiac diagnoses requiring open-heart surgery developed M fortuitum infection at the sternotomy site . As successful chemotherapy, in addition to surgical debridement, relies on in vitro susceptibility testing, ofloxacin and amikacin were thus assessed and found to have very satisfactory MIC . For the former: 1.25 mg/L for eight isolates, 2.5 mg/L for one isolate, and greater than 20 mg/L for one isolate were found . For the latter: 1 mg/L for six isolates, 2 mg/L for two isolates, and 4 mg/L and 8 mg/L for the remaining two isolates were found, respectively . These patients were given ofloxacin (300 mg once daily to 1,200 mg daily in divided doses) for three to six months and 500 mg amikacin daily (in two divided doses intravenously or intramuscularly) for three to eight weeks . The clinical outcome was favorable except for one patient who died of bacteremia due to M fortuitum coupled with many medical complications . Encouraged by these preliminary results, a future prospective study with ofloxacin as single agent for soft tissue, particularly postoperative sepsis due to M fortuitum, will be planned.

Mikrobiol Zh, 1989 May-Jun, 51(3), 81 - 4
{Choice of a method for determining the sensitivity of Escherichia coli to silver}; Potapchenko NG et al.; Different methods (methods of discs, of stamps and of minimal inhibitory concentration determination) aimed to determine the Escherichia coli sensitivity to the action of silver on the nutrient media are studied . It is shown possible to use the method of stamps for preliminary estimation under extensive tests . It is established that the data obtained by these methods correlate between themselves with a high degree of trustworthiness and do not correlate with those data obtained in the studies of the antimicrobic action of silver in water.

J Hosp Infect, 1989 May, 13(4), 395 - 8
Prophylactic parenteral cefuroxime: subcutaneous concentrations in laparotomy wounds; Huizinga WK et al.; Plasma and subcutaneous adipose tissue cefuroxime concentrations were measured in laparotomy wounds, by means of high-pressure liquid chromatography, in 12 patients undergoing elective abdominal operations . After intravenous administration of 1.5 g cefuroxime at induction of anaesthesia, the measured concentrations in serum and wound tissue during a 2 h period were above the MIC 90 of most micro-organisms derived from the alimentary tract . Tissue peak levels were reached within 15 min and the tissue half life was 1.5 h.

Pathol Biol (Paris), 1989 May, 37(5), 394 - 6
{In vitro activity of 5 new quinolones against Gardnerella vaginalis}; Lefevre JC et al.; The minimal inhibitory concentrations (MICs) of five new quinolones were determined by agar dilution, for 50 clinical isolates of Gardnerella vaginalis . They are compared with those of metronidazole, ampicillin, erythromycin and tetracycline which are widely used for the treatment of lower genital tract infections in women . The MICs of rosoxacin and pefloxacin are high, but those of ofloxacin (MIC 50, 2 mg/l), fleroxacin (MIC 50, 2 mg/l) and ciprofloxacin (MIC 50, 1 mg/l) are lower . They can explain the effectiveness observed with this latter antibiotic in vivo, and allow their clinical experiment.

J Virol, 1989 May, 63(5), 2002 - 7
Conformational change in the floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors; Pevear DC et al.; A series of eight antiviral compounds complexed with human rhinovirus 14 (HRV-14) were previously shown to displace segments of polypeptide chains in the floor of the "canyon" by as much as 0.45 nm in C-alpha positions from the native conformation (J . Badger, I . Minor, M . J . Kremer, M . A . Oliveira, T . J . Smith, J . P . Griffith, D . M . A . Guerin, S . Krishnaswamy, M . Luo, M . G . Rossman, M . A . McKinlay, G . D . Diana, F . J . Dutko, M . Fancher, R . R . Rueckert, and B . A . Heinz, Proc . Natl . Acad . Sci . USA 85:3304-3308, 1988) . Because the canyon is thought to serve as the viral receptor-binding site (M . G . Rossmann, E . Arnold, J . W . Erickson, E . A . Frankenberger, J . P . Griffith, H . J . Hecht, J . E . Johnson, G . Kamer, M . Luo, A . G . Mosser, R . R . Rueckert, B . Sherry, and G . Vriend, Nature {London} 317:145-153, 1985; M . G . Rossmann and R . R . Rueckert, Microbiol . Sci . 4:206-214, 1987), these compounds were assessed for their ability to block adsorption of HRV-14 to HeLa cell membrane receptors . In parallel experiments, the compounds were assessed directly for antiviral activity in an in vitro plaque reduction assay in intact HeLa cells . All eight compounds blocked the adsorption of 50% of HRV-14 at approximately the same concentration required to reduce the number of visible plaques by 50% (MIC) . A structurally related compound which was inactive in the plaque reduction assay had no effect on HRV-14 binding . A drug-resistant mutant of HRV-14 (Leu-1188), which was less sensitive to the eight compounds in plaque reduction assays was similarly less sensitive in the adsorption assay . We propose that the conformational changes in the floor of the HRV-14 canyon induced by these compounds substantially decrease adsorption of the virion to its receptor . These results provide further evidence for the role of the HRV canyon in receptor binding.

Res Microbiol, 1989 May-Jun, 140(4-5), 301 - 9
Rapid radiometric method for pyrazinamide susceptibility testing of Mycobacterium tuberculosis; Salfinger M et al.; Pyrazinamide (PZA) is one of the most important drugs in modern chemotherapy of tuberculosis . Since PZA is active only at an acid pH, testing the susceptibility of Mycobacterium tuberculosis to PZA is difficult and timeconsuming . Therefore, we evaluated the BACTEC system for rapid testing of PZA susceptibility at pH 6 . A total of 91 M . tuberculosis strains and 2 different strains of M . bovis BCG were screened for susceptibility to PZA . Each strain was tested in special 7H12 broth supplemented with polyoxyethylene stearate containing 25, 50 and 100 micrograms PZA/ml . Strains resistant to 100 micrograms/ml were retested against 25-100 micrograms/ml and at an extended range of PZA concentrations from 200-6,400 micrograms/ml . The MIC was determined with all strains within 4-20 (mean 7) days . Of the 77 susceptible strains, based on the pyrazinamidase test, MIC were less than or equal to 25 micrograms/ml for 34 strains, 50 for 38 and 100 for 2 strains . Three pyrazinamidase-positive strains had still higher MIC, 1 at 800 and 2 at 3,200 micrograms/ml . PZA-resistant strains had MIC of 800 or greater . Monoresistance to PZA has not been detected to date . The clear bimodal distribution of MIC in this method could enable the routine clinical microbiology laboratory to perform PZA susceptibility testing as easily as the 4 drugs now tested in the BACTEC system.

Kekkaku, 1989 May, 64(5), 345 - 9
{Evaluation of cycloserine in the treatment of infections caused by nontuberculous mycobacteria viewed from in vitro experiments}; Tsukamura M; Evaluation of cycloserine as a drug in the treatment of infections caused by nontuberculous mycobacteria was made from in-vitro studies, in which Mycobacterium tuberculosis strains were used as the standard of the evaluation . The susceptibility testing to cycloserine was made using Ogawa egg medium . Bacterial suspensions, 10 mg wet weight/ml, prepared from 10 day-old cultures (M . tuberculosis, 14 day-old cultures) growing on Ogawa egg medium were used as the source of inoculation . A 0.02 ml-sample of the suspensions was inoculated onto Ogawa egg medium containing cycloserine or containing no drug, and the media inoculated were incubated at 37 degrees C . The minimal inhibitory concentration (MIC) was determined after incubation for 14 days (M . tuberculosis, for 21 days) . The MIC was determined as the lowest concentration of the drug, on which the growth of test strains was completely inhibited . However, residual growth was sometimes observed . This was regarded as growth inhibition, because control medium containing no drug showed always abundant, membraneous growth . The results are shown in Fig. . The growth of M . tuberculosis strains was inhibited by the concentrations of 6.25 to 25 micrograms/ml . However, considering our previous observations on the relationship between the cycloserine resistance and the drug efficacy (reference 1), we regarded the MIC 12.5 micrograms/ml as critical concentration for presumable clinical efficacy . The ratios of strains of various mycobacterial species showing the MICs lower than the critical concentration are shown in Table . As seen in this table, clinical efficacy of cycloserine was expected in the treatment of infections caused by Mycobacterium kansasii, M . malmoense, M . simiae, M . scrofulaceum and M . marinum.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathol Biol (Paris), 1989 May, 37(5), 382 - 5
{In vitro comparative activity of five macrolides against 190 Branhamella catarrhalis strains}; Chardon H et al.; We compared the in vitro activity of 5 macrolides against 190 strains of Branhamella catarrhalis; 48 strains were isolated at Centre Hospitalier, Aix-en-Provence, the 142 others were isolated during 1987, in 15 different Centres-Hospitaliers-Generaux in France . 153 strains were betalactamase producing strains; no difference in susceptibility to erythromycin was observed on betalactamase producing and non producing strains . Three active macrolides against 100% of strains were: erythromycin (MIC 50 = 0.25 mg/l - MIC 90 = 0.50 mg/l), roxithromycin (MIC 50 = 0.50 mg/l - MIC 90 = 0.50 mg/l) and josamycin (MIC 50 = 0.50 mg/l - MIC 90 = 1 mg/l); A lower activity was noted on midecamycin (mic 50 = 2 mg/l - MIC 90 = 2 mg/l) and spiramycin (MIC 50 = 4 mg/l - MIC 90 = 8 mg/l).

J Burn Care Rehabil, 1989 May-Jun, 10(3), 209 - 12
Sensibility assay for topical agents . A new method; Lorenti AS et al.; We present a new laboratory method to test the sensibility of clinically isolated strains to topical agents . It is a method of dilution of the whole cream in a solid medium . The cream is weighted, suspended in sterile water, and maintained at 45 degrees C . Then a volume of that suspension is added to the agar, maintained at 45 degrees C also . The mixture is agitated and plated . Afterwards 25 strains are inoculated by a Multinoculator (Cetin, Bs . As., Argentina) . After incubation (18 hours at 37 degrees C), the results are obtained by observing the presence or absence of bacterial development . The minimal inhibitory concentration is calculated as the lowest concentration that inhibited growth . It is a simple, economical, and reproducible method.

Indian J Exp Biol, 1989 Apr, 27(4), 347 - 9
Effect of subacute exposure to methyl isocyanate on testicular histomorphology in mice; Arora U et al.; Mice exposed to methyl isocyanate (MIC; 134 mg.m-3 for 30 min = 4020 mg.min-1.m-3) showed a marked loss of body weight after 24 hr and the mean body weight of the exposed group was significantly less than the control, even 15 days after the exposure . No significant change was observed on relative testicular weight . Spermatozoa in the seminiferous tubules disappeared 3 days post exposure . Primary and secondary spermatocytes were hypertrophied . Normalization occurred after 15 days.

Antibiot Khimioter, 1989 Apr, 34(4), 291 - 3
{Sensitivity to antibiotics of pneumococci isolated from patients with chronic nonspecific pneumonia and bronchitis}; Molochko VA et al.; Four hundred and twenty two pneumococcal strains isolated from 300 patients with chronic nonspecific pneumonia and bronchitis were studied with respect to their sensitivity to 18 antibiotics within a period from 1982 to 1985 . It was shown with the method of serial dilutions on solid media that 91.7, 87.8, 85 and 81 per cent of the isolates were sensitive to benzylpenicillin, ampicillin, lincomycin and cefuroxime, respectively . A significant percentage of the pneumococcal strains had decreased sensitivity to benzylpenicillin (MIC close to the therapeutic concentration) . On this basis it was recommended to use lower concentrations of benzylpenicillin (less than 0.25 units/ml) in assay of sensitivity in clinical strains of Pneumococcus.

Kekkaku, 1989 Apr, 64(4), 313 - 7
{Sulfadimethoxine as a promising drug in the treatment of infections caused by Mycobacterium kansasii and Mycobacterium xenopi--differentiation between M . kansasii and M . marinum and between M . gordonae and M . scrofulaceum by the susceptibility testing to sulfadimethoxine}; Tsukamura M; Susceptibility testing to sulfadimethoxine of various mycobacteria was made using Ogawa egg medium containing various concentrations of the drug . Each medium was inoculated by a 0.02 ml-sample of bacterial suspensions (10 mg wet weight per ml) prepared from 10 day-old (M . tuberculosis, 14 day-old) cultures growing on Ogawa egg medium after homogenizing the bacteria by shaking with glass beads . The media inoculated were incubated at 37 degrees C for 14 days (M . marinum, at 28 degrees C) . The minimal inhibitory concentration (MIC) was determined as the lowest drug concentration on which the growth of bacteria was completely inhibited . However, residual growth occurred often . This was regarded as negative growth, because control medium containing no drug always exhibited abundant membraneous growth . Of the mycobacteria tested, M . kansasii (MICs, 0.8-3.2 micrograms/ml) and M . xenopi (MICs, 0.2-3.2 micrograms/ml) were most susceptible to this drug . Other mycobacteria showed the MICs higher than 3.2 micrograms/ml . The drug seemed to be useful in the treatment of infections caused by M . kansasii and M . xenopi . Furthermore, the susceptibility testing to sulfadimethoxine was considered to be useful for differentiation between two photochromogens, M . kansasii and M . marinum and for differentiation between two scotochromogens, M . scrofulaceum and M . gordonae (Fig . 3 and 4).

Antimicrob Agents Chemother, 1989 Apr, 33(4), 583 - 4
Pseudomonas cepacia susceptibility to sulbactam; Jacoby GA et al.; For 25 of 32 Pseudomonas cepacia isolates, predominantly from sputum of adult patients, agar dilution MICs of sulbactam were 2.5 micrograms/ml, and for only one was the MIC more than 80 micrograms/ml . Susceptibility was reliably predicted by response to a commercial sulbactam-ampicillin disk.

J Clin Periodontol, 1989 Apr, 16(4), 259 - 64
The in vitro effects of chlorhexidine on subgingival plaque bacteria; Stanley A et al.; The purpose of this study was to determine the susceptibility to chlorhexidine of a range of bacteria which may be isolated from subgingival plaque . In addition, the effect of chlorhexidine on the survival of bacteria in subgingival plaque samples from patients with chronic inflammatory periodontal disease was investigated . The minimum inhibitory concentration (MIC) of chlorhexidine for 52 strains of bacteria ranged from 8 to 500 micrograms/ml . The modal value of the MIC was found to be 62 micrograms/ml, 64% of the strains tested being inhibited at this concentration . A concentration of 250 micrograms/ml of chlorhexidine inhibited the growth of all bacteria in the 25 subgingival plaque samples investigated . The MIC of chlorhexidine for the samples ranged from 31 to 250 micrograms/ml, the modal value being 125 micrograms/ml.

Antimicrob Agents Chemother, 1989 Apr, 33(4), 591 - 2
Comparative antimycobacterial activities of difloxacin, temafloxacin, enoxacin, pefloxacin, reference fluoroquinolones, and a new macrolide, clarithromycin; Gorzynski EA et al.; The activities of fluoroquinolones and a new macrolide against 30 clinical isolates of Mycobacterium tuberculosis were determined in vitro by agar diffusion . In order of relative potencies against M . tuberculosis, temafloxacin (MIC for 90% of isolates {MIC90}, 2.3 micrograms/ml) was at least as active as the reference quinolones ofloxacin (MIC90, 2.4 micrograms/ml) and ciprofloxacin (MIC90, 4.3 micrograms/ml) . Less active were difloxacin (MIC90, 4.7 micrograms/ml), pefloxacin (MIC90, 6.7 micrograms/ml), and enoxacin (MIC90, 8.3 micrograms/ml) . The macrolide clarithromycin was more potent than erythromycin but less potent than the fluoroquinolones . Our results suggest that the newer fluoroquinolones and clarithromycin should be included with ciprofloxacin and ofloxacin in pharmacokinetic studies that may lead to trials in human subjects with mycobacterial infections.

Mikrobiyol Bul, 1989 Apr, 23(2), 145 - 9
{Identification of Pseudomonas species isolated from various clinical specimens and their susceptibility to ofloxacin}; Tunckanat F et al.; In this study Pseudomonas species isolated from various clinical specimens were identified and susceptibility of these species to ofloxacin was investigated . The identification of 88 Pseudomonas isolates was performed according to their pigment production, type of haemolysis, growth on cetrimide medium and growth at 42 degrees C . Oxidase test was also employed to all of these strains . Macrodilution method was used in order to investigate in vitro activity of ofloxacin against these strains . All of 88 isolates were identified as P . aeruginosa . Ofloxacin was found to have an MIC 50 value of 2 micrograms/ml and an MIC 90 value of 16 micrograms/ml for these isolates . Susceptibility to ofloxacin was observed in 86.4% of 88 P . aeruginosa.

Kansenshogaku Zasshi, 1989 Apr, 63(4), 417 - 23
{A case of infective endocarditis (IE) improving with orally administered amoxicillin (AMPC)}; Sakaki T et al.; Progress in chemotherapy and cardiosurgery has remarkably decreased the mortality due to infective endocarditis (IE) in recent years . In chemotherapy for IE, parental administration of antibiotics has been used routinely, the patients suffer from the psychological and physiological burden due to frequent injections and long period of therapy, even though the therapy for IE is successful . In this report, we present a case of IE caused by S . mitis, which was remarkably improved by oral administration of AMPC . A case, 69 . y.o . female . She felt like a common cold and visited a G.P . Cardiomegaly was pointed out and positive inflammatory findings in serological examination were found . A low grade fever continued, and she was admitted to the hospital . Blood cultures were positive for S . mitis . For further examination, she was transferred to the university hospital . Based on the extensive blood cultures and cardioechogram, she was diagnosed IE caused by S . mitis . Because there were no symptoms of heart failure, we decided to try oral administration of AMPC, 4 g/day or 6 g/day at an interval of 6 hours . On the second day of therapy, the blood culture turned to be negative for pathogens, and on the fourth day body temperature became normal . On about the 60th day, the CRP finding became negative . Concentrations in the serum of AMPC were more than 10 folds of AMPC-MIC (0.5 microgram/ml) for S . mitis . The patient, however, suffer from complications of lung embolism and was operated for exchange of heart valves . After surgery, she has been well without any symptoms from IE.

Arzneimittelforschung, 1989 Apr, 39(4), 428 - 31
Influence of various concentrations of cefotiam and ceftizoxime on the phagocytosis of gonococci by polymorphonuclear granulocytes; Korting HC et al.; Both cefotiam and ceftizoxime stimulate the uptake of gonococci by polymorphonuclear granulocytes in vitro as can be seen by light microscopy . Although this already holds true of antibiotic concentrations lower than the minimum inhibitory concentration (MIC: 1/4 x) this effect is much more marked at concentrations highly exceeding the MIC (4000 x) . As light microscopic investigation allows the analysis of large numbers of cells but no final judgement on actual bacterial engulfment definite phagocytosis is demonstrated by electron microscopy.

Hinyokika Kiyo, 1989 Apr, 35(4), 705 - 9
{Treatment of gonococcal urethritis with norfloxacin}; Mitsuya H et al.; Fifty six males with gonococcal urethritis were administered 600 mg of norfloxacin (NFLX) daily for 7 days, before the effects were examined . The pharmaceutical effects were studied on the third and the seventh day after administration . Pronounced effectiveness of 77.8%, effectiveness of 19.4% and ineffectiveness of 2.8% were found on the third day after administration, and pronounced effectiveness of 94.4%, effectiveness of 5.6% and ineffectiveness of 0% were found on the seventh day after administration . Effectiveness of 100% was obtained up to the seventh day . Minimum inhibitory concentration (MIC) of NFLX and ampicillin (AMPC) were determined for 14 strains . The peak of MIC of NFLX was found at 0.05 micrograms/ml and all strains were 0.78 micrograms/ml or lower . The peak of MIC of AMPC was 0.1 microgram/ml . MICs of both drugs were 0.78 micrograms/ml or lower, and resistant bacteria were not found . In view of the analyses of age distribution of patients and source of infection, the peak was found in the twenties and the source of infection in 64.7% were, so-called, professional women.

Zhonghua Yi Xue Za Zhi (Taipei), 1989 Mar, 43(3), 171 - 6
Colposcopic assessment in microinvasive carcinoma of the cervix; Liu WM et al.; Forty of the 87 patients with microinvasive carcinoma (MIC) of the uterine cervix who underwent surgery were diagnosed colposcopically and the results were compared with the cytological and histological diagnoses . The cytology showed preinvasive carcinoma in 20 (50.0%) patients and invasive carcinoma in 19 (47.5%) patients . A correct colposcopic diagnosis was made in nine (22.5%) patients as having microinvasive carcinoma, 21 (52.5%) patients preinvasive carcinoma and eight (20%) patients invasive carcinoma, to sum up accuracy rate as 32.1% . The abnormalities most commonly observed in colposcopy were mosaic, punctuation and white epithelium . In microinvasive carcinoma, the triad co-existed in 43% of the patients . Atypical vessels, characteristic of invasion, were found in only one third of the patients . Microinvasion, therefore, may not be evident on colposcopy alone . It is therefore necessary to apply cone biopsy, prior to definite therapy, to make an accurate assessment of the maximum depth and extent of the invasion prior to definitive therapy.

Diagn Microbiol Infect Dis, 1989 Mar-Apr, 12(2), 181 - 7
Pharmacokinetics and safety of lomefloxacin following multiple doses; Hunt TL et al.; This was a randomized, double-blind, placebo-controlled study comparing the safety and tolerance of 400 mg lomefloxacin, given orally twice daily, to that of placebo administered to eight and four subjects, respectively, for 2 wk . This dose, interval, and duration of dosing were chosen to be identical to the highest anticipated clinical dose for the longest anticipated clinical duration . Subject assessments included ophthalmological examinations performed prior to the study, at midstudy, and after the dosing . No clinically significant differences from baseline were observed for any test result . Analysis of trough plasma concentrations, CMIN, showed that steady state was achieved on Day 4 (Fig . 2) . At steady-state, mean plasma concentrations of lomefloxacin ranged from a maximum of 4.86 micrograms/ml to a minimum of 1.47 micrograms/ml . Mean time to maximum plasma concentration on Day 14 was 1.23 hr in the morning and 3.81 hr in the evening . Plasma half-life was approximately 8 hr . Lomefloxacin was well tolerated at 400 mg administered twice daily for 2 wk; plasma concentrations were maintained at a level that is above the MIC of most clinically significant isolates.

J Clin Microbiol, 1989 Mar, 27(3), 405 - 10
Variation in penicillin-binding protein patterns of penicillin-resistant clinical isolates of pneumococci; Markiewicz Z et al.; A large number of pneumococcal isolates (over 80 strains) from a variety of geographic locales and representing a spectrum of resistance levels from a penicillin MIC of 0.003 microgram/ml up to an MIC of 16 micrograms/ml were analyzed for their penicillin-binding protein (PBP) patterns . With a few exceptions, the great majority of strains with penicillin MICs up to about 0.05 microgram/ml contained the same set of five PBPs with molecular sizes typical of those of susceptible pneumococci . In strains with penicillin MICs of about 0.1 microgram/ml and up, virtually all isolates showed two common features: (i) all isolates showed loss of PBP 1A (98 kilodaltons) with or without a parallel appearance of a "new" PBP that ranged in molecular size between 96 and 97 kilodaltons; and (ii) in strains with penicillin MICs of 0.5 microgram/ml or more, PBP 2B could not be detected on the fluorograms even with very high concentrations of radioactive penicillin . Beyond these two common features, resistant strains with similar penicillin MICs showed a surprising variety of PBP profiles (i.e., in the number and molecular sizes of PBPs), each characteristic of a given isolate . We suggest that in pneumococci remodeling of critical PBPs in more than one way may result in comparable levels of penicillin resistance.

Diagn Microbiol Infect Dis, 1989 Mar-Apr, 12(2), 171 - 5
Effects of Escherichia coli spheroplast formation on assays of H2 and adenosine triphosphate based ampicillin susceptibility tests; Hornsten EG et al.; The present study examined the effects of ampicillin on one strain of Escherichia coli in lactose peptone broth with an osmolality of 342 mosm/L under anaerobic conditions . Spheroplast formation occurred at 10 X MIC of ampicillin . The metabolic changes that took place during spheroplast formation disfavored the production of molecular hydrogen . The intracellular bacterial adenosine triphosphate (ATP) level remained normal or slightly elevated during spheroplast formation while viability (cfu/ml) decreased . Thus spheroplast formation did not interfere significantly with ampicillin susceptibility as interpreted by assaying molecular hydrogen and viability . The effect on the ATP assay was, however, pronounced . It was found that the reversion of spheroplasts to bacterial cells for this particular strain (as recorded by cfu/ml) did not occur in quantitative numbers . The ATP assay thus indicated an approximate of the density of cells, while viability studies reported a lower cell density . When using a broth with lower osmolality (50 mosm/L) no spheroplast formation occurred and a close relation between viability and intracellular ATP was observed.

J Antimicrob Chemother, 1989 Mar, 23 Suppl C, 75 - 83
Lytic and bactericidal activity of FCE 22101; Jabes D et al.; We have examined the lytic and cidal activities of FCE 22101 against bacteria exhibiting genetic tolerance (pneumococcal mutants) and bacteria phenotypically tolerant to penicillin (Escherichia coli, deprived of an essential amino acid) . The pneumococcal strains included lyt- mutants in which the autolysin gene was inactivated or deleted and clinical isolates with penicillin MIC greater than 1.0 mg/l . The killing activity of FCE 22101 was superior to that of penicillin for all strains . FCE 22101 was also capable of inducing considerable lysis in all the lyt- strains in spite of the virtually complete inhibition (or actual absence) of the major autolysin . FCE 22101 also possessed bacteriolytic and cidal activity against a lysine-starved E . coli auxotroph (5 log kill in 24 h by 10 x MIC) . Assays of the binding of FCE 22101 to the pneumococcal penicillin binding proteins (PBPs) suggest that the superior performance of FCE 22101 may be related to a uniquely high affinity for bacterial targets specifically involved with the bactericidal activity of beta-lactam antibiotics.

Rev Infect Dis, 1989 Mar-Apr, 11(2), 335 - 7
Cure of bacille Calmette-Guérin vaccination abscesses with erythromycin; Murphy PM et al.; Postvaccination subcutaneous abscess due to bacille Calmette-Guerin (BCG) is an uncommon complication and is especially rare in the United States, where the general population is not vaccinated with BCG . This type of abscess is usually chronic, and optimal therapy has not been defined . Two Americans, a husband and wife, underwent primary BCG vaccination abroad and developed chronic subcutaneous abscesses at the primary inoculation site . Four months after vaccination, Mycobacterium bovis strain BCG was cultured from material aspirated from both lesions . Direct susceptibility studies revealed a minimal inhibitory concentration of less than 3.0 micrograms of erythromycin/mL for both isolates . Erythromycin was given orally to the husband and wife for 3 and 4 weeks, respectively, during which time complete healing occurred in both cases.

J Gen Microbiol, 1989 Mar, 135 ( Pt 3), 639 - 43
Inhibition of the binding of penicillin to the pneumococcal penicillin-binding proteins (PBPs) by exogenous cell wall peptides; Tuomanen E et al.; Incubation of pneumococci with D-alanine-containing peptides naturally occurring in peptidoglycan protected cells against lysis and killing by beta-lactam antibiotics near MIC . Such peptides caused decreased binding of the antibiotic to penicillin-binding proteins (PBPs), primarily PBP 2B . This provides direct evidence in vivo for the hypothesis that beta-lactams act as substrate analogues and identifies PBP 2B as a killing target in pneumococci.

Afr J Med Med Sci, 1989 Mar, 18(1), 63 - 7
An in-vitro study on ciprofloxacin and other anti-microbials against gram-negative bacteria isolated from patients in Ibadan, Nigeria; Rotowa NA et al.; The high prevalence of common clinical isolates that are resistant to multiple antibiotics calls for regular review of the anti-microbial sensitivity pattern among bacteria of clinical significance in our environment . In the present study an increasing percentage of common isolates from hospitalized patients have been found to be resistant to Gentamicin and Cefotaxime, which play an important role in the chemotherapy of infections . Of special significance is the finding that over 60% of pseudomonads are now resistant to Gentamicin . The new fluoroquinolone, Ciprofloxacin, showed strong activity against all the isolates tested, with MIC values within the range of those reported as sensitive from many overseas centres . It should prove to be a valuable agent in the management of infections due to these organisms.

J Infect, 1989 Mar, 18(2), 131 - 41
Genital gonorrhoea in women: a serovar correlation with concomitant rectal infection; Coghill DV et al.; Strains of gonococci isolated from 383 episodes of infection in women were classified serologically by means of two independently developed panels (Pharmacia (Ph) and Genetic Systems (GS} of monoclonal coagglutination reagents . Strains isolated from two groups of patients-those with concomitant genital and rectal infection (Group R) and those with genital infection in the absence of rectal infection (Group G)-were compared in order to determine whether certain strains of gonococci are isolated more often from women with concomitant rectal infection . Group R patients accounted for 126 (33%) episodes and Group G patients accounted for 223 (58%) episodes . Strains belonging to serogroup WII/III accounted for 61 (48%) Group R infections and 86 (39%) Group G infections . The difference was not statistically significant (0.1 greater than P greater than 0.05) . Strains of serogroup WI could be resolved into 7 Ph- and 10 GS-serovars while strains of serogroup WII/III could be resolved into 19 Ph- and 14 GS-serovars . One GS-serovar, Bajk, was isolated from 34 (27%) Group R patients compared with 39 (17%) Group G patients . This difference was statistically significant (P = 0.05) . Compared with non-Bajk isolates, Bajk strongly correlated with reduced susceptibility to penicillin: 60 (92%) Bajk isolates had minimum inhibitory concentrations (MIC) greater than or equal to 0.06 mg/l penicillin compared with 81 (33%) non-Bajk isolates (P less than 0.001) . The GS-serovar Bacejk, however, was significantly less susceptible to penicillin than was serovar Bajk: 26 (90%) Bacejk isolates had MICs greater than or equal to 0.12 mg/l penicillin compared with 29 (44%) Bajk isolates (P less than 0.001) . Therefore decreased susceptibility to penicillin does not lead in itself to rectal colonisation . It was concluded that certain gonococcal strains are more likely to cause concomitant rectal infection than others and that their reduced susceptibility to penicillin suggests that rectal test-of-cure cultures are essential in those women treated for anogenital infection.

J Med Chem, 1989 Feb, 32(2), 450 - 5
Synthesis and structure-activity studies of some disubstituted phenylisoxazoles against human picornavirus; Diana GD et al.; A number of 2,6-disubstituted analogues of disoxaril, a broad spectrum antipicornavirus agent, have been prepared and evaluated against several rhinovirus serotypes . A QSAR study revealed that the mean MIC (MIC) against five rhinovirus serotypes correlated well with log P . The 2,6-dichloro analogue, 15, was highly effective in vitro against rhinoviruses with an MIC80 of 0.3 microM, as well as against several enteroviruses, and was also effective in preventing paralysis in mice infected with coxsackievirus A-9.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1989 Feb, 22(1), 59 - 67
Isolation and in vitro susceptibility of Acanthamoeba from a patient with keratitis; Lee GS et al.; The acanthamoebae are facultative parasites of man, and may infect the brain, skin, bone, respiratory passages and eyes . Over the past several years, Acanthamoeba keratitis has become a growing problem . This is the first case isolating Acanthamoeba polyphaga from a corneal biopsy of an ophthalmic patient in Taiwan . Direct impression smear by trichrome stain gave positive result . To provide effective clinical treatment, chemotherapeutic agents available for ophthalmic use were tested for its susceptibility with a microtiter plate method . Reading at 24- and 48-hour intervals, only amphotericin B, clotrimazole and neomycin-polymyxin B had an MIC (minimal inhibition concentration) lower than 1,000 micrograms/ml . If reading interval was prolonged to one week, neomycin, 5-flucytosine and gentamicin also showed appreciable activity . Amoebicidal concentrations (AC) and cysticidal concentrations (CC) were much higher than MIC . Only neomycin-polymyxin B, neomycin, and amphotericin B of high concentration were proved to be cysticidal.

Pharmazie, 1989 Feb, 44(2), 131 - 2
In vitro release of gentamicin from beads, an original galenic form, and in vivo efficacy in abdomino-perineal surgery; Arminot du Chatelet AM et al.; The kinetics of the in vitro release of gentamicin by beads, an original galenic form (Gentabilles, Laboratoires Unicet-Unilabo France) was studied for 85 d during which time considerable quantities of antibiotic were released . A very large quantity was released on the 1st d (415 micrograms every 24 h per bead) and overall-there was a considerable time-effect, since on the 85th d, an average of 10 micrograms per 24 h per bead was still being released . The assessment of criteria of bacteriological effectiveness in the use in the in vivo treatment of abdomino-perineal excisions has shown that the MIC of gentamicin determined in relation to isolated organism is much lower than the tissue concentrations . The very low serum concentrations eliminate the possibility of an eventual cochleovestibulary toxicity or renal toxicity . The clinical results, the absence of infectious complications, the shortening of healing time and of duration of hospitalization are in favour of the extended use of this antibiotic prophylaxis in colo-rectal surgery.

