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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 completed symptom diaries or returned for a two-week follow-up visit . Patients treated with erythromycin reported a more rapid improvement in subjective ratings of cold symptoms, general health, sputum production, and a mean symptom score . Fewer patients in the erythromycin group required cough or cold medications or were congested by day 10 (P less than .05) . The treatment group was also less likely to have purulent sputum (9 percent vs 36 percent, P less than .05) and abnormal lung examinations (0 percent vs 29 percent, P less than .01) at a two-week follow-up visit . These results support the use of erythromycin in acute bronchitis.

Biochimie, 1987 Aug, 69(8), 901 - 4
Elongating ribosomes in vivo are refractory to erythromycin; Andersson S et al.; We have studied the kinetics of erythromycin inhibition of translation in growing bacteria . In order to simplify the interpretation of our data, we have used a mutant (envA), known to have an increased permeability to several antibiotics, including erythromycin . The data clearly show that an initial stage of translation is sensitive to erythromycin, but that the elongating ribosome is insensitive to the antibiotic.

Biochimie, 1987 Aug, 69(8), 879 - 84
Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA; Moazed D et al.; Using dimethyl sulfate and kethoxal, we have probed antibiotic-ribosome complexes, and identified sites of interaction of chloramphenicol, erythromycin, carbomycin, vernamycin B and viomycin with 23S rRNA . Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping nonequivalent sites in the central loop of domain V . From the known functional effects of these drugs and their protection patterns, we infer that peptidyl transferase is inhibited as a result of binding antibiotics proximal to A-2451, whereas antibiotics bound proximal to A-2058 interfere with growth of the nascent polypeptide chain . Vernamycin B also strongly protects A-752, implying that this region of domain II is proximal to the central loop of domain V . Viomycin, which affects translocation and subunit dissociation, protects U-913 and G-914.

Biochimie, 1987 Aug, 69(8), 891 - 900
A plasmid-coded and site-directed mutation in Escherichia coli 23S RNA that confers resistance to erythromycin: implications for the mechanism of action of erythromycin; Vester B et al.; Primer-directed mutagenesis was employed to introduce an A2058----G transition in plasmid-encoded Escherichia coli 23S RNA at a site that has been implicated, indirectly, in erythromycin binding . The mutation raises the growth tolerance of cells from 30 to 300 micrograms/ml of erythromycin, and cells grown in the presence of erythromycin contain ribosomes with high levels of mutated 23S RNA . In these cells, wild type 50S subunits 'fall off' the message and are selectively degraded, possibly as a result of an erythromycin-induced conformational change . A fast in vitro poly(U) assay revealed minimal effects of erythromycin on elongation beyond tetrapeptides . We correlated these results with the literature data and concluded that erythromycin acts immediately post-initiation and directly, or indirectly, destabilizes mRNA-bound 70S ribosomes, and prevents their recycling by causing 50S subunit degradation.

Arzneimittelforschung, 1987 Jul, 37(7), 799 - 802
Kinetics of erythromycin uptake into Ehrlich mouse ascites tumor cells; Dette GA et al.; The uptake was studied with freshly isolated Ehrlich ascites tumor (EMAT) cells and with 14C-labelled erythromycin . Erythromycin was accumulated by EMAT cells . The uptake rates and quotes of erythromycin increased with increasing temperature and with increasing pH value (alkaline pH) . The uptake was reduced by SH-group reagents, by inhibitors of electron transport and of oxidative phosphorylation and by ouabain . The uptake was saturable (Km = 6.0 X 10(-4) mol/l) . The release of the accumulated erythromycin followed first order kinetics (k = 4.5 X 10(-2) min-1) . The uptake and accumulation of erythromycin cannot be explained by non-ionic partition . An active uptake mechanism is suggested.

Med Trop (Mars), 1987 Jul-Sep, 47(3), 273 - 8
{Syphilis in 1987}; Normand P; The author recalls the main features of primary-secondary syphilis observed nowadays under any climat . Still present and in more young people, syphilis is no longer the plague it was in the past centuries, thanks to a quick and efficient treatment: penicillin . In case of allergia, cyclines and erythromycin are used . Serological, reaginic and specific tests must be associated and quantitative . Qualitative serology exposed by crosses is obsolete and without possible interpretation . Modern American terminology of early syphilis has no other interest than the therapy which varies according to the stage of the disease.

Br J Clin Pharmacol, 1987 Jul, 24(1), 57 - 61
Enprofylline disposition in the presence and absence of amoxycillin or erythromycin; Sitar DS et al.; 1 The kinetic disposition of a novel xanthine bronchodilator, enprofylline, was determined in young healthy male volunteers in the presence and absence of amoxycillin or erythromycin . These data were compared to those derived from a similar study of theophylline disposition in the presence and absence of erythromycin . 2 Erythromycin inhibited theophylline disposition only in those subjects in whom the control kinetic study was done after antibiotic ingestion, but the effect was modest . Erythromycin had no effect on enprofylline disposition . 3 Amoxycillin reduced the renal clearance of enprofylline, but the change was not statistically significant.

Pediatrics, 1987 Jul, 80(1), 1 - 5
Health codes for newborn care; Caravella SJ et al.; A survey was conducted of the health departments in each of the 50 states, Washington, DC, and the Commonwealth of Puerto Rico to determine the present legal mandates for newborn care . Each of the 52 health departments were queried regarding birth certificates, identification procedures, prophylactic eye care, umbilical cord care, use of vitamin K, Apgar scoring, and metabolic screening . In each category, the departments were asked whether the procedures were mandatory or optional . Birth certificates are uniformly required within the health codes of all states . Although in-hospital identification of newborns is required in most states, four states specifically require arm banding, and only New York State requires footprinting . Eye prophylaxis with silver nitrate is required in 49 states, with erythromycin or tetracycline allowed as topical alternatives in 42 states . Clamping of the umbilical cord is addressed by eight states . Parenteral vitamin K administration is mandated by only five states . Apgar scoring is addressed by 25 states . Newborn metabolic screening is available in every health department, although significant variations exist in the tests available.

J Biol Chem, 1987 Jun 25, 262(18), 8591 - 7
Kinetics of binding of macrolides, lincosamides, and synergimycins to ribosomes; Di Giambattista M et al.; The synergistic effect of type A (virginiamycin M (VM)) and type B (virginiamycin S (VS)) synergimycins and their antagonistic effect against erythromycin (a 14-membered macrolide) for binding to the large ribosomal subunit (50 S) have been related . This investigation has now been extended to 16-membered macrolides (leucomycin A3 and spiramycin) and to lincosamides (lincomycin) . A dissociation of VS-ribosome complexes was induced as well by 16-membered macrolides as by lincosamides . The observed dissociation rate constant of VS-ribosome complexes was identified with the kappa-vs in the case of 16-membered macrolides, but linearly related to lincomycin concentration, suggesting a direct binding of the latter antibiotic to VS-ribosome complexes and the triggering of a conformational change of particles entailing VS release . Two different mechanisms were also involved in the VM-promoted reassociation to ribosomes of VS previously displaced by either macrolides or lincosamides . By binding to lincosamide-ribosome complexes, VM induced a conformational change of ribosomes resulting in higher affinity for VS and lower affinity for lincosamides . On the contrary, an incompatibility for a simultaneous binding of VM and 16-membered macrolides to ribosomes was observed . These results have been interpreted by postulating specific (nonoverlapping) and aspecific (overlapping) antibiotic binding sites at the peptidyltransferase domain . All the kinetic constants of five antibiotic families (type A and B synergimycins, 14- and 16-membered macrolides, and lincosamides) and a topological model of peptidyltransferase are presently available.

J Chromatogr, 1987 Jun 19, 396, 191 - 8
Improved high-performance liquid chromatographic assay of erythromycin in pharmaceutical solid dosage forms; Geria T et al.; A reversed-phase high-performance liquid chromatography method for the assay of erythromycins in pharmaceutical preparations is described . Detailed experimental procedures and results are given . The major erythromycins are well separated, very good recoveries were obtained and detection limits for erythromycins B and C were estimated.

CMAJ, 1987 Jun 15, 136(12), 1271 - 3
Mycoplasma pneumoniae infections in a rural setting in Canada; Dular R et al.; Mycoplasma pneumoniae infection was monitored in patients with symptoms of acute respiratory tract infection in a village in southeastern Ontario from April 1983 to April 1984 . M . pneumoniae was isolated from 51 (48%) of the 106 patients . The incidence began to increase in May 1983, reached a peak in July and declined to normal by mid-August . During the epidemic period M . pneumoniae was detected in 36 of the 43 symptomatic patients . The most prominent features of the outbreak were the considerable intrafamilial attack rate and the high frequency of pneumonia among infected patients . Treatment with tetracyclines and erythromycin reduced the duration of the illness and accelerated the resolution of symptoms.

Antimicrob Agents Chemother, 1987 Jun, 31(6), 964 - 5
Methylation of demethylavermectins; Schulman MD et al.; Demethylavermectins, which lack methyl groups on the oleandrose moiety, were fed to wild-type "Streptomyces avermitilis," which produces the normal avermectin components, and the bioconversion products were identified . The oleandrose units of the demethylavermectins were not methylated by the wild-type strain, but the C-5 of the macrolide ring was methylated . This demonstrates that methylation of the oleandrose units is not a terminal step in avermectin biosynthesis and that it occurs before attachment of the sugars to the macrolide ring . Avermectin biosynthesis thus differs from that of tylosin and erythromycin, in which methylation of the hexose moieties is a terminal reaction.

Antimicrob Agents Chemother, 1987 Jun, 31(6), 954 - 5
Erythromycin bioactivity is stable in ophthalmic ointment used for prophylaxis of neonatal gonococcal conjunctivitis; Bialer MG et al.; Erythromycin ophthalmic ointment (E . Fougera & Co., Melville, N.Y.) and erythromycin gluceptate standards prepared in ointment base were stored at room temperature and heated at temperatures up to 45 degrees C for as long as 6 h before being assayed for bioactivity . We were unable to detect any significant loss of antibiotic bioactivity.

Br J Clin Pharmacol, 1987 Jun, 23(6), 776 - 8
Cyclosporin-erythromycin interaction in normal subjects; Freeman DJ et al.; We studied the pharmacokinetic interaction between cyclosporin (CYA) and erythromycin in normal subjects . Plasma CYA concentrations were measured by high performance liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA) and estimates of metabolite formation were obtained from inter-assay differences between these measurements . Erythromycin significantly increased the maximum concentration and the area under concentration-time curve . Time to maximum concentration and apparent oral clearance of CYA were significantly decreased . The half-life, however, was not altered . Significant reductions in the proportion of apparent metabolite were observed at times of maximum CYA concentrations but not at later time periods (12 and 24 h) . The mechanism of the drug interaction appears to be decreased hepatic first-pass metabolism but an effect on CYA absorption cannot be excluded . These results on normal subjects confirm that patients administered CYA and erythromycin risk CYA toxicity . However, the risk can be reduced by dose reduction based on more frequent CYA monitoring or by using a different antibiotic.

Br J Clin Pharmacol, 1987 Jun, 23(6), 753 - 7
Pharmacokinetics of erythromycin in patients with severe cirrhosis . Respective influence of decreased serum binding and impaired liver metabolic capacity; Barre J et al.; Pharmacokinetic parameters were studied after i.v . infusion of erythromycin (500 mg) in five patients with alcoholic cirrhosis and six normal subjects . Serum AAG levels were 4.7 +/- 2.4 mumol l-1 in cirrhotics and 10.3 +/- 2.1 +/- mumol l-1 in normals . The unbound fraction (fu) of erythromycin was significantly higher in cirrhotic patients (58.3 +/- 17.7%) than in normal subjects (30.5 +/- 2.8%, P less than 0.01), and a negative correlation was found between fu values and serum AAG (r = -0.867, P less than 0.01) . Due to increase in fu, volume of distribution (Vss) was significantly augmented in cirrhotics (85.5 +/- 23.8 l vs 57.6 +/- 14.8 l, P less than 0.05) . Serum clearance of unbound erythromycin (CLu) was significantly reduced in cirrhotic patients (42.2 +/- 10.1 l h-1 vs 113.2 +/- 44.2 l h-1 in normal subjects, P less than 0.01) . This led to marked elevation of serum concentrations of unbound drug and was entirely explained by the decrease of non renal (i.e . hepatic intrinsic) clearance (31.6 +/- 7.5 l h-1 in cirrhotics, 98.6 +/- 41.5 l h-1 in normals, P less than 0.02); renal clearance remained unchanged . It is concluded that in cirrhotic patients, low serum AAG levels and reduced liver metabolic capacity may lead to marked changes in pharmacokinetics of erythromycin, and that similar results might be expected for drugs which exhibit the same serum binding and pharmacokinetic behaviour as erythromycin.

Transplantation, 1987 Jun, 43(6), 847 - 51
Nosocomial Legionnaires' disease following renal transplantation; Wilczek H et al.; A cluster of five cases of Legionnaires' disease in renal transplant patients is described . They were treated with erythromycin and rifampicin, and all five survived . Two of them had rejected their grafts prior to their Legionella pneumonia; two rejected their transplants after reduction of immunosuppressive therapy to combat the infection . L pneumophila was present in the water distribution system of the hospital . Eradication measures included flushing the water pipes to the transplantation ward with hot and hyperchlorinated water, raising the warm water temperature to 60 degrees C, and installing ultraviolet (UV) irradiation units on the warm and cold water pipes to the ward . These measures were successful in that no new cases of legionellosis occurred after wards . L pneumophila could subsequently not be demonstrated by culture in plastic shower hoses supplied with UV-irradiated water . L pneumophila could be demonstrated by direct fluorescent antibody technique, but nonspecific reactions cannot be excluded . A higher prevalence of elevated L pneumophila antibody titers was observed in patients nursed for more than four weeks in the hospital than in patients with a shorter hospital stay, in hospital staff members, or in the general population . It seems that, with appropriate control measures, transplantation activities need not be discontinued in the presence of a minor cluster of Legionnaires' disease in renal transplant patients.

Arch Biochem Biophys, 1987 May 15, 255(1), 27 - 41
Regulation of testosterone hydroxylation by rat liver microsomal cytochrome P-450; Sonderfan AJ et al.; The pathways of testosterone oxidation catalyzed by purified and membrane-bound forms of rat liver microsomal cytochrome P-450 were examined with an HPLC system capable of resolving 14 potential hydroxylated metabolites of testosterone and androstenedione . Seven pathways of testosterone oxidation, namely the 2 alpha-, 2 beta-, 6 beta-, 15 beta-, 16 alpha-, and 18-hydroxylation of testosterone and 17-oxidation to androstenedione, were sexually differentiated in mature rats (male/female = 7-200 fold) but not in immature rats . Developmental changes in two cytochrome P-450 isozymes largely accounted for this sexual differentiation . The selective expression of cytochrome P-450h in mature male rats largely accounted for the male-specific, postpubertal increase in the rate of testosterone 2 alpha-, 16 alpha, and 17-oxidation, whereas the selective repression of cytochrome P-450p in female rats accounted for the female-specific, postpubertal decline in testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activity . A variety of cytochrome P-450p inducers, when administered to mature female rats, markedly increased (up to 130-fold) the rate of testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylation . These four pathways of testosterone hydroxylation were catalyzed by partially purified cytochrome P-450p, and were selectively stimulated when liver microsomes from troleandomycin- or erythromycin estolate-induced rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and these macrolide antibiotics . Just as the testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activity reflected the levels of cytochrome P-450p in rat liver microsomes, so testosterone 7 alpha-hydroxylase activity reflected the levels of cytochrome P-450a; 16 beta-hydroxylase activity the levels of cytochrome P-450b; and 2 alpha-hydroxylase activity the levels of cytochrome P-450h . It is concluded that the regio- and stereoselective hydroxylation of testosterone provides a functional basis to study simultaneously the regulation of several distinct isozymes of rat liver microsomal cytochrome P-450.

Pediatr Med Chir, 1987 May-Jun, 9(3), 343 - 5
{Mucha-Habermann disease . Description of a case in childhood}; Falcini F et al.; The authors report a case of Mucha-Habermann disease in childhood . Mucha-Habermann disease is not a very well known, though not infrequent, disease . It is characterized by recurrent erythematous-papular-vesicular skin lesions associated with arthralgia or arthritis or large joints . Prognosis is generally favourable although an evolution towards Pityriasis Lichenoides Chronica and/or Mycosis Fungoides is possible . There are not specific laboratory findings for this form . Diagnosis is essentially based on histology showing an immunopathogenetic vasculitis . At the present time there is not a safe therapy for the disease; there are however indications for the use of Erythromycin and we followed these in our therapy with positive results.

Arzneimittelforschung, 1987 May, 37(5), 524 - 7
Whole body tissue distribution of {14C}-erythromycin in the guinea pig . An autoradiographic study; Dette GA et al.; The distribution of 14C-labelled erythromycin following intravenous administration to the guinea pig has been studied by whole body autoradiographic technique . Erythromycin was quickly and extensively distributed throughout the body although penetration into some compartments like brain, spinal cord or vitreous body was limited . High radioactivity concentrations were detected in kidney, liver, lung, upper respiratory tract and in bone marrow . Lung tissue and bone marrow were characterized by delayed elimination of erythromycin . The prenetration of erythromycin into skin could be shown . 24 h after the administration of erythromycin still high amounts of radioactivity were detected in the faeces.

Am J Med Sci, 1987 May, 293(5), 309 - 14
Legionella pneumophila lung abscess in a patient with systemic lupus erythematosus; Senecal JL et al.; Lung abscess is an infrequently reported complication of Legionella pneumophila pneumonia associated with a high mortality rate . The risk factors, natural course, optimal method of diagnosis, and optimal therapy of this complication are not well defined . One case of Legionella pneumophila lung abscess occurring in a patient with systemic lupus erythematosus is described, and the reports of 26 other cases are reviewed . This complication is usually hospital-acquired and occurs predominantly in transplant recipients and systemic lupus erythematosus patients treated with corticosteroids with or without a cytotoxic drug . The time interval between the onset of immunosuppressive therapy and infection is usually of several weeks . Progression from pneumonia to abscess formation may be rapid, more commonly within an upper lobe . Transthoracic aspiration within the abscess cavity may be diagnostic, thus obviating the need for open lung biopsy . The prompt institution of erythromycin 4 gm daily intravenously followed by oral therapy for at least 4 weeks is associated with a high survival rate . Adequate drainage from the abscess cavity must be maintained . Radiologic healing may be slow . Long-term survival without relapse does occur . That the clinical spectrum of Legionella pneumophila infection includes lung abscess has not been sufficiently emphasized . This agent should be considered early in the differential diagnosis of lung abscess.

J Pediatr Surg, 1987 May, 22(5), 447 - 50
Whole bowel irrigation: experience in pediatric patients; Vila JJ et al.; Whole bowel irrigation (WBI) was used in 50 children aged 16 months to 14 years in preparation for surgery (n = 30) and colonoscopy (n = 20) . The patients were divided into three groups according to age: group A, 12 to 36 months; group B, 3 to 6 years; and group C, 6 to 14 years . A hydroelectrolytic solution (Na 150 mEq/L, K 30 mEq/L, Cl 130 mEq/L, HCO3 50 mEq/L) was administered to all the groups at a variable rate established according to tolerance, weight, and age . Neomycin (1 g) and erythromycin (50 mg/kg) were administered in the last liter of the solution of the patients being prepared for colorectal surgery . Vital signs (heartbeat, arterial tension, and central venous pressure) and blood parameters (Na, K, HCO3, pH, and Hct) were assessed before and after irrigation and remained stable in all the groups . The rate of administration of the solution was best tolerated in each group as follows: group A, 75 mL/kg/h; group B, 60 mL/kg/h; and group C, 45 mL/kg/h . Colonic preparation was satisfactory in 49 of the 50 cases . Postoperative infectious complications were reduced to 3.3% . WBI in pediatric patients is a fast, simple, and well-tolerated method that gets a colon in excellent condition for surgery and colonoscopy exploration and considerably decreases the number of postoperative complications.

