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 </