Diagn Microbiol Infect Dis, 1985 Mar, 3(2), 179 - 83 The in vitro activity of sulphones alone and in combination with ampicillin or amoxicillin against Legionella pneumophila and other Legionella spp . including beta-lactamase studies; Jones RN et al.; Penicillinate sulphone beta-lactamase inhibitors, sulbactam, and BL-P2013, were very effective alone and in combination with ampicillin-like penicillins against 34 strains of Legionellae . The minimum concentrations inhibiting 50% of tested isolates (MIC50) results were as follows: sulbactam, BL-P2013, and amoxicillin = 2.0 micrograms/ml; ampicillin = 1.0 microgram/ml; erythromycin = 0.5 microgram/ml; and rifampin = 0.03 microgram/ml . Synergy was commonly observed when the sulphones were combined with ampicillin or amoxicillin, generally reducing the drug minimum inhibitory concentrations (MICs) fourfold to eightfold (synergy rates 85-91%) . BL-P2013 was a slightly more active inhibitor of Legionella spp . beta-lactamase than dicloxacillin or sulbactam. J Am Acad Dermatol, 1985 Mar, 12(3), 526 - 31 An evaluation of a 2% erythromycin ointment in the topical therapy of acne vulgaris; Lesher JL Jr et al.; Two hundred eight patients completed a 12-week, multicenter, double-blind, controlled study comparing a 2% erythromycin ointment to its vehicle . Patients were evaluated by inflammatory lesion counts and Cook acne severity grade at the initial visit and at weeks 2, 4, 8, 10, and 12 . The 2% erythromycin ointment proved to be statistically more effective than the vehicle in reducing lesion counts and acne severity grade at weeks 4, 8, 10, and 12 . The ointment caused few side effects and was well tolerated by most patients. Antimicrob Agents Chemother, 1985 Feb, 27(2), 272 - 4 Isolation and preliminary characterization of erythromycin-resistant variants of Legionella micdadei and Legionella pneumophila; Dowling JN et al.; Erythromycin-resistant Legionella spp . variants were obtained by a single passage of the naturally occurring bacteria on medium containing various concentrations of erythromycin . By disk diffusion susceptibility testing, at least three different phenotypic patterns of cross-resistance to macrolide, lincosamide, and streptogramin B antibiotics were observed among the 26 erythromycin-resistant strains examined. Arch Neurol, 1985 Feb, 42(2), 187 - 8 Carbamazepine toxicity induced by concurrent erythromycin therapy; Carranco E et al.; We describe a 41-year-old woman receiving carbamazepine for epilepsy, in whom concurrent erythromycin stearate administration led to carbamazepine toxicity, including inappropriate antidiuretic hormone syndrome . We review the literature on erythromycin-carbamazepine interaction and discuss the mechanism for such interaction. J Urol, 1985 Feb, 133(2), 290 - 1 Actinomycosis of the prostate; de Souza E et al.; We report a case of actinomycosis of the prostate with symptoms of acute prostatitis . Laparotomy was required to establish an etiological diagnosis . Long-term therapy with erythromycin resulted in a clinical cure. Experientia, 1985 Jan 15, 41(1), 133 - 6 Effects of the virulence plasmid ColV, I-K94 on the sensitivity of Escherichia coli to putative environmental inhibitory agents; de Pacheco CS et al.; Derivatives of Escherichia coli carrying the virulence plasmid, ColV, I-K94 were more resistant than the ColV- parents to phage Mel but were more sensitive to the hydrophobic inhibitors deoxycholate, erythromycin and lysozyme . The basis for these changes in sensitivity has been examined in ColV+ mutants with altered colicin or VmpA protein levels and in ColV+ strains with repressed transfer properties. Ann Dermatol Venereol, 1985, 112(10), 799 - 802 {Quantitative study of the number of Langerhans cells per surface unit in allergic contact eczema}; Gengoux P et al.; The key role of the Langerhans cell (LC) in the immune response and particularly in allergic contact dermatitis is well documented . At first, we determined in the epidermis of the forearm by a non-sensitized adult volunteer, the variations in the density of LC (number/mm2), following the application of various chemicals: nickel sulphate 5 p . 100; erythromycin base 2 p . 100, 2,4-dinitro-1-chlorobenzene (DNCB) 0.02 p . 100 in white petrolatum . Measurements were made at 6, 24 and 48 hours . In a second stage, the volunteer was sensitized to DNCB and a similar study was performed after application of DNCB 0.02 p . 100 at 6 and 24 hours . Normal skin was used as control . The epidermis was obtained by using the suction blister method: LC were identified by the enzymatic ATPase technique and by the immunocytological OKT6 technique . Surfaces were determined by means of a computerized digital tablet . Results obtained with the ATPase technique cannot be interpreted . The density of LC determined by the OKT6 is not significantly modified when the various chemicals are applied on the skin of the non-sensitized volunteer . After sensitization to DNCB, the number of LC is significantly increased after 6 hours of application of DNCB 0.02 p . 100 but not after 24 hours . Further studies are needed to confirm these preliminary observations. Drug Chem Toxicol, 1985, 8(4), 219 - 37 Comparison of dantrolene sodium with erythromycin estolate using primary cultures of rat hepatocytes; Sorensen EM et al.; Using primary cultures of parenchymal hepatocytes as a model system, the cytotoxic potential of dantrolene sodium (DS) was compared with that of erythromycin estolate (EE)--a known hepatotoxin . Parallel morphological and functional comparisons were made, following 4-, 8-, or 24-h exposures of hepatocyte cultures, using phase contrast microscopy and lactate dehydrogenase (LDH) leakage, respectively . Four-hour exposures of cultures to rather low concentrations of EE (i.e . 50 microM) resulted in cellular necrosis and significantly elevated LDH release . As the concentration of this hepatotoxin was increased, the changes were more pronounced . However, even 4- or 8-h exposures of cultures to a maximum of 100 microM DS did not affect LDH leakage or morphological integrity, although marginally detectable morphological changes did not occur at the highest concentration after 24-h . The value of using primary parenchymal hepatocyte cultures as a model system for the assessment of xenobiotic-induced hepatotoxicity was confirmed. Gene, 1985, 35(3), 259 - 70 An erythromycin-resistance gene from an erythromycin-producing strain of Arthrobacter sp; Roberts AN et al.; A gene (ermA) coding for a presumed erythromycin-resistance (ErR) determinant from an Er-producing Arthrobacter sp . strain (NRRLB3381) was isolated from a gene bank in phage vector lambda 2001 by probing with a Streptomyces ErR gene . Strongly hybridizing fragments were subcloned and the appropriate segments sequenced . The ermA gene is 76 mol% G + C in content and specifies a protein of 340 aa with an Mr of 37454 . S1 nuclease mapping and primer extension identified the putative promoter, which resembles the consensus sequence of Escherichia coli promoters particularly in the -10 region . A potential ribosome-binding site (RBS) (AGGAG) was also located . Unexpectedly, the majority of in vivo ermA transcripts detected were only 245 nt long, suggesting that expression of ErR may be regulated post-transcriptionally . Substantial homology is observed between the predicted aa sequences of the ermA-coded protein and the products of three other ErR determinants, from organisms that do not produce Er. Eur J Clin Pharmacol, 1985, 28(2), 231 - 3 Effect of concomitant food intake on absorption kinetics of erythromycin in healthy volunteers; Hovi T et al.; The steady state absorption of erythromycin from enteric-coated pellets of erythromycin base was compared with that from enteric-coated tablets in a randomized, two-way cross-over study in 24 healthy adult volunteers . A higher mean individual peak concentration (p less than 0.01), and a greater mean area under the serum concentration-time (0-8 h) curve (AUC, p less than 0.01) was produced by the enteric-coated pellets, when the preparations were administered 1 hour before breakfast . No significant differences in the kinetic parameters between the two preparations were observed when they were taken during a non-standardized breakfast, as concomitant food intake was found to reduce both the peak levels and the AUC-values (p less than 0.01) produced by the pelleted preparation. J Antimicrob Chemother, 1985 Jan, 15(1), 17 - 22 Determination of the activity on Legionella of eight macrolides and related agents by comparative testing on three media; Bornstein N et al.; It has proved difficult to develop a standard method for the determination of minimum inhibitory concentrations (MICs) of antibiotics against the Legionellaceae . A major obstacle has been the inactivation of certain antibiotics by components of Charcoal Yeast Extract agar, especially charcoal . To determine the MICs of eight macrolides and related agents (erythromycin, spiramycin, oleandomycin, josamycin, midecamycin, lincomycin, clindamycin and pristinamycin) for 36 strains of Legionella, we used two charcoal-free media: Buffered Yeast Extract agar and Buffered Antibiotic Medium no . 1 (BAM1), the latter having been developed in our own laboratory . The inhibitory effect of charcoal was most marked on josamycin and pristinamycin . This effect was absent on the charcoal-free media, which both, however, inhibited spiramycin . BAM1 agar seemed the better of the two charcoal-free media as it gave more consistent growth . The most active agents were josamycin (0.06-0.25 mg/l), pristinamycin (0.06-0.5 mg/l) and erythromycin (0.12-0.5 mg/l) . Midecamycin (0.12-1 mg/l) and spiramycin (1-5 mg/l) also had useful activity. Curr Genet, 1985, 9(8), 627 - 40 The origin of mutant cells: mechanisms by which Saccharomyces cerevisiae produces cells homoplasmic for new mitochondrial mutations; Backer JS et al.; Haploid yeast cells have about 50 copies of the mitochondrial genome, and a mutational event is unlikely to affect more than one of these at a time . This raises the question of how such cells, or their progeny, become fixed (homoplasmic) for the mutant alele . We have tested the roles of six hypothetical mechanisms in producing erythromycin-resistant mutant cells: (i) random partitioning of mitochondrial genomes at cell division; (ii) intracellular selection for mtDNA molecules of one genotype; (iii) intracellular random drift of mitochondrial allele frequencies; (iv) intercellular selection for cells of a particular mitochondrial genotype; (v) induction of mitochondrial gene mutations by the antibiotic used to select mutants; and (vi) reduction in the number of mitochondrial genomes per cell by the antibiotic . Our experiments indicate that intracellular selection plays the major role in producing erythromycin-resistant mutant cells in the presence of the antibiotic . In the absence of the antibiotic, the combined effects of random drift and random partitioning are most important in determining the fate of new mutations, most of which are lost rather than fixed . Our experiments provide no evidence for mutation induction or ploidy reduction by erythromycin. Gene, 1985, 35(3), 271 - 8 Nucleotide sequence of the gene ereA encoding the erythromycin esterase in Escherichia coli; Ounissi H et al.; We have cloned and determined the nucleotide sequence of the gene ereA of plasmid pIP1100 which confers high-level resistance to erythromycin (Em) in Escherichia coli . The gene was defined by initiation and termination codons and by in vitro insertion-inactivation into an open reading frame (ORF) of 1032 bp corresponding to a product with an Mr of 37 765 . However, the enzyme, an Em esterase, displayed an apparent Mr of 43 000 upon electrophoresis of a minicell extract on the SDS-polyacrylamide gels . The G + C content (50.5%) of the gene ereA and the preferential codon usage in its ORF suggest that this resistance determinant should be indigenous to E . coli. Allerg Immunol (Leipz), 1985, 31(2), 67 - 78 {Effect of drugs on granulocyte motility}; Schmidt D et al.; The in-vitro influence of drugs on the chemokinesis and chemotaxis of neutrophils was investigated in order to prevent additional drug-induced motility impairment of cells in cases of already existing host defense disorders and for an eventual specific treatment of motility defects . Granulocyte motility is unimpaired by penicillin, ampicillin, carbenicillin, streptomycin, nystatin, and cyclophosphamide . The chemokinesis and chemotaxis of neutrophils are inhibited by erythromycin, oxytetracycline, doxycycline, chloramphenicol, hydrocortisone, g-strophanthin, digoxin, and digitoxin and in higher concentrations also by sulfonamides, gentamycin, prednisolone, methylprednisolone, dexamethasone, and phenylbutazone . Chemotaxis is selectively or rather more inhibited than chemokinesis by amphotericin B, griseofulvin, vinblastine++, trifluoperazine, and promethazine . Granulocyte motility is, however, stimulated by ascorbic acid, potassium thiocyanate, levamisole, lithium, and metofenazate. FEBS Lett, 1985 Jan 1, 179(1), 37 - 40 tRNA binding to programmed ribosomes increases the ribosomal affinity for tuberactinomycin O; Yamada