Drug Metab Dispos, 1987 May-Jun, 15(3), 335 - 43
Induction and inhibition of rat hepatic drug metabolism by N-substituted imidazole drugs; Ritter JK et al.; Three daily administrations of N-substituted imidazole antimycotics, clotrimazole (CloTZ, 75 mg/kg/day), miconazole (MCZ, 150 mg/kg/day), or tioconazole (TCZ, 150 mg/kg/day), but not the 4,5-disubstituted imidazole cimetidine (350 mg/kg/day) or imidazole (200 mg/kg/day for 4 days), induced rat hepatic cytochrome P-450 and other drug-metabolizing enzymes . These findings paralleled in vitro observations where CloTZ, MCZ, and TCZ were several orders of magnitude more potent as inhibitors of p-nitroanisole O-demethylase activity in control male rat liver microsomes than cimetidine or imidazole . Although no marked difference in inhibitory potency was evident among the N-substituted imidazoles, there were qualitative and quantitative differences in the profiles and extents of induction of various cytochrome P-450-dependent monooxygenases and Phase II conjugation enzymes . Cytochrome P-450 was elevated dramatically by CloTZ (3-4 times the control) and to a lesser extent by MCZ and TCZ (congruent to 1.5 times the control) . For all agents, there was an increase in metyrapone binding approximately equivalent to the additional (i.e . above control) cytochrome P-450 . Despite the large difference in cytochrome P-450 induction by CloTZ, MCZ, and TCZ, these agents elevated p-nitroanisole demethylase and aniline hydroxylase to similar extents (3-5 X and 1-2 X control, respectively) . All agents induced erythromycin and ethylmorphine demethylation in proportion to cytochrome P-450 . Ethoxyresorufin O-de-ethylation was not substantially affected by any agent . Large differences in the extent and specificity of induction of microsomal glucuronide conjugations were also evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex Transm Dis, 1987 Apr-Jun, 14(2), 102 - 6
Treatment of Chlamydia trachomatis infections: comparison of 1- and 2-g doses of erythromycin daily for seven days; Linnemann CC Jr et al.; Erythromycin is recommended as the alternative to tetracyclines for the treatment of Chlamydia trachomatis infections . However, the usual dose of erythromycin (2 g daily for a week) is frequently associated with gastrointestinal side effects . The goal of this study was to determine whether 1 g of erythromycin daily for a week would be as effective as the 2-g daily dose but without the adverse gastrointestinal effects associated with the larger dose . A total of 114 patients were entered into a randomized double-blind study; 76 patients completed treatment, 13 patients discontinued treatment because of adverse effects, and 25 failed to complete therapy or to return after treatment was initiated . Twelve (27%) of the 45 patients treated with 1 g of erythromycin had cultures positive for C . trachomatis after therapy, as compared with three (10%) of 31 patients treated with a 2-g dose . Only 34% of those treated with 1 g of erythromycin developed adverse gastrointestinal effects, as compared with 71% of those who received 2 g of the drug . Of the 13 patients who discontinued treatment because of side effects, 11 were receiving the 2-g dose . This study indicates that the smaller 1-g dose of erythromycin is inadequate therapy for C . trachomatis infections and that the standard 2-g dose is frequently associated with adverse effects that require discontinuation of therapy.

Xenobiotica, 1987 Apr, 17(4), 493 - 7
The interaction between chronic oral slow-release theophylline and single-dose intravenous erythromycin; Pasic J et al.; Eight volunteers were each given 300 mg of erythromycin lactobionate by i.v . infusion over 15 min in the presence and absence of chronic dosing with slow-release theophylline . Pharmacokinetic profiles were obtained for theophylline in the presence and absence of erythromycin and for erythromycin in the presence and absence of theophylline . A very small, clinically unimportant, but statistically significant increase occurred in mean (+/- S.E.M.) serum theophylline concentration from 4.9 +/- 0.3 mg/l to 5.2 +/- 0.3 mg/l in the presence of erythromycin (P = less than 0.01) . The theophylline pharmacokinetic parameters did not change significantly . The only changes in erythromycin pharmacokinetics were an increase in the renal excretion (0-12 h) from 5.5 +/- 4.0 mg to 11.2 +/- 6.0 mg (P less than 0.03) and an increase in renal clearance (0-2 h) from 9.0 +/- 6.0 ml/min to 21.6 +/- 15 ml/min (P less than 0.05) in the presence of theophylline.

Am J Clin Pathol, 1987 Apr, 87(4), 498 - 503
Clinical interpretation of beta-lactamase-producing strains of Branhamella catarrhalis in sputum Gram's stain and culture; Robinson A et al.; Branhamella catarrhalis has been implicated previously as a cause of bronchopulmonary infections . Sputum Gram's stain and culture results suggesting significant infection with beta-lactamase-producing strains of B . catarrhalis were correlated with a retrospective chart review of eight pediatric and ten adult patients . Preexisting pulmonary disease was observed in 12 patients; 5 had a history of aspiration; and 13 were intubated . Clinically, ten patients had pneumonia, five had bronchitis, and three manifested no disease . Only three sputum specimens grew a pure culture of B . catarrhalis, and six specimens yielded B . catarrhalis in the presence of normal upper respiratory flora . Analysis of broth microdilution susceptibility test results showed that 90% of the strains were inhibited at the following minimum inhibitory concentrations (MICs90): ampicillin, 8 micrograms/mL; cefotaxime, 0.5 microgram/mL; cefoxitin, 0.5 microgram/mL; cephalexin, 4 micrograms/mL; cephalothin, 8 micrograms/mL; chloramphenicol, 1 microgram/mL; clindamycin, 4 micrograms/mL; erythromycin, 0.25 microgram/mL; methicillin, 16 micrograms/mL; mezlocillin, 16 micrograms/mL; moxalactam less than or equal to 0.6 microgram/mL; penicillin, 16 micrograms/mL; piperacillin, 8 micrograms/mL; tetracycline, less than or equal to 0.3 microgram/mL; and trimethoprim/sulfamethoxazole, 1.6/30 micrograms/mL . Therapy may have been adequate in only eight (44%) of the cases . However, all but four of the patients, who died of unrelated causes, exhibited resolution of disease . The data indicate that Gram's stain and culture results of sputum specimens suggesting B . catarrhalis bronchopulmonary infection should be interpreted with caution by clinicians.

J Am Acad Dermatol, 1987 Apr, 16(4), 822 - 7
Erythromycin 2% gel in comparison with clindamycin phosphate 1% solution in acne vulgaris; Leyden JJ et al.; One hundred two patients with mild to moderate facial acne vulgaris completed a 12-week, investigator-masked, randomized, parallel-group comparison of a gel formation of erythromycin (2%) with clindamycin phosphate 1% solution . Patients were evaluated at a baseline visit and after 4, 8, and 12 weeks of twice-daily treatment . Both medications significantly reduced the numbers of papules and open and closed comedones . No significant differences in lesion count reductions were detected between the treatment groups after 8 and 12 weeks of treatment . By the end of 12 weeks, 48% of the patients in the erythromycin group and 47% in the clindamycin group had good or excellent responses to treatment . No patient was terminated from the study for side effects . Most patients, 65% in the erythromycin 2% gel group and 67% in the clindamycin phosphate 1% solution group, had a favorable impression of the overall cosmetic characteristics of their study medication.

Clin Pediatr (Phila), 1987 Mar, 26(3), 117 - 9
Erythromycin-induced drug interactions . An illustrative case and review of the literature; Zitelli BJ et al.; The authors report a case of erythromycin-induced carbamazepine toxicity in a 6-year-old child following use of erythromycin ethylsuccinate (50 mg/kg/day) . Within 5 days of erythromycin use, vomiting, weakness, lethargy, ataxia, nystagmus, and cogwheeling movements developed . A serum carbamazepine concentration had increased from 11.9 mg/L (measured 1 week prior to antibiotic use) to 25.8 mg/L . Following erythromycin withdrawal, serum concentrations returned toward baseline, and symptoms resolved . Erythromycin has known effects on hepatic enzyme function, with altered cytochrome P-450 function . The dramatic reduction in carbamazepine clearance observed in this patient is similar to that reported when erythromycin is used concurrently with other drugs . A brief review of potentially significant erythromycin drug interactions is presented.

Clin Nephrol, 1987 Mar, 27(3), 147 - 50
Changes in erythromycin pharmacokinetics induced by renal failure; Kanfer A et al.; As erythromycin ototoxicity appears to be favored by renal insufficiency, its pharmacokinetics were assessed in chronic uremic patients treated by maintenance hemodialysis in comparison with normal subjects . Two groups of 8 patients each were studied, the first one on an interdialytic day, the second immediately after the end of an hemodialysis session . All subjects ingested a single dose of 1 gram of erythromycin ethylsuccinate . Times of peak serum concentration and biological half-lifes were similar in patients and in controls . Maximum serum concentrations and areas under the serum concentration time-curve were higher in patients than in controls whereas apparent oral clearances were lower in the former . The differences between the two groups of patients were not significant . These pharmacokinetic changes are suggestive of an enhanced bioavailability of erythromycin in chronic renal failure which might predispose uremics to the ototoxicity of the drug.

Conn Dent Stud J, 1987 Mar, 7, 7 - 8
Pharmacologic considerations for patients taking oral contraceptives; Hassan T; PIP: This is a brief review of the theoretical and known drug reactions with oral contraceptives . There are at least 6 possible types of drug reactions that may affect the action of oral contraceptives, not including malabsorption related to changes in intestinal motility or flora . Ampicillin is an example of an antibiotic that may cause diarrhea, thereby reducing absorption of pill steroids . The steroids in orals are subject to enterohepatic circulation, which is in turn affected by the gut flora . Antibiotics known to suppress gut flora include: penicillins, cephalosporins, tetracyclines, sulfas, neomycin and erythromycin . Although controlled clinical trials of antibiotic intake with oral contraception have not shown significant interactions, anecdotal reports of pill failures have been published . The other important drug interaction affecting contraception by orals is enhanced hepatic degradation, as seen with rifampicin . Other drugs such as cimetidine, MAO-inhibitor antidepressants, chloramphenicol, influenza or BCG vaccine, isoniazid, warfarin, metronidazole and disulfiram may delay steroid metabolism and possibly increase side effects . When prescribing drugs it is important to realize that certain drugs decrease oral contraceptive concentrations: antibiotics anticonvulsants, griseofulvin, purgatives and rifampicin .

Geburtshilfe Frauenheilkd, 1987 Feb, 47(2), 81 - 6
{Clinical aspects, diagnosis and therapy of syphilis in pregnancy and in newborn infants}; Meurer M et al.; A clinically manifest primary or secondary syphilis that develops during pregnancy has become an extremely rare occurrence . What is more frequently found in pregnant women, however, is a reactive syphilis serology where there is otherwise an absence of clinical symptoms or where, at least, there are untypical symptoms . What has to be decided in these cases is whether one is dealing with latent seropositive syphilis that can be transmitted to the child and thus needs to be treated, or with a serum scar resulting from an infection which occurred some time before . As a rule, this decision can be reached serologically by demonstrating Treponema-specific IgM antibodies by means of the 19S-IgM-FTA-ABS test or some similar methods . In the case of specific IgM detection, immediate treatment of the mother, and thus of the child, is important . Daily intramuscular injections of 1 million I.U . penicillin over a total of 21 days are recommended . Only in proved cases of penicillin allergy should one resort to erythromycin; although it must be said that there is no guarantee that this will produce a therapeutically sufficient fetal blood level . In rare cases such as these, the child must therefore be retreated with penicillin after birth . Today, the clinical signs of premature or retarded congenital syphilis are hardly ever seen in their classic form . Symptoms are frequently uncharacteristic - especially in the case of premature births - and can only be distinguished from other congenital infections with difficulty.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplantation, 1987 Feb, 43(2), 263 - 70
Exacerbation of cyclosporine toxicity by concomitant administration of erythromycin; Jensen CW et al.; Cyclosporine (CsA), an immunosuppressive drug widely used in clinical organ transplantation, causes a variety of side effects, including parenchymal complications of nephrotoxicity and hepatotoxicity . Erythromycin ethinylsuccinate (EES), a macrolide antibiotic frequently administered to transplant patients afflicted with pneumonias caused by Mycoplasma pneumoniae and Legionella pneumophila, markedly potentiated parenchymal drug toxicity in nine (three renal and six cardiac) CsA-treated allograft recipients . The mean and median blood urea nitrogen (BUN), creatinine, and total bilirubin increased upon initiation of EES treatment: in the renal recipients from 27, 1.7, and 0.5 mg/dl, respectively, before, to a mean and median of 81/101, 8.3/3.9, and 2.1/1.2 mg/dl during, and to 72/22, 1.9/1.7, and 0.6/0.5 mg/dl after cessation of EES treatment . The median serum radioimmunoassay (RIA)-determined CsA trough value of 147 ng/ml prior, rose to a zenith of 1125 ng/ml during, EES therapy . In the six cardiac recipients, the mean and median BUN, creatinine, and total bilirubin of 51/45, 1.5/1.3, 1.2/1.3 mg/dl, respectively, before, rose to 100/91, 3.7/3.6, and 2.3/2.1 mg/dl during, and fell to 49/44, 1.8/2.1, and 1.0/0.8 mg/dl after, cessation of EES . The mean serum CsA trough value of 185 ng/ml rose to 815 ng/ml during EES administration . Since EES and CsA are both metabolized by the hepatic cytochrome P450 mixed-function oxidase system, simultaneous use of these two drugs may decrease CsA metabolism, with consequent elevation of blood levels and induction of CsA toxicity . Therefore, blood level monitoring and careful regulation of CsA dose are necessary, in order to achieve the safe use of EES in transplant recipients.

Obstet Gynecol, 1987 Feb, 69(2), 202 - 7
Effect on birth weight of erythromycin treatment of pregnant women; McCormack WM et al.; To test the hypothesis that treatment with antibiotics prevents low birth weight, pregnant women whose vaginal cultures contained Ureaplasma urealyticum or Mycoplasma hominis (or both) and who gave written informed consent were treated with one of the following: identical looking capsules containing 250 mg of either erythromycin estolate or stearate (active against U urealyticum), or 150 mg of clindamycin hydrochloride (active against M hominis), or placebo, four times daily for six weeks in a randomized double-blind study . Treatment with clindamycin had no effect . Treatment with erythromycin initiated during the second trimester had no effect on mean birth weight or on the frequency of low-birth-weight infants . In contrast, women whose treatment with erythromycin was initiated in the third trimester gave birth to infants with a heavier mean birth weight (3331 g) than infants born to placebo-treated women (3187 g) (P = .042) . Similarly, in women whose erythromycin was begun during the third trimester, the birth rate of infants weighing 2500 g or less was 3%, whereas in women treated with placebo, the birth rate for low-birth-weight infants was 12% (P = .047) . These data suggest that treatment with erythromycin during the third trimester prevents low birth weight in mycoplasma-colonized pregnant women . Whether the effect is due solely to the action of erythromycin on U urealyticum is uncertain.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 352 - 6
Treatment of Lyme disease; Steere AC et al.; We compared phenoxymethyl penicillin, erythromycin, and tetracycline, in each instance 250 mg four times a day for 10 days, for the treatment of early Lyme disease (stage 1) . None of 39 patients given tetracycline developed major late complications compared with 3 of 40 penicillin-treated patients and 4 of 29 given erythromycin (p = 0.07) . However, with all three antibiotic agents, nearly half of patients had minor late symptoms . For neurologic abnormalities (stage 2), 12 patients were treated with high-dose intravenous penicillin, 20 million U a day for 10 days . Pain usually subsided during therapy, but a mean of 7 to 8 weeks was required for complete recovery of motor deficits . For the treatment of established arthritis (stage 3), 20 patients were assigned treatment with intramuscular benzathine penicillin (7.2 million U) and 20 patients received saline . Seven of the 20 penicillin-treated patients (35%) were apparently cured, but all 20 patients given placebo continued to have attacks of arthritis (P less than 0.02) . Of 20 arthritis patients treated with intravenous penicillin G, 20 million U a day for 10 days, 11 (55%) were apparently cured . Thus, all 3 stages of Lyme disease can be treated with antibiotic therapy, but some patients with late disease may not respond.

Mol Pharmacol, 1987 Feb, 31(2), 135 - 9
Clotrimazole induction of cytochrome P-450: dose-differentiated isozyme induction; Ritter JK et al.; Treatment of male rats for 3 days with the N-substituted imidazole, clotrimazole, produced up to a 4-fold induction of hepatic microsomal cytochrome P-450 . The monooxygenase activities induced varied with the dose administered . At low doses (less than 25 mg/kg), p-nitroanisole demethylase and aniline hydroxylase activities were induced . Only at higher doses were other monooxygenase activities (erythromycin and ethylmorphine demethylases and cytochrome P-450 metabolic-intermediate complex formation from troleandomycin) induced . Microsomal UDP-glucuronosyltransferase activity toward morphine was induced at low doses in a manner similar to that of p-nitroanisole demethylase . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomes indicated that low doses of clotrimazole caused the intensification of a 48,000 molecular weight protein band, whereas at high doses, there was a marked intensification of an additional 50,500 molecular weight protein, the same molecular weight band as was intensified in phenobarbital- and dexamethasone-induced microsomes . The observations suggest a phenomenon of "dose-differentiated" isozyme induction for cytochrome P-450.

Br J Exp Pathol, 1987 Feb, 68(1), 67 - 70
The effect of tetracycline and erythromycin in a model of acne-type inflammation; Dalziel K et al.; The effects of systemically administered oxytetracycline and erythromycin in a guinea pig model of acne-type inflammation were assessed histologically and by tissue measurement techniques . It was found that oxytetracycline significantly reduced the volume and maximum area of inflammation compared with both control and erythromycin treated groups . Oxytetracycline also altered the morphology of the inflammatory infiltrate significantly reducing the proportion of polymorphonuclear leucocytes present . In this model, erythromycin did not alter the inflammatory response but did seem to reduce the amount of transepidermal elimination of inflammatory debris.

Wien Klin Wochenschr, 1987 Jan 9, 99(1), 1 - 14
{Epidemiology, clinical aspects and therapy of infections with Chlamydia trachomatis serotype D-K}; Luger A; Chlamydia trachomatis serotype D-K is one of the most important pathogens of communicable diseases . 3 to 5 million new infections are observed annually in the USA . 10% to 30% of young sexually active persons in the age group 15 to 20 years are affected . The organism was isolated from 20% to 30% of patients attending dispensaries for sexually transmitted diseases, 5% to 10% of gynaecological outpatients, 1% to 8% of pregnant women and 0% to 5% of asymptomatic control persons . In men, C . trachomatis was found in 30% to 70% of patients with urethritis (15% to 25% simultaneously with gonorrhoea), in 30% to 60% of persons suffering from nongonoccocal urethritis and in 65% to 70% with postgonoccocal urethritis . 20% of newborns from mothers with positive cultures develop pneumonia and 37% conjunctivitis . Complications such as endometritis, salpingitis, periappendicitis, perihepatitis, ectopic pregnancy, premature birth, proctitis, cystitis, deferenitis, epididymitis, reactive arthritis, morbus Reiter, conjunctivitis, pneumonia (in infants and adults) may cause long lasting disease and may leave behind irreversible sequelae . Treatment with tetracyclines or erythromycin is always effective.

An Esp Pediatr, 1987 Jan, 26(1), 37 - 9
{Evaluation study of laparatomy in HodgkinÅ› disease}; Rivilla Parra F et al.; We report 30 patients with Hodgkin's disease treated at "La Paz" Children Hospital of Madrid, from 1965 to 1984, to determine the role of the laparotomy in modifying the presurgical clinic stage . Laparotomy changed this stage in 40% of patients, in whom stage advanced from I or II to III or IV . The only side effect of surgery was pneumococcal sepsis in two patients . All children were treated with polyvalent pneumococcal vaccine and penicillin or erythromycin, before laparotomy.

