J Antimicrob Chemother, 1988 Jun, 21(6), 765 - 72 Uptake of erythromycin by McCoy and HEp2 cells: its dependence on cellular pH gradients; Knowles DJ; The accumulation of erythromycin, a weak lipophilic base, was studied in two mammalian cell lines . Uptake was similar in both cell types, being highly pH dependent and not saturated even at external concentrations of 1000 mg/l . At pH 6.7 the ratio of cellular:extracellular erythromycin concentrations (C/E) was only 2.0, whereas at pH 7.5 it was as high as 7.0 . Carbonylcyanide-m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation which was used to collapse cellular pH gradients, caused a 50% reduction in C/E ratio within five minutes when the external pH was greater than 6.9 but had no effect at or below pH 6.7 . These results suggest that ion-trapping plays a major role in the accumulation of erythromycin by these cells. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 93 - 9 Erythromycin acistrate and enterocoated pellets of erythromycin base in acute respiratory infections of hospitalized conscripts; Gordin A et al.; The efficacy and tolerability of a new erythromycin ester, erythromycin acistrate (EA), and erythromycin base (EB) as enterocoated pellets were studied in 100 conscripts at the Central Military Hospital . The patients were admitted to hospital for acute respiratory tract infection . The dosage of EA was 400 mg tid and that of EB 500 mg tid . The patients were hospitalized during the treatment which ranged from seven to 12 days . The cure rate was good in both groups, 96% in the EA- and 87% in the EB-group . Gastrointestinal side effects were reported in 18% of the patients in the EA-group and in 46% in the EB-group (P less than 0.01) . The gastrointestinal side effects were mild in all patients in the EA-group, while they were moderate in half and mild in half in the EB-group . None of the patients in the EA-group discontinued treatment because of gastrointestinal side effects, while the number in the EB-group was five (P less than 0.05) . However one EA patient discontinued treatment because of testicular pain and one because of an urticarial rash . Neither of the drugs caused elevations of clinical significance in liver enzymes, and there were no changes in the measured laboratory safety parameters . In this trial EA was as effective as and caused significantly less gastrointestinal side effects than EB. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 9 - 27 Comparative liver toxicity of various erythromycin derivatives in animals; Viluksela M et al.; The hepatotoxicity of a new erythromycin derivative, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared with that of erythromycin stearate (ES), erythromycin estolate (EE) and erythromycin-11,12 cyclic carbonate (EC) in 4-5-day, 28-day and 6-month oral toxicity studies in rats and dogs . In the 4-day rat study, EC caused fatty metamorphosis in the liver . ES caused similar, but milder changes at a dose nearly five times higher . The 5-day dog study revealed markedly increased serum alanine aminotransferase (S-ALAT), serum aspartate aminotransferase (S-ASAT), serum alkaline phosphatase (S-APHOS) and serum gamma-glutamyl transpeptidase (S-gamma-GT) values in the EC- and EE-groups, and slightly elevated S-ALAT values also in the EA- and ES-groups . Microscopy revealed cholangitis, pericholangitis and phlebitis in the portal areas in the EC-group at all doses . Epithelial hyperplasia was observed also in the bile ducts . EE caused similar but milder changes . The changes in the EA-group were small, but mildly atypical bile duct epithelium was seen in female dogs receiving 2 x 200 mg/kg of EA . The ES-group was practically without changes and very much like the EA-group . Thus the dog proved to be a more sensitive model for assessing the hepatotoxicity of erythromycin derivatives . In the 28-day studies, only EA and ES were investigated . In the rat study, slightly elevated serum enzyme levels within the normal range were measured in the high-dose regimens of both drugs . In the dog study, 300 mg/kg of EA caused slightly elevated S-ALAT in males, but the values returned to normal after a 2-week off-dose period . Only EA was studied in the 6-month study . In male rats, 400 mg/kg of EA caused slightly elevated enzyme levels and neutral fat droplets in centrilobular hepatocytes . In male dogs given 150 mg/kg of EA, S-ALAT, S-APHOS, and S-gamma-GT values were elevated after four weeks of treatment but returned to normal thereafter . No severe changes were seen in the liver histopathology . In conclusion, EC and EE were clearly hepatotoxic in dogs, and EC also in rats . EA, and to a somewhat lesser extent ES, showed signs of mild hepatotoxicity only at high doses . This evidently reversible effect was considered a common characteristic of erythromycins. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 85 - 92 Comparison of erythromycin acistrate and enterocoated erythromycin base in acute respiratory infections; Gordin A et al.; The efficacy and tolerability of erythromycin acistrate (EA), a new erythromycin derivative, and enterocoated erythromycin base (EB) were studied in 183 outpatients belonging to the personnel of Helsinki University Central Hospital . The patients had acute respiratory tract infections . The dosage of EA was 400 mg tid and that of EB 500 mg tid, and the treatment period ranged from seven to 14 days . The cure rate of patients taking full courses of treatment was good in both treatment groups, 96% in the EA-(n = 81) and 93% in the EB-group (n = 73) . EA caused statistically significantly (P less than 0.05) less gastrointestinal side effects than EB . These side effects were also milder in the EA- than in the EB-group . The treatment was discontinued in seven patients (7%) in the EA- and in 12 patients (13%) in the EB-group because of gastrointestinal side effects . Neither of the drugs caused clinically important elevations in liver enzymes, nor were changes observed in the laboratory safety parameters measured . EA seems thus to be as effective as and better tolerated than enterocoated EB. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 73 - 84 Tonsillar penetration of erythromycin and its 2'-acetyl ester in patients with chronic tonsillitis; Savolainen S et al.; Concentrations of erythromycin and 2'-acetyl erythromycin were analysed in serum or plasma and tonsil tissue after repeated dosage of erythromycin acistrate (EA), a new erythromycin prodrug, in two separate studies in 61 young patients . The reference preparations were: (1) enterocoated tablets of erythromycin base (EB enterotablets, (2) erythromycin base as enterocoated pellets (EB enterocapsules) and (3) erythromycin stearate (ES) . All drugs were given 500 mg tid for three days before scheduled tonsillectomy . Tonsils were removed about 3 h after intake of the last dose . Blood samples were collected at 0, 2 and 6 h and at the time of tonsillectomy . At all time points EA produced several-fold higher total drug (erythromycin + 2'-acetyl erythromycin) concentrations in serum or plasma than any of the reference preparations . Similarly, after EA the mean total antibiotic levels in tonsil tissue exceeded the erythromycin levels after the reference preparations by at least a factor of 3 . Tonsil/serum or plasma ratios of the total antibiotic were quite similar with all preparations (means 38-50%) . Peak erythromycin levels in circulation did not differ significantly from each other in spite of two nonabsorbers after EB enterotablets . The same was true of tonsil tissue . There were, however, 15 tonsils with undetectable erythromycin: 4/25 (16%) with EA, 5/12 (42%) with EB enterotablets, 2/12 (17%) with EB enterocapsules and 4/12 (33%) with ES . The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 23-43% higher in tonsil tissue than in circulation. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 67 - 72 Determination of 2'-acetyl erythromycin and erythromycin in human tonsil tissue by HPLC with coulometric detection; Haataja H et al.; A simple and sensitive high-performance liquid chromatographic method was developed for the determination of 2'-acetyl erythromycin and erythromycin in human tonsil tissue . Methyl tert-butyl ether was used as the extraction solvent after alkalization of tissue homogenates . Separation was achieved on a reverse phase C-18 column . The mobile phase consisted of acetonitrile-methanol-tetrahydrofuran-sodium acetate buffer, pH 4.5 . Eluted compounds were monitored by a coulometric detector in the oxidative screen mode . The quantitation limits of 2'-acetyl erythromycin and erythromycin were 0.20 and 0.30 mg/kg of tissue, respectively . The method was linear over the concentration range of 0.60-10.0 mg/kg of tissue for 2'-acetyl erythromycin and erythromycin. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 45 - 55 Absorption of erythromycin acistrate and erythromycin base in the fasting and non-fasting state; Tuominen RK et al.; Absorption of erythromycin acistrate (EA) and two erythromycin base (EB) preparations (enterotablet A and B) taken after an overnight fast or immediately before a standard breakfast was studied in 29 healthy volunteers in three separate studies, in a cross-over, randomized design . In Study I, the absorption of a single dose (400 mg) of EA was similar in the fasting and non-fasting state . There was, however, more interindividual variation and in two subjects absorption was markedly impaired in the presence of food . Cimetidine given at two doses (400 + 800 mg) had no effect on the pharmacokinetics of erythromycin acistrate . In Study II, the effect of food on the bioavailability of the two EB preparations was studied after a single dose of 500 mg (2 x 250 mg enterocoated tablets) and after multiple dosing (2 x 250 mg tid) . When given with a standard breakfast, erythromycin base was significantly better absorbed from enterotablet A than from enterotablet B, whether given as a single dose or in repeated doses . Study III followed the same design as Study II except that the tablet size of both enterotablets A and B was now 500 mg . Even in this study the absorption of enterotablet A was significantly better than that of enterotablet B . EA is adequately absorbed when taken before a meal . Cimetidine does not interfere with its elimination . Concomitant food intake produced considerably dissimilar absorption of two commercially available enterocoated EB preparations . Although at steady-state this was less prominent than after a single dose, it may have some clinical significance. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 33 - 43 Fate of single oral doses of erythromycin acistrate, erythromycin stearate and pelleted erythromycin base analysed by mass-spectrometry in plasma of healthy human volunteers; Mannisto PT et al.; The kinetics of erythromycin acistrate (EA) . a new ester prodrug of erythromycin, were studied in three comparative, randomized, cross-over studies in 29 healthy volunteers . A new mass-spectrometric method was used to assay separately erythromycin, 2'-acetyl erythromycin and their anhydro (spiroketal) forms . In Part I, the total antibiotic concentration was higher after EA than after erythromycin stearate (ES; 1.8-fold) and enterocoated pellets of erythromycin base (EB, enterocapsules; 1.4-fold) . In plasma, however, only about one third of 2'-acetyl erythromycin was hydrolysed to active erythromycin . Moreover, after unprotected EA tablets, a considerable proportion of erythromycin and 2'-acetyl erythromycin was inactivated by gastric acid as reflected by high concentrations of respective anhydro (spiroketal) forms . In Part II, the unprotected (regular tablets) and acid-protected tablets (dissolution starts at pH 4.5) were compared . The protected tablet, albeit not an enterotablet, was not destroyed by gastric acid . Its absorption was slightly delayed but the bioavailability was good . In this study, the absorption of total antibiotic was 2.8-fold (unprotected tablet) and 3.9-fold (protected tablet) that after enterocapsules . In Part III, the bioavailabilities of 200 and 400 mg tablets (both acid-protected) were equal. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 107 - 12 Treatment of respiratory tract infections with erythromycin acistrate and two formulations of erythromycin base; Wuolijoki E et al.; Erythromycin acistrate (EA)--a new ester of erythromycin--was compared with erythromycin base as enterocoated pellets in capsules (EB enterocapsules) and enterocoated tablets of erythromycin base (EB enterotablets) in the treatment of respiratory tract infections . The present double-blind, multicentre study, conducted in eight occupational health centres, included 474 patients; 236 treated with EA, 117 with EB enterocapsules and 121 with EB enterotablets . The diagnoses included tonsillitis, sinusitis, otitis media, bronchitis and pneumonia . The patients were examined on admission and at the end of the treatment . The dosage of EA was 400 mg tid and that of the two erythromycin base preparations 500 mg tid . The treatment was given for seven to 14 days . In the EA-group, 97% of patients were clinically cured by the end of the treatment, while the cure rates for EB enterocapsules and EB enterotablets were 95% and 94%, respectively . Gastrointestinal side effects were reported by 36% of the patients on EA, 54% on EB enterocapsules and 50% on EB enterotablets . Discontinuations due to adverse effects occurred in 8% in the EA, in 21% in the EB enterocapsule and in 12% in the EB enterotablet groups . All three preparations were thus equally effective, but EA caused statistically significantly less gastrointestinal side effects overall (P less than 0.01), especially nausea (P less than 0.01) and abdominal pain (P less than 0.05), than the two formulations containing erythromycin base . Also discontinuations due to side effects occurred statistically significantly less frequently in the EA-group. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 1 - 8 Hydrolysis of 2'-esters of erythromycin; Taskinen J et al.; Hydrolysis rates were determined for 2'-acetyl erythromycin, three of its homologues (2'-propionyl, 2'-butyryl and 2'-valeryl) and 2'-ethylsuccinyl erythromycin in buffer solution (pH 7.0, 37 degrees C) and in human plasma (37 degrees C) at concentrations of 5 and 100 mg/l . Ester concentrations were measured by fast atom bombardment mass spectrometry . Hydrolysis in buffer followed pseudo first-order kinetics . The half-lives of the esters ranged from 24.3 to 89.5 min (2'-ethyl-succinyl less than 2'-acetyl less than 2'-propionyl less than 2'-valeryl less than 2'-butyryl) . Hydrolysis in plasma followed more complex kinetics . The half-lives were generally longer than in buffer and dependent on the initial ester concentration . Apparent first-order half-lives ranged from 35.5 to 492 min (2'-ethylsuccinyl less than 2'-acetyl less than 2'-propionyl less than 2'-butyryl less than 2'-valeryl) . In case of homologous esters, the stabilizing effect of plasma and concentration dependence varied with lipophilicity . In buffer solution the hydrolysis half-life of 2'-acetyl erythromycin was dependent on the concentration of alpha 1-acid glycoprotein . Of the homologous esters, 2'-acetyl erythromycin was hydrolysed most rapidly, but it was hydrolysed more slowly than 2'-ethylsuccinyl erythromycin. Dis Colon Rectum, 1988 Jun, 31(6), 427 - 9 A prospective, randomized trial of perioperative prophylactic cefamandole in elective colorectal surgery for malignancy; Petrelli NJ et al.; The impact on wound infection of the addition of perioperative cefamandole to a mechanical bowel preparation with oral antibiotics was studied in a prospective randomized series of patients undergoing elective colectomy for biopsy-proven carcinoma or adenomatous polyps . Seventy patients were randomized, all underwent mechanical bowel preparation and received oral neomycin and erythromycin base . Thirty-four patients also received a preoperative and four postoperative doses of cefamandole, while 36 patients were randomized to receive no parenteral antibiotics . The two groups were well stratified for age, sex, and risk factors . The Dukes stage was similar and the surgical procedures were equally distributed in the two groups . There were no wound infections in the 34 patients receiving cefamandole and only one wound infection (2.8 percent) in the 36 control patients . Therefore, the addition of perioperative intravenous cefamandole to a good mechanical bowel preparation with oral antibiotics was of no benefit in reducing wound infections following resection of colorectal malignancies in this select group of patients. J Infect Dis, 1988 Jun, 157(6), 1134 - 41 Risk factors for community- and household-acquired pertussis during a large-scale outbreak in central Wisconsin; Biellik RJ et al.; To identify risk factors associated with community- and household-acquired pertussis, we studied 61 households (HHs) with members with culture-positive illnesses and compared their characteristics with 58 neighborhood control-HHs and 62 randomly selected control-HHs . Case-HHs were more likely than either control group to have members 12-18 y of age (P less than .01); these individuals accounted for 34% of all primary cases . A history of exposure outside the home was the most important predictor of community-acquired infection (P less than .001), with adolescents being at higher risk than other age-groups (odds ratio, 3.2; P less than .001) . After known exposure to a culture-positive case in the same HH, the risk of illness was unrelated to age; lengthy delays in initiating erythromycin therapy and prophylaxis were the only factors associated with secondary spread (P less than .01) . The risk of pertussis may be related more to the likelihood of exposure than to age-related increases in susceptibility, and the risk can be reduced with appropriate use of erythromycin. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 29 - 32 Effects of two erythromycins, doxycycline and phenoxymethylpenicillin on human leucocyte chemotaxis in vitro; Aho P et al.; The effect of erythromycin, doxycycline and phenoxymethylpenicillin on human polymorphonuclear leucocyte (PMNL) chemotaxis was studied in vitro with Boyden's filter technique . Both erythromycin base and 2'-acetyl erythromycin stearate increased the PMNL chemotaxis significantly at concentrations greater than or equal to 50 microM, 2'-acetyl erythromycin stearate also at concentrations of 2.5-5 microM . Phenoxymethyl-penicillin reduced migration at 500 microM but lower concentrations had no significant effect . Doxycycline prevented migration significantly at concentrations greater than or equal to 50 microM. Z Hautkr, 1988 May 15, 63(5), 366 - 8, 373 {Combined topical treatment of acne with erythromycin and tretinoin}; Pfannschmidt N et al.; Vitamin A acid is the most effective comedolytic agent in the therapy of acne vulgaris . Antibiotics are suitable for the treatment of inflammatory lesions (papulo-pustules) . Even topically applied, some antibiotics show a sufficient anti-inflammatory effect . Above all, erythromycin is reliable in the topical treatment of acne . Combined therapy with both topical tretinoin and erythromycin is more effective than either alone . During the first weeks of treatment, tretinoin leads to temporary deterioration of the disease, which can mostly be avoided by the anti-inflammatory effect of erythromycin simultaneously applied. Int J Dermatol, 1988 May, 27(4), 243 - 5 Chancroid in El Salvador . Increasing incidence, clinical features, and therapeutics; Orellana-Diaz O et al.; Ninety-five cases of chancroid were studied during a 6-month period in a dermatologic service in San Salvador; 88 (92.6%) were men and 7 (7.4%) were women, with a ratio of 12.5:1 . The minimum age was 13 years and the maximum 46, with an average of 21 years . In most of the cases (81.05%), the incubation period varied from 1 to 7 days . Very painful adenopathies, enough to make walking difficult, were a striking feature in 69 cases (72.6%) . Treatment was curative in all cases, except two, who received treatment with co-trifamole (sulfatrifamole 400 mg/trimethoprim 80 mg) . In two cases in which it was not possible to use co-moxole (allergy, pregnancy), treatment was also curative using erythromycin. Mol Pharmacol, 1988 May, 33(5), 493 - 9 Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by alpha-naphthoflavone; Schwab GE et al.; Rifampicin induces cytochrome P-450 3c, progesterone 16 alpha- and 6 beta-hydroxylation, 17 beta-estradiol 2-hydroxylation, benzo{a} pyrene hydroxylation, and erythromycin N-demethylation in rabbit liver microsomes . Kinetic analysis of the 6 beta-hydroxylation of progesterone as catalyzed by liver microsomes prepared from rifampicin-treated B/J rabbits exhibits a curvilinear double-reciprocal plot, suggestive of substrate activation . Further experimentation demonstrated that alpha-naphthoflavone could augment the catalytic efficiency {Vmax/Km} observed for the 16 alpha- and 6 beta-hydroxylation of progesterone and the 2-hydroxylation of 17 beta-estradiol, whereas erythromycin N-demethylase activity was partially inhibited . Allosteric activation of these steroid hydroxylases by alpha-naphthoflavone is also found for human liver microsomes, indicating that the activation of these enzymes is conserved in man and rabbit. Gut, 1988 May, 29(5), 593 - 7 Cryptosporidial diarrhoea in AIDS and its treatment; Connolly GM et al.; Of 234 patients with AIDS diagnosed at St . Stephen's Hospital between January 1981 and June 1987, 26 (11%) were found to have cryptosporidiosis . Stool examination was positive in all patients, but an average of three specimens (range 1-6) were required before a positive diagnosis was made . Other methods of diagnosis included jejunal and rectal biopsy and aspiration of the duodenal contents . Twenty three (89%) lived for six months from the time of diagnosis and 16 (60%) were alive at one year . Only five patients died as a direct result of cryptosporidial infection, while 10 other patients died from another complication of AIDS . Fifteen patients were enrolled in a prospective controlled study of erythromycin or spiramycin in the treatment of cryptosporidial diarrhoea . Most patients showed a significant response to antibiotic therapy but treatment was limited because of side effects . All patients responded to antidiarrhoeal agents, particularly long acting morphine sulphate . Three of our patients recently given zidovudine (AZT) have responded with a cessation of diarrhoea and cryptosporidia are no longer isolated from the stools. Postgrad Med J, 1988 May, 64(751), 382 - 3 Cerebellar disturbance in psittacosis; Shee CD; A previously fit man developed psittacosis with marked cerebellar symptoms and signs . He was febrile but not confused, and he responded rapidly to treatment with erythromycin . Even if respiratory symptoms are minimal, psittacosis and other atypical pneumonias should be considered in any patient presenting with fever and cerebellar involvement. Pathol Biol (Paris), 1988 May, 36(5), 477 - 81 {Sensitivity of 7 mycobacterial species to new quinolones}; Gevaudan MJ et al.; The authors have tested the sensibility to three new quinolones of forty one strains of mycobacteria belonging to seven different species . They have observed, in particular, susceptibility for the species M . tuberculosis, M . fortuitum, M . kansasii, M . marinum and M . xenopi to ciprofloxacin and ofloxacin and a limited sensibility for these same species to pefloxacin . In association with others antibiotics, amikacin, erythromycin, thienamycin, trimethoprim-sulfamethoxazole, the three have shown some additive effects and in a few cases synergistic effects. Pathol Biol (Paris), 1988 May, 36(5), 544 - 7 {Multicenter study of the clinical efficacy and tolerance of roxithromycin compared to erythromycin ethylsuccinate in lower respiratory tract infections}; Bertrand A et al.; In a double blind, randomised investigation in 193 hospitalized patients, with low respiratory infections, roxithromycin (150 mg bd) and erythromycin ethylsuccinate (1 g bd) were compared . Assessment of safety was made in 183 patients and clinical response in 155 patients . The mean duration of treatment was 11 days in both groups . Clinical effectiveness was 82% (67/82) for roxithromycin and 77% (56/73) for erythromycin ethylsuccinate . Roxithromycin appears to have a good effectiveness and to be effective as erythromycin ethylsuccinate . The safety profile is satisfactory in both groups. Pharmacol Toxicol, 1988 May, 62(5), 337 - 43 Acute hepatocellular effects of erythromycin, gentamicin, and trospectomycin in the perfused rat liver: lack of correlation between lamellar body induction potency and cytotoxicity; Cox JW et al.; The formation of multilamellar inclusion bodies in cytoplasm is a generalized cellular response to treatment with a variety of chemical agents . The present study was conducted to determine if a correlation exists between acute lamellar body induction potency and cytotoxicity in the perfused rat liver . Livers were perfused for 3 hrs with various concentrations of erythromycin, gentamicin, sulfate, or trospectomycin sulfate, all of which are known to produce lamellar bodies in the rat in vivo . At the end of the experiments, the livers were perfusion fixed for transmission electron microscopy . Based on the bile flow rate, perfusion rate at constant pressure, and cytoplasmic enzyme release, neither gentamicin nor trospectomycin was hepatotoxic at concentrations up to 1.8 mM, whereas erythromycin was toxic at 0.1 mM . Gentamicin caused no ultrastructural changes compared to controls, but trospectomycin caused the dose-dependent formation of lamellar bodies in hepatocytes without other cytoplasmic alterations . Erythromycin caused cellular degeneration accompanied by an increase in the number of secondary lysosomes, but these lacked lamellated inclusions . It is concluded that hepatic lamellar bodies can be induced in acute ex vivo experiments, but that their formation does not appear to be linked with acute cytotoxicity. J Gen Microbiol, 1988 May, 134 ( Pt 5), 1251 - 63 Reversion from erythromycin dependence in Escherichia coli: strains altered in ribosomal sub-unit association and ribosome assembly; Wild DG; A mutant of Escherichia coli dependent on erythromycin for growth spontaneously gives erythromycin-independent strains with altered or missing ribosomal proteins . strains with defects in ribosome assembly were sought and obtained from among these revertants . Two organisms in which ribosomal protein L19 is altered and absent respectively have 70S ribosomes whose dissociation into sub-units is particularly sensitive to pressures generated during centrifuging . The mutant that lacks protein L19 also accumulates ribosome precursor particles during exponential growth as do others including mutants that lack proteins S20 or L1 . These strains also show unbalanced synthesis of RNA and so will be useful in investigating both the pathways and the regulation of ribosome assembly. FEBS Lett, 1988 Apr 11, 231(1), 183 - 6 Sex-related difference in oxidative metabolism of testosterone and erythromycin by hamster liver microsomes; Miura T et al.; The activities of testosterone hydroxylases and erythromycin N-demethylase were significantly higher in liver microsomes from female hamsters than in the male counterparts . SDS-polyacrylamide gel electrophoresis revealed a difference in protein composition between male and female liver microsomes in the molecular mass region comprising cytochrome P-450 . Western blot analysis showed further that antibodies to rat male-specific cytochrome P-450 crossreacted with at least two proteins in both male and female hamster microsomes, but one of the female proteins had a different molecular mass from that of the male proteins . It is concluded that sex difference in liver microsomal cytochrome P-450 is not restricted to rats and mice, as has previously been believed. An Esp Pediatr, 1988 Apr, 28(4), 293 - 6 {Mediterranean spotted fever in childhood . Prospective study of 130 cases}; Lopez Pares P et al.; Authors present a prospective study of 130 cases of Mediterranean spotted fever treated between 1983 and 1985 in two Departments of Paediatrics of the Valles Occidental, area near Barcelona . Thirty-eight percent of the children came from suburban areas, an urban areas, an urban or rural origin being less frequent . Previous contacts with dogs existed in 86% of the cases . Most frequent clinical signs were fever (100%) maculo-papular rash (97%) and arthromyalgias (70%) . The "tache noire" was found in 87% of the cases . Presence of arthritis in two patients is underlined . Indirect immunofluorescence to Rickettsia conorii was positive (much greater than 1/40) in 75% of the cases . All patients improved after treatment with tetracycline or erythromycin . There were no relapse. J Antibiot (Tokyo), 1988 Apr, 41(4), 563 - 9 Effects of roxithromycin, a new semisynthetic macrolide, and two erythromycins on drug metabolizing enzymes in rat liver; Villa P et al.; The effects of a new semisynthetic macrolide, roxithromycin, on drug metabolizing enzymes of rat liver were compared with two erythromycins, the base (EB) and the estolate (EE), after 7 days' treatment with high oral doses (400 and 800 mg/kg daily) . Dose-related higher concentrations of roxithromycin were reached in serum and liver than after EB or EE . The two reference erythromycins induced the synthesis of microsomal enzymes and formed inactive cytochrome P-450-metabolite complexes . N-Demethylation of erythromycin itself and aminopyrine was increased by the treatment . Liver microsomal enzyme activities were not induced and the inactive cytochrome P-450-metabolite complex was not formed after 400 mg/kg of roxithromycin and only to a very limited extent after 800 mg/kg (10% vs . 50% after EE) . At the higher dose microsomal activities were not changed by roxithromycin and only aminopyrine N-demethylation was reduced. Am J Kidney Dis, 1988 Apr, 11(4), 357 - 9 Drug hypersensitivity causing granulomatous interstitial nephritis; Singer DR et al.; In association with treatment for pharyngitis, a 47-year-old white man developed a systemic illness with fever, myalgia, episcleritis, hemoptysis, pleurisy, eosinophilia, and renal impairment . Renal biopsy revealed granulomatous interstitial nephritis, which resolved due to no specific treatment other than withdrawing all medication . Both the severe systemic manifestations and spontaneous recovery are unusual in association with drug-induced granulomatous nephritis . The drugs that may have caused the reaction included dihydrocodeine, phenylpropanolamine, erythromycin, and amoxycillin . Although the latter three drugs have been previously implicated in the development of interstitial nephritis, there have been no previous reports of granulomatous interstitial nephritis with any of these drugs. J Bioenerg Biomembr, 1988 Apr, 20(2), 243 - 59 Expression of the primary biliary cirrhosis antigens in yeast: aspects of mitochondrial control; Ghadiminejad I et al.; The mitochondria of 21 yeast strains were tested for the expression of primary biliary cirrhosis (PBC) specific antigens . The amounts of the antigens in the mitochondrial preparations varied with the strains . Genetic analysis of the strain differences in antigen expression indicated nuclear control which was complex . Those strains expressing the least amounts of antigens exhibited coagulating mitochondria in organellar preparations . Additional evidence relating expression of antigens to the physiological/structural state of mitochondria was that cells grown in the presence of the mitochondrial uncoupling agent, 2,4-dinitrophenol (DNP), failed to produce any antigens, and that glucose repression of mitochondria suppressed antigen expression . Blockage of mitochondrial protein synthesis either through petite mutation or by culture in the presence of erythromycin decreased the content of antigens in the mitochondria but did not completely block antigen production . The presence of the PBC antigen in the mitochondria of these cells with nonfunctional mitochondrial synthesizing machinery further indicates that these antigens are cytoplasmically synthesized . Analysis of the pre- and postmitochondrial fractions of all homogenates confirmed that the antigens are not only cytoplasmically synthesized but also have an extramitochondrial location in cells, probably in the plasma membrane. J Bacteriol, 1988 Apr, 170(4), 1800 - 11 Translational attenuation control of ermSF, an inducible resistance determinant encoding rRNA N-methyltransferase from Streptomyces fradiae; Kamimiya S et al.; An inducible resistance determinant, ermSF, from the tylosin producer Streptomyces fradiae NRRL 2338 has been cloned, sequenced, and shown to confer inducible macrolide-lincosamide-streptogramin B resistance when transferred to Streptomyces griseofuscus NRRL 23916 . From mapping studies with S1 nuclease to locate the site of transcription initiation, the ermSF message contains a 385-nucleotide 5' leader sequence upstream from the 960-nucleotide major open reading frame that encodes the resistance determinant . On the basis of the potential secondary structure that the ermSF leader can assume, a translational attenuation model similar to that for ermC is proposed . The model is supported by mutational analysis involving deletions in the proposed attenuator . By analysis with restriction endonucleases, ermSF is indistinguishable from the tlrA gene described by Birmingham et al . (V . A . Birmingham, K . L . Cox, J . L . Larson, S . E . Fishman, C . L . Hershberger, and E . T . Seno, Mol . Gen . Genet . 204:532-539, 1986) which comprises one of at least three genes from S . fradiae that can confer tylosin resistance when subcloned into S . griseofuscus . When tested for inducibility, ermSF appears to be strongly induced by erythromycin, but not by tylosin. Baillieres Clin Gastroenterol, 1988 Apr, 2(2), 385 - 422 Acute and chronic drug-induced hepatitis; Pessayre D et al.; Adverse drug reactions may mimic almost any kind of liver disease . Acute hepatitis is often due to the formation of reactive metabolites in the liver . Despite several protective mechanisms (epoxide hydrolases, conjugation with glutathione), this formation may lead to predictable toxic hepatitis after hugh overdoses (e.g . paracetamol), or to idiosyncratic toxic hepatitis after therapeutic doses (e.g . isoniazid) . Both genetic factors (e.g . constitutive levels of cytochrome P-450 isoenzymes, or defects in protective mechanisms) and acquired factors (e.g . malnutrition, or chronic intake of alcohol or other microsomal enzyme inducers) may explain the unique susceptibility of some patients . Formation of chemically reactive metabolites may also lead to allergic hepatitis, probably through immunization against plasma membrane protein epitopes modified by the covalent binding of the reactive metabolites . This may be the mechanism for acute hepatitis produced by many drugs (e.g . amineptine, erythromycin derivatives, halothane, imipramine, isaxonine, alpha-methyldopa, tienilic acid, etc.) . Genetic defects in several protective mechanisms (e.g . epoxide hydrolase, acetylation) may explain the unique susceptibility of some patients, possibly by increasing exposure to allergenic, metabolite-altered plasma membrane protein epitopes . Like toxic idiosyncratic hepatitis, allergic hepatitis occurs in a few patients only . Unlike toxic hepatitis, allergic hepatitis is frequently associated with fever, rash or other hypersensitivity manifestations; it may be hepatocellular, mixed or cholestatic; it promptly recurs after inadvertent drug rechallenge . Lysosomal phospholipidosis occurs frequently with three antianginal drugs (diethylaminoethoxyhexestrol, amiodarone and perhexiline) . These cationic, amphiphilic drugs may form phospholipid-drug complexes within lysosomes . Such complexes resist phospholipases and accumulate within enlarged lysosomes, forming myeloid figures . This phospholipidosis has little clinical importance . In a few patients, however, it is associated with alcoholic-like liver lesions leading to overt liver disease and, at times, cirrhosis . Subjects with a deficiency in a particular isoenzyme of cytochrome P-450 poorly metabolize perhexiline and are at higher risk of developing liver lesions . Prolonged, drug-induced liver-cell necrosis may also lead to subacute hepatitis, chronic hepatitis or even cirrhosis . This usually occurs when the drug administration is continued, either because the liver disease remains undetected or because its drug aetiology is overlooked . Several autoantibodies may be present.(ABSTRACT TRUNCATED AT 400 WORDS) Biochem Pharmacol, 1988 Mar 15, 37(6), 1137 - 44 Tolbutamide hydroxylation by human liver microsomes . Kinetic characterisation and relationship to other cytochrome P-450 dependent xenobiotic oxidations; Miners JO et al.; Tolbutamide hydroxylation has been investigated in human liver microsomes . Anti-human liver NADPH-cytochrome P-450 reductase IgG inhibited hydroxytolbutamide formation and this metabolite was not formed when NADPH-generating system was omitted from microsomal incubations . Tolbutamide hydroxylation followed Michaelis-Menten kinetics, consistent with the involvement of a single form of cytochrome P-450 in this reaction . Mean apparent Km and Vmax values for hydroxytolbutamide formation were 120 +/- 41 microM and 0.273 +/- 0.066 nmol min-1 mg-1, respectively . A range of clinically used drugs and xenobiotics used as probes for cytochrome P-450 activity in laboratory animals was screened for inhibitory effects on hydroxytolbutamide formation . Caffeine, paraxanthine, theophylline, theobromine, debrisoquine, erythromycin, phenacetin, propranolol, aminopyrine, benzo(a)pyrene and 7-ethoxycoumarin were all found not to inhibit tolbutamide hydroxylation . In contrast, sulphaphenazole, phenylbutazone, nifedipine, verapamil, cimetidine, aniline, dextropropoxyphene and mephenytoin were competitive inhibitors of tolbutamide hydroxylation . The respective apparent Ki values for these compounds were 0.12 microM, 11 microM, 15 microM, 118 microM, 140 microM, 182 microM, 225 microM and 375 microM . Sulphinpyrazone inhibited tolbutamide hydroxylation with atypical kinetics . The in vitro data is in good agreement with in vivo drug interactions with tolbutamide . The data also confirm that tolbutamide hydroxylation is not associated with the cytochromes P-450 responsible for methylxanthine metabolism or with the form responsible for the polymorphic oxidation of debrisoquine. Antibiot Khimioter, 1988 Mar, 33(3), 217 - 23 {Isolation and properties of the protoplasts of Streptomyces erythraeus}; Zakharova GM et al.; The paper is concerned with development of conditions for cultivation of the erythromycin-producing organism and preparation and maintenance of its stable viable protoplasts . Optimal conditions for the culture growth and protoplasting were developed . Two-stage cultivation of the organism on media PB and S provided dense diffuse or diffuse local growth characterized by low differentiation and higher homogenicity . The incubation time at stage I was 66 hours and that at stage II was not more than 24 hours at respective temperatures . The culture was incubated on a shaker in the presence of glycine at the minimum concentration . The presence of glycine in the medium altered the culture cell walls which was evident from changing of staining by Gram from + to +/- . Treatment of such a culture with lysozyme for 30 minutes provided formation of up to 2.10(9) protoplasts per 1 . ml . It is possible to maintain the protoplasts in frozen state at -20 degrees C in medium P for 1 month . Under such storage conditions the titer of the viable protoplasts