T et al.; The binding of 14C-labelled tuberactinomycin O was analysed in equilibrium dialysis cells . The ionic conditions and the concentration of the labelled drug used in the binding assays allowed the binding of just one drug molecule per non-programmed ribosome . Under these conditions, the occupation of the ribosomal P-site by deacylated tRNAPhe in the presence of poly(U) increased the amount of {14C}tuberactinomycin O bound by a factor of two . Kanamycin, gentamicin and neomycin reduced the binding of tuberactinomycin O, whereas chloramphenicol, tetracycline, streptomycin and puromycin had no effect . A stimulation of the binding of tuberactinomycin O was found upon addition of erythromycin. Diagn Immunol, 1985, 3(4), 177 - 81 Modifications of the lymphocyte transformation test in a case of drug-induced cholestatic hepatitis; Victorino RM et al.; We analyzed several factors that might influence the ability to detect lymphocyte sensitization to a drug by the lymphocyte transformation test in a patient with erythromycin ethylsuccinate cholestatic hepatitis . Weak lymphocyte reactivity to the drug was demonstrated in standard conditions, but this could be substantially increased in the presence of a prostaglandin inhibitor, providing evidence for the presence of prostaglandin-producing suppressor cells . In contrast, no evidence for short-lived suppressor cells influencing the drug reactivity was found . Reactivity to "drug metabolite containing serum" could by recorded when reactivity to the drug itself had disappeared . Such modifications of the lymphocyte transformation test may be of help in the in vitro diagnosis of drug hypersensitivity. Dev Biol Stand, 1985, 61, 281 - 8 Changes within the genus Bordetella influenced by phages; Mebel S et al.; Bordetella phages give rise to changes in the important phenotypic properties of all three Bordetella species . The changes depend on the phage system used . The treatment of Bordetella parapertussis with phages from B . pertussis led to toxic clones with manifold combinations of agglutinogens specific for all three Bordetella species . Under the influence of B . pertussis phages clones are formed which differ phenotypically from the recipient strain . Some of these clones are sensitive to some phages . In addition, the converted strains were able to propagate in the brain tissues of mice and gave rise to paralytic symptoms or death . Adhesive and hemagglutinating activities were detected in the converted strains and biochemical properties of the converted strains changed in comparison to the recipient strain . The sensitivity of converted strains to antibiotics was investigated and the tolerance of converted strains to erythromycin was used as a marker of conversion . As to their most striking features the converted strains resembled wild strains of B . bronchiseptica isolated from rabbits . While it was not possible to show the ability of pertussis phages to propagate in strains of homologous species by the agar layer method, pertussis phages did adsorb maximally on strains of B . pertussis. Rev Mal Respir, 1985, 2 Suppl 1, S39 - 44 Pharmacodynamic and pharmacokinetic interactions of almitrine bismesylate; Campbell DB et al.; Repeated administration of almitrine bismesylate, 50 mg b.i.d., to six healthy volunteers for 14 days did not alter any of the kinetic parameters of antipyrine, a test compound which measures the hydroxylating capacity of hepatic drug metabolising enzymes . Similarly, almitrine has no effect on the absorption, distribution or elimination of either erythromycin or digoxin, thus, it is unlikely that drug-kinetic interactions are likely to be important in clinical practice . Arterial oxygen tension (PaO2) is significantly increased (p less than 0.05) in 34 chronic bronchitic patients administrated almitrine bismesylate, 50 mg b.i.d . for 3 months . This improvement in hypoxia (9%) is negatively related to the initial PaO2 (p less than 0.01) and positively related to almitrine plasma concentrations (p less than 0.05) . Thus, for each 100 ng X ml-1 increase in drug levels, there is an approximate 2 mmHg increase in PaO2, but there is a suggestion that levels greater than 800 ng X ml-1 may reduce or inhibit activity . The results suggest that the hypoxic state of the individual may modulate the activity of almitrine and influence the drug levels, but further work is required to substantiate these preliminary findings. S Afr Med J, 1984 Dec 22-29, 66(25), 955 - 8 Chemoprophylaxis with erythromycin stearate or amoxycillin in patients with chronic bronchitis--effects on cellular and humoral immune functions; Ras GJ et al.; Twenty-six patients aged between 27 and 71 years with chronic bronchitis were divided into a control group of 6 and two groups of 10 patients each who received either erythromycin stearate or amoxycillin 1500 mg/d for 2 weeks and 1000 mg/d for 12 weeks thereafter . Immunological function tests were performed before starting chemotherapy and thereafter at 2 weeks and 14 weeks . Clinical evaluations and lung function tests showed no significant changes in any of the groups during the study period . In the control group no changes in cellular and humoral immune functions were noted . In the group receiving amoxycillin decreased responses of lymphocytes to the mitogen phytohaemagglutinin were observed after 14 days . In the erythromycin-treated group, increased polymorphonuclear leucocyte (PMNL) motility and mitogen-induced transformation were observed at 14 days but these increases were not statistically significant . In this group the markedly depressed PMNL migration found in 3 individuals before treatment improved considerably . These results indicate that chemotherapy and chemoprophylaxis with either amoxycillin or erythromycin stearate do not compromise the host immunodefences. Can Med Assoc J, 1984 Dec 15, 131(12), 1449 - 52 Excipients and additives: hidden hazards in drug products and in product substitution; Napke E et al.; The excipients and additives in drug formulations have been described as inert because they do not have an active role in the prevention or treatment of particular ailments . This has led to the misconception among physicians, pharmacists, drug manufacturers and the public that excipients are harmless and unworthy of mention . In fact, pharmacists are allowed to substitute drug formulations, without regard to the excipients, as long as they ensure that the active ingredients in the substitute are the same as those in the formulation prescribed . The inappropriateness of the term inert is becoming increasingly apparent as evidence of adverse reactions--some fatal--to excipients mounts . The likelihood that some "active" constituents, particularly erythromycin, have been blamed for such reactions deserves to be investigated . The public deserves to be better protected . For example, the United States has legislation requiring complete labelling of all food, drugs and cosmetics that incorporate more than one ingredient, no matter how innocuous the constituents are believed to be . In Canada, drug manufacturers are not even required to share this information with physicians or pharmacists when they introduce a new drug or reformulate a product already being marketed, nor are pharmacists required to disclose the contents of formulations that they prepare in the absence of commercially available products. Br J Vener Dis, 1984 Dec, 60(6), 387 - 9 Erythromycin stearate in treating chlamydial infection of the cervix; Hunter JM et al.; A total of 157 women attending departments of genitourinary medicine were treated for chlamydial infection of the cervix with erythromycin stearate 500 mg twice a day . Chlamydiae were eradicated from the cervix in 64/80 women treated for seven days and in 51/77 women treated for 14 days . In 12 of those treated for seven days and 15 of those treated for 14 days, reinfection was the probable cause of reisolation after treatment . The possibility of latent infection with Chlamydia trachomatis could not be excluded in five women, but was not more likely to occur with the shorter treatment course . Erythromycin stearate 500 mg twice daily for seven days appears to be an effective regimen for the treatment of uncomplicated chlamydial infection of the cervix. Arch Intern Med, 1984 Dec, 144(12), 2413 - 4 Warfarin interaction with erythromycin; Sato RI et al.; The drug interaction between warfarin and erythromycin is not well known . We report a case in which erythromycin was observed to markedly potentiate warfarin anticoagulation, resulting in hemorrhage in a patient treated for Legionella pneumonia . The morbidity of this drug interaction is enhanced in elderly patients who have infection accompanied by anorexia and/or fever and who are receiving intravenous erythromycin . The well-documented, temporal relationship established erythromycin as the interacting drug. Am J Physiol, 1984 Dec, 247(6 Pt 1), G688 - 94 Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog; Itoh Z et al.; The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs . It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50-100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum . The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration . The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions . Like motilin, EM stimulated motor activity only during the interdigestive state . We conclude that EM induces IMC associated with the release of endogenous motilin in the dog. Am J Med, 1984 Dec, 77(6), 1105 - 7 Ocular and pericardial involvement in Legionnaires' disease; Friedland L et al.; Legionnaires' disease can exhibit protean extrapulmonary manifestations . Pericardial involvement is rare and has been described in three case reports . A patient is described with Legionnaires' disease and pericardial and ocular involvement, an entity that has not been reported previously . This patient was successfully treated with intravenous erythromycin with resolution of his pericardial effusion and ophthalmologic findings. Rhinology, 1984 Dec, 22(4), 247 - 54 Treatment of acute maxillary sinusitis . Erythromycin base and phenoxymethyl-penicillin (penicillin V); von Sydow C et al.; One hundred patients with acute maxillary sinusitis have been studied . The diagnosis was made clinically and confirmed radiologically, using a roentgenological 6-point score for mucous membrane thickening and secretion . Fifty patients in each group were treated with either erythromycin base or phenoxymethyl-penicillin (penicillin V) . The roentgenological state of each sinus was classified on the 1st, 5th, 10th, and 15th day, giving an objective evaluation of the treatment effect . There was no significant difference between the two treatment modes as to therapeutic outcome, and the results are compared with those of a larger material of 1220 patients with acute maxillary sinusitis studied in the same way at Lundby Hospital since 1970 (25 different treatment modes). Otolaryngol Head Neck Surg, 1984 Dec, 92(6), 678 - 84 Erythromycin ototoxicity: analysis and conclusions based on 22 case reports; Haydon RC et al.; Although the majority of patients receiving erythromycin experience no hearing loss, certain patients are susceptible . Erythromycin ototoxicity data were analyzed on 20 patients from 13 reports in the English language literature as well as on two patients from the University of Missouri-Columbia . Patients were classified with respect to age, sex, premorbid diagnosis, renal/hepatic function, type of erythromycin used, dosage, duration of therapy, and route of administration . The following auditory effects were considered: onset of symptoms, degree and configuration of hearing loss, and recovery of hearing . The factors which, when combined with the use of high-dose erythromycin (greater than or equal to 2 gm/day), might place patients at risk for erythromycin ototoxicity are preexisting renal or hepatic disease, age (elderly), and perhaps being female . With knowledge of the predisposing factors and auditory effects, the clinician can more easily recognize hearing loss caused by erythromycin and properly counsel referring physicians and affected patients. J Antibiot (Tokyo), 1984 Dec, 37(12), 1692 - 6 Enzymic hydrolysis of erythromycin by a strain of Escherichia coli . A new mechanism of resistance; Barthelemy P et al.; Escherichia coli BM2195 is highly resistant to erythromycin by inactivation of the antibiotic . We have determined the structure of the modified antibiotic by physico-chemical techniques including mass spectrometry, infrared spectrophotometry, 13C nuclear magnetic resonance, and circular dichroism . The results obtained indicate that E . coli BM2195 resists erythromycin by the production of an erythromycin esterase which hydrolyzes the lactone ring of the antibiotic. Arch Intern Med, 1984 Dec, 144(12), 2373 - 5 Legionnaires' disease and hairy-cell leukemia . An unfortuitous association? Cordonnier C, Farcet JP, Desforges L, Brun-Buisson C, Vernant JP, Kuentz M, Dournon E. Four cases of legionnaires' disease were diagnosed by specific serologic tests in a group of 33 immunocompromised patients admitted to the same hematologic department for acute febrile pneumonitis . The underlying disease of these four patients was hairy-cell leukemia (HCL) in three cases and allogeneic bone marrow transplantation in the other . This article stresses the enhanced susceptibility of patients with HCL to Legionella pneumophila and discusses its possible causes, especially monocyte deficiency . We propose the use of erythromycin as part of the initial empiric antibiotic therapy in immunocompromised hosts with acute pneumonitis until the results of specific serologic tests or isolation of L pneumophila is obtained. Z Hautkr, 1984 Dec 1, 59(23), 1623 - 34 {Double-blind group comparison of topical meclocycline, erythromycin and placebo in the treatment of papulo-pustulosa acne}; Rozman TA et al.; Ten institutions participated in a controlled clinical trial in order to evaluate the efficacy of topical meclocycline and erythromycin in comparison to placebo with regard to papulopustular acne . Both drugs had been incorporated in the same galenic formulation that served as placebo . The vehicle employed in this study guaranteed equally favorable drug relies for both preparations . At the end of the trial, 419 patients could be evaluated for efficacy . As impartial criterion for evaluation, the number of inflammatory lesions on the right side of the face was counted before and after three months of treatment . In addition, we recorded the patients' and physicians' overall judgment at the end of the study . As compared with placebo, meclocycline as well as erythromycin brought about statistically significant improvement already after two months of treatment . After three months, the results were statistically very highly significant (p less than 0.001) . At any time of the study, there could not be demonstrated any difference between the two groups treated with meclocycline and erythromycin. Nucleic Acids Res, 1984 Nov 26, 12(22), 8313 - 8 Erythromycin and spiramycin resistance mutations of yeast mitochondria: nature of the rib2 locus in the large ribosomal RNA gene; Sor F et al.; Two linked genetic loci, rib 2 and rib 3, of yeast mitochondrial genome are the sites of mutations that confer resistance to erythromycin and/or spiramycin . We have examined two mutations at the rib 2 locus . Mutation ER354 was found at the nucleotide position 3993 of the large ribosomal RNA gene; it corresponded to a C to G transversion leading to a double resistance to erythromycin and spiramycin . Mutation SR551 was found also at the same position, but the C was replaced by a T, conferring resistance to spiramycin only . Rib 2 and rib 3 are 836 base pairs apart on the gene sequence, but are very close to each other in the secondary structure of ribosomal RNA. Res Commun Chem Pathol Pharmacol, 1984 Nov, 46(2), 207 - 17 Single dose phenytoin clearance during erythromycin treatment; Bachmann K et al.; The effects of erythromycin on the single dose kinetics of phenytoin (PHT) were studied in eight healthy, male volunteers in a crossover study . PHT was administered in a single, oral 300 mg dose either alone or after 5 days of a 7 day erythromycin regimen . Erythromycin base (333 mg) was taken orally every 8 hr . PHT concentrations were measured in plasma collected at 0, 2, 4, 8, 12, 24, 36, and 48 hr after PHT administration and in saliva at 48 hr . PHT was assayed by a polarized immunofluorescent technique . Mean (+/- SD) control values for PHT intrinsic clearance, CLint/F; volume of distribution, V/F; and half-life, t 1/2 were 0.028 (+/- 0.009) 1 X hr-1 X kg-1, 0.97, (+/- 0.33) l/kg, and 27.3 (+/- 12.4) hr, respectively . During erythromycin treatment CLint/F was 0.026 (+/- 0.011) 1 X hr-1 X kg-1, V/F was 0.87 (+/- 0.23) l/kg, and t 1/2 was 31.2 (+/- 26.1) hr . None of the mean values changed significantly due to erythromycin treatment (p greater than 0.05) . Estimates of intrinsic unbound PHT clearance, CL'int/F, based upon the 48 hr salivary PHT values were 0.403 (+/- 0.170) 1 X hr-1 X kg-1 and 0.352 (+/- 0.152) 1 X hr-1 X kg-1 for the control and erythromycin phases, respectively (p greater than 0.05) . When intrinsic unbound PHT clearance, CL'int/F, was calculated from CLint/F using a mean free PHT fraction, fu, of 0.069 a good correlation between CL'int/F and CL'int/F could be shown . Evaluation of the interaction on the basis of multiple plasma sample data and single salivary sample data led to the same conclusion . Even though erythromycin failed to significantly decrease mean PHT clearance, occasionally large changes in PHT clearance accompanying erythromycin treatment provide sufficient incentive to closely monitor patients taking both drugs. J Clin Pharmacol, 1984 Nov-Dec, 24(11-12), 523 - 7 Influence of bariatric surgery on erythromycin absorption; Prince RA et al.; Seven adult, morbidly obese patients scheduled for bariatric surgery were studied in an identical manner preoperatively and postoperatively . Six patients underwent gastroplasties, and one patient underwent a gastric bypass procedure . A single 250-mg dose of erythromycin as a Filmtab was administered orally after an overnight fast . Multiple venous blood samples were collected over a 12-hour period . After surgery, each patient had a decrease in peak concentration and an increase in the time to reach peak concentration compared to presurgery values . Mean peak concentration was reduced from 1.04 micrograms/ml preoperatively to 0.55 micrograms/ml postoperatively, and the mean time to peak increased from 3.9 hours to 6.7 hours . Mean weight-corrected AUC was reduced 41 per cent, with two patients having no detectable serum levels postoperatively . The results suggest that the erythromycin product evaluated is of questionable value for use in bariatric surgery patients. Pathol Biol (Paris), 1984 Nov, 32(9), 965 - 8 {Osteoarthritis and tenosynovitis of the finger due to Mycobacterium intracellulare . A case report and review of the literature}; Demoulin L et al.; The authors present one case of osteo-arthritis and tenosynovitis of the right forefinger due to Mycobacterium intracellulare, in a 61-year old woman . The treatment consists of a synovectomy of the finger's proximal interphalangeal joint and of the sheath of the flexor tendons and a drug regimen associating erythromycin and cotrimoxazole for 2 1/2 months . This therapy proves successful, as the patient is clinically cured . A literature review records 19 similar osteo-articular and peri-articular infections due to the Mycobacterium avium-intracellulare group, reported during these last 25 years. J Biochem (Tokyo), 1984 Nov, 96(5), 1559 - 64 Inversions in mitochondrial DNA of a petite mutant of yeast; Wakabayashi K et al.; Mitochondrial DNA of an erythromycin-resistant petite mutant of yeast, E734, showed physical maps of inversion, which occurred between two cross-over sites in the fragments Hae A and Hae B . The pair of cross-over sites was inferred to be accommodated within a repeat unit of E734 mtDNA during petite mutation by joining two fragments excised from non-adjacent region of wild type mtDNA. Chest, 1984 Nov, 86(5), 675 - 80 A comparative study of Legionella micdadei and other nosocomial acquired pneumonia; Rudin JE et al.; The clinical and laboratory characteristics of 27 patients during an outbreak of pneumonia due to Legionella micdadei were reviewed . These patients were compared with a group of 46 patients who had other causes of nosocomial acquired pneumonia . Patients with pneumonia due to L micdadei typically had nosocomial acquisition of the disease and were immunosuppressed . Symptoms, physical findings, and laboratory tests were nonspecific; however, patients with pneumonia due to L micdadei had an increased frequency of pleuritic pain in the chest, dyspnea, cough, and changes in mental status compared to the nosocomial group . Direct fluorescent antibody staining and culture of sputum and other respiratory secretions established the diagnosis of infection with L micdadei . Unusual features included dual infections in three patients and pulmonary cavitation in five patients . Therapy with erythromycin, when instituted early, decreased mortality . Trimethoprim-sulfamethoxazole, used as alternative therapy in patients with persistent infection, was also curative . Because of the high mortality associated with a delay in diagnosis, it is important to consider the diagnosis of pneumonia due to L micdadei in immunosuppressed patients. Presse Med, 1984 Oct 6, 13(35), 2133 - 5 {Neonatal syphilis despite erythromycin treatment of the mother}; Hartmann JF et al.; A one-month old infant whose mother had been treated with erythromycin during pregnancy exhibited signs of severe congenital syphilis with collapse requiring admission to an intensive care unit . Erythromycin has low placental transfer and other treatments would have probably been more adequate . Some authors advocate the use of the latest tetracyclines and doxycycline could also be administered . The WHO's recommendations that all children born of mothers who were not treated with penicillin should receive this antibiotic after birth is still valid. J Fam Pract, 1984 Oct, 19(4), 497 - 501 Multicenter study of family physician prescribing; Carter BL et al.; The objective of this study was to examine differences in prescribing characteristics among four Iowa family practice offices, each associated with family practice residency programs . This prospective study collected data over a four-month period, utilizing duplicate, carbon-copy prescriptions . The prescriptions were tabulated according to individual drug and therapeutic categories . Differences in prescribing frequency among offices were analyzed using chi-square 2 X 2 contingency tables . The number of prescriptions written at each office (designated A through D) were as follows: A, 1,034; B, 1,449; C, 2,965; and D, 2,335 . The most frequently prescribed drug category was systemic antibiotics, followed by cough, cold, or allergy products, analgesic and anti-inflammatory drugs or muscle relaxants, diuretics, and topical anti-infectives . There were statistically significant differences in the frequencies of these categories among offices . The most frequently prescribed drug was amoxicillin at offices A, B, and C, and erythromycin at office D . There were statistically significant differences in the frequencies of the top ten drugs at each office . From these data the family practice faculty and clinical pharmacists can identify therapeutic areas that may require additional educational emphasis for the resident. Int J Androl, 1984 Oct, 7(5), 383 - 8 A controlled trial of the use of erythromycin for men with asthenospermia; Baker HW et al.; A double-blind crossover controlled trial of Erythromycin was conducted in 78 men with asthenospermia (mean pretreatment sperm concentration greater than or equal to 20 X 10(6)/ml and motility less than 60%) . Sperm motility increased above the pretreatment mean after the first one month course of treatment for both Erythromycin (7.9 +/- 2.6% P less than 0.01; mean +/- SEM) and the placebo group (7.5 +/- 2.2% P less than 0.01) and also after the second one month course of treatment, given one month after the first, for both Erythromycin (11.8 +/- 2.7% P less than 0.001) and placebo (11.4 +/- 2.8% P less than 0.001) . There was no significant difference between the changes in sperm motility with Erythromycin and placebo . Twelve pregnancies occurred during the four month trial time--eight with Erythromycin and four with placebo (chi 2 = 2.51 P = NS) . It is concluded that in infertile men, sperm motility tends to increase spontaneously with time . Erythromycin treatment has no significant effect on semen quality and a larger trial will be required to determine if Erythromycin increases fertility. Infection, 1984 Sep-Oct, 12(5), 345 - 8 Absorption of erythromycin stearate and enteric-coated erythromycin base after a single oral dose immediately before breakfast; Schreiner A et al.; To study the absorption of different preparations of erythromycin in the fasting state, 500 mg stearate (tablets) and 500 mg base (enteric-coated pellets) were given immediately before a standardised breakfast to 24 young, healthy volunteers in an open, random, cross-over trial . The serum peak concentration appeared earlier and was higher after intake of the stearate tablets than after intake of the base pellets; however, there was no difference in the area under the serum concentration vs . time curves (AUC) between the two preparations . The bioavailability of erythromycin stearate in tablet form and of erythromycin base in the form of enteric-coated pellets thus appears comparable when taken on an empty stomach. Drug Intell Clin Pharm, 1984 Sep, 18(9), 692 - 6 Evaluation of drugs used in the prophylaxis of neonatal conjunctivitis; Zola EM; Administration of silver nitrate 1% solution into the eyes of the newborn has proven effective in the prophylaxis of gonococcal neonatal conjunctivitis . Silver nitrate, however, is not active against Chlamydia trachomatis, the most common cause of neonatal conjunctivitis . Also, silver nitrate commonly is associated with substantial chemical irritation . For these reasons, alternative agents are receiving increasing attention . Recently, erythromycin 0.5% and