J Fam Pract, 1987 Jan, 24(1), 47 - 51
Use of long half-life parenteral cephalosporins in ambulatory practice; Sauerwein M et al.; Cefonicid (Monocid) and ceftriaxone (Rocephin) are long half-life cephalosporins that may be used for serious infections in the outpatient setting . They may be used as an extension of initial hospital treatment, or therapy can be initiated and completed in many cases with the patient remaining at home . Sufficient clinical experience exists with both ceftriaxone and cefonicid to recommend these agents for selected patients having pyelonephritis, osteomyelitis, or soft tissue infections . Cefonicid, perhaps in combination with erythromycin, will provide excellent coverage for complicated community-acquired pneumonias . Ceftriaxone is effective as single-dose therapy for even complicated gonococcal infections . The use of long half-life cephalosporins in ambulatory practice may result in substantial cost savings for certain patients.

Eur J Clin Pharmacol, 1987, 32(5), 493 - 8
The interaction of erythromycin with theophylline; Paulsen O et al.; We have studied the interaction of erythromycin with theophylline . We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg X kg-1) over 1 h, followed by a maintenance infusion (0.5 mg X kg-1 X h-1) for 5 h . A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods . The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion . Concentrations within the therapeutic range were obtained with both drugs . A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment . The plasma clearance of theophylline was reduced in 9 of the 10 subjects . Renal clearance increased correspondingly, but the change was not statistically significant . Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication . We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.

Rev Med Univ Navarra, 1987 Jan-Mar, 31(1), 31 - 5
{Primary hepatic actinomycosis}; Suarez J et al.; We present a patient complaining of abdominal pain during eighteen months, localized in left subcostal region, weight loss, asthenia and anorexia for the previous 5 months and fever one month before his admission . He presented painful hepatomegaly, leukocytosis, with an increased percentage of mature and inmature neutrophils, anemia, elevated erythrocyte sedimentation, thrombocytosis, hypergammaglobublinemia and dissociated cholestasis . Complementary exams demonstrated the presence of a poorly vascularized occupying process, localized in the left hepatic lobe . Following laparotomy and biopsy-resection of the process in hepatic left lobe, staining revealed isolated, Gram + filaments and histopathological study showed multiple micro-abcesses displaying actinomyces-like characteristics . There was no evidence of any other pathological process except for previous history of dental abscesses and extractions, which could represent the primary focus for hematogenous dissemination . There was satisfactory response to erythromycin.

Int J Tissue React, 1987, 9(1), 77 - 85
Cutaneously applied erythromycin base reduces various types of inflammatory reactions in mouse ear; Tarayre JP et al.; Erythromycin base was tested by brushing a solution onto the skin in various models of non-immune and immune inflammation produced in mouse ear, namely inflammations induced by croton oil and cantharidin, primary irritation by picryl chloride, and contact hypersensitivity reactions to oxazolone and picryl chloride . On the non-immune inflammations, erythromycin displayed a greater effect than indomethacin, phenylbutazone or acetylsalicylic acid, though less than that of hydrocortisone acetate . It inhibited the hypersensitivity reactions less well . These results suggest some participation of an anti-inflammatory mechanism in the clinical effectiveness of cutaneously applied erythromycin base in some forms of acne.

Postgrad Med, 1987 Jan, 81(1), 83 - 90
Syphilis . Updated approach to an old disease; Siegel D et al.; Syphilis, a sexually transmitted disease caused by Treponema pallidum, is widespread but most common in large cities . The various stages include primary, secondary, latent, tertiary (late), and congenital syphilis and neurosyphilis . Definitive diagnosis is made by finding spirochetes on a darkfield examination of material from a chancre or moist mucosal lesion . Serologic tests for syphilis in common use in the United States include the VDRL and the FTA-ABS . Penicillin is the drug of choice for all stages of syphilis, with tetracycline or erythromycin indicated in certain patients . Accurate and prompt reporting of syphilis cases is an important factor in disease control.

J Perinatol, 1987 Summer, 7(3), 232 - 4
Diagnostic methods for Chlamydia trachomatis disease in neonates; Rodriguez EM et al.; Chlamydia trachomatis is an obligate intracellular parasite responsible for many clinical syndromes, including neonatal conjunctivitis and pneumonia . The gold standard of diagnosis has been isolation in cell culture . However, this requires days of processing . Several rapid diagnostic tests are available . Giemsa staining of conjunctival smears, enzyme immunoassay, and the fluorescein-conjugated monoclonal antibody test . Both the EIA and the FA tests show promise as ideal rapid diagnostic tests . Treatment of chlamydial conjunctivitis must focus upon the eradication of nasopharyngeal carriage as well as cure of ophthalmic symptoms . The need for nasopharyngeal eradication is underscored by the fact that it is the source for chlamydial pneumonia as well as for conjunctival re-infection . Clinical studies have shown that oral erythromycin estolate or ethylsuccinate suspension 50 mg/kg/day twice-daily or four times a day for 14 to 21 days are the therapeutic regimens of choice . Neonatal ocular prophylaxis is currently under study . One per cent silver nitrate does not prevent chlamydial conjunctivitis but preliminary studies do show favorable results with topical erythromycin . Nevertheless, neither 1 per cent silver nitrate nor topical erythromycin eradicate nasopharyngeal carriage, elimination of which is necessary for the prevention of neonatal chlamydial pneumonia.

Eur J Clin Pharmacol, 1987, 33(5), 529 - 30
Erythromycin ethyl succinate: diffusion through interstitial dermal fluid; Vaillant L et al.; Erythromycin is widely used in dermatology . There are few studies of its diffusion in the skin . The diffusion of erythromycin ethyl succinate (EES) in dermal fluid has now been investigated by the suction blister method . Suction blister fluid (SBF) and blood samples were collected from 10 volunteers before administration of 1 g EES and 10 times during the following 24 h . The median peak serum level was 2.05 micrograms/ml and in SBF it was 0.34 microgram/ml . The median ratio of the areas under curves (f SBF/f serum) was 43% . In all subjects EES concentrations in SBF between the second and twelfth hours exceeded 0.1 g/ml . The results show good diffusion of EES through normal skin from the second to the twelfth hours after oral administration.

Scand J Urol Nephrol Suppl, 1987, 104, 159 - 63
Chlamydial infections in gynaecology and obstetrics; Hoyme UB; Chlamydia trachomatis is a sexually transmitted intracellularly growing rod, causing cervicitis, endometritis, salpingitis and urethritis . Inclusion conjunctivitis and pneumonia are the sequelae of maternal cervicitis in newborns . In treatment tetracyclines and erythromycin are the drugs of choice.

Bull Soc Pathol Exot Filiales, 1987, 80(3 Pt 2), 447 - 51
{2 cases of multiresistant Plasmodium falciparum malaria contracted in Douala with atypical clinical presentation}; Charmot G et al.; We present two cases of Plasmodium falciparum malaria contracted in Douala despite adequate prophylaxis by Fansidar for one and by chloroquine for the other . Failure of curative treatment by Fansidar for the first case (in vitro chloroquine-resistant strain) and by amodiaquine plus erythromycin for the second . After these therapeutic failures, both patients presented without fever, but with splenomegaly and anaemia . The successful therapeutic was mefloquine.

Clin Ther, 1987, 9(3), 263 - 6
Comparison of cefatrizine and erythromycin for pediatric ear, nose, and throat infections; Cremonesi G et al.; A comparison was made of cefatrizine in dosages of 75 mg/kg/day administered once daily or twice daily and erythromycin in a mean daily dosage of 50 mg/kg given in three divided doses for the treatment of acute infections of the ear, nose, and throat in children . Temperature was recorded twice a day during therapy . At the end of treatment, a clinical evaluation of cure, improvement, or failure was made, based on defervescence and abatement of symptoms . All ten children given cefatrizine once daily were cured (P less than or equal to 0.05), as were eight of ten given cefatrizine twice daily and four of ten given erythromycin . The remaining eight patients were improved . One patient given cefatrizine had diarrhea, which appeared on the fifth day of treatment . No other side effects were observed . Cefatrizine appeared to be similarly effective whether given once a day or twice a day; further trials are warranted to confirm the efficacy of once-daily treatment with this cephalosporin.

Gene, 1987, 55(2-3), 319 - 25
Expression of the macrolide-lincosamide-streptogramin-B-resistance methylase gene, ermE, from Streptomyces erythraeus in Escherichia coli results in N6-monomethylation and N6,N6-dimethylation of ribosomal RNA; Katz L et al.; The ermE gene was cloned from Streptomyces erythraeus into Escherichia coli on a series of plasmids . When transcribed from the lac promoter, ermE conferred high-level resistance to erythromycin and other macrolide-lincosamide-streptogramin-B (MLS) antibiotics . A methylase activity capable of N6-mono- and N6,N6-dimethylation of adenine residues in E . coli rRNA was detected in extracts of MLS-resistant cells . In addition, rRNA extracted from MLS-resistant E . coli contained N6-mono- and N6,N6-dimethylated adenine residues.

J Hyg Epidemiol Microbiol Immunol, 1987, 31(1), 83 - 9
Effect of oxytetracycline and erythromycin on Syrian hamsters after intratracheal infection with Mycoplasma pneumoniae; Ritter E et al.; Male Syrian hamsters were infected intratracheally with Mycoplasma pneumoniae and treated here after for ten days with either OTC or erythromycin . The purpose of this study was to investigate whether there exists a relation between the persistence of M . pneumoniae in the lungs and the infection dose respectively the days passed after infection before starting treatment with antibiotics . The influence of antibiotic therapy on the immune response of the hamsters was also investigated.

Gene, 1987, 53(1), 73 - 83
Cloning and nucleotide sequence of a carbomycin-resistance gene from Streptomyces thermotolerans; Epp JK et al.; Two plasmids (pOJ158 and pOJ159) containing DNA fragments from the carbomycin(Cb)-producing strain Streptomyces thermotolerans were identified in Streptomyces griseofuscus based on their ability to confer resistance to Cb . The Cb-resistance determinants on pOJ158 and pOJ159 were designated carA and carB, respectively . In S . griseofuscus, pOJ159 also confers resistance to spiramycin, rosaramicin, lincomycin, and vernamycin B, but not to tylosin; in Streptomyces lividans, pOJ159 additionally confers resistance to erythromycin and oleandomycin . The carB gene was localized on pOJ159 to a 1.25-kb region whose nucleotide sequence was determined . The sequence has a G + C content of 68% and contains the coding sequence for carB and portions of the 5' and 3' untranslated regions . A comparison of the amino acid sequence of the protein encoded by carB (as deduced from the nucleotide sequence) with the deduced amino acid sequence of the RNA methylase from Streptomyces erythraeus (encoded by ermE) revealed extensive homology, suggesting that carB also encodes an RNA methylase . The region 5' to the coding sequence does not contain a small ORF or regions of complementarity that are commonly associated with translationally regulated macrolide-lincosamide-streptogramin B resistance genes . The 3' untranslated region contains an inverted repeat sequence that potentially can form a stable RNA stem-loop structure with a calculated delta G of -70 kcal.

Zentralbl Gynakol, 1987, 109(5), 295 - 9
{Chlamydia infections and pelviscopic findings}; Giese KP; Contact infections by chlamydia trachomatis have been observed more frequently in the last years, may be by better isolation methods . 1985 in all pelviscopies a cervical swab and cul-de-sac secretion have been examined using immunofluorescent test for chlamydia . In non selected 80 patients a positive cervical test could be found in 11 cases (13.8 per cent) . In cul-de-sac secretions only 3 cases (3.8 per cent) in result was positive . We saw wide spread adhesions near the adnexa, which could be the reason of sterility, in 3 chlamydia positive cases and in 6 chlamydia negative cases . Results of chlamydia examinations are discussed with regard to sterility and the necessity of treatment with tetracyclines or erythromycin including the sexual partner.

Schweiz Med Wochenschr, 1986 Dec 6, 116(49), 1739 - 41
{Roxithromycin (RU 28965), a new macrolide effective against pulmonary infections}; Lachat JM et al.; Roxithromycin, a new macrolide, has favorable pharmacological properties: it is acid stable and well absorbed, and its prolonged half-life allows b.i.d . prescription of 150 mg . In our open prospective study we found an etiologic infectious agent in 16 (80%) of 20 patients presenting with "atypical" pneumonia . Ten of the 16 pneumonias were due to an organism sensitive to roxithromycin (gram+ cocci, gram- rods, mycoplasma and chlamydia), and 6 to a virus . Therapeutic success was obtained in greater than or equal to 90% . The treatment was well tolerated with fewer gastrointestinal disorders than with erythromycin.

J Antimicrob Chemother, 1986 Dec, 18(6), 747 - 56
Comparison of the side effects and gastrointestinal motility observed after administration of erythromycin and josamycin to dogs; Qin XY et al.; The effects of intravenous erythromycin and josamycin on gastrointestinal motility in dogs have been compared . Erythromycin interrupted the basal motility pattern in the fasted state and induced irregular bursts of spikes in both the fasted and fed states . Emesis occurred in all the dogs in the fasted state experiments and in four out of six dogs in the fed state experiments . Josamycin did not disturb gastrointestinal motility and no dog showed signs of discomfort . The difference in the chemical structure of erythromycin and josamycin is the main reason for their differential effect on the gastrointestinal tract.

Eur J Clin Microbiol, 1986 Dec, 5(6), 612 - 4
Evaluation of roxithromycin in the treatment of non-gonococcal urethritis in males; van der Willigen AH et al.; One-hundred and fifty-two male patients suffering from non-gonococcal urethritis were treated with an oral dosage of 300 mg roxithromycin daily for seven days . Chlamydia trachomatis was isolated from the urethra in 53 patients (35%), and Ureaplasma urealyticum in 42 patients (28%) . After treatment, 49 (92%) of the 53 patients with positive Chlamydia trachomatis cultures and 34 (81%) of the 42 patients with positive Ureaplasma urealyticum cultures had negative cultures at follow-up . A clinical cure was observed in 137 patients (90%) . Ten patients (7%) showed side effects consisting of nausea, sensation of distended abdomen, headache and fatigue . Seventy-eight male patients suffering from nongonococcal urethritis were treated with an oral dosage of 2 X 150mg roxithromycin daily for seven days . Chlamydia trachomatis was isolated from the urethra in 22 patients (28%), and Ureaplasma urealyticum in 30 patients (38%) . After treatment, all of the 22 patients with formerly positive Chlamydia trachomatis cultures and 23 (77%) of the 30 patients with formerly positive Ureaplasma urealyticum cultures were negative at follow-up . A clinical cure was observed in 70 patients (90%) . Three patients (4%) showed side-effects consisting of nausea and headache . It is concluded that roxithromycin is a good alternative to tetracycline and erythromycin in the treatment of non-gonococcal urethritis in males.

Scand J Prim Health Care, 1986 Nov, 4(4), 209 - 12
The prevalence of Chlamydia trachomatis in the cervix of puerperal women, and its consequences for the outcome of pregnancy; Skjeldestad FE et al.; During a five-month period all puerperal women at the Department of Obstetrics, University Hospital of Trondheim, Norway, were screened for Chlamydia trachomatis (C . trachomatis) from the cervix uteri on the 4-6th day postpartum . Outcomes of the pregnancies were examined . The prevalence of C . trachomatis in the total population of 599 eligible women was 5.8% (35:599), while 3.0% (18:599) of the cultures were inconclusive . The prevalence of C . trachomatis in women aged less than 20 years was 25.8%; aged 20-24 years, 8.9% and greater than 24 years, 2.3% . The prevalence of C . trachomatis among women living alone was 17.2%; among women in cohabitation, 9.2% and among married women, 3.2% . There was no relationship between the presence of C . trachomatis and preterm birth, birth weight and birth weight for gestation, stillbirth or neonatal death . During the first fourteen postpartum days no puerperal infections were seen among chlamydia-positive mothers . The chlamydia-positive women and their partners were then treated with erythromycin stearat 1,000 mg daily for 12 days . Samples for cervix 14 days after completion of the treatment were chlamydia-negative for all 35 women . Screening all pregnant women under the age of 25 years would detect 80% of the pregnant population harbouring C . trachomatis in the cervix uteri . Based on findings from this study and from cost-benefit analyses, we recommend screening of all pregnant women under the age of 25 years in our attachment area.

J Clin Pharmacol, 1986 Nov-Dec, 26(8), 633 - 7
Outpatient drug-induced parenchymal liver disease requiring hospitalization; Beard K et al.; A case-history study of drug-induced liver disorders requiring hospitalization was carried out at the Group Health Cooperative of Puget Sound, a health maintenance organization with about 280,000 members, for the five-year period from January 1, 1977 to December 31, 1981 . During this time, there were 12 instances of hospitalization for liver disorders judged to be probably (nine cases) or possibly (three cases) attributable to outpatient drug ingestion (other than antitumor agents) . The rate was on the order of one per 100,000 person-years at risk . Drugs implicated as probable causes were ampicillin (two cases), carbamazepine (one case), erythromycin (one case), methyldopa (one case), sulfasalazine (one case), quinidine (one case), trimethoprim/sulfamethoxazole (one case), and multiple drugs (one case).

Arch Intern Med, 1986 Nov, 146(11), 2159 - 64
Enhanced bleeding with cefoxitin or moxalactam . Statistical analysis within a defined population of 1493 patients; Brown RB et al.; Most cases of beta-lactam-associated coagulopathy occur in patients with other risk factors . This study analyzed temporally related clinical bleeding events in 1493 patients who received one antibiotic for at least three days . Univariate and multivariate analyses controlled for condition variables (nutritional status, renal, hepatic, or hematologic dysfunction, intensive care unit stay) and treatment variables (use of antiplatelet agents, anticoagulants, vitamin K, antitumor chemotherapy or antiulcer therapy, steroids) that could have been associated with bleeding independently . Rates of bleeding ranged from 0% (chloramphenicol sodium succinate, vancomycin hydrochloride, erythromycin lactobionate) to 8.2% (cefoxitin) to 22.2% (moxalactam disodium) . Multiple logistic regression analyses revealed that only moxalactam (odds ratio, 9.9) and cefoxitin (odds ratio, 2.1) exhibited significantly higher likelihoods of bleeding than other agents . This study statistically confirms increased risk of bleeding with moxalactam, heretofore reported only anecdotally . Cefoxitin may carry risks greater than previously believed.

Am J Surg, 1986 Nov, 152(5), 479 - 82
Perioperative blood transfusion associated with infectious complications after colorectal cancer operations; Tartter PI et al.; We prospectively studied 168 consecutive patients with colorectal cancer to identify perioperative determinants of infectious complications . All patients received preoperative bowel preparation with laxatives, enemas, oral neomycin and erythromycin base, and intravenous cefazolin . Age, sex, admission hematocrit value, operative procedure, specimen length, duration of operation, blood loss, transfusions, tumor size, tumor differentiation, nodal status, and Dukes' stage were evaluated in relation to infectious complications using multivariate analysis . Infectious complications developed in 24 of the 168 patients in the study (14 percent) and these accounted for the four deaths . Blood transfusion (p = 0.0100) and admission hematocrit value (p = 0.0191) were significantly related to postoperative infectious complications . Low admission hematocrit values appeared to protect patients from infectious complications . Patients who had postoperative infectious complications received 2.14 +/- 2.75 units of blood compared with 0.82 +/- 1.37 units in patients without infectious complications (p = 0.0005) . Although blood transfusion was associated with high operative blood loss, prolonged procedures, and large specimens (p less than 0.005), none of these factors was significantly associated with infectious complications (p greater than 0.10) . Blood transfusion is immunosuppressive in other clinical situations and may be a more significant factor affecting postoperative immune function and susceptibility to infectious complications than previously recognized.