as compared to the initial one decreased only 2-fold after the one-month storage. Acta Paediatr Scand, 1988 Mar, 77(2), 207 - 13 Neonatal chlamydial conjunctivitis . A long term follow-up study; Sandstrom I et al.; Chlamydia trachomatis (Ct) was isolated from eyes of 33 out of 160 infants with neonatal conjunctivitis . In nineteen (58%) of the infants with chlamydial conjunctivitis Ct could also be isolated from the nasopharynx . All infants were treated with oral erythromycin ethylsuccinate 25 mg/kg every 12 hours for 14 days combined with lid hygiene . All were clinically cured, and none had a relapse of clinical Ct conjunctivitis during an observation period of one year . However, one infant had persistent asymptomatic chlamydial eye infection, two displayed a persistent infection of the nasopharynx, and one infant's vagina was infected despite therapy . Serum IgG antibodies to Ct were significantly more often detected in clinical cases (90%) than in controls (33%) (p less than 0.01) . Infants with conjunctivitis developed detectable IgM antibodies to Ct in 43% as compared to 7% in controls (p less than 0.01). J Infect Dis, 1988 Mar, 157(3), 434 - 40 Evidence for a high attack rate and efficacy of erythromycin prophylaxis in a pertussis outbreak in a facility for the developmentally disabled; Steketee RW et al.; During an outbreak of pertussis in residents and staff of a facility for the developmentally disabled, 149 persons had laboratory evidence of Bordetella pertussis infection; 130 (87%) reported respiratory illness . Infection rates (IR) in affected wards ranged from 6% to 91% . Most residents were adolescents and adults and had received a full course of diphtheria-tetanus toxoids-pertussis (DTP) vaccine; IRs increased with increasing time after the last DTP dose in fully vaccinated residents . The IR was lower in residents on wards where erythromycin treatment/prophylaxis was started two or fewer weeks after the onset of illness in the first case on the ward (IR, 16%), compared with four or more weeks after onset (IR, 75%; P less than 10(-6)) . Respiratory symptoms were milder in ill residents treated within seven days of onset of illness . Although B . pertussis transmission was substantial, erythromycin treatment of patients and prophylaxis of exposed persons was effective in decreasing transmission and disease severity . Carbamazepine toxicity occurred in seven (19%) of 37 residents when carbamazepine was administered with erythromycin. N Z Med J, 1988 Feb 10, 101(839), 44 - 5 Chlamydial infections in young infants--a cause for concern; Broadbent R et al.; Two cases of infant chlamydial pneumonia are described, both associated with severe apnoea . In one, the apnoeas occurred in association with seizures . All symptoms resolved rapidly upon treatment with erythromycin . Specific diagnostic tests are available for this condition . One unit in this country has demonstrated a vaginal carriage rate in pregnancy of 4% . The rate is higher in subgroups with overt promiscuity . Efforts at primary prophylaxis should be directed at high risk groups . Every effort should also be made to improve the secondary prophylaxis of chlamydial pneumonia by identifying and adequately treating newborn infants with chlamydial conjunctivitis. Oral Surg Oral Med Oral Pathol, 1988 Feb, 65(2), 228 - 32 Prophylactic penicillin versus penicillin taken at the first sign of swelling in cases of asymptomatic pulpal-periapical lesions: a comparative analysis; Morse DR et al.; In order to ascertain whether the time of administration of an antibiotic affects the occurrence of flare-ups and non-flare-up-associated swelling and pain, an analysis of components of two prospective endodontic studies on patients having asymptomatic teeth with pulpal necrosis and associated periapical radiolucent lesions (PN/PL) was done . In the first study, prophylactic penicillin was used . In the second study, penicillin (or erythromycin for patients allergic to penicillin) was taken by the patient at the first sign of swelling (patient controlled) . For the patient-controlled group, as compared to the prophylactic penicillin group, there was statistically significantly more (1) incidence of flare-ups (p less than 0.05); (2) non-flare-up-associated swelling (p less than 0.001); (3) non-flare-up-associated pain (p less than 0.05); (4) combined moderate and severe pain (p less than 0.05); (5) combined incidence of flare-ups and swelling (p less than 0.001); (6) combined incidence of flare-ups and pain (p less than 0.01); and (7) combined incidence of flare-ups and both swelling and pain (p less than 0.001) . There were statistically significantly fewer instances of (1) no patient post-treatment problems (p less than 0.001) and (2) combined mild pain and no patient post-treatment problems (p less than 0.001) . Hence, for asymptomatic teeth with PN/PL, it appears that prophylactic antibiotics are preferable to antibiotics taken by the patient at the first sign of swelling. Antimicrob Agents Chemother, 1988 Feb, 32(2), 164 - 9 In vitro assay to demonstrate high-level erythromycin resistance of a clinical isolate of Treponema pallidum; Stamm LV et al.; We have previously demonstrated that cells of Treponema pallidum freshly extracted from infected rabbit testes can be intrinsically radiolabeled with {35 S}methionine to very high specific activities . In this study we used the inhibition of {35 S}methionine incorporation into trichloroacetic acid-precipitable protein in vitro as an assay to test the susceptibilities of three different pathogenic treponemal strains to various antibiotics . In general, the results correlated very well with the known efficacies of these antibiotics in treating human patients with syphilis . One of the strains tested, however, a clinical isolate of T . pallidum designated street strain 14, was found to exhibit high-level resistance to erythromycin and a closely related macrolide, roxithromycin (RU 965) . Street strain 14 was originally isolated from a human patient with active secondary syphilis who failed to respond to erythromycin therapy . Thus, our results indicate that an erythromycin-resistant strain of T . pallidum can be responsible for erythromycin treatment failure . In addition, street strain 14 treponemes were found to be generally less susceptible by this assay to a variety of antibiotics than were treponemes of the T . pallidum Nichols strain . These findings suggest that the outer envelope of street strain 14 treponemes may be generally less permeable to antibiotics than is that of Nichols strain treponemes. Surgery, 1988 Feb, 103(2), 226 - 30 Preoperative lymphocyte subsets and infectious complications after colorectal cancer surgery; Tartter PI; Peripheral lymphocytes, T cells, and T cell subsets of 141 consecutive patients with colorectal cancer were measured preoperatively to determine whether infectious complications could be predicted from derangements of T cell subsets . T cell subset abnormalities reportedly precede sepsis in patients with burn injuries . All patients received preoperative bowel preparation with laxatives, enemas, oral neomycin and erythromycin base, and intravenous cefazolin . Eighteen (13%) of the 141 patients had infectious complications and these complications accounted for two deaths . The variables of age, sex, tumor location, admission hematocrit, white blood count, lymphocytes, T cells (Leu-1), helper cells (Leu-3), suppressor cells (Leu-2), natural killer cells (Leu-7), operative blood loss, procedure, specimen length, duration of surgery, tumor size, tumor differentiation, nodal status, and Dukes' staging were not significantly (p greater than 0.05) related to the development of infectious complications . These results indicate that preoperative evaluation of T cell subsets in patients with colorectal cancer is not useful for predicting postoperative septic complications. Eur J Clin Microbiol Infect Dis, 1988 Feb, 7(1), 73 - 6 Bioassay for A-56268 (TE-031) and identification of its major metabolite, 14-hydroxy-6-O-methyl erythromycin; Fernandes PB et al.; A-56268 is a new macrolide which is generally two-fold more potent than erythromycin . A new bioassay is described in which plasma samples are extracted with acetonitrile prior to bioassay . The concentration range for the assay is between 0.05-4.0 micrograms/ml, and the concentrations measured are within 6% of those measured by high-power liquid chromatography . An active metabolite which is as active as erythromycin was identified in the plasma . The plasma half-life and area under the plasma curve values of A-56268, as determined by bioassay, were significantly greater than those of erythromycin. Cutis, 1988 Feb, 41(2), 132 - 6 Erythromycin 2 percent gel in the treatment of acne vulgaris; Pochi PE et al.; A gel formulation of erythromycin 2 percent was compared with its vehicle in a double-blind multicenter study involving patients with mild to moderate acne vulgaris . In an analysis of 187 patients treated twice daily for 8 weeks, erythromycin 2 percent gel proved to be significantly more effective than vehicle in reducing the numbers of both inflammatory and noninflammatory lesions . After 8 weeks, 60 percent of erythromycin-treated patients had good or excellent responses compared with 36 percent of those using vehicle (p = 0.001); the lesions in two patients using erythromycin were completely cleared . The majority of patients had a favorable impression of the cosmetic characteristics of the gel formulation. Antibiot Khimioter, 1988 Feb, 33(2), 87 - 93 {Identification and characteristics of plasmids of the strains of erythromycin-producing Streptomyces erythreus}; Ukhabotina LS et al.; Presence of plasmid DNA was investigated in laboratory strains 2 and 4 (NRRL 2338) of S . erythreus, as well as in strains 1 and 3 of S . erythreus subjected to improvement with respect to erythromycin production . Families of plasmids close by their molecular weights were identified in S . erythreus strains 3 and 4 (NRRL 2338) . A plasmid DNA fraction of S . erythreus strain 3 was studied with electron microscopy . It enabled to identify 5 plasmids: pSE11, pSE12, pSE13, pSE14 and pSE15 with length of 5.3, 12.4, 16.3, 29.6 and 86.9 kb respectively . Using of various procedures for isolation of extrachromosomal DNA did not provide its detection in S . erythreus strains 1 and 2 . At least a part of the plasmids detected in S . erythreus strains 3 and 4 (NRRL 2338) was conjugative . 32R-Labeled plasmid DNA of S . erythreus strain 3 was subjected to hydridization according to Sauthern with total DNA of the 4 strains treated with restrictases BamHI, PstI and BgIII . The studies showed that the genome of S . erythreus strain 2 was not homologous with the probe while S . erythreus strain 1 contained one of the plasmids or its part in chromosome-integrated state . In strains 3 and 4 (NRRL 2338) of S . erythreus certain plasmid DNAs were present in both autonomous and chromosome-inserted states . 32P-Labeled gene of erythromycin resistance (ermE) was subjected to hybridization according to Southern with total DNA of the 4 strains and with DNA plasmid fraction of S . erythreus strain 3 . The signal was positive only in hydridization of the probe with total DNA of S . erythreus strains 1, 3, and 4 (NRRL 2338).(ABSTRACT TRUNCATED AT 250 WORDS) Biochim Biophys Acta, 1988 Jan 25, 949(1), 71 - 8 Inhibition of polypeptide synthesis in cell-free systems by virginiamycin S and erythromycin . Evidence for a common mode of action of type B synergimycins and 14-membered macrolides; Chinali G et al.; Macrolides, lincosamides and type B synergimycins are powerful inhibitors of protein synthesis in vivo, but many of them were found to be inactive in vitro . In the present work, we confirm that virginiamycin S (a type B synergimycin) and erythromycin (a 14-membered macrolide) have no effect on poly(U)-directed poly(Phe) synthesis . However, the amino-acid polymerization reactions directed by poly(U,G), poly(U,C), poly(A,G) and poly(A,C) were increasingly inhibited (20-50%) by both antibiotics . The action of these inhibitors proved to be template-dependent and favored by the incorporation of proline and of basic amino acids into peptides . Under these conditions, virginiamycin S and erythromycin markedly stimulated a release of peptidyl-tRNA from the ribosomes . In the poly(A,C) model system, these antibiotics produced a 50% inhibition of amino-acid incorporation into total peptides, a 70% release of ribosome-bound peptidyl-tRNA, and a 95% repression of the synthesis of long peptide chains . The production of equivalent effects at saturating concentrations of these antibiotics in the four model systems examined is suggestive of a similarity in their mode of action . Our results indicate that 14-membered macrolides and type B synergimycins can act on ribosomes during the whole elongation process . The functional block produced by both antibiotics is usually reversible, but may result in a premature release of peptidyl-tRNA when the stability of ribosomal complexes is lowered by the incorporation of basic amino acids. J Biol Chem, 1988 Jan 5, 263(1), 58 - 63 Protein components of the erythromycin binding site in bacterial ribosomes; Arevalo MA et al.; Two derivatives of erythromycin have been prepared carrying