J Rheumatol, 1989 Feb, 16(2), 175 - 80
Evidence of a new antigen-antibody system (anti-Mic-1) in patients with systemic lupus erythematosus and hyperthyroidism; Salazar-Paramo M et al.; Autoimmune thyroid diseases may occur in association with systemic rheumatic disorders, and usually they show a high prevalence of antithyroglobulin and antimicrosomal antibodies . We report 6 patients with the clinical association of systemic lupus erythematosus (SLE) and hyperthyroidism . Of interest, in 5 of the 6 patients (83%), we found an antibody directed against a microsomal extract of human thyroid gland which was different than previous microsomal antibodies in that it was a precipitating antibody; we have called it anti-Mic-1 antibody . We investigated the prevalence of this specific autoimmune reaction in 58 patients with idiopathic SLE, 30 with hyperthyroidism, 15 with Hashimoto's thyroiditis, 25 with insulin dependent diabetes mellitus, 45 with rheumatoid arthritis, and 25 healthy controls . No control had anti-Mic-1 antibody . In addition, this antibody was shown to be organ specific . We suggest that patients with the combined association of SLE and hyperthyroidism may represent a different subset in the spectrum of SLE . The high prevalence of this antigen-antibody reaction in these cases may serve as a serological marker of this association.

Antimicrob Agents Chemother, 1989 Feb, 33(2), 176 - 80
Amikacin, ciprofloxacin, and imipenem treatment for disseminated Mycobacterium avium complex infection of beige mice; Inderlied CB et al.; The Mycobacterium avium complex (MAC) is a common cause of disseminated infection in patients with acquired immunodeficiency syndrome and is increasingly seen as a cause of infection in other immunocompromised patients . Traditional antimycobacterial therapy often is ineffective, and there is a clear need for antibiotics with proven activity against the MAC . Three agents, amikacin, ciprofloxacin, and imipenem, were tested in vitro for activity against MAC strain 101 . Amikacin was bacteriostatic, with an MIC of 4.8 micrograms/ml, which is significantly lower than the concentration in serum obtained with standard dosing . Imipenem and ciprofloxacin had little or no activity alone (MICs, greater than 16 and 4.7 micrograms/ml, respectively), but when they were combined with amikacin there was bactericidal activity . Each agent was tested individually and in combination by using the beige mouse model of disseminated MAC infection . There was no mortality in a group of animals infected with MAC 101 and treated with amikacin alone; also, there was a significant decrease in the infection of the blood, liver, and spleen . There was no apparent improvement in therapeutic effectiveness when amikacin was combined with the other agents . Neither ciprofloxacin nor imipenem was active as a single agent, which was consistent with the in vitro activities of these agents . Amikacin in combination with traditional antimycobacterial agents warrants further study as potential therapy for disseminated MAC infections.

Antimicrob Agents Chemother, 1989 Feb, 33(2), 167 - 70
Multicenter randomized study of single-dose ofloxacin versus amoxicillin-probenecid for treatment of uncomplicated gonococcal infection; Black JR et al.; The safety and efficacy of ofloxacin, 400 mg orally, were compared with those of amoxicillin, 3.0 g, plus probenecid, 1.0 g orally, as single-dose therapy in 201 heterosexual patients (101 men and 100 women) with uncomplicated gonococcal infection . Treatment groups were comparable in age, duration of symptoms, number of sexual partners within the previous month, and number of previous episodes of sexually transmitted diseases . The cure rate for men treated with ofloxacin was 98% (47 of 48), and that for women was 100% (52 of 52) . Cure rates for both men and women treated with amoxicillin-probenecid were 96% (51 of 53 men; 46 of 48 women) . All 13 patients with positive rectal cultures and 7 of 8 patients with positive pharyngeal cultures treated with ofloxacin were cured . Neither regimen reliably eradicated coexistent infection with Chlamydia trachomatis . The MIC of ofloxacin for all but two of 198 pretreatment isolates was 0.3 microgram/ml or less . The MIC of amoxicillin for 90% of isolates tested was 1.0 microgram/ml . Single oral doses of ofloxacin and of amoxicillin plus probenecid were equally effective for treatment of urethral and cervical gonorrhea . Ofloxacin appears promising as treatment for rectal and pharyngeal infection, but studies with larger numbers of patients with rectal or pharyngeal infection or both are required for confirmation . Relative contraindications in children and possibly pregnant women plus the potential for single-step, high-level resistance may limit the usefulness of quinolone therapy for gonorrhea.

Antimicrob Agents Chemother, 1989 Feb, 33(2), 136 - 41
Chloramphenicol resistance in Pseudomonas cepacia because of decreased permeability; Burns JL et al.; The mechanism of chloramphenicol resistance was examined in a high-level-resistant isolate of Pseudomonas cepacia from a patient with cystic fibrosis . We investigated potential resistance mechanisms, including production of chloramphenicol acetyltransferase, ribosomal resistance, and decreased permeability . This strain (MIC, 200 micrograms/ml) had no detectable chloramphenicol acetyltransferase activity . In in vitro translation experiments in which we compared the resistant isolate with a susceptible strain of P . cepacia, inhibition of amino acid incorporation was equivalent even in organisms that were preincubated with sub-MICs of chloramphenicol . A 21.9-kilobase (kb) fragment of DNA was cloned which coded for chloramphenicol resistance; this fragment was expressed in P . cepacia but not in Escherichia coli . Quantitation of chloramphenicol uptake in the isogenic pair of susceptible and resistant organisms revealed a nearly 10-fold decrease of drug entry into the resistant strain . Comparison of isolated outer membrane proteins and lipopolysaccharide patterns identified no significant differences between the isogenic pair of organisms . We concluded that the mechanism of chloramphenicol resistance in this strain is decreased permeability.

Antiviral Res, 1989 Feb, 11(1), 15 - 26
Comparison of the anti-respiratory syncytial virus activity and toxicity of papaverine hydrochloride and pyrazofurin in vitro and in vivo; Wyde PR et al.; Based on reports describing their broad antiviral activity, the toxicity and antiviral efficacy of papaverine hydrochloride and pyrazofurin against respiratory syncytial virus (RSV) infection were tested in vitro in tissue culture cells and in vivo in cotton rats . Papaverine inhibited RSV replication in vitro; however, the median minimal toxic dose-median minimal inhibitory concentration ratios (MTD50:MIC50) in vitro and in vivo for papaverine were less than 4 . Further work with this compound was discontinued . In contrast, pyrazofurin inhibited RSV replication in vitro (a mean MIC50 of 0.04 microgram/ml was obtained) and in vivo (RSV pulmonary titers were significantly reduced consistently in cotton rats given daily 10 mg/kg doses compared to untreated control animals) . However, some toxic effects were observed in both the in vitro and in vivo tests of this compound . The remaining potential of pyrazofurin as an anti-RSV compound is discussed.

Arch Ophthalmol, 1989 Jan, 107(1), 93 - 5
Minocycline levels in tears of patients with active trachoma; Tabbara KF et al.; We determined minocycline levels in human tears and plasma samples using high-performance liquid chromatography . In the first study, we determined the trough tear and plasma levels of minocycline in patients with active trachoma 24 hours after an oral dose . After a single dose of minocycline, the mean concentration of the drug in tear samples was 189 +/- 58 ng/mL and corresponding plasma levels were 578 +/- 290 ng/mL . In a second study, we monitored the pharmacokinetics of the drug in tear and plasma samples of healthy nonfasting adults . Tear and plasma samples were collected at 1 through 6, 12, 24, 48, 72, and 96 hours . The pharmacokinetics study revealed that 48 hours following a single 200-mg dose of minocycline, the mean tear level of minocycline was 68 ng/mL, which is above the in vitro minimal inhibitory concentration required for Chlamydia trachomatis and other susceptible organisms.

J Infect Dis, 1989 Jan, 159(1), 16 - 25
Penicillin-binding protein families: evidence for the clonal nature of penicillin resistance in clinical isolates of pneumococci; Jabes D et al.; In view of the worldwide emergence of penicillin-resistant pneumococci among clinical isolates it was of importance to examine a large number of strains to test the uniformity of the resistance mechanism . Among 160 clinical isolates of pneumococci (minimum inhibitory concentration {MIC}, 0.005-16 micrograms/mL), susceptible strains showed a common pattern of five penicillin-binding proteins (PBPs) with high penicillin affinities (PBP 3 greater than 1A greater than or equal to 2A greater than 1B greater than 2B) . PBPs 1A, 2A, and 2B (but not PBP 3) each showed distinct stepwise decreases in penicillin affinities parallel with increasing levels of antibiotic resistance . The number and molecular sizes of PBPs became variable in strains with MIC values greater than 1.0 microgram/mL; among 39 strains with a MIC of greater than or equal to 1.0 microgram/mL, 11 distinct and stable PBP patterns could be identified . Using PBP profiles, serotypes, and antibiotic resistance patterns, as well as data on isolation dates and sites, we identified at least three groups of resistant strains that showed clear indication of clonal origin.

Chemotherapy, 1989, 35(2), 83 - 7
Penetration of imipenem into human pancreatic juice following single intravenous dose administration; Brattstrom C et al.; The penetration of imipenem into the human pancreatic juice following a single intravenous dose of 500 mg was investigated in five patients who had undergone pancreatic transplantation . With a special technique for segmental pancreatic transplantation it was possible to collect pure pancreatic juice at regular intervals . Simultaneous blood and pancreatic juice samples were collected immediately before drug administration and then at 0.5, 1, 1.5, 2.5, 3.5 and 5.5 h thereafter . The antibiotic concentrations were determined by the agar diffusion method . The mean peak level in serum was 24.6 +/- (SE) 2.6 mg/l and occurred 0.5 h after administration . The mean peak concentration in pancreatic juice was not reached until 1.5 h after administration, and the level was then 1.7 +/- (SE) 0.3 mg/l . Thereafter the levels in serum and pancreatic juice declined in parallel, and the concentration in pancreatic juice was then about 13% of that in serum . Although imipenem penetrates into the pancreatic juice at a very low degree, the concentrations exceeded the MIC values for many bacteria associated with pancreatic infections . Imipenem could therefore be an alternative as monotherapy in the treatment of pancreatic infections.

Ann Rech Vet, 1989, 20(2), 145 - 52
{In vitro antibiotic sensitivity of French strains of Mycoplasma bovis}; Poumarat F et al.; The in vitro activity of 15 antibiotics was tested with 30-90 Mycoplasma bovis representative strains of bovine lung pathology in France . The distribution of minimal inhibitory concentration (MIC) is homogeneous with low values for spectinomycin, lincomycin, tylosin, gentamicin and baytril, intermediate for chloramphenicol and neomycin, high for nalidixic acid, Flumequine and erythromycin . The MIC distribution is heterogeneous with intermediate values for spiramycin and tetracyclines, and high values for streptomycin . For the later antibiotics, the heterogeneity of the susceptibility suggests a mechanism of acquired resistance.

Ann Rech Vet, 1989, 20(2), 135 - 43
{Design and evaluation of an opacimetric method for determining the in vitro antibiotic sensitivity of Mycoplasma bovis}; Poumarat F et al.; A micromethod for the in vitro determination of Mycoplasma bovis sensitivity to antibiotics, based upon growth inhibition in liquid medium in which growth is directly estimated by measuring medium turbidity is described . The variability of inoculum density has little influence on corresponding minimal inhibitory concentration values . This method, regardless of the mycoplasma species used, gives results similar to those obtained with standardized procedures for other bacteria in liquid media.

Mycoses, 1989 Jan, 32(1), 39 - 45
Skin blister fluid levels of ketoconazole during repetitive administration in healthy man; Korting HC et al.; Ketoconazole administered orally is used in the treatment of superficial and deep mycoses . To evaluate its active concentrations in skin tissue, serum, suction blister fluid (SBF), and cantharides blister fluid (CBF) levels of total and non-protein bound ketoconazole were determined . In general, only the free drug is considered to be the active one . Six healthy subjects received 200 mg once daily for 5 days . Total ketoconazole concentrations were determined by HPLC . The unbound fractions of ketoconazole in SBF (2.3%) and CBF (1.2%) were calculated from plasma protein binding (99.0%) . Before the ultimate dose, levels of unbound ketoconazole in SBF and CBF were 0.64 +/- 0.16 and 0.70 +/- 0.25 ng/ml and were thus in accordance with free ketoconazole serum levels (0.52 +/- 0.24 ng/ml; p greater than 0.05) . Furthermore, following the ultimate dose, the areas under the blister fluid level-time curves of unbound ketoconazole did not differ from the respective areas under the serum level time curves, thus distribution equilibrium between serum and skin blister fluid was obtained . Peak concentrations of free ketoconazole were (SBF) 8.6 +/- 2.9 ng/ml and (CBF) 8.9 +/- 2.3 ng/ml . Free concentrations in SBF and CBF were far below the MIC values for dermatophytes and Candida ssp . reported in the literature, leaving the concentration-effect relationship of ketoconazole still open for discussion.

Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 51 - 5
Activity of cefotaxime/desacetylcefotaxime with two aminoglycosides against gram-negative pathogens: an example of interactive synergy; Jenkins SG; The susceptibility patterns of clinical Gram-negative isolates were determined to cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination with gentamicin (GENT) or tobramycin (TOB) by an agar dilution technique . A constant ratio of 1:1 (CTX to dCTX) was tested throughout the study . Isolates were challenged with subinhibitory levels of TOB or GENT in combination with clinically achievable levels of CTX, dCTX and CTX/dCTX to examine the interactions of the agents . Results of this study demonstrate that CTX/dCTX interacts synergistically with aminoglycosides against many Gram-negative pathogens . Synergy (defined as a fourfold or greater decrease in minimum inhibitory concentration (MIC) when CTX/dCTX was compared to CTX/dCTX/TOB) was demonstrable for 55% of isolates tested . Similarly, 45% were synergistically inhibited by CTX/dCTX/GENT . Additivism (a 2-fold decrease in MIC with the same comparisons) was evident for an additional 18 isolates for CTX/dCTX/TOB and 19 with CTX/dCTX/GENT . When data for Pseudomonas spp . were excluded from the analysis, synergy or additivism was evident with CTX/dCTX/TOB for 88% of the organisms tested and 72% with CTX/dCTX/GENT . Synergistic synergy for CTX/dCTX/TOB (an 8- to greater than 16-fold decrease in MIC for CTX) was demonstrable for 35 and 32 of 82 nonspeudomonal isolates respectively with the TOB and GENT combinations . Ninety nine percent of the nonspeudomonal isolates were inhibited by less than 4 micrograms/ml of CTX, 4 micrograms/ml of dCTX and 0.12 micrograms/ml of TOB, or 0.25 micrograms/ml of GENT, respectively.

Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 1 - 4
Susceptibility of nosocomial isolates of Candida species to LY121019 and other antifungal agents; Pfaller MA et al.; LY121019 is a novel analog of the polypeptide antifungal antibiotic echinocandin B . We investigated the in vitro activity of LY121019, amphotericin B, ketoconazole and 5-fluorocytosine against 131 nosocomial isolates of Candida species: C . albicans (n = 50), C . tropicalis (n = 30), C . rugosa (n = 12), C . parapsilosis (n = 11), C . lusitaniae (n = 10), C . guillermondii (n = 9), and C . krusei (n = 9) . In vitro susceptibility testing was performed using a broth microdilution method . The minimal inhibitory concentrations (MIC) of LY121019 were less than or equal to that of the other antifungal agents against C . albicans and C . tropicalis but were generally higher for the other species of Candida . Paradoxical growth at high concentrations, but not at low concentrations, of LY121019 was observed with isolates of C . albicans and C . tropicalis.

Kekkaku, 1989 Jan, 64(1), 1 - 5
{Cross-resistance relationships of antituberculosis drugs in Mycobacterium avium complex}; Tsukamura M; At present, infection caused by Mycobacterium avium complex is usually treated by chemotherapy of antituberculosis drugs . However, cross-resistance relationships of antituberculosis drugs in the M . avium complex have not yet been studied . In the present study, we studied on this subject using three strains which were isolated from sputum specimens of patients who were not treated by any antituberculosis drugs: strain 13008 (serotype 20), strain 13016 (serotype 4) and strain 13034 (serotype 18) . The methods used for isolating mutants resistant to rifampicin, isoniazid, ethambutol, streptomycin, kanamycin and/or enviomycin were described previously (Tsukamura, M: Kekkaku 62: 445-458, 1987) . Mutants resistant to ethionamide were isolated from strains 13008 and 13016 at a rate of 10(-6) and mutants resistant to kitasamycin at a rate of 10(-5) to 10(-6) (these were not isolated from strain 13034) . In contrast, mutants resistant to minocycline were isolated from strain 13034 only at a rate of 10(-4) . Susceptibility testings to antituberculosis drugs were carried out as follows . Bacterial suspensions, 10 mg wet weight/ml, were prepared from ten day-old cultures of the strains growing on Ogawa egg medium slants . Each 0.02 ml-sample of the suspensions was inoculated onto Ogawa egg medium with or without a drug by a spiral loop . The media inoculated were incubated at 37 degrees C for 14 days . Minimal inhibitory concentration was determined as a concentration, on which no membraneous growth could occur . The results are shown in Tables 1 to 3 . Cross-resistance relationships were observed only between ethionamide and isoniazid . Ethionamide-resistant mutant strains were resistant to isoniazid.(ABSTRACT TRUNCATED AT 250 WORDS)

Ophtalmologie, 1989 Jan-Mar, 3(1), 73 - 6
{Advances in the medical treatment of bacterial endophthalmitis}; Bron A et al.; Currently, the systemic antibiotics intraocular penetration's rate is low and we have to perform intraocular antibiotics injections to reach levels above the minimal inhibitory concentration of the bacterial agents found commonly in endophthalmitis . Authors try to specify a rational strategy based on pharmacokinetics and bacteriological aspects of a new class of antibiotics, the fluoroquinolones, using their own studies and those from other teams about the intraocular distribution of these antibiotics . Further investigation is mandatory to assess the safety and efficacy of our first clinical results.

Chemotherapy, 1989, 35(5), 326 - 9
Penetration of third-generation cephalosporins into human peritoneal tissue; Berger SA et al.; Each of 40 patients underwent elective laparotomy following administration of a single 1.0-gram intravenous dose of ceftizoxime, ceftriaxone, cefoperazone or cefotaxime . Therapeutic concentrations of cefoperazone and ceftriaxone were achieved in peritoneal tissue in 20/20 patients . Only 9/20 samples from patients receiving the other two antibiotics had detectable antibiotic activity . The antibiotic concentration in peritoneal fluid (7 samples) was 2.36-11.15 times higher than that of concurrently obtained peritoneal tissue . When adjusted for the in vitro susceptibility (MIC) of potential peritoneal pathogens, our data suggest that ceftriaxone and cefoperazone may be preferable to other third-generation cephalosporins for the prophylaxis and therapy of intraabdominal infection.

Bull World Health Organ, 1989, 67(2), 197 - 202
Response of Plasmodium falciparum to chloroquine treatment: relation to whole blood concentrations of chloroquine and desethylchloroquine; Hellgren U et al.; A standard treatment with 25 mg chloroquine base per kilogram body weight was given to 39 semi-immune asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia . Whole blood chloroquine and desethylchloroquine concentrations were monitored 12 times during 30 days of follow-up using 100 microliters capillary blood dried on filter-paper . All but three children had detectable amounts of chloroquine (greater than or equal to 10 nmol/l) in their blood before treatment . The interindividual variations in concentrations during the first week were 3.3 to 5.1-fold for chloroquine and 3.5 to 6.3-fold for desethylchloroquine . In seven children with RII response in vivo, the highest determined chloroquine concentration was lower (P = 0.029) than in the others . After treatment, a rough approximation of the minimum inhibitory concentration in vivo was made by calculating the average of the chloroquine concentrations before and after the time when parasites increased or reappeared again . RII-resistant parasites increased in number when the median residual whole blood concentration in the children was approximately 790 (range, 444-869) nmol/l . Parasites reappeared when the median residual whole blood concentrations was approximately 147 (range, 44-673) nmol/l . We conclude that interindividual variations of chloroquine concentrations have an impact on the outcome of treatment and the classification of resistance in vivo.

Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 107 - 11
Comparative study of three different dosing regimens of cefotaxime for treatment of gram-negative bacteremia; Trenholme GM et al.; Thirty-one patients with Gram-negative bacteremia with organisms susceptible to cefotaxime (CTX) (MIC of 1 microgram/ml or less) were randomized to receive 2 g of CTX every 6, 8, or 12 hr . Five-hour susceptibility studies were performed on a bacterial pellet obtained from the patient's positive blood culture vial . Thus, patients were enrolled within hours after Gram-negative organisms were demonstrated in their blood cultures . All bacteremias were cleared although two patients had unsatisfactory responses to therapy . Trough serum bactericidal levels were 1:2 or greater in all patients . This study supports that CTX can be used at an 8- or 12-hr intervals in selected patients with Gram-negative bacteremia.

Clin Pharmacokinet, 1989, 16 Suppl 1, 25 - 31
Clinical significance of antibiotic tissue penetration; Schentag JJ; The concentrations achieved by a particular antibiotic in serum and tissues can be predicted from pharmacokinetic data . These predictions must be evaluated in the broader context of the patient's infection, particularly the MIC of the drug for the infecting organism . What is the relevant measurement - the serum concentration or the tissue to serum ratio? Are the serum and/or tissue concentrations achieved at the site of infection sufficiently in excess of the MIC to eradicate the organism? How long are these levels sustained? How often must the drug be given to keep the concentrations sufficiently in excess of the MIC to eradicate the organisms? This presentation will review these questions in the context of the major classes of antibiotics: the beta-lactams, aminoglycosides and quinolones.

J Clin Microbiol, 1989 Jan, 27(1), 192 - 5
Quality control limits for the standard anaerobic reference agar dilution susceptibility test procedure of the National Committee for Clinical Laboratory Standards; Barry AL et al.; Multilaboratory studies were performed to develop MIC quality control limits for the National Committee for Clinical Laboratory Standards reference agar dilution method for anaerobic susceptibility tests . Acceptable MICs were defined as those which include greater than 95% of all 100 MICs generated by the study . Most MIC control limits included either 2- or 3-dilution intervals rather than the more traditional 3-dilution intervals that are described as the mode +/- 1 doubling dilution.

Cytobios, 1989, 59(238-239), 167 - 76
Genotoxicity studies on mice after short term inhalation exposure to methyl isocyanate; Kar RN et al.; Mutagenicity testing is an important aspect of the toxicological evaluation of environmental chemicals for safety . Methyl isocyanate (MIC), a very hazardous chemical used for the manufacture of insecticides, was studied for its genotoxic effects on the somatic cells of mice after inhalation exposure by means of an in vivo micronucleus test and chromosomal analysis of bone marrow cells . Animals were exposed for 10 min to different concentrations (2.40, 4.80 or 7.20 microliters) of MIC in a 22 litre chamber at 0 and 24 h . Bone marrow smears prepared 6 h after the second treatment were examined for the occurrence of micronuclei (MN) in polychromatic (P) and normochromatic (N) erythrocytes . The frequencies of cells with MN and the P/N ratio did not differ significantly from those of the control at all the exposure levels . Chromosomal preparations revealed few structural and numerical abnormalities . Aberrations encountered were of the chromatid type only . Quantitative analyses failed to exhibit any significant increase in aberration rates in the three treated groups . Numerical abnormalities were within the control range.

Mikrobiyol Bul, 1989 Jan, 23(1), 64 - 70
{In vitro susceptibility of dermatophyte strains to imidazole derivatives}; Bozkurt M et al.; Recently, imidazole derivatives are being successfully used for the dermatomycoses . These drugs have the strongest antimycotic activity . 44 dermatophyte strains were isolated from our out-patient with dermatomycosis . Imidazole derivatives such as isoconazole, oxiconazole, bifonazole and tioconazole were studied their efficacy on these fungal agents in vitro . 4 imidazole derivatives were effective on all of the dermatophyte strains in less than or equal to 5 micrograms/ml concentration . Whereas, there were differences in Minimal Inhibition Concentration (MIC) and MIC50 values.

Eur J Clin Pharmacol, 1989, 37(6), 577 - 80
Penetration of cefoperazone into ascites; Van Gossum A et al.; The pharmacokinetics of cefoperazone was studied in eleven cirrhotic patients with ascites after i.v . administration of a single dose of 15 mg.kg-1 (n = 7) or after three doses of 15 mg.kg-1 given at 12 h intervals (n = 4) . The concentrations of cefoperazone in serum and ascitic fluid were determined by HPLC . The peak serum cefoperazone concentration after a single i.v . injection of 15 mg.kg-1 was 96.0 mg.l-1 . The serum elimination half-life was longer (5.0 h) than in normal subjects . The penetration of cefoperazone into ascites was satisfactory (32.3% and 58.3% after single and repeated injections, respectively) . Ascitic fluid concentrations of cefoperazone exceeded 5.4 mg.ml-1 from 0.5 to 6 h after the single i.v . injection, levels which are well above the MIC of most pathogens found in spontaneous bacterial peritonitis . Adjustment of the dose of cefoperazone in cases of severe hepatic insufficiency does not appear to be necessary provided that renal function is normal.

Ann Biomed Eng, 1989, 17(5), 495 - 505
Comparison of two impedance cardiographic techniques for measuring cardiac output; Gotshall RW et al.; The purpose of the present study was to compare cardiac outputs obtained by both the Kubicek (MIC) and Sramek (NCCOM3) impedance cardiographic techniques with thermodilution (TD) in critically ill patients . The two impedance techniques were also compared in normal subjects . Seven healthy subjects and ten patients in the intensive care unit were enlisted in the study . Only those subjects with successful measurements by all three methods were used in the data analysis . Three measurements of cardiac output were made in each subject . In patients, there were no significant differences in cardiac outputs as measured by TD (6.61/min), MIC (6.3 1/min), NCCOM3 (6.4 1/min) . MIC and NCCOM3 cardiac outputs were correlated and approximated the line of identify when compared to TD . In normals, however, the NCCOM3 overestimated the cardiac output (NCCOM3, 9.2 1/min; MIC, 6.2 1/min) . Because of these inconsistent results, caution is urged when interpreting the values obtained by the NCCOM3 . In contrast, the use of the MIC in both populations has been reaffirmed.

Acta Pol Pharm, 1989, 46(2), 101 - 13
{Studies on pyrazine derivatives . XXVI . Synthesis and tuberculostatic activity of N-pyrazinylthiourea}; Wisterowicz K et al.; 2-Amino-3-chloropyrazine and 2-amino-6-chloropyrazine were reacted with appropriate sodium alkoxides to give 2-aminopyrazine derivatives with the methoxy, benzyloxy, chlorobenzyloxy, dichlorobenzyloxy, bromobenzyloxy or dibromobenzyloxy group at positions 3 and 6 (I-XIV) . The obtained compounds were converted into N-pyrazinyl-N'-benzoylthioureas (XV-XXXI) by reacting with benzoyl isothiocyanate . Their hydrolysis yielded N-pyrazinylthioureas XXXII-XLVII . Analogical reactions of alkoxyaminopyrazines with p-chlorophenyl isothiocyanate or 2,6-dichlorophenyl isothiocyanate afforded corresponding N-pyrazinyl-N'-(p-chlorophenyl)thioureas and N-pyrazinyl-N'- (2,6-dichlorophenyl)thioureas (XLVIII-LVIII) . The obtained compounds were found to display tuberculostatic in vitro activity with MIC values from 8 meg/cm3 to 1000 mu meg/cm3.

Chemotherapy, 1989, 35(6), 423 - 30
Correlation between growth curves and killing curves of Escherichia coli in the presence of fleroxacin and ampicillin; Yourassowsky E et al.; Fleroxacin, a new long-acting quinolone, induces rapid killing and bacterial filamentation as do other quinolones . Ten strains of Escherichia coli were exposed comparatively to fleroxacin and ampicillin in order to determine the effect of sub- and supra-inhibitory concentrations of each of these two compounds on turbidimetric growth curves and viable counts . By comparing the maximal early increase in optical density (OD, PIOD) as colony-forming units per milliliter (CFU/ml) after 2 and 6 h of exposure to antibiotics, we observed a reduced number of CFU/ml in comparison with the control after the 2-hour exposure at 1/4 the minimum inhibition concentration (MIC) and after 6 h at 1/8 MIC, but a high OD value was also seen among the fleroxacin exposed bacteria . For ampicillin, PIOD rates and killing rates were slower and dose dependent . This discrepancy was due to filament formation, which increased the PIOD value to the same extent as the control curve . After exposure to fleroxacin at 1/2 MIC the PIOD decreased significantly and after 2 and 6 h E . coli killing rates of 99 and 99.9%, respectively, were observed . With exposure to 2 and 4 x MIC, both PIOD values and CFU/ml decreased substantially . Combined analysis of continuous turbidimetric monitoring and viable counts showed that subinhibitory concentrations of fleroxacin and beta-lactam had different effects on E . coli . Fleroxacin's rapid killing rate, despite filament formation, contrasted with the result obtained with ampicillin . The minimum antibiotic concentration of fleroxacin against E . coli was around 1/8 MIC.

Acta Leprol, 1989, 7 Suppl 1, 44 - 7
Beta-lactamase production and biological characteristics in nitrosoguanidine induced Mycobacterium fortuitum mutants; Fattorini L et al.; In order to elucidate the role of beta-lactamase in the resistance of M . fortuitum to beta-lactams, M . fortuitum ATCC 19542 and three mutants, strains D 316, D 319 and D 170 obtained from it by nitrosoguanidine treatment, were studied . Furthermore the kinetics of the beta-lactamase production during the bacterial growth and many biochemical and enzymatic characteristics of parent and mutant strains were investigated . Amoxicillin MICs well correlated with the beta-lactamase production in the high producer strains D 316 and D 319; on the contrary in strain D 170 a high MIC was joined with a moderate production of the enzyme showing that not only beta-lactamase but also other mechanisms can be effective in the resistance of M . fortuitum to beta-lactams . Clavulanic acid, an inhibitor of beta-lactamase, reduced MICs to amoxicillin in high and in low producer strains . The production of extracellular beta-lactamase occurred in a M . fortuitum mutant strain mainly during the stationary phase, indicating that a cell wall damage or initial autolysis could be responsible for the release of enzyme . Enzymatic and biochemical characteristics were not affected by nitrosoguanidine treatment except for nitrate test which showed only a weak positivity in high producer strains.

Kansenshogaku Zasshi, 1989 Jan, 63(1), 35 - 8
{In vitro susceptibility of a strain of Rickettsia recently isolated from a case of Japanese spotted fever to chemotherapeutic agents}; Suto T et al.; The in vitro susceptibilities to five chemotherapeutic agents against a rickettsial strain which was isolated from a case of Japanese spotted fever were determined by cell culture system . Minocycline was the most effective (MIC, 0.15 micrograms/ml) followed by Tetracycline and Demethylchlor tetracycline (0.31 micrograms/ml 0.16 micrograms/ml) . Chloramphenicol was less effective (5 micrograms/ml) and Aminobenzyl-penicillin was not effective with the MIC of 10 micrograms/ml or less . Thus, the earlier administration of Minocycline is recommended to clinically suspicious cases of Japanese spotted fever as well as Tsutsugamushi disease.

Autoimmunity, 1989, 3(2), 113 - 23
Immunocytochemical study of localization and traffic of thyroid peroxidase/microsomal antigen; Alquier C et al.; We studied the distribution of binding sites for anti-peroxidase monoclonal antibody and anti-microsomal antibodies on isolated human thyroid follicles and a human thyroid cell line . Both open follicles and cells were incubated first with antibodies at +4 degrees C, then with colloidal gold labelled protein A . The topography of the binding sites for monoclonal anti-peroxidase antibody corresponded closely to the expected cell surface distribution of endogenous thyroid peroxidase since labelling was observed at the apical cell surface of the follicles . Furthermore, labelling was restricted to the microvilli level; while smooth membrane territories were devoid of binding sites . In some cases, incubations at 4 degrees C were followed by warming the follicles and cells up to 37 degrees C for 20 minutes in order to study internalization of ligands . Ligands were then observed in intracellular organelles: endosomes and lysosomes . Essentially the same results were observed when human antibodies to the microsomal antigen were used . Controls with microsomal antibodies depleted in anti-peroxidase were negative . In conclusion these findings show that: 1) thyroid peroxidase is present in limited areas on the apical cell surface, 2) labelling of follicles and cells by the anti-microsomal antibodies had the same pattern of distribution as the monoclonal anti-peroxidase antibody, thus suggesting that they recognize the same apical antigens, and 3) TPO/MIC antigen traffics from the cell surface towards lysosomes when the cells are incubated at 37 degrees C.

Boll Ist Sieroter Milan, 1989, 68(1), 17 - 23
{In vitro sensitivity of 3 strains of Leptospira interrogans to 3 different antibiotics}; Benzi Cipelli R et al.; Leptospirosis, anthropo-zoonosis ubiquitously widespread, is a social and economic problem still to be solved . The experimental and therapeutic employment of many antibiotics has largely been tested "in vitro" and "in vivo" . In the following research we tried to evaluate, by experimental "in vitro" method, the sensitivity difference of three serovar strains of Leptospira interrogans to two macrolides, Erythromycin and Josamycin, compared with Penicillin . From standard cultures, previously treated with serial dilution of these antibiotics, the MIC and MSC, as quantitative parameters, have been stated . For the qualitative evaluation of the damages induced at ultrastructural level by the drug activity . Electron Microscopy investigations were performed on specimens from cultures treated for 6 hr with twice and tenfold the MSC . The present research confirms the good sterilizing efficaciousness "in vitro" of the tested macrolides (MSC less than 1 mcg/ml) and their different activity pathway.