tetracycline 1% ophthalmic ointments were recommended by the Centers for Disease Control Venereal Disease Control Division for prophylaxis of neonatal conjunctivitis . Erythromycin has proven at least as effective as silver nitrate for gonococcal prophylaxis, can prevent chlamydial conjunctivitis in infants born to Chlamydia-positive mothers, and is associated with minimal complications . Clinical studies, however, demonstrating significant differences between erythromycin and tetracycline ophthalmic ointments are lacking . Well-controlled clinical studies comparing silver nitrate, erythromycin, and tetracycline prophylaxis are needed to determine the relative effectiveness of these agents. Am J Public Health, 1984 Aug, 74(8), 835 - 6 An outbreak of community-acquired Legionnaires' disease pneumonia; Helms CM et al.; In October 1981, an outbreak of 29 cases of community-acquired pneumonia occurred among adult residents of Johnson County, Iowa . Retrospective study revealed 12 cases (41 per cent) had laboratory evidence of Legionnaires' disease (LD) . No significant differences in clinical or epidemiological features were found between LD cases and the other pneumonias in the outbreak . All LD cases received erythromycin; one case died for a case-fatality rate of 8 per cent . The outbreak's focus could not be identified. J Protozool, 1984 Aug, 31(3), 475 - 9 Effects of mitochondrial protein synthesis inhibitors on the incorporation of isoleucine into Plasmodium falciparum in vitro; Blum JJ et al.; Plasmodium falciparum was grown in human erythrocytes in vitro and the effect of chloramphenicol, erythromycin, and tetracycline on growth and maturation of the parasites and on their ability to incorporate {3H}isoleucine into protein was observed . Exposure of rings to high concentrations of chloramphenicol had little effect on subsequent maturation of the rings whereas brief (4 h) exposure of trophozoites caused a dose-dependent inhibition of subsequent ring formation . Incorporation of {3H}isoleucine into protein was not affected during at least 6 h of exposure to high concentration of the three drugs examined, but appreciable inhibition was observed after 21 h, with chloramphenicol being the least effective inhibitor . These results suggest that there is a stage-specific effect of inhibition of mitochondrial protein synthesis on subsequent development and that the mitochondria are essential for growth and development even though they lack a functional Krebs cycle. J Antimicrob Chemother, 1984 Aug, 14(2), 157 - 63 The pharmacokinetics and tolerance of oral erythromycin stearate compared with erythromycin ethylsuccinate: implications for preventing endocarditis; Shanson DC et al.; Serum concentrations of erythromycin were monitored in 11 healthy adult volunteers following single dose oral administration of erythromycin stearate, 1.5 g, and erythromycin ethylsuccinate 3.0 g . Peak serum concentrations occurred at 30 min to 2 h after the dose, usually at 1 h . Mean serum peak erythromycin concentrations (standard deviation) were 4.8 mg/l (+/- 2.0) following 1.5 g erythromycin stearate and 2.8 mg/l (+/- 1.4) after 3.0 g erythromycin ethylsuccinate . Both types of erythromycin frequently caused mild gastrointestinal side-effects but there were fewer side-effects associated with erythromycin ethylsuccinate . However, because of the increased serum erythromycin concentrations between 1 and 6 h after the dose of the stearate preparation compared to ethylsuccinate we recommend erythromycin stearate, 1.5 g, as the preferred loading dose, given 1 h before the dental procedure, for preventing endocarditis in susceptible patients allergic to penicillin. Chemioterapia, 1984 Aug, 3(4), 255 - 7 Comparative clinical study of josamycin and erythromycin in pertussis; Torre D et al.; Forty children with pertussis were treated in a randomized trial with josamycin or erythromycin . The pathogen was isolated in 15 cases by immunofluorescent antibody (IFA) technique . The clinical response of both groups was good and comparable . A 15-day course of therapy was able to eradicate the pathogen in all but one patient . Three patients showed minor side effects: diarrhea (2), rash (1). Antibiotiki, 1984 Aug, 29(8), 576 - 80 {Hydrogen bond and acid-base interactions in erythromycin solutions}; Gusakova GV et al.; The association and conformational structure of the molecule of erythromycin in solutions of CCl4, C2Cl4 and CHCl3 were studied by the IR spectra in the region of v OH and vC = O . The analysis of the concentration and temperature changes showed that the erythromycin association was accounted for by the hydrogen linkage of OH .. . O = C to the ester group . In the monomer molecule of erythromycin, all hydroxyl groups participated in the intramolecular hydrogen linkage . Band 3513 cm-1 belonged to the OH group in the five-membered cycles of OH .. . O . Components 3500, 3530 and 3560 cm-1 of the wide band vOH were assigned to the cycles with OH .. . N and OH .. . O linkages of a larger size . The association was due to a break in a part of the intramolecular hydrogen linkages . Addition of strong acceptors of proton-hexamethanol and trioctylphosphinoxide to the solution resulted in attenuation of these bands and appearance of a strong band vOH of the erythromycin-acceptor complexes . In the presence of monochloroacetic acid in the solution of CHCl3 stoichiometric protonization of erythromycin was observed . The total acid was in the form of anion (vaCO-2 1610 cm-1) up to a ratio of 1:1 . The protonization proceeded according to the nitrogen atom since the antibiotic spectrum in the region of vC=O did not change . Propionic acid titrated erythromycin in methanol solution and in mixtures of water and methanol up to a ratio of 1:5 (v/v) . However, in the solution of CHCl3 equilibrium between the neutral and ionized molecules of the acid was seen. Yale J Biol Med, 1984 Jul-Aug, 57(4), 453 - 64 The clinical spectrum and treatment of Lyme disease; Steere AC et al.; Lyme disease was recognized as a separate entity because of close geographic clustering of affected children in Lyme, Connecticut, with what was thought to be juvenile rheumatoid arthritis . It then became apparent that Lyme disease is a complex, multisystem disorder . The illness usually begins in summer with erythema chronicum migrans and associated symptoms (stage 1) . Weeks to months later, some patients develop neurologic or cardiac abnormalities (stage 2), and weeks to years later, many patients develop intermittent attacks of arthritis (stage 3), which may become chronic, with erosion of cartilage and bone . Patients with severe and prolonged illness have an increased frequency of the B-cell alloantigen, DR2 . For patients with early Lyme disease, tetracycline appears to be the most effective drug, then penicillin, and finally erythromycin . High-dose intravenous penicillin is effective for the later stages of the disease. Cutis, 1984 Jul, 34(1), 55 - 6, 58 Perioral dermatitis; Coskey RJ; Perioral dermatitis is an eruption that has a characteristic perioral localization . It usually responds rapidly to systemic tetracycline and low-potency topical corticosteroids . In a study of eighty-seven patients it was found that systemic erythromycin is also effective and that in some instances topical antibiotics combined with 1 per cent hydrocortisone may be effective. Am J Med Sci, 1984 Jul-Aug, 288(1), 2 - 12 Sporadic Legionnaires' disease: clinical observations on 87 nosocomial and community-acquired cases; Helms CM et al.; To add information about sporadic Legionnaires' disease, 87 cases of L . pneumophila pneumonia were reviewed . Twenty cases were nosocomial infections and 67 cases were community-acquired . Most cases (64%) occurred between July and October . The mean age of patients was 51.4 years and males outnumbered females 2.5:1.0 . Thirty-one percent of patients were receiving corticosteroid, immunosuppressive, or antineoplastic chemotherapy when illness began . Immunosuppression at onset of illness was more common in nosocomial infections (90%) than in community-acquired infections (14%) . Seventy percent of patients had underlying diseases . Malignancies, renal failure, and transplantation were the most common conditions underlying nosocomial infections . Chronic lung disease and malignancies were the most common diseases underlying community-acquired infections . The case-fatality rate in nosocomial infection (70%) was greater than that in community-acquired disease (22%) . Clinical, laboratory, and radiologic features of the cases were examined . Illness ranged from mild to severe . Extrapulmonary findings of encephalopathy and renal failure were more common in fatal than in non-fatal cases . Indirect immunofluorescent and microagglutination antibody responses plateaued by the fourth week of illness . Twenty-nine patients died . The case-fatality rate of patients receiving erythromycin (6%) was less than that of patients receiving penicillin (36%), ampicillin (28%), cephalosporin (32%), or aminoglycosides (41%) . Despite erythromycin therapy, the case fatality rate for nosocomial L . pneumophilia pneumonia was unacceptably high (25%). J Bacteriol, 1984 Jul, 159(1), 381 - 4 Regulation of a macrolide resistance-beta-galactosidase (ermC-lacZ) gene fusion in Escherichia coli; Kirsch DR et al.; A fusion constructed between the putative attenuator plus the first 219 nucleotides of the ermC (erythromycin resistance) structural gene and a 5' terminally deleted lacZ gene produced a moderate, basal level of beta-galactosidase which was increased by erythromycin addition . Another construction containing an intact ermC gene in addition to the fusion produced lower levels of beta-galactosidase, suggesting that the ermC gene product exerts negative feedback control on expression. Z Hautkr, 1984 Jul 1, 59(13), 888 - 93 {Experiences in dermatologic practice with combined external treatment of acne with benzoyl peroxide and erythromycin}; Gerny H; Fifty patients consulting my dermatologic practice because of facial papulopustular acne varying from grade I up to grade IV (according to Plewig and Kligman) have been treated with benzoyl peroxide and erythromycin . The more severe cases (grades III and IV) received additional treatment, such as tetracycline or cyproterone acetate internally and/or, externally, removal of comedones as well as UV-A-radiation . As a result, 68 percent of all patients showed remission in at least 70 percent of their inflammatory skin eruptions. Clin Pharmacokinet, 1984 Jul-Aug, 9(4), 309 - 34 Pharmacokinetic drug interactions with theophylline; Jonkman JH et al.; PIP: Since up to 90% of a theophylline dose is biotransformed, drugs influencing microsomal enzyme systems in the liver may affect the elimination of theophylline . Other integrated mechanisms (e.g., hepatic uptake) may also be altered by concurrent administration of other drugs . Whatever the mechanism, the interaction may be sufficient to necessitate adjustment of the theophylline dosage, preferably guided by plasma theophylline determinations . Comedication with phenobarbitone may require an increase in theophylline dose by about 30% due to increased clearance resulting from enzyme induction . Similarly, with phenytoin and carbamazepine, a dose increase of about 40-50% may be required . In the case of rifampicin, isoniazid, or sulphinpyrazone comedication, an increase in dose of theophylline by about 20-25% may be needed . On the other hand, other drugs decrease theophylline clearance, making a reduction in the dose of concurrent theophylline advisable; with usual doses of erythromycin, propranolol, and isoprenaline (isoproterenol), a reduction of about 25% is needed; with cimetidine and oral contraceptive by about 30% or more; and with triacetyloleandomycin (troleandomycin), by about 50% . In high doses, the xanthine oxidase inhibitor allopurinol can also retard theophylline elimination, and a reduction of the theophylline dose by about 20% may be advisable . Conflicting results have been reported on the influence of frusemide (furosemide) and influenza vaccines, while data regarding the effect of corticosteroids, benzodiazepines, and verapamil on theophylline kinetics are not yet conclusive . Many drugs, however, appear not to significantly affect theophylline clearance . Some are from the same therapeutic group as the drugs mentioned above and offer clinical alternatives for coadministration with theophylline . Examples of drugs not found to have a significant effect on theophylline pharmacokinetics are ranitidine, josamycin, midecamycin, amoxycillin, tetracycline, cephalexin, cefaclor, orciprenaline, metoprolol, antacids, medroxyprogesterone acetete, metoclopramide, and metronidazole . Most of the drugs discussed in this review appear to not affect the volume of distribution of theophylline significantly . author's modified Ann Intern Med, 1984 Jul, 101(1), 63 - 73 Theophylline reassessed; Bukowskyj M et al.; Advances have recently been made in understanding the pharmacokinetics of theophylline . To correlate the new knowledge of theophylline pharmacokinetics with the drug's current status in therapy, we have critically reviewed the relevant