either an aryl azide or a 4-nitroguaiacol as a photoreactive group . Both derivatives bind to the specific erythromycin ribosomal site as shown by saturation and competition studies . The derivatives were isotopically labeled either with tritium or with 125I, and radioactivity is covalently incorporated to the ribosome upon irradiation at the appropriate wavelength . The ribosomal proteins labeled were identified by either mono- and two-dimensional gel electrophoresis or high performance liquid chromatography . It has been found that protein L22 is the protein mainly, and under some conditions exclusively, labeled by the erythromycin derivatives . These results were confirmed using ribosomes from erythromycin-resistant mutants having a protein L22 with modified electrophoretical mobility . Protein L15 is also labeled in both cases, and the aromatic azide derivative labels to a lesser extent proteins L2 and L4 . Competition experiments with erythromycin indicate that labeling in protein L22, and probably in L15, is specific, while the specificity of labeling in proteins L2 and L4 is questionable . These results indicate that the erythromycin derivatives label different ribosomal proteins than the spiramycin type of macrolides (Tejedor, F., and Ballesta, J.P.G . (1985) Biochemistry 24, 467) suggesting that the binding sites of both macrolide types are probably not identical. Am J Hosp Pharm, 1988 Jan, 45(1), 135 - 42 Sweetener content of common pediatric oral liquid medications; Hill EM et al.; The types and concentrations of sweeteners in common prescription liquid and chewable medications for pediatric use were determined by manufacturer survey . Oral-liquid and chewable antibiotic, antifungal, bronchodilator, antihistamine, anticonvulsant, and miscellaneous products were identified . The manufactures were asked by telephone the type and amount of sweeteners in their products . Two follow-up letters requested confirmation of the sweetener contents; manufacturers' approval for publication of the information was also requested by mail . Sweetener information on 160 preparations was obtained . For antibiotics such as ampicillin, amoxicillin, erythromycin ethylsuccinate, and penicillin VK, products from different manufacturers had a wide range of sucrose concentration (18%-80%) . Only four antibiotic preparations were sucrose free . The bronchodilators and antihistamines contained either sucrose, sorbitol, or saccharin . The anticonvulsants contained 0%-60% sucrose . Health-care practitioners who prescribe or dispense oral liquid or chewable prescription drug products should know that products in a given category can vary in type and amount of sweetener. Tokai J Exp Clin Med, 1988, 13 Suppl, 117 - 23 Outbreaks of pertussis in the United States: the Wisconsin experience; Partiarca PA et al.; To identify risk factors for pertussis in older age groups and to examine the effectiveness of erythromycin therapy and prophylaxis in reducing secondary spread, epidemiologic investigations of two outbreaks involving teenagers and adults were conducted . The first outbreak occurred in 1984 among residents of a facility for developmentally disabled persons (median age 17 years) . Rates of culture-and/or serologically confirmed infection ranged from 6% to 91% in exposed wards (42% overall), with transmission continuing over a five-month period . Although residents age 10-19 years experienced the highest rates of infection, they were also more likely to be exposed compared with residents in other age groups . Infection rates were significantly lower on wards where erythromycin treatment and prophylaxis were initiated less than 2 weeks after onset of illness in the index case (overall attack rate = 16% vs . 75% in wards where more than 4 weeks had elapsed; p less than .0001) . Early treatment with erythromycin was also effective in reducing pertussis severity . The second outbreak occurred over a six-month period among residents of a 3-county area in central Wisconsin in 1985, with adults accounting for 38% of 161 culture-positive cases . Exposure outside the home was the most important predictor of community-acquired infection (p less than .001), with adolescents being at higher risk than persons in other age groups (odds ratio 3.2; p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) Drugs Exp Clin Res, 1988, 14(5), 319 - 25 Comparative study on effects of 14- and 16-membered macrolides on gastrointestinal motility in unanaesthetized dogs; Nakayoshi T et al.; Comparative studies on the effects of 14-membered and 16-membered macrolides on gastrointestinal motility were conducted in unanaesthetized dogs . Midecamycin acetate, a new 16-membered macrolide, and leucomycin, another 16-membered macrolide, did not disturb the gastrointestinal motility and no dogs showed any adverse effects . In contrast, erythromycin stearate, erythromycin ethylsuccinate and triacetyloleandomycin, 14-membered macrolides, caused adverse effects such as strong contractile motility, nausea, vomiting and diarrhoea . The adverse effects of macrolides on the gastrointestinal tract are related to their chemical structure. Antonie Van Leeuwenhoek, 1988, 54(6), 509 - 20 Columnaris infection among cultured Nile tilapia Oreochromis niloticus; Amin NE et al.; Flexibacter columnaris was isolated from 13 cultured Oreochromis niloticus showing respiratory disorders . The isolates developed typical swarming rhizoid colonies on Cytophaga agar medium . Antibiotic sensitivity test revealed the susceptibility of F . columnaris isolated to oxytetracycline, chloramphenicol and erythromycin . A marked difference in the pathogenicity of seven tested isolates was observed: two were highly virulent, one was moderately virulent and four were avirulent . No experimental infection could be induced with the highly virulent isolates except after injuring one of the natural barriers of the fish body . The severity of the disease and the increased median death time shortened by keeping infected fishes with injured gills in water containing ammonia . In naturally infected O . niloticus, the disease became chronic as indicated by the presence of excessive proliferative and necrotic changes . On the other hand, severe dilatation of branchial blood vessel, oedema and round cell infiltration proved that, the disease among experimentally infected tilapias was acute. Vox Sang, 1988, 55(4), 233 - 6 Erythromycin-induced immune hemolytic anemia; Nance SJ et al.; A 3-year-old female receiving Pediazole (erythromycin ethylsuccinate and sulfisoxazole) for tonsillitis and otitis media developed severe hemolytic anemia . No serum drug-dependent antibodies could be demonstrated with an in vitro 'immune-complex' method using Pediazole, pure erythromycin ethylsuccinate or pure sulfisoxazole . However, a method using red cells coated with erythromycin base showed in vitro lysis of the erythromycin-coated red cells . This is only the second case of immune hemolytic anemia associated with erythromycin and the first where in vitro drug-dependent hemolysis was demonstrable. Chemotherapy, 1988, 34(5), 374 - 9 Serum, sputum and bronchial concentrations of erythromycin in chronic bronchitis after single and multiple treatments with either propionate-N-acetylcysteinate or stearate erythromycin; Ricevuti G et al.; Serum and bronchial concentrations of erythromycin were determined in 30 chronic bronchitic patients during an exacerbation phase of bacterial infections . The levels were measured after single and multiple oral treatments with erythromycin-propionate-N-acetylcysteinate (EPAC) or erythromycin stearate (ES) in a double-blind design . EPAC showed higher and longer-lasting erythromycin levels in serum, sputum and pure bronchial mucus than ES . It is believed that EPAC is better absorbed because of its greater stability in the gastrointestinal juices . Higher concentrations in bronchial secretions not always depend on the blood levels . It seems to be possible that the N-acetylcysteine moiety in the molecule of EPAC drug can facilitate antibiotic penetration because of its mucolytic activity . The clinical response (disappearance of fever, clearance of bacterial pathogens from sputum, reduction of quantity and viscosity of sputum) also occurred faster in the EPAC than in the ES group. J Biochem Toxicol, 1988 Summer, 3, 131 - 45 Purification of rat liver microsomal cytochrome P-450b without the use of nonionic detergent; Dutton DR et al.; Sodium cholate, Emulgen 911, and (3-{(-cholamidopropyl)-dimethyl-ammonio}-1-propanesulfonate) (CHAPS) were selected to examine the effects of ionic, nonionic, and zwitterionic detergents on testosterone hydroxylation catalyzed by four purified isozymes of rat liver microsomal cytochrome P-450, namely P-450a, P-450b, P-450c, and P-450h, in reconstituted systems containing optimal amounts of dilauroylphosphatidylcholine and saturating amounts of NADPH-cytochrome P-450 reductase (reductase) . The major phenobarbital-inducible form of rat liver microsomal cytochrome P-450, designated P-450b, was extremely sensitive to the inhibitory effects of Emulgen 911, which is used in several procedures to purify this and other forms of cytochrome P-450 . In contrast, sodium cholate and CHAPS had little effect on the catalytic activity of cytochrome P-450b, even at ten times the concentration of Emulgen 911 effecting 50% inhibition (IC-50) . By substituting the zwitterionic detergent CHAPS for Emulgen 911, we purified cytochrome P-450b without the use of nonionic detergent . The protein is designated cytochrome P-450b* to distinguish it from cytochrome P-450b purified with the use of Emulgen 911 . NADPH-cytochrome P-450 reductase was also purified both with and without the use of nonionic detergent . The absolute spectra of cytochrome P-450b and P-450b* were indistinguishable, as were the carbon monoxide (CO)- and metyrapone-difference spectra of the dithionite-reduced hemoproteins . When reconstituted with NADPH-cytochrome P-450 reductase and dilauroylphosphatidylcholine, cytochromes P-450b and P-450b* catalyzed the N-demethylation of benzphetamine and aminopyrine, the 4-hydroxylation of aniline, the O-dealkylation of 7-ethoxycoumarin, the 3-hydroxylation of hexobarbital, and the 6-hydroxylation of zoxazolamine . Both hemoproteins catalyzed the 16 alpha- and 16 beta-hydroxylation of testosterone, as well as the 17-oxidation of testosterone to androstenedione . Both hemoproteins were poor catalysts of erythromycin demethylation and benzo{a}pyrene 3-/9-hydroxylation . The rate of biotransformation catalyzed by cytochrome P-450b* was up to 50% greater than the rate catalyzed by cytochrome P-450b when reconstituted with either reductase or reductase* . The activity of cytochrome P-450b and P-450b* increased up to 50% when reconstituted with reductase* instead of reductase . In addition to establishing the feasibility of purifying an isozyme of rat liver microsomal cytochrome P-450 without the use of nonionic detergent, these results indicate that the catalytic activity of cytochrome P-450 is not unduly compromised by residual contamination with the nonionic detergent Emulgen 911. Scand J Infect Dis, 1988, 20(6), 601 - 10 Detection of specific IgM antibodies for the diagnosis of Mycoplasma pneumoniae infections: a clinical evaluation; Vikerfors T et al.; The diagnostic value of detection of specific IgM antibodies was analysed in Mycoplasma pneumoniae infections . In a retrospective clinical and serological study, M . pneumoniae IgM antibodies were determined by a mu-capture ELISA using enzyme-labelled antigen . The study group consisted of 91 patients with significantly raised titers in paired sera or a single high titer of complement fixation antibodies . About 40% of the patients had been treated with antibiotics ineffective against M . pneumoniae infections prior to admission to hospital . Treatment with erythromycin or tetracycline was shown to give a shorter period of fever compared to if no or ineffective therapy was given . Specific IgM antibodies were detected in about 80% of sera sampled 9 days or more after onset of symptoms . In sera sampled at 7-8 days after onset IgM antibodies were found in about 40% of the sera but only occasionally in sera sampled earlier . In the age group 0-20 years 88% of the patients developed an IgM response . In the higher ages (greater than 60 years) a significantly lower rate of IgM responders was observed. Trans R Soc Trop Med Hyg, 1988, 82(4), 554 - 7 Multiple drug resistant Plasmodium falciparum malaria in a pregnant indigenous Zambian woman; Rolfe M; A 24 year old Zambian female presented with falciparum malaria when 27 weeks pregnant . She had recently travelled to the copperbelt from Solwezi in the North-West Province of Zambia . Oral chloroquine in a dose of 29 mg/kg failed to clear the parasitaemia . Chloroquine resistance was confirmed by testing in vitro and in vivo . In addition, Fansidar (2 courses), amodiaquine, quinine and quinine plus erythromycin failed to achieve radical cure . Quinine resistance was confirmed in vitro and in vivo . She was eventually cured by 10 d of quinine plus clindamycin, which was greatly assisted by the spontaneous delivery of a live normal infant at 37 weeks gestation . The baby's birth weight was 2.68 kg and its blood slide was negative for malaria. Trans