Perit Dial Int, 1989, 9(1), 57 - 9
Pharmacokinetics of aztreonam administered i.p . in continuous ambulatory peritoneal dialysis (CAPD) patients; Nikolaidis P et al.; The pharmacokinetics of Aztreonam (AZT) administered i.p . in six stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for end-stage renal disease (ESRD) were studied . One gram of AZT was added into a 2 L bag of dialysate (Medital-Bieffe) just prior to infusion into the peritoneal cavity . The dwell time was 8 h . The serum maximum concentration of AZT was 42.5 +/- 12.4 mg/L (mean +/- SD), achieved in 4.6 +/- 1.0 h . The elimination half-life was 2.4 +/- 0.8 h, almost equal to that found in normal subjects (1.7-2 h) . The pharmacokinetic parameters of elimination, as elimination rate constant and clearance of AZT from peritoneal cavity were found 0.305 +/- 0.101 h-1 and 10.05 +/- 3.7 mL/min, respectively, while the bioavailability via the peritoneal membrane was 90.8 +/- 3.05% of administered dose . It is concluded that AZT is eliminated from dialysate at a high rate after i.p . administration and its dialysate and serum levels exceed the MIC for the majority of sensitive organisms including Pseudomonas species . Aztreonam appears to be a potentially useful antibiotic for CAPD peritonitis.

J Ethnopharmacol, 1988 Dec, 24(2-3), 233 - 46
Wheat rootlet growth inhibition test of Rwandese medicinal plants: active principles of Tetradenia riparia and Diplolophium africanum; van Puyvelde L et al.; A series of 50 medicinal plants of Rwanda (121 plant samples) has been screened for wheat rootlets inhibition activity . The minimum inhibitory concentration (MIC) of the active principle of Tetradenia riparia, i.e . 8(14),15-sandaracopimaradiene-7 alpha, 18-diol (7.81 micrograms/ml), and of the active principle of Diplolophium africanum, i.e . scoparone (62.5 micrograms/ml), in this test was determined.

J Antimicrob Chemother, 1988 Dec, 22(6), 899 - 904
Use of a continuous culture system for susceptibility testing of gram-negative bacterial isolates to piperacillin; Godwin PG et al.; Fifteen (15.2%) of 99 Gram-negative bacteria isolated from patients during episodes of fever and neutropenia had minimum inhibitory concentrations ranging from less than 2 to 32 mg/l but were not fully sensitive to piperacillin by disc diffusion testing . These 15 isolates were further examined using a chemostat system, in which susceptible isolates were rapidly killed by piperacillin . Only three of the 15 isolates were susceptible to piperacillin when compared to sensitive control strains using the chemostat system . The results of this study suggest that an increase in the MIC to piperacillin is a less sensitive indicator of resistance to piperacillin amongst Gram-negative isolates than a reduction in the zone of inhibition in disc diffusion testing.

J Antimicrob Chemother, 1988 Dec, 22(6), 891 - 7
Activity of cilofungin (LY121019) against Candida species in vitro; Odds FC; Cilofungin (LY121019) was compared with amphotericin B in vitro for its inhibitory and fungicidal activity against Candida species . In minimal inhibitory concentration (MIC) tests the two compounds showed comparable inhibitory activity against 31 isolates of C . albicans and C . tropicalis . However, cilofungin was by comparison only weakly active against 19 isolates representing the species C . glabrata, C . kefyr and C . krusei, and essentially inactive against 11 isolates representing C . guilliermondii and C . parapsilosis . The inhibitory activity of cilofungin, unlike that of amphotericin B, was reduced in medium containing serum . Relative inhibition factors (RIFs) for the two compounds confirmed the MIC data: RIFs of 85% and more were obtained in tests with species other than C . albicans and C . tropicalis: for the latter two species, RIFs were in the range 41-66%, indicating drug activity comparable to that of systematically active azole compounds . (RIFs for amphotericin B were less than 40% for all isolates.) Cilofungin was generally less fungicidal than amphotericin B, and it was only rarely fungicidal in tests done in medium containing serum . Because of its inhibitory action and its low toxicity, the compound may prove to be therapeutically useful in infections caused by the two most commonly encountered pathogenic Candida species.

J Clin Microbiol, 1988 Dec, 26(12), 2667 - 8
Microtiter method for MIC testing with spherule-endospore-phase Coccidioides immitis; Hector RF et al.; A method was developed for susceptibility testing with spherule-endospore-phase Coccidioides immitis by using a microtiter format . Isolated endospores were used to inoculate wells containing modified Converse medium with various concentrations of azole or nikkomycin antifungal substances which then were sealed with an acetate film . The plate was incubated at 37 degrees C with shaking for 96 h, after which the control wells had visible turbidity and endpoints were discernible . Microscopic examination revealed that both control and treatment wells maintained cells predominantly in the spherule-endospore phase of growth.

Arzneimittelforschung, 1988 Dec, 38(12), 1778 - 83
{Synthesis and antimycobacterial action of lipophilic substituted 2,4-diamino-5-benzylpyrimidines}; Hachtel G et al.; 2,4-Diamino-5-benzylpyrimidines 1-23 with lipophilic substitution in the benzylic moiety were synthesized by the morpholino-anilino-procedure . Their effects against various mycobacteria were verified by MIC (minimum inhibitory concentration) in whole cells and I50-measurements in whole cell and cell-free systems . Especially the substances 7-12 are strong inhibitors of some atypical mycobacterial strains which are sometimes associated with tuberculosis in the elderly and with AIDS . They might be promising candidates for therapy.

Pharmazie, 1988 Dec, 43(12), 837 - 9
{Structure-activity relationships applied to quinoxaline-1,4-dioxides}; Schonfelder D et al.; Studies on structure-activity relationships applied to quinoxaline 1,4-dioxides were performed on the basis of Hansch analysis . It could be demonstrated that correlations exist between MIC values (Escherichia coli) and physicochemical parameters . On the other hand, correlations were also found between nutritive effects determined on chicken and structural parameters . The results obtained could be confirmed by means of Free-Wilson analysis.

Eur J Clin Microbiol Infect Dis, 1988 Dec, 7(6), 713 - 20
Antibiotic uptake into gram-negative bacteria; Hancock RE et al.; Antibiotics taken up into gram-negative bacteria face two major diffusion barriers, the outer and cytoplasmic membranes . Of these, the former has been most studied and is discussed in detail here . Evidence from antibiotic MIC studies on porin-deficient mutants compared with their porin-sufficient parent strains has provided strong support for the proposal that some antibiotics, particularly beta-lactams, pass across the outer membrane through the water-filled channels of a class of proteins called porins . Nevertheless substantial evidence has accumulated for the importance of non-porin pathways of antibiotic uptake across the outer membranes of gram-negative bacteria . Examples discussed include the uptake of polycationic antibiotics via the self-promoted pathway, the uptake of hydrophobic antibiotics in some bacterial species and in mutants of others via the hydrophobic pathway, and the possible importance of poorly understood non-porin pathways of uptake of a variety of antibiotics . Other potential barriers to diffusion, including the cytoplasmic membrane, are briefly discussed.

Proc Soc Exp Biol Med, 1988 Dec, 189(3), 304 - 9
Dextran sulfate as an inhibitor against the human immunodeficiency virus; Chang RS et al.; Dextran sulfate (DS) is a potent inhibitor of the growth of human immunodeficiency virus type 1 (HIV-1) in the H9 cell . Its minimal inhibitory concentration is about 1 microgram/ml . Its therapeutic index is greater than or equal to 200 which is higher than that of 38 for zidovudine . At the ID100 range, DS blocks the synthesis of HIV-1 antigens completely for at least 21 days; zidovudine at the subtoxic concentration of 3 micrograms/ml is incapable of achieving such a complete blockage . DS is still active when added to H9 cell cultures 4 hr after the addition of HIV-1 . DS does not inactivate extracellular HIV-1 and is incapable of inducing interferons . It interferes partially with the infection of the H9 cells by the HIV-1 . It inhibits the activity of HIV-1 reverse transcriptase . These activities may account, at least in part, for the inhibitory activity of dextran sulfate against the HIV-1 . DS has a narrow antiviral spectrum; it is noninhibitory to the herpes simplex, vesicular stomatitis, polio, or adeno viruses . Dextran is not inhibitory to HIV-1 . After sulfonation, the sulfonated dextran is highly inhibitory . Therefore, the sulfate group in the DS molecule appears to be essential for its anti-HIV-1 activity . The molecular weights of DS within the range 4000 to 12,000 do not appear to influence its anti-HIV potency.

Arch Fr Pediatr, 1988 Nov, 45(9), 679 - 82
{Comparison of plasma levels of amoxicillin administered by oral and intravenous routes in neonatal bacterial colonization}; Autret E et al.; Twenty-one full-term neonates who had a diagnosis of bacterial colonization were randomly assigned to receive amoxicillin 40 mg.kg-1 every 12 hours by either IV or oral route . Plasma levels of amoxicillin were assayed by HPLC at 0.5 (H0.5), 2 (H2), 6 (H6), 9 (H9) hours after the amoxicillin dose for both administration routes and also at the end of the infusion for the IV route . Average levels of plasma amoxicillin with IV and oral routes were not different except at H0.5 where they were higher with the IV route . With oral route Cmax was measured at H2 (6 times) or H6 (4 times) . At the end of the infusion, plasma levels were between 55 and 154 mg.l-1 (81 +/- 32 mg.l-1) . They decreased quickly so half life of amoxicillin by IV route was between 1.79 and 8.9 hs (4.28 +/- 2.4 hs) . They were always above MIC for germs encountered in neonates except at H9 twice with IV and once with oral route . Pharmacokinetic data of this study allow to use oral route for amoxicillin for bacterial colonization in neonates: this administration route could also be proposed in infections following IV route as soon as hemodynamic and gastrointestinal conditions permit . The efficacy of such an attitude could be evaluated by a clinical trial.

Methods Find Exp Clin Pharmacol, 1988 Nov, 10(11), 677 - 82
Streptozotocin-induced diabetes in rat . I . Influence of hypertension and myocardial infarction on the development of vascular complications; Somova L et al.; Streptozotocin diabetes in rats was complicated by spontaneous hypertension (SHR) and myocardial infarction (MIC), considered as "risk groups" . Renal function was assessed on the basis of blood urea nitrogen (BUN) and albuminuria . BUN increased by 36% in Wistar diabetic group, by 100% in SHR + diabetes, and by 51% in MIR + diabetes . Morphologic changes were assessed by estimation of PAS-positive glycosaminoglycans and measurement of vascular wall thickness of glomerular arterioles . The risk groups showed exaggerated tendency for development of diabetic angiopathy . A significant imbalance between TXA2 and prostacyclin was found, which was reflected by TXB2/6-keto-PGF1 alpha (the stable metabolites of TXA2 and prostacyclin, respectively) ratio, which increased by 38% in Wistar diabetic rats, by 61% in SHR + diabetes, and by 133% in MIR + diabetes . These changes correlated very well with increased platelet aggregability (r = 0.70; p less than 0.05) and with increased lipid peroxide level (r = 0.60; p less than 0.05), but neither with total plasma cholesterol (r = 0.20), nor with plasma triglycerides (r = 0.34) . Lipid peroxides increased 5-fold in Wistar diabetic rats, 6-fold in SHR + diabetes, and 5.5-fold in MIR + diabetes . A causative relationship between TXA2/PGI2 imbalance and lipid peroxide changes on one hand, and diabetic angiopathy, on the other, was suggested.

Antibiot Khimioter, 1988 Nov, 33(11), 814 - 7
{Chemical modification of ristomycin A with bifunctional reagents}; Trifonova ZhP et al.; Various bifunctional reagents by the free NH2 group of ristomycinic acid of ristomycin A were used for selective chemical modification of the antibiotic . The bifunctional reagents were the following: di-N-hydroxysuccinimide ether of suberic acid and 4,4'-difluoro-3,3'-dinitrodiphenylsulfone . Bis-N,N'-derivatives of ristomycin A were prepared using these reagents . The derivatives inhibited the growth of Bac . subtilis but the concentrations required for the inhibition were 2-4 times higher than those of ristomycin A . It was noted that the MIC of the bis-N,N'-derivatives depended on the length and flexibility of the "binding foot" . The MIC of the bis-N,N'-derivative prepared with using suberic acid was 2 times higher than that of the derivative prepared with the use of 4,4'-difluoro-3,3'-dinitrodiphenylsulfone.

J Infect Dis, 1988 Nov, 158(5), 1046 - 55
Diagnosis and successful treatment of fusariosis in the compromised host; Merz WG et al.; We present six cases of fusariosis caused by Fusarium solani that were diagnosed over a three-year period in 166 adult patients undergoing chemotherapy for acute leukemia . Necrotic skin lesions were evident in four patients, fungemia in three, and a deep cellulitis around a great toe nail at the time of a febrile illness in two . The mean minimal inhibitory concentration (MIC) of amphotericin B was 3.3 micrograms/mL and of miconazole, 5.3 micrograms/mL; all isolates were resistant to 5-fluorocytosine . All patients received amphotericin B (1.0-1.5 mg/kg per d) plus 5-fluorocytosine . In contrast to results found in the literature, five patients had resolution of their infections, and the one patient who died had necropsy evidence of disseminated fusariosis . Review of our cases and of the literature did not reveal a definitive source for the organism or its portal of entry . Fusarium spp . must be recognized as opportunistic pathogens that cause a potentially fatal infection in compromised patients.

J Antimicrob Chemother, 1988 Nov, 22(5), 637 - 41
Interpretative criteria for the agar diffusion susceptibility test with azithromycin; Barry AL et al.; Azithromycin (CP-62,993) is a macrolide with a tendency to concentrate in various body tissues . Difficulties that arise when establishing tentative minimum inhibitory concentration (MIC) breakpoints for such a drug include the question of whether MICs should be compared with the achievable concentrations in blood or in tissue . Pending clinical experience with this drug, we recommend the following tentative criteria for interpreting tests with 15 micrograms azithromycin discs: susceptible greater than or equal to 18 mm (MIC less than or equal to 2 mg/l) and resistant less than or equal to 13 mm (MIC greater than or equal to 8 mg/l).

J Antimicrob Chemother, 1988 Oct, 22(4), 457 - 62
Sensitivity and resistance of Legionella pneumophila to some antibiotics and combinations of antibiotics; Moffie BG et al.; For the treatment of Legionella pneumophila infections erythromycin and rifampicin are the antibiotics of choice . In view of reported therapy failures other antibiotics, e.g . the quinolones, are currently under investigation . The sensitivity of L . pneumophila to four antibiotics and to combinations of antibiotics was investigated and the rate of mutations was calculated . For 20 L . pneumophila strains we determined the MIC of rifampicin (0.002-0.004 mg/l), erythromycin (0.063-0.125 mg/l), norfloxacin (0.125 mg/l) and ciprofloxacin (0.016-0.032 mg/l) . Mutation rates ranged from 1 x 10(-8) for ciprofloxacin to greater than 1 x 10(-7) for erythromycin, resulting in high-level resistance to rifampicin in most strains and erythromycin resistance in one strain, but not in resistance to the quinolones . The combination of erythromycin and rifampicin was synergistic (FIC index less than 0.5) against four of the L . pneumophila strains and showed indifference (FIC index 0.5-2.0) for the remainder (mean FIC index 0.79) . Combinations of ciprofloxacin and erythromycin and of rifampicin and ciprofloxacin showed only indifference (mean FIC index respectively 1.05 and 1.21) . Combining rifampicin with ciprofloxacin was not effective in reducing the number of mutants for either of these antibiotics, whereas the other combinations did prevent this.

Ann Allergy, 1988 Oct, 61(4), 282 - 6
Methacholine inhalation challenge in young children: results of testing and follow-up; Adinoff AD et al.; The diagnosis of asthma is often difficult in young children because their symptoms may not be typical and pulmonary function testing cannot be performed by the patient . We therefore performed methacholine inhalation challenges (MIC) in 24 patients 1 to 5.8 years of age in whom the diagnosis of asthma was uncertain . These patients had histories of recurrent respiratory symptoms for a mean duration of 2.4 years (range = 0.5 to 5.1) in the absence of other systemic diseases . Testing was done by either the 5-breath technique or 1-min inhalation via face mask until wheezing or coughing and retractions developed or a maximum methacholine concentration of 5 to 25 mg/mL was reached . Eighteen MIC were positive and six negative . The mean provocative dose was 3.0 mg/mL (range = 0.6 to 10) . No patients suffered serious or delayed reactions and all symptoms reversed with inhaled bronchodilators (BD) . During the MIC, the progression of symptoms often mimicked progression of those observed in the past and was useful in teaching the parents . Patients were followed for 0.5 to 3.8 years (mean = 2.3) . All patients with a positive MIC have continued to have recurrent respiratory symptoms and require regular or intermittent BD . Only one patient with a negative MIC at 5 mg/mL has recurrent respiratory symptoms and requires daily BD 3 years after the initial evaluation . We conclude that MIC can safely be performed in young children in whom the diagnosis of asthma is uncertain . A positive MIC in this context demonstrates increased bronchial reactivity and is supportive of a clinical diagnosis of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicology, 1988 Oct, 51(2-3), 223 - 40
Acute toxicity of methyl isocyanate, administered subcutaneously in rabbits: changes in physiological, clinico-chemical and histological parameters; Jeevarathinam K et al.; Subcutaneous administration of methyl isocyanate (MIC) in 0.5 LD50 and 1 LD50 doses in female rabbits resulted in significant changes in physiological, clinico-chemical and histological parameters . There was a fall in arterial blood pressure and cardioacceleration in both the 0.5 LD50 and 1 LD50 groups, while the respiration showed a differential response in these groups with the former showing hyperpnoea and the latter showing respiratory inhibition . A significant increase in the arterial blood lactic acid, lactate/pyruvate ratio and 2,3-diphosphoglycerate levels, and the significant changes in acid-base status of both arterial and venous blood indicated tissue hypoxia of a stagnant type . Histopathological observations revealed a mild to moderate degree of congestion, focal lymphocytic infiltrations and necrosis in all visceral organs examined . These findings suggest that acute toxicity of MIC in vivo may be mediated by its effects on vascular beds.

J Antimicrob Chemother, 1988 Oct, 22 Suppl D, 65 - 70
In-vitro activity of fleroxacin against Chlamydia trachomatis; Steele-Mortimer O et al.; The in-vitro activities of fleroxacin, tetracycline, erythromycin and clindamycin against two clinical isolates of Chlamydia trachomatis were compared . The MIC of fleroxacin (4.0 mg/l) was comparable to that of clindamycin (2.0 mg/l), but was higher than the MICs of both tetracycline (0.4 mg/l) and erythromycin (0.2-0.4 mg/l) . Repeated passaging of C . trachomatis in the presence of sub MIC concentrations of fleroxacin did not affect the MIC and resulted in a rapid and complete loss of inclusions . The effect of combining fleroxacin with the other antibiotics was investigated by chequerboard titrations of pairs of antibiotics . The mean fractional inhibitory concentration index was calculated for each combination . Results showed indifference for the combinations fleroxacin/tetracycline, fleroxacin/erythromycin and fleroxacin/clindamycin and synergism for the combination tetracycline/clindamycin.

Dan Med Bull, 1988 Oct, 35(5), 422 - 37
Correlation of in vitro activity and pharmacokinetic parameters with effect in vivo for antibiotics . Observations from experimental pneumococcus infection; Frimodt-Moller N; The correlation between in vitro activity, pharmacokinetic properties and effect in vivo of antibiotics has so far received relatively little attention, and the optimal dosing strategy for most antibiotics is still a matter of dispute . A review on this subject is presented based on observations from an experimental pneumococcus infection model in mice . The pneumococcus is particularly suitable as pathogen in experimental infection models for antibiotic research, since it is clinically relevant, susceptible to a range of antibiotics, and naturally virulent to most laboratory animals without the need for potentiating factors . The course of pneumococcus infection in animals is discussed in detail, including the parameters for measuring antibiotic effect in vivo . In screening models the most simple and relevant parameter is survival/death of the animal, which is usually incorporated in the determination of a 50% endpoint, e.g . the ED50 (50% effective dose) . Among the variety of factors of potential influence upon the ED50, the importance of the bacterial growth kinetics in vivo is emphasized . Considering the correlation of pharmacokinetic properties with effect in vivo three parameters are considered important: The peak antibiotic concentration, the area under the drug concentration curve (AUC), and the time the antibiotic concentration remains above the minimal inhibitory concentration (time greater than MIC) . For the beta-lactam antibiotics evidence is accumulating that the time greater than MIC is the most important . Comparing 14 cephalosporins in the mouse-protection test with intraperitoneal inoculation of a pneumococcus type 3, the time greater than MIC calculated from the pharmacokinetic profiles of a 5 mg/mouse dose for all the 14 cephalosporins showed a high correlation with the ED50 . When studying the serum antibiotic concentrations at doses similar to the ED50's for various cephalosporins and penicillins, the time greater than MIC was the parameter that varied the least . Neither the peak drug concentrations nor the AUC's showed any correlation with effect in vivo . The role of the time greater than MIC in context with other factors such as extravascular penetration of antibiotics, serum protein binding and the post-antibiotic effect is discussed . Most other experimental studies concerning dosing strategy for the beta-lactam antibiotics, including the few clinical studies available, confirm the importance of the time factor . The clinical implication for this group of antibiotics therefore is to strive for a constant, not necessarily high, concentration above the MIC.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemioterapia, 1988 Oct, 7(5), 292 - 4
Plasmid "curing" by some recently synthetized 4-quinolone compounds; Selan L et al.; Nalidixic acid and two recently synthetized 4-quinolones eliminated F'lac and R-plasmids from E . coli at concentrations of one half or one quarter of the minimum inhibitory concentration (MIC) . Two of the three plasmids tested were cured by all derivatives, although with different frequencies . Pefloxacin was the most effective compound compared with the other quinolones and nalidixic acid the least active.

J Trop Med Hyg, 1988 Oct, 91(5), 265 - 73
Serial studies on the evolution of drug resistance in malaria in an area of east Africa: findings from 1979 up to 1986; Draper CC et al.; Observations, previously reported for 1979-82, have been continued up to 1986 on the development of drug resistance in P . falciparum in the North Mara area of Tanzania, where a chloroquine chemosuppression campaign was attempted from 1977 to 1982 . The WHO micro in-vitro test for chloroquine and other drugs was used . Because of the large number of tests done, each test was characterized by the mean minimum inhibitory concentrations (MIC) of drug needed to prevent schizont development instead of counting the numbers of schizonts . The MIC for chloroquine has risen progressively each year but changes in the findings of in-vivo tests were less dramatic possibly due to the effects of immunity . Resistance to amodiaquine has followed that to chloroquine at a lower level, and in the last years the MIC for quinine has risen . Sporadic resistance to mefloquine was found and, by in-vivo test, to sulphadoxine-pyrimethamine . Possible factors in the evolution of drug resistance are discussed together with implications for the future.

Antimicrob Agents Chemother, 1988 Oct, 32(10), 1500 - 2
In vitro susceptibilities of mycoplasmas and ureaplasmas to new macrolides and aryl-fluoroquinolones; Waites KB et al.; In vitro activities of the new macrolides clarithromycin, previously designated A-56268 (TE-031), and A-63075 and of the aryl-fluoroquinolones difloxacin (A-56619) and temafloxacin (A-62254) against 14 strains of Mycoplasma pneumoniae, 20 strains of Mycoplasma hominis, and 28 strains of Ureaplasma urealyticum were compared with that of erythromycin . All three macrolides inhibited growth of M . pneumoniae at less than 0.125 micrograms/ml . No macrolide was active against M . hominis . For five strains of U . urealyticum, MICs were greater than 256 micrograms/ml for all 3 macrolides . Excluding these, no other strain of U . urealyticum had an initial MIC of clarithromycin of greater than 1 microgram/ml, while five had initial MICs of erythromycin which were greater than 4 micrograms/ml . A-63075 was the least active of the three macrolides against ureaplasmas . Temafloxacin and difloxacin had similar activities against all three species, initially inhibiting 90% of M . pneumoniae strains at 2 and 8 micrograms/ml, 90% of M . hominis strains at 2 and 4 micrograms/ml, and 90% of U . urealyticum strains at 4 and 8 micrograms/ml, respectively . Additional pharmacokinetic and clinical trials with the new macrolides and quinolones with mycoplasmal or ureaplasmal infections are indicated.

Tubercle, 1988 Sep, 69(3), 179 - 86
Clofazimine and other rimino-compounds: minimal inhibitory and minimal bactericidal concentrations at different pHs for Mycobacterium avium complex; Lindholm-Levy PJ et al.; Clofazimine (Lamprene, B663) and 11 rimino-compounds were tested for activity against Mycobacterium avium by finding the minimal inhibitory concentrations (MIC) of these drugs in liquid medium . The activity of these compounds was affected in acidic conditions (pH 6.0 and 5.0), but the MICs observed even at pH 5.0 were significantly lower than the concentrations achievable in macrophages . This information is especially useful in the light of four important facts: that these drugs tend to accumulate within macrophages; that M . avium tends to multiply within macrophages; that this intracellular environment has a low pH; and that M . avium tolerates these low pH conditions . Such data confirm the expectation that rimino-compounds inhibit the intracellular M . avium bacterial population . The minimal bactericidal concentrations (MBC) of clofazimine and B746, the most active analogue, were from 64 to 256 times higher than the MIC, but it is not clear whether these drugs can accumulate within the macrophages in concentrations high enough to produce the bactericidal effect as well.

Jpn J Antibiot, 1988 Sep, 41(9), 1223 - 30
{A study on the disc sensitivity test for clavulanic acid/amoxicillin combination}; Kanazawa Y et al.; Susceptibilities of 179 strains of 30 bacterial species or subspecies to clavulanic acid/amoxicillin (CVA/AMPC) combination were determined by the 2-fold agar dilution method as well as by diameters of inhibition zones in the single-disc method, under the experimental conditions established by Kanazawa . The experiments demonstrated significant correlation between MICs by the dilution method and diameters of inhibition zones in each of conventional assays of the over-night (about 16 hours) incubation, the delayed assay (about 24 hours incubation), and the rapid assay (after 3-4 or 5-6 hours incubation), thus confirming applicability of the single-disc assay for activities of CVA/AMPC combination . From an analysis of the data obtained using CVA/AMPC (1:2) combination of disc containing 45 micrograms, the primary regression equations were obtained as follows: D (diameter, mm) = 27.4-10.1 log MIC (micrograms/ml) in the conventional assay; D = 33.7-13.4 log MIC (micrograms/ml) in the delayed assay; D = 20.7-6.6 log MIC (micrograms/ml) in the 5-6 hours rapid assay, and D = 14.5-3.6 log MIC (micrograms/ml) in the 3-4 hours rapid assay . The range of variations in MICs of CVA/AMPC combination estimated from diameters of inhibition zones by the disc test was then calculated in comparison with that in MICs determined by the 2-fold agar dilution method to estimate experimental errors involved in assaying MICs of CVA/AMPC combination by the single-disc assay.

J Int Med Res, 1988 Sep-Oct, 16(5), 376 - 85
Clinical evaluation of rectally administered ampicillin in acute otitis media; Bergstrom BK et al.; An ampicillin suppository was compared with amoxycillin suspension in the treatment of acute otitis media in children . Both antibiotics were given three times daily for 5 days in a daily dose of 25-50 mg/kg body weight . Safety was evaluated in 454 patients in the group given suppository and in 229 given the suspension, and 421 and 229 patients, respectively, were evaluable for efficacy . Ampicillin was rapidly absorbed and produced plasma concentrations well above the minimum inhibitory concentration for common respiratory pathogens . The overall clinical outcome was satisfactory (cured plus improved) in 89% of the patients given the suppository and in 86% given the suspension . Gastro-intestinal disturbances occurred in 28.4% of the patients given the suppository compared with 14.4% of those given the suspension . Perianal irritation was recorded in 12.1% of the patients given the suppository and in 5.2% of those given the suspension . Treatment was interrupted in 9.8% of patients given the suppository and in 0.9% of those given the suspension . In spite of these discomforts rectally administered ampicillin is considered to be a good alternative in children when oral medication is not feasible.

Antimicrob Agents Chemother, 1988 Sep, 32(9), 1427 - 9
Efficacy of NY-198 against experimental Legionnaires disease; Kohno S et al.; The in vitro and in vivo effects of NY-198 against Legionella pneumophila were compared with those of ciprofloxacin . The MIC of NY-198 against 15 standard reference strains of Legionella of various species, between 0.03 and 0.125 micrograms/ml, was the same as that of ciprofloxacin . The peak concentration of NY-198 in the lungs and sera of guinea pigs with experimentally induced Legionella pneumonia was higher than that of ciprofloxacin after oral administration . The overall survival rate was higher in animals treated with NY-198 than in those treated with ciprofloxacin . Thus, NY-198 appears valuable in the treatment of Legionnaires disease.

J Antimicrob Chemother, 1988 Sep, 22 Suppl C, 85 - 9
The penetration of ofloxacin into lung tissue; Wijnands WJ et al.; After a single oral 600 mg dose, ofloxacin concentrations were measured in lung tissue, whole blood and plasma in 11 patients undergoing thoracotomy for a bronchial malignancy . To correct for blood contamination in the tissue samples, the tissue haemoglobin content was measured using a method based on the binding of haemoglobin by haptoglobin . Ofloxacin concentrations in plasma and whole blood did not differ significantly . The calculated blood content in the tissue samples was 0.12 +/- 0.05 ml/g lung tissue . After correction for blood admixture, the mean lung tissue concentration 2 h after administration of ofloxacin was 17.7 +/- 9.2 micrograms/g . At the same time the mean plasma concentration was 8.7 +/- 4.2 mg/l (P less than 0.02) . The high concentration of ofloxacin obtained in lung tissue does not result from the preparation technique . After a single 600 mg dose the tissue concentrations proved to exceed MIC values for most pathogens frequently involved in respiratory tract infections.

J Antimicrob Chemother, 1988 Sep, 22 Suppl C, 53 - 7
The effect of ofloxacin on the intracellular growth of Legionella pneumophila in guinea pig alveolar phagocytes; Fitzgeorge RB et al.; Ofloxacin was evaluated as an antibiotic for possible use in the therapy of Legionnaires' disease in relation to its ability to penetrate alveolar phagocytes and inhibit Legionella pneumophila intracellular replication . A comparison with two other antibiotics used in the treatment of Legionnaires' disease, ciprofloxacin and erythromycin, was also made . Ofloxacin was found to be the most effective antibiotic, eliminating viable L . pneumophila from alveolar phagocytes at 0.001 mg/l . This was followed by ciprofloxacin, eliminating intracellular organisms at 0.01 mg/l . Erythromycin was shown to be much less effective, requiring a much higher concentration, of 0.1 mg/l . All three antibiotics had approximately similar MIC values and the considerable differences in intracellular penetration shown by these antibiotics indicate how discrepancies between in-vitro and in-vivo estimates of efficacy can occur.

Diagn Microbiol Infect Dis, 1988 Sep, 11(1), 11 - 9
Effects of surface-active agents on drug susceptibility levels and ultrastructure of Mycobacterium avium complex organisms isolated from AIDS patients; Naik SP et al.; The multiple-drug-resistance property of Mycobacterium avium complex (MAC) is mainly attributed to a cell envelope permeability barrier . MAC treated with subinhibitory levels of dimethyl sulfoxide (DMSO) and ethylenediaminetetraacetic acid (disodium salt) (EDTA) did not have altered minimum inhibitory concentration (MIC) levels or show ultrastructural changes; the effect of sodium dodecyl sulfate (SDS) was variable . With SDS, the visualization of the nucleoid and ribosomes decreased, and amorphous electron-dense material accumulated near the structurally altered cytoplasmic membrane and cell wall . Use of 0.005% Tween-80 resulted in a 2-4-fold reduction in MIC in the case of rifampicin, ansamycin (LM 427), cephapirin, and ciprofloxacin . Tween-80 treated cells were swollen, and deposits of low electron-density accumulated in the cytoplasm; distortions in the outer-cell integuments were observed . These findings are consistent with the idea that Tween-80 increases cell-envelope permeability, thereby enhancing drug penetrability and reducing MIC levels . Because of the action of Tween-80, its use in drug-susceptibility media or diluent fluids should be avoided.

Br J Cancer, 1988 Sep, 58(3), 359 - 61
Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare; Cullen MH et al.; Mitomycin, ifosfamide and cis-platin are three of the most active single agents in the chemotherapy of non-small cell lung cancer . We have combined them for a phase 2 study in patients with inoperable non-small cell lung cancer . The regimen ('MIC') comprised: mitomycin 6 mg m-2, ifosfamide 3 g m-2 and cis-platin 50 mg m-2, with routine use of lorazepam, dexamethasone and high dose metoclopramide for anti-emesis . Seventy-four ambulatory patients with untreated, limited (LD) or extensive (ED) disease have entered this study, and 66 are evaluable for response . Thirty patients (45%) have achieved partial remission and 7 (11%) complete remission, as assessed radiologically . The overall response rate is thus 56% (95% confidence interval 44%-68%) . There have been 29/43 responses in LD (67%, 95% CI 53%-81%) and 8/23 in ED (35%, 95% CI 15%-55%) . The median response duration, measured from the start of treatment is 8.75 months . The median survival for the whole group is 9.2 months . The principal toxicity was nausea and vomiting which was severe or prolonged (greater than 48 h) for one or more courses, in 9% of patients . Performance status (PS) and weight were assessed before, and 3 weeks after the last course of chemotherapy . Fifteen (of 31 evaluable) responders improved their PS and only 1 responder deteriorated . Twenty-one of the 28 evaluable non-responders had no change in PS . The difference in PS change between responders and non-responders is highly significant (P = 0.002) . Thirty evaluable responders experienced a mean increase in weight of 2.9% with treatment, whereas 24 evaluable non-responders had a mean weight loss of 3.8% . This change is also highly significant (P = 0.0013) . MIC is clearly a well tolerated regime and among the most active combinations in non-small cell lung cancer . It will now be tested in a randomized trial against no chemotherapy.