Antimicrob Agents Chemother, 1986 Nov, 30(5), 774 - 6
Disk diffusion susceptibility of Branhamella catarrhalis and relationship of beta-lactam zone size to beta-lactamase production; Luman I et al.; We tested 231 isolates of Branhamella catarrhalis for beta-lactamase production and drug susceptibility by the National Committee for Clinical Laboratory Standards disk diffusion method . The nitrocephin disk (Cefinase) identified beta-lactamase in 98% of the enzyme-producing strains, and a zone diameter of inhibition of less than or equal to 29 mm for penicillin correctly predicted the presence of beta-lactamase in 99% of the isolates . No resistance to erythromycin, tetracycline, trimethoprim-sulfamethoxazole, or amoxicillin-clavulanic acid was observed.

J Clin Psychopharmacol, 1986 Oct, 6(5), 297 - 9
A pharmacokinetic drug interaction between erythromycin and triazolam; Phillips JP et al.; The effect of erythromycin on the pharmacokinetics of triazolam was studied in 16 normal male volunteers . Triazolam in 0.5-mg doses was administered alone and after 3 days of receiving erythromycin (333 mg tid) in a randomized complete crossover design . Plasma samples were collected for 24 hours post doses and analyzed for triazolam by electron-capture gas chromatography . Erythromycin administration resulted in a 52% decrease in triazolam clearance, significantly higher triazolam concentrations at the majority of sampling times, significantly longer triazolam half-lives of elimination (5.9 vs . 3.6 hours), and a 30% decrease in the triazolam apparent volume of distribution . No differences were observed in the times of peak triazolam concentration occurrence . In accordance with previously reported drug interactions involving macrolide antibiotics, erythromycin appears to significantly inhibit the metabolism of triazolam.

Ann Acad Med Singapore, 1986 Oct, 15(4), 610 - 6
Legionnaires' disease--report of Singapore's first local case; Lim HS et al.; A previously healthy 27 year-old male plumber presented with six days of fever, nausea, vomiting, malaise and headache . The subsequent development of cough, dyspnoea and pleuritic pain coincided with the simultaneous development of progressive bilateral cavitary pneumonia with pleural effusion . Leucocytosis, thrombocytopenia, hyponatraemia, hypoalbuminaemia, hypophosphataemia and hypoxaemia were the main laboratory abnormalities . Clinical suspicion of Legionnaires' disease was confirmed by the presence of serum antibody to Legionella pneumophila (titre 1:512) by an indirect fluorescent antibody test . Treatment with erythromycin and rifampicin resulted in clinical recovery with minimal residual bilateral pleural effusion six months after presentation . This patient is the first to acquire Legionnaires' disease in Singapore.

Eur J Clin Microbiol, 1986 Oct, 5(5), 563 - 8
Diagnosis of genital Chlamydia trachomatis infection in males by cell culture and antigen detection test; Moi H et al.; Urethral Chlamydia trachomatis infection was diagnosed in 204 of 1,011 (20.2%) male patients by cell culture, in 219 (21.7%) by an antigen detection test consisting of a solid phase immunoassay, and in 247 (24.4%) patients by both methods combined . The positive results of the two methods agreed for 176 patients, and both positive and negative results of the tests agreed for 940 patients (93%) . With cell culture as the reference method, the antigen detection test had a sensitivity of 86.3%, a specificity of 94.7%, a positive predictive value of 80.4% and a negative predictive value of 96.5% . It gave false negative results in 28 patients . In 43 patients the antigen detection test gave a positive result, whereas culture was negative . Thirty-nine of these males were treated with antibiotics (tetracycline or erythromycin), 19 because their consorts had a proven Chlamydia trachomatis infection, and 20 for obvious clinical and/or microscopic findings of urethritis requiring treatment . According to this analysis there were 19 probable misses by cell culture test and four true false-positives by the antigen detection test, i.e . less than 0.4% of all patients examined . Since one-third of males with a final diagnosis of Chlamydia trachomatis infection were clinically asymptomatic efforts to control genital chlamydial infections must identify this reservoir . The antigen detection test provides an alternative diagnostic method to the more laborious and time-consuming cell culture procedure.

Arch Dis Child, 1986 Oct, 61(10), 1027 - 9
Erythromycin versus tetracycline for treatment of Mediterranean spotted fever; Munoz-Espin T et al.; Eighty one children aged between 1 and 13 years participated in a randomised comparative trial of tetracycline hydrochloride and erythromycin stearate for treatment of Mediterranean spotted fever . Both therapeutic regimens proved effective, but in patients treated with tetracycline both clinical symptoms and fever disappeared significantly more quickly . Likewise, when those patients who began treatment within the first 72 hours of illness are considered the febrile period had a significantly shorter duration in the group treated with tetracycline . One patient was switched to tetracycline because there was no improvement of clinical manifestations, with persistence of fever, myalgias, and prostration, after receiving eight days of treatment with erythromycin . These results suggest that tetracyclines are superior to erythromycin in the treatment of Mediterranean spotted fever.

J Allergy Clin Immunol, 1986 Oct, 78(4 Pt 2), 736 - 42
Therapeutic consequences of drug interactions with theophylline pharmacokinetics; Jonkman JH; Elimination of theophylline from the body occurs mainly (approximately 90%) by biotransformation, followed by excretion of the metabolites . Consequently, drugs affecting microsomal enzyme systems in the liver may alter the elimination of theophylline . Since theophylline has a rather narrow therapeutic window, dose adjustment might be necessary . Of the sympathomimetics, isoproterenol reduces theophylline clearance by 25%, but metaproterenol and terbutaline do not . Of the antibiotics, erythromycin and troleandomycin decrease theophylline clearance by 25% and 50%, respectively . No effect was observed with tetracycline, doxycycline, amoxicillin, cefaclor, and co-trimoxazole . On the other hand, rifampin (antituberculotic agent) increases theophylline clearance by 30% . Corticosteroids (hydrocortisone, methylprednisolone, and prednisone) do not affect theophylline kinetics . Influenza vaccination also has no influence . The antiulcerative agent (H2 antagonist) cimetidine decreases theophylline clearance by 30%, but the agent ranitidine does not have any effect . Oral contraceptives may decrease theophylline elimination by 30% . Barbiturates and phenytoin may enhance theophylline clearance substantially (up to 75%) . If an interaction is expected, careful monitoring of theophylline plasma concentrations is required to optimize the dose.

J Antibiot (Tokyo), 1986 Sep, 39(9), 1304 - 13
Transformation of Streptomyces erythraeus; Yamamoto H et al.; Streptomyces erythraeus strains were transformed efficiently with six different plasmid DNA vectors by a protocol that uses 0.2 mM Ca2+, 5 mM Mg2+ and 10% DMSO to enhance the stability of protoplasts to storage at -80 degrees C and their transformability at 30 degrees C . The primary thiostrepton-resistant (Thior) transformants for most vectors were unstable even when grown selectively . This instability did not appear to be due to incompatibility with indigenous S . erythraeus plasmids . Conversely, stable transformation was not the result of plasmid or host mutations . Transformation instability or plasmid copy number thus prevented successful shotgun-cloning of DNA that complemented the eryD mutation, which blocks the biosynthesis of erythromycin A, because only plasmid DNA without an insert could be isolated from a Thior Ery+ clone.

Biopharm Drug Dispos, 1986 Sep-Oct, 7(5), 479 - 85
Time-dependent inhibition of theophylline elimination by erythromycin stearate; Adebayo GI et al.; The effect of erythromycin stearate at a dose of 1 g daily on theophylline disposition was studied in six healthy adult males . The mean value of 5.46 h for the theophylline half-life after 48 h pretreatment with erythromycin stearate was not significantly different from the control value of 5.24 h . The half-life value of 8.48 h after a 1-week course of the antibiotic, however, represented a significant increase (p less than 0.005) . Theophylline disposition 1 week after the last dose of the antibiotic was not significantly different from the control . It is suggested that therapeutic doses of erythromycin stearate for a week or more could impair the disposition of concurrently administered theophylline . The impairment however, is reversible, being absent a week after the last antibiotic dose.

Antibiot Med Biotekhnol, 1986 Sep, 31(9), 674 - 8
{IR spectral research on erythromycin mono- and dihydrates}; Gusakova GV et al.; The IR spectra of crystalline and amorphous forms of erythromycin monohydrate and dihydrate were investigated and their characteristic spectral features were described . Differences in the system of the intermolecular hydrogen bonds and in the level of perfection of the crystalline structures of the monohydrate and dihydrate were detected . It was shown that both crystallohydrates of erythromycin might exist in two polymorphous modifications . The crystalline structure of the low temperature modification of the monohydrate was of low perfection . At 75-80 degrees C irreversible polymorphous conversion of erythromycin monohydrate and erythromycin dihydrate accompanied by changes in the hydration water state was observed . The crystalline structures of high temperature modifications of the erythromycin crystallohydrates were identical.

Mycopathologia, 1986 Sep, 95(3), 159 - 66
Cutaneous alternariosis: a rare chromohyphomycosis . Report of a case; Di Silverio A et al.; A 66-year-old woman presented 3 groups of scaly granulomatous lesions on the right forearm and elbow of six months duration . Direct examination of the scales showed hyphae and culture in lactrimel medium grew Alternaria sp . considered a contaminant . No improvement was observed after six months of treatment with oral griseofulvin . A second culture using half of a biopsy grew Alternaria sp . again and in histologic examination short pigmented fragments of hyphae surrounded by a granulomatous reaction were seen in the derma . The patient had marked improvement after treatment with erythromycin per os and miconazole topically; an atrophic scar remained as the only sign of the fungal infection.

Am J Clin Pathol, 1986 Sep, 86(3), 348 - 51
Legionella feeleii-associated pneumonia in humans; Palutke WA et al.; Legionella feeleii has been implicated by serologic studies as the causative agent in an outbreak of Pontiac fever and has been recovered from an institutional water source . Pneumonia caused by this agent has not been described previously . The authors have isolated L . feeleii from two immunosuppressed patients with community-acquired pneumonia and from an institutional water source . One patient survived after treatment with erythromycin . The other patient was leukopenic and died of pneumonia . Isolates exhibited typical cultural and biochemical features of L . feeleii and reacted with L . feeleii serogroup 1 antiserum . L . feeleii serogroup 1 is now known to cause not only Pontiac fever but also pneumonia in humans.

J Antimicrob Chemother, 1986 Sep, 18(3), 307 - 15
Antagonistic interactions of macrolides and synergimycins on bacterial ribosomes; Di Giambattista M et al.; The affinity of ribosomes for VS (virginiamycin S, a type B synergimycin) is known to be increased by VM (virginiamycin M, a type A synergimycin) . Erythromycin, a macrolide, displaces ribosome-bound VS in the absence of VM, but is ineffective in its presence . In the present work, the ability of spiramycin and tylosin (macrolide subgroups) derivatives to displace ribosome-bound VS, in the presence and in the absence of VM, has been explored . All macrolides with in-vitro activity displaced ribosome-bound VS: the displacement curves produced by tylosin and spiramycin derivatives virtually overlapped . When VM was added to these systems, displaced VS became readily attached to ribosomes in the case of erythromycin, did not bind appreciably within 20 min incubation in the presence of tylosin, and underwent a slow binding in the case of an N-substituted tylosin . The 16-membered macrolides (leucomycin, spiramycin and tylosin subgroups) can therefore be distinguished from the 14-membered macrolides (erythromycin subgroup) by the antagonistic effect displayed toward VM.

Nucleic Acids Res, 1986 Aug 11, 14(15), 5999 - 6015
Cloning of a cDNA coding for P-450 LM3c from rabbit liver microsomes and regulation of its expression; Dalet C et al.; Liver cytochromes P-450 LM3c in the rabbit and P-450p in the rat are two related forms, inducible by macrolide antibiotics such as triacetyloleandomycin (TAO) and glucocorticoids such as dexamethasone . We prepared a cDNA library from TAO induced rabbit liver mRNA and characterized a cDNA (pLM3c-4.1) that hybridized to pDex 3.22, a cDNA complementary to cytochrome P-450p mRNA . Northern blots of liver poly(A)RNA from untreated or TAO, erythromycin and rifampicin treated animals, revealed two mRNA species of approximately 1700 and 1850 nucleotides in length, that hybridized to LM3c cDNA and to pDEX 3.22 . The level of both mRNAs was increased five fold over control by macrolide antibiotics but unaffected by both phenobarbital and B-naphthoflavone . After 5 days of TAO treatment LM3c mRNA had increased 5 fold while LM3c protein had increased 25 fold . However, the rate of P-450 LM3c gene transcription measured in isolated liver nuclei remained unchanged throughout five days of TAO treatment . We conclude that TAO may induce cytochrome P-450 LM3c by post-transcriptional effects.

Life Sci, 1986 Aug 4, 39(5), 453 - 60
Prevention of the toxicity of erythromycin estolate in the perfused rat liver by endotoxin; Gaeta GB et al.; The possibility that endotoxin pretreatment could prevent the hepatotoxic effects of erythromycin estolate (EE) was investigated using the isolated perfused rat liver . The addition of E . coli endotoxin (25 micrograms/ml) to the perfusate, 30 min prior to EE administration at 150 or 200 microM, significantly ameliorated the decreases in bile and perfusate flow caused by either concentrations of the drug in control liver preparations . This phenomenon was also studied using liver isolated from rats pretreated in vivo with endotoxin for three days . In these preparations, EE at both concentrations did not alter bile flow and caused reductions of perfusate flow which were far less than those observed in untreated control livers . Furthermore, in livers from endotoxin-treated rats EE induced less reduction of bile acid excretion and, at 150 microM, it did not increase the bile to perfusate ratio of sucrose seen in control preparations after the drug, which may be an expression of altered hepatocytic membrane permeability . Since it is known that both endotoxin and EE interact with membranes, it is suggested that the "protective" effects of endotoxin may occur at the membrane level.

Thorax, 1986 Aug, 41(8), 635 - 40
Legionnaires' disease: a review of 79 community acquired cases in Nottingham; Woodhead MA et al.; Seventy nine cases of sporadic, community acquired legionnaires' disease have been reviewed . Annual and seasonal variation in incidence was noted . The mean age of the patients was 53 years and 50 (63%) were male . Pre-existing chronic diseases were present in only 23 (29%), including two patients receiving immunosuppressive treatment . Common symptoms included unproductive cough, dyspnoea, chest pain, headache, confusion, nausea, vomiting, and diarrhoea . Respiratory symptoms were absent, however, in 17 (22%) . Localising chest signs were present in 74 (95%) cases . Frequent laboratory findings included lymphopenia, high erythrocyte sedimentation rate, hyponatraemia, raised urea and creatinine concentrations, abnormal liver function, hypophosphataemia, hypoalbuminaemia, proteinuria, and haematuria . Thirteen patients died (16%), including nine of 20 who received assisted ventilation . The mortality rate in patients treated with erythromycin (11%) was lower than in those who received other antibiotics (23%), but this difference was not statistically significant . Of the features noted on admission, only a high plasma urea concentration was significantly associated with death . Sporadic community acquired legionnaires' disease is a not uncommon disorder, which with appropriate treatment has a prognosis similar to that of other forms of community acquired pneumonia.

Antimicrob Agents Chemother, 1986 Aug, 30(2), 323 - 4
Activity of roxithromycin (RU 28965), a macrolide, against Toxoplasma gondii infection in mice; Chan J et al.; Roxithromycin (RU 28965), an ether oxime derivative of erythromycin, protected mice against a lethal infection with the virulent RH strain of Toxoplasma gondii . Therapy begun 24 h before, 2 h after, and 24 h after infection with 2 X 10(3) tachyzoites protected 90, 80, and 50% of the mice, compared with 0% of untreated controls (P less than 0.05 to 0.001) . Toxoplasma was isolated in less than 20% of surviving roxithromycin-treated mice.

Am J Pathol, 1986 Aug, 124(2), 216 - 25
Characterization of the proteoglycans synthesized by rabbit testis in response to infection by Treponema pallidum; Strugnell RA et al.; Organ cultures of syphilitic and normal rabbit testes were incubated with 35S-sulfate for labeling of proteoglycans . Syphilitic rabbit testes synthesized three macromolecular fractions (I, II, and III) which were not detected in extracts of normal uninfected tissue . The three fractions comprised a larger (approximately 10(6) mol wt) chondroitin sulfate/dermatan sulfate proteoglycan (Fraction I), a smaller (approximately 10(5) mol wt) chondroitin sulfate/dermatan sulfate proteoglycan (Fraction II), and a putative sulfated glycoprotein of Mr 40 kd (Fraction III) . The glycosaminoglycan chains of both proteoglycans eluted with a Kav of 0.45 on Sepharose CL-6B, consistent with a molecular weight of 25,000 . The smaller proteoglycan was not a cleavage product of the larger species . Erythromycin had no significant effect on the synthesis of any of the three macromolecules . In contrast, the synthesis of both proteoglycans was totally inhibited by a 2-hour preincubation with cycloheximide, which suggests that the constitutive "pools" of the two core proteins were small . The putative sulfated 40-kd glycoprotein was insensitive to a 2-hour preincubation with cycloheximide.

J Fam Pract, 1986 Aug, 23(2), 119 - 22
Erythromycin in the treatment of acute bronchitis in a community practice; Brickfield FX et al.; To assess the efficacy of erythromycin in treating acute bronchitis, 52 adults were enrolled in a randomized trial comparing a one-week course of erythromycin with placebo . Among smokers, no difference in outcome was noted . Among nonsmokers, trends favored more rapid resolution of key symptoms in the erythromycin group, but these trends did not generally achieve statistical significance . These results suggest a trial with a larger sample size.

N Engl J Med, 1986 Jul 17, 315(3), 161 - 8
A new Chlamydia psittaci strain, TWAR, isolated in acute respiratory tract infections; Grayston JT et al.; During a 2 1/2-year period, we studied 386 University of Washington students with acute respiratory disease, to determine whether a Chlamydia psittaci strain, here designated TWAR, is an important respiratory pathogen . Serologic evidence of recent TWAR infection was found in 13 students, and the organism was isolated from 8 of these . TWAR infection occurred in 12 percent of the students who had pneumonia (9 of 76), 5 percent of those with bronchitis (3 of 63), and 1 percent of those with pharyngitis (1 of 150) . The TWAR infections occurred throughout the study period . Pharyngitis, often accompanied by laryngitis, was a common first symptom . Clinically, the infections resembled those with Myco-plasma pneumoniae; therefore, the patients were given courses of erythromycin used for the treatment of M . pneumoniae infections . This therapy proved to be inadequate . The limited data available suggest that the TWAR strain is a "human" C . psittaci that is spread from human to human, without a bird or animal host.

J Antimicrob Chemother, 1986 Jul, 18(1), 73 - 82
Kinetics of erythromycin uptake and release by human lymphocytes and polymorphonuclear leucocytes; Dette GA et al.; The uptake of 14C-labelled erythromycin by human lymphocytes and polymorphonuclear leucocytes was studied . Erythromycin was concentrated by the cells . The amount of accumulated erythromycin was correlated with the cell count and was found to increase with alkaline pH and with increasing temperature of the incubation medium . The uptake of erythromycin could be reduced by compounds which inhibit cell respiration, glycolysis and (Na+-K+)membrane ATPase . Furthermore, the uptake was saturable and followed Michaelis-Menten kinetics (Km = 0.7 and 1.6 mM for lymphocytes and polymorphonuclear leucocytes, respectively) . The intracellular concentrations cannot be explained by the principle of non ionic diffusion . It is suggested that erythromycin is actively transported via the nucleoside transport system . The accumulated erythromycin was rapidly released when the cells were washed and re-incubated in antibiotic-free medium . Probably, no strong intracellular binding takes place.

Am Fam Physician, 1986 Jul, 34(1), 81 - 92
Diagnosis and treatment of chlamydial infections; Pruessner HT et al.; The major chlamydial infections are conjunctivitis and pneumonia in infants and urethritis, cervicitis, salpingitis and ocular infection in adults . Tetracyclines are usually the drugs of choice for the treatment of chlamydial infections . Erythromycin therapy is preferred for pregnant women and for neonates with conjunctivitis . Follow-up examination and treatment of sexual partners are required for the control of chlamydial infections.