investigations of the last 5 years . We consider data on its presumed mechanisms of action, factors affecting its clearance, its use in pregnancy, treatment of overdoses, and important drug interactions . Theophylline clearance is decreased by concomitant use of erythromycin, cimetidine, high-dose allopurinol, oral contraceptives, and caffeine . Clearance is increased by concomitant use of phenobarbital and phenytoin . Newly discovered actions of theophylline include dose-dependent improvement of diaphragmatic contractility, augmentation of ventilatory response to hypoxia, and sleep disturbances (especially with high-dose treatments) . Points clinically relevant to the daily use of theophylline derivatives and the importance of sustained-release preparations are discussed . Theophylline continues to play a major role in therapy for reactive airways disease. Proc Natl Acad Sci U S A, 1984 Jun, 81(12), 3607 - 11 Identification of a site on 23S ribosomal RNA located at the peptidyl transferase center; Barta A et al.; 3-(4'-Benzoylphenyl)propionyl{3H} Phe-tRNA bound to the peptidyl site of the ribosome is photo-crosslinked exclusively to 23S RNA on irradiation at 320 nm . The site of reaction has been identified both by hybridization and primer-extension experiments as uridine-2584 and uridine-2585, located within the central loop of domain V according to the secondary structure model of 23S RNA . The fact that the covalently crosslinked tRNA retains its ability to form a peptide bond, together with the proximity of this site to the position of several mutations leading to chloramphenicol or erythromycin resistance strongly argue that this region of the 23S-like rRNAs is an integral component of the peptidyl transferase site . On the basis of these results, and from comparative analysis of the 16 available large subunit rRNA sequences, we propose a model for the functional organization of the peptidyl transferase site involving interaction of domains II and V of 23S rRNA. Clin Rheumatol, 1984 Jun, 3(2), 243 - 6 Severe vascular spasm due to erythromycin-ergotamine interaction; Francis H et al.; We report a case of ergotism due to the interaction of erythromycin with a small dose of ergotamine tartrate (2 mg) . Besides severe peripheral vasospasm with dysaesthesiae there was transient renal ischaemia . Recovery occurred after several weeks without sodium nitroprusside therapy . Cases previously reported in the literature are reviewed. J Assoc Off Anal Chem, 1984 May-Jun, 67(3), 532 - 4 Spectrophotometric determination of bromhexine hydrochloride in pharmaceutical preparations; Santoro MI et al.; The presence of an aromatic primary amino group in bromhexine HCl enables the use of diazotization-coupling, according to the classic Bratton-Marshall method, for its analysis in pharmaceutical preparations . Spectrophotometric parameters were established for standardization of the method, including statistical analysis of data . Substances such as potassium guaiacolsulfonate, ampicillin, cephalexin, oxytetracycline HCl, amoxycillin, and erythromycin ethylsuccinate do not interfere with the determination . The precision of the method is about 2.0%. J Infect, 1984 May, 8(3), 251 - 5 Pneumonia due to Legionella bozemanii: first report of a case in Europe; Mitchell RG et al.; Pneumonia caused by Legionella bozemanii and acquired by a 75-year-old man while on holiday in Majorca is described . This appears to be the first report of such a case from Europe . Despite artificial ventilation and intravenous erythromycin the patient died . The causative organism was isolated from part of the lung obtained post mortem . Examination of a single sample of serum by means of an indirect immunofluorescence test gave a titre of 32 in respect of L . bozemanii antigen. J Infect Dis, 1984 May, 149(5), 714 - 8 Erythromycin uptake and accumulation by human polymorphonuclear leukocytes and efficacy of erythromycin in killing ingested Legionella pneumophila; Miller MF et al.; Studies were undertaken to demonstrate the efficacy of erythromycin in killing Legionella pneumophila organisms that have been ingested by human polymorphonuclear leukocytes . With use of an electron microscope-autoradiography method in conjunction with an antibiotic-uptake assay, it was shown that {3H}-labeled erythromycin A base penetrated into the cytoplasm of human polymorphonuclear leukocytes in concentrations up to 24 times higher than the extracellular drug level . Similar studies using {14C}benzyl penicillin revealed that this antibiotic penetrated human polymorphonuclear leukocytes very poorly . Removal of erythromycin from the extracellular environment resulted in rapid leakage of radioactivity from the cells; an assay for bioactivity showed that this material was unaltered drug . Human polymorphonuclear leukocytes were permitted to ingest L . pneumophila and were then treated with erythromycin A base . The erythromycin killed the ingested legionellae, as evidenced by bacterial plate counts and morphological destruction of ingested organisms . These data clearly demonstrate the efficacy of erythromycin in killing susceptible intracellular pathogens. J Fam Pract, 1984 May, 18(5), 719 - 22 Clinical features and treatment of acute bronchitis; Dunlay J et al.; Although several surveys rank acute bronchitis as one of the ten most frequent diagnoses made by primary care physicians, its clinical features are poorly defined and treatment with antibiotics is controversial . This study was designed to determine the clinical characteristics that providers use to diagnose acute bronchitis and to examine the use of antibiotics in treating this illness . Charts of patients with the diagnosis of acute bronchitis or upper respiratory tract infection (URI) were randomly selected and progress notes from these visits were reviewed . Signs, symptoms, laboratory tests, and antibiotics prescribed were recorded . Patients with a diagnosis of acute bronchitis had more productive cough, purulent sputum, and abnormal lung examinations than patients with a diagnosis of URI (P less than .05 for each characteristic) . Laboratory tests, including chest roentgenograms, were not frequently used in making the diagnosis of acute bronchitis . Antibotics were prescribed for 27 of 29 patients (92 percent) with a diagnosis of acute bronchitis but for only 4 of 19 patients (21 percent) with a diagnosis of URI . Erythromycin was prescribed for 60 percent of patients with acute bronchitis . From this study it can be concluded that providers use the term acute bronchitis to designate a specific clinical syndrome that they treat with antibiotics . Further clinical trials are needed to evaluate the efficacy of such antibiotic therapy. Am J Med, 1984 May, 76(5), 931 - 4 Cholestatic hepatitis from erythromycin ethylsuccinate . Report of two cases; Diehl AM et al.; Cholestatic hepatitis developed in two patients while they were receiving erythromycin ethylsuccinate . Both patients had received the drug without apparent problem within two months of the episode of drug-related cholestatic injury . In both, there was complete resolution of the hepatic injury upon withdrawal of the drug . Erythromycin ethylsuccinate should be added to the list of drugs causing cholestatic hepatitis. Hautarzt, 1984 May, 35(5), 254 - 8 {Bullous pemphigoid in childhood}; Mensing H et al.; Bullous pemphigoid is a rather rare disease in childhood . A case report is given about a seven-year-old girl suffering from juvenile bullous pemphigoid and the differential diagnosis is discussed with regard to the other bullous diseases in children . Some clues were noted in the case history of our patient concerning an effective treatment using erythromycin in bullous pemphigoid . A short summary is presented about the theoretical basis with respect to this therapeutical procedure. Br J Dis Chest, 1984 Apr, 78(2), 192 - 4 Erythromycin in the management of troublesome BCG lesions; Power JT et al.; We have recently seen six persons with troublesome post-BCG lesions . All lesions healed whilst on therapy with erythromycin for a period of 2-4 weeks . Erythromycin has some effect on the atypical mycobacteria ( Wolinsky et al . 1957) but its use has not previously been described for treatment of BCG lesions. Arch Otolaryngol, 1984 Apr, 110(4), 258 - 60 Ototoxic effect of erythromycin therapy; Schweitzer VG et al.; Thirty-two cases of sudden, symmetrical, high-frequency, sensorineural hearing loss associated with intravenous (IV) and oral erythromycin therapy have been published since 1973 . We treated a patient with reversible ototoxicity associated with IV erythromycin for the treatment of legionnaire's disease. Food Chem Toxicol, 1984 Apr, 22(4), 269 - 74 Susceptibilities of drugs to nitrosation under standardized chemical conditions; Gillatt PN et al.; Of 22 drugs with either a N,N-dimethylamino, N,N-diethylamino or N-morpholino group in the molecule, eight were converted to volatile N-nitrosamines by nitrosative cleavage in reactions of nitrite and drug in a molar ratio of 4:1 at pH 3 . Under standardized conditions yields were greatest with aminopyrine and minocycline which contains two N,N-dimethylamino groups in the molecule . Oxytetracycline, chlortetracycline, tetracycline, promethazine, chlorpromazine, imipramine and disulfiram gave much lower yields and amitriptyline, clomiphene, clomipramine, dextropropoxyphene, diphenhydramine, disopyramide, erythromycin, mepyramine, methapyrilene, penicillin G procaine salt, procaine, tamoxifen, trimeprazine and tripelennamine yielded no detectable levels of volatile N-nitrosamines . Nitrosation products of 57 drugs were also examined by a group selective procedure estimating both volatile and non-volatile N-nitroso compounds . Virtually all of the yield obtained from aminopyrine or minocycline could be accounted for by N-nitrosodimethylamine (NDMA) . However, compounds yielding excess N-nitrosamines compared to NDMA were obtained from the other three tetracyclines, presumably as a result of the cleavage of a methyl group from the N,N-dimethylamino substituent to form desmethyl-N-nitroso compounds . In general, the drugs giving the highest yields of N-nitroso compounds were those containing secondary rather than tertiary amino groups . A considerable range of susceptibilities towards nitrous acid was observed overall; ten drugs containing a secondary or tertiary amino- or amido- or hydrazido - group did not react with nitrous acid to form N-nitroso compounds. S Afr Med J, 1984 Mar 24, 65(12), 462 - 7 The importance and frequency of mixed infections with Chlamydia trachomatis and mycoplasmas in acute gonococcal urethritis; Jahn G et al.; Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis are frequently involved in gonococcal urethritis . We investigated 143 male White and Black patients with gonococcal urethritis (average age 22,5 years) . Of these 29% had coexisting Chlam . trachomatis infection, 34% U . urealyticum infection and 13% Mycoplasma hominis infection . Conventional penicillin therapy did not affect Chlam . trachomatis, U . urealyticum or Mycoplasma hominis, which persisted in the lower urogenital tract, causing a so-called 'post-gonococcal urethritis.' Additional therapy with tetracycline or erythromycin was successful in most cases. Am J Ophthalmol, 1984 Mar, 97(3), 344 - 8 A cluster of cases of Mycobacterium chelonei keratitis associated with outpatient office procedures; Newman PE et al.; We studied three cases of keratitis caused by Mycobacterium chelonei, a nontuberculous mycobacterial species . The cases occurred in two women, 76 and 80 years old, and one man, 67 years old, treated as outpatients in the same office . One case followed suture removal and the other two occurred after posterior capsulotomy . Corneal lesions appeared within two to three weeks of trauma and were white, round infiltrates with indistinct margins and radiating projections . The lesions were found at all levels of the stroma and were associated with an epithelial defect . Anterior chamber reaction varied from a minimal response to a hypopyon . One patient responded to topical therapy with amikacin and erythromycin, but the other two patients required penetrating keratoplasties because of deep abscesses, which progressed toward the sclera despite therapy . These cases emphasized the possibility of rapidly growing nontuberculous mycobacteria producing serious ocular infections. Radiology, 1984 Mar, 150(3), 633 - 7 Pneumonia caused by Pittsburgh pneumonia agent: radiologic manifestations; Muder RR et al.; Using an objective scoring system, chest radiographs were reviewed in 23 cases of pneumonia due to the Pittsburgh pneumonia agent (PPA, Tatlockia micdadei, Legionella micdadei), including six cases of pneumonia with simultaneous isolation of PPA and L pneumophila (Legionnaires' disease) . Infiltrates were typically segmental to lobar; nodular infiltrates were noted in three cases . Spread to additional lobes after presentation occurred in four of 17 PPA infections . Pneumonia caused by both PPA and L pneumophila was unusually severe, with involvement of all lobes occurring in four of six cases, compared with one of 17 cases of PPA infection (p less than 0.02) . Radiographic