Crit Care Med, 1988 Aug, 16(8), 769 - 72
Cardiopulmonary effect of various inspiratory flow profiles during controlled mechanical ventilation in a porcine lung model; Smith RA et al.; We studied the influence of inspiratory flow (VI) patterns on gas exchange and hemodynamics after metacholine inhalation challenge (MIC) in seven swine mechanically ventilated with a constant, sinusoidal, accelerating, and decelerating flow pattern . Blood gas and expired CO2 tensions, pulmonary mechanics, and hemodynamics were measured during each pattern . Flow pattern sequence was randomized and MIC was repeated at 30 to 45-min intervals . MIC reliably reduced PaO2, and increased PaCO2 and peak tracheal pressure (PT) . There was no significant difference in gas exchange or hemodynamics between various VI curves . Insufflation with an accelerated VI manifested a significantly higher PT than any other pattern . We conclude that no VI contour studied offers a unique advantage for gas exchange after MIC in swine . However, since accelerated gas flow generates significantly higher PT values, it is not recommended in the presence of significant airway resistance.

Antibiot Khimioter, 1988 Aug, 33(8), 605 - 12
{Pharmacokinetic study of implantable gentamycin preparations . I . Antibiotic pharmacokinetics in the implantation area and an evaluation of the prolonged effect of the preparations}; Nazarov AD et al.; Gentamicin pharmacokinetics was studied in the zone of subcutaneous implantation to rats of Septopal, a dosage form based on polymethylmethacrylate stable in vivo (4.5 mg of the antibiotic) and of preparations based on biodegradable polymers such as monocarboxycellulose, alginic acid, nonmodified and modified collagens (1 and 5 mg of the antibiotic) . A three-phase pattern of gentamicin level changing in the implantation zone was observed: (1) rapid increasing and decreasing of the antibiotic concentration, (2) stabilization of the gentamicin content at a practically constant level and (3) slow lowering of the antibiotic level in the tissue . Comparison of the areas under the concentration/time curves showed that the modified collagen, alginic acid and monocarboxycellulose had the highest prolongation effect among the biodegradable polymers . Their use in the compositions provided during the first hours after the implantation the antibiotic concentrations in the administration site equal to tens micrograms per 1 g of the tissue . After that during 14 days the concentration of gentamicin in the implantation zone maintained at the level higher than its MIC for the main pathogens of wound infections.

Lab Anim Sci, 1988 Aug, 38(4), 430 - 4
Pharmacokinetics of long acting oxytetracycline in the laboratory rat; Curl JL et al.; Pharmacokinetic parameters of a slow release form of oxytetracycline were determined in the rat . Triexponential pharmacokinetics were displayed after intravenous administration . The half-life of the distribution phase was 0.097 hours, the rapid elimination half-life was 3.74 hours and the slow elimination half-life was 27.26 hours . Subcutaneous and intramuscular injection resulted in a rapid elimination half-life of 6.09 and 6.02 hours, respectively . In comparison, a standard form of oxytetracycline given subcutaneously had a rapid elimination half-life of 4.22 hours . The slow release form of oxytetracycline has a half-life in the rat long enough to maintain serum levels greater than the minimum inhibitory concentration of Mycoplasma pulmonis with a dose interval of 72 hours.

Chemioterapia, 1988 Aug, 7(4), 229 - 32
The pharmacokinetic properties of cefotetan and its relevance for prophylaxis in elective colorectal surgery; Kujath P et al.; In an open, prospective, non-randomised study involving 112 patients undergoing elective colorectal surgery, the effect of perioperative prophylaxis with cefotetan was investigated . Cefotetan (2g) was administered, pre- and intra-operatively only . Preoperative bowel preparation was done by the standardised "Wurzburg Method" i.e . oral metronidazole pre and post orthograde lavage . Mucosal biopsies were obtained from the resected colon and simultaneously serum samples were taken to determine tissue and serum levels respectively . Antibiotic serum and gut mucosal levels were well in excess of the minimum inhibitory concentration (MIC90) levels of the isolated bacteria . Wound infections occurred in only 2 patients . Cefotetan was well tolerated and no adverse events were noted . In prolonged colorectal surgery, an antibiotic such as cefotetan with a long half-life is to be recommended.

J Antimicrob Chemother, 1988 Aug, 22(2), 213 - 9
Penetration of ciprofloxacin and ofloxacin into human allograft pancreatic juice; Brattstrom C et al.; The penetration of ciprofloxacin (500 mg) and ofloxacin (400 mg) into pancreatic juice following a single oral dose, was investigated in seven patients who had undergone pancreatic transplantation . With a special technique for segmental pancreatic transplantation it was possible to collect pure pancreatic juice at regular intervals for up to 24 h after drug intake . The antibiotic concentrations were determined by the agar-well diffusion method . The concentration of ciprofloxacin in pancreatic juice was 36% of that in serum . The same figure for ofloxacin was 92% . The mean peak level in pancreatic juice was 0.5 +/- 0.0 mg/l (+/- S.E.) for ciprofloxacin and occurred at 4 h after drug intake . The same figure for ofloxacin was 2.7 +/- 0.7 mg/l (+/- S.E.) occurring at 3.6 h . The decrease in concentrations with time was parallel to the serum concentration curves for both antibiotics . The concentrations of ofloxacin in pancreatic juice exceeded the MIC values for most of the organisms causing infections in the pancreas for several hours after an oral dose . The concentrations of ciprofloxacin only briefly exceeded the MIC for the same organisms.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Aug, 269(2), 245 - 50
Susceptibility of Ureaplasma urealyticum to ten chemotherapeutic agents; Sobetzko R et al.; Tetracyclines and erythromycin are the chemotherapeutic agents most often used in the Federal Republic of Germany for eradication of U . urealyticum from the male urogenital tract . Few data on current susceptibility in the FRG are available . Therefore, we investigated the minimal inhibitory concentration (MIC) values of 10 chemotherapeutic agents against 27 isolates from the male urethra and 4 ATCC strains of U . urealyticum by a micro broth dilution method using a modified U-9 medium . The MIC90 values (microgram/ml) of the chemotherapeutic agents tested were as follows: minocycline-0.25, doxycycline-1.0, tetracycline and chlortetracycline-2.0, erythromycin and streptomycin-4.0, chloramphenicol, gentamicin, rosoxacin-8.0, spectinomycin-32.0 . According to the blood levels attained in treatment, the chemotherapeutic agents can be divided into three groups based on the MIC90-values, i.e . sensitive: chloramphenicol, doxycycline, minocycline and streptomycin; weakly effective: chlortetracycline, tetracycline, spectinomycin and erythromycin; and resistant: gentamicin and rosoxacin.

Antimicrob Agents Chemother, 1988 Aug, 32(8), 1131 - 6
MIC as a quantitative measurement of the susceptibility of Mycobacterium avium strains to seven antituberculosis drugs; Heifets L; MICs of isoniazid, rifampin, ethionamide, streptomycin, amikacin, kanamycin, and capreomycin were determined for Mycobacterium avium complex strains by two methods: broth dilution in 7H12 medium radiometrically and agar dilution on 7H10 agar plates . The broth-determined MICs of all drugs with the exception of isoniazid were two to eight times lower than the agar-determined MICs for most of the tested M . avium strains, which is probably due to the higher absorption and degradation of the drugs in solid media . The MICs, especially those determined in broth, are suggested as quantitative measurements of the degree of susceptibility of M . avium complex strains . For a certain percentage of the M . avium strains the broth-determined MICs were within the limits of MICs found for wild susceptible Mycobacterium tuberculosis strains . These M . avium strains were classified as presumably susceptible . In contrast to M . tuberculosis, the MICs for M . avium strains had a wide range . When the MICs for M . avium strains were only one dilution higher than those for M . tuberculosis, they were tentatively classified as moderately susceptible . The designation moderately resistant or resistant, respectively, is suggested for those M . avium strains for which the MICs were at or above the concentrations achievable in blood . The quantitation of the degree of susceptibility by the MICs and the tentative interpretation of the MICs are suggested for future use in clinical trials as a means of evaluating the patients' responses to chemotherapy compared with the degree of susceptibility of the initial strain isolated before treatment.

Toxicol Lett, 1988 Jul, 42(1), 65 - 71
Cytogenetic activity of methyl isocyanate in vivo in the mouse micronucleus test; Meshram GP et al.; The ability of methyl isocyanate (MIC) to induce mutagenic and cytotoxic effects in vivo in the mouse micronucleus test was evaluated by assessing the induction of micronuclei and depression of polychromatic erythrocytes in bone marrow and peripheral blood smears . Animals were exposed to MIC through intraperitoneal injection for 2 and 5 days in separate experiments, and bone marrow and peripheral blood were sampled 6 and 48 h after the last injection, respectively . MIC did not significantly increase the frequencies of micronucleated polychromatic erythrocytes (MN-PCE) and micronucleated normochromatic erythrocytes (MN-NCE) in bone marrow and peripheral blood samples respectively in either twice or multiply treated mice . However, a dose-dependent depression in percentage PCE observed was significant . This indicates that MIC exposure led to the cytotoxic effect by inhibition of bone marrow cell proliferation.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 824 - 9
Accuracy of microdilution and the AutoMicrobic System in detection of beta-lactam resistance in gram-negative bacterial mutants with derepressed beta-lactamase; Washington JA 2nd et al.; Microdilution and the AutoMicrobic System (AMS) were compared with macrodilution for accuracy in detecting beta-lactam resistance in 16 isogenic pairs of gram-negative wild-type bacterial strains and mutant strains with derepressed class I beta-lactamase; an additional 12 gram-negative derepressed mutants were also tested . Of a total of 352 organism-beta-lactam combinations resulting in 840 determinations of minimum inhibitory concentration, the overall rates of very major discrepancy were 3% between macrodilution and microdilution and 2% between macrodilution and AMS . The corresponding rates of very major discrepancies with the derepressed mutants were both 2.7% . All but three of the wild-type strains were susceptible to all beta-lactam drugs tested but cefoxitin, while nearly 90% of derepressed mutants were resistant to these antibiotics . When careful attention was given to inoculum size and incubation time, microdilution and the AMS yielded results comparable to those obtained by macrodilution.

Int J Dermatol, 1988 Jul-Aug, 27(6), 391 - 5
Hendersonula toruloidea infection in Thailand; Kotrajaras R et al.; Hendersonula toruloidea infection is present in Thailand, where the clinical picture of tinea pedis is scales 61%, erythema 22%, maceration 10.8%, and hyperkeratosis 9% . The diagnosis was confirmed by repeated isolation of H . toruloidea . The slow-growing type was found more often than the fast-growing in the ratio of 2.8:1 . In patients with H . toruloidea infection, skin test with Hs antigen of 1:10 was positive . Griseofulvin sensitivity test revealed that the MIC of 20 cultures was more than 100 micrograms/ml . Only 2 out of 93 cases (0.02%) were cured with half-strength Whitfield ointment for 4 months . Pathomechanism of the infection is being studied.

Infection, 1988 Jul-Aug, 16(4), 225 - 8
Bile levels of imipenem in patients with T-drain following the administration of imipenem/cilastatin; Mayer M et al.; Twenty-four patients undergoing gall bladder surgery and placement of a Kehr T-tube were examined for imipenem pharmacokinetics in plasma and bile fluid following an intravenous short-term infusion (20 min) of 500 mg respectively 1000 mg each of imipenem and cilastatin . In group I (500 mg; 12 patients) a mean peak concentration in bile fluid of 10.5 mg/l (range 1.5 to 16.7 mg/l) was reached just after 10 min . 60 min after the end of infusion the imipenem concentration was between 8 and 9 mg/l . In group I the half-life of imipenem in bile was 0.84 h . In group II (1000 mg; 12 patients) the mean peak level in bile fluid was 1&.5 mg/l (range 3.5 to 51.3 mg/l) . The half-life in bile was 1.24 h in this group . The data indicated that 4 h after the administration of either 1000 mg or 500 mg, imipenem serum and bile concentrations were markedly above the MIC values for pathogens expected to be found in infections of the biliary tract.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 53 - 6
Spiramycin: in-vitro activity on Branhamella catarrhalis; Riou JY et al.; This in-vitro study of susceptibility to spiramycin of 103 strains of Branhamella catarrhalis isolated between 1982 and 1987 was performed by evaluation of their MICs . More than 97% of strains remained susceptible with MIC less than or equal to 8 mg/l (two strains) . One strain presented a MIC of 16 mg/l . There were no significant differences of susceptibility to spiramycin between penicillinase-producing and non-producing strains.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 761 - 4
Effect of interaction between outer membrane permeability and beta-lactamase production on resistance to beta-lactam agents in gram-negative bacteria; Sawai T et al.; The effect of the interaction of beta-lactamase production and outer membrane permeability on the bacterial resistance to beta-lactam antibiotics was investigated using the Escherichia coli K12 substrains, which have outer membrane mutation and produce TEM-type penicillinase . Experiments confirmed that the cefazolin concentrations in the periplasm of cells exposed to the MIC were restricted to 2.4-4.6 microM among the bacteria, even though the MICs for the bacterial strains were distributed from 13 microM to 1,726 microM . The drug concentrations in the periplasm could be calculated on the basis of parameters obtained experimentally, and the calculated values were in fair agreement with the experimental values . The effect of beta-lactamase activity (Vmax/Km) and the outer membrane barrier on the elevation of MICs was observed to be synergistic, and the contribution of beta-lactamase was more effectively expressed in the bacterial cells with higher outer membrane barrier.

Res Vet Sci, 1988 Jul, 45(1), 134 - 5
Effect of subinhibitory concentrations of tiamulin on the haemagglutinating properties of fimbriated Escherichia coli (K88, K99); Larsen JL; The haemagglutinating properties (HA) of Escherichia coli possessing the fimbrial antigens K88 and K99 were significantly affected by tiamulin . HA for K88-positive strains was reduced at 1/10 to 1/40 minimum inhibitory concentration (MIC), while the corresponding values for the K99 strains were 1/2 to 1/10 MIC . Tiamulin concentrations of 3 to 12 micrograms ml-1 increased salt aggregation test values from between 1.4 and 1.5, to more than 2.

Antimicrob Agents Chemother, 1988 Jul, 32(7), 1080 - 1
In vitro activities of T-3262, NY-198, fleroxacin (AM-833; RO 23-6240), and other new quinolone agents against clinically isolated Chlamydia trachomatis strains; Maeda H et al.; The in vitro activities of three newly developed quinolone drugs (T-3262, NY-198, and fleroxacin {AM-833; RO 23-6240}) against 10 strains of clinically isolated Chlamydia trachomatis were assessed and compared with those of other quinolones and minocycline . T-3262 (MIC for 90% of isolates tested, 0.1 microgram/ml) was the most active of the quinolones . The NY-198 and fleroxacin MICs for 90% of isolates were 3.13 and 62.5 micrograms/ml, respectively.

Antimicrob Agents Chemother, 1988 Jun, 32(6), 928 - 9
Activities of five new fluoroquinolones against Pseudomonas pseudomallei; Winton MD et al.; Thirty-four isolates of Pseudomonas pseudomallei were tested by a broth microdilution technique for susceptibility to amifloxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin . Ciprofloxacin was the most active agent tested, with an MIC for 90% of the strains tested of 8 micrograms/ml . These in vitro results suggest that the fluoroquinolones tested would not be optimal for therapy of melioidosis.

Genetics, 1988 Jun, 119(2), 303 - 15
Cycloheximide-resistant temperature-sensitive lethal mutations of Saccharomyces cerevisiae; McCusker JH et al.; We describe the isolation and preliminary characterization of a set of pleiotropic mutations resistant to the minimum inhibitory concentration of cycloheximide and screened for ts (temperature-sensitive) growth . These mutations fall into 22 complementation groups of cycloheximide resistant ts lethal mutations (crl) . None of the crl mutations appears to be allelic with previously isolated mutations . Fifteen of the CRL loci have been mapped . At the nonpermissive temperature (37 degrees), these mutants arrest late in the cell cycle after several cell divisions . Half of these mutants are also unable to grow at very low temperatures (5 degrees) . Although mutants from all of the 22 complementation groups exhibit similar temperature-sensitive phenotypes, an extragenic suppressor of the ts lethality of crl3 does not relieve the ts lethality of most other crl mutants . A second suppressor mutation allows crl10, crl12, and crl14 to grow at 37 degrees but does not suppress the ts lethality of the remaining crl mutants . We also describe two new methods for the enrichment of auxotrophic mutations from a wild-type yeast strain.

Hinyokika Kiyo, 1988 Jun, 34(6), 1101 - 3
{Enoxacin in the seminal fluid of prostatitis patients}; Yasumoto R et al.; Ten patients with prostatitis were administered with Enoxacin (ENX), and the changes in its concentration in the seminal fluid were studied . For acute prostatitis patients, 600 mg/day of ENX was administered for 5 to 7 days, and for chronic prostatitis patients, 400 to 600 mg/day was administered for 7 to 17 days . Seminal fluid was obtained in the morning of examination and frozen until measurement . ENX was measured by the agar well method using E . coli . The concentration of ENX was 2.69 +/- 0.85 micrograms/ml and 3.98 +/- 2.49 micrograms/ml in acute and chronic prostatitis patients, respectively, and there was no significant difference between the two groups . When the dose and method of administration were compared, the mean ENX concentration was 3.65 micrograms/ml in the group administered 600 mg of ENX, while it was 2.60 micrograms/ml in the group administered 400 mg of ENX and not significantly different . When ENX was administered for 7 days, the mean ENX concentration was 3.13 micrograms/ml, but when it was administered for 14 days, it was 3.46 micrograms/ml slightly higher . These results indicate that since the concentration of ENX in the seminal fluid was higher than the minimum inhibitory concentration for the pathogens of prostatitis, ENX may be a clinically effective drug.

Eur J Clin Microbiol Infect Dis, 1988 Jun, 7(3), 410 - 2
In vivo significance of the inoculum effect of antibiotics on Escherichia coli; Soriano F et al.; The minimum dosage of antibiotics which reduced mortality in rats intraperitoneally inoculated with an Escherichia coli isolate was determined . Low mortality rates (0-10%) were obtained when antibiotics with minimal or no inoculum effect (cefoxitin, cefmetazole and gentamicin) were administered to yield serum levels 3 to 20 times the MIC, while antibiotics with a pronounced inoculum effect (cefotaxime and aztreonam) had to be administered to yield serum levels 200 to 1,000 times the MIC determined with a standard (low) inoculum . Thus, it seems that the inoculum effect observed in vitro with some antibiotics for Escherichia coli may have clinical significance.

Eur J Clin Microbiol Infect Dis, 1988 Jun, 7(3), 407 - 10
In vitro activity of antibiotics against Ureaplasma urealyticum and Chlamydia trachomatis strains from patients with nongonococcal urethritis; Busolo F et al.; The activity of minocycline, doxycycline, tetracycline, erythromycin, mepartricin and lincomycin against 35 freshly isolated Ureaplasma urealyticum strains was tested . Doxycycline was the most active . Twelve strains were resistant to minocycline and four of these were sensitive to erythromycin . Mepartricin showed no activity against the organisms at a concentration of 10 micrograms/ml . The susceptibility of 30 low-laboratory-passage Chlamydia trachomatis strains against tetracycline and erythromycin was tested . A variable degree of sensitivity to tetracycline and erythromycin was found, the median MIC values being 0.13 micrograms/ml and 0.025 micrograms/ml respectively . No resistant Chlamydia trachomatis strain was found.

J Antimicrob Chemother, 1988 Jun, 21(6), 731 - 6
In-vitro activity of trospectomycin sulphate against Mycoplasma and Ureaplasma species isolated from humans; Yancey RJ Jr et al.; Trospectomycin sulphate, a novel analogue of spectinomycin, was compared to spectinomycin, tetracycline, lincosamide, macrolide, quinolone and naphthalenic ansamycin-class antibiotics for in-vitro activity against Mycoplasma pneumoniae, M . hominis and Ureaplasma urealyticum . MIC determinations were conducted by the agar dilution method using either SP-4 (Mycoplasma spp.) or A8 (U . urealyticum) agars . Trospectomycin compared favorably with tetracycline for all the strains of M . pneumoniae, M . hominis or U . urealyticum tested . Ciprofloxacin was the most active of the newer quinolones tested . Trospectomycin was as active as this quinolone antibiotic, or more active, in vitro . Other antibiotics such as the macrolides and lincosamides were highly active against one or more of the three mycoplasma groups tested but none was active against all three . The results suggest that trospectomycin may be useful in the treatment of mycoplasma-induced respiratory or genital tract infections in man.

J Infect Dis, 1988 Jun, 157(6), 1150 - 7
Penicillin resistance and defective lysis in clinical isolates of pneumococci: evidence for two kinds of antibiotic pressure operating in the clinical environment; Moreillon P et al.; Seventy percent of clinical isolates of penicillin-resistant pneumococci also exhibit defective lysis when treated with penicillin exceeding the minimal inhibitory concentration (MIC) . To provide a possible explanation for the frequent association of these two traits, we exposed penicillin-susceptible pneumococci to two kinds of antibiotic pressures in the laboratory . Treatment of cultures with cycles of high concentrations of penicillin (20 X MIC) followed by growth of the survivors in drug-free medium selected for lysis-defective mutants that died only slowly during antibiotic treatment but had unchanged MICs . Exposure to sustained, low levels of penicillin produced resistant mutants, with elevated MICs, that lysed normally with penicillin . We suggest that the cyclic antibiotic exposure generally used in the clinical setting may select primarily for enhanced survival . From these survivors a second type of antibiotic exposure--sustained antibiotic concentrations just above the MIC (concentrations that may be restricted to the tail-end trough of a dosing interval)--selects for penicillin-resistant mutants.

JAMA, 1988 May 27, 259(20), 3023 - 6
Concurrent zidovudine levels in semen and serum determined by radioimmunoassay in patients with AIDS or AIDS-related complex; Henry K et al.; Zidovudine was present in the semen and serum of six patients with acquired immunodeficiency syndrome or the related complex who were receiving 200 mg of the drug orally every four to six hours . Mean semen zidovudine levels (as measured by a new radioimmunoassay) in samples collected 0.75 to 1.25 hours after oral dosing were 3.63 to 7.19 mumol/L . Levels in semen samples collected 3.0 to 4.5 hours after oral dosing were 1.68 to 6.43 mumol/L . These values are above the in vitro minimum inhibitory concentration for the human immunodeficiency virus type 1 (HIV-1) . Mean serum concentrations at the early and late times after oral dosing were 0.22 to 3.07 mumol/L and 0.10 to 1.42 mumol/L, respectively . Ratios of semen/serum zidovudine levels ranged from 1.3 to 20.4 . It is possible that a pH-dependent trapping mechanism, which has been described in the prostate for other antibiotics, was responsible for the relatively high semen levels observed.

Schweiz Med Wochenschr, 1988 May 21, 118(20), 786 - 8
{Plasma and tissue concentration of ceftriaxone following a one-time i.v . dose of 2 g}; Kuttel JC et al.; The concentration of ceftriaxon found in plasma and in fatty, muscular and colonic tissue after a single intravenous dose of 2 g are reported . 20 patients undergoing elective surgery of the colon were divided into five groups of 4, and ceftriaxon was given 45 min, 3, 6, 12 and 24 h before surgery . Even after 24 h the plasma and tissue concentrations were above MIC 90 for most microorganisms sensitive to ceftriaxon.

Surgery, 1988 May, 103(5), 563 - 7
Penetration of clindamycin, cefoxitin, and piperacillin into pancreatic juice in man; Brattstrom C et al.; In our segmental pancreatic transplantation technique the pancreatic juice is temporarily diverted to the exterior via a pancreatic duct catheter . This permits studies on pure pancreatic juice to be carried out . In 11 such patients we studied the penetration of clindamycin, cefoxitin, and piperacillin into pancreatic juice . These three antibiotics all have good effect against the bacteria commonly isolated during pancreatic infections . Simultaneous blood and pancreatic juice samples were collected immediately before drug administration and at 30, 60, 90, and 120 minutes and 3, 4, 5, 6, and 8 hours after administration . The concentration of clindamycin in pancreatic juice was 34% of that in serum and exceeded the minimum inhibitory concentration for most bacteria associated with pancreatic infections . In spite of adequate serum concentrations of cefoxitin and piperacillin, the concentrations in pancreatic juice were only 8% and 5%, respectively, and did not exceed the minimum inhibitory concentration for the relevant bacteria . In view of these findings, clindamycin seems to be preferable in the treatment of pancreatic infections.

Am Rev Respir Dis, 1988 May, 137(5), 1217 - 22
Qualitative and quantitative drug-susceptibility tests in mycobacteriology; Heifets L; Qualitative methods of susceptibility testing have been employed widely around the world during the last 37 years and have proved to be a generally reliable tool to guide the chemotherapy of tuberculosis with conventional antituberculosis drugs . However, we believe there is a need now for application of modern quantitative methods to mycobacteriology: (1) for susceptibility testing of Mycobacterium avium complex, (2) for evaluation of the bactericidal activity of the antimycobacterial drugs, (3) for evaluation of the inhibitory and bactericidal activity of drug combinations, (4) for search and evaluation of new drugs against both Mycobacterium tuberculosis and Mycobacterium avium complex . Newly developed technology (radiometric automated bacterial growth recording in the BACTEC system) has opened new opportunities for development of quantitative methods in mycobacteriology using liquid culture medium . This paper analyzes the potential applications to mycobacteriology of 4 quantitative criteria: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), Fractional Inhibitory Concentration (FIC), and Fractional Bactericidal Concentration (FBC).

Antimicrob Agents Chemother, 1988 May, 32(5), 780 - 1
MIC and fungicidal activity of terbinafine against clinical isolates of Aspergillus spp; Schmitt HJ et al.; Terbinafine and amphotericin B MICs for 90% of strains tested were 1.6 and 0.4 micrograms/ml against Aspergillus fumigatus (16 strains), 0.8 and 3.2 micrograms/ml against Aspergillus flavus (10 strains), and 0.4 and 1.6 micrograms/ml against Aspergillus niger (10 strains), respectively . For all species tested, the minimal inhibitory and fungicidal concentrations for 90% of strains of both drugs were identical and the inoculum size did not have a major effect on the results.

Pathol Biol (Paris), 1988 May, 36(5), 507 - 10
{Pharmacokinetics of piperacillin during continuous ambulatory peritoneal dialysis}; Ryckelynck JP et al.; We studied the kinetics of piperacillin in patients under continuous ambulatory peritoneal dialysis . Piperacillin 2 g was injected intravenously in 6 patients whereas 1 g was given intraperitoneally either a single dose in 3 patients without infection or the same dose every six-hours in 4 patients with peritonitis . Piperacillin was assayed by HPLC . After intravenous administration, the mean plasma piperacillin concentration was 3.1 +/- 5.6 mg/l at 12 h, the mean plasma t1/2 at 2.43 +/- 0.84 h, the volume of distribution at 20.4 +/- 6.3 l and the peritoneal clearance at 0.19 +/- 0.04 ml/min . After iterative intraperitoneal administration, serum and dialysate concentrations of piperacillin were above the minimum inhibitory concentration for susceptible pathogens without antibiotic accumulation . Peritoneal absorption was higher during peritonitis (83.4 +/- 4.8%) than without peritonitis (67.8 +/- 8.5%) . Piperacillin 2 g IV every 8 hours or 1 g IP every 6 hours seemed to be the appropriate regimen in patients with chronic renal failure on CAPD.

Pathol Biol (Paris), 1988 May, 36(5), 394 - 7
{Sensitivity to antibiotics of 64 strains of Stomatococcus mucilaginosus isolated in human clinical cases . Demonstration of erythromycin resistance}; Rochette A et al.; Susceptibility to fifteen antibiotics of 64 stains of Stomatococcus mucilaginosus isolated from bronchial secretions was tested by susceptibility antibiotics diffusion and MIC method . Sixteen phenotypic profiles were determined by MIC . Some of these profiles and the spontaneous loss of resistance to erythromycin indicate plasmidic origin of this resistance.

Microb Pathog, 1988 May, 4(5), 369 - 77
Mutations in cloned Escherichia coli P fimbriae genes that makes fimbriae-production resistant to suppression by trimethoprim; Vaisanen-Rhen V et al.; The effect of sublethal concentrations of trimethoprim on the expression of P fimbriae was tested in Escherichia coli HB101 recombinant strains . Fimbriation was inhibited at trimethoprim concentrations down to at least 1/64 of the minimal inhibitory concentration . However, the expression of the P fimbrillin by recombinant plasmids containing deletions in front of the fimbrillin gene did not respond to the inhibitory effect of trimethoprim indicating that trimethoprim may act at the level of gene regulation.

Pathol Biol (Paris), 1988 May, 36(5), 377 - 80
{Demonstration of an inoculum effect on the estimation of the minimal inhibitory concentration of LY 146032}; Flandrois JP et al.; This work has been performed to study the inoculum effect on the in vitro activity of LY 146032, a new lipopeptide antibiotic . A statistical analysis (X2 and t test) of the data concerning the MIC of different bacterial groups has been carried out to appreciate the phenomenon . The activity of vancomycin has been compared . A major inoculum effect has been detected for LY 146032 . It must be taken into account to evaluate the activity of this new antibiotic.

Hinyokika Kiyo, 1988 May, 34(5), 932 - 6
{Study of the prostatic tissue cefbuperazone (CBPZ) level}; Fjuii H et al.; The concentration of Cefbuperazone (CBPZ) was determined in the prostatic tissue and serum of 23 patients with benign prostatic hypertrophy . One or 2 of CBPZ was injected intravenously prior to transurethral prostatectomy . The mean CBPZ level in prostatic tissue and tissue/serum ratio at 1 hour was 17.4 +/- 7.2 micrograms/g (28.9 +/- 9.1%) in 10 patients administered 1 g of CBPZ, and 34.7 +/- 1C.2 micrograms/g (35.7 +/- 13.2%) in 13 patients administered 2 g of CBPZ . Serum and prostatic tissue CBPZ levels responded satisfactorily to the dose of CBPZ . Weights of resected prostatic tissue were not correlated to the tissue CBPZ level . Judging from the inhibitory concentration of CBPZ (minimum inhibitory concentration 80), the prostatic tissue CBPZ level was sufficient against pathogenic bacteria, particularly E . coli, K . pneumoiae and P . mirabilis for a relatively long time . For this reason CBPZ is a very useful drug for treatment of bacterial prostatitis and postoperative infection of prostate.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Apr, 268(2), 251 - 8
Further studies on colistin (polymyxin E)-induced cell leakage in mycobacteria: Mg++ efflux in Mycobacterium avium and its effects on drug-susceptibility; Rastogi N et al.; Action of colistin (polymyxin E) was investigated on the opportunistic pathogenic species Mycobacterium avium ATCC 15769 (resistant strain, MIC greater than 100 micrograms/ml) . Mycobacterium intracellulare ATCC 13950: a colistin-susceptible strain (MIC 25 micrograms/ml), was used as a parallel control for Mg++ efflux experiments . After the addition of 100 micrograms/ml of colistin to bacteria suspended in a buffer, both loss of viability and Mg++ efflux were followed for one week . Although there was an initial Mg++ efflux in both strains, it soon attained a plateau in case of the resistant strain without any loss of viability until 48 h, whereas in case of the susceptible strain, Mg++ efflux was about 3 times higher than former, a plateau was attained only 24 h after the drug addition, and the loss of viability started only 6 h after the drug addition . Consequently, the loss of viability of M . avium with later incubation times (6 days) was not due to the action of colistin on the cytoplasmic Mg++ efflux solely, but some additional effect was implicated . The drug-susceptibility of extracellularly-growing and intracellularly-growing (in the J-774 macrophage cell line) M . avium to the antibiotics tested could not be potentiated when they were used in combination with 5 micrograms/ml of colistin (maximal obtainable serum level in man) or the polymyxin B nonapeptide (PMBN), nor in the case of bacteria pretreated with these molecules.

Br J Ind Med, 1988 Apr, 45(4), 269 - 74
Effects of methyl isocyanate on rat muscle cells in culture; Anderson D et al.; Since the Bhopal disaster, in which the causal agent was methyl isocyanate (MIC), exposed people have complained of various disorders including neuromuscular dysfunction . In an attempt to gain some information about the response of muscle tissue to MIC its effects were investigated in cells in culture isolated from muscle of 2 day old rats . After treatment with a range of MIC concentrations (0.025-0.5 microliter/5 ml culture) the total number of nuclei of the two main cell types (fibroblasts and myoblasts) and the number of nuclei in muscle fibres (myotubes) were recorded . At lower doses which had little effect on the total number of nuclei, the formation of muscle fibres--that is, fusion of muscle cells--was prevented as the proportion of nuclei in myotubes was decreased . At higher doses both cell types were killed . This would suggest either an effect on muscle differentiation or a selective toxicity towards myoblasts . The observations were supported by light and electron microscopy.