R Soc Trop Med Hyg, 1988, 82(3), 363 - 5 Failure of erythromycin to improve chloroquine treatment of Plasmodium falciparum malaria in Kenya; Brandling-Bennett AD et al.; 58 children aged 1 to 10 years who had pure Plasmodium falciparum infections acquired on the coast of Kenya were treated with chloroquine 25 mg/kg given over 3 d and erythromycin 10 mg/kg 4 times a day given for 7 d . After 4 weeks follow-up, 62% had recurrent infections and 11% failed to clear their parasitaemia (1 had an RIII pattern of resistance) . Of 38 children treated with chloroquine 25 mg/kg alone, 55% had recurrences and 21% failed to clear (including 1 RIII) . In vitro microtests classified 74% of isolates from initial infections and 91% of isolates from recurrent infections as resistant . Erythromycin does not improve chloroquine treatment in children with infections due to P . falciparum having low to moderate levels of chloroquine resistance. J Asthma, 1988, 25(4), 195 - 204 The theophylline-erythromycin interaction; Rieder MJ et al.; Since its publication in 1976, the original report of an interaction between erythromycin and theophylline by Cummin, Kozak, and Gillman has generated considerable interest and controversy . Many studies with considerably different designs have been performed to address this question . Those studies that most closely simulate the clinical setting suggest that a 7- to 10-day course of concurrent theophylline and erythromycin therapy will result in variable changes in theophylline clearance . It may be that as many as 25% of patients, especially when maintained with serum theophylline concentrations at the upper portion of the therapeutic range, display elevations in serum theophylline concentrations that might lead to clinical symptoms of theophylline toxicity . There has been a suggestion, based on the mean changes in several studies, that the interaction may lead to a 25% increase in serum theophylline concentrations; however, it is clear that there may be a much larger increase in some patients . This toxicity can be anticipated and avoided if careful attention is paid to monitoring the serum theophylline concentrations of such high-risk patients when erythromycin therapy is contemplated as an addition to theophylline therapy . Other macrolide antibiotics may display interactions with theophylline, which may be due in part to the ability of the various antibiotics to form complexes with isoenzymes of the cytochromes P-450 . The growing impression of the importance of mycoplasma in asthmatics and the introduction of new macrolides onto the market make the appreciation of this possible interaction of extreme importance to primary care and chest physicians. Drugs Exp Clin Res, 1988, 14(7), 441 - 4 Effect of dosing intervals on efficacy of clarithromycin and erythromycin in mouse infection models; Fernandes PB et al.; Clarithromycin is a new macrolide with a serum half-life which is at least twice that of erythromycin . In order to select the appropriate dosing intervals, the in vitro post-antibiotic effect (PAE) of clarithromycin and erythromycin were compared and the efficacies of clarithromycin and erythromycin when administered once (q.d.), twice (b.i.d.) and three (t.i.d.) times a day in mouse protection tests were measured . The doses were selected from achievable peak serum concentrations in man and were 18 mg/kg for clarithromycin which gave a peak blood level of 2.0 micrograms/ml and a serum half-life of 0.82 h, and 10 mg/kg for erythromycin which gave a peak blood level of 0.9 microgram/ml and a serum half-life of 0.46 h . The PAE of clarithromycin for Staph . aureus is 6.25 h compared to 2.35 h for erythromycin . Clarithromycin was effective against Staph . aureus, Strep . pyogenes and Strep . pneumoniae when administered q.d., b.i.d . and t.i.d . and there was no difference in the cumulative mortalities in the three treatment groups . For erythromycin, there was also no difference in the survival of Strep . pyogenes and Strep . pneumoniae-infected mice, but when tested against Staph . aureus it was more effective when administered t.i.d . than b.i.d., and b.i.d . was more effective than q.d . Clarithromycin administered q.d . was more effective than erythromycin administered t.i.d . against Staph . aureus. J Chromatogr, 1987 Dec 25, 423, 189 - 97 Determination of erythromycin in human plasma, using column liquid chromatography with a polymeric packing material, alkaline mobile phase and amperometric detection; Nilsson LG et al.; A method based on column liquid chromatography was developed for determination of plasma concentrations of erythromycin . PRP-1, a polymeric type of packing material suitable for chromatography and amperometric detection at high pH, was used . The effect of pH on the column performance and on the electrochemical response was studied . A pH of ca . 10 was found to be optimal . After extraction with tert.-butyl methyl ether, plasma concentrations down to 0.2 mumol/l could be measured, using automated sample injection . Oleandomycin was used as internal standard . The method was used for determination of plasma concentrations in a pharmacokinetic study under steady-state conditions. Dtsch Med Wochenschr, 1987 Dec 4, 112(49), 1896 - 901 {Extra-pulmonary complications in Mycoplasma pneumoniae infections}; Weiss M et al.; It is not rare that extrapulmonary complications and not pneumonia dominate the clinical picture in infections with Mycoplasma pneumoniae, as is illustrated by three cases . In the first, a young woman developed an acute, but ultimately completely reversible, polyradiculitis after a Mycoplasma pneumonia . The second patient sustained a thoracic transverse myelitis which regressed rapidly and completely under treatment with erythromycin and prednisone . In the third one, the Mycoplasma pneumonia was complicated by a generalized hypersensitivity vasculitis affecting many organs . A largely reversible renal vasculitis was demonstrated angiographically. Tubercle, 1987 Dec, 68(4), 297 - 9 Mycobacterium chelonei and abscess formation in soft tissues; Hanson PJ et al.; Mycobacterium chelonei was isolated from a breast abscess in a healthy 46-year-old non-lactating Caucasian woman . In-vitro testing showed the organism to be resistant to conventional anti-tuberculosis agents but sensitive to tetracycline and erythromycin . Treatment with isoniazid, pyrazinamide and rifampicin initially produced a good response but the subsequent development of multiple abscesses required the addition of tetracycline and finally a change to erythromycin and trimethoprim, on which recovery was complete. Br J Clin Pharmacol, 1987 Dec, 24(6), 836 - 8 Inhibition by erythromycin of the conversion of carbamazepine to its active 10,11-epoxide metabolite; Barzaghi N et al.; The serum levels of carbamazepine (CBZ) and its 10,11-epoxide metabolite (CBZ-E) were determined in seven subjects after a single dose of CBZ (400 mg) in the control state and during co-administration of erythromycin (500 mg three times daily for 10 days) . Erythromycin treatment was associated with a decrease in CBZ clearance and a prolongation of CBZ half-life, while CBZ-E levels were markedly reduced . These data provide evidence that erythromycin inhibits the conversion of CBZ to its epoxide metabolite. Br Heart J, 1987 Dec, 58(6), 663 - 4 Combined pericarditis and pneumonia caused by Legionella infection; Svendsen JH et al.; During a one year period acute pericarditis was diagnosed in 16 consecutive patients without acute infarction or malignancy . In two of these patients with both pericarditis and pneumonia Legionella infection was present . One case was caused by Legionella longbeachae and the other by both Legionella longbeachae and Legionella jordanis . When pericarditis is associated with pneumonia Legionella infection should be sought so that effective treatment with erythromycin may be started early. Semin Respir Infect, 1987 Dec, 2(4), 270 - 3 Therapeutic considerations in the treatment of Legionella infections; Keys TF; Selection of therapy for legionella infections originated with the clinical observation after the 1976 Philadelphia outbreak that patients treated with erythromycin or tetracycline did better than those who received cephalosporins or aminoglycosides . Early in vitro antibiotic susceptibility studies suggested that rifampin and erythromycin were both active against Legionella pneumophila . However, subsequent in vitro susceptibility studies to other antibiotics have produced variable results, depending on the medium and methodology used . Antibiotic studies within polymorphonuclear leukocytes and alveolar macrophages indicate that those actively concentrated within these cells are predictive of successful therapy . These include erythromycin, rifampin, and certain quinolones . On the other hand, beta-lactam antibiotics such as penicillin, cefoxitin, and imipenem are less likely to be successful because of their lack of concentration within phagocytes . These observations have been confirmed in animal model studies where erythromycin, rifampin, and quinolones have demonstrated efficacy . The addition of rifampin to erythromycin or to doxycycline may be more effective than therapeutic results with either antibiotic alone . Although erythromycin is presently the treatment of choice for legionellosis, the addition of rifampin is recommended, particularly in immunocompromised patients . Doxycycline has served as an appropriate alternative agent, the newer quinolones may be useful and are deserving of carefully designed clinical trials. Semin Respir Infect, 1987 Dec, 2(4), 262 - 6 Infections caused by the Pittsburgh pneumonia agent; Fang GD et al.; Of the Legionellaceae family, Pittsburgh pneumonia agent (Tatlockia micdadei, Legionella micdadei) is second only to Legionella pneumophila in causing human pneumonia . In nosocomial infection, the patients tend to be immunosuppressed . The clinical presentation is nonspecific, although in immunosuppressed hosts the presentation may mimic that of pulmonary embolus (pleuritic chest pain, nonproductive cough, pleural-based densities on chest rontgenogram) . The reservoir for the organism is water, and prevention of nosocomial infections can be accomplished by disinfection of the water supply . Diagnosis is best established by isolation of the organism from respiratory secretions by using selective, dye-containing buffered charcoal-yeast extract agar . The organisms can be acid-fast when clinical specimens are stained . Erythromycin is the antibiotic of choice, although tetracyclines, trimethoprim-sulfamethoxazole, and rifampin have also proved to be efficacious. FEBS Lett, 1987 Nov 16, 224(1), 133 - 6 A small, discrete acyl carrier protein is involved in de novo fatty acid biosynthesis in Streptomyces erythraeus; Hale RS et al.; A heat-stable factor, required for de novo synthesis of fatty acids in the erythromycin-producing organism Streptomyces erythraeus, has been purified to homogeneity and identified as an acyl carrier protein (ACP) . We conclude that, contrary to previous belief, fatty acid synthase in S . erythraeus more closely resembles the dissociable complex of E . coli than the tightly associated, multifunctional enzyme complex found in the related actinomycete Mycobacterium smegmatis. Biochem Pharmacol, 1987 Nov 15, 36(22), 3859 - 66 Studies on the pregnenolone-16 alpha-carbonitrile-inducible form of rat liver microsomal cytochrome P-450 and UDP-glucuronosyltransferase; Arlotto MP et al.; Treatment of rats with pregnenolone-16 alpha-carbonitrile (PCN) markedly induces rat liver microsomal cytochrome P-450p and UDP-GT-dt1, a glucuronosyltransferase active towards the digitoxin metabolite, digitoxigenin monodigitoxoside . The present study characterizes the regulation of these two enzymes in rats treated with different xenobiotics . Like PCN, treatment of rats with dexamethasone, spironolactone, troleandomycin or erythromycin estolate markedly induced both UDP-GT-dt1 and cytochrome P-450p (measured as erythromycin demethylase and testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activities) . However, compared to PCN and dexamethasone, both troleandomycin and erythromycin estolate preferentially induced cytochrome P-450p, whereas spironolactone preferentially induced UDP-GT-dt1 . Treatment of rats with the polychlorinated biphenyl mixture, Aroclor 1254, increased both cytochrome P-450p and UDP-GT-dt1 activity to about 40% of that in liver microsomes from rats induced with PCN or dexamethasone . Treatment of rats with phenobarbital or chlordane caused a relatively small increase in cytochrome P-450p and UDP-GT-dt1 activity . Neither enzyme was induced by treatment of rats with 3-methylcholanthrene, rifampin or digitoxin . The induction of cytochrome P-450p and UDP-GT-dt1 by PCN followed similar dose-response curves . Although cytochrome P-450p and UDP-GT-dt1 are differentially affected by the age and the sex of rats, the enzymes responded similarly, but not identically, to xenobiotic treatment . This suggests that cytochrome P-450p and UDP-GT-dt1 are co-inducible but not coordinately regulated. J Chromatogr, 1987 Nov 13, 409, 91 - 100 Optimization of the separation of erythromycin and related substances by high-performance liquid chromatography; Cachet T et al.; An improved high-performance liquid chromatographic method for analysis of erythromycin is described . The separation can be performed under mild conditions of pH (6.5) and temperature (35 degrees C) on C8 and C18 silica-based reversed-phase materials of different origins . The mobile phase, with a flow-rate of 1.5 ml/min, contained various amounts of acetonitrile (25-40%, v/v), 5% (v/v) 0.2 M ammonium phosphate buffer pH 6.5, 20% (v/v) 0.2 M tetramethylammonium phosphate and water . UV detection at 215 nm allows quantitation of erythromycins A, B and C, N-demethylerythromycin A, erythromycin A enol ether and anhydroerythromycin A . The column history plays a major role, older columns often giving better separations. S Afr Med J, 1987 Nov 7, 72(9), 620 - 2 Prophylaxis against gonococcal ophthalmia neonatorum . A prospective study; Lund RJ et al.; The incidence of gonococcal ophthalmia neonatorum (GON) in the area served by the Peninsula Maternity and Neonatal Services in Cape Town is 273/100,000 live births . Two prophylactic agents, 1% silver nitrate ophthalmic solution and 0.5% erythromycin ophthalmic ointment, were introduced in routine eye care of the newborn in the main academic obstetric units . These agents resulted in a significant decrease in the incidence of GON to 34/100,000 live births . The alternative forms of prophylaxis against GON are discussed and the need for reinstitution of prophylaxis is emphasised. Arch Biochem Biophys, 1987 Nov 1, 258(2), 436 - 51 Degradation of rat hepatic cytochrome P-450 heme by 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine to irreversibly bound protein adducts; Correia MA et al.; Administration of 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP) (a structural analog of the dihydropyridine Ca2+ antagonists) to untreated, phenobarbital-, or dexamethasone-pretreated rats results in time-dependent losses of hepatic cytochrome P-450 content . Functional markers for various cytochrome P-450 isozymes have permitted the identification of P-450h, P-450 PB-1/k, and P-450p as the isozymes inactivated preferentially by the drug . DDEP-mediated cytochrome P-450 destruction may be reproduced in vitro, is most prominent after pretreatment of rats with dexamethasone, pregnenolone 16 alpha-carbonitrile or phenobarbital, and is blocked by triacetyloleandomycin . These findings together with the observation that DDEP markedly inactivates hepatic 2 beta- and 6 beta-testosterone hydroxylase and erythromycin N-demethylase tend to indict the steroid-inducible P-450p isozyme as a key protagonist in this event . The precise mechanism of such DDEP-mediated P-450p heme destruction is unclear, but involves prosthetic heme alkylation of the apocytochrome at its active site in what appears to be a novel mechanism-based "suicide" inactivation . Such inactivation appears to involve fragmentation of the heme to reactive metabolites that irreversibly bind to the protein, but the chemical structure of the heme-protein adducts is yet to be established . Intriguingly, such DDEP-mediated P-450p destruction in vivo also results in accelerated loss of immunochemically detectable apocytochrome P-450p . It remains to be determined whether or not this loss is due to enhanced proteolysis triggered by the structural modification of the apocytochrome. Am J Dis Child, 1987 Nov, 141(11), 1213 - 4 Is medical therapy effective for regional lymphadenitis following BCG vaccination? Caglayan S, Yegin O, Kayran K, Timocin N, Kasirga E, Gun M. We describe 120 patients with regional lymphadenitis following intradermal BCG vaccination . Seventy-eight of the patients were given medical therapy to prevent drainage and suppuration, and 42 patients were followed up without such treatment . The medical therapy group is divided into three subgroups: 36 were given erythromycin stearate, 21 isoniazid, and 21 isoniazid plus rifampin . No statistical difference in the incidence of spontaneous drainage and suppuration was found between the "no therapy" and the "medical therapy" groups . No significant superiority of any specific therapy was shown . If lymphadenitis develops rapidly (in two months), the incidence of spontaneous drainage and suppuration is significantly higher than in patients with slowly developing lesions . Total surgical excision is recommended to prevent spontaneous drainage and chronic suppuration in these rapidly evolving instances. J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 179 - 83 An evaluation of tolerance of roxithromycin in adults; Blanc F et al.; This review deals with tolerance of a new macrolide, roxithromycin from data collected from a number of studies in adults . A total of 2917 adults, 2519 given roxithromycin 150 mg bid, were recruited into 17 multicentre comparative or non-comparative studies . Nine studies were double-blind, against doxycycline, erythromycin estolate (EES), lymecycline or cephradine . Overall the drug was well tolerated: side-effects possibly or probably related to roxithromycin were noted in only 4.1% (120/2917) of all patients, and in 3.1% (15/480) of elderly subjects . The gastrointestinal tolerance of roxithromycin was significantly better than that of doxycycline in four trials, and better than that of erythromycin ethylsuccinate in one study . The incidence of drug-related liver function test abnormalities following roxithromycin therapy was low and compared favourably with data published on erythromycin . Roxithromycin shows a satisfactory safety profile at the recommended daily dosage of 150 mg bid in adults. Biomed Environ Mass Spectrom, 1987 Nov, 14(11), 659 - 62 Quantitative determination of erythromycin 2'-ethylsuccinate in human plasma by fast atom bombardment mass spectrometry; Ottoila P et al.; A method for simultaneous quantitative determination of erythromycin 2'-ethylsuccinate and erythromycin in human plasma is described . After extracting the deuterium-labelled internal standards and analytes from alkalinized plasma to diethyl ether the extracts were analysed by fast atom bombardment mass spectrometry . The quantification limit for 2'-ethylsuccinate ester was 50 ng ml-1 and for erythromycin 100 ng ml-1 . The calibration curves were linear up to 5 micrograms ml-1 for both . The precision of the method at higher concentration was less than 2% and at the quantification limit approximately 6% for both analytes. J Clin Invest, 1987 Oct, 80(4), 1029 - 36 Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man; Watkins PB et al.; We used monoclonal antibodies and complementary DNAs (cDNAs) to glucocorticoid-inducible liver cytochromes P-450 in rats (P-450p) and in man (HLp) to search for related cytochromes in intestinal mucosa . In rat enterocytes, we found two dexamethasone-inducible proteins related to the steroid-inducible liver cytochromes P-450 . Induction of these proteins in enterocytes was associated with increases in the amount of a P-450p-related messenger RNA and of erythromycin demethylase, an activity highly characteristic of P-450p and HLp . Similar studies on human jejunal enterocytes revealed a microsomal protein indistinguishable from HLp on immunoblots and an abundance of RNA hybridizing with HLp cDNA . In human enterocytes the specific concentration of the HLp-related cytochrome (measured immunochemically or as erythromycin demethylase activity) was similar to that found in human liver and could account for all of the CO-binding hemo-protein detected . We conclude that the intestinal mucosa contains prominent form(s) of cytochromes P-450 similar to liver cytochrome P-450p in their structure, function, and some regulatory characteristics. Sex Transm Dis, 1987 Oct-Dec, 14(4), 195 - 200 Comparison of ophthalmic silver nitrate solution and erythromycin ointment for prevention of natally acquired Chlamydia trachomatis; Bell TA et al.; During prospective studies of infants born vaginally to women with cervical Chlamydia trachomatis infection, we evaluated 27 infants given 0.5% erythromycin ointment and 93 given 1% silver nitrate solution as eye prophylaxis, according to the preference of the parents or delivery room personnel . The cumulative proportion of infants developing chlamydial conjunctivitis was 25% for both groups (P = 0.37, Mantel-Cox test) . The cumulative proportion of infants developing chlamydial infection at any anatomic site was 74% for those given erythromycin and 70% for those given silver nitrate (P = 0.93) . The two groups did not differ significantly in cumulative proportions developing nonchlamydial conjunctivitis . These results indicate that, as it is routinely used in our hospital, erythromycin ointment was not more effective than silver nitrate as prophylaxis against chlamydial conjunctivitis . The influence of delayed administration on efficacy of prophylaxis requires further evaluation. Bone Marrow Transplant, 1987 Oct, 2(3), 307 - 13 Legionnaires' disease after bone marrow transplantation; Meletis J et al.; Four patients developed legionnaires' disease after bone marrow transplantation . Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply . The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge . The outcome was good in two patients . In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin . The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin . During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination . The fourth patient in this report was receiving no antibiotics . Thus pefloxacin seems to be effective as prophylaxis against L . pneumophila infection . When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared. Allergy, 1987 Oct, 42(7), 502 - 6 Antibodies to penicillin in children receiving long-term secondary prophylaxis for rheumatic fever; Strannegard IL et al.; The occurrence of IgE and IgG antibodies to penicillin G and V in children on long-term treatment with penicillin as secondary prophylaxis for rheumatic fever was studied using Phadebas RAST (Pharmacia Diagnostics, Uppsala, Sweden) and ELISA respectively . The duration of the prophylaxis ranged between 1.5 months and 5 years (mean 1.8 years) . Of 18 patients who had been given penicillin for more than 1.5 months, two had IgE antibodies and 12 had IgG antibodies to penicillin . Patients with acute rheumatic fever who had not yet received long-term treatment with penicillin had antibodies of the IgG class in two out of 12 cases . The patients gave no history of adverse reactions to the penicillin injections and there were no signs of immune complex-mediated disease . The two children who had IgE antibodies were switched to oral erythromycin instead of the penicillin injections . Penicillin is the drug of choice in the prophylaxis of rheumatic fever and can apparently be safely given as intramuscular injections of depot-penicillin to prevent recurrences of the disease and ensuing cardiac damage. Ann Emerg Med, 1987 Sep, 16(9), 945 - 9 The diagnosis and treatment of brown recluse spider bites; Rees R et al.; We reviewed our experience with 95 patients who carried the diagnosis of brown recluse spider bite between 1983 and 1986 and identified a reference group of 17 with confirmed bites . Eight men and seven women, average age 32 years, presented within 33 hours following the bites . The most common symptoms were pain, pruritus, malaise, chills, sweats, and rash . Patients were randomized into three treatment groups: dapsone, brown recluse spider antivenom, or combination therapy . All patients were treated with erythromycin . If two patients with very severe lesions were excluded, patients in all groups healed their wounds in an average of 20 days . A comparison of our treatment was attempted with all other bites previously confirmed in the literature, but historical data were incomplete and no conclusions could be drawn. Invest Ophthalmol Vis Sci, 1987 Sep, 28(9), 1569 - 74 Prophylactic effects of silver nitrate and erythromycin on Chlamydia psittaci conjunctivitis; Sandstrom IK et al.; An animal model has been developed to study the effects of various prophylaxis agents on acquisition of chlamydial conjunctivitis . When Hartley strain newborn guinea pigs received ocular inoculations of Chlamydia psittaci followed by the instillation of various agents, 1% AgNO3 significantly lowered the risk of developing chlamydial conjunctivitis if it was administered within 15 min after the inoculation with C . psittaci . However, if the AgNO3 was administered at either 1 hr or 2 hr following inoculation, it did not have any prophylactic effect on the development of chlamydial conjunctivitis . Erythromycin ointment, 0.5%, was also found to prevent chlamydial conjunctivitis . The prophylactic effect was similar to placebo when the drug was given at 15 min; however, erythromycin ointment prophylaxis 1 hr or 2 hr after inoculation with C . psittaci was statistically superior to placebo. Drug Intell Clin Pharm, 1987 Sep, 21(9), 734 - 8 Gastrointestinal side effects with erythromycin preparations; Carter BL et al.; This study was designed to determine the incidence and severity of gastrointestinal (GI) side effects in patients taking erythromycin . More patients complained of GI side effects with the enteric-coated tablet (70.8 percent) than with the stearate (51.4 percent) or the ethylsuccinate (48.9 percent) salts . The enteric-coated tablet was associated with a higher incidence of individual adverse reactions; more patients discontinued it because of adverse GI effects . These data demonstrate a high incidence of GI side effects to erythromycin . Additionally, GI side-effect incidence appears to be higher with the enteric-coated tablet. Allerg Immunol (Paris), 1987 Sep, 19(7), 287 - 9 {A technic for human basophil degranulation}; Harrabi S et al.; We had studied the human basophil degranulation test (HBDT) in 26 cases of allergic patients with drugs (penicillin, erythromycin, josamycin) one month after their anaphylactic reaction . This test was negative in 7 cases on 8 for penicillin, positive in 8 cases on 10 for erythromycin and in 6 cases on 8 for josamycin . The failure of this test with penicillin can be explained by a sensitization to a metabolic penicillin product or to the complex hapten-carrier. Urologe A, 1987 Sep, 26(5), 263 - 7 {Latent and manifest acquired syphilis--clinical aspects, diagnosis and therapy}; Meurer M et al.; The annual reported incidence of new syphilis infections in the FRG is decreasing; cases with atypical or oligosymptomatic forms of syphilis, however, show a relative increase . In contrast to the primary or secondary stage, the late stages of syphilis are very rare . Of great diagnostic importance is the serological examination which today can be limited to the VDRL and TPHA tests for screening and the FTA-ABS test for confirmation . In cases with an atypical clinical picture or history, the necessity for treatment can be verified with the 19S-IgM-FTA-ABS test and demonstration of treponemal IgM antibodies . Penicillin is still the drug of choice for the treatment of syphilis . In patients who are allergic to penicillin, the administration of erythromycin, tetracycline and, recently, of cephalosporins can be considered. Urologe A, 1987 Sep, 26(5), 246 - 51 {Genital Mycoplasma infections--clinical aspects, diagnosis and therapy}; Hofmann H; Ureaplasma urealyticum und Mycoplasma hominis are frequently isolated from the urogenital tract of sexually active persons . Their pathogenetic role in urogenital infections and infertility are still controversial . U . urealyticum can cause urethritis and most likely also chronic prostatitis . M . hominis can cause cystitis, salpingitis, and postpartal fever in women and meningitis in newborns . M . genitalium was recently isolated from patients with urethritis and salpingitis . The diagnosis is made by the cultivation of mycoplasmas in high concentrations and rising antibody titers in the serum . As in chlamydial infections, the therapy of first choice is tetracyclin . M . hominis can also be treated with clindamycin, U . urealyticum with erythromycin. J Med Microbiol, 1987 Sep, 24(2), 105 - 11 Increased sensitivity to erythromycin in Escherichia coli associated with the presence of the ColV,I-K94 virulence plasmid; Alfa CE et al.; Introduction of the virulence plasmid, ColV,I-K94, into Escherichia coli strains led to increased sensitivity to erythromycin . This was the result of increased passage of antibiotic into ColV,I-K94+ organisms because the plasmid effect was abolished in bacteria which had been made permeable by chemical treatment . Full sensitivity in ColV+ strains appears to depend on the simultaneous presence of transfer and colicin components . Increased erythromycin sensitivity associated with the plasmid was demonstrated in organisms grown at 37 degrees C; the sensitivity of ColV,I-K94+ organisms grown at 25 degrees C was similar to that of the parent strain . Added Mg++ or Ca++ ions reversed erythromycin inhibition in strains with the basal level of sensitivity (i.e., the Col- parent grown at 25 degrees C or 37 degrees C or the ColV,I-K94+ derivative grown at 25 degrees C) and in those with the plasmid-associated increase in sensitivity . Addition of phosphate or EDTA to broth increased erythromycin sensitivity in Col- and ColV,I-K94+ strains although the latter was affected most . Erythromycin was more inhibitory at pH 8.5 than at pH 7.4 . This enhanced activity was more marked against the ColV,I-K94+ strain than against the Col- strain . The effects of growth in phosphate-containing medium and at alkaline pH were partially additive . We suggest that ColV,I-K94+ strains may be sensitive to erythromycin because ColV-specified proteins are extruded by a process of "self-promoted transfer" and that the effects of these proteins on the lipopolysaccharide component of the outer membrane facilitates antibiotic influx. Mol Gen Genet, 1987 Sep, 209(2), 313 - 8 Tests of the ribosome editor hypothesis . III . A mutant Escherichia coli with a defective ribosome editor; Anderson RP et al.; Peptidyl-tRNA dissociates from the ribosomes of Escherichia coli during protein biosynthesis . The ribosome editor hypothesis states that incorrect peptidyl-tRNAs dissociate preferentially . Editing would therefore prevent the completion of proteins containing misincorporated amino acids . We have isolated a mutant strain of E . coli that dissociates some peptidyl-tRNAs at a fivefold lower rate than its parent strain, and that synthesizes significantly more erroneous complete proteins . This strain is also partially resistant to the antibiotic erythromycin, which in wild-type E . coli stimulates the dissociation of peptidyl-tRNA from ribosomes . The data suggest that in this mutant all peptidyl-tRNAs are bound to the ribosome more tightly than normally during protein synthesis . Because of the inverse correlation between the accuracy of synthesis of complete proteins and the rate of dissociation of peptidyl-tRNA from the ribosome, we propose that the mutant contains a defective ribosomal editor. Br Heart J, 1987 Sep, 58(3), 293 - 5 Aortic valve endocarditis associated with Legionella infection after Mycoplasma pneumonia; Littrup P et al.; A 38 year old woman with diabetes mellitus and bronchial asthma was admitted to hospital with pneumonia caused by Mycoplasma pneumoniae; she recovered promptly on erythromycin treatment . Six weeks later she presented with aortic valve endocarditis without concurrent lung disease . A concurrent increase in titres of antibody to Legionella bozemanii, L longbeachae, and L jordanis indicated a Legionella infection . Legionella infection should be considered, even in the absence of pneumonia, in cases of endocarditis where no other cause can be detected. Klin Wochenschr, 1987 Sep 1, 65(17), 840 - 4 {Familial Mycoplasma pneumonia . The varied picture of pulmonary and extrapulmonary manifestations}; Lohmoller G et al.; Mother, father (26 y.o.) and their only child (5 y.o.) developed nonproductive cough, fever (39.5 to 40.4 degrees C) and bilateral pulmonary infiltrates within three weeks . In addition the mother developed a small left pleural effusion and a pericardial effusion, a relative bradycardia, a pruritic vesicular exanthem of the extremities and the trunk, an erythema nodosum and arthritis of the tarsal joints . The father's coulter counter red blood count was distorted by microagglutination at room temperature (hemoglobin 13.2 gr/dl; erythrocytes 1,91 X 10(6) mm-3 and MCH 69.1 pg; MCV 120 fl and hematocrit 23.8%) but not at 37 degrees C (13.2; 4.15 and 31.8; 92 and 39.3, respectively) . In the daughter myringitis, pharyngitis, cervical lymphadenopathy and splenomegaly were observed . Cold agglutinins and serologic evidence for mycoplasma pneumoniae infection were demonstrable in all three . Treatment with Tetracycline (parents) and Erythromycin (child) was effective. Rev Med Interne, 1987 Sep-Oct, 8(4), 433 - 6 {Psychotic disorders linked to the inhibition of benzodiazepine catabolism}; Hugues FC et al.; Five clinical cases of interaction between benzodiazepines on one hand and erythromycin, troleandomycin, josamycin and cimetidine on the other hand have been analyzed . These interactions resulted in severe disorders of behaviour, amnesia (including amnesia-automatism syndrome in one case), disturbances of consciousness and withdrawal syndrome . These disorders were consecutive to inhibition of the hepatic cytochrome P-450 system . Practical means of avoiding this risk consists in limiting such drug combinations, reducing benzodiazepine dosage and, if a combined treatment is necessary, using by preference either benzodiazepines degraded by conjugation instead of oxidation, or macrolides, or anti-H2 compounds with reduced inhibitory effect on microsomes. Eur J Clin Microbiol, 1987 Aug, 6(4), 424 - 6 In vitro and in vivo susceptibility of Borrelia burgdorferi; Mursic VP et al.; The antispirochetal activity in vitro and in vivo of several antibiotics against ten isolates of Borrelia burgdorferi from human spinal fluids and skin biopsies was determined . Borrelia burgdorferi was most susceptible in vitro to erythromycin, ceftriaxone and cefotaxime (MIC90: 0.06, 0.06, 0.12 mcg/ml respectively) . Less activity was observed with tetracycline, amoxycillin and lincomycin (MIC90: 0.50 mcg/ml), imipenem and augmentin (MIC90: 0.25 mcg/ml), oxacillin (MIC90: 1 mcg/ml), ciprofloxacin (MIC90: 2 mcg/ml) and ofloxacin (MIC90: 4 mcg/ml) . Penicillin G, normally regarded as appropriate treatment for Lyme disease, had an MIC90 of only 4 mcg/ml . With the exception of erythromycin, activity in vitro corresponded to the activity in vivo . Erythromycin, however, was less active in vivo, and penicillin G showed poor activity both in vitro and in vivo. Br J Dermatol, 1987 Aug, 117(2), 207 - 15 Binding of 8-methoxypsoralen to human serum proteins and red blood cells; Pibouin M et al.; Serum binding of 8-methoxypsoralen (8-MOP) was studied by equilibrium dialysis . In therapeutic concentrations, 8-MOP binding in serum was high, 91.4%, and constant, indicating concentration-independent kinetics . This binding involved the two main proteins, human serum albumin and alpha 1-acid glycoprotein, in a saturable process with one class of binding sites (n) and affinity constants (Ka) of 1.295 X 10(4) mol/l and 2.115 X 10(4) mol/l, respectively . Binding to lipoproteins and gamma globulins was negligible and non-saturable in therapeutic concentrations, with nKa values of 0.35, 0.024, 0.013 and 0.0004 mumol/l for VLDL, LDL, HDL and gamma globulins, respectively . Inhibition of 8-MOP serum binding was observed with salicylic acid and indomethacin, but not with diazepam, warfarin or erythromycin . Over a range of therapeutic concentrations, the ration of 8-MOP concentration in red blood cells (RBCs) and in serum was constant at 20.3% and three times higher than would be expected if a simple diffusion of the 8-MOP plasma free fraction (fu) occurred . According to the measured and calculated parameters, simulations of 8-MOP blood binding in pathological states (hypoalbuminaemia with or without inflammation) showed variations of fu which were partially 'buffered' by RBCs . Simulation of 8-MOP protein binding at cutaneous interstitial fluid level showed that fu is approximately 30% and permitted prediction of a decrease of fu available to the epidermis in case of local or systemic inflammation . This may imply an increase in the minimum phototoxic dose relevant for PUVA and explain some cases of 'poor' responsiveness of psoriatic patients to PUVA therapy. Br J Clin Pharmacol, 1987 Aug, 24(2), 179 - 83 The penetration of erythromycin into human bronchial mucosa; Mattie H et al.; 1 In this paper the pharmacokinetic relation between concentrations of erythromycin in plasma and in bronchial mucosa was established . 2 Sixteen patients undergoing bronchoscopy received 1 g erythromycin by continuous infusion in 30 min . 3 Two bronchial mucosal samples were taken from each patient sometime after drug administration . Concentrations were determined in the mucosal sample and in several plasma samples collected at different times before the mucosal sample . 4 Rate constants for the distribution between plasma and tissue were calculated on the basis of the assumption of passive diffusion of the free drug . 5 Mean values of the distribution rate constants, calculated by a nonlinear curve fitting procedure, were 2.40 h-1 for distribution from plasma to tissue and 1.28 h-1 for that from tissue to plasma . 6 These values correspond to a half-life for the distribution of the free drug of 33 min and a free fraction of the drug in mucosal tissue of 0.20. S Afr Med J, 1987 Aug 1, 72(3), 213 - 4 Tick-bite fever in pregnancy . A case report; England MJ et al.; Despite the frequency of tick-bite fever in southern Africa and its doubtless occurrence in pregnancy, this report documents the first case in a pregnant woman . Consequently, the natural history of tick-bite fever in pregnancy and concomitant placental involvement must be regarded as conjectural . Accordingly a register has been opened by the Department of Obstetrics and Gynaecology, University of the Witwatersrand, for recording similar cases . At this stage of our knowledge, erythromycin 500 mg 6-hourly until 3-5 days after defervescence is the therapy of choice for such patients. J Fam Pract, 1987 Aug, 25(2), 137 - 41 A placebo-controlled, double-blind trial of erythromycin in adults with acute bronchitis; Dunlay J et al.; Sixty-three otherwise healthy adults with acute productive cough and no clinical evidence of pneumonia were randomized to receive a ten-day course of erythromycin or placebo . Fifty-seven of these patients returned