severity did not correlate with underlying disease, immune status, or outcome . The majority of patients receiving erythromycin demonstrated objective radiologic improvement . In a patient population that included nonimmunosuppressed patients, nodule formation and rapid radiologic progression were not found to be characteristic of PPA pneumonia. Infect Control, 1984 Mar, 5(3), 138 - 40 Non-gonococcal ophthalmitis associated with erythromycin ointment prophylaxis of gonococcal ophthalmia neonatorum; Mooney BR et al.; Substitution of erythromycin ointment for silver nitrate in the prophylaxis of gonococcal ophthalmia neonatorum (GON) was accompanied by eight infections in 749 (1.1%) well-born and 21 infections in 285 (7.4%) intensive care infants during an eight-month period . This was significantly higher than previous rates of ophthalmitis during the use of silver nitrate, 0.3% (5/1877) and 2.1% (19/904) for well and intensive care infants, (P less than 0.01) . Multiple bacteria were isolated, polymicrobial infection occurred frequently and the pattern of bacterial isolates did not favor cross-contamination between infants . Observation suggested the frequent unintentional introduction of ungloved fingers into neonatal eyes during attempts to insert erythromycin ointment . Replacement of ophthalmic ointment with a liquid tetracycline preparation resulted in a decrease in non-gonococcal ophthalmitis to rates similar to the baseline period 8/997 (0.8%) for both nurseries . The increased number of infections appear related to the ointment vehicle, difficulty in its application and the mechanical introduction of bacteria . It is inferred that appropriate application of liquid medication also reduced the risk of inadequate prophylaxis. Arch Biochem Biophys, 1984 Mar, 229(2), 426 - 39 Malonyl-CoA decarboxylase from Streptomyces erythreus: purification, properties, and possible role in the production of erythromycin; Hunaiti AR et al.; Malonyl-CoA decarboxylase was purified (800-fold) from an erythromycin-producing strain of Streptomyces erythreus using DEAE-cellulose, Sephadex G-100, SP-Sephadex, and gel filtration with Sephadex G-75 . The molecular weight of the native enzyme was 93,000 as determined by gel filtration and the subunit molecular weight was 45,000 as estimated by sodium dodecyl sulfate-polyacrylamide electrophoresis, suggesting an alpha 2 subunit composition for the native enzyme . Evidence is presented that during the purification procedure and storage a proteolytic cleavage occurred resulting in the formation of 30- and 15-kDa peptides . The enzyme showed a pH optimum of about 5.0 whereas the vertebrate enzyme showed an optimum at alkaline pH . The enzyme decarboxylated malonyl-CoA with a Km of 143 microM and V of 250 nmol min-1 mg-1 . For the decarboxylation of methylmalonyl-CoA this enzyme showed the opposite stereospecificity to that shown by vertebrate enzyme; the (R) isomer was decarboxylated at 3% of the rate observed with malonyl-CoA while the (S) isomer was not a substrate . Neither avidin nor biotin affected the rate of malonyl-CoA decarboxylation, suggesting that biotin is not involved in catalysis . Acetyl-CoA and free CoA were found to be competitive inhibitors . Propionyl-CoA, butyryl-CoA, succinyl-CoA, and methylmalonyl-CoA showed little inhibition, and neither thiol-directed reagents nor chelating agents inhibited the enzyme . High ionic strength and sulfate ions caused reversible inhibition of the enzymatic activity . Under two different cultural conditions the time course of appearance of malonyl-CoA decarboxylase was determined by measuring the enzyme activity and the level of enzyme protein by an immunological method using rabbit antibodies prepared against the enzyme . In both cases the increase and decrease in the decarboxylase correlated with the rate of production of erythromycin, suggesting a possible role for this enzyme in the antibiotic production. Am J Surg, 1984 Mar, 147(3), 402 - 5 Cavitary Legionnaires' pneumonia: nosocomial infection in renal transplant recipients; Gombert ME et al.; Cavitation is an unusual manifestation of legionnaires' pneumonia . Mortality rates range from 24 to 58 percent with effective therapy . Antibiotic therapy is not standardized and is largely based on anecdotal reports . This report has described nosocomially acquired cavitary legionnaires' pneumonia in five renal transplant recipients . The diagnosis was made by seroconversion and immunofluorescent staining of lung tissue or transtracheal aspirates . Frequently seen associated symptoms were not present . All patients were successfully treated with 2 to 4 g of erythromycin for at least 4 weeks. Proc Natl Acad Sci U S A, 1984 Mar, 81(5), 1561 - 5 Construction of shuttle vectors capable of conjugative transfer from Escherichia coli to nitrogen-fixing filamentous cyanobacteria; Wolk CP et al.; Wild-type cyanobacteria of the genus Anabaena are capable of oxygenic photosynthesis, differentiation of cells called heterocysts at semiregular intervals along the cyanobacterial filaments, and aerobic nitrogen fixation by the heterocysts . To foster analysis of the physiological processes characteristic of these cyanobacteria, we have constructed a family of shuttle vectors capable of replication and selection in Escherichia coli and, in unaltered form, in several strains of Anabaena . Highly efficient conjugative transfer of these vectors from E . coli to Anabaena is dependent upon the presence of broad host-range plasmid RP-4 and of helper plasmids . The shuttle vectors contain portions of plasmid pBR322 required for replication and mobilization, with sites for Anabaena restriction enzymes deleted; cyanobacterial replicon pDU1, which lacks such sites; and determinants for resistance to chloramphenicol, streptomycin, neomycin, and erythromycin. Arch Dermatol, 1984 Mar, 120(3), 351 - 5 Topical erythromycin v clindamycin therapy for acne . A multicenter, double-blind comparison; Shahlita AR et al.; The efficacy and safety of topical 1.5% erythromycin solution and 1% clindamycin phosphate solution were compared in the treatment of acne . The number of inflammatory lesions was significantly reduced at 12 weeks by 62% and 59% and the number of noninflammatory lesions by 43% and 39% in the erythromycin and clindamycin groups, respectively . The reduction in lesions was also reflected in the clinical evaluation of the overall facial condition; 73% of the 74 patients treated with erythromycin solution and 62% of the 80 patients treated with clindamycin solution had excellent or good responses at 12 weeks . The results of this study show that topically applied 1.5% erythromycin and 1.0% clindamycin solutions are both effective and comparable in reducing the clinical manifestation of acne in patients with moderate disease. Lancet, 1984 Feb 11, 1(8372), 300 - 2 Failure of chloroquine-erythromycin and chloroquine-tetracycline combinations in treatment of chloroquine-resistant falciparum malaria in eastern Thailand; Phillips RE et al.; In Eastern Thailand the increasing resistance of Plasmodium falciparum to all available antimalarial drugs prompted a reassessment of chloroquine in combination with either erythromycin or tetracycline . Both combinations had produced encouraging results in vitro, in experimental animal models, or in preliminary clinical trials . In patients with uncomplicated falciparum malaria presenting with moderate parasitaemia the trial of chloroquine and tetracycline was abandoned after RIII resistance with clinical deterioration was encountered in 2 out of the first 5 patients studied . Of 16 patients treated with chloroquine+erythromycin, 11 showed resistance (RI-RIII) . These regimens appear ineffective and potentially dangerous in Eastern Thailand. Mod Vet Pract, 1984 Feb, 65(2), 107 - 14 Management of liver disease in dogs and cats; Tams TR; Ampicillin or amoxicillin is a good initial choice for treatment of liver disease involving bacteria . Cephalosporins, among other antibiotics, can be used with aminoglycosides for a broad-spectrum effect . Metronidazole may benefit patients with hepatic encephalopathy . Tetracycline, penicillins and cephalosporins are good choices for biliary disease . Corticosteroids are indicated for chronic active hepatitis, cholangiohepatitis, immune-mediated hepatopathy, and hepatic lymphosarcoma and mast-cell tumors . D-penicillamine is used to treat hepatic Cu toxicosis . Colchicine has been used to combat hepatic fibrosis . Lactulose is used in long-term management of hepatic encephalopathy . Diuretics and a low-Na diet help control ascites . Cimetidine is used to control GI ulcers . Anabolic steroids help reverse protein catabolism . Acetylcysteine is an antidote for acetaminophen toxicity . Use of hetacillin, chloramphenicol, lincomycin, sulfonamides, erythromycin, acetaminophen and methyltestosterone should be avoided in patients with liver disease. Am J Med, 1984 Feb, 76(2), 318 - 20 Failure of erythromycin in treatment of Legionella micdadei pneumonia; Rudin JE et al.; A 59-year-old immunocompromised woman had nosocomial Legionella micdadei infection that failed to respond to two weeks of erythromycin in high intravenous doses and oral rifampin . Treatment with intravenous trimethoprim-sulfamethoxazole and oral rifampin, which previously has not been used in this infection, resulted in cure. J Appl Bacteriol, 1984 Feb, 56(1), 63 - 79 Effects of the resistance plasmid R124 on the level of the OmpF outer membrane protein and on the response of Escherichia coli to environmental agents; Rossouw FT et al.; The introduction of the F-like resistance plasmid R124 into an ompC mutant of Escherichia coli K12 conferred altered sensitivity to a wide range of inhibitory agents . Sensitivity to ampicillin, chloramphenicol, ethionine, copper ions, deoxycholate, two fatty acids and colicins L and M was decreased by the plasmid . In contrast the plasmid-bearing ompC derivatives were more sensitive than the plasmid-free ompC mutant to erythromycin, cetyltrimethylammonium bromide and phenol . Introduction of R124 into the ompC strain also decreased the level of the OmpF protein and some (but not all) of the changed sensitivities listed above clearly resulted from this outer membrane protein deficiency . The presence in the ompC mutant of R124 (rather than the more efficient introduction of the plasmid into variants of the ompC strain) led to at least most of the changes described above because those tested were accentuated by the presence of a copy mutant of R124 and reversed by plasmid curing. Antimicrob Agents Chemother, 1984 Feb, 25(2), 173 - 8 Source of methylmalonyl-coenzyme A for erythromycin synthesis: methylmalonyl-coenzyme A mutase from Streptomyces erythreus; Hunaiti AA et al.; Streptomyces erythreus produces erythromycin, presumably from methylmalonyl-coenzyme A (CoA), which could be generated by the isomerization of succinyl-CoA . In S . erythreus cultures, {1,4-14C,2,3-3H}succinate was incorporated into erythromycin with a doubling of the 3H/14C ratio . This result is consistent with the hypothesis that succinyl-CoA is isomerized to methylmalonyl-CoA before incorporation into the macrocyclic lactone of erythromycin . The presence of methylmalonyl-CoA mutase, which catalyzes this isomerization, was demonstrated in cell-free extracts prepared from this organism . Consistent with the suggested role for this enzyme, methylmalonyl-CoA mutase activity increased over 12-fold at the time of the most rapid antibiotic production, and the activity level drastically declined when the antibiotic production ceased . The mutase was partially purified from this organism with DEAE-cellulose, ammonium sulfate precipitation, and affinity chromatography on a B12-coenzyme Sepharose column . The enzyme was stimulated 2.5-fold by the addition of B12-coenzyme . The enzyme showed a typical Michaelis-Menten type substrate saturation patterns, with KmS of 0.31 mM and 0.09 microM for methylmalonyl-CoA and B12-coenzyme, respectively, and a V of 0.5 mumol/min per mg . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a major band with a molecular weight of 63,000 . The properties of this enzyme appear to be fairly similar to those of the mutase previously obtained from other sources. Cancer, 1984 Jan 15, 53(2), 329 - 35 Prophylaxis of fever and infection in adult cancer patients . A placebo-controlled trial of oral trimethoprim-sulfamethoxazole plus erythromycin; Kramer BS et al.; Oral trimethoprim-sulfamethoxazole (Bactrim) plus erythromycin (TMZ-E) was tested versus placebo (P) as prophylaxis for bacterial infection in a randomized, double-blind trial in adult cancer patients receiving cytotoxic chemotherapy expected to result in significant neutropenia . The incidence of adverse reactions attributable to TMZ and/or E was higher in drug-treated episodes (18 of 28 vs 3 of 29 for P, P less than 0.0005) resulting in poorer compliance . The incidence of fever was not significantly different between episodes treated with TMZ-E (18/27) and those treated with P (17/29), nor was there a significant difference in the median interval between the onset of neutropenia and the onset of fever . However, 14 of 18 fevers in TMZ-E recipients were without a documented infectious source compared with only 6 of 17 in P recipients (P less than 0.05) . The same patterns were apparent even when episodes in which compliance with the regimen was either excellent or good were considered separately . There was no significant difference in the number of deaths from infection between TMZ-E and P recipients (3/27 vs 1/29) . It is concluded that TMZ-E prophylaxis is of no practical benefit, may mask the cause of infection in febrile neutropenic cancer patients, and is associated with substantial toxicity. Pharmacology, 1984, 28(3), 171 - 6 The effect of erythromycin on the disposition kinetics of warfarin; Bachmann K et al.; Erythromycin is generally regarded as innocuous in regard to adverse interactions with other drugs . Recently, however, its potentiation of theophylline and warfarin has been reported . The present investigation defined more specifically the kinetics of the interaction between erythromycin and warfarin . Warfarin kinetics were evaluated in 12 normal subjects who took a single 1 mg/kg dose of warfarin with and without erythromycin . Erythromycin (250 mg p.o.) every 6 h for 8 days decreased warfarin clearance by 14% (p less than 0.001) . Warfarin's apparent volume of distribution was not affected . Further, the effect of erythromycin was greatest among subjects whose control phase warfarin clearance was relatively slow, and least among those whose control phase warfarin clearance was relatively fast . The magnitude of the decrease in warfarin clearance correlated negatively with control warfarin clearance (r = -0.89, p less than 0.005) . These data are consistent with the interpretation that erythromycin can potentiate warfarin-induced hypoprothrombinemia by slowing warfarin clearance. J Infect, 1984 Jan, 8(1), 61 - 3 Prolonged Q fever associated with inappropriate secretion of anti-diuretic hormone; Biggs BA et al.; A man with acute Q fever developed hyponatraemia associated with inappropriate secretion of anti-diuretic hormone . The pyrexial illness lasted for 9 weeks and failed to respond to tetracycline, erythromycin and intravenous lincomycin . Subsequently seroconversion indicated chronic Q fever. Arch Toxicol Suppl, 1984, 7, 298 - 302 Erythromycin estolate impairs the mitochondrial and microsomal calcium homeostasis: correlation with hepatotoxicity; Richelmi P et al.; The effects of erythromycin estolate, a well known hepatotoxic macrolide antibiotic, on isolated rat hepatocyte viability and on subcellular Ca2+ transport have been investigated . Erythromycin estolate (0.5 mM), but not erythromycin base and erythromycin ethylsuccinate, induced 100% cell death after 60 min incubation, and caused maximal inhibition of mitochondrial and microsomal Ca2+ sequestration activities at 0.1 mM concentration . Sodium lauryl sulphate, which is the surfactant moiety of the erythromycin estolate molecule, caused effects similar to those exhibited by erythromycin estolate . Disorders of the intracellular calcium homeostasis seem to play a role in the lauryl sulphate-mediated hepatotoxic action of erythromycin estolate. Ann Otolaryngol Chir Cervicofac, 1984, 101(8), 643 - 7 {Ototoxic potential of erythromycin}; Demaldent JE et al.; On the basis of a personal case and a review of the literature, the authors raise the problem of the potential ototoxicity of erythromycin in patients with renal failure . The cochlear toxicity of this antibiotic is very different from that of the aminoglycosides, as in all of the reported cases, hypoacusis appears very early and always resolved once the antibiotic was stopped . The actual mechanism of the cochlear damage has not been studied . Although this iatrogenic reaction is uncommon, the authors recommend caution when prescribing erythromycin to patients with renal failure. Rev Epidemiol Sante Publique, 1984, 32(6), 352 - 9 {Contribution of pneumococcal serotyping and antibiotyping to the prevention and treatment of pneumococcal infections (1980-1982) . Pneumococcal typing and vaccination (1980-1982)}; Rouhan D et al.; During a 3-year period (1980-1982), 594 pneumococcal strains taken from 565 patients were serotyped . The distribution of the serotypes and their prevalence varied by sample and year . The theoretic vaccinal coverage, evaluated for the four main pathologies: pneumonia, otitis, meningitis, bacteriemia, is 79,1% . Among vaccinal serotypes, the types 19, 7, 3, 6, 1, and 23 are the most frequent, representing a cumulative incidence of 57,7% . In our region (Grenoble), the pneumococcus remains very sensitive to antibiotics . No strain resistant to penicillin G was observed . Erythromycin, doxycyclin, chloramphenicol, and cotrimoxazole preserve their potency with, respectively, 2,1%, 1,8%, 1,1%, and 1,9% resistant strains. Akush Ginekol (Sofiia), 1984, 23(5), 415 - 9 {Drug interactions with oral contraceptive steroids}; Chernev T; PIP: Various drugs are capable of enhancing or inhibiting the effect of oral contraceptives (OCs) . Drugs of the rifampicin group are active enzyme inductive agents which affect both the estrogenic and progestagenic components of OCs . This was demonstrated by the following pharmacokinetic study . 8 women received a single dose of Minovlar (50 mg of ethinyl estradiol and 1 mg of norethindrone acetate) during a rifampicin course, and another dose of the same OC was administered after the completion of the drug course . Rifampicin reduced the half-life of ethinyl estradiol from 6.2 to 3.2 hours and that of norethindrone acetate from 6.5 to 2.9 hours . Anticonvulsive drugs, e.g., phenytoin, phenobarbital, methylphenobarbital, and carbamazepine, often cause failures of contraceptive programs using OCs . A recent study followed the effect of phenobarbital in 4 women taking OCs . In two cases, the concentration of estrogen in blood plasma decreased significantly and hemorrhages occurred . In such cases, other methods of contraception should be recommended . Statistics show that, in 1982, 38 English women experienced unsuccessful contraception because they took various antibiotics simultaneously with OCs . This effect was reported for ampicillin, tetracycline, erythromycin, nitrofurantoin, and other antibiotics . On the other hand, ascorbic acid (Vitamin C) enhances the effect of OCs . The above studies prove that the interactions of rifampicin, anticonvulsive drugs, and antibiotics with OCs are pharmacodynamic, rather than pharmacokinetic, interactions . There is no clinical evidence to prove that OCs interfere with the metabolism of certain drugs . Future clinical and paraclinical studies are needed for a better understanding of these effects . Curr Med Res Opin, 1984, 9(3), 192 - 6 Treatment of acute tonsillo-pharyngitis: a comparative study of spiramycin and erythromycin; Suprihati et al.; A comparative study was carried out to determine the clinical efficacy of spiramycin and erythromycin in the treatment of acute tonsillo-pharyngitis . Patients were allocated at random to receive either 500 mg spiramycin 3-times daily for 3 days or 500 mg erythromycin 3-times daily for 5 days . Details were recorded daily by patients of subjective complaints such as fever, sore throat and difficulty in swallowing, and objective signs and symptoms of inflammation were assessed by the physician before and after treatment . Results were analyzed for 32 patients in each group and showed both treatments resulted in a rapid relief of their clinical condition in over 90% of patients . Although all patients showed marked improvements, a few still complained of symptoms at the end of the treatment period . Neither treatment regimen proved adequate for the eradication of the initial pathogen identified from throat swab cultures and leucocytosis persisted in at least 1 patient in each group . Seven patients on erythromycin complained of nausea and/or epigastric pain and 1 patient on spiramycin had urticaria. Microbios, 1984, 41(165-166), 205 - 8 Cytoplasmic transformation of Saccharomyces cerevisiae using purified mtDNA; Maqueda M et al.; Transformation of cytoplasmic mutants of Saccharomyces cerevisiae proved to be successful using plasmid or intact mitochondria, but not when mtDNA was used as the transforming principle . The sphaeroplasts of two cytoplasmic mutants, respiratory deficient and erythromycin sensitive cells, were transformed using purified mtDNA from respiratory competent or erythromycin resistant donor strains. Acta Otolaryngol Suppl, 1984, 407, 67 - 9 Neonatal conjunctivitis caused by Chlamydia trachomatis; Sandstrom I; Chlamydia trachomatis is a common cause of neonatal infection in industrialized countries and is acquired from the infected maternal cervix . Multiple mucosal surfaces, including the respiratory and the gastrointestinal tract as well as the conjunctiva, will be colonized by the organism . Conjunctivitis and pneumonia are the illnesses presently recognized as manifestations of these infections . C . trachomatis is isolated from the eye in 14 to 25% of patients with neonatal conjunctivitis and there is often an associated nasopharyngeal infection . The conjunctivitis is often the first clinical manifestation of these potentially systemic infections and therefore systemic therapy is required . The recommended treatment in neonatal chlamydial conjunctivitis is oral erythromycin 25 mg/kg every 12 hours for 14 days . This dose is well tolerated by the infant . Parents of infants with chlamydia infection should be treated with oral erythromycin or tetracyclines . Erythromycin should be given to breast feeding mothers. Pharmacology, 1984, 29(6), 305 - 11 Relative bioavailability of enteric coated pellets, stearate and ethylsuccinate formulations of erythromycin; Tjandramaga TB et al.; In a randomized three-phase crossover study, 12 healthy male volunteers were given three 12-hourly 500-mg doses of erythromycin base, as enteric coated pellets in capsules (2 X 250 mg), erythromycin stearate tablet (1 X 500 mg), or erythromycin ethylsuccinate sachet (1 X 500 mg) . The reaction time after administration of the pellets is significantly longer than after the stearate or ethylsuccinate formulations . The peak serum concentrations are higher for the pellets after both the 1st and 3rd dose . The time to reach peak concentrations is significantly longer for the pellets than for the stearate and ethylsuccinate formulations . The area under the serum concentration/time curve during 0-8 h after both doses is highest for the pellets . In conclusion, these findings indicate that despite the longer lag (1.8-1.2 h), the extent of gastrointestinal absorption and bioavailability of erythromycin is apparently greater for the base pellets than for the stearate and ethylsuccinate formulations. Infect Immun, 1984 Jan, 43(1), 263 - 9 Genetic analysis of phase change in Bordetella pertussis; Weiss AA et al.; Avirulent-phase derivatives of Bordetella pertussis (those which have simultaneously lost the ability to synthesize several virulence-associated factors) and the genetic mechanism of the phase change were studied . Increased tolerance to erythromycin was shown to be an avirulent-phase marker . By the use of efficiency of plating on erythromycin, the proportion of avirulent-phase (Vir) variants in a virulent-phase (Vir+) population was determined to be between 10(-3) and 10(-6), depending on the strain . We showed that the phase shift is reversible and detected a complete Vir- to Vir+ to Vir- to cycle . In other experiments, hybridization studies with avirulent-phase mutants obtained by Tn5 mutagenesis suggested that a single region located at a unique site in the B . pertussis chromosome controls the phase change . One of the avirulent Tn5 mutants was used as a recipient in a conjugative cross with a virulent-phase donor . All recombinants which had reacquired the virulence-associated factors also lost Tn5, indicating the loss of Tn5 was required to restore the Vir+ phenotype . The Tn5 avirulent-phase mutants behave as if the insertion interrupted the function of a transacting gene product which is required for the expression of the other virulent-phase genes . A model of the molecular basis of the phase regulation is presented. Infect Immun, 1984 Jan, 43(1), 217 - 23 Isolation and characterization of Bordetella pertussis phenotype variants capable of growing on nutrient agar: comparison with phases III and IV; Peppler MS et al.; Unsupplemented nutrient agar (NA) was used to select spontaneous phenotype variants (PVs) of Bordetella pertussis Tohama I and 3779 which, by their growth on NA, could possibly be considered equivalent to phase IV in the system of Leslie and Gardner (P.H . Leslie and A.D . Gardner, J . Hyg . 31:423-434, 1931) or phase III in the system of Kasuga et al . (T . Kasuga, Y . Nakase, K . Ukishima, and K . Takatsu, Kitasato Arch . Exp . Med . 