Antimicrob Agents Chemother, 1988 Apr, 32(4), 458 - 61
In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae; Hayashi T et al.; Sedecamycin (lankacidin A), one of the lankacidin-group antibiotics, showed potent activity against Treponema hyodysenteriae . The MICs of sedecamycin against 79 field isolates of T . hyodysenteriae ranged from 0.78 to 12.5 micrograms/ml, the MIC for 90% of the strains tested (MIC90) being 3.13 micrograms/ml . The protective and therapeutic effects of sedecamycin were compared with those of carbadox, tiamulin, and lincomycin against experimental infection with T . hyodysenteriae in mice . The protective effect of sedecamycin was similar to that of carbadox, two times more potent than that of tiamulin, and three times greater than that of lincomycin . In the therapeutic test, sedecamycin showed activity similar to that of carbadox and was two times more active than both tiamulin and lincomycin . At doses of 10 mg or more of sedecamycin per kg, the recurrence of shedding of T . hyodysenteriae into the feces of mice was not detected for at least 8 weeks postmedication.

Pediatr Res, 1988 Apr, 23(4), 388 - 92
The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis; Dickinson CJ et al.; The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis . Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule . In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes . The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P . Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation . Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable . Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens . This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement . The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.

Gan To Kagaku Ryoho, 1988 Apr, 15(4 Pt 1), 619 - 24
{Preoperative treatment of lymph node metastases of gastric cancer by local injection of 5-FU adsorbed on activated carbon--clinical study of 5-FU concentration in resected lymph nodes}; Kobayashi O et al.; The concentration of 5-fluorouracil (5-FU) in blood and lymph node of 55 patients with gastric cancer who were endoscopically injected 250 mg of 5-FU alone or adsorbed on activated carbon into the gastric wall or 300 mg of 5-FU dry syrup orally before operation, were measured chronologically . The concentration of 5-FU in blood were similar in all cases but higher in lymph node in the group given adsorbed preparation than other cases . In the cases given adsorbed preparation, the lymph node concentration was remained high 7 days after injection, and in 37% cases more than the minimum inhibitory concentration of 5-FU remained . Therefore, for the purpose to elicit anticancer effect on micrometastasis in lymph nodes in the patients with gastric cancer, endoscopically preoperative injection of 5-FU adsorbed on activated carbon seemed to be useful.

Antimicrob Agents Chemother, 1988 Apr, 32(4), 450 - 3
Comparison of two methods for determining in vitro postantibiotic effects of three antibiotics on Escherichia coli; Rescott DL et al.; The postantibiotic effect (PAE) for 10 isolates of Escherichia coli was measured by two methods after 1 h of exposure to ampicillin, ciprofloxacin, or tobramycin . The reference method involved serial colony counting to determine growth after antibiotic exposure in relation to control growth . A spectrophotometric procedure was developed with the Abbott MS-2 research system . This method measured the time to detection of growth after exposure and compared this with the time for growth detection in control chambers having the same initial colony count . A reference curve of time to growth versus log initial CFU per milliliter was used to standardize control growth . PAE was determined after exposure to antibiotic at two and six times the MIC and with inocula ranging from 10(3) to 10(9) CFU/ml . There was a statistically significant correlation between PAE measured by the spectrophotometric and the reference methods, and the residuals about the regression line were normally distributed . The mean PAE determined by both methods was statistically different for tobramycin-exposed, but not for ampicillin- or ciprofloxacin-exposed, organisms . There was a concentration-dependent PAE for ciprofloxacin and tobramycin . The PAEs for ciprofloxacin (151 min) and tobramycin (108 min) at concentrations six times the MIC were prolonged compared with those measured at two times the MIC (69 and 66 min, respectively) . PAE was inversely related to the exposed inoculum for ciprofloxacin and tobramycin . The PAE for E . coli exposed to ampicillin was minimal and was not affected by either concentration or inoculum . The MS-2 method for determining PAE yields similar results, but is less laborious than the reference method.

Diagn Microbiol Infect Dis, 1988 Apr, 9(4), 231 - 7
Further in vitro studies with oxiconazole nitrate; Shadomy S et al.; Oxiconazole nitrate was compared in vitro with ketoconazole and econazole nitrate in tests with 96 dermatophytes, 18 isolates of Malassezia furfur, and seven isolates of Exophiala werneckii . An agar dilution procedure was used employing either Kimmig's agar or Sabouraud's dextrose agar supplemented with Olive oil and Tween 80 . Econazole was the more active compound in tests with Microsporum species (41 isolates) and most isolates of Trichophyton species (45 isolates) . Oxiconazole was the more active compound in tests with T . tonsurans and T . rubrum . However, differences between results for oxiconazole and econazole and the dermatophytes were only marginal . Ketoconazole was the most active compound in tests with M . furfur; some cross resistance on the part of several isolates of M . furfur between oxiconazole and econazole was noted . All three compounds were active against E . werneckii with MIC90 values of either 0.25 or 0.5 microgram/ml . Epidermophyton floccosum was the most susceptible of all organisms tested with all MIC values for all three drugs being less than or equal to 0.063 microgram/ml, the lowest concentration tested.

Antimicrob Agents Chemother, 1988 Apr, 32(4), 438 - 42
Routes of quinolone permeation in Escherichia coli; Chapman JS et al.; The uptake of quinolone antibiotics by Escherichia coli was investigated by using fleroxacin (RO 23-6240, AM 833) as a prototype compound . The uptake of fleroxacin was reduced and its MIC was increased in the presence of magnesium . Quinolones induced lipopolysaccharide release, increased cell-surface hydrophobicity and outer membrane permeability to B-lactams, and sensitized cells to lysis by detergents . These effects were also antagonized by magnesium and were very similar to those seen with EDTA and gentamicin . MICs of quinolones in portin-deficient strains were increased relative to those of the parent strain, consistent with a porin pathway of entry . However, MICs were further increased in the presence of magnesium; the size of the additional increase showed a positive correlation with quinolone hydrophobicity in an OmpF- OmpC- OmpA- strain . When quinolones were mixed with divalent cations in solution, changes in quinolone fluorescence suggestive of metal chelation were observed . The addition of fleroxacin to a cell suspension resulted in a rapid initial association of fluorescence with cells, followed by a brief decrease and a final time-dependent linear increase in cell-associated fluorescence . We interpret these results as representing chelation of outer membrane-bound magnesium by fleroxacin and other quinolones, dissociation of the quinolone-magnesium complex from the outer membrane, and diffusion of the quinolone through both porins and exposed lipid domains on the outer membrane . For a given quinolone, the contribution of the porin and nonporin pathways to total uptake is influenced by the hydrophobicity of the quinolone.

J Ultrastruct Mol Struct Res, 1988 Apr, 99(1), 18 - 26
Structure and location of tellurium deposited in Escherichia coli cells harbouring tellurite resistance plasmids; Taylor DE et al.; The plasmids RP4Ter and pHH1508a, which belong to the P and HII incompatibility groups, respectively, confer resistance to potassium tellurite (K2TeO3) on Escherichia coli . The genes for tellurite resistance were cloned from each plasmid onto the vector pUC8 to create pDT1366 and pD1364, respectively . Unstained, unfixed bacteria carrying these plasmids contained black intracellular deposits when grown on media containing tellurite . Thin sections of these bacteria fixed with glutaraldehyde were prepared and examined by electron microscopy . The black deposits were located inside the cell and were frequently associated with the inner membrane of the bacterium . Bacteria containing pDT1366 or pDT1364, and therefore a higher gene dosage of the Ter determinant, contained more black deposits, but had a decreased resistance, as measured by the minimum inhibitory concentration using the agar dilution method . Using the technique of electron spectroscopic imaging, the black intracellular deposits were shown to contain predominantly reduced metallic tellurium, and significant amounts of oxygen or carbon, thereby confirming earlier results using X-ray diffraction analysis of whole cells.

Am Rev Respir Dis, 1988 Mar, 137(3), 719 - 21
Rifabutine: minimal inhibitory and bactericidal concentrations for Mycobacterium tuberculosis; Heifets LB et al.; The minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of rifabutine (ansamycin LM427, spiropiperidyl rifamycin) against rifampin-susceptible and rifampin-resistant strains of Mycobacterium tuberculosis were determined . The MICs for 17 rifampin-susceptible strains were low, falling in a narrow range of 0.06 microgram/ml or less when determined by either the agar-dilution method (in 7H10 or 7H11 agar) or in 7H12 broth (radiometrically or by sampling and colony-forming units {CFU/ml} determination) . The MICs of rifabutine for 21 rifampin-resistant strains were much higher, ranging from 0.25 to 16.0 micrograms/ml . The MBCs of rifabutine were 0.125 or 0.25 microgram/ml for rifampin-susceptible strains, and were 4.0 and 32.0 micrograms/ml for two tested rifampin-resistant strains . The MIC/MBC ratio was 1:4 for rifampin-susceptible strains.

Am J Med, 1988 Feb, 84(2), 359 - 62
Pseudallescheria boydii brain abscess . Complication of an intravenous catheter; Perez RE et al.; An adult patient survived a brain abscess with Pseudallescheria boydii . She received intraventricular miconazole, 20 mg every 72 hours (minimal inhibitory concentration = 0.4 microgram/ml), and surgery . The abscess resulted from an infected central venous catheter (Port-A-Cath) and steroid therapy . Miconazole caused a ventriculitis . There are 12 reported cases of P . boydii brain abscesses from 1965 to 1985 with only two survivors.

J Med Chem, 1988 Feb, 31(2), 390 - 3
Adenosine deaminase inhibitors . Synthesis and biological activity of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine; Cristalli G et al.; Two new deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 1), 7-deaza-EHNA (6) and 1,3-dideaza-EHNA (11), were synthesized and evaluated for adenosine deaminase (ADA) inhibitory activity and compared with EHNA, 1-deaza-EHNA (2), and 3-deaza-EHNA (3) . Substitution of a methine group for a nitrogen atom in the 7-position of the purine moiety of EHNA produces a dramatic drop in the inhibitory activity (Ki = 4 X 10(-4) M) whereas compounds 2 and 3 are still good inhibitors (Ki = 1.2 X 10(-7) M and 6.3 X 10(-9) M respectively) . EHNA and its deaza analogues so far synthesized were also tested in vitro for their antiviral and antitumor activity in a range of cellular systems . EHNA and 1-deaza-EHNA are equiactive as inhibitors of human respiratory syncytial virus (HRSV) replication (MIC = 6.25 micrograms/mL) while the other compounds are inactive . On the other hand, all the examined compounds displayed an antitumor activity comparable to that of the reference compound 1-beta-D-arabinofuranosyladenine (ara-A), 7-deaza-EHNA being the most active of all . The results obtained showed that there is no correlation between adenosine deaminase inhibition and antiviral or antitumor activity in this series of compounds . 3-Deaza-EHNA, the most active inhibitor of ADA among the EHNA deaza analogues, greatly potentiates the antitumor activity of ara-A in vitro . In vivo activity was observed only when the two compounds were used in combination.

Pathol Biol (Paris), 1988 Feb, 36(2), 139 - 43
{In vitro sensitivity of Aspergillus to terbinafine: comparative study on amphotericin B, 5-fluorocytosine and ketoconazole}; Goudard M et al.; Terbinafine, a new antifungal agent derived from allylamine, effective by oral route, was tested against 32 different strains of Aspergilli to determine its in vitro efficiency compared with amphotericin B, 5-fluorocytosine and ketoconazole . Antifungal sensitivity was determine by the MIC method in liquid and solid mediums (Sabouraud, Casitone, YMA, YMB, YNB): with MIC between 0.005 and 5 micrograms/ml, whatever the species and the techniques, terbinafine is more efficient than amphotericin B, ketoconazole (0.5 to 100 micrograms/ml) and 5-FC (1-greater than 100 micrograms/ml).

Genitourin Med, 1988 Feb, 64(1), 25 - 9
Managing trichomonal vaginitis refractory to conventional treatment with metronidazole; Ahmed-Jushuf IH et al.; Three patients with vulvovaginitis caused by Trichomonas vaginalis, which was refractory to conventional treatment with metronidazole are described . The T vaginalis strain isolated from one patient was resistant to metronidazole (minimum inhibitory concentration (MIC) more than 100 mg/l) under aerobic conditions, although under anaerobic conditions it was as susceptible as a normal reference strain . The effect of the concomitant use of other medication and the influence of other vaginal pathogens on the efficacy of metronidazole are highlighted.

Z Hautkr, 1988 Jan 18, 63(1), 29 - 32
{In vitro effectiveness of ofloxacin and ciprofloxacin in genital Chlamydia trachomatis isolates measured by minimal inhibitory concentration and minimal bactericidal concentration}; Hartinger A et al.; Although Chlamydia trachomatis is usually susceptible to the most frequently applied chemotherapeutic agents in non-gonococcal urethritis in men and its counterpart in women--i.e., tetracycline and erythromycin--the clinical results are less satisfying than those in comparable gonococcal infections . Therefore, potent therapeutical alternatives are urgently called for . From this point of view, we investigated the in vitro susceptibility of 35 recent isolates of genital Chlamydia trachomatis from Munich to the new quinolones ciprofloxacin and ofloxacin . With both chemotherapeutics, the highest minimum inhibitory concentration amounted to 2.0 micrograms/ml; 1.0 micrograms/ml of ofloxacin inhibited 97% of the strains, ciprofloxacin but 57% . The highest minimum bactericidal concentration was 6.0 micrograms/ml . 5.0 micrograms/ml of ciprofloxacin killed all infectious particles in 91% of the strains, the corresponding figure for ofloxacin read 74% . Thus both quinolones of the second generation proved more or less equally effective in vitro . In view of the limited clinical experience gained so far with regard to these chemotherapeutic agents, we suggest further clinical study in this matter.

Drugs Exp Clin Res, 1988, 14(1), 39 - 43
A pharmacokinetic study of clofoctol in human plasma and lung tissue by using a microbiological assay; Danesi R et al.; A microbiological assay was undertaken to measure the amounts of clofoctol in human plasma and pulmonary tissue, and to investigate its pharmacokinetics . Clofoctol was extracted from samples using ethanol and the concentration of drug in the extracts was determined by the broth macrodilution method using as reference microorganisms S . aureus ATCC 29213 and B . cereus NCIB 8122, whose MIC values were 0.537 and 1.074 micrograms/ml respectively . This procedure allows the almost complete recovery of the drug and makes it possible to detect amounts of clofoctol as low as 5.5 micrograms/ml . Results indicate that clofoctol is well absorbed after a single rectal dose of 1.5 g, with a plasma Cmax at the 30th min after administration and an average AUC value of 80.91 micrograms/ml/h . The Cmax of lung tissue (which was higher than the plasmatic one) occurred at the 90th min and the average AUC value was 229.65 micrograms/ml/h, indicating good penetration of clofoctol into human lung tissue and appreciable tissue storage of the drug.

Vet Q, 1988 Jan, 10(1), 34 - 41
Some pharmacokinetic observations of carbadox medication in pigs; de Graaf GJ et al.; Concentrations of carbadox and a first metabolite, desoxycarbadox, were measured in contents of the porcine gastrointestinal tract after in-feed administration of carbadox in therapeutic dosages (100-150 ppm) . The levels of carbadox in the relevant parts of the gastrointestinal tract were found to be lower than the MIC-values reported for enteropathogenic microorganisms at their sites of action . The presented observations do not provide a pharmacological rationale for the therapeutic use of carbadox in the treatment of dysentery and diarrhoea in swine . The carbadox levels encountered in the proximal part of the gut (stomach, duodenum) however, seem to indicate that in-feed administration of 50 ppm carbadox can provide an effective prophylaxis against Treponema hyodysenteriae, a causative agent in swine dysentery . The timecourse of the blood levels of carbadox and desoxycarbadox after in-feed administration of carbadox (50 ppm) and the concentration profiles in the gastrointestinal tract are discussed with regard to the disposition of this drug in pigs.

Microbiol Immunol, 1988, 32(1), 57 - 65
Inhibitory activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine on the salmonid herpesviruses, Oncorhynchus masou virus (OMV) and Herpesvirus salmonis; Kimura T et al.; The highly potent and selective anti-herpesvirus agent, (E)-5-(2-bromovinyl)-2'deoxyuridine (BVdU), was examined for its inhibitory effect on the salmonid herpesviruses Oncorhynchus masou virus (OMV) and Herpesvirus salmonis (H . salmonis) . Minimum inhibitory concentrations (MIC) of BVdU for OMV and H . salmonis were 1.25 and 3.0 micrograms/ml, respectively; these values were equal to or higher than those obtained for acyclovir or cytarabine . OMV DNA polymerase activity was reduced in a dose-dependent fashion by BVdU 5'-triphosphate (BVdUTP) within the concentration range of 3 to 30 microM . However, BVdUTP could also be substituted for the natural substrate, TTP, in the OMV DNA polymerase assay . It is postulated that the inhibitory action of BVdU on the salmonid herpesviruses is more or less similar to that on other herpesviruses and resides with respect to the inhibition of the virus DNA polymerase activity as well as incorporation of BVdU into the viral DNA.

J Toxicol Environ Health, 1988, 24(1), 93 - 101
Inhibition of methyl isocyanate toxicity in mice by starvation and dexamethasone but not by sodium thiosulfate, atropine, and ethanol; Varma DR et al.; Effects of starvation (24 and 48 h), dexamethasone, sodium thiosulfate, atropine, and ethanol on the toxicity of methyl isocyanate (MIC) vapor, which escaped during the Bhopal accident of December 3, 1984, were studied in male Swiss-Webster mice . Toxicity to MIC appeared to be biphasic; majority of animals died between 1 and 2 d or between 7 and 21 d after exposure to 40 ppm MIC . Starvation (24 or 48 h) or an injection of 2 mg dexamethasone/kg prior to exposure inhibited the toxicity of MIC, especially during the first 6-7 d; administrations of sodium thiosulfate, alcohol, and atropine before or of dexamethasone after the exposure to MIC were ineffective . Starvation increased serum corticosterone levels . The antidotal effects of both starvation and dexamethasone might be due to suppression of the inflammatory response to MIC.

Chemotherapy, 1988, 34(1), 8 - 12
Correlation between plasma and tonsillar levels of cefroxadine; Fraschini F et al.; Serum and tonsillary tissue levels of cefroxadine, a new broad-spectrum cephalosporin, proving to be effective in several infections, particularly in the ENT ones, were measured in patients scheduled for tonsillectomy . Twenty patients (12 males, 8 females) aged between 11 and 25 years (mean 18.0 years) were given cefroxadine for 2 days (500 mg every 12 h), and on the 3rd day 500 mg of the drug was given before surgical operation . Tonsillar tissues were taken 2 h after dosing and blood samples before, 1, 2, 4 and 6 h after the drug administration in 8 out of 20 enrolled patients . Cefroxadine concentrations were measured according to microbiological methods . Cefroxadine tonsillary levels were 1.13 +/- 1.73 micrograms/g, approaching the MIC for sensitive bacteria . The time course of plasma levels is superimposable to previous studies . These findings suggest a rapid penetration of cefroxadine in tonsillar tissue and seem to confirm the clinical efficacy of the drug in ENT infections.

Am Rev Respir Dis, 1988 Jan, 137(1), 144 - 8
Evidence that antituberculosis drugs are really effective in the treatment of pulmonary infection caused by Mycobacterium avium complex; Tsukamura M; Successful chemotherapy of pulmonary disease caused by Mycobacterium avium complex by antituberculosis drugs has been reported by a number of investigators . However, no certain evidence of the efficacy has yet been demonstrated in a controlled clinical trial . The present study has approached this problem in 2 ways: serial analysis of minimal inhibitory concentrations (MIC) during treatment and correlation of response to therapy with initial MIC . It was observed that after administration of antituberculosis drugs (rifampin, isoniazid, kanamycin, enviomycin, and minocycline), MIC values for the M . avium complex strain increased significantly . This change may be considered a result of suppression of relatively susceptible bacteria and as evidence of the efficacy of drugs . Furthermore, a correlation between the MIC values determined before chemotherapy with the conversion of sputum to negative was shown . The M . avium complex strains varied markedly in their susceptibility to antituberculosis drugs, and these susceptibilities were correlated with the chemotherapeutic effect . The fate of patients seemed to be greatly influenced by the susceptibilities of the strains that caused infection.

Scand J Infect Dis, 1988, 20(4), 429 - 33
Levels of erythromycin in tear fluid and serum in infants with conjunctivitis; Sandstrom I et al.; 38 newborns with purulent conjunctivitis were treated with oral erythromycin ethylsuccinate 25 mg/kg every 12 h for 14 days . 3-4 days after initiation of therapy, erythromycin levels in serum and tear fluid were measured 1 and 12 h after the administration of erythromycin . The level of erythromycin in tear fluid was significantly higher than that in serum 1 and 12 h after administration of the antibiotic . On both occasions the concentrations of erythromycin in tear fluid and in serum exceeded the minimum inhibitory concentration (MIC) in vitro for Chlamydia trachomatis.

Rev Chir Orthop Reparatrice Appar Mot, 1988, 74(6), 493 - 503
{Antibiotic-loaded orthopedic cements . Pharmacokinetics and bone level}; Langlais F et al.; A mechanical study in the laboratory of 10 types of cement has shown that the characteristics of low viscosity antibiotic-loaded cements are comparable with those of standard cement without antibiotic and of standard viscosity . A study of the release of Gentamycin in 26 patients treated by total hip replacement showed that the concentration of antibiotic in the drainage fluid was much greater than the minimum inhibitory concentration whereas the low blood concentration gave no risk of ototoxicity or nephrotoxicity . This method of administration achieved antibiotic concentrations in the tissues in contact with the prosthesis 10 times greater than those obtained by injection . In sheep, the intra-osseous concentration was studied in 32 femora after insertion of low viscosity Gentamycin-loaded cement . The levels remained raised to 4 times the minimum inhibitory concentration for up to one year after operation, even with cements with a low concentration of antibiotic of 0.6 g/dose . The concentrations obtained in the drainage fluid, in the peri-prosthetic tissues and especially in bone, confirm the effectiveness and the prolonged action of antibiotic therapy by cement and its value in the revision of infected prostheses and in prophylaxis in primary surgery . This justifies the further study of combinations of cement with new antibiotics with a broader spectrum than Gentamycin since there is no concern with the cements currently in use that the mechanical quality is less than that of standard cement.

Jpn J Ophthalmol, 1988, 32(4), 392 - 400
Ocular penetration of subconjunctivally injected gentamicin, sisomicin and cephaloridine; Jain MR et al.; The intraocular penetration of three current bactericidal broad-spectrum antibiotics, namely, gentamicin sulphate, sisomicin sulphate (Ensamycin) and cephaloridine, following subconjunctival injection was studied in 95 patients undergoing elective cataract surgery . Rapid and high penetration of all three drugs was evidenced by the fact that the first samples assayed by modified disc diffusion technique 15 minutes after injection showed drug levels effective against all susceptible pathogens . Peak levels of gentamicin, sisomicin and cephaloridine attained one hour after injection were 14.913 +/- 0.310, 19.000 +/- 0.408 and 30.830 +/- 1.195 micrograms/ml, respectively . Such high drug titres would provide drug concentrations 6 to 8 times the minimum inhibitory concentration necessary against susceptible organisms . The duration of the effective bioavailability of the drugs studied varied from 12 to 18 hours . We believe our study is the first to document the excellent penetration of sisomicin and the little-studied drug cephaloridine, and hope our results will open an avenue for in vivo studies to evaluate their clinical use.

Boll Ist Sieroter Milan, 1988, 67(2), 97 - 104
In vitro effect of cefoxitin and amikacin combination on M . fortuitum; Orefici G et al.; The possible in vitro synergistic effect between amikacin and cefoxitin against 29 clinical isolates of M.fortuitum was studied either by the agar dilution checkerboard technique and by the killing curve on Mueller Hinton agar plus OADC enrichment and on 7H11 . As evaluated by FIC index on MHA a synergistic effect was noted on 20 (68.96%) strains tested, an additive effect on 8 (27.60%) isolates, and a possible antagonistic effect only on 1 (3.44%) isolate . On 7H11 a synergistic effect was shown on 10 (38.50%) isolates, an additive effect on 12 (46.10%) and an antagonistic effect on 4 (15.40%) isolates . The killing curve observed on three strains (562, 565 and 505), specially selected as representative of synergistic (562), additive (565) and antagonistic effect (505) on the basis of their checkerboard results, showed synergistic effect on strains 562 and 565 as well as on strain 505 where complete killing was obtained in 24 h by a combination of two antibiotics used at 1/2 Mic . By the killing curve technique both antibiotics were found to be bactericidal but the effect was earlier for amikacin than for cefoxitin.

Ann N Y Acad Sci, 1988, 544, 338 - 47
Sterol biosynthesis inhibitors . Secondary effects and enhanced in vivo efficacy; Berg D et al.; Sterol biosynthesis inhibitors such as the imidazoles and 1,2,4-triazoles are generally regarded as inhibitors of sterol C-14 demethylation . Neither the MIC values nor the data for direct interaction with the cytochrome P-450 responsible for oxidative C-14 methyl removal, however, fully explain the observed in vivo efficacy . The first generation of azoles, which includes clotrimazole and miconazole, has been supplemented by a second generation, and azoles of the new generation are capable of additional effects on sterol biosynthesis . With the new azoles, for example, delta 5 sterols may accumulate, the accumulation being due to additional sites of inhibition in sterol biosynthesis or to direct membrane-azole interactions . Ketoconazole, itraconazole, and vibunazole are representative of the azoles of the second generation . Finally, a third generation of azoles has been discovered . Azoles of this generation, which include fluconazole, show almost negligible in vitro potency against saprophytically grown fungi but excellent in vivo efficacy . These compounds specifically affect parasitic forms of fungi, thus blocking invasion processes, and interfere directly with the plasma membrane, as shown in leakage experiments . Such secondary effects obviously enhance in vivo potency.

Hell Stomatol Chron, 1988 Jan-Mar, 32(1), 29 - 31
{Antibiotic levels in blood serum and mandibular bone in rats with and without phenylbutazone administration}; Teseromati C et al.; Antibiotics' level was estimated in mandible and serum of wistar albino rats with and without co-administration of phenylbutazone, 5 groups of animals were used . The animals of group A were injected with 1 g/kg ampicillin and these of group B 1g/kg ampicillin and 100 mg/kg phenylbutazone im . To the animals of group C cephapirin was given 1 g/kg and these of group D 1g/kg cephapirin with 100 mg/kg phenylbutazone . The animals of group E were injected only with phenylbutazone . All the drugs, were given at a single dose . The level of antibiotics was estimated in serum and in mandible with the method of minimal inhibitory concentration (MIC) . An increase of the levels of antibiotics (ampicillin, cephapirin) was observed in those groups (B, D) to the animals of which phenylbutazone was given (together with antibiotics), compared with the groups (A, C) which had received antibiotics alone.

Drugs Exp Clin Res, 1988, 14(8), 501 - 10
Mucoid and pigmentation characters can be suppressed by non-anti-Pseudomonas aeruginosa antibiotics in cystic fibrosis: a report of promising preliminary results; Lapointe JR et al.; In an effort to develop new strategies, the authors are exploring the hypothesis that non-anti-Pseudomonas aeruginosa antibiotics can affect some major virulence factors in cystic fibrosis P . aeruginosa . Recent samples (127) of P . aeruginosa isolated from the sputum of cystic fibrosis patients and manifesting a mucoid growth were stored at -70 degrees C until experimentation . The mucoid character was retested after thawing and one 24-h in-vitro passage at 37 degrees C onto 100-mm blood agar plates to prepare a bacterial suspension for inoculation (Steers or MIC-2000 plus replicator) and cultivation (48 h, 37 degrees C) onto different 100-mm or 150-mm Mueller-Hinton agar plates containing either no antibiotics or antibiotics alone, and antibiotic combinations without presumed anti-P . aeruginosa activity . Some isolates (49, 38.6%) of P . aeruginosa expressed again the mucoid character on antibiotic-free Mueller-Hinton agar and growth was prevented by antibiotics in a number of them: 7 with doxycycline (16.0 micrograms/ml), 2 with rifampicin (16.0 micrograms/ml), 6 with roxithromycin-sulfamethoxazole (16.0-304.0 micrograms/ml) and 23 with trimethoprim-sulfamethoxazole . In the remaining evaluable isolates, the mucoid was modified towards the rough character in 36 out of 42 with doxycyline, 36 out of 47 with rifampicin, 31 out of 43 with roxithromycin-sulfamethoxazole and 20 out of 26 with trimethoprim-sulfamethoxazole . In parallel, the pigmentation was lost in the presence of antibiotics in those P . aeruginosa isolates having manifested this character on Mueller-Hinton agar . These results suggest that non-anti-P . aeruginosa antibiotics can modify the in vitro markers of virulence in cystic fibrosis P . aeruginosa and that they merit further investigation.

Drugs Exp Clin Res, 1988, 14(4), 231 - 51
Ultrastructure of Mycoplasma pneumoniae exposed to macrolide antibiotics during cultivation on a glass surface and in an organ culture, in relation to their mycoplasma-killing activity; Watanabe T; The macrolide antibiotics midecamycin acetate (MOM), erythromycin (EM), midecamycin (MDM), josamycin (JM) and rokitamycin (RKM) showed killing activity against Mycoplasma pneumoniae strain FH-P24 . The activity of MOM, EM and JM was not influenced by the number of organisms inoculated, but that of RKM was markedly decreased by a large inoculum . Scanning electron microscopic observations showed many long filaments crossing over each other with small colonies when the organisms were cultivated on a glass surface without any drug for 72 h . When they were exposed to four times the MIC of MOM, the filamentous forms were decreased and the colonies did not grow to a large size . However, after exposure to the other macrolides, the colonies grew larger . Transmission electron micrographs revealed that intracellular vacuolization of the organisms was induced by exposure to MOM, EM and JM, but a mixture of vacuolized cells and "young" organisms was observed after exposure to MDM and RKM . In hamster tracheal organ cultures, the number of organisms was greatly decreased by exposure to four times the MIC of MOM, and the remaining filamentous and colonized organisms were lysed . However, treatment with four times the MIC of the other macrolides induced hardly any lysis of the organisms . In transmission electron micrographs, filamentous and rounded organisms filling the ribosome-like matrix could be seen on the epithelial surface . Treatment with four times the MIC of these macrolides decreased the number of organisms and vacuolized filamentous organisms could be seen on the epithelial cells.

Trans R Soc Trop Med Hyg, 1988, 82(3), 366 - 8
Evaluation of the sensitivity in vivo and in vitro of Plasmodium falciparum malaria to quinine in an area of full sensitivity to chloroquine; Salako LA et al.; The sensitivity of Plasmodium falciparum to quinine in Nigeria was examined in vivo and in vitro prior to the re-introduction of the drug into malaria therapy in that country in the face of spreading chloroquine resistance in Africa . The parasites showed full sensitivity in vivo to quinine, with a mean parasite clearance time of 2.4 d and a mean fever clearance time of 1.4 d . Using the in vitro microculture technique, the Nigerian isolates were found to have a minimum inhibitory concentration (IC) of 1.28 mumol quinine/litre blood-medium mixture . The IC50 and IC99 were 0.25 mumol/litre and 0.8 mumol/litre respectively . The study afforded an opportunity to compare the sensitivity of P . falciparum to quinine and chloroquine in a population in which chloroquine resistance was not a problem and the results showed slower parasitological and clinical response to quinine than to chloroquine.

Scand J Infect Dis, 1988, 20(5), 531 - 4
In vitro selection of Escherichia coli mutants with decreased susceptibility to norfloxacin; Forsgren A et al.; In 10 clinical isolates of Escherichia coli the frequency of spontaneous mutation to high levels of resistance to nalidixic acid was greater than 300-fold higher than that to norfloxacin . Norfloxacin resistant mutants could not be detected (mutation frequency: less than 10(-12) . However, nalidixic acid resistant mutants of E . coli developed decreased susceptibility to norfloxacin at a rate of approximately 10(-9) . Mutants with decreased susceptibility to norfloxacin could also be obtained when the same clinical isolates of E . coli were exposed to norfloxacin in 2 steps . However, mutants with MIC values greater than 8 micrograms/ml for norfloxacin were never obtained even after repeated exposure . Widespread use of cinoxacin or nalidixic acid may select resistant strains and reduce the efficacy of norfloxacin and other 4-quinolones.

Soc Sci Med, 1988, 27(10), 1105 - 12
Some international law aspects of the Bhopal disaster; Tyagi YK et al.; This article explores certain international law aspects of the Bhopal disaster, namely the principles and rules of international law establishing international accountability for environmental damage; the criteria for determining the liability of the Union Carbide Company (U . S . A.) for the Bhopal disaster; the criteria for determining compensation; and the international remedies available to the Indian government in the event that Bhopal victims fail to get justice within the Indian court system . The article discusses two applicable sets of proposed international standards--the U . N . Draft Code of Conduct on Transnational Corporations, and the U . N . International Law Commission's Draft on International Liability for Injurious Consequences Arising out of Acts Not Prohibited by International Law . The scattered 'hard' and 'soft' jurisprudence of international environmental law establishes liability and accountability for environmental hazards . It makes both state and non-state entities liable to pay compensation to the victims of environmental pollution . This jurisprudence, in addition to domestic law analogies, can influence Indian courts in determining the amount of damages payable to the victims of the Bhopal disaster . The authors conclude that the Bhopal disaster has demonstrated that enforceable international standards are clearly and urgently needed for hazardous industries, especially those operating in developing countries . Such standards would eliminate, or at least narrow, the gap between standards prevailing in the developed countries and those in the Third World . Even without enforcement, international standards could provide norms for measuring the performance of individual companies engaged in hazardous activities such as the manufacture of MIC at Bhopal.