Drug Intell Clin Pharm, 1986 Jul-Aug, 20(7-8), 601 - 2
Asymptomatic liver injury due to erythromycin stearate; Alcalay J et al.; A 73-year-old woman with rosacea, who had started treatment with erythromycin stearate 2 g/d, developed asymptomatic liver injury . The drug was discontinued and the laboratory findings of liver damage disappeared within 11 days . This is the first report of erythromycin stearate-induced asymptomatic hepatotoxicity.

J Am Acad Dermatol, 1986 Jul, 15(1), 66 - 70
Pityriasis lichenoides in children: therapeutic response to erythromycin; Truhan AP et al.; Fifteen of twenty-two children with pityriasis lichenoides were treated with oral erythromycin . Eleven (73%) had a remission, usually within 2 months . Two others showed partial improvement, and two were unimproved . Seven of the children who experienced a remission were off erythromycin and free of lesions after 2 to 5 months of therapy . A trial of erythromycin as described herein should be considered in children with pityriasis lichenoides before other, possibly more toxic, measures are instituted.

Nucleic Acids Res, 1986 Jun 25, 14(12), 4987 - 99
Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II; Arthur M et al.; We have determined the nucleotide sequence of the ereB gene of plasmid pIP1527 which confers high-level resistance to erythromycin by inactivation in Escherichia coli . The open reading frame of the ereB gene, 1257-bp, was defined by initiation and termination codons and by cloning in vitro . The corresponding protein has a calculated Mr of 48,118 in close agreement with a previous estimation, 51,000, by electrophoresis of minicell extracts in SDS-polyacrylamide gels . The structure of the modified erythromycin was determined by physico-chemical techniques including mass spectrometry, infrared spectrophotometry and 13C nuclear magnetic resonance . The data obtained indicated that like ereA (Ounissi and Courvalin, 1985) ereB encodes an erythromycin esterase . Comparison of the amino acid sequences of the two isozymes did not reveal any statistically significant homology . Analysis of the nucleotide sequence of the ereB gene suggests that this resistance determinant should be exogenous to E . coli.

Biochemistry, 1986 Jun 17, 25(12), 3540 - 7
Localization of virginiamycin S binding site on bacterial ribosome by fluorescence energy transfer; Di Giambattista M et al.; Virginiamycin S, a type B synergimycin inhibiting protein synthesis in bacteria, competes with erythromycin for binding to the 50S ribosomal subunits; the mechanism of action of the two antibiotics is unclear . Energy-transfer experiments between virginiamycin S (which is endowed with inherent fluorescence due to its hydroxypicolinyl moiety) and fluorescent coumarinyl derivatives of ribosomal proteins L7 and L10 have been carried out to locate the binding site of this antibiotic on the ribosome . Previous studies have indicated that two L7/L12 dimers can attach respectively to a strong binding site located on the central protuberance and to a weak binding site located on the stalk of the 50S subunits and that protein L10 is located at the base of the stalk . The distance between ribosome-bound virginiamycin S and a fluorophore located at the strong binding site of proteins L7/L12 (Lys-51 of L7) was found to be 56 (+/- 15) A . Virginiamycin S, on the other hand, was located at a distance exceeding 67 A from the weak binding site of L7/L12 dimers . A fluorophore positioned on the unique cysteine (Cys-70) of protein L10 and ribosome-bound virginiamycin S proved to be more than 60 A apart . From data available on the location of proteins L7/L12 and L10, a model is proposed, whereby the virginiamycin S binding site is placed at the base of the central protuberance of the 50S subunits, in proximity of the presumptive peptidyl transferase center . The binding sites of macrolides and lincosamides (related antibiotics of the MLS group) are expected to be very close to that of virginiamycin S.

Clin Orthop, 1986 Jun, (207), 263 - 9
Variations in the density of bone cement after centrifugation; Skinner HB et al.; Barium sulfate added to bone cement to provide radiopacity has a density about four times greater than that of polymerized radiolucent bone cement . Because centrifugation might make a clinically significant change in the distribution of barium sulfate, this process was studied . Radiolucent and radiopaque Simplex-P bone cement (Howmedica, Inc., Rutherford, New Jersey) were mixed with and without cooling and centrifuged for two or four minutes at 2,000 g or 1,000 g (gravity acceleration) . The density of sections of the hardened bone cement was measured using the Archimedes principle . Erythromycin and colistin were added to cement batches to test whether or not centrifugation affected the distribution of antibiotics . Direct and radiographic observation and density measurements (cooled specimens, 2,000 g, p less than 0.01) verified that barium sulfate does accumulate at the bottom of the centrifugation tubes . Thin sections of the bone cement revealed that only larger particles (20-100 micron) of barium sulfate were deposited at the bottom . No evidence of redistribution of antibiotics after centrifugation was seen . It is recommended that Simplex-P bone cement be reformulated to eliminate concern about inhomogeneities that arise from centrifugation . Further, it is recommended that cooled, centrifuged antibiotic cement be used for long-stem revision hip surgery, where longer setting times are necessary, and room temperature cement for "fresh" hip surgery . A total centrifuge time of two minutes with a 2,000 g maximum force is recommended.

Arch Intern Med, 1986 May, 146(5), 897 - 9
Erythromycin ototoxicity and acute psychotic reaction in cancer patients with hepatic dysfunction; Umstead GS et al.; Two cases of severe hearing loss due to intravenous administration of erythromycin lactobionate are described . Documented, bilateral sensorineuronal hearing loss developed in both patients and gradually improved when the dose of erythromycin was decreased . Neither patient had severe renal dysfunction (documented clearances of 25 to 30 mL/min), but both had hepatic dysfunction with elevated bilirubin levels . Additionally, both were receiving other ototoxic drugs concurrently . Both patients also had an acute psychotic reaction that was temporally related to the ototoxicity and high-dose erythromycin therapy.

J Dermatol Surg Oncol, 1986 May, 12(5), 490 - 1
Nonsurgical management of an electrical burn of the scalp; Shelley ED et al.; The remarkable regenerative capability of the scalp reduces the need for skin grafting in electrical burns of this area . We report on a deep 7.5 cm electrical burn of the scalp which healed completely under conservative management with 20% urea compresses, benzoyl peroxide gel, and systemic erythromycin.

Int J Clin Pharmacol Ther Toxicol, 1986 Apr, 24(4), 167 - 70
Screening for the influence of host factors on warfarin clearance using a single dose single sample procedure; Bachmann K; A single dose, single sample procedure for estimating warfarin clearance for screening purposes was evaluated . Single sample estimates of warfarin clearance, CL/F, were closest to actual values for warfarin clearance, CL/F, calculated from multiple sample data when the sample was collected 120 h after warfarin ingestion . An apparent volume of distribution, V/F, of 0.17 l/kg was used in calculating CL/F . After a single dose of warfarin single sample values of CL/F averaged 0.243 l/h +/- 0.042 (N = 12) which compared well with a multiple sample-based value of CL/F which was 0.243 l/h +/- 0.046 (N = 12) . When an erythromycin pretreatment was started before warfarin ingestion and continued throughout the period of warfarin elimination CL/F decreased to 0.208 l/h +/- 0.047 while CL/F decreased to 0.210 l/h +/- 0.061 . Mean prediction error for CL/F relative to CL/F was -0.001 l/h with a 95% confidence interval of -0.010 to 0.009 l/h . Warfarin is a drug with pharmacokinetic characteristics enabling it to be used in a single dose single sample procedure in screening for host factor influences on its clearance.

J Am Vet Med Assoc, 1986 Apr 1, 188(7), 728 - 9
Cutaneous nocardiosis in a cat; Davenport DJ et al.; A 7-year-old cat was found to have multiple cutaneous lesions caused by Nocardia asteroides infection . The cat was treated successfully with potentiated sulfonamides and a combination of ampicillin and erythromycin.

Biochem Pharmacol, 1986 Mar 15, 35(6), 959 - 66
The binding protein of erythromycin in human serum; Dette GA et al.; Erythromycin binding to human serum albumin and to alpha 1-acid glycoprotein was measured under conditions of binding equilibrium . At therapeutical concentrations of erythromycin the binding to albumin is not saturable . The fraction of total erythromycin bound to alpha 1-acid glycoprotein is proportionally related to the protein concentration and is bound to a single class of binding sites with an apparent association constant Ka = 0.16 X 10(6) M-1 (38 degrees) . About one mole of erythromycin is bound per mole of alpha 1-acid glycoprotein . The binding affinity can be enhanced and vice versa lowered by increasing the concentrations of NaCl and urea, respectively . The semilogarithmic plot of bound/free ratios vs log concentration of NaCl or urea exhibits linear relationships . Erythromycin binding can be competitively inhibited by mersalyl (Ki = 11-16 microM) but not by other SH-reagents or by neuraminidase treatment . A marked reduction of erythromycin binding to alpha 1-acid glycoprotein is seen with dithiothreitol . alpha 1-acid glycoprotein is the main erythromycin binding protein in human serum.

JAMA, 1986 Mar 7, 255(9), 1165 - 7
Carbamazepine-erythromycin interaction . Case studies and clinical significance; Wroblewski BA et al.; Because of significant and seemingly haphazard fluctuations in serum carbamazepine concentrations, we decided to investigate the possible link between erythromycin administration and potential changes in serum carbamazepine concentration . We studied four cases involving this combination . In every case, serum carbamazepine concentrations either rose dramatically (doubled or tripled previous steady-state concentrations) or dropped precipitously once erythromycin therapy was discontinued . In all cases, we report serum carbamazepine concentrations obtained before, during, and after concurrent erythromycin administration . We conclude that the combination of erythromycin and carbamazepine represents a clinically significant drug interaction and should be avoided where possible.

J Clin Psychiatry . 1986 Mar;47(3):147.
A case of erythromycin-induced carbamazepine toxicity; Berrettini WH; A case of serious carbamazepine toxicity as a result of concomitant erythromycin therapy is presented . Carbamazepine competes with erythromycin for metabolism by hepatic microsomal enzymes, resulting in decreased clearance of carbamazepine . Carbamazepine drug interactions will become increasingly important to psychiatrists as this anticonvulsant becomes more widely used to treat affective disorders.

Pediatr Emerg Care, 1986 Mar, 2(1), 10 - 4
Leukocyte counts in children with acute otitis media; Schwartz RH et al.; Peripheral blood leukocyte counts were performed in 167 children with acute otitis media who underwent myringotomy with culture of the middle ear exudate . A markedly elevated (greater than 97th percentile for age) leukocyte count was noted at initial presentation among 28% of these children, and counts exceeded 20,000/microL among 9% . Children older than six years were more likely than younger children to have marked leukocyte (41 v 24%, P less than 0.1) . Children with culture-positive and culture-negative acute otitis media had similar leukocyte counts . There was no difference in frequency of posttreatment leukocytosis between those children who had complete resolution of acute otitis media and those children who had persistent otitis media with effusion . At follow-up 10 to 14 days later, relative leukopenia was observed significantly more often than at initial presentation (13 v 2%, P less than 0.001), and was most common among children two to five years old . Absolute neutropenia was likewise more common at the follow-up than at initial presentation (10 v 2%, P less than 0.01) . Children treated with the fixed combination of erythromycin ethyl succinate-sulfisoxazole acetyl were somewhat more likely to have absolute neutropenia than those children who were treated with amoxicillin, but this difference was not statistically significant (14 v 6%, P less than 0.1) . Acute otitis media, and perhaps the specific antibiotic therapy prescribed for acute otitis media, may exert marked effects upon peripheral blood counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopharm Drug Dispos, 1986 Mar-Apr, 7(2), 163 - 71
Intra- and intersubject variation of erythromycin absorption from single-unit and multiple-unit enteric-coated products; Graffner C et al.; Based on the in vitro dissolution test for erythromycin capsules introduced in USP XX, Suppl . 3, there are no reasons to expect any difference in bioavailability after administration of two enteric-coated products, tablets and pellets in hard capsules . The present results in vivo are contradictory and, following duplicate administrations of the two preparations to 12 volunteers after a standardized breakfast, it is apparent that the multiple-unit, pellets, produce a better reproducibility in absorption both within and between subjects than the single-unit tablets . All subjects attained measurable levels of erythromycin on all occasions after administration of pellets, while levels were below the detectable limit on six out of the 24 occasions tested after administration of tablets . The better reproducibility of serum levels after pellets than after tablets was also shown in a descriptive way and is given as a low median discrepancy value of 23.5 per cent (moderate) compared to 73.2 per cent (large).

Antimicrob Agents Chemother, 1986 Mar, 29(3), 515 - 8
Plasmid-mediated high-level resistance to erythromycin in Escherichia coli; Andremont A et al.; Escherichia coli BM2195 was found to be resistant to high levels of erythromycin . This new resistance phenotype was due to the constitutive synthesis of an erythromycin esterase which inactivates the antibiotic . The gene conferring resistance to erythromycin in this strain is carried on a 61-kilobase self-transferable plasmid, pIP1100, belonging to incompatibility group X.

J Antibiot (Tokyo), 1986 Mar, 39(3), 463 - 8
Effects of a new fluorinated macrolide (P-0501A) and other erythromycins on drug metabolizing enzymes in rat liver; Villa P et al.; The effects of a new fluorinated macrolide (P-0501A) on drug metabolizing enzymes of rat liver were compared with three erythromycins--the base, the stearate and the estolate--after 7 days of dosing (1.36 mmol/kg po daily) . The three erythromycins induced the synthesis of microsomal enzymes, but the products of their metabolism inactivated cytochrome P-450 in the order base less than or equal to stearate less than estolate . N-Demethylation of erythromycin and aminopyrine increased, while O-demethylation of 4-nitroanisole was reduced and hydroxylation of aniline was not changed after in vivo treatment . Pentobarbital sleeping time was prolonged and liver glutathione levels were lower in treated rats than in controls . In contrast to the three erythromycins, P-0501A did not induce the synthesis of microsomal enzymes, did not form an inactive complex with cytochrome P-450 and did not affect mono-oxygenase activities or pentobarbital narcosis.

Br J Dermatol, 1986 Mar, 114(3), 353 - 8
Evaluation of a therapeutic strategy for the treatment of acne vulgaris with conventional therapy; Greenwood R et al.; Four hundred and twenty patients with moderate to severe acne vulgaris were treated with oral erythromycin and topical benzoyl peroxide to determine the optimum dose regimes . Our results show that the response was significantly less in patients with a greater severity of acne, with truncal acne and in those with a higher sebum excretion rate . There was a significantly better clinical result in patients given Ig erythromycin daily than in those given 0.5 g daily (plus topical therapy in both groups) . The relapse rate on stopping antibiotics is also significantly less in patients given I g daily and this dosage did not produce any increase in side effects . We suggest that any patient requiring oral antibiotics should initially be given I g daily of erythromycin (or tetracycline) for up to six months, plus topical therapy.

Am J Vet Res, 1986 Feb, 47(2), 447 - 50
In vitro sulfoxidation of albendazole by ovine liver microsomes: assay and frequency of various xenobiotics; Galtier P et al.; The in vitro biological oxidation of albendazole to its pharmacologically active sulfoxide and its sulfone by ovine liver microsomes has been studied . Sulfoxidation (maximal rate = 0.412 nmole/min/mg of protein, Michaelis constant = 185 X 10(-6) M) was 107 times more potent than formation of albendazole sulfone . The sulfoxidation corresponds to a reduced nicotinamide-adenine dinucleotide phosphate-dependent enzymatic system characterized by a pH optima value around 8 . Flavin adenine dinucleotide-containing monooxygenase could be responsible for this S-oxygenation because of the strong inhibitory effect of methimazole . Albendazole sulfoxidase is inhibited competitively by the related anthelmintic drug fenbendazole (inhibitory constant = 243 X 10(-6) M) and noncompetitively by chlorpromazine (inhibitory constant = 135 X 10(-6) M) . At high concentration, chloramphenicol, erythromycin, nalidixic acid, and hexobarbital are less active inhibitors, whereas dexamethasone acetate significantly enhances the reaction which is not inhibited by either carbon monoxide, griseofulvin, imidazole, phenylbutazone, or proadifen.

J Allergy Clin Immunol, 1986 Feb, 77(2), 330 - 4
Excessive accumulation of mucus in children with asthma: a potential role for erythromycin? A case discussion; Suez D et al.; A case of severe, life-threatening, reactive airway disease with excessive accumulation of mucus was treated with erythromycin . A sudden remarkable improvement in mobilization of mucus was observed after erythromycin treatment . With the addition of aerosol steroids and cromolyn, the incidence of acute respiratory distress diminished considerably . This occurred after ineffective trials of nebulized beta-adrenergic agents, atropine, cromolyn, aerosol beclomethasone, N-acetylcysteine, and high-dose daily prednisone.

Dig Dis Sci, 1986 Feb, 31(2), 157 - 61
Erythromycin induces migrating motor complex in human gastrointestinal tract; Tomomasa T et al.; Fifteen healthy subjects, fasted at least 8 hr, were studied by means of an infused manometric method . Twenty minutes after termination of the natural phase III activity in the duodenum, erythromycin or normal saline was administered intravenously for 15 min . When normal saline (N = 5) was infused, the next migrating motor complex (MMC) was initiated 151.2 +/- 42.1 min after the infusion . On the other hand, when erythromycin was infused at a rate of 1.0 mg/kg/hr (N = 5) or 3.0 mg/kg/hr (N = 5), MMC-like contractions were initiated at shorter intervals, ie, 47.8 +/- 40.9 min (P less than 0.005) or 23.0 +/- 13.0 min (P less than 0.001) respectively . The duration, frequency, amplitude, and migrating velocity of the naturally occurring MMC (N-MMC) were not significantly different from those of the erythromycin-induced contractions except for the duration of the phase III contractions in the stomach; the duration (5.3 +/- 2.2 min) of the erythromycin-induced contractions being significantly (P less than 0.05) longer than that (3.2 +/- 0.9 min) of the naturally occurring MMC . The immunoreactive motilin (IRM) concentration did not increase significantly after the infusion of erythromycin, when compared to that after infusion of normal saline . It is concluded that erythromycin at a dose of 1-3 mg/kg/hr for 15 min during the interdigestive state, similar to motilin, has a significant influence upon the initiation of MMC in the human gastrointestinal tract, but further investigations are required to confirm whether endogenous motilin is involved or not.

J Antimicrob Chemother, 1986 Feb, 17(2), 195 - 203
Macrolides and immunity: effects of erythromycin and spiramycin on human mononuclear cell proliferation; Roche Y et al.; Macrolides are actively concentrated by leucocytes . The dose-effect responses of spiramycin (Sp) and erythromycin (Er) on phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) stimulated human mononuclear leucocytes (MNL) were studied . Cell viability was not altered at any antibiotic concentration (1-100 mg/l) . Both Sp and Er showed dose-related inhibition of the proliferative response of PHA and PWM stimulated MNL . Very marked effects were observed at high antibiotic concentrations and the effects observed at low concentrations (1-10), although small, were also significant . Similar results were observed for the mitogen PWM . A decrease in tritiated thymidine (3H-TdR) incorporation occurred only if Sp and Er were added during the first 8 h of culture . Sp and Er also induced a decrease in tritiated uridine (3H-UdR) uptake . These data suggest that Sp and Er interfered with an early event in the cell cycle . However Sp did not affect PHA binding to MNL . The clinical significance of these findings is discussed.