26:121-134, 1953) . NA growers (Gna+) were selected from the flat, nonhemolytic, non-NA grower (Dom- Hly- Gna-) PV of both strains at a rate of between 10(-7) to 10(-8) per cell per generation . When cultured on Bordet-Gengou agar (BGA), more than one colony type was observed in strain 3779; these all retained the Gna+ characteristic during 10 to 30 passages on BGA . Analysis of 125I-surface-labeled whole cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed no major changes between the Dom- Hly- Gna+ PV and their Dom- Hly- Gna- PV parents in polypeptide profile (by Coomassie stain), in surface exposure of proteins (by autoradiography), or in lipopolysaccharide profile (by silver stain) . Increased resistance to oleic acid, tetracycline, erythromycin, rifampin, and penicillin G, however, was characteristic for the Dom- Hly- Gna+ PV . Five phase IV strains and a phase III B . pertussis strain had similar antibiotic and oleic acid sensitivity profiles as the Dom- Hly- Gna+ isolates and plated with similar efficiency on NA, despite heterogeneity in BGA colonial morphology and lipopolysaccharide profile. Acta Derm Venereol, 1984, 64(3), 272 - 3 Fixed drug eruption to erythromycin; Pigatto PD et al.; A case of repeated eruption after administration of erythromycin is described . It is the first report of erythromycin as proven agent of such an allergic reaction. Pharmacology, 1984, 28(3), 139 - 49 Multiple binding of bepridil in human blood; Albengres E et al.; Using radiolabelled bepridil, equilibrium dialysis experiments and direct ligand-binding studies were conducted to characterize the binding of bepridil to some human serum proteins, and to blood cells and platelets, respectively . Bepridil was bound to serum albumin with K = 26 +/- 1.6 X 10(3) mol-1 X 1, n = 1.07 +/- 0.04; to alpha 1-acid glycoprotein with K = 442 +/- 68 X 10(3) mol-1 X 1, n = 0.90 +/- 0.04; and with a lesser extent to lipoproteins and gamma-globulins . Bepridil, propranolol, quinidine and erythromycin were found to share the same site on alpha 1-acid glycoprotein . The binding of bepridil to both RBC and WBC was nonspecific with the following parameters: NK = 10.55 +/- 0.10 per 5 X 10(6) RBC/mm3 and NK = 0.34 +/- 0.01 per 10(3) WBC/mm3, whereas the binding to platelets was saturable with N = 10.97 +/- 1.06 mumol/l per 108 +/- 10(3) platelets/mm3 and K = 40 +/- 8 X 10(3) mol-1 X 1 . The binding parameters were used to simulate the distribution of bepridil between serum proteins, blood cells and platelets over the therapeutic range and showed that serum albumin, alpha 1-acid glycoprotein and RBC were the major binding components. J Biol Chem, 1983 Dec 10, 258(23), 14233 - 8 Fluorescence stopped flow analysis of the interaction of virginiamycin components and erythromycin with bacterial ribosomes; Moureau P et al.; The kinetics of the interaction between the 50 S subunits (R) of bacterial ribosomes and the antibiotics virginiamycin S (VS), virginiamycin M (VM), and erythromycin have been studied by stopped flow fluorimetric analysis, based on the enhancement of VS fluorescence upon its binding to the 50 S ribosomal subunit . Virginiamycin components M and S exhibit a synergistic effect in vivo, which is characterized in vitro by a 5- to 10-fold increase of the affinity of ribosomes for VS, and by the loss of the ability of erythromycin to displace VS subsequent to the conformational change (from R to R*) produced by transient contact of ribosomes with VM . Our kinetic studies show that the VM-induced increase of the ribosomal affinity for VS (K*VS = 25 X 10(6) M-1 instead of KVS = 5.5 X 10(6) M-1) is due to a decrease of the dissociation rate constant (k*-VS = 0.008 s-1 instead of 0.04 s-1) . The association rate constant remains practically the same (k+VS approximately k*+VS = 2.8 X 10(5) M-1 s-1), irrespective of the presence of VM . VS and erythromycin bind competitively to ribosomes . This effect has been exploited to determine the dissociation rate constant of VS directly by displacement experiments from VS . 50 S complexes, and the association rate constant of erythromycin (k+Ery = 3.2 X 10(5) M-1 S-1) on the basis of competition experiments for binding of free erythromycin and VS to ribosomes . By making use of the change in competition behavior of erythromycin and VS, after interaction of ribosomes with VM, the conformational change induced by VM has been explored . Within the experimentally available concentration region, the catalytic effect of VM has been shown to be coupled to its binding kinetics, and the association rate constant of VM has been determined (k+VM = 1.4 X 10(4) M-1 S-1) . Evidence is presented for a low affinity binding of erythromycin (K*Ery approximately 3.3 X 10(4) M-1) to ribosomes altered by contact with VM . A model involving a sequence of 5 reactions has been proposed to explain the replacement of ribosome-bound erythromycin by VS upon contact of 50 S subunits with VM. Pediatrics, 1983 Dec, 72(6), 828 - 30 Interaction of theophylline with erythromycin base in a patient with seizure activity; Parish RA et al.; A pediatric patient who was taking carefully monitored doses of theophylline for chronic asthma, was placed on erythromycin base for bronchitis . She subsequently developed theophylline toxicity which caused her to experience seizure activity . Any patient taking a theophylline preparation who is then placed on ANY of the available erythromycin compounds must have close monitoring of serum theophylline levels. Biochem Int, 1983 Dec, 7(6), 719 - 25 Identification by affinity chromatography of Escherichia coli ribosomal proteins that bind erythromycin and chloramphenicol; Suryanarayana T; Erythromycin and chloramphenicol have been coupled to epoxy-activated Sepharose-6B . Extracted ribosomal proteins from 30S and 50S ribosomal subunits of Escherichia coli have been chromatographed on the coupled columns under reconstitution buffer conditions . Proteins bound to the columns were recovered and identified by two-dimensional polyacrylamide gel electrophoresis . Proteins L4, L5 and L21 bound to both columns . Proteins S5 and S7 showed weak binding to erythromycin-Sepharose. J Am Acad Dermatol, 1983 Dec, 9(6), 933 - 6 A double-blind study of the effectiveness of a 3% erythromycin and 5% benzoyl peroxide combination in the treatment of acne vulgaris; Chalker DK et al.; One hundred sixty-five subjects completed a 10-week, double-blind controlled study comparing the following: (1) a combination of 3% erythromycin and 5% benzoyl peroxide in a gel, (2) 5% benzoyl peroxide gel, (3) 3% erythromycin gel, and (4) the gel vehicle . The benzoyl peroxide gel and the erythromycin gel were superior to the control gel; however, the combination product was more effective than any of the others . This was true for both pustular and papular lesions, but the most dramatic effect was on combined inflammatory lesions, i.e., papules and pustules. J Antibiot (Tokyo), 1983 Nov, 36(11), 1439 - 50 New fluorinated erythromycins obtained by mutasynthesis; Toscano L et al.; Following the previously described semisynthetic preparation of new aglycones (8S)-8-fluoroerythronolide A (I), (8S)-8-fluoroerythronolide B (II) and the monoglycoside 3-O-mycarosyl-(8S)-8-fluoroerythronolide B (III), their conversion into new fluoroerythromycins was attempted by mutational biosynthesis . The strain Streptomyces erythraeus ATCC 31772, a mutant blocked in the biosynthesis of erythromycin, was employed in the present investigation . Four new antibiotics, (8S)-8-fluoroerythromycin A (IV), (8S)-8-fluoroerythromycin B (V), (8S)-8-fluoroerythromycin C (VI) and (8S)-8-fluoroerythromycin D (VII) were successfully derived by such an approach . The result is also discussed in terms of the substrate specificity of the enzymes involved in the biosynthesis of erythromycins . The new antibiotics exhibited promising biological properties. J Antimicrob Chemother, 1983 Nov, 12(5), 511 - 4 The activity of miokamycin (MOM) against Chlamydia trachomatis and mycoplasmas in vitro; Ridgway GL et al.; The activity of miokamycin, a new macrolide, was investigated against Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis, in vitro . Miokamycin was found to be similar in activity to doxycycline and erythromycin against Chlam . trachomatis and U . urealyticum . Against Mycopl . hominis, miokamycin had an activity clearly superior to erythromycin. Presse Med, 1983 Oct 29, 12(38), 2375 - 8 {Malignant form of Mediterranean boutonneuse fever . 6 cases}; Raoult D et al.; Six cases of severe Mediterranean boutonneuse fever are reported . The clinical diagnosis, based on the presence of summer fever with an erythematous rash plus an escharr in three patients, was confirmed by serology (microagglutination in 1 case, indirect immunofluorescence in 4) . The symptoms resembled those of Rocky Mountain spotted fever associating, as they did, a purpuric rash with neurological signs (impaired consciousness in all 6 cases, convulsion in 2), respiratory symptoms (5) and digestive signs (diarrhoea in 1 case, enlargement of the liver in 4) . Laboratory examinations showed thrombopenia (6), rise in serum transaminases (5), LDH (5) and CPK (6), increased in blood urea and creatinine levels (6), hyponatraemia (6), hypokaliaemia (5) and hypocalcaemia (5) . Two patients treated with doxycycline recovered and 4 died . Among these, 1 had received erythromycin, 1 a tetracycline and 1 doxycycline. Hum Toxicol, 1983 Oct, 2(4), 593 - 605 Study of serum levels, venous irritation and gastrointestinal side-effects with intravenous erythromycin lactobionate in patients with bronchopulmonary infection; Marlin GE et al.; Sixteen patients with bronchopulmonary infection received 500 mg erythromycin lactobionate by intravenous infusion every 8 h for 2 days . The duration of infusion was either 30 (8 patients) or 60 min (8 patients) . An inline filterset (0.22 micrometer) was included in the intravenous administration set in 4 patients of each infusion group . Serum erythromycin levels were obtained before and at various times for 8 h after the first and fourth doses and before and immediately after the other doses . The incidence and severity of venous irritation and gastrointestinal side-effects were assessed . Mean (S.D.) peak erythromycin levels for the 30 min infusion were 26.31 (6.89) micrograms/ml (first dose) and 26.85 (6.11) micrograms/ml (fourth dose) and for the 60 min infusions, 23.96 (7.91) micrograms/ml (first dose) and 23.65 (6.55) micrograms/ml (fourth dose) . Venous irritation was experienced by 12 patients, ranging from localized discomfort to thrombophlebitis, but the severity was significantly reduced by inline filtration (P less than 0.005) . Gastrointestinal side-effects were reported by 8 patients and 1 patient withdrew because of severe abdominal pain and nausea . These symptoms were usually relieved by spasmolytic agents and possibly could be explained by high concentrations reaching the gut wall either by biliary excretion or direct transport from blood and stimulating smooth muscle motility. Ann Surg, 1983 Oct, 198(4), 525 - 30 Cefoxitin versus erythromycin, neomycin, and cefazolin in colorectal operations . Importance of the duration of the surgical procedure; Kaiser AB et al.; Perioperative parenteral cefoxitin was compared with oral erythromycin, neomycin and parenteral cefazolin in a prospective, double-blind, randomized evaluation of 119 patients undergoing colorectal operations . Patients receiving cefoxitin had a higher wound infection rate than patients receiving erythromycin-neomycin-cefazolin (12.5% v 3.2%, respectively, p = .06) . A direct correlation existed between the duration of the operation and the infection rate . Cefoxitin prophylaxis was as effective as erythromycin-neomycin-cefazolin in patients undergoing surgical procedures of 4 hours or less (infection rates of 4.8% and 4.0%, respectively) . However, for surgical procedures lasting more than 4 hours, 5 of 14 patients (37.5%) receiving cefoxitin developed a wound infection v 0 of 13 patients receiving erythromycin-neomycin-cefazolin (p less than .05) . It is speculative as to whether frequent two-gram doses of cefoxitin given during the operation would provide prophylaxis equivalent to erythromycin-neomycin-cefazolin. Can Med Assoc J, 1983 Sep 15, 129(6), 554 - 5 Recommendations for prevention of neonatal ophthalmia . Infectious Diseases and Immunization Committee, Canadian Paediatric Society; Tularemia pneumonia mimicking legionnaires' disease: isolation of organism on CYE agar and successful treatment with erythromycin; A 46-year-old man showed a clinical response when treated with parenteral erythromycin for what was initially thought to be legionnaires' disease, but an organism isolated from his pleural fluid on CYE agar was subsequently identified as Francisella tularensis . Tularemia should be suspected in all cases of atypical pneumonia in the appropriate setting . Erythromycin may be effective empiric therapy in such cases . Because of the possibility of inadvertent isolation of Francisella tularensis on CYE agar, all cultures for suspected Legionella should be handled with extreme caution, preferably in a biological hood. Can J Microbiol, 1983 Sep, 29(9), 1149 - 53 {Genetic toxicity of methylmercuric chloride (CH3HgCl) on mitochondria of Saccharomyces cerevisiae}; Phipps J et al.; Among the strains of the yeast Saccharomyces cerevisiae we investigated, the organic form of mercury:methylmercury (II) does not seem to induce any cytoplasmic mutant "petite colonie" rho- . However, it induces a significant number of the erythromycin-resistant mutant Eryr . A dose