Ann N Y Acad Sci, 1988, 539, 352 - 61
New chemotherapeutic approaches in the treatment of Lyme borreliosis; Luft BJ et al.; 1 . It was demonstrated that while B . burgdorferi may be sensitive to relatively small concentrations of penicillin and ceftriaxone, the organism is killed slowly . This implies that, as in syphilis, prolonged blood levels of these drugs may be necessary in order to ensure cure . In contrast, the activity of tetracycline is more rapid in its action but is more dependent on drug concentration achieved . Unfortunately, the MIC and MBC for some strains are at or above the peak level achieved under optimal conditions . 2 . Increasing the concentrations of penicillin or ceftriaxone above the MIC for the organism has little effect on the rate of killing . In contrast, the killing by tetracycline can be augmented by increasing concentrations of the drug . 3 . Ceftriaxone is more active than penicillin, as measured by MIC, against the five strains of B . burgdorferi tested . 4 . Ceftriaxone was efficacious in the treatment of Lyme borreliosis, which was recalcitrant to penicillin therapy . In a randomized trial comparing ceftriaxone to high-dose penicillin therapy, ceftriaxone was significantly more efficacious than penicillin in the treatment of the late complications of Lyme borreliosis.

Scand J Infect Dis, 1988, 20(2), 205 - 12
Efficacy and safety of once daily versus intermittent dosing of tobramycin in rabbits with acute pyelonephritis; Herscovici L et al.; Unilateral pyelonephritis was induced in 50 rabbits by injecting Escherichia coli (minimum inhibitory concentration of tobramycin 0.25 mg/l) into the left kidney and by obstructing the ureter temporarily . Tobramycin treatment (daily dose 10 mg/kg) was started 4 days after surgery, either in a single daily dose or in 3 divided doses at 8 h intervals, for 2, 3, 5, 7 or 10 days . Comparison of bacteriology, renal morphology, and renal functions (BUN, serum creatinine, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, cathepsin B, sphingomyelinase) suggests better efficacy and renal tolerance of the single daily dose regimen in the treatment of experimental acute pyelonephritis.

Ann N Y Acad Sci, 1988, 544, 348 - 53
Activity of triazole derivatives against Pityrosporum orbiculare in vitro and in vivo; Faergemann J; The in vitro antimycotic activity and the in vivo antimycotic activity (in a rabbit model) of itraconazole against P . orbiculare were compared to the corresponding activities of ketoconazole . Fluconazole's in vitro antimycotic activity and in vivo antimycotic activity against P . orbiculare were tested in the same models . The MIC values of itraconazole against P . orbiculare were 0.1-0.2 micrograms/ml compared to 0.02-0.05 micrograms/ml for ketoconazole . For fluconazole, the MIC values were 12.5-50.0 micrograms/ml against P . orbiculare . In a rabbit model, orally administered itraconazole (5 mg/kg) afforded protection against experimental pityriasis (tinea) versicolor in four out of five rabbits . Ketoconazole (1 mg/kg) was effective in all four animals . The in vivo results with fluconazole were in contrast to its low in vitro activity . Fluconazole (5 mg/kg) afforded protection against experimental pityriasis (tinea) versicolor in five out of six animals.

Rev Mal Respir, 1988, 5(4), 401 - 6
{Study of the minimal inhibitory concentration of rifabutine (Ansamycin LM 427) for Mycobacterium tuberculosis, Mycobacterium xenopi and Mycobacterium avium-intracellulare}; Truffot-Pernot C et al.; Ansamycin LM 427 (or rifabutine) is a spiropiperidyl-rifamycin which has been proposed as a treatment for tuberculosis and mycobacterial infections resistant to rifampicin . The minimal inhibitory concentration (MCI) of rifabutine and of rifampicin for 10 strains of M . tuberculosis sensitive to rifampicin, 15 strains of M . tuberculosis resistant to rifampicin, 10 strains of M . xenopi and 15 of M . avium-intracellulare have been measured in a comparative fashion on gel DIFCO 7H11 medium and also on a Loewenstein-Jensen medium . The MCI of rifampicin and of rifabutine inhibiting 90% of the strains (MCI 90) of M . tuberculosis sensitive to rifampicin have been 0.06 mg/l on 7H11 media and 1 mg/l on Loewenstein-Jensen media respectively . For strains of M . tuberculosis resistant to rifampicin they were respectively 256 and 8 mg/l on 7H11 and of 1024 and 128 Loewenstein-Jensen, for the strains of M . xenopi they were 8 and 0.5 on 7H11 and 64 and 4 mg/l on Loewenstein-Jensen respectively, and finally for strains of M . avium-intracellulare they were 64 and 2 mg on 7H11 and 256 and 16 on Loewenstein-Jensen media . With rare exceptions for proven mycobacterial infections there was a link of the order of 20:1 between the values for CMI of rifampicin and rifabutine measured on Loewenstein-Jensen medium and on 7H11; the MCIs were ten times more elevated on the first than on the second and the liaison between the MCI of rifampicin and the MCI of rifabutine tended to show that these two antibiotics have the same mode of action.(ABSTRACT TRUNCATED AT 250 WORDS)

J Basic Microbiol, 1988, 28(1-2), 129 - 36
Cloning and preliminary characterization of the streptothricin resistance determinants of the transposons Tn1825 and Tn1826; Tietze E et al.; Streptothricin resistance determinants have been cloned from the transposons Tn1825 and Tn1826 to the vector plasmid pUC8 . The recombinant plasmids were characterized with respect to their physical structure . The resistance properties of their hosts were characterized with respect to the minimal inhibitory concentration of streptothricin and the activity of the streptothricin acetyltransferase . The proteins encoded by the cloned resistance determinants were analysed in a maxicell system . The results of our investigations suggest that the resistance to streptothricin is mediated by the activity of a streptothricin acetyltransferase with both, Tn1825 and Tn1826 . However, the resistance determinant of Tn1825 is more complex than Tn1826 and additional functions involved in realizing the resistance phenotype must be recognized.

Acta Microbiol Pol, 1988, 37(3-4), 261 - 70
Mutants of Saccharomyces cerevisiae resistant to a quaternary ammonium salt; Oblak E et al.; Three quaternary ammonium salts were compared in respect of their ability to select resistant mutants of S . cerevisiae . The mutants tolerating slightly higher IM compound concentration were analysed . They appeared to be the products of nuclear gene mutation segregating monogenically but strongly influenced by genetic background . The mutant IMR when transformed to rho degrees lost resistance below the level of minimal inhibitory concentration of original strain . Possible hypothesis explaining this phenomenon is presented.

Presse Med, 1987 Dec 16, 16(43), 2143 - 7
{Indications and limits of cefotaxime monotherapy}; Carbon C; Single drug therapy using a third generation cephalosporin of the cefotaxime type is possible in a number of situations where host defenses are intact, the causative microorganism is very sensitive (MIC less than 1 mg/l) and not concerned with phenomena of resistance by mutation, and the antibiotic is able to reach the site of infection at high concentrations . In contrast, the indications for two-drug therapy including an aminoglycoside appear to be better identified in patients with granulocytopenia . The possibility of single drug therapy preceded by a short period of two-drug therapy is also discussed.

Antiviral Res, 1987 Dec, 8(5-6), 273 - 81
Phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of African swine fever virus replication in vitro; Gil-Fernandez C et al.; Several phosphonylmethoxyalkylpurine and -pyrimidine derivatives related to (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine {(S)-HPMPA} and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated as inhibitors of African swine fever virus (ASFV) replication in Vero cells . (S)-HPMPA has previously been shown to inhibit ASFV replication at a minimum inhibitory concentration (MIC) of 0.01 microgram/ml with a selectivity index of 15000 . Of the new compounds tested, the following emerged as the most potent and selective inhibitors of ASFV replication: the cyclic phosphonate of (S)-HPMPA {(S)-cHPMPA} with an MIC of 0.2 microgram/ml and a selectivity index of 2500, the 2,6-diaminopurine analogue of (S)-HPMPA {(S)-HPMPDAP} with an MIC of 0.5 microgram/ml and a selectivity index of 1400, and the cytosine {(S)-HPMPC} and guanine {(RS)-HPMPG} analogues with an MIC of 1 microgram/ml and a selectivity index of 600-700.

Acta Pathol Microbiol Immunol Scand {B}, 1987 Dec, 95(6), 325 - 9
Susceptibility of small-sized oral spirochetes to eight antibiotics and chlorhexidine; Fiehn NE; The purpose of the study was to examine the susceptibility of two different small-sized spirochete morphotypes from subgingival plaque to eight antibiotics and chlorhexidine . MIC-values were determined by a broth dilution method and related to achievable antibiotic tissue- and blood concentrations . The spirochetes were characterized as susceptible, moderate susceptible, and resistant to the different antibiotics . The MICs of tetracycline hydrochloride, doxycycline, penicillin G, and chlorhexidine were all considerably lower for spirochete strains with a 2:4:2 endoflagella system (two endoflagella from each cell-end) than for strains with a 1:2:1 endoflagella system (one endoflagellum from each cell-end) . No differences were observed for the remaining antibiotics . Spirochetes containing one endoflagellum from each cell-end were found to be susceptible to metronidazole and doxycycline, susceptible to moderate susceptible to tetracycline hydrochloride, moderate susceptible to penicillin G, and resistant to the remaining antibiotics . Spirochetes containing two endoflagella from each cell-end were susceptible to doxycycline, tetracycline hydrochloride, and metronidazole . Susceptible to moderate susceptible to penicillin G . These spirochetes were resistant to the remaining agents . The significance of these observations is discussed in relation to obtainable gingival crevicular fluid concentrations and treatment of marginal periodontitis.

Toxicol Appl Pharmacol, 1987 Dec, 91(3), 502 - 5
Evaluating the potential for genotoxic carcinogenicity of methyl isocyanate; Ennever FK et al.; The carcinogenicity prediction and battery selection method was used to predict the probability of carcinogenicity of methyl isocyanate (MIC) based upon the results of short-term tests . The analysis predicts that MIC has a significant potential for inducing cancer in rodents . However, the pattern of response suggests that the carcinogenic potency would be low . Obviously, the realization of the identified risk would be dependent upon level, duration, and mode of exposure.

Southeast Asian J Trop Med Public Health, 1987 Dec, 18(4), 438 - 43
In vitro mefloquine resistance of Plasmodium falciparum isolated from the Burmese border region of Thailand; Childs GE et al.; The in vitro susceptibility of twenty isolates of Plasmodium falciparum from Tha Song Yang, Tak province, Thailand were determined . The isolates were resistant to chloroquine (IC50 = 220 nM; MIC = 762 nM), quinine (IC50 = 252 nM; MIC = 1010 nM), and pyrimethamine (IC50 = 16400 nM; MIC = 43100 nM) but generally sensitive to mefloquine (IC50 = 6.90 nM; MIC = 20.9 nM) and halofantrine (IC50 = 8.73 nM; MIC = 2.71 nM) . Two isolates were identified which appeared resistant to mefloquine (IC50 = 23.1 nM; MIC = 56.6 nM) . These isolates may represent an extension of a population of parasites from eastern Thailand.

Tubercle, 1987 Dec, 68(4), 267 - 76
Bacteriostatic and bactericidal activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex; Heifets LB et al.; MICs of ciprofloxacin were lower than MICs of ofloxacin for both M . tuberculosis and M . avium complex strains . The MICs of both drugs for 41 M . tuberculosis strains were in a narrow range, and significantly lower than the achievable serum concentrations . The MICs of ciprofloxacin for 46 M . avium strains were in a wide range, and in only 28% were the broth-determined MICs of ciprofloxacin within the same range as for M . tuberculosis and lower than the achievable serum level . When compared with the concentrations achievable in macrophages, the broth-determined MICs of ciprofloxacin were lower than this level for 61% of M . avium strains . Both drugs were bactericidal against M . tuberculosis and M . avium, with a low MIC/MBC ratio.

Eur J Clin Microbiol, 1987 Dec, 6(6), 682 - 4
Comparative activity of LY146032 against anaerobic cocci; Greenwood D et al.; Fifty strains of anaerobic gram-positive cocci were tested in vitro against benzylpenicillin, teicoplanin, vancomycin and LY146032 . The organisms displayed a wide range of susceptibility to penicillin and the minimum inhibitory concentration for 11 of the strains was greater than or equal to 1 mg penicillin/L . The activity of teicoplanin exceeded that of vancomycin by a factor of two . The activity of LY 146032 varied in different culture media and was dramatically potentiated by the addition of a physiological concentration of calcium . Peptococci were, in general, more susceptible than peptostreptococci to penicillin and to LY146032 in the absence of added calcium.

J Antimicrob Chemother, 1987 Nov, 20(5), 725 - 8
Imipenem kinetics in serum, lung tissue and pericardial fluid in patients undergoing thoracotomy; Benoni G et al.; Imipenem serum pharmacokinetics, lung tissue and pericardial fluid concentrations were measured in 10 patients undergoing thoracotomy, following a 1 g intravenous infusion of imipenem-cilastatin . The serum concentrations of imipenem 0.5 h and 4 h after the end of the 40 min infusion were 53.3 (+/- 16.7) and 2.0 (+/- 0.3) mg/l, respectively . The concentration of imipenem in lung tissue at 1 h was lower than in pericardial fluid and at 2.25 h the mean concentration of imipenem in pericardial fluid was 10.5 mg/l, vs . 0.28 mg/kg of lung tissue . Imipenem concentrations in pericardial fluid remained above 5 mg/l, well above the MIC for most pathogens, for 1 h whereas in pericardial fluid the concentration was 10.5 mg/l at 2.25 h.

Bull Eur Physiopathol Respir, 1987 Nov-Dec, 23(6), 591 - 7
The antibody response to methyl isocyanate: experimental and clinical findings; Karol MH et al.; Sera from 99 subjects exposed to the industrial gas leak in Bhopal on December 2, 1984 were studied along with sera from guinea pigs exposed to methyl isocyanate (MIC) to determine the production of antibodies specific to (MIC) . Each of the four guinea pigs injected with the reactive isocyanate produced MIC-specific antibodies in titres of 1:5120 to 1:10240, when tested with MIC-guinea pig albumin antigen conjugate . Analogous antigens prepared by reaction of MIC with human serum albumin were used to probe production of antibodies in 264 serially obtained human sera from 99 subjects from Bhopal . MIC-specific antibodies belonging to IgG, IgM and IgE classes were detected in eleven subjects . Though titres were low and transient (declining after several months) these findings indicate that the single large exposure to MIC resulted in an immunologic response . This finding was concomitant with chronic respiratory effects following MIC exposure.

Bull Eur Physiopathol Respir, 1987 Nov-Dec, 23(6), 587 - 90
Disaster at Bhopal: the accident, early findings and respiratory health outlook in those injured; Weill H; In December, 1984, in Bhopal, India, a massive leak of methyl isocyanate (MIC) resulted from operational and equipment malfunctions in a pesticide plant . Many thousands of residents of the city, most in proximity to the plant, suffered sublethal and lethal respiratory injuries, the expected consequences of high-level exposure to this type of potent irritant chemical vapour . Animal toxicologic information was limited prior to the accident, but has since confirmed that the lung is the major target of these lethal injuries, invariably with pulmonary oedema . Early concerns regarding acute cyanide intoxication were not supported by subsequent scientific inquiry . Superficial corneal erosions did not result in permanent eye injury . The primary medical (and, presumably, legal) issue which is unresolved, and perhaps unresolvable, is the incidence and determinants of long-term respiratory injury in the survivors . Available evidence, which is limited, suggests that chronic damage, when present, is, or resembles, fibrosing bronchiolitis obliterans, the expected consequence when permanent injury results from acute, high-level irritant gas exposure . Definition of the follow-up population is uncertain, and exposure information is lacking . Dose-response relationships are not likely to emerge from follow-up studies.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1775 - 8
Synergistic action of amphotericin B and rifampin against Rhizopus species; Christenson JC et al.; A 16-year-old diabetic patient developed Rhizopus pneumonia and was initially treated with amphotericin B for 7 days . Because of clinical deterioration of the patient, rifampin was added empirically . The patient improved clinically, and lung tissue removed surgically 8 weeks later showed no fungal elements by histopathological studies or by culture . An in vitro study of amphotericin B alone and in combination with rifampin against the isolate from the patient and 11 additional isolates of Rhizopus spp . was designed . The activity of amphotericin B in the presence of rifampin (10 or 5 micrograms/ml) increased fourfold against 9 of 10 clinical and 1 of 2 environmental isolates . Amphotericin B activity in the presence of 2 micrograms of rifampin per ml increased fourfold against 6 of 10 clinical isolates and increased twofold against an additional 3 clinical isolates . Amphotericin B in the presence of 1 microgram of rifampin per ml inhibited 9 of 10 isolates at a concentration of one-half the MIC of amphotericin B alone . These findings were confirmed by dose-response curves calculated from fungal dry weight determinations of Rhizopus spp . incubated in serial dilutions of amphotericin B combined with rifampin . These observations demonstrate in vitro, and possibly in vivo, synergy between amphotericin B and rifampin against Rhizopus spp.

J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 75 - 80
Activity of macrolides against organisms responsible for respiratory infection with emphasis on Mycoplasma and Legionella; Hara K et al.; The activity of roxithromycin against Legionella pneumophila in vitro was approximately the same as that of rokitamycin and superior to those of erythromycin and josamycin . In experimental pneumonia due to L . pneumophila none of the animals in the roxithromycin and rifampicin groups died by day 10 of the infection . The MIC ranges of roxithromycin, erythromycin and rokitamycin for Mycoplasma pneumoniae were 0.008-0.063, 0.004-0.008 and 0.016-greater than 125, respectively . In experimental pneumonia caused by M . pneumoniae, roxithromycin showed good activity similar to that of erythromycin.

J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 167 - 70
Clinical evaluation of roxithromycin in odontogenic orofacial infections; Sasaki J; An open multicentre clinical trial was conducted in Japan to study the efficacy and safety of roxithromycin in the treatment of acute odontogenic infections . Specimens were collected by needle aspiration only from closed abscesses . The MICs were determined for the pathogens isolated by an agar dilution method . Before and after administration of roxithromycin, whenever possible, a biological safety evaluation was performed . The drug was orally administered in a dosage of 200-400 mg daily, in two divided doses, before the morning and evening meals . Evaluation was objectively performed in accordance with the 'Evaluation Criteria for the Efficacy of Antibiotics by the Japan Society of Oral Surgeons' . A total of 144 bacterial strains were isolated from 73 of the 193 analysed subjects . The proportion of the strains sensitive to roxithromycin (MIC less than or equal to 3.13 mg/l) was 85.4% . One hundred and ninety three of a total of 216 subjects were included in the final analysis . The efficacy of the drug was assessed to be 85.5% . No dose-dependent difference in the clinical effect was observed . Adverse reactions were mainly gastrointestinal disorder, seen in five of 211 subjects (2.4%), while increased hepatic transaminases were observed in two of 92 subjects (2.2%).

Infection, 1987 Nov-Dec, 15(6), 465 - 8
Activity of fosmidomycin in an in vitro model of the treatment of bacterial cystitis; Kanimoto Y et al.; The response to fosmidomycin of four strains of Escherichia coli was studied in an in vitro model of the treatment of bacterial cystitis . Three susceptible strains of E . coli responded well to relatively low concentrations of fosmidomycin: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for 13 h or more; however, when the surviving bacteria were challenged with a second dose, a reduced response was observed . When a fully resistant strain was exposed to fosmidomycin, bacterial growth was also suppressed for 13 h or more, even when the peak concentration achieved was below the conventionally determined minimum inhibitory concentration . Resistant variants which emerged after exposure to fosmidomycin were also resistant to fosfomycin in the absence of the potentiating agent, glucose-6-phosphate . In the presence of glucose-6-phosphate, complete (or partial) susceptibility to fosmidomycin and fosfomycin was retained by three of the four strains . These results suggest that fosmidomycin and fosfomycin are transported into E . coli by a similar mechanism, and that deletion of the hexose phosphate transport system does not occur following exposure to fosmidomycin in the absence of glucose-6-phosphate.

Ann Inst Pasteur Microbiol, 1987 Nov-Dec, 138(6), 737 - 44
Aspects of the antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine; Toyohara M; The antituberculous activity of 27753-RP (RP), a new semisynthetic derivative of griselimycine, was determined both in vitro and in vivo, and its activity against atypical mycobacteria was also studied in vitro . 1) The minimal inhibitory concentration of RP against H37Rv and its mutants resistant to streptomycin, isoniazide, kanamycin, rifampicin and enviomycin was 0.5 microgram/ml in liquid media, showing no cross-resistance . However, loss of potency occurred in Ogawa's egg media, and 50 micrograms/ml of RP were required for inhibition of growth . 2) In the therapeutic study of experimental tuberculosis in mice, RP was shown to have a remarkable effect . In particular, when treatment was started immediately after infection, RP showed a therapeutic efficacy comparable to that of rifampicin, although a double dose of the drug was required . When treatment was started 3 weeks after infection, RP was inferior to rifampicin in therapeutic efficacy . 3) RP also showed excellent antituberculous activity against experimental tuberculosis in guinea-pigs . Twice-a-week treatment had a therapeutic efficacy comparable to that obtained by daily treatment, but with an increased dosage . 4) Among atypical mycobacteria, RP showed some degree of activity against Mycobacterium kansasii in vitro, while its activity against M . intracellulare appeared to be extremely low.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1843 - 5
Effects of rokitamycin and other macrolide antibiotics on Mycoplasma pneumoniae in L cells; Misu T et al.; Fifty strains of Mycoplasma pneumoniae in L cells were tested for susceptibility to macrolide antibiotics . Rokitamycin, a new macrolide antibiotic, was most active against these organisms, with an MIC for 90% of strains of 0.007 microgram/ml . The MICs of erythromycin, josamycin, and kitasamycin for 90% of strains were 0.03, 0.03, and greater than or equal to 0.06 microgram/ml, respectively . Based on these results, rokitamycin is a promising antibiotic for the treatment of mycoplasmal infections, and further clinical investigations are needed.

J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 31 - 7
Factors affecting the in-vitro activity of roxithromycin; Andrews JM et al.; The effect of human serum and CO2 on the activity of roxithromycin and erythromycin was assessed . Protein binding of roxithromycin in serum from various animal sources, acid alpha 1-glycoprotein and human albumin V was determined . There was a four- to eight-fold increase in MIC and MBC of roxithromycin in the presence of 70 and 100% human serum (minimum effect seen with erythromycin) and for both compounds there was a four- to eight-fold increase in MIC for fastidious organisms in the presence of CO2 . Roxithromycin appears to be selectively bound to acid alpha 1-glycoprotein, binding decreases with an increase in roxithromycin concentration (saturable at 10 mg/l) and protein binding is variable depending on animal source (86% human, 10% guinea pig) and this must be considered when data on activity from animal studies are evaluated.

Fundam Appl Toxicol, 1987 Oct, 9(3), 480 - 95
Four-day repeated inhalation and recovery study of methyl isocyanate in F344 rats and B6C3F1 mice; Mitsumori K et al.; F344 rats and B6C3F1 mice of both sexes were exposed by inhalation to 0, 1, and 3 ppm methyl isocyanate (MIC) for 4 consecutive days (6 hr/day) followed by a recovery period of 91 days . Five mice and rats/sex/group except the 3 ppm group (5 rats/sex on Day 7 and 2 males on Day 28) were killed on Days 7, 28, 49, and 91 after the exposure and examined histopathologically . Forty-nine of 56 male rats, 51 of 56 female rats, and 1 of 56 male mice in the 3 ppm group died by 28 days; early death animals were also examined histologically . Exposure-related changes occurred in rats and mice of both sexes in the 3 ppm group only . Lesions of the nasal cavity in rats and mice were characterized by regeneration of the olfactory and respiratory epithelia secondary to epithelial erosion . By Day 28 the olfactory and respiratory epithelia in mice appeared normal, while in rats incomplete regeneration of the olfactory epithelium was still present . Regeneration of the respiratory epithelium in the trachea of rats occurred in the 3 ppm group and the epithelium appeared to return to normal by Day 28 . Lung lesions in rats consisted of mural and/or intraluminal fibrosis secondary to extensive erosion of the respiratory epithelium in the major bronchi to the terminal bronchioles . Acute inflammation of the small airways, occasional hyaline membranes of alveolar walls, and pulmonary atelectasis were also seen . Alveolar fibrosis was observed in rats found dead from Day 14 on and in male rats killed on Day 28 . Atrophy of the thymus and spleen, atrial thrombosis of the heart, and hepatocellular necrosis were frequently seen in rats dying following MIC exposure . The lung lesions in mice were qualitatively similar to those in rats, but were restricted to the major bronchi . Minimal intraluminal or mural fibrosis was still present in mice on Day 91 . In a separate study, a single 6-hr exposure of five male rats to 3 ppm MIC was followed by a recovery period of 7 days . The lesions of the respiratory system were essentially the same as those in the 3 ppm group killed on Day 7 after the 4-day repeated exposure of MIC, but the alveolar lesions were more severe.

Appl Environ Microbiol, 1987 Oct, 53(10), 2567 - 73
Flow microcalorimetry investigation of the influence of surfactants on a heterogeneous aerobic culture; Beaubien A et al.; The influence of various surfactants on the biological activity of a mixed aerobic culture has been investigated by using flow microcalorimetry . The response of the culture to the addition of homologous n-alkylcarboxylates (C2 to C16) and n-alkylpyridinium bromides (C11 to C14) has been examined under endogenous and substrate saturation conditions, and inhibitory concentrations (MIC or the concentration which decreased the initial activity (heat flux) of the culture by 50%) were determined for each state . Under both conditions, the n-alkylpyridinium bromides were found to be more toxic than the n-alkylcarboxylates of identical chain length, thus confirming that the head group of the amphiphiles plays an important role in the microbial toxicity of surfactants . The relationship observed between the concentration at which 50% of the activity is lost and the chain length of the surfactant further confirms that cellular toxicity is also dependent on surfactant hydrophobicity . In relation to the biodegradability of surfactants in mixed aerobic cultures, the low concentration effects of n-alkylcarboxylates on endogenous culture were investigated in some detail . There appear to be compounded indications that these surfactants are rapidly metabolized by the microorganisms of the mixed culture, at least for homologs lower than C10.

Mycopathologia, 1987 Oct, 100(1), 17 - 22
Keratomycosis due to Alternaria alternata corneal transplant infection; Ando N et al.; A 53-year-old woman was found to have an ulcer on her successfully transplanted corneal graft . Many fungal elements were observed in the smear of the ulcerated tissue, and Alternaria alternata was cultured . The ulcer was treated with pimaricin and thimerosol topically, and 5-fluorocytocin (5FC) generally and healed to scar after two months . The ulcer did not invade the host cornea, but remained in the donner cornea in all clinical course . The MIC of five drugs on the isolated strain was following; thimerosal 0.0063, pimaricin 2.0, amphotericin B 3.2, aystatin 6.3 and 5FC 100.0 micrograms/ml each.

Diagn Microbiol Infect Dis, 1987 Oct, 8(2), 131 - 3
Susceptibility of Bordetella pertussis to five quinolone antimicrobic drugs; Appleman ME et al.; Five quinolone antimicrobic agents were tested to determine the mean inhibitory concentration (MIC) of each of 17 clinical strains of Bordetella pertussis by the agar dilution method . Ciprofloxacin demonstrated the best in vitro activity with an MIC90 of 0.06 microgram/ml . Norfloxacin, ofloxacin and enoxacin were also highly active with MIC90s of 0.25, 0.25, and 0.5, respectively . Cinoxacin was only moderately active (MIC90 4.0 microgram/ml).

Biull Eksp Biol Med, 1987 Oct, 104(10), 490 - 2
{Combined action of nucleosides and alpha-interferon in inhibiting the reproduction of the herpes simplex type-II virus}; Temicheva EV et al.; Therapeutic effect of four combinations of antiherpetic chemical preparations--acyclovir (ACV), 9-beta-D-arabinofuranosyladenine (ARA-A) and E-5-(2-bromovinyl)-2'-desoxyuridine (BVDU)--has been studied . Mutual enhancement was observed in all the combinations studied, except for ACV and ARA-A combination, where partial antagonism was observed . ACV + BVDU was shown to be the most optimal combination, with the minimum inhibitory concentration (MIC) of BVDU decreasing 400-fold . A significant enhancement of nucleosides antiviral effect was noted when the human leucocyte interferon was used with the combinations . Along with synergistic effect during the interaction of alpha-interferon with ACV the antagonism in the combination of alpha-interferon with ARA-A was observed.

J UOEH, 1987 Sep 1, 9(3), 299 - 303
In vitro effects of monobactams on Legionella pneumophila; Yoshida S et al.; The effects of azthreonam and carumonam against Legionella pneumophila Philadelphia-1 strain in liquid medium and in phagocytic cells were examined . The minimum inhibitory concentration (MIC) of azthreonam for the bacteria was 12.5 micrograms/ml at a concentration of 1.4 X 10(4) colony forming units (CFU) and 25 micrograms/ml at a concentration of 1.4 X 10(5) CFU . MIC of carumonam was 25 micrograms/ml in both concentrations of the bacterial suspension . In guinea pig macrophages, both azthreonam and carumonam at a concentration of 100 micrograms/ml did not inhibit the multiplication of the bacteria.

Mycopathologia, 1987 Sep, 99(3), 175 - 81
In vitro sensitivity of environmental isolates of pathogenic dematiaceous fungi to azole compounds and a phenylpropyl-morpholine derivative; Okeke CN et al.; The in vitro sensitivity (minimum inhibitory concentrations; MICs) of 42 environmental isolates of pathogenic dematiaceous fungi to 7 azole compounds, viz . thiabendazole, ketoconazole, miconazole, econazole bifonazole, Bay n 7133, Bay 1 9139 and phenylpropyl-morpholine derivative, Ro14-4767/002 was studied by an agar dilution method using Emmon's Sabouraud dextrose agar (ESDA) as the culture medium . The isolates of Fonsecaea pedrosoi, Cladosporium carrionii, Exophiala jeanselmei and Ramichloridium subulatum were most sensitive to bifonazole with mean MICs of 0.06 microgram/ml or less; Phialophora verrucosa had an MIC of 0.05 microgram/ml to ketoconazole and Ro14-4767/002, respectively . Ochroconis sp had an MIC of 0.025 microgram/ml to Ro14-4767/002 and Cladosporium tennuisimum 0.39 microgram/ml to ketoconazole . Econazole and thiabendazole also showed good antifungal activity . The fungi were relatively resistant to the more recently developed azoles, viz . Bay n 7133 and Bay 1 9139, the later failing to inhibit C . tennuisimum at a concentration of 100 micrograms/ml . The minimum fungicidal concentrations (MFC) of the drugs were mostly within 2 to 8 fold of the MICs.

Immunol Lett, 1987 Aug, 15(4), 311 - 6
Production and characterization of heat-aggregated IgG complexes with pre-determined molecular masses: light-scattering study; Ostreiko KK et al.; A method for the preparation of model immune complexes of heat-aggregated human IgG with predetermined molecular masses is described . IgG complexes with different molecular masses were produced by incubation of human IgG for 20 min at 63 degrees C, the protein concentration varying from 0.5 to 5 mg/ml before heat treatment . To determine the bulk of IgG molecules included in the aggregates, the IgG complexes obtained were precipitated by 7% polyethylene glycol . The relative molecular masses of the heat-aggregated IgG preparations were calculated using light-scattering measurements, being expressed as the number of IgG molecules per aggregate (MIC/MIgG) . The dependence of the MIC/MIgG value upon IgG concentration in aggregation was plotted . This dependence makes it possible to produce IgG model immune complexes with pre-determined molecular masses.

Am Rev Respir Dis, 1987 Aug, 136(2), 349 - 52
Determination of minimal inhibitory concentrations of antituberculosis drugs by radiometric and conventional methods; Lee CN et al.; Minimal inhibitory Concentrations (MIC) of 5 antituberculosis drugs (isoniazid, rifampin, streptomycin, ethionamide, and ethambutol) were determined by the radiometric (BACTEC) broth method and by the agar plate proportion method . Seventeen M . tuberculosis strains, isolated from patients before treatment, were tested . The MIC values of 4 of the 5 drugs (the exception was streptomycin) were 2 to 4 times lower in 7H12 broth than in 7H11 agar . The broth-determined MIC were also at least 2 to 4 times lower than the achievable serum concentrations . The broth-determined MIC are probably much closer to the true MIC values than those determined in agar plates because of the lower degree of absorption and degradation in the liquid medium . The radiometric broth method is a simple and rapid quantitative method for accurate determination of the MIC values of the antituberculosis drugs . The data obtained in this study will be used for further evaluation of the MIC values as complementary or alternative to the conventional qualitative testing against critical concentrations.

Eur J Clin Microbiol, 1987 Aug, 6(4), 367 - 77
World-wide development of antibiotic resistance in pneumococci; Appelbaum PC; Antibiotic-resistant pneumococci, especially penicillin-resistant strains, are being increasingly isolated . Pneumococci with intermediate penicillin-resistance (MIC 0.1-1.0 micrograms/ml) have been reported from many parts of the world over the past two decades, and highly resistant strains (penicillin MICs greater than or equal to 2 micrograms/ml) have also appeared . Infection may be acquired in the hospital or community, and nosocomial outbreaks may occur which require control measures to limit organism spread . Most infections occur in children with diminished host responses . Disease caused by pneumococci with intermediate penicillin-resistance may be treated with high doses of penicillin, but disease caused by highly resistant strains, especially meningitis, may require alternative therapy . Pneumococci resistant to sulfonamides, tetracyclines, erythromycin, lincomycin, clindamycin, chloramphenicol, aminoglycosides and rifampin have also appeared . Strains resistant to all the above-mentioned agents, including all beta-lactam antibiotics tested, have been reported from South Africa and Spain . Alternative therapy for resistant strains may include vancomycin, cefotaxime, cefoperazone, ceftriaxone and imipenem . Pneumococci isolated from sites suggestive of infection, especially blood and cerebrospinal fluid, should be routinely tested for penicillin-susceptibility.

Chemioterapia, 1987 Aug, 6(4), 256 - 60
Effect of subinhibitory concentrations of ampicillin on the R plasmid transfer in Escherichia coli; Palomares JC et al.; The effects of subinhibitory concentrations (sub-MICs) of ampicillin on R plasmid transfer in Escherichia coli were studied . Each donor strain culture was separated into two parts; one was mixed with a recipient strain culture for mating, the other was treated with the sub-MIC of ampicillin and then mixed with the recipient strain culture . In both cases the R plasmid transfer frequency was determined at 30, 60, 90 and 120 min of mating . Results showed that there exists a general decrease in the transfer frequencies under sub-MIC treatment (two plasmids did not transfer at all) . The proportion of aggregates and the number of cells that compose them were not affected by the sub-MIC of ampicillin . Our study supports the idea that the changes induced in E . coli by sub-MICs of ampicillin did not affect the function of the surface structures responsible for aggregation but did affect the proteins implicated in DNA transfer, situated on the cell surface.

Surgery, 1987 Aug, 102(2), 206 - 14
Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis; Browder W et al.; To assess the role of combined immunomodulator and antibiotic therapy in sepsis, glucan--a beta 1,3 polyglucose--and gentamicin were administered in a model of murine peritonitis . ICR/HSD mice received one of four treatment regimens: 5% dextrose; gentamicin 0.02 mg intramuscularly (sub-MIC) 2 hours before peritonitis; glucan 0.1 mg intraperitoneally 24 hours before peritonitis; combined glucan-gentamicin treatment . All animals were challenged with 1 X 10(8) Escherichia coli intraperitoneally . Long-term survival was significantly enhanced in the combined therapy group (56%, p less than 0.05) when compared with D5W (0%), gentamicin alone (0%), or glucan alone (9%) . Macrophage secretory activity, as assayed by interleukin-1 (IL-1) production, was significantly enhanced by combined therapy when compared with the other three treatment groups . Combined therapy significantly reduced E . coli bacteremia at 8 hours after inoculation, when compared with the other three groups . Availability of host neutrophils was assessed by peripheral counts and bone marrow proliferation assay . Combined glucan-gentamicin significantly enhanced bone marrow proliferation when compared with the other three groups and this enhancement correlated with increased circulating neutrophils . Combined immunomodulator and antibiotic therapy had synergistic effects on survival in E . coli peritonitis . This combined therapy enhanced macrophage secretory activity and bone marrow proliferation . Clinical use of immunomodulators may alter conventional use and dosage of antibiotics.

Arch Environ Health, 1987 Jul-Aug, 42(4), 230 - 7
An evaluation of respiratory effects following exposure to 2.0 ppm formaldehyde in asthmatics: lung function, symptoms, and airway reactivity; Witek TJ Jr et al.; Fifteen asthmatic volunteers were exposed in a double-blind, random manner to room air and 2.0 ppm formaldehyde for 40 min in an environmental chamber . These exposures were repeated on a separate day during moderate exercise (450 kpm/min) for 10 min . Ambient and dew point temperatures were 23.0 +/- 0.0 degrees C and 11.5 +/- 1.0 degrees C, respectively . No significant airway obstruction as measured by flow-volume parameters and airway resistance was noted in this group during or immediately after exposure . Furthermore, sequential measurements of peak flow for 24 hr following formaldehyde exposure revealed no delayed airway response . In contrast, in comparison to the baseline methacholine inhalation challenge (MIC) test on the screening day, 8 of 12 asthmatics demonstrated a lower threshold to MIC following 2.0 ppm exposure for 40 min; however, the mean and median decrements of threshold in methacholine concentration of 10.4 mg/ml and 24.3 mg/ml were not significant (p = .12) . Bad odor, sore throat, and eye irritation were common during exposure but symptoms were infrequent afterward.

Anaesthesist, 1987 Jul, 36(7), 333 - 9
{Nitrous oxide in combination anesthesia . Quantitative aspects of the effect of nitrous oxide}; Rothhammer A; Minimal Alveolar Concentration (MAC) defines the anesthetic potency of nitrous oxide (N2O) combined with an inhalational anesthetic only for the moment of skin incision . For the complete operation, the proportional action of N2O is unknown . This prospective, randomized study reports the mean intraoperative concentration (MIC) of halothane with and without 70% N2O in combination with premedication, i.v . induction, and muscle relaxation for the duration of operation . METHODS: Forty ASA I-II patients scheduled for hysterectomies gave informed consent . All patients received atropine 0.5 mg, promethazine and pethidine 1 mg/kg i.m . 30-45 min prior to anesthesia, i.v . induction with thiopental, and neuromuscular blockade with alcuronium at the beginning of the operation . Post-induction, patients received randomized halothane in 30% O2/70% N2 (group 1, n = 20) or in 30% O2/70% N2O (group 2, n = 20) . In the course of this observation (before induction and up to 15 min after extubation), the following parameters were measured (Table 1): arterial pressure (AP), heart rate (HR), plasma concentrations of growth hormone, prolactin, and cortisol in central venous blood, esophageal temperature, "train-of-four" ratio, and expiratory CO2 concentration . MIC had been computed from the integral of end-expiratory halothane concentration during the course of the operation . RESULTS: Biometric data and concomitant conditions were equivalent within the two groups (Table 2) . MIC halothane was 0.72 +/- 0.014 vol% in group 1 (O2/N2) and 0.52 +/- 0.01 vol% in group 2 (O2/N2O).(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicol Lett, 1987 Jul, 37(2), 131 - 4
Inhibition of rat brain cytochrome oxidase activity by pyrolysed products of methyl isocyanate; Bhattacharya BK et al.; The effects were studied of methyl isocyanate (MIC) and its thermally degraded products (dMIC) on rat brain cytochrome oxidase activity . Pure MIC did not inhibit brain cytochrome oxidase activity . A significant inhibition of brain cytochrome oxidase activity by dMIC was observed both in vivo and in vitro . The presence of cyanide in pyrolysed products of MIC has also been confirmed by chemical methods.

J Hosp Infect, 1987 Jul, 10(1), 58 - 66
The effect of antibiotic prophylaxis and topical antiseptics on the bacterial flora of the skin after cardiac surgery; Wilson AP et al.; A controlled trial of antibiotic prophylaxis in cardiac surgery compared a two-dose regimen of teicoplanin with a longer conventional course of flucloxacillin and tobramycin . In 12 patients the susceptibility of the bacterial skin flora of four different sites to each of the three antibiotics was determined and the results are reported here . Less than 1% of the Gram-positive colonies showed reduced sensitivity to teicoplanin (MIC greater than or equal to 4 mg l-1) . Before operation, 99% inhibition of Gram-positive growth was achieved at 26 (54%) of 48 sites by 1 mg l-1 of flucloxacillin and 13 (27%) sites by 2 mg l-1 tobramycin . By the 7th day after operation there was a significant reduction in the number of sites showing similar sensitivity to flucloxacillin {16 (33%) sites, P less than 0.05} . The use of teicoplanin was not associated with the emergence of Gram-negative skin flora but tobramycin promoted acquisition of aminoglycoside-resistant strains.

Antiviral Res, 1987 Jul, 7(6), 341 - 52
Inactivation of herpes simplex virus by protein components of bovine neutrophil granules; Zerial A et al.; From an acid extract of granules of bovine neutrophils we isolated fractions of cationic proteins, exhibiting significant anti-herpesvirus activity at concentrations which were devoid of cytotoxicity and of activity against a picornavirus (rhinovirus) . The mechanism of action seems to involve a direct neutralization of the virions . Two antiviral peptides with an approximate MW 7500 were purified to homogeneity by reversed phase high-performance liquid chromatography . Proline and arginine accounted for about 43% and 26-27% of their amino acid residues . One of these peptides (IIIa2 beta) had an MIC of 2 microM.

Environ Health Perspect, 1987 Jun, 72, 71 - 5
Two-hour methyl isocyanate inhalation exposure and 91-day recovery: a preliminary description of pathologic changes in F344 rats; Bucher JR et al.; The accidental release of methyl isocyanate (MIC) in Bhopal, India, was reportedly responsible for the deaths of more than 2,000 people . To study the pathology of acute inhalation exposure to MIC, the tissues of male and female Fischer 344 rats were evaluated immediately after a single 2-hr exposure to 0, 3, 10, or 30 ppm MIC, and through day 91 . Early gross pathologic changes in the 30 ppm-exposed rats included a reddish white encrustation around the mouth and nose, a small thymus, and distension of the gastrointestinal tract with gas . Lungs (middle and median lobes) showed consolidation and hemorrhage and failed to deflate when the chest cavity was opened . Microscopic changes in the upper respiratory tract 3 hr after exposure included marked erosion and separation of olfactory and respiratory epithelia from the basement membrane with accumulation of serofibrinous fluid . On day 1, acute inflammation and fibrinopurulent exudate partially blocked the nasal passages . Epithelial cells had sloughed from the nasopharynx, trachea, bronchi, and major bronchioles, leaving the basement membrane covered with fibrin and exudate . Granulomatous inflammation and intraluminal fibrosis of the airways were observed by day 3, with increased intraluminal fibrosis by day 7 . Lower airways became blocked by exfoliated cells, mucous plugs, and/or intraluminal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Environ Health Perspect, 1987 Jun, 72, 45 - 51
Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals; Adkins B Jr et al.; Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC) . Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages . MIC was delivered with nitrogen via stainless steel and Teflon supply lines . Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector . Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min) . The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

Environ Health Perspect, 1987 Jun, 72, 39 - 44
Biological effects of short-term, high-concentration exposure to methyl isocyanate . V . Morphologic evaluation of rat and guinea pig lungs; Fowler EH et al.; The morphologic changes induced in the lungs of rats and guinea pigs exposed to high concentrations of MIC vapor (100, 600, and 1000 ppm in the rat and 25, 125, 225, and 675 ppm in the guinea pig) for a short time (15 min) in a static exposure chamber were evaluated at varying postexposure periods (0, 1, 2, 4, and 16 hr) . The 675 ppm-exposed guinea pigs were evaluated only immediately following removal from the chamber . Attention was primarily focused on the intrapulmonary conducting airways and the parenchyma (gas exchange region) of the lungs . The severity of morphologic changes observed by light microscopy was directly correlated with exposure concentration and time postexposure in both species . Specifically, degenerative changes were observed in the bronchial, bronchiolar, and alveolar epithelium in both species . Quantitative differences were observed; 100 ppm of MIC in the rat resulted in much less damage than did 125 ppm of MIC in the guinea pig . Morphologic evidence of sloughing of large sheets of conducting airway epithelium with fibrin buildup and increased mucus production resulted in plugging of major airways and atelectasis . These observations support the hypothesis that tissue hypoxia was a major contributing factor resulting in death.

Environ Health Perspect, 1987 Jun, 72, 35 - 8
Biological effects of short-term, high-concentration exposure to methyl isocyanate . IV . Influence on the oxygen-binding properties of guinea pig blood; Maginniss LA et al.; Whole blood oxygen equilibrium curves (O2 ECs), blood buffer lines, and several hematologic properties were determined for adult guinea pigs exposed to 700 ppm methyl isocyanate (MIC) for 15 min . MIC inhalation effected a significant reduction of blood O2 affinity; the half-saturation pressure (P50) at 38 degrees C increased from the control (untreated) level of 22.8 +/- 0.1 mm Hg to values ranging from 28.5 to 43.7 mm Hg for experimental animals . MIC exposure had no apparent influence on O2 EC shape or CO2 Bohr effect . Erythrocyte volume, {metHb}, O2 binding capacity, and combined red cell organic phosphate concentration (DPG + ATP) were not affected by MIC treatment . However, experimental animals experienced a severe metabolic acid-base disturbance; blood lactate concentration ranged from 8.6 to 24.0 mmole/L . Results indicate that lactic acidosis was solely responsible for increased blood P50 of MIC-treated animals . No direct effects of MIC on hemoglobin function were observed . Reduced Hb-O2 affinity, in conjunction with severe hypoxemia, compromised the guinea pigs' capacity for pulmonary O2 loading; at PaO2 of 30 mm Hg, Hb-O2 saturation (S) decreased from 66% S for controls to 42% S for MIC-treated animals.

Environ Health Perspect, 1987 Jun, 72, 29 - 33
Biological effects of short-term, high-concentration exposure to methyl isocyanate . III . Influence on gas exchange in the guinea pig lung; Fedde MR et al.; The influence of methyl isocyanate (MIC) inhalation on the gas exchange function of the lungs in guinea pigs was studied by measuring arterial blood gases, pH, and tracheal pressure during constant-volume, artificial ventilation with air or 100% O2 at 40 and 120 min after exposure . A 15 min exposure to MIC at concentrations of 240 to 628 ppm caused a marked reduction in PaO2 and pHa and an elevated tracheal pressure during artificial ventilation . The low PaO2 was only slightly elevated when the animals were ventilated with 100% O2 . Although the dry-wet lung weight ratio was reduced at the highest exposure concentration, the effect was not severe and no significant increase in lung water was found at the lower concentrations . MIC inhalation caused severe pulmonary blood shunting and ventilation/perfusion imbalance . This, in turn, led to hypoxemia, metabolic acidosis, and tissue hypoxia, which could produce death . The pulmonary gas exchange deficit likely resulted from bronchial and bronchiolar obstruction caused by sloughed epithelium and other debris from intra- and extrapulmonary airways.

Environ Health Perspect, 1987 Jun, 72, 21 - 8
Biological effects of short-term, high-concentration exposure to methyl isocyanate . II . Blood chemistry and hematologic evaluations; Troup CM et al.; Human, rat, and guinea pig packed erythrocytes exposed to 100, 500, or 1000 ppm of methyl isocyanate (MIC) vapor in vitro showed a concentration-related inhibition of cholinesterase (ChE) activity . Rat and guinea pig packed erythrocytes showed an almost complete inhibition of ChE activity at 2000 ppm . In vitro exposures of human and guinea pig blood to 1000 or 2000 ppm of MIC vapor resulted in qualitative alterations in the electrophoretic mobility of hemoglobin (Hb) as measured by citrated agar electrophoresis . In rats and guinea pigs, neither IV injection of liquid MIC nor in vivo exposure to 1000 ppm of MIC by inhalation resulted in any inhibition of erythrocyte ChE activity or alteration in Hb electrophoretic mobility . As a result of these observations, it was concluded that neither ChE inhibition nor structural alteration of Hb were major contributing factors to death resulting from MIC exposure . Rats and guinea pigs receiving IV injections of liquid MIC showed an increase in creatine kinase (CK) levels . This increase could not be attributed to a specific isoenzyme of CK by ion exchange chromatography . Rats exposed to 100, 600, or 1000 ppm of MIC and guinea pigs exposed to 25, 125, or 225 ppm of MIC and bled immediately following a 15-min exposure or at 1, 2, 4, or 16 hr postexposure had the following alterations in blood parameters: an increase in CK, increases in hemoglobin concentration and hematocrit, reticulocytosis (rats only), neutrophilia, a decrease in blood pH and PO2, and an increase in blood PCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Environ Health Perspect, 1987 Jun, 72, 189 - 95
Biological effects of short-term, high-concentration exposure to methyl isocyanate . VI . In vitro and in vivo complement activation studies; Kolb WP et al.; The ability of MIC to induce complement activation in vitro and in vivo was investigated . For the in vitro studies, both human and guinea pig serum or EDTA-plasma samples were exposed to 1167 to 1260 ppm MIC vapor for 15 min at room temperature . The human serum samples exposed to MIC showed significant reductions in Factor B, C2, C4, C3, C5, and total hemolytic complement CH50 activity levels . C6 functional activity was unaffected . The C3, C5, and CH50 functional activities in guinea pig serum (the only functional tests conducted on these samples) were more sensitive to MIC-mediated reduction than the corresponding activity reductions observed in the human serum samples . The human and single guinea pig EDTA-plasma samples exposed to MIC vapor showed no evidence of C3 consumption but did show significant reductions in CH50 levels . Thus, MIC vapor was able to activate, and thereby reduce serum complement C3 activity in vitro by a complement-dependent process . However, the data suggest at least one complement component other than C3 was inactivated in EDTA-plasma by a complement-independent mechanism . For the in vivo studies, five pairs of guinea pigs were exposed to 644 to 702 ppm MIC vapor until one of the pair died (11-15 min) . MIC exposure was then discontinued, the surviving guinea pig was sacrificed, and EDTA-plasma was obtained from both animals and analyzed for complement consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Environ Health Perspect, 1987 Jun, 72, 177 - 82
Evaluation of sister chromatid exchange and cytotoxicity in murine tissues in vivo and lymphocytes in vitro following methyl isocyanate exposure; Conner MK et al.; The purpose of this study was to assess sister chromatid exchange (SCE) levels and cell cycle kinetics in various murine tissues following MIC exposure . Following exposure of mice to MIC, these parameters were measured in bone marrow and alveolar macrophages labeled with BrdUrd in vivo and in peripheral blood and spleen lymphocytes cultured in the presence of BrdUrd in vitro . Target concentrations of MIC were 2, 15, and 30 ppm (3 hr) . Neither elevated SCE frequencies nor inhibition of cell cycling were evident in lipopolysaccharide (LPS)- or concanavalin A (ConA)-stimulated spleen lymphocytes, or in LPS-stimulated peripheral blood lymphocyte (PBL) cultures from mice exposed for 3 hr to MIC concentrations as high as 30.5 ppm . Inhibition of cell cycling and poor culture success rates were apparent in ConA-stimulated PBLs following MIC exposures as low as 2.3 +/- 0.4 ppm for 3 hr . At the lowest MIC dose employed, the cycling characteristics of bone marrow and alveolar macrophages were not altered, and SCE frequencies were at control levels . However, severe cell cycle inhibition was observed in these tissues at MIC concentrations of 15 ppm or greater . A marker of cytotoxicity at this dose was a high frequency (approximately 33-90%) of occurrence of first division cells containing a late-replicating Y chromosome . Despite its apparent cellular toxicity, MIC is not genotoxic as measured by SCE analysis in the tissues examined in this study.

Environ Health Perspect, 1987 Jun, 72, 169 - 75
The antibody response to methyl isocyanate: experimental and clinical findings; Karol MH et al.; As a result of the industrial accident in Bhopal, India (December 1984) in which thousands of people were exposed to methyl isocyanate (MIC), concern was raised for possible long-term health effects . The well-recognized immunologic consequences of exposure to other industrial isocyanates prompted investigation of an antibody response to MIC . Using procedures which had been developed in this laboratory to evaluate isocyanate immunotoxicity, animal studies were undertaken to develop and test reagents which could be used to detect antibodies to MIC in the exposed population . Guinea pigs were injected with MIC in its reactive isocyanate form . Three weeks later, blood was drawn and serum evaluated using ELISA . To detect antibodies, an antigen was prepared by reaction of MIC with guinea pig serum albumin . Antibodies were detected in each of the four animals injected with MIC . Titers achieved were 1:5120 to 1:10,240 . Inhibition assays revealed antibody specificity directed toward the MIC hapten . Analogous antigens prepared by reaction of MIC with human serum albumin were used to evaluate sera from individuals exposed in Bhopal to MIC . Antibodies were detected in 12 of 144 exposed persons . Antibodies were specific for MIC, as evidenced by inhibition assays, and belonged to the IgG, IgM and IgE classes . However, titers were generally low and transient and were found in persons having had the highest MIC exposures . Total IgE values of sera were not significantly different from those of control sera obtained from Bombay residents . The results indicate that exposure to methyl isocyanate resulted in production of specific antibodies . However, the low titers observed and the transient nature of the response suggest little health consequence should result form the antibody response.

Environ Health Perspect, 1987 Jun, 72, 159 - 67
Sensory and pulmonary irritation of methyl isocyanate in mice and pulmonary irritation and possible cyanidelike effects of methyl isocyanate in guinea pigs; Alarie Y et al.; Methyl isocyanate (MIC) was evaluated for sensory and pulmonary irritation in mice . MIC was found to be both a potent sensory and pulmonary irritant in this species . From these results, a safe level of exposure for a period of 8 hr was estimated to be about 0.02 ppm for humans . Guinea pigs were also exposed to MIC for a single 3-hr exposure at a concentration of 37 ppm . During exposure to MIC, coughing was observed in all animals . Pulmonary function was evaluated immediately following exposure and intermittently on the next 35 days using CO2 challenges and flow-volume loops . Highly abnormal responses to CO2 were observed immediately after exposure in all animals . Six of the eight animals exposed to MIC died . In the two survivors, an apparent recovery was seen during the 5 days following exposure, but a worsening effect was observed at days 21 and 28, with a partial recovery at day 35 . The data clearly demonstrated that the primary pulmonary effect of MIC was one of airways obstruction . Oxygen uptake and carbon dioxide output were also measured in the guinea pigs following exposure to MIC . No evidence of a cyanidelike effect was observed, in contrast to a severe depression of oxygen uptake following exposure to hydrogen cyanide.

Environ Health Perspect, 1987 Jun, 72, 153 - 7
Epidemiological and experimental studies on the effects of methyl isocyanate on the course of pregnancy; Varma DR; PIP: Both epidemiological and experimental studies conducted by the author clearly indicate that methyl isocyanate (MIC) exposure can have an adverse effect on pregnancy outcome . 9 months after the December 1984 accident in Bhopal, India, in which 3270 families residing adjacent to the Union Carbide pesticide plant were exposed to MIC vapor, a preliminary survey was conducted to assess pregnancy outcomes in these households . 865 of these women indicated they were pregnant at the time of the accident . 44% of these pregnancies did not result in a live birth . Moreover, of the 486 live births, 14% of infants died within 30 days of birth . The rate of pregnancy loss was higher among women who were in their 1st trimester at the time of the accident . Similarly, exposure of pregnant mice to relatively low doses of MIC (9 and 15 ppm) for 3 hours caused complete resorption in more than 75% of the animals; a decrease in fetal and placental weights was noted at doses of 2-15 ppm MIC . There was no evidence of external malformations, although there appeared to be an increased incidence of visceral anomalies . In summary, both sets of data indicate that MIC exerts selective fetal toxicity, the exact mechanism of which remains to be established . For example, it is not clear whether the fetal toxicity is due only to effects on the mother or due to both maternal and fetal effects . The 43% pregnancy loss rate recorded in Bhopal in the post-accident period is 3-4 times higher than the normal incidence of spontaneous abortion .

Environ Health Perspect, 1987 Jun, 72, 149 - 52
Methyl isocyanate: reproductive and developmental toxicology studies in Swiss mice; Schwetz BA et al.; Studies were conducted in Swiss (CD-1) mice to evaluate the potential of inhaled vapors of methyl isocyanate (MIC) to affect reproduction and development . Inhaled MIC at concentrations of 0, 1, or 3 ppm, 6 hr per day during days 14 through 17 of gestation caused a significant increase in the number of dead fetuses at birth and caused a significant decrease in neonatal survival during lactation . In contrast, exposure of male and female mice to 1 or 3 ppm given 6 hr per day for 4 consecutive days had no effect on reproduction during mating trials conducted 1, 8, and 17 weeks after the exposure period . Similarly, there was no evidence of a dominant lethal effect in exposed male mice.

Environ Health Perspect, 1987 Jun, 72, 143 - 8
Myelotoxicity induced in female B6C3F1 mice by inhalation of methyl isocyanate; Hong HL et al.; The effects of a 4-day inhalation exposure (6 hr/day) to 0, 1, and 3 ppm methyl isocyanate (MIC) on bone marrow parameters in female mice were examined at 5, 8, and 21 days following exposure . The MIC exposure was associated with myelotoxicity as evidenced by hypocellularity, suppression of pluripotent stem cells (CFU-S), granulocyte-macrophage progenitors (CFU-GM) and erythroid precursors (CFU-E) in both dose groups . Hematopoietic parameters returned to normal by 21 days in the 1 ppm dose group, but not in the 3 ppm dose group . This indicates that the alterations in the bone marrow parameters persist for a relatively long period at dose levels where there are little or no changes in body weight, clinical pathology, or immunological parameters, suggesting that the bone marrow may be a sensitive endpoint for MIC exposure in mice . MIC is a highly reactive chemical that appears to exert its effect directly on the lining epithelium of the nasal cavity and major airways; there was no histological evidence of a systemic effect . The pathogenesis of the bone marrow depression is unknown; however, there were chronic bronchitis and bronchial fibrosis in the 3 ppm dose group . One possible explanation is that the cell injury induced in the lung is associated with the release of inhibitory factors for hematopoiesis, as the rodent lung is a potent source of both stimulatory and inhibitory growth factors for bone marrow progenitor cells . A second possibility is that the thymic atrophy found in MIC-exposed mice might be related to myelotoxicity . The pathogenesis of myelotoxicity in MIC exposure and its relationship with pulmonary injury require further study.

Environ Health Perspect, 1987 Jun, 72, 13 - 9
Biological effects of short-term, high-concentration exposure to methyl isocyanate . I . Study objectives and inhalation exposure design; Dodd DE et al.; Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC) . Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations . The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage . All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration (ranging from 25-3506 ppm) . MIC vapors were statically generated in a double chamber exposure design . Precautionary measures taken during exposures are discussed . Guinea pigs were more susceptible than rats to MIC exposure-related early mortality . A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration . For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing . Fifteen minute LC50 tests with 14-day postexposure follow-up were conducted, and the LC50 (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs . Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established . A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.

Environ Health Perspect, 1987 Jun, 72, 125 - 32
Eighty-five day postexposure follow-up study in Fischer 344 rats after repeated exposures to methyl isocyanate vapor; Fowler EH et al.; The objectives of this study were to describe the microscopic lesions in the respiratory tract of Fischer 344 rats as a result of 4- or 8-days exposure (6 hr/day) of 3 ppm MIC and to characterize the postexposure development of these lesions up to day 85 . All rats survived the exposure regimen, although significant decreases in body weight and encrustation of the eyes, nose, or mouth were observed . During the first 15 days of postexposure, the rats were hypoactive and had increased respiratory rates . Male mortality was as high as 63%; only 5% of the MIC-exposed females died . The cause of death was interpreted to be respiratory compromise complicated by anorexia and probably dehydration as well . During the next 28 postexposure days, 48% of the male survivors died, while only 3% of the female survivors died . Throughout the 85-day postexposure period, body weight gains in the MIC-treated groups were consistently below control values . Inflammatory and squamous metaplastic lesions of the respiratory tract, observed the day following completion of either the 4- or 8-day exposure regimen, decreased in both frequency and/or severity in survivors of the 85-day postexposure period, indicating recovery from the cytotoxic and irritating effects of MIC vapor . The squamous metaplastic epithelium was replaced by regenerative epithelium beginning in the deeper portion of the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Environ Health Perspect, 1987 Jun, 72, 117 - 23
Methyl isocyanate eight-day vapor inhalation study with Fischer 344 rats; Dodd DE et al.; Groups of ten male and ten female Fischer 344 rats were exposed by inhalation 3.1, 0.6, 0.15, or 0.0 (control) ppm of methyl isocyanate (MIC) vapor 6 hr per day for 8 days (two 4-day sessions separated by a 2-day rest) . Evaluation of toxic effects included body weight, food consumption, organ weights, and selected hematologic, ophthalmic, neurologic, gross anatomic, and histologic examinations . There were no deaths during the study . Rats of the 3.1 ppm exposure group had decreased body weights, food consumption, and blood oxygen saturation (males only) . An increase in hemoglobin concentration (males only) and in lung weights (absolute and as a percentage of body weight) were also observed in the 3.1 ppm rats . Ophthalmic or neurofunctional behavior evaluations were negative for all MIC exposure groups . Only 3.1 ppm of MIC vapor resulted in lesions in the respiratory tract, 0.6 or 0.15 ppm did not . The types of lesions observed were inflammation and squamous metaplasia in the nasal cavity, trachea, and bronchi; inflammation of the bronchioles and alveoli; and submucosal fibroplasia of the bronchioles . No significant lesions were observed in tissues other than those of the respiratory tract in all MIC exposure groups . The results of this study indicate the current 0.02 ppm threshold limit value for MIC is not too high regarding toxicity.

Environ Health Perspect, 1987 Jun, 72, 109 - 16
Respiratory tract changes in guinea pigs, rats, and mice following a single six-hour exposure to methyl isocyanate vapor; Fowler EH 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 . The majority of deaths occurred during postexposure days 1 through 3 . 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 . Body weight losses were common in all species following MIC exposures of 2.4 ppm or greater . Microscopic lesions included acute necrosis of the epithelial lining throughout the respiratory tract in animals that died shortly after exposure, coupled with congestion, edema, and inflammation . A microscopic lesion that appeared unique to guinea pigs was bronchiolitis obliterans (where the products of necrosis and inflammation 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Environ Health Perspect, 1987 Jun, 72, 105 - 8
Effect of methyl isocyanate (MIC) gas on the eyes of Fischer 344 rats; Gupta BN et al.; The accidental release of methyl isocyanate gas in Bhopal, India, was reported to cause temporary blindness and other eye injuries in many of the exposed people . Methyl isocyanate (MIC) is known to be corrosive and to irritate intact skin and mucous membranes, but little is known about the extent of ocular damage incurred during exposure to its vapors . The eyes of male and female Fischer 344 rats were evaluated immediately after a 2-hr exposure to 0, 3, 10, or 30 ppm of MIC, and periodically thereafter during a 91-day recovery period . During exposure to 10 ppm and higher concentrations, rats kept their eyes partially closed . Copious lacrimation and occasional frothy nasal discharge were evident . Eyes were examined under ultraviolet light after topical application of sodium fluorescein, and histopathologic examination included lids, cornea, lens, retina, optic nerve, and Harderian gland . There was no significant gross or microscopic evidence of epithelial erosion or ulceration of the cornea, or of adjacent tissues immediately after, or at any time following exposures . No skin irritation was noted . It would appear that the natural protective mechanisms of the eye of rats were adequate to prevent ocular damage at these exposure levels.

Antimicrob Agents Chemother, 1987 Jun, 31(6), 951 - 3
In vitro activity of systemic antifungal agents against Malassezia furfur; Marcon MJ et al.; The activity of four antifungal agents against 15 systemic (blood and vascular catheter) and 10 superficial (skin) Malassezia furfur isolates was evaluated . MIC ranges were similar for the two groups of organisms: amphotericin B, 0.3 to 2.5 micrograms/ml; flucytosine, greater than 100 micrograms/ml; miconazole, 0.4 to 1.5 micrograms/ml; and ketoconazole, 0.025 to 0.4 micrograms/ml.

Antimicrob Agents Chemother, 1987 Jun, 31(6), 870 - 5
Assessment of formulas for calculating critical concentration by the agar diffusion method; Drugeon HB et al.; The critical concentration of antibiotic was calculated by using the agar diffusion method with disks containing different charges of antibiotic . It is currently possible to use different calculation formulas (based on Fick's law) devised by Cooper and Woodman (the best known) and by Vesterdal . The results obtained with the formulas were compared with the MIC results (obtained by the agar dilution method) . A total of 91 strains and two cephalosporins (cefotaxime and ceftriaxone) were studied . The formula of Cooper and Woodman led to critical concentrations that were higher than the MIC, but concentrations obtained with the Vesterdal formula were closer to the MIC . The critical concentration was independent of method parameters (dilution, for example).

Pathol Biol (Paris), 1987 Jun, 35(5 Pt 2), 882 - 6
{Antifungal spectrum of epicarin . In vitro study}; Goudard M et al.; Epicarine, 3-(2 hydroxy-1-naphthylmethyl) salicylic acid, has been used for a long time for the topical treatment of different dermatological diseases . We studied the in vitro antifungal activity of epicarine and its sodium salt by the dilution method in solid medium (221 pathogenic strains belonging to 23 different species) . The results show that the acid is two or three fold more potent than the salt and that dermatophytes (MIC 20 to 1,000 micrograms/ml are more sensitive than yeasts and moulds (MIC 500 to 2,000 micrograms/ml) . Because of the usual concentrations in topical applications (2 to 10%) and the absence of toxicity of this molecule, these results seem to show that the therapeutic use of this product is perfectly legitimate.

Pathol Biol (Paris), 1987 Jun, 35(5 Pt 2), 781 - 4
{Diffusion, in the bronchial mucus, of enoxacin administered by oral route in man}; Morel C et al.; The diffusion of Enoxacin into the bronchial mucus was studied in 34 patients admitted because of an acute infectious episode over chronic bronchopathy . They received via the oral route 400 mg of Enoxacin twice daily . The antibiotic concentrations were measured in sputum and serum by microbiological assay and HPLC . The patients were divided into 5 groups according with the timing of sampling: 1, 3, 6, 12 hours after dosing at day 3 (group I, II, III, IV), 3 hours after dosing at day 1, 2 and 3 (group V) . Serum concentrations of Enoxacin were low (2.46 mg/l at 3rd hour) . Bronchial concentrations exceed blood levels (mean 3.06 mg/l at 3rd hour) . The bronchial levels of Enoxacin were above the mean MIC of many respiratory bacterial pathogens.

Pathol Biol (Paris), 1987 Jun, 35(5 Pt 2), 746 - 9
{Effects of rifampicin on the pharmacodynamics of doxycycline}; Garraffo R et al.; Because of the potential of doxycycline-rifampicin for oral therapy of infectious diseases with intracellular bacteria, specially brucellosis and the well known cytochrome P450 enzyme system inductive activity of rifampicin, we may speculate that this antibiotic can altered the serum concentration-time profile of doxycycline when given in combination . So, the main pharmacokinetic parameters of doxycycline (200 mg/day orally) in seven patients before and after rifampicin association (10 mg/kg/day) . According to the results two groups may be individualized: the first (n = 3) showed no variation in the doxycycline++ pharmacokinetic; the second (n = 4) had significant differences (p less than 0.05) for all pharmacokinetic parameters (AUC, T1/2, Cl, Cmax) after association with rifampicin (AUC were half reduced) . Moreover, as regard doxycycline half-life, a difference was observed between these two groups before rifampicin treatment: in one case T1/2 was of 17.9 + 6.6 hours, while in the other it was of 9.2 + 2.3 hours . The group with obvious enzyme induction had the longer half life . This suggests that the inductive rifampicin effect would be essentially observed in patients considered as "poor metabolizers" . The pharmacokinetic modifications observed are likely of clinical significance on account of the doxycycline serum concentrations decrease under the MIC of most agents of intracellular infections.

Pathol Biol (Paris), 1987 Jun, 35(5 Pt 2), 742 - 5
{Antipneumococcal activity of erythromycin and spiramycin in 2 experimental models in mice}; Rolin O et al.; Macrolides often remain the first intention treatment in many chest infections caused by S . pneumoniae . Antipneumococcal activities of spiramycin and erythromycin have then been tested in a septicaemia model and in a pulmonary infection model in mice . In the septicaemia model, spiramycin has been found 5 to 15 times more active than erythromycin by subcutaneous route and 1.5 to 6 times by oral route . In the pneumonia model, spiramycin has been found as active (one strain) to 5 times more active than erythromycin (three strains) by both subcutaneous and oral route . These data might indicate that better tissular penetration of spiramycin is responsible for better in vivo activity . These facts also support the statement that MIC should not be the only choice standard of infectious chemotherapy.

Nippon Sanka Fujinka Gakkai Zasshi, 1987 Jun, 39(6), 925 - 32
{An immunohistochemical study with monoclonal antibodies on lymphocytes infiltrating in cervical cancer}; Okamoto Y et al.; We investigated lymphocytes infiltrating cervical cancer by an immunohistochemical method . Frozen sections (20 with frank invasive cancer, 4 with MIC, 5 with CIS, 6 with dysplasia, 3 normal) were stained by the ABC (avidin-biotin-peroxidase complex) method using monoclonal antibodies to identify functional subsets of lymphocytes . The monoclonal antibodies used were anti Leu 1 (T cell), anti Leu 2a (cytotoxic/suppressor T cell), anti Leu 3a (helper/inducer T cell), anti Leu 10 (B cell) and anti Leu 7 (NK cell) . The results were as follows: Many lymphocytes infiltrated and surrounded the cancer nests, and there, T cells predominated over B cells . The intensity of infiltration of T cells was not correlated with the grade and prognosis of cervical cancer . The ratio of Leu 2a+ cells to Leu 3a+ cells tended to change with the advance of cancer . Leu 2a+ cells were relatively predominant in early cases and cases with a good prognosis . There were very few B cells close to cancer nests, and they were not correlated with the grade and prognosis of cervical cancer . NK cells were identified in many cases, but they were scattered and were not correlated with grade and prognosis of cervical cancer.

Epidemiol Infect, 1987 Jun, 98(3), 361 - 8
Antibiotic sensitivity and mutation rates to antibiotic resistance in Mycoplasma mycoides ssp . mycoides; Lee DH et al.; The antibiotic resistance of Mycoplasma mycoides ssp . mycoides strain T1 was investigated . This strain was resistant to high levels (greater than 100 micrograms ml-1) of rifampicin and nalidixic acid . It was sensitive to streptomycin, spectinomycin and novobiocin; however, single step mutants with high levels of resistance (greater than 100 micrograms ml-1) were readily isolated . With erythromycin and tylosin for which the minimum inhibitory concentration (MIC) for the parent strain was less than 0.1 microgram ml-1, mutants resistant to greater than 100 micrograms ml-1 were obtained in two and three steps respectively . The MIC of tetracycline in single step resistant mutants (0.6 microgram ml-1) was tenfold higher than the parent strain, but could not be increased further . There was only a twofold increase in resistance to chloramphenicol in single step mutants . The frequency of resistant mutants varied with the antibiotic and was between 4 X 10(-6) and 2 X 10(-8) . The mutation rate to antibiotic resistance to streptomycin, spectinomycin, novobiocin, erythromycin and tylosin was between 3 X 10(-8) and 5 X 10(-9) per cell per generation . There was a fivefold decrease in mutation rate to resistance to 60 micrograms ml-1 streptomycin compared to that to 20 micrograms ml-1.

Tubercle, 1987 Jun, 68(2), 113 - 8
In vitro properties of rifapentine (MDL473) relevant to its use in intermittent chemotherapy of tuberculosis; Dickinson JM et al.; In a comparison of in vitro properties of rifapentine (RIF) and rifampicin (RMP), the minimal inhibitory concentration of RIF against Mycobacterium tuberculosis in Tween-albumin liquid medium was usually 0.02 micrograms/ml, 2-3 times lower than for RMP; the bactericidal activity against a log phase culture was slightly less than that of RMP and the recovery after pulsed exposures to 1 microgram/ml of RIF or RMP lasting 6, 24 and 96 h was identical for the two rifamycins . These findings are used to interpret published data from the chronic experimental murine tuberculosis model and support the view that in the mouse, the efficacy of RIF in widely spaced intermittent chemotherapy is the result of its long half-life.

J Antibiot (Tokyo), 1987 Jun, 40(6), 882 - 6
Polycations which disorganize the outer membrane inhibit conjugation in Escherichia coli; Viljanen P; Outer membrane disorganizing polycation, polymyxin B nonapeptide (PMBN), reduced drastically the production of recombinants when present at sub-MIC concentrations during F'-mediated Escherichia coli conjugation . The decrease of recombinants was accompanied by a less marked decrease of viability in the recipient population in a manner resembling lethal zygosis . No reduction was seen when either donor or recipient was grown in the same PMBN concentration, washed and resuspended to PMBN-free medium before mating . The same concentration of outer membrane disorganizing polycations of higher bactericidal activity (protamine and polylysine) caused only a moderate reduction in transconjugant frequency when present during mating . Spermine and tetralysine, which are not effective disorganizers of the outer membrane, did not reduce the recombinant frequency or the viability of the recipients.

Environ Health Perspect, 1987 Jun, 72, 95 - 103
Cardiopulmonary effects in awake rats four and six months after exposure to methyl isocyanate; Tepper JS et al.; Cardiopulmonary function was assessed four and six months after Fischer 344 rats were exposed to 2 hr to 0, 3, or 10 ppm methyl isocyanate (MIC) . During assessment, the rats were challenged with 4 and 8% carbon dioxide (CO2) to stimulate ventilatory drive . Minute ventilation (VE) during CO2 challenge was increased in MIC-treated rats compared to controls when examined 4 months after exposure to 10 ppm MIC, suggesting a ventilation/perfusion inequality . An increase in maximum expiratory flow and a decrease in expiratory time indicated increased lung recoil in these rats . Evidence of pulmonary hypertension was observed in electrocardiograms (ECGs) and supported by postmortem analysis that showed a positive association between increased ECG abnormalities and increased right ventricular weights in the rats treated with 10 ppm MIC . At 6 months, forced expiratory flow-volume curves indicated persistent airway obstruction; however, no changes in inspiratory or expiratory resistance were evident . Decreased dynamic compliance and changes in two new measures of lung function (volume and time at zero expiratory intrapleural pressure) suggest that MIC-induced lung dysfunction also exhibited elements of a restrictive disease.

J Clin Microbiol, 1987 Jun, 25(6), 1140 - 2
Evaluation of anaerobic microdilution MIC results with the Prompt Inoculation System; Mangels JI; The Prompt Inoculation System (3M Co.) was compared with the overnight suspension inoculation procedure used with a broth microdilution anaerobic commercial system (Micro-Media Systems) for differences in MIC . MIC results from both suspension methods using six National Committee for Clinical Laboratory Standards-recommended quality control organisms were identical in 18 instances (75%) and within +/- 1 log2 dilution in 96% of the comparisons . Results with 45 anaerobic clinical isolates also compared satisfactorily; 83% of the results were identical and 97% were within +/- 1 log2 dilution . In addition, the direct (Prompt)-inoculated microdilution trays produced better growth and more valid MIC results; 92% of the clinical isolates produced MIC results versus 79% by the overnight suspension procedure.

Microbiol Sci, 1987 May, 4(5), 143 - 6
An explicit model for bacterial resistance: application to beta-lactam antibiotics; Waley SG; The effectiveness of beta-lactam antibiotics against Gram-negative bacteria that contain beta-lactamases is considered in terms of three factors . These are a rate constant for reaction of the beta-lactam antibiotic with a transpeptidase, the kinetic parameters for hydrolysis of the antibiotic by the beta-lactamase, and the permeability of the outer membrane . The concept of a dimensionless permeability number (Pn) is developed . When the permeability number is much less than one then permeability is important, and the MIC may be raised by a factor of up to 1/Pn . When the antibiotic is sufficiently reactive its effectiveness is given by the 'reactivity-permeability' product.

Diagn Microbiol Infect Dis, 1987 May, 7(1), 83 - 7
Quality control limits for microdilution susceptibility tests with aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid; Barry AL et al.; A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid) . Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

Pathol Biol (Paris), 1987 May, 35(5), 595 - 8
{Study of bactericidal effect of the spiramycin and minocycline on Mycoplasma pneumoniae}; Renaudin H et al.; This study was designed to determine if the inhibitory effect of a macrolide (spiramycin) and a tetracycline (minocycline) on the in vitro growth of Mycoplasma pneumoniae is due to a bacteriostatic or a bactericidal activity . M . pneumoniae, strain FH-Liu, susceptible to spiramycin and minocycline was exposed to various inhibitory concentrations of these antibiotics (within the range of 0.5-32 mg/l) for various periods of time (1-9 days) . The bactericidal activity was determined by subculturing material from tubes using serial dilution . Spiramycin was bactericidal after 4 days (greater than or equal to 3 log10 decrease of the inoculum) only when high concentrations were used (16 mg/l) . Minocycline was bactericidal after 4 days at a concentration of 32 mg/l . These results show a 64-fold difference between minimum inhibitory concentration and minimum bactericidal concentration for spiramycin and a 128-fold difference for minocycline . Our data confirm the bacteriostatic effect of these drugs on M . pneumoniae.

J Antimicrob Chemother, 1987 May, 19(5), 605 - 9
Comparative in-vitro activity of five fluoroquinolones against mycobacteria; Davies S et al.; Fifty distinct strains of mycobacteria were investigated to determine their in-vitro susceptibility to five new fluoroquinolones (norfloxacin, pefloxacin, ofloxacin, enoxacin and ciprofloxacin) . Ofloxacin and ciprofloxacin were found to be the most active, with minimum inhibitory concentrations (MIC) of 1.25 mg/l or less to all strains of Mycobacterium tuberculosis, M . bovis, M . xenopi, M . kansasii and BCG tested . All agents showed little activity against M . malmoense and M . avium-intracellulare complex with MIC values of greater than 2.5 mg/l.

Pediatr Infect Dis J, 1987 May, 6(5), 458 - 61
Erythromycin in the treatment of pertussis: a study of bacteriologic and clinical effects; Bergquist SO et al.; In an open randomized study 17 patients with a positive culture for Bordetella pertussis were treated for 10 days with erythromycin (50 mg/kg/day divided in 2 doses) . The bacterium could not be isolated during therapy and in only one patient was it isolated 5 days after cessation of treatment . In comparison B . pertussis was isolated 10 and 15 days after diagnosis from 10 and 4 patients, respectively, of a group of 21 untreated controls . The treated group developed significantly fewer whoops than did the control group, even though most of the individuals had reached the paroxysmal stage at diagnosis . The dose of erythromycin (ethylsuccinate and stearate preparations) gave serum concentrations about 100 times larger than the minimal inhibitory concentration of isolated bacteria and was well-tolerated . Thus adequate erythromycin treatment eliminates B . pertussis from the nasopharynx and reduces symptoms in patients having a history of pertussis of less than 14 days . Adequate dosage and length of treatment might be crucial for these results.

J Antimicrob Chemother, 1987 May, 19(5), 637 - 46
In-vitro antibiotic inactivation by mammalian cell and killed bacterial preparations; Hunt GH et al.; Inactivation of a range of antibiotics acting at different points in the metabolism of the bacterial cell was detected by estimating the MIC and MBC in the presence of liver and other tissue preparations . High temperature treatment and sonication of liver cells increased their ability to inactivate antibiotic action . This treatment would have almost completely destroyed enzyme activity, which was, therefore, not thought likely to be the cause of the phenomenon . The loss of antibiotic activity may be related to "protein binding" and a dialysis experiment showed that penicillin binding with liver homogenate was very much greater than with human albumin . It may be that increased disruption of tissue cells by physical methods exposes more active binding sites which reduces the bioavailability of antibiotics . Some degree of binding specificity was indicated in experiments in which DNA was shown to block antibiotics acting primarily on DNA--related synthesis and RNA blocked antibiotics acting on RNA--related metabolism . Suggestions are made for the cause of failure of antibiotic treatment in certain clinical situations.

Am J Med, 1987 Apr 27, 82(4A), 376 - 80
In vitro study with ciprofloxacin: interpretive criteria of agar diffusion test according to standards of the NCCLS and DIN; Grimm H; Regression analyses to determine the correlation between minimal inhibitory concentrations (MICs) and inhibition zones produced by ciprofloxacin disks were carried out using 400 freshly isolated cultures of infective organisms (approximately 20 strains from each of 22 species) . It was found in pilot studies that the correlation becomes weaker with increasing disk loads (1, 5, 10, and 30 micrograms) . Disks containing 5 micrograms of ciprofloxacin were chosen for comparative studies using Mueller-Hinton agar and methods of the National Committee for Clinical and Laboratory Standards (NCCLS) as well as of the Deutsches Institut fur Normung (DIN 58940) . Based on preliminary MIC breakpoints (susceptible, 1 microgram/ml or less; intermediate, 2 micrograms/ml; and resistant, 4 micrograms/ml or more) and calculations from regression equations (limited to the MIC range of 0.25 to 32 micrograms/ml), the following zone interpretations using the NCCLS method are recommended: resistant, 15 mm or less; intermediate, 16 to 20 mm; and susceptible, 21 mm or more . The respective values with the DIN method are resistant, 18 mm or less; intermediate, 19 to 22 mm; and susceptible, 23 mm or more.

Am J Med, 1987 Apr 27, 82(4A), 196 - 201
Ciprofloxacin therapy in cystic fibrosis; Scully BE et al.; There is great need for an oral agent that could be used to treat pulmonary exacerbations in patients with cystic fibrosis . In this study, the use of oral ciprofloxacin as sole therapy was evaluated in 18 patients with 39 infectious episodes; 13 episodes were classified as severe, 19 were classified as moderate, and seven were classified as mild . Patients ranged in age from eight to 36 years (mean, 23 years) . Dosage varied according to severity of disease, body size, and the susceptibility of the Pseudomonas isolate to ciprofloxacin; the dose ranged from 750 to 2,250 mg daily (mean, 1,800 mg) . Ten patients received one course of ciprofloxacin, and eight received repeated courses . The overall clinical response rate was 82 percent . There was a response to the initial treatment course in 96 percent of the patients . Those in whom therapy failed had been re-treated with ciprofloxacin and were severely ill . Failure to respond correlated poorly with pretreatment minimal inhibitory concentration (MIC) values (0.6 microgram/ml for failures versus 0.4 microgram/ml for responses) . Pseudomonas could not be eradicated from the sputum of any of the patients, although there was a marked reduction in purulence and bacterial counts . In general, patients who did not require re-treatment for three months would again have susceptible organisms . When organisms became resistant to ciprofloxacin (MIC greater than 2 micrograms/ml), they showed no concomitant new aminoglycoside or beta-lactam resistance . No serious toxicity occurred in any of the 39 episodes of treatment . In seven patients treated with combination therapy (tobramycin or azlocillin), the infecting organisms were reduced in number, but eradication of Pseudomonas generally could not be achieved . Increases in MIC occurred during combination therapy . Ciprofloxacin is a major advance in the treatment of bronchopulmonary infection in patients with cystic fibrosis.

Am J Med, 1987 Apr 27, 82(4A), 23 - 6
Activity of ciprofloxacin and other fluorinated quinolones against mycobacteria; Young LS et al.; The new fluorinated quinolones display interesting but variable activity against mycobacteria . Almost all compounds tested (ciprofloxacin, ofloxacin, enoxacin, norfloxacin, difloxacin, CI-934, A-56620, and megalone) inhibit Mycobacterium tuberculosis at achievable serum concentrations, with ciprofloxacin and ofloxacin most active by weight (minimal inhibitory concentration at which growth of 90 percent of strains is inhibited is equal to 1 microgram/ml or less) . The growth of Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium fortuitum is also well inhibited by these agents in the same range of concentrations . Activity against the Mycobacterium avium complex is method-dependent, with growth of perhaps one third of the strains isolated from patients with the acquired immune deficiency syndrome inhibited by ciprofloxacin . Determination of individual drug efficacy data in experimental mycobacterial infections is not a practical goal . However, combination therapy studies are in progress using murine models of both M . tuberculosis and M . avium challenges . Ofloxacin has been used with some success in human patients with pulmonary tuberculosis . Oral administration may be an important advantage, and, when used in combination with other active agents, the new quinolones may have a useful role in treating mycobacterial infections.

J Appl Toxicol, 1987 Apr, 7(2), 147 - 8
Sensory irritation of methylisocyanate vapor; James JT et al.; The respiratory-depression (RD) profile in mice exposed to methylisocyanate (MIC) vapor is reported . The RD50 value calculated from this profile was 2.9 (2.7-3.2) ppm . Concentrations of MIC that have been reported to be unbearable in humans were of approximately the same magnitude as RD50 concentrations in mice for brief exposures.

Am Ind Hyg Assoc J, 1987 Apr, 48(4), 324 - 9
Methyl isocyanate liquid and vapor permeation through selected respirator diaphragms and chemical protective clothing; Berardinelli SP et al.; Initially, a study was undertaken to evaluate selected chemical protective clothing suitable for use by emergency response personnel confronted with methyl isocyanate (MIC) . Twenty-two chemical protective clothing materials were tested against liquid methyl isocyanate . Chemical permeation breakthrough times for these clothing materials demonstrate that only one of these garments can be considered as a candidate material against liquid MIC . In a subsequent study, three chemical protective clothing materials were evaluated against approximately 800 ppm MIC vapor . Chemical permeation breakthrough times demonstrate that these materials can be considered candidate materials . A final study tested self-contained breathing apparatus (SCBA) diaphragms . Four SCBA diaphragms were tested and all experienced rapid breakthrough when exposed to liquid MIC . Next, three SCBA diaphragms were exposed to approximately 800 ppm MIC vapor . The data demonstrate that the SCBA should be worn inside a total encapsulating suit.

Am Ind Hyg Assoc J, 1987 Apr, 48(4), 315 - 23
Penetration of methyl isocyanate through organic vapor and acid gas respirator cartridges; Moyer ES et al.; Methyl isocyanate (MIC) is a volatile, toxic chemical {Threshold Limit Value (TLV) = 0.02 ppm} used to manufacture carbamate pesticides . The principal manufacturer of MIC is Union Carbide, and the site of production is Institute, West Virginia . In light of the December 1984 Bhopal, India disaster and possible safety problems at the Institute facility, NIOSH conducted this research as a basis upon which to recommend protective equipment that might be used in an emergency situation where extremely high MIC concentrations might be encountered . Both protective clothing and respirators were evaluated . In particular, NIOSH studied air-purifying respirators in order to assess their effectiveness against MIC vapor penetration . NIOSH does not recommend any air purifying respirator for MIC because of its high toxicity and lack of warning properties and because no effective end of service life indicator currently is available for MIC . This report addresses only MIC penetration through air-purifying cartridges at challenge concentrations designed to simulate emergency escape conditions . Another report addresses the protective clothing issue . The results presented are for two different manufacturers' organic vapor (OV) and acid gas cartridges . Penetration tests were conducted at three or four MIC challenge concentrations and at three different humidity conditions . In general, breakthrough times (1% of challenge concentration) were very short (less than 20 min) . Also, high relative humidity was found to decrease the breakthrough time of MIC.

J Antimicrob Chemother, 1987 Apr, 19(4), 493 - 503
Ciprofloxacin in plasma and peritoneal dialysate after oral therapy in patients on continuous ambulatory peritoneal dialysis; Fleming LW et al.; The quinolone antibiotic ciprofloxacin offers the possibility of effective oral treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) if a sufficiently high concentration is attained in peritoneal dialysate . The pharmacokinetics of oral ciprofloxacin have been studied in ten CAPD patients given 250 mg qds for two days . Five patients were being treated for peritonitis with gentamicin and cefuroxime; the remaining five were receiving inpatient training for CAPD or were being treated for other problems . Ciprofloxacin concentration in plasma and in dialysate were determined by HPLC . There were not differences in plasma and dialysate kinetics in patients with and without peritonitis . Plasma levels were higher and the elimination half-life was longer than those reported for healthy subjects . Dialysate and plasma levels were significantly correlated (r2 = 0.87, P = 0.001), with dialysate levels consistently lower than plasma levels . Dialysate levels exceeded 1 mg/l in seven patients . The mean peak dialysate level (2.17 +/- 1.63 mg/l) exceeded the MIC of ciprofloxacin for 32 of 34 bacterial strains responsible for peritonitis . Ciprofloxacin shows promise as a useful oral treatment of CAPD-associated peritonitis.

Parassitologia, 1987 Apr, 29(1), 87 - 91
In vitro inhibition of Trichomonas vaginalis growth by some ortho-phenacyloxy-benzyl alcohols and their derivatives; Chiarini F et al.; Some phenacyl ethers of different ortho-hydroxy-benzyl alcohols and analogues have been synthesized and tested for the in vitro activity towards Trichomonas vaginalis . The most active compounds had a minimum inhibitory concentration of 6.25 micrograms/ml and appeared to be of a certain interest as representative of a new type of anti-Trichomonas substances not containing a nitro group.

Ann Trop Med Parasitol, 1987 Apr, 81 Suppl 1, 98 - 104
Changing response to chloroquine of Plasmodium falciparum in Saradidi, Kenya, from 1981 to 1984; Spencer HC et al.; From 1981 through 1984, the response of Plasmodium falciparum to chloroquine was monitored in Saradidi, Kenya, as a part of a community-based health programme to provide treatment for malaria in each village . Before 1983, all 71 infections treated with chloroquine were sensitive in vivo; parasitaemia cleared by day 3 and remained absent to day 7 . In June 1983, 23.1% of 26 infections treated with chloroquine base 10 mg kg-1 either recrudesced in seven days (RI resistance, five infections) or decreased but failed to clear (RII resistance, one infection) . In September 1983, 16.2% of 68 and in February 1984, 13.2% of 53 infections were resistant in vivo after treatment with chloroquine base 10 mg kg-1 . A course of chloroquine base 25 mg kg-1 over three days remained effective; only two (1.6%) of 129 infections examined were resistant in vivo; in both, parasitaemia cleared then recurred (RI) . In September 1984, however, nine (10.2%) infections were resistant after treatment with chloroquine base 25 mg kg-1; in four of these parasitaemia decreased but never cleared (RII) . Similar results were observed in vitro . In the Rieckmann macro in vitro test, 63.3% of 30 P . falciparum isolates tested were resistant to chloroquine (minimal inhibitory concentration (MIC) greater than or equal to 1.25 X 10(-6) mol 1(-1) blood) in June 1983, as were 61.8% of 34 isolates in the Rieckmann micro test (MIC greater than or equal to 1.14 X 10(-6) mol 1(-1) blood).(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Trop Med Parasitol, 1987 Apr, 81(2), 79 - 84
Plasma concentrations and toxicity of chloroquine after slow intravenous infusion in patients with falciparum malaria; Edwards G et al.; Five male patients with acute Plasmodium falciparum or Plasmodium vivax infections were infused with chloroquine diphosphate (15 mg kg-1) over four hours . Further does of chloroquine diphosphate (5 mg kg-1) were given at 12, 24, 36 and 60 hours . Plasma chloroquine concentrations were determined before and four hours after each dose and then daily until discharge . No serious cardiovascular toxicity was observed, and plasma chloroquine concentrations exceeding the putative minimum inhibitory concentration (MIC) of sensitive P . falciparum strains were reached within four hours of starting treatment . Further doses produced plasma concentrations which were sustained above the putative MIC, but showed no rapid increase into the range associated with toxicity.

Antimicrob Agents Chemother, 1987 Apr, 31(4), 531 - 4
Inhibition of R-plasmid transfer in Escherichia coli by 4-quinolones; Weisser J et al.; Inhibition of transfer of four conjugative R plasmids by ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and pipemidic acid was investigated in an Escherichia coli mating system . The absolute concentrations needed for inhibition of conjugation varied from 0.12 microgram/ml for ciprofloxacin to 16 micrograms/ml for pipemidic acid, but the relationship to the MICs for the parent strains was identical for all substrates . Concentrations for a 90% reduction of transconjugants were in the range of one to six times the MIC for the parent strains, which also had lethal effects on donors and recipients . A similar effect on conjugation was found with chloramphenicol . These observations question the specificity of transfer inhibition by quinolones and cast doubt on the clinical importance of such an effect.

Nucleic Acids Res, 1987 Mar 25, 15(6), 2431 - 43
23S ribosomal RNA mutations in halobacteria conferring resistance to the anti-80S ribosome targeted antibiotic anisomycin; Hummel H et al.; Halobacterium (H.) halobium and H . cutirubrum mutants resistant to the anti-80S ribosome targeted inhibitor anisomycin were isolated . Three classes of mutants were obtained: Class I displayed a minimal inhibitory concentration (MIC) to anisomycin of 10 micrograms/ml, class II of 25 micrograms/ml and class III of at least 400 micrograms/ml . In vitro polyphenylalanine synthesis assays demonstrated that in those cases tested resistance was a property of the large ribosomal subunit . By primer extension analysis, each mutation class could be correlated with a distinct base change within the peptidyltransferase loop of 235 rRNA . In class I A2472 was changed to C, in class II G2466 was changed to C and in the high-level resistant class III C2471 was replaced by U . A . double mutant - obtained by selection of a class I mutant for high-level anisomycin resistance - acquired the C2471 to U replacement of class III in addition to the class I mutation . The results provide information on the action of a eukaryotic protein synthesis inhibitor on archaebacterial ribosomes and demonstrate the suitability of organisms with a single rRNA transcriptional unit on the chromosome for direct selection of mutations in ribosomal RNA.

Antiviral Res, 1987 Mar, 7(3), 151 - 60
Comparative efficacy of broad-spectrum antiviral agents as inhibitors of African swine fever virus replication in vitro; Gil-Fernandez C et al.; Various nucleoside analogues, selected on the basis of their previously established broad-spectrum antiviral properties, were evaluated for their potency and selectivity as inhibitors of the in vitro replication of the iridovirus, African swine fever virus (ASFV) . The test compounds included (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine {(S)-HPMPA}, 9-(2-phosphonylmethoxyethyl)adenine, (RS)-3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, (S)-9-(2,3-dihydroxypropyl)adenine, carbocyclic 3-deazaadenosine (C-c3Ado), 3'-azido-2',3'-dideoxythymidine, pyrazofurin and ribavirin . As the most efficacious inhibitors of ASFV replication emerged (S)-HPMPA followed by C-c3Ado . The minimum inhibitory concentration of (S)-HPMPA for ASFV replication was 0.01 microgram/ml, and its selectivity index was 15,000 . The corresponding values for C-c3Ado were 0.025 micrograms/ml and 8000, respectively . It would seem justified to further pursue these compounds for their anti ASFV activity in vivo.

J Antimicrob Chemother, 1987 Mar, 19(3), 307 - 12
In-vitro bacterial killing kinetics of ticarcillin/clavulanic acid; Gould IM et al.; An in-vitro model was developed to study the rates of killing by ticarcillin/clavulanic acid combinations of various beta-lactamase producing, ticarcillin resistant, logarithmic phase clinical isolates . Killing, defined as a 3 log reduction, was dependent on the organism, the concentration of clavulanic acid and the duration of exposure . For most isolates studied an optimum period of exposure to and concentration of clavulanic acid could be defined . Certain test strains showed optimum response to readily attainable in-vivo concentrations of clavulanic acid while other strains, although sensitive by MIC data showed a poor response . The clinical implications of this are discussed.

J Antimicrob Chemother, 1987 Mar, 19(3), 303 - 5
Susceptibility of Rickettsia conorii and R . rickettsii to pefloxacin, in vitro and in ovo; Raoult D et al.; The activity of pefloxacin against Rickettsia conorii and R . rickettsii was determined by several methods . The mean survival time of embryonated eggs infected with R . conorii was increased by pefloxacin 50 micrograms/egg; plaque formation in Vero cells was inhibited by 1 mg/l . In a microplate assay, the MIC of pefloxacin was 0.5 mg/l for R . conorii and 1 mg/l for R . rickettsii . The results support the use of pefloxacin in treating spotted fever rickettsioses.

J Med Microbiol, 1987 Mar, 23(2), 149 - 54
The effect of antibiotics on the cell morphology of Legionella pneumophila; Chan EL et al.; Legionella pneumophila, in Buffered Yeast Extract broth, was treated for 5 h at 37 degrees C with rosaramicin, erythromycin, cefotaxime, dibekacin, penicillin, methicillin, cefoxitin, cephalothin, ticarcillin, carbenicillin or polymyxin B at near-MIC levels and above . Electronmicroscopy demonstrated morphological changes to the bacteria in some, but not all, of the antibiotic-treated suspensions . Penicillin, at 1000 micrograms/ml (40 X MIC) but not less, produced smooth bubble-like structures on cell surfaces; methicillin produced rough bubble-like structures at 100 micrograms/ml (MIC) but not at 1000 micrograms/ml . In each case, these structures resembled spheroplasts . Polymyxin B induced small-bleb formation on the bacterial cell surfaces at all concentrations tested (MIC-10 X MIC) . The other eight antibiotics did not induce any morphological changes at any concentration tested.

Dev Biol, 1987 Mar, 120(1), 259 - 69
A germ line specific DNA sequence is transcribed in Tetrahymena; Stein-Gavens S et al.; In the ciliated protozoan Tetrahymena 10-20% of the DNA sequences are micronucleus (germ line) specific . Six members of a family of repeated mic-specific DNA sequences are homologous to a 1.5-kb poly(A)+ RNA . The transcript is present in mature cells starved in 10 or 60 mM Tris, in starved immature cells, and in stationary cells . RNA from log-phase and heat-shocked cells does not have detectable levels of the transcript . These data indicate that at least one germ line limited DNA sequence is transcribed in the micronucleus of Tetrahymena.

Drug Intell Clin Pharm, 1987 Feb, 21(2), 187 - 92
Potential impact of quantitative susceptibility tests on the design of aminoglycoside dosing regimens; McCormack JP et al.; Therapeutic drug monitoring of aminoglycosides currently applies pharmacokinetic principles to maintain peak concentrations between 4 and 10 micrograms/ml and troughs less than 2 micrograms/ml . These predetermined concentrations are based on statistical rates of cure and incidences of adverse effects . At present, recommended serum concentration ranges for aminoglycosides (as with other antibiotics) do not specifically target the susceptibility of the individual organism, but compensate only for altered clearance due to diseases . The design of antibiotic regimens based on both pharmacokinetics and pharmacodynamics is called dual individualization . Logically, the pharmacodynamic parameters, the minimum inhibitory concentration (MIC) of the organism and the postantibiotic effect (PAE), should also play a significant role in design of the dosing regimen . Simulations were performed to examine the consequences of designing aminoglycoside regimens considering both disease effects on excretion and bacterial susceptibility (MIC and PAE) . The application of dual individualization concepts to aminoglycosides argues for a wider range of dosage requirements than observed with regimens that maintain desired peaks and troughs . If these concepts are accepted, some patients will clearly require more aminoglycoside than is currently used, and others can be managed with substantially less . The aminoglycoside therapeutic window, as it is now conceived, could be markedly different in the future.

What Is Bioassay?, What Is Environmental Microbiology?, What Is Listeria Monocytogenes?, What Is Bioengineering?, What Is Bioreactor?, i, Bacterium, c, Bacteria, s, Bacteriology, r, Microorganisms, r, Microorganism, n, Vibriosis, a, Enterobacters, a, Antibiotics, s, Clostridia, i, Enterobacteriacea, e, Bactericidal, r, Biofilms, c, Microorganism, c, E coli O157, o, Sepsis, c, Bacillus anthracis, n, Fermentations, i, Streptococcal, e, Prokaryotes, i, Bacteriophages, o, Salmonella typhimurium, n, Sepsis, r, Salmonella, o, Streptococci, i, Multidrug resistant, c, Escherichia coli

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005