J Am Acad Dermatol, 1986 Feb, 14(2 Pt 1), 183 - 6
Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne vulgaris . A double-blind study; Gammon WR et al.; The efficacy of erythromycin base (E-Mycin tablets, 333 mg) and the efficacy of tetracycline hydrochloride (Panmycin tablets) were compared in this double-blind, randomized study . Two hundred patients with moderate to moderately severe acne vulgaris were randomly assigned to the study . One hundred patients received 1 gm of erythromycin base by mouth per day for 4 weeks, followed by 333 mg/day for 8 weeks, plus placebo for tetracycline . The second group of patients received 1 gm of tetracycline by mouth per day for 4 weeks, followed by 500 mg/day for 8 weeks, plus placebo for erythromycin . Both drugs reduced acne severity to the same extent . Pustules, papules, and open comedo counts decreased significantly over the 12-week period . Seventy-seven percent of the erythromycin-treated patients and 89% of the tetracycline-treated patients stated that their acne was markedly improved or improved by week 12 . Most of the side effects in patients treated with erythromycin were gastrointestinal symptoms . Among the side effects in patients treated with tetracycline were Candida vaginitis in one patient and pseudotumor cerebri in one patient.

N Engl J Med, 1986 Jan 30, 314(5), 276 - 9
Experience with the routine use of erythromycin for chlamydial infections in pregnancy; Schachter J et al.; In an effort to prevent perinatal acquisition of Chlamydia trachomatis, we offered treatment with erythromycin ethylsuccinate (400 mg four times a day for seven days, given at 36 weeks' gestation) to 184 pregnant women with cervical chlamydial infections . Thirty-two women refused treatment; 24 of their infants were followed and served as the controls . Therapy was discontinued by 5 of 10 women who had gastrointestinal disturbances . Forty-seven women who completed therapy refused infant follow-up; in four (9 percent) of these women, therapy had failed to eradicate the infection . Sixty women and 59 infants completed the entire protocol; 55 (92 percent) of the women had negative cultures for chlamydia at follow-up . Chlamydial infection developed in 4 (7 percent) of the 59 infants of treated mothers, as compared with 12 (50 percent) of the 24 infants of untreated mothers; this difference was significant (P less than 0.001) . With a success rate of 92 percent (98 of 107 patients) in treating maternal infection and with a relatively low intolerance rate (3 percent; 5 of 152), this regimen appears to be an effective, although not ideal, therapy for chlamydial infection in pregnant women . We conclude that in settings in which the prevalence of chlamydia infection is high, a routine program of screening pregnant women for cervical C . trachomatis, followed by treatment of those infected, would be cost effective and would reduce infant morbidity.

J Reprod Med, 1986 Jan, 31(1), 19 - 22
Chlamydial infections in pregnancy; FitzSimmons J et al.; Chlamydia trachomatis is recognized as a common sexually transmitted cervical pathogen that may be transmitted to the neonate at delivery . Neonatal infection may be manifested as conjunctivitis, pneumonitis or both . Additionally, cervical infection may be related to premature rupture of the membranes and premature delivery . Women registering for prenatal care in the first half of pregnancy were cultured for Chlamydia to further define its role as a cause of perinatal complications and to evaluate a method of preventing transmission to the neonate . Positive cultures were obtained in 33 of 221 women evaluated (14.9%) . No significant differences were found in pregnancy or neonatal complications between the groups with positive and negative cultures . Women with positive cultures were treated at 36 weeks' gestation with erythromycin; 18 received an adequate course of therapy . Of these 18, 16 returned with their infants four to eight weeks postpartum . No symptoms of conjunctivitis or pneumonitis were noted at that time, and cultures of the conjunctiva and nasopharynx were negative in all the infants . Thus, surveillance for Chlamydia and treatment late in pregnancy appear to have no adverse impact on pregnancy and effectively block vertical transmission of the organism.

Clin Nucl Med, 1986 Jan, 11(1), 10 - 2
Erythromycin hepatotoxicity . A rare cause of a false-positive technetium-99m DISIDA study; Swayne LC et al.; An unusual cause of a cholescintigraphic, false-positive, erythromycin-induced hepatotoxicity is presented . This occurred in the presence of preservation of hepatic uptake and the normal appearance of gut activity . Serial scintigraphy and serum chemistries documented underlying gallbladder normalcy.

Transplantation, 1986 Jan, 41(1), 52 - 4
Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment; Vereerstraeten P et al.; Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease . Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions . In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized . From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded . During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group . We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.

Ann Med Interne (Paris), 1986, 137(5), 415 - 9
{Intravenous theophylline: adaptation of dosage to blood theophylline levels at admission and to clearance}; Laaban JP et al.; Intravenous infusions of aminophylline expose the patient to the risk of overdosage related to the narrow safety margin of the therapeutic concentrations and to the great individual variability of its excretion . The aim of this study was to evaluate a simplified protocol designed to determine the optimal dose of theophylline based on total body clearance . Forty-four patients (average age: 63 years) admitted with decompensation of chronic respiratory failure (N = 33) or with status asthmaticus (N = 11) were studied . Theophylline was administered initially at a constant rate R0 (mg/kg/h) depending on serum theophylline concentrations on admission T0 (mg/l): R0 = 0.75 - 0.75 T0/20 . Serum theophylline concentrations were measured at the 6th and 12th hours (T6 and T12) for calculation of clearance (Chiou et al . J . Pharmacokinet . Biopharm., 1978, 6, 135-151) and for adjusting dosage R . After 48 hours of treatment at this infusion rate, serum theophylline was again measured (T48) to check the adjustment of the dosage and recalculate clearance . In 11 patients T0 was greater than 15 mg/l (max = 44) and T12 was 10.5 +/- 6.4 mg/l . Theophylline was withdrawn in 6 patients with initial clearances less than 5 ml/kg/h (zero in 5 cases) . T48 was within therapeutic values (10-20 mg/l) in 55 p . 100 of cases (21/38) . Twelve patients had T48 less than 10 mg/l due to an increase in theophylline clearance (+ 80 p . 100 on average) related to improved right ventricular function in 7 cases . In 5 patients T48 was greater than 20 mg/l (max = 27.5) due to a fall in clearance (average -47 p . 100) which could have been caused by administration of erythromycin in 1 case and by dose-dependent kinetics in 2 cases . This protocol which is simple to carry out in practice allows early adjustment of dosage to give effective serum theophylline concentrations in over 50 p . 100 of cases . No serious cases of overdosage were observed, even in patients with high T0 and/or low initial clearances . Under-dosage and overdosage are related to large individual variations in theophylline clearance.

Antonie Van Leeuwenhoek, 1986, 52(4), 295 - 308
The respiratory activities of four Hansenula species; Viola AM et al.; The respiratory activities and the cytochrome spectra from four species belonging to the genus Hansenula have been analysed . The results obtained and described in this paper show that H . glucozyma possesses only the primary, antimycin A-sensitive respiration, H . anomala and H . californica possess primary and secondary (salicylhydroxamate-sensitive) respirations, whereas H . saturnus possesses three respiratory activities (AA-sensitive, SHAM-sensitive, and AA + SHAM-insensitive) . The respiratory activity of H . glucozyma is glucose-repressible, whereas the activities of the other species are not . In addition, antimycin A (AA) and erythromycin (ERY) in the culture media differently inhibit the growth of the four species and regulate the respiratory pathways in the species analysed.

Acta Med Scand, 1986, 220(1), 89 - 92
The significance of the enterohepatic circulation on the metabolism of digoxin in patients with the ability of intestinal conversion of the drug; Norregaard-Hansen K et al.; A cardiac patient had to be given a very high dosage of digoxin to attain therapeutic plasma level . The increased dosage requirement could partly be explained by reduced bioavailability due to intestinal conversion of digoxin . Consequently, the kinetics of the drug was examined before and after erythromycin treatment . Before treatment the determination of the area under the concentration versus time curve (AUC) following a single dose of digoxin given orally or intravenously demonstrated a substantial reduction in the absolute bioavailability . Erythromycin administration during 20 days caused a dramatic rise in AUC when the single oral dose was repeated, exceeding the two AUC obtained prior to initiation of the antibiotic therapy, and the steady state plasma digoxin level was 2-3-fold increased . The fact that the AUC obtained for a single oral dose of digoxin after erythromycin treatment exceeded that obtained when given intravenously before erythromycin indicated the presence of an enterohepatic circulation of digoxin . This may contribute substantially to the elimination of digoxin in patients with the capability of intestinal conversion of digoxin.

Eur J Clin Pharmacol, 1986, 30(4), 505 - 7
Spiramycin has no effect on serum theophylline in asthmatic patients; Debruyne D et al.; Fifteen asthmatic patients receiving a sustained-release theophylline preparation were also treated with spiramycin for at least 5 days . The macrolide antibiotic had no significant effect on the steady-state theophylline concentration, unlike erythromycin and troleandomycin, which belong to the same class of antibiotics . The latter two drugs have different chemical structures and decrease theophylline clearance . Accordingly, spiramycin comedication does not require special serum level drug monitoring or adjustment of the dose of theophylline.

Drugs, 1986, 31 Suppl 3, 109 - 12
Bronchopulmonary infection due to B . catarrhalis . Clinical features and therapeutic response; McLeod DT et al.; A study was made of the clinical features and therapeutic response of 144 patients from whose sputum Branhamella catarrhalis was isolated . Typically, features of bronchopulmonary infection with cough productive of moderate amounts of purulent sputum, fever and dyspnoea were present . Of 74 patients who were infected in the community, 50 required hospital admission . Nosocomial infection occurred in the remaining 70 patients . Most patients had chronic pulmonary diseases or carcinoma bronchus; pneumonia occurred in 12 patients . Acute tracheobronchitis developed in 4 healthy non-smokers after viral illnesses . B . catarrhalis contributed to the death of 8 patients . Overall, 59% of isolates produced beta-lactamase but the proportion had risen to 70% by the end of the study; half of these were community acquired . 41% of patients who were treated initially with ampicillin did not respond . Clavulanic acid plus amoxycillin, co-trimoxazole, erythromycin, tetracycline, cefuroxime and cefotaxime are useful alternative antibiotics . All strains of B . catarrhalis were resistant to trimethoprim.

Chemotherapy, 1986, 32(4), 379 - 82
Effects of erythromycin, josamycin and spiramycin on rat polymorphonuclear leukocyte chemotaxis; Eyraud A et al.; The effects of three macrolide antibiotics were studied on rat polymorphonuclear leukocyte chemotaxis . Rats were given 25 mg/kg twice a day of either erythromycin, josamycin or spiramycin by gastric intubation for 5 days . In all cases, chemotaxis was found to be impaired by 10-20% only . As macrolides are known to reach high intracellular concentrations within polymorphonuclear leukocytes, our results suggest that these antibiotics are unlikely to exert a deleterious influence on the chemotactic response of treated patients.

J Int Med Res, 1986, 14(3), 137 - 41
RV11 (propionyl erythromycin mercaptosuccinate) pharmacokinetics in bronchial secretions; Concia E et al.; The kinetics of RV11 (propionyl erythromycin mercaptosuccinate) in serum and bronchial secretions was investigated in heterogeneous bronchopneumopathic patients requiring diagnostic bronchoscopy . A single oral dose, equivalent to 500 mg of erythromycin base, was administered to all patients and the bronchial secretion and plasma concentrations were determined after 2, 3 and 4 hr . The bronchial secretion and plasma levels consistently exceeded those reported previously for erythromycin per os, suggesting that RV11 may have an unusually high affinity for bronchial secretions in humans . The results of this study also suggested that RV11 might have different kinetics in bronchial secretions and serum, though further studies are required to provide definitive evidence.

Scand Audiol, 1986, 15(1), 41 - 2
Irreversible ototoxic effect of erythromycin; Levin G et al.; Between 30 and 40 cases of reversible ototoxic side effects of erythromycin therapy have been reported previously but to our knowledge none with irreversible adverse reactions . A case of persistent tinnitus after intravenous erythromycin therapy is reported in the following.

Monatsschr Kinderheilkd, 1986 Jan, 134(1), 40 - 2
{Neonatal blennorrhea caused by Chlamydia trachomatis}; Mang K et al.; Chlamydial conjunctivitis was diagnosed in a 5-day-old male newborn . Under treatment with erythromycin the clinical picture of intense swelling of the lid and the copious purulent discharge abated during the following 2 days . Chlamydia trachomatis has become worldwide the most prevalent causative agent of neonatal conjunctivitis.

Vet Hum Toxicol, 1986, 28 Suppl 1, 18 - 20
Use of erythromycin in reducing vertical transmission of bacterial kidney disease; Bullock GL et al.; Studies were conducted in 1980-1982 to determine uptake and retention of erythromycin when eggs of chinook salmon (Oncorhynchus tshawytscha) were water hardened for 1 hr in 2 ppm of the antibiotic as a means of preventing vertical transmission of bacterial kidney disease (BKD) . Although eggs absorbed up to 1 ppm during water hardening, they retained the drug less than 24 hr . Injection of adult female chinook salmon with 11 mg of erythromycin/kg of body weight to prevent prespawning mortality from BKD resulted in deposition of drug in the eggs . Erythromycin persisted in the eggs at concentrations up to 0.6 ppm for 30 to 60 d postinjection--a period that would allow prolonged contact of drug with the causative agent of BKD, Renibacterium salmoninarum . Injection of prespawning female chinook salmon with erythromycin seemingly is potentially more effective than the water hardening of eggs in erythromycin in preventing vertical transmission of BKD.

Postgrad Med J, 1986 Jan, 62(723), 55 - 7
T-cell lymphoblastic lymphoma of the uterus complicated by Chlamydia trachomatis pneumonia; Cunningham D et al.; This is the first documented case of a T-cell lymphoblastic lymphoma arising in the uterus . At presentation, the patient also had a life-threatening pneumonia due to Chlamydia trachomatis which responded to erythromycin and tetracycline . Cytotoxic therapy produced partial tumour regression, but the patient died 14 weeks after diagnosis, probably as a result of intercurrent infection.

Ther Drug Monit, 1986, 8(3), 305 - 17
Carbamazepine drug interactions; Baciewicz AM; Carbamazepine (CBZ) is commonly prescribed as an anticonvulsant or for the pain of trigeminal neuralgia . The potential for clinically important drug interactions exists because CBZ may induce the hepatic metabolism of other drugs or, conversely, other drugs may induce or inhibit the metabolism of CBZ . Studies and case reports demonstrate that CBZ may accelerate the metabolism of phenytoin, phenobarbital (PB), primidone, valproic acid, and warfarin . Likewise, phenytoin, PB, and primidone may increase the hepatic metabolism of CBZ . Inhibition of the metabolism of CBZ has been caused by triacetyloleandomycin, erythromycin, propoxyphene, isoniazid, and cimetidine . Future investigations will document the clinical significance of the CBZ interactions as well as reveal new interactions.

Boll Ist Sieroter Milan, 1986, 65(1), 47 - 53
{Occurrence of drug reactions}; Pastorello E et al.; The aim of this prospective study was to evaluate the incidence of allergic reactions to drugs compared to other kinds of medical emergencies admitted to the main Hospital in Milan during a 6 months period . At the same time we drew a list of drugs most frequently involved in allergic reactions, and a list of the most frequent symptoms . Using special forms, the medical staff collected patients' data: age, history of atopy, identification of the drug causing the reaction, and any previous reactions . Among 11,407 cases of medical emergencies, we found 163 (1.43%) patients showing drug reactions: the mean age was 27.3; 58.90% were female; atopy was present in 16.56% . The drugs most frequently involved were: pyrazon group (22%); ASA (20.86%); penicillin and derivatives (9.20%); sulfa drugs (6.14%); group B vitamins (4.30%); tetanus toxoid (4.30%); hyposensitizing extracts (3.68%); propionic acid derivatives (2.46%); paracetamol (1.84%); indomethacin (1.23%); rifampicin (1.23%); erythromycin (1.23%); glafenine (1.23%); others (17.80%) . Urticaria and/or angioedema were the most frequent symptoms (86.51%), then anaphylactic shock (9.81%) and asthma (3.68%) with regard to anaphylactic shock only 6.20% of the patients had had a previous reaction to the same drug . From these data we can see that the incidence of drug reactions is very low compared to other medical emergencies; penicillin evidenced fewer reactions than expected, while the pyrazon group and ASA confirmed the data from literature.

Chemotherapy, 1986, 32(2), 178 - 82
Management of pediatric patients with otitis media in the emergency department; Nahata MC et al.; We designed a study to evaluate the pattern and appropriateness of the use of drugs and the laboratory data or procedure in 100 patients (age 1 month-17 years) seen in the emergency department with the diagnosis of otitis media during 178 visits . Patients were selected randomly among those seen during 1983 . All patients had usual signs and symptoms of otitis media . Antibiotics prescribed were amoxicillin during 94 visits, trimethoprim/sulfamethoxazole during 33 visits, erythromycin/sulfisoxazole during 14 visits, cefaclor during 5 visits and ampicillin during 3 visits . Due to incomplete dose strength of regimen, only 60% of antibiotic orders were evaluable . The antibiotic doses were within the recommended range in 40% of evaluable cases . Antihistamines and decongestants were used in 28 cases . Analgesics, a variety of ear drops and vinegar irrigation solutions were utilized in 40 cases . Otoscopy was performed in all patients and tympanogram was done in two patients . Ear exudate culture was performed in 5 patients and was found to be positive in 3 cases . All patients were asked to return but only 33 patients came back for a total of 42 follow-up visits to the hospital . Otitis media was reported resolved during 31 visits, resolving during 7 visits, persisting during 3 visits and worsening during 1 visit . The results of this study demonstrate that (1) antibiotic selection was appropriate but the antibiotic orders were incomplete and the doses were frequently out of recommended range; (2) adjunctive drugs seemed to be utilized appropriately; (3) laboratory data and procedures were used appropriately.(ABSTRACT TRUNCATED AT 250 WORDS)

J Hyg (Lond), 1985 Dec, 95(3), 677 - 84
Pneumococcal carriage amongst Australian aborigines in Alice Springs, Northern Territory; Hansman D et al.; In Alice Springs and its vicinity, a single nasal swab was collected from 282 Australian aborigines in May 1981 to determine nasal carriage rates of pneumococci . Each swab was inoculated on blood agar and on gentamicin blood agar . The carriage rates were 89% in children, 39% in adolescents and 34% in adults . In all, 27 serotypes of pneumococci were met with and 15 (4%) of subjects yielded two or more serotypes . In children, types 23, 19, 6, 22 and 6 were predominant (in that order), whereas type 3 was commonest in older subjects . Approximately 25% children and 5% adults yielded drug-insensitive pneumococci . Resistance to benzylpenicillin, tetracycline and co-trimoxazole was met with, resistant pneumococci showed five resistance patterns and belonged to nine serotypes, predominantly types 19 and 23 . All isolates were sensitive to chloramphenicol, erythromycin, lincomycin and rifampicin . The carriage rate of drug-insensitive pneumococci was 100-fold higher amongst children sampled than in non-aboriginal children in Australia.

Eur J Biochem, 1985 Nov 15, 153(1), 131 - 5
About the specificity of photoinduced affinity labeling of Escherichia coli ribosomes by dihydrorosaramicin, a macrolide related to erythromycin; Siegrist S et al.; Photoactivation of the {3H}dihydrorosaramicin chromophore at a wavelength above 300 nm allows the covalent attachment of the macrolide antibiotic to the bacterial ribosome . Bidimensional electrophoresis shows that the radioactivity is mainly associated with proteins L1, L5, L6, L15, L18, L19, S1, S3, S4, S5 and S9 . When photoincorporation of the drug is conducted in the presence of puromycin as effector of {3H}dihydrorosaramicin-binding sites, a decrease in the labeling of most proteins is observed, except for L18 and L19, which are radiolabeled to a larger extent . These results allow us to speculate that L18 and L19 belong to the high-affinity binding site of rosaramicin antibiotic.

Minerva Med, 1985 Nov 3, 76(42), 2019 - 27
{A small epidemic focus of pulmonitis caused by Legionella}; Morini A et al.; A mini-epidemic consisting of 5 cases of Legionnaire's disease treated during september 1983 is reported . These patients shared many of the symptoms distinguishing the most common form of this disease in its severe or very severe form and some characteristic features of this case series are emphasised . It was impossible to trace the source of the outbreak, in spite of the fact that the mini-epidemic took place in an open situation . It is underlined that diagnosis is mainly clinical . The Legionella pneumophila bacteria should always be considered as one of the causal agents of bronchopneumonia, particularly when the following conditions are fulfilled: a) the disease takes the form of a confined, out-of-season, mini-epidemic; b) it is accompanied by multisystemic symptomatology and/or much greater involvement of general conditions that is usually to be expected in normal cases of bronchopneumonia . Since the disease is often fatal, erythromycin or rifampicin treatment should be started upon the slightest suspicion of contagion.

J Antimicrob Chemother, 1985 Nov, 16(5), 589 - 95
A comparison of the in-vitro activity of some 5-nitroimidazoles and other compounds against Giardia intestinalis; Boreham PF et al.; The activities of 11 5-nitroimidazole compounds have been compared against Giardia intestinalis in vitro using a 3H-thymidine incorporation assay . All the compounds were at least equipotent to, or more active than metronidazole with the exception of panidazole . Satranidazole, ronidazole and S75 0400 A were all about five times more active than metronidazole and warrant further study as potential chemotherapeutic agents for man . No major differences in the response to these compounds was found between two stocks of Giard . intestinalis with the exception of flunidazole . Several other antiprotozoal drugs showed activity against Giard . intestinalis . Berberine sulphate, paromomycin sulphate, erythromycin estolate and sulphasalazine, all of which have been used to treat human patients, showed no activity in vitro.

Infection, 1985 Nov-Dec, 13(6), 263 - 6
Efficacy of maternal screening and therapy in the prevention of chlamydia infection of the newborn; McMillan JA et al.; Routine cervical cultures for chlamydia were obtained during the third trimester of pregnancy to identify infected mothers whose infants may also be infected . The effectiveness of maternal erythromycin therapy in preventing disease due to chlamydia among infants born to these women was also assessed . Clinical outcome of treated mothers and infants was compared to that of untreated subjects . Of 1082 women who were cultured, 85 (7.8%) were positive for chlamydia . Erythromycin therapy was prescribed for 38 of these women . Nasopharyngeal/conjunctival chlamydia cultures were obtained from 16 infants of culture-positive, treated mothers and 21 infants of culture-positive, untreated mothers . None of the infants born to culture-positive, treated mothers developed infection with chlamydia, while five of 21 infants of untreated mothers (p less than 0.04) were culture-positive and symptomatic (four with conjunctivitis, one with pneumonia) . On follow-up of the infants born to chlamydia-positive mothers, there was no evidence that chlamydia-infected infants had more frequent episodes of upper respiratory infection and otitis media during the first six months of life . This study demonstrated that diagnosis and treatment of cervical chlamydia infection during the third trimester of pregnancy provides a practical approach to the prevention of infection in the newborn.

Exp Neurol, 1985 Nov, 90(2), 300 - 7
Effect of mitochondrial protein synthesis inhibitors on the trophic action of nerve stump in mice; Komatsu K et al.; We studied the effect of mitochondrial protein synthesis inhibitors on the neurotrophic action of the nerve stump in mice . The sciatic nerve was cut as close to, or as far from the extensor digitorum longus muscles as possible . At 2 and 3 days after denervation, depolarization in the resting membrane potential of muscles with long nerve stumps (14-16 mm) was significantly smaller than in muscles with very short (less than 2 mm) nerve stumps . Chloramphenicol (100 mg/kg, p.o.), erythromycin (4 micrograms/kg, i.p.), ethidium bromide, (10 micrograms/kg, i.p.) or acridine (10 micrograms/kg, i.p.), administered for 2 or 3 days after denervation, increased depolarization in the resting membrane potential of muscles with long nerve stumps; muscles with very short nerve stumps were not affected by these drugs . The administration of chloramphenicol and erythromycin resulted in an earlier increase in the depolarization than ethidium bromide and acridine . Activities of cathepsin B and L of lysosomal proteases in the nerve stumps were enhanced by nerve degeneration; they were not affected by the administration of chloramphenicol or ethidium bromide . We suggest that proteins synthesized in mitochondria of the nerve may participate in trophic actions.

Nucleic Acids Res, 1985 Oct 25, 13(20), 7307 - 26
Evidence for the translational attenuation model: ribosome-binding studies and structural analysis with an in vitro run-off transcript of ermC; Narayanan CS et al.; Several features of the translational attenuation model of ermC regulation were tested . This model predicts two possible secondary structures for the leader of the ermC transcript and requires that the leader contains two Shine-Dalgarno (SD) sequences . The ribosome binding site for a leader peptide (SD1) is predicted to be accessible, whereas that for the rRNA methylase protein that confers erythromycin (Em) resistance (SD2) is sequestered by base pairing . The model suggests that in the presence of inducer (Em), a ribosome stalls while translating the peptide, altering the mRNA conformation, thereby exposing SD2 . The results of our ribosome binding studies demonstrate that SD1 is exposed and binds to ribosomes, whereas SD2 is unavailable . Also, the secondary structure of the 5' region of the ermC transcript was analyzed using methidium propyl-EDTA.Fe (II), T1 nuclease, and nucleases from cobra venom and mung bean sprouts as structure probes . Our results support the previously proposed model for folding of ermC mRNA, and demonstrate that SD1 is single-stranded, while SD2 and its neighboring sequences are largely base paired, consistent with the ribosome-binding results.

Lancet, 1985 Oct 12, 2(8459), 805 - 8
Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria; Looareesuwan S et al.; In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h . All patients were clinically cured--mean fever clearance time 37.8 h (range 24-60), mean parasite clearance time 64.9 h (18-164) . There were no serious toxic effects . 33 patients aged over 5 years with uncomplicated falciparum malaria were given oral amodiaquine dihydrochloride (mean total dose 41 mg base/kg over 3 days) combined with erythromycin estolate (mean dose 48 mg base/kg daily for 5 days) . 2 patients failed to respond . In the other 31 patients mean fever clearance time was 55.9 h (range 10-104) and mean parasite clearance time was 65.4 h (40-120) . In both studies, more than half the patients followed-up had recurrent parasitaemia but reinfection could not be excluded . Parasites isolated from 18 patients were highly resistant to chloroquine in vitro.

Br J Dis Chest, 1985 Oct, 79(4), 393 - 5
Hairy cell leukaemia and Legionnaires' disease; Chowdhury VJ et al.; A 69-year-old man who had recently returned from a holiday in Majorca, presented with haemoptysis and fever . Chest radiograph showed right lower lobe consolidation . A diagnosis of Legionnaires' disease was made . He was treated with erythromycin and made an uneventful recovery.

J Bacteriol, 1985 Oct, 164(1), 425 - 33
Genetic analysis of erythromycin production in Streptomyces erythreus; Weber JM et al.; Streptomyces erythreus produces the 14-membered macrolide antibiotic erythromycin A . The properties of erythromycin A nonproducing mutants and their genetic linkage to chromosomal markers were used to establish the rudiments of genetic organization of antibiotic production . Thirty-three Ery- mutants, produced by mutagenesis of S . erythreus NRRL 2338 and affecting the formation of the macrolactone and deoxysugar intermediates of erythromycin A biosynthesis, were classified into four phenotypically different groups based on their cosynthesis behavior, the type of biosynthetic intermediate accumulated, and their ability to biotransform known biochemical intermediates of erythromycin A . Demonstration of the occurrence of natural genetic recombination during conjugal mating in S . erythreus enabled comparison of the genetic linkage relationships of three different ery mutations with seven other markers on a simple chromosome map . This established a chromosomal location for the ery mutations, which appear to be located in at least two positions within one interval of the map.

Genitourin Med, 1985 Oct, 61(5), 293 - 301
Survival of treponemes after treatment: comments, clinical conclusions, and recommendations; Dunlop EM; Treponemes may persist after treatment that has been accepted as effective; the reasons for this are discussed . Nevertheless, the epidemic of syphilis after the second world war was not followed by an epidemic of late syphilis, and the results of treatment with penicillin are excellent . Neurological signs may progress in some treated patients, and the standard doses of soluble penicillin and any dose of benzathine penicillin (even with added probenecid by mouth) cannot be relied on to achieve treponemicidal concentrations in the cerebrospinal fluid (CSF) . There are no large scale studies of CSF findings after treatment of early syphilis with benzathine penicillin . Standard dosage, such as procaine penicillin G 600 000 international units (IU) by intramuscular injection for 10 days, is the treatment of choice for the patient suffering from uncomplicated early syphilis; this should be preferred to benzathine penicillin, which should only be used when standard treatment as above cannot be given . Treponemicidal concentrations of penicillin should be achieved in the CSF of patients suffering from neurosyphilis by schedules of probenecid by mouth and procaine penicillin by single daily intramuscular injections; treatment should last for 17 to 21 days . Benzathine penicillin should not be used for the treatment of patients suffering from neurosyphilis or from the iritis of late syphilis including that accompanying interstitial keratitis . Treatment for interstitial keratitis should initially be as for neurosyphilis, but in recurrent cases it may have to be prolonged to eradicate Treponema pallidum that is dividing slowly . Doxycycline 200 mg by mouth daily for 21 days provides a supervisable outpatient schedule for patients allergic to penicillin . Cephaloridine (and probably cefuroxime and the new cephalosporins) may be useful for patients who are allergic to penicillin but have not developed anaphylactic allergy . If erythromycin is used for treating syphilis in pregnant women who are allergic to penicillin, then the newborn babies should be treated with penicillin.

Schweiz Med Wochenschr, 1985 Sep 21, 115(38), 1306 - 12
{Drug damage to the liver: role of reactive metabolites and pharmacokinetics}; Lauterburg BH; Metabolism of drugs by the drug-metabolizing enzyme system usually results in the formation of less toxic substances that are readily excreted . A major advance in toxicology, however, has been the observation that the same enzyme system can also activate innocuous drugs into reactive and highly toxic metabolites . Depending on their chemical nature, these metabolites either covalently bind to cellular macromolecules, give rise to toxic oxygen species, or react with membrane lipids to form lipid peroxides . Glutathione, vitamin E and possibly other antioxidants play an important role in protecting the cell from these toxic species . Alteration of a cellular protein by a chemically reactive metabolite may lead to the formation of an antigen and result in an allergic reaction with not only hepatic, but also systemic, manifestations . The formation of toxic metabolites has been postulated in the hepatotoxicity of acetaminophen, isoniazid, halothane, erythromycin and valproic acid . With other drugs, altered pharmacokinetics in the poor metabolizer phenotype and elderly patients may predispose to toxic reactions.

Z Hautkr, 1985 Sep 15, 60(18), 1486 - 505
{Genital mycoplasma infections}; Werni R et al.; Clinical and experimental investigations on the significance of Mycoplasma hominis and Ureaplasma urealyticum have revealed different and contradictory results . Both germs are frequently discovered in young, sexually active persons . Ureaplasma urealyticum might be the cause of some cases of non-gonococcal urethritis . M . hominis seems to be one causative agent of endometritis, salpingitis, parametritis and septicaemia after birth; we do not know yet, however, how often this may be the case . M . hominis may also infect the newborn, e.g., it may cause meningitis and encephalitis . The diagnosis of an infection with mycoplasmas is mainly based on the isolation of the organism, the lack of other pathogens in the lesions, and the demonstration of a significant change of titer of homologous antibodies . Tetracycline is the drug of choice; alternatives are clindamycin for M . hominis and erythromycin for U . urealyticum.

Toxicol Appl Pharmacol, 1985 Sep 15, 80(2), 185 - 92
Characterization of the effects of erythromycin estolate and erythromycin base on the excretory function of the isolated rat liver; Gaeta GB et al.; To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination . EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration . The alterations of the excretory function were only in part due to the decreased perfusate flow . In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile . LS did not affect hepatic excretory functions . However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone . EE, but not EB, increased canalicular permeability to {14C}sucrose as measured by bile to plasma (B:P) ratio . Neither drugs altered {14C}erythritol B:P ratio . In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB . The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.

J Pharm Sci, 1985 Sep, 74(9), 943 - 6
Interspecies correlation of the pharmacokinetics of erythromycin, oleandomycin, and tylosin; Duthu GS; Knowledge of the disposition of macrolides in a single animal species has been insufficient for the prediction of the pharmacokinetics of macrolides in humans . To better understand the species differences in the pharmacokinetics of macrolide antibiotics, the disposition of erythromycin, oleandomycin, and tylosin in several mammalian species was examined . Generally, the serum concentration versus time profiles of these drugs after intravenous administration were described by two-compartment kinetic models and were similar within each species . These drugs were rapidly cleared, resulting in terminal half-lives of less than 2 h . Comparison of their pharmacokinetics showed greater variation in antibiotic disposition among animal species than noted for the differences within a species . When the pharmacokinetic data was fitted to an allometric model, the logarithms of volume of distribution, clearance, and half-life were linearly related to the logarithms of body weight . From these relationships, the human pharmacokinetics of erythromycin and oleandomycin were extrapolated and found to approximate observed human pharmacokinetics.

Toxicol Lett, 1985 Sep, 27(1-3), 73 - 82
Erythromycin estolate-induced toxicity in cultured rat hepatocytes; Sorensen EM et al.; Primary cultures of rat hepatocytes were exposed to several concentrations of erythromycin estolate (EE) . Hepatotoxicity was evaluated using lactate dehydrogenase (LDH) leakage and morphometric analysis of representative populations of cells examined optically . Results of the two techniques provided parallel information: cells exposed to the higher concentrations of EE had significantly greater LDH release and higher percentages of morphologically damaged cells . Planimetric analysis of a second set of hepatocytes showed increasing swelling of cells with increasing concentration of EE . Severe cellular swelling preceded disintegration, as hepatocytes became progressively more damaged by EE.

Proc Natl Acad Sci U S A, 1985 Sep, 82(18), 6310 - 4
Identification of an inducible form of cytochrome P-450 in human liver; Watkins PB et al.; It has not yet been determined whether human liver contains inducible cytochromes P-450 similar to those that catalyze the oxidative metabolism of foreign substances in animals . We carried out immunoblot analyses of liver microsomes isolated from eight patients and found that each contained a cytochrome P-450, termed HLp, that reacted with antibodies directed against P-450p, a rat liver cytochrome that is inducible by the anti-glucocorticoid pregnenolone-16 alpha-carbonitrile, by glucocorticoids, by anti-seizure drugs, and by such macrolide antibiotics as triacetyloleandomycin . In the two patients who received dexamethasone and anti-seizure medications and in the one patient who was given triacetyloleandomycin, the concentrations of immunoreactive HLp and the ability to demethylate erythromycin and/or to convert triacetyloleandomycin to a metabolite that forms a spectral complex with cytochrome P-450 heme (catalytic properties unique to P-450p in rat liver) were significantly higher as compared to the values for patients who received no inducing drugs . We purified HLp to homogeneity and found that it was immunochemically related to P-450p and to its homologue in the rabbit (LM3c), actively demethylated erythromycin in a reconstituted system, exhibited electrophoretic mobility identical to that of P-450p, and shared 57% homology in its NH2-terminal amino acid sequence with that of a pregnenolone-16 alpha-carbonitrile-inducible rat cytochrome P-450 . We conclude that HLp is a human representative of the multigene family of the glucocorticoid-inducible cytochromes P-450.

Arch Intern Med, 1985 Sep, 145(9), 1711 - 3
Rapidly progressive glomerulonephritis accompanying Legionnaires' disease; Wegmuller E et al.; A rapidly progressive, crescentic glomerulonephritis with acute oliguric renal failure occurred simultaneously with legionnaires' disease (LD) in a 52-year-old man . The diagnosis of LD was based on a sixfold rise in indirect fluorescent antibody titer against Legionella pneumophila serogroup 4 . Treatment with erythromycin lactobionate resulted in a clinical resolution of pulmonary manifestations . The impairment of kidney function, however, was progressive and within two weeks led to end-stage renal failure requiring regular hemodialysis . This observation suggests that LD may trigger severe acute glomerulonephritis.

Mol Pharmacol, 1985 Sep, 28(3), 312 - 21
Demonstration in multiple species of inducible hepatic cytochromes P-450 and their mRNAs related to the glucocorticoid-inducible cytochrome P-450 of the rat; Wrighton SA et al.; We have recently demonstrated that P-450p, a form of rat liver cytochrome P-450 inducible by steroids such as dexamethasone and pregnenolone-16 alpha-carbonitrile, by the macrolide antibiotic triacetyloleandomycin, and by phenobarbital, is immunochemically related to and shares 73% NH2-terminal amino acid sequence homology with rabbit cytochrome LM3c . Extending this interspecies comparison we now report that liver microsomes prepared from the rabbit, hamster, gerbil, and mouse contain inducible cytochromes P-450 that resemble P-450p in: (a) converting triacetyloleandomycin to a metabolite that forms a distinct spectral complex with cytochrome P-450 heme, (b) catalyzing the demethylation of erythromycin, and (c) reacting on immunoblots with antibodies directed against P-450p or LM3c . These three characteristics changed in parallel within treatment groups of a given species receiving different inducers of cytochrome P-450 . However, there were striking qualitative and quantitative interspecies differences in the responses to inducers . For example, rifampicin was the most efficacious inducer of LM3c in the rabbit and yet was not at all an inducer of P-450p in the rat whereas pregnenolone-16 alpha-carbonitrile, an inducer in the rat, failed to induce LM3c in the rabbit . Immunoblot analysis of these microsomes revealed in each species except the rabbit a single immunochemically related protein . A second immunoreactive protein was present in microsomes from male and female and rifampicin- and dexamethasone-treated female rabbits . Two cloned cDNAs, which hybridized to a species of liver mRNA directing the synthesis of P-450p in a cell-free translation system, were used to probe Northern blots of liver RNAs . These revealed a single band of hybridizable mRNA in each species (except RNA from the rabbit which gave no signal even under conditions of reduced stringency) that was induced in qualitative proportions to that of the accumulated immunoreactive protein . We conclude that P-450p appears to be conserved in evolution and is represented in each of the species tested by one or more immunochemically related proteins which exhibit similar catalytic activities to those of P-450p.

J Infect Dis, 1985 Sep, 152(3), 500 - 14
Treatment of nonpulmonary infections due to Mycobacterium fortuitum and Mycobacterium chelonei on the basis of in vitro susceptibilities; Wallace RJ Jr et al.; One hundred twenty-three patients with nonpulmonary infections due to Mycobacterium fortuitum or Mycobacterium chelonei were treated by wound debridement and with chemotherapy on the basis of in vitro susceptibilities of the organism . Of 76 patients with infections caused by M . fortuitum, 13 required no therapy or were adequately treated with surgery alone . Patients with active localized disease received single drug therapy (usually with a sulfonamide) for a mean period of 10.6 weeks for cellulitis and seven months for osteomyelitis . Patients with extensive disease received amikacin or amikacin plus cefoxitin (mean, four weeks) followed by a sulfonamide (mean, six months) . The 47 patients with infections caused by M . chelonei received no therapy or were treated with surgery alone (6); with amikacin (10), erythromycin (6), doxycycline (3), or cefoxitin (1); or with amikacin plus cefoxitin followed by cefoxitin alone for a total of 10-12 weeks (20); or other multiple-drug regimens (1) . Surgery was performed on 74 (60%) patients . Schlichter tests or serum drug levels were determined for 81 (66%) patients . Response to therapy was excellent; 68 (90%) infections with M . fortuitum and 34 (72%) with M . chelonei were successfully treated . Cultures became negative within six weeks of chemotherapy, except for sternal osteomyelitis, for which cultures were not negative until up to 14 weeks . Follow-up for a mean period of 12 months following therapy was possible in 80% of cases . Relapses were rare except in patients with disseminated disease, and drug resistance developed in only one patient . These studies demonstrate the value of routine susceptibility testing of these mycobacterial species and the benefit of chemotherapy on the basis of in vitro susceptibilities.

J Chromatogr, 1985 Aug 23, 330(2), 275 - 86
Separation of erythromycin and related substances by high-performance liquid chromatography on poly(styrene-divinylbenzene) packing materials; Kibwage IO et al.; A comparative evaluation of three brands of poly(styrene-divinylbenzene) copolymers, Hamilton PRP-1 (10 micron), Rogel (8 micron) and TSK-Gel (10 micron), as column packing materials for high-performance liquid chromatographic separation of erythromycins is presented . Erythromycins A, B and C, anhydroerythromycin A, erythromycin A enol ether, N-demethylerythromycin A, anhydro N-demethylerythromycin A and N-demethylerythromycin A enol ether were chromatographed . The effects of column temperature, concentration of organic modifier in the mobile phase, concentration of phosphate buffer, the addition of quaternary ammonium salts and pH are described . The best separations were obtained on TSK-Gel with the mobile phase acetonitrile-methanol-0.2 M tetramethylammonium hydroxide pH 8.0-0.2 M phosphate buffer pH 8.0-water (30:15:25:5:25) . PRP-1 and Rogel gave equally good separations but with higher retention volumes.

Xenobiotica, 1985 Aug-Sep, 15(8-9), 767 - 73
Erythromycin toxicity in primary cultures of rat hepatocytes; Villa P et al.; Cultured rat hepatocytes were used to study the toxicity of erythromycin base (EB), erythromycin estolate (EE) and a new fluorinated derivative, (8S)-8-fluoroerythromycin A (EF) . EF was not cytotoxic after 18 h incubation at concentrations up to 8 X 10(-4) M and EE was much more toxic than EB at all concentrations studied . EE toxicity was greater in a serum-free medium and was not increased by induction of cytochrome P-450 with phenobarbitone . In hepatocytes co-cultured with rat-liver epithelial cells EE, but not EF, raised the cytochrome P-450 content and formed stable cytochrome P-450 complexes with about 40% of the haemoprotein . The lack of correlation between cytochrome P-450 content and cytotoxicity suggests that some of the parent erythromycin drugs and not their metabolites are the toxic entities.

South Med J, 1985 Aug, 78(8), 1015 - 6
Suspected interaction: warfarin and erythromycin; Hassell D et al.; The patient described had a markedly enhanced response to warfarin when he was given erythromycin concomitantly . Before the initiation of erythromycin, his warfarin anticoagulation had been well controlled . After withdrawal of erythromycin, his response to warfarin returned to normal . These findings and previously reported clinical and laboratory data lead to the conclusion that, at least in some patients, a potentially serious interaction between erythromycin and warfarin can occur.

Arch Surg, 1985 Aug, 120(8), 957 - 9
Colostomy wound closure; Berne TV et al.; The management of the wound at the time of colostomy closure has been controversial, and wound infection is a frequently cited complication of this procedure . We have conducted a prospective randomized study of colostomy wound closure in 105 patients with three study groups: (1) primary closure (n = 38); (2) primary closure with subcutaneous drains (n = 29); and (3) delayed primary closure (n = 38) . All patients had mechanical bowel preparation with whole gut lavage as well as oral neomycin sulfate/erythromycin estolate and perioperative parenteral cefazolin sodium (Ancef) . Five wound infections (4.8%) occurred . Three infections were in the delayed primary closure group and one infection in each of the other two study groups . No statistical difference in wound infection was demonstrated . On the basis of the findings in this study, we would not recommend delayed primary closure for the management of colostomy closure wounds when careful mechanical and antibiotic preparation has been utilized.

Ann Intern Med, 1985 Aug, 103(2), 205 - 10
Waterborne Legionella bozemanii and nosocomial pneumonia in immunosuppressed patients; Parry MF et al.; From October 1983 to February 1984, five episodes of nosocomial pneumonia caused by Legionella bozemanii occurred in immunosuppressed patients at a 300-bed community hospital . Pulmonary infiltrates were predominantly patchy and present in multiple lobes and bilaterally; cavitation occurred in one patient . Patients responded promptly and completely to treatment with erythromycin and rifampin . Epidemiologic studies showed that all patients had been continuously or recently hospitalized at the same institution . Legionella bozemanii was cultured from four of the five infected patients, from tapwater in patient care areas, from the hospital's hotwater holding tank, and from soil in an area of excavation and new construction on hospital property . Chlorination and heat sterilization of the tank eliminated L . bozemanii from the water and no further cases were seen . This outbreak reaffirms that excavation and construction are risk factors for the outbreak of nosocomial legionella pneumonia and is the first description of nosocomial infection due to L . bozemanii.

Biochem Pharmacol, 1985 Jul 15, 34(14), 2445 - 50
Triacetyloleandomycin as inducer of cytochrome P-450 LM3c from rabbit liver microsomes; Bonfils C et al.; A cytochrome P-450 LM3 isozyme has been isolated and purified to electrophoretic homogeneity from liver microsomes of New Zealand white rabbits treated with TAO . On the basis of N-terminal sequence analysis and Ouchterlony double diffusion experiments, this isozyme appeared to be closely related to P-450 LM3c isolated from control animals and was designated LM3c (TAO) . Anti LM3c (TAO) IgG totally inhibited both erythromycin demethylase and P-450-TAO metabolite complex formation, two monooxygenase activities specifically stimulated by TAO in liver microsomes from male and female rabbits . Moreover, immunoquantitation experiments showed that the level of LM3c (TAO) was increased 10-15 times above control values in liver microsomes from TAO treated male and female rabbits . We conclude that an isozyme identical or closely related to LM3c is the major form of P-450 induced by TAO in rabbit liver microsomes.

Dis Colon Rectum, 1985 Jul, 28(7), 526 - 7
Enterocutaneous fistulization due to Actinomyces odontolyticus . Report of a case; Klaaborg KE et al.; A case of abdominal actinomycosis originating from the sigmoid colon is presented . Actinomyces odontolyticus was isolated; it is a rarity, but should be suspected in the case of a palpable mass and several fistulas developing after a latent period of weeks to months following surgical or inflammatory trauma . The diagnosis is made by anaerobic cultivation . Primary treatment with large doses of penicillin for several weeks may be supplemented by surgery . The strain isolated in the present case was only moderately sensitive to penicillin and was successfully treated with erythromycin.

J Antimicrob Chemother, 1985 Jul, 16 Suppl A, 23 - 34
Functional consequences of binding macrolides to ribosomes; Menninger JR; Macrolide antibiotics bind to the large subunit of procaryotic ribosomes and perturb protein synthesis . There are two competing models to explain this perturbation: (1) shortly after initiation of the polypeptide chain, peptide bond formation and/or translocation is inhibited by the presence of macrolides that are bound in the ribosome 'tunnel' through which the nascent peptide travels; (2) bound macrolides loosen the interaction between the ribosome and peptidyl-tRNA, which therefore, dissociates with a higher probability . The former view cannot easily explain the observed enhancement by macrolides of the dissociation of peptidyl-tRNAs from ribosomes, while the latter view is consistent with the available data . Peptidyl-tRNAs are bound to ribosomes through non-specific and decoding-specific interactions . If macrolides preferentially weaken the non-specific interactions, a greater fraction of the binding energy will be due to decoding-specific interactions and better discrimination between erroneous and correct peptidyl-tRNAs should result . This idea has been tested with low doses of erythromycin, which was observed to counteract the error-inducing effects of streptomycin and of ethanol on the synthesis of beta-galactosidase by Escherichia coli . A specific error near the C-terminus of the enzyme was also responsive to this effect of erythromycin, which therefore must have exerted its influence long after the initiation of the polypeptide synthesis . These results are more easily explained by the idea that the primary mechanism of inhibition of protein synthesis by macrolides is to stimulate the dissociation of peptidyl-tRNA from the ribosome.

Acta Virol, 1985 Jul, 29(4), 329 - 33
The use of molecular hybridization to evaluate the divergence of some altered Rickettsia prowazekii strains; Ogarkova OA et al.; Molecular DNA/DNA hybridization was used to investigate the degree of divergence of different Rickettsia prowazekii strains, namely strain Breinl, the vaccine strain E, its spontaneous erythromycin-resistant mutant, nitrosoguanidine-induced rifampicin-resistant mutant and a variant of strain E with increased virulence upon mouse lung passaging . Hybridization of highly polymerised rickettsial DNAs was carried out on nitrocellulose filters with in vitro labelled fragments of reference DNA of the Breinl strain . Nucleotide composition of the strains was also studied . The results obtained suggest the high degree of homology of nucleotide sequences in DNAs of R . prowazekii strains under study; the existing differences found are within the intraspecies range.

Arch Intern Med, 1985 Jun, 145(6), 1138 - 9
Fatal Legionnaires' disease coincident with initiation of immunosuppressive therapy; Sheldon PA et al.; A fatal relapse of legionnaires' disease occurred coincidental with the initiation of chemotherapy in a patient who had received previous parenteral erythromycin gluceptate therapy for 30 days . Sputum examinations utilizing the direct fluorescent antibody test for Legionella pneumophila suggested persistence of infection during the course of antibiotic therapy . This case suggests that administration of immunosuppressive agents should be delayed in patients whose sputum is positive on direct fluorescent antibody testing, regardless of previous antibiotic therapy.

Am J Dis Child, 1985 Jun, 139(6), 564 - 6
Topical sulfacetamide vs oral erythromycin for neonatal chlamydial conjunctivitis; Heggie AD et al.; Conjunctival and nasopharyngeal cultures for Chlamydia trachomatis were obtained from infants 30 days of age or younger with purulent conjunctivitis . Conjunctival specimens were also tested for other bacterial pathogens and for viruses . Most of the infants studied were black and came from a low-income, urban population . By random assignment infants received either topical treatment with 10% sulfacetamide sodium ophthalmic solution or systemic treatment with oral erythromycin estolate (50 mg/kg/day) . Treatment was continued for 14 days if C trachomatis was isolated from the conjunctivae . Treatment was considered to be effective if conjunctivitis resolved and if follow-up chlamydial cultures of the conjunctivae and nasopharynx were negative at completion of therapy and two to four weeks later . Chlamydia trachomatis was isolated in the absence of other pathogens from the eyes of 37 (73%) of 51 infants with conjunctivitis . Other bacterial pathogens were isolated from four infants (8%) and viruses from none . Chlamydial infection was eradicated from 14 (93%) of 15 infants treated orally . In contrast, persistent conjunctival infection was detected in eight infants (57%) and nasopharyngeal colonization in three (21%) of 14 infants after topical treatment . It was concluded that C trachomatis is the most frequent cause of neonatal conjunctivitis in the low-income, urban population studied; that erythromycin estolate administered orally for 14 days eradicates chlamydial conjunctival and nasopharyngeal infection; and that topical sulfacetamide therapy may result in persistent conjunctival infection and nasopharyngeal colonization.

Biochem Biophys Res Commun, 1985 May 16, 128(3), 1434 - 9
Some erythromycin derivatives are strong inducers in rats of a cytochrome P-450 very similar to that induced by 16 alpha-pregnenolone carbonitrile; Sartori E et al.; Erythromycin derivatives having lost the cladinose moiety, erythralosamine and its mono- and diacetate, are strong inducers of liver cytochrome P-450, better than troleandomycin, in rats . The major cytochrome P-450 form induced by all these macrolides is electrophoretically and immunologically indistinguishable from the major form induced in rats by pregnenolone carbonitrile . This form is particularly able to metabolize the macrolides and to lead to the corresponding 456 nm absorbing cytochrome P-450 metabolite complexes in vivo and in vitro.

J Bacteriol, 1985 May, 162(2), 551 - 7
Chloramphenicol-erythromycin resistance mutations in a 23S rRNA gene of Escherichia coli; Ettayebi M et al.; Two chloramphenicol resistance mutations were isolated in an Escherichia coli rRNA operon (rrnH) located on a multicopy plasmid . Both mutations also confer resistance to 14-atom lactone ring macrolide antibiotics, but they do not confer resistance to 16-atom lactone ring macrolide antibiotics or other inhibitors of the large ribosomal subunit . Classic genetic and recombinant DNA methods were used to map the two mutations to 154-base-pair regions of the 23S RNA genes . DNA sequencing of these regions revealed that chloramphenicol-erythromycin resistance results from a guanine-to-adenine transition at position 2057 of the 23S RNA genes of both independently isolated mutants . These mutations affect a region of 23S RNA strongly implicated in peptidyl transfer and known to interact with a variety of peptidyl transferase inhibitors.

J Antimicrob Chemother, 1985 May, 15(5), 629 - 32
Susceptibility of Bordetella pertussis to doxycycline, cinoxacin, nalidixic acid, norfloxacin, imipenem, mecillinam and rifampicin; Zackrisson G et al.; The susceptibility of Bordetella pertussis to doxycycline, cinoxacin, nalidixic acid, norfloxacin, imipenem (N-formimidoyl-thienamycin), mecillinam and rifampicin was studied by agar and broth dilution . There were discrepancies between MICs registered on solid medium and in fluid medium . There seems to be a need for methodological studies on the antibiotic susceptibility of Bord . pertussis using different techniques . None of the compounds tested seemed to be realistic alternatives to the well documented erythromycin.

Biochim Biophys Acta, 1985 Apr 19, 824(4), 273 - 83
Defective assembly of the mitochondrial ribosomes in yeast cells grown in the presence of mitochondrial protein synthesis inhibitors; Maheshwari KK et al.; The involvement of mitochondrial protein synthesis in the assembly of the mitochondrial ribosomes was investigated by studying the extent to which the assembly process can proceed in the presence of mitochondrial protein synthesis inhibitors erythromycin and chloramphenicol . Yeast cells grown in the presence of erythromycin (2 mg/ml) do not appear to contain any detectable amounts of the mitochondrial small (37 S) ribosomal subunit . Instead, a ribonucleoparticle with a sedimentation coefficient of 30 S was observed; this particle could be shown to be related to the mitochondrial small ribosomal subunit by two-dimensional gel electrophoretic analysis of its protein components . Since the var1 protein is the only mitochondrial translation product known to be associated with the mitochondrial ribosome, our results suggest that this protein is essential for the assembly of the mature small subunit, and that the var1 protein enters the pathway for the assembly of the small subunit at a late step . In at least one strain of yeast the accumulation of the 30-S particle appears to be very sensitive to catabolite repression . When yeast cells are grown in the presence of chloramphenicol instead of erythromycin, assembly of the small subunit appears to be only partially inhibited, and the presence of the 30-S particle could not be clearly demonstrated . This observation is consistent with the fact that in yeast, chloramphenicol inhibits mitochondrial protein synthesis by about 95% only and that the synthesis of the var1 protein appears to be the least sensitive to this inhibition.

Am J Ophthalmol, 1985 Apr 15, 99(4), 465 - 8
Erythema multiforme after use of topical sulfacetamide; Genvert GI et al.; An 8-year-old boy developed erythema multiforme major after topical administration of sodium sulfacetamide for conjunctivitis . He had received systemic treatment with trimethoprim-sulfamethoxazole four months previously without evidence of drug allergy . There was no history of recent exposure to other drugs or evidence of herpes simplex or Mycoplasma infection . After 12 days of treatment with erythromycin ointment, 1% prednisolone eyedrops, systemic prednisone, and intravenous nafcillin, the patient's condition improved dramatically . A slit-lamp examination showed only superficial punctate keratitis . Two months later his visual acuity had improved from 20/200 bilaterally to R.E.: 20/40 and L.E.: 20/30.

J Hyg (Lond), 1985 Apr, 94(2), 151 - 61
The severity of whooping cough in hospitalised children--is it declining?
Johnston ID, Anderson HR, Lambert HP.
Four hundred and sixty admissions for whooping cough to three hospitals between 1974-9 were reviewed . Many children had a long illness . More than half of them had severe or moderately severe coughing spasms and a quarter had pronounced feeding difficulties . The incidence of clinical pneumonia and convulsions was low and there were no deaths . The disease continues to be much more severe in infancy . There was some evidence that the disease declined in severity over the period studied . A number of factors including increased use of erythromycin may have contributed to this change.

Ann Allergy, 1985 Apr, 54(4), 276 - 9
Theophylline-associated seizures in children; Richards W et al.; Four patients are reported who experienced seizures in association with serum theophylline concentrations which were in the mildly toxic range . In three patients, erythromycin administration was a probable factor contributing to the elevated theophylline levels . One patient suffered severe neurologic damage as a result of the seizure.

Ann Thorac Surg, 1985 Apr, 39(4), 308 - 11
Legionnaires' disease after heart transplantation; Fuller J et al.; The cases of 8 heart transplant recipients with legionnaires' disease are reviewed . The diagnosis in each patient was made by fluorescent antibody stains or direct culture of the sputum, transtracheal aspirate, or fine needle aspirate of the lung . All patients were successfully treated with erythromycin alone or in combination with rifampin . Radiographic and clinical variations of legionnaires' disease as seen in the immunocompromised host are presented.

J Infect Dis, 1985 Apr, 151(4), 646 - 9
Neutralizing antibodies to pertussis toxin in whooping cough; Granstrom M et al.; The development and duration of neutralizing antibodies (antitoxin) to pertussis toxin were studied in 38 patients with culture-verified infections due to Bordetella pertussis and one patient with infection due to Bordetella parapertussis . An in vitro neutralization test in microplate culture of Chinese hamster ovary cells was used . An antitoxin response was recorded in 36 patients, the exceptions being two patients treated early with erythromycin (one of whom developed clinical pertussis two years later) and the patient with infection due to B . parapertussis . A long-term follow-up for several months to several years after disease showed maintenance of high antitoxin levels . These results are in accordance with the hypothesis that antibodies to pertussis toxin mediate long-term immunity to whooping cough.

Pharmacotherapy, 1985 Mar-Apr, 5(2), 91 - 4
Oral neomycin sulfate and erythromycin base before colon surgery: a comparison of serum and tissue concentrations; DiPiro JT et al.; It is accepted that the use of oral neomycin sulfate and erythromycin base before colon surgery results in decreased numbers of intestinal bacteria . Intraluminal levels of these agents are reported to be very high, but systemic availability is still debated . The systemic levels were studied in 8 patients undergoing colon surgery . Each patient received neomycin sulfate and erythromycin base, 1 g each, 19, 18 and 9 hours preoperatively . Twelve samples from serum, one from wound muscle and one from the intestinal wall were obtained from each patient in the 26 hours after the initial dose . Considerable variation was observed among levels . The following means were calculated: peak serum levels were 3.4 and 0.59 micrograms/ml, muscle levels were 1.68 and 0.23 micrograms/g and intestinal wall levels were 6.4 and 12.9 micrograms/g for erythromycin and neomycin respectively . Observed times to peak levels were 19 and 12 hours after the initial dose for erythromycin and neomycin respectively . The detectable systemic concentrations that result when these agents are given orally for bowel preparation before colon surgery may contribute to the drugs' efficacy.

Antimicrob Agents Chemother, 1985 Mar, 27(3), 314 - 9
Uptake, accumulation, and egress of erythromycin by tissue culture cells of human origin; Martin JR et al.; The ability of erythromycin A base to penetrate and accumulate in tissue culture cells of human origin was investigated . The antibiotic was highly concentrated by early passage cells of normal bronchus, kidney, liver, lung, and skin and by cancer cells derived from breast, liver, and lung . Intracellular levels 4 to 12 times that of the extracellular milieu were obtained in both early-passage and transformed cells . The total quantity of erythromycin accumulated depended on the extracellular concentration of antibiotic, but the cellular/extracellular ratios were, for the most part, independent of the initial extracellular drug concentration . In all cell types tested, the accumulated antibiotic rapidly egressed when cells were incubated in antibiotic-free medium . Bioactivity assays demonstrated that the expelled drug was unmetabolized, fully active antibiotic . The concentration of erythromycin by a variety of human cell types probably accounts, in part, for the effectiveness of the antibiotic against intracellular parasites such as Legionella and